Antioxidant properties of enzymatic hydrolysates from royal jelly.
Enzymatic hydrolysates were prepared from royal jelly using three enzymes (pepsin, trypsin, and papain), and their antioxidative properties were evaluated. The yield of these hydrolysates was very high, about 20-26% on a raw weight basis. In comparison with the antioxidative activities of water extract and alkaline extract of royal jelly, the antioxidative activities and scavenging activities against active oxygen species such as superoxide anion radical and hydroxyl radical of each hydrolysate were high in the sample with a low protein concentration. These results suggest that once royal jelly is hydrolyzed using enzyme, the hydrolysate possesses much higher antioxidative activity and scavenging activity against active oxygen species. Royal jelly will act as a medicinal food in the human body.


Is intrapartum asphyxia preventable?
The contribution of intrapartum events to asphyxia-related mortality and morbidity and the degree to which it may be prevented are controversial. We examined trends in asphyxia-related mortality and morbidity in a single large regional perinatal centre. Between 1994 and 2005, the rate of asphyxia fell from 2.86/1000 births in 1994 to 0.91/1000 births in 2005 (P < 0.001). Hypoxic-ischaemic encephalopathy of all grades fell from 2.41 to 0.77/1000 live births (P < 0.001). This substantial and steady fall in the rate of asphyxia-related mortality and morbidity over a 12-year period suggests that a significant proportion of cases of intrapartum asphyxia may be preventable.


The effect of crude guava leaf tannins on motility, viability, and intact plasma membrane of stored spermatozoa of Etawa crossbred goats.
The aim of this study was to know crude guava leaf tannins effect on motility, viability, and intact plasma membrane of stored spermatozoa of Etawa crossbred goats. Macroscopic assessment of normal Etawa crossbred semen was followed by dilution with a glucose solution at a 1:10 ratio to increase volume. The diluted semen was treated by adding crude guava leaf tannins into 1 ml of the semen glucose diluent, and five treatments were obtained, namely, control group (C), with no added tannins; treatment Group 1 (T1), with 3%; treatment Group 2 (T2), with 6% tannins; treatment Group 3 (T3), with 12% tannins; and treatment Group 4 (T4), with 24% tannins. Each treatment used five replications. Then, microscopic analysis of the treated and control semen was carried out after 15 days of storage at 4-5°C temperature. The parameters observed were motility, pH, viability, abnormality, and intact spermatozoa plasma membrane. The spermatozoa motility in Group C was the highest (76.60±1.47). The motility in Group T1 did not differ from that in Group C, but was different and higher than that in Groups T2, T3, and T4. The pH of Group C tended to be acidic after 15 days of storage (4.78±0.01) as compared to the initial pH of fresh semen (6.76±0.12). The pH in Group C did not differ from that in the Groups T1 and T2, but differed from that in the T3 and T4 groups; the pH in the T3 and T4 groups was similar. The viability of spermatozoa in the T1 group was higher than that in all treatments (64.60±2.76); the lowest values were found in Group C (28.94±1.02). Group C had the lowest number of normal spermatozoa, with a mean of 72.58±3.48. The total number of abnormalities in the T2 group did not differ from those in the T3 group, and abnormalities in the T4 group did not differ from those in Group C, which exhibited the highest abnormalities in the head, neck, and tail. The most significant decrease was observed in the intact plasma membrane of spermatozoa on addition of 12% and 24% crude guava leaf tannin in glucose diluents. The addition of 3% crude guava leaf tannin to crossbred Etawa goat semen diluted with glucose diluent and stored for 15 days at 4-5°C resulted in a significant effect on spermatozoa motility, viability, and intact plasma membrane, whereas the administration of 24% crude guava leaf tannin resulted in low live percentage of spermatozoa.


No antibiotic and toxic metabolites produced by the biocontrol agent Pseudomonas putida strain B2017.
Pseudomonas putida and closely-related species such as Pseudomonas fluorescens and Pseudomonas brassicacearum have been reported as potential biocontrol agents and plant growth-promoters. Recently, we have described the biocontrol activity of P. putida B2017 against several phytopathogens of agricultural relevance. In this study, its ability to produce potential antibiotic / toxic metabolites was assessed by functional, chromatography-mass spectrometry and genomic analysis. Our results show that B2017 is not able to synthesize surfactants and common antibiotics produced by Pseudomonas spp., i.e. pyrrolnitrin, 2,4-diacetylphloroglucinol, pyoluteorin and pyocyanin, but it produces pyoverdine, a siderophore which is involved in its biocontrol activity. The non-production of other metabolites, such as cyanide, safracin, promysalin and lipopeptides between others, is also discussed. Our data suggest that the mode of action of B2017 is not mainly due to the production of antimicrobial / toxic metabolites. Moreover, these features make P. putida B2017 a promising biocontrol microorganism for plant protection without side effects on environment, non-target organisms and human health.


[Nursing outcomes and the reform of care processes (III). A problem of maximal and minimal levels].
This article presents a reflection about the different focus which exists between analysis of the role nurses play, investigating what nurses role is and about the product of nurses' professional activities, and the definition and evaluation of the nursing product. Nursing products approach viability, optimization and maximization of resources. From the tension between both aspects, the best possible nursing professional should develop. This article also presents an analysis of some of the systems used to evaluate the hospital product; among these are APACHE II, PMC, DS, CPHA, GRD, SIGNO.


Clinical significance of duodenal erosions.
In 2436 duodenoscopies performed in 1979-1980, 142 cases of duodenal erosions were found. In 68% of the cases erosions were autonomous, while in the remaining 32% they were associated with peptic ulcer. Either autonomous or associated erosions were mainly present in males with prevalence of the 4th, 5th and 6th decades of life. Moreover, autumn and spring were the most common times of appearance. With respect to symptomatology, 125 cases complained of dyspepsia with a prevalence of ulcer-like symptoms in both autonomous and associated erosions: in the remaining 17 patients hematemesis and melena were the main symptoms. The intake of alcohol and of coffee, as well as the smoking habit did not reveal any particular pattern in these cases, while the association with recent consumption of potentially mucolytic drugs was frequent. In addition, the last 38 cases of autonomous duodenal erosions were studied from the anatomo-functional point of view, revealing the presence of normochlorhydria in 42%, hyperchlorhydria in 47% and hypochlorhydria in 11%: in contrast, fasting gastrinemia was always within normal limits. The histological evaluation of the fundic mucosa showed normal patterns in 71% of the cases, superficial gastritis in 18%, and preatrophic gastritis in 11%. The parietal index was normal in 42% of the cases, high in 47% and low in 11%. The results would seem to suggest that duodenal erosions should be included in the wide spectrum of peptic pathology.


Comparison of Standardized Uptake Values in Normal Structures Between PET/CT and PET/MRI in a Tertiary Pediatric Hospital: A Prospective Study.
The purpose of this study was to compare standardized uptake values (SUVs) of normal tissues using MR attenuation-corrected versus CT attenuation-corrected (18)F-FDG PET in a pediatric population. Thirty-five patients (21 boys; mean age, 13.3 years) referred for 47 PET/CT scans were recruited to undergo PET/MRI. MR attenuation correction was performed using an automated three-segment model. ROIs were drawn over nine normal structures to estimate SUV(min), SUV(mean), and SUV(max). Pearson rank correlation coefficients were calculated to compare SUVs obtained from MR and CT attenuation correction. In nine patients who underwent multiple PET/MRI studies, coefficients of variance and intraclass correlation coefficients were calculated to evaluate intrapatient SUV(max) variation. Mean (± SD) time to imaging after FDG injection was 108 ± 17 minutes for PET/CT and 61 ± 6 minutes for PET/MRI. PET/MRI SUVs in all tissues were lower than those for PET/CT (mean difference, -28.9% ± 31.1%; p < 0.05). Very high or high correlation between PET/MRI and PET/CT SUV(max) was found in brain (r = 0.72), myocardium (r = 0.95), and bone marrow (r = 0.85) (p < 0.001). Moderate correlation was found in liver (r = 0.54), fat (r = 0.41), mean blood pool (r = 0.40), and psoas muscle (r = 0.38) (p < 0.01). Weak correlation was found in lung (r = 0.12) and iliacus muscle (r = 0.12). Compared with PET/CT, PET/MRI systematically undermeasured SUV. In nine patients who underwent multiple PET/MRI examinations, moderate or strong agreement was found in the SUV(max) of six of nine tissues, similar to the corresponding PET/CT examinations. Our study showed overall high correlation for SUV measurements obtained from MR attenuation correction compared with CT attenuation correction, although PET/MRI underestimated SUV compared with PET/CT. SUVs measured from PET/MRI indicated good intrapatient reliability.


Making outdoor field experiences more inclusive for the LGBTQ+ community.
Outdoor field experiences have not historically been welcoming to marginalized communities. Recent calls to address the lack of diversity in outdoor field experiences have accelerated efforts to make programs more inclusive for multiple marginalized identity groups. Despite these efforts, many cultural and procedural changes are still needed to support the Lesbian, Gay, Bisexual, Transgender, Queer or Questioning (LGBTQ+) community when participating in outdoor field experiences. Here we use results from a survey of leaders from 17 outdoor programs and expertise gained from our own experiences cultivating inclusion in field programs to outline strategies that outdoor field experience providers can use to foster greater support for the LGBTQ+ community. We define key terminology to increase awareness of LGBTQ+ identities and pronouns. We then highlight important actions that field experience leaders can take to make their internships, education programs, and trips more accessible and inclusive for the LGBTQ+ community. We use results from our survey of outdoor programs to highlight practices currently being used to support LGBTQ+ inclusion and accessibility and synthesize how current practice aligns with our overall recommendations. The LGBTQ+ community deserves to be welcomed into outdoor field experiences and to participate fully as students, researchers, educators, recreators, and professionals.


