cssi/SciSciGPT-SciSciNet huggingface dataset:
DIRECT AND INDIRECT FLUORESCENT-ANTIBODY TECHNIQUES FOR THE PSITTACOSIS-LYMPHOGRANULOMA VENEREUM-TRACHOMA GROUP OF AGENTS

Ross, Martin R. (Connecticut State Department of Health, Hartford) and Earle K. Borman. Direct and indirect fluorescent-antibody techniques for the psittacosis-lymphogranuloma venereum-trachoma group of agents. J. Bacteriol. 85:851-858. 1963.-Direct and indirect fluorescent-antibody (FA) techniques were developed for the detection of group antigen in infected tissue cultures and the titration of group antibody in human antiserum. The growth of the agent of meningopneumonitis (MP) in mouse embryo lung cell monolayers was followed by infectivity and complement-fixing (CF) antigen titrations, and cytological examination of FA stained cultures. Although infectivity and CF antigen reached a peak at 2 days and remained constant for an additional 3 days, only cells tested 2 to 3 days after infection were suitable for FA staining with labeled anti-MP serum because of excessive artifacts in the older cultures. Fluorescein isothiocyanate-labeled rooster and guinea pig anti-MP serums and human antipsittacosis serums were titrated in direct FA and hemagglutination-inhibition (HI) tests. The rooster conjugate showed brighter staining and higher antibody titers than the guinea pig or human conjugates and was more effective in detecting minimal amounts of virus antigen. FA staining reactions with 1 and 2 units of labeled rooster serum were inhibited by unlabeled rooster serum but clear-cut inhibition with human antipsittacosis serum could not be demonstrated. The indirect FA technique was successfully used for the titration of group antibody in human serum. A comparison of the indirect FA, HI, and CF tests showed the indirect FA technique to be intermediate in sensitivity between the HI and CF tests. None of the three tests showed significant cross reactions with human serums reactive for influenza A and B; parainfluenza 1, 2, and 3; respiratory syncytial virus; Q fever; or the primary atypical pneumonia agent.
Alterations in neurogenically mediated contractile responses of urinary bladder in rats with diabetes.

Diabetic bladder dysfunction (DBD) is among the most common and bothersome complications of diabetes mellitus. Autonomic neuropathy has been counted as the cause of DBD. In the present study, we co...
Observed trends in extreme precipitation events in China during 1961–2001 and the associated changes in large‐scale circulation

[1] The observed trends in extreme precipitation events, and those in annual and seasonal mean precipitation in China during 1961–2001 are analyzed. The results show that the annual mean precipitation increases significantly in southwest, northwest, and east China, and decreases significantly in central, north and northeast China. The increasing trends in east China occurred mainly in summer, while the decreasing trends in central, north, and northeast China occurred in both spring and autumn. The increasing trends in most of northwest China occurred in all seasons. Patterns of the trends in extreme daily precipitation events are similar to those in the annual and seasonal mean precipitation except in the northwest China where most areas show increasing trends in extreme events only in summer. The extreme precipitation events in the Yangtze River basin increased dramatically by 10%–20% every 10 years in summer, consistent with the increasing trends in summer mean precipitation in the region. The circulation over East Asia shows a weakening trend in the summer monsoon over central-east China.
The effect of asynchronism on the total capacity of Gaussian multiple-access channels

The degradation due to complete asynchronism (at the codeword and symbol levels) in the total capacity, maximum rate-sum, of white Gaussian multiple-access channels is investigated. It is shown that asynchronism reduces the total capacity of a K-user channel by at most a factor of K. Moreover, this bound is achieved, in asymptotically high signal-to-noise ratios, by the TDMA signaling strategy. When the signaling strategies are optimally designed to maximize the asynchronous total capacity under bandwidth constraints, the authors find that in a two-user channel: (1) for a certain set of signal-to-noise ratios there is no degradation due to asynchronism, (2) for any bandwidth and signal-to-noise ratios the asynchronous total capacity is at least 88% of the synchronous total capacity, and (3) asynchronism has a vanishing small effect on total capacity for both low and high signal-to-noise ratios. >
Highly Ionized Carbon Plasma Generation by Dual-Laser Ablation for Diamond-Like Carbon Film Growth

Carbon plasmas produced by excimer laser ablation show a low ionization yield of about 8-10%. The coupling of a second CO2 laser pulse into the plasma in the dual-laser ablation process significantly increases the plasma temperature and the ionization. The resulting rapid expansion of the plasma gives rise to high ion kinetic energies and broader ion expansion profiles [1]. Optical emission spectroscopy and an ion probe have been used to investigate the dynamics of the carbon plasma. Single and dual-laser ablated carbon plumes have been deposited on DC-biased silicon substrates to form amorphous carbon films. The diamond-like behavior of these films was studied by Raman spectroscopy. The Raman spectra were deconvolved to gauge the effect of the density and the energy of ions on the formation of diamond-like sp 3 -bonded carbon (DLC) films. The advantage offered by the dual-laser process for the growth of DLC films is discussed.
Helix propensities of short peptides: Molecular dynamics versus bioinformatics

