Evaluation of Radius Microstructure and Areal Bone Mineral Density Improves Fracture Prediction in Postmenopausal Women.
A majority of low-trauma fractures occur in subjects with only moderate decrease of areal bone mineral density (aBMD), ie, osteopenia, assessed by dual-energy X-ray absorptiometry (DXA) or low fracture probability assessed by FRAX. We investigated whether peripheral bone microstructure and estimated strength improve the prediction of incident fractures beyond central DXA and FRAX. In this population-based study of 740 postmenopausal women (aged 65.0 ± 1.4 years) from the Geneva Retirees Cohort (ISRCTN registry 11865958), we assessed at baseline cortical (Ct) and trabecular (Tb) volumetric bone mineral density (vBMD) and microstructure by peripheral quantitative computed tomography (HR-pQCT); bone strength by micro-finite element analysis; aBMD and trabecular bone score (TBS) by DXA; and FRAX fracture probability. Eighty-five low-trauma fractures occurred in 68 women over a follow-up of 5.0 ± 1.8 years. Tb and Ct vBMD and microstructure predicted incident fractures, independently of each other and of femoral neck (FN) aBMD and FRAX (with BMD ± TBS). However, the associations were markedly attenuated after adjustment for ultra-distal radius aBMD (same bone site). The best discrimination between women with and without fracture was obtained at the radius with total vBMD, the combination of a Tb with a Ct parameter, or with failure load, which improved the area under the curve (AUC) for major osteoporotic fracture when added to FN aBMD (0.760 versus 0.695, p = 0.022) or to FRAX-BMD (0.759 versus 0.714, p = 0.015). The replacement of failure load by ultra-distal aBMD did not significantly decrease the AUC (0.753, p = 0.747 and 0.750, p = 0.509, respectively). In conclusion, peripheral bone microstructure and strength improve the prediction of fractures beyond central DXA and FRAX but are partially captured in aBMD measured by DXA at the radius. Because HR-pQCT is not widely available for clinical purposes, assessment of ultra-distal radius aBMD by DXA may meanwhile improve fracture risk estimation. © 2017 American Society for Bone and Mineral Research.


Ebola Preparedness in the Netherlands: The Need for Coordination Between the Public Health and the Curative Sector.
During the Ebola outbreak in West Africa in 2014-2015, close cooperation between the curative sector and the public health sector in the Netherlands was necessary for timely identification, referral, and investigation of patients with suspected Ebola virus disease (EVD). In this study, we evaluated experiences in preparedness among stakeholders of both curative and public health sectors to formulate recommendations for optimizing preparedness protocols. Timeliness of referred patients with suspected EVD was used as indicator for preparedness. In focus group sessions and semistructured interviews, experiences of curative and public health stakeholders about the regional and national process of preparedness and response were listed. Timeliness recordings of all referred patients with suspected EVD (13) were collected from first date of illness until arrival in the referral academic hospital. Ebola preparedness was considered extensive compared with the risk of an actual patient, however necessary. Regional coordination varied between regions. More standardization of regional preparation and operational guidelines was requested, as well as nationally standardized contingency criteria, and the National Centre for Infectious Disease Control was expected to coordinate the development of these guidelines. For the timeliness of referred patients with suspected EVD, the median delay between first date of illness until triage was 2.0 days (range: 0-10 days), and between triage and arrival in the referral hospital, it was 5.0 hours (range: 2-7.5 hours). In none of these patients Ebola infection was confirmed. Coordination between the public health sector and the curative sector needs improvement to reduce delay in patient management in emerging infectious diseases. Standardization of preparedness and response practices, through guidelines for institutional preparedness and blueprints for regional and national coordination, is necessary, as preparedness for emerging infectious diseases needs a multidisciplinary approach overarching both the public health sector and the curative sector. In the Netherlands a national platform for preparedness is established, in which both the curative sector and public health sector participate, in order to implement the outcomes of this study.


Palladium-catalyzed amination of aryl and heteroaryl tosylates at room temperature.
Mild palladium-catalyzed aminations of aryl tosylates and the first aminations of heteroaryl tosylates are described. In the presence of the combination of L2Pd(0) (L = P(o-tol)3) and the hindered Josiphos ligand CyPF-t-Bu, a variety of primary alkylamines and arylamines react with both aryl and heteroaryl tosylates at room temperature to form the corresponding secondary arylamines in high yields with complete selectivity for the monoarylamine. These reactions at room temperature occur in many cases with catalyst loadings of 0.1 mol % and 0.01 mol % in one case, constituting the most efficient aminations of aryl tosylates by nearly 2 orders of magnitude. This catalyst is made practical by the development of a convenient method to synthesize the L2Pd(0) precursor. This complex is stable to air as a solid. In contrast to conventional relative rates for reactions of aryl sulfonates, the reactions of aryl tosylates are faster than parallel reactions of aryl triflates, and the reactions of aryl tosylates are faster than parallel or competitive reactions of aryl chlorides.


One-step generation of cell-laden microgels using double emulsion drops with a sacrificial ultra-thin oil shell.
Cell-laden microgels with highly uniform sizes have significant potential in tissue engineering and cell therapy due to their capability to provide a physiologically relevant three-dimensional (3D) microenvironment for living cells. In this work, we present a simple and efficient microfluidic approach to produce monodisperse cell-laden microgels through the use of double emulsion drops with an ultra-thin oil shell as the sacrificial template. Specifically, the thin oil shell in double emulsion spontaneously dewets upon polymerization of the innermost precursor drop and subsequent transfer into an aqueous solution, resulting in direct dispersion of microgels in the aqueous phase. Compared to conventional single emulsion-based techniques for cell encapsulation, this one-step approach prevents prolonged exposure of cells to the oil phase, leading to high-throughput cell encapsulation in microgels without compromising the cell viability. Moreover, this approach allows us to culture cells within a 3D microgel which mimics the extracellular matrix, thus enabling long-term cell functionality. This microfluidic technique represents a significant step forward in high-throughput cell microencapsulation technology and offers a potentially viable option to produce cell-laden microgels for widespread applications in tissue engineering and cell therapies.


[Early diagnosis of vision disorders].
In recent years some pilot-studies were performed at health centres in Amsterdam, on infants of 8-9 months of age, concerning early detection of visual disorders. The method consisted of a programme of corneal light reflexes, cover test, monocular following movements and inspection of the cornea, the pupil and the pupillary reaction. The aim of the studies was: 1. Is this programme efficient for early detection of organic eye disorders and strabismus at this age? 2. Is the method reliable, if performed by doctors of the health centres? The results of the studies were positive. In at least 1,9% of the 1200 children of the pilot-study a visual disorder was detected. The method can be incorporated in the regular working scheme of the health centres and can be performed on infants from the age of 6 1/2 months.


[End-to-end anastomosis as a method of choice in right hemicolectomy].
The newest and long-term results of treatment of 239 patients were analyzed in whom right hemicolectomy with ileotransverse anastomoses "end-to side", "side-to side" and "end-to-end" were fulfilled. When estimating the results, the data of original methods developed and tested in the clinic were used for studying the motility and bioelectrical activity of the intestine in addition to clinical parameters. The main regularities of the development of postoperative complications were found in randomized groups. It was established that choice of the optimum variant of the anastomosis in right hemicolectomy was dependent on the understanding of pathophysiological consequences of either intestinal anastomosis. The anastomosis "end-to-end" is the quickest to fulfil, less traumatic and safe of the 3 types of ileotransverse anastomosis.


Annual changes of bacterial mortality due to viruses and protists in an oligotrophic coastal environment (NW Mediterranean).
The impact of viruses and protists on bacterioplankton mortality was examined monthly during 2 years (May 2005-April 2007) in an oligotrophic coastal environment (NW Mediterranean Sea). We expected that in such type of system, (i) bacterial losses would be caused mainly by protists, and (ii) lysogeny would be an important type of virus-host interaction. During the study period, viruses and grazers together were responsible for 50.6 +/- 40.1% day(-1) of bacterial standing stock losses (BSS) and 59.7 +/- 44.0% day(-1) of bacterial production losses (BP). Over the first year (May 2005-April 2006), protists were the principal cause of bacterial mortality, removing 29.9 +/- 20.4% day(-1) of BSS and 33.9 +/- 24.3% day(-1) of BP, whereas viral lysis removed 13.5 +/- 17.0% day(-1) of BSS and 12.3 +/- 12.3% day(-1) of BP. During the second year (May 2006-April 2007), viruses caused comparable bacterial losses (29.2 +/- 14.8% day(-1) of BSS and 40.9 +/- 20.7% day(-1) of BP) to protists (28.6 +/- 25.5% day(-1) of BSS and 32.4 +/- 20.0% day(-1) of BP). In 37% of cases higher losses of BP due to viruses than due to protists were found. Lysogenic infection was detected in 11 of 24 samplings. Contrary to our expectations, lytic infections dominated over the two years, and viruses resulted to be a significant source of bacterial mortality in this oligotrophic site.


Multiscale biophysical models of cardiomyopathies reveal complexities challenging existing dogmas.
Mutations in sarcomeric proteins, including myosin, cause a variety of cardiomyopathies. A prominent hypothesis has been that myosin mutations causing hypercontractility of the motor lead to hypertrophic cardiomyopathy, while those causing hypocontractility lead to dilated cardiomyopathy; however, recent biophysical studies using multiscale computational and experimental models have revealed complexities not captured by this hypothesis. We summarize recent publications in Biophysical Journal challenging this dogma and highlighting the need for multiscale modeling of these complex diseases.


Ovulation rate and inhibin levels in gonadotrophin-treated mice.
Ovarian follicular growth was induced in immature female mice with varying doses of pregnant mare's serum gonadotrophin. The numbers of ovulations were determined either by counting tubal oocytes or corpora lutea in the ovary. Ovarian and circulatory levels of inhibin rose progressively with increasing doses of PMSG and a positive correlation (P less than 0.01) was found between circulating inhibin levels and ovulation rate. The latter correlation makes it likely that the growing preovulatory ovarian follicles are the predominant source for the secretion of inhibin into the circulatory system.