[Application for Inpatient Psychosomatic Rehabilitation: Frequency, Quality, and Approval Rates].
There has been a steady increase in psychiatric primary diagnoses in medical rehabilitation services carried out by the statutory pension insurance (DRV). To date, no data are available regarding frequency, quality, and approval rates of applications for psychosomatic rehabilitation. Pension insurance physicians reviewing the application require sufficient information on rehabilitation-related needs, motivation, abilities, and prognosis of an insured person. Medical reports accompanying application for rehabilitation are often provided by a family physician. Psychiatric disorders are often misdiagnosed by general practitioners. In a 2-week period, all decisions made by pension insurance physicians evaluating applications for rehabilitation were recorded. For each incoming application, the following data were documented: psychiatric and somatic primary diagnosis; availability of medical reports; information on prior treatment/therapy; request for further information; decision made by the physician. 1,366 applications (with 81% first-time applications) were included in the analysis. 16.2% of all applications were from insurants with psychiatric primary diagnoses. 44.0% of these applications included a medical report from the family physician only. The proportion of rejected applications (34.7%) and undecided applications (27.2%) was higher in the group of applicants with psychiatric primary diagnosis vs. somatic primary diagnosis (19.6% rejected; 12.7% undecided; χ2=79.8(4), p=0.001). Applications from patients with psychiatric primary diagnosis that lacked a medical report from a psychiatrist/psychotherapist were more likely to be rejected (45.3 vs. 32.3%) or to remain undecided (28.0 vs. 18.3%; χ2=10.2(2), p=0.006). In contrast, among applicants with a history of psychiatric/psychotherapeutic treatment, there was a higher proportion of undecided applications accompanied by a medical report from the family physician (35.7 vs. 18.2%). It might be useful to have medical reports generally provided by medical specialists. This may help both to increase the informative value of applications for psychosomatic rehabilitation and enable quicker decisions and better diagnosis.


Stable, Yet Highly Reactive Nonclassical Iron(II) Polyhydride Pincer Complexes: Z-Selective Dimerization and Hydroboration of Terminal Alkynes.
The synthesis, characterization, and catalytic activity of nonclassical iron(II) polyhydride complexes containing tridentate PNP pincer-type ligands is described. These compounds of the general formula [Fe(PNP)(H)2(η2-H2)] exhibit remarkable reactivity toward terminal alkynes. They efficiently promote the catalytic dimerization of aryl acetylenes giving the corresponding conjugated 1,3-enynes in excellent yields with low catalyst loadings. When the reaction is carried out in the presence of pinacolborane, vinyl boronates are obtained. Both reactions take place under mild conditions and are highly chemo-, regio-, and stereoselective with up to 99% Z-selectivity.


Inhibition of renin by plasma linoleic acid.
The authors have demonstrated previously that human plasma contains an inhibitor(s) of the enzymatic activity of renin. The purpose of this study is to identify the circulating renin inhibitor. Plasma initially was fractionated with preparative sephacryl S-300 chromatography. A fraction with low protein content inhibited the in vitro enzymatic activity of human renin by 76%. The inhibitory activity of this fraction was not altered by boiling and/or acidification. This fraction was applied to an affinity column, using purified mouse submaxillary renin as ligand. The inhibitor was recovered after elution with hypertonic NaCl. Linoleic acid, a previously identified renin inhibitor, was present in this fraction. The authors conclude that circulating linoleic acid inhibits renin. Conceivably, the overall activity of the renin-angiotensin-aldosterone cascade may be modified by alterations of plasma fatty acid concentrations.


Biological motion shown backwards: the apparent-facing effect.
We examined how showing a film backwards (reverse transformation) affects the visual perception of biological motion. Adults and 6-year-old children saw first a point-light quadruped moving normally as if on a treadmill, and then saw the same display in reverse transformation. For other groups the order of presentation was the opposite. Irrespective of the presentation mode (normal or reverse) and of the facing of the point-light figure (rightward or leftward), a pronounced apparent-facing effect was observed: the perceptual identification of a display was mainly determined by the apparent direction of locomotion. The findings suggest that in interpreting impoverished point-light biological-motion stimuli the visual system may neglect distortions caused by showing a film backwards. This property appears to be robust across perceptual development. Possible explanations of the apparent-facing effect are discussed.


[Endocrinology of cancer and age: early and late stages of ontogenesis].
Processes important for hormone-mediated carcinogenesis are present on different, even very early, ontogenesis stages. Early shifts in hormone-metabolic status often display opposite correlations with the risk of most common age-associated non-communicable pathologies (namely, hormone-dependent cancers and cardiovascular diseases). Additional known contradiction is the raise of reproductive system tumors incidence in the age associated with lower production of mitogenic hormones. Consequently, one should take into account production of steroids in target tissues themselves, recognize the importance of progenotoxic effect, which, apart from mitogenic function, is characteristic for estrogens and their derivatives, as well as the role of endocrine-genotoxic switchings forming so called basic triad, which is born under the influence of age-associated endocrine shifts and environmental factors. Aside from steroids-related system of increased cancer risk, attention should be paid to non-steroid ones (in particular insulin resistance- and inflammatory cytokines-associated), with their close connection to immune system functional state, low-grade chronic inflammation, obesity phenotype, and pro-/anti-inflammatory lipid factors ratio. In total, it confirms and importance of timely preventive interventions on both ontogenesis stages, early and late ones, which are often separated by several decades.


Designed to deter: Barriers to facilities at secondary schools in Ghana.
There are varied and complex problems associated with the admission of students with disabilities into secondary (senior high) schools all over the world. This situation is further complicated by difficulties encountered in the built environment of these institutions and, in this, Ghana is no exception. This exploratory study investigated the level of accessibility of the built environment in secondary schools in eight out of the ten regions of Ghana, in order to determine whether they conform to guidelines provided in international building standards and also assess the extent to which they have been designed and constructed to meet the provisions of the Persons with Disability Act 2006, which allows for equal access to public buildings in Ghana. In total, 705 building elements in 264 facilities were surveyed using international standards, building codes, regulations and guidelines. These facilities included car parks, classrooms, dormitories, assembly halls, telephone booths and administration blocks. Our findings revealed that most of the building elements were barring and not disability-friendly. Just to name a few: there were obstructions on access routes to and around buildings, absence of designated car parks, unfriendly vertical and horizontal means of circulation in buildings and lack of accessible sanitary accommodations. In addition, the general lighting and signage were poor. As a result, very few students with disabilities are admitted and retained in these schools. Mainstreaming of people with disabilities into the Ghanaian educational system remains impossible unless urgent action is taken to alter the facilities at secondary schools. Based on this research outcome, recommendations have been made to the Ghanaian government and the Ghana Education Service, as well as non-governmental organisations and relevant professional bodies for the amelioration of the present situation in our secondary schools.


[Geographic distribution of wild rabies risk and evaluation of the factors associated with its incidence in Colombia, 1982-2010].
To update the information on the geographic distribution of bat-transmitted rabies foci in Colombia and evaluate the biotic and abiotic conditions associated with the incidence of this disease in the country. Observational study of a database containing information on the wild rabies foci identified between 1982 and 2010 and the cattle population in each municipality. The municipalities were classified according to the disease's risk of transmission, and an environmental characterization of 15 variables was carried out. A maximum entropy model was developed to predict which areas had conditions appropriate for the presence of the Desmodus rotundus vector infected by the virus and to evaluate the importance of the variables employed. There were 2 330 foci in 359 (31.8%) of the country's 1 128 municipalities; 144 municipalities were classified as high risk. The highest incidence rates were found in Montería, Valledupar, Riohacha, Aguachica, Unguía, Acandí, Río de Oro, Tibú, Sahagún, and San Onofre. Rabies foci were found year-round but were more frequent (linear correlation [r] = 0.64) during the dry months (January to April). Temperature and precipitation were the variables contributing the greatest robustness to the prediction model. Prevention and control measures should be implemented in high-risk municipalities. The best months for conducting vaccination campaigns are June, November, and December. In future analyses, biotic interaction variables should be included to improve the predictive capacity of the model.


Inhibitory effects of Enterococcus strains obtained from a probiotic product on in vitro growth of Salmonella enterica serovar enteritidis strain IFO3313.
Enterococcus faecium and Enterococcus gallinarum strains were isolated from a commercial probiotic product and the effects of these strains on the growth of Salmonella enterica serovar Enteritidis strain IFO3313 were investigated. Viable cell counts of Salmonella Enteritidis in mixed cultures with the probiotic product isolate of E. faecium were significantly (P < 0.05) lower than those in pure cultures after 6, 8, and 24 h when the cultures were incubated in heart infusion broth at 37 and 41 degrees C. Significant differences in viable cell counts of Salmonella Enteritidis in mixed cultures with the probiotic product isolate of E. gallinarum and those in pure cultures were also observed after 8 and 24 h at 37 and 41degrees C. Similar observations were shown in mixed cultures of Salmonella Enteritidis with the reference strains of E. faecium GIFU8355 and E. gallinarum ATCC 49573. Significant differences in viable cell counts of these enterococcal strains were not shown among pure and mixed cultures with Salmonella Enteritidis. The pH values in pure and mixed cultures were 7.0 or 7.5 throughout the experiments. E. faecium strains were found to harbor the genes encoding enterocins A and B and showed inhibitory zones with a diameter of 4 to 6 mm against growth of Salmonella Enteritidis in the enterocin production assays. However, the E. gallinarum strains possessed neither of the enterocin genes tested and exhibited no inhibition zone in the enterocin production assays. These results indicated that enterococcal strains exhibit inhibitory effects on the growth of Salmonella Enteritidis and these effects were due to both enterocin and nonenterocin factors.


Radiation-induced soft-tissue and bone sarcoma.
From the records of Memorial Hospital of the past 50 years, 47 cases with an established diagnosis of radiation-induced sarcoma were identified and divided into two groups: the first included 20 cases of soft-tissue sarcoma arising from irradiated tissues, and the second comprised 27 cases of bone sarcoma arising from normal bones in the irradiated field. Medians for the latent periods from irradiation to diagnosis of bone and soft-tissue sarcoma were 11 and 12, years, respectively. In bone sarcomas, the latent period was longer after larger radiation doses and children appeared to be more susceptible to cancer induction than adults. Criteria for establishing the diagnosis of radiation-induced sarcoma and the magnitude of the risk of bone sarcoma are discussed.