Knowledge-based potential functions for protein structure prediction assume that the frequency of occurrence of a given structure or a contact in the protein database is a measure of its free energy. Here, we put this assumption to test by comparing the results obtained from sequence-structure cluster analysis with those obtained from long all-atom molecular dynamics simulations. Sixty-four eight-residue peptide sequences with varying degrees of similarity to the canonical sequence pattern for amphipathic helix were drawn from known protein structures, regardless of whether they were helical in the protein. Each was simulated using AMBER6.0 for at least 10 ns using explicit waters. The total simulation time was 1176 ns. The resulting trajectories were tested for reproducibility, and the helical content was measured. Natural peptides whose sequences matched the amphipathic helix motif with greater than 50% confidence were significantly more likely to form helix during the course of the simulation than peptides with lower confidence scores. The sequence pattern derived from the simulation data closely resembles the motif pattern derived from the database cluster analysis. The difficulties encountered in sampling conformational space and sequence space simultaneously are discussed.
Hereditary motor and sensory neuropathy with diaphragm and vocal cord paresis

We describe two kindreds with an autosomal dominant inherited disorder characterized by a variable degree of muscle weakness of limbs, vocal cords, and intercostal muscles and by asymptomatic sensory loss, beginning in infancy or childhood in severely affected persons. Life expectancy in severely affected patients is shortened because of respiratory failure. Because nerve conduction velocities are normal and it is an inherited axonal neuropathy, we classify the disorder as a variety of hereditary motor and sensory neuropathy type II (HMSN II) (HMSN IIc). The present report provides further evidence for heterogeneity among the hereditary motor and sensory neuropathy type II disorders. In one large pedigree with the type IIc disorder, no linkage to DNA markers known to map near the HMSN IA locus on chromosome 17p or the HMSN IB locus on chromosome 1q was demonstrated.
Metabolic engineering of Agrobacterium sp. strain ATCC 31749 for production of an α-Gal epitope

Background: Oligosaccharides containing a terminal Gal-a1,3-Gal moiety are collectively known as a-Gal epitopes. a-Gal epitopes are integral components of several medical treatments under development, including flu and HIV vaccines as well as cancer treatments. The difficulty associated with synthesizing the a-Gal epitope hinders the development and application of these treatments due to the limited availability and high cost of the a-Gal epitope. This work illustrates the development of a whole-cell biocatalyst for synthesizing the a-Gal epitope, Gala1,3-Lac. Results: Agrobacterium sp. ATCC 31749 was engineered to produce Gal-a1,3-Lac by the introduction of a UDPgalactose 4’-epimerase:a1,3-galactosyltransferase fusion enzyme. The engineered Agrobacterium synthesized 0.4 g/L of the a-Gal epitope. Additional metabolic engineering efforts addressed the factors limiting a-Gal epitope production, namely the availability of the two substrates, lactose and UDP-glucose. Through expression of a lactose permease, the intracellular lactose concentration increased by 60 to 110%, subsequently leading to an improvement in Gal-a1,3-Lac production. Knockout of the curdlan synthase gene increased UDP-glucose availability by eliminating the consumption of UDP-glucose for synthesis of the curdlan polysaccharide. With these additional engineering efforts, the final engineered strain synthesized approximately 1 g/L of Gal-a1,3-Lac. Conclusions: The Agrobacterium biocatalyst developed in this work synthesizes gram-scale quantities of a-Gal epitope and does not require expensive cofactors or permeabilization, making it a useful biocatalyst for industrial production of the a-Gal epitope. Furthermore, the engineered Agrobacterium, with increased lactose uptake and improved UDP-glucose availability, is a promising host for the production of other medically-relevant oligosaccharides.
Contradictory intent? US federal legislation on integrating societal concerns into nanotechnology research and development

This paper argues that the 21st Century Nanotechnology Research and Development (RD and mounting pressure to conduct technology development with more effective regard to societal considerations. The tension emerges when comparing various ‘Program Activities’ set forth in the Act that require divergent policy models, by which the legislation attempts to balance international competition with concern over the perceived risks of nanotechnology applications. By prescribing the integration of societal and technical concerns during nanotechnology R&D, the Act could mark a radical shift in S&T policy in so far as it allows the consideration of societal concerns to influence technological activities and outcomes. Copyright , Beech Tree Publishing.
Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells

Intestinal stem cells (ISCs) in the adult Drosophila melanogaster midgut can respond to damage and support repair. We demonstrate in this paper that the tuberous sclerosis complex (TSC) plays a critical role in balancing ISC growth and division. Previous studies have shown that imaginal disc cells that are mutant for TSC have increased rates of growth and division. However, we report in this paper that loss of TSC in the adult Drosophila midgut results in the formation of much larger ISCs that have halted cell division. These mutant ISCs expressed proper stem cell markers, did not differentiate, and had defects in multiple steps of the cell cycle. Slowing the growth by feeding rapamycin or reducing Myc was sufficient to rescue the division defect. The TSC mutant guts had a thinner epithelial structure than wild-type tissues, and the mutant flies were more susceptible to tissue damage. Therefore, we have uncovered a context-dependent phenotype of TSC mutants in adult ISCs, such that the excessive growth leads to inhibition of division.
Radiographic analysis of spondylolisthesis and sagittal spinopelvic deformity

