Selecting 'convenient observers' to probe the atomic structure of CVD graphene on Ir(111) via photoelectron diffraction.
CVD graphene grown on metallic substrates presents, in several cases, a long-range periodic structure due to a lattice mismatch between the graphene and the substrate. For instance, graphene grown on Ir(111), displays a corrugated supercell with distinct adsorption sites due to a variation of its local electronic structure. This type of surface reconstruction represents a challenging problem for a detailed atomic surface structure determination for experimental and theoretical techniques. In this work, we revisited the surface structure determination of graphene on Ir(111) by using the unique advantage of surface and chemical selectivity of synchrotron-based photoelectron diffraction. We take advantage of the Ir 4f photoemission surface state and use its diffraction signal as a probe to investigate the atomic arrangement of the graphene topping layer. We determine the average height and the overall corrugation of the graphene layer, which are respectively equal to 3.40 ± 0.11 Å and 0.45 ± 0.03 Å. Furthermore, we explore the graphene topography in the vicinity of its high-symmetry adsorption sites and show that the experimental data can be described by three reduced systems simplifying the moiré supercell multiple scattering analysis.


Physicians' approaches to providing asthma education to patients and the level of patient involvement in management decisions.
The objectives of this study were to describe physicians' self-reported approaches to providing disease-specific education to adults with asthma in an outpatient setting and their opinions about the level of patient involvement in management decisions. A mailed questionnaire was completed by 163 randomly selected physicians, representing an 80% response rate. The educational actions provided most frequently included information about prescribed medications (90%-100% of physicians), general asthma information (87%-98%), and inhaler demonstration (85%-95%). Educational activities provided least frequently were action plans (7%-74%) and referral to a nonprofit community asthma organization for further information (18%-36%). The reported provision of asthma education was related to patients' asthma severity (p < 0.0001) and physician specialty (p < 0.005). Physicians indicated that their patients were less involved in asthma management decisions than they would prefer (p < 0.001). The results suggest that physicians vary markedly in their approaches to providing asthma education to patients. Future descriptive and intervention studies are needed to identify the most effective models for providing education and patient involvement.


Cultivation of leptospires: fatty acid requirements.
Both the parasitic and the saprophytic leptospires grow well on a pair of fatty acids (one saturated, the other unsaturated) if they contain at least 15 carbon atoms.


A simple and robust quantitative PCR assay to determine CYP21A2 gene dose in the diagnosis of 21-hydroxylase deficiency.
Correct diagnosis of 21-hydroxylase deficiency (21OHD) requires the identification of CYP21A2 gene deletions and CYP21A1P/CYP21A2 chimeric genes, which are disease-causing alleles, and gene duplications, which can lead to false-positive 21OHD allele results. Because lack of suitable CYP21A2 dosage assessment methods hampers correct 21OHD diagnosis, we developed a new assay based on the relative quantification of the CYP21A2 gene using the DSP gene as a reference. The assay to determine CYP21A2 copy number is based on real-time PCR. The method also detects the presence of the CYP21A1P/CYP21A2 chimeric gene. We used a duplex PCR to coamplify the DSP gene, included as an internal control, along with CYP21A2. The difference in threshold cycles between CYP21A2 and DSP genes (DeltaCt) was used to assess CYP21A2 copy number. The DeltaCt values obtained from 24 samples used to set up the method clearly differentiated 3 nonoverlapping intervals, which corresponded to the number of CYP21A2 copies: -1.35 to -0.25 defined 2 gene copies, +0.20 to +2.00 defined 1 copy, and -2.50 to -1.50 defined 3 copies. With these intervals we were able to assess the gene copy number in 24 additional samples. This new method for gene copy assessment detects homozygous and heterozygous CYP21A2 gene deletions, CYP21A1P/CYP21A2 chimeric genes, and gene duplications. Moreover, the method is robust, fast, and easy to use in a molecular diagnosis laboratory. This method together with CYP21A2 gene sequencing can provide a definitive system for the detection of almost all, common as well as rare, 21OHD alleles.


Quantitative computed tomography of the liver in juvenile green sea turtles (Chelonia mydas).
Quantitative computed tomography (QCT) is a highly sensitive, applicable technique for determining the x-ray attenuation of organs. This technique reveals great precision in the detection of alterations in the x-ray attenuation of hepatic parenchyma, although the lack of studies establishing normal values limits its application in wild animals. The objective of this study was to establish mean hepatic attenuation values in four healthy juvenile sea turtles (Chelonia mydas) using QCT. Helical computed tomography scans were performed and regions of interest selected in the liver after multi-planar reconstruction images were obtained. The mean attenuation value for the hepatic parenchyma in these four turtles was 60.09 +/- 5.3 standard deviation Hounsfield units. Determining normal x-ray attenuation values of the liver increases knowledge of the computed tomographic anatomy of this species and may be useful in the investigation of hepatic diseases.


Expression of the secretory leukoprotease inhibitor gene in epithelial cells.
The secretory leukoprotease inhibitor (SLPI) gene codes for a 12-kD protein that within the lung protects the airway epithelium from neutrophil elastase. Screening of 228 alleles in 114 individuals for sequence differences by RNase protection of genomic DNA revealed no detectable polymorphisms in SLPI gene exons II-IV. SLPI gene expression in the lung was demonstrated by identifying SLPI mRNA transcripts in bronchial epithelial cells freshly isolated from normals. Cell lines derived from mucosal surfaces (HS-24 bronchial squamous cell carcinoma, HeLa cervical carcinoma) actively transcribe the SLPI gene and contain SLPI mRNA transcripts, while lung fibroblasts demonstrate no evidence of SLPI gene expression. SLPI mRNA transcripts appear to be relatively stable, with mRNA levels only mildly affected by inhibition of RNA synthesis. Chromatin DNA of HS-24 cells demonstrates two DNase I hypersensitivity sites within the 5' flanking region of exon I of the SLPI gene, whereas fibroblast chromatin has no DNase I accessible sites in the same region. Further analysis of the 5' flanking region demonstrated two contiguous transcription start sites, CAAT and TATA boxes, and several potential regions of known DNA binding proteins. Overall, the SLPI gene appears to be a relatively nonpolymorphic, stable gene that is constitutively expressed at specific tissue sites, but has the potential to be modulated at both the transcriptional and posttranscriptional levels.


[Clinical experience in the use of clonidine in regional anesthesia and early postoperative period (1984-1989)].
Clonidine attracts attention as a sole agent for local anesthesia. This review analyzes the role of alpha 2-adrenergic agents in modern regional anesthesiology, both practical and experimental. Recent controlled studies showed that an alpha 2-adrenoreceptor clonidine administered spinally is characterized by a dose-dependent antinociceptive effect and is as effective as epinephrine in prolonging local anesthetic blocks. Moreover, in combination with spinal opioids, intraspinal clonidine possesses a synergic analgesic effect, potentiating the intensity and duration of opioid anesthesia. Use of clonidine as an adjuvant to various plexus blockades and for caudal block in children is discussed. Regional administration of clonidine involves side effects, such as hypotension, bradycardia, and sedation. Minimization of the dose of alpha 2-adrenergic agonists minimizes the complications. Regional clonidine effects (analgesia, hemodynamic changes, and sedation) and their recognized mechanisms of action are described.


Combinatorial parameter space as an empirical tool for predicting water chemistry: Fe(II) oxidation across a watershed.
Fe(II) oxidation kinetics in surface waters are a complex function of the concentration of several dissolved species that vary geographically and temporally across watersheds. This work reports an empirical, combinatorial investigation of Fe(II) oxidation that simultaneously evaluated these variations across the pH, Fe(II), PO₄³⁻, Cl⁻, Br(-), CO₃²⁻, and natural organic matter (NOM) axes. The work assayed the effects of independent and dependent variables through application of a novel experimental design that varied Fe(II), PO₄³⁻, Cl⁻, Br⁻, and CO₃²⁻ along the pH axis. Each factor was varied across concentration ranges corresponding to the natural variation between typical fresh and salt water. The system was designed to describe the oxidation of Fe(II) that occurs when Fe(II)-rich groundwaters are mixed rapidly with oxic overlaying waters as a result of tidal movement, bioturbation, dredging, and other mixing/resuspension events. Factors and interfactor interactions were statistically evaluated to determine their importance to Fe(II) oxidation at the 95% level of confidence. Significant factors were retained and used to construct predictive numerical models of Fe(II) oxidation rates. Two models (M1 and M2) were constructed to represent the conditional endmembers of unrestricted Fe cycling (M1) and restricted Fe cycling (due to forced precipitation of Fe(III), M2). The models were challenged to predict net Fe(II) oxidation rates across a watershed (the Congaree/Santee rivers, sampled at ten different locations in South Carolina). The models were generally capable of predicting Fe(II) oxidation rates to within the 95% confidence interval, although M2 consistently overpredicted the rate relative to M1. The minimum initial Fe(II) concentration needed to observe Fe cycling is estimated based on the model output.


Lapatinib and platinum-based chemotherapy ameliorate breast cancer with choroidal metastasis and restore visual acuity.
Involvement of the central nervous system in metastatic breast cancer is a particularly dismal occurrence because of its effects on mortality and quality of life. Development of choroidal metastasis in a breast cancer patient indicates poor prognosis and has become the major life-limiting problem. Various treatment modalities for choroidal metastasis have been applied with different efficacy. Here we describe a patient with HER2-overexpressing breast cancer and limited choroidal metastasis who responded to an HER2 tyrosine kinase inhibitor after failure of radiotherapy and chemotherapy. Her visual acuity was completely and durably restored after the targeted therapy. This case provides a unique treatment experience of breast cancer with choroidal metastasis.


Incubation, not sleep, aids problem-solving.
Solving a novel problem and finding innovative solutions requires a flexible and creative recombination of prior knowledge. It is thought that setting a problem aside before giving it another try aids problem-solving. The underlying mechanisms of such an incubation period could include unconscious processing that fosters spreading activation along associated networks and the restructuring of problem representations. Recently, it has been suggested that sleep may also support problem-solving by supporting the transformation and restructuring of memory elements. Since the effect of sleep on problem-solving has been mainly tested using the Remote Associates Test, we chose three different tasks-classical riddles, visual change detection, and anagrams-to examine various aspects of problem-solving and to pinpoint task-specific prerequisites for effects of sleep or incubation to emerge. Sixty-two participants were given two attempts to solve the problems. Both attempts either occurred consecutively or were spaced apart by a 3-hour incubation interval that was spent awake or asleep. We found that a period of incubation positively affected solutions rates in classical riddles, but not in visual change detection or anagram solving. Contrary to our hypothesis, spending the incubation period asleep, did not yield any additional benefit. Our study thus supports the notion that a period of letting a problem rest is beneficial for its solution and confines the role of sleep to memory transformations that do not directly impact on problem-solving ability.


