Bio-Characterization and Liquid Chromatography-Mass Spectrometry Analysis of Exopolysaccharides in Biofilm-Producing Cyanobacteria Isolated from Soil Crust: Exploring the Potential of Microalgal Biomolecules.
Exopolysaccharide-producing cyanobacterial strains in biological soil crusts are described, in addition to their chemical properties and antioxidant and flocculation activities. The EPSs from Pudukkottai blackish biological soil crusts (PBBSCs) showed significant amounts of total soluble proteins (0.1687 mg/mL) and carbohydrates (0.8056 mg/mL) compared with the Ariyalur blackish biological soil crusts (ABBSCs). LC-MS analysis of the cyanobacterial polysaccharides revealed the presence of natural sugars such as ribose and glucose/mannose, and uronic acids. The FTIR spectrum showed specific peak for OH and -NH stretching, C-H stretching, and carboxylic acids as the dominant groups in EPS. The in vitro DPPH assay of EPSs from PBBSCs showed 74.3% scavenging activity. Furthermore, the reducing power was determined to be 0.59 ata 500 mg/mL concentration, respectively. The extracted EPSs from the biological soil crust flocculated Kaolin clay suspension maximum at 500 mg/mL. Consequently, the cyanobacterial strain and exopolysaccharide characterization from the sacred forest's biological soil crust were analyzed for their bioactive potential, bio-crust diversity, and distribution.


Emergency Department Utilization for Patients Living With Sickle Cell Disease: Psychosocial Predictors of Health Care Behaviors.
Individuals living with sickle cell disease (SCD) often require urgent care; however, some patients hesitate to present to the emergency department (ED), which may increase the risk of serious clinical complications. Our study aims to examine psychosocial, clinical, and demographic factors associated with delaying ED care. This was a cross-sectional study of 267 adults with SCD from the national INSIGHTS Study. The binary outcome variable asked whether, in the past 12 months, participants had delayed going to an ED when they thought they needed care. Logistic regression was performed with clinical, demographic, and psychosocial measures. Approximately 67% of the participants reported delaying ED care. Individuals who delayed care were more likely to have reported higher stigma experiences (odds ratio [OR]=1.09; 95% confidence interval [CI] 1.03 to 1.16), more frequent pain episodes (OR=1.15; 95% CI 1.01 to 1.32), lower health care satisfaction (OR= 0.74; 95% CI 0.59 to 0.94), and more frequent ED visits (OR=6.07; 95% CI 1.18 to 31.19). Disease severity and demographics, including sex, age, and health insurance status, were not significantly associated with delay in care. Psychosocial factors, including disease stigma and previous negative health care experiences, are associated with delay of ED care in this SCD cohort. There is a need to further investigate the influence of psychosocial factors on the health care-seeking behaviors of SCD patients, as well as the downstream consequences of these behaviors on morbidity and mortality. The resulting knowledge can contribute to efforts to improve health care experiences and patient-provider relationships in the SCD community.


Neural evidence that three dimensions organize mental state representation: Rationality, social impact, and valence.
How do people understand the minds of others? Existing psychological theories have suggested a number of dimensions that perceivers could use to make sense of others' internal mental states. However, it remains unclear which of these dimensions, if any, the brain spontaneously uses when we think about others. The present study used multivoxel pattern analysis (MVPA) of neuroimaging data to identify the primary organizing principles of social cognition. We derived four unique dimensions of mental state representation from existing psychological theories and used functional magnetic resonance imaging to test whether these dimensions organize the neural encoding of others' mental states. MVPA revealed that three such dimensions could predict neural patterns within the medial prefrontal and parietal cortices, temporoparietal junction, and anterior temporal lobes during social thought: rationality, social impact, and valence. These results suggest that these dimensions serve as organizing principles for our understanding of other people.


The development of environmental assessment tools to support the creation of dementia friendly care environments: Innovative practice.
The need for more dementia friendly design in hospitals and other care settings is now widely acknowledged. Working with 26 NHS Trusts in England as part of a Department of Health commissioned programme, The King's Fund developed a set of overarching design principles and an environmental assessment tool for hospital wards in 2012. Following requests from other sectors, additional tools were developed for hospitals, care homes, health centres and housing with care. The tools have proven to be effective in both disseminating the principles of dementia friendly design and in enabling the case to be made for improvements that have a positive effect on patient outcomes and staff morale. This paper reports on the development, use and review of the environmental assessment tools, including further work that is now being taken forward by The Association for Dementia Studies, University of Worcester.


Differential effects of exercise intensities in hippocampal BDNF, inflammatory cytokines and cell proliferation in rats during the postnatal brain development.
It has been established that low intensities of exercise produce beneficial effects for the brain, while high intensities can cause some neuronal damage (e.g. exacerbated inflammatory response and cell death). Although these effects are documented in the mature brain, the influence of exercise intensities in the developing brain has been poorly explored. To investigate the impact of exercise intensity in developing rats, we evaluated the hippocampal level of brain derived neurotrophic factor (BDNF), inflammatory cytokines (TNFα, IL6 and IL10) and the occurrence of hippocampal cell degeneration and proliferation at different stages of postnatal brain development of rats submitted to two physical exercise intensities. To this point, male rats were divided into different age groups: P21, P31, P41 and P51. Each age group was submitted to two exercise intensities (low and high) on a treadmill over 10 consecutive days, except the control rats. We verified that the density of proliferating cells was significantly higher in the dentate gyrus of rats submitted to low-intensity exercise from P21 to P30 compared with high-intensity exercise and control rats. A significant increase of proliferative cell density was found in rats submitted to high-intensity exercise from P31 to P40 when compared to low-intensity exercise and control rats. Elevated hippocampal levels of IL6 were detected in rats submitted to high-intensity exercise from P21 to P30 compared to control rats. From P41 to P50 period, higher levels of BDNF, TNFα and IL10 were found in the hippocampal formation of rats submitted to high-intensity exercise in relation to their control rats. Our data show that exercise-induced neuroplastic effects on BDNF levels and cellular proliferation in the hippocampal region are dependent on exercise intensity and developmental period. Thus, exercise intensity is an inflammation-inducing factor and exercise-induced inflammatory response during the postnatal brain development is also related to developmental stage. Our findings indicate that neuroplastic changes induced by exercise in developing rats depend on both age and training intensity.


Photochemical elimination of leaving groups from zwitterionic intermediates generated via electrocyclic ring closure of alpha,beta-unsaturated anilides.
Methacrylanilides, ArN(CH3)COC(CH2LG)=CH2, with allylic leaving groups (LG(-) = BocAla, PhCO2(-), PhCH2CO2(-), PhO(-)) undergo photochemical electrocyclic ring closure to produce a zwitterionic intermediate. Further reaction of the intermediate results in expulsion of the leaving group to give an alpha-methylene lactam as the major product. In addition, a lactam product that retains the leaving group is formed via a 1,5-H shift in the intermediate. Elimination of the leaving group is generally preferred, even for LG(-) = PhO(-), although in benzene as the solvent the lactam retaining the phenolate group becomes the sole photoproduct. The electrocyclic ring closure occurs in the singlet excited-state for the para-COPh-substituted anilide derivative and is not quenched by 0.15 M piperylene or 0.01 M sodium 2-naphthalenesulfonate (2-NPS) as triplet quenchers. Comparable concentrations of 2-NPS strongly quench the transient absorption of the triplet excited state observed at 450-700 nm according to laser flash photolysis experiments. In aqueous media, quantum yields for total products are insensitive to leaving group ability, and Phi(tot)(para-CO2CH3) = 0.04-0.06 at 310 nm and Phi(tot)(para-COPh) = 0.08-0.1 at 365 nm, for which Phi(isc) = 0.15.


Anaplastic Lymphoma Kinase-Negative Anaplastic Large Cell Lymphoma Manifesting as a Scalp Hematoma After an Acute Head Injury-a Case Report and Literature Review.
Anaplastic large cell lymphoma (ALCL) is a malignant non-Hodgkin lymphoma, typically associated with anaplastic lymphoma kinase (ALK) expression. In some cases, lack of ALK translocation correlated with a more unfavorable prognosis. We describe a case of ALK(-) ALCL that manifested as a progressive, enlarged, swollen mass on the scalp after an acute head injury in an 84-year-old man. Neither palpable lymph nodes nor any B symptoms were noted on admission. Brain computed tomography showed a hematoma in the right posterior occipital region of the scalp as the only remarkable finding. Débridement and biopsy were performed. Histologic and immunohistochemical analysis of the specimen revealed an ALK(-) ALCL of the scalp. The lymphoma was resistant to bendamustine-containing chemotherapies, ultimately leading to the patient's death within 2 months. This case report highlights the importance of recognizing the possibility of an ALCL manifesting as a focal inflammatory swelling mass on the scalp.


Patient selection in outpatient parenteral antimicrobial therapy.
Outcome data as well as reported anecdotal experience over the past 20 years indicate that any infection can be safely treated with parenteral antimicrobials outside the hospital setting. However, outpatient parenteral antimicrobial therapy (OPAT) is a reasonable option only when the final decision for patient selection is based on the judgment of a knowledgeable, experienced physician, and when an experienced qualified provider is available. Criteria to be considered include clinical status, patient acceptance, ability to comply with the plan of treatment, home environment, support systems, and reimbursement. Physician direction and participation in appropriate patient selection will become increasingly important as the growth of managed care increases the importance of cost-savings.


The Protistan Microbiome of Grassland Soil: Diversity in the Mesoscale.
Genomic data for less than one quarter of ∼1.8 million named species on earth exist in public databases like GenBank. Little information exists on the estimated one million small sized (1-100μm) heterotrophic nanoflagellates and ciliates and their taxa-area relationship. We analyzed environmental DNA from 150 geo-referenced grassland plots representing topographical and land-use ranges typical for Central Europe. High through-put barcoding allowed the identification of operational taxonomic units (OTUs) at species level, with high pairwise identity to reference sequences (≥99.7%), but also the identification of sequences at the genus (≥97%) and class (≥80%) taxonomic level. Species richness analyses revealed, on average, 100 genus level OTUs (332 unique individual read (UIR) and 56 class level OTUs per gram of soil sample in the mesoscale (1-1000km). Database shortfalls were highlighted by increased uncertain taxonomic lineages at lower resolution (≥80% sequence identity). No single barcode occurred ubiquitously across all sites. Taxa-area relationships indicated that OTUs spread over the entire mesoscale were more similar than in the local scale and increased land-use (fertilization, mowing and grazing) promoted taxa-area separation. Only a small fraction of sequences strictly matched reference library sequences, suggesting a large protistan "dark matter" in soil which warrants further research.