Traditional radiographic analysis of spondylolisthesis focuses on the regional sagittal deformity at the lumbosacral junction. Pelvic morphology has also been cited as an important factor that contributes to the development of high-grade spondylolisthesis. However, the importance of global sagittal balance of the spine and pelvis in patients with spondylolisthesis has been emphasized recently. Patients with this condition can develop abnormal sagittal spinopelvic balance; restoration of sagittal spinal alignment can improve their health-related quality of life. Reduction has been used to restore alignment, but its role in the management of high-grade spondylolisthesis is controversial. None of the current classification systems take sagittal sacropelvic and spinopelvic balance into account. Improved understanding of the relationship between the spine and pelvis has led to the development of a new classification system that incorporates analysis of spinopelvic balance in the radiographic assessment. This new system may aid surgeons in identifying patients who would benefit from a partial reduction procedure.
On the energetics of maximum-entropy temperature profiles

The problem of determining a maximum-entropy state in an atmospheric column has different solutions depending on the constraints imposed. As was first shown by J. W. Gibbs, maximization of entropy in a thermally-isolated, i.e. energy-conserving, atmosphere yields an isothermal temperature distribution. It has since been argued that conservation of the mass-weighted integral of potential temperature, or of the column potential enthalpy, is more appropriate for certain dynamical processes. The solution of the maximization problem satisfying this second constraint is quite different: an adiabatic temperature profile. Here, the comparative energetics of entropy maximization is examined in more detail. The main new result is that some exact statements may be formulated as inequalities. It can be rigorously shown, for example, that maximization of entropy under the conservation of potential enthalpy in an initially stable stratification always requires additional energy, and so cannot be accomplished in an isolated layer. Conversely, a temperature profile satisfying the second condition always possesses less entropy than an isothermal state with the same total energy, and so cannot be in thermodynamic equilibrium. Starting with these fundamental results, this paper discusses basic properties, and specific examples, of dynamical processes transporting heat vertically and generating entropy under various constraints, and demonstrates the importance of their physically-consistent parametrization in atmospheric models. Copyright © 2008 Royal Meteorological Society
Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) contains hypoxia response elements: relevance to lytic induction by hypoxia

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), also known as human herpesvirus 8, is an etiologic agent of KS, primary effusion lymphoma (PEL), and multicentric Castleman's disease. We recently demonstrated that hypoxia can induce lytic replication of KSHV in PEL cell lines. Hypoxia induces the accumulation of hypoxia-inducible factors (HIF), and we hypothesized that the KSHV genome may respond to hypoxia through functional hypoxia response elements (HREs). Here, we demonstrate the presence of at least two promoters within the KSHV genome that are activated by hypoxia or hypoxia mimics. One is in the promoter region of the gene for Rta, the main lytic switch gene, and the other is within the promoter region of ORF34, a lytic gene of unknown function. The ORF34 promoter contains three putative consensus HREs oriented in the direction of the gene. Dissection and site-directed mutagenesis studies confirmed that one of the HREs of the ORF34 promoter is functional. Under conditions of hypoxia, the ORF34 promoter was strongly upregulated by HIF-1 alpha and HIF-2 alpha. By contrast, the promoter of the gene for Rta appeared to be preferentially upregulated by HIF-2 alpha. Reverse transcription-PCR analysis revealed that specific messages for ORF34 and ORF50 are upregulated in BCBL-1 cells exposed to hypoxia. An HIF-1 binding and competition assay demonstrated that the HRE sequence from the ORF34 promoter can compete for HIF-1 alpha binding to an erythropoietin HRE oligonucleotide while a mutant sequence cannot. Thus, we demonstrated that a viral gene can be activated by hypoxia through activation of a functional viral HRE. To our knowledge, this is the first example of a functional HRE in a viral promoter.
Collaborative Dialogue in Learner–Learner and Learner–Native Speaker Interaction

This study analyses intermediate and advanced learner–learner and learner–native speaker (NS) interaction looking for collaborative dialogue. It investigates how the presence of a NS interlocutor affects the frequency and nature of lexical language-related episodes (LREs) spontaneously generated during task-based interaction. Twenty-four learners of English as a foreign language and eight English NSs participated in the study. The results obtained confirm that lexical LREs tend to be more frequent and more likely to be successfully resolved in learner–NS than in learner–learner interaction. However, the analysis of the patterns of interaction of two selected dyads reveals that not all NSs can be expected to provide the same kind of linguistic assistance to the learner. The participants’ collaborative or non-collaborative orientation to the activity, shaped by their goals and level of involvement in the task, seems to have a stronger effect on the nature of the interaction and the opportunities this offers for LREs and learning than the overall proficiency of the dyad.
Understanding The Brain-Drain From The Capital District Of New York State

