TFEB phosphorylation on Serine 211 is induced by autophagy in human synovial fibroblasts and by p62/SQSTM1 overexpression in HEK293 cells.
Autophagy receptor p62/SQSTM1 signals a complex network that links autophagy-lysosomal system to proteasome. Phosphorylation of p62 on Serine 349 (P-Ser349 p62) is involved in a cell protective, antioxidant pathway. We have shown previously that P-Ser349 p62 occurs and is rapidly degraded during human synovial fibroblasts autophagy. In this work we observed that fingolimod (FTY720), used as a medication for multiple sclerosis, induced coordinated expression of p62, P-Ser349 p62 and inhibitory TFEB form, phosphorylated on Serine 211 (P-Ser211 TFEB), in human synovial fibroblasts. These effects were mimicked and potentiated by proteasome inhibitor MG132. In addition, FTY720 induced autophagic flux, LC3B-II up-regulation, Akt phosphorylation inhibition on Serine 473 but down-regulated TFEB, suggesting stalled autophagy. FTY720 decreased cytoplasmic fraction contained TFEB but induced TFEB in nuclear fraction. FTY720-induced P-Ser211 TFEB was mainly found in membrane fraction. Autophagy and VPS34 kinase inhibitor, autophinib, further increased FTY720-induced P-Ser349 p62 but inhibited concomitant expression of P-Ser211 TFEB. These results suggested that P-Ser211 TFEB expression depends on autophagy. Overexpression of GFP tagged TFEB in HEK293 cells showed concomitant expression of its phosphorylated form on Serine 211, that was down-regulated by autophinib. These results suggested that autophagy might be autoregulated through P-Ser211 TFEB as a negative feedback loop. Of interest, overexpression of p62, p62 phosphorylation mimetic (S349E) mutant and phosphorylation deficient mutant (S349A) in HEK293 cells markedly induced P-Ser211 TFEB. These results showed that p62 is involved in regulation of TFEB phosphorylation on Serine 211 but that this involvement does not depend on p62 phosphorylation on Serine 349.


Nuclear import of LIKE HETEROCHROMATIN PROTEIN1 is redundantly mediated by importins α-1, α-2 and α-3.
LIKE HETEROCHROMATIN PROTEIN1 (LHP1) encodes the only plant homologue of the metazoan HETEROCHROMATIN PROTEIN1 (HP1) protein family. The LHP1 protein is necessary for proper epigenetic regulation of a range of developmental processes in plants. LHP1 is a transcriptional repressor of flowering-related genes, such as FLOWERING LOCUS T (FT), FLOWERING LOCUS C (FLC), AGAMOUS (AG) and APETALA 3 (AP3). We found that LHP1 interacts with importin α-1 (IMPα-1), importin α-2 (IMPα-2) and importin α-3 (IMPα-3) both in vitro and in vivo. A genetic approach revealed that triple mutation of impα-1, impα-2 and impα-3 resulted in Arabidopsis plants with a rapid flowering phenotype similar to that of plants with mutations in lhp1 due to the upregulation of FT expression. Nuclear targeting of LHP1 was severely impaired in the impα triple mutant, resulting in the de-repression of LHP1 target genes AG, AP3 and SHATTERPROOF 1 as well as FT. Therefore, the importin proteins IMPα-1, -2 and -3 are necessary for the nuclear import of LHP1.


Effect of the Mn Oxidation State on Single-Molecule-Magnet Properties: Mn(III) vs Mn(IV) in Biologically Inspired DyMn3O4 Cubanes.
Inspired by the ferromagnetic coupling in the cubane model CaMn(IV)3O4 of the oxygen-evolving complex of photosystem II, 3d-4f mixed-metal DyMn3O4 clusters were prepared for investigation of the magnetic properties. For comparison, YMn(IV)3O4 and YMn(IV)2Mn(III)O4 clusters were investigated as well and showed ferromagnetic interactions, like the calcium analogue. DyMn(IV)3O4 displays single-molecule-magnet properties, while the one-electron-reduced species (DyMn(IV)2Mn(III)O4) does not, despite the presence of a Mn(III) center with higher spin and single-ion anisotropy.


Placental characteristics and neonatal weights among women with malaria-preeclampsia comorbidity and healthy pregnancies.
Malaria and preeclampsia are leading causes of maternal morbidity and mortality in sub-Saharan Africa. They contribute significantly to poor perinatal outcomes like low neonatal weight by causing considerable placental morphological changes that impair placental function. Previous studies have described the effects of either condition on the placental structure but the structure of the placenta in malaria-preeclampsia comorbidity is largely understudied despite its high burden. This study aimed to compare the placental characteristics and neonatal weights among women with malaria-preeclampsia comorbidity versus those with healthy pregnancies. We conducted a retrospective cohort study among 24 women with malaria-preeclampsia comorbidity and 24 women with healthy pregnancies at a County Hospital in Western Kenya. Neonatal weights, gross and histo-morphometric placental characteristics were compared among the two groups. There was a significant reduction in neonatal weights (P<0.001), placental weights (P = 0.028), cord length (P<0.001), and cord diameter (P<0.001) among women with malaria-preeclampsia comorbidity compared to those with healthy pregnancies. There was also a significant reduction in villous maturity (P = 0.016) and villous volume density (P = 0.012) with increased villous vascularity (P<0.007) among women with malaria-preeclampsia comorbidity compared to those with healthy pregnancies. Placental villous maturity and villous volume density are significantly reduced in patients with malaria-preeclampsia comorbidity with a compensatory increase in villous vascularity. This leads to impaired placental function that contributes to lower neonatal weights.


The natural history and osteodystrophy of mucolipidosis types II and III.
To assess the natural history and impact of the secondary bone disease observed in patients with mucolipidosis (ML) II and III. Affected children and adults were ascertained from clinical genetics units around Australia and New Zealand. Diagnoses were confirmed by the National Referral Laboratory in Adelaide. The study encompassed all patients ascertained between 1975 and 2005. Data focussing on biochemical parameters at diagnosis, and longitudinal radiographic findings were sought for each patient. Where feasible, patients underwent clinical review and examination. Examinations included skeletal survey, bone densitometry, and measurement of serum and urine markers of bone metabolism. In a subset of patients, functional assessment using the Pediatric Evaluation and Disability Inventory (PEDI) and molecular analysis of GNPTAB were performed. Twenty-five patients with mucolipidosis were ascertained over a 30-year period. Morbidity and functional outcomes on living patients were described. Serum calcium and phosphate were normal. All, but one patient, had normal alkaline phosphatase. Serum osteocalcin and urine deoxypyridinoline/creatinine were elevated. Two radiological patterns were observed (i) transient neonatal hyperparathyroidism in infants with ML II and (ii) progressive osteodystrophy in patients with ML intermediate and ML III. Molecular analyses of GNPTAB in nine subjects are reported. ML is characterised by a progressive bone and mineral disorder which we describe as the 'osteodystrophy of mucolipidosis'. The clinical and radiographic features of this osteodystrophy are consistent with a syndrome of 'pseudohyperparathyroidism'. Much of the progressive skeletal and joint pathology is attributable to this bone disorder.


Hypotensive central spinal cord infarction: a clinicopathological study of 3 cases of aortic disease.
Neuropathological studies of 3 cases of aortic disease, complicated by severe prolonged hypotension, revealed a spectrum of central spinal cord infarction not corresponding to a specific arterial territory. The findings support the concept that the central grey matter of the caudal spinal cord is most vulnerable to oligaemic hypoxia. Variation in the longitudinal distribution of ischaemic damage in the individual case depends primarily on the anatomical pattern of the spinal arterial net and on the nature and distribution of the vascular pathology.


Molecular mapping of 36 soybean male-sterile, female-sterile mutants.
Mutability of the w(4) flower color locus in soybean [Glycine max (L.) Merr.] is conditioned by an unstable allele designated w(4)-m. Germinal revertants, purple-flower plants, recovered among self-pollinated progeny of mutable flower plants were associated with the generation of necrotic root, chlorophyll-deficiency, and sterility mutations. Thirty-seven male-sterile, female-sterile mutant lines were generated from 37 independent reversion events at the w(4)-m locus. The first germinal revertant study had one male-sterile, female-sterile mutant (st8, T352), located on Molecular Linkage Group (MLG) J. The second study had 36 germinal-revertant derived sterility mutants descended from four mutable categories of w(4)-m. The mutable categories were designated; (1) low frequency of early excisions, (2) low frequency of late excisions, (3) high frequency of early excisions, and (4) high frequency of late excisions. The objectives of the present study were to; (1) molecularly map the 36 male-sterile, female-sterile mutants, and to (2) compare map locations of these mutants with T352 (st8), identified from the first germinal revertant study. Thirty-three of 36 male-sterile, female-sterile mutations were derived from germinal reversions that were classified in the late excision categories. Thirty-five male-sterile mutants mapped to the st8 region on MLG J. The only exception mapped to MLG G. Most likely mutants were generated through insertion of a putative transposon that was excised from the w(4) locus. The location of 36 of 37 mutations to a single chromosomal region suggests preference for sequence-dependent insertion.


Adventure tourism and adventure sports injury: the New Zealand experience.
The primary aims of this study were to establish a client injury baseline for the New Zealand adventure tourism and adventure sport sector, and to examine patterns and trends in claims for injury during participation in adventure activities. Content analysis of narrative text data for compensated injuries occurring in a place for recreation and sport over a 12-month period produced over 15,000 cases involving adventure tourism and adventure sport. As found in previous studies in New Zealand, highest claim counts were observed for activities that are often undertaken independently, rather than commercially. Horse riding, tramping, surfing and mountain biking were found to have highest claim counts, while hang gliding/paragliding/parasailing and jet boating injuries had highest claim costs, suggesting greatest injury severity. Highest claim incidence was observed for horse riding, with female claimants over-represented for this activity. Younger male claimants comprised the largest proportion of adventure injuries, and falls were the most common injury mechanism.