Restoration of microRNA-708 sensitizes ovarian cancer cells to cisplatin via IGF2BP1/Akt pathway.
A previous study has shown that microRNA-708 (miR-708) functions as a metastasis suppressor in ovarian cancer. In this study, we aimed to explore its implication in regulating cisplatin sensitivity in ovarian cancer cells. To this end, ovarian cancer cells were transfected with miR-708-expressing plasmids or vector before treatment with different concentrations of cisplatin for 48 h. The 50% inhibitory concentration (IC50 ) value was calculated. Apoptosis was analyzed by measuring caspase-3 activity. The target gene mediating the function of miR-708 was identified. Ectopic expression of miR-708 sensitized SKOV3 and A2780 cells to cisplatin, decreasing the IC50 value by two- to threefold. miR-708 overexpression significantly augmented cisplatin-induced apoptosis in ovarian cancer cells, which was coupled with increased caspase-3 activity by two- to fourfold. Similarly, overexpression of miR-708 increased the sensitivity of cisplatin-resistant SKOV3/DDP and A2780/DDP cells to cisplatin-induced toxicity, reducing the IC50 by three- and fivefold, respectively. Delivery of miR-708 enhanced cisplatin-induced elevation in caspase-3 activity in both cisplatin-resistant and parental ovarian cancer cells. Mechanistically, miR-708 downregulated the expression of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and suppressed Akt phosphorylation. Silencing of IGF2BP1 markedly blocked the phosphorylation of Akt. Overexpression of IGF2BP1 restored cisplatin resistance and Akt phosphorylation in miR-708-overexpressing ovarian cancer cells. Collectively, miR-708 increases the susceptibility of ovarian cancer cells to cisplatin by targeting IGF2BP1 and inhibiting Akt signaling. Delivery of miR-708 may represent a promising strategy for improving cisplatin chemotherapy.


Molecular engineering of mechanophore activity for stress-responsive polymeric materials.
Force reactive functional groups, or mechanophores, have emerged as the basis of a potential strategy for sensing and countering stress-induced material failure. The general utility of this strategy is limited, however, because the levels of mechanophore activation in the bulk are typically low and observed only under large, typically irreversible strains. Strategies that enhance activation are therefore quite useful. Molecular-level design principles by which to engineer enhanced mechanophore activity are reviewed, with an emphasis on quantitative structure-activity studies determined for a family of gem-dihalocyclopropane mechanophores.


Translation and Initial Psychometric Evaluation of Spanish Versions of Three Psychedelic Acute Effects Measures: Mystical, Challenging, and Insight Experiences.
This study translated and tested the psychometric properties of acute psychedelic effects measures among Spanish-speaking people. The Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ) were translated before being incorporated into a web-based survey. We recruited native Spanish-speakers (N = 442; Mage = 30.8, SD = 10.9; Latino/Latina = 62%; Hispanic = 91.4%; male = 71.5%) to assess their previous experience with one of two psychedelics (LSD = 58.4%; Psilocybin = 41.6%) and their acute and enduring effects. Confirmatory factor analysis (confirming factor structure based on the English version) revealed a good fit for the MEQ, PIQ and the CEQ. Repeating our analysis in each drug subsample revealed consistency in factor structure for each assessment tool. Construct validity was supported by significant positive associations between the PIQ and MEQ, and between the PIQ and MEQ and changes in cognitive fusion and negative associations between changes in prosocial behaviors. As a signal of predictive validity, persisting effects (PEQ) were strongly related to scores on the MEQ and PIQ. Findings demonstrate that the Spanish versions of these measures can be reliably employed in studies of psychedelic use or administration in Spanish-speaking populations.


The IRE gene encodes a protein kinase homologue and modulates root hair growth in Arabidopsis.
We identified an Arabidopsis mutant, incomplete root hair elongation (ire), whose root hairs are about 40% shorter than the wild type owing to the early cessation of their growth. In contrast, the hy5 mutant has root hairs about twice as long as the wild type, possibly because of delayed cessation of growth. Thus IRE and HY5 are likely to modify the duration of growth of root hairs. We cloned the IRE locus using the T-DNA tagged line. The IRE locus encodes a protein that includes a serine/threonine protein kinase domain. The primary structure of this kinase domain shows significant similarity to a group of protein kinases among various eukaryotes. In the Arabidopsis genome there are at least three genes that are closely related to IRE. The IRE transcript was detected in every organ examined. However, the IRE promoter-GUS fusion gene was strongly expressed in the elongating root hair cells, suggesting the cell-autonomous function of IRE in root hairs. GUS activity was also detected in pollen grains, which develop by tip growth, suggesting that IRE has a common role in the tip growth of plant cells.


Lack of genetic association of the UCHL1 gene with Alzheimer's disease and Parkinson's disease with dementia.
Several candidate genes were suggested to modify the susceptibility to both Alzheimer's disease (AD) and Parkinson's disease (PD). Symptoms of dementia are found in approximately 30% of PD patients. Both apolipoprotein E (APO E) and ubiquitin carboxyl-terminal esterase L1 (UCHL1) are neuropathogenic proteins for both diseases. The aim of this study was to investigate whether polymorphisms of both genes are associated with AD and PD with dementia (PDD). The APO E polymorphism and 5 common single-nucleotide polymorphisms (SNPs) of the UCHL1 gene were analyzed using a case-control study design. Although APO E4 affected the onset of AD, the 5 SNPs of the UCHL1 gene were not associated with risk for AD. Linkage disequilibrium (LD) analysis of our Japanese data set showed that the SNPs of the UCHL1 gene are part of one LD block. Although one SNP, rs4861387, of the UCHL1 gene showed marginal association with PDD, we did not detect any association between the other SNPs and PDD. The common SNPs of UCHL1 are not major risk factors for AD. Since our analyses on PDD are preliminary, further genetic studies on APO E, UCHL1 and PD with and without dementia are needed.


Do adult Magicicada (Hemiptera: Cicadidae) feed? Historical perspectives and evidence from molecular gut content analysis.
The periodical cicadas in the genus Magicicada are remarkable for their unusual life histories and dramatic synchronized emergences every 13 or 17 years. While aspects of their evolution, mating behaviors, and general biology have been well-characterized, there is surprising uncertainty surrounding the feeding habits of the short-lived adult stage. Despite a tentative scientific consensus to the contrary, the perception that adult Magicicada do not feed has persisted among the general public, and recent studies are lacking. We directly investigated the feeding behavior of Magicicada spp. through high-throughput sequencing (HTS)-based dietary analysis of nymphs, freshly molted (teneral) adults, and fully sclerotized adults collected from orchard and wooded habitats during the 2021 emergence of Brood X. Identifiable plant DNA (trnF, ITS amplicons) was successfully recovered from nymphs and adults. No plant DNA was recovered from teneral adults, suggesting that all DNA recovered from sclerotized adults was ingested during the post-teneral adult stage. Both nymphs and adults were found to have ingested a range of woody and herbaceous plants across 17 genera and 14 families. Significantly more plant genera per individual were recovered from adults than from nymphs, likely reflecting the greater mobility of the adult stage. We hypothesize that the demonstrated ingestion of plant sap by Magicicada adults is driven by a need to replace lost water and support specialized bacteriome-dwelling endosymbionts that cicadas depend upon for growth and development, which constitutes true feeding behavior.


Physicochemical homogeneity of stingless bee honey (Heterotrigona itama) produced in the west coast, east coast and inland area of Peninsular Malaysia.
The nutritional composition of stingless bee honey (SBH) can be affected by different climates and soil composition across different geographical areas. However, the range of attributes set for a honey quality standard should be inclusive. This study analysed the sugar profile's physiochemical properties, including quantifying the rare sugar trehalulose, organic acid and mineral composition of SBH collected from inland, and west and east coasts of Peninsular Malaysia. Forty-three SBH (Heterotrigona itama) samples were collected and labelled as <20 and <40 West Coast (<20WC, <40WC), <20 and <40 East Coast (<20EC, <40EC) and Inland, according to their distance from the coasts. The moisture, pH and sugar composition of all SBH samples adhered to the Malaysian Kelulut Honey Standard (MS2683:2017) but not to the International Codex Standard (CODEX) for honey. Trehalulose presence in all samples, regardless of geographical area, was predominant alongside fructose and glucose. Only hydroxymethylfurfural (HMF) content and electrical conductivity (EC) results complied with both standards. The principal component analysis biplot showed that the discrimination of SBH according to the five different areas was not feasible, indicating sample homogeneity. The physicochemical evaluation of SBH from Peninsular Malaysia shows mainly homogeneous attributes of samples across geographical locations. These findings demonstrated that the current MS2683:2017 is relevant and accommodates all SBH of H. itama species produced in Peninsular Malaysia. Furthermore, the trehalulose range calculated in this study can be implemented as a new benchmark for the indicator of SBH honey quality standard by national and international food standard committees. © 2023 Society of Chemical Industry.


[Stress on the radiocarpal joint. CT studies of subchondral bone density in vivo].
Most concepts about the mechanism of load transmission through the radiocarpal joint have been mostly acquired from the study of cadaveric specimens. Apart from this, however, it is possible to derive direct knowledge about the actual mechanical conditions of a joint from certain morphological parameters, particularly by analysis of the subchondral mineralization. CT-osteoabsorptiometry (CT-OAM) has provided a non-invasive investigative tool by which the distribution of subchondral mineralization within the radiocarpal joint can be determined. Seventeen wrist-joints in healthy young subjects were investigated by means of CT-OAM, and the results evaluated both topographically and quantitatively. In most cases, two density maxima were found on the articular radial surface, one corresponding to the scaphoid and one to the lunate. These matched the positions of pressure peaks described in reports of research on mechanical models. The density maximum on the articular surface of the radius opposing the scaphoid is, however, rather more dorsally placed, whereas that opposing the lunate lies palmar to the radioulnar midline. This explains the transmission of force to the forearm and the geometrical configuration of the joint components. On the other hand, our quantitative results do not confirm the existence of a generally greater degree of mineralization of either one of the joint compartments. We cannot confirm theories attributing transmission of the main force through either the scaphoid or the lunate. We assume rather that the type of stress indicated by the predominantly monocentric density maxima either on the scaphoid or the lunate surface of the radius, together with the equally balanced bicentric degree of mineralization, are to be regarded as physiological.


Mismatch-targeted transposition of Mu: a new strategy to map genetic polymorphism.
Phage Mu DNA transposes to duplex target DNA sites with limited sequence specificity. Here we demonstrate that Mu transposition exhibits a strong target site preference for all single-nucleotide mismatches. This finding has implications for the mechanism of transposition and provides a powerful tool for genomic research. A single mismatch could be detected as a preferred target of Mu transposition in the presence of 300,000-fold excess of nonmismatched sites. We demonstrate the detection of both heterozygous and homozygous mutations in the cystic fibrosis transmembrane conductance regulator gene and single nucleotide polymorphism in HLA region by Mu transposition mismatch analysis procedure.