The Capital District Region of New York State, home to twenty-five colleges and universities with a combined 14,000 students per year is attempting to leverage this educational resource to transform its economy away from its traditional government services, industrial, and manufacturing base towards high-technology. Millions of dollars have been invested to develop the infrastructure necessary to have economic growth fueled by high-technology. However, many of these highly skilled college graduates leave the area. This exodus, or brain drain, is a major concern for regional economic developers and policy-makers because the social and economic vitality of a region is at risk. For the high-tech industry to be successful in any region there must be complementary support industries and services. Therefore, the retention of college graduates in various fields, not just those in technology disciplines, of study is vital for regional economic development. Due to the considerable threat that the brain drain poses for a region in terms of social and economic vitality, one must have a complete understanding of the problem before attempting to correct it. This study will answer the following questions: (1) How big is brain drain from the region; (2) What are the characteristics of the graduates who leave the region; (3) What are the differences between the graduates that stay in the region and those that leave; and (4) What factors can be changed to increase the probability of retaining graduates?
Simulation and measurement of effective propagation constant of cut-wire array

The wave propagation inside a periodic cut-wire array is investigated. The effective propagation constant is extracted from numerical simulation and measurement. Both the plasmonic cutoff behaviour and the cut-wire resonance are presented and analysed.
Oxidation Kinetics of Aluminum Nitride

Etude par analyse thermogravimetrique de la cinetique d'oxydation thermique de poudres de nitrure d'aluminium de differentes distributions granulometriques.
Endonasal Endoscopic Surgery in the Management of Sinonasal and Anterior Skull Base Malignancies

Sinonasal malignancies represent a rare subset of tumors with a wide variety of histopathologic diagnoses and overall poor prognosis. These tumors tend to have an insidious onset with non-specific symptoms which often leads to delayed diagnosis and advanced local disease at presentation. The principal goal of surgery is to obtain a negative margin resection. Open craniofacial techniques are well established in the management of sinonasal malignancies and remain the treatment of choice for many advanced tumors. Over the past couple of decades, there has been tremendous application of endoscopic techniques to skull base pathologies including sinonasal malignancies. For selected cases, endonasal endoscopic techniques can be performed with curative intent and reduced surgical morbidity and mortality. Here we discuss principles of surgical management of sinonasal malignancies, review the techniques of endonasal endoscopic resection of sinonasal malignancies, and highlight the importance of pathology in the multi-disciplinary management of patients with these complex lesions.
The contribution of alpha synuclein to neuronal survival and function – Implications for Parkinson's disease

The aggregation of alpha synuclein (α-syn) is a neuropathological feature that defines a spectrum of disorders collectively termed synucleinopathies, and of these, Parkinson's disease (PD) is arguably the best characterized. Aggregated α-syn is the primary component of Lewy bodies, the defining pathological feature of PD, while mutations or multiplications in the α-syn gene result in familial PD. The high correlation between α-syn burden and PD has led to the hypothesis that α-syn aggregation produces toxicity through a gain-of-function mechanism. However, α-syn has been implicated to function in a diverse range of essential cellular processes such as the regulation of neurotransmission and response to cellular stress. As such, an alternative hypothesis with equal explanatory power is that the aggregation of α-syn results in toxicity because of a toxic loss of necessary α-syn function, following sequestration of functional forms α-syn into insoluble protein aggregates. Within this review, we will provide an overview of the literature linking α-syn to PD and the knowledge gained from current α-syn-based animal models of PD. We will then interpret these data from the viewpoint of the α-syn loss-of-function hypothesis and provide a potential mechanistic model by which loss of α-syn function could result in at least some of the neurodegeneration observed in PD. By providing an alternative perspective on the etiopathogenesis of PD and synucleinopathies, this may reveal alternative avenues of research in order to identify potential novel therapeutic targets for disease modifying strategies. The correlation between α-synuclein burden and Parkinson's disease pathology has led to the hypothesis that α-synuclein aggregation produces toxicity through a gain-of-function mechanism. However, in this review, we discuss data supporting the alternative hypothesis that the aggregation of α-synuclein results in toxicity because of loss of necessary α-synuclein function at the presynaptic terminal, following sequestration of functional forms of α-synuclein into aggregates.
Two-Color Surface Plasmon Polariton Enhanced Upconversion in NaYF4:Yb:Tm Nanoparticles on Au Nanopillar Arrays

Spectroscopic imaging and time-resolved spectroscopy are used to study the surface plasmon polariton (SPP) enhanced infrared to visible upconversion luminescence from NaYF4:Tm:Yb nanoparticles embedded in polymethyl methylacrylate (PMMA) supported on Au nanopillar arrays. The arrays have a lattice resonance associated with the SPP near 980 nm, near-resonant with the peak absorption of the Yb3+ ion, while a local surface plasmon resonance (LSPR) associated with the individual pillars is seen to enhance the near-infrared emission of Tm3+ ions near 780 nm. The two combined channels of enhancement result in a significantly higher enhancement of the near-infrared emission when compared to the visible upconversion lines of the Tm3+ ion, consistent with the interpretation of sequential surface plasmon assisted absorption and emission at two separate and disparate energies. The presence of SPP and LSPR was confirmed by spectrally resolved reflectivity, and the mechanisms for luminescence enhancement were further ...
Major organ-specific glycoproteins in isolated brain and kidney membranes identified as Na,K-ATPase subunits by combined glycan-, lectin-, and immunoblotting