Antiplatelet medications and evolving antithrombotic medication.
In treatment and prevention of thromboembolic events, the two major classes of anticoagulants are the antiplatelet agents and the antithrombotic agents. The antithrombotic agents have traditionally been heparin and warfarin, both of which were isolated in the 1930s, and have been used effectively since becoming commercially available in treatment and thromboprophylaxis of venous thromboembolic events (VTE). Though effective, they have a narrow therapeutic window and the antithrombotic response is variable, depending on the patient, and requires regular monitoring and adjustment to maintain the necessary therapeutic range. Recently developed novel anticoagulants in the prevention and treatment of VTE are now available and are increasingly encountered in day-to-day practice. A general understanding of these agents is essential in the planning of any interventional procedure in order to optimally balance the risk of hemorrhage, during or after a procedure, with the risk of periprocedural thrombosis.


Coding for new technology.
New procedures and new technology often outpace the development of medical codes to report these services to the insurance payors. Although unlisted procedure codes are not the first choice for reimbursement, it is essential that services be reported with only the code that accurately describes the procedure. For new equipment and techniques, this may result in an increased need for preauthorizing, reporting an unlisted procedure code, and ensuring that complete documentation accompany the claim. Practices should educate the insurance community where necessary to ensure that everyone is working toward the same goal: the best patient care possible.


Molecular profile of mouse stromal mesenchymal stem cells.
We determined a transcriptional profile specific for clonal stromal mesenchymal stem cells from adult and fetal hematopoietic sites. To identify mesenchymal stem cell-like stromal cell lines, we evaluated the adipocytic, osteoblastic, chondrocytic, and vascular smooth muscle differentiation potential and also the hematopoietic supportive (stromal) capacity of six mouse stromal cell lines from adult bone marrow and day 14.5 fetal liver. We found that two lines were quadripotent and also supported hematopoiesis, BMC9 from bone marrow and AFT024 from fetal liver. We then ascertained the set of genes differentially expressed in the intersection set of AFT024 and BMC9 compared with those expressed in the union set of two negative control lines, 2018 and BFC012 (both from fetal liver); 346 genes were upregulated and 299 downregulated. Using Ingenuity software, we found two major gene networks with highly significant scores. One network contained downregulated genes that are known to be implicated in osteoblastic differentiation, proliferation, or transformation. The other network contained upregulated genes that belonged to two categories, cytoskeletal genes and genes implicated in the transcriptional machinery. The data extend the concept of stromal mesenchymal stem cells to clonal cell populations derived not only from bone marrow but also from fetal liver. The gene networks described should discriminate this cell type from other types of stem cells and help define the stem cell state.


Does ischemic burden on stress testing influence patient survival in subjects with known severe multi-vessel CAD?
Ischemic burden observed during stress testing has been postulated to predict prognosis irrespective of anatomic atherosclerotic burden observed on angiography. However, it is not known if the stress test result influences the long-term prognosis of subjects with diffuse coronary artery disease. We sought to determine the prognostic importance of stress test false negativity amongst patients with severe multi-vessel coronary artery disease (CAD) undergoing stress testing in the previous decade. We selected subjects from the dates of 1/1/2000 to 12/31/2005 who underwent a nuclear stress test (MPI) or stress echocardiogram (SE) within six months of a coronary angiogram demonstrating severe, multi-vessel CAD. We excluded those with a prior MI, PCI, CABG, resting wall motion abnormality, or perfusion defect at rest. Determination of patient death during the followup period was performed using the U.S. social security index. 139 subjects (MPI 81, SE 58) were studied; stress tests were positive for ischemia in 80%. Rates of death were similar at 1 year (MPI 9%, SE 5%, p-value 0.44), 5 years (MPI 20%, SE 14%, p-value 0.36) and 10 years (MPI 30%, SE 26%, p-value 0.63). Using multivariate analysis, mortality at each time period was not affected by stress test positivity. Amongst subjects with diffuse and severe atherosclerosis with preserved ventricular function, ischemic burden on stress testing did not influence short or long-term survival.


Some observations on the biology of two rarely seen deep-sea chimaerids, Chimaera carophila and Hydrolagus homonycteris.
Chimaera carophila (n = 45) and Hydrolagus homonycteris (n = 11), two deep-sea chimaerids rarely caught in the waters off New Zealand, were collected from research trawl catches and commercial fishery catches around New Zealand at depths between 400 and 1300 m, between 2014 and 2016. Additional preserved specimens of both species (n = 58) from museum collections were analysed for size, sex and maturity. External assessment of male claspers and a combination of internal assessments of female gonad mass and oviducal gland width, were used to determine maturity. For both species, length at first maturity was 0·70-0·82 of their maximum observed chimaera length (LC ), with females maturing at a larger size. Length at maturity for C. carophila (LC range: 28·7-103·9 cm) was estimated at 72·5 cm LC for males (n = 163) and 82·5 LC for females (n = 58). In H. homonycteris, length at maturity (length range: 78·6-99·8 cm LC ) was estimated at 79·1 cm LC for males (n = 51) and 80·1 cm LC for females (n = 17). Ovarian fecundity was up to 31 for C. carophila and sperm storage was confirmed in the oviducal gland of this species. Both species preyed on benthic invertebrates. Some C. carophila and H. homonycteris inhabit depths beyond most current fisheries, but both species appear to be relatively rare and have reproductive parameters characteristic of low productivity, which may make these species vulnerable to population decline if mortality was to increase in the future.


Penzigomyces catalonicus, a new species of hyphomycetes from Spain.
Penzigomyces catalonicus sp. nov., collected on dead branches of an unknown tree species in Spain, is described and illustrated. This fungus is characterized by short, dark brown, percurrent conidiophores, usually doliiform conidiogenous cells and ellipsoidal or slightly obclavate, (2-)3-4(-6) euseptate, thin-walled conidia. The new taxon is compared with species from other morphologically similar genera, and a key to the known species of Penzigomyces is provided.


Building informed trust: developing an educational tool for injection practices and health insurance in Cambodia.
Unnecessary injections increase the risk of blood-borne infections as well as pose an avoidable financial burden on patients. Perceptions in rural Cambodia that medical drug injections provide the best quality medical care have resulted in a large proportion of the population seeking injections across medical conditions. As private providers have a higher propensity to offer injections, patients pursue more expensive care contributing to a greater financial burden. This study aimed to use an educational intervention to improve participant knowledge about injections and health insurance in order to build informed trust in safer injection practices and health insurance. Using an experimental study design, villages in rural Cambodia were randomly assigned to an intervention or control arm. Community educational workshops were implemented to improve participant knowledge about injections and health insurance. Pre-and post-intervention assessments were used to record the resulting changes in knowledge and trust in providers. Statistical analysis of survey results from the two study arms showed increases of 16.8% and 15.9% in study participant knowledge regarding injections and health insurance, respectively. Trust in health insurance increased by 12.9%. However, trust in healthcare providers proved to be resilient with small to no change. These results show that knowledge about injection safety and health insurance, as well as trust in health insurance, can be increased through information dissemination in rural Cambodia. However, health information campaigns may not easily influence people's trust in healthcare providers. Education of the general populace about safe injection practices and health insurance can contribute toward the country's efforts to reach universal health coverage.


Note: Tesla based pulse generator for electrical breakdown study of liquid dielectrics.
In the process of studying charge holding capability and delay time for breakdown in liquids under nanosecond (ns) time scales, a Tesla based pulse generator has been developed. Pulse generator is a combination of Tesla transformer, pulse forming line, a fast closing switch, and test chamber. Use of Tesla transformer over conventional Marx generators makes the pulse generator very compact, cost effective, and requires less maintenance. The system has been designed and developed to deliver maximum output voltage of 300 kV and rise time of the order of tens of nanoseconds. The paper deals with the system design parameters, breakdown test procedure, and various experimental results. To validate the pulse generator performance, experimental results have been compared with PSPICE simulation software and are in good agreement with simulation results.


Glucose versus fructose metabolism in the liver measured with deuterium metabolic imaging.
Chronic intake of high amounts of fructose has been linked to the development of metabolic disorders, which has been attributed to the almost complete clearance of fructose by the liver. However, direct measurement of hepatic fructose uptake is complicated by the fact that the portal vein is difficult to access. Here we present a new, non-invasive method to measure hepatic fructose uptake and metabolism with the use of deuterium metabolic imaging (DMI) upon administration of [6,6'-2H2]fructose. Using both [6,6'-2H2]glucose and [6,6'-2H2]fructose, we determined differences in the uptake and metabolism of glucose and fructose in the mouse liver with dynamic DMI. The deuterated compounds were administered either by fast intravenous (IV) bolus injection or by slow IV infusion. Directly after IV bolus injection of [6,6'-2H2]fructose, a more than two-fold higher initial uptake and subsequent 2.5-fold faster decay of fructose was observed in the mouse liver as compared to that of glucose after bolus injection of [6,6'-2H2]glucose. In contrast, after slow IV infusion of fructose, the 2H fructose/glucose signal maximum in liver spectra was lower compared to the 2H glucose signal maximum after slow infusion of glucose. With both bolus injection and slow infusion protocols, deuterium labeling of water was faster with fructose than with glucose. These observations are in line with a higher extraction and faster turnover of fructose in the liver, as compared with glucose. DMI with [6,6'-2H2]glucose and [6,6'-2H2]fructose could potentially contribute to a better understanding of healthy human liver metabolism and aberrations in metabolic diseases.


Sexuality: the challenge to espoused holistic care.
Nurses, by virtue of the close relationship with patients, are in a unique position to promote sexual health and provide sexual health advice to people in their care. Although nurses espoused the ideals of person-centred and holistic care, evidence from research studies suggested that, for a number of reasons, nurses did not consciously and proactively engage with patients in relation to sexual concerns. In today health-care environment, where patients are seeking information about the impact of illness and treatments on their sexual function, nurses have a responsibility to proactively engage with patients' sexual health concerns in an informed and sensitive manner. The aim of this paper is to provide nurses with guidelines on how they might include this aspect of care within their everyday work.


Deficits in social problem solving in adolescents with prenatal exposure to alcohol.
This study evaluated the social problem solving skills of adolescents with histories of prenatal alcohol exposure. Adolescents (28 alcohol-exposed, 15 controls) completed a standardized questionnaire of social problem solving, and caregivers completed a parent-report measure of executive functioning. Both questionnaires were mailed to families, and caregivers were asked to recruit a non-exposed control. Results suggest that alcohol-exposed adolescents have substantial impairments in their abilities to solve problems in their everyday life, even in the absence of mental retardation. Such impairments are likely to have a significant impact on social and academic functioning and reflect their need for critical services otherwise unavailable to them.


