Impurity effects on solid-solid transitions in atomic clusters.
We use the harmonic superposition approach to examine how a single atom substitution affects low-temperature anomalies in the vibrational heat capacity (CV) of model nanoclusters. Each anomaly is linked to competing solidlike "phases", where crossover of the corresponding free energies defines a solid-solid transition temperature (Ts). For selected Lennard-Jones clusters we show that Ts and the corresponding CV peak can be tuned over a wide range by varying the relative atomic size and binding strength of the impurity, but excessive atom-size mismatch can destroy a transition and may produce another. In some tunable cases we find up to two additional CV peaks emerging below Ts, signalling one- or two-step delocalisation of the impurity within the ground-state geometry. Results for Ni74X and Au54X clusters (X = Au, Ag, Al, Cu, Ni, Pd, Pt, Pb), modelled by the many-body Gupta potential, further corroborate the possibility of tuning, engineering, and suppressing finite-system analogues of a solid-solid transition in nanoalloys.


Apolipoprotein E genotype, vascular risk and early cognitive impairment in an African Caribbean population.
A reduced risk of Alzheimer's disease (AD) associated with the apolipoprotein E (APOE) epsilon4 allele is reported in populations of African origin. In order to clarify possible reasons for this, we examined the association between APOE genotype and early cognitive impairment in a community-based African Caribbean UK population aged 55-75 years. APOE genotype was available for 202 participants, 57 (28%) of whom were classified as having relative cognitive impairment on a battery of neuropsychological tests. Cognitive impairment was negatively associated with epsilon2 and positively but more weakly associated with epsilon4. Effects of both alleles increased markedly after age 70. The effect of epsilon4 was increased in combination with hypertension, diabetes or lower educational attainment, but these factors did not influence epsilon2 effects. Cholesterol and triglyceride levels partially explained effects of epsilon2, but did not account for those of epsilon4. A reduced association between epsilon4 and later AD in populations of African origin is unlikely to be explained by reduced cognitive effects or by differential mortality. However, it may be accounted for by vascular comorbidity. The different patterns of association between epsilon2 and epsilon4 alleles suggest different pathways of effect.


Thymus-specific serine protease, a protease that shapes the CD4 T cell repertoire.
The lifespan of T cells is determined by continuous interactions of their T cell receptors (TCR) with self-peptide-MHC (self-pMHC) complexes presented by different subsets of antigen-presenting cells (APC). In the thymus, developing thymocytes are positively selected through recognition of self-pMHC presented by cortical thymic epithelial cells (cTEC). They are subsequently negatively selected by medullary thymic epithelial cells (mTEC) or thymic dendritic cells (DC) presenting self-pMHC complexes. In the periphery, the homeostasis of mature T cells is likewise controlled by the interaction of their TCR with self-pMHC complexes presented by lymph node stromal cells while they may be tolerized by DC presenting tissue-derived self-antigens. To perform these tasks, the different subsets of APC are equipped with distinct combination of antigen processing enzymes and consequently present specific repertoire of self-peptides. Here, we discuss one such antigen processing enzyme, the thymus-specific serine protease (TSSP), which is predominantly expressed by thymic stromal cells. In thymic DC and TEC, TSSP edits the repertoire of peptide presented by class II molecules and thus shapes the CD4 T cell repertoire.


Standing cough test for evaluation of post-prostatectomy incontinence: a pilot study.
We implemented a standardized Standing Cough Test (SCT) for assessment of men with post-prostatectomy incontinence (PPI) and stratified results according to an objective clinical grading scale in an attempt to facilitate male anti-incontinence surgical procedure selection. SCT was routinely performed during the initial outpatient consultation for PPI. Incontinence severity was recorded based on a novel Male Stress Incontinence Grading Scale (MSIGS) to stratify PPI. Each patient was assigned an incontinence grade score of 0 through 4 during the SCT. Men with mild stress urinary incontinence (SUI) (grades 0-2) were offered sling surgery while those with heavier SUI (grades 3-4) were offered artificial urinary sphincter (AUS). MSIGS grade was correlated to preoperative patient-reported pads per day (PPD), and patient-reported outcomes of anti-incontinence surgery were assessed. Among 62 consecutive PPI patients, 20 (32%) were graded as mild based on SCT, while the majority (42/62, 68%) were graded as moderate-severe. Average time from prostatectomy to treatment was 6 years. MSIGS grade demonstrated a strong correlation with preoperative PPD (r = 0.74). Among the 53 patients who underwent surgery for PPI, 14 with mild SUI received a sling, while 39 (74%) more severe cases received an AUS. Patient-reported improvement was high overall in both groups (median 95%). Most men with chronic PPI present for definitive treatment in a delayed manner after prostatectomy despite having severe incontinence. The SCT provides immediate, objective information about the severity of PPI which strongly correlates with patient-reported pads-per-day and may expedite anti-incontinence surgical procedure selection.


Vaccine efficacies of elastase, exotoxin A, and outer-membrane protein F in preventing chronic pulmonary infection by Pseudomonas aeruginosa in a rat model.
The protective efficacies of eight vaccine preparations consisting of Pseudomonas aeruginosa outer-membrane protein F, elastase and exotoxin A toxoid, administered either individually or in various combinations, were determined in a rat model of chronic pulmonary infection. Rats were immunised intramuscularly at 2-week intervals (days 0, 14 and 28). On day 42, blood was collected and antisera were obtained from each vaccine group for use in an enzyme-linked immunosorbent assay which determined the titre of IgG antibodies elicited by each vaccine. Also on day 42, rats were challenged by intratracheal inoculation of a clinical isolate of P. aeruginosa encased within agar beads. On day 49, the animals were killed and the lungs were examined macroscopically for the presence of lesions and fixed for histological examination. When compared with control rats immunised with bovine serum albumin, rats immunised with protein F alone as a vaccine received significant protection against the development of severe pulmonary lesions. Elastase used alone as a vaccine provided some protection against severe lung lesions and reduced the incidence of microscopic peribronchial inflammation. However, the combination of protein F plus elastase as a vaccine did not afford protection from severe lesions, and there was an increased incidence of necrotising granulomas in the lungs from this vaccine group. Protection against lung lesions from the three-component vaccine consisting of protein F, elastase and exotoxin A toxoid was similar to that provided by the protein F vaccine. Neither macroscopic nor histological evidence showed any enhancement of protective efficacy for the three-component vaccine over that of the protein F vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)


Phytolith evidence for early Holocene Cucurbita domestication in southwest Ecuador.
Cucurbita (squash and gourd) phytoliths recovered from two early Holocene archaeological sites in southwestern Ecuador and directly dated to 10,130 to 9320 carbon-14 years before the present (about 12,000 to 10,000 calendar years ago) are identified as derived from domesticated plants because they are considerably larger than those from modern wild taxa. The beginnings of plant husbandry appear to have been preceded by the exploitation of a wild species of Cucurbita during the terminal Pleistocene. These data provide evidence for an independent emergence of plant food production in lowland South America that was contemporaneous with or slightly before that in highland Mesoamerica.


A key to the adult Costa Rican "helicopter" damselflies (Odonata: Pseudostigmatidae) with notes on their phenology and life zone preferences.
We present a key to the Costa Rican species of Pseudostigmatidae, comprising three genera with the following species: Megaloprepus caerulatus, Mecistogaster linearis, M. modesta, M. ornata and Pseudostigma aberrans. Pseudostigma accedens, which may occur in the region, is also included. For each species we give a brief account of morphology, phenology and life zone preferences, including distributional maps based on more than 270 records. These are not all of the known specimens from the area, but a high enough number to give a relatively good picture of the distribution and status of the species. We found M. caerulatus to be active during the first half of the year in seasonal, tropical semi-dry lowland forest and tropical moist forest at mid-elevation, but like M. linearis, M. caerulatus was active all year round in non-seasonal, tropical wet lowland forest and tropical moist forest at mid-elevation. Mecistogaster modesta also flew year round in non-seasonal, tropical wet lowland forest and tropical moist evergreen forest at mid-elevation, and likewise in seasonal and non-seasonal, tropical premontane moist forest. Only a few findings, however, have been made of M. modesta in seasonal, tropical semi-dry deciduous forest and seasonal, tropical moist evergreen forest. Mecistogaster ornata was missing entirely from non-seasonal, tropical wet lowland forest and non-seasonal, tropical moist forest at mid-elevation, while this species was active year round in seasonal, tropical dry lowland forest and tropical semi-dry forest, as well as in seasonal, tropical moist evergreen forest and tropical premontane moist forest, both at mid-elevation. Pseudostigma aberrans has so far been found too few times in Costa Rica for any indication of flight time preference.


Treatment of systemic mycoses with ketoconazole: emphasis on toxicity and clinical response in 52 patients. National Institute of Allergy and Infectious Diseases collaborative antifungal study.
The pharmacology, in vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institutes of Health and National Institute of Allergy and Infectious Disease Mycoses Study Group. This report emphasizes the toxicity and clinical response data in 52 patients with the following systemic mycoses: blastomycosis in 16 patients; nonmeningeal coccidioidomycosis in 13; histoplasmosis in 8; nonmeningeal cryptococcosis in 7; sporotrichosis in 7; and both blastomycosis and nonmeningeal coccidioidomycosis in 1. Maximum daily doses of ketoconazole were 100 mg in 1 patient; 200 mg in 23; 400 mg in 12; and 600 mg in 16. In 52% of the patients, duration of therapy ranged from less than 1 to 6 months, whereas in 35%, duration ranged from 7 to 12 months, and in 13%, from 12 to 22 months. In 35 patients (67%), evidence of toxicity was not seen. Nausea, anorexia, or vomiting occurred in 21%. Cure or marked improvement was shown in 27 patients (52%), whereas failure of the primary course was seen in 14 (27%) and relapse after ketoconazole was discontinued in 11 (21%). Although this evaluation did not provide clear-cut clinical response data, our results indicate that ketoconazole, in the dosage regimens used, was more effective in patients with histoplasmosis and nonmeningeal cryptococcosis than in patients with blastomycosis and nonmeningeal coccidioidomycosis, and least effective in patients with sporotrichosis.


Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man.
Alpha-linolenic acid (18:3n-3) is the major n-3 (omega 3) fatty acid in the human diet. It is derived mainly from terrestrial plant consumption and it has long been thought that its major biochemical role is as the principal precursor for long chain polyunsaturated fatty acids, of which eicosapentaenoic (20:5n-3) and docosahexaenoic acid (22:6n-3) are the most prevalent. For infants, n-3 long chain polyunsaturated fatty acids are required for rapid growth of neural tissue in the perinatal period and a nutritional supply is particularly important for development of premature infants. For adults, n-3 long chain polyunsaturated fatty acid supplementation is implicated in improving a wide range of clinical pathologies involving cardiac, kidney, and neural tissues. Studies generally agree that whole body conversion of 18:3n-3 to 22:6n-3 is below 5% in humans, and depends on the concentration of n-6 fatty acids and long chain polyunsaturated fatty acids in the diet. Complete oxidation of dietary 18:3n-3 to CO2 accounts for about 25% of 18:3n-3 in the first 24 h, reaching 60% by 7 days. Much of the remaining 18:3n-3 serves as a source of acetate for synthesis of saturates and monounsaturates, with very little stored as 18:3n-3. In term and preterm infants, studies show wide variability in the plasma kinetics of 13C n-3 long chain polyunsaturated fatty acids after 13C-18:3n-3 dosing, suggesting wide variability among human infants in the development of biosynthetic capability to convert 18:3n-3 to 22:6n3. Tracer studies show that humans of all ages can perform the conversion of 18:3n-3 to 22:6n3. Further studies are required to establish quantitatively the partitioning of dietary 18:3n-3 among metabolic pathways and the influence of other dietary components and of physiological states on these processes.


Influence of symmetry on the luminescence and radiative lifetime of nine-coordinate europium complexes.
Homoleptic mononuclear nine-coordinate lanthanum(III) and europium(III) tris-complexes [Ln(N(∧)N(∧)O)3]·nH2O with two tridentate N-benzylbenzimidazole pyridine-2-carboxylates exhibit a rare C3-symmetry of the lanthanide coordination polyhedron in the solid state, as confirmed by luminescence spectroscopy and by X-ray crystallography (the three N(∧)N(∧)O ligands are arranged "up-up-up" around the lanthanide ion). The symmetry, however, is changed to the more common C1 upon dissolution of the complexes in dichloromethane, as revealed by luminescence spectroscopy (the three ligands are likely to be arranged "up-up-down"). The new europium complexes emit efficient ligand-sensitized metal-centered luminescence with excited-state lifetimes of 1.56-2.18 ms and quantum yields of 25-41% in the solid and in solution. The change of the symmetry from (a higher) C3 to (a lower) C1 alters the luminescence spectrum, shortens the radiative lifetime, and increases the luminescence efficiency of the europium complexes.


Lactoferrin reduces in vitro osteoclast differentiation and resorbing activity.
Lactoferrin (LF) is a key modulator of inflammatory response. Since bone and immune systems are genetically and functionally linked, we were interested to know if LF could influence bone remodeling. Bovine LF (bLF) inhibited in vitro bone resorbing activity (IC50, 200 microg/ml) in a rabbit mixed bone cell culture, consisting of authentic osteoclasts in an environment of osteoblast and stromal cells. Using human CD14 selected cells committed toward osteoclasts, bLF (10 microg/ml) stimulated cell proliferation, however, led to an inhibition of calcitonin receptor mRNA expression, a main marker of osteoclast phenotype, and decreased the global resorbing activity. No modulation of RANK mRNA expression was observed and mRNA for RANKL and OPG were not detected in this culture system, suggesting that bLF inhibits osteoclastogenesis and reduces bone resorption through a mechanism independent of OPG/RANKL/RANK. In conclusion, bLF appears to modulate bone remodeling. Its mechanism of action remains to be elucidated.


Marsupial relationships and a timeline for marsupial radiation in South Gondwana.
Recent marsupials include about 280 species divided into 18 families and seven orders. Approximately 200 species live in Australia/New Guinea. The remaining species inhabit South America with some of these secondarily ranging into North America. In this study, we examine marsupial relationships and estimate their divergences times using complete mitochondrial (mt) genomes. The sampling, which includes nine new mtDNAs and a total number of 19 marsupial genomes, encompasses all extant orders and 14 families. The analysis identified a basal split between Didelphimorphia and remaining orders about 69 million years before present (MYBP), while other ordinal divergences were placed in Tertiary times. The monotypic South American order Microbiotheria (Dromiciops gliroides, Monito del Monte) was solidly nested among its Australian counterparts. The results suggest that marsupials colonized Australia twice from Antarctica/South America and that the divergence between Microbiotheria and its Australian relatives coincided with the geological separation of Antarctica and Australia. Within Australia itself, several of the deepest divergences were estimated to have taken place close to the Eocene/Oligocene transition.


Ultrasonic characterization of the fat source and composition of formulated dry-cured meat products.
The aim of this work was to test the feasibility of using ultrasonic measurements to estimate the fat content and identify the fat sources used in formulated dry-cured pork meat products. For that purpose, dry-cured sausages were prepared using different fat sources (two Iberian pork backfats, Iberian lard, and sunflower oil) and contents (fat content from 3% to 17% wet basis) and characterized by measuring the ultrasonic velocity (at 2 degrees C, 6 degrees C, 10 degrees C, 15 degrees C, 20 degrees C, and 25 degrees C), fatty acid profile, thermal behavior, and composition. The fatty acid composition affected the melting behavior of the sausages, which also involved different ultrasonic velocities, depending on the fat source used for the sausage formulation. Significant (p < 0.05) linear relationships were established between the ultrasonic velocity and the percentage of melted fat, by means of which the sausage batches were differentiated according to the fat source used. The ultrasonic velocity temperature dependence allowed the determination of the fat content (explained variance 96.1%) by measuring the ultrasonic velocity in the dry-cured sausages at 2 degrees C and 25 degrees C and using a semi-empirical equation. Therefore, the ultrasonic measurements could be considered as a reliable tool for the characterization and differentiation of formulated dry-cured meat products with different fat sources and contents.


Development of the Migrant Friendly Maternity Care Questionnaire (MFMCQ) for migrants to Western societies: an international Delphi consensus process.
Through the World Health Assembly Resolution, 'Health of Migrants', the international community has identified migrant health as a priority. Recommendations for general hospital care for international migrants in receiving-countries have been put forward by the Migrant Friendly Hospital Initiative; adaptations of these recommendations specific to maternity care have yet to be elucidated and validated. We aimed to develop a questionnaire measuring migrant-friendly maternity care (MFMC) which could be used in a range of maternity care settings and countries. This study was conducted in four stages. First, questions related to migrant friendly maternity care were identified from existing questionnaires including the Migrant Friendliness Quality Questionnaire, developed in Europe to capture recommended general hospital care for migrants, and the Mothers In a New Country (MINC) Questionnaire, developed in Australia and revised for use in Canada to capture the maternity care experiences of migrant women, and combined to create an initial MFMC questionnaire. Second, a Delphi consensus process in three rounds with a panel of 89 experts in perinatal health and migration from 17 countries was undertaken to identify priority themes and questions as well as to clarify wording and format. Third, the draft questionnaire was translated from English to French and Spanish and back-translated and subsequently culturally validated (assessed for cultural appropriateness) by migrant women. Fourth, the questionnaire was piloted with migrant women who had recently given birth in Montreal, Canada. A 112-item questionnaire on maternity care from pregnancy, through labour and birth, to postpartum care, and including items on maternal socio-demographic, migration and obstetrical characteristics, and perceptions of care, has been created--the Migrant Friendly Maternity Care Questionnaire (MFMCQ)--in three languages (English, French and Spanish). It is completed in 45 minutes via interview administration several months post-birth. A 4-stage process of questionnaire development with international experts in migrant reproductive health and research resulted in the MFMCQ, a questionnaire measuring key aspects of migrant-sensitive maternity care. The MFMCQ is available for further translation and use to examine and compare care and perceptions of care within and across countries, and by key socio-demographic, migration, and obstetrical characteristics of migrant women.


Bioethics in the twenty-first century: why we should pay attention to eighteenth-century medical ethics.
Those of us who work in the field of bioethics tend to think that, because the word "bioethics" is new, so too the field is new in all respects, but we are not the first to do bioethics. John Gregory (1724-1773) did bioethics just as we do it, at least two centuries before we thought to do it. He deployed philosophical methods as sophisticated as our own. Indeed, Gregory took up the very best moral philosophy available to thinkers of the Scottish Enlightenment, namely, David Hume's moral philosophy and its core concept of sympathy. Gregory also responded in a conceptually powerful and clinically applicable way to the problems of his time, just as we do. I want here to outline Gregory's accomplishment and to identify some aspects of its importance for bioethics in the twenty-first century.


Aspergillus nidulans synthesize insect juvenile hormones upon expression of a heterologous regulatory protein and in response to grazing by Drosophila melanogaster larvae.
Secondary metabolites are known to serve a wide range of specialized functions including communication, developmental control and defense. Genome sequencing of several fungal model species revealed that the majority of predicted secondary metabolite related genes are silent in laboratory strains, indicating that fungal secondary metabolites remain an underexplored resource of bioactive molecules. In this study, we combine heterologous expression of regulatory proteins in Aspergillus nidulans with systematic variation of growth conditions and observe induced synthesis of insect juvenile hormone-III and methyl farnesoate. Both compounds are sesquiterpenes belonging to the juvenile hormone class. Juvenile hormones regulate developmental and metabolic processes in insects and crustaceans, but have not previously been reported as fungal metabolites. We found that feeding by Drosophila melanogaster larvae induced synthesis of juvenile hormone in A. nidulans indicating a possible role of juvenile hormone biosynthesis in affecting fungal-insect antagonisms.


MAP detection for impairment compensation in coherent WDM systems.
We propose a novel recursive-algorithm based maximum a posteriori probability (MAP) detector in spectrally-efficient coherent wavelength division multiplexing (CoWDM) systems, and investigate its performance in a 1-bit/s/Hz on-off keyed (OOK) system limited by optical-signal-to-noise ratio. The proposed method decodes each sub-channel using the signal levels not only of the particular sub-channel but also of its adjacent sub-channels, and therefore can effectively compensate deterministic inter-sub-channel crosstalk as well as inter-symbol interference arising from narrow-band filtering and chromatic dispersion (CD). Numerical simulation of a five-channel OOK-based CoWDM system with 10Gbit/s per channel using either direct or coherent detection shows that the MAP decoder can eliminate the need for phase control of each optical carrier (which is necessarily required in a conventional CoWDM system), and greatly relaxes the spectral design of the demultiplexing filter at the receiver. It also significantly improves back-to-back sensitivity and CD tolerance of the system.