Phosphatase activity in anaerobic bioreactors for wastewater treatment.
Phosphatase (PO4ase) activity was investigated in continuous and fed-batch anaerobic bioreactors for wastewater treatment. PO4ase levels were high in continuously fed reactors (880-2632 micromol/L/h), compared to a fed-batch reactor (FBR) (540-1249 micromol/L/h). Alkaline and acid PO4ases were present in all the reactors, but in varying magnitudes and total PO4ase activity exhibited a 10-30% variation even at steady-state reactor conditions. The PO4ase activity was not affected by the inorganic phosphate (Pi) level in the reactors, but biomass level and wastewater type, including specific PO4ases (either alkaline or acid), strongly influenced the PO4ase activity in a reactor. Both flocculated and suspended cells produced PO4ase, and 60-65% of the enzyme was cell bound, remaining entrapped in the extracellular matrix and in cell-free form. Batch studies with anaerobic sludge showed a negative correlation between Pi and PO4ase activity. An increase in PO4ase activity was observed under starvation and higher salinity (above 15 g/L). Glucose and propionate (at 10 mM level) induced PO4ase activity, whereas acetate and butyrate (10 mM) addition had no response. This study also reveals that Archaea and bacteria contributed 45% and 55%, respectively, of total PO4ase activity in anaerobic sludge.


Relationship of behavioral inhibition to separation anxiety in a sample (N = 377) of adult individuals with mood and anxiety disorders.
Behavioral Inhibition (BI) is an early temperamental trait characterized by shyness, withdrawal, avoidance, uneasiness, and fear of unfamiliar situations, people, objects, and events. The DSM-5 refers to behavioral inhibition as a temperamental factor related to neurodevelopmental conditions in childhood, including attention deficit hyperactivity disorder, selective mutism, and specific phobias; and to its influence on adult anxiety disorders including social anxiety disorder, agoraphobia, and generalized anxiety disorder, but, interestingly, not separation anxiety disorder (SAD). However, there are phenomenological overlaps between BI and SAD. We aimed to explore whether there is a correlation between BI as an early temperamental trait and childhood or adult separation anxiety disorder. The study was conducted in 377 consecutive adults (mean age 40.2±12.4 years) outpatients with anxiety and mood disorders as the principal diagnosis, grouped on the presence/absence of a DSM-5 diagnosis of childhood or adult separation anxiety disorder. Separation anxiety was assessed by the Structured Clinical Interview for Separation Anxiety (SCI-SAS) and the Adult Separation Anxiety Checklist (ASA27). Behavioral inhibition was assessed by the Retrospective Self-Report of Inhibition (RSRI). The four comparison groups included: 1) 168 patients without childhood or adult SAD, 2) 81 with adult SAD, 3) 97 with both adult SAD and childhood SAD, and 4) 31 with childhood SAD only. The group with both adult and childhood SAD had the highest scores on RSRI total and sub-scale scores. Both groups with adult SAD had significantly higher RSRI scores than the group with only childhood SAD or without SAD. Significant bivariate correlations were found between ASA-27 scores and RSRI scores. Correlations between RSRI scores and measures of anxiety and depressive symptoms were significantly weaker than those on the ASA-27. Regression analyses showed a significant predictive value of RSRI scores on ASA-27 total score, but not of age of onset of SAD. BI has an onset in the very first years of life and may represent a potential developmental endophenotype for later anxiety disorders. Our findings indicate that BI and separation anxiety are connected in individuals with affective and anxiety disorders. This may have important clinical and therapeutic implications for preventive interventions.


Mental health status of Chinese physicians working in intensive care unit.
Physicians working in intensive care unit (ICU) are prone to suffer from mental health problems, but there are still very limited data of mental health status of ICU physicians in China. Therefore, this study was to investigate their psychological status. ICU physicians were contacted electronically and asked to complete the Symptom Check-list 90 (SCL-90) for Chinese from December 13 to December 14 in 2018. A total of 1749 valid questionnaires were collected. Fifteen potential relevant factors that could affect the mental health status of ICU physicians were also analyzed by multivariate logistic regression. The total mean score of SCL-90 for surveyed subjects was 175.49 ± 65.79. Near half of the respondents were identified with psychological symptoms. The pooled estimates of all the nine factors, including somatization, obsession-compulsion, interpersonal-sensitivity, depression, anxiety, hostility, phobic anxiety, and paranoid ideation among ICU physicians, were significantly higher than those in the general population (P < 0.001). Multivariate analysis revealed that education, title, working hours per week, frequency of night shift were risk factors for psychological symptoms. The situation of psychological health of ICU physicians in China is worrying, and it is urgent to take some effective measures to improve their mental health.


Towards a FRET-based immunosensor for continuous carbohydrate monitoring.
In this report we have evaluated the potential of using fluorescence/Förster resonance energy transfer (FRET) in a competitive immunosensor for continuous monitoring of the carbohydrate hapten maltose. The cyanine dyes Cy5 and Cy5.5 were used as a donor-acceptor pair by conjugation to maltose-labeled bovine serum albumin (BSA) and the monoclonal antibody IgG 39.5, giving Cy5-BSA-maltotriitol (3.1/1/18) and Cy5.5-mAb39.5 (2.2/1), respectively. This antibody with weak affinity towards maltose showed full reversibility to both the free maltose and the maltose-labeled conjugate. It allowed us to measure continuously the maltose content by monitoring the FRET signal change over time due to displacement of Cy5-BSA-maltotriitol from Cy5.5-mAb39.5 inside a semipermeable capsule. A near 22% total increase was seen in the fluorescence intensity ratio I(670)/I(700) in the presence of maltose, with a calculated EC(50)=1.87+/-0.13 mM (R(2)=0.9984) from the sigmoidal dose-response curve at 25 degrees C. Specificity of the immunosensor was shown with the structural analog to maltose, cellobiose, and it generated no detectable response. A minor drift in the sensor baseline was seen with 0.4% per 24 h, which was in the same magnitude as the signal-to-noise ratio, during the 4 weeks of measurements. The immunosensor was applied to crude samples of oat drinks for direct quantification of the maltose content. Overall, this work demonstrates the potential to use an immunosensor based on weakly binding antibodies and FRET technology for remote and non-invasive carbohydrate monitoring.


Studies on mosquitoes (Diptera: Culicidae) and anthropic environment. 5--breeding of Anopheles albitarsis in flooded rice fields in south-eastern Brazil.
Studies on breeding Anopheles albitarsis and association with rice growth in irrigated paddy fields were carried out during the rice cultivation cycle from December 1993 to March 1994. This period corresponded to the length of time of permanent paddy flooding. Breeding occurred in the early stage up until five weeks after transplantation when rice plant height was small. That inverse correlation may give potential direction to control measures.


Change in practice due to COVID-19 - Early experiences of a United Kingdom district general hospital in trauma & orthopaedics.
COVID-19 is a significant worldwide challenge to many healthcare systems. In Trauma and Orthopaedics, there has been a significant change in the workload but departments have been compelled to change their practice in order to match the demand, as well as respond to the escalating situation of COVID. Some guidance is available on these changes from bodies such as the National Health Service (NHS), Public Health England and the British Orthopaedic Association (BOA). We have implemented certain changes in our university district general hospital trauma and orthopaedic department with regard to staff roles, outpatient and inpatient care and operative protocols. We aim to present some of these changes and their effects on patient care in an attempt to share these with colleagues who may face similar pressures and make some recommendations to help others prepare for a possible second wave of COVID-19.


Proteomic profiling reveals that Th2-inducing dendritic cells stimulated with helminth antigens have a 'limited maturation' phenotype.
Dendritic cells (DCs) are important in the initiation of primary immune responses against pathogens. To aid understanding of how DCs guide T helper (Th)2-type responses, we employed 2-DE in association with MS/MS to identify proteins which characterise pro-Th2 DCs (matured with zero-to-three hours released proteins (0-3hRP), released by Schistosoma mansoni cercariae) versus pro-Th1 DCs (matured with lipopolysaccharide, LPS) and immature DCs. Software analysis of average 2-DE gels (three replicates per DC type) showed many similarities in the pattern of spots between the three groups of DCs but also marked changes. The major and significant changes in protein expression mainly affected cytoskeletal proteins. Other differences included chaperone proteins and enzymes involved in protein folding, S100 calcium-binding proteins, peroxiredoxin 1, superoxide dismutase 1, several annexins and arginase 1. Our study demonstrates that pro-Th2 DCs matured with 0-3hRP exhibit a proteome that is intermediate between that of immature DCs and pro-Th1 DCs. Finally, the differential regulation of protein spots identified by MALDI-MS/MS as having cytoskeletal and morphological functions was confirmed by contrast, confocal and scanning electron microscopy examination of DCs. Together, our results support the view that Th2 differentiation results from a 'limited maturation' of DCs.


Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial.
In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24Gag vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses were investigated as predictors of Vacc-4x effect (VE) on viral load (VL) and CD4 count during ATI. All analyses of week 28 responses and fold-changes relative to baseline considered per-protocol participants (Vacc-4x:placebo=72:32) resuming cART after week 40. Linear regression models with interaction tests were used. VE was estimated as the Vacc-4x-placebo difference in log10-transformed VL (VEVL) or CD4 count (VECD4). A lower fold-change of CD4+ T-cell proliferation was associated with VECD4 at week 48 (p=0.036, multiplicity adjusted q=0.036) and week 52 (p=0.040, q=0.080). A higher fold-change of IFN-γ in proliferation supernatants was associated with VEVL at week 44 (p=0.047, q=0.07). A higher fold-change of TNF-α was associated with VEVL at week 44 (p=0.045, q=0.070), week 48 (p=0.028, q=0.070), and week 52 (p=0.037, q=0.074). A higher fold-change of IL-6 was associated with VEVL at week 48 (p=0.017, q=0.036). TNF-α levels (>median) were associated with VECD4 at week 48 (p=0.009, q=0.009). These exploratory analyses highlight the potential value of investigating biomarkers in T-cell proliferation supernatants for VE in clinical studies.