Senior synonyms for three Neotropical birds described by Louis Vieillot based on Félix de Azara (Passeriformes: Thraupidae, Tyrannidae, Tityridae).
The nomenclatural history of three species described by Vieillot based on the descriptions of Félix de Azara is examined. Adherent to the Principle of Priority under the International Code of Zoological Nomenclature, old available names and senior synonyms are identified for the thraupid Uniform Finch Haplospiza plumbea (Vieillot, 1818a); tyrannid Tropical Pewee Contopus sylvestris (Vieillot, 1816); and tityrid White-winged Becard Pachyramphus cyanocephalus (Vieillot, 1816). These names were based respectively on Azara's Number 111 "Pico de punzón obscuro aplomado", Number 168 "Tachurí obscurito mayor" and Number 217 "Batará obscuro y negro". It is recommended that these names should all be suppressed as nomina oblita in the interests of stability.


Prioritizing zoonoses: a proposed one health tool for collaborative decision-making.
Emerging and re-emerging zoonotic diseases pose a threat to both humans and animals. This common threat is an opportunity for human and animal health agencies to coordinate across sectors in a more effective response to zoonotic diseases. An initial step in the collaborative process is identification of diseases or pathogens of greatest concern so that limited financial and personnel resources can be effectively focused. Unfortunately, in many countries where zoonotic diseases pose the greatest risk, surveillance information that clearly defines burden of disease is not available. We have created a semi-quantitative tool for prioritizing zoonoses in the absence of comprehensive prevalence data. Our tool requires that human and animal health agency representatives jointly identify criteria (e.g., pandemic potential, human morbidity or mortality, economic impact) that are locally appropriate for defining a disease as being of concern. The outcome of this process is a ranked disease list that both human and animal sectors can support for collaborative surveillance, laboratory capacity enhancement, or other identified activities. The tool is described in a five-step process and its utility is demonstrated for the reader.


The orientation anisotropy and orientation constancy: a visual evoked potential study.
Two experiments were conducted on the orientation anisotropy in which averaged visual evoked potentials (VEPs) were recorded from the occipital scalp. The first experiment confirmed the findings of Maffei and Campbell (1970) that obliquely oriented gratings alternated back and forth produced smaller-amplitude VEPs than when the gratings were oriented horizontally or vertically. Since no asymmetry was found in VEPs produced by a Julesz figure presented under identical conditions, it was concluded that direction of displacement could not have been contributing to the effect. In a second experiment head tilt of the subject was manipulated together with grating orientation and the results indicated that the orientation anisotropy is retinally rather than gravitationally referenced. It was concluded that the site of orientation constancy is located either at higher levels of the primary visual system or in the second visual system.


Exploration of the conserved A+C wobble pair within the ribosomal peptidyl transferase center using affinity purified mutant ribosomes.
Protein synthesis in the ribosome's large subunit occurs within an active site comprised exclusively of RNA. Mutational studies of rRNA active site residues could provide valuable insight into the mechanism of peptide bond formation, but many of these mutations cause a dominant lethal phenotype, which prevents production of the homogeneous mutant ribosomes needed for analysis. We report a general method to affinity purify in vivo assembled 50S ribosomal subunits containing lethal active site mutations via a U1A protein-binding tag inserted onto the 23S rRNA. The expected pH-dependent formation of the A2450+C2063 wobble pair has made it a potential candidate for the pH-dependent conformational change that occurs within the ribosomal active site. Using this approach, the active site A2450+C2063 pair was mutated to the isosteric, but pH-independent, G2450*U2063 wobble pair, and 50S subunits containing the mutations were affinity purified. The G*U mutation caused the adjacent A2451 to become hyper-reactive to dimethylsulfate (DMS) modification in a pH-independent manner. Furthermore, the G*U mutation decreased both the rate of peptide bond formation and the affinity of the post-translocation complex for puromycin. The reaction rate (k(pep)) was reduced approximately 200-fold for both puromycin and the natural aminoacyl-tRNA A-site substrate. The mutations also substantially altered the pH dependence of the reaction. Mutation of this base pair has significant deleterious effects upon peptidyl transferase activity, but because G*U mutation disrupts several tertiary contacts with the wobble pair, the assignment of A2450 as the active site residue with the neutral pK(a) important for the peptidyl transferase reaction cannot be fully supported or excluded based upon these data.


Educational interventions to improve cytology visual diagnostic reasoning measured by eye tracking.
The teaching of visual diagnostic reasoning skills, to date, has been conducted in a largely unstructured apprenticeship manner. The purpose of this study was to assess if the introduction of two educational interventions improved the visual diagnostic reasoning skills of novices. These were (1) the active use of key diagnostic features and (2) image repetition. A pre-test and post-test research design was used to compare the two teaching interventions to a traditional teaching group and an expert group using eye tracking as an assessment method. The time to diagnosis and the percentage of time spent viewing an area of diagnostic interest (AOI) were compared using independent t-tests, paired t-tests, and analysis of covariance (ANCOVA). Diagnostic accuracy as a dichotomous variable was compared using Chi-square tables. Students taught in an active-learning manner with image repetition behaved most like experts, with no significant difference from experts for percentage of time spent in the AOIs and a significantly faster time to diagnosis than experts (p<.017). Our results from the educational interventions suggest a greater level of improvement in the eye tracking of students that were taught key diagnostic features in an active-learning forum and were shown multiple case examples.


Learning Curve of Internal Fixation for Nondisplaced Femoral Neck Fractures: A Cumulative Sum Analysis.
The purpose of this study was to determine whether there is a learning curve for internal fixation for nondisplaced femoral neck fractures using the cumulative sum (CUSUM) technique. We applied the CUSUM technique in monitoring performance of a single surgeon in internal fixation for nondisplaced femoral neck fractures. Fifty consecutive patients who underwent internal fixation for nondisplaced femoral neck fractures were evaluated retrospectively. Loss of fixation within 6 months postoperatively was considered as failure of treatment. Patients were stratified into the early experience group (cases 1 to 25) and the late experience group (cases 26 to 50). The CUSUM method was used to analyze the learning curve. There was no failure of treatment during study period. The operation time became shorter with experience. Using the CUSUM analysis to plot the learning curve, there was no significant learning curve observed for multiple pinning for nondisplaced femoral neck fractures. The CUSUM analysis revealed there was no obvious learning curve to become proficient at internal fixation for nondisplaced femoral neck fractures, if technical principles were followed during the procedure.


Label-free blood serum detection by using surface-enhanced Raman spectroscopy and support vector machine for the preoperative diagnosis of parotid gland tumors.
It is difficult for the parotid gland neoplasms to make an accurate preoperative diagnosis due to the restriction of biopsy in the parotid gland neoplasms. The aim of this study is to apply the surface-enhanced Raman spectroscopy (SERS) method for the blood serum biochemical detection and use the support vector machine for the analysis in order to develop a simple but accurate blood serum detection for preoperative diagnosis of the parotid gland neoplasms. The blood serums were collected from four groups: the patients with pleomorphic adenoma, the patients with Warthin's tumor, the patients with mucoepidermoid carcinoma and the volunteers without parotid gland neoplasms. Au nanoparticles (Au NPs) were mixed with the blood serum as the SERS active nanosensor to enhance the Raman scattering signals produced by the various biochemical materials and high quality SERS spectrum were obtained by using the Raman microscope system. Then the support vector machine was utilized to analyze the differences of the SERS spectrum from the blood serum of different groups and established a diagnostic model to discriminate the different groups. It was demonstrated that there were different intensities of SERS peaks assigned to various biochemical changes in the blood serum between the parotid gland tumor groups and normal control group. Compared with the SERS spectra of the normal serums, the intensities of peaks assigned to nucleic acids and proteins increased in the SERS spectra of the parotid gland tumor serums, which manifested the differences of the biochemical metabolites in the serum from the patients with parotid gland tumors. When the leave-one-sample-out method was used, support vector machine (SVM) played an outstanding performance in the classification of the SERS spectra with the high accuracy (84.1 % ~ 88.3 %), sensitivity (82.2 % ~ 97.4 %) and specificity (73.7 % ~ 86.7 %). Though the accuracy, sensitivity and specificity decreased in the leave-one-patient-out cross validation, the mucoepidermoid carcinoma was still easier to diagnose than other tumors. The specific molecular differences of parotid gland tumors and normal serums were significantly demonstrated through the comparison between the various SERS spectra.But compared with the serum SERS spectra reported in the other studies, some differences exist between the spectra in this study and the ones reported in the lietratures. These differences may result from the various nano-particles, the different preparation of serum and equipment parameters, and we could need a further research to find an exact explanation.Based on the SERS spectra of the serum samples, SVM have shown a giant potential to diagnose the parotid gland tumors in our preliminary study. However, different cross validaiton methods could effect the accuracy and a further study involing a great number of samples should be needed. This exploratory research demonstrated the great potential of SERS combined with SVM into a non-invasive clinical diagnostic method for preoperative diagnosis of parotid gland tumors. And the internal relation between the spectra and patients should be established in the further study.


Perforation during colonoscopy in endoscopic ambulatory surgical centers.
Perforation as a complication of colonoscopy is estimated to occur in 0.01% to 0.3% of procedures, but the frequency in ambulatory settings is unknown. This study determined the number of perforations occurring within a network of endoscopic ambulatory surgery centers. A total of 116,000 colonoscopies were performed within one network of 45 endoscopic ambulatory surgery centers in the United States during 1999. All identified perforations were reported to the network clinical director and reviewed by a panel of 3 gastroenterologists. There were 37 (0.03%) perforations; 27 in women and 10 in men. Median patient age was 75 years (range 39-87 years); 18 patients (49%) had diverticular disease and 20 (54%) had a history of pelvic or colonic surgery. Twenty-four (65%) procedures were diagnostic, and 13 (35%) were therapeutic. The most common site of perforation was the sigmoid colon (62%); followed by the ascending colon (16%); cecum, transverse colon, and splenic flexure (11%); and rectum, anastomotic, or unknown (11%). The time to diagnosis ranged from immediate to 72 hours (29 <1 hour, 8 >1 hour). All patients were hospitalized; 35 (95%) underwent exploratory laparotomy, and 2 (5%) were treated conservatively. No patient died. Reported perforations for procedures performed in endoscopic ambulatory surgery centers occurred most frequently during diagnostic colonoscopy in older woman with a history of surgery or diverticular disease. Reported perforations in endoscopic ambulatory surgery centers were uncommon.