Compliance in schizophrenia: psychopathology, side effects, and patients' attitudes toward the illness and medication.
In a cross-sectional study, we investigated the influence of several factors on compliance in schizophrenia outpatients, including patients' attitudes toward the illness and medication, specifically antipsychotic medication; adverse effects; and attitudes of caregivers and relatives toward the illness and medication. Patients suffering from schizophrenia (ICD-10 diagnosis) of at least 1-year's duration whose discharge from an inpatient ward was at least 6 weeks prior to inclusion in the study were investigated. Study instruments included a semi-structured compliance interview, the Positive and Negative Syndrome Scale, the Udvalg for Klinske Undersogelser Side Effect Rating Scale, the St. Hans Rating Scale, and the Hillside Akathisia Scale. Data were collected from May 1998 to December 2001. 52.5% (N = 32) of the 61 investigated patients were fully compliant, 39.3% (N = 24) were partially compliant, and only 8.2% (N = 5) were noncompliant. We found positive correlations between compliance and the patients' feelings of a positive effect of the drug on the illness, between compliance and negative symptoms, and between compliance and antipsychotic-induced psychological side effects. Our findings reemphasize the importance of taking subjective attitudes and concerns of patients with respect to their illness and medication seriously. Therefore, it is indispensable to include patients and, if possible, their relatives in the treatment decision process to enhance medication compliance in schizophrenia patients.


Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization.
Hepatitis C virus (HCV) is the most important etiologic agent of non-A, non-B hepatitis and is a major cause of chronic liver disease and hepatocellular carcinoma. Development of an effective vaccine would be the most practical method for prevention of the infection, but whether infection with HCV elicits protective immunity in the host is unclear. Neutralization of HCV in vitro was attempted with plasma of a chronically infected patient, and the residual infectivity was evaluated by inoculation of eight seronegative chimpanzees. The source of HCV was plasma obtained from a patient during the acute phase of posttransfusion non-A, non-B hepatitis, which had previously been titered for infectivity in chimpanzees. Neutralization was achieved with plasma obtained from the same patient 2 yr after the onset of primary infection but not with plasma obtained 11 yr later, although both plasmas contained antibodies against nonstructural and structural (including envelope) HCV proteins. Analysis of sequential viral isolates from the same patient revealed significant genetic divergence as early as 2 yr after infection. However, the HCV recovered from the patient 2 yr after the infection had a striking sequence similarity with the HCV recovered from one of the chimpanzees inoculated with the acute-phase virus, suggesting that the progenitor of the new strain was already present 2 yr earlier. This evidence, together with the different sequences of HCV recovered from the chimpanzees that received the same inoculum, confirms that HCV is present in vivo as a quasispecies. These results provide experimental evidence in vivo that HCV infection elicits a neutralizing antibody response in humans but suggest that such antibodies are isolate-specific. This result raises concerns for the development of a broadly reactive vaccine against HCV.


Challenges and issues in health professions education in Africa.
The challenges facing health professions education in Africa focus on physical infrastructure, accreditation systems, student selection and faculty recruitment, retention, and development. Higher education in the health professions must be closely aligned with community health needs, and with the training and support of community health workers. A key ingredient in changing institutions in this way is implementation of effective strategies for strengthening the faculty. In addition, information systems, and their prerequisite stable electric power supply, must be supported by internal public resources combined with external aid. These infrastructure investments will facilitate better quality education, improved diffusion of information among schools, and more useful data for self study by institutions.


Scaffold-free vascular tissue engineering using bioprinting.
Current limitations of exogenous scaffolds or extracellular matrix based materials have underlined the need for alternative tissue-engineering solutions. Scaffolds may elicit adverse host responses and interfere with direct cell-cell interaction, as well as assembly and alignment of cell-produced ECM. Thus, fabrication techniques for production of scaffold-free engineered tissue constructs have recently emerged. Here we report on a fully biological self-assembly approach, which we implement through a rapid prototyping bioprinting method for scaffold-free small diameter vascular reconstruction. Various vascular cell types, including smooth muscle cells and fibroblasts, were aggregated into discrete units, either multicellular spheroids or cylinders of controllable diameter (300-500 microm). These were printed layer-by-layer concomitantly with agarose rods, used here as a molding template. The post-printing fusion of the discrete units resulted in single- and double-layered small diameter vascular tubes (OD ranging from 0.9 to 2.5mm). A unique aspect of the method is the ability to engineer vessels of distinct shapes and hierarchical trees that combine tubes of distinct diameters. The technique is quick and easily scalable.


Phospholipase A2 activity triggers the wound-activated chemical defense in the diatom Thalassiosira rotula.
The activation of oxylipin-based chemical defense in the diatom Thalassiosira rotula is initiated by phospholipases that act immediately after cell damage. This lipase activity is responsible for the preferential release of free mono- and polyunsaturated fatty acids. Among these, eicosatetraenoic- and eicosapentaenoic acid are further converted by lipoxygenases to reactive defensive metabolites such as the antiproliferative alpha,beta,gamma,delta-unsaturated aldehydes 2,4-decadienal and 2,4,7-decatrienal. We show that mainly saturated free fatty acids are present in the intact diatom T. rotula, whereas the amount of free polyunsaturated eicosanoids is drastically increased in the first minutes after wounding. Using fluorescent probes, the main enzyme activity responsible for initiation of the aldehyde-generating lipase/lipoxygenase/hydroperoxide lyase cascade was characterized as a phospholipase A2. All enzymes involved in this specific defensive reaction are active in seawater over several minutes. Thus, the mechanism allows the unicellular algae to overcome restrictions arising out of potential dilution of defensive metabolites. Only upon predation are high local concentrations of aldehydes formed in the vicinity of the herbivores, whereas in times of low stress, cellular resources can be invested in the formation of eicosanoid-rich phospholipids. In contrast to higher plants, which use lipases acting on galactolipids to release C18 fatty acids for production of leaf-volatile aldehydes, diatoms rely on phospholipids and the transformation of C20 fatty acids to form 2,4-decadienal and 2,4,7-decatrienal as an activated defense.


Tuning the magnetic properties of nanoparticles.
The tremendous interest in magnetic nanoparticles (MNPs) is reflected in published research that ranges from novel methods of synthesis of unique nanoparticle shapes and composite structures to a large number of MNP characterization techniques, and finally to their use in many biomedical and nanotechnology-based applications. The knowledge gained from this vast body of research can be made more useful if we organize the associated results to correlate key magnetic properties with the parameters that influence them. Tuning these properties of MNPs will allow us to tailor nanoparticles for specific applications, thus increasing their effectiveness. The complex magnetic behavior exhibited by MNPs is governed by many factors; these factors can either improve or adversely affect the desired magnetic properties. In this report, we have outlined a matrix of parameters that can be varied to tune the magnetic properties of nanoparticles. For practical utility, this review focuses on the effect of size, shape, composition, and shell-core structure on saturation magnetization, coercivity, blocking temperature, and relaxation time.


Magneto-aerotaxis in marine coccoid bacteria.
Magnetotactic cocci swim persistently along local magnetic field lines in a preferred direction that corresponds to downward migration along geomagnetic field lines. Recently, high cell concentrations of magnetotactic cocci have been found in the water columns of chemically stratified, marine and brackish habitats, and not always in the sediments, as would be expected for persistent, downward-migrating bacteria. Here we report that cells of a pure culture of a marine magnetotactic coccus, designated strain MC-1, formed microaerophilic bands in capillary tubes and used aerotaxis to migrate to a preferred oxygen concentration in an oxygen gradient. Cells were able to swim in either direction along the local magnetic field and used magnetotaxis in conjunction with aerotaxis, i.e., magnetically assisted aerotaxis, or magneto-aerotaxis, to more efficiently migrate to and maintain position at their preferred oxygen concentration. Cells of strain MC-1 had a novel, aerotactic sensory mechanism that appeared to function as a two-way switch, rather than the temporal sensory mechanism used by other bacteria, including Magnetospirillum megnetotacticum, in aerotaxis. The cells also exhibited a response to short-wavelength light (< or = 500 nm), which caused them to swim persistently parallel to the magnetic field during illumination.


A Rare Case of Spontaneous Tumor Lysis Syndrome in Idiopathic Primary Myelofibrosis.
BACKGROUND Tumor lysis syndrome (TLS) is an oncologic emergency resulting from the massive destruction of tumor cells after cytotoxic chemotherapy for chemosensitive malignancies with a high tumor burden. Its clinical manifestations include severe electrolyte disturbances, metabolic acidosis, acute renal failure secondary to urate deposition in the kidney, heart, and skeletal muscle, and nervous system dysfunction. We report an extremely rare case of spontaneous TLS (STLS) in idiopathic primary myelofibrosis (PMF). CASE REPORT A 51-year-old Korean man was admitted to our hospital with general weakness and left-side abdominal pain. The patient was diagnosed with acute urate nephropathy with hyperphosphatemia, hyperkalemia, hypocalcemia, and metabolic acidosis. Splenomegaly was accompanied by leukocytosis and a peripheral blood smear revealed immature granulocytes without blast cells. Bone marrow biopsy showed PMF. Initially, we presumed it was a spontaneous tumor lysis syndrome of PMF. We immediately performed emergency hemodialysis. We concluded that the patient, who had chronic hyperuricemia due to undiagnosed PMF, was recently admitted to the emergency room with STLS due to overwork and dehydration. CONCLUSIONS We present an extremely rare case of STLS in idiopathic PMF. The mechanism of chronic hyperuricemia in our case might be rapid cell turnover due to ineffective erythropoiesis of PMF.