Integrated Assessment of Artisanal and Small-Scale Gold Mining in Ghana - Part 3: Social Sciences and Economics.
This article is one of three synthesis reports resulting from an integrated assessment (IA) of artisanal and small-scale gold mining (ASGM) in Ghana. Given the complexities that involve multiple drivers and diverse disciplines influencing ASGM, an IA framework was used to analyze economic, social, health, and environmental data and to co-develop evidence-based responses in collaboration with pertinent stakeholders. We look at both micro- and macro-economic processes surrounding ASGM, including causes, challenges, and consequences. At the micro-level, social and economic evidence suggests that the principal reasons whereby most people engage in ASGM involve "push" factors aimed at meeting livelihood goals. ASGM provides an important source of income for both proximate and distant communities, representing a means of survival for impoverished farmers as well as an engine for small business growth. However, miners and their families often end up in a "poverty trap" of low productivity and indebtedness, which reduce even further their economic options. At a macro level, Ghana's ASGM activities contribute significantly to the national economy even though they are sometimes operating illegally and at a disadvantage compared to large-scale industrial mining companies. Nevertheless, complex issues of land tenure, social stability, mining regulation and taxation, and environmental degradation undermine the viability and sustainability of ASGM as a livelihood strategy. Although more research is needed to understand these complex relationships, we point to key findings and insights from social science and economics research that can guide policies and actions aimed to address the unique challenges of ASGM in Ghana and elsewhere.


Identification of potent and novel alpha4beta1 antagonists using in silico screening.
The antigen alpha4beta1 (very late antigen-4, VLA-4) plays an important role in the migration of white blood cells to sites of inflammation. It has been implicated in the pathology of a variety of diseases including asthma, multiple sclerosis, and rheumatoid arthritis. We describe a series of potent inhibitors of alpha4beta1 that were discovered using computational screening for replacements of the peptide region of an existing tetrapeptide-based alpha4beta1 inhibitor (1; 4-[N'-(2-methylphenyl)ureido]phenylacetyl-Leu-Asp-Val) derived from fibronectin. The search query was constructed using a model of 1 that was based upon the X-ray conformation of the related integrin-binding region of vascular cell adhesion molecule-1 (VCAM-1). The 3D search query consisted of the N-terminal cap and the carboxyl side chain of 1 because, upon the basis of existing structure-activity data on this series, these were known to be critical for high-affinity binding to alpha4beta1. The computational screen identified 12 reagents from a virtual library of 8624 molecules as satisfying the model and our synthetic filters. All of the synthesized compounds tested inhibit alpha4beta1 association with VCAM-1, with the most potent compound having an IC(50) of 1 nM, comparable to the starting compound. Using CATALYST, a 3D QSAR was generated that rationalizes the variation in activities of these alpha4beta1 antagonists. The most potent compound was evaluated in a sheep model of asthma, and a 30 mg nebulized dose was able to inhibit early and late airway responses in allergic sheep following antigen challenge and prevented the development of nonspecific airway hyperresponsiveness to carbachol. Our results demonstrate that it is possible to rapidly identify nonpeptidic replacements of integrin peptide antagonists. This approach should be useful in identification of nonpeptidic alpha4beta1 inhibitors with improved pharmacokinetic properties relative to their peptidic counterparts.


Vagotomy reveals the importance of the imidazoline receptors in the cardiovascular effects of marsanidine and 7-ME-marsanidine in rats.
The recently synthesized novel benzazole derivates - marsanidine (1-[(imidazolidin-2-yl)imino]indazole) and 7-Me-marsanidine (1-[(imidazolidin-2-yl)imino]-7-methylindazole) display promising effects on the circulatory system. We previously indicated that i.v. administration of both compounds decreased the mean arterial blood pressure (MAP) and heart rate (HR) in rats. The cardiovascular effect of the tested compounds may consist not only in inhibiting the sympathetic, but also in activating the parasympathetic pathways related to vagal nerves. Present experiments were performed to determine how vagotomy, with or without an α2 adrenoreceptor blockade, may affect hypotensive and HR limiting actions of marsanidine and 7-Me-marsanidine. Both compounds were infused i.v. (10 μg/kg b.w.) to anesthetized rats, half of which underwent vagotomy. Half the intact, and half the vagotomised rats received RX821002, an α2 adrenorereceptor inhibitor. MAP and HR were monitored directly throughout the experiment. Vagotomy enhanced hypotension observed after marsanidine administration. The α2 adrenergic blockade abolished the action of marsanidine in both the intact and vagotomised rats. Vagotomy did not affect the 7-Me-marsanidine-induced decrease of MAP or HR. However, it abolished the reducing effect of the α2 adrenergic receptor blockade on the hypotension triggered by 7-Me-marsanidine. The results show that although cardiovascular effects of marsanidine and 7-Me-marsanidine are not mediated by the vagal nerves, vagotomy enhanced sensitivity of the sympathetic pathways for the tested compounds. While the action of marsanidine in vagotomised and intact rats may be explained by activation of the α2 adrenoreceptors, the effects of 7-Me-marsanidine seem to be α2 adrenoreceptor-independent. It seems likely that activation of I1 imidazoline receptors could mediate the observed effects.


Do Sleep Disorders Influence the Prognosis and the Response to the Therapy in Enuretic Children?
The current study describes the prevalence of sleep disorders in enuretic children, playing as influencing factors in the response to treatment and risk of relapse. Data were collected from September 2020 to February 2021 in 114 children aged between 5 and 14 years, with a diagnosis of nocturnal enuresis and concomitant sleep disorders, referred to the Pediatric Unit, Campus BioMedico University, Rome. Enuretic children were subjected to an anamnestic and clinical assessment. Sleep disorders investigated were sleep apnea, sleep talking, snoring, bruxism, restless sleep, and somnambulism. Each patient was subjected both to pharmacological and to non-pharmacological treatments and monitored for 3 months to identify the presence of relapse. Patients were divided into 2 groups according to therapy response, and statistical analysis was performed to evaluate possible variables involved in enuresis relapse. A high prevalence of sleep disorders was documented: 8/114 children (7%) had sleep apnea, 47/114 (41.2%) had bruxism, 66/114 (57.8%) had snoring, 54/114 (47.3%) had sleep talking, 18/114 (15.7%) had restless sleep. Forty-three of 114 children (37.7%) had relapses: 21/43 (49%) relapses occurred in children with only 1 sleep disorder, while 22/43 (51%) relapses occurred in children with 2 or more sleep disorders. Lower risk of relapses was reported in children subjected to dual therapy. Sleep disorders were widely associated with nocturnal enuresis, acting as comorbidities in the clinical course of nocturnal enuresis. Combined therapy seems to be associated with a lower rate of relapse of enuresis in a 3-month follow-up. A multidisciplinary approach is required to improve patients' management.


Mini-Review on Capacity-Building for Data-Driven Early Childhood Systems: The Consortium for Pre-primary Data and Measurement in Sub-Saharan Africa.
Low- and middle-income countries (LMIC) are increasing investments in early childhood development programs, including early childhood education. As programs reach scale, there is increasing demand for evidence on impacts of investments. Little work to date has examined capacity required to effectively use data at scale in LMIC, including opportunities and barriers to integrating data into ongoing program implementation and tracking child development and quality of services at scale. Below, we outline the rationale and approach of the Consortium for Pre-primary Data and Measurement in Sub-Saharan Africa, focused on building capacity for data-driven decision-making in early childhood systems. Themes from the first phase include the importance of building diverse groups of stakeholders to define priorities for data and measurement, the need for coordinated and strategic investments in data and measurement, and the value of long-term investments in government/civil society/university partnerships to generate locally relevant data on early childhood education.


Phylogeny and phylogeography of squirrel monkeys (genus Saimiri) based on cytochrome b genetic analysis.
Squirrel monkeys (genus Saimiri) are distributed over a wide area encompassing the Amazon Basin: French Guiana, Suriname, and Guyana, together with Western Panama and Western Costa Rica. The genus Saimiri includes a complex of species and subspecies displaying considerable morphological variation. Taxonomic and systematic studies have identified, in this genus, one to seven species comprising up to 16 subspecies. The phylogenetic relationships between these taxa are poorly understood. Molecular markers have yielded a consistent framework for the systematics of Central and South American Saimiri, identifying four distinct clades: S. oerstedii, S. sciureus, S. boliviensis, and S. ustus. Here, we reconsider the phylogenetic and biogeographic history of Saimiri on the basis of mitochondrial (mtDNA) sequence data, focusing mostly on individuals originating from the Amazon Basin. We studied 32 monkeys with well-defined geographic origins and inferred the phylogenetic relationships between them on the basis of full-length cytochrome b gene nucleotide sequences. The high level of gene diversity observed (0.966) is consistent with the high level of behavioral and morphological variation observed across the geographic range of the genus: 20 mtDNA haplotypes were identified with a maximum divergence of 4.81% between S. b. boliviensis and S. ustus. In addition to confirming the existence of the four clades previously identified on the basis of molecular characters, we suggest several new lineages, including S. s. macrodon, S. s. albigena, S. s. cassiquiarensis, and S. s. collinsi. We also propose new patterns of dispersion and diversification for the genus Saimiri, and discuss the contribution of certain rivers and forest refuges to its structuring.