Decitabine and vitamin D3 differentially affect hematopoietic transcription factors to induce monocytic differentiation.
Standard chemotherapy is not curative for many patients with acute myeloid leukemia (AML). New treatment strategies combining demethylating agents, such as decitabine, and drugs that induce myelomonocytic differentiation (i.e. Vitamin D3) may re-establish functional hematopoiesis in these patients. We studied the effects of decitabine alone or in combination with Vitamin D3 (VD3) on U937 cells and AML blasts. Preincubation with decitabine (0.1-1 microM) and subsequent exposure to VD3 (3 nM) synergistically induced monocytic differentiation. To elucidate the mechanisms of decitabine- and VD3-induced monocytic differentiation, we investigated the effects of the two drugs on transcription factors implicated in monocytic differentiation. Northern and Western blotting showed that decitabine induced transcription of c-jun but not PU.1, while VD3 increased PU.1, IRF8, and C/EBPbeta but not c-jun. Using electromobility shift assays, we demonstrated increased DNA binding of nuclear proteins from decitabine- and VD3-induced U937 cells to the CD11b promoter. In addition, we investigated whether the myeloid transcription factor Sp1 played a role in decitabine- and VD3-induced CD14 expression. Indeed, we found that mithramycin A, a specific inhibitor of Sp1, inhibited both VD3- and decitabine-induced upregulation of CD14, which is in line with previous data showing that Sp1 is critical for CD14 promoter activity. Induction of CD11b and/or CD14 by decitabine and/or VD3 was confirmed in primary AML patient samples at the time of diagnosis. In conclusion, decitabine synergizes with Vitamin D3 to induce CD11b and CD14 expression, likely by enhancing PU.1/c-jun and Sp1 transcriptional activity.


Observation scales for pain assessment in older adults with cognitive impairments or communication difficulties.
Several pain observation scales have been developed to accurately assess and manage pain in older adults with severe cognitive impairments, communication difficulties, or both. To review relevant pain observation scales and the psychometric qualities of these scales. The literature was searched for articles reporting the use of a pain observation scale in an empirical study and describing psychometric properties in older adults with cognitive impairments, communication difficulties, or both. Thirteen pain observation scales were included. Scales differed in numbers of items, types of categories, and psychometric properties. Facial expression, vocalization, motor behavior, and social behavior or mood are categories present in most of the scales. In terms of reliability and validity, however, most studies are too limited or incomplete to allow definite conclusions to be drawn about usefulness in daily practice. As different methods of evaluating reliability and validity were used, and different aims (e.g., type of pain) were pursued, the available scales cannot be compared easily. Nevertheless, a few are promising, given preliminary results. These should be examined further on psychometric properties and usefulness in different populations because optimal pain assessment is necessary for efficient and effective pain treatment.


Primary intimal sarcoma of the left atrium presenting with constitutional symptoms.
Intimal (spindle-cell) sarcomas are exceptionally rare and are highly aggressive cardiac tumors. The authors describe a case of a 43-year-old female, presenting with a 3-month history of constitutional symptoms with fever, night sweats, anorexia and weight loss, associated with productive cough and pleural effusion that was admitted with clinical suspicion of pulmonary tuberculosis. The patient developed sudden acute heart failure symptoms during hospitalization, leading to mechanical ventilation. Computed tomography scan with contrast showed a cardiac tumor filling the left atrium causing compression of pulmonary veins. Surgical resection was performed and histologic examination revealed an intimal sarcoma. Although commenced on adjuvant chemotherapy, local tumor recurrence occurred with pericardium invasion. The patient died within 4 months of initial diagnosis. This report aims to describe an unusual presentation of this rare disease entity, and to discuss its highly aggressive clinical course.


Celiac Disease Is Associated with Childhood Psychiatric Disorders: A Population-Based Study.
To determine the risk of future childhood psychiatric disorders in celiac disease, assess the association between previous psychiatric disorders and celiac disease in children, and investigate the risk of childhood psychiatric disorders in siblings of celiac disease probands. This was a nationwide registry-based matched cohort study in Sweden with 10 903 children (aged <18 years) with celiac disease and 12 710 of their siblings. We assessed the risk of childhood psychiatric disorders (any psychiatric disorder, psychotic disorder, mood disorder, anxiety disorder, eating disorder, psychoactive substance misuse, behavioral disorder, attention-deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and intellectual disability). HRs of future psychiatric disorders in children with celiac disease and their siblings was estimated by Cox regression. The association between previous diagnosis of a psychiatric disorder and current celiac disease was assessed using logistic regression. Compared with the general population, children with celiac disease had a 1.4-fold greater risk of future psychiatric disorders. Childhood celiac disease was identified as a risk factor for mood disorders, anxiety disorders, eating disorders, behavioral disorders, ADHD, ASD, and intellectual disability. In addition, a previous diagnosis of a mood, eating, or behavioral disorder was more common before the diagnosis of celiac disease. In contrast, siblings of celiac disease probands were at no increased risk of any of the investigated psychiatric disorders. Children with celiac disease are at increased risk for most psychiatric disorders, apparently owing to the biological and/or psychological effects of celiac disease.


Contemporary Outcomes of Endovascular Intervention for Critical Limb Ischemia.
Critical limb ischemia (CLI) remains a significant cause of morbidity and mortality in patients with peripheral arterial disease. Optimal treatment strategies for CLI remain controversial. The only randomized trial comparing surgical with endovascular revascularization suggests no significant difference in limb salvage between open surgical bypass and angioplasty. Although novel endovascular strategies are now available, their efficacies remain largely untested in a randomized fashion. This review provides an overview of the data surrounding contemporary outcomes of endovascular therapy with an emphasis on current knowledge gaps.


Use of the Cobra catheter for targeted temperature management during cardiopulmonary bypass in swine.
The purpose of this investigation was to determine whether temperatures of the aortic arch and descending aortic circulations could be controlled independently during cardiopulmonary bypass with a cannula possessing an endoaortic baffle (Cobra; Cardeon, Cupertino, Calif). After Institutional Animal Care and Use Committee approval, 12 pigs weighing 60 kg were started on bypass through a sternotomy. A dual-lumen endoaortic cannula with a deployable baffle was used for arterial cannulation. Bypass was initiated at 37 degrees C, and control measurements were obtained. The baffle was then inflated with saline solution, segmenting blood flow along the greater and lesser curvatures of the aortic arch. Parallel heat exchangers were used to independently control temperature of the arch and descending aortic perfusates. Cerebral and systemic temperatures were recorded continuously. During cardiopulmonary bypass, mean flow and arterial pressure were maintained at 2.4 to 2.6 L x min(-1) x m(-2) and 60 to 70 mm Hg, respectively. With aortic flow distributed by the baffle, a 5 degrees C temperature differential between brain (30 degrees C) and body (35 degrees C) was established in a mean of 5 +/- 2 minutes. Mean brain and corporeal temperatures of 27 degrees C and 35 degrees C were then maintained over 60 minutes. Relative to control, internal jugular and inferior vena cava oxygen saturations increased during targeted temperature control with the device. The Cobra cannula allows for independent control of brain and body temperature while providing satisfactory hemodynamics. Application of this temperature management strategy may offer cerebral protection and the advantages of warm systemic bypass temperature.


Origin of power laws for reactions at metal surfaces mediated by hot electrons.
A wide range of experiments have established that certain chemical reactions at metal surfaces can be driven by multiple hot-electron-mediated excitations of adsorbates. A high transient density of hot electrons is obtained by means of femtosecond laser pulses and a characteristic feature of such experiments is the emergence of a power law dependence of the reaction yield on the laser fluence Y approximately F(n). We propose a model of multiple inelastic scattering by hot electrons which reproduces this power law and the observed exponents of several experiments. All parameters are calculated within density functional theory and the delta self-consistent field method. With a simplifying assumption, the power law becomes exact and we obtain a simple physical interpretation of the exponent n, which represents the number of adsorbate vibrational states participating in the reaction.


* Demineralized Bone Matrix as a Carrier for Bone Morphogenetic Protein-2: Burst Release Combined with Long-Term Binding and Osteoinductive Activity Evaluated In Vitro and In Vivo.
To allow bone defect regeneration, autologous bone grafting still represents the gold standard. However, autograft harvesting has limitations, including an additional surgery, donor site morbidity, and limited availability. Demineralized bone matrix (DBM) would represent an alternative, yet lacks sufficient osteoinductive properties. Combining DBM with a potent agent, such as bone morphogenetic protein-2 (BMP-2) might be a feasible alternative approach, optimizing an established grafting material with strong osteoinductive properties. A unique mixing device has been developed that enables perioperative handling to reach a homogeneous and standardized paste for bone defect filling. DBM proved in vitro to be a suitable carrier for BMP-2, with a documented release over 56 days at concentrations sufficient to stimulate osteogenic differentiation. At the end of the elution experiment, 56 days, bioactive BMP was still captured within the DBM. Using a sheep drill hole defect model, DBM perioperatively mixed with BMP-2 showed strong osteoinductive properties comparable to those of autologous bone and outnumbering the one of DBM alone or empty defects. Bone defect healing was enabled at diaphyseal and metaphyseal defects and thus BMP-2-doped DBM represented an easy perioperative enriching method and an efficient carrier for BMP-2. With the comparability to the clinical gold standard autologous bone, DBM mixed with BMP-2 might serve as possible alternative grafting material enabling a controlled osteogenic stimulation.


