Effect of pentoxifylline, administered in preterm labour, on the foetal-placental circulation and neonatal outcome: a randomized, prospective pilot study.
The aim of the study was to evaluate the pentoxifylline administration on the foetal-placental circulation and neonatal outcome in women with threatened preterm labour. Pentoxifylline was given as a supplement to standard tocolytic therapy in a group of 43 patients (pentoxifylline group) as an intravenous infusion and oral supplementation in a total dosage of 800 mg/day. The drug was administered within 3 weeks after admission. No pentoxifylline was given in the control group (53 patients). Doppler velocimetry of pulsatility indices (PI) of the umbilical (UA) and middle cerebral (MCA) arteries as well as cerebro-placental ratio (CPR) were calculated. Also, the neonatal outcome was estimated in both groups. From the second week of therapy with pentoxifylline, the PI decreased in umbilical artery and increased in the MCA, whereas in the control group, there were no changes. The value of PIUA, evaluated after the third week of pentoxifylline administration, was statistically significantly lower when compared to data obtained on admission (mean: 0.99 ± 0.22 versus 0.82 ± 0.12; p =0.016). Pentoxifylline significantly increased CPR values calculated after third week of drug administration, which were statistically significantly higher in the pentoxifylline group when compared with respective data in the control group (mean: 2.30 versus 1.61; p = 0.001). The risk of severe neonatal complications was significantly lower in the pentoxifylline group (p = 0.026). Pentoxifylline changed foetal-placental blood circulation in patients with threatened preterm labour and improved neonatal outcome.


Reimbursement of sole community hospitals under Medicare's prospective payment system.
Under the prospective payment system (PPS), designated sole community hospitals (SCH's), usually smaller than other rural hospitals but offering comparable services, have had higher average cost levels, in part because of underutilization of plant and equipment. This has resulted in negative operating margins on patient revenues, although local financial support and other revenue sources bring margins on total revenues into the positive range. The PPS legislation has also provided SCH's temporary protection from volume declines. SCH's are more likely than other rural hospitals to experience large volume swings, but only for declines greater than the threshold specified under PPS.


Scaling of the dynamics of homogeneous states of one-dimensional long-range interacting systems.
Quasistationary states of long-range interacting systems have been studied at length over the last 15 years. It is known that the collisional terms of the Balescu-Lenard and Landau equations vanish for one-dimensional systems in homogeneous states, thus requiring a new kinetic equation with a proper dependence on the number of particles. Here we show that the scalings discussed in the literature are mainly due either to small size effects or the use of unsuitable variables to describe the dynamics. The scaling obtained from both simulations and theoretical considerations is proportional to the square of the number of particles, and a general form for the kinetic equation valid for the homogeneous regime is obtained. Numerical evidence is given for the Hamiltonian mean field and ring models, and a kinetic equation valid for the homogeneous state is obtained for the former system.


Polyblend nanofibers for biomedical applications: perspectives and challenges.
Advances in disease treatment and tissue regeneration are buoyed by new, multifaceted materials that emulate and coercively interact with the local microenvironment. Polyblend nanofibers represent an emerging class of biomimetic nanostructures that can act as proxies of the native tissue, while providing topographical and biochemical cues that promote healing. These fibers are prepared with mixtures of synthetically and naturally derived polymers that can behave cooperatively to demonstrate unique combinations of mechanical, biochemical and structural properties. This flexibility has led to the application of polyblend nanofibers in a wide assortment of tissue engineering and drug delivery systems. In this review, we will examine design criteria and properties of polymer-blend nanofibers and their use in tissue engineering and local therapeutic delivery applications.


Site-specific backbone dynamics from a crystalline protein by solid-state NMR spectroscopy.
Site-specific nitrogen-15 longitudinal relaxation rates are measured for the microcrystalline dimeric form of the protein Crh using multidimensional high-resolution solid-state NMR methods. The measured rates are used to provide a qualitative description of the site-specific internal mobility of the protein present in the solid state.


Extended NO analysis in a healthy subgroup of a random sample from a Swedish population.
There is an interest in modelling exhaled nitric oxide (NO). Studies have shown that flow-independent NO parameters i.e. NO of the alveolar region (C(A)NO), airway wall (C(aw)NO), diffusing capacity (D(aw)NO) and flux (J(aw)NO), are altered in several disease states such as asthma, cystic fibrosis, alveolitis and chronic obsmuctive pulmonary disease (COPD). However, values from a healthy population are missing. To calculate NO parameters in a healthy population by collecting NO values at different exhalation flow rates. A random sample from the ECRHS II study was investigated. Among the 281 subjects that had performed a bronchial hyperreactivity (BHR)-test, FEV(1.0), IgE and NO-analyses 89 were found to be healthy. There were no differences in F(E)NO(0.05) or NO parameters between men and women. There were weak correlations between height and both F(E)NO(0.05) (r = 0.23, P = 0.03) and C(aw)NO (r = 0.22, P = 0.04). There was also a correlation between age and C(A)NO (r = 0.28, P = 0.007). When controlled for gender, this correlation was more powerful in women (r = 0.51, P = 0.001) but did not remain for male subjects. Extended NO analysis is a simple non-invasive tool that gives by far more information than F(E)NO(0.05). Based on our results, we suggest that the values for healthy subjects should be considered to fall between the following ranges: F(E)NO(0.05), 10-30 ppb; C(aw)NO, 50-250 ppb; D(aw)NO, 5-15 ml s(-1); J(aw)NO, 0.8-1.6 nl s(-1); and C(A)NO, 0-4 ppb. Values outside these intervals indicate the need for further investigation to exclude a state of disease.


Laboratory criteria of the obstetrical antiphospholipid syndrome. Data from a multicentric prospective European women cohort.
A debate on updating the laboratory criteria of antiphospholipid syndrome (APS) was recently opened in view to lower the risk of over diagnosis of the syndrome. Based on data related to thrombotic APS, it proposes the exclusion of anticardiolipin antibodies (aCL) and anti-beta2-glycoprotein 1 (a-beta2-GPI) IgM detection. Here, we examine this possibility in a study which focuses on obstetrical APS (OAPS). We report new data on a prospective multicenter European cohort of 109 pregnant women having APS. Among them, 73 had purely obstetrical APS, not associated to autoimmune diseases or thrombosis. Isolated antibodies and isolated aCL positivity were present in 50/109 (46%) and in 34/109 (31%) of the women, respectively. An isolated a-beta2-GPI IgM was present in three women. These results suggest that aCL and a-beta2-GPI IgM cannot be dropped for the diagnosis and classification of OAPS. The low level of some antibodies associated with severe obstetrical complications raise the issue of keeping or not the same laboratory criteria for OAPS and for thrombotic APS and whether additional criteria after large prospective studies could further improve diagnosis.