Molecular characterization of primary gene pool of chickpea based on ISSR markers.
Genetic diversity and relationships within and among members of the primary gene pool of chickpea, including 38 accessions of Cicer arietinum, six of C. reticulatum,, and four of C. echinospermum, were investigated using 31 ISSR markers. The study revealed moderate diversity, detecting 141 fragments, of which 79 (56%) were polymorphic. Averages were 0.125 for polymorphic information content, 0.350 for marker index, and 0.715 for resolving power. The UPGMA dendrogram and the principal coordinate analysis revealed a clear differentiation between wild and cultivated accessions. The clustering pattern did not strictly follow the grouping of accessions by geographic origin but was in good agreement with the pedigree data and the seed type. The study demonstrates that ISSRs provide promising marker tools in revealing genetic diversity and relationships in chickpea and can contribute to efficient identification, conservation, and utilization of germplasm for plant improvement through conventional as well as molecular breeding approaches.


An Evaluation of the Results of the Steroid and Non-steroidal Anti-inflammatory Drug Treatments in Subacute Thyroiditis in relation to Persistent Hypothyroidism and Recurrence.
Subacute thyroiditis (SAT) is an inflammatory thyroid disease. The main purpose of the treatment is to relieve pain and control the inflammatory process. The aim of the present study was to evaluate the therapeutic effects of steroid and non-steroidal anti-inflammatory drugs (NSAIDs) in SAT. Initial laboratory data, treatment response, and long-term results of 295 SAT patients treated with ibuprofen or methylprednisolone were evaluated. After the exclusion of 78 patients, evaluation was made of 126 patients treated with 1800 mg ibuprofen and 91 patients treated with 48 mg methylprednisolone. In 59.5% of 126 patients treated with ibuprofen, there was no adequate clinical response at the first control visit. In 54% of patients, the treatment was changed to steroids in mean 9.5 days. Symptomatic remission was achieved within two weeks in all patients treated with methylprednisolone. The total recurrence rate was 19.8%, and recurrences were observed more frequently in patients receiving only steroid therapy than in patients treated with NSAID only (23% vs. 10.5% p:0.04). Persistent hypothyroidism developed in 22.8% of patients treated only with ibuprofen and in 6.6% of patients treated with methylprednisolone only. Treatment with only ibuprofen (p:0.039) and positive thyroid peroxidase antibody (anti-TPO) (p:0.029) were determined as the main risk factors for permanent hypothyroidism. NSAID treatment is not as effective as steroid treatment in early clinical remission. Steroid treatment was detected as a protective factor against permanent hypothyroidism. Therefore, steroid therapy may be considered especially in anti-TPO positive SAT patients and patients with high-level acute phase reactants.


Rapid systemic responses of Arabidopsis to waterlogging stress.
Waterlogging stress (WLS) negatively impacts the growth and yield of crops resulting in heavy losses to agricultural production. Previous studies have revealed that WLS induces a systemic response in shoots that is partially dependent on the plant hormones ethylene and abscisic acid. However, the role of rapid cell-to-cell signaling pathways, such as the reactive oxygen species (ROS) and calcium waves, in systemic responses of plants to WLS is unknown at present. Here, we reveal that an abrupt WLS treatment of Arabidopsis (Arabidopsis thaliana) plants growing in peat moss triggers systemic ROS and calcium wave responses and that the WLS-triggered ROS wave response of Arabidopsis is dependent on the ROS-generating RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD), calcium-permeable channels GLUTAMATE-LIKE RECEPTOR 3.3 and 3.6 (GLR3.3 and GLR3.6), and aquaporin PLASMA MEMBRANE INTRINSIC PROTEIN 2;1 (PIP2;1) proteins. We further show that WLS is accompanied by a rapid systemic transcriptomic response that is evident as early as 10 min following waterlogging initiation, includes many hypoxia-response transcripts, and is partially dependent on RBOHD. Interestingly, the abrupt WLS of Arabidopsis resulted in the triggering of a rapid hydraulic wave response and the transient opening of stomata on leaves. In addition, it induced in plants a heightened state of tolerance to a subsequent submergence stress. Taken together, our findings reveal that the initiation of WLS in plants is accompanied by rapid systemic physiological and transcriptomic responses that involve the ROS, calcium, and hydraulic waves, as well as the induction of hypoxia acclimation mechanisms in systemic tissues.


Identification of key residues in Debaryomyces hansenii carbonyl reductase for highly productive preparation of (S)-aryl halohydrins.
Key residues of Debaryomyces hansenii carbonyl reductase in the determination of the reducing activity towards aryl haloketones were identified through combinatorial mutation of conserved residues. This study provides a green and efficient biocatalyst for the synthesis of (S)-aryl halohydrins.


Microcystic adenoma of the pancreas.
Three cases of pancreatic microcystic adenoma (PMA) are presented. These tumors comprise less than 1% of all pancreatic tumors in a large series, and exhibit a benign course, in contrast to mucinous cystadenomas, which have a definite malignant potential. The cases here presented are middle and advanced aged women who complained of epigastric discomfort and mild weight loss. Two of them also had a palpable epigastric mass and one of them diabetes mellitus. They were treated surgically with total excision of the tumor. During surgery and thereafter no evidence of spreading beyond the pancreas was found. CT scan shows a characteristic image of PMA, which may then be confirmed by a percutaneous biopsy. If the patient is asymptomatic or a poor surgical risk, it is reasonable to rely on this evidence and follow the patient rather than operate.


MiR-181a Reduces Platelet Activation via the Inhibition of Endogenous RAP1B.
Since RAP1B is critical for platelet functions, including hemostasis, this study was conducted to identify RAP1B regulating microRNAs (miRNAs) in ex vivo stored platelets. Previous studies with platelets identified factors affecting RAP1B activity but regulatory miRNAs that affect RAP1B protein expression have not been reported. To understand the functional significance of miRNA mediated regulation of RAP1B in stored platelets, using microRNA, miR-181a as an example. A Tagged RNA Affinity approach (MS2-TRAP) was employed to identify miRNAs that bound to the 3` untranslated region (3`UTR) of the RAP1B mRNA in HeLa cells as an assay system. And subsequently, the mRNA 3'UTR:miRNA interactions were verified in platelets through the ectopic expression of miR-181a mimic and appropriate controls. The interaction of such miRNAs with RAP1B mRNA was also validated by qRT-PCR and Western analysis. Sixty-two miRNAs from MS2 assay were then compared with already known 171 platelet abundant miRNAs to identify a common set of miRNAs. This analysis yielded six miRNAs (miR- 30e, miR-155, miR-181a, miR-206, miR-208a and miR-454), which are also predicted to target RAP1B mRNA. From this pool, miR-181a was selected for further study since RAP1B harbors two binding sites for miR-181a in its 3'UTR. Ectopic expression of miR-181a mimic in platelets resulted in lowering the endogenous RAP1B at both mRNA and protein levels. Further, miR-181a ectopic expression reduced the surface expression of the platelet activation marker, P-selectin. MicroRNA-181a can target RAP1B and this interaction has the potential to regulate platelet activation during storage.


NIH deltanoids meeting on Vitamin D and cancer. Conclusion and strategic options.
A meeting on "Cancer Chemoprevention and Cancer Treatment; role of vitamin D, 1alpha,25-(OH)(2)D(3) and deltanoids" was held on the NIH Congres, Bethesda in November 2004. The following conclusions were presented at the end of this symposium. Vitamin D deficiency and insufficiency are worldwide problems and are associated with several health problems including higher cancer prevalence. There is convincing evidence that the active vitamin D hormone, 1alpha,25(OH)(2)D(3), can decrease cell proliferation, modify cell apoptosis and control malignant cell growth. Therefore academia, public funding agencies and industry should urgently design appropriate studies to better define the causal relationship between vitamin D nutrition and cancer, define the optimal vitamin D nutrition based on accurate 25(OH)D measurement and inform the public and medical profession accordingly. Selective vitamin D receptor modulators are a potentially interesting new class of chemopreventive and chemotherapeutic agents as demonstrated by several first generation analogs have provided a convincing proof of concept. In the mean time, the public should be informed about the risks of vitamin D deficiency and insufficiency and appropriate steps should be taken to improve the vitamin D nutritional status of large parts of the world population.


Repair of DNA-containing pyrimidine dimers.
Ultraviolet light-induced pyrimidine dimers in DNA are recognized and repaired by a number of unique cellular surveillance systems. The most direct biochemical mechanism responding to this kind of genotoxicity involves direct photoreversal by flavin enzymes that specifically monomerize pyrimidine:pyrimidine dimers monophotonically in the presence of visible light. Incision reactions are catalyzed by a combined pyrimidine dimer DNA-glycosylase:apyrimidinic endonuclease found in some highly UV-resistant organisms. At a higher level of complexity, Escherichia coli has a uvr DNA repair system comprising the UvrA, UvrB, and UvrC proteins responsible for incision. There are several preincision steps governed by this pathway, which includes an ATP-dependent UvrA dimerization reaction required for UvrAB nucleoprotein formation. This complex formation driven by ATP binding is associated with localized topological unwinding of DNA. This same protein complex can catalyze an ATPase-dependent 5'----3'-directed strand displacement of D-loop DNA or short single strands annealed to a single-stranded circular or linear DNA. This putative translocational process is arrested when damaged sites are encountered. The complex is now primed for dual incision catalyzed by UvrC. The remainder of the repair process involves UvrD (helicase II) and DNA polymerase I for a coordinately controlled excision-resynthesis step accompanied by UvrABC turnover. Furthermore, it is proposed that levels of repair proteins can be regulated by proteolysis. UvrB is converted to truncated UvrB* by a stress-induced protease that also acts at similar sites on the E. coli Ada protein. Although UvrB* can bind with UvrA to DNA, it cannot participate in helicase or incision reactions. It is also a DNA-dependent ATPase.


Development of multimetal binding model and application to binary metal biosorption onto peat biomass.
Biosorption of Cr(3+), Cu(2+) and Cd(2+) from binary metal solutions onto peat in the batch systems was investigated at pH 4. The order of maximum uptake was Cr>or=Cu>Cd and maximum uptake levels of ca. 0.4 mmol/g were observed for chromium and copper while cadmium was taken up to a maximum of ca. 0.2 mmol/g. Co-ion competition resulted in up to 70 percent decrease of primary metal uptake. A novel approach to multicomponent sorption modelling involving regression to the total metal taken up was adopted. Two extended Langmuir-type models were found to exhibit good fit to the experimental data. Using the simpler model of these, three-dimensional sorption surfaces were generated which describe the metal uptake as a function of equilibrium concentrations of both metals. These methods allow prediction of metal uptakes over a continuum of concentrations of both metals in binary systems.