Potential Distribution Predicted for Rhynchophorus ferrugineus in China under Different Climate Warming Scenarios.
As the primary pest of palm trees, Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae) has caused serious harm to palms since it first invaded China. The present study used CLIMEX 1.1 to predict the potential distribution of R. ferrugineus in China according to both current climate data (1981-2010) and future climate warming estimates based on simulated climate data for the 2020s (2011-2040) provided by the Tyndall Center for Climate Change Research (TYN SC 2.0). Additionally, the Ecoclimatic Index (EI) values calculated for different climatic conditions (current and future, as simulated by the B2 scenario) were compared. Areas with a suitable climate for R. ferrugineus distribution were located primarily in central China according to the current climate data, with the northern boundary of the distribution reaching to 40.1°N and including Tibet, north Sichuan, central Shaanxi, south Shanxi, and east Hebei. There was little difference in the potential distribution predicted by the four emission scenarios according to future climate warming estimates. The primary prediction under future climate warming models was that, compared with the current climate model, the number of highly favorable habitats would increase significantly and expand into northern China, whereas the number of both favorable and marginally favorable habitats would decrease. Contrast analysis of EI values suggested that climate change and the density of site distribution were the main effectors of the changes in EI values. These results will help to improve control measures, prevent the spread of this pest, and revise the targeted quarantine areas.


A unified call to action from Australian nursing and midwifery leaders: ensuring that Black lives matter.
Nurses and midwives of Australia now is the time for change! As powerfully placed, Indigenous and non-Indigenous nursing and midwifery professionals, together we can ensure an effective and robust Indigenous curriculum in our nursing and midwifery schools of education. Today, Australia finds itself in a shifting tide of social change, where the voices for better and safer health care ring out loud. Voices for justice, equity and equality reverberate across our cities, our streets, homes, and institutions of learning. It is a call for new songlines of reform. The need to embed meaningful Indigenous health curricula is stronger now than it ever was for Australian nursing and midwifery. It is essential that nursing and midwifery leadership continue to build an authentic collaborative environment for Indigenous curriculum development. Bipartisan alliance is imperative for all academic staff to be confident in their teaching and learning experiences with Indigenous health syllabus. This paper is a call out. Now is the time for Indigenous and non-Indigenous nurses and midwives to make a stand together, for justice and equity in our teaching, learning, and practice. Together we will dismantle systems, policy, and practices in health that oppress. The Black Lives Matter movement provides us with a 'now window' of accepted dialogue to build a better, culturally safe Australian nursing and midwifery workforce, ensuring that Black Lives Matter in all aspects of health care.


Field test of quantum key distribution in the Tokyo QKD Network.
A secure communication network with quantum key distribution in a metropolitan area is reported. Six different QKD systems are integrated into a mesh-type network. GHz-clocked QKD links enable us to demonstrate the world-first secure TV conferencing over a distance of 45km. The network includes a commercial QKD product for long-term stable operation, and application interface to secure mobile phones. Detection of an eavesdropper, rerouting into a secure path, and key relay via trusted nodes are demonstrated in this network.


Single-Stage Cartilage Repair Using Platelet-Rich Fibrin Scaffolds With Autologous Cartilaginous Grafts.
To avoid complicated procedures requiring in vitro chondrocyte expansion for cartilage repair, the development of a culture-free, 1-stage approach combining platelet-rich fibrin (PRF) and autologous cartilage grafts may be the solution. To develop a feasible 1-step procedure to combine PRF and autologous cartilage grafts for articular chondral defects. Controlled laboratory study Methods: The chemotactic effects of PRF on chondrocytes harvested from the primary culture of rabbit cartilage were evaluated in vitro and ex vivo. The rabbit chondrocytes were cultured with different concentrations of PRF media and evaluated for their cell proliferation, chondrogenic gene expression, cell viability, and extracellular matrix synthesis abilities. For the in vivo study, the chondral defects were created on established animal models of rabbits. The gross anatomy, histology, and objective scores were evaluated to validate the treatment results. PRF improved the chemotaxis, proliferation, and viability of the cultured chondrocytes. The gene expression of the chondrogenic markers, including type II collagen and aggrecan, revealed that PRF induced the chondrogenic differentiation of cultured chondrocytes. PRF increased the formation and deposition of the cartilaginous matrix produced by cultured chondrocytes. The efficacy of PRF on cell viability was comparable with that of fetal bovine serum. In animal disease models, morphologic, histological, and objectively quantitative evaluation demonstrated that PRF combined with cartilage granules was feasible in facilitating chondral repair. PRF enhances the migration, proliferation, viability, and differentiation of chondrocytes, thus showing an appealing capacity for cartilage repair. The data altogether provide evidence to confirm the feasibility of 1-stage, culture-free method of combining PRF and autologous cartilage graft for repairing articular chondral defects. The single-stage, culture-free method of combining PRF and autologous cartilage is useful for repairing articular chondral defects. These advantages benefit clinical translation by simplifying and potentiating the efficacy of autologous cartilage transplantation.


Characterization of the recalcitrant CYP1 phenotype found in Atlantic killifish (Fundulus heteroclitus) inhabiting a Superfund site on the Elizabeth River, VA.
Fundulus heteroclitus (Atlantic killifish) found at the Atlantic Wood Industries Superfund site on the Elizabeth River (ER) in Portsmouth, VA (USA), have been shown to be resistant to the teratogenic effects of creosote-contaminated sediments found at this highly contaminated site. Many of the polycyclic aromatic hydrocarbons (PAHs) found at the ER are known to activate the aryl hydrocarbon receptor (AHR), and are thought to mediate their toxic effects through this pathway. Activation of the AHR results in the induction of several Phase I and II metabolic enzymes. It has been previously shown that the AHR of killifish from the ER are refractory to induction by AHR agonists. To more fully characterize this altered AHR response, we exposed embryos from the ER and from a reference site on King's Creek, VA (KC) to two PAHs, benzo[alpha]pyrene (BaP) and benzo[k]fluoranthene (BkF), and to the dioxin-like compound (DLC), 3,3',4,4',5-pentachlorobiphenyl (PCB126). We compared their developmental and molecular responses by screening the embryos for CYP1A enzyme activity, cardiac deformities, and mRNA expression of CYP1A, CYP1B1, CYP1C1, and AHR2. Basal gene expression of both CYP1A and CYP1B1 was 40% higher in the KC control embryos compared to those from the ER, while AHR2 and CYP1C1 were not significantly different between the populations. Exposure of KC embryos to BaP, BkF, and PCB126 induced CYP1A activity and cardiac deformities. In contrast, CYP1A activity was induced in ER embryos only in response to BkF exposure, although this induction in ER embryos was significantly lower than that observed in KC fish at comparable concentrations. ER embryos did not develop cardiac deformities in response to any of the chemicals tested. CYP1A, CYP1B1 and CYP1C1 mRNA were all significantly induced in the KC embryos after exposure to BaP, BkF and PCB126. Exposure to BaP and BkF in ER embryos resulted in a significant induction of CYP1A mRNA, albeit significantly lower than observed in KC fish. Interestingly, BaP exposure resulted in induction of CYP1B1 at comparable levels in embryos from both populations. CYP1s were not induced in ER embryos in response to PCB126, nor was CYP1C1 for any treatment examined. Additionally, AHR2 was not significantly induced for any of the treatment groups. This study further characterizes the AHR response in killifish, and provides greater insight into the adapted ER phenotype. The ER adaptation involves the suppression of normal AHR-inducible gene expression for all three CYP1 genes, and therefore is likely an alteration in AHR signaling or control.


The whole story: treatment outcomes with Symbicort.
Asthma is a chronic inflammatory disorder of the airways that has a considerable socioeconomic impact. Asthma management guidelines have been introduced to help provide better long-term control of asthma. Although recommended guidelines may increase the direct medication costs, the overall direct costs of asthma may be reduced due to fewer exacerbations. In addition, indirect costs due to lost productivity and mortality are reduced and patients have an improved quality of life. Inhaled corticosteroids are first-line therapy in the treatment of persistent asthma. Against this background, we have assessed the cost-effectiveness of Symbicort (budesonide and formoterol in a single inhaler), a treatment that provides better control of asthma compared with budesonide alone. While the prescribing costs of Symbicort were found to be higher than for budesonide alone, these were partially offset by reduced costs due to fewer asthma exacerbations and a reduced need for other medications. Combined long-term therapy with budesonide and formoterol also improves patient quality of life compared with budesonide alone. Two other factors associated with asthma treatment success and cost-effectiveness are patient/physic an education and good patient adherence to prescribed therapy. The introduction of a single inhaler that is easy to use in simple treatment regimens may improve patient adherence to prescribed medication, thus resulting in improved asthma control and fewer exacerbations. Treatment with Symbicort is more cost-effective than treatment with budesonide alone.


Shati/Nat8l deficiency disrupts adult neurogenesis and causes attentional impairment through dopaminergic neuronal dysfunction in the dentate gyrus.
Successful completion of daily activities relies on the ability to select the relevant features of the environment for memory and recall. Disruption to these processes can lead to various disorders, such as attention-deficit hyperactivity disorder (ADHD). Dopamine is a neurotransmitter implicated in the regulation of several processes, including attention. In addition to the higher-order brain function, dopamine is implicated in the regulation of adult neurogenesis. Previously, we generated mice lacking Shati, an N-acetyltransferase-8-like protein on a C57BL/6J genetic background (Shati/Nat8l-/- ). These mice showed a series of changes in the dopamine system and ADHD-like behavioral phenotypes. Therefore, we hypothesized that deficiency of Shati/Nat8l would affect neurogenesis and attentional behavior in mice. We found aberrant morphology of neurons and impaired neurogenesis in the dentate gyrus of Shati/Nat8l-/- mice. Additionally, research has suggested that impaired neurogenesis might be because of the reduction of dopamine in the hippocampus. Galantamine (GAL) attenuated the attentional impairment observed in the object-based attention test via increasing the dopamine release in the hippocampus of Shati/Nat8l-/- mice. The α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, and dopamine D1 receptor antagonist, SCH23390, blocked the ameliorating effect of GAL on attentional impairment in Shati/Nat8l-/- mice. These results suggest that the ameliorating effect of GAL on Shati/Nat8l-/- attentional impairment is associated with activation of D1 receptors following increased dopamine release in the hippocampus via α7 nicotinic acetylcholine receptor. In summary, Shati/Nat8l is important in both morphogenesis and neurogenesis in the dentate gyrus and attention, possible via modulation of dopaminergic transmission. Cover Image for this issue: https://doi.org/10.1111/jnc.15061.