Oxidative stress (glutathionylation) and Na,K-ATPase activity in rat skeletal muscle.
Changes in ion distribution across skeletal muscle membranes during muscle activity affect excitability and may impair force development. These changes are counteracted by the Na,K-ATPase. Regulation of the Na,K-ATPase is therefore important for skeletal muscle function. The present study investigated the presence of oxidative stress (glutathionylation) on the Na,K-ATPase in rat skeletal muscle membranes. Immunoprecipitation with an anti-glutathione antibody and subsequent immunodetection of Na,K-ATPase protein subunits demonstrated 9.0±1.3% and 4.1±1.0% glutathionylation of the α isoforms in oxidative and glycolytic skeletal muscle, respectively. In oxidative muscle, 20.0±6.1% of the β1 units were glutathionylated, whereas 14.8±2.8% of the β2-subunits appear to be glutathionylated in glycolytic muscle. Treatment with the reducing agent dithiothreitol (DTT, 1 mM) increased the in vitro maximal Na,K-ATPase activity by 19% (P<0.05) in membranes from glycolytic muscle. Oxidized glutathione (GSSG, 0-10 mM) increased the in vitro glutathionylation level detected with antibodies, and decreased the in vitro maximal Na,K-ATPase activity in a dose-dependent manner, and with a larger effect in oxidative compared to glycolytic skeletal muscle. This study demonstrates the existence of basal glutathionylation of both the α and the β units of rat skeletal muscle Na,K-ATPase. In addition, the study suggests a negative correlation between glutathionylation levels and maximal Na,K-ATPase activity. Glutathionylation likely contributes to the complex regulation of Na,K-ATPase function in skeletal muscle. Especially, glutathionylation induced by oxidative stress may have a role in Na,K-ATPase regulation during prolonged muscle activity.


Markers of renal function and acute kidney injury in acute heart failure: definitions and impact on outcomes of the cardiorenal syndrome.
Acute kidney injury (AKI) in patients hospitalized for acute heart failure (AHF) is part of the cardiorenal syndrome and has been associated with increased morbidity and mortality. However, definitions and prognostic impact of AKI in AHF have been variable. Cystatin C is a prospective new marker of AKI. The objective of this study was to investigate the use of cystatin C as a marker of early AKI in AHF. Patients (n = 292) hospitalized for AHF had measurements of cystatin C on admission and at 48 h. We assessed the incidence of a rise in cystatin C between the two measurements and evaluated the effect of an increase in cystatin C on outcomes up to 12 months. The population was on average 75 years old and 49% were female. On admission, median cystatin C was 1.25 mg/L (interquartile range 0.99-1.61 mg/L). A rise in cystatin C by >0.3 mg/L within 48 h after hospitalization (AKI(cysC)) occurred in 16% of patients and resulted in 3 days (P = 0.01) longer hospital stay and was associated with significantly higher in-hospital mortality, odds ratio 4.0 [95% confidence intervals (CI) 1.3-11.7, P = 0.01]. During follow-up, AKI(cysC) was an independent predictor of 90 days mortality, adjusted odds ratio 2.8 (95% CI 1.2-6.7, P = 0.02). Cystatin C appears to be a useful marker of early AKI in patients hospitalized for AHF. A decline in renal function detected by cystatin C during the first 48 h after hospitalization occurs frequently in AHF and has a detrimental impact on prognosis.


[Expression of ras P21 oncoprotein in Syrian golden hamster embryo cells transformation induced by water pollutants].
Carcinogenic activities of organic pollutants in freshwater collected from Taihu Lake, Chaohu Lake and Dianshanhu Lake in Jiangsu Province were analyzed by in vitro Syrian hamster embryo (SHE) cell transformation and immunohistochemical methods. Results revealed organic pollutants in the originally collected water could, to the different extent, induce morphological changes of SHE cells, with a certain dose-response relationship. Expression of ras P21 oncoprotein increased in typical transformation cells of type I, which showed a positive immunohistochemical stain. And, ras P21 oncoprotein expressed to a certain extent in types I and II transformation cells during transition stage. It suggests water pollutants in the above-mentioned lakes had certain carcinogenic activities, and activation of ras oncogene may be one of the mechanisms to induce malignant transformation of SHE cells.


Supersymmetric Higgs bosons in weak boson fusion.
We compute the complete supersymmetric next-to-leading-order corrections to the production of a light Higgs boson in weak-boson fusion. The size of the electroweak corrections is of similar order as the next-to-leading-order corrections in the standard model. The supersymmetric QCD corrections turn out to be significantly smaller than expected and than their electroweak counterparts. These corrections are an important ingredient to a precision analysis of the (supersymmetric) Higgs sector at the LHC, either as a known correction factor or as a contribution to the theory error.


The use of a resin-bonded prosthesis while maintaining the diastemata: a clinical report.
A dental arch with diastemata and missing lateral incisors represents a challenge because of discrepancies in tooth size. If an implant-supported prosthesis is not possible or not selected as a treatment option, a modified resin-bonded fixed partial denture may be a treatment option to eliminate the esthetic problems of conventional fixed partial dentures. This clinical report describes the procedures to replace congenitally missing lateral incisors with a resin-bonded prosthesis, while maintaining diastemata.


Horizontal directional drilling: a green and sustainable technology for site remediation.
Sustainability has become an important factor in the selection of remedies to clean up contaminated sites. Horizontal directional drilling (HDD) is a relatively new drilling technology that has been successfully adapted to site remediation. In addition to the benefits that HDD provides for the logistics of site cleanup, it also delivers sustainability advantages, compared to alternative construction methods.