Interaction of Necl-4/CADM4 with ErbB3 and integrin α6 β4 and inhibition of ErbB2/ErbB3 signaling and hemidesmosome disassembly.
Nectin-like molecule 4 (Necl-4)/CADM4, a transmembrane cell-cell adhesion molecule with three Ig-like domains, was shown to serve as a tumor suppressor, but its mode of action has not been elucidated. In this study, we showed that Necl-4 interacted in cis with ErbB3 through their extracellular regions, recruited PTPN13 and inhibited the heregulin-induced activation of the ErbB2/ErbB3 signaling. In addition, we extended our previous finding that Necl-4 interacts in cis with integrin α6 β4 through their extracellular regions and found that Necl-4 inhibited the phorbol ester-induced disassembly of hemidesmosomes. These results indicate that Necl-4 serves as a tumor suppressor by inhibiting the ErbB2/ErbB3 signaling and hemidesmosome disassembly.


Regulome-based characterization of drug activity across the human diseasome.
Drugs are expected to recover the cell system away from the impaired state to normalcy through disease treatment. However, the understanding of gene regulatory machinery underlying drug activity or disease pathogenesis is far from complete. Here, we perform large-scale regulome analysis for various diseases in terms of gene regulatory machinery. Transcriptome signatures were converted into regulome signatures of transcription factors by integrating publicly available ChIP-seq data. Regulome-based correlations between diseases and their approved drugs were much clearer than the transcriptome-based correlations. For example, an inverse correlation was observed for cancers, whereas a positive correlation was observed for immune system diseases. After demonstrating the usefulness of the regulome-based drug discovery method in terms of accuracy and applicability, we predicted new drugs for nonsmall cell lung cancer and validated the anticancer activity in vitro. The proposed method is useful for understanding disease-disease relationships and drug discovery.


Transient feelings of compulsion caused by hemispheric lesions: three cases.
There was strong evidence of a neurological explanation for transient feelings of compulsion reported by three patients. In at least two cases the mechanism was epileptic. The frontal lobe was implicated in all three. A feeling of compulsion, divorced from action, has rarely if ever been reported in epilepsy or other neurological disorders.


Quantitative ultrastructural studies on rat gastric zymogen cells under different physiological and experimental conditions.
Quantitative electron microscopical measurements performed on gastric zymogen cells were aimed at determinations of size and volume density of the zymogen granules, and size of cell and nuclear profiles. 17 groups of rats each comprising 6-8 animals were investigated: five of these groups were used to study the influence of fasting and feeding, three groups were killed at different intervals after a pilocarpine injection, and four other groups were investigated after an atropine injection. The remaining five groups of rats were operated on: vagotomy was performed on one group, vagotomy + pyloroplasty on another, pyloroplasty on the third group, and antrectomy on the last two groups. The operated rats were sacrificed 4 or 10 weeks after the operations. Pilocarpine was more effective than feeding in reducing the size and the amount of zymogen granules. After atropine the size and amount of zymogen granules tended to increase. Ten weeks after pyloroplasty, vagotomy + pyloroplasty, or antrectomy the mean size of the zymogen cells was reduced. Loss of trophic vagal impulses, duodenal regurgitation, and abnormal serum gastrin levels are factors which might be responsible for the zymogen cell hypotrophy in operated rats.


Transarterial detachable coil embolization of direct carotid-cavernous fistula: immediate and long-term outcomes.
Transarterial embolization is a standard method for management of direct carotid-cavernous fistula (DCCF). The purpose of this study was to report our experiences, and immediate and long-term outcomes of endovascular embolization of DCCFs by using detachable coils (DCs). Over 8 years, 24 patients with 25 DCCFs underwent endovascular DC embolization. There were 15 men and nine women; age ranged from 8 to 82 years (mean, 39 years). Immediate and long-term angiographic as well as clinical outcomes after endovascular DC embolization were retrospectively analyzed. The number and the length of DCs used to occlude the fistula were also evaluated. Eighteen DCCFs were successfully occluded by single-session endovascular embolization with preservation of the parent artery. Retreatments by transvenous (n = 5) and/ or transorbital routes (n = 3) had to be performed in seven patients because of residual fistula (n = 4) or recurrent fistula (n = 4) occurring within 3 weeks after embolization. The average numbers and length of coils to occlude the fistulas were 14 (range, 2-31) and 189 cm (range, 16-756 cm), respectively. Four patients had small residual fistulas with spontaneous thrombosis on follow-up angiography. Three patients had transient cranial nerve impairment of the third (n = 1) or sixth (n = 2) nerve. There was no significant procedure-related neurological complication. The follow-up period was 3-48 months (mean, 19 months) Endovascular DC embolization of DCCFs was proved both efficacious and safe in managing high-flow fistulas with sustained angiographic and clinical effects, particularly in those DCCFs with small fistula track and/or cavernous sinus. However, retreatment via various routes may be necessary in some patients because of residual or recurrent fistulas.


Percutaneous Patent Foramen Ovale Closure After Stroke.
Percutaneous patent foramen ovale (PFO) closure in patients with a prior PFO-associated stroke showed a risk reduction of the stroke recurrence compared to the medical therapy alone in recent several studies. Nevertheless, optimal patient selection for PFO closure has not been clarified. In this paper, we discuss the characteristics of PFO-associated strokes and discuss the recently published evidence and patient selection for PFO closure in patients with ischemic stroke. The lesions characteristics of PFO-associated stroke are associated with multiple scattered lesion, small sized cerebral cortical lesion, or posterior circulation. Overcoming the failure of early studies in CLOSURE I, PC, and RESPECT trials, PFO closure showed a significant reduction in recurrent stroke in recently published REDUCE, CLOSE, DEFENSE-PRO trials, and long-term follow-up data of RESPECT study. However, considering that PFO closure cannot completely prevent stroke recurrence and that complications including atrial fibrillation, we should be selectively performed in patients with high-risk PFO.


Probabilistic model checking of cancer metabolism.
Cancer cell metabolism is often deregulated as a result of adaption to meeting energy and biosynthesis demands of rapid growth or direct mutation of key metabolic enzymes. Better understanding of such deregulation can provide new insights on targetable vulnerabilities, but is complicated by the difficulty in probing cell metabolism at different levels of resolution and under different experimental conditions. We construct computational models of glucose and glutamine metabolism with focus on the effect of IDH1/2-mutations in cancer using a combination of experimental metabolic flux data and patient-derived gene expression data. Our models demonstrate the potential of computational exploration to reveal biologic behavior: they show that an exogenously-mutated IDH1 experimental model utilizes glutamine as an alternative carbon source for lactate production under hypoxia, but does not fully-recapitulate the patient phenotype under normoxia. We also demonstrate the utility of using gene expression data as a proxy for relative differences in metabolic activity. We use the approach of probabilistic model checking and the freely-available Probabilistic Symbolic Model Checker to construct and reason about model behavior.


A model of developmental evolution: selection, pleiotropy and compensation.
Development and physiology translate genetic variation into phenotypic variation and determine the genotype-phenotype map, such as which gene affects which character (pleiotropy). Any genetic change in this mapping reflects a change in development. Here, we discuss evidence for variation in pleiotropy and propose the selection, pleiotropy and compensation model (SPC) for adaptive evolution. It predicts that adaptive change in one character is associated with deleterious pleiotropy in others and subsequent selection to compensate for these pleiotropic effects. The SPC model provides a unifying perspective for a variety of puzzling phenomena, including developmental systems drift and character homogenization. The model suggests that most adaptive signatures detected in genome scans could be the result of compensatory changes, rather than of progressive character adaptations.


Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity.
To develop and validate a new risk-of-bias tool for nonrandomized studies (NRSs). We developed the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). A validation process with 39 NRSs examined the reliability (interrater agreement), validity (the degree of correlation between the overall assessments of RoBANS and Methodological Index for Nonrandomized Studies [MINORS], obtained by plotting the overall risk of bias relative to effect size and funding source), face validity with eight experts, and completion time for the RoBANS approach. RoBANS contains six domains: the selection of participants, confounding variables, the measurement of exposure, the blinding of the outcome assessments, incomplete outcome data, and selective outcome reporting. The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial. There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS. The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies. The mean time required to complete RoBANS was approximately 10 min. The external experts who were interviewed evaluated RoBANS as a "fair" assessment tool. RoBANS shows moderate reliability, promising feasibility, and validity. The further refinement of this tool and larger validation studies are required.


A hemolytic factor from Haemonchus contortus alters erythrocyte morphology.
A hemolytic factor from adult Haemonchus contortus caused distinct morphological changes in the surface of sheep red blood cells (RBCs). After a 15 min exposure to the hemolytic factor, hemolysis was not detected in incubation media, but RBCs were spherical in shape with numerous surface projections compared to control cells that were smooth-surfaced biconcave disks. After 30 min, a time at which significant hemolysis occurred, echinocytes were formed, and after 90 min, cells were severely disrupted with many visible holes in membranes. No RBC ghosts were observed. RBCs from four other mammalian species were lysed by the H. contortus hemolytic factor. However, the rate of hemolysis varied with a relative order of sheep approximately rabbit>goat>pig>calf. The morphology of RBCs from all four species was significantly altered after 30 min incubation with the degree of morphological changes related to the degree of hemolysis. These results support the hypothesis that the hemolytic factor acts as a pore-forming agent, although a phospholipase or other enzyme might play a role in solubilization of cell membranes.


HEADS AND TAILS: A CHORDATE PHYLOGENY.
Abstract- A cladistic analysis of chordates is presented, based on some 320 nested characters. All the principal higher taxa are defined by synapomorphies, including extinct acanthodians and placoderms. The data base draws broadly from adult anatomy (including osteological data for Recent and fossil taxa), embryology, physiology, and biochemistry. A conventional sequence of chordate higher taxa is generated (hemichordates, urochordates, cephalochordates, craniates). Among the craniates, cyclostomes are considered paraphyletic. Gnathostomes are monophyletic, but two fossil "agnathan" groups (galeaspids, osteostracans) are regarded as stem gnathostomes. Chondrichthyans and osteichthyans are monophyletic. New arguments for osteichthyan affinity of acanthodians are presented. The phylogenetic position of placoderms is still problematic, but they can no longer be perceived as stem chondrichthyans or even as "elasmobranchiomorphs." Recent dipnoans and tetrapods are sister groups, but new paleontological discoveries refute many of their supposed osteological synapomorphies, thereby reopening the possibility of a closer relationship between tetrapods and osteolepiform rhipidistians.