Stationary and integrated autoregressive neural network processes.
We consider autoregressive neural network (AR-NN) processes driven by additive noise and demonstrate that the characteristic roots of the shortcuts-the standard conditions from linear time-series analysis-determine the stochastic behavior of the overall AR-NN process. If all the characteristic roots are outside the unit circle, then the process is ergodic and stationary. If at least one characteristic root lies inside the unit circle, then the process is transient. AR-NN processes with characteristic roots lying on the unit circle exhibit either ergodic, random walk, or transient behavior. We also analyze the class of integrated AR-NN (ARI-NN) processes and show that a standardized ARI-NN process "converges" to a Wiener process. Finally, least-squares estimation (training) of the stationary models and testing for nonstationarity is discussed. The estimators are shown to be consistent, and expressions on the limiting distributions are given.


Synthesis and application of a new hexamethyl-1,1'-spirobiindane-based chiral bisphosphine (HMSI-PHOS) ligand in asymmetric allylic alkylation.
The emerging and versatile application of chiral bisphosphine ligands in diverse asymmetric reactions has resulted in great demand for novel bisphosphine ligands containing different innovative backbones. Herein, a new type of chiral spiro bisphosphine ligand (HMSI-PHOS) has been developed on the basis of a hexamethyl-1,1'-spirobiindane motif. A series of new HMSI-PHOS ligands were synthesized and used in Pd-catalyzed asymmetric allylic alkylation reactions, and moderate to good yields and enantioselectivities were obtained with phenyl substituted ligands.


Activation of epidermal growth factor receptor is required for NTHi-induced NF-κB-dependent inflammation.
Inflammation is a hallmark of many serious human diseases. Nontypeable Haemophilus influenzae (NTHi) is an important human pathogen causing respiratory tract infections in both adults and children. NTHi infections are characterized by inflammation, which is mainly mediated by nuclear transcription factor-kappa B (NF-κB)-dependent production of proinflammatory mediators. Epidermal growth factor receptor (EGFR) has been shown to play important roles in regulating diverse biological processes, including cell growth, differentiation, apoptosis, adhesion, and migration. Its role in regulating NF-κB activation and inflammation, however, remains largely unknown. In the present study, we demonstrate that EGFR plays a vital role in NTHi-induced NF-κB activation and the subsequent induction of proinflammatory mediators in human middle ear epithelial cells and other cell types. Importantly, we found that AG1478, a specific tyrosine kinase inhibitor of EGFR potently inhibited NTHi-induced inflammatory responses in the middle ears and lungs of mice in vivo. Moreover, we found that MKK3/6-p38 and PI3K/Akt signaling pathways are required for mediating EGFR-dependent NF-κB activation and inflammatory responses by NTHi. Here, we provide direct evidence that EGFR plays a critical role in mediating NTHi-induced NF-κB activation and inflammation in vitro and in vivo. Given that EGFR inhibitors have been approved in clinical use for the treatment of cancers, current studies will not only provide novel insights into the molecular mechanisms underlying the regulation of inflammation, but may also lead to the development of novel therapeutic strategies for the treatment of respiratory inflammatory diseases and other inflammatory diseases.


PHF19 promotes multiple myeloma tumorigenicity through PRC2 activation and broad H3K27me3 domain formation.
Dysregulation of polycomb repressive complex 2 (PRC2) promotes oncogenesis partly through its enzymatic function for inducing trimethylation of histone H3 lysine 27 (H3K27me3). However, it remains to be determined how PRC2 activity is regulated in normal and diseased settings. We here report a PRC2-associated cofactor, PHD finger protein 19 (PHF19; also known as polycomb-like 3), as a crucial mediator of tumorigenicity in multiple myeloma (MM). Overexpression and/or genomic amplification of PHF19 is found associated with malignant progression of MM and plasma cell leukemia, correlating to worse treatment outcomes. Using various MM models, we demonstrated a critical requirement of PHF19 for tumor growth in vitro and in vivo. Mechanistically, PHF19-mediated oncogenic effect relies on its PRC2-interacting and chromatin-binding functions. Chromatin immunoprecipitation followed by sequencing profiling showed a critical role for PHF19 in maintaining the H3K27me3 landscape. PHF19 depletion led to loss of broad H3K27me3 domains, possibly due to impaired H3K27me3 spreading from cytosine guanine dinucleotide islands, which is reminiscent to the reported effect of an "onco"-histone mutation, H3K27 to methionine (H3K27M). RNA-sequencing-based transcriptome profiling in MM lines also demonstrated a requirement of PHF19 for optimal silencing of PRC2 targets, which include cell cycle inhibitors and interferon-JAK-STAT signaling genes critically involved in tumor suppression. Correlation studies using patient sample data sets further support a clinical relevance of the PHF19-regulated pathways. Lastly, we show that MM cells are generally sensitive to PRC2 inhibitors. Collectively, this study demonstrates that PHF19 promotes MM tumorigenesis through enhancing H3K27me3 deposition and PRC2's gene-regulatory functions, lending support for PRC2 blockade as a means for MM therapeutics.


Cellulose synthase (CesA) genes in the green alga Mesotaenium caldariorum.
Cellulose, a microfibrillar polysaccharide consisting of bundles of beta-1,4-glucan chains, is a major component of plant and most algal cell walls and is also synthesized by some prokaryotes. Seed plants and bacteria differ in the structures of their membrane terminal complexes that make cellulose and, in turn, control the dimensions of the microfibrils produced. They also differ in the domain structures of their CesA gene products (the catalytic subunit of cellulose synthase), which have been localized to terminal complexes and appear to help maintain terminal complex structure. Terminal complex structures in algae range from rosettes (plant-like) to linear forms (bacterium-like). Thus, algal CesA genes may reveal domains that control terminal complex assembly and microfibril structure. The CesA genes from the alga Mesotaenium caldariorum, a member of the order Zygnematales, which have rosette terminal complexes, are remarkably similar to seed plant CesAs, with deduced amino acid sequence identities of up to 59%. In addition to the putative transmembrane helices and the D-D-D-QXXRW motif shared by all known CesA gene products, M. caldariorum and seed plant CesAs share a region conserved among plants, an N-terminal zinc-binding domain, and a variable or class-specific region. This indicates that the domains that characterize seed plant CesAs arose prior to the evolution of land plants and may play a role in maintaining the structures of rosette terminal complexes. The CesA genes identified in M. caldariorum are the first reported for any eukaryotic alga and will provide a basis for analyzing the CesA genes of algae with different types of terminal complexes.


Short-chain dehydrogenases/reductases (SDRs).
Short-chain dehydrogenases/reductases (SDRs) are enzymes of great functional diversity. Even at sequence identities of typically only 15-30%, specific sequence motifs are detectable, reflecting common folding patterns. We have developed a functional assignment scheme based on these motifs and we find five families. Two of these families were known previously and are called 'classical' and 'extended' families, but they are now distinguished at a further level based on coenzyme specificities. This analysis gives seven subfamilies of classical SDRs and three subfamilies of extended SDRs. We find that NADP(H) is the preferred coenzyme among most classical SDRs, while NAD(H) is that preferred among most extended SDRs. Three families are novel entities, denoted 'intermediate', 'divergent' and 'complex', encompassing short-chain alcohol dehydrogenases, enoyl reductases and multifunctional enzymes, respectively. The assignment scheme was applied to the genomes of human, mouse, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana and Saccharomyces cerevisiae. In the animal genomes, the extended SDRs amount to around one quarter or less of the total number of SDRs, while in the A. thaliana and S. cerevisiae genomes, the extended members constitute about 40% of the SDR forms. The numbers of NAD(H)-dependent and NADP(H)-dependent SDRs are similar in human, mouse and plant, while the proportions of NAD(H)-dependent enzymes are much lower in fruit fly, worm and yeast. We show that, in spite of the great diversity of the SDR superfamily, the primary structure alone can be used for functional assignments and for predictions of coenzyme preference.


Structural conformation and leaching from in vitro aged and retrieved Invisalign appliances.
The objectives of this study were to investigate the structure of Invisalign appliances (Align Technology, Santa Clara, Calif) after intraoral exposure, and to qualitatively and quantitatively characterize the substances leached from the aligners after accelerated in vitro aging. Samples of Invisalign appliances were randomly selected from 10 patients before intraoral placement and after retrieval, and the prepared specimens were subjected to (1) bright-field optical reflection microscopy to study the surface morphology; (2) Fourier transform infrared microspectroscopy to characterize the in vivo changes in molecular composition induced on appliance surfaces, (3) scanning electron microscopy and energy dispersive X-ray microanalysis to identify the elemental composition of integuments formed on the surface, and (4) Vickers hardness (HV 200) testing. Another set of reference and retrieved appliances was subjected to artificial aging for 2 weeks, and the extracts were subjected to gas chromatography-mass spectroscopy. The retrieved appliances demonstrated substantial morphological variation relative to the as-received specimens involving abrasion at the cusp tips, adsorption of integuments, and localized calcification of the precipitated biofilm at stagnation sites. Buccal segments of retrieved appliances showed an increase in hardness, which might be attributed to mastication-induced cold work; however, the clinical implication of this effect on mechanotherapy is unknown. In vitro aged and retrieved appliances were found to leach no traceable amount of substances in an ethanol aging solution.


Targeting IκB Kinase β/NF-κB Signaling in Human Prostate Cancer by a Novel IκB Kinase β Inhibitor CmpdA.
NF-κB plays an important role in many types of cancer, including prostate cancer, but the role of the upstream kinase of NF-κB, IKKβ, in prostate cancer has neither been fully documented nor are there any effective IKKβ inhibitors used in clinical settings. Here, we have shown that IKKβ activity is mediated by multiple kinases including IKKα in human prostate cancer cell lines that express activated IKKβ. IHC analysis (IHC) of human prostate cancer tissue microarrays (TMA) demonstrates that phosphorylation of IKKα/β within its activation loop gradually increases in low to higher stage tumors as compared with normal tissue. The expression of cell proliferation and survival markers (Ki-67, Survivin) and epithelial-to-mesenchymal transition (EMT) markers (Slug, Snail), as well as cancer stem cell (CSC)-related transcription factors (Nanog, Sox2, Oct-4), also increase in parallel among the respective TMA samples analyzed. IKKβ, but not NF-κB, is found to regulate Nanog, which, in turn, modulates the levels of Oct4, Sox2, Snail, and Slug, indicating an essential role of IKKβ in regulating CSCs and EMT. The novel IKKβ inhibitor CmpdA inhibits constitutively activated IKKβ/NF-κB signaling, leading to induction of apoptosis and inhibition of proliferation, migration, and stemness in these cells. CmpdA also significantly inhibits tumor growth in xenografts without causing apparent in vivo toxicity. Furthermore, CmpdA and docetaxel act synergistically to inhibit proliferation of prostate cancer cells. These results indicate that IKKβ plays a pivotal role in prostate cancer, and targeting IKKβ, including in combination with docetaxel, may be a potentially useful strategy for treating advanced prostate cancer. Mol Cancer Ther; 15(7); 1504-14. ©2016 AACR.