Emerging roles of phosphatidylinositol 3-monophosphate as a dynamic lipid second messenger.
The lipid products of phosphoinositide 3-kinase (PI3K) are involved in many cellular responses such as proliferation, migration and survival. Disregulation of PI3K-activated pathways is implicated in different disease including diabetes and cancer. Among the different products of PI3Ks, phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) has a well established role in signal transduction whereas the monophosphate phosphatidylinositol-3-phosphate (PtdIns-3-P) has been considered for a long time just a cellular component confined in endosomal structures. Only recently several evidence have indicated that PtdIns-3-P can also act as a dynamic intracellular second messenger. The role of PtdIns-3-P as mediator of crucial intracellular signals is therefore just beginning to be appreciated. Here we review some of the latest evidence showing that pools of PtdIns-3-P can be generated upon cellular stimulation in compartments different from the "classical" endosomal region. We describe several proteins that can be targets in mediating signals deriving from such stimulated PtdIns-3-P pools. In addition we describe the potential mechanism of switching on and off such signals. Taken together all this evidence suggest a novel, key role for PtdIns-3-P in signal transduction.


The impact of aging on vasa nervorum, nerve blood flow and vasopressin responsiveness.
Aging impacts microvessels in a number of tissue beds. Vasopressin acts as a vasoconstrictor in most blood vessels but may also cause vasodilation. We evaluated the role of aging and vasopressin in the regulation of nerve blood flow (NBF) in rat peripheral nerve. We undertook a dose-response study to examine the impact of aging on resting NBF and its vasoreactivity to vasopressin. Nerve blood flow was measured using microelectrode hydrogen polarography. Arginine-vasopressin was administered both intra-arterially and topically. In young adult rats (two months old) topical epineurial application of arginine-vasopressin produced a concentration-dependent reduction of NBF (ED50 = 3.8 x 10(-5) mol/L). Intra-arterial arginine-vasopressin also reduced NBF. Nerve blood flow was lower in aged rats (12 months old) and less responsive to topically applied vasopressin. The aging group had significantly higher concentrations of vasopressin in plasma than did the younger group. The results suggest that vasopressin constricts vessels in peripheral nerve and that there is an age related decline in the vasoconstrictive response to vasopressin. There may be a reduction in receptor sensitivity in vascular smooth muscle cells in peripheral nerve with increasing age.


Younger age at diagnosis is associated with panenteric, but not more aggressive, Crohn's disease.
Crohn's disease (CD) diagnosed in pediatric patients has been reported to have a more aggressive phenotype and course, with a greater prevalence of upper gastrointestinal involvement, than in adults. However, studies have not accounted for differences in diagnostic tests. We aimed to discern whether, in fact, CD diagnosed in childhood has a different outcome than CD diagnosed in adults. We performed comprehensive medical chart reviews of 571 patients with CD (451 with complete data) who were followed in a single referral inflammatory bowel disease clinic in Winnipeg, Canada, from 1993-2012. For specific time intervals, we determined types and numbers of imaging studies performed and parameters of disease phenotype, including age at diagnosis according to the Montreal classification (A1 diagnosed <17 years of age, A2 diagnosed 17-40 years, and A3 diagnosed >40 years). Within 1 year of diagnosis, a higher proportion of A1 patients had upper gastrointestinal involvement and ileocolonic (L3) disease than A2 or A3 patients. These differences could be partly accounted for by the diagnostic tests performed during this time period. Although A1 patients underwent more extensive imaging studies, they had a lower prevalence of complicated disease, particularly compared with A3 patients. After a median follow-up period of 11.1 years, complicated disease behavior (B2 [structuring] or B3 [penetrating]) was similar among the 3 groups. Nonetheless, at the end of the study period, rates of inflammatory bowel disease-related abdominal surgery were significantly lower for A1 than A2 patients (odds ratio, 0.63; 95% confidence interval, 0.41-0.98) but not for A3 patients (odds ratio, 0.71; 95% confidence interval, 0.40-1.27). On the basis of a database analysis of different age groups of patients with CD, studies of disease phenotypes among different cohorts should account for different patterns of diagnostic imaging evaluation. Our data show that although children are at increased risk of panenteric disease, they are not more likely to have more complicated disease or undergo surgery than adults.


Spatiotemporal relationships among D-serine, serine racemase, and D-amino acid oxidase during mouse postnatal development.
To elucidate the spatiotemporal relationships among D-serine, serine racemase, and D-amino acid oxidase (EC 184.108.40.206; DAO) in mouse cortex, striatum, cerebellum, heart, lung, liver, spleen, kidney, and skeletal muscle during mouse postnatal development. The transcription levels of serine racemase and DAO were assayed by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of serine racemase were examined by Western blot. DAO activities were assayed by colorimetric method. D-serine was measured by HPLC. In cortex, striatum, and cerebellum, free D-serine increased drastically after birth and coincided well with the increase of serine racemase expression. However, among the 9 tissues examined, DAO activities were detected only in cerebellum and kidney. During the 3rd week, DAO activity in cerebellum and kidney increased dramatically, which concurred with the drastic decline of D-serine content in these tissues. On the other hand, while D-serine and serine racemase fall to trace level in cerebellum and kidney at the 3rd weekend, DAO activities in these tissues increased continuously. The free D-serine is mainly synthesized by serine racemase. However, novel mechanisms might be involved in D-serine deposition in mouse tissues with high level of D-serine and no detectable DAO activity such as cortex and striatum. DAO in cerebellum and kidney might have other physiological functions in addition to degrading D-amino acid.


Postoperative Clinical and Radiological Analysis of Deviated Noses.
Anatomical deformities can greatly alter nasal function, which can be largely corrected during septoplasty and septorhinoplasty operations. In this study, we aimed to objectively measure the results of septoplasty surgeries of deviated noses with radiological analysis and compare the results with clinical evaluations. Forty patients who were undergoing septorhinoplasty were included in the study. Patients were evaluated with preoperative and postoperative paranasal computed tomography scan measurements and satisfaction surveys. Preoperative and postoperative mean ± SD septal deviation angle measurements were 11.9 ± 5.3 degrees and 6.5 ± 3.1 degrees, respectively. Preoperative and postoperative mean ± SD septal deviation distance measurements were 7.3 ± 4 and 3 ± 1.3 mm, respectively. Preoperative and postoperative mean ± SD oblique conchal measurement on the deviated side was 17.3 ± 3.2 and 13.4 ± 2.8, respectively. Preoperative and postoperative mean ± SD patient satisfaction survey scores were 17 ± 1.9 and 4.5 ± 1.9 points, respectively. To obtain a nose with a greatly improved functional gains, especially in heavy deviated noses, is an important goal in septorhinoplasty surgery. It is essential to apply the technique that will benefit the patient. The most important success criterion seems to be the regression of the clinical complaints of the patients, which can be proven objectively with computed tomography scan measurements.


Effect measures in prevalence studies.
There is still considerable confusion and debate about the appropriate methods for analyzing prevalence studies, and a number of recent papers have argued that prevalence ratios are the preferred method and that prevalence odds ratios should not be used. These arguments assert that the prevalence ratio is obviously the better measure and the odds ratio is "unintelligible." They have often been accompanied by demonstrations that when a disease is common the prevalence ratio and the prevalence odds ratio may differ substantially. However, this does not tell us which measure is the more valid to use. In fact, the prevalence odds ratio a) estimates the incidence rate ratio with fewer assumptions than are required for the prevalence ratio; b) can be estimated using the same methods as for the odds ratio in case-control studies, namely, the Mantel-Haenszel method and logistic regression; and c) provides practical, analytical, and theoretical consistency between analyses of a prevalence study and prevalence case-control analyses based on the same study population. For these reasons, the prevalence odds ratio will continue to be one of the standard methods for analyzing prevalence studies and prevalence case-control studies.


Inhibition of PAF-induced expression of CD11b and shedding of L-selectin on human neutrophils and eosinophils by the type IV selective PDE inhibitor, rolipram.
We quantitatively determined whether the selective phosphodiesterase (PDE) inhibitor, rolipram, inhibits changes in the adhesion molecules CD11b and L-selectin on platelet-activating factor (PAF)-stimulated human neutrophils and eosinophils in vitro. Incubations were performed in human whole blood obtained from healthy volunteers, to restrict activation by purification procedures and to simulate in vivo conditions, in which different cell types may interact, more closely. Receptor expression was measured after fixation of cells, using monoclonal antibodies and flow cytometry. Concentration-dependent inhibition of the PAF-induced CD11b expression and L-selectin shedding for neutrophils and eosinophils was observed with rolipram, dibutyryl cyclic adenosine monophosphate (cAMP), prostaglandin E2 (PGE2), and isoproterenol. However, these inhibitions did not exceed 50%. Preincubation with rolipram (10(-8) M) and subsequent incubation with isoproterenol (0.5x10(-8) M) or PGE2 (10(-8) M) induced a cumulative, but not synergistic, effect. Using the combination of rolipram with isoproterenol or PGE2, inhibition of PAF-induced L-selectin shedding from eosinophils was as high as 71+/-28 and 67+/-21%, respectively. Other inhibitions were below 50%. In conclusion, rolipram inhibits CD11b expression and L-selectin shedding of platelet-activating factor-stimulated neutrophils and eosinophils in whole blood in a concentration-dependent fashion. Inhibitions did not exceed 50%, even at high concentrations. The inhibition of platelet-activating factor induced shedding of L-selectin from eosinophils with a combination of rolipram and prostaglandin E2 or isoproterenol, however, was found to be approximately 70%. Inhibition of rolling adhesion of eosinophils may, therefore, be a mode of action of type IV phosphodiesterase inhibitors.


Protein profiling and tps23 induction in different maize lines in response to methyl jasmonate treatment and Diabrotica virgifera infestation.
Plant responses to herbivore insects involve direct and indirect defense with the production of signal molecules including jasmonic acid (JA) and its derivatives (e.g. methyl jasmonate, MeJA). In maize (Zea mays), root feeding by Diabrotica virgifera larvae activates an indirect defense mechanism, through enthomopathogenic nematodes that are recruited after Terpene Synthase 23 (tps23) upregulation and (E)-β-caryophyllene root emission. In order to gain insight into the correlation between JA signaling and response to Diabrotica attack, we analyzed tps23 expression and protein profiles in maize roots in response to MeJA treatment and insect infestation. Similar to herbivore feeding, MeJA treatment was found to increase tps23 transcript accumulation, with consistent variations for both treatments in maize lines differing in (E)-β-caryophyllene production. Analysis of root protein profiles showed specific alterations leading to the identification of three proteins that were induced by MeJA treatment. We focused on a peroxidase-like protein (Px-like) showing that the corresponding transcripts accumulated in all tested lines. Results show that exogenous application of MeJA upregulates tps23 expression and specifically alters protein patterns in maize roots. Parallel effects on tps23 transcript accumulation were observed upon hormone exposure and insect infestation in different maize lines. In contrast, Px-like transcript profiling showed differences between treatments. These results support the possible involvement of MeJA in mediating the upregulation of tps23 in response to Diabrotica attack.


Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study.
Only recently have neuroimaging studies moved away from describing regions activated by noxious stimuli and started to disentangle subprocesses within the nociceptive system. One approach to characterizing the role of individual regions is to record brain responses evoked by different stimulus intensities. We used such a parametric single-trial functional MRI design in combination with a thulium:yttrium-aluminium-granate infrared laser and investigated pain, stimulus intensity and stimulus awareness (i.e. pain-unrelated) responses in nine healthy volunteers. Four stimulus intensities, ranging from warm to painful (300-600 mJ), were applied in a randomized order and rated by the subjects on a five-point scale (P0-4). Regions in the dorsolateral prefrontal cortex and the intraparietal sulcus differentiated between P0 (not perceived) and P1 but exhibited no further signal increase with P2, and were related to stimulus perception and subsequent cognitive processing. Signal changes in the primary somatosensory cortex discriminated between non-painful trials (P0 and P1), linking this region to basic sensory processing. Pain-related regions in the secondary somatosensory cortex and insular cortex showed a response that did not distinguish between innocuous trials (P0 and P1) but showed a positive linear relationship with signal changes for painful trials (P2-4). This was also true for the amygdala, with the exception that, in P0 trials in which the stimulus was not perceived (i.e. 'uncertain' trials), the evoked signal changes were as great as in P3 trials, indicating that the amygdala is involved in coding 'uncertainty', as has been suggested previously in relation to classical conditioning.


The supratrochlear foramen of the humerus and its relation to the medullary canal: a potential surgical application.
The supratrochlear foramen of the humerus is located at the septum separating the coronoid from the olecranon fossa. Beyond its anthropologic interest, that trait seems to have clinical significance as well. The supratrochlear foramen was studied in 240 macerated adult humeri. The foramen was recorded in each sex and each side. We attempted to enlighten the likely relation of the foramen with the inferior edge of the medullary canal, as well as that of the dimensions of that canal of humerus and compare it to contralateral humeri without foramen. The medullary canal width at the entry point of a retrograde intramedullary nail was statistically smaller in humeri with foramen than in humeri without it. Furthermore, the medullary canal of the humeri with foramen ends more proximally than the canal of nonforamen humeri. In cases of humeral fractures of the supratrochlear foramen, the surgeon must keep in mind that it is better to perform an antegrade medullary nailing than a retrograde one; as there is higher chance of a secondary fracture, due to the extreme narrowness of the canal at the distal portion of humeri with the supratrochlear foramen.


Plasma amyloid precursor protein is decreased in Alzheimer's disease.
Alzheimer's disease is characterized by amyloid deposits whose major protein component is beta A4. beta A4 is a product of the amyloid precursor protein (APP). APP was assayed in partially purified plasma samples from 16 sporadic Alzheimer's disease patients, 12 age-matched controls, 15 Down's syndrome individuals aged 19-36 years and 8 young to middle-aged controls (22-51 years). 14 of the 16 Alzheimer's disease patients had decreased plasma APP when compared with age-matched controls. 14 of the 15 Down's syndrome individuals had similar levels of APP when compared with age-matched and elderly non-demented controls by immunoblotting, whereas one had levels of APP less than controls. Taken together with results from a previous report (Lancet 1992; 340: 453-454), the decreased plasma APP levels mirror the changes observed with cerebrospinal fluid APP levels in Alzheimer's disease.


Programmable Codelivery of Doxorubicin and Apatinib Using an Implantable Hierarchical-Structured Fiber Device for Overcoming Cancer Multidrug Resistance.
Multiple drug resistance (MDR) of cancer cells is a major cause of chemotherapy failure. It is currently a great challenge to develop a direct and effective strategy for continuously inhibiting the P-glycoprotein (P-gp) drug pump of MDR tumor cells, thus enhancing the intracellular concentration of the therapeutic agent for effectively killing MDR tumor cells. Here, a new implantable hierarchical-structured ultrafine fiber device is developed via a microfluidic-electrospinning technology for localized codelivery of doxorubicin (DOX) and apatinib (AP). An extremely high encapsulation efficiency of ≈99% for the dual drugs is achieved through this strategy. The release of the loaded dual drugs can be controlled in a programmable release model with a rapid release of the micelles, while AP is slowly released. The sustained release of AP can continuously inhibit the P-gp drug pump of MDR tumor cells, increasing the intracellular DOX accumulation. The in vivo DOX biodistribution displays that the DOX accumulation in the tumor tissues achieves 17.82% after implanting the fiber device for 72 h, which is 6.36-fold higher than that of the intravenously injected DOX. Importantly, the fiber device shows an excellent antitumor effect on MDR tumor-bearing mice with low systemic toxicity.


Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma.
In the present study, epithelium derived lesions of various pathological manifestations were examined histologically and immunohistochemically for mononuclear cell infiltration. The infiltrate under the transformed epithelium of oral lesions, was examined for differences in the composition of immune mononuclear cells as the epithelium moves from hyperkeratosis through various degrees of dysplasia to squamous cell carcinoma. The study was performed on 53 human tongue tissues diagnosed as hyperkeratosis (11 cases), mild dysplasia (nine cases), moderate and severe dysplasia (14 cases) and squamous cell carcinoma (19 cases). A similar analysis was performed on 30 parotid gland tissues diagnosed as pleomorphic adenoma (14 cases) and carcinoma ex-pleomorphic adenoma (16 cases). Immunohistochemical analysis of various surface markers of the tumour infiltrating immune cells was performed and correlated with the transformation level as defined by morphology and the expression of p53 in the epithelium. The results revealed that, in the tongue lesions, the changes in the epithelium from normal appearance to transformed were accompanied by a corresponding increase in the infiltration of CD4, CD8, CD14, CD19+20, and HLA/DR positive cells. The most significant change was an increase in B lymphocytes in tongue lesions, that was in accordance with the transformation level (P<0.001). In the salivary gland, a significant number of cases did not show an infiltrate. In cases where an infiltrate was present, a similar pattern was observed and the more malignant tissues exhibited a higher degree of immune cell infiltration.


Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus).
Recent studies from our laboratories and others suggest that calorie restriction (CR) may benefit Alzheimer's disease (AD) by preventing amyloid-beta (Abeta) neuropathology in the mouse models of AD. Moreover, we found that promotion of the NAD+-dependent SIRT1 mediated deacetylase activity, a key regulator in CR extension of life span, may be a mechanism by which CR influences AD-type neuropathology. In this study we continued to explore the role of CR in AD-type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). Monkeys were maintained on the normal and CR diets throughout the entire lifespan until they died of natural causes. We found that 30% CR resulted in reduced contents of Abeta1-40 and Abeta1-42 peptides in the temporal cortex of Squirrel monkeys, relative to control (CON) fed monkeys. The decreased contents of cortical Abeta peptide inversely correlated with SIRT1 protein concentrations in the same brain region; no detectable change in total full-length amyloid-beta protein precursor (AbetaPP) level was found. Most interestingly, we found that 30% CR resulted in a select elevation of alpha- but not beta- or gamma- secretase activity which coincided with decreased ROCK1 protein content in the same brain region, relative to CON group. Collectively, the study suggests that investigation of the role of CR in non-human primates may provide a valuable approach for further clarifying the role of CR in AD.


Mitochondrial deafness.
Hearing impairment is a common disorder, largely genetic in origin, and showing classical features of a heterogeneous genetic disease. Up to 100 independently acting nuclear genes are involved in the disorder, of which around 30 have been mapped, but only a handful identified. Mutations in mitochondrial DNA also play a significant role in both syndromic and nonsyndromic sensorineural hearing impairment. Environmental agents such as aminoglycoside antibiotics and as yet unidentified nuclear genes interact with mitochondrial mutations in the expression of auditory phenotypes. The spectrum of different mitochondrial mutations associated with hearing impairment, taken together with mechanistic studies at the molecular level, suggests that the pathogenic process involves the accumulation of abnormal translation products inside mitochondria, in sensitive cells of the auditory system. This leads to a prediction of the involvement of a novel class of nuclear genes in hearing impairment, namely those with roles in 'mitochondrial protein quality control'.


Transcriptome analysis of the Dickeya dadantii PecS regulon during the early stages of interaction with Arabidopsis thaliana.
PecS is one of the major global regulators controlling the virulence of Dickeya dadantii, a broad-host-range phytopathogenic bacterium causing soft rot on several plant families. To define the PecS regulon during plant colonization, we analysed the global transcriptome profiles in wild-type and pecS mutant strains during the early colonization of the leaf surfaces and in leaf tissue just before the onset of symptoms, and found that the PecS regulon consists of more than 600 genes. About one-half of these genes are down-regulated in the pecS mutant; therefore, PecS has both positive and negative regulatory roles that may be direct or indirect. Indeed, PecS also controls the regulation of a few dozen regulatory genes, demonstrating that this global regulator is at or near the top of a major regulatory cascade governing adaptation to growth in planta. Notably, PecS acts mainly at the very beginning of infection, not only to prevent virulence gene induction, but also playing an active role in the adaptation of the bacterium to the epiphytic habitat. Comparison of the patterns of gene expression inside leaf tissues and during early colonization of leaf surfaces in the wild-type bacterium revealed 637 genes modulated between these two environments. More than 40% of these modulated genes are part of the PecS regulon, emphasizing the prominent role of PecS during plant colonization.