Histone is able to associate with radioactive RNA to form a complex which is retained on a millipore filter; 500 &mgr;g of histone F(1) from bone marrow is able to combine with 100 &mgr;g of RNA. Chromatin acidic proteins reduce this association up to 50%. The binding between RNA and histone does not occur in the presence of urea and NaCl.


Occurrence of some rare earth elements in vineyard soils under semiarid Mediterranean environment.
A comprehensive investigation has been carried out into the concentrations of a range of REEs (neodymium Nd, cerium Ce, lanthanum La, yttrium Y, scandium Sc) in soils of vineyards belonging to the protected denomination of origin (PDO) Valdepeñas (Central Spain). The mean concentrations (expressed in mg kg-1) are Ce 70.6, Nd 32.9, La 36.2, Y 21.6, and Sc 13.7 in surface horizons (Ap), while in subsurface horizons (Bt or Bw and some Ck), the values are Ce 67.6, Nd 31.8, La 34.4, Y 19.6, and Sc 13.9. The relative abundance in these soils is Ce > La > Nd > Y > Sc in both the surface and subsurface horizons. These values are close to, or slightly higher than, the regional levels but similar to national and global averages, although relatively high values have been detected at certain sampling points. Another aim was to explain the spatial variations in these elements within the territory under study. It was found that the spatial variations are due to the nature of the parent materials and the pedogenetic processes, although the sparse spatial distribution patterns with prominent anomalies are interpreted arising from anthropogenic sources (fertilization). However, these anomalies did not present any environmental risk in the studied zone.


CO2 lasers in the management of potentially malignant and malignant oral disorders.
The CO2 laser was invented in 1963 by Kumar Patel. Since the early 1970s, CO2 laser has proved to be an effective method of treatment for patients with several types of oral lesions, including early squamous cell carcinoma.Laser surgery of oral premalignant disorders is an effective tool in a complete management strategy which includes careful clinical follow-up, patient education to eliminate risk factors, reporting and biopsying of suspicious lesions and any other significant lesions. However, in a number of patients, recurrence and progression to malignancy remains a risk. CO2 laser resection has become the preferred treatment for small oral and oropharyngeal carcinomas. Laser resection does not require reconstructive surgery. There is minimal scarring and thus, optimum functional results can be expected.New and improved applications of laser surgery in the treatment of oral and maxillofacial/head and neck disorders are being explored. As more surgeons become experienced in the use of lasers and as our knowledge of the capabilities and advantages of this tool expands, lasers may play a significant role in the management of different pathologies.


Timing attention: cuing target onset interval attenuates the attentional blink.
Three experiments tested whether the attentional blink (AB; a deficit in reporting the second of two targets when it occurs 200-500 msec after the first) can be attenuated by providing information about the target onset asynchrony (TOA) of the second target relative to the first. Blocking the TOA did not improve second-target performance relative to a condition in which the TOA varied randomly from trial to trial (Experiment 1). In contrast, explicitly cuing the TOA on a trial-by-trial basis attenuated the AB without a cost to first-target identification (Experiments 2 and 3). The results suggest that temporal cues influence the allocation of attentional resources by adding temporal information to the perceptual description of the second target that can then be used to filter targets from nontargets, resulting in enhanced accuracy.


Polyurethane-coated Dacron-covered stent-grafts for TIPS: results in swine.
To evaluate shunt patency after placing a new polyurethane-coated Dacron-covered spiral Z stent-graft to create a transjugular intrahepatic portosystemic shunt (TIPS). TIPS stent-grafts were placed in six young swine, using polyurethane-coated, Dacron-covered spiral Z stent-grafts. Animals were followed weekly by transhepatic portal venography until shunt occlusion or up to 6 weeks, then were sacrificed for gross and histologic evaluation. Five of six TIPS stent-grafts were found to be occluded by 3 weeks and none were patent at 6 weeks. Histologic evaluation demonstrated a marked foreign body reaction with superimposed thrombosis occluding the graft lumen. Polyurethane-coated Dacron-covered stent-grafts do not improve TIPS patency.


BODY SOMATIC TYPE INFLUENCE ON THE SPINAL CURVATURES IN EARLY AGE SCHOOL CHILDREN: PRELIMINARY REPORT.
Sedentary lifestyle and its consequences are becoming a serious problem not only among the elderly but also relate to children. Reduced muscle mass, disorder of normal spinal curves or problems related to the percentage of body fat are part of physical activity limitation. The aim of this study was to assess the relationship between somatic type of the body and spinal curvatures in school children. This study included 94 randomly selected children from 1-3 elementary schools grades, 49 girls and 45 boys. The subjects were divided into 3 groups: a group of children with a BMI indicating underweight (BMI <14.5, n=25), a group of children with normal BMI (BMI = 14.5-17.5, n = 33) and children BMI indicating overweight (BMI > 17.5, n = 36). The Posturometr-S was a device used for measurement and evaluation of the formation of the spine in the sagittal plane. There were three angles of inclination of anterior-posterior curvature of the spine identified: the α angle-upper thoracic spine, the β angle-thoraco-lumbar spine and the γ angle-lumbosacral spine. Analysing the results of the different angles of curvature of the spine in the sagittal plane we can notice a statistically significant difference between the groups only in the a angle. The own investigations have showed that the somatic type of the body does not affect the shape of the spine in school children assessed using Posturometr-S. Ther investigations are needed.


[Diagnostic study of 5 cases of allergic asthma due to sensitization to silk allergens in textile workers from the Prato area].
Five cases of allergic asthma due to sensitivity to silk allergens have been studied. All the patients worked in the Prato textile industry. The presence of specific antibodies against extracts of silk has been shown by the direct RAST and confirmed by the indirect RAST. The onset of the symptoms, with regard to the various stages in the processing of silk, leads one to assume that the allergen involved is sericin.


The histopathologic features of lithium-associated thyroiditis.
The case of a 62-year-old woman with lithium-associated thyroiditis is presented. Lithium can produce goiters associated with hypothyroidism and, less commonly, hyperthyroidism and euthyroidism. The characteristic histopathologic features of the affected thyroid gland included fibrosis, lymphoid follicles with atrophy, and hyperplasia of thyroid follicles. The pathogenetic mechanism appears to be immunologic, with lithium acting as a haptene with a thyroid antigen to induce an "autoimmune" type of thyroiditis.


Assessment of Intraoperative Blood Loss at Different Surgical Stages During Posterior Spinal Fusion Surgery in the Treatment of Adolescent Idiopathic Scoliosis.
Prospective clinical study. To analyze the amount of blood loss at different stages of Posterior Instrumented Spinal Fusion (PSF) surgery in adolescent idiopathic scoliosis (AIS) patients. Knowing the pattern of blood loss at different surgical stages may enable the surgical team to formulate a management strategy to reduce intraoperative blood loss. One hundred AIS patients who underwent PSF from January 2013 to December 2014 were recruited. The operation was divided into six stages; stage 1-exposure, stage 2-screw insertion, stage 3-release, stage 4-correction, stage 5-corticotomies and bone grafting, and stage 6-closure. The duration and blood loss at each stage was documented. The following values were calculated: total blood loss, blood loss per estimated blood volume, blood loss per minute, blood loss per vertebral level fused, and blood loss per minute per vertebral level fused. There were 89 females and 11 males. The mean age was 17.0 ± 5.8 years old. Majority (50.0%) were Lenke 1 curve type. The mean preoperative major Cobb angle was 64.9 ± 15.0°. The mean number of levels fused was 9.5 ± 2.3 levels. The mean operating time was 188.5 ± 53.4 minutes with a mean total blood loss 951.0 ± 454.0 mLs. The highest mean blood loss occurred at stage 2 (301.0 ± 196.7 mL), followed by stage 4 (226.8 ± 171.2 mL) and stage 5 (161.5 ± 146.6 mL). The highest mean blood loss per minute was at stage 5 (17.1 ± 18.3 mL/min), followed by stage 3 (12.0 ± 10.8 mL/min). The highest mean blood loss per vertebral levels fused was at stage 2 (31.0 ± 17.7 mL/level), followed by stage 4 (23.9 ± 18.1 mL/level) and stage 5 (16.6 ± 13.3 mL/level). All stages were significant contributors to the total blood loss except exposure (stage 1) and closure (stage 6). Blood loss per minute and blood loss per minute per level was highest during corticotomies (stage 5), followed by release (stage 3). However, the largest amount of total blood loss occurred during screw insertion (stage 2). 2.


Variable deterioration in cortical function during insulin-induced hypoglycemia.
Cortical function during insulin-induced hypoglycemia was studied in 14 normal controls and 12 type I diabetic patients by measuring the reaction time to a visual stimulus. Each subject was studied on two occasions, during insulin-induced hypoglycemia and under euglycemic conditions. The mean reaction time during euglycemic conditions was 260 +/- 6 ms in the controls and 309 +/- 11 ms in the diabetic subjects (P less than 0.001) and did not change significantly over a 2-h period. Intravenous (i.v.) insulin administration to both groups of subjects resulted in similar reductions in glucose concentrations, which were maintained below 50 mg/dl for at least 30 min. Under these conditions, the reaction time increased significantly (mean increase 104 +/- 37 ms [P less than 0.02] in the controls and 75 +/- 28 ms [P less than 0.02] in the diabetic subjects). However, significant variability in responsiveness was observed in individual subjects. Three of the 14 controls and 4 of the 12 diabetic subjects showed no significant change in reaction time during hypoglycemia, while the remainder demonstrated significant increases. Individual differences were not correlated with severity or duration of hypoglycemia or counterregulatory hormone responses. The maximum increase in reaction time occurred as long as 60 min after the nadir glucose and returned to baseline 10-40 min after normalization (greater than 60 mg/dl) of the plasma glucose level. Subjective awareness of hypoglycemia was unrelated to the change in reaction time.(ABSTRACT TRUNCATED AT 250 WORDS)


Positron emission tomography after MPTP: observations relating to the cause of Parkinson's disease.
The dopa analogue 6-fluorodopa (6-FD) used with positron emission tomography (PET) allows in vivo visualization of dopamine and its metabolites in nigrostriatal nerve endings. We have now found abnormal 6-FD scans in four subjects exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). None had parkinsonism. The results suggest subclinical damage to the nigrostriatal pathway. This is the first direct evidence that dopaminergic impairment can exist without clinical deficits. Here we discuss this finding in the context of the hypothesis that Parkinson's disease may stem from clinically silent damage to the substantia nigra, followed by slow attrition of neurones in this region because of its particular vulnerability to cell loss as a normal consequence of ageing.


