Ultrastructural localization and biochemical features of immunoreactive LEU-enkephalin in monkey dorsal horn.
Leu-enkephalin is an opioid peptide that has been found to modulate nociception in the spinal cord. Both pre- and postsynaptic interactions by enkephalins have been proposed. By the peroxidase . anti-peroxidase immunocytochemical method, we studied the distribution and ultrastructure of neuronal elements in the monkey dorsal horn to elucidate possible morphological substrates for postulated opioid actions. Biochemical analysis of immunoreactive Leu-enkephalin-like peptides in the cord was performed to characterize the forms present in labeled neurons and terminals. At the light microscopic level, fiber immunostaining was found in most areas of gray matter, especially in laminae I to V, and in the dorsolateral funiculus. Cell bodies were located in laminae I, II, III, and V. At the ultrastructural level, in the superficial dorsal horn, we found that neurons with Leu-enkephalin receive numerous types of axon inputs, some of which have been identified previously as originating from the dorsal root. Leu-enkephalin terminals formed primarily axosomatic and axodendritic synapses and less frequently synapsed with other axons. With the same Leu-enkephalin antiserum as used in the immunocytochemistry, a peptide physicochemically similar to intact Leu-enkephalin and two larger Leu-enkephalin-like peptides were identified in monkey spinal cord extracts. It is likely that a family of Leu-enkephalin-like peptides is present in monkey spinal cord and that the labeled elements may contain any or all of these substances. It is concluded that both pre- and postsynaptic physiologic effects of Leu-enkephalin are possible, although the preponderance of axodendritic synapses favors a principal postsynaptic site of action. The anatomical results suggest that neurons containing immunoreactive Leu-enkephalin in the dorsal horn, some of which may receive input from primary afferents, modulate nociception by directly synapsing with cells of origin of the spinothalamic tract and also by interacting with primary afferent terminals.


Impedance magnetocardiogram.
We have developed an impedance magnetocardiogram (IMCG) system to detect the change of magnetic field corresponding to changes in blood volume in the heart. A low magnetic field from the electrical activity of the human heart--the so-called magnetocardiogram (MCG)--can be simultaneously detected by using this system. Because the mechanical and electrical functions in the heart can be monitored by non-invasive and non-contact measurements, it is easy to observe the cardiovascular functions from an accurate sensor position. This system uses a technique to demodulate induced current in a subject. A flux-locked circuit of a superconducting quantum interference device has a wide frequency range (above 1 MHz) because a constant current (40 kHz) is fed through the subject. It is shown for the first time that the system could measure IMCG signals at the same time as MCG signals.


Enhanced biosynthesis of human skin collagenase in fibroblast cultures from recessive dystrophic epidermolysis bullosa.
Using a sensitive, specific immunoprecipitation method, the biosynthesis of human skin collagenase was studied in fibroblast cultures from patients with recessive dystrophic epidermolysis bullosa. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of solubilized immunoprecipitates showed two 3H-labeled procollagenase species that comigrated with those harvested from control cultures. Recessive dystrophic epidermolysis bullosa cultures accumulated increased amounts of collagenase. Both the initial rate of accumulation of intracellular enzyme and the rate of secretion were enhanced, suggesting that excessive accumulation is related to increased synthesis. Because the turnover of labeled collagenase was unaltered, the accumulation could not be attributed to diminishing enzyme degradation. No preferential incorporation of [3H]leucine into recessive dystrophic epidermolysis bullosa collagenase occurred. Furthermore, the mutant cultures displayed no alteration in total protein synthesis, the intracellular leucine pool, or the growth kinetics of the cells. Cells from a patient with dominant epidermolysis bullosa did not show enhanced accumulation of collagenase. The levels of collagenase synthesized in vitro correlated with those observed previously in vivo in recessive dystrophic epidermolysis bullosa patients, suggesting that this biochemical trait is pathogenetically significant in the disorder.


Ratiometric G-Quadruplex Assay for Robust Lead Detection in Food Samples.
Lead (Pb2+) pollution is a serious food safety issue, rapid detection of Pb2+ residual in food is vital to guarantee food quality and safety. Here we proposed ratiometric aptamer probes, allowing robust Pb2+ supervision in food samples. Pb2+ specific aptamer can bolster a transition of G-quadruplex structural response to Pb2+; this process can be monitored by N-methyl mesoporphyrin IX (NMM), which is highly specific to G-quadruplex. Particularly, the utilization of G-quadruplex specific dye and terminal-labeled fluorophore allowed to endue ratiometric signal outputs towards Pb2+, dramatically increase the robustness for lead detection. The ratiometric G-quadruplex assay allowed a facile and one-pot Pb2+ detection at room temperature using a single-stranded DNA aptamer. We demonstrated its feasibility for detecting lead pollution in fresh eggs and tap water samples. The ratiometric G-quadruplex design is expected to be used for on-site Pb2+ testing associated with food safety.


Stop Using the Modified Work APGAR to Measure Job Satisfaction.
Background. The psychometric properties of the Modified Work APGAR (MWA) scale are not established, yet researchers use this scale as an overall measure of job satisfaction. Objective. Perform psychometric analyses on the MWA scale using data from two populations. Methods. A landmark occupational cohort and a clinical cohort are populations with low back pain studied. The first five items of the MWA scale measure social support from coworkers, one item measures dissatisfaction with job tasks, and the sixth item measures lack of social support from a supervisor. Exploratory principal components analyses were conducted in both cohorts. Results. In both cohorts, the first five items of the MWA scale loaded consistently onto one factor, social support from coworkers subscale. Conclusions. Unless researchers are interested in measuring social support from coworkers only, future studies should use other reliable and valid instruments to measure a broad range of psychosocial work characteristics.


Looking back at the 10th anniversary year of Journal of Materials Chemistry A, B and C.
The Editors-in-Chief for Journal of Materials Chemistry A, B and C look back at the 10th anniversary year and the celebratory activities that took place.


Phenotypic variation in Azospirillum brasilense exposed to starvation.
Bacteria have developed mechanisms that allow them maintaining cell viability during starvation and resuming growth when nutrients become available. Among these mechanisms are adaptive mutations and phase variation, which are often associated with DNA rearrangements. Azospirillum brasilense is a Gram-negative, nitrogen-fixing, plant growth-promoting rhizobacterium. Here we report phenotypic variants of A. brasilense that were collected after exposure to prolonged starvation or after re-isolation from maize roots. The variants differed in several features from the parental strains, including pigmentation, aggregation ability, EPS amount and composition and LPS structure. One of the phenotypic variants, overproducing EPS and showing an altered LPS structure, was further characterized and showed differential response to several stresses and antibiotics relative to its parental strain. Characterization of the variants by repetitive-PCR revealed that phenotypic variation was often associated with DNA rearrangements.


Mortality and morbidity during a five-year follow-up of diabetics with myocardial infarction.
In 787 patients with acute myocardial infarction originally participating in the Göteborg Metoprolol Trial, mortality and morbidity during 5 years' follow-up were assessed and related to whether patients had diabetes mellitus. Diabetes occurred in 78 patients (10%). Patients with diabetes had a different risk factor pattern, including higher age, higher occurrence of angina pectoris and hypertension, whereas smoking habits did not differ. In the early phase (hospitalization), patients with diabetes had a higher mortality (12% versus 8%), required more treatment for heart failure and stayed longer in hospital. Other morbidity aspects, such as severity of pain, occurrence of severe supraventricular and ventricular arrhythmias, high-degree AV-block and infarct size did not differ. During 5 years' follow-up mortality rate in patients with diabetes mellitus was 55% as compared with 30% among patients with no diabetes (p less than 0.001). Reinfarction rate during 5 years was 42% in diabetics versus 25% in non-diabetics (p less than 0.001). In a multivariate analysis, taking into account the differences in risk factor pattern, diabetes turned out to be an independent determinant for long-term mortality and reinfarction (p less than 0.001). We conclude that patients with diabetes mellitus, developing acute myocardial infarction, is a group with particularly high risk of death and reinfarction. Interventions aiming at its reduction have priority.


Sitagliptin improves cardiac function after myocardial infarction through activation of autophagy in streptozotocin-induced diabetic mice.
The aim of this study was to investigate the protective effect of sitagliptin on cardiac function in mice with diabetes and myocardial infarction (MI), and to explore its possible mechanism using the mouse models of diabetes and MI. The models of diabetes and MI were established using C57BL/6 mice. All mice were randomly divided into 5 groups, including the control sham (CS) group, the control MI (CMI) group, the diabetes sham (DS) group, diabetes + MI (DMI) group and the DMI + sitagliptin (DMI+SGL) group. After modeling, mice in the DMI+SGL group were intragastrically administrated with sitagliptin (10 mg/kg/day) for 21 d and the survival rate of mice was recorded. Before and 7, 14, 21 days after MI, the cardiac function of mice in each group was detected via ultrasound. 21 days after MI, the area of MI was measured via 2,3,5-triphenyl tetrazolium chloride (TTC). Meanwhile, the degree of fibrosis in the peripheral region of MI was determined via Masson staining. Moreover, myocardial autophagosomes of mice in each group were observed by transmission electron microscope (TEM). 7 days after MI, the expressions of autophagy-related proteins LC3II and P65 were detected via Western blotting. The expressions of myocardial inflammatory factors, interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected via enzyme-linked immunosorbent assay (ELISA). In addition, the expression of nuclear factor-κB (NF-κB) was also detected via Western blotting. Sitagliptin increased survival rate, improved cardiac function, reduced infarction area, alleviated myocardial fibrosis, enhanced autophagy in the peripheral region and inhibited inflammation in the peripheral region in mice with diabetes after MI. Sitagliptin can improve cardiac function and reduce the mortality rate in diabetic rats after MI. The possible underlying mechanism may be related to the fact that sitagliptin activates autophagy and inhibits inflammatory response in diabetes after MI.