Non-invasive monitoring of multiple wildlife health factors by fecal microbiome analysis.
Fecal microbial biomarkers represent a less invasive alternative for acquiring information on wildlife populations than many traditional sampling methodologies. Our goal was to evaluate linkages between fecal microbiome communities in Rocky Mountain elk (Cervus canadensis) and four host factors including sex, age, population, and physical condition (body-fat). We paired a feature-selection algorithm with an LDA-classifier trained on elk differential bacterial abundance (16S-rRNA amplicon survey) to predict host health factors from 104 elk microbiomes across four elk populations. We validated the accuracy of the various classifier predictions with leave-one-out cross-validation using known measurements. We demonstrate that the elk fecal microbiome can predict the four host factors tested. Our results show that elk microbiomes respond to both the strong extrinsic factor of biogeography and simultaneously occurring, but more subtle, intrinsic forces of individual body-fat, sex, and age-class. Thus, we have developed and described herein a generalizable approach to disentangle microbiome responses attributed to multiple host factors of varying strength from the same bacterial sequence data set. Wildlife conservation and management presents many challenges, but we demonstrate that non-invasive microbiome surveys from scat samples can provide alternative options for wildlife population monitoring. We believe that, with further validation, this method could be broadly applicable in other species and potentially predict other measurements. Our study can help guide the future development of microbiome-based monitoring of wildlife populations and supports hypothetical expectations found in host-microbiome theory.


Advancements in high throughput biophysical technologies: applications for characterization and screening during early formulation development of monoclonal antibodies.
The formulation development of monoclonal antibodies is extremely challenging, due to the diversity and complexity contained within this class of molecules. The physical and chemical properties of a monoclonal antibody dictate the behavior of the protein drug during manufacturing, storage and clinical administration. In the past few years, the use of high throughput technologies has been widely adapted to delineate unique properties of individual immunoglobulin G's (IgG's) important for their development. Numerous screening techniques have been designed to reveal physical and chemical characteristics of a protein relevant to stability under production, formulation and delivery conditions. In addition, protein stability under accelerated stresses has been utilized to predict long-term storage behavior for monoclonal antibodies in the formulation. In this review, we summarize the recent advancements in the field of biophysical technology, with a specific focus on the techniques that can be directly applied to the formulation development of monoclonal antibodies. Several case studies are also presented here to provide examples of combining existing biophysical methods with high throughput screening technology in the formulation development of monoclonal antibody drugs.


Effects of microplastics on the feeding rates of larvae of a coastal fish: direct consumption, trophic transfer, and effects on growth and survival.
Microplastics are now found throughout the world's oceans, and although many organisms ingest microplastics, less is known about how plastics in seawater may affect key processes such as feeding rate, growth, and survival. We used a series of laboratory experiments to test whether microplastics in seawater affected the feeding rates of larvae of the California Grunion, Leuresthes tenuis. In addition, we tested whether trophic transfer of microplastics from zooplankton to larval fish can occur and affect growth and survival of fish. We measured feeding rates of grunion larvae at various concentrations of 75-90 µm and 125-250 µm polyethylene microplastics and under both still water and turbulent conditions. In these experiments, exposure to microplastics had modest effects on feeding rates, though responses may be somewhat complex. Low concentrations of microplastics increased feeding rates compared to the control, but at higher concentrations, feeding rates were indistinguishable from those in the control group, though effects were small compared to natural variation in feeding rates among individual fish. Experiments to test for trophic transfer of microplastics revealed that grunion larvae that were fed brine shrimp exposed to high concentrations of microplastics had lower growth rates and elevated mortality rates. Overall, our results suggest that the direct effects of microplastics on feeding rates of California Grunion during the early larval phase are minor, while the trophic transfer of microplastics from zooplankton to larval fish may have significant effects on their growth and survival. The online version contains supplementary material available at 10.1007/s00227-021-04010-x.


Transit From Autotrophism to Heterotrophism: Sequence Variation and Evolution of Chloroplast Genomes in Orobanchaceae Species.
The family Orobanchaceae including autotrophic, hemiparasitic, and holoparasitic species, is becoming a key taxa to study the evolution of chloroplast genomes in different lifestyles. But the early evolutionary trajectory in the transit from autotrophism to hemiparasitism still maintains unclear for the inadequate sampling. In this study, we compared 50 complete chloroplast genomes in Orobanchaceae, containing four newly sequenced plastomes from hemiparasitic Pedicularis, to elucidate the sequence variation patterns in the evolution of plastomes. Contrasted to the sequence and structural hypervariabilities in holoparasites, hemiparasitic plastomes exhibited high similarity to those of autotrophs in gene and GC contents. They are generally characterized with functional or physical loss of ndh/tRNA genes and the inverted small-single-copy region. Gene losses in Orobanchaceae were lineage-specific and convergent, possibly related to structural reconfiguration and expansion/contraction of the inverted region. Pseudogenization of ndh genes was unique in hemiparasites. At least in Pedicularis, the ndhF gene might be most sensitive to the environmental factors and easily pseudogenized when autotrophs transit to hemiparasites. And the changes in gene contents and structural variation potentially deeply rely on the feeding type. Selective pressure, together with mutational bias, was the dominant factor of shaping the codon usage patterns. The relaxed selective constraint, potentially with genome-based GC conversion (gBGC) and preferential codon usage, drive the fluctuation of GC contents among taxa with different lifestyles. Phylogenetic analysis in Orobanchaceae supported that parasitic species were single-originated while holoparasites were multiple-originated. Overall, the comparison of plastomes provided a good opportunity to understand the evolution process in Orobanchaceae with different lifestyles.


Growth promotion of Lactuca sativa in response to volatile organic compounds emitted from diverse bacterial species.
Agrochemicals are currently used in horticulture to increase crop production. Nevertheless, their indiscriminate use is a relevant issue for environmental and legal aspects. Alternative tools for reducing fertilizers and synthetic phytohormones are being investigated, such as the use of volatile organic compounds (VOCs) as growth inducers. Some soil bacteria, such as Pseudomonas and Bacillus, stimulate Arabidopsis and tobacco growth by releasing VOCs, but their effects on vegetables have not been investigated. Lactuca sativa was used as model vegetable to investigate bacterial VOCs as growth inducers. We selected 10 bacteria strains, belonging to Bacillus, Staphylococcus and Serratia genera that are able to produce 3-hydroxy-2-butanone (acetoin), a compound with proven growth promoting activity. Two-day old-seedlings of L. sativa were exposed to VOCs emitted by the selected bacteria grown in different media cultures for 7 days. The results showed that the VOCs released from the bacteria elicited an increase in the number of lateral roots, dry weight, root growth and shoot length, depending on the media used. Three Bacillus strains, BCT53, BCT9 and BCT4, were selected according to its their growth inducing capacity. The BCT9 strain elicited the greatest increases in dry weight and primary root length when L. sativa seedlings were subjected to a 10-day experiment. Finally, because acetoin only stimulated root growth, we suggest that other volatiles could be responsible for the growth promotion of L. sativa. In conclusion, our results strongly suggest that bacteria volatiles can be used as growth-inducers as alternative or complementary strategies for application in horticulture species.