Dynamics of spread of HIV-I infection in a rural district of Uganda.
To define the geographical distribution of HIV infection and the community characteristics associated with HIV prevalence in a rural population of Uganda. Seroprevalence survey and interviews of the population aged 13 years and older in 21 randomly selected clusters. Rural population of Rakai district, south west Uganda. 1292 adults, of whom 594 men and 698 women gave a blood sample and answered the questionnaire. HIV status determined by ELISA and western blotting in relation to community characteristics. The weighted seroprevalence of HIV for the district was 12.6% with prevalence by cluster varying from 1.2% to 52.8%. Seroprevalence was highest in main road trading centres (men 26%, women 47%), intermediate in rural trading villages on secondary roads (men 22%, women 29%), and lowest in rural agricultural villages (men 8%, women 9%). For both men and women, multiple regression showed a strong negative association between cluster seroprevalence and the proportion of the population employed in agriculture (beta = -0.677 for men, -0.807 for women). Among women, cluster seroprevalence increased with a higher proportion of the population reporting multiple sex partners (beta = 0.814), external travel (beta = 0.579), and injections (beta = 0.483). Community characteristics, particularly the proportion of the population in agriculture, are associated with HIV prevalence and can be used for targeting interventions. The seroprevalences of HIV suggest spread of infection from main road trading centres, through intermediate trading villages, to rural agricultural villages.


Optimization of targeted RNA recombination and mapping of a novel nucleocapsid gene mutation in the coronavirus mouse hepatitis virus.
We have recently described a method of introducing site-specific mutations into the genome of the coronavirus mouse hepatitis virus (MHV) by RNA recombination between cotransfected genomic RNA and a synthetic subgenomic mRNA (C. A. Koetzner, M. M. Parker, C. S. Ricard, L. S. Sturman, and P. S. Masters, J. Virol. 66:1841-1848, 1992). By using a thermolabile N protein mutant of MHV (Alb4) as the recipient virus and synthetic RNA7 (the mRNA for the nucleocapsid protein N) as the donor, we selected engineered recombinant viruses as heat-stable progeny resulting from cotransfection. We have now been able to greatly increase the efficiency of targeted recombination in this process by using a synthetic defective interfering (DI) RNA in place of RNA7. The frequency of recombination is sufficiently high that, with Alb4 as the recipient, recombinants can be directly identified without using thermal selection. The synthetic DI RNA has been used to demonstrate that the lesion in another temperature-sensitive and thermolabile MHV mutant, Alb1, maps to the N gene. Sequencing of the Alb1 N gene revealed two closely linked point mutations that fall in a region of the N molecule previously noted as being the most highly conserved region among all of the coronavirus N proteins. Analysis of revertants of the Alb1 mutant revealed that one of the two mutations is critical for the temperature-sensitive phenotype; the second mutation is phenotypically silent.


The combined effect of calcium channel blocker Lercanidipine and antioxidants on low-grade systemic inflammation parameters in essential hypertension patients.
The influence of oxidative stress (OS) and inflammation on up-regulation of blood pressure (BP) has been well established. Peripheral polymorphonuclear leukocytes (PMNLs) are primed in essential hypertension (EH) patients, releasing uncontrolled superoxide anion contributing to OS in these patients. PMNL priming correlates with PMNL intracellular calcium [Ca2+]i. Previous studies have shown that treatment by calcium channel blockers lowers BP, OS and inflammation. In the same time, there are some trials showing down regulation influence of ''anti-oxidative'' drugs as Vitamin E and C to inflammation and OS. The data of clinical significance of anti-oxidative drugs to BP is controversial. The aim of this paper was to evaluate the benefit of combined treatment by calcium channel blockers (Lercanidipine) and antioxidative drugs (Vitamins C and E) on BP and on parameters of inflammation and OS. Sixteen new diagnosed patients with mild to moderate BP were sampled to 2 groups after randomization by age, sex, and mean arterial pressure (MAP), cholesterol and glucose level. The first group was treated by Lercanidip-ine only, the second group by combination of Lercanidipine and antioxidative drugs both for 6 months. PMNL priming was assessed by the rate of superoxide release from separated, phorbol ester-stimulated PMNLs and by PMNL-CD11b level. Inflammation was reflected by plasma C-reactive protein (CRP) and albumin levels, white blood cells (WBC) and PMNL counts and by PMNL apoptosis. In both groups, BP decreased after 6 months of treatment, and in a more pronounced manner following the combined treatment. In both groups PMNL priming parameters remained unchanged after 6 months of treatment, with transient differences between the two groups during the experimental period. In both groups inflammation parameters remained unchanged after 6 months of treatment, without difference between the two groups, except a pronounced decrease in the percentage of apoptotic PMNLs in the combined treatment group. Our trial shows a clinical benefit combining calcium channel blockers treatment with antioxidants in BP treatment, although it did not reveal significant influence of complementation of antioxidants to calcium channel blockers on OS and inflammation parameters. Additional clinical and laboratory investigations are needed to clear this issue. Conflicting data are reported on the influence of vitamins E and C on OS and inflammation together with controversy regarding anti-oxidative drugs and their effect on BP.


Behavioral science in video games for children's diet and physical activity change: key research needs.
Innovative intervention programs are needed to overcome the limitations in previous programs that promoted change in diabetes risk behaviors in children. Serious video games show promise of changing dietary and physical activity behaviors, but research is needed on the optimal design of behavior-change procedures in video games, the mechanisms that account for changes obtained, and the groups in which these interventions work best. Such research will permit the optimal design of serious video games for diabetes and obesity prevention in the future.


Trophallaxis-inspired model for distributed transport between randomly interacting agents.
Trophallaxis, the regurgitation and mouth to mouth transfer of liquid food between members of eusocial insect societies, is an important process that allows the fast and efficient dissemination of food in the colony. Trophallactic systems are typically treated as a network of agent interactions. This approach, though valuable, does not easily lend itself to analytic predictions. In this work we consider a simple trophallactic system of randomly interacting agents with finite carrying capacity, and calculate analytically and via a series of simulations the global food intake rate for the whole colony as well as observables describing how uniformly the food is distributed within the nest. Our model and predictions provide a useful benchmark to assess to what level the observed food uptake rates and efficiency in food distribution is due to stochastic effects or specific trophallactic strategies by the ant colony. Our work also serves as a stepping stone to describing the collective properties of more complex trophallactic systems, such as those including division of labor between foragers and workers.


CT screening and follow-up of lung nodules: effects of tube current-time setting and nodule size and density on detectability and of tube current-time setting on apparent size.
The purpose of the study was to quantify and compare the effect of CT dose and of size and density of nodules on the detectability of lung nodules and to quantify the influence of CT dose on the size of the nodules. From 50 patients a total of 125 cuboidal regions of interest (3 × 3 × 1.5 cm volumes) showing a single nodule (≤ 8 mm) and 27 normal cuboids were selected. Image sets were reconstructed with the software from raw data simulating different dose levels: 300 (original dose), 220, 180, 140, 100, 80, 60, 50, 40, 30, 20, 10, and 5 reference mAs. A logistic regression model was used to analyze detectability for three blinded readers. Odds ratios were calculated for nodule size smaller than 3 mm versus 3 mm and larger and for nodule attenuation of -300 HU and greater versus less than -300 HU. Tube current-time settings of 10 mAs and greater were not associated with a significant difference in individual reader sensitivity compared with the standard setting of 300 mAs. At 5 mAs only one reader had a significant decrease in sensitivity, from 82% to 77% (p = 0.0035). According to the odds ratios and logistic regression results, the strongest negative effect on sensitivity can be assumed for low nodule density followed by small nodule size and dose level. The mean nodule volume measurement error between 5 and 300 mAs was 2.2% ± 18% (SD) and much lower than the interobserver volume measurement error rate of 38% ± 45%. The results show the feasibility of a low-dose CT protocol at 10 mAs for follow-up of lung nodules. Computer-aided volume measurement in follow-up of lung nodules decreases interobserver variability.


Characteristics of substance-abusing women on welfare. Findings from the evaluation of CASAWORKS for Families pilot demonstration.
To describe and compare the characteristics and needs of substance-abusing women on Temporary Assistance to Needy Families (TANF) who enroll in a multi-service "welfare to work" program (n = 673) with two other relevant groups: (a) women from the general TANF population in the same locales (n = 157) and (b) a sample of substance-abusing women on TANF who entered standard outpatient substance-abuse treatment programs (n = 520). A field study with repeated measures and intent-to-treat sampling. The CASAWORKS for Families (CWF) program was delivered in 11 sites in 9 states across the country. The CWF intervention featured integration of substance-abuse treatment and employment-work readiness services, using case management to tailor needed services (parenting, victimization, mental health, physical health, legal, and basic needs). The Addiction Severity Index, supplemented with subject-appropriate questions, was used at treatment admission. The CWF sample exhibited multiple serious problems in the areas of substance abuse, victimization, medical and psychiatric health, and basic needs. The severity of their lifetime problems and their recent service needs were significantly higher in all these areas, except physical health, than were those of the general welfare sample of women in the same locales. Compared with women on TANF from standard addiction-treatment programs, CWF women exhibited similar substance-use problems but generally more severe co-occurring problems.


Measuring High-Resolution Sleep Position in Adolescents over 4 Nights with Smartphone Accelerometers.
Sleep position affects sleep quality and the severity of different diseases. Classical methods to measure sleep position are complex, expensive, and difficult to use outside the laboratory. Wearables and smartphones can help to address these issues to track sleep position at home over several nights. In this study, we monitor high-resolution sleep position in 13 adolescents over 4 nights using smartphone accelerometer data. We aim to investigate the distribution of sleep positions and position changes in adolescents, study their variability across nights, and propose new measures related to nocturnal body movements. We developed a new index, the mean sleep angle change per hour, and calculated three other measures: position shifts per hour, mean time at each position, and periods of immobility. Our results indicate that participants spent 56% of the time on the side (32% right and 24% left), 32% in supine, and 12% in prone position, similar to what happens in adults. However, adolescents moved more than adults during sleep according to all measures. There was some variability between nights, but lower than the inter-subject variability. In conclusion, this work systematically analyzes sleep position over several nights in adolescents, a largely unstudied population, and offers innovative solutions and measures for high-resolution sleep position monitoring in a simple and cost-effective way.Clinical Relevance- Our study characterizes sleep position in adolescents and provides novel unobtrusive methods and quantitative indices to monitor high-resolution sleep position at home during multiple nights.