High-Performance Piezoelectric Nanogenerators with Imprinted P(VDF-TrFE)/BaTiO3 Nanocomposite Micropillars for Self-Powered Flexible Sensors.
Piezoelectric nanogenerators with large output, high sensitivity, and good flexibility have attracted extensive interest in wearable electronics and personal healthcare. In this paper, the authors propose a high-performance flexible piezoelectric nanogenerator based on piezoelectrically enhanced nanocomposite micropillar array of polyvinylidene fluoride-trifluoroethylene (P(VDF-TrFE))/barium titanate (BaTiO3 ) for energy harvesting and highly sensitive self-powered sensing. By a reliable and scalable nanoimprinting process, the piezoelectrically enhanced vertically aligned P(VDF-TrFE)/BaTiO3 nanocomposite micropillar arrays are fabricated. The piezoelectric device exhibits enhanced voltage of 13.2 V and a current density of 0.33 µA cm-2 , which an enhancement by a factor of 7.3 relatives to the pristine P(VDF-TrFE) bulk film. The mechanisms of high performance are mainly attributed to the enhanced piezoelectricity of the P(VDF-TrFE)/BaTiO3 nanocomposite materials and the improved mechanical flexibility of the micropillar array. Under mechanical impact, stable electricity is stably generated from the nanogenerator and used to drive various electronic devices to work continuously, implying its significance in the field of consumer electronic devices. Furthermore, it can be applied as self-powered flexible sensor work in a noncontact mode for detecting air pressure and wearable sensors for detecting some human vital signs including different modes of breath and heartbeat pulse, which shows its potential applications in flexible electronics and medical sciences.


[Pelvic bone radionecrosis as a late consequence of short-distance radiation therapy].
The paper deals with the estimation of the capabilities and role of different radiation techniques in the detection of late postradiation therapy local tissue responses that are evident as radionecrosis. To specify the nature of changes, it is necessary to take into account clinicoanamnestic data, results of laboratory and instrumental studies (standard X-ray study, multislice computed tomography, and magnetic resonance imaging) at any examination stage. A set of the studies can provide the means of significantly analyzing the bone structures and soft tissues and the degree of injury and identifying complications.


Glutathione and ascorbic acid in spinach (Spinacia oleracea) chloroplasts. The effect of hydrogen peroxide and of Paraquat.
The stroma of spinach chloroplasts contains ascorbic acid and glutathione at millimolar concentrations. [Reduced glutathione]/[oxidized glutathione] and [ascorbate]/[dehydroascorbate] ratios are high under both light and dark conditions and no evidence for a role of oxidized glutathione or dehydroascorbate in the dark-deactivation of fructose bisphosphatase could be obtained. Addition of H2O2 to chloroplasts in the dark decreases the above ratios, an effect that is reversed on illumination. Addition of Paraquat to illuminated chloroplasts caused a rapid oxidation of reduced glutathione and ascorbate, and apparent loss of dehydroascorbate. Paraquat rapidly inactivated fructose bisphosphatase activity, as assayed under physiological conditions.


Iron regulatory proteins, iron responsive elements and iron homeostasis.
The discovery of iron regulatory proteins (IRPs) has provided a molecular framework from which to more fully understand the coordinate regulation of vertebrate iron metabolism. IRPs bind to iron responsive elements (IREs) in specific mRNAs and regulate their utilization. The targets of IRP action now appear to extend beyond proteins that function in the storage (ferritin) or cellular uptake (transferrin receptor) of iron to include those involved in other aspects of iron metabolism as well as in the tricarboxylic acid cycle. To date, it appears that IRPs modulate the utilization of six mammalian mRNAs. Current studies are aimed at defining the mechanisms responsible for the hierarchical regulation of these mRNAs by IRPs. In addition, much interest continues to focus on the signaling pathways through which IRP function is regulated. Multiple factors modulate the RNA binding activity of IRP1 and/or IRP2 including iron, nitric oxide, phosphorylation by protein kinase C, oxidative stress and hypoxia/reoxygenation. Because IRPs are key modulators of the uptake and metabolic fate of iron in cells, they are focal points for the modulation of cellular iron homeostasis in response to a variety of agents and circumstances.


DNA polymerase alpha and beta activity in gamma-irradiated HeLa S3 cells.
The acute effects (less than 2 hours) of gamma-irradiation on DNA polymerase alpha and beta activity in HeLa S3 cells were studied. The enzyme activities were measured in sonicates of the irradiated cells, using an exogenous DNA as template. Both DNA alpha- and beta-polymerase activities decreased following irradiation of the cells. Doses as low as 100 rad significantly reduced the activities of the enzymes. While the activities of both DNA polymerases decreased as the dose received by the cells increased, the major reduction in enzyme activity occurred with doses of 100--200 rad. The reduction in DNA alpha- and beta-polymerase activities was maximal by 30 min post-irradiation and recovered to control values by 2 hours post-irradiation.


Bovine papillomavirus type 2 infection and microscopic patterns of urothelial tumors of the urinary bladder in water buffaloes.
Microscopic patterns of thirty-four urothelial tumors of the urinary bladder of water buffaloes from the Marmara and Black Sea Regions of Turkey are here described. All the animals grazed on lands rich in bracken fern. Histological diagnosis was assessed using morphological parameters recently suggested for the urinary bladder tumors of cattle. Papillary carcinoma was the most common neoplastic lesion (22/34) observed in this study, and low-grade carcinoma was more common (seventeen cases) than high-grade carcinoma (five cases). Papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP), and invasive carcinomas were less frequently seen. Carcinoma in situ (CIS) was often detected associated with some papillary and invasive carcinomas. De novo (primary) CIS was rare representing 3% of tumors of this series. A peculiar feature of the most urothelial tumors was the presence in the tumor stroma of immune cells anatomically organized in tertiary lymphoid organs (TLOs). Bovine papillomavirus type-2 (PV-2) E5 oncoprotein was detected by molecular and immunohistochemistry procedures. Early protein, E2, and late protein, L1, were also detected by immunohistochemical studies. Morphological and molecular findings show that BPV-2 infection contributes to the development of urothelial bladder carcinogenesis also in water buffaloes.


Mechanisms of immunity in typhus infections. 3. Influence of human immune serum and complement on the fate of Rickettsia mooseri within the human macrophages.
Preincubation of Rickettsia mooseri with human typhus convalescent serum, which is not rickettsiacidal but which confers passive protection to animals, opsonizes the rickettsiae for enhanced phagocytosis by monocyte-derived human macrophages in cell culture and renders them susceptible to destruction within the macrophages. Nonspecific opsonization by preincubation of the rickettsia with methylated bovine serum albumin enhances phagocytosis, but the rickettsiae are not prepared for intracellular destruction. Instead, they grow within the macrophages and eventually destroy these cells. Thus, immune serum and macrophages, neither of which is capable of killing these rickettsiae alone, act in concert to destroy the virulent organisms. In this system, immune serum appears to exert two distinct, possibly dissociable, actions on the rickettsiae: enhancement of phagocytosis and preparation for intracellular destruction. Complement is not required for this action but, when present with immune serum, markedly enhances phagocytosis of the rickettsiae, often leading to rapid destruction of the macrophage.


Understanding modern contraception uptake in one Ethiopian community: a case study.
In the last decade, the proportion of Ethiopian women using contraceptive methods has increased substantially (from 14% in 2005 to 35% in 2016 among married women). Numerous factors have contributed to the increased uptake. An important one is the implementation of the Health Extension Program, a government-led health service delivery strategy that has deployed more than 38,000 health extension workers (HEWs) throughout the country. Key mechanisms underlying the success of this program are not well understood. Using a case study approach, the goal of this study is to describe how key features of local contexts, community perceptions, and messaging by HEWs have contributed to the increased use of modern contraception in one community in Ethiopia. We conducted focus groups and individual interviews with men, women, adolescents, and key informants, including (HEWs), in Oromia, Ethiopia. We used a random sampling protocol to recruit all participants except key informants, with whom purposive sampling was used to ensure participants were knowledgeable on family planning in the village. Interviews were audio recorded, translated, transcribed, and then analyzed using applied thematic analysis and NVivo v.11 qualitative research software. We identified four themes that may explain uptake of contraception: (1) HEWs are seen as trusted and valued community members who raised awareness about family planning; (2) the HEW messaging that contraception is useful to space pregnancies among married women was effective; (3) the message that spacing is healthy for mother and child was also effective; and (4) communicating to the entire community (including men, women, adolescents, and religious leaders), contributed to changing attitudes around contraception. The four aspects of the Health Extension Program approach increased uptake of contraception in our sample. In contexts where community health workers are valued by the health systems and local communities they serve, this type of approach to widening modern contraception use could help increase uptake and address unmet need. Understanding these granular aspects of the program in one local context may help explain how use of contraception increased in the country as a whole.


Asymmetric superstructure formed in a block copolymer via phase separation.
Self-assembly of amphiphilic block copolymers into well-ordered structures has attracted significant interest over the past decade. An especially attractive application of block-copolymer self-assembly is the formation of isoporous membranes. A major problem in this process is the lack of sufficient long-range order and the difficulty of up-scaling due to the time-consuming preparation steps. Here, we report an innovative and simple method to prepare isoporous membranes with nanometre-sized pores. The combination of the industrially well-established membrane formation method by non-solvent-induced phase separation with the self-assembly of a block copolymer is demonstrated. The result is the creation of an integral asymmetric membrane of a block copolymer with a highly ordered thin layer on top of a non-ordered sponge-like layer. This straightforward and very fast one-step procedure for membrane formation is reported for the first time. The developed membrane has the potential for highly selective separation.


The impact of flood and post-flood cleaning on airborne microbiological and particle contamination in residential houses.
In January 2011, Brisbane, Australia, experienced a major river flooding event. We aimed to investigate its effects on air quality and assess the role of prompt cleaning activities in reducing the airborne exposure risk. A comprehensive, multi-parameter indoor and outdoor measurement campaign was conducted in 41 residential houses, 2 and 6 months after the flood. The median indoor air concentrations of supermicrometer particle number (PN), PM10, fungi and bacteria 2 months after the flood were comparable to those previously measured in Brisbane. These were 2.88 p cm(-3), 15 μg m(-3), 804 cf um(-3) and 177 cf um(-3) for flood-affected houses (AFH), and 2.74 p cm(-3), 15 μg m(-3), 547 cf um(-3) and 167 cf um(-3) for non-affected houses (NFH), respectively. The I/O (indoor/outdoor) ratios of these pollutants were 1.08, 1.38, 0.74 and 1.76 for AFH and 1.03, 1.32, 0.83 and 2.17 for NFH, respectively. The average of total elements (together with transition metals) in indoor dust was 2296 ± 1328 μg m(-2) for AFH and 1454 ± 678 μg m(-2) for NFH, respectively. In general, the differences between AFH and NFH were not statistically significant, implying the absence of a measureable effect on air quality from the flood. We postulate that this was due to the very swift and effective cleaning of the flooded houses by 60,000 volunteers. Among the various cleaning methods, the use of both detergent and bleach was the most efficient at controlling indoor bacteria. All cleaning methods were equally effective for indoor fungi. This study provides quantitative evidence of the significant impact of immediate post-flood cleaning on mitigating the effects of flooding on indoor bioaerosol contamination and other pollutants.