Chemical Approaches to 2D Materials.
Chemistry plays an ever-increasing role in the production, functionalization, processing and applications of graphene and other 2D materials. This special issue highlights a selection of enlightening chemical approaches to 2D materials, which nicely reflect the breadth of the field and convey the excitement of the individuals involved in it, who are trying to translate graphene and related materials from the laboratory into a real, high-impact technology.


A systematic approach to analyse the sequelae of LCPD.
The analysis and treatment of hips with healed Legg-Calvé-Perthes disease (LCPD) differs substantially from the treatment in the acute phase of the disease. More specifically, the treating orthopaedic surgeon is often faced with a complex three-dimensional pathomorphology of the hip that is difficult to understand and correct. To date, none of the current classification systems provide a useful decision-making algorithm with regards to the type of surgical intervention necessary to improve hip function in patients with sequelae of LCPD. The conceptual recognition of the femoroacetabular impingement (FAI) and the ability to safely dislocate the hip have revolutionised our diagnostic and therapeutic algorithm for joint-preserving surgery of hips with structural residuals of LCPD. We present a systematic approach to analyse femoral and acetabular pathomorphologic features. The resulting pathomechanisms and the surgical treatment options are presented.


Imatinib-resistant CML cells have low ENT activity but maintain sensitivity to gemcitabine.
Philadelphia chromosome-positive chronic myelogenus leukemia (CML) is widely treated with imatinib mesylate (imatinib), a potent inhibitor of the Bcr-Abl tyrosine kinase. However, resistance to this compound remains a concern. Current treatment approaches include combinations of imatinib with nucleoside analogs such as gemcitabine, which requires equilibrative nucleoside transporters (ENTs) for uptake, to overcome this resistance. Here we report that imatinib treatment decreased ENT1-dependent activity and mRNA expression. Although, imatinib-resistant cells showed decreased levels of both ENT1 and ENT2 activity and expression, these cells remained sensitive to gemcitabine, suggesting that nucleoside analogs can be used as adjunctive therapy.


Double Cu-Catalyzed Direct Csp3 -H Azidation/CuAAC Reaction: A Direct Approach towards Demanding Triazole Conjugates.
The first one-pot procedure for the double copper(I)-catalyzed oxidative Csp3 -H azidation-CuAAC process, implying unstable azide intermediates and easy-to-remove reagents under water-tolerant conditions, is presented. The combination of tert-butyl hydroperoxide as oxidant and TMSN3 as azide source for the C-H bond azidation, which produces harmless side-products such as tBuOH and H2 O, probed to be perfectly compatible with the following cycloaddition step. Highly demanding 1,2,3-triazoles could be then directly obtained in good overall yields by extraction or simple crystallization, thus avoiding chromatography purifications. The potential of this methodology, has also being highlighted by the successful reaction of alkynes presenting interesting complex biological moieties based for example on biotin, DNA base or cinchona alkaloid units.


Direct Oral Anticoagulants for the Prevention and Acute Treatment of Cancer-Associated Thrombosis.
Cancer is a major risk factor for venous thromboembolism (VTE), and cancer-associated thrombosis (CAT) constitutes approximately 15-25% of all VTE cases. For decades, the standard treatment for CAT used to be daily subcutaneous low molecular weight heparin (LMWH). Data on the safety and efficacy of the direct oral anticoagulants (DOACs) in this population emerged only in recent years and specific DOACs were included into recent guidelines recommendations. In this narrative review of the literature, we reported the results of the phase III randomized controlled trials that evaluated the DOACs for the prevention and the acute treatment of CAT. For the acute phase treatment, the anti-Xa inhibitors (apixaban, edoxaban, rivaroxaban) showed better efficacy than LMWH in preventing VTE recurrence; however, rivaroxaban and edoxaban were also associated with an increased risk of bleeding events. For primary prevention of CAT in ambulatory cancer patients starting chemotherapy, apixaban and rivaroxaban showed better efficacy than placebo but a trend towards higher bleeding rates. Recent guidelines suggest the DOACs for the treatment of CAT in selected cancer patients (eg, low bleeding risk, no luminal gastrointestinal or genitourinary malignancies, no interfering medications). The DOACs are also suggested for primary thromboprophylaxis in selected ambulatory cancer patients at high risk of VTE (eg, Khorana score ≥2 prior to starting new chemotherapy, low bleeding risk, no interfering medications).


Tomato Prenylated RAB Acceptor Protein 1 Modulates Trafficking and Degradation of the Pattern Recognition Receptor LeEIX2, Affecting the Innate Immune Response.
Plants recognize microbial/pathogen associated molecular patterns (MAMP/PAMP) through pattern recognition receptors (PRRs) triggering an immune response against pathogen progression. MAMP/PAMP triggered immune response requires PRR endocytosis and trafficking for proper deployment. LeEIX2 is a well-known Solanum lycopersicum RLP-PRR, able to recognize and respond to the fungal MAMP/PAMP ethylene-inducing xylanase (EIX), and its function is highly dependent on intracellular trafficking. Identifying protein machinery components regulating LeEIX2 intracellular trafficking is crucial to our understanding of LeEIX2 mediated immune responses. In this work, we identified a novel trafficking protein, SlPRA1A, a predicted regulator of RAB, as an interactor of LeEIX2. Overexpression of SlPRA1A strongly decreases LeEIX2 endosomal localization, as well as LeEIX2 protein levels. Accordingly, the innate immune responses to EIX are markedly reduced by SlPRA1A overexpression, presumably due to a decreased LeEIX2 availability. Studies into the role of SlPRA1A in LeEIX2 trafficking revealed that LeEIX2 localization in multivesicular bodies/late endosomes is augmented by SlPRA1A. Furthermore, inhibiting vacuolar function prevents the LeEIX2 protein level reduction mediated by SlPRA1A, suggesting that SlPRA1A may redirect LeEIX2 trafficking to the vacuole for degradation. Interestingly, SlPRA1A overexpression reduces the amount of several RLP-PRRs, but does not affect the protein level of receptor-like kinase PRRs, suggesting a specific role of SlPRA1A in RLP-PRR trafficking and degradation.


Bacteraemia with Escherichia coli in diabetic patients. Studies on bacterial virulence and host factors.
A total of 70 episodes of E. coli bacteraemia occurred in 10 patients with insulin-dependent, and 54 patients with non-insulin-dependent diabetes mellitus. The bacteraemic strains were tested for aerobactin mediated iron uptake, a property that is regarded as a virulence factor of E. coli. Aerobactin mediated iron uptake was present in 60% of the isolated strains from the diabetic patients. A similar prevalence, 54%, was noted in E. coli from a control group of non-diabetic patients with bacteraemia. The prevalence of aerobactin positive strains, isolated from both diabetic and non-diabetic patients, was significantly higher than in faecal E. coli strains (39%) obtained from healthy subjects. In E. coli from diabetic patients, another bacterial virulence factor, P-fimbriae, was present on 62% of the aerobactin positive strains but only on 33% of strains lacking aerobactin mediated iron uptake. No examined host factors in the diabetic patients, such as age, sex, duration of diabetes, serum creatinine and presence of proteinuria, influenced the prevalence of aerobactin mediated iron uptake. In conclusion, bacterial virulence mediated by the aerobactin system occurs as frequently in diabetic as in non-diabetic patients with E. coli bacteraemia, and furthermore seems to co-exist with P-fimbriation.


Adsorption studies of Orange II onto polyaniline/bentonite nanocomposite.
Modification of bentonite is essential for the adsorption of anionic dyes, as its negative surface charge. In this study, polyaniline/bentonite (PAni-Bent) nanocomposite was synthesized by in-situ intercalative polymerization technique and used to remove anionic dye Orange II (ORII) from synthetic wastewater. Its structure was confirmed by X-ray diffraction (XRD), scanning electron microscopy, Fourier-transform infrared spectra and Brunauer-Emmett-Teller specific surface area measurements. The adsorption behaviours of PAni-Bent towards ORII in the single anionic dye wastewater, the cationic/anionic mixture dye wastewater, with or without salt or surfactant, were investigated principally. The results show that cetyl trimethyl ammonium bromide have an obviously suppressing effect on dye removal in the MB/ORII mixture system. The Langmuir and Temkin isotherm models described the adsorption process better than Freundlich or Dubinin-Radushkevich (D-R) model, and the pseudo-second-order and Boyd kinetic models fit better with the experimental data. Considering all these unique characteristics, PAni-Bent can be considered as effective adsorbent material for potential removal of dye from aqueous solution in industry.


Effect of high flow nasal cannula on peripheral muscle oxygenation and hemodynamic during paddling exercise in patients with chronic obstructive pulmonary disease: a randomized controlled trial.
Exercise training for patients with chronic obstructive pulmonary disease (COPD) improves their endurance and oxygenation. Supplemental oxygen delivered by high flow nasal cannula (HFNC) reportedly improves the clinical outcomes during high-intensity exercise. However, the physical benefits of the provision of supplemental oxygen with HFNC for the improvement of exercise performance have not been fully investigated. This randomized trial aimed to evaluate the effect of HFNC on the hemodynamic status and peripheral muscle microcirculation during exercise training. In this multicenter, randomized controlled parallel two-group study, 32 patients with moderate to severe COPD were randomly assigned into the nasal cannula (NC) group (n=15) with a flow rate of 2-3 L/min or the HFNC group (n=17) with a flow rate of 45 L/min for twelve 40 min exercise training sessions. The mean cardiac index (CI) and stroke volume (SV) of the NC group in the first session were significantly lower than those of the HFNC group (3.68±0.76 vs. 4.5±0.76 L/min/m2, P=0.014; 63.03±9.87 vs. 74.22±19.48, P=0.002, respectively). The systemic vascular resistance (SVR) of the NC group was significantly lower in the seventh session than in the first session (891±287 vs. 1,138±381 dyn-s/cm5, respectively, P=0.048). The mean deoxyhemoglobin level was higher in the HFNC group in the 1st session and lower in the 12th session (1.09±9.04 vs. 7.3±7.3 µm, P=0.046). The COPD Assessment Test score, Modified Medical Research Council scale score, maximum inspiratory pressure (MIP), and maximum expiratory pressure were different within and between the groups. HFNC, with a lower oxygen concentration than that used with a traditional NC, yielded lower deoxygenated hemoglobin levels after 12 suboptimal exercise training sessions. In contrast, the higher oxygen concentration delivered by NC reduced SVR. The COPD assessment score improved on exercise training, regardless of the supplemental oxygen delivery method.