Plant Essential Oils Synergize and Antagonize Toxicity of Different Conventional Insecticides against Myzus persicae (Hemiptera: Aphididae).
Plant-derived products can play an important role in pest management programs. Essential oils from Lavandula angustifolia (lavender) and Thymus vulgaris (thyme) and their main constituents, linalool and thymol, respectively, were evaluated for insecticidal activity and synergistic action in combination with insecticides against green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae). The essential oils and their main constituents exerted similar insecticidal activity when aphids were exposed by direct sprays, but were non-toxic by exposure to treated leaf discs. In synergism experiments, the toxicity of imidacloprid was synergized 16- to 20-fold by L. angustifolia and T. vulgaris essential oils, but far less synergism occurred with linalool and thymol, indicating that secondary constituents of the oils were probably responsible for the observed synergism. In contrast to results with imidacloprid, the insecticidal activity of spirotetramat was antagonized by L. angustifolia and T. vulgaris essential oils, and linalool and thymol. Our results demonstrate the potential of plant essential oils as synergists of insecticides, but show that antagonistic action against certain insecticides may occur.


Occupational eye injuries experienced by migrant farmworkers.
Migrant farmworkers in North Carolina (n = 300) reported eye injuries, circumstances of injuries, and outcomes during lifetime U.S. agriculture work. Seventeen injuries were reported by 15 farmworkers; five resulted in lost work time. Most reported injuries were penetrating or open wounds, often caused by branches or other foreign objects. Injuries were seldom reported to employers; and treatment at clinics, when received, was often delayed. The incidence rate of lost work-time injuries of 23.8/10,000 worker years (95% confidence interval 7.5, 55.9), exceeds the 2009 national incidence rate (6.9/10,000). Migrant farmworkers constitute a vulnerable population; better occupational safety protections should be considered.


Rate of decline of forced vital capacity predicts future arterial hypertension: the Coronary Artery Risk Development in Young Adults Study.
Lung function studies in middle-aged subjects predict cardiovascular disease mortality. We studied whether greater loss of forced vital capacity (FVC) early in life predicted incident hypertension. The sample was 3205 black and white men and women in the Coronary Artery Risk Development in Young Adults Study examined between 1985 and 1986 (Coronary Artery Risk Development in Young Adults year 0, ages 18-30 years) and 2005-2006 and who were not hypertensive by year 10. FVC was assessed at years 0, 2, 5, 10, and 20. Proportional hazard ratios and linear regression models predicted incident hypertension at years 15 or 20 (n=508) from the change in FVC (FVC at year 10 - peak FVC, where peak FVC was estimated as the maximum across years 0, 2, 5, and 10). Covariates included demographics, center, systolic blood pressure, FVC maximum, smoking, physical activity, asthma, and body mass index. Unadjusted cumulative incident hypertension was 25% in the lowest FVC loss quartile (Q1; median loss: 370 mL) compared with 12% cumulative incident hypertension in those who achieved peak FVC at year 10 (Q4). Minimally adjusted hazard ratio for Q1 versus Q4 was 2.21 (95% CI: 1.73-2.83), and this association remained significant in the fully adjusted model (1.37; 95% CI: 1.05-1.80). Decline in FVC from average age at peak (29.4 years) to 35 years old predicted incident hypertension between average ages 35 and 45 years. The findings may represent a common pathway that may link low normal FVC to cardiovascular disease morbidity and mortality.


Utilization of teledentistry as a tool to screen for dental caries among 12-year-old school children in a rural region of India.
The study aims to assess the reliability of video-graphic method as a tool to screen the dental caries among 12-year-old school children in a rural region of India. A total of 139 school children participated in the study. Visual tactile examinations were conducted using the Decayed, Missing, and Filled Teeth (DMFT) index. Simultaneously, standardized video recording of the oral cavity was performed. Sensitivity and specificity values were calculated for video-graphic assessment of dental caries. Bland-Altman plot was used to assess agreement between the two methods of caries assessment. Likelihood ratio (LR) and receiver-operating characteristic (ROC) curve were used to assess the predictive accuracy of the video-graphic method. Mean DMFT for the study population was 2.47 ± 2.01 and 2.46 ± 1.91 by visual tactile and video-graphic assessment (P = 0.76; > 0.05). Sensitivity and specificity values of 0.86 and 0.58 were established for video-graphic assessment. A fair degree of agreement was noted between the two methods with Intraclass correlation coefficient (ICC) value of 0.56. LR for video-graphic assessment was 2.05. Bland-Altman plot confirmed the level of agreement between the two assessment methods. The area under curve was 0.69 (CI 0.57, 0.80, P = 0.001). Teledentistry examination is comparable to clinical examination when screening for dental caries among school children. This study provides evidence that teledentistry may be used as an alternative screening tool for assessment of dental caries and is viable for remote consultation and treatment planning. Teledentistry offers to change the dynamics of dental care delivery and may effectively bridge the rural-urban oral health divide.


Intestinal absorption of cholecalciferol in alcoholic liver disease and primary biliary cirrhosis.
The intestinal absorption of (3H)cholecalciferol was studied in five patients with alcoholic liver disease, six patients with primary biliary cirrhosis, and 15 healthy subjects. The rate of appearance in plasma of (3H)cholecalciferol after oral ingestion and the subsequent appearance of (3H) polar metabolites in the alcoholic subjects were similar to those in the healthy subjects. In subjects with primary biliary cirrhosis the rate of appearance in plasma of (3H)cholecalciferol was significantly reduced. The rate of appearance of labelled polar metabolites of cholecalciferol was also lower in this group, suggesting that increased removal of labelled vitamin by conversion into more polar metabolites could not account for the reduced plasma (3H)cholecalciferol response. It is suggested that intestinal absorption of cholecalciferol is usually normal in alcoholic liver disease but impaired in primary biliary cirrhosis. Hepatic 25-hydroxylation is normal in alcoholic liver disease but may be defective in primary biliary cirrhosis.


Communication and social interaction anxiety enhance interleukin-1 beta and cortisol reactivity during high-stakes public speaking.
Worry or fear related to speaking in front of others, or more broadly, communicating and interacting with others, is common. At elevated levels, however, it may contribute to heightened stress reactivity during acute speaking challenges. The purpose of this study was to examine multi-system physiological stress reactivity in the context of high-stakes public speaking while considering the impact of hypothesized individual difference risk factors. University student participants (n = 95) delivering speeches as a heavily-weighted component of their final grade had saliva samples collected immediately prior to speaking, immediately after, and 20 min after speech completion. Saliva samples were assayed for alpha amylase (sAA), cortisol, and interleukin-1 beta (IL-1β). Self-reported communication anxiety, social interaction anxiety, rejection sensitivity, and sex were assessed as risk factors for heightened stress reactivity. Salivary sAA, cortisol, and IL-1β significantly changed following speech delivery. Multivariate analyses demonstrated that elevated levels of self-reported communication anxiety and social interaction anxiety were independently associated with increased cortisol and IL-1β responses and combined to enhance HPA axis and inflammatory cytokine activity further (i.e., cortisol and IL-1β AUCI). Sex and rejection sensitivity were unrelated to physiological stress reactivity. These findings suggest that individuals with elevated communication and interaction fears may be at increased risk of heightened neuroendocrine and inflammatory responses following exposure to acute social stressors. Both types of anxiety may combine to increase physiological reactivity further, with unknown, though likely insalubrious, health consequences over time.


Identification of genes and pathways related to lymphovascular invasion in breast cancer patients: A bioinformatics analysis of gene expression profiles.
Surgery is the most effective treatment for breast cancer patients. However, some patients developed recurrence and distant metastasis after surgery. Adjuvant therapy is considered for high-risk patients depending on several prognostic markers, and lymphovascular invasion has become one of such prognostic markers that help physicians to identify the risk for distant metastasis and recurrence. However, the mechanism of lymphovascular invasion in breast cancer remains unknown. This study aims to unveil the genes and pathways that may involve in lymphovascular invasion in breast cancer. In total, 108 breast cancer samples were collected during surgery and microarray analysis was performed. Significance analysis of the microarrays and limma package for R were used to examine differentially expressed genes between lymphovascular invasion-positive and lymphovascular invasion-negative cases. Network and pathway analyses were mapped using the Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery. In total, 86 differentially expressed genes, including 37 downregulated genes and 49 upregulated genes were identified in lymphovascular invasion-positive patients. Among these genes, TNFSF11, IL6ST, and EPAS1 play important roles in cytokine-receptor interaction, which is the most enriched pathway related to lymphovascular invasion. Moreover, the results also suggested that an imbalance between extracellular matrix components and tumor micro-environment could induce lymphovascular invasion. Our study evaluated the underlying mechanisms of lymphovascular invasion, which may further help to assess the risk of breast cancer progression and identify potential targets of adjuvant treatment.


Value of structured reporting in neuromuscular disorders.
To assess whether structured reports (SRs) of MRI in patients with inherited neuromuscular disorders (IND) provide more clinically relevant information than non-structured reports (NSRs) and whether neuroradiologists' expertise affects completeness of reports. Lower limbs' MRI reports of patients with IND produced by neuroradiologists with different level of expertise (> 15 years vs. < 15 years of experience in reading IND-MRI) before and after implementation of a SR template were included. Reports were assessed for the presence of 9 key features relevant for IND management. Reports and images were evaluated by neurologists who assessed: disease-specific muscular involvement pattern; presence of sufficient information to order the appropriate genetic/diagnostic tests; presence of sufficient information to make therapeutic decision/perform biopsy and necessity to review MRI images. Mann-Whitney and Fisher's exact tests were used to compare the number of key features for NSR and SR and neurologists' answers for reports produced by neuroradiologists with different experience. Thirty-one SRs and 101 NSRs were reviewed. A median of 8 and 6 key features was present in SR and NSR, respectively (p value < 0.0001). When reports were produced by less expert neuroradiologists, neurologists recognized muscular involvement pattern, had sufficient information for clinical decision-making/perform biopsy more often with SR than NSR (p values: < 0.0001), and needed to evaluate images less often with SR (p value: 0.0001). When reports produced by expert neuroradiologists were evaluated, no significant difference in neurologists' answers was observed. SR of IND-MRI contained more often clinically relevant information considered important for disease management than NSR. Radiologist's expertise affects completeness of NSR reports.