In the present work combined glycan-, lectin-, and immunoblotting of isolated brain and kidney membranes shows that the alpha and beta subunits of Na,K-ATPase are the most abundant glycoproteins. Further, Datura stramonium and Galanthus nivalis agglutinins recognize the Na,K-ATPase subunits in a mutually exclusive manner in membranes from human, rabbit and rat brain or human, rabbit, rat, pig and dog kidney indicating the presence of species-independent organ-typical glycoforms. The glycosylation status is not related to the ouabain-sensitivity. Taken together, the data reveals organ-specific glycoforms of Na,K-ATPase which might have roles for organ identification and recognition.
Chrysanthemum Cultivar Preferences Exhibited by Spodoptera exigua (Lepidoptera: Noctuidae)

Chrysanthemum ( Dendranthema grandiflora Tzvelev) cultivar preference studies were conducted with both larval and adult stages of the beet armyworm, Spodoptera exigua (Hubner). Despite a distinct nonpreference for ‘Hoof Lane’ by fifth instars, female ovipositional preference was independent of cultivar. No significant differences were found in the mean proportion of plants infested or in the mean number of egg masses laid among the cultivars tested. Additionally, females did not appear to discriminate against a nonhost plant species. Egg masses were confined primarily to the undersides of leaves within the bottom one-fourth of the plant. No correlation was found between egg mass location and number of eggs per mass.
A review of vascular anomalies: genetics and common syndromes

Vascular tumors and malformations are unique in that affected cells exhibit disrupted angiogenesis. The current treatment options often yield suboptimal results. New insight into the genetics and molecular basis of vascular anomalies may pave the way for potential development of targeted therapy. The authors review the genetic and molecular basis of vascular anomalies and common associated syndromes.
Experimental observation on purification efficacy of electronic air cleaner

Objective To evaluate purification efficacy of electronic air cleaner. Methods Field experimental observation on purification efficacy of electronic air cleaner on particle and natural bacteria in the air was made. Results After 1 hour purification, particle purification rate was 68.00%, natural bacteria eliminating rate was 83.70%. There was no obvious difference in the purification rate between 1 hour and 2 hours purification. Conclusion electronic air cleaner is an effective air cleaner device.
Long-Term Assessment of Genital Reconstruction in Female Pseudohermaphrodites

The cases involving 32 women who had undergone early revision of ambiguous genitalia were reviewed 5 to 22 years postoperatively. Seven clitoridectomies, 25 clitoral recessions, 17 Y-V introitoplasties and 10 midline episiotomies were performed. There were 16 patients available for followup. The results of clitoral recessions were cosmetically and functionally satisfactory. Introital revisions done before puberty all required further revision and suggested that vaginoplasty should be deferred until after puberty.
Laparoscopic pelvic lymphadenectomy and radical perineal prostatectomy: a viable alternative to radical retropubic prostatectomy.

AbstractLaparoscopic pelvic lymphadenectomy and radical perineal prostatectomy performed under the same anesthetic provide accurate surgical resection of localized carcinoma of the prostate with reduced intraoperative blood loss, minimal postoperative discomfort, short hospital stay (mean 4.1 days), high level of postoperative continence (81% completely dry after 4 months postoperatively) and low morbidity (4 complications). The clinical records of 37 patients undergoing this combined procedure during the last 22 months were reviewed retrospectively and the efficacy of the procedure was evaluated. This combined treatment modality avoids an abdominal incision and pelvic drains, and is associated with minimal postoperative discomfort and a short hospital stay. Laparoscopic pelvic lymphadenectomy combined with radical perineal prostatectomy is an alternative to open pelvic lymph node dissection and radical retropubic prostatectomy.
Mini-workshop: revisiting the Denver model for groupware design

Participants in an earlier workshop at the CHI’95 conference in Denver Colorado created the Denver model for groupware design [Salvador 95]. Illustrated in Figure 1, this high level model identified a hierarchy of submodels for describing various aspects of groupware designs. The first level of decomposition consisted of three submodels, (1) system requirements, (2) design model, and (3) technology model. The technology model describes the technology used to enable multiple participants to be aware of and control various aspects of the groupware system. The design model was further partitioned into five submodels, (1) the people model which describes users and the various roles they may assume, (2) the task model which describes the scenarios, tasks, and activities which users may perform, (3) the artifact model which describes the objects and their attributes and relationships which users may manipulate, (4) the interactive situation model which describes the participant locations (same, different), the number of participants (small, large), synchrony (asynchronous, synchronous), dependency (loose, tight), and degree of planning (planned, spontaneous), and (5) the interactive protocol model which describes the floor control mechanism, contention resolution, formality of address, and direction of conversation (unidirectional, multidirectional). Software practitioners have devised several models for people, tasks, and artifacts. Groupware systems are relatively new, and models for interactive situation and interactive protocols are just beginning to emerge.
Modified release itraconazole amorphous solid dispersion to treat Aspergillus fumigatus: importance of the animal model selection