The NHS Plan: nurse satisfaction, commitment and retention strategies.
The NHS Plan envisages a paradigm shift from a centralized, producer-led National Health Service (NHS) to a devolved, patient-centred health care service, fuelled by a substantial investment in human resources, beds, hospitals and infrastructure. The planned net increase of 20,000 nurses by 2004 is examined in the light of findings from a qualitative study of nurse satisfaction, commitment or intention to leave their hospital, nursing or the NHS, involving 124 nurses in four London hospitals. This paper presents nurses' perceptions and rankings of retention strategies and we compare these with the Plan's proposals. Lastly we propose an integrated approach to examining and dealing with the complex issue of nurse recruitment, retention and quality of patient care, based on a conceptual framework, the Nurse Satisfaction, Service Quality and Nurse Retention Chain, which highlights the scope of the challenges confronting the Plan, in both design and implementation of proposals designed to improve working conditions as a foundation for nurse recruitment and retention. Our principal findings are that just 57% of our interviewees may be viewed as 'core loyals' to the profession, 12% are serious in their intention to leave and the remainder may be sensitive to further deterioration in working conditions or a failure to meet expectations on pay. Such findings if realized clearly threaten the Plan's success.


HO2*: the forgotten radical.
HO2*, usually termed either hydroperoxyl radical or perhydroxyl radical, is the protonated form of superoxide; the protonation/deprotonation equilibrium exhibits a pK(a) of around 4.8. Consequently, about 0.3% of any superoxide present in the cytosol of a typical cell is in the protonated form. This ratio is rather accurately reflected by the published literature on the two species, as identified by a PubMed search; at the time of writing only 28 articles mention "HO2," "hydroperoxyl" or "perhydroxyl" in their titles, as against 9228 mentioning superoxide. Here it is argued that this correlation is not justifiable: that HO2*'s biological and biomedical importance far exceeds the attention it has received. Several key observations of recent years are reviewed that can be explained much more economically when the participation of HO2* is postulated. It is suggested that a more widespread appreciation of the possible role of HO2* in biological systems would be of considerable benefit to biomedical research.


Abdominal angina: an unusual presentation of Takayasu's arteritis.
Takayasu's arteritis (TA) is an idiopathic large vessel vasculitis of young adults that affects the aorta and its major branches. The authors hereby present a case of TA that presented with abdominal aorta thrombosis. She was put on low-molecular weight heparin, antiplatelets, corticosteroids, cyclophosphamide along with haematinics and was referred to Department of Cardiothoracic and Vascular Surgery for further management.


Randomized clinical trial of zoledronic acid in multiple myeloma patients undergoing high-dose chemotherapy and stem-cell transplantation.
A growing body of evidence is demonstrating that the nitrogen-containing bisphosphonate zoledronic acid (zol) improves clinical outcomes in various cancer settings, including multiple myeloma. Those findings provided the rationale for conducting an open-label randomized controlled phase iii trial to evaluate the effect of zol on overall survival (os) and progression-free survival (pfs) in patients with previously untreated high-risk multiple myeloma. The trial randomly assigned 308 adult patients less than 65 years of age with previously untreated symptomatic multiple myeloma (1:1) to receive zol 4 mg intravenously once every 28 days for 24 months (n = 151) or no zol (n = 157). Before autologous stem-cell transplantation (asct), all patients received a high-dose noncytotoxic induction regimen of dexamethasone, all-trans-retinoic acid, and interferon alpha 2b. After a median follow-up of 69.8 months (range: 36.5-96 months), the 10-year pfs (66% vs. 52%, p < 0.001) and os (67% vs. 48%, p < 0.001) rates were significantly higher in treated patients than in control patients. Overall response (77% zol vs. 75% control), complete response (52% vs. 46%), and very good partial response (25% vs. 29%) rates were similar between the groups. Treatment was generally well tolerated, with no reports of renal impairment or osteonecrosis of the jaw. In symptomatic previously untreated multiple myeloma patients, zol combined with high-dose therapy followed by asct improved os and pfs without appreciable toxicity. These findings provide additional evidence of the meaningful anticancer activity of zol in this patient population.


Effects of the Training of Aerobic Function on Clinical Symptoms and Quality of Life in Patients with Medium and Advanced Lung Cancer.
To investigate the effects of the training of aerobic function on clinical symptoms and quality of life in patients with medium and advanced lung cancer. The study objects were 84 patients with medium and advanced lung cancer who were treated in our hospital (July 2019-July 2021) and their materials were retrospectively reviewed. Depending on the different intervention modes, they were equally divided into control group (routine nursing intervention measures) and experiment group (training of aerobic function), with 42 cases in each group. The clinical symptoms and living quality were compared between the two groups. After intervention, affective meaning, behavior/severity, cognitive/mood, and sensory scores in both groups were decreased, and the various indexes in the experiment group were lower compared with the control group (P < 0.05). After intervention, the patients' clinical symptoms, such as pain, inappetence, insomnia, and dyspnea in the two groups were improved, and the experiment group achieved eminently better improvement compared with the control group (P < 0.05). After intervention, the walking distances in 6 minute walk test (6MWT) in both groups were increased, and the experiment group achieved observably longer walking distance compared with the control group (P < 0.05). After intervention, the patients' pulmonary function indexes of forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and FEV1/FVC% level in the two groups were all improved, and the experiment group had signally better indexes compared with the control group (P < 0.05). After intervention, the patients' scores of Quality of Life Questionnaire-Core Questionnaire (QLQ-C30) in both groups were decreased, and the experiment group achieved much lower score compared with the control group (P < 0.05). The training of aerobic function has obvious therapeutic effect on medium and advanced lung cancer. This training can mitigate the patients' cancer-related fatigue and clinical symptoms, improve their pulmonary function, and enhance their athletic ability and quality of life.


Repeated Stand-Replacing Crown Fires Affect Seed Morphology and Germination in Aleppo pine.
Post-fire reproductive niche of Aleppo pine (Pinus halepensis) is deeply interlaced with fire products. Indeed, the high pH and low osmotic potentials of ash beds under burnt crowns constitute the main constraints to seed germination. In this study, we aim to investigate whether fire recurrence, through the physico-chemical constraints imposed by the ash beds, affects the reproduction ability of P. halepensis at the germination stage. To this aim, Aleppo pine seeds were collected in neighboring even-aged stands subjected to 0, 1, or 2 fires (namely fire cohorts), and seed morphology and germination performance, in terms of cumulative germination and germination kinetics, were studied under increasing osmotic potentials (from 0.0 to -1.2 MPa) and pH (from 6 to 11). Besides fire history, the role of ontogenetic age of mother plants on seed morphology and germination was also investigated. Differences in seed morphology among the three cohorts have been highlighted in a multivariate context, with anisotropic enlargement of the seeds produced by pine stands experiencing repeated fires. The patterns of seed germination varied primarily in relation to the fire cohort, with seeds from the pine stand experiencing repeated fires exhibiting enhanced tolerance to pH stress. Conversely, germination performances under osmotic constraints mainly depends on tree ontogenetic stage, with an involvement of fire history especially in the timing of seed germination. Our results suggest that, at least in the short term, fire recurrence does not constrain the reproduction ability of Aleppo pine. These results highlight the need for further research to elucidate the mechanisms behind these responses to recurrent fires.


[Atrial pacing with the A-V paceport pulmonary artery catheter].
Atrial pacing is often necessary during cardiac surgery. A total of 20 patients undergoing cardiac surgery were atrially paced with either a multipurpose pulmonary artery catheter (PAC) or an A-V paceport PAC (n = 10 each). Atrial pacing was successful in all the patients before cardiopulmonary bypass. The output threshold was 4.2 +/- 0.7 mA for a multipurpose PAC and 3.8 +/- 0.7 mA for A-V paceport PAC. Atrial pacing with both PAC's was readily performed and useful during cardiac surgery.


Fast-phase space computation of multiple arrivals.
We present a fast, general computational technique for computing the phase-space solution of static Hamilton-Jacobi equations. Starting with the Liouville formulation of the characteristic equations, we derive "Escape Equations" which are static, time-independent Eulerian PDEs. They represent all arrivals to the given boundary from all possible starting configurations. The solution is numerically constructed through a "one-pass" formulation, building on ideas from semi-Lagrangian methods, Dijkstra-like methods for the Eikonal equation, and Ordered Upwind Methods. To compute all possible trajectories corresponding to all possible boundary conditions, the technique is of computational order O(N log N), where N is the total number of points in the computational phase-space domain; any particular set of boundary conditions then is extracted through rapid post-processing. Suggestions are made for speeding up the algorithm in the case when the particular distribution of sources is provided in advance. As an application, we apply the technique to the problem of computing first, multiple, and most energetic arrivals to the Eikonal equation.


Temporal dynamics of neural adaptation effect in the human visual ventral stream.
When the same visual stimulus is repeatedly presented with a brief interval, the brain responses to that stimulus are attenuated relative to those at first presentation [neural adaptation (NA)]. Although this effect has been widely observed in various regions of human brain, its temporal dynamics as a neuronal population has been mostly unclear. In the present study, we used a magnetoencephalography (MEG) and conducted a macrolevel investigation of the temporal profiles of the NA occurring in the human visual ventral stream. The combination of MEG with our previous random dot blinking method isolated the neural responses in the higher visual cortex relating to shape perception. We dissociated three dimensions of the NA: activation strength, peak latency, and temporal duration of neural response. The results revealed that visual responses to the repeated compared with novel stimulus showed a significant reduction in both activation strength and peak latency but not in the duration of neural processing. Furthermore, this acceleration of peak latency showed a significant correlation with reaction time of the subjects, whereas no correlation was found between the reaction time and the temporal duration of neural responses. These results indicate that (1) the NA involves the brain response changes in the temporal domain as well as the response attenuation reported previously, and (2) this temporal change is primarily observed as a rapid rising of "what" responses, rather than a temporal shortening of neural response curves within the visual ventral stream as considered previously.