Super-resolution video microscopy of live cells by structured illumination.
Structured-illumination microscopy can double the resolution of the widefield fluorescence microscope but has previously been too slow for dynamic live imaging. Here we demonstrate a high-speed structured-illumination microscope that is capable of 100-nm resolution at frame rates up to 11 Hz for several hundred time points. We demonstrate the microscope by video imaging of tubulin and kinesin dynamics in living Drosophila melanogaster S2 cells in the total internal reflection mode.


Reproductive and Environmental Drivers of Time and Activity Budgets of Striped Skunks.
The regulation of daily and circannual activity patterns is an important mechanism by which animals may balance energetic requirements associated with both abiotic and biotic variables. Using collar-mounted accelerometers, we assess the relative importance of reproductive stage and environmental conditions on the overall dynamic body acceleration (ODBA) of free-living striped skunks (Mephitis mephitis). We found that activity timing relative to photoperiod varied across seasonal stages for both sexes. Surprisingly, male skunks did not commence activity earlier than females during the mating interval. Moreover, while female skunks began activity before dusk and terminated activity after dawn during mid- through late summer (lactation period), the duration of activity bouts in females during this period was not different from other seasons. Both male and female skunks exhibited high variability and fragmentation in daily activity rhythms except during the lactation period, when females appear to switch to prolonged bouts of nocturnal activity. Overall, ODBA varied by season and sex, with changes in ODBA indicative of seasonal reproductive requirements such as conspecific competition for mates in males and lactation in females. Weather conditions had little effect on skunk activity levels except during the winter season, when snow cover and temperature negatively influenced daily ODBA. Taken together, the activity patterns of striped skunks appear to be primarily driven by seasonal investment in reproduction and secondarily by thermoregulatory constraints during the non-winter months. Our results highlight the importance of considering how environmental and reproductive drivers may interact to affect activity across both the daily and seasonal cycle.


Imprinting of the MEDEA polycomb gene in the Arabidopsis endosperm.
In flowering plants, two cells are fertilized in the haploid female gametophyte. Egg and sperm nuclei fuse to form the embryo. A second sperm nucleus fuses with the central cell nucleus that replicates to generate the endosperm, which is a tissue that supports embryo development. MEDEA (MEA) encodes an Arabidopsis SET domain Polycomb protein. Inheritance of a maternal loss-of-function mea allele results in embryo abortion and prolonged endosperm production, irrespective of the genotype of the paternal allele. Thus, only the maternal wild-type MEA allele is required for proper embryo and endosperm development. To understand the molecular mechanism responsible for the parent-of-origin effects of mea mutations on seed development, we compared the expression of maternal and paternal MEA alleles in the progeny of crosses between two Arabidopsis ecotypes. Only the maternal MEA mRNA was detected in the endosperm from seeds at the torpedo stage and later. By contrast, expression of both maternal and paternal MEA alleles was observed in the embryo from seeds at the torpedo stage and later, in seedling, leaf, stem, and root. Thus, MEA is an imprinted gene that displays parent-of-origin-dependent monoallelic expression specifically in the endosperm. These results suggest that the embryo abortion observed in mutant mea seeds is due, at least in part, to a defect in endosperm function. Silencing of the paternal MEA allele in the endosperm and the phenotype of mutant mea seeds supports the parental conflict theory for the evolution of imprinting in plants and mammals.


The Presence of Real Food Usurps Hypothetical Health Value Judgment in Overweight People.
To develop more ecologically valid models of the neurobiology of obesity, it is critical to determine how the neural processes involved in food-related decision-making translate into real-world eating behaviors. We examined the relationship between goal-directed valuations of food images in the MRI scanner and food consumption at a subsequent ad libitum buffet meal. We observed that 23 lean and 40 overweight human participants showed similar patterns of value-based neural responses to health and taste attributes of foods. In both groups, these value-based responses in the ventromedial PFC were predictive of subsequent consumption at the buffet. However, overweight participants consumed a greater proportion of unhealthy foods. This was not predicted by in-scanner choices or neural response. Moreover, in overweight participants alone, impulsivity scores predicted greater consumption of unhealthy foods. Overall, our findings suggest that, while the hypothetical valuation of the health of foods is predictive of eating behavior in both lean and overweight people, it is only the real-world food choices that clearly distinguish them.


Leveraging single-cell genomics to expand the fungal tree of life.
Environmental DNA surveys reveal that most fungal diversity represents uncultured species. We sequenced the genomes of eight uncultured species across the fungal tree of life using a new single-cell genomics pipeline. We show that, despite a large variation in genome and gene space recovery from each single amplified genome (SAG), ≥90% can be recovered by combining multiple SAGs. SAGs provide robust placement for early-diverging lineages and infer a diploid ancestor of fungi. Early-diverging fungi share metabolic deficiencies and show unique gene expansions correlated with parasitism and unculturability. Single-cell genomics holds great promise in exploring fungal diversity, life cycles and metabolic potential.


The association of bone mineral density with HIV infection and antiretroviral treatment in women.
Low bone mineral density (BMD) has been reported in HIV-infected women and men. We analysed cross-sectional BMD measured by regional dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN) in 152 HIV-negative and 274 HIV-positive (HIV+) women, adjusted for traditional low BMD risk factors. BMD was significantly lower in protease inhibitor (PI) users than in all other groups, and highest in HIV-negative women. In multivariate analyses the prevalence of T-score < -1.0 was significantly higher in the HIV+ women naive to antiretroviral therapy (ART; odds ratio [OR] 4.36, 95% confidence interval [CI] 1.61, 11.8) and the women receiving PI-containing HAART (OR 3.72, CI 1.43, 9.68), with a non-significant difference in non-PI HAART users (OR 2.43, CI 0.92, 6.45), compared with HIV-negative women. In pair-wise adjusted comparisons, BMD was lower in ART-naive than in HIV-negative women (1.22 versus 1.30 g/cm2 at LS; P = 0.004), in PI compared with non-PI HAART users (1.00 versus 1.05 g/cm2 at FN; P = 0.014) and with those ART-naive (1.00 versus 1.03 g/cm2 at FN; P = 0.146). Potential confounders, including duration of ART, prior treatment regimens and traditional risk factors for low BMD did not explain these differences. Longer lopinavir use was significantly correlated with lower BMD (r2 = -0.39, P = 0.024 and r2 = -0.46, P = 0.006 at LS and FN, respectively) and longer efavirenz use with higher BMD (r2 = +0.32, P = 0.004 at FN). HIV infection was associated with lower BMD in women, independent of the traditional risk factors for low BMD. PI-containing HAART compared with non-PI-containing HAART, and longer lopinavir use, were both associated with lower BMD, and efavirenz use was associated with higher BMD.


The effect of pegylated interferon-alpha on the treatment of lamivudine resistant chronic HBeAg positive hepatitis B virus infection.
To determine the response to pegylated interferon-alpha treatment of HBeAg-positive hepatitis B patients with proven lamivudine resistance. Sixteen HBeAg-positive HBV patients with YMDD mutations were treated with pegylated interferon. Median treatment duration was 52 weeks (range 20-53), with a 26-week follow-up. Two of 16 (12.5%) patients seroconverted to HBeAg negative and achieved sustained virological (HBV-DNA levels below 10log 5 copies/ml) together with biochemical (normalization of serum ALT levels) responses. Compared with the strong signal in all other patients, only these two patients had a faint signal in the lamivudine resistance assay. For all patients, the median viral load decreased from 10log 9.4 to 7.9 copies/ml (P = 0.001) during treatment but rebounded to a median of 10log 8.7 copies/ml after treatment cessation. Similarly, elevated median ALT levels at baseline decreased with treatment but rebounded after the end of treatment. In the largest cohort study to date, pegylated interferon-alpha therapy showed marginal efficacy in the presence of lamivudine resistance but such therapy may be beneficial in patients with only small amounts of mutant virus. In our opinion, an analysis of the patient subgroup harbouring an YMDD-mutation should be included in all future studies of pegylated interferon-alpha in chronic hepatitis B.


D-dimer assays in diagnosis and management of thrombotic and bleeding disorders.
D-dimer is a global indicator of coagulation activation and fibrinolysis and, therefore, an indirect marker of thrombotic activity. The utility of D-dimer measurement has been evaluated in several clinical situations including the exclusion of venous thromboembolism (VTE), prediction of future risk of VTE, and the diagnosis and monitoring of disseminated intravascular coagulation (DIC). Assay standardization remains problematic and clinicians need to be aware of variability in D-dimer assay performance and the characteristics of their institution's test when making clinical decisions. This article will review the available evidence for the utilization of D-dimer antigen measurement in the management of thrombotic and bleeding disorders.


Time trend of exposure to dechloranes: Plasma samples of German young adults from the environmental specimen bank collected from 1995 to 2017.
Dechloranes, like Dechlorane Plus® are commonly used flame retardants identified by the EU as substances of very high concern (SVHC) because of their persistence and bioaccumulation potential. To characterize the dechlorane exposure of Germans in the last two decades, 180 archived blood plasma samples of the German Environmental Specimen Bank (students aged 20-29 years) collected at six time points between 1995 and 2017 were analyzed for four dechloranes; namely Dechlorane Plus® (syn- and anti-DDC-CO), dechlorane 602 (DDC-DBF), and dechlorane 603 (DDC-Ant). These were quantified using a GC-MS/MS method. Overall, anti- and syn-DDC-CO were detected in 88% and 98% of the samples, whereas DDC-DBF and DDC-Ant were found in 40% and 37% of the samples, respectively. The median (95th percentile) values were 1.0 ng/g lipid weight (l.w.) (3.0 ng/g l.w.). for anti-DDC-CO, 0.6 ng/g l.w (1.9 ng/g l.w.). for syn-DDC-CO, 0.1 ng/g l.w (0.6 ng/g l.w.). for DDC-DBF, and 0.1 ng/g l.w (0.2 ng/g l.w.). for DDC-Ant. The 95th percentile concentrations of the sum of syn- and anti-DDC-CO decreased from 4.2 ng/g l.w. in 1995, to 2.9 ng/g l.w. in 1999, and subsequently increased to 3.7 ng/g l.w. in 2008, and up to 5.9 ng/g l.w. in 2017. A statistically significant decrease with time was observed for DDC-DBF and DDC-Ant, but not for DDC-CO. Our medians found in blood samples in 2017 are similar to those observed in Germany in 2013/14, but higher compared to values reported in other European countries. Overall, more toxicological and monitoring data is needed to better characterize the potential impact on health.