Oral manifestations in children with AIDS and in controls.
Thirty children with AIDS, aging 2 to 6 years, of both genders, treated as outpatients at the hospital Santa Casa de Misericórdia, São Paulo, were evaluated for oral manifestations and compared to a control group of age- and sex-matched healthy subjects. The correlation between oral lesions and the degree of immunosuppression was analyzed. The most prevalent oral manifestations--lymphadenopathy, followed by gingival alterations--were observed in the children with the highest levels of immunosuppression. Other manifestations observed in the AIDS group were: pseudomembranous and erythematous candidosis, enlargement of the parotids and ulcers. The results did not indicate a higher frequency of lesions. However, the observed oral manifestations had an early occurrence, which indicates that the early diagnosis is an important component in the management of those patients.


Enzymatic fabrication of protein-decorated gold nanoparticles by the aid of artificial peptides with gold-binding affinity.
Here, we report a new approach for the biofabrication of protein-immobilized gold nanoparticles (Au NPs), using oxidoreductase with gold-binding peptide-tagged recombinant proteins. The reduction of Au ions to Au(0) was achieved using a natural electron-donating cofactor, nicotinamide adenine dinucleotide, which was regenerated by the glycerol dehydrogenase (GLD) enzyme. First, we selected the A3 peptide (AYSSGAPPMPPF) as a gold binding moiety. The A3 peptide was introduced to the C-terminus of fusion proteins of immunoglobulin G (IgG)-binding domains of protein G and protein A. In the presence of the recombinant protein, the GLD-catalyzed cofactor reduction resulted in the efficient in situ fabrication of Au NPs immobilized with the fusion protein. Moreover, the protein-immobilized Au NPs were shown to have IgG binding activity. Although the A3 peptide had the ability to stabilize Au NPs, the results suggested that its binding affinity for Au NPs was unexpectedly weaker than that of His-tag. A cysteine residue was thus introduced to a recombinant protein adjacent to the A3 peptide. Finally, an artificial peptide, comprising A3 sequence with the C-terminal single cysteine residue, enabled the stable display of a fusion protein while maintaining its IgG binding activity through the Au-S bond. This enzyme-assisted one-pot methodology for protein-Au NPs conjugation offers one potent route for the facile fabrication of biomolecule-decorated metal NPs.


Halolamina pelagica gen. nov., sp. nov., a new member of the family Halobacteriaceae.
Two extremely halophilic archaeal strains, TBN21(T) and TBN49, were isolated from the Taibei marine solar saltern near Lianyungang city, Jiangsu province, China. Cells of the two strains were pleomorphic and gram-negative and colonies were red. Strains TBN21(T) and TBN49 were able to grow at 25-50 °C (optimum 37 °C), at 1.4-5.1 M NaCl (optimum 3.4-3.9 M) and at pH 5.5-9.5 (optimum pH 7.0-7.5) and neither strain required Mg(2+) for growth. Cells lysed in distilled water and the minimal NaCl concentration to prevent cell lysis was 8 % (w/v). The major polar lipids of the two strains were phosphatidic acid, phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and eight glycolipids; three of these glycolipids (GL3, GL4 and GL5) were chromatographically identical to sulfated mannosyl glucosyl diether (S-DGD-1), galactosyl mannosyl glucosyl diether (TGD-1) and mannosyl glucosyl diether (DGD-1), respectively. Phylogenetic analysis revealed that strains TBN21(T) and TBN49 formed a distinct clade with their closest relative, Halobaculum gomorrense JCM 9908(T) (89.0-89.5 % 16S rRNA gene sequence similarity). The DNA G+C contents of strains TBN21(T) and TBN49 were 64.8 and 62.7 mol%, respectively. DNA-DNA hybridization between strains TBN21(T) and TBN49 was 90.1 %. The phenotypic, chemotaxonomic and phylogenetic properties suggest that strains TBN21(T) and TBN49 represent a novel species in a new genus within the family Halobacteriaceae, for which the name Halolamina pelagica gen. nov., sp. nov. is proposed. The type strain of Halolamina pelagica is TBN21(T) ( = CGMCC 1.10329(T) = JCM 16809(T)).


Acute pancreatitis: a lethal disease of increasing incidence.
Between 1968 and 1979 650 patients in the Bristol clinical area suffered 737 attacks of acute pancreatitis. Sex distribution was approximately equal and mean age was 60 years. Comparison with the previous decade shows an increase in mean annual incidence of first attacks from 53.8 to 73.0 cases per million population. Case mortality was unchanged at 20%. In no less than 35% of fatal cases the diagnosis was first made at necropsy. Gall stones were detected in 50% of first attacks, predominantly in women. The proportion of alcoholics (8% overall) increased three-fold during the period of the study. In 23% of cases no aetiological cause was identified. Eighty patients suffered 99 recurrent attacks of acute pancreatitis, with a mortality rate (12%) that was not significantly lower than that of the first attack. Neglected gall stones accounted for 51% of these subsequent attacks.


Biochemical characterization of amandin, the major storage protein in almond (Prunus dulcis L.).
The almond major storage protein, amandin, was prepared by column chromatography (amandin-1), cryoprecipitation (amandin-2), and isoelectric precipitation (amandin-3) methods. Amandin is a legumin type protein characterized by a sedimentation value of 14S. Amandin is composed of two major types of polypeptides with estimated molecular weights of 42-46 and 20-22 kDa linked via disulfide bonds. Several additional minor polypeptides were also present in amandin. Amandin is a storage protein with an estimated molecular weight of 427,300 +/- 47,600 Da (n = 7) and a Stokes radius of 65.88 +/- 3.21 A (n = 7). Amandin is not a glycoprotein. Amandin-1, amandin-2, and amandin-3 are antigenically related and have similar biochemical properties. Amandin-3 is more negatively charged than either amandin-1 or amandin-2. Methionine is the first essential limiting amino acid in amandin followed by lysine and threonine.


Infant ERPs separate children at risk of dyslexia who become good readers from those who become poor readers.
Dyslexia is heritable and associated with phonological processing deficits that can be reflected in the event-related potentials (ERPs). Here, we recorded ERPs from 2-month-old infants at risk of dyslexia and from a control group to investigate whether their auditory system processes /bAk/ and /dAk/ changes differently. The speech sounds were presented in an oddball paradigm. The children were followed longitudinally and performed a word reading fluency test in second grade. The infant ERPs were subsequently analyzed according to high or low reading fluency in order to find a neurophysiological precursor of poor reading fluency. The results show that the fluent reading children (from both the at-risk and the control group) processed the speech sound changes differentially in infancy as indicated by a mismatch response (MMR). In the control group the MMR was frontally positive and in the fluent at-risk group the MMR was parietally positive. The non-fluent at-risk group did not show an MMR. We conclude that at-risk children who became fluent readers were better at speech processing in infancy than those who became non-fluent readers. This indicates a very early speech processing deficit in the group of later non-fluent readers.


Ultrastructure of the stomach of the small short-tailed shrew, Blarina brevicauda c.
The normal gastric ultrastructure has been characterized for the small short-tailed shrew, Blarina brevicauda c., which is a primitive eutherian and one of the smallest living mammals with extraordinarily high metabolic rate. In general the cell types present and cytologic character of gastric mucosal, submucosal, and muscularis cells were similar to that reported for other more advanced small mammalian species. Chief cells, endocrine cells, and lamina proprial elements were morphologically identical to their counterpart in rats, ferrets and other small carnivores. Distinctive cytologic features in this species of shrew included the scanty monolayer or small number of mucous granules in the simple columnar surface epithelial cells of the mucosa, and the thin elongated shape of their microvilli. Dense bodies were absent in the parietal cell mitochondria of the shrew, though usually abundant in other mammalian parietal cells. Our data indicate few morphologic specializations in the shrew stomach which can be correlated with their high rate of food assimilation and metabolic demands, though future studies of mucosal biochemistry and lower gut morphology may reveal such adaptations.


Design and analysis of a broadband dispersion compensating photonic crystal fiber Raman amplifier operating in S-band.
This paper presents an optimized design of a dispersion compensating photonic crystal fiber (PCF) to achieve gain-flattened Raman performances over S-band using a single pump. Genetic algorithm interfaced with an efficient full-vectorial finite element modal solver based on curvilinear edge/nodal elements is used as an optimization tool for an accurate determination of PCF design parameters. The designed PCF shows high negative dispersion coefficient (-264 ps/nm/km to -1410 ps/nm/km) and negative dispersion slope, providing coarse dispersion compensation over the entire S-band. The module comprised of 1.45-km long optimized PCF exhibits +/-0.46 dB gain ripples over 50 nm wide bandwidth and shows a very low double Rayleigh backscattering value (-59.8 dB). The proposed module can compensate for the dispersion accumulated in one span (80-km) of standard single mode fiber with a residual dispersion of +/-700 ps/nm, ensuring its applicability for 10 Gb/s WDM networks. Additionally, the designed PCF remains single mode over the range of operating wavelengths.


Past racial discrimination exacerbates the effects of racial exclusion on negative affect, perceived control, and alcohol-risk cognitions among Black young adults.
Racial discrimination is associated with alcohol use and risky sex cognitions and behaviors, which are risk factors for negative health outcomes, including human immunodeficiency virus infection. The current study investigated the causal impact of racial discrimination on alcohol and sexual-risk cognitions while exploring potential mediators that might help explain this relation: negative affect, perceived control, and meaningful existence. We also examined if past discrimination impacts the strength of (moderates) these effects. Participants were 287 Black/African American young adults aged 18-25. They were randomly assigned to be excluded or included by White peers via the game Cyberball. Racial exclusion (vs. inclusion) predicted greater: perceived racial discrimination, negative affect, alcohol use willingness, and reduced perceived control and meaningful existence. Furthermore, excluded participants who experienced more past racial discrimination reported the lowest perceived control, and greatest negative affect and alcohol-risk cognitions. The findings suggest that past racial discrimination exacerbates the harmful health effects of immediate experiences of discrimination.