Associations of serum alkaline phosphatase level with all-cause and cardiovascular mortality in the general population.
There are few population studies on the associations of serum alkaline phosphatase (AlkP) with all-cause and cardiovascular mortality. We aimed to investigate the relevancy of serum AlkP with all-cause and cardiovascular mortality in the general population. Our research included 34,147 adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Cox proportional hazards regression models were used to assess the associations of serum AlkP with all-cause and cardiovascular mortality. Mediation analysis was used to analyze mechanisms that might link serum AlkP to all-cause and cardiovascular mortality. After 139.7 ± 57.8 months of follow-up, 5413 participants experienced all-cause death and 1820 participants experienced cardiovascular death. Mortality rates per 1000 person-years from various diseases increased with increasing serum concentrations of AlkP, especially all-cause death, cerebrovascular disease and cardiovascular death. High serum AlkP level significantly increased all-cause and cardiovascular mortality. After multivariate adjustment, the highest AlkP group had the highest risk to experience all-cause (hazard ratio [HR] = 1.30, P < 0.001) and cardiovascular mortality (HR = 1.39, P < 0.001) than the lowest AlkP group. γ-glutamyl transpeptidase (GGT) (13.33% and 15.79%), followed by Vitamin D (8.33% and 7.14%) and C-reactive protein (CRP) (7.69% and 10.35%) were identified as possible major mediators. Higher AlkP concentrations were associated with higher all-cause and cardiovascular mortality, largely related to mediated factors such as GGT, Vitamin D, and CRP. These findings suggest that lower serum AlkP level may reduce all-cause and cardiovascular mortality in general population.


Mitochondria-Targeted Delivery Strategy of Dual-Loaded Liposomes for Alzheimer's Disease Therapy.
Liposomes modified with tetradecyltriphenylphosphonium bromide with dual loading of α-tocopherol and donepezil hydrochloride were successfully designed for intranasal administration. Physicochemical characteristics of cationic liposomes such as the hydrodynamic diameter, zeta potential, and polydispersity index were within the range from 105 to 115 nm, from +10 to +23 mV, and from 0.1 to 0.2, respectively. In vitro release curves of donepezil hydrochloride were analyzed using the Korsmeyer-Peppas, Higuchi, First-Order, and Zero-Order kinetic models. Nanocontainers modified with cationic surfactant statistically better penetrate into the mitochondria of rat motoneurons. Imaging of rat brain slices revealed the penetration of nanocarriers into the brain. Experiments on transgenic mice with an Alzheimer's disease model (APP/PS1) demonstrated that the intranasal administration of liposomes within 21 days resulted in enhanced learning abilities and a reduction in the formation rate of Aβ plaques in the entorhinal cortex and hippocampus of the brain.


Prevalence of Metabolic Syndrome among Working Adults in Ethiopia.
Objective. To evaluate the prevalence of metabolic syndrome (MetS) according to the International Diabetes Federation (IDF) and Adult Treatment Panel (ATP) III criteria among working East African adults. Design. This cross-sectional study of 1,935 individuals (1,171 men and 764 women) was conducted among working adults in Addis Ababa, Ethiopia. The study was conducted in accordance with the STEPwise approach of the World Health Organization. Results. According to ATP III and IDF definitions, the overall prevalence of MetS was 12.5% and 17.9%, respectively. Using ATP III criteria, the prevalence of MetS was 10.0% in men and 16.2% in women. Application of the IDF criteria resulted in a MetS prevalence of 14.0% in men and 24.0% in women. The most common MetS components among women were reduced high-density lipoprotein-cholesterol (HDL-C) (23.2%) and abdominal obesity (19.6%); whilst reduced HDL-C concentrations (23.4%) and high blood pressure (21.8%) were most common among men. Conclusion. MetS and its individual components are prevalent among an apparently healthy working population in Ethiopia. These findings indicate the need for evidence-based health promotion and disease prevention programs; and more robust efforts directed towards the screening, diagnosis and management of MetS and its components among Ethiopian adults.


QTL region-specific microarrays reveal differential expression of positional candidate genes of signaling pathways associated with the liability for the inverted teat defect.
The inverted teat defect is the most common disorder of the mammary complex in pigs. It is characterized by the failure of teats to protrude from the udder surface, preventing normal milk flow and thus limiting the rearing capacity and increasing the risk of mastitis. The inverted teat defect is a liability trait with a complex mode of inheritance. We previously identified QTL for inverted teats. As a complementary approach that integrates map-based efforts to identify candidate genes for the inverted teat defect with function-driven expression analysis, application-specific microarrays were constructed that cover 1525 transcripts mapping in QTL regions on pig chromosomes 2, 3, 4, 6 and 11. About 950 transcripts were expressed in epithelial and mesenchymal teat tissue. The expression of three categories of teats was compared: normal teats of both non-affected and affected animals and inverted teats of affected animals. In epithelium and mesenchyme, 62 and 24 genes respectively were significantly differentially expressed (DE). The majority of biofunctions to which a significant number of DE genes were assigned are related to the following: (1) cell maintenance, proliferation, differentiation and replacement; (2) organismal, organ and tissue development; or (3) genetic information and nucleic acid processing. Moreover, the DE genes belong almost exclusively to canonical pathways related to signaling rather than metabolic pathways. This is in line with findings obtained by genome-wide catalogue microarrays. This study adds another piece to the puzzle of the etiology of inverted teats by indicating that causal genetic variation leading to the disorder is likely among the genes encoding for members of the signaling cascades of growth factors.


Oral Doxycycline Reduces the Total Number of Intraocular Bevacizumab Injections Needed to Control Neovascular Age-related Macular Degeneration.
Tetracyclines, especially doxycycline, play a role in the regulation of inflammation, immunomodulation, cell proliferation, and angiogenesis. Treatment of corneal angiogenesis or choroidal neovascularization with tetracyclines has been shown to be effective in animal models. The aim of this study was to evaluate the efficacy of oral doxycycline in reducing the total number of intraocular injections needed for controlling neovascular age-related macular degeneration in human patients. In this interventional case series, 28 random consecutive patients with neovascular age-related macular degeneration from Farabi Eye Hospital, Tehran, Iran were treated for 4 months with 200 mg doxycycline once a day after the first intravitreal bevacizumab injection in addition to standard therapy in agreement with as-needed regimen. After 12 months of follow-up, total number of injections, foveal thickness and visual acuity were compared to those at baseline and of similar studies. Similar to standard treatment, co-treatment with doxycycline was able to control active disease (intraretinal or subretinal fluid or leakage, new-onset of macular hemorrhage, and reduction of visual acuity more than 5 letters based on Early Treatment Diabetic Retinopathy Study [ETDRS] charts) yet with fewer injections (for current study and standard treatment, respectively 3.14 vs. 5.92, P < 0.001). Furthermore, while better control of the foveal thickness was achieved (P < 0.001), vision improvement was similar to that achieved with standard therapy (P > 0.05). If confirmed in larger studies, the findings of this interventional case series could provide a strategy to control neovascular age-related macular degeneration with fewer intraocular bevacizumab injections by co-administering a well-known oral agent-doxycycline.


Improvisations in classic and modified techniques of flap surgery to improve the success rate for pressure ulcer healing in patients with spinal cord injury.
The recurrence of pressure ulcers (PrUs) and dehiscence of reconstructive flap have always been a problem. The present study aimed to evaluate the results of reconstructive flap surgeries in patients with spinal cord injury (SCI) having PrUs, using classic and modified flaps with improvisations to decrease wound dehiscence, flap necrosis and tension in flap. This is a prospective clinical study. The setting was a tertiary care centre in northern India. Thirty-five patients with SCI having 37 stage III and IV PrUs. PrUs were treated using classic and modified flaps with improvisations. The outcome was evaluated using criteria of wound dehiscence, flap necrosis and recurrence. The results of flap surgery were excellent in 32 (86·48%) patients, good in 4 (10·81%) patients and poor in 1 (2·7%) patient. Partial flap necrosis (2·7%), low incidence of PrU recurrence rate at flap site (5·4%) and overall PrU recurrence (11·4%) were the complications observed. Improvisation of classic and modified techniques of flap surgeries along with reinforcement of general care principles of paraplegia can be effective in minimising complications often associated with PrU reconstructive surgery thus improving the ultimate outcome.


Ward leadership: balancing the clinical and managerial roles.
This qualitative study investigated ward managers' experiences of combining a clinical leadership role with the managerial and administrative parts of their job. Ward managers saw their main task as one of developing their staff and improving the quality of their service, yet found balancing their different roles problematic.


Detection of lectins using ligand blotting and polyacrylamide-type glycoconjugate probes.
A sensitive and convenient method for detection of the carbohydrate-binding activity of lectins was established using the combination of blotting of lectins on polyvinylidene difluoride membranes, carbohydrate-conjugated biotinylated polyacrylamide-type probes (carbohydrate-bp probes), horseradish peroxidase-streptavidin, and detection by enhanced chemiluminescence of the enzyme reaction. This method was tested for detection of four plant lectins blotted on the membrane: concanavalin A was detectable down to 100 ng by mannose-bp probe, Ricinus communis agglutinin 120 to as low as 5 ng by N-acetyllactosamine-bp probe, soybean agglutinin to 1 microgram by beta-N-acetyl-D-galactosamine-bp probe, and wheat germ agglutinin to 5 ng by beta-N-acetyl-D-glucosamine-bp probe. All four lectins were detectable on an electroblotted membrane after SDS-polyacrylamide gel electrophoresis. This method was used to detect recombinant human galectin-3 in Escherichia coli cell lysates and mannan-binding protein in human serum. These results indicate that this method is widely applicable to convenient detection and characterization of lectins in crude samples.


Biomimetic zinc funnel complexes based on calix[6]N3ArO ligands: an acid-base switch for guest binding.
The coordination chemistry of Zn in an N(3)ArOH environment has been explored. The ligands are based on calix[6]arenes that present two imidazole arms and an amino phenol moiety at the narrow rim. Three different types of complexes have been characterized. One is dicationic with Zn(2+) coordinated to the three nitrogen atoms and to the oxygen of the phenol group of the calix[6]ligand. This complex is very sensitive to exogenous coordinating molecules and exists as a 5-coordinate species due to the endo-complexation of a guest. The second species is a monocationic complex for which the phenol group has been deprotonated. The resulting N(3)ArOZn complex can also bind a guest ligand albeit with a lower affinity than the dicationic complex. The third species is neutral. It can be obtained upon reaction with a base to yield a hydroxo complex or with an anion such as a chloride that coordinates the metal center from the outside of the calixarene cavity. The simultaneous binding of two anionic donors decreases the Zn Lewis acidity, allowing an impressive conformational reorganization of the system. One imidazole arm is released by the metal center. The other one undergoes self-inclusion into the pi-basic calixarene cavity because the low affinity of the metal center for neutral ligand does not allow the endo-coordination of an exogenous guest. Hence, the calix[6]N(3)ArOH-based Zn complexes act as an acid-base switch for guest binding. Several aspects of this system appear reminiscent of Zn-peptidases of the astacin and serralisin families.