A Pathophysiologic Approach Combining Genetics and Insulin Resistance to Predict the Severity of Nonalcoholic Fatty Liver Disease.
Nonalcoholic fatty liver disease (NAFLD) is a complex disease dictated by both genetic and environmental factors. While insulin resistance (IR) is a key pathogenic driver, two common genetic variants in patatin-like phospholipase domain containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) also impart significant risk for disease progression. Traditional approaches to NAFLD risk stratification rely on biomarkers of fibrosis, an end result of disease progression. We hypothesized that by combining genetics and a novel measurement for IR we could predict disease progression by the NAFLD activity score (NAS) and histologic presence of significant fibrosis. A total of 177 patients with biopsy-proven NAFLD were enrolled in this cross-sectional study. PNPLA3 I148M and TM6SF2 E167K genotypes were determined by TaqMan assays. The enhanced lipoprotein IR index (eLP-IR) was calculated from serum biomarkers using nuclear magnetic resonance (NMR) spectroscopy. Multivariate regression models were used to study the relationships between genetics, IR, and histologic features of NAFLD. In the multivariate analysis, the eLP-IR was strongly associated with histologic features of NAFLD activity and hepatic fibrosis (P < 0.001 to 0.02) after adjustment for potential confounders. PNPLA3 148M and TM6SF2 E167K genotypes were significantly associated with steatosis (P = 0.003 and P = 0.02, respectively). A combination of the eLP-IR and genetic score was able to predict the presence of NAS ≥3 with an area under the receiver operating characteristic curve (AUROC) of 0.74. Adding age to this model predicted stages 3-4 liver fibrosis with an AUROC of 0.82. Conclusion: This proof-of-concept study supports the hypothesis that genetics and IR are major determinants of NAFLD severity and demonstrates the feasibility of a new risk stratification paradigm using exclusively pathogenic factors.


Watch for pitfalls of discounted cash flow techniques.
Discounted cash flow (DCF) techniques can enhance the effectiveness of a healthcare organization's capital budgeting decisions. But a financial manager unaware of common misapplications of DCF techniques may make capital decisions with a hidden bias against long-term projects, an inaccurate evaluation of options, or inappropriate estimations of expected inflation and risk. Social and psychological factors also can impede effective decisions on projects already introduced.


Effect of selenium-vitamin E on hematologic alterations of adriamycin toxicosis in young pigs.
In 3 experiments, 45 castrated male weanling pigs (4 to 6 weeks old) were used to determine the hematologic alterations induced by adriamycin (ADR) given IV at 0.64, 1.6, or 3.2 mg/kg of body weight/week. The effect of selenium-vitamin E (Se-E) supplements on ADR toxicosis was evaluated. Mortality, decreased survival time, growth depression, leukopenia, and anemia were dose related in ADR-treated pigs. At 0.64 mg of ADR/kg/week for 16 weeks, important clinical or hematologic alterations did not develop. At 1.6 mg of ADR/kg/week for 13 weeks, mortality was 100%, mean survival time ws 65.7 days (min-max, 49 to 92 days), and moderate growth depression and marked leukopenia and anemia were present from weeks 7 to 13. At 3.2 mg of ADR/kg/week for 4 weeks, mortality was 100% and mean survival time was 22.0 days (min-max, 18 to 26 days); marked growth depression, leukopenia, and mild anemia developed (week 4). Cytologic study of smears of bone marrow from pigs that died of ADR toxicosis (3.2 mg/kg/week) revealed marked hypoplasia and evidence of decreased production and increased destruction of erythroid and myeloid cells. Beneficial effect of Se-E supplementation against ADR toxicosis was seen only in the pigs given 1.6 mg/kg/week, where prolonged survival and delayed onset of leukopenia and anemia was observed.


Efficacy of combined ultrasound-guided hydrodilatation with hyaluronic acid and physical therapy in patients with adhesive capsulitis: A randomised controlled trial.
To evaluate the therapeutic effect of combining ultrasound-guided hydrodilatation with hyaluronic acid and physical therapy compared with physical therapy alone in patients with adhesive capsulitis. A prospective, single-blinded, randomised controlled trial. Single medical centre. Patients with adhesive capsulitis (N = 62) were divided into group A: ultrasound-guided hydrodilatation with hyaluronic acid + physical therapy (N = 31) and group B: physical therapy alone (N = 31). Group A received three doses of ultrasound-guided hydrodilatation with hyaluronic acid-based injectates (20 mL in total). Both groups underwent structured physical therapy. The primary outcome measure was Constant score, while secondary outcomes included Shoulder Pain and Disability Index score, numerical rating scale (at rest, night, and during motion), 36-item Short Form Health Survey, and range of motion of the shoulder. All measurements were collected at baseline, 6 weeks, and 12 weeks post-injection. At week 12, the Constant scores were 68.29 ± 14.55 and 62.77 ± 14.44 for groups A and B, respectively. There was a greater reduction in the Constant score, Shoulder Pain and Disability Index, and numerical rating scale between the baseline and 6 weeks and between the baseline and 12 weeks in group A (Constant score: p < 0.05, Shoulder Pain and Disability Index: p < 0.01, and numerical rating scale: p < 0.05). The combination of ultrasound-guided hydrodilatation with hyaluronic acid in conjunction with physical therapy provides additional benefits compared to physical therapy alone for the treatment of adhesive capsulitis at up to 12 weeks. ClinicalTrials.gov: NCT02708706.


[The diagnostic potentialities of determining alpha-fetoprotein in the blood of patients with mucoviscidosis].
Measurements of alpha-fetoprotein levels in 21 patients with mucoviscidosis have found them increased vs. a group of patients with chronic hepatitis, particularly so in cases with liver involvement. This fact recommends this test as an auxiliary one to be used when prescribing combined therapy to such patients, hepatotropic agents among other things.


Duration of pneumoperitoneum in the dog.
The duration of pneumoperitoneum was examined in 12 adult and 4 immature dogs. Four dogs were given intra-abdominal injections of 110 ml of air/kg (group 1), 4 were given 55 ml of air/kg (group 2), and 4 were given 27.5 ml of air/kg (group 3). Also, 4 immature dogs were given 110 ml of air/kg (group 4). The number of days from creation of pneumoperitoneum until the radiographic absence of pneumoperitoneum averaged 25 days for group 1, 14 days for group 2, 9 days for group 3, and 17 days for group 4.


Systemic lupus erythematosus mimicking retinal migraine: a case report.
Retinal migraine is a diagnosis of exclusion and is characterized by repeated episodes of transient monocular blindness associated with migraine. We report a case of systemic lupus erythematosus with acute episodes mimicking retinal migraines. A 46-year-old woman with a history of migraine with aura since her 20s and Evans syndrome presented with episodic transient monocular blindness. Retinal migraine was considered as the cause, and migraine prophylaxis initially reduced its frequency. After 5 months, the frequency increased, with chilblain-like lupus lesions on her extremities. Laboratory testing revealed lymphopenia and hypocomplementemia, fulfilling the diagnostic criteria for systemic lupus erythematosus, which may have caused Evans syndrome and transient monocular blindness, mimicking retinal migraines. After intravenous methylprednisolone and rituximab therapy, the transient monocular blindness episodes did not recur. Given the clinical presentation, systemic lupus erythematosus should be considered as a cause of transient monocular blindness and should be distinguished from retinal migraine.


How to perform RT-qPCR accurately in plant species? A case study on flower colour gene expression in an azalea (Rhododendron simsii hybrids) mapping population.
Flower colour variation is one of the most crucial selection criteria in the breeding of a flowering pot plant, as is also the case for azalea (Rhododendron simsii hybrids). Flavonoid biosynthesis was studied intensively in several species. In azalea, flower colour can be described by means of a 3-gene model. However, this model does not clarify pink-coloration. The last decade gene expression studies have been implemented widely for studying flower colour. However, the methods used were often only semi-quantitative or quantification was not done according to the MIQE-guidelines. We aimed to develop an accurate protocol for RT-qPCR and to validate the protocol to study flower colour in an azalea mapping population. An accurate RT-qPCR protocol had to be established. RNA quality was evaluated in a combined approach by means of different techniques e.g. SPUD-assay and Experion-analysis. We demonstrated the importance of testing noRT-samples for all genes under study to detect contaminating DNA. In spite of the limited sequence information available, we prepared a set of 11 reference genes which was validated in flower petals; a combination of three reference genes was most optimal. Finally we also used plasmids for the construction of standard curves. This allowed us to calculate gene-specific PCR efficiencies for every gene to assure an accurate quantification. The validity of the protocol was demonstrated by means of the study of six genes of the flavonoid biosynthesis pathway. No correlations were found between flower colour and the individual expression profiles. However, the combination of early pathway genes (CHS, F3H, F3'H and FLS) is clearly related to co-pigmentation with flavonols. The late pathway genes DFR and ANS are to a minor extent involved in differentiating between coloured and white flowers. Concerning pink coloration, we could demonstrate that the lower intensity in this type of flowers is correlated to the expression of F3'H. Currently in plant research, validated and qualitative RT-qPCR protocols are still rare. The protocol in this study can be implemented on all plant species to assure accurate quantification of gene expression. We have been able to correlate flower colour to the combined regulation of structural genes, both in the early and late branch of the pathway. This allowed us to differentiate between flower colours in a broader genetic background as was done so far in flower colour studies. These data will now be used for eQTL mapping to comprehend even more the regulation of this pathway.


The agglutination reactions of Haemophilus paraphrophilus and H. paraphrohaemolyticus, and some observations on the agglutination of H. Aphrophilus and H. haemoglobinophilus (H. canis).
Agglutination tests were used to study the surface antigens of two recently described species of the genus Haemophilus, H. paraphrophilus and H. paraphrohaemolyticus, and their antigenic relationship to other members of the genus. The results obtained with a few strains of H. haemoglobinophilus and H. aphrophilus are also reported. The species H. paraphrophilus appears to be homogeneous; no major cross-reactions were observed. The species H. paraphrohaemolyticus contains at least three serotypes, of which two have been defined in terms of agglutination reactions. Cross-agglutinations occurred between one strain of H. paraphrohaemolyticus and strains of the other V-dependent species, H. parainfluenzae and H. parahaemolyticus. Of the X-dependent species, H. haemoglobinophilus seems to be homogeneous, and the species H. aphrophilus is not. A non-specific antibody against horse blood in the medium occurred erratically and was present in only two antisera, those raised to H. aphrophilus strain Khairat and H. haemoglobinophilus strain no. NCTC8540.