Severity of Ongoing Post-Concussive Symptoms as a Predictor of Cognitive Performance Following a Pediatric Mild Traumatic Brain Injury.
This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury. 203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8-18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1-11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (~4 months) phase. Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not. The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.


Evaluation of toll-like receptors 2 and 4 polymorphism and intestinal microbiota in children with food allergies.
Mutual regulation between immune system and gut microbiota is achieved through several mechanisms including the engagement of toll-like receptors (TLRs) which is expressed on numerous cell types. In this study we aimed to explore the association between food allergies and TLR gene polymorphisms in association with gut microbiota. Toll-like receptors polymorphism frequencies and some bacteria in the gut microbiota in 130 infants aged 1-24 months with egg and/or milk allergy in a prospective cohort were compared with 110 non-food allergic controls. Four candidate polymorphisms (TLR2 rs1898830/rs5743708 and TLR4 rs4986790/rs4986791) were genotyped by allelic discrimination polymerase chain rection (PCR) method. Gut microbiota analysis was achieved by using high-throughput sequencing. The TLR4 rs4986790 (Asp299Gly) single nucleotide polymorphism (SNP) major/minor allele frequency was 0.788/0.212 in food allergy patients and 0.719/0.280 in controls (p=0.017). There was a statistically significant difference between groups in terms of genotype frequencies (AA, AG, GG). Gut microbiota analysis revealed increased Firmicutes phylum in stool of the patients with food allergy. Except for TLR4 rs4986791 (Thr399lle) allele, the other TLR polymorphisms were not associated with food allergies in children. When the bacteria in the intestinal microbiota and TLR2 and TLR4 gene polymorphisms were compared; we determined a statistically significant increase in Bifidobacterium concentration in the intestinal microbiota in TLR4 rs4986791 CT heterozygous genotype (p=0.004). This study demonstrated a partial role of TLR4 gene polymorphism and gut microbiota in the development of food allergies. Future work in this area will be required to clarify the roles of different microbial strains that modulate gut microbiota composition and function in conjunction with TLR transcription pathways.


Contracting for visitation with families.
Visitation in adult critical care units is an important aspect of patient care, and thus should be incorporated into the patient's plan of care. There is no longer a question as to whether visitation should be liberalized or restricted; instead, visitation is individualized in each situation to best meet the patient's needs. One method of incorporating visitation into the care plan is by contracting with patients and family members.


Around-the-clock medical coverage.
Marrying workers' compensation and health insurance plans to reduce administrative workloads and get a firm grip on expenses. Can it work?


Transient confinement of a glycosylphosphatidylinositol-anchored protein in the plasma membrane.
Glycosylphosphatidylinositol (GPI)-anchored proteins participate in many cell surface functions; however, the molecular associations of these lipid-linked proteins within the plasma membrane are not well understood. Recent biochemical analyses of detergent insoluble membrane fractions have suggested that GPI-anchored proteins may be associated with glycosphingolipid (GSL)-enriched domains that also contain cholesterol and signaling molecules such as Src family kinases and, in some cases, caveolae. The movements of two components of the putative GSL-enriched domains, Thy-1, a GPI-anchored protein, and GM1, a GSL, were followed with single particle tracking on C3H 10T1/2 cell surfaces and categorized into four modes of lateral transport, fast diffusion, slow anomalous diffusion, diffusion confined to 325-370 nm diameter regions, and a fraction of molecules that was essentially stationary on the 6.6 s time scale. Longer observations (60 s) showed that Thy-1 and GM1 are transiently confined for 7-9 s to regions averaging 260-330 nm in diameter. Approximately 35-37% of both Thy-1 and GM1 undergo confined diffusion, whereas only 16% of fluorescein phosphatidylethanolamine, a phospholipid analog which is not expected to be found in the GSL domains, experience confined diffusion to regions averaging approximately 230 nm in diameter. Further, when glycosphingolipid expression was reduced approximately 40% with the glucosylceramide synthase inhibitor, d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, the percentage of trajectories exhibiting confinement and the size of the confining domain for Thy-1 were reduced approximately 1.5-fold. In contrast, extraction of cells with Triton X-100 leaves the fraction of molecules confined and the domain sizes of Thy-1 and GM1 unchanged. Our results are consistent with the preferential association of GPI-anchored proteins with glycosphingolipid-enriched domains and suggest that the confining domains may be the in vivo equivalent of the detergent insoluble membrane fractions.


Jugular thrombophlebitis in horses: a review of fibrinolysis, thrombus formation, and clinical management.
Thrombophlebitis of the jugular vein is commonly observed in horses, particularly during intensive care, and leads to local and systemic inflammatory responses as well as head and neck circulatory impairment. Thrombolytic therapy is widely used in human practice with the aim of thrombus dissolution and recanalization of the injured vessels. There are similarities between human and horse coagulation and fibrinolytic processes. This review examines the fibrinolytic system, thrombus formation, and the clinical management of jugular thrombophlebitis, including thrombolytic therapy. There is evidence that early regional thrombolytic therapy for jugular thrombophlebitis in horses may be effective to achieve sustained recanalization.


Two Distinct Assembly States of the Cysteine Regulatory Complex of Salmonella typhimurium Are Regulated by Enzyme-Substrate Cognate Pairs.
Serine acetyltransferase (SAT) and O-acetylserine sulfhydrylase (OASS), which catalyze the last two steps of cysteine biosynthesis, interact and form the cysteine regulatory complex (CRC). The current model of Salmonella typhimurium predicts that CRC is composed of one [SAT]hexamer unit and two molecules of [OASS]dimer. However, it is not clear why [SAT]hexamer cannot engage all of its six high-affinity binding sites. We examined the assembly state(s) of CRC by size exclusion chromatography, analytical ultracentrifugation (AUC), isothermal titration calorimetry (ITC), and surface plasmon resonance (SPR) approaches. We show that CRC exists in two major assembly states, low-molecular weight (CRC1; 1[SAT]hexamer + 2[OASS]dimer) and high-molecular weight (CRC2; 1[SAT]hexamer + 4[OASS]dimer) states. Along with AUC results, ITC and SPR studies show that [OASS]dimer binds to [SAT]hexamer in a stepwise manner but the formation of fully saturated CRC3 (1[SAT]hexamer + 6[OASS]dimer) is not favorable. The fraction of CRC2 increases as the [OASS]dimer/[SAT]hexamer ratio increases to >4-fold, but CRC2 can be selectively dissociated into either CRC1 or free enzymes, in the presence of OAS and sulfide, in a concentration-dependent manner. Together, we show that CRC is a regulatable multienzyme assembly, sensitive to OASS-substrate(s) levels but subject to negative cooperativity and steric hindrance. Our results constitute the first report of the dual-assembly-state nature of CRC and suggest that physiological conditions, which limit sulfate uptake, would favor CRC1 over CRC2.


Methods for the quantitative comparison of molecular estimates of clade age and the fossil record.
Approaches quantifying the relative congruence, or incongruence, of molecular divergence estimates and the fossil record have been limited. Previously proposed methods are largely node specific, assessing incongruence at particular nodes for which both fossil data and molecular divergence estimates are available. These existing metrics, and other methods that quantify incongruence across topologies including entirely extinct clades, have so far not taken into account uncertainty surrounding both the divergence estimates and the ages of fossils. They have also treated molecular divergence estimates younger than previously assessed fossil minimum estimates of clade age as if they were the same as cases in which they were older. However, these cases are not the same. Recovered divergence dates younger than compared oldest known occurrences require prior hypotheses regarding the phylogenetic position of the compared fossil record and standard assumptions about the relative timing of morphological and molecular change to be incorrect. Older molecular dates, by contrast, are consistent with an incomplete fossil record and do not require prior assessments of the fossil record to be unreliable in some way. Here, we compare previous approaches and introduce two new descriptive metrics. Both metrics explicitly incorporate information on uncertainty by utilizing the 95% confidence intervals on estimated divergence dates and data on stratigraphic uncertainty concerning the age of the compared fossils. Metric scores are maximized when these ranges are overlapping. MDI (minimum divergence incongruence) discriminates between situations where molecular estimates are younger or older than known fossils reporting both absolute fit values and a number score for incompatible nodes. DIG range (divergence implied gap range) allows quantification of the minimum increase in implied missing fossil record induced by enforcing a given set of molecular-based estimates. These metrics are used together to describe the relationship between time trees and a set of fossil data, which we recommend be phylogenetically vetted and referred on the basis of apomorphy. Differences from previously proposed metrics and the utility of MDI and DIG range are illustrated in three empirical case studies from angiosperms, ostracods, and birds. These case studies also illustrate the ways in which MDI and DIG range may be used to assess time trees resultant from analyses varying in calibration regime, divergence dating approach or molecular sequence data analyzed.


Auditory and visual attention assessed with PET.
Brain mechanisms involved in the maintenance of attention to auditory and visual stimuli at different spatial locations were assessed using positron emission tomography with [15O]water to measure regional cerebral blood flow (rCBF) changes in 13 normal volunteers. Simultaneous auditory [dichotically presented consonant-vowel-consonants (CVCs)] and visual stimuli (vertically oriented, CVCs presented to the left and right of fixation) were presented on every trial. In different conditions subjects attended for targets in a specified stimulus channel (left or right ears or left or right visual fields) while maintaining fixation on a central x. Attending left or right for auditory stimuli increased rCBF in primary auditory cortex in Heschl's gyrus and in temporal lobe auditory association cortices in both hemispheres. Attending left or right for visual stimuli did not change rCBF in primary visual cortex, and only attention to the right significantly increased rCBF in contralateral occipital cortex. Visual attention caused significant rCBF changes in a widespread network that included frontal, parietal, and temporal cortical regions as well as the cerebellum, whereas rCBF changes due to auditory attention were largely localized in the temporal lobes. The results suggest that spatially directed attention is mediated by different mechanisms in the auditory and visual modalities.