Three genes, lgtF, lic2C and lpsA, have a primary role in determining the pattern of oligosaccharide extension from the inner core of Haemophilus influenzae LPS.
Lipopolysaccharide (LPS) is a virulence determinant of Haemophilus influenzae and exhibits substantial heterogeneity in structure within and between strains. Key factors contributing to this heterogeneity are the genes required to add the first glycose to each of the three heptose residues of the LPS inner core. In each case this addition can facilitate further oligosaccharide extension. lgtF is invariably present in strains and the product has a function in adding the glucose to the first heptose. lic2C is present in half the strains and was found to add a glucose to the second heptose. Insertion of lic2C into a strain that does not naturally contain it resulted in hexose incorporation from the second heptose of the LPS. The product of the lpsA gene can add a glucose or galactose to the third heptose. By allelic replacement of lpsA between strains it is shown that the sequence of the gene can be the sole determinant of this specificity. Thus, lgtF, lic2C and lpsA make significant but very distinct contributions to the conservation and variable patterns of oligosaccharide extensions seen in H. influenzae LPS.


Vascular senescence and ageing: a role for the MEOX proteins in promoting endothelial dysfunction.
In the vascular system, ageing is accompanied by the accrual of senescent cells and is associated with an increased risk of vascular disease. Endothelial cell (EC) dysfunction is a hallmark of vascular disease and is characterized by decreased angiogenic potential, reduced nitric oxide bioavailability, impaired vasodilation, increased production of ROS, and enhanced inflammation. In ECs, the major producer of nitric oxide is the endothelial nitric oxide synthase (eNOS) enzyme that is encoded by the NOS3 gene. NOS3/eNOS function is tightly regulated at both the transcriptional and post-transcriptional levels to maintain normal vascular function. A key transcriptional regulator of eNOS expression is p53, which has been shown to play a central role in mediating cellular senescence and thereby vascular dysfunction. Herein, we show that, in ECs, the MEOX homeodomain transcription factors decrease the expression of genes involved in angiogenesis, repress eNOS expression at the mRNA and protein levels, and increase the expression of p53. These findings support a role for the MEOX proteins in promoting endothelial dysfunction.


Health related quality of life after orthotopic neobladder construction and its comparison with normative values in the Japanese population.
We report the difference in quality of life (QOL) between patients with an orthotopic neobladder and normative values in the age matched Japanese population. Between November 1996 and June 2003, 75 patients underwent orthotopic neobladder construction at our institution, of whom 47 males and 9 females were enrolled in this study. A total of 19 patients were excluded because of death or insufficient followup (less than 6 months). Two types of questionnaire, namely the RAND 36-Item Health Survey, version 2 and the Functional Assessment of Cancer Therapy-Bladder Cancer, were mailed to all 56 patients. The 48 patients (86%) who returned the completed forms were included in our analysis. Postoperative QOL was compared with age matched normative values in the control Japanese population. Overall there was no significant difference in any scale between patients with a neobladder and the age matched control Japanese population. The patient bodily pain score in the seventh decade of life and the role-physical score in those older than 70 years were better than age matched normative values in the Japanese population (p < 0.005 and p < 0.05, respectively). Male patients in the seventh decade of life were more likely to have better QOL in the physical functioning, role-physical and role-emotional subscales in addition to the bodily pain subscale compared to age matched control values (p < 0.05, < 0.05, < 0.001 and < 0.001, respectively). Likewise in male patients older than 70 years role-physical scores remained better than age matched normative values in the Japanese population (p < 0.01). Further analysis of bladder cancer related QOL showed that patients followed more than 24 months were more likely to have a lower incontinence score than those followed less than 24 months (p < 0.05). In addition, the continence related QOL change alone did not affect any health related QOL scales, as analyzed by RAND 36-Intem Health Survey. Our study shows that there is no essential difference in health related QOL between patients with a neobladder and the age matched Japanese control population. The current results provide some primary evidence to help in decision making and eliminate potential anxiety about worse QOL after cystectomy.


Is it SLE?
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease, as yet of unknown aetiology, with diverse clinical manifestations and a variable course and prognosis. The diagnosis is based on recognizing the overall pattern of clinical and laboratory abnormalities. However, even today, there is often a significant delay between onset of symptoms and diagnosis. Over the last two decades there has been great progress in identifying the profile of antinuclear antibodies that characterizes SLE, and in this chapter we describe how serological techniques can be important tools for the clinician in the early diagnosis of this disorder. Also described is the lupus band test, which has rather fallen out of favour as a diagnostic tool but which can still provide valuable evidence for the diagnosis in patients in whom the clinical and serological features are inconclusive. Nevertheless, because the presentation of lupus is protean, and the early manifestations are often non-specific, SLE can still be easily confused with a wide range of other conditions. Here, we describe some of the common clinical conundrums encountered in patients referred to the Lupus Clinic to 'rule out lupus', providing a framework for diagnosis. Finally, the chapter considers the major problem that clinicians who treat patients with SLE frequently face in distinguishing between a flare of lupus and infection. Diagnosis of SLE is still a great clinical challenge, and while it is important to recognize patients with potentially aggressive disease and treat them appropriately at an early stage it is also important to be able to recognize patients with potentially benign disease and avoid over-treatment.


Hierarchical recruitment by AMPA but not staurosporine of pro-apoptotic mitochondrial signaling in cultured cortical neurons: evidence for caspase-dependent/independent cross-talk.
Excitotoxicity mediated via the (S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtype of receptor for l-glutamate contributes to various neuropathologies involving acute brain injury and chronic degenerative disorders. In this study, AMPA-induced neuronal injury and staurosporine (STS)-mediated apoptosis were compared in primary neuronal cultures of murine cerebral cortex by analyzing indices up- and downstream of mitochondrial activation. AMPA-mediated apoptosis involved induction of Bax, loss of mitochondrial transmembrane potential (deltapsi(m)), early release of cytochrome c (cyt c), and more delayed release of second mitochondrial activator of caspases (SMAC), Omi, and apoptosis-inducing factor (AIF) with early calpain and minor late activation of caspase 3. STS-induced apoptosis was characterized by a number of differences, a more rapid time course, non-involvement of deltapsi(m), and relatively early recruitment of SMAC and caspase 3. The AMPA-induced rise in intracellular calcium appeared insufficient to evoke feltapsi(m) as release of cyt c preceded mitochondrial depolarization, which was followed by the cytosolic translocation of SMAC, Omi, and AIF. Bax translocation preceded cyt c release for both stimuli inferring its involvement in apoptotic induction. Inclusion of the broad spectrum caspase inhibitor zVAD-fmk reduced the AMPA-induced release of cyt c, SMAC, and AIF, while only affecting the redistribution of Omi and AIF in the STS-treated neurons. Only AIF release was affected by a calpain inhibitor (calpastatin) which exerted relatively minor effects on the progression of cellular injury. AMPA-mediated release of apoptogenic proteins was more hierarchical relative to STS with its calpain activation and caspase-dependent AIF redistribution arguing for a model with cross-talk between caspase-dependent/independent apoptosis.


Prefrontally-mediated alterations in the retrieval of negative events: Links to memory vividness across the adult lifespan.
Prior research has identified age-by-valence interactions in both behavior and neural recruitment; age has been associated with increased retrieval of positive relative to negative information as well as an increased tendency to recruit prefrontal regions during negative event retrieval and for this recruitment to correspond to decreased hippocampal connectivity. To date, the explicit relation between prefrontal recruitment and memory phenomenology has not been examined. The current study examined the link between these two measures by examining age-by-valence interactions in the relation between prefrontal recruitment and subjective ratings of memory vividness. Participants (ages 18-85) encoded visual images paired with verbal titles. During a scanned retrieval session, they were presented with titles and asked whether each had been seen with an image during encoding. Participants provided vividness ratings following retrieval of each image. Age was associated with greater prefrontally-mediated alterations in negative event phenomenology, with age-related increases in the relation between ventral prefrontal regions and negative event vividness and age-related decreases in the relation between dorsal prefrontal regions and negative event vividness. This analysis confirmed a critical role of PFC regions in age-by-valence interactions, where age reversed the relation between PFC recruitment and the subjective richness of retrieved memory representation. These findings are consistent with studies that reveal age-related enhancements in emotion regulation, and suggest that older adults may be engaging in these processes during retrieval of negative events.


New safety margins for chin bone harvesting based on the course of the mandibular incisive canal in CT.
Altered pulp sensitivity of anterior lower teeth is a frequent finding following chin bone harvesting. Persistent loss of tooth sensitivity has been reported in up to 20% of the patients. The aim of this study was to evaluate current recommendations for the location of the harvest zone with respect to the course of the mandibular incisive canal (MIC), the intrabony continuation of the mandibular canal mesial to the mental foramen. On computed tomographic (CT) scans of 50 dentate mandibles, the MIC was located and its distance to the root apices, to the labial bony surface, and to the inferior margin of the mandible was assessed. The risk of nerve injury and the percentage of patients suitable for chin bone grafting were calculated. Respecting current recommendations for chin bone grafting, the content of the MIC was endangered in 57% of the CTs. Therefore, new safety margins are suggested: the chin bone should be harvested at least 8 mm below the tooth apices with a maximum harvest depth of 4 mm. Applying the new safety recommendations and proper patient selection in chin bone harvesting could reduce the risk of altered postoperative tooth sensitivity due to injury of the mandibular incisive nerve.