The 5-year risk of MS after optic neuritis. Experience of the optic neuritis treatment trial.
The objective of our study was to assess the 5-year risk of and prognostic factors for the development of clinically definite multiple sclerosis (CDMS) following optic neuritis. In a prospective cohort study design, 388 patients, who did not have probable or definite MS at study entry enrolled in the Optic Neuritis Treatment Trial between 1988 and 1991, and were followed for the development of CDMS. The 5-year cumulative probability of CDMS was 30% and did not differ by treatment group. Neurologic impairment in the patients who developed CDMS was generally mild. Brain MRI performed at study entry was a strong predictor of CDMS, with the 5-year risk of CDMS ranging from 16% in the 202 patients with no MRI lesions to 51% in the 89 patients with three or more MRI lesions. Independent of brain MRI, the presence of prior nonspecific neurologic symptoms was also predictive of the development of CDMS. Lack of pain, the presence of optic disk swelling, and mild visual acuity loss were features of the optic neuritis associated with a low risk of CDMS among the 189 patients who had no brain MRI lesions and no history of neurologic symptoms or optic neuritis in the fellow eye. The 5-year risk of CDMS following optic neuritis is highly dependent on the number of lesions present on brain MRI. However, even a normal brain MRI does not preclude the development of CDMS. In these patients with no brain MRI lesions, certain clinical features identify a subgroup with a particularly low 5-year risk of CDMS.


Correlates of obsessive-compulsive and related disorders symptom severity during the COVID-19 pandemic.
We investigated changes in the severity of obsessive-compulsive and related disorders (OCRDs) symptoms as a result of the COVID-19 pandemic. An Amazon Mechanical Turk sample of 829 individuals was evaluated with a series of instruments assessing the severity of the OCRDs before and during the pandemic. Additional questionnaires about sociodemographic factors, personal and family histories of OCRD, COVID-19 related events, compulsivity and impulsivity traits, schizotypal symptoms, and the severity of depression, anxiety and stress levels, were also used. Participants reported that OCD, hoarding disorder (HD) and skin picking disorder (SPD) symptoms significantly worsened during the pandemic along with increased disability, more affective symptoms and reduced quality of life. Female gender, a higher number of COVID-19 related stressful events, and higher pre-COVID-19 fear of harm and symmetry symptoms predicted more severe OCD symptoms during the pandemic, whereas lack of a HD diagnosis by a mental health professional and more severe schizotypal symptoms predicted worsened hoarding symptoms. Greater compulsivity traits were associated with more severe COVID-19 pandemic obsessive-compulsive and hoarding symptoms. These data indicate that the immense distress resulting from the COVID-19 included significant deterioration of OCRDs' symptoms, particularly of OCD, HD and SPD. It was also possible to identify a pre-pandemic profile of people most at risk of pandemic-related deterioration in OCRDs' symptoms, which may prove valuable for preventative initiatives in relation to the likely future waves of COVID-19 or of other communicable diseases. Future studies should follow up these findings longitudinally.


NODULATION FACTOR FOR RHIZOBIUM-LEGUME SYMBIOSIS.
Valera, Concepcion L. (Cornell University, Ithaca, N.Y.), and M. Alexander. Nodulation factor for Rhizobium-legume symbiosis. J. Bacteriol. 89:1134-1139. 1965.-Nodulation of excised roots of Medicago sativa was enhanced by an extract of alfalfa seeds but not by several other substances. Coconut water exerted a similar influence upon the formation of nodules on excised roots of Glycine max and Phaseolus vulgaris. Direct evidence for a host factor concerned in nodule genesis was obtained by demonstrating that, although P. vulgaris seedlings developing from embryos devoid of cotyledons nodulated in the presence of an infective Rhizobium strain, nodules did not appear on explants derived from hypocotyls obtained from ungerminated seed. The legume factor, when examined by a soybean hypocotyl bioassay procedure, could be replaced by a water-soluble, thermostable, dialyzable fraction of coconut water, but not by meso-inositol, scyllitol, sorbitol, yeast extract, or a number of amino acids.


Functional analysis of a cell cycle-associated, tumor-suppressive gene, protein tyrosine phosphatase receptor type G, in nasopharyngeal carcinoma.
Functional studies to identify the potential role of a chromosome 3p14-21 gene, protein tyrosine phosphatase receptor type G (PTPRG), were performed. PTPRG was identified as a candidate tumor suppressor gene (TSG) in nasopharyngeal carcinoma (NPC) by differential gene profiling of tumorigenic and nontumorigenic NPC chromosome 3 microcell hybrids (MCH). Down-regulation of this gene was found in tumor segregants when compared with their corresponding tumor-suppressive MCHs, as well as in NPC cell lines and tumor biopsies. Promoter hypermethylation and loss of heterozygosity were found to be important mechanisms contributing to PTPRG silencing. PTPRG overexpression in NPC cell lines induces growth suppression and reduced anchorage-independent growth in vitro. This is the first study to use a tetracycline-responsive vector expression system to study PTPRG stable transfectants. Results indicate its ability to induce significant tumor growth suppression in nude mice under conditions activating transgene expression. These studies now provide functional evidence indicating critical interactions of PTPRG in the extracellular matrix milieu induce cell arrest and changes in cell cycle status. This is associated with inhibition of pRB phosphorylation through down-regulation of cyclin D1. These novel findings enhance our current understanding of how PTPRG may contribute to tumorigenesis.


A Mineralized Collagen-Polycaprolactone Composite Promotes Healing of a Porcine Mandibular Defect.
A tissue engineering approach to address craniofacial defects requires a biomaterial that balances macro-scale mechanical stiffness and strength with the micron-scale features that promote cell expansion and tissue biosynthesis. Such criteria are often in opposition, leading to suboptimal mechanical competence or bioactivity. We report the use of a multiscale composite biomaterial that integrates a polycaprolactone (PCL) reinforcement structure with a mineralized collagen-glycosaminoglycan scaffold to circumvent conventional tradeoffs between mechanics and bioactivity. The composite promotes activation of the canonical bone morphogenetic protein 2 (BMP-2) pathway and subsequent mineralization of adipose-derived stem cells in the absence of supplemental BMP-2 or osteogenic media. We subsequently examined new bone infill in the acellular composite, scaffold alone, or PCL support in 10 mm dia. ramus mandibular defects in Yorkshire pigs. We report an analytical approach to quantify radial, angular, and depth bone infill from micro-computed tomography data. The collagen-PCL composite showed improved overall infill, and significantly increased radial and angular bone infill versus the PCL cage alone. Bone infill was further enhanced in the composite for defects that penetrated the medullary cavity, suggesting recruitment of marrow-derived cells. These results indicate a multiscale mineralized collagen-PCL composite offers strategic advantages for regenerative repair of craniofacial bone defects.


Immune response and biochemistry of calves immunized with rMSP1a ( Anaplasma marginale) using carbon nanotubes as carrier molecules.
Vaccination against Anaplasma marginale has been considered an important control strategy for bovine anaplasmosis. Recently, mice immunized with rMSP1 a linked to carbon nanotubes (MWNT) showed significant immune responses, generating a new possibility for use of an inactivated vaccine. The objective of this study was to investigate the cellular and humoral responses in calves immunized with MWNT+rMSP1a , associated with inactivated vaccine of A. marginale produced in vitro, and evaluate the toxic effects of the MWNT on renal and hepatic function. rMSP1a was covalently linked to MWNT. Inactivated vaccine (AmUFMG2) was produced by cultivating A. marginale in IDE8 cells. Twenty-four Holstein calves were divided (four groups) and immunized subcutaneously with PBS and non-carboxylated MWNT (control, G1), AmUFMG2 (G2), MWNT+rMSP1a (G3), and AmUFMG2 with MWNT+rMSP1a (G4). Blood samples were collected for total leukocyte counts, biochemical profiling and evaluation of the cellular and humoral response. Immunization with MWNT+rMSP1a induced increase in the total number of leukocytes, NK cells, in the lymphocyte populations and higher levels of antibodies compared to calves immunized only with AmUFMG2. Furthermore, MWNT did not induce changes in the biochemical profile. These data indicate that MWNT+rMSP1a were able to induce the immune responses more efficiently than AmUFMG2 alone, without generating toxicity.


Dynamic profiling of immune microenvironment during anti-PD-1 immunotherapy for head and neck squamous cell carcinoma: the IPRICE study.
Immune checkpoint inhibitors of programmed cell death protein 1 (PD-1) represent a significant breakthrough in treating head and neck squamous cell carcinoma (HNSCC), with long-lasting responses and prolonged survival observed in first- and second-line therapy. However, this is observed in < 20% of patients and high primary/secondary resistance may occur. The primary objective of the identification of predictive factors for the response to anti-PD-1 immunotherapy in head and neck squamous cell carcinoma (IPRICE) study is to identify predictive factors of response to anti-PD-1 immunotherapy. The IPRICE study is a single-center, prospective, non-randomized, open-label, and interventional clinical trial. Liquid and tumor biopsies will be performed in 54 patients with recurrent/metastatic (R/M) HNSCC undergoing anti-PD-1 immunotherapy alone to compare the evolution of gene expression and immunological profile between responders and non-responders. We will use a multidisciplinary approach including spatial transcriptomics, single seq-RNA analysis, clinical data, and medical images. Genes, pathways, and transcription factors potentially involved in the immune response will also be analyzed, including genes involved in the interferon-gamma (IFN-γ) pathway, immunogenic cell death and mitophagy, hypoxia, circulating miRNA-mediated immunomodulation, cytokines, and immune repertoire within the tumor microenvironment (TME). With a follow-up period of 3-years, these data will help generate effective biomarkers to define optimal therapeutic strategy and new immunomodulatory agents based on a better understanding of primary/secondary resistance mechanisms. Tumor biopsy will be performed initially before the start of immunotherapy at the first tumor assessment and is only proposed at tumor progression. Clinical data will be collected using a dedicated Case Report Form (CRF). Identifying predictive factors of the response to anti-PD-1 immunotherapy and optimizing long-term immune response require a thorough understanding of the intrinsic and acquired resistance to immunotherapy. To achieve this, dynamic profiling of TME during anti-PD-1 immunotherapy based on analysis of tumor biopsy samples is critical. This will be accomplished through the anatomical localization of HNSCC, which will allow for the analysis of multiple biopsies during treatment and the emergence of breakthrough technologies including single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. Clinicaltrial.gov. Registered April 14, 2022, https://www. gov/study/NCT05328024 .