Lactase persistence variants in Arabia and in the African Arabs.
Lactase persistence (LP), the state enabling the digestion of milk sugar in adulthood, occurs only in some human populations. The convergent and independent origin of this physiological ability in Europe and Africa is linked with animal domestication that either had started in both places independently or had spread from the Near East by acculturation. However, it has recently been shown that at least in its southern parts, the population of Arabia not only has a different LP-associated mutation profile than the rest of Africa and Europe but also had experienced an independent demographic expansion occurring before the Neolithic around the Pleistocene-Holocene boundary. In Arabia, LP is associated with mutation -13,915*G and not, as in Europe, with -13,910*T or, as in Africa, with -13,907*G and -14,010*C. We show here that, in Arabia, -13,915*G frequency conforms to a partial clinal pattern and that this specific mutation has likely been spread from Arabia to Africa only recently from the sixth century AD onward by nomadic Arabs (Bedouins) looking for new pastures. Arabic populations in Africa that still maintain a nomadic way of life also have more -13,915*G variants and fewer sub-Saharan L-type mitochondrial DNA haplogroups; this observation matches archaeological and historical records suggesting that the migration of Arabic pastoralists was accompanied by gradual sedentarization that allowed for admixture with the local African population.


Strengthening ties towards a highly-connected world.
Online social networks provide a forum where people make new connections, learn more about the world, get exposed to different points of view, and access information that were previously inaccessible. It is natural to assume that content-delivery algorithms in social networks should not only aim to maximize user engagement but also to offer opportunities for increasing connectivity and enabling social networks to achieve their full potential. Our motivation and aim is to develop methods that foster the creation of new connections, and subsequently, improve the flow of information in the network. To achieve our goal, we propose to leverage the strong triadic closure principle, and consider violations to this principle as opportunities for creating more social links. We formalize this idea as an algorithmic problem related to the densest k-subgraph problem. For this new problem, we establish hardness results and propose approximation algorithms. We identify two special cases of the problem that admit a constant-factor approximation. Finally, we experimentally evaluate our proposed algorithm on real-world social networks, and we additionally evaluate some simpler but more scalable algorithms.


Duration of red cell storage influences mortality after trauma.
Although previous studies have identified an association between the transfusion of relatively older red blood cells (RBCs) (storage ≥ 14 days) and adverse outcomes, they are difficult to interpret because the majority of patients received a combination of old and fresh RBC units. To overcome this limitation, we compared in-hospital mortality among patients who received exclusively old versus fresh RBC units during the first 24 hours of hospitalization. Patients admitted to a Level I trauma center between January 2000 and May 2009 who received ≥ 1 unit of exclusively old (≥ 14 days) vs. fresh (< 14 days) RBCs during the first 24 hours of hospitalization were identified. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for the association between mortality and RBC age, adjusted for patient age, Injury Severity Score, gender, receipt of fresh frozen plasma or platelets, RBC volume, brain injury, and injury mechanism (blunt or penetrating). One thousand six hundred forty-seven patients met the study inclusion criteria. Among patients who were transfused 1 or 2 RBC units, no difference in mortality with respect to RBC age was identified (adjusted RR, 0.97; 95% CI, 0.72-1.32). Among patients who were transfused 3 or more RBC units, receipt of old versus fresh RBCs was associated with a significantly increased risk of mortality, with an adjusted RR of 1.57 (95% CI, 1.14-2.15). No difference was observed concerning the mean number of old versus fresh units transfused to patients who received 3 or more units (6.05 vs. 5.47, respectively; p = 0.11). In trauma patients undergoing transfusion of 3 or more RBC units within 24 hour of hospital arrival, receipt of relatively older blood was associated with a significantly increased mortality risk. Reservation of relatively fresh RBC units for the acutely injured may be advisable.


The need for gender-specific prostheses in TKA: does size make a difference?
Aging boomers and younger patients requiring total knee arthroplasty demand and/or expect better function, improved durability, and a quicker recovery. In response to this demand, surgeons are modifying surgical techniques, and industry is examining implant design. One proposal is the gender-specific implant, but the development of separate systems for men and women may prove to be unnecessary.


Environmental and phenotype-related risk factors for owner-reported allergic/atopic skin symptoms and for canine atopic dermatitis verified by veterinarian in a Finnish dog population.
The aim of this cross-sectional study was to observe whether environmental factors and phenotypic traits are associated with owner-reported skin problems and with veterinary diagnosed canine atopic dermatitis (CAD). Data were collected using the validated online DOGRISK questionnaire. Out of the data that the questionnaire provides for analysis, focus was first turned towards addressing questions regarding 'Atopy/allergy (skin symptoms)' using a total of 8643 dogs: 1585 dogs with owner-reported allergic/atopic skin symptoms and 7058 dogs without. A subsequent analysis compared dogs with veterinary-verified CAD (n = 322) as a case group against the 7058 dogs without owner-reported skin symptoms. The association between 21 factors related to the environment, canine phenotypes and breed groups within both populations were analysed using univariable and multivariable logistic regression. The environmental factors that showed a significant inverse association with the risk of owner-reported allergic/atopic skin symptoms were as following: whether the dog was living in a detached house, whether there were other dogs in the household, and whether the dog was born in the current household. Having over 50% white colour in the coat and living in an extremely clean household were significantly associated with an increased risk of owner-reported allergic/atopic skin symptoms. The five breeds demonstrating the highest proportion of owner-reported allergic/atopic skin symptoms were West Highland white terrier, Boxer, English bulldog, Dalmatian and French bulldog. The Fédération Cynologique Internationale dog breed groups 3 (Terriers) and 6 (Scent hounds and related breeds) showed a significantly higher risk for owner-reported allergic/atopic skin symptoms than mixed breed dogs. In the second population, the inverse association was observed between the risk of CAD and the presence of other dogs in the household, and whether the dog had been born in the current household. The results indicate that some environmental factors and canine phenotypes are associated with CAD and owner-reported skin symptoms, but they still do not prove causality.


From genome to epigenome.
The success of the human genome sequencing project has created wide-spread interest in exploring the human epigenome in order to elucidate how the genome executes the information it holds. Although all (nucleated) human cells effectively contain the same genome, they contain very different epigenomes depending upon cell type, developmental stage, sex, age and various other parameters. This complexity makes it intrinsically difficult to precisely define 'an' epigenome, let alone 'the' epigenome. What is clear, however, is that in order to unravel any epigenome, existing and novel high-throughput approaches on the DNA, RNA and protein levels need to be harnessed and integrated. Here, we review the current thinking and progress on how to get from the genome to the epigenome(s) and discuss some potential applications.


A probabilistic transmission model of Salmonella in the primary broiler production chain.
Annual data from the Finnish National Salmonella Control Programme were used to build up a probabilistic transmission model of salmonella in the primary broiler production chain. The data set consisted of information on grandparent, parent, and broiler flock populations. A probabilistic model was developed to describe the unknown true prevalences, vertical and horizontal transmissions, as well as the dynamical model of infections. By combining these with the observed data, the posterior probability distributions of the unknown parameters and variables could be derived. Predictive distributions were derived for the true number of infected broiler flocks under the adopted intervention scheme and these were compared with the predictions under no intervention. With the model, the effect of the intervention used in the programme, i.e., eliminating salmonella positive breeding flocks, could be quantitatively assessed. The 95% probability interval of the posterior predictive distribution for (broiler) flock prevalence under current (1999) situation was [1.3%-17.4%] (no intervention), and [0.9%-5.8%] (with intervention). In the scenario of one infected grandparent flock, these were [2.8%-43.1%] and [1.0%-5.9%], respectively. Computations were performed using WinBUGS and Matlab softwares.


Microspherophakic Angle Closure Glaucoma in a Patient with Coffin-Siris Syndrome: Case Report.
Bilateral secondary angle closure glaucoma is a presenting symptom of microspherophakia and ectopia lentis. Characterizing the associated syndrome and confirmation by genetic testing can identify associated systemic abnormalities and provide appropriate genetic counseling. A 42-year-old woman with severe intellectual disability presented with light perception visual acuity and glaucoma, with intraocular pressure (IOP) in her right and left eyes of 69 and 70 mmHg, respectively. She underwent two sessions of 270-degree laser diode transscleral cytophotocoagulation treatment at a 6-month interval and was prescribed topical anti-glaucoma medication. Her family noticed a progressive decrease in her vision while on treatment for 2 years. She was diagnosed with apparent Weill-Marchesani syndrome, accompanied by angle closure glaucoma and microspherophakia. Cataract surgery and intraocular lens implantation were successful in both eyes and post-operative IOP was controlled with anti-glaucoma medication but her vision did not improve from severe glaucomatous optic neuropathy. Her underlying syndrome was investigated genetically by whole exome sequencing. Sequencing showed a pathogenic variant in ARID1B, c.3955dupC (p.Gln1319Profs*14), diagnostic of Coffin-Siris syndrome. This is the first report of Coffin-Siris syndrome associated with microspherophakia and angle closure glaucoma. Bilateral angle closure glaucoma from ectopia lentis in patients with genetic syndromes could be an indicator of microspherophakia in adulthood. Ophthalmological surveillance is important in patients with Coffin-Siris syndrome.


Rapid Engineering of Foot-and-Mouth Disease Vaccine and Challenge Viruses.
There are seven antigenically distinct serotypes of foot-and-mouth disease virus (FMDV), each of which has intratypic variants. In the present study, we have developed methods to efficiently generate promising vaccines against seven serotypes or subtypes. The capsid-encoding gene (P1) of the vaccine strain O1/Manisa/Turkey/69 was replaced with the amplified or synthetic genes from the O, A, Asia1, C, SAT1, SAT2, and SAT3 serotypes. Viruses of the seven serotype were rescued successfully. Each chimeric FMDV with a replacement of P1 showed serotype-specific antigenicity and varied in terms of pathogenesis in pigs and mice. Vaccination of pigs with an experimental trivalent vaccine containing the inactivated recombinants based on the main serotypes O, A, and Asia1 effectively protected them from virus challenge. This technology could be a potential strategy for a customized vaccine with challenge tools to protect against epizootic disease caused by specific serotypes or subtypes of FMDV.IMPORTANCE Foot-and-mouth disease (FMD) virus (FMDV) causes significant economic losses. For vaccine preparation, the selection of vaccine strains was complicated by high antigenic variation. In the present study, we suggested an effective strategy to rapidly prepare and evaluate mass-produced customized vaccines against epidemic strains. The P1 gene encoding the structural proteins of the well-known vaccine virus was replaced by the synthetic or amplified genes of viruses of seven representative serotypes. These chimeric viruses generally replicated readily in cell culture and had a particle size similar to that of the original vaccine strain. Their antigenicity mirrored that of the original serotype from which their P1 gene was derived. Animal infection experiments revealed that the recombinants varied in terms of pathogenicity. This strategy will be a useful tool for rapidly generating customized FMD vaccines or challenge viruses for all serotypes, especially for FMD-free countries, which have prohibited the import of FMDVs.