Assessment of the Level of Pain Intensity and the Level of Anxiety Treated as State and Trait in Patients with Osteoarthritis of the Limbs.
Osteoarthritis of the musculoskeletal system is accompanied with chronic pain which is the main factor in mood lowering, causing anxiety. Rehabilitation conducted in the framework of spa therapy and outpatient care aims at eliminating or reducing pain and improving physical fitness. Pain relief is an expected phenomenon because it improves the quality of life. Aim of the study. The aim of the study was to evaluate the effect of rehabilitation in the spa and in outpatient clinic on the level of pain and anxiety in patients with degenerative joints and disc disease. Material and methods. The study included a comprehensive treatment conducted in the spa and in outpatient clinic. Observation included 120 persons with disorders of the musculoskeletal system treated in the spa Przerzeczyn-Zdrój. The second group of patients was treated in the rehabilitation clinic. The examinations were performed before and after treatment. The scope of the observations included self-evaluation of anxiety treated as a state and a trait, the level of intensity of pain, medical history, and sociodemographic background interview. In the observations, there were VAS scale and State Trait Anxiety Inventory STAI used. As a result of the spa therapy and therapy performed in an outpatient clinic, there was an improvement in lowering the level of pain and anxiety noted. 1. Spa therapy and treatment performed in an outpatient clinic reduce the level of pain and anxiety in patients with degenerative disease of the musculoskeletal system. 2. It was found that the therapy conducted in the spa was more effective in lowering the level of pain and anxiety. This trial is registered with NCT03405350.


An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly.
Spliced leader (SL) trans-splicing is a critical element of gene expression in a number of eukaryotic groups. This process is arguably best understood in nematodes, where biochemical and molecular studies in Caenorhabditis elegans and Ascaris suum have identified key steps and factors involved. Despite this, the precise details of SL trans-splicing have yet to be elucidated. In part, this is because the systematic identification of the molecules involved has not previously been possible due to the lack of a specific phenotype associated with defects in this process. We present here a novel GFP-based reporter assay that can monitor SL1 trans-splicing in living C. elegans. Using this assay, we have identified mutants in sna-1 that are defective in SL trans-splicing, and demonstrate that reducing function of SNA-1, SNA-2 and SUT-1, proteins that associate with SL1 RNA and related SmY RNAs, impairs SL trans-splicing. We further demonstrate that the Sm proteins and pICln, SMN and Gemin5, which are involved in small nuclear ribonucleoprotein assembly, have an important role in SL trans-splicing. Taken together these results provide the first in vivo evidence for proteins involved in SL trans-splicing, and indicate that continuous replacement of SL ribonucleoproteins consumed during trans-splicing reactions is essential for effective trans-splicing.


Children and adults successfully comprehend subject-only sentences online.
In many offline studies, children show selectively better comprehension of sentences with the focus particle only when it modifies the object argument (Jane only ate an apple) than they do when it modifies the subject argument (Only Jane ate an apple). Here we explore the nature of this asymmetry by examining performance in a different kind of task: the moment-to-moment comprehension of unambiguous sentences. If past errors reflect a fundamental difference in representation or complexity of computation, we would expect the same asymmetry in this task. We observed that adults were able to successfully predict the target referent for both types of only-sentences, as indicated by anticipatory looks, while 6- to 8-year-old children could do so only for subject-modifying only-sentences. These findings suggest that much of the asymmetry in past work may be due to task demands. We discuss the implications of these results for children's syntactic and pragmatic development.


Genetic parameters for large-scale behavior traits and type traits in Charolais beef cows.
In the last decades, beef cattle breeding mainly focused on improving production and reproduction traits. Nowadays, there is a growing interest to include behavior and type traits in the breeding goal. There is an interest in behavior as it is associated with human safety and workability and in type traits as they might be associated with longevity of cows. The objective of the current study was to estimate the heritability for behavior and type traits in Charolais and to estimate the genetic correlations among these traits. Behavior traits, including aggressiveness at parturition, aggressiveness during gestation period, and maternal care, were scored by farmers using an on-farm recording system to enable large-scale collection of phenotypes. Type traits, including udder traits ( = 3), teat traits (3), feet and leg traits (5), and locomotion (1), were scored by 10 trained classifiers. Data was available on 6,649 cows in parity 1 to 12 and located in 380 herds. Results showed that differences between herds explained up to 23% of the total phenotypic variance in behavior traits. This might be due to differences in management or to consistent differences in scoring between farmers. Aggressiveness at parturition had higher heritability (0.19) and higher genetic coefficient of variation (CV = 11%) than aggressiveness during gestation ( = 0.06 and CV = 4%) and maternal care ( = 0.02 and CV = 2%). Heritabilities for udder traits (0.14 to 0.20) and teat traits (0.17 to 0.35) were higher than for feet and leg traits (0.02 to 0.19). Genetic coefficients of variation for udder and teat traits were also higher (up to 21%) than for feet and leg traits (up to 11%). Strong genetic correlations were found between behavior traits (with absolute values from 0.71 to 0.98). The genetic correlations indicate that it is difficulty to simultaneously improve maternal care and reduce aggressiveness. We concluded that there are good opportunities to implement selection for improved udder and teat traits and against aggressiveness at parturition using a simple on-farm recording system of behavior.


Eudragit S100-Coated Chitosan Nanoparticles Co-loading Tat for Enhanced Oral Colon Absorption of Insulin.
In order to improve oral absorption of insulin, especially the absorption at the colon, Eudragit S100® (ES)-coated chitosan nanoparticles loading insulin and a trans-activating transcriptional peptide (Tat) were employed as the vehicle. In vitro releases of insulin and Tat from ES-coated chitosan nanoparticles had a pH-dependant characteristic. A small amount of the contents was released from the coated nanoparticles at pH 1.2 simulated gastric fluid, while a fairly fast and complete release was observed in pH 7.4 medium. Caco-2 cell was used as the model of cellular transport and uptake studies. The results showed that the cellular transport and uptake of insulin for ES-coated chitosan nanoparticles co-loading insulin and Tat (ES-Tat-cNPs) were about 3-fold and 4-fold higher than those for the nanoparticles loading only insulin (ES-cNPs), respectively. The evaluations in vivo of ES-Tat-cNPs were conducted on diabetic rats and normal minipigs, respectively. The experimental results on rats revealed that the pharmacodynamical bioavailability of ES-Tat-cNPs had 2.16-fold increase compared with ES-cNPs. After oral administration of nanoparticle suspensions to the minipigs, insulin bioavailability of ES-Tat-cNPs was 1.73-fold higher than that of ES-cNPs, and the main absorption site of insulin was probably located in the colon for the two nanoparticles. In summary, this report provided an exploratory means for the improvement of oral absorption of insulin.


Using localized surface plasmon resonances to probe the nanoscopic origins of adsorbate-driven ordering transitions of liquid crystals in contact with chemically functionalized gold nanodots.
We report that localized surface plasmon resonances (LSPRs) of gold nanodots immersed under liquid crystals (LCs) can be used to characterize adsorbate-induced ordering transitions of the LCs on the surfaces of the nanodots. The nanoscopic changes in ordering of the LCs, as measured by LSPR, were shown to give rise to macroscopic ordering transitions of the LCs that were observed by polarized light microscopy. The results reported herein suggest that (i) LCs may be useful for enhancing the sensitivity of LSPR-based detection of binding events and (ii) that LSPR measurements of gold nanodots provide a means to characterize the nanoscopic origins of macroscopic, adsorbate-induced LC ordering transitions.


Cytoprotection, proliferation and epidermal differentiation of adipose tissue-derived stem cells on emu oil based electrospun nanofibrous mat.
Electrospun nanofibrous scaffolds containing natural substances with wound healing properties such as Emu oil (EO) may have a great potential for increasing the efficiency of stem cell-based skin bioengineering. For this purpose, EO blended PCL/PEG electrospun nanofibrous mats were successfully fabricated and characterized using FE-SEM, FTIR and Universal Testing Machine. The efficiency of the scaffolds in supporting the adherence, cytoprotection, proliferation and differentiation of adipose tissue-derived stem cells (ADSCs) to keratinocyte was evaluated. GC/MS and HPLC were used to determine the composition of pure EO, which revealed to be mainly fatty acids and carotenoids. FE-SEM and cell proliferation assays showed that adhesion and proliferation of ADSCs on EO-PCL/PEG nanofibers was significantly higher than on PCL/PEG nanofibers. Additionally, EO-PCL/PEG nanofibers with free radical scavenging properties conferred a cytoprotective effect against cell-damaging free radicals, while the ability to support cell adhesion and growth was maintained or even improved. Immunostaining of ADSCs on EO-PCL/PEG nanofibers confirmed the change in morphology of ADSCs from spindle to polygonal shape suggesting their differentiation toward an epidermal linage. Moreover, the expression levels of the keratin 10, filaggrin, and involucrin that are involved in epidermal differentiation were upregulated in a stage-specific manner. This preliminary study shows that EO-PCL/PEG nanofibers could be a good candidate for the fabrication of wound dressings and skin bioengineered substitutes with ADSCs.


Eyewitness testimony in the Lockerbie bombing case.
It was in 1988 that a Pan Am flight blew up over Lockerbie, Scotland, killing 270 people. A Libyan named Al-Megrahi was convicted of the crime. His conviction was based in large part on the testimony of a single eyewitness, a shopkeeper who identified him as the person who had purchased clothing allegedly packed in the suitcase that contained the explosives that blew up the plane. But careful analysis of the eyewitness evidence leads to suspicions about the accuracy of the evidence. This analysis was presented to the Scottish Criminal Cases Review Commission which concluded that the conviction might have been a miscarriage of justice.


Bone-targeting drug delivery system of biomineral-binding liposomes loaded with icariin enhances the treatment for osteoporosis.
Osteoporosis is a bone-incapacitating malady and it is characterized by obvious bone mass loss and bone microarchitecture deterioration. Current treatments for osteoporosis have many limitations, including the non-obvious therapeutic effect and long-term safety issues. Icariin is a pharmacologically active flavonoid glycoside, which shows potential application in treatment of osteoporosis. But its clinical application is limited by the inherent disadvantages such as poor water solubility, first pass effect after oral administration, and low bioavailability. Moreover, due to lack of targeting ability, icariin cannot accumulate at the local diseased region to provide early protection from fractures. To solve the application problems of icariin and enhance its therapeutic effects on osteoporosis, this work aimed to design a targeting drug delivery system of biomineral-binding liposomes (BBL) mediated by pyrophosphate ions. Biomineral-binding liposomes enhanced the binding ability of liposomes with hydroxyapatite particles. It increased the serum level of alkaline phosphatase and reduced that of tartrate-resistant acid phosphatase 5b. Meanwhile, BBL increased the mechanical strength of femoral midshaft, preserving the trabecular bone microarchitecture. Moreover, BBL could initiate bone turnover/remodeling of rats with osteoporosis. This drug targeting delivery system of BBL loading with icariin showed more therapeutic advantages than the free icariin for the treatment of osteoporosis, which may be a kind of valid candidate in future osteoporosis therapy.