Previously, modified release itraconazole in the form of a melt-extruded amorphous solid dispersion based on a pH dependent enteric polymer combined with hydrophilic additives (HME-ITZ), exhibited improved in vitro dissolution properties. These properties agreed with pharmacokinetic results in rats showing high and sustained itraconazole (ITZ) systemic levels. The objective of the present study was to better understand the best choice of rodent model for evaluating the pharmacokinetic and efficacy of this orally administered modified release ITZ dosage form against invasive Aspergillus fumigatus. A mouse model and a guinea pig model were investigated and compared to results previously published. In the mouse model, despite similar levels as previously reported values, plasma and lung levels were variable and fungal burden was not statistically different for placebo controls, HME-ITZ and Sporanox® (ITZ oral solution). This study demonstrated that the mouse model is a poor choice for studying modified release ITZ dosage forms based on pH dependent enteric polymers due to low fluid volume available for dissolution and low intestinal pH. To the contrary, guinea pig was a suitable model to evaluate modified release ITZ dosage forms. Indeed, a significant decrease in lung fungal burden as a result of high and sustained ITZ tissue levels was measured. Sufficiently high intestinal pH and fluids available for dissolution likely facilitated the dissolution process. Despite high ITZ tissue level, the primary therapeutic agent voriconazole exhibited an even more pronounced decrease in fungal burden due to its reported higher clinical efficacy specifically against Aspergillus fumigatus.
Does an Open Recirculation Line Affect the Flow Rate and Pressure in a Neonatal Extracorporeal Life Support Circuit With a Centrifugal or Roller Pump

The objective of this study is to evaluate the impact of an open or closed recirculation line on flow rate, circuit pressure, and hemodynamic energy transmission in simulated neonatal extracorporeal life support (ECLS) systems. The two neonatal ECLS circuits consisted of a Maquet HL20 roller pump (RP group) or a RotaFlow centrifugal pump (CP group), Quadrox-iD Pediatric oxygenator, and Biomedicus arterial and venous cannulae (8 Fr and 10 Fr) primed with lactated Ringer's solution and packed red blood cells (hematocrit 35%). Trials were conducted at flow rates ranging from 200 to 600 mL/min (200 mL/min increments) with a closed or open recirculation line at 36°C. Real-time pressure and flow data were recorded using a custom-based data acquisition system. In the RP group, the preoxygenator flow did not change when the recirculation line was open while the prearterial cannula flow decreased by 15.7-20.0% (P < 0.01). Circuit pressure, total circuit pressure drop, and hemodynamic energy delivered to patients also decreased (P < 0.01). In the CP group, the prearterial cannula flow did not change while preoxygenator flow increased by 13.6-18.8% (P < 0.01). Circuit pressure drop and hemodynamic energy transmission remained the same. The results showed that the shunt of an open recirculation line could decrease perfusion flow in patients in the ECLS circuit using a roller pump, but did not change perfusion flow in the circuit using a centrifugal pump. An additional flow sensor is needed to monitor perfusion flow in patients if any shunts exist in the ECLS circuit.
IRON REPLACEMENT AS A THERAPEUTIC APPROACH FOR RENAL PHOSPHATE WASTING WITH ASSOCIATED IRON DEFICIENCY

ABSTRACT Objective: Fibroblast growth factor 23 (FGF23) dysregulation is implicated in the pathogenesis of hypophosphatemic disorders, including X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets, and tumor-induced osteomalacia (TIO). Studies have suggested a role of iron deficiency in triggering FGF23 dysregulation in ADHR. Methods: We report a case of adult-onset FGF23-mediated hypophosphatemic osteomalacia with associated iron deficiency that had significant clinical improvement and reduction in FGF23 with iron replacement. Results: A 41-year-old female presented with progressively worsening muscle weakness and diffuse pain for 4 years, resulting in wheelchair dependence. She had hypophosphatemia, renal phosphate wasting, and an elevated FGF23. Extensive imaging for TIO was nonlocalizing. Family history was negative for bone disease. Despite phosphorus and calcitriol therapy, her phosphorus remained low and she had progres...
Science Education Research Trends in Latin America