Influence of summer daylight saving time on scattered erythemal solar ultraviolet exposures.
The research question of whether there are any influences in the scattered or diffuse erythemal UV exposures to a horizontal plane over a five month period due to the change from standard time to daylight saving time, has been investigated by using physical measurements and applying them to both standard time and daylight saving time. The diffuse erythemal UV was considered for fixed lunch break times and fixed morning and afternoon break times. The cases considered were for groups of the population who are predominantly indoors and who spend their break times outdoors in shade. The biggest influence on the diffuse UV exposures of changing to daylight saving time is the timing of the outdoor meal and break times. The change causes a reduction in diffuse erythemal exposure for early or morning breaks and an increase in the diffuse erythemal exposure for late or afternoon breaks. Similarly, for the lunch break times, the changes in exposure are influenced by the timing of the break with respect to solar noon. Indoor workers who take their breaks outside in a shaded area may have a change in their exposure to diffuse UV due to a shift to daylight saving time, however the magnitude of this change and whether it is a positive or negative change in exposure will depend on the timing of the break. The increase in diffuse UV exposure due to the afternoon break may be negated by the decrease in exposure due to the morning break. In this case, the effect on diffuse UV exposures due to changing to daylight saving time will be minimal.


The impact of small groups on pre- and postcopulatory sexual selection in polyandrous populations.
Sexual selection is a key evolutionary force but varies widely between populations. Two key factors that influence sexual selection are the extent to which females copulate with multiple males (polyandry) and variation in the social environment. Increasing research demonstrates populations are structured by complex socio-sexual networks, and the structure of these networks can influence sexual selection by shaping the relationship between male precopulatory mating success and the intensity of postcopulatory competition. However, comparatively less attention has been dedicated to the influence of group structure on sexual selection and how differences in the size of groups may impact on the relative force of pre- and postcopulatory sexual selection in polyandrous populations. The presence of groups (i.e., group structure) and the size of groups varies widely in nature and forms an implicit part of much experimental sexual selection research under laboratory conditions. Here I use simulations of mating competition within populations that vary in the size of groups they contain, to show that variation in group size, and in particular small groups, can influence sexual selection. Specifically, I show that null expectations for the operation of pre- and postcopulatory sexual selection is governed by the size of groups within populations because smaller group sizes constrain the structure of sexual networks leading to reinforcing episodes of pre- and postcopulatory sexual selection. Given broad variation in group structure in nature and the tendency for experimental sexual selection research to study replicate small groups, these effects have implications for our understanding of the operation of sexual selection in polyandrous populations.


Detailed examination of cartilage formation and endochondral ossification using human mesenchymal stem cells.
1. Cartilage formation is one of the most complex processes in biology. The aim of the present study was to produce a simplified in vitro system to resolve its complexities. 2. Human mesenchymal stem cells (hMSC) were maintained in alginate beads with a chondrogenesis-induction medium containing 10 ng/mL transforming growth factor (TGF)-beta3. 3. At days 0, 2, 4, 8, 12, 16 and 19 of culture, we examined the cells using a light microscope and a transmission electron microscope. We also evaluated the cells using immunocryo-ultramicrotomy. 4. The present study demonstrated that hMSC produced numerous extracellular matrices containing abnormal collagen fibres following their exposure to a chondrogenesis-induction medium in alginate beads. At this time, calcification was detected by alizarin red staining and electron-dense particles, composed of hydroxyapatite, appeared in both the cytoplasm and the extracellular spaces. 5. In addition immunocryo-ultramicrotomy revealed that collagen type II, type X and proteoglycan were prominent and that osteocalcin was detectable at day 2. During 8-16 days of culture, collagen type X maintained its strong expression and the expression of osteocalcin increased markedly. In contrast, the expression of collagen type II and proteoglycan decreased with time. 6. These findings demonstrate that hMSC rapidly differentiate into chondrocytes expressing collagen type II and proteoglycan. 7. The expression of collagen type II and proteoglycan then dropped and the activity of collagen type X was the same as before (4-8 days). As a result, the cells developed into the next cell type, so-called hypertrophic chondrocytes. Finally, both osteocalcin activity and the calcification of cell bodies and extracellular matrices became evident, indicating endochondral ossification. Thus, we conclude that hMSC rapidly differentiate into chondrocytes, followed by the development of hypertrophic chondrocytes. Endochondral ossification is the final form in this culture. 8. The findings of the present study indicate that our three-dimensional culture is a convenient in vitro model for the investigation of the regulatory mechanisms of cartilage formation and endochondral ossification.


Dynamics of Mouth Opening in Hydra.
Hydra, a simple freshwater animal famous for its regenerative capabilities, must tear a hole through its epithelial tissue each time it opens its mouth. The feeding response of Hydra has been well-characterized physiologically and is regarded as a classical model system for environmental chemical biology. However, due to a lack of in vivo labeling and imaging tools, the biomechanics of mouth opening have remained completely unexplored. We take advantage of the availability of transgenic Hydra lines to perform the first dynamical analysis, to our knowledge, of Hydra mouth opening and test existing hypotheses regarding the underlying cellular mechanisms. Through cell position and shape tracking, we show that mouth opening is accompanied by changes in cell shape, but not cellular rearrangements as previously suggested. Treatment with a muscle relaxant impairs mouth opening, supporting the hypothesis that mouth opening is an active process driven by radial contractile processes (myonemes) in the ectoderm. Furthermore, we find that all events exhibit the same relative rate of opening. Because one individual can open consecutively to different amounts, this suggests that the degree of mouth opening is controlled through neuronal signaling. Finally, from the opening dynamics and independent measurements of the elastic properties of the tissues, we estimate the forces exerted by the myonemes to be on the order of a few nanoNewtons. Our study provides the first dynamical framework, to our knowledge, for understanding the remarkable plasticity of the Hydra mouth and illustrates that Hydra is a powerful system for quantitative biomechanical studies of cell and tissue behaviors in vivo.


Size-dependent biological effect of copper oxide nanoparticles exposure on cucumber (Cucumis sativus).
Copper oxide nanoparticles (CuO NPs) have received considerable attention for their toxic effects on crops and potential application in agriculture. In order to investigate the biological effects of CuO NPs on plants, we exposed cucumber (Cucumis sativus) to two sizes of CuO NPs (510 nm, μCuO and 43 nm, nCuO). Results indicated that with concentration increased, the available Cu content in soil increased significantly. The addition of CuO NPs increased Cu content and other nutrient element (e.g., K, P, Mn, and Zn) content in plants. However, diverse particle sizes had different effects. The nCuO treatment had larger translocation factor, higher nutrient element content in fruits, and lower oxidative damage than μCuO treatment. Moreover, nCuO of 100 mg/kg could stimulate cucumber growth, while μCuO had no obvious effects on growth. Conclusively, CuO NPs could be used as copper fertilizer to supply copper to cucumber. The nCuO had better effects on improving the bioavailability of Cu and nutritional value of fruits. These results can help develop strategies for safe disposal of CuO NPs as agricultural fertilizer.


Effects of eccentric-focused and conventional resistance training on strength and functional capacity of older adults.
The aim of the study was to assess the effect of eccentric training using a constant load with longer exposure time at the eccentric phase on knee extensor muscle strength and functional capacity of elderly subjects in comparison with a conventional resistance training program. Twenty-six healthy elderly women (age = 67 ± 6 years) were randomly assigned to an eccentric-focused training group (ETG; n = 13) or a conventional training group (CTG; n = 13). Subjects underwent 12 weeks of resistance training twice a week. For the ETG, concentric and eccentric phases were performed using 1.5 and 4.5 s, respectively, while for CTG, each phase lasted 1.5 s. Maximum dynamic strength was assessed by the one-repetition maximum (1RM) test in the leg press and knee extension exercises, and for functional capacity, subjects performed specific tests (6-m walk test, timed up-and-go test, stair-climbing test, and chair-rising test). Both groups improved knee extension 1RM (24-26 %; p = 0.021), timed up-and-go test (11-16 %; p < 0.001), 6-m walk test (9-12 %; p = 0.004), stair-climbing test (8-13 %; p = 0.007), and chair-rising test (15-16 %; p < 0.001), but there was no significant difference between groups. In conclusion, the strategy of increasing the exposure time at the eccentric phase of movement using the same training volume and intensity does not promote different adaptations in strength or functional capacity compared to conventional resistance training in elderly woman.


RBANS index discrepancies: base rates for older adults.
The present study expands upon the data available in the manual of the Repeatable Battery for the Assessment of Neuropsychological Status, by providing base rate data on Index discrepancies that are organized by general level of ability and include both age and education corrections. The data presented are based on the performances of a sample of 718 community dwelling older adults. These findings offer the possibility of increased sensitivity at detecting clinically significant differences that might not be identified when relying on base rate data from a greater age range. Similarly, these data highlight the mediating effects of the global level of cognitive functioning on discrepancy scores.


Aceclofenac and methotrexate combination therapy could influence Th1/Th17 axis to modulate rheumatoid-arthritis-induced inflammation.
Rheumatoid arthritis (RA) is an inflammatory, autoimmune and connective-tissue arthropathy. The methotrexate (MTX) and aceclofenac (ACL) combination drug regimen is known to regulate the immunological pathways. Also, RA-elicited inflammation is decreased by the combination drug treatment. ACL and MTX combination treatment has been shown to regulate the signaling pathway controlled by NF-κB and FOXO1. The present manuscript reviews the importance of the combination drug regimen to treat and/or manage RA. The combination drug regimen could affect the Th1/Th17 axis to switch the balance toward the immunoregulatory (Th1) phenotype for establishing immune homeostasis. In conclusion, we propose the study of the immunological signaling pathways in experimental humanized RA mice.