How will climate change pathways and mitigation options alter incidence of vector-borne diseases? A framework for leishmaniasis in South and Meso-America.
The enormous global burden of vector-borne diseases disproportionately affects poor people in tropical, developing countries. Changes in vector-borne disease impacts are often linked to human modification of ecosystems as well as climate change. For tropical ecosystems, the health impacts of future environmental and developmental policy depend on how vector-borne disease risks trade off against other ecosystem services across heterogeneous landscapes. By linking future socio-economic and climate change pathways to dynamic land use models, this study is amongst the first to analyse and project impacts of both land use and climate change on continental-scale patterns in vector-borne diseases. Models were developed for cutaneous and visceral leishmaniasis in the Americas-ecologically complex sand fly borne infections linked to tropical forests and diverse wild and domestic mammal hosts. Both diseases were hypothesised to increase with available interface habitat between forest and agricultural or domestic habitats and with mammal biodiversity. However, landscape edge metrics were not important as predictors of leishmaniasis. Models including mammal richness were similar in accuracy and predicted disease extent to models containing only climate and land use predictors. Overall, climatic factors explained 80% and land use factors only 20% of the variance in past disease patterns. Both diseases, but especially cutaneous leishmaniasis, were associated with low seasonality in temperature and precipitation. Since such seasonality increases under future climate change, particularly under strong climate forcing, both diseases were predicted to contract in geographical extent to 2050, with cutaneous leishmaniasis contracting by between 35% and 50%. Whilst visceral leishmaniasis contracted slightly more under strong than weak management for carbon, biodiversity and ecosystem services, future cutaneous leishmaniasis extent was relatively insensitive to future alternative socio-economic pathways. Models parameterised at narrower geographical scales may be more sensitive to land use pattern and project more substantial changes in disease extent under future alternative socio-economic pathways.


A chromosome-level genome assembly provides insights into ascorbic acid accumulation and fruit softening in guava (Psidium guajava).
Guava (Psidium guajava) is an important fleshy-fruited tree of the Myrtaceae family that is widely cultivated in tropical and subtropical areas of the world and has attracted considerable attention for the richness of ascorbic acid in its fruits. However, studies on the evolution and genetic breeding potential of guava are hindered by the lack of a reference genome. Here, we present a chromosome-level genomic assembly of guava using PacBio sequencing and Hi-C technology. We found that the genome assembly size was 443.8 Mb with a contig N50 of ~15.8 Mb. We annotated a total of 25 601 genes and 193.2 Mb of repetitive sequences for this genome. Comparative genomic analysis revealed that guava has undergone a recent whole-genome duplication (WGD) event shared by all species in Myrtaceae. In addition, through metabolic analysis, we determined that the L-galactose pathway plays a major role in ascorbic acid biosynthesis in guava fruits. Moreover, the softening of fruits of guava may result from both starch and cell wall degradation according to analyses of gene expression profiles and positively selected genes. Our data provide a foundational resource to support molecular breeding of guava and represent new insights into the evolution of soft, fleshy fruits in Myrtaceae.


Impact of race on asthma treatment failures in the asthma clinical research network.
Recent studies suggest that people with asthma of different racial backgrounds may respond differently to various therapies. To use data from well-characterized participants in prior Asthma Clinical Research Network (ACRN) trials to determine whether racial differences affected asthma treatment failures. We analyzed baseline phenotypes and treatment failure rates (worsening asthma resulting in systemic corticosteroid use, hospitalization, emergency department visit, prolonged decrease in peak expiratory flow, increase in albuterol use, or safety concerns) in subjects participating in 10 ACRN trials (1993-2003). Self-declared race was reported in each trial and treatment failure rates were stratified by race. A total of 1,200 unique subjects (whites = 795 [66%]; African Americans = 233 [19%]; others = 172 [14%]; mean age = 32) were included in the analyses. At baseline, African Americans had fewer asthma symptoms (P < 0.001) and less average daily rescue inhaler use (P = 0.007) than whites. There were no differences in baseline FEV(1) (% predicted); asthma quality of life; bronchial hyperreactivity; or exhaled nitric oxide concentrations. A total of 147 treatment failures were observed; a significantly higher proportion of African Americans (19.7%; n = 46) experienced a treatment failure compared with whites (12.7%; n = 101) (odds ratio = 1.7; 95% confidence interval, 1.2-2.5; P = 0.007). When stratified by treatment, African Americans receiving long-acting β-agonists were twice as likely as whites to experience a treatment failure (odds ratio = 2.1; 95% confidence interval, 1.3-3.6; P = 0.004), even when used with other controller therapies. Despite having fewer asthma symptoms and less rescue β-agonist use, African-Americans with asthma have more treatment failures compared with whites, especially when taking long-acting β-agonists.


Reactivity of a Nickel Sulfide with Carbon Monoxide and Nitric Oxide.
The reactivity of the "masked" terminal nickel sulfide complex, [K(18-crown-6)][(L(tBu))Ni(II)(S)] (L(tBu) = {(2,6-(i)Pr2C6H3)NC((t)Bu)}2CH), with the biologically important small molecules CO and NO, was surveyed. [K(18-crown-6)][(L(tBu))Ni(II)(S)] reacts with carbon monoxide (CO) via addition across the Ni-S bond to give a carbonyl sulfide complex, [K(18-crown-6)][(L(tBu))Ni(II)(S,C:η(2)-COS)] (1). Additionally, [K(18-crown-6)][(L(tBu))Ni(II)(S)] reacts with nitric oxide (NO) to yield a nickel nitrosyl, [(L(tBu))Ni(NO)] (2), and a perthionitrite anion, [K(18-crown-6)][SSNO] (3). The isolation of 3 from this reaction confirms, for the first time, that transition metal sulfides can react with NO to form the biologically important [SSNO](-) anion.