Insulin stimulates the release of the glycosyl phosphatidylinositol-anchored membrane dipeptidase from 3T3-L1 adipocytes through the action of a phospholipase C.
Membrane dipeptidase (MDP; EC 184.108.40.206) enzymic activity that was inhibited by cilastatin has been detected on the surface of 3T3-L1 cells. On differentiation of the cells from fibroblasts to adipocytes the activity of MDP increased 12-fold. Immunoelectrophoretic blot analysis indicated that on adipogenesis the increase in the amount of MDP preceded the appearance of GLUT-4. MDP on 3T3-L1 adipocytes was anchored in the bilayer by a glycosyl phosphatidylinositol (GPI) moiety as evidenced by its release into the medium in a hydrophilic form on treatment of the cells with bacterial phosphatidylinositol-specific phospholipase C and the appearance of the inositol 1,2-cyclic monophosphate cross-reacting determinant. Incubation of 3T3-L1 adipocytes with either insulin or the sulphonylurea glimepiride led to a rapid concentration- and time-dependent release of MDP from the cell surface. The hydrophilic form of MDP released from the cells on stimulation with insulin was recognized by antibodies against the inositol 1,2-cyclic monophosphate cross-reacting determinant, indicating that it had been generated by cleavage of its GPI anchor through the action of a phospholipase C.


The relationship of vitamin D status to risk of cardiovascular disease and mortality.
Vitamin D is essential for bone mineralisation, but a growing body of evidence points at a broader role; vitamin D deficiency has been found to be associated with mortality and several diseases ranging from cardiovascular disease to autoimmune diseases and liver diseases. The evidence is, however, inconclusive and the possible pathways remain unresolved. The aims of the thesis were to investigate the association of vitamin D status to 5-year changes in cardiovascular risk factors such as blood pressure, lipid profile, the metabolic syndrome and urine albumin creatinine ratio (UACR); the association of a known genetic determinant of vitamin D status to cardiovascular risk factors; the association of vitamin D status to the incidence of cardiovascular disease (CVD) and all-cause mortality; and the association of vitamin D status to cause-specific mortality. Data from the 3 population-based studies Monica10 (n = 2,656, 1993-94), Inter99 (n = 6,794, 1999-2001) and Health2006 (n = 3,471, 2006-2008) conducted at the Research Centre for Prevention and Health were used. The studies included questionnaires, physical examinations, and blood tests. Vitamin D status was measured at baseline. Participants were genotyped for the most frequent filaggrin mutations. Registry-based diagnoses and causes of death were obtained from The Danish National Patient Register and the Danish Registry of Causes of Death, respectively. Linear, logistic, Cox and instrumental variable regressions were used to model the associations between vitamin D status and cardiovascular risk factors, disease and mortality. With a 10 year mean follow-up time, we found a significant association between vitamin D status and all-cause mortality with a HR=0.95 (p = 0.005) per 10 nmol/l higher vitamin D level. We found no association between vitamin D status and incidence of ischaemic heart disease or stroke (HR = 1.01, p = 0.442 and HR = 1.00, p = 0.920, respectively). We found a baseline level of vitamin D that was 10 nmol/l higher to be associated with a decrease in triglycerides and very low density lipoprotein cholesterol by 0.52% (p = 0.03) and 0.66% (p = 0.005), respectively. The odds ratios per 10 nmol/l higher baseline vitamin D level were 0.95 (p < 0.05) and 0.94 (p = 0.01) for the development of the metabolic syndrome and hypercholesterolaemia, respectively. There was no association between vitamin D and blood pressure. With filaggrin genotype as an instrumental variable, we found a 23.8% (95% confidence interval, CI: 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were no longer statistically significant when applying the Bonferroni-adjusted significance level. The remaining lipids showed non-significant changes in a favourable direction. A doubling of vita-min D gave a non-significantly lower odds ratio = 0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure or anthropometrics. With a total of 832 deaths and a 10.3 year median follow-up time, we found significant associations between vitamin D status and death caused by respiratory diseases, digestive diseases, and endocrine, nutritional and metabolic diseases with hazard ratios (HRs) 0.26 (ptrend = 0.0042), 0.28 (ptrend = 0.0040), and 0.21 (ptrend = 0.035), respectively, for the fourth vitamin D quartile compared to the first. We found non-significantly lower HRs for death caused by mental and behavioural diseases and diseases of the nervous system, but no association between vitamin D status and death caused by diseases of the circulatory system or neoplasms. We found a baseline level of vitamin D that was 10 nmol/l higher was associated with a small but statistically significant decrease in UACR by 0.92% (p = 0.02), but a non-significantly lower PTH. The odds ratio for an increased UACR were 0.96 (p = 0.0006) per 10 nmol/l higher baseline vitamin D level. Our studies support the idea that vitamin D can affect lipid status in a favourable direction as well as the incidence of metabolic syndrome and increased UACR but neither blood pressure nor anthropometrics. Vitamin D status was inversely associated with mortality, but this was not explained by an association with cardiovascular disease. Rather, the association seemed to be caused by an inverse association with death caused by digestive disease, endocrine, metabolic and nutritional diseases, and respiratory disease. Further studies, e.g. RCTs or Mendelian randomisation studies, are needed to clarify whether low vitamin D status is a causal and reversible factor to prevent disease and mortality.


Energy-based adaptive focusing of waves: application to noninvasive aberration correction of ultrasonic wavefields.
An aberration correction method based on the maximization of the wave intensity at the focus of an emitting array is presented. The potential of this new adaptive focusing technique is investigated for ultrasonic focusing in biological tissues. The acoustic intensity is maximized noninvasively through direct measurement or indirect estimation of the beam energy at the focus for a series of spatially coded emissions. For ultrasonic waves, the acoustic energy at the desired focus can be indirectly estimated from the local displacements induced in tissues by the ultrasonic radiation force of the beam. Based on the measurement of these displacements, this method allows determination of the precise estimation of the phase and amplitude aberrations, and consequently the correction of aberrations along the beam travel path. The proof of concept is first performed experimentally using a large therapeutic array with strong electronic phase aberrations (up to 2pi). Displacements induced by the ultrasonic radiation force at the desired focus are indirectly estimated using the time shift of backscattered echoes recorded on the array. The phase estimation is deduced accurately using a direct inversion algorithm which reduces the standard deviation of the phase distribution from sigma = 1.89 radian before correction to sigma = 0.53 radian following correction. The corrected beam focusing quality is verified using a needle hydrophone. The peak intensity obtained through the aberrator is found to be -7.69 dB below the reference intensity obtained without any aberration. Using the phase correction, a sharp focus is restored through the aberrator with a relative peak intensity of -0.89 dB. The technique is tested experimentally using a linear transmit/receive array through a real aberrating layer. The array is used to automatically correct its beam quality, as it both generates the radiation force with coded excitations and indirectly estimates the acoustic intensity at the focus with speckle tracking. This technique could have important implications in the field of high-intensity focused ultrasound even in complex configurations such as transcranial, transcostal, or deep seated organs.


trans-Hydrogenation: application to a concise and scalable synthesis of brefeldin A.
The important biochemical probe molecule brefeldin A (1) has served as an inspirational target in the past, but none of the many routes has actually delivered more than just a few milligrams of product, where documented. The approach described herein is clearly more efficient; it hinges upon the first implementation of ruthenium-catalyzed trans-hydrogenation in natural products total synthesis. Because this unorthodox reaction is selective for the triple bond and does not touch the transannular alkene or the lactone site of the cycloalkyne, it outperforms the classical Birch-type reduction that could not be applied at such a late stage. Other key steps en route to 1 comprise an iron-catalyzed reductive formation of a non-terminal alkyne, an asymmetric propiolate carbonyl addition mediated by a bulky amino alcohol, and a macrocyclization by ring-closing alkyne metathesis catalyzed by a molybdenum alkylidyne.


The role of M cells in the protection of mucosal membranes.
The mucosa-associated lymphoid tissues continuously take up antigenic matter from the lumen to generate immune responses or to maintain immune tolerance. This antigen sampling is performed by highly specialised epithelial cells, the membranous (M) cells of the dome epithelia. M cells possess a unique ultrastructure and lie in close contact to lymphoid cells. They endocytose soluble and solid substances, including entire microorganisms, at their apical membrane, transport these in vesicles to their basolateral membrane and exocytose them to the intercellular space. This review summarises the structural and functional peculiarities of M cells in different species and at the different sites of lymphoid tissue along the digestive and respiratory tracts. Specialisations of M cells for antigen uptake and transport comprise the composition of their apical membrane and its glycocalyx, a modified cytoskeleton as compared to enterocytes and a pocket-like invagination of the basolateral membrane populated by lymphocytes and macrophages. Besides ultrastructural characteristics, histochemical markers are listed that are currently available for detecting M cells by light microscopy. The origin, differentiation and distribution of M cells and other epithelial cell types of the dome epithelium are outlined. As M cells are used as entry sites by various pathogens and, in the future, might be employed for the oral application of vaccines and drugs, the clinical relevance of M cells in health and disease is discussed.