[Complementary to notification required by the national Protection against Infection Act. State-specific mandatory infectious disease notification in Saxony-Anhalt].
In May 1991 a decree supplementing the federal Epidemic Law concerning the mandatory notification of communicable diseases was implemented by the Ministry of Health in Saxony-Anhalt. This was updated and newly implemented in 1997. With implementation of the national Protection against Infection Act in 2001 further amendment of the state regulation (published in April 2005) be came necessary. The following diseases or laboratory evidence of the underlying pathogens, respectively, will now be notifiable with inclusion of the affected individual's name: aseptic meningitis, mumps, rubella, varicella, epidemickera to conjunctivitis, pertussis, and pneumococcal meningitis. The possibility of preventing further spread of the pathogen to others though immediate implementation of preventive measures by the public health service justifies notification of the individual's name. Furthermore, the epidemiological situation is to be monitored and evaluated. This also applies to Lyme disease, which will be anonymously notifiable. Particular emphasis is placed on vaccine-preventable diseases in the state regulation for mandatory notification in Saxony-Anhalt, since priority is placed on attaining the health goal "age-appropriate vaccination status in over 90% of the population". The state-specific notification regulation of Saxony-Anhalt has worked well in preventing and controlling communicable diseases. It is a source of reliable data, which may be helpful in the discussion regarding the amendment of the Protection against Infection Act. Non-anonymous notification should be enforced nationally at least for all vaccine-preventable diseases for which a post-exposure vaccination is recommended by the Standing Committee on Vaccination (STIKO).


Nutrient composition and antioxidant activity of gonads of sea urchin Stomopneustes variolaris.
The study investigated, for the first time, proximate nutritional composition and antioxidant activity of gonads from the sea urchin, Stomopneustes variolaris, inhabiting the coastal area of Visakhapatnam (India). Moisture, ash, proteins, lipids and carbohydrate content were 77.53%±0.80, 3.76%±0.25, 12.10%±0.41, 4.98%±0.36 and 1.63%±0.18, respectively, based on dry weight. The gonads were rich in essential amino acids (ca. 32.1% of total amino acids) with the most predominant being phenylalanine, lysine and valine. The essential to non-essential amino acid ratio was 0.5. Polyunsaturated fatty acids (PUFA) constituted 22.01%±2.2 of total fatty acids. The ω6:ω3 ratio was 0.94. Total phenol content of the gonad was 9.90±0.01 mg GAE/g and the IC50 of the extract, using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, was 57.81 μg/ml.


SCA: recovering single-cell heterogeneity through information-based dimensionality reduction.
Dimensionality reduction summarizes the complex transcriptomic landscape of single-cell datasets for downstream analyses. Current approaches favor large cellular populations defined by many genes, at the expense of smaller and more subtly defined populations. Here, we present surprisal component analysis (SCA), a technique that newly leverages the information-theoretic notion of surprisal for dimensionality reduction to promote more meaningful signal extraction. For example, SCA uncovers clinically important cytotoxic T-cell subpopulations that are indistinguishable using existing pipelines. We also demonstrate that SCA substantially improves downstream imputation. SCA's efficient information-theoretic paradigm has broad applications to the study of complex biological tissues in health and disease.


Top-down design of a picture archiving and communications system (PACS) by means of simulation.
The development of picture archiving and communications systems (PACS) for medical applications can be regarded as a challenging field in medical informatics. Since 1982, several projects have been started into this direction worldwide. The Dutch IMAGIS (Image Information System) project, started in 1984, is one of them. Within this project, a top-down design strategy is chosen, with the following first steps: (1) A thorough information analysis for a Radiology Department, in which both qualitative and quantitative aspects are included. Such an analysis can be used to estimate the workload on a future PACS system. (2) The construction of a flexible performance prediction tool, based on discrete even simulation. Such a tool can be used to predict the performance of a certain computer system configuration under a certain workload. Based on the information analysis, and using the performance prediction tool, a PACS system is drafted for the thorax section of the Diagnostic Radiology Department of the Leiden University Hospital. In this first design attempt, the assumption was made that current working procedures concerning images will be maintained as much as possible.


Antimicrobial susceptibility of Lactobacillus species isolated from commercial ethanol plants.
Bacterial contamination of commercial fermentation cultures is a common and costly problem to the fuel ethanol industry. Antimicrobials such as virginiamycin (VIR) and penicillin (PEN) are frequently used to control contamination but there are little data available on the susceptibility of bacterial contaminants to these agents. A survey of bacterial contaminants from a wet-mill ethanol plant with no history of using antibiotics and a dry-grind facility that periodically doses with VIR found that the majority of contaminants were species of Lactobacillus. Thirty-seven isolates of Lactobacillus species from the wet-mill and 42 isolates from the dry-grind facility were tested for antimicrobial susceptibility using broth dilution and agar dilution methods. In general, the Lactobacillus isolates from the dry-grind plant had higher minimum inhibitory concentrations (MICs) for the tested agents than the isolates from the wet-mill facility. The MIC(90) for VIR was 4 microg/ml for the dry-grind isolates versus 0.25 microg/ml for the wet-mill isolates; and for PEN, the MIC(90)'s were >8 and 2 microg/ml for the dry-grind and wet-mill isolates, respectively. Sixteen Lactobacillus isolates from the dry-grind plant but none from the wet-mill possessed vatE, a gene that encodes a streptogramin acetyltransferase associated with resistance to virginiamycin. Despite decreased susceptibility to virginiamycin, most dry-grind isolates had MICs lower than the maximal recommended application rate of 6 ppm.


Effects of Cd2+, Pb2+ and CH3Hg+ on high voltage-activated calcium currents in pheochromocytoma (PC12) cells: potency, reversibility, interactions with extracellular Ca2+ and mechanisms of block.
Effects of the neurotoxic heavy metals Cd2+, Pb2+ and CH3Hg+ on current carried by Ca2+ ions (I(Ca)) through high-voltage activated Ca2+ channels in nerve growth factor (NGF)-differentiated pheochromocytoma (PC12) cells were examined to characterize possible differences in the mechanism of action of these metals on Ca2+ channel function. Specifically, the potency and reversibility of effect on I(Ca) by each metal was examined, as well as the relationship between extracellular [Ca2+] and potency of block of I(Ca) by Cd2+ and Pb2+. In addition, the effect of each of these metals on Ca2+ channels when applied to the intracellular side of the membrane was also examined. When extracellular solution contained 20, 10 or 5 mM Ca2+, the estimated IC50 values (total metal concentration) for block of I(Ca) were 15, 10, and 6.5 microM for Cd2+ and 7.5, 2.0 and 1.1 microM for Pb2+, respectively. CH3Hg+ (1-10 microM) blocked I(Ca) (20 mM Ca2+) in a time- and concentration-dependent manner. When cells were washed with metal-free solutions, block of I(Ca) by Cd2+ was reversed rapidly, whereas block by Pb2+ was reversed only partially, and block of I(Ca) by CH3Hg+ was not reversed. When Pb2+ and CH3Hg+ treated cells were washed in metal-free solutions containing 50 microM D-penicillamine (DPEN), block of I(Ca) by 10 microM Pb2+ was rapidly and completely reversed, whereas, block of I(Ca) by 5 microM CH3Hg+ was not reversed. Higher concentrations (500 microM) of 2,3-dimercapto-1-propane sulfonic acid (DMPS) did reverse partially the block of I(Ca) by 5 and 10 microM CH3Hg+. When Cd2+, Pb2+ or CH3Hg+ was present in the intracellular solution, Ca2+ channel currents were significantly reduced. These results characterize effects of Cd2+ on Ca2+ channels and demonstrate that Cd2+, Pb2+ and CH3Hg+ differ in their actions on Ca2+ channels.


Divergent access to a novel 3,4-diaminophytosphingosine-like ceramide via sequential Overman rearrangement.
A straightforward approach to a novel phytosphingosine-like ceramide has been accomplished. The cornerstone features of this divergent synthesis are a cascade Overman rearrangement of tris(imidate) to introduce three desired stereogenic centres via sequential chirality transfer and an effective olefin cross-metathesis to install a long side chain. The final unusual phytoceramides were evaluated for their capacity to inhibit the proliferation of cancer cell lines. The preliminary results revealed that compound 21 exhibits promising anticancer activity against HeLa and HCT-116 cells as well as the excellent selectivity in cytotoxicity (malignant vs non-malignant cell lines).


Preventing the most common firearm deaths: Modifiable factors related to firearm suicide.
More than 20,000 firearm suicides occur every year in America. Firearm restrictive legislation, firearm access, demographics, behavior, access to care, and socioeconomic metrics have been correlated to firearm suicide rates. Research to date has largely evaluated these contributors singularly. We aimed to evaluate them together as they exist in society. We hypothesized that state firearm laws would be associated with reduced firearm suicide rates. We acquired the 2013 to 2016 data for firearm suicide rates from The Centers for Disease Control Wide-ranging Online Data for Epidemiologic Research. Firearm laws were obtained from the State Firearms Law Database. Depression rates and access to care were obtained from the Behavioral Risk Factor Surveillance System and Occupational Employment and Wage Statistics program. Population demographics, poverty, and access to social support were obtained from the American Community Survey. Firearm access estimates were retrieved from the National Instant Criminal Background Check System. We used a univariate panel linear regression with fixed effect for state and firearm suicide rates as the outcome. We created a final multivariable model to determine the adjusted associations of these factors with firearm suicide rates. In univariate analysis, firearm access, heavy drinking behavior, demographics, and access to care correlated to increased firearm suicide rates. The state proportion identifying as white and the proportion of those in poverty receiving food benefits correlated to decreased firearm suicide rates. In multivariable regression, only heavy drinking (β, 0.290; 95% confidence interval, 0.092-0.481; P = .004) correlated to firearm suicides rates increases. During our study, few firearm laws changed. Heavy drinking behavior association with firearm suicide rates suggests an opportunity for interventions exists in the health care setting.