An unusually simple HP1 gene set in Hymenopteran insects.
The heterochromatin protein 1 (HP1) gene family includes a set of paralogs in higher eukaryotes that serve fundamental roles in heterochromatin structure and maintenance, and other chromatin-related functions. At least 10 full and 16 partial HP1 genes exist among Drosophila species, with multiple gene gains, losses, and sub-functionalizations within this insect group. An important question is whether this diverse set of HP1 genes and their dynamic evolution represent the standard rule in eukaryotic groups. Here we have begun to address this question by bio-informatically identifying the HP1 family genes in representative species of the insect order Hymenoptera, which includes all ants, bees, wasps, and sawflies. Compared to Drosophila species, Hymenopterans have a much simpler set of HP1 genes, including one full and two partial HP1s. All 3 genes appear to have been present in the common ancestor of the Hymenopterans and they derive from a Drosophila HP1B-like gene. In ants, a partial HP1 gene containing only a chromoshadow domain harbors amino acid changes at highly conserved sites within the PxVxL recognition region, suggesting that this gene has undergone sub-functionalization. In the jewel wasp Nasonia vitripennis, the full HP1 and partial chromoshadow-only HP1 are expressed in both germ line and somatic tissues. However, the partial chromodomain-only HP1 is expressed exclusively in the ovary and testis, suggesting that it may have a specialized chromatin role during gametogenesis. Our findings demonstrate that the HP1 gene family is much simpler and evolutionarily less dynamic within the Hymenopterans compared to the much younger Drosophila group, a pattern that may reflect major differences in the range of chromatin-related functions present in these and perhaps other insect groups.


Strategies and tools for managing change.
Continuous change in complex healthcare environments is a challenge for nurse leaders, but it can also be a boon. Change can leverage the introduction of innovations that improve the quality of care delivery. It all depends on how change is managed. The author describes major leadership strategies and tools to effectively manage change, particularly innovative changes that result in better outcomes for patients, staff, and the organization.


Structures of Streptococcus pneumoniae hyaluronate lyase in complex with chondroitin and chondroitin sulfate disaccharides. Insights into specificity and mechanism of action.
Streptococcus pneumoniae hyaluronate lyase is a surface enzyme of this Gram-positive bacterium. The enzyme degrades hyaluronan and chondroitin/chondroitin sulfates by cleaving the beta1,4-glycosidic linkage between the glycan units of these polymeric substrates. This degradation helps spreading of this bacterial organism throughout the host tissues and facilitates the disease process caused by pneumococci. The mechanism of this degradative process is based on beta-elimination, is termed proton acceptance and donation, and involves selected residues of a well defined catalytic site of the enzyme. The degradation of hyaluronan alone is thought to proceed through a processive mode of action. The structures of complexes between the enzyme and chondroitin as well as chondroitin sulfate disaccharides allowed for the first detailed insights into these interactions and the mechanism of action on chondroitins. This degradation of chondroitin/chondroitin sulfates is nonprocessive and is selective for the chondroitin sulfates only with certain sulfation patterns. Chondroitin sulfation at the 4-position on the nonreducing site of the linkage to be cleaved or 2-sulfation prevent degradation due to steric clashes with the enzyme. Evolutionary studies suggest that hyaluronate lyases evolved from chondroitin lyases and still retained chondroitin/chondroitin sulfate degradation abilities while being specialized in the degradation of hyaluronan. The more efficient processive degradation mechanism has come to be preferred for the unsulfated substrate hyaluronan.


[Epidemiologic aspects of viral hepatitis A and vaccination].
Epidemiological problems connected with hepatitis A in twentieth century and in the first years of twenty-first were mentioned with special attention of self-limiting of cases in the periods of very high, high, medium, low and very low endemicity. Decreasing of percentage of immunised persons was observed especially among children and young persons. It may be a cause in future of increasing of numbers of cases of hepatitis A even epidemics. Therefore vaccination against hepatitis A some people in risk groups is now recommended. Especially are included persons with some professions (health workers, persons employed in food and meals industry, travellers to the region of high or medium endemicity etc), persons living in territory of poor sanitary conditions, children, adolescents and young adults as well as persons with some chronic diseases, drug addicts, homosexuals.


An ultrastructural morphometric study of the effects of chronic melatonin administration on the zona fasciculata of rat adrenal cortex.
The effects of a long-term administration of melatonin on the adrenal zona fasciculata were investigated both in 'normal' rats and in animals whose hypothalamo-hypophyseal-adrenal axis had been interrupted by a prolonged infusion with dexamethasone or dexamethasone plus maintenance doses of ACTH. In the 'normal' rats, melatonin caused a notable atrophy of zona fasciculata cells, coupled with a significant lowering in the plasma concentration of corticosterone. On the contrary, in dexamethasone- or dexamethasone plus ACTH-infused animals, melatonin induced an evident hypertrophy of zona fasciculata cells which, however, was not associated with a rise in the corticosterone blood level. The hypothesis is advanced that the direct stimulatory effect of melatonin on the growth of zona fasciculata in 'normal' rats can be masked by the concurrent inhibition of the hypophyseal release of ACTH. The possible mechanism of the direct effect of melatonin on the zona fasciculata is discussed in the light of evidence indicating that this hormone enhances the intracellular catabolism of corticosterone, which is well-known to exert a powerful direct depression of the growth and steroidogenic capacity of rat adrenocortical cells.


Dosimetric Comparison Study Between Free Breathing and Breath Hold Techniques in Patients Treated by Liver-Directed Stereotactic Body Radiation Therapy.
Background Breathing motion management is the key to delivering stereotactic body radiation therapy (SBRT) for liver lesions. This study aimed to compare the dosimetric parameters of liver SBRT using two different techniques: free breathing and breath hold. Method The study included 11 patients with liver metastases or hepatocellular carcinoma who underwent liver-directed SBRT. A dosimetric comparison was performed using dose-volume histogram analysis, evaluating parameters such as the maximum dose to 5 cc of bowel volume, mean liver dose (MLD), and liver V20 and V30. Statistical analyses were performed to compare results. Results The findings revealed that the breath hold technique resulted in significantly lower doses to the bowel and smaller volumes of normal liver tissue receiving 20 Gy (V20) and 30 Gy (V30) than the free breathing. Although there was no statistically significant difference in the MLD between the two techniques, the breath hold technique resulted in a lower MLD. Conclusion This dosimetric comparison study suggests that the breath hold technique is associated with lower radiation exposure to the bowel and normal liver tissues. Although this may not be feasible for all patients, it may be an appropriate procedure for selected individuals. Further research is needed to validate these findings in different patient populations and explore their impact on clinical outcomes and patient-reported quality of life.


Exogenous Calcium Induces Different Hydraulic Strategies in Response to Osmotic Stress in Maize Seedlings.
Recent discoveries regarding the signal molecules involved in abiotic stresses require integration into the field of plant hydraulic property research. Although calcium (Ca) is an important second messenger involved in numerous complex, abiotic stress-induced signaling pathways, it remains unclear how exogenous calcium mediates cellular signaling to promote plant drought resistance. We investigated the effects of calcium on the water balance and hydraulic properties in maize seedlings (Zea mays L.) under osmotic stress simulated by 10% (m/v) PEG-6000 in a hydroponic culture. The osmotic stress dramatically decreased the photosynthetic rate, transpiration rate, stomatal conductance, leaf water content, and root water absorption. However, the short-term (2 h) and long-term (10 d) exogenous Ca2+ (CaCl2: 10 mM) treatments had different effects on the maize gas exchange parameters and leaf water status. The short-term treatment improved the leaf transpiration by inhibiting the abscisic acid (ABA) synthesis and accumulation in the leaves, generating a stronger transpiration pull and enhancing the root water absorption and axial flow path water transport by increasing the root hydraulic conductance to relieve the osmotic stress-induced inhibition. The long-term treatment induced the ABA and H2O2 accumulation in the roots and leaves. Under osmotic stress, the accumulation of ABA, H2O2, and Ca2+ rapidly repressed the transpiration and enhanced the radial flow path water transport, decreasing the water loss and improving the stress tolerance. These insights suggest a role for a judicious use of Ca fertilizer in reducing the adverse effects of drought on agricultural production.


Ketamine intervention limits pathogen expansion in vitro.
Ketamine is one of several clinically important drugs whose therapeutic efficacy is due in part to their ability to act upon ion channels prevalent in nearly all biological systems. In studying eukaryotic and prokaryotic organisms in vitro, we show that ketamine short-circuits the growth and spatial expansion of three microorganisms, Stachybotrys chartarum, Staphylococcus epidermidis and Borrelia burgdorferi, at doses efficient at reducing depression-like behaviors in mouse models of clinical depression. Although our findings do not reveal the mechanism(s) by which ketamine mediates its antifungal and antibacterial effects, we hypothesize that a function of L-glutamate signal transduction is associated with the ability of ketamine to limit pathogen expansion. In general, our findings illustrate the functional similarities between fungal, bacterial and human ion channels, and suggest that ketamine or its metabolites not only act in neurons, as previously thought, but also in microbial communities colonizing human body surfaces.


Growth Control of Cyanobacteria by Three Submerged Macrophytes.
To illustrate the control of harmful cyanobacterial growth and the removal of nutritients from fresh water, three submerged macrophytes were grown in the raw water of Guishui Lake. Lindernia rotundifolia, Hygrophila stricta, and Cryptocoryne crispatula were grown together in situ to assess their effectiveness in nutrient removal in microcosms. Results revealed the inhibitory effects of these species on cyanobacterial growth. In addition, water quality in the planted microcosms showed improvement when compared to the water quality of the unplanted microcosm. At all treatments studied, the chemical oxygen demand in the planted microcosms was lower than that in the unplanted microcosms, and the removal rate of all the nitrogen and phosphate in the planted microcosms was better than that of the microcosm without plants. Our study offers a useful algal control method for the lakes or reservoirs that suffer from harmful cyanobacterial blooms.