Juvenile hormone diol kinase. II. Sequencing, cloning, and molecular modeling of juvenile hormone-selective diol kinase from Manduca sexta.
The gene sequence of Manduca sexta juvenile hormone diol kinase (JHDK) codes for an enzyme that has 59% sequence identity to Drosophila melanogaster sarcoplasmic calcium-binding protein-2 (dSCP2). JHDK and dSCP2 are similar to G-proteins with three conserved sequence elements involved in purine nucleotide binding. Both proteins contain two pairs of EF-hand motifs. Characterization and partial purification of the D. melanogaster homolog of M. sexta JHDK from adult D. melanogaster gave material with JHDK activity. This activity has an experimental pI and molecular mass that are nearly identical to those of dSCP2. Moreover, D. melanogaster phosphotransferase activity has very similar chromatographic retention in three systems compared with M. sexta JHDK. Substrate docking to three-dimensional models of JHDK has shown that the three conserved nucleotide-binding elements surround the putative substrate-binding site and align with conserved sequence elements of p21(Ras) and adenylate kinase. D. melanogaster dSCP2 is a homolog of M. sexta JHDK, and these proteins constitute a novel kinase family that binds nucleotides using the scaffold of an SCP (Protein Data Bank code ).


An evaluation of I Can Cope. Insights into program design and implementation.
The I Can Cope program is an educational program developed to provide information on how to promote physical and emotional well-being to individuals with cancer, their families, and friends. Through focus group and individual interviews and a mailed survey, the effectiveness of the selection, marketing, implementation, and support processes associated with implementing the program in the central Arizona and greater Las Vegas, Nevada, regions was evaluated. Findings, recommendations, lessons learned, and use of findings are discussed.


Docking protein FRS2 links the protein tyrosine kinase RET and its oncogenic forms with the mitogen-activated protein kinase signaling cascade.
The receptor tyrosine kinase RET functions as the signal transducing receptor for the GDNF (for "glial cell-derived neurotrophic factors") family of ligands. Mutations in the RET gene were implicated in Hirschsprung disease (HSCR), multiple endocrine neoplasia type 2 (MEN 2), and thyroid carcinomas. In this report we demonstrate that the docking protein FRS2 is tyrosine phosphorylated by ligand-stimulated and by constitutively activated oncogenic forms of RET. Complex formation between RET and FRS2 is mediated by binding of the phosphotyrosine-binding domain of FRS2 to pY1062, a residue in RET that also functions as a binding site for Shc. However, overexpression of FRS2 but not Shc potentiates mitogen-activated protein (MAP) kinase activation by RET oncoproteins. We demonstrate that oncogenic RET-PTC proteins are associated with FRS2 constitutively, leading to tyrosine phosphorylation of FRS2, MAP kinase stimulation, and cell proliferation. However, loss-of-function HSCR-associated RET mutants exhibit impaired FRS2 binding and reduced MAP kinase activation. These experiments demonstrate that FRS2 couples both ligand-regulated and oncogenic forms of RET, with the MAP kinase signaling cascade as part of the response of RET under normal biological conditions and pathological conditions, such as MEN 2 and papillary thyroid carcinomas.


Protein Changes After 6 weeks of Walking and the Relationship to Pain in Adults with Knee Osteoarthritis.
Background: Knee osteoarthritis (KOA) affects 22.9% of individuals over the age of 40 and causes significant pain and disability. Pain is the most prevalent and troublesome symptom of KOA leading patients to seek medical interventions for relief. Knee osteoarthritis pain has both peripheral and central mechanisms that vary by individual. Non-pharmacological pain management strategies such as walking is the first step in reducing KOA pain. However, initiation of a walking regime can induce knee pain for some and the mechanism by which habitual walking reduces KOA pain is unclear. Purpose: The purpose of this study was to use a discovery proteomics approach and quantitative sensory testing (QST) to determine the molecular changes that occur after habitual walking and their relationship to pain sensitivity. Research Design and Study Sample: We conducted a pre-test/post-test study using QST to measure neurophysiological parameters at the knee and contralateral forearm and examined platelet protein signatures before and after 6 weeks of walking 3 days per week for 30 minutes among six adults with KOA and six healthy controls. Results: Knee pain sensitivity did not change significantly after 6 weeks of walking among either KOA or healthy participants. However, forearm pressure pain sensitivity decreased for both groups after walking, indicating reduction in central pain pathways. Protein signatures showed downregulation of immune and inflammatory, pathways among KOA participants after walking which were upregulated in healthy controls. Conclusion: These differences may contribute differences in centralized pain thresholds seen between KOA and healthy participants.


The emerging landscape of circular RNA in life processes.
Circular RNAs (circRNAs) are a novel class of non-coding RNA that assumes a covalently closed continuous conformation. CircRNAs were previously thought to be the byproducts of splicing errors caused by low abundance and the technological limitations. With the recent development of high-throughput sequencing technology, numerous circRNAs have been discovered in many species. Recent studies have revealed that circRNAs are stable and widely expressed, and often exhibit cell type-specific or tissue-specific expression. Most circRNAs can be generated from exons, introns, or both. Remarkably, emerging evidence indicates that some circRNAs can serve as microRNA (miRNA) sponges, regulate transcription or splicing, and can interact with RNA binding proteins (RBPs). Moreover, circRNAs have been reported to play essential roles in myriad life processes, such as aging, insulin secretion, tissue development, atherosclerotic vascular disease risk, cardiac hypertrophy and cancer. Although circRNAs are ancient molecules, they represent a newly appreciated form of noncoding RNA and as such have great potential implications in clinical and research fields. Here, we review the current understanding of circRNA classification, function and significance in physiological and pathological processes. We believe that future research will increase our understanding of the regulation and function of these novel molecules.


Public Figure Fixation: Cautionary Findings for Mental Health Practitioners.
Research in western nations has found that pathologically fixated individuals pose a risk of serious harm to public figures, and that many of these fixated persons are mentally ill and require treatment. Over the past decade, integrated fixated threat assessment agencies have been established in western Europe and Australia to specifically assess and manage this group. The current study examines 400 consecutive referrals to a fixated threat assessment center in Queensland, Australia, with a particular focus on the mental health and risk profile of those who engage in inappropriate contact with public office holders. It considers the high proportion of delusional disorders in this cohort, and their identification and management by psychiatric services. The authors conclude with a discussion of the mental health response to this group and impediments to mitigating the risks posed by fixated persons. Copyright © 2016 John Wiley & Sons, Ltd.