Ultrathin-Film Titania Photocatalyst on Nanocavity for CO2 Reduction with Boosted Catalytic Efficiencies.
Photocatalytic CO2 reduction with water to hydrocarbons represents a viable and sustainable process toward greenhouse gas reduction and fuel/chemical production. Development of more efficient catalysts is the key to mitigate the limits in photocatalytic processes. Here, a novel ultrathin-film photocatalytic light absorber (UFPLA) with TiO2 films to design efficient photocatalytic CO2 conversion processes is created. The UFPLA structure conquers the intrinsic trade-off between optical absorption and charge carrier extraction efficiency, that is, a solar absorber should be thick enough to absorb majority of the light allowable by its bandgap but thin enough to allow charge carrier extraction for reactions. The as-obtained structures significantly improve TiO2 photocatalytic activity and selectivity to oxygenated hydrocarbons than the benchmark photocatalyst (Aeroxide P25). Remarkably, UFPLAs with 2-nm-thick TiO2 films result in hydrocarbon formation rates of 0.967 mmol g-1 h-1, corresponding to 1145 times higher activity than Aeroxide P25. This observation is confirmed by femtosecond transient absorption spectroscopic experiments where longer charge carrier lifetimes are recorded for the thinner films. The current work demonstrates a powerful strategy to control light absorption and catalysis in CO2 conversion and, therefore, creates new and transformative ways of converting solar energy and greenhouse gas to alcohol fuels/chemicals.


Nonmuscle and muscle tropomyosin isoforms are expressed from a single gene by alternative RNA splicing and polyadenylation.
The molecular basis for the expression of rat embryonic fibroblast tropomyosin 1 and skeletal muscle beta-tropomyosin was determined. cDNA clones encoding these tropomyosin isoforms exhibit complete identity except for two carboxy-proximal regions (amino acids 189 to 213 and 258 to 284) and different 3'-untranslated sequences. The isoform-specific regions delineate the troponin T-binding domains of skeletal muscle tropomyosin. Analysis of genomic clones indicates that there are two separate loci in the rat genome that contain sequences complementary to these mRNAs. One locus is a pseudogene. The other locus contains a single gene made up of 11 exons and spans approximately 10 kilobases. Sequences common to all mRNAs were found in exons 1 through 5 (amino acids 1 to 188) and exons 8 and 9 (amino acids 214 to 257). Exons 6 and 11 are specific for fibroblast mRNA (amino acids 189 to 213 and 258 to 284, respectively), while exons 7 and 10 are specific for skeletal muscle mRNA (amino acids 189 to 213 and 258 to 284, respectively). In addition, exons 10 and 11 each contain the entire 3'-untranslated sequences of the respective mRNAs including the polyadenylation site. Although the gene is also expressed in smooth muscle (stomach, uterus, and vas deferens), only the fibroblast-type splice products can be detected in these tissues. S1 and primer extension analyses indicate that all mRNAs expressed from this gene are transcribed from a single promoter. The promoter was found to contain G-C-rich sequences, a TATA-like sequence TTTTA, no identifiable CCAAT box, and two putative Sp1-binding sites.


Industrial injuries in a plant.
This is a five year study of types of lost-time industrial injuries in a plant dealing with paper manufacturing and timber production. Back injuries accounted for 26% of all lost-time work accidents. Thirty-three point six percent of all back injuries were due to lifting or pulling of timbers at work. This occurred mainly in the timber yard of the plant where heavy manual work occurred. Males up to the age of 35 accounted for about 60% of back injuries. They have a higher tendency to injure their backs than do older males who were longer and more experienced workers. Back injuries were uncommon in the female workers. They accounted for a mere 0.3% of all back injuries. They were mainly clerical workers or cleaners reflecting lighter nature of their work. This study helps the company to plan better occupational safety programmes to reduce work hazards.


Reactive molecular simulations of protonation of water clusters and depletion of acidity in H-ZSM-5 zeolite.
Using reactive molecular dynamics (RMD), we present an atomistic insight into the interaction between water molecules and acidic centers of H-ZSM-5 zeolite. The reactive force field method, ReaxFF, was used to evaluate the adsorption and diffusion of water as well as to study the protonation of water molecules inside zeolite channels. The existing Si/Al/O/H parameters were refitted against DFT calculations to improve the ReaxFF description of interaction between water molecules and the acidic sites of zeolites. The diffusion coefficient of water in the zeolite obtained from refitted parameters is in excellent agreement with experimental results. The molecular dynamics (MD) simulations indicate that protonation of water molecules and acidity of the zeolite catalyst depend on water loadings and temperature and the observed trends compare favorably with existing experimental and theoretical studies. At higher water loadings, protonation of water molecules is more frequent leading to formation and growth of protonated water clusters inside zeolite channels. From the analysis of various reaction channels that were observed during the simulations, we found that such water clusters have relatively short life due to frequent interchange of protons and water molecules among the water clusters. Such proton hopping events play a key role in moving the protons between different acidic centers of zeolite. These simulations show the capability of ReaxFF in providing atomistic details of complex chemical interactions between the water phase and solid acid zeolites.


Stem cell factor Sox2 and its close relative Sox3 have differentiation functions in oligodendrocytes.
Neural precursor cells of the ventricular zone give rise to all neurons and glia of the central nervous system and rely for maintenance of their precursor characteristics on the closely related SoxB1 transcription factors Sox1, Sox2 and Sox3. We show in mouse spinal cord that, whereas SoxB1 proteins are usually downregulated upon neuronal specification, they continue to be expressed in glial precursors. In the oligodendrocyte lineage, Sox2 and Sox3 remain present into the early phases of terminal differentiation. Surprisingly, their deletion does not alter precursor characteristics but interferes with proper differentiation. Although a direct influence on myelin gene expression may be part of their function, we provide evidence for another mode of action. SoxB1 proteins promote oligodendrocyte differentiation in part by negatively controlling miR145 and thereby preventing this microRNA from inhibiting several pro-differentiation factors. This study presents one of the few cases in which SoxB1 proteins, including the stem cell factor Sox2, are associated with differentiation rather than precursor functions.


External electric field effect on fluorescence spectra of pyrene in solution.
Electrophotoluminescence (E-PL) spectra, i.e., plots of the electric-field-induced change in photoluminescence intensity as a function of wavenumber, have been measured for pyrene solution. At high concentrations of pyrene where excimer fluorescence is observed along with the monomer fluorescence emitted from the locally excited state, both excimer fluorescence and monomer fluorescence are enhanced by application of electric fields. The results show that the nonradiative decay process at the excimer emitting state is decelerated by application of electric fields. It is also found that molecular polarizability of pyrene excimer is larger than that of pyrene monomer in the ground state by ~270 ± 90 Å(3), based on the analysis of the Stark shift of the excimer fluorescence.


863 genomes reveal the origin and domestication of chicken.
Despite the substantial role that chickens have played in human societies across the world, both the geographic and temporal origins of their domestication remain controversial. To address this issue, we analyzed 863 genomes from a worldwide sampling of chickens and representatives of all four species of wild jungle fowl and each of the five subspecies of red jungle fowl (RJF). Our study suggests that domestic chickens were initially derived from the RJF subspecies Gallus gallus spadiceus whose present-day distribution is predominantly in southwestern China, northern Thailand and Myanmar. Following their domestication, chickens were translocated across Southeast and South Asia where they interbred locally with both RJF subspecies and other jungle fowl species. In addition, our results show that the White Leghorn chicken breed possesses a mosaic of divergent ancestries inherited from other subspecies of RJF. Despite the strong episodic gene flow from geographically divergent lineages of jungle fowls, our analyses show that domestic chickens undergo genetic adaptations that underlie their unique behavioral, morphological and reproductive traits. Our study provides novel insights into the evolutionary history of domestic chickens and a valuable resource to facilitate ongoing genetic and functional investigations of the world's most numerous domestic animal.


Fluid Shear Stress Enhances the Phagocytic Response of Astrocytes.
Astrocytes respond to brain injury at a cellular level by the process of reactive astrogliosis, and are able to adjust their response according to the severity of the insult. Included in the reactive response is the process of phagocytosis, where astrocytes clean up surrounding cellular debris from damaged cells. In this study, we observe the process of phagocytosis by primary cortical astrocytes in the presence of media flow across the apical surface of the cells. Both static and cells under flow conditions respond consistently via phagocytosis of laser-induced cellular debris. We found that astrocytes exposed to shear flow initiate phagocytosis at a consistently faster rate than cells observed under static conditions. Shear forces created by laminar flow were analyzed as well as the flow fields created around astrocyte cells. Results suggest astrocyte phagocytosis is a mechanosensitive response, thus revealing the potential to enhance astrocyte phagocytic cleanup of damaged nervous tissue.


Phosphoinositide metabolism and the morphology of human erythrocytes.
ATP-depleted human erythrocytes lose their smooth discoid shape and adopt a spiny, crenated form. This shape change coincides with the conversion of phosphatidylinositol-4,5-bisphosphate to phosphatidylinositol and phosphatidic acid to diacylglycerol. Both crenation and lipid dephosphorylation are accelerated by iodoacetamide, and both are reversed by nutrient supplementation. The observed changes in lipid populations should shrink the membrane inner monolayer by 0.6%, consistent with estimates of bilayer imbalance in crenated cells. These observations suggest that metabolic crenation arises from a loss of inner monolayer area secondary to the degradation of phosphatidylinositol-4,5-bisphosphate and phosphatidic acid. A related process, crenation after Ca2+ loading, appears to arise from a loss inositides by a different pathway.


Insertion sequence duplication in transpositional recombination.
Insertion sequences (IS) are discrete segments of DNA that can transpose from one genomic site to another and promote genetic rearrangements. A question that is central to understanding the mechanism of transpositional recombination is whether genetic rearrangements are accompanied by duplication of the IS that promotes them. Analysis of adjacent deletions mediated by IS903 provides the strongest evidence to date than any IS-mediated transpositional recombination can occur by an efficient replicative mechanism.