Preconception origins of perinatal maternal mental health.
Perinatal maternal symptoms of depression and anxiety compromise psychosocial function and influence developmental outcomes in the offspring. The onset of symptoms remains unclear with findings that suggest a preconceptual origin. We addressed this issue with a prospective analysis of anxiety and depressive symptom profiles from preconception through to parturition. Women were recruited into a preconception study to assess (a) variation in symptom levels of depression and anxiety from pre- to post-conception and (b) if the symptom network profiles of depression and anxiety change from pre-conception to post-conception. A within-subject intraclass correlation analyses revealed that symptoms of depression or anxiety in the preconception phase strongly predicted those across pregnancy and into the early postnatal period. The symptom network analysis revealed that the symptom profiles remained largely unchanged from preconception into the second trimester. Our findings suggest that for a significant portion of women, maternal mental health remains stable from preconception into pregnancy. This finding highlights the need for early intervention studies on women's mental health to be targeted during the preconception period and to be extended across the population.


The influence of mitigation evidence, ethnicity, and SES on death penalty decisions by European American and Latino venire persons.
The purpose of the research was to determine whether European American and Latino mock jurors would demonstrate bias in death penalty decision making when mitigation evidence and defendant ethnicity and socioeconomic status (SES) were varied. A total of 561 actual venire persons acted as mock jurors and read a trial transcript that varied a defendant's case information (mitigating circumstances: strong/weak, defendant ethnicity: European American/Latino, and defendant SES: low/high). European American jurors recommended the death penalty significantly more often for the low SES Latino defendant when strength of mitigation evidence was weak. In addition, they also assigned this defendant higher culpability ratings and lower ratings on positive personality trait measures compared with all other conditions. Strong mitigation evidence contributed to lower guilt ratings by European American jurors for the high SES European American defendant. Latino jurors did not differ in their death penalty sentencing across defendant mitigation, ethnicity, or SES conditions. Discussion of in-group favoritism and out-group derogation, as well as suggestions for procedures to diminish juror bias in death penalty cases, is provided.


Exercise training increases creatine kinase capacity in canine myocardium.
The creatine kinase (CK) energy shuttle of cardiomyocytes channels metabolic energy from the mitochondria to sites of energy utilization at contracting myofibrils and sarcolemmal and sarcoplasmic reticular ion pumps. Although plasticity of the myocardial CK system in response to hemodynamic overload has been repeatedly demonstrated, the effects of aerobic exercise training on myocardial CK are less well understood. This investigation tested the hypothesis that aerobic exercise training increases the capacity of the CK system in canine myocardium. Mongrel dogs were conditioned by a 9-wk treadmill running program or cage-rested for 4 wk. Total CK activity was measured colorimetrically; CK(MB) was separated from other CK isoforms and measured by electrophoresis. Relative to sedentary controls, training increased left ventricular total CK activity 46% (P < 0.05) but did not alter total CK activity in right ventricular myocardium. Also in left ventricular myocardium, training increased CK(MB) isoenzyme activity 4.5-fold and the CK(MB) fraction of total CK threefold from 1.1+/-0.4 to 3.4+/-0.8% (P < 0.05). In contrast to left ventricle, CK(MB) activity and its fraction of total CK activity were not altered by training in right ventricular myocardium. Aerobic exercise training increases total myocardial CK activity and CK(MB) content in canine left ventricular myocardium, although CK(MB) remains a minor component of the myocardial CK system. The right ventricular CK system was not affected by training.


Platelet activating factor and U44069 stimulate a GTPase activity in human platelets which is distinct from the guanine nucleotide regulatory proteins, Ns and Ni.
Platelet-activating factor (PAF, 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine) and the stable thromboxane-receptor agonist U44069 (9 alpha, 11 beta-epoxymethanoprostaglandin H2) stimulated GTPase activity in platelet membranes in a dose-dependent fashion, yielding Ka values of 12 nM and 27 nM respectively. The degree of GTPase activation elicited by these agents was found to be additive with the GTPase activation due to either the stimulatory (Ns) or inhibitory (Ni) guanine nucleotide regulatory proteins when activated by prostaglandin E1 and adrenaline (+propranolol) respectively. Treatment of membranes with either cholera or pertussis toxins, which inhibited markedly the receptor-mediated stimulation of the GTPase activities of Ns and Ni respectively, had no or only a small effect, respectively, on the GTPase activity stimulated by PAF and U44069. It is suggested that PAF and U44069, which stimulate inositol phospholipid metabolism in platelets, exert actions through a guanine nucleotide regulatory protein which is distinct from Ns and Ni.


Testing Drugs and Trying Cures: Experiment and Medicine in Medieval and Early Modern Europe.
This article examines traditions of testing drugs (as substances) and trying cures (on patients) in medieval and early modern Europe. It argues that the history of drug testing needs to be a more central story to overall histories of scientific experiment. The practice of conducting thoughtful-and sometimes contrived-tests on drugs has a rich and varied tradition dating back to antiquity, which expanded in the Middle Ages and early modern period. Learned physicians paired text-based knowledge (reason) with hands-on testing (experience or experiment) in order to make claims about drugs' properties or effects on humans. Lay practitioners similarly used hands-on testing to gain knowledge of pharmaceutical effects. Although drug testing practices expanded in scale, actors, and sites, therpublished a work extolling the virtues of drugs froe was significant continuity from the Middle Ages to the eighteenth century.


Sustained Implementation of Evidence-based Programs in Disadvantaged Communities: A Conceptual Framework of Supporting Factors.
This paper presents a review of the empirical literature for studies evaluating factors that facilitate and create barriers to sustained program implementation in disadvantaged communities. It outlines study methodology and sustainment outcomes and proposes a conceptual model that involves implementation sustainment support for providers delivering evidence-based health and family services in disadvantaged communities. Sustained program implementation in the community setting is a significant issue as only 43% of studies reported successfully sustained programs. The review identified 18 factors that facilitate success and create barriers to program sustainment. The factors are synthesized into three themes; program characteristics, workplace capacity, and process and interaction factors. The majority of factors map onto commonly cited sustainability influences in implementation science. However, there was an additional focus for studies included in this review on the importance of factors such as program burden, program familiarity and perceived competence in program skills, workplace support for the program, staff mobility and turnover, supervision and peer support, and ongoing technical assistance. The need to use a conceptual framework and develop measures to guide and evaluate capacity building in EBP implementation and sustainment in low-resource community settings is highlighted.


The management of risk in foreign and defence policy: the precautionary principle and decisions on war.
This article develops a concept that originated in environmental risk decision making, and investigates whether the Precautionary Principle (PP) may be usefully deployed by policymakers in the realm of foreign and defence matters. Drawing on the literature on precaution in the environmental arena, and in its weaker form, we develop an operational model of the PP, which has four main characteristics: an acceptance of the limits of knowledge on a given issue; an openness to alternative solutions; proportionality of response; and reversing the onus of proof. It concludes that the Precautionary Principle is a more inclusive way of deliberating on decisions on war, and the model we propose might provide a useful guideline for policy-makers in today's uncertain world.


Supercritical carbon dioxide application using hydantoin acrylamide for biocidal functionalization of polyester.
Biocidal functionalization in polyester fibers is a really tough challenge because of the lack of tethering groups. This study indicated supercritical carbon dioxide application using N-halamine would be an alternative solution for obtaining antibacterial function on the polyester surface. Firstly, N-(2-methyl-1-(4-methyl-2,5-dioxo-imidazolidin-4 yl)propan-2 yl)acrylamide was synthesized and applied to the polyester in supercritical carbon dioxide medium, at 120 °C, 30 MPa for different processing times. The addition of N-halamine on the surface significantly brought antibacterial activity against E. coli. The chlorine loadings showed that 6 -h exposure time was critical to obtain sufficient antibacterial activity. This treatment caused a reasonable and tolerable loss in color and mechanical properties. But, the durability to abrasion, stability, and rechargeability of oxidative chlorine, and the durability of N-halamine on the surface were remarkably good. Conclusively, it can be available to work on polyester surfaces with resource-efficient and eco-friendly supercritical carbon dioxide technique for getting more functionalization and modification.


Surface engineering of iron oxide nanoparticles for targeted cancer therapy.
Nanotechnology provides a flexible platform for the development of effective therapeutic nanomaterials that can interact specifically with a target in a biological system and provoke a desired response. Of the nanomaterials studied, iron oxide nanoparticles have emerged as one of top candidates for cancer therapy. Their intrinsic superparamagnetism enables noninvasive magnetic resonance imaging (MRI), and their biodegradability is advantageous for in vivo applications. A therapeutic superparamagnetic iron oxide nanoparticle (SPION) typically consists of three primary components: an iron oxide nanoparticle core that serves as both a carrier for therapeutics and contrast agent for MRI, a coating on the iron oxide nanoparticle that promotes favorable interactions between the SPION and the biological system, and a therapeutic payload that performs the designated function in vivo. Often, the design may include a targeting ligand that recognizes the receptors over-expressed on the exterior surface of cancer cells. The body is a highly complex system that imposes multiple physiological and cellular barriers to foreign objects. Thus, the success of a therapeutic SPION largely relies on the design of the iron oxide core to ensure its detection in MRI and the coatings that allow the nanoparticles to bypass these barriers. Strategies to bypass the physiological barriers, such as liver, kidneys, and spleen, involve tuning the overall size and surface chemistry of the SPION to maximize blood half-life and facilitate the navigation in the body. Strategies to bypass cellular barriers include the use of targeting agents to maximize uptake of the SPION by cancer cells and the employment of materials that promote desired intracellular trafficking and enable controlled drug release. The payload can be genes, proteins, chemotherapy drugs, or a combination of these molecules. Each type of therapeutic molecule requires a specific coating design to maximize the loading and to achieve effective delivery and release. In this Account, we discuss the primary design parameters in developing therapeutic SPIONs with a focus on surface coating design to overcome the barriers imposed by the body's defense system. We provide examples of how these design parameters have been implemented to produce SPIONs for specific therapeutic applications. Although there are still challenges to be addressed, SPIONs show great promise in the successful diagnosis and treatment of the most devastating cancers. Once the critical design parameters have been optimized, these nanoparticles, combined with imaging modalities, can serve as truly multifunctional theranostic agents that not only perform a therapeutic function but also provide instant clinical feedback, allowing the physician to adjust the treatment plan.