The purpose of this study was to survey and report on the empirical literature at the intersection of science education research in Latin American and previous studies addressing international research trends in this field. Reports on international trends in science education research indicate that authors from English-speaking countries are major contributors of publications. Despite the internationalization of the science education community, as represented by the publication of the work generated in non-English-speaking countries, research trends in science education in Latin America are uncommon in the literature. Therefore, it was deemed important to explore the scholarly productivity of science education researchers from Latin America to learn about the research orientations pursued by scholars from this region. Collective review findings are presented with respect to author’s nationality, publication volume generated in each country, research type and topic, collaborative research, and areas for future research. Of the ten countries represented in this study, Brazilian authors were the most research active scholars followed by their colleagues from Venezuela, Mexico, and Argentina. The History, Philosophy and the Nature of Science (HPNOS) was the topic that most attracted the interest of Latin American science education researchers, and the Empirical Qualitative studies was the most frequent research type combination in the analyzed publications. Findings in this study suggest a relationship between investment power in Research and Development (R&D) and the scholarly productivity not only in science education but also in the scientific field in the countries of the region.
Localized Amyloidosis of the Breast Mimicking Breast Cancer: Radiologic-Pathologic Correlation

Amyloidosis localized to the breast is uncommon. It may present with nonspecific imaging characteristics including a suspicious mass with or without calcifications, calcifications alone, or even with features mimicking inflammatory carcinoma of the breast. Amyloidosis has also been described coexistent with primary carcinoma of the breast, further confounding the imaging spectrum. We describe a case of amyloidosis localized to the breast presenting as a new mass with imaging features highly suggestive of malignancy.
Gene Therapy as a Curative Option for β-Thalassemia.

With an estimated global prevalence of 288,000 cases, β-thalassemia is one of the most common genetic diseases in the world, and every year another 60,000 infants are born with the disease. Of thes...
Does tumor grade influence the rate of lymph node metastasis in apparent early stage ovarian cancer

To evaluate the prevalence of regional lymph node (LN) metastasis in patients with non-clear cell epithelial ovarian cancer apparently confined to the ovary, stratified by tumor grade. The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database was accessed (1988–2014). We identified patients with epithelial ovarian carcinoma of serous, endometrioid and mucinous histology apparently confined to the ovary who underwent extensive lymphadenectomy (defined as at least 20 lymph nodes removed). Demographics, tumor histology, grade and lymph node status were collected. Comparisons were made with Chi square and Mann–Whitney U tests. A total of 1242 women met the inclusion criteria. Endometrioid adenocarcinoma was the most common histology (564 patients (45.4%)) while 443 (35.7%) and 235 (18.9%) patients had serous, and mucinous adenocarcinoma, respectively. The rate of LN metastasis in low-grade serous was 9.0% (6/67) vs. 14.4% (54/376) in high-grade serous histology (OR, 1.71, 95% CI 0.70, 4.14, p = 0.24). In patients with low-grade endometrioid tumors, the rate of LN metastasis was 1.7% (7/407) vs. 5.1% (8/157) observed in those with high-grade tumors (OR: 3.07, 95% CI 1.09, 8.61, p = 0.033). Lastly, the rate of LN metastasis in mucinous histology was 1.7% (3/177) in low-grade vs. 8.6% (5/58) in high-grade tumors (OR: 5.47, 95% CI 1.27, 23.66, p = 0.024). Regional LN metastasis in apparent stage I low-grade mucinous and endometrioid ovarian tumors is infrequent.
PURPA’s midlife crisis: Will its 40th birthday be one of fundamental change?

Abstract The Public Utility Regulatory Policies Act of 1978 has played a key role in the spread of independent power producers and the dislodgment of the classic monopoly utility model. As its 41st anniversary arrives, the possibility of changes at the national level seems likely, particularly tweaks by the Federal Energy Regulatory Commission to the one-mile rule. In the less likely chance that Congress passes a bill on PURPA, then the changes could be drastic.
Fungal infections of the oral cavity.

Although several strains of Candida can infect the oral mucosa, the most commonly encountered oral fungal infection is Candida albicans, which may be highly infective because of its greater level of pathogenicity and adherence properties. C. albicans is an oral commensal in as many as 40% to 65% of healthy adult mouths. The papillated dorsal surface of the tongue and palatal mucosa beneath a maxillary denture are favored reservoir sites. Oral candidal infection almost always involves a compromised host. The compromise may be local or systemic. Local factors include decreased salivation and the weaning of dentures. Systemic factors include diabetes mellitus, pernicious anemia, and AIDS. Some have even implicated advanced age and the female gender as being mild predisposing factors. Furthermore, the C. albicans infection itself can depress a host's immune system. A patient with oral candidiasis can present with one or more of the following clinical forms: pseudomembranous, erythematous, hyperplastic, and denture erythematous. Many investigators accept median rhomboid glossitis as a form of chronic oral candidiasis. In some patients with angular cheilitis, genesis of the lesions is secondary to monilial infestation. Because C. albicans is a normal inhabitant in many mouths, diagnostic confirmation of infection often rests with successful response (i.e., resolution of lesions) to antifungal medications. This form of diagnostic confirmation can be further enhanced by culturing the offending microbe, preparing a fungal smear, or even incisional biopsy. The microscopic demonstration of fungal hyphae is highly diagnostic of the candidal infection, whether the hyphae are demonstrated on a PAS smear or on a biopsy within surface stratified squamous epithelium. Numerous medications exist for the treatment of oral candidiasis. They include the antibiotic nystatin as well as clotrimazole, ketoconazole, and fluconazole. Nystatin is safe and is used as a topical agent in rinse or pastille forms. Clotrimazole is used as a topical agent in lozenge form; it is highly effective but can cause liver enzyme changes. Ketoconazole, which is usually prescribed systemically, is highly effective but also capable of causing adverse liver changes. Chlorhexidine can be used as an oral rinse or as a disinfectant for dentures.
Modeling the Sorption Behavior of Aromatic Amine Onto Sediment Under Acidic Conditions