Auditory Brainstem Pathology in Autism Spectrum Disorder: A Review.
Atypical responses to sound are common in individuals with autism spectrum disorder (ASD), and growing evidence suggests an underlying auditory brainstem pathology. This review of the literature provides a comprehensive account of the structural and functional evidence for auditory brainstem abnormalities in ASD. The studies reviewed were published between 1975 and 2016 and were sourced from multiple online databases. Indices of both the quantity and quality of the studies reviewed are considered. Findings show converging evidence for auditory brainstem pathology in ASD, although the specific functions and anatomical structures involved remain equivocal. Two main trends emerge from the literature: (1) abnormalities occur mainly at higher levels of the auditory brainstem, according to structural imaging and electrophysiology studies; and (2) brainstem abnormalities appear to be more common in younger than older children with ASD. These findings suggest delayed maturation of neural transmission pathways between lower and higher levels of the brainstem and are consistent with the auditory disorders commonly observed in ASD, including atypical sound sensitivity, poor sound localization, and difficulty listening in background noise. Limitations of existing studies are discussed, and recommendations for future research are offered.


[The basis of rehabilitation and treatment in acute period of perinatal cerebral pathology].
We have examined 89 newborns with perinatal CNS lesions due to critical states at birth. Disturbances of vital functions of the organism developed as a result of severe posthypoxia states at birth that exert a significant effect on patient's quality of life in the following age periods, including the formation of "rough" polyorganic injuries, have been studied. Therefore, the adequate treatment of post-critical states in the neonatal period demands understanding of pathogenetic mechanisms of their development that has formed the basis for using peptide drugs with neuroprotective effect, in particular, cortexin.


[Ultrastructural alterations in larvae of Aedes aegypti subject to labdane diterpene isolated from Copaifera reticulata (Leguminosae) and a fraction enriched with tannins of Magonia pubescens (Sapindaceae)].
Dengue is an important public health problem in many countries and its main vector Aedes aegypti, is the mosquito most adapted to urban areas. For the first time, the mechanism of action of labdane diterpenoid extracted from Copaifera reticulata and the fraction enriched of catechin tannins extracted from Magonia pubescens is demonstrated through ultrastructural alterations of Aedes aegypti larvae. Experiments were performed using a 0.9 ppm solution of diterpenoid and 3.7 ppm of the fraction as the main catechin tannin of molecular mass 846 Da. The compounds were obtained by thin layer chromatography and identified by nuclear magnetic resonance of hydrogen and mass spectrometry. Larvae that achieved lethargic state were collected and dissected. Next, they were contrasted with 1% uranyl acetate, dehydrated, embedded and polymerized. Ultrathin sections were made, mixed with 3% uranyl acetate and lead citrate and placed in an electron microscope. The main ultrastructural alterations caused by the diterpenoid and by tanins in larvae of Aedes aegypti were: cytoplasmic vacuolation, alteration of microvilli, cellular aging, cell disruption and degeneration, formation of secretion vesicles and structural changes in microvilli, irregular nuclei and displacement of cells in the basal lamina. The fraction containing tannins and the diterpenoid caused the death of Aedes aegypti larvae by cell destruction in the midgut.


Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system.
From a multivariate analysis of more than 14,200 patient-years' experience with papillary thyroid carcinoma (PTC), we devised a prognostic scoring system based on patient age, tumor grade, extent, and size (AGES). This scoring system can identify patients at increased risk of PTC mortality and was employed as an adjustment variable for analyzing the role of different types of surgical treatment in 860 PTC patients. Cancer mortality at 25 years in patients with an AGES score of 3.99 or less was 1% after ipsilateral lobectomy (n = 131) and 2% after bilateral resection (n = 603), whether subtotal or total (p = 0.15). Of patients with an AGES score of 4 or more, those who underwent lobectomy alone (n = 30) had a mortality rate from PTC at 25 years of 65%, while those undergoing bilateral resection (n = 86) had a lower rate of 35% (p = 0.06). For patients at minimal risk (score of 3.99 or less) of PTC death, no improvement in survival was demonstrable when patients underwent more than ipsilateral lobectomy. However, in a subgroup (score of 4 or more) identified to be at significant risk of PTC death, the survival after bilateral resection was much higher than after ipsilateral lobectomy alone. In neither the "minimal" nor the "higher" risk subgroup was PTC survival significantly improved by the performance of total thyroidectomy.


Management of peripheral nerve problems in the upper and lower extremity using quantitative sensory testing.
Elective microsurgery of the peripheral nervous system concerns nerve decompression, neurolysis, nerve repair, and forms of nerve reconstruction with grafts or tubes. Management skills for the peripheral nerve too often rely on antiquated assessment techniques and depend upon traditional electrodiagnostic testing. Quantitative sensory testing is an approach to the evaluation of peripheral nerve function that is available now to all physicians interested in managing peripheral nerve problems. This article introduces quantitative sensory testing, with particular regard to the management of peripheral nerve problems.


cis-acting ompF mutations that result in OmpR-dependent constitutive expression.
OmpR and EnvZ differentially control the transcription of the major outer membrane porin genes, ompF and ompC, in Escherichia coli in response to the osmolarity of the medium. We have previously provided evidence that OmpR works both positively and negatively at the ompF promoter to give the characteristic switch from OmpF to OmpC production with increasing osmolarity. Here, we describe the isolation of cis-acting ompF mutations that affect negative regulation by OmpR by affecting the three-dimensional structure of the promoter region as measured by agarose gel mobility. These results further clarify the mechanism by which OmpR negatively regulates ompF expression, suggesting a model in which OmpR forms a repressive loop in the ompF promoter region.


Validating an infrared thermal switch as a novel access technology.
Recently, a novel single-switch access technology based on infrared thermography was proposed. The technology exploits the temperature differences between the inside and surrounding areas of the mouth as a switch trigger, thereby allowing voluntary switch activation upon mouth opening. However, for this technology to be clinically viable, it must be validated against a gold standard switch, such as a chin switch, that taps into the same voluntary motion. In this study, we report an experiment designed to gauge the concurrent validity of the infrared thermal switch. Ten able-bodied adults participated in a series of 3 test sessions where they simultaneously used both an infrared thermal and conventional chin switch to perform multiple trials of a number identification task with visual, auditory and audiovisual stimuli. Participants also provided qualitative feedback about switch use. User performance with the two switches was quantified using an efficiency measure based on mutual information. User performance (p = 0.16) and response time (p = 0.25) with the infrared thermal switch were comparable to those of the gold standard. Users reported preference for the infrared thermal switch given its non-contact nature and robustness to changes in user posture. Thermal infrared access technology appears to be a valid single switch alternative for individuals with disabilities who retain voluntary mouth opening and closing.


A new Loewia Egger (Diptera: Tachinidae) from Turkey, with taxonomic and nomenclatural remarks on congeners.
The new species Loewia papei sp. nov. from southern Anatolia (Turkey) is described, illustrated and compared with congeners. A brief diagnosis of Loewia Egger is provided and the systematics of the genus are discussed. Loewia nudigena Mesnil, 1972 is fixed as the type species of Fortisia Rondani, 1861 (junior synonym of Loewia). A full list of previously known valid species of Loewia is provided along with information on primary types, type repositories (where known), and type localities. A lectotype is designated for Thrychogena brevifrons Rondani, 1856 (= Loewia brevifrons (Rondani, 1856)).


A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model.
There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction (AMI), for which the effectiveness of interventional reperfusion therapy is hampered by myocardial ischemia-reperfusion (IR) injury. Pretreatment with statins before ischemia is shown to reduce MI size in animals. However, no benefit was found in animals and patients with AMI when administered at the time of reperfusion, suggesting insufficient drug targeting into the IR myocardium. Here we tested the hypothesis that nanoparticle-mediated targeting of pitavastatin protects the heart from IR injury. In a rat IR model, poly(lactic acid/glycolic acid) (PLGA) nanoparticle incorporating FITC accumulated in the IR myocardium through enhanced vascular permeability, and in CD11b-positive leukocytes in the IR myocardium and peripheral blood after intravenous treatment. Intravenous treatment with PLGA nanoparticle containing pitavastatin (Pitavastatin-NP, 1 mg/kg) at reperfusion reduced MI size after 24 hours and ameliorated left ventricular dysfunction 4-week after reperfusion; by contrast, pitavastatin alone (as high as 10 mg/kg) showed no therapeutic effects. The therapeutic effects of Pitavastatin-NP were blunted by a PI3K inhibitor wortmannin, but not by a mitochondrial permeability transition pore inhibitor cyclosporine A. Pitavastatin-NP induced phosphorylation of Akt and GSK3β, and inhibited inflammation and cardiomyocyte apoptosis in the IR myocardium. Nanoparticle-mediated targeting of pitavastatin induced cardioprotection from IR injury by activation of PI3K/Akt pathway and inhibition of inflammation and cardiomyocyte death in this model. This strategy can be developed as an innovative cardioprotective modality that may advance currently unsatisfactory reperfusion therapy for AMI.


Determination of the bioavailability of selected pharmaceutical residues in fish plasma using liquid chromatography coupled to tandem mass spectrometry.
Aquatic systems near major urban centers are constantly contaminated with effluent from wastewater treatment plants. Pharmaceuticals are part of the contamination and several classes of drugs have been detected in surface waters in the last decade. To better understand the impact of those pharmaceuticals in ecosystems, the exposure to aquatic species needs to be investigated. This study presents a new simple and rugged quantitative method for the determination of several classes of drugs using 100μL of plasma from fish environmentally exposed to a major but highly diluted urban effluent. Six common drugs (i.e., diclofenac, ibuprofen, naproxen, salbutamol, sulfamethoxazole and trimethoprim) and one major metabolite (2-hydroxy-ibuprofen), present in significant amount in impacted waterways have been selected for the development and validation of the method. First, all drugs were extracted using cation exchange solid phase extraction (SPE) and eluted with two solvent mixtures. Then, the extracts were analyzed using a reverse-phase analytical column Waters® CORTECS C18+ (150×2.1mm, 2.7μm) within 14min. MS/MS was performed with an electrospray (ESI) interface in positive ion mode, with multiple reaction monitoring (MRM) experiment acquiring two product ions per drugs. Quantification has been made with standard curves for each analyte using isotopically labeled internal standards. This method has high sensitivity with limits of quantification of 1ngmL-1 for each drug, except for ibuprofen and its metabolite 2-hydroxy-ibuprofen at 2ngmL-1. The precision of the method was below 11%, the accuracy between 94 and 105% and overall recovery between 94 and 111% for all drugs, with high selectivity. Application of the method to plasma samples from wild northern pike inhabiting the St. Lawrence River collected over a three-year period showed the presence of naproxen, diclofenac, trimethoprim and salbutamol at very low concentrations (around 1ngmL-1).