Impact of bacterial volatiles on phytopathogenic fungi: an in vitro study on microbial competition and interaction.
Microorganisms in the rhizosphere are abundant and exist in very high taxonomic diversity. The major players are bacteria and fungi, and bacteria have evolved many strategies to prevail over fungi, among them harmful enzyme activities and noxious secondary metabolites. Interactions between plant growth promoting rhizobacteria and phytopathogenic fungi are potentially valuable since the plant would benefit from fungal growth repression. In this respect, the role of volatile bacterial metabolites in fungistasis has been demonstrated, but the mechanisms of action are less understood. We used three phytopathogenic fungal species (Sclerotinia sclerotiorum, Rhizoctonia solani, and Juxtiphoma eupyrena) as well as one non-phytopathogenic species (Neurospora crassa) and the plant growth promoting rhizobacterium Serratia plymuthica 4Rx13 in co-cultivation assays to investigate the influence of bacterial volatile metabolites on fungi on a cellular level. As a response to the treatment, we found elevated lipid peroxidation, which indirectly reflected the loss of fungal cell membrane integrity. An increase in superoxide dismutase, catalase, and laccase activities indicated oxidative stress. Acclimation to these adverse growth conditions completely restored fungal growth. One of the bioactive bacterial volatile compounds seemed to be ammonia, which was a component of the bacterial volatile mixture. Applied as a single compound in biogenic concentrations ammonia also caused an increase in lipid peroxidation and enzyme activities, but the extent and pattern did not fully match the effect of the entire bacterial volatile mixture.


Effect of histones from brain on DNA-synthesis in vitro.
The results of these experiments demonstrate that histones from brain inhibit the replication of DNA in vitro. A similar effect is observed with polylysine or polyarginine. The reversion of inhibition by polyglutamic acid or acidic proteins is completed in all cases except when the DNA is previously complexed with histones, polyarginine or polylysine. This suggest that histones masking of DNA towards the polymerases involves electrostatic forces.


Effect of ascorbate on the contractile response induced by DMPP in guinea-pig ileal longitudinal muscle strip.
The study concerned the effect of ascorbate on the contractile response induced by DMPP in the guinea-pig ileal longitudinal muscle. At 0.5-10 mM, sodium ascorbate shifted the dose-response curve for DMPP to the left and enhanced the maximum contraction. On the other hand, in the presence of ascorbate, the high potassium (40 mM)-induced contraction was not altered, and the contraction by acetylcholine and histamine in concentrations higher than 1 microM and 0.3 microM, respectively, was slightly reduced. Thus, ascorbate enhanced the contractile response caused by DMPP which induced acetylcholine release from nerve terminals indirectly by stimulating the ganglia of the Auerbach's plexus elements. This potentiating effect of ascorbate was studied with a dual organ bath which was partitioned into two compartments. When the oral half of the muscle strip was directly stimulated by DMPP applied to the oral compartment, a contraction of the unstimulated anal part was observed. This contraction was blocked by atropine or adenosine applied to the unstimulated part. Tetrodotoxin, applied to the stimulated part, abolished the contraction of the unstimulated part. The contraction of the unstimulated part was enhanced by ascorbate applied to the stimulated part but not to the unstimulated part. These results indicate that the contraction observed in the unstimulated part may have been caused by acetylcholine release from cholinergic nerves as a result of conduction of the oral part excitation by DMPP along cholinergic nerve fibers; ascorbate may have affected the ganglion cells in Auerbach's plexus to potentiate the action of DMPP.


The plasma angiotensin II level increases in very low-birth weight infants with neonatal chronic lung disease.
Angiotensin II (AII) has been reported to play an important role in organ fibrosis, and a local renin-angiotensin-system (RAS) has been demonstrated in the lungs. However, the relationship of the RAS to chronic lung disease of the newborn (CLD) remains obscure. To investigate the plasma AII levels throughout the neonatal period in very low-birth weight (VLBW) infants and examine the possible factors that might affect the AII levels. The study includes 20 VLBW infants. Blood samples were collected on days 0, 7, 21 and 35 and plasma AII levels were assayed using an enzyme immunoassay. The data were analyzed by a multiple linear regression analysis with the plasma AII level as the dependent variable and significant factors determined based on a univariate analysis as independent variables. The geometric mean of the plasma AII concentrations on days 0, 7, 21 and 35 was 51 pg/mL, 86 pg/mL, 132 pg/mL, and 50 pg/mL, respectively. On day 21, only CLD (p<0.01) had a highly significant association with the plasma AII level. On day 35, birth weight (p<0.05) and CLD (p<0.01) had a highly significant association with the plasma AII level. This analysis confirmed CLD to be the most significant factor associated with plasma AII level on days 21 and 35. These findings suggest that higher levels of plasma AII in VLBW infants appear to be related to the development of CLD.


Epithelial distribution of a myelomonocytic antigen LI in relation to cutaneous malignancies and melanocytic naevi.
The distribution of LI antigen in four common skin tumours was examined immunohistochemically in 40 samples of formalin-fixed routine biopsy material. Presence of LI in the dermis depended on the extent and composition of the inflammatory infiltrate; LI was found mainly in reactive histiocytes and neutrophils. Intense epidermal staining was seen adjacent to squamous cell carcinoma, basal cell carcinoma and malignant melanoma, but not adjacent to melanocytic naevi. In specimens of melanocytic naevi, LI staining around pilosebaceous units was weak or absent. Around the three malignant types of lesion, epidermal LI positivity faded distally--thereby indicating the extent of the tumour. LI was, in addition, expressed by the most highly differentiated cells in squamous cell carcinomas, whereas the other neoplasms were negative. Antibody to LI may, thus, be a useful adjunct for distinction between various types of skin tumours.


Remotely recorded cochlear microphonic in the cat.
The cochlear microphonic (CM) was recorded differentially with subcutaneous electrodes at the vertex and a variety of positions on the head and neck of the cat, and the phase and amplitude were compared with simultaneous recordings from vertex and contralateral ear electrodes. Recordings were made in bilaterally hearing animals, both with and without ear canal occlusion, following unilateral labyrinthectomy, and in white-coat cats with hereditary unilateral deafness, and in different age-groups. The cochlear microphonic was in phase with the contralateral recording at all electrode sites except those in the immediate vicinity of the stimulus ear. The amplitude was less at the circumaural positions and greater at cervical locations. The results were consistent in all age-groups and in bilaterally and unilaterally hearing animals. Precise electrode placement in the near-field conditions around the stimulus ear is therefore critical, especially for phase, while far-field conditions would appear to predominate at the remaining electrode sites.


A novel and simple method using pocket-sized echocardiography to screen for aortic stenosis.
Pocket-sized echocardiography may serve as an initial tool to screen for aortic stenosis (AS). The purpose of this study was to evaluate the usefulness of a novel and simple method using pocket-sized echocardiography to screen for AS. Subjects (n= 130) with systolic ejection murmur or known AS were studied. After physical examination, each aortic cusp's opening was visually scored using pocket-sized echocardiography as follows: 0= not restricted, 1= restricted, or 2= severely restricted. The sum of the scores was defined as the visual AS score. On the basis of high-end echocardiography, an aortic valve area index <0.60 cm(2)/m(2) and an aortic valve area index of 0.60 to 0.85 cm(2)/m(2) were considered to indicate severe and moderate AS, respectively. For diagnosing severe AS (n= 27), a visual AS score ≥ 4 had sensitivity of 85% and specificity of 89%. For diagnosing moderate to severe AS (n= 57), a visual AS score ≥ 3 had sensitivity of 84% and specificity of 90%. The areas under the receiver operating characteristic curves for diagnosing severe and moderate to severe AS with a visual AS score (0.946 and 0.936, respectively) were slightly larger than those for a skilled physical examination (0.917 and 0.898, respectively) (P= NS for both) but were significantly larger than for an aortic valve calcification score also obtained using pocket-sized echocardiography (areas under the curve, 0.816 [P= .0015] and 0.827 [P= .0001], respectively). A novel and simple method using pocket-sized echocardiography is useful for rapid grading of AS in subjects with systolic ejection murmur.


Respiratory vaccination.
Vaccinations are among the most cost-effective preventive health strategies to reduce healthcare costs and prevent morbidities. Every year, many adults and elderly encounter hospitalization because of infectious respiratory diseases. Among these, viral and bacterial pneumonia, tuberculosis, diphtheria and pertussis infections are some of the diseases that can be prevented and managed with fewer complications, with adequate preventive immunization. This review tries to outline the vaccines available for the prevention of these respiratory ailments along with their schedule and dosages.


Changes in liver nuclear protein metabolism after a single dose of urethane to suckling mice.
Treatment of 8-9-day-old C57BL/A mice with a single carcinogenic dose of urethane, at 1.2 mg/g body wt., resulted in an immediate decrease in liver DNA synthesis reaching a maximum at about 16-18 h after injection, the rate of synthesis returning to normal after 48 h. When the nuclear proteins were radiolabelled, the non-histone protein (NHP) fraction showed a significant decrease in specific activity 8-18 h after injection of urethane and slight increase in specific activity after 24 h. Histone and residual proteins did not show any significant change. The liver NHP were analysed by isoelectric focusing (IEF) and sodium dodecyl sulphate (SDS) electrophoresis in polyacrylamide gels. The latter technique failed to show any distinctive differences but IEF results indicated some quantitative and qualitative changes in protein content and synthesis were induced by the urethane treatment. The most noticeable change in the stained gels was an increase in a protein component having a pI of 7.35 and the appearance of new bands at pI's of 7.85 and 5.55 in the 18 h treated livers. However, the [3H]tryptophan labelling pattern indicated that this was not due to an increased synthesis of these components. 24 h after urethane there appeared to be an increased rate of synthesis of some of the major components of the mixture, particularly at the pI 5.65 region. Histone and residual protein fractions were also analysed by electrophoresis and showed no difference between treated and control livers.


Evaluating models in systems ergonomics with a taxonomy of model attributes.
A model, as the term is used here, is a way of representing knowledge for the purpose of thinking, communicating to others, or implementing decisions as in system analysis, design or operations. It can be said that to the extent that we can model some aspect of nature we understand it. Models can range from fleeting mental images to highly refined mathematical equations of computer algorithms that precisely predict physical events. In constructing and evaluating models of ergonomic systems it is important that we consider the attributes of our models in relation to our objectives and what we can reasonably aspire to. To that end this paper proposes a taxonomy of models in terms of six independent attributes: applicability to observables, dimensionality, metricity, robustness, social penetration and conciseness. Each of these attributes is defined along with the meaning of different levels of each. The attribute taxonomy may be used to evaluate the quality of a model. Examples of system ergonomics models having different combinations of attributes at different levels are provided. Philosophical caveats regarding models in system ergonomics are discussed, as well as the relation to scientific method.