In this study the sorption behavior of an aromatic amine (benzidine) in the aqueous-sediment systems was investigated. Three sorption mechanisms including hydrophobic partitioning, covalent binding and cation exchange govern the fate of benzidine after its entry into the ecosystems. A sorption equilibrium model was presented to investigate these sorption mechanisms under acidic conditions. Model simulation results indicated that the model fits the experimental data very well. The results also indicated that hydrophobic partitioning and covalent binding contributed more to the overall sorption than cation exchange did with increasing solution pH from 3.1 to near neutral.
The Accuracy of Self-Reported Smoking Among Blacks

Government agencies rely on surveys in which individuals self-report their smoking activities, which raises questions about biases in responses. To validate self-reported smoking numbers, medical researchers often rely on urinary concentrations of cotinine, the main metabolite of nicotine. But virtually all existing studies investigate whether self-reported nonsmokers misreport their smoking status. Such investigations leave unanswered whether individuals who admit smoking nonetheless smoke more than they claim. This article produces two findings of interest, both pertaining to self-reported smoking among Blacks. First, among self-reported nonsmokers, a Black person is approximately 47% more likely to smoke compared with a non-Black person. Second, among individuals who admit to smoking, the average Black smoker underreports his smoking activity by a larger amount than 70% of all self-reported smokers. Slower metabolism of cotinine among Blacks explains some, but not all, of those numbers.
Work-related upper extremity musculoskeletal disorders in the United States: 2006, 2009, and 2014 National Health Interview Survey.

Background The annual incidence rate of work-related upper extremity musculoskeletal disorders (WUEMSDs) is increasing in US workers according to the United States Bureau of Labor Statistics (BLS). However, the prevalence of WUEMSDs among US total workers has not been estimated. Objective We aimed to estimate the prevalence of WUEMSDs among US total workers and among each of major occupations and industries. Methods We analyzed data from the National Health Interview Survey Arthritis supplements (2006, 2009, and 2014) among 50,218 current workers (age ≥18 years) to estimate the 30-day prevalence of WUEMSDs and of WUEMSDs affecting work using the SAS-callable SUDAAN software. Results About 11.2 million workers reported WUEMSDs based on three surveys (2006, 2009, and 2014). The 30-day prevalence of WUEMSDs was 8.23% the prevalence of WUEMSDs affecting work was 1.24%. The Construction occupation and industry had the highest age- and sex-adjusted 30-day prevalence of WUEMSDs (10.98% for Construction occupation; 9.94% for Construction industry) and WUEMSDs affecting work (3.32% for Construction occupation; 2.31% Construction industry). Conclusions Our results show that construction workers had the highest prevalence of both WUEMSDs and WUEMSDs affecting work. They may be a priority group for interventions to reduce upper extremity musculoskeletal disorders.
Multi-line Adaptive Perimetry (MAP): A New Procedure for Quantifying Visual Field Integrity for Rapid Assessment of Macular Diseases.

Author(s): Thurman, Steven M; Maniglia, Marcello; Davey, Pinakin G; Biles, Mandy K; Visscher, Kristina M; Seitz, Aaron R | Abstract: PurposeIn order to monitor visual defects associated with macular degeneration (MD), we present a new psychophysical assessment called multiline adaptive perimetry (MAP) that measures visual field integrity by simultaneously estimating regions associated with perceptual distortions (metamorphopsia) and visual sensitivity loss (scotoma).MethodsWe first ran simulations of MAP with a computerized model of a human observer to determine optimal test design characteristics. In experiment 1, predictions of the model were assessed by simulating metamorphopsia with an eye-tracking device with 20 healthy vision participants. In experiment 2, eight patients (16 eyes) with macular disease completed two MAP assessments separated by about 12 weeks, while a subset (10 eyes) also completed repeated Macular Integrity Assessment (MAIA) microperimetry and Amsler grid exams.ResultsResults revealed strong repeatability of MAP and high accuracy, sensitivity, and specificity (0.89, 0.81, and 0.90, respectively) in classifying patient eyes with severe visual impairment. We also found a significant relationship in terms of the spatial patterns of performance across visual field loci derived from MAP and MAIA microperimetry. However, there was a lack of correspondence between MAP and subjective Amsler grid reports in isolating perceptually distorted regions.ConclusionsThese results highlight the validity and efficacy of MAP in producing quantitative maps of visual field disturbances, including simultaneous mapping of metamorphopsia and sensitivity impairment.Translational relevanceFuture work will be needed to assess applicability of this examination for potential early detection of MD symptoms and/or portable assessment on a home device or computer.