Short rDNA barcodes for species identification in foraminifera.
Ribosomal DNA (rDNA) sequences have been shown to be very useful for identification of microbial eukaryotes. Usually, complete or long partial sequences of the rDNA genes are analysed. However, the development of new massive sequencing technologies producing a large amount of relatively short sequences raises the question about the minimum length of rDNA fragments necessary for species distinction in environmental sampling. To answer this question, we compared six variable regions of the small subunit (SSU) rDNA of foraminifera, known to have rapidly evolving ribosomal genes. For each region, we analysed (1) the sequence divergence between and within foraminiferal morphospecies, (2) the intraspecific polymorphism, and (3) the ability of each region to recognize the phylotypes inferred from analysis of a longer fragment. Our results show that although the variable regions differ considerably between taxonomic groups, most of them perform very well as species identifiers. Taking into account different analyses, the expansion segment of Helix 37 appears to be the best candidate for barcoding foraminifera. We propose that this relatively short region, averaging 50-60 nt in length, could be an ideal barcode for identification of foraminifera in environmental samples using massive sequencing approach.


Effect of hunters' switch from lead to steel shot on potential for oral lead poisoning in ducks.
Mallards and black ducks (n = 409) killed by hunters during the 1980 and 1981 hunting seasons in Pennsylvania (Susquehanna River and Crawford County) were examined to evaluate the effectiveness of regulations that converted the studied areas from lead to steel shotgun pellets in 1977-1978. Gizzards were examined for ingested lead and steel shot, and liver specimens were analyzed for lead. Since there is no evidence to suggest that ducks preferentially ingest steel or lead shot, it was concluded that ducks with steel shot would have contained lead shot. Therefore, we concluded that the conversion to steel shotgun pellets accounted for the decreased prevalence of ingested lead shot from 11.2% to 5.6%. Toxic concentrations of lead (greater than or equal to 6 ppm, wet weight) in the liver were found in 6 of 23 ducks that contained lead shot, whereas only 2 of 386 ducks without lead pellets had toxic concentrations. It was concluded that the conversion to steel shotgun pellets in the studied areas probably has decreased the exposure of ducks to lead shot, thereby decreasing the potential for lead poisoning.


Prospective Predictors of Receiving Disclosures of Intimate Partner Violence and Sexual Assault Among College Students.
Previous research has indicated that many undergraduates receive disclosures of sexual assault and intimate partner violence (IPV) from their peers; however, much of this research has been cross-sectional. The present study assessed the extent to which demographic characteristics and victimization history predicted whether participants received disclosures over the subsequent 6 months. Directional hypotheses assessed whether psychological symptoms and attitudes predicted, or were consequences of, disclosures at follow-up. College students (n = 867) from a broader treatment intervention study completed pretest (Time 1) and 6-month follow-up surveys (Time 2). Individuals who reported new disclosures at follow-up (56%) were more likely to be women, have previous experience receiving either sexual assault or IPV disclosures, and have experienced sexual assault or IPV victimization in their lifetime and across the follow-up period. Sexual orientation did not predict receipt of disclosures at follow-up; intervention group did not moderate these relationships. Results of longitudinal structural equation models found that although higher Time 1 posttraumatic stress disorder symptoms and depressive symptoms predicted disclosure status at follow-up, Time 1 disclosure status did not predict subsequent increases in posttraumatic stress disorder and depressive symptoms. Attitudinal variables were not significantly associated with disclosures reported at Time 1 or follow-up. Findings suggest the importance of attending to personal experiences of victimization within interventions aiming to improve responses to disclosure. Although individuals with higher distress are more likely to receive subsequent disclosures, disclosure does not appear to lead to increases in long-term psychological distress.


Differential requirements for VirB1 and VirB2 during Brucella abortus infection.
The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface, where they could potentially interact with host cells. Studies to date have focused on characterization of transposon mutations in these genes, which are expected to exert polar effects on downstream genes in the operon. In order to determine whether VirB1 and VirB2 are required for the function of the T4SS apparatus, we constructed and characterized nonpolar deletion mutations of virB1 and virB2. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection. In contrast, the nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection.


[Effect of morphine on the cAMP level of lymphocytes].
A study was made of the effect of morphine on the cAMP level in peripheral blood lymphocytes in tobacco smoking and non-smoking donors. Morphine was shown to produce the naloxone-removable activation of adenylate cyclase, the relationship between enzymatic activity and opiate concentration in the medium being complex in nature. In tobacco smoking donors, the maximal effect on cAMP was produced by morphine at concentrations that were one order of magnitude higher than those in non-smoking ones. On the basis of the data obtained the assumptions are made (1) about the presence on the lymphocytes of opiate receptors whose action mode is associated with adenylate cyclase control, and (2) about the development during tobacco smoking of morphine tolerance at the level of opiate-dependent adenylate cyclase of lymphocytes.


Enhanced genome-wide association reveals the role of YABBY11-NGATHA-LIKE1 in leaf serration development of Populus.
Leaf margins are complex plant morphological features that contribute to leaf shape diversity, which affects plant structure, yield, and adaptation. Although several leaf margin regulators have been identified to date, the genetic basis of their natural variation has not been fully elucidated. In this study, we profiled two distinct leaf morphology types (serrated and smooth) using the persistent homology mathematical framework (PHMF) in two poplar species (Populus tomentosa and Populus simonii, respectively). A combined genome-wide association study (GWAS) and expression quantitative trait nucleotide (eQTN) mapping were applied to create a leaf morphology control module using data from P. tomentosa and P. simonii populations. Natural variation in leaf margins was associated with YABBY11 (YAB11) transcript abundance in poplar. In P. tomentosa, PtoYAB11 carries a premature stop codon (PtoYAB11PSC), resulting in the loss of its positive regulation of NGATHA-LIKE1 (PtoNGAL-1) and RIBULOSE BISPHOSPHATE CARBOXYLASE LARGE SUBUNIT (PtoRBCL). Overexpression of PtoYAB11PSC promoted serrated leaf margins, enlarged leaves, enhanced photosynthesis, and increased biomass. Overexpression of PsiYAB11 in P. tomentosa promoted smooth leaf margins, higher stomatal density, and greater light damage repair ability. In poplar, YAB11-NGAL1 is sensitive to environmental conditions, acts as a positive regulator of leaf margin serration, and may also link environmental signaling to leaf morphological plasticity.


Recent advances in petroleum microbiology.
Recent advances in molecular biology have extended our understanding of the metabolic processes related to microbial transformation of petroleum hydrocarbons. The physiological responses of microorganisms to the presence of hydrocarbons, including cell surface alterations and adaptive mechanisms for uptake and efflux of these substrates, have been characterized. New molecular techniques have enhanced our ability to investigate the dynamics of microbial communities in petroleum-impacted ecosystems. By establishing conditions which maximize rates and extents of microbial growth, hydrocarbon access, and transformation, highly accelerated and bioreactor-based petroleum waste degradation processes have been implemented. Biofilters capable of removing and biodegrading volatile petroleum contaminants in air streams with short substrate-microbe contact times (<60 s) are being used effectively. Microbes are being injected into partially spent petroleum reservoirs to enhance oil recovery. However, these microbial processes have not exhibited consistent and effective performance, primarily because of our inability to control conditions in the subsurface environment. Microbes may be exploited to break stable oilfield emulsions to produce pipeline quality oil. There is interest in replacing physical oil desulfurization processes with biodesulfurization methods through promotion of selective sulfur removal without degradation of associated carbon moieties. However, since microbes require an environment containing some water, a two-phase oil-water system must be established to optimize contact between the microbes and the hydrocarbon, and such an emulsion is not easily created with viscous crude oil. This challenge may be circumvented by application of the technology to more refined gasoline and diesel substrates, where aqueous-hydrocarbon emulsions are more easily generated. Molecular approaches are being used to broaden the substrate specificity and increase the rates and extents of desulfurization. Bacterial processes are being commercialized for removal of H(2)S and sulfoxides from petrochemical waste streams. Microbes also have potential for use in removal of nitrogen from crude oil leading to reduced nitric oxide emissions provided that technical problems similar to those experienced in biodesulfurization can be solved. Enzymes are being exploited to produce added-value products from petroleum substrates, and bacterial biosensors are being used to analyze petroleum-contaminated environments.


The number of strides required for treadmill running gait analysis is unaffected by either speed or run duration.
Participation in running events has increased recently, with a concomitant increase in the rate of running related injuries (RRI). Mechanical overload is thought to be a primary cause of RRI, it is often detected using motion analysis to examine running mechanics during either overground or treadmill running. In treadmill running, no clear consensus for the number of strides required to establish stable kinematic data exists. The aim of this study was to establish the number of strides needed for stable data when analysing gait kinematics in the stance phase of treadmill running. Twenty healthy, masters age group, club runners completed a high intensity interval training run (HIIT) and an energy-expenditure matched medium intensity continuous run (MICR). Thirty consecutive strides at start and end of each run were identified. Sequential averaging was employed to determine the number of strides required to establish a stable value. No significant differences existed in the number of strides required to achieve stable values. Twenty consecutive strides are required to be 95% confident stable values exist for maximum angle, angle at initial foot contact, and range of motion at the ankle, knee, and hip joints variables at the ankle, knee, and hip joints, in all three planes of motion, and spatiotemporal regardless of running speed and time of capture.


Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: A report from the Children's Cancer Group and the Pediatric Oncology Group.
Previous studies demonstrated that chemotherapy with either cisplatin, vincristine, and fluorouracil (regimen A) or cisplatin and continuous infusion doxorubicin (regimen B) improved survival in children with hepatoblastoma. The current trial is a randomized comparison of these two regimens. Patients (N = 182) were enrolled onto study between August 1989 and December 1992. After initial surgery, patients with stage I-unfavorable histology (UH; n = 43), stage II (n = 7), stage III (n = 83), and stage IV (n = 40) hepatoblastoma were randomized to receive regimen A (n = 92) or regimen B (n = 81). Patients with stage I-favorable histology (FH; n = 9) were treated with four cycles of doxorubicin alone. There were no events among patients with stage I-FH disease. Five-year event-free survival (EFS) estimates were 57% (SD = 5%) and 69% (SD = 5%) for patients on regimens A and B, respectively (P =.09) with a relative risk of 1.54 (95% confidence interval, 0.93 to 2.5) for regimen A versus B. Toxicities were more frequent on regimen B. Patients with stage I-UH, stage II, stage III, or stage IV disease had 5-year EFS estimates of 91% (SD = 4%), 100%, 64% (SD = 5%), and 25% (SD = 7%), respectively. Outcome was similar for either regimen within disease stages. At postinduction surgery I, patients with stage III or IV disease who were found to be tumor-free had no events; those who had complete resections achieved a 5-year EFS of 83% (SD = 6%); other patients with stage III or IV disease had worse outcome. Treatment outcome was not significantly different between regimen A and regimen B. Excellent outcome was achieved for patients with stage I-UH and stage II hepatoblastoma and for subsets of patients with stage III disease. New treatment strategies are needed for the majority of patients with advanced-stage hepatoblastoma.


Household food security is inversely associated with undernutrition among adolescents from Kilosa, Tanzania.
Household food insecurity contributes to poor nutritional health, with negative consequences on growth and development during childhood. Although early childhood nutrition needs have received much attention, another important nutritional phase is adolescence. In a sample of 670 adolescents from Kilosa District, Tanzania, this study used 3 approaches to better understand the relationship between food insecurity and undernutrition. First, this study examined the associations between 3 commonly used measures of household food security and undernutrition among 670 adolescents from Kilosa District, Tanzania. The measures of household food security, energy adequacy per adult equivalent, dietary diversity score, and coping strategies index, were strongly correlated with each other and household assets (P < 0.05). Second, this study measured the nutritional status of adolescents in this district, finding a high prevalence of undernutrition (21% with BMI-for-age <5th percentile of the National Center for Health Statistics/WHO reference). Third, this study measured the association between the log odds of undernutrition (as the dependent variable) and each of the 3 measures of household food security. In separate models, household energy adequacy per adult equivalent and household dietary diversity score were inversely associated with undernutrition after adjusting for gender, age, puberty, and the interaction between age and puberty. By contrast, a greater use of coping strategies was not associated with undernutrition. Strategies focused on increasing household energy intake and improving dietary diversity among the most vulnerable households could improve the nutritional health of adolescents.


Effects of local anesthetics on membrane properties. I. Changes in the fluidity of phospholipid bilayers.
The effect of the local anesthetic dibucaine on the solid to liquid-crystalline phase transition in phospholipid vesicles was studied by calorimetry and fluorescence polarization. The partition coefficient (greater than 3000) of dibucaine in the membranes of vesicles prepared from acidic phospholipids was more than 20 times higher than in neutral phospholipid membranes under the same conditions. Calorimetric measurements on vesicles prepared form acidic phospholipids (bovine brain phosphatidylserine; dipalmitoylphosphatidylglycerol) showed that dibucaine (1 with 10(-4) M) produced a significant reduction in the gel-liquid crystalline transition temperature (Tc). This fluidizing effect of dibucaine on acidic phospholipid membranes was even more marked in the presence of Ca2+. In contrast, dibucaine at the same concentration did not alter the Tc of neutral phospholipids (dipalmitoylphosphatidylcholine). Significant increase in the fluidity of neutral phospholipid membranes occurred only at higher dibucaine concentrations (2 with 10(-3) M). Measurements of the fluorescence polarization and lifetime of the probe, 1,6-diphenylhexatriene, in acidic phospholipid vesicles revealed that dibucaine (1 with 10(-4) M) caused an increase in the probe rotation rate indicating an increase in the fluidity of the phospholipid membranes. A good correlation was obtained between fluorescence polarization data on dibucaine-induced changes in membrane fluidity and calorimetric measurements on vesicles of the same type.


Primary care nurses' attitudes, beliefs and own body size in relation to obesity management.
This paper is a report of a study to explore primary care nurses' attitudes, beliefs and perceptions of own body size in relation to giving advice about obesity. Primary care nurses have a key role in the management of obesity. Their responses to the stigma of obesity and the effects of their own body size in this context have not been investigated. A purposive sample of 15 primary care nurses of markedly different body size were interviewed in a qualitative study undertaken in 2006 in the north of England. Participants were aware of obesity stigma and this, among other factors, contributed to perceptions of obesity as being a sensitive issue to discuss. Communication tactics were employed in managing the sensitivity, with emphasis placed on maintaining good rapport. Participants took care to avoid stereotypes in presenting their beliefs about obesity, which were complex and in some respects ambivalent. They were conscious of their own body size in interactions with patients. A slim build appeared to amplify sensitivities surrounding obesity and add concerns about appearing to lack empathy or authentic experience. Those with a large body size made a virtue of their perceived greater empathy and experience, but had concerns about being poor role models. Self-disclosure techniques oriented to demonstrating personal understanding and rapport were employed to manage impressions made by body size. It is important to consider the effects of own body size in educating nurses, and further research should investigate its effects on patient outcomes.


The Changes of Electromyography in the Upper Trapezius and Supraspinatus of Women College Students According to the Method of Bag-carrying and Weight.
[Purpose] The purpose of this study was to investigate differences in upper extremity muscle activities of women college students' due to method of bag-carrying and weight. [Subjects] Thirty healthy adult females participated in this study. The exclusion criteria were orthopedic or neurologic disease, or a dominant left side. [Methods] Electromyographic activities of the supraspinatus and upper trapezius were recorded bilaterally under two conditions: crossbody bag, ipsilateral bag. [Results] There were no significant differences in the supraspinatus and upper trapezius muscles according to the weight carried; however, there was significant difference in the right supraspinatus and both upper trapezius muscles according to the method of carrying. [Conclusion] An effective backpack safety program for female college students is necessary to educate them how to prevent possible musculoskeletal pain related to the weight carried and the method of carrying from the perspective of an ergonomical approach.


A coupled fiber-matrix model demonstrates highly inhomogeneous microstructural interactions in soft tissues under tensile load.
A soft tissue's macroscopic behavior is largely determined by its microstructural components (often a collagen fiber network surrounded by a nonfibrillar matrix (NFM)). In the present study, a coupled fiber-matrix model was developed to fully quantify the internal stress field within such a tissue and to explore interactions between the collagen fiber network and nonfibrillar matrix (NFM). Voronoi tessellations (representing collagen networks) were embedded in a continuous three-dimensional NFM. Fibers were represented as one-dimensional nonlinear springs and the NFM, meshed via tetrahedra, was modeled as a compressible neo-Hookean solid. Multidimensional finite element modeling was employed in order to couple the two tissue components and uniaxial tension was applied to the composite representative volume element (RVE). In terms of the overall RVE response (average stress, fiber orientation, and Poisson's ratio), the coupled fiber-matrix model yielded results consistent with those obtained using a previously developed parallel model based upon superposition. The detailed stress field in the composite RVE demonstrated the high degree of inhomogeneity in NFM mechanics, which cannot be addressed by a parallel model. Distributions of maximum/minimum principal stresses in the NFM showed a transition from fiber-dominated to matrix-dominated behavior as the matrix shear modulus increased. The matrix-dominated behavior also included a shift in the fiber kinematics toward the affine limit. We conclude that if only gross averaged parameters are of interest, parallel-type models are suitable. If, however, one is concerned with phenomena, such as individual cell-fiber interactions or tissue failure that could be altered by local variations in the stress field, then the detailed model is necessary in spite of its higher computational cost.


Development of structural analysis of sulfated N-glycans by multidimensional high performance liquid chromatography mapping methods.
Although the biological importance of sulfated oligosaccharides has been widely recognized, there are only a few reports that describe detailed structures of sulfated N-glycans. This is largely due to the lack of a convenient method to identify structures of sulfated glycans found in low incidence. Here we develop multidimensional high performance liquid chromatography (HPLC) mapping methods for rapid and convenient identification of sulfated N-glycans. By using adequate quantities of sulfated N-glycans derived from LS12 cells, which are transfected with sulfotransferase cDNA, 40 different sulfated glycans have been successfully mapped. Furthermore, we have applied the HPLC data to identification of isomeric products resulting from an enzymatic reaction of N-acetylglucosamine 6-O-sulfotransferase-1 in vitro and revealed that this enzyme preferentially catalyzes sulfation of the GlcNAcbeta1-->2Manalpha1-->3Man branch in a biantennary acceptor.


Soil nutrient assessment for urban ecosystems in Hubei, China.
Recent urban landscape vegetation surveys conducted in many cities in China identified numerous plant nutrient deficiencies, especially in newly developed cities. Soil nutrients and soil nutrient management in the cities of Hubei province have not received adequate attention to date. The aims of this study were to characterize the available nutrients of urban soils from nine cities in Hubei province, China, and to assess how soil nutrient status is related to land use type and topography. Soil nutrients were measured in 405 sites from 1,215 soil samples collected from four land use types (park, institutional [including government building grounds, municipal party grounds, university grounds, and garden city institutes], residential, and roadside verges) and three topographies (mountainous [142-425 m a.s.l], hilly [66-112 m a.s.l], and plain [26-30 m a.s.l]). Chemical analyses showed that urban soils in Hubei had high pH and lower soil organic matter, available nitrogen (N), available phosphorus (P), and available boron (B) concentrations than natural soils. Nutrient concentrations were significantly different among land use types, with the roadside and residential areas having greater concentrations of calcium (Ca), sulfur (S), copper (Cu), manganese (Mn), and zinc (Zn) that were not deficient against the recommended ranges. Topographic comparisons showed statistically significant effects for 8 of the 11 chemical variables (p < 0.05). Concentrations of N, Ca, Mg, S, Cu, and Mn in plain cities were greater than those in mountainous cities and show a negative correlation with city elevation. These results provide data on urban soils characteristics in land use types and topography, and deliver significant information for city planners and policy makers.