Efficacy and safety of nebulized formoterol as add-on therapy in COPD patients receiving maintenance tiotropium bromide: Results from a 6-week, randomized, placebo-controlled, clinical trial.
Current guidelines for the treatment of chronic obstructive pulmonary disease (COPD) recommend the use of long-acting bronchodilators in the maintenance management of COPD. Combining bronchodilators that work through different mechanisms is recommended in patients with continuous symptoms. We conducted this study to confirm and further investigate the efficacy and safety of nebulized formoterol as an add-on therapy to maintenance tiotropium in patients with COPD. This randomized, double-blind, placebo-controlled, parallel-group study (NCT00507234) was conducted at 24 US sites from March to October 2007 in 155 patients aged > or =40 years with post-bronchodilator forced expiratory volume in 1 second (FEV(1)) > or =25% to <65% predicted normal. COPD patients receiving open-label tiotropium bromide 18 microg once daily during a 1- to 2-week run-in period were randomized to receive either formoterol fumarate inhalation solution 20 microg or placebo by nebulization twice daily for 6 weeks while continuing treatment with tiotropium. Outcomes included serial spirometry, inspiratory capacity (IC), baseline dyspnoea index/transition dyspnoea index (BDI/TDI), daily symptom scores, salbutamol (albuterol) use and health status measured by the St George's Respiratory Questionnaire (SGRQ). The primary efficacy endpoint was standardized absolute FEV(1) area under the curve over 3 hours (AUC(0-3)) at week 6. Treatment groups (formoterol plus tiotropium, n = 78; placebo plus tiotropium, n = 77) were comparable at baseline. At 6 weeks, FEV(1) AUC(0-3) was significantly greater in the formoterol group compared with the placebo group (1.57 vs 1.38 L [p < 0.0001]). Similarly, formoterol plus tiotropium improved other lung function measures, including FEV(1), forced vital capacity and post-dose IC at day 1, and maintained efficacy through week 6. Formoterol plus tiotropium decreased rescue albuterol use throughout the study (p < 0.05). Mean TDI, SGRQ and most symptom scores did not differ between the two treatment groups. Overall, 37% of formoterol plus tiotropium recipients experienced adverse events versus 51% of those receiving placebo plus tiotropium. The addition of nebulized formoterol to tiotropium in maintenance treatment of COPD provided clinically meaningful, statistically significant and sustained improvements in pulmonary function without additional adverse effects.


Age-related changes in the biomechanics of left ventricular twist measured by speckle tracking echocardiography.
The increasing number and proportion of aged individuals in the population warrants knowledge of normal physiological changes of left ventricular (LV) biomechanics with advancing age. LV twist describes the instantaneous circumferential motion of the apex with respect to the base of the heart and has an important role in LV ejection and filling. This study sought to investigate the biomechanics behind age-related changes in LV twist by determining a broad spectrum of LV rotation parameters in different age groups, using speckle tracking echocardiography (STE). The final study population consisted of 61 healthy volunteers (16-35 yr, n=25; 36-55 yr, n=23; 56-75 yr, n=13; 31 men). LV peak systolic rotation during the isovolumic contraction phase (Rot(early)), LV peak systolic rotation during ejection (Rot(max)), instantaneous LV peak systolic twist (Twist(max)), the time to Rot(early), Rot(max), and Twist(max), and rotational deformation delay (defined as the difference of time to basal Rot(max) and apical Rot(max)) were determined by STE using QLAB Advanced Quantification Software (version 6.0; Philips, Best, The Netherlands). With increasing age, apical Rot(max) (P<0.05), time to apical Rot(max) (P<0.01), and Twist(max) (P<0.01) increased, whereas basal Rot(early) (P<0.001), time to basal Rot(early) (P<0.01), and rotational deformation delay (P<0.05) decreased. Rotational deformation delay was significantly correlated to Twist(max) (R(2)=0.20, P<0.05). In conclusion, Twist(max) increased with aging, resulting from both increased apical Rot(max) and decreased rotational deformation delay between the apex and the base of the LV. This may explain the preservation of LV ejection fraction in the elderly.


Functions for Drosophila brachyenteron and forkhead in mesoderm specification and cell signalling.
The visceral musculature of the larval midgut of Drosophila has a lattice-type structure and consists of an inner stratum of circular fibers and an outer stratum of longitudinal fibers. The longitudinal fibers originate from the posterior tip of the mesoderm anlage, which has been termed the caudal visceral mesoderm (CVM). In this study, we investigate the specification of the CVM and particularly the role of the Drosophila Brachyury-homologue brachyenteron. Supported by fork head, brachyenteron mediates the early specification of the CVM along with zinc-finger homeodomain protein-1. This is the first function described for brachyenteron or fork head in the mesoderm of Drosophila. The mode of cooperation resembles the interaction of the Xenopus homologues Xbra and Pintallavis. Another function of brachyenteron is to establish the surface properties of the CVM cells, which are essential for their orderly migration along the trunk-derived visceral mesoderm. During this movement, the CVM cells, under the control of brachyenteron, induce the formation of one muscle/pericardial precursor cell in each parasegment. We propose that the functions of brachyenteron in mesodermal development of Drosophila are comparable to the roles of the vertebrate Brachyury genes during gastrulation.


Renal vasoconstrictor responses to static exercise during orthostatic stress in humans: effects of the muscle mechano- and the baroreflexes.
Renal circulatory adjustments to stress contribute to blood pressure and volume regulation. Both handgrip (HG) and disengagement of baroreflexes with lower body negative pressure (LBNP) can engage the sympathetic nervous system (SNS). However, the effect of simultaneous HG and LBNP on the renal circulation in humans is not known. Eighteen young healthy volunteers were studied. Beat-to-beat changes in renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres) and heart rate (ECG) were monitored during (a) 15 s HG at 30% maximum voluntary contraction (MVC); (b) LBNP at -10 and -30 mmHg (each level for 5 min); and (c) 15 s HG (at 30% MVC) during LBNP at both levels. Renal vascular resistance index (RVR units) was calculated by dividing MAP by RBV. The increases in RVR during HG alone (12 +/- 6%) were not different from the responses noted during combined HG and LBNP (17 +/- 6% at -10 mmHg and 25 +/- 8% at -30 mmHg). These results suggest occlusion occurs between a neural circuit engaged during 15 s of HG (central command and/or the muscle mechanoreflex) and a circuit activated by LBNP. In additional experiments (n = 6), similar non-algebraic summation of RVR was seen during 15 s involuntary biceps contractions (engages only muscle reflexes) and LBNP. With respect to RVR, neural occlusion occurs between baroreflexes and the muscle mechanoreflex. Muscle mechanoreflex mediated renal vasoconstriction during short bouts of HG is not influenced by baroreflex disengagement.


Centers for cardiovascular outcomes research: defining a collaborative vision.
Recognizing the value of outcomes research to understand and bridge translational gaps, to establish evidence in clinical practice and delivery of medicine, and to generate new hypotheses on ongoing questions of treatment and care, the National Heart, Lung, and Blood Institute of the National Institutes of Health established the Centers for Cardiovascular Outcomes Research program in 2010. The National Heart, Lung, and Blood Institute funded 3 centers and a research coordinating unit. Each center has an independent project focus, including (1) characterizing care transition and predicting clinical events and quality of life for patients discharged after an acute coronary syndrome; (2) identifying center and regional factors associated with better patient outcomes across several cardiovascular conditions and procedures; and (3) examining the impact of healthcare reform in Massachusetts on overall and disparate care and outcomes for several cardiovascular conditions and venous thromboembolism. Cross-program collaborations seek to advance the field methodologically and to develop early-stage investigators committed to careers in outcomes research. The Centers for Cardiovascular Outcomes Research program represents a significant investment in cardiovascular outcomes research by the National Heart, Lung, and Blood Institute. The vision of this program is to leverage scientific rigor and cross-program collaboration to advance the science of healthcare delivery and outcomes beyond what any individual unit could achieve alone.


Interferon-induced transmembrane protein-3 rs12252-CC is associated with low differentiation and progression of hepatocellular carcinoma.
Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. The association between IFITM3 and hepatocellular carcinoma (HCC) has been reported. While the relationship between this genetic variation and the progress of HCC remains unclear. To address this issue, we explore the relationship between the IFITM3-rs12252 genetic variants and the progression of HCC in this study.A total of 336 candidates were enrolled in the study, including 156 patients with HBV related HCC and 180 patients with chronic Hepatitis B infections or liver cirrhosis. Liver cirrhosis or chronic hepatitis B were diagnosed with clinical characteristics and staging, laboratory testing, and imaging results of viral infection and hepatic damage. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3, and analyzed with the GraphPad Prism v 5.The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC as compared with the patients with chronic HBV infection or liver cirrhosis. Moreover, the distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Furthermore, the patients with CC genotype were found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes.This study indicates a correlation between the IFITM3-rs12252 CC genotype and the progression of HCC.


Is iron-deficiency anemia associated with migraine? Is there a role for anxiety and depression?
In this study, we determined the frequency of migraine headache in iron-deficiency anemia (IDA) patients and whether it was related to anxiety, depression, and somatization. We included 127 consecutive IDA patients into the study. All patients were asked validated questions about headache and migraine face-to-face. They were administered validated questionnaires for anxiety-depression The Hospital Anxiety and Depression Scale and somatization. The quality of life (QoL) disturbance associated with headache was marked on a 0-10 VAS. Of all IDA patients, 79.5 % defined headache at any time of their life. In addition, 36.2 % of all IDA patients defined the criteria for migraine. IDA patients with migraine were more frequently smokers and had significantly lower hemoglobin and mean corpuscular volume values (p values < 0.05). The IDA group with migraine had significantly higher mean anxiety score (p = 0.046) and headache-related QoL disturbance score (p = 0.021) than the IDA group without migraine. Migraine patients with aura had lower hemoglobin values (p = 0.02), higher depression scores (p = 0.005), and higher migraine-related QoL disturbance scores than others. IDA patients have a high frequency of migraine headache. The presence of anxiety and depression have great influence on the presence of migraine in IDA patients.