Overcoming blinding confounds in psychedelic randomized controlled trials using biomarker driven causal mediation analysis.
There is great interest in the use of psychedelic-assisted therapies to treat a range of mental health conditions and initial randomized controlled trials (RCTs) have generated positive results. However, the effect sizes reported in psychedelic RCTs are likely inflated due to expectancy effects due to the de-blinding of both participants and study personnel to treatment allocation caused by the distinctive psychoactive effects of psychedelic drugs. An introduction to causal inference for RCTs, the underlying assumptions, and potential confounders along with graphical illustrations is provided. It is proposed that causal mediation analysis using objectively measured mediating biomarkers could be used to identify causal pathways between treatment and outcome in psychedelic RCTs, even with de-blinding of participants and give greater confidence as to the mechanistic basis and efficacy of psychedelic therapies. It is argued that psychedelic therapies should not be approved as licensed medicines until causal pathways are clearly established between treatment and outcome. Potential downsides of doing so include, future indication expansion based on low quality clinical trial evidence, the approval of other therapies based on similarly low-quality evidence, and the potential for efficacy to change over time after approvals has been granted.


Metabolic Disruption Early in Life is Associated With Latent Carcinogenic Activity of Dichloroacetic Acid in Mice.
Early-life environmental factors can influence later-life susceptibility to cancer. Recent evidence suggests that metabolic pathways may mediate this type of latency effect. Previously, we reported that short-term exposure to dichloroacetic acid (DCA) increased liver cancer in mice 84 weeks after exposure was stopped. Here, we evaluated time course dynamics for key events related to this effect. This study followed a stop-exposure design in which 28-day-old male B6C3F1 mice were given the following treatments in drinking water for up to 93 weeks: deionized water (dH2O, control); 3.5 g/l DCA continuously; or 3.5 g/l DCA for 4-52 weeks followed by dH2O. Effects were evaluated at eight interim time points. A short-term biomarker study was used to evaluate DCA effects at 6, 15, and 30 days. Liver tumor incidence was higher in all DCA treatment groups, including carcinomas in 82% of mice previously treated with DCA for only 4 weeks. Direct effects of DCA in the short-term study included decreased liver cell proliferation and marked mRNA changes related to mitochondrial dysfunction and altered cell metabolism. However, all observed short-term effects of DCA were ultimately reversible, and prior DCA treatment did not affect liver cell proliferation, apoptosis, necrosis, or DNA sequence variants with age. Key intermediate events resulting from transient DCA exposure do not fit classical cytotoxic, mitogenic, or genotoxic modes of action for carcinogenesis, suggesting a distinct mechanism associated with early-life metabolic disruption.


Prenatal Mouth Movements: Can We Identify Co-Ordinated Fetal Mouth and LIP Actions Necessary for Feeding?
Observations of prenatal movement patterns of mouth and lips essential for feeding could have the potential for an assessment of the readiness to feed after birth. Although there is some research on sucking per se, we know very little about prenatal preparatory movements for sucking, namely, the ability to co-ordinate opening the mouth widely and then pursing the lips as if around a teat or nipple in utero. The purpose of the present study was to test two hypotheses using an adapted version of the Facial Action Coding Scheme: first that mouth stretch (AU 27) will be followed by lip pucker (AU 18), and second that these coordinated movement patterns will increase as a function of gestational age. Fifteen healthy fetuses were scanned four times between 24 and 36 weeks gestation using 4D ultrasound visualization. Results showed a decreased number of mouth stretches with increasing fetal age. Contrary to our expectations, we did not find an increase in movement patterns of mouth stretch followed by lip pucker in preparation for feeding ex utero. The results are discussed in terms of sensory triggers in utero required to elicit preparatory movements for feeding ex utero.


Frailty, cognitive impairment, and depressive symptoms in Chinese older adults: an eight-year multi-trajectory analysis.
Frailty, cognitive impairment, and depressive symptoms are closely interrelated conditions in the aging population. However, limited research has longitudinally analyzed the concurrent trajectories of these three prominent conditions in older adults in China. This study aimed to explore the eight-year trajectories of frailty, cognitive impairment, and depressive symptoms, and to identify individual-level and structural-level factors associated with the trajectories. Four waves of data from the China Health and Retirement Longitudinal Study (2011-2018) were used to identify 6,106 eligible older adults. The main measures included frailty by the frailty index constructed using 30 indicators, cognitive impairment by the summary score of immediate and delayed word recall, figure drawing, serial subtraction, and orientation, and depressive symptoms by the Center for Epidemiologic Studies Depression Scale. Multi-trajectory models identified the trajectories of frailty, cognitive impairment, and depressive symptoms over time. Multinomial logistic regression was employed to estimate the associations between individual-level capital factors and one structural factor (hukou and geographic residency) with the identified trajectories, adjusting for demographic characteristics. Four trajectories emerged: (1) worsening frailty, worsening cognitive impairment, depression (14.0%); (2) declining pre-frailty, declining cognition, borderline depression (20.0%); (3) pre-frailty, worsening cognitive impairment, no depression (29.3%); and (4) physically robust, declining cognition, no depression (36.7%). Using the "physically robust, declining cognition, no depression" as the reference, not working, no social activity participant, worse childhood family financial situation, and poorer adult health were most strongly associated with the "worsening frailty, worsening cognitive impairment, depression" trajectory; worse health during childhood had the highest association with the "declining pre-frailty, declining cognition, borderline depression" trajectory; less education, lower household consumption, and rural hukou had the greatest association with the increased likelihood of the "pre-frailty, worsening cognitive impairment, no depression" trajectory. Findings could inform the understanding of the interrelationship of frailty, cognitive impairment, and depressive symptoms in older adults in China and may help practitioners detect adults at risk for adverse trajectories to implement strategies for proper care.


Hydroxyapatite-magnetite-MWCNT nanocomposite as a biocompatible multifunctional drug delivery system for bone tissue engineering.
New magnetic hydroxyapatite-based nanomaterials as bone-specific systems for controlled drug delivery have been synthesized. The synthesized hydroxyapatite, HA, decorated with magnetite nanoparticles by a deposition method (HA/Fe3O4) and the nanocomposite system obtained using magnetic multi-walled carbon nanotubes (HA/MWCNT/Fe3O4) as a filler for HA have been characterized by chemical and morphological analyses, and their biological behavior was investigated. The systems have also been doped with clodronate in order to combine the effect of bone biomineralization induced by hydroxyapatite-based composites with the decrease of osteoclast formation induced by the drug. An analysis of the preosteoclastic RAW264.7 cell proliferation by MTT assay confirmed the high biocompatibility of the three systems. TRAP staining of RAW 264.7 conditioned with sRAKL to induce osteoclastogenesis, cultured in the presence of the systems doped and undoped with clodronate, showed the inhibitory effect of clodronate after we counted the MNC TRAP(+)cells but only in the osteoclast formation; in particular, the system HA/Fe3O4-Clo exerted a high inhibitory effect compared to the drug alone. These results demonstrate that the synthesized nanocomposites are a biocompatible magnetic drug delivery system and can represent a useful multimodal platform for applications in bone tissue engineering.


Optimization of gelatin extraction from chicken deboner residue using RSM method.
This study aims to investigate the optimization of gelatin extraction from chicken deboner residue. An optimization procedure using a central composite design with three factors (HCl concentration, extraction temperature, and extraction time) was used in order to investigate the effects of these parameters on extraction yield, g-f, viscosity, and lightness. It was found that the optimum conditions for producing gelatin using response surface methodology (RSM) included an acid concentration of 6.73% and an extraction temperature of 86.8 °C for 1.95 h. The predicted responses for these extraction conditions included a yield of 10.2%, a g-f of 526 g, a viscosity of 5.85 cP, and a lightness of 70.0. Verification experiments were conducted under optimal conditions to compare predicted and actual values of the dependent variables. Both actual and predicted values were found to nearly coincide, confirming that the estimation models were capable of reasonably and accurately predicting the dependent variables.


Plant defences on land and in water: why are they so different?
Plants (attached photosynthesizing organisms) are eaten by a wide variety of herbivorous animals. Despite a vast literature on plant defence, contrasting patterns of antiherbivore adaptation among marine, freshwater and land plants have been little noticed, documented or understood. Here I show how the surrounding medium (water or air) affects not only the plants themselves, but also the sensory and locomotor capacities of herbivores and their predators, and I discuss patterns of defence and host specialization of plants and herbivores on land and in water. I analysed the literature on herbivory with special reference to mechanical defences and sensory cues emitted by plants. Spines, hairs, asymmetrically oriented features on plant surfaces, and visual and olfactory signals that confuse or repel herbivores are common in land plants but rare or absent in water-dwelling plants. Small terrestrial herbivores are more often host-specific than their aquatic counterparts. I propose that patterns of selection on terrestrial herbivores and plants differ from those on aquatic species. Land plants must often attract animal dispersers and pollinators that, like their herbivorous counterparts, require sophisticated locomotor and sensory abilities. Plants counter their attractiveness to animal helpers by evolving effective contact defences and long-distance cues that mislead or warn herbivores. The locomotor and sensory world of small aquatic herbivores is more limited. These characteristics result from the lower viscosity and density of air compared with water as well as from limitations on plant physiology and signal transmission in water. Evolutionary innovations have not eliminated the contrasts in the conditions of life between water and land. Plant defence can be understood fully when herbivores and their victims are considered in the broader context of other interactions among coexisting species and of the medium in which these interactions occur.


[Immediate results of deep suture of the common bile duct].
The continuous suture of the common bile duct was used in 304 patients. It was used with the curative, curative-diagnostic and diagnostic purposes in mind. The indications for this suture were a complete removal of all stones from the bile ducts and a good passability of the distal portion of ductus choledochus. The authors analyze complications of the continuous suture of the common bile duct, such as "forgotten" stones in the ducts, incompetence of its sutures, peritonitis etc. Their causes are disclosed and the means of prevention are recommended. It is concluded that the continuous suture of the common bile duct is the most physiological method for the completion of choledochotomy with the corresponding indications. Peritonitis, pancreatitis and suppurative cholangitis are believed to be contraindications for using the continuous suture.


Elimination of aqueous myelographic contrast media from the subarachnoid space.
Elimination of aqueous contrast media from the lumbar subarachnoid space was measured. Iodine concentrations in serum and cisterna magna cerebrospinal fluid were studied in animals undergoing myelography with metrizamide, iocarmate, Iopamidol, or P-297. We found that all four contrast media were eliminated rapidly into the serum and urine, and transported slowly into the basal cisterns.