Additive protective effects of colostral antipili antibodies in calves experimentally infected with enterotoxigenic Escherichia coli.
With oral infection of calves by an enterotoxigenic Escherichia coli strain carrying K99, F41, and FY adhesins, colostrums from cows vaccinated against either K99+F41 or FY did not provide protection, but a mixture of the two colostrums did. The association of antibodies directed against the different adhesins is more effective than antibodies directed against one adhesin alone for colostral protection against enterotoxigenic E. coli carrying several adhesins.


2-D optical/opto-mechanical microfluidic sensing with micro-bubble resonators.
In this paper a new sensing scheme by simultaneously measuring optical refractive index change and sound speed change in an optofluidic thin wall micro-bubble resonator is reported. Sensitivity of sound speed is 4.2-6.8 MHz/ (km/s) for 3 types of mechanical modes. A 2-D optical/opto-mechanical sensing map is plotted by detecting both the whispering gallery mode resonance shift and the optomechanical resonance shift. This novel scheme provides a supplementary support to optical sensing when analytes do not respond to refractive index (RI) change.


Congenital diaphragmatic hernia in a family segregating a reciprocal translocation t(5;15)(p15.3;q24).
Congenital diaphragmatic hernia (CDH) is a relatively common malformation of unknown cause with high mortality due to hypoplasia of the lungs and pulmonary hypertension. We studied a family in which two fetuses had CDH, and two pregnancies resulted in first trimester missed abortions. Both fetuses with CDH had an apparently normal karyotype. In a subsequent pregnancy, fluorescent in situ hybridization analysis of amniocytes showed a balanced translocation 46,XY, t(5;15) (p15.3;q24) also present in the mother and in a normal child, suggesting that the diaphragmatic hernia in the first two fetuses was caused by a cryptic unbalanced translocation. This hypothesis is supported by a previous observation of CDH in a distal deletion of 15q as part of a multiple congenital anomalies syndrome. It is suggested that a gene distal to 15q21 is important for the normal development of the diaphragm.


[Magnetic resonance imaging as a non-invasive detection tool for extraovarian endometriosis--own experience].
Endometriosis--due to its high incidence, associated pain and infertility--constitutes an important problem in gynecological practice. The Polish Gynecological Society Expert Panel recommends to perform magnetic resonance imaging (MRI) prior to laparoscopy The purpose of this study is to present the usefulness of MRI in the diagnosis of extraovarian endometriosis on the basis of own experience. The material consisted of 35 patients, aged 15-52 (mean 36.5 years), who were diagnosed with extraovarian endometriosis on MRI. MR examinations were performed with 1.5 T scanners according to a routine protocol, which incorporates the LAVA sequence of dynamic contrast studies protocol because of thin sections. Extraovarian endometriosis was isolated in 24 patients (68.6%), while in 11 (31.4%) it coexisted with ovarian endometriomas. In 23 cases (65.7%) extraovarian endometriosis was found in one place, in 12 (34.3%)--in two or more locations. Endometriosis was found in the following locations: abdominal wall--11 cases (37.4%), uterine body--9 (25.7%), posterior vaginal fornix--7 (20%), wall of the rectum and sigmoid colon--5 (14.3%), pararectal space--5, uterine cervix--4 (11.4%), Douglas pouch--3 (8.6%), Fallopian tube--2 (5.7%), wall of the small intestine--1 (2.8%), and urinary bladder--1. Adhesions were observed in 28.6% of the patients. MRI is an important addition to the non-invasive diagnosis of extraovarian endometriosis and should be performed before treatment, especially surgical one. The inclusion of fat saturated T1 sequence from the dynamic contrast examination in the study protocol increases the likelihood of detecting small endometrial implants.


Investigation on the aggregation behaviors and filament morphology of tau protein by a simple 90° angle light-scattering assay.
The in vitro aggregation of tau constructs was monitored by a simple 90° angle light-scattering (LS) approach which was conducted directly on fluorescence instrument. At the optimum incident wavelength (550 nm, unpolarized), the sensitivity of LS was high enough to detect tau aggregation at micromolar range. The nucleation and elongation, different events in the aggregation process of 4RMBD construct (corresponding with the four repeated units of tau Microtubule Binding Domain) could be observed by this approach, as compared with ThS fluorescence assay. The validity of this technique was demonstrated over a range of tau concentrations with different tau filaments. Linear regression of scattering light against concentration yielded the x-intercept, the critical concentrations of tau constructs. The critical concentrations of 4RMBD and its S305N mutant are 5.26 μM and 4.04 μM respectively, indicating point mutation S305N, which is associated with FTDP-17, appear to enhance the heparin-induced tau aggregation in vitro. Furthermore, the slopes of concentration dependence curves, as well as the angle dependence, were discussed based on the filaments morphology examined by electron microscopy and ultrasonication experiment.


Parthenogenesis in non-rodent species: developmental competence and differentiation plasticity.
An oocyte can activate its developmental process without the intervention of the male counterpart. This form of reproduction, known as parthenogenesis, occurs spontaneously in a variety of lower organisms, but not in mammals. However, it must be noted that mammalian oocytes can be activated in vitro, mimicking the intracellular calcium wave induced by the spermatozoon at fertilization, which triggers cleavage divisions and embryonic development. The resultant parthenotes are not capable of developing to term and arrest their growth at different stages, depending on the species. It is believed that this arrest is due to genomic imprinting, which causes the repression of genes normally expressed by the paternal allele. Human parthenogenetic embryos have recently been proposed as an alternative, less controversial source of embryonic stem cell lines, based on their inherent inability to form a new individual. However many aspects related to the biology of parthenogenetic embryos and parthenogenetically derived cell lines still need to be elucidated. Limited information is available in particular on the consequences of the lack of centrioles and on the parthenote's ability to assemble a new embryonic centrosome in the absence of the sperm centriole. Indeed, in lower species, successful parthenogenesis largely depends upon the oocyte's ability to regenerate complete and functional centrosomes in the absence of the material supplied by a male gamete, while the control of this event appears to be less stringent in mammalian cells. In an attempt to better elucidate some of these aspects, parthenogenetic cell lines, recently derived in our laboratory, have been characterized for their pluripotency. In vitro and in vivo differentiation plasticity have been assessed, demonstrating the ability of these cells to differentiate into cell types derived from the three germ layers. These results confirmed common features between uni- and bi-parental embryonic stem cells. However data obtained with parthenogenetic cells indicate the presence of an intrinsic deregulation of the mechanisms controlling proliferation vs. differentiation and suggest their uni-parental origin as a possible cause.