Osteoblastic and osteoclastic metastases in a single vertebra-a rare presentation.
Malignancies may produce bony metastases which may be osteoclastic or osteoblastic. Vertebrae are a common site for bony metastases. Prostatic adenocarcinoma is an important source of vertebral metastases that are mainly osteoblastic in nature. As the osteoblastic metastases are developing there is an ongoing osteoclastic activity which is going on at the microscopic level. Presence of gross osteoblastic and osteoclastic lesions, in the same vertebra, have not been reported at the time of presentation. Here a rare case of vertebral metastases is being presented which shows osteoblastic and osteoclastic gross lesions in the same vertebra.


How I treat unexplained arterial thrombosis.
Most arterial thrombotic events have a clear atherosclerotic or cardioembolic etiology, but hematologists are frequently asked to assist in the diagnosis and management of a patient with a nonatherosclerotic and noncardioembolic arterial event, referred to here as an unexplained arterial thrombosis. Because there is an assorted list of factors that can precipitate an arterial event, we present a systematic diagnostic approach to ensure consideration of not only primary hypercoagulable disorders, but also pro-thrombotic medications or substances, vascular and anatomic abnormalities, and undiagnosed systemic disorders, such as malignancy and autoimmune diseases. We also review existing literature of the role of hypercoagulable disorders in arterial thrombosis and discuss our approach to thrombophilia workup in patients after an unexplained arterial event. We conclude with 3 representative cases to both illustrate the application of the outlined diagnostic schema and discuss common management considerations, specifically the selection of anticoagulation vs antiplatelet therapy for secondary prevention.


Impact of polysomy 17 on HER-2/neu immunohistochemistry in breast carcinomas without HER-2/neu gene amplification.
Her-2/neu, a proto-oncogene located on chromosome 17, is an important biomarker in breast carcinoma. Immunohistochemistry (IHC) is currently the most widely used method for assessing Her-2/neu status. Some IHC-positive cases do not show Her-2/neu gene amplification by fluorescence in situ hybridization (FISH). It has been suggested that some of these IHC "false positive" results may in part be due to increased copy number of chromosome 17 resulting in increased Her-2/neu protein expression. We analyzed IHC and FISH data from 561 cases of invasive breast carcinoma to test this hypothesis. IHC and FISH for Her-2/neu were performed on formalin-fixed, paraffin-embedded sections of 561 invasive breast carcinomas. The IHC results were interpreted as 0, 1+, 2+, or 3+ according to the manufacturer's recommended criteria. The FISH results were expressed as a ratio of Her-2/neu/chromosome 17 and were interpreted as positive (> = 2.0) or negative (<2.0) for gene amplification according to the manufacturer's recommended scoring system. We found that in IHC 3+/FISH-negative cases (n = 15) both the average chromosome 17 copy number and the average Her-2/neu copy number were significantly higher than that in IHC (0 to 2+)/FISH-negative cases (n = 411) (2.45 vs. 1.68; P < 0.0001, and 3.19 vs. 1.95; P < 0.0001, respectively). In contrast, the IHC 2+/FISH-negative cases did not exhibit a significantly increased number of chromosome 17 compared to IHC 0 to 1+ cases. In addition, the average copy number of chromosome 17 in FISH-positive cases (n = 135) was significantly higher than that in FISH-negative cases (n = 426) (2.27 vs. 1.70; P < 0.0001), indicating a general association of increased chromosome 17 copy number with Her-2/neu gene amplification. Thus, our data suggest that IHC 3+ immunostaining without scorable gene amplification may indeed be, at least in some cases, the result of increased Her-2/neu protein expression secondary to an increased copy number of chromosome 17, associated with an increased total number of Her-2/neu gene copies per tumor cell.


[Testicular microlithiasis associated with infertility].
A case of testicular microlithiasis that had been incidentally diagnosed by ultrasound in a patient undergoing evaluation for infertility is described and the literature briefly reviewed. The clinical, laboratory (routine blood and urine tests, hormone studies, spermiogram) and testicular ultrasound findings in a 28-year-old male who consulted for infertility are presented. Serum FSH and LH were raised and testosterone fell within the lower ranges. The spermiogram revealed azoospermia. US evaluation showed bilateral small hyperechoic foci without posterior acoustic shadowing, dispersed within a normal testicular parenchyma. Testicular microlithiasis is a rare entity which is usually discovered incidentally during testicular ultrasound evaluation for other conditions such as infertility. The underlying condition (calcium in the seminiferous duct lumen) has a specific ultrasonographic appearance and further studies are not required to make the diagnosis. The patho-genesis and the clinical implications of microlithiasis remain unclear, therefore any associated pathology, such as tumor, infertility, systemic diseases, or chromosomal disorders, must be ruled out. Regular US follow-up is advocated.


Impact of rising seawater temperature on a phagocytic cell population during V. parahaemolyticus infection in the sea anemone E. pallida.
Climate change is increasing ocean temperatures and consequently impacts marine life (e.g., bacterial communities). In this context, studying host-pathogen interactions in marine organisms is becoming increasingly important, not only for ecological conservation, but also to reduce economic loss due to mass mortalities in cultured species. In this study, we used Exaiptasia pallida (E. pallida), an anemone, as an emerging marine model to better understand the effect of rising temperatures on the infection induced by the pathogenic marine bacterium Vibrio parahaemolyticus. The effect of temperature on E. pallida was examined at 6, 24, or 30 h after bath inoculation with 108 CFU of V. parahaemolyticus expressing GFP (Vp-GFP) at 27°C (husbandry temperature) or 31°C (heat stress). Morphological observations of E. pallida and their Hsps expression demonstrated heat stress induced increasing damage to anemones. The kinetics of the infections revealed that Vp-GFP were localized on the surface of the ectoderm and in the mucus during the first hours of infection and in the mesenterial filaments thereafter. To better identify the E. pallida cells targeted by Vp-GFP infection, we used spectral flow cytometry. E. pallida cell types were identified based on their autofluorescent properties. corresponding to different cell types (algae and cnidocytes). We identified an AF10 population whose autofluorescent spectrum was identical to that of human monocytes/macrophage, suggesting that this spectral print could be the hallmark of phagocytic cells called "amebocytes''. AF10 autofluorescent cells had a high capacity to phagocytize Vp-GFP, suggesting their possible role in fighting infection. This was confirmed by microscopy using sorted AF10 and GFP-positive cells (AF10+/GFP+). The number of AF10+/GFP+ cells were reduced at 31°C, demonstrating that increased temperature not only damages tissue but also affects the immune response of E. pallida. In conclusion, our study provides a springboard for more comprehensive studies of immune defense in marine organisms and paves the way for future studies of the dynamics, activation patterns, and functional responses of immune cells when encountering pathogens.


Expression of a complete soybean leghemoglobin gene in root nodules of transgenic Lotus corniculatus.
The complete soybean leghemoglobin lbc(3) gene was transferred into the legume Lotus corniculatus using an Agrobacterium rhizogenes vector system. Organ-specific expression of the soybean gene was observed in root nodules formed on regenerated transgenic plants after infection with Rhizobium loti. The primary transcript was processed in the same way as in soybean nodules and the resulting mRNA was translated into Lbc(3) protein. Quantitative determination of the Lbc(3) protein in nodules of transgenic plants indicated that the steady-state level of the soybean protein is comparable to that of endogenous Lotus leghemoglobin.


Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients.
Infection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specifically, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.


The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation.
Several studies support an association between periodontal disease and atherosclerosis with a crucial role for the pathogen Porphyromonas gingivalis. This study aims at investigating the proteolytic and oxidative activity of P. gingivalis on LDL in a whole blood system using a proteomic approach and analysing the effects of P. gingivalis-modified LDL on cell proliferation. The cellular effects of P. gingivalis in human whole blood were assessed using lumi-aggregometry analysing reactive oxygen species production and aggregation. Blood was incubated for 30 min with P. gingivalis, whereafter LDL was isolated and a proteomic approach was applied to examine protein expression. LDL-oxidation was determined by analysing the formation of protein carbonyls. The effects of P. gingivalis-modified LDL on fibroblast proliferation were studied using the MTS assay. Incubation of whole blood with P. gingivalis caused an extensive aggregation and ROS production, indicating platelet and leucocyte activation. LDL prepared from bacteria-exposed blood showed an increased protein oxidation, elevated levels of apoM and formation of two apoB-100 N-terminal fragments. Porphyromonas gingivalis-modified LDL markedly increased the growth of fibroblasts. Inhibition of gingipain R suppressed the modification of LDL by P. gingivalis. The ability of P. gingivalis to change the protein expression and proliferative capacity of LDL may represent a crucial event in periodontitis-associated atherosclerosis.


Subhuman primate pregnancy complicated by streptozotocin-induced diabetes mellitus.
Polydipsia, polyuria, polyphagia, and glucosuria followed the administration of streptozotocin to 6 nonpregnant and 15 pregnant monkeys (Macaca mulatta) in the first trimester of pregnancy. The diabetogenic action of the drug was also reflected in an induced but variable deterioration in maternal intravenous glucose tolerance and a marked attenuation of maternal plasma insulin responsiveness to intravenous glycemic stimuli. The products of conception were examined in 29 pregnancies. The neonates and the placentas of the streptozotocin-treated pregnant animals were significantly heavier than average for the period of gestation, polyhydramnios was consistently present, and there was an increase in the incidence of third trimester stillbirths. The fetal and maternal plasma glucose, insulin, and growth hormone concentrations were examined after the intravascular administration of glucose or a solution of mixed amino acids to the fetus in the third trimester. The neonatal plasma responses to similar insulinogenic stimuli were also examined.Fetal and neonatal base line plasma insulin concentrations were significantly elevated compared to those of the controls. The administration of intravascular glucose to the fetus, mother, or neonate was associated with a prompt 2-to 5-fold increase in fetal or neonatal plasma insulin concentrations. These findings contrast to the unresponsiveness of the pancreatic islet tissue we reported in normal subhuman primate pregnancy. The intravascular infusion of a relatively low concentration of mixed amino acids (2 mg/min) to the conceptii from the streptozotocin-treated pregnancies was associated with an elevation in fetal and neonatal plasma insulin levels, whereas normal monkey fetuses and neonates required a 10-fold greater concentration of amino acids in the infusate for similar responses. The induced hyperaminoacidemia or hyperglycemia did not consistently alter plasma growth hormone concentrations in the conceptii from normal or streptozotocin-treated pregnancies. These data provide evidence that maternal glucose intolerance during pregnancy is associated with enhanced fetal and neonatal pancreatic islet cell responsiveness to glucose and mixed amino acids. Although the specific mechanism(s) that alters both the sensitivity and responsiveness of the normal pancreatic fetal islet to insulinogenic stimuli remains unclear, the data do indicate that insulin-dependent maternal hyperglycemia and hyperaminoacidemia, separately or in combination could contribute to the fetal hyperinsulinemia of pregnancies complicated by diabetes mellitus. Moreover, the overall experiences with these streptozotocin-treated animals suggest that a subhuman primate model may be available to examine directly the antenatal pathophysiology of abnormal carbohydrate metabolism.