Branching and oscillations in the epigenetic landscape of cell-fate determination.
The well-known Waddington's epigenetic landscape of cell-fate determination is not static but varies because of the dynamic gene regulation during development. However, existing mathematical models with few state variables and fixed parameters are inadequate in characterizing the temporal transformation of the landscape. Here we simulate a decision-switch model of gene regulation with more than two state variables and with time-varying repression among regulatory factors. We are able to demonstrate multi-lineage differentiation at different timescales that portrays the branching canals in Waddington's illustration. We also present a repressilator-type system that activates suppressed genes via sustained oscillations in a flattened landscape, hence providing an alternative scheme for cellular reprogramming. The time-dependent parameters governed by gradient-based dynamics regulate cell differentiation, dedifferentiation and transdifferentiation. Our prediction integrates the theories of branching and structural oscillations in cell-fate determination, which reveals key temporal patterns of cell differentiation and associated diseases, such as cancer.


Ozonized sunflower oil reduces oxidative damage induced by indomethacin in rat gastric mucosa.
This study was carried out in order to investigate the potential cytoprotective effects of ozonized sunflower oil (OSO) in the damage of rat gastric mucosa induced by indomethacin and also to elucidate the role of reactive oxygen species (ROS), lipid peroxidation and some constituents of antioxidant defense such as superoxide dismutase (SOD) and catalase (CAT) in these effects. The gastric damage was induced by indomethacin (20 mg/kg) as solution in 0.5% sodium bicarbonate and given intragastrically. Three hours later OSO (4, 12 and 24 mg/kg) and cimetidine 25 mg/kg were administered also by oral route. Four hours thereafter the rats were killed and the stomachs were removed for biochemical analysis and histological study. The gastric ulcer index was reduced by OSO and cimetidine. OSO also reduced TBARS concentration, but it increased SOD activity in gastric mucosa homogenates. In contrast, CAT activity was not significantly modified the treatment. Histological study confirmed the cytoprotective effects of OSO in rat gastric mucosa damaged by indomethacin. It was concluded that cytoprotective effects of OSO in rat gastric mucosa are mediated at least partially by upregulation of the antioxidant system and mainly SOD.


Effects of Oxytocin Administration on the Response of Piglets to Weaning.
Weaning is often an abrupt and stressful process. We studied the effects of administering oxytocin, subcutaneously or intranasally, on the ability of pigs to cope with weaning. On a commercial farm 144, 30 day-old pigs from 24 litters were used. On the day of weaning, one male and one female in each litter were administered one of three treatments: intranasal oxytocin (24 International Unit), subcutaneous oxytocin (10 International Unit per kg of body weight), or handled as a control. The pigs were placed in one of eight weaner pens, split by sex and with an equal representation of treatments. Data included body weight and growth, physiology (neutrophil:lymphocyte ratio, plasma cortisol, C-reactive protein and Tumor Necrosis Factor-α concentrations), and behavior (feeding, drinking, social behavior). Both oxytocin treatments tended to result in higher levels of mild aggression within groups (p = 0.08), specifically between oxytocin-administered and control pigs (subcutaneous to control p = 0.03; intranasal to control p = 0.10). Subcutaneously-administered pigs tended to frequent the feeder more often than intranasally-administered pigs (p < 0.10), with the latter having slightly lower body weight 38 days post-weaning (p = 0.03). However, acute oxytocin administration did not result in any noticeable physiological changes 4 or 28 h post-weaning. Hence, the use of a single administration of oxytocin prior to weaning in pigs is not recommended, at least not in the conditions studied here.


No sustained attention differences in a longitudinal randomized trial comparing mindfulness based stress reduction versus active control.
Mindfulness Based Stress Reduction (MBSR) is a secular form of meditation training. The vast majority of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons. Previous studies have found that meditation training over several months is associated with improvements in cognitive control and attention. We used a visual continuous performance task (CPT) to test the effects of eight weeks of mindfulness training on sustained attention by comparing MBSR to the Health Enhancement Program (HEP), a structurally equivalent, active control condition in a randomized, longitudinal design (ClinicalTrials.gov, NCT01301105) focusing on a non-clinical population typical of MBSR participants. Researchers were blind to group assignment. 63 community participants were randomized to either MBSR (n = 31) or HEP (n = 32). CPT analyses were conducted on 29 MBSR participants and 25 HEP participants. We predicted that MBSR would improve visual discrimination ability and sustained attention over time on the CPT compared to HEP, with more home practice associated with greater improvements. Our hypotheses were not confirmed but we did find some evidence for improved visual discrimination similar to effects in partial replication of other research. Our study had sufficient power to demonstrate that intervention groups do not differ in their improvement over time in sustained attention performance. One of our primary predictions concerning the effects of intervention on attentional fatigue was significant but not interpretable. Attentional sensitivity is not affected by mindfulness practice as taught in MBSR, but it is unclear whether mindfulness might positively affect another aspect of attention, vigilance. These results also highlight the relevant procedural modifications required by future research to correctly investigate the role of sustained attention in similar samples. ClinicalTrials.gov, NCT01301105.


Adding a reaction-restoration type transmission rate dynamic-law to the basic SEIR COVID-19 model.
The classical SEIR model, being an autonomous system of differential equations, has important limitations when representing a pandemic situation. Particularly, the geometric unimodal shape of the epidemic curve is not what is generally observed. This work introduces the βSEIR model, which adds to the classical SEIR model a differential law to model the variation in the transmission rate. It considers two opposite thrives generally found in a population: first, reaction to disease presence that may be linked to mitigation strategies, which tends to decrease transmission, and second, the urge to return to normal conditions that pulls to restore the initial value of the transmission rate. Our results open a wide spectrum of dynamic variabilities in the curve of new infected, which are justified by reaction and restoration thrives that affect disease transmission over time. Some of these dynamics have been observed in the existing COVID-19 disease data. In particular and to further exemplify the potential of the model proposed in this article, we show its capability of capturing the evolution of the number of new confirmed cases of Chile and Italy for several months after epidemic onset, while incorporating a reaction to disease presence with decreasing adherence to mitigation strategies, as well as a seasonal effect on the restoration of the initial transmissibility conditions.


Paper-based microchip electrophoresis for point-of-care hemoglobin testing.
Nearly 7% of the world's population live with a hemoglobin variant. Hemoglobins S, C, and E are the most common and significant hemoglobin variants worldwide. Sickle cell disease, caused by hemoglobin S, is highly prevalent in sub-Saharan Africa and in tribal populations of Central India. Hemoglobin C is common in West Africa, and hemoglobin E is common in Southeast Asia. Screening for significant hemoglobin disorders is not currently feasible in many low-income countries with the high disease burden. Lack of early diagnosis leads to preventable high morbidity and mortality in children born with hemoglobin variants in low-resource settings. Here, we describe HemeChip, the first miniaturized, paper-based, microchip electrophoresis platform for identifying the most common hemoglobin variants easily and affordably at the point-of-care in low-resource settings. HemeChip test works with a drop of blood. HemeChip system guides the user step-by-step through the test procedure with animated on-screen instructions. Hemoglobin identification and quantification is automatically performed, and hemoglobin types and percentages are displayed in an easily understandable, objective way. We show the feasibility and high accuracy of HemeChip via testing 768 subjects by clinical sites in the United States, Central India, sub-Saharan Africa, and Southeast Asia. Validation studies include hemoglobin E testing in Bangkok, Thailand, and hemoglobin S testing in Chhattisgarh, India, and in Kano, Nigeria, where the sickle cell disease burden is the highest in the world. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. Study design, methods, and results are presented according to the Standards for Reporting Diagnostic Accuracy (STARD). HemeChip correctly identified all subjects with hemoglobin S, C, and E variants with 100% sensitivity, and displayed an overall diagnostic accuracy of 98.4% in comparison to reference standard methods. HemeChip is a versatile, mass-producible microchip electrophoresis platform that addresses a major unmet need of decentralized hemoglobin analysis in resource-limited settings.


Hierarchy of bound states in the one-dimensional ferromagnetic Ising chain CoNb2O6 investigated by high-resolution time-domain terahertz spectroscopy.
Kink bound states in the one-dimensional ferromagnetic Ising chain compound CoNb2O6 have been studied using high-resolution time-domain terahertz spectroscopy in zero applied magnetic field. When magnetic order develops at low temperature, nine bound states of kinks become visible. Their energies can be modeled exceedingly well by the Airy function solutions to a 1D Schrödinger equation with a linear confining potential. This sequence of bound states terminates at a threshold energy near 2 times the energy of the lowest bound state. Above this energy scale we observe a broad feature consistent with the onset of the two particle continuum. At energies just below this threshold we observe a prominent excitation that we interpret as a novel bound state of bound states--two pairs of kinks on neighboring chains.


Conceiving modernity: discourses on reproduction in a community of Tibetan refugees.
This article examines the trope of reproduction in narratives of Tibetan refugees living in Dharamsala, India. As they make sense of their personal histories, Tibetan refugees invoke a collective story that mirrors human rights literature on Tibet. Women come into contact with this literature through its incorporation into a political discourse expressed by the exile government and health institutions. The article traces facets of this discourse that deal centrally with reproduction. Political discourse on reproduction articulates pronatalism as a solution to the refugee community's concern with survival, and the discourse frames modernity as a site of violence through China's reproductive regulations. And yet, Tibetan refugees also employ the notion of modernity when discussing their own free reproductive decision-making, positioning modern reproductive interventions in opposition to Indian society. The article demonstrates that Tibetan refugees navigate competing figurations of modernity by expressing political resistance and affiliation through the idiom of reproduction.