Efficacy and Safety of Albumin-Bound Paclitaxel Compared to Docetaxel as Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer.
Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as neoadjuvant chemotherapy (NAC) for breast cancer remains controversial. We conducted a retrospective study to compare the efficacy and safety of nab-paclitaxel with those of docetaxel as neoadjuvant regimens for HER2-negative breast cancer. In this retrospective analysis, a total of 159 HER2-negative breast cancer patients who had undergone operation after NAC were consecutively analyzed from May 2016 to April 2018. Patients were classified into the nab-paclitaxel group (n = 79, nab-paclitaxel 260 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2) and the docetaxel group (n = 80, docetaxel 75 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2) according to the drug they received for neoadjuvant treatment. The efficacy and adverse events were evaluated in the two groups. The pathological complete response (pCR)(ypT0/isN0) rate was significantly higher in the nab-paclitaxel group than in the docetaxel group (36.71% vs 20.00%; P = 0.031). The multivariate analysis revealed that therapeutic drugs, lymph node status, and tumor subtype were the most significant factor influencing treatment outcome. At a median follow-up of 47 months, disease-free survival (DFS) was not significantly different in those assigned to nab-paclitaxel compared with docetaxel (82.28% vs 76.25%; P = 0.331). The incidence of peripheral sensory neuropathy in the nab-paclitaxel group was higher than that in the docetaxel group (60.76% vs 36.25%; P = 0.008), while the incidence of arthralgia was observed more frequently in the docetaxel group (57.50% vs 39.97%; P = 0.047). Compared with docetaxel, nab-paclitaxel achieved a higher pCR rate, especially those patients with triple-negative breast cancer or lymph node negative breast cancer. However, there was no significant difference in DFS between the two groups. This study provides a valuable reference for the management of patients with HER2-negative breast cancer.


5'-AMP-activated protein kinase plays an essential role in geniposide-regulated glucose-stimulated insulin secretion in rat pancreatic INS-1 β cells.
Our previous work showed that geniposide affected glucose-stimulated insulin secretion (GSIS) via regulating glucose uptake and metabolism in pancreatic β cells; however, the molecular mechanisms remain largely unknown. Substantial evidence suggests that activation of 5'-AMP-activated protein kinase (AMPK) plays a central role in GSIS. Here, we aim to determine the role of AMPK on geniposide-regulated GSIS in rat pancreatic INS-1 cells. The results demonstrated that 6-[4-(2-piperidin-1-yletoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-α] pyrimidine (Compound C; an AMPK inhibitor) significantly attenuated the effects of geniposide on glucose uptake, energy metabolism, and insulin secretion in INS-1 cells. We also observed that geniposide induced phosphorylation of acetyl-CoA carboxylase (ACC), a marker of AMPK activity, in a time-dependent manner in INS-1 cells; however, in the presence of Compound C, the influence of geniposide on ACC phosphorylation was obviously inhibited. Furthermore, the knockdown of AMPK protein with AMPK siRNA treatment decreased the effects of geniposide on glucose uptake, adenosine triphosphate production, and GSIS. All these data indicate that AMPK plays an essential role in geniposide-regulated GSIS in pancreatic β cells.


Hidradenoma papilliferum with mixed histopathologic features of syringocystadenoma papilliferum and anogenital mammary-like glands: report of a case and review of the literature.
Hidradenoma papilliferum of the anogenital region was previously believed to originate from apocrine glands but has recently been accepted as originating from anogenital mammary-like glands. We describe a case of hidradenoma papilliferum with mixed features of syringocystadenoma papilliferum and mammary-like glands from the left labia majora of a 25-year-old woman. Histopathologically, the lesion showed an epithelial lining with apocrine secretion, and like syringocystadenoma papilliferum, the lesion extended from the epithelium as invaginations into the dermis. Adjacent to this lesion were ductal and glandular structures resembling normal mammary tissue. This review of the literature highlights the heterogeneity and complexity of lesions arising from anogenital mammary-like glands, and this case serves as further documentation of the association between anogenital mammary-like glands and hidradenoma papilliferum.


Tolerance to biodegraded crude oil in marine invertebrate embryos and larvae is associated with expression of a multixenobiotic resistance transporter.
The toxicity of water-soluble fractions of biodegraded crude oil (BWSF) to embryos and larvae of two marine invertebrates, the white sea urchin (Lytechinus anamesus) and the fat innkeeper (Urechis caupo), was studied. Santa Barbara Channel crude oil was artificially weathered and subjected to biodegradation using a mixed microbe culture obtained from natural oil seep sites. The degradation culture inoculated with seep sediment microbes accumulated 43.7 microg/l water-soluble hydrocarbons. In contrast water-soluble fractions from the non-degraded cultures (NWSF) only accumulated 3.05 microg/l. BWSF proved deleterious to Lytechinus embryo development at low concentrations (EC50 = 0.33 mg/l) but was essentially non-toxic to Urechis embryos/larvae up to 3.0 mg/l. An established mechanism for handling of a wide array of xenobiotics in Urechis embryos is the multixenobiotoic resistance transporter multixenobiotic response (MXR, also known as multidrug resistance, MDR). This mechanism is primarily mediated by ATP-dependent, efflux pumps that extrude a wide array of xenobiotic compounds. In this study, we show that Lytechinus larvae do not appear to express MXR efflux protein nor MXR mediated dye efflux capacity. In contrast, BWSF acts as a competitive inhibitor of MXR transport-mediated dye efflux in Urechis larvae. These results suggest that MXR may be an important mechanism for extrusion of the by-products of crude oil degradation by microbes, and that the level of its expression may determine the susceptibility of organisms to degraded oil hydrocarbons.