Characteristics of BDS Signal-in-Space User Ranging Errors and Their Effect on Advanced Receiver Autonomous Integrity Monitoring Performance.
Signal-In-Space User Range Errors (SIS UREs) are assumed to be overbounded by a normal distribution with a standard deviation represented by the User Range Accuracy (URA). The BeiDou Navigation Satellite System (BDS) broadcast URA is not compatible with the historical SIS URE performance that affects the Advanced Receiver Autonomous Integrity Monitoring (ARAIM) False Alert Probability (Pfa) and availability evaluation. This study compares the BDS broadcast and precise ephemeris from 1 March 2013 to 1 March 2017 to obtain SIS UREs. Through analyzing the statistical characteristics of the SIS UREs, we obtain the standard deviation σURE for the accuracy and continuity and σURA used for the integrity of the SIS UREs. The results show that the broadcast σURA of 2 m cannot completely overbound SIS UREs for all BDS satellites, but the σURA of 2.4 m can. Then, we use the σURA of 2.4 m to evaluate the ARAIM Pfa and availability. The results show that the Pfa may increase to 2 × 10-5 and exceed its limit by an order of magnitude. We also consider the differences between the SIS UREs of Geostationary Earth Orbit (GEO), Inclined Geo-Synchronous Orbit (IGSO), and Medium Earth Orbit (MEO). The results indicate that all Pfa values calculated by the computed σURE are less than the Pfa in the Integrity Support Message (ISM) for the worst-performing GEO satellite. The approximately 55% Pfa calculated by the computed σURE is less than the Pfa in ISM for the worst-performing IGSO satellite. Most Pfa values calculated by the computed σURE is less than the Pfa in the ISM for the worst-performing MEO satellite. For BDS satellites, the Pfa is mainly affected by σURE. When the σURA of 2.4 m is used to evaluate the availability, the computed availability is lower than the availability calculated by the broadcast σURA/σURE and the greatest degradation can reach 25%.


Aberrations induced by anti-ASE cap on thin-disk active element.
Optical aberrations induced in thin-disk laser elements with an undoped layer, performing as an anti-ASE cap, are analyzed. A numerical model, used for calculations of the optical path difference (OPD) induced by temperature distribution inside the laser element and by deformation of surfaces, was confirmed experimentally. Results of numerical modeling manifest that adding an undoped layer on the thin-disk has detrimental effect on the reflected laser beam brightness and scaling. It is also shown that brightness of a thin-disk laser may be enhanced by the use of the Gaussian pump beam profile.


Maternally responsive neurons in the bed nucleus of the stria terminalis and medial preoptic area: Putative circuits for regulating anxiety and reward.
Postpartum neuropsychiatric disorders are a major source of morbidity and mortality and affect at least 10% of childbearing women. Affective dysregulation within this context has been identified in association with changes in reproductive steroids. Steroids promote maternal actions and modulate affect, but can also destabilize mood in some but not all women. Potential brain regions that mediate these effects include the medial preoptic area (mPOA) and ventral bed nucleus of the stria terminalis (vBNST). Herein, we review the regulation of neural activity in the mPOA/vBNST by environmental and hormonal concomitants in puerperal females. Such activity may influence maternal anxiety and motivation and have significant implications for postpartum affective disorders. Future directions for research are also explored, including physiological circuit-level approaches to gain insight into the functional connectivity of hormone-responsive maternal circuits that modulate affect.


Exploring the significance of morphological diversity for cerebellar granule cell excitability.
The relatively simple and compact morphology of cerebellar granule cells (CGCs) has led to the view that heterogeneity in CGC shape has negligible impact upon the integration of mossy fibre (MF) information. Following electrophysiological recording, 3D models were constructed from high-resolution imaging data to identify morphological features that could influence the coding of MF input patterns by adult CGCs. Quantification of MF and CGC morphology provided evidence that CGCs could be connected to the multiple rosettes that arise from a single MF input. Predictions from our computational models propose that MF inputs could be more densely encoded within the CGC layer than previous models suggest. Moreover, those MF signals arriving onto the dendrite closest to the axon will generate greater CGC excitation. However, the impact of this morphological variability on MF input selectivity will be attenuated by high levels of CGC inhibition providing further flexibility to the MF → CGC pathway. These features could be particularly important when considering the integration of multimodal MF sensory input by individual CGCs.


Expression of proteoglycan core proteins in human bone marrow stroma.
Heparan sulphate proteoglycans (HSPGs) present on the surface of bone marrow stromal cells and in the extracellular matrix (ECM) have important roles in the control of adhesion and growth of haemopoietic stem and progenitor cells. The two main groups of proteoglycans which contain heparan sulphate chains are members of the syndecan and glypican families. In this study we have identified the main surface membrane and matrix-associated HSPGs present in normal human bone marrow stroma formed in long-term culture. Proteoglycans were extracted from the adherent stromal layers and treated with heparitinase and chondroitinase ABC. The core proteins were detected by Western blotting using antibodies directed against syndecans-1-4, glypican-1 and the ECM HSPG, perlecan. Stromal cell expression at the RNA level was detected by Northern blotting and by reverse transcription PCR. Glypican-1, syndecan-3 and syndecan-4 were the major cell-membrane HSPG species and perlecan was the major ECM proteoglycan. There was no evidence for expression of syndecan-1 protein. Syndecan-3 was expressed mainly as a variant or processed 50-55 kDa core protein and in lower amounts as the characteristic 125 kDa core protein. These results suggest that syndecan-3, syndecan-4 and glypican-1 present on the surface of marrow stromal cells, together with perlecan in the ECM, may be responsible for creating the correct stromal 'niche' for the maintenance and development of haemopoietic stem and progenitor cells. The detection of a variant form of syndecan-3 as a major stromal HSPG suggests a specific role for this syndecan in haemopoiesis.


Solvent effect on the sensitized photooxygenation of 2,3-dihydropyrazine derivatives.
Detection of O(2)((1)Delta(g)) phosphorescence emission, lambda(max) = 1270 nm, following laser excitation and steady-state methods was employed to determine the total rate constant, k(T), and the chemical reaction rate constant, k(R), for reaction between 5,6-disubstituted-2,3-dihydropyrazines and singlet oxygen in several solvents. Values of k(T) ranged from 0.26 x 10(5) M(-1) s(-1) in hexafluoro-2-propanol to 58.9 x 10(5) M(-1) s(-1) in N,N-dimethylacetamide for 5,6-dimethyl-2,3-dihydropyrazine (DMD) and from 5.74 x 10(5) M(-1) s(-1) in trifluoroethanol to 159.0 x 10(5) M(-1) s(-1) in tributyl phosphate for 5-methyl-6-phenyl-2,3-dihydropyrazine (MPD). Chemical reaction rate constants, k(R), for DMD are similar to k(T) in polar solvents such as propylencarbonate, whereas for MPD in this solvent, the contribution of the chemical channel to the total reaction is about of 4%. Dependence of the total rate constant on solvent microscopic parameters, alpha and pi, for DMD can be explained in terms of a reaction mechanism that involves formation of a perepoxide exciplex. Replacement of the methyl by a phenyl substituent enhances dihydropyrazine ring reactivity toward singlet oxygen and modifies the dependence of k(T) on solvent parameters, specially on the Hildebrand parameter. These results are explained in terms of an additional reaction path, involving a perepoxide-like exciplex stabilized by the interaction of the negative charge on the terminal oxygen of the perepoxide with the aromatic pi system.


[Applicability and validity of the Dutch version of the Montreal Cognitive Assessment (moCA-d) in diagnosing MCI].
The MoCA is a new screening test to detect Mild Cognitive Impairment (MCI). Purpose of this study is validating the Dutch version (MoCA-D). We administered the MoCA-D to healthy control subjects and to elderly with MCI or dementia from a memory disorder outpatient clinic and a geriatric (outpatient) clinic (n = 30, 32, 37 respectively, age > or = 60). Neuropsychological testing was part of the standard procedure for patients to diagnose MCI. Sensitivity, specificity and predictive values (positive: PPV and negative: NPV) of the MoCA-D were assessed. A significant effect of group was found on MoCA-D total score (F (2.95) =67.9; p < 0.01). With a cutoff score of < or = 25, sensitivity and specificity to detect MCI in relation to healthy controls were 72% and 73%, respectively. PPV and NPV were 84% and 56%, respectively. With a cut-off score of < or = 20, sensitivity to detect dementia in relation to MCI was 100% for severe dementia and 75% for mild dementia. Specificity for dementia was 81%, PPV 94% and NPV 55%. The MoCA-D distinguishes between healthy elderly, MCI patients and dementia patients. However, in this study, insufficient sensitivity and poor specificity were found. For the present, applying a broader and flexible screening procedure in order to detect MCI seems a more useful method than the interpretation of one test result in particular.


Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects.
Psychostimulants such as methylphenidate and modafinil are increasingly used by healthy people for cognitive enhancement purposes, whereas the acute effect of 3,4-methylenedioxymethamphetamine (ecstasy) on cognitive functioning in healthy subjects remains unclear. This study directly compared the acute effects of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine on the neural mechanisms underlying response inhibition in healthy subjects. Using a double-blind, within-subject, placebo-controlled, cross-over design, methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine were administrated to 21 healthy subjects while performing a go/no-go event-related functional magnetic resonance imaging task to assess brain activation during motor response inhibition. Relative to placebo, methylphenidate and modafinil but not 3,4-methylenedioxymethamphetamine improved inhibitory performance. Methylphenidate significantly increased activation in the right middle frontal gyrus, middle/superior temporal gyrus, inferior parietal lobule, presupplementary motor area, and anterior cingulate cortex compared with placebo. Methylphenidate also induced significantly higher activation in the anterior cingulate cortex and presupplementary motor area and relative to modafinil. Relative to placebo, modafinil significantly increased activation in the right middle frontal gyrus and superior/inferior parietal lobule, while 3,4-methylenedioxymethamphetamine significantly increased activation in the right middle/inferior frontal gyrus and superior parietal lobule. Direct comparison of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine revealed broad recruitment of fronto-parietal regions but specific effects of methylphenidate on middle/superior temporal gyrus, anterior cingulate cortex, and presupplementary motor area activation, suggesting dissociable modulations of response inhibition networks and potentially the superiority of methylphenidate in the enhancement of cognitive performance in healthy subjects.


Evaluation of the API 20 Strep system for species identification of streptococci isolated from bovine mastitis.
A new commercial system (API 20 Strep) for the species identification of streptococci associated with bovine mastitis was compared with the conventional biochemical methods. A total of 84 strains, including Streptococcus agalactiae (13), S. dysgalactiae (16), S. uberis (24), S. faecalis (12), S. faecium (5), and S. bovis (14) were tested. Using profile index and table data issued by the manufacturer, we identified 71.4% of strains by the API 20 Strep system. Our results indicate that improvement of the identification key is needed for accurate identification of streptococci isolated from bovine mastitis.