[Ultrasonically established cystic periventricular leukomalacia (PVL): incidence and associated factors in Switzerland 1995-1997].
Cystic periventricular leukomalacia (PVL) is an ischemic brain lesion that mainly affects preterm infants and causes severe neurological damage. Diagnosis is made by cranial ultrasonography. Objectives of this study were to determine the incidence, to identify associated factors and to evaluate the frequency of neurological abnormality at discharge. Infants with PVL in Switzerland were systematically registered (Swiss Pediatric Surveillance Unit, Swiss Neonatal Network) over three years (1995 to 1997). They were compared to a control group matched for gestational age. Over the three year period 40 infants with PVL defined as at least 2 cysts with diameter = 2 mm in the periventricular region were registered (35 of them were preterm babies). In comparison with the matched controls the infants with PVL had received significantly less frequently antenatal corticosteroids (44 vs 78%, Event Rate Ratio 0.57, 95% Confidence Interval 0.38-0.68), they had lower umbilical cord arterial pH and lower Apgar scores; there was a trend to arterial hypotonia and hypocapnia associated with PVL. The infants of the study group needed more often mechanical ventilation or nasal CPAP (92% versus 67%; ERR 1.38, CI 1.07-1.77) and had more often intracranial hemorrhage (39 versus 14%; ERR 2.8, CI 1.13-6.96). 56% of the infants with PVL were considered abnormal at the neurological examination at discharge compared to 28% in the control group (p < 0.02). The incidence of PVL in Switzerland is 1.2% for preterm infants with a birth weight less than 1500 g. Cranial ultrasonography on infants at risk for PVL is important because 44% of the infants with PVL didn't show neurologic abnormalities at discharge.


Improved naming in patients with Broca's aphasia with tDCS.
Language impairment (aphasia) is a common neurological deficit after strokes. For individuals with chronic aphasia (beyond 6 months after the stroke), language improvements with speech therapy (ST) are often limited. Transcranial direct current stimulation (tDCS) is a promising approach to complement language recovery but interindividual variability in treatment response is common after tDCS, suggesting a possible relationship between tDCS and type of linguistic impairment (aphasia type). This current study is a subgroup analysis of a randomised controlled phase II futility design clinical trial on tDCS in chronic post-stroke aphasia. All participants received ST coupled with tDCS (n=31) vs sham tDCS (n=39). Confrontation naming was tested at baseline, and 1, 4, and 24 weeks post-treatment. Broca's aphasia was associated with maximal adjunctive benefit of tDCS, with an average improvement of 10 additional named items with tDCS+ST compared with ST alone at 4 weeks post-treatment. In comparison, tDCS was not associated with significant benefits for other aphasia types F(1)=4.23, p=0.04. Among participants with Broca's aphasia, preservation of the perilesional posterior inferior temporal cortex was associated with higher treatment benefit (R=0.35, p=0.03). These results indicate that adjuvant tDCS can enhance ST to treat naming in Broca's aphasia, and this may guide intervention approaches in future studies.


Toward a neurobiology of delusions.
Delusions are the false and often incorrigible beliefs that can cause severe suffering in mental illness. We cannot yet explain them in terms of underlying neurobiological abnormalities. However, by drawing on recent advances in the biological, computational and psychological processes of reinforcement learning, memory, and perception it may be feasible to account for delusions in terms of cognition and brain function. The account focuses on a particular parameter, prediction error--the mismatch between expectation and experience--that provides a computational mechanism common to cortical hierarchies, fronto-striatal circuits and the amygdala as well as parietal cortices. We suggest that delusions result from aberrations in how brain circuits specify hierarchical predictions, and how they compute and respond to prediction errors. Defects in these fundamental brain mechanisms can vitiate perception, memory, bodily agency and social learning such that individuals with delusions experience an internal and external world that healthy individuals would find difficult to comprehend. The present model attempts to provide a framework through which we can build a mechanistic and translational understanding of these puzzling symptoms.


1alpha-Hydroxylase gene ablation and Pi supplementation inhibit renal calcification in mice homozygous for the disrupted Npt2a gene.
Disruption of the major renal Na-phosphate (Pi) cotransporter gene Npt2a in mice leads to a substantial decrease in renal brush-border membrane Na-Pi cotransport, hypophosphatemia, and appropriate adaptive increases in renal 25-hydroxyvitamin D3-1alpha-hydroxylase (1alphaOHase) activity and the serum concentration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D]. The latter is associated with increased intestinal Ca absorption, hypercalcemia, hypercalciuria, and renal calcification in Npt2-/- mice. To determine the contribution of elevated serum 1,25(OH)2D levels to the development of hypercalciuria and nephrocalcinosis in Npt2-/- mice, we examined the effects of 1alphaOHase gene ablation and long-term Pi supplementation on urinary Ca excretion and renal calcification by microcomputed tomography. We show that the urinary Ca/creatinine ratio is significantly decreased in Npt2-/-/1alphaOHase-/- mice compared with Npt2-/- mice. In addition, renal calcification, determined by estimating the calcified volume to total renal volume (CV/TV), is reduced by 80% in Npt2-/-/1alphaOHase-/- mice compared with that in Npt2-/- mice. In Npt2-/- mice derived from dams fed a 1% Pi diet and maintained on the same diet, we observed a significant decrease in urinary Ca/creatinine that was also associated with 80% reduction in CV/TV when compared with counterparts fed a 0.6% diet. Taken together, the present data demonstrate that both 1alphaOHase gene ablation and Pi supplementation inhibit renal calcification in Npt2-/- mice and that 1,25(OH)2D is essential for the development of hypercalciuria and nephrocalcinosis in the mutant strain.


First-principles investigation of nonmetal doped single-layer BiOBr as a potential photocatalyst with a low recombination rate.
Nonmetal doping is an effective approach to modify the electronic band structure and enhance the photocatalytic performance of bismuth oxyhalides. Using density functional theory, we systematically examine the fundamental properties of single-layer BiOBr doped with boron (B) and phosphorus (P) atoms. The stability of the doped models is investigated based on the formation energies, where the substitutional doping is found to be energetically more stable under O-rich conditions than under Bi-rich ones. The results showed that substitutional doping of P atoms reduced the bandgap of pristine BiOBr to a greater extent than that of boron substitution. The calculation of the effective masses reveals that B doping can render the electrons and holes of pristine BiOBr lighter and heavier, respectively, resulting in a slower recombination rate of photoexcited electron-hole pairs. Based on the results of HOMO-LUMO calculations, the introduction of B atoms tends to increase the number of photocatalytically active sites. The top of the valence band and the conduction band bottom of the B doped BiOBr monolayer match well with the water redox potentials in an acidic environment. The absorption spectra propose that B(P) doping causes a red-shift. Overall, the results predict that nonmetal-doped BiOBr monolayers have a reduced bandgap, a slow recombination rate, more catalytically active sites, enhanced optical absorption edges, and reduced work functions, which will contribute to superior photocatalytic performance.


Typhonium flagelliforme inhibits the proliferation of murine leukemia WEHI-3 cells in vitro and induces apoptosis in vivo.
Typhonium flagelliforme (TF) is a tropical plant, traditionally used by the ethnic population of Malaysia for the cure of various cancers. This plant had shown to induce antiproliferative effect as well as apoptosis in cancer cells. However, there is no available information to address that TF affects murine leukemia cells in vitro and in vivo. Here, we investigated in vitro and in vivo effects of TF on murine leukemia WEHI-3 cells. It was found that the growth of leukemia cells in vitro was inhibited by the various extracts of TF. Among these fractions, the dichloromethane (DCM) tuber extracts of TF showed the lowest IC(50) (24.0 ± 5.2 μg/ml) and had demonstrated apoptogenic effect when observed under fluorescent microscope. We investigated the in vivo effects of DCM tuber extracts of TF on murine leukemia cells, and the results showed that the counts of immature granulocytes and monocytes were significantly decreased in peripheral blood of BALB/c leukemia mice after the oral administration of DCM tuber extracts of TF for 28 days with three doses (200, 400 and 800 mg/kg). These results were confirmed by observing the spleen histopathology and morphology of enlarged spleen and liver in leukemia mice when compared with the control. Furthermore, the cell death mechanism in the spleen tissue of treated mice was found via apoptosis.


Re-evaluating the Contribution of a Fe-Based Current Collector to Bioelectrochemical Methanogenesis: Role and Mechanisms.
The metal-based current collector has been adopted as an essential component of cathodes for electron delivery in microbial electrosynthesis (MES) cells, while the effect of its corrosion on biofilm development and electromethanogenesis activity was overlooked. In this study, the corrosion of the Fe-based current collector was identified to in situ decorate cathode naturally which substantially boosted the performance of CO2 electromethanogenesis in terms of taking over two-thirds less time starting up MES and increasing the CH4 production rate by 3.5 times. Despite the low concentration of Fe (0.13 at%), the electrochemical analysis indicated that it was possible for these Fe deposits to act as electron shuttles and catalysts for H2 production to benefit methanogenesis. The Fe aggregates weakened the dependence of methanogens on electroactive bacteria (EABs) to conduct methanogenesis via interspecies electron transfer as the proportion of EABs on Bio FeCF (with Fe current collector, where CF is carbon felt) was only 25.5% of that on Bio CF (without Fe current collector). On the contrary, the abundance of genes encoding the proteins to uptake extracellular electrons of methanogens on Bio FeCF was 2.3 times higher than that on Bio CF. The enhanced energy transfer maintained high amounts of methanogens and live microorganisms. This study comprehensively explored the multiple roles of Fe-based current collectors in enhancing CO2 electromethanogenesis.