Mass spectrometry and computational study of collision-induced dissociation of 9-methylguanine-1-methylcytosine base-pair radical cation: intra-base-pair proton transfer and hydrogen transfer, non-statistical dissociation, and reaction with a water ligand.
A combined experimental and theoretical study is presented on the collision-induced dissociation (CID) of 9-methylguanine-1-methylcytosine base-pair radical cation (abbreviated as [9MG·1MC]˙+) and its monohydrate ([9MG·1MC]˙+·H2O) with Xe and Ar gases. Product ion mass spectra were measured as a function of collision energy using guided-ion beam tandem mass spectrometry, from which cross sections and threshold energies for various dissociation pathways were determined. Electronic structure calculations were performed at the DFT, RI-MP2 and DLPNO-CCSD(T) levels of theory to identify product structures and map out reaction potential energy surfaces. [9MG·1MC]˙+ has two structures: a conventional structure 9MG˙+·1MC (population 87%) consisting of hydrogen-bonded 9-methylguanine radical cation and neutral 1-methylcytosine, and a proton-transferred structure [9MG - H]˙·[1MC + H]+ (less stable, population 13%) formed by intra-base-pair proton transfer from the N1 of 9MG˙+ to the N3 of 1MC within 9MG˙+·1MC. The two structures have similar dissociation energies but can be distinguished in that 9MG˙+·1MC dissociates into 9MG˙+ and 1MC whereas [9MG - H]˙·[1MC + H]+ dissociates into neutral [9MG - H]˙ radical and protonated [1MC + H]+. An intriguing finding is that, in both Xe- and Ar-induced CID of [9MG·1MC]˙+, product ions were overwhelmingly dominated by [1MC + H]+, which is contrary to product distributions predicted using a statistical reaction model. Monohydration of [9MG·1MC]˙+ reversed the populations of the conventional structure (43%) vs. the proton-transferred structure (57%) and induced new reactions upon collisional activation, of which intra-base-pair hydrogen transfer produced [9MG + H]+ and the reaction of the water ligand with a methyl group in [9MG·1MC]˙+ led to methanol elimination from [9MG·1MC]˙+·H2O.


Panendoscopic removal of sutured retained Penrose drain.
Presented is a case in which panendoscopic removal of a sutured retained Penrose drain averted possible major reoperation. The drain had been sutured inadvertently during a pyelolithotomy and had fragmented during a subsequent unsuccessful attempt to advance the drain.


Assessment of recurrent laryngeal nerve function during thyroid surgery.
There is disparity in the reported incidence of temporary and permanent recurrent laryngeal nerve (RLN) palsy following thyroidectomy. Much of the disparity is due to the method of assessing vocal cord function. We sought to identify the incidence and natural history of temporary and permanent vocal cord palsy following thyroid surgery. The authors wanted to establish whether intraoperative nerve monitoring and stimulation aids in prognosis when managing vocal cord palsy. Prospective data on consecutive thyroid operations were collected. Intraoperative nerve monitoring and stimulation, using an endotracheal tube mounted device, was performed in all cases. Endoscopic examination of the larynx was performed on the first postoperative day and at three weeks. Data on 102 patients and 123 nerves were collated. Temporary and permanent RLN palsy rates were 6.1% and 1.7%. Most RLN palsies were identified on the first postoperative day with all recognised at the three-week review. No preoperative clinical risk factors were identified. Although dysphonia at the three-week follow-up visit was the only significant predictor of vocal cord palsy, only two-thirds of patients with cord palsies were dysphonic. Intraoperative nerve monitoring and stimulation did not predict outcome in terms of vocal cord function. Temporary nerve palsy rates were consistent with other series where direct laryngoscopy is used to assess laryngeal function. Direct laryngoscopy is the only reliable measure of cord function, with intraoperative monitoring being neither a reliable predictor of cord function nor a predictor of eventual laryngeal function. The fact that all temporary palsies recovered within four months has implications for staged procedures.


Savior siblings, parenting and the moral valorization of children.
Philosophy has long been concerned with 'moral status'. Discussions about the moral status of children, however, seem often to promote confusion rather than clarity. Using the creation of 'savior siblings' as an example, this paper provides a philosophical critique of the moral status of children and the moral relevance of parenting and the role that formative experience, regret and relational autonomy play in parental decisions. We suggest that parents make moral decisions that are guided by the moral significance they attach to children, to sick children and most importantly, to a specific sick child (theirs). This moral valorization is rarely made explicit and has generally been ignored by both philosophers and clinicians in previous critiques. Recognizing this, however, may transform not only the focus of bioethical discourse but also the policies and practices surrounding the care of children requiring bone marrow or cord blood transplantation by better understanding the values at stake behind parental decision making.


Investigation of monoclonal antibody CSX-1004 for fentanyl overdose.
The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, we present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Moreover, toxicokinetic evaluation in a repeat-dose rat study and human tissue cross-reactivity study reveals a favorable pharmacokinetic profile of CSX-1004 with no safety-related issues. Using a highly translational non-human primate (NHP) model of respiratory depression, we demonstrate CSX-1004-mediated protection from repeated fentanyl challenges for 3-4 weeks. Furthermore, treatment with CSX-1004 produces up to a 15-fold potency reduction of fentanyl in NHP respiration, antinociception and operant responding assays without affecting non-fentanyl opioids like oxycodone. Taken together, our data establish the feasibility of CSX-1004 as a promising candidate medication for preventing and reversing fentanyl-induced overdose.


Phosphorylase kinase isozymes in normal and electrically stimulated skeletal muscles.
Phosphorylase kinase was quantitatively immunoprecipitated from extracts of different rabbit skeletal muscles, subjected to electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate, and stained with silver. Amounts of the two isozymes, enzymes r and w. were determined by the staining intensities of the alpha'- and alpha -subunits, respectively. The kinase in muscles composed primarily of slow oxidative fibers was almost entirely enzyme r, but several times more of this isozyme was found in muscles with a high proportion of fast oxidative-glycolytic fibers. Enzyme w predominated in muscles composed mostly of fast glycolytic fibers. To investigate the possible role of muscle activity in controlling isozyme levels, tibialis anterior muscles were activated by chronic electrical stimulation of the peroneal nerves. After 10 wk of continuous stimulation, the amount of phosphorylase kinase was decreased by approximately 80%, and the ratio of enzyme r to enzyme w was doubled. These results demonstrate that increased muscle activity can decrease levels of phosphorylase kinase and suggest that activity may regulate the expression of the isozymes in different muscle fiber types.


Aflatoxins and ochratoxin A in pistachios sampled in Spain: occurrence and presence of mycotoxigenic fungi.
A survey of the fungal contamination and occurrence of aflatoxins and ochratoxin A (OTA) in 50 pistachio nut samples collected from commercial stores around Catalonia (Spain) was carried out. Aspergillus flavus was found in 30% of samples, whereas Aspergillus section Nigri, Aspergillus ochraceus, and Penicillium verrucosum were found in 40%, 2% and 26% of samples, respectively. A total of 204 fungal isolates were obtained; 70.8% of A. flavus isolates were able to produce aflatoxin B1 and B2, whereas OTA production capacity was detected in 54.4% of the A. section Nigri biseriate isolates. Aflatoxins were detected in five samples (10% of total), all exceeding the maximum legal limit set for aflatoxin B1 (2 µg kg(-1)) or for total aflatoxins (4 µg kg(-1)), with one sample having a very high level of contamination (1134.5 µg kg(-1)). Only one sample of pistachio showed OTA contamination at 0.67 µg kg(-1). Simultaneous contamination by aflatoxins and OTA was not observed in these samples. It was concluded that the frequency of aflatoxins and OTA contamination in pistachio samples available in the Spanish market is relatively low. Thus, no significant contribution to health risk should be expected from aflatoxin consumption through pistachios among healthy consumers. However, the existence of single samples with an extremely high aflatoxin concentration reinforces the need for effective prevention strategies in pistachio processing and commercialization.


Integration of a palliative and terminal care center into a comprehensive pediatric oncology department.
The sharp division between curative cancer therapy and palliative care results in the late introduction of palliative care and a high incidence of suffering in children with cancer. We established a Palliative Care Unit (PCU) that is fully integrated with the Pediatric Hematology Oncology Department (PHOD). We wished to explore the impact of such integrative model on patterns of hospitalizations and exposure to palliative care of pediatric oncology patients. Retrospective search of medical records of patients admitted to the PHOD since PCU establishment in 1999, and of children who died from progressive disease between 1990 and 2005 was performed. Differences in clinical and prognostic variables between PCU and non-PCU patients, and differences in location of death before and after PCU establishment were evaluated. The majority (59%) of patients, who were hospitalized after the PCU establishment, were hospitalized in the PCU, including 49% of the good prognosis patients and 91% of the poor prognosis patients. Poor prognosis patients were hospitalized in the PCU earlier and with higher frequency compared to children with curable disease. After PCU opening there was a significant decline in the percentage of patients who died in the general pediatric ward, hematology-oncology ward, and at home from 40%, 26% and 28% to 4%, 8%, and 16%, respectively. Our integrative model results in exposure of the majority of children with cancer to palliative care. For poor prognosis patients, palliative care is introduced early enough to allow gradual transition from symptom control after diagnosis to end of life care.


Cleavage of the human C5A receptor by proteinases derived from Porphyromonas gingivalis: cleavage of leukocyte C5a receptor.
The anaerobic bacteria P. gingivalis has been implicated as a primary causative agent in adult periodontitis. Several proteinases are produced by this bacteria and it is suggested that they contribute to virulence and to local tissue injury resulting from infection by P. gingivalis. Collagenases and cysteine proteinases (i.e., the gingipains) have been characterized as the predominant vesicular enzymes produced by this bacterium. It has been shown that an arginine-specific cysteine proteinase from P. gingivalis, called gingipain-1 or Arg-gingipain, can selectively cleave complement components C3 and C5. In the case of C5, cleavage by Arg-gingipain results in the generation of C5a, a potent chemotactic factor for PMNs. Since these bacterial proteinases are capable of generating pro-inflammatory factors at sites of infection, we examined the possibility that gingipains or other proteinases from this bacterium might attack or destroy cell surface proteins, such as receptor molecules. Using an affinity-purified rabbit antibody raised against residues 9-29 of the C5a receptor (i.e., C5aR; CD88), the signal transmitting element for the pro-inflammatory mediator C5a, we demonstrated that the mixture of proteinases in P. gingivalis vesicles cleaves the C5a receptor on human neutrophils. This vesicular proteinase activity did not require cysteine activation which indicates that proteinases other than the gingipains may be responsible for cleavage of the C5aR molecule. in addition, the purified Lys-gingipain, but not Arg-gingipain, also cleaved C5aR on the human neutrophils. The N-terminal region of CaR (residues 9-29, PDYGHYDDKDTLDLNTPVDKT) was readily cleaved by chymotrypsin, but not by trypsin, despite the presence of potential trypsin (i.e., lysyl-X) cleavage sites. The specific sites of C5aR 9-29 peptide cleavage were determined by mass spectroscopy for both chymotrypsin and Lys-gingipain. These studies suggest that the proteolytic activity in the bacterial vesicles that is responsible for cleaving C5aR is primarily a non-tryptic proteinase, distance from either Arg- or Lys-gingipain. Consequently, there appear to be additional proteinase(s) in the vesicles that attacks the cell surface molecule C5aR which are not the same (i.e., Arg- and Lys-gingipain) as were shown to generate pro-inflammatory activity from complement components C3 and C5. Evidence that the proteinases which attack the inflammatory precursor molecules (i.e., C3 and C5) exhibit different specificities than those that attack receptors to these bioactive complement products makes a particularly interesting story of how this bacteria avoids major host defense mechanisms. It is well known that generation of pro-inflammatory factors such as C3a and C5a at extra-vascular sites can promote edema, leukocyte recruitment and cellular activation responses that could lead to the release of toxic oxygen products and to phagocytosis of the bacteria. Destruction of receptors to these cellular activating factors generated by bacterial proteinases may eliminate the ability of these (i.e., complement-derived) and other mediators to carry out their anti-bacterial actions and thereby limit the host's defense mechanisms in responses to the infecting bacteria. The concept of anti-bacterial responses (i.e., oxygen radical generation and phagocytosis) being effectively eliminated at the injury site, by bacterial proteinases acting at the cellular receptor level, has not been studied in detail. In this case, the situation is particularly unusual because, once the bacterial gingipains generate potent plasma-derived inflammatory factors that can enhance edema and deliver essential nutrients to the bactgeria, other bacterial proteinases may destsroy their cellular receptors. These receptors transmit the signal activation mechanisms in the infiltrating cells that elicit bacterial killing.(ABSTRACT TRUNCATED)


Application of the Hurdle Technology Concept to the Fresh Za'atar (Origanum syriacum) Preservation.
Oregano (Origanum syriacum) is popularly called za'atar in the Middle East region. It is widely used in the Mediterranean diet as an aromatic herb. This study aimed to evaluate the preservation effect of natural additives, vacuum packaging, and refrigeration on the quality traits of fresh oregano. In total, 132 fresh oregano samples were formulated and split into 4 groups (n = 33) labeled group A (100% fresh oregano leaves, Control), group B (fresh oregano 63.2%, 15% fresh onion, 20% oil, 1.8% salt), group C (fresh oregano 61.91%, 15% fresh Allium cepa, 20% oil, 1.8% salt, 1.29% sumac), and group D (fresh oregano 59.2%, 15% fresh Allium cepa, 20% corn oil, 1.8% salt, 4% lactic acid, ultimate pH 4.4). Different quality traits such as color index (L*a*b*), microbiological analysis (total aerobic, anaerobic, and psychrotrophic bacteria and yeasts and molds), and sensory features (taste, flavor, appearance, saltiness, and overall acceptance) were assessed during the storage period (42 days) for all groups. Our study showed that the addition of lactic acid (group D) exhibited a strong preservation effect against aerobic and anaerobic bacteria. In this context, group D had significantly lower aerobic and anaerobic bacterial counts (5.12 vs. 6.7, 6, and 6.7 log (cfu/g); p < 0.05) and (4.75 vs. 6.6, 6.1, 6.77 (cfu/g); p < 0.05) than group A, B, and C; respectively. Group D exhibited significantly (p < 0.05) lower psychrotrophic bacterial count (3.6 log (cfu/g)) during the whole period of storage compared with control. Group B had a lower redness index (a*) (−3.3 vs. −1.8, −1.65, −1.23; p < 0.05) than groups A, C, and D; respectively. In conclusion, our study showed that there is a possibility of improving the preservation of oregano (Origanum syriacum) by using lactic acid and sumac combined with vacuum packaging under refrigeration conditions.


Resolving the assembly state of herpes simplex virus during axon transport by live-cell imaging.
Neurotropic herpesviruses depend on long-distance axon transport for the initial establishment of latency in peripheral ganglia (retrograde transport) and for viral spread in axons to exposed body surfaces following reactivation (anterograde transport). Images of neurons infected with herpes simplex virus type 1 (HSV-1), acquired using electron microscopy, have led to a debate regarding why different types of viral structures are seen in axons and which of these particles are relevant to the axon transport process. In this study, we applied time-lapse fluorescence microscopy to image HSV-1 virion components actively translocating to distal axons in primary neurons and neuronal cell lines. Key to these findings, only a small fraction of viral particles were engaged in anterograde transport during the egress phase of infection at any given time. By selective analysis of the composition of the subpopulation of actively transporting capsids, a link between transport of fully assembled HSV-1 virions and the neuronal secretory pathway was identified. Last, we have evaluated the seemingly opposing findings made in previous studies of HSV-1 axon transport in fixed cells and demonstrate a limitation to assessing the composition of individual HSV-1 particles using antibody detection methods.


VO2/power output relationship and the slow component of oxygen uptake kinetics during cycling at different pedaling rates: relationship to venous lactate accumulation and blood acid-base balance.
In this experiment we studied the effect of different pedalling rates during cycling at a constant power output (PO) 132+/-31 W (mean+/-S.D.), corresponding to 50% VO2 max, on the oxygen uptake and the magnitude of the slow component of VO2 kinetics in humans. The PO corresponded to 50% of VO2 max, established during incremental cycling at a pedalling rate of 70 rev.min(-1). Six healthy men aged 22.2+/-2.0 years with VO2 max 3.89+/-0.92 l.min(-1), performed on separate days constant PO cycling exercise lasting 6 min at pedalling rates 40, 60, 80, 100 and 120 rev.min(-1), in random order. Antecubital blood samples for plasma lactate [La]pl and blood acid-base balance variables were taken at 1 min intervals. Oxygen uptake was determined breath-by-breath. The total net oxygen consumed throughout the 6 min cycling period at pedalling rates of 40, 60, 80, 100 and 120 rev.min(-1) amounted to 7.727+/-1.197, 7.705+/-1.548, 8.679+/-1.262, 9.945+/-1.435 and 13.720+/-1.862 l, respectively for each pedalling rate. The VO2 during the 6 min of cycling only rose slowly by increasing the pedalling rate in the range of 40-100 rev.min(-1). This increase, was 0.142 l per 20 rev.min(-1) on the average. Plasma lactate concentration during the sixth minute of cycling changed little within this range of pedalling rates: the values were 1.83+/-0.70, 1.80+/-0.48, 2.33+/-0.88 and 2.52+/-0.33 mmol.l(-1). The values of [La]pl reached in the 6th minute of cycling were not significantly different from the pre-exercise levels. Blood pH was also not affected by the increase of pedalling rate in the range of 40-100 rev.min(-1). However, an increase of pedalling rate from 100 to 120 rev.min(-1) caused a sudden increase in the VO2 amounting to 0.747 l per 20 rev.min(-1), accompanied by a significant increase in [La]pl from 1.21+/-0.26 mmol.l(-1) in pre-exercise conditions to 5.92+/-2.46 mmol.l(-1) reached in the 6th minute of cycling (P<0.01). This was also accompanied by a significant drop of blood pH, from 7.355+/-0.039 in the pre-exercise period to 7.296+/-0.060 in the 6th minute of cycling (P < 0.01). The mechanical efficiency calculated on the basis of the net VO2 reached between the 4th and the 6th minute of cycling amounted to 26.6+/-2.7, 26.4+/-2.0, 23.4+/-3.4, 20.3+/-2.6 and 14.7+/-2.2%, respectively for pedalling rates of 40, 60, 80, 100 and 120 rev.min(-1). No significant increase in the VO2 from the 3rd to the 6th min (representing the magnitude of the slow component of VO2 kinetics) was observed at any of the pedalling rates (-0.022+/-0.056, -0.009+/-0.029, 0.012+/-0.073, 0.030+/-0.081 and 0.122+/-0.176 l.min(-1) for pedalling rates of 40, 60, 80, 100 and 120 rev.min(-1), respectively). Thus a significant increase in [La]pl and a decrease in blood pH do not play a major role in the mechanism(s) responsible for the slow component of VO2 kinetics in humans.


Unreliability of epidural venography in lumbar disc disease.
Lumbar epidural venography has been compared with myelography and discography in 69 patients suspected of having nerve root compression from herniated lumbar intervertebral discs. Only 78% agreement occurred when venograms were interpreted as unknowns by two radiologists. Twenty-three percent of the venographic examinations were suboptimal, most of these in patients operated upon previously. False-negative venography occurred in 13%. Midline disc herniations were missed more often than lateral herniations.


[Corticosteroid therapy of acute viral myocarditis in patients with severe clinical course of disease].
The article is devoted to the issue of great current interest--that of treatment of patients with acute viral myocarditis. Topicality of the subject in touched upon in some detail, positive and negative sides of use of corticosteroids in patients with acute viral myocarditis are outlined. Comparative data are submitted of treatment of patients with acute viral myocarditis running a grave clinical course with heparin, thiotriasoline, complex heparin--thiotriasoline--prednisolone. The presented results of treatment show expediency of administration of corticosteroids leading to a statistically significant decrease in concentration of titres of antiviral antibodies Coxsackie B1-4 viruses, increase in ejection fraction, rises in platelet count in patients with acute viral myocarditis running a grave clinical course.


Compartmentalization of the precheliceral neuroectoderm in the spider Cupiennius salei: development of the arcuate body, optic ganglia, and mushroom body.
Similarly to vertebrates, arthropod brains are compartmentalized into centers with specific neurological functions such as cognition, behavior, and memory. The centers can be further subdivided into smaller functional units. This raises the question of how these compartments are formed during development and how they are integrated into brain centers. We show here for the first time how the precheliceral neuroectoderm of the spider Cupiennius salei is compartmentalized to form the distinct brain centers of the visual system: the optic ganglia, the mushroom bodies, and the arcuate body. The areas of the visual brain centers are defined by the formation of grooves and vesicles and express the proneural gene CsASH1, followed by expression of the neural differentiation marker Prospero. Furthermore, the transcription factor dachshund, which is strongly enriched in the mushroom bodies and the outer optic ganglion of Drosophila, is expressed in the optic anlagen and the mushroom bodies of the spider. The developing brain centers are further subdivided into single neural precursor groups, which become incorporated into the grooves and vesicles but remain distinguishable throughout development, suggesting that they encode spatial information for neural subtype identity. Several molecular and morphological aspects of the development of the optic ganglia and the mushroom bodies are similar in the spider and in insects. Furthermore, we show that the primary engrailed head spot contributes neurons to the optic ganglia of the median eyes, whereas the secondary head spot, which has been associated with the optic ganglia in insects and crustaceans, is absent.


Extended harmonic phase tracking of myocardial motion: improved coverage of myocardium and its effect on strain results.
To extend the harmonic phase (HARP) tracking method in order to track the myocardial tissue that appears near the epicardial contour during systole and reappears near the endocardial contour during diastole, due to the longitudinal motion and conical shape of the heart. A mathematical model of myocardial deformation was used to quantify the accuracy of the extended HARP tracking and of the strain computation. For six healthy volunteers, the number of tracked points and the two-dimensional strain components were computed with the extended and with the original HARP tracking version. High accuracy was obtained for the circumferential strain (maximum error is 0.5% relative to analytical strain). The extended version tracked 22 +/- 7%, 51 +/- 19%, and 67 +/- 20% more points than the original version on the basal, mid, and apical slices, respectively (P < or = 0.001 for each slice), and yielded a decreased circumferential shortening (relative decrease: 2 +/- 4%, 9 +/- 4%, and 12 +/- 5% for the three slices; P < 0.005 for mid and apex), at end systole. These differences in circumferential strain were related to the more complete coverage of the myocardial wall with tracked points. The extended HARP tracking also provides strain values from myocardial regions that were not covered by the original HARP tracking.


Verification of a European corn borer (Lepidoptera: Crambidae) loss equation in the major corn production region of the northeastern United States.
Field studies in Pennsylvania and Maryland were conducted during 2000, 2001, and 2002 to test the applicability of published yield loss relationships developed in central Pennsylvania for European corn borer, Ostrinia nubilalis (Hübner), management in warmer, longer season corn, Zea mays L., grain production regions of the northeastern United States. Both isoline hybrids and non-Bt lead hybrids were compared against Bacillus thuringiensis (Bt) hybrids to measure effects of the pest on yield. The European corn borer economic analysis model was used to make site-specific predictions of loss per European corn borer larva for comparison with measured yield loss per larva. Although the model did not predict loss per larva at a field level, it did predict loss at a regional level. The model predicted an overall percentage of yield loss per larva of 2.69+/-0.12% over the region, which was similar to the measured yield loss per larva of 2.66+/-0.59% for isoline hybrids and 3.08+/-0.51% for lead hybrids. The model, on average, provided a good prediction of percentage of yield loss per larva within the climatic zones of 1100-1700 degree-days (DD) (base threshold 12.5 degrees C). Our results suggest that the yield loss relationship developed in Central Pennsylvania, when matched to the timing of third instar second generation European corn borer stalk tunneling is adequate for major corn grain production zones of the northeast United States.


Orbital pneumosinus dilatans.
Pneumosinus dilatans consists of an abnormal dilatation of the paranasal air sinuses which contain air only and are lined by normal epithelium. The condition is most commonly observed when it affects the sphenoid sinus as a response to a local meningioma of the tuberculum sellae or planum sphenoidale. Pneumosinus dilatans affecting the walls of the paranasal sinuses which form the boundaries of the orbit is less common; six patients reported here presented with either unilateral or bilateral exophthalmos. The frontal sinus and ethmoid cells were affected unilaterally in four patients and the maxillary antra bilaterally in two. The condition was associated with a meningioma in three patients and fibro-osseous disease in three patients. The importance of recognising this condition is in alerting the radiologist to the possible presence of an occult meningioma requiring soft-tissue imaging techniques (computed tomography or nuclear magnetic resonance imaging). The presence of fibro-osseous disease can usually be recognised by plain radiography.


Light and temperature controls of aquatic plant photosynthesis downstream of a hydropower plant and the effect of plant removal.
Many rivers worldwide are regulated, and the altered hydrology can lead to mass development of aquatic plants. Plant invasions are often seen as a nuisance for human activities leading to costly remedial actions with uncertain implications for aquatic biodiversity and ecosystem functioning. Mechanical harvesting is often used to remove aquatic plants and knowledge of plant growth rate could improve management decisions. Here, we used a simple light-temperature theoretical model to make a priori prediction of aquatic plant photosynthesis. These predictions were assessed through an open-channel diel change in O2 mass balance approach. A Michaelis-Menten type model was fitted to observed gross primary production (GPP) standardised at 10 °C using a temperature dependence from thermodynamic theory of enzyme kinetics. The model explained 87 % of the variability in GPP of a submerged aquatic plant (Juncus bulbosus L.) throughout an annual cycle in the River Otra, Norway. The annual net plant production was about 2.6 (1.0 ± 4.2) times the standing biomass of J. bulbosus. This suggests a high continuous mass loss due to hydraulic stress and natural mechanical breakage of stems, as the biomass of J. bulbosus remained relatively constant throughout the year. J. bulbosus was predicted to be resilient to mechanical harvesting with photosynthetic capacity recovered within two years following 50-85 % plant removal. The predicted recovery was confirmed through a field experiment where 72 % of J. bulbosus biomass was mechanically removed. We emphasise the value of using a theoretical approach, like metabolic theory, over statistical models where a posteriori results are not always easy to interpret. Finally, the ability to predict ecosystem resilience of aquatic photosynthesis in response to varying management scenarios offers a valuable tool for estimating aquatic ecosystem services, such as carbon regulation. This tool can benefit the EU Biodiversity Strategy and UN Sustainable Development Goals.


Multispecies probiotic protects gut barrier function in experimental models.
To investigate the effect of the probiotic combination Lactibiane Tolerance(®) (LT) on epithelial barrier function in vitro and in vivo. The effect of the multispecies probiotic LT was assessed on several models of epithelial barrier function both in vitro (in basal and inflammatory conditions) and in vivo [visceral hypersensitivity induced by chronic stress or by colonic perfusion of a fecal supernatant (FSN) from patients with irritable bowel syndrome (IBS)]. In vitro, we measured the permeability of confluent T84 cell monolayers incubated with or without LT by evaluating the paracellular flux of macromolecules, in basal conditions and after stimulation with lipopolysaccharide (LPS) or with conditioned medium of colonic biopsies from IBS patients (IBS-CM). In vivo, male C57/Bl6 mice received orally NaCl or LT for 15 d and were submitted to water avoidance stress (WAS) before evaluating visceral sensitivity by measuring the myoelectrical activity of the abdominal muscle and the paracellular permeability with (51)Cr-EDTA. Permeability and sensitivity were also measured after colonic instillation of FSN. Tight-junctions were assessed by immunoblotting and TLR-4 expression was evaluated by immunohistochemistry Incubation of T84 cell monolayers with LT in basal conditions had no significant effect on permeability (P > 0.05 vs culture medium). By contrast, addition of LT bacterial bodies (LT) completely prevented the LPS-induced increase in paracellular permeability (P < 0.01 vs LPS 10 ng/mL (LPS 10); P < 0.01 vs LPS 100 ng/mL (LPS 100), P > 0.05 vs culture medium). The effect was dose dependent as addition of 10(9) LT bacterial bodies induced a stronger decrease in absorbance than 10(6) LT (10(9) LT + LPS 10: -20.1% ± 13.4, P < 0.01 vs LPS 10; 10(6) LT + LPS 10: -11.6% ± 6.2, P < 0.01 vs LPS 10; 10(9) LT + LPS 100: -14.4% ± 5.5, P < 0.01 vs LPS 100; 10(6) LT + LPS 100: -11.6% ± 7.3, P < 0.05 vs LPS 100). Moreover, the increase in paracellular permeability induced by culturing T84 cells with conditioned medium of colonic biopsies from IBS patients (IBS-CM) was completely inhibited in the presence of 10(9) LT (P < 0.01 vs IBS-CM). LT also significantly prevented the epithelial disruption induced by intracolonic infusion of fecal supernatant from IBS patients (P < 0.01 vs IBS FSN) or water avoidance stress P < 0.01 vs WAS) in C57/Bl6 mice and increased the expression of occludin in vitro and in vivo, as assessed by immnunoblotting. The WAS-induced effect on visceral sensitivity was prevented by LT treatment since values obtained for all steps of colorectal distension were significantly (P < 0.01) different from the WAS group. Finally, LT down-regulated the response mediated through TLR-4 in vitro (decrease in tumor necrosis factor α secretion in response to LPS: -65.8% for 10(9) LT and -52.5% for 10(6) LT, P < 0.01 vs LPS) and in vivo (inhibition of WAS induced an increase in TLR-4 expression in the LT treated mice colon, P < 0.01 vs WAS). The probiotic LT mix prevented the disruption to the epithelial barrier induced by LPS, stress or colonic soluble factors from IBS patients and prevented visceral hypersensitivity.


Foveal processing and word skipping during reading.
An eyetracking experiment is reported examining the assumption that a word is skipped during sentence reading because parafoveal processing during preceding fixations has reached an advanced level in recognizing that word. Word n was presented with reduced contrast, with case alternation, or normally. Reingold and Rayner (2006) reported that, in comparison to the normal condition, reduced contrast increased viewing times on word n but not on word n+1, whereas case alternation increased viewing times on both words. These patterns were reflected in the fixation times of the present experiment, but a striking dissociation was observed in the skipping of word n+1: The reduced contrast of word n decreased skipping of word n+1, whereas case alternation did not. Apart from the amount of parafoveal processing, the decision to skip word n+1 is also influenced by the ease of processing word n: Difficulties in processing word n lead to a more conservative strategy in the decision to skip word n+1.