Ischemia/reperfusion is an independent trigger for increasing myocardial content of mRNA B-type natriuretic peptide.
This study aims to determine whether a relation exists between ischemia/reperfusion and myocardial B-type natriuretic peptide (BNP) mRNA expression independent of variations in intracavitary diastolic volume and consequently, of cardiomyocyte stretching. Twenty-three rats were subjected to the following conditions: control (C), 15 min of ischemia (I15), or ischemia plus 15 (R15), 30 (R30), or 45 (R45) min of reperfusion in the in situ hearts. Isolated hearts of sixteen additional rats (sham, n = 8; occlusion, n = 8) were perfused for studies in the absence of ventricular distension. All hearts were divided in two segments (ischemic and nonischemic). Ventricular distension was avoided by excluding the atria and mitral valves. In both experiments, BNP mRNA was quantified by real-time polymerase chain reaction in both nonischemic and ischemic regions. In the in situ hearts, myocardial BNP mRNA values at R15 (4.24 +/- 0.75) in the ischemic region were higher than in other groups (C: 1.43 +/- 0.81, P = 0.044; I15: 3.05 +/- 0.62, P = 0.048; R30: 0.76 +/- 0.84, P = 0.001; R45: 1.47 +/- 0.60, P = 0.046, [analysis of variance]). In isolated hearts without ventricular distension, myocardial BNP mRNA (arbitrary units) content at R15 in ischemic regions (4.54 +/- 0.26) was greater than in nonischemic regions in both occlusion (3.51 +/- 0.20, P < 0.001) and sham (3.38 +/- 0.25, P = 0.0001 and 3.47 +/- 0.19, P = 0.0001) groups. The present data show that ischemia/reperfusion is responsible for increased BNP mRNA myocardial content independent of changes of ventricular cavity diastolic volume.


TP53 c.455C>T p.(Pro152Leu) pathogenic variant is a lower risk allele with attenuated risks of breast cancer and sarcoma.
Germline (likely) pathogenic TP53 variants cause Li-Fraumeni syndrome (LFS), typically associated with sarcoma, brain, breast and adrenal tumours. Although classical LFS is highly penetrant, the p.R337H variant, common in Brazil, is typically associated with childhood adrenal tumours and an older onset age of other LFS tumours. Previously, we reported the finding of p.P152L in 6 children from 5 families with adrenal tumours. We have now assessed cancer risks over the subsequent 23 years, and in one further family with p.P152L. Cancer risks were compared with those in the 11 families known to our service with classical dominant negative mutations affecting neighbouring codons 245 and 248 (codon 245/248).Compared with codon 245/248 families, we found lower age-related risks for all non-adrenal tumours in codon 152 families (p<0.0001) with an absence of breast cancer as compared with 100% penetrance by age 36 years in codon 245/248 families (p<0.0001), and lower rates of sarcoma in non-irradiated individuals (p=0.0001). Although there were more adrenal tumours in codon 152 families (6/26 individuals, 1/27 for codon 245/248), this was not significant (p=0.05).Understanding codon-specific cancer risks in LFS is important for accurate personalised cancer risk assessment, and subsequent prevention and early detection strategies.


Requirement of glycosylation machinery in TLR responses revealed by CRISPR/Cas9 screening.
The Toll family of receptors sense microbial products and activate a defense response. The molecular machinery required for the TLR response is not yet fully understood. In the present study, we used a clustered, regularly interspaced, short palindromic repeats (CRISPR)/CAS9 screening system to study TLR responses. We employed a cell line expressing TLR with an NF-κB-driven GFP reporter. The cell line was transduced with a guide RNA (gRNA) library and stimulated with TLR ligands. The cells impaired in GFP induction were sorted, and gRNAs were sequenced. Identified genes were ranked according to the count of sequence reads and the number of gRNA target sites. The screening system worked correctly, as molecules that were already known to be required for the TLR response were identified by the screening. Furthermore, this system revealed that the oligosaccharide transferase complex (OSTC) mediating co-translational glycosylation was required for TLR5, 7 and 9 responses. Protein expression of TLR5, but not an irrelevant molecule (CD44), was abolished by the lack of OSTC, suggesting the essential role of glycosylation in TLR5 protein stability. These results demonstrate that the screening system established here is able to reveal molecular mechanisms underlying the TLR response.


Differential effects of foliar endophytic fungi on insect herbivores attacking a herbaceous plant.
Foliar endophytic fungi appear to be ubiquitous in nature, occurring in a very wide range of herbaceous plants. However, their ecological role within forbs is very poorly known and interactions with foliar-feeding insects virtually unexplored. In this study, leaves of Cirsium arvense were infected with different combinations of endophyte fungi that had been previously isolated from this plant species. Two months later, leaf material was fed to larvae of a generalist insect, Mamestra brassicae, and adults of a specialist feeder, Cassida rubiginosa. Endophytes had different effects on the two insects; one species, Chaetomium cochliodes, reduced growth of M. brassicae but increased feeding by C. rubiginosa. Another species, Cladosporium cladosporioides, increased beetle feeding also, but had no effect on M. brassicae. Interactions were also seen between fungal species and dual infection with C. cladosporioides and Trichoderma viride greatly reduced beetle feeding. It is concluded that endophytes have significant effects on foliar feeding insects that differ with degree of specialism of the herbivore. We suggest that these effects are due to chemical changes in the host, brought about by fungal infection. These fungi have received remarkably little attention in the study of insect-plant interactions and yet could be important determinants of insect growth and even population dynamics.


Tongue pressure modulation during swallowing: water versus nectar-thick liquids.
Evidence of tongue-palate pressure modulation during swallowing between thin and nectar-thick liquids stimuli has been equivocal. This mirrors a lack of clear evidence in the literature of tongue and hyoid movement modulation between nectar-thick and thin liquid swallows. In the current investigation, the authors sought to confirm whether tongue-palate pressures are modulated between discrete swallows of water and nectar-thick juice. Tongue-palate pressures were measured at 3 sites (anterior, medial, and posterior palate) using an adhered 3-bulb pressure strip in 20 healthy, young adults during discrete swallows of water and nectar-thick apple juice. Pressure modulation was not noted with respect to pressure amplitudes (in mm Hg), but was identified both in the pressure patterns observed (the sites and number of bulbs activated) and temporal aspects of pressure duration. Tongue-palate pressure amplitude modulation does not occur for nectar-thick swallows compared to thin liquid swallows. Modulation does, however, occur with respect to the tongue-palate contact surface area and pressure durations. The authors introduce the concept of pressure slope as a meaningful way to examine tongue-palate pressure application in swallowing.


Fujifilm Finepix IS-Pro: a review.
As part of a series of investigations into the utility of digital SLR cameras for IR and UV photography, the authors tested a Fujifilm Finepix IS-Pro DSLR camera using the previously reported test procedures.


The natural history of untreated phenylketonuria over 20 years.
Fifty-one adults with untreated phenylketonuria (PKU), have been reviewed after a 20 year interval, at ages ranging from 28.8 to 71.8 years. Five died of causes unrelated to PKU. Three severely affected individuals had shown a progressive loss of motor function and three had developed epilepsy, bringing the total with this problem to 12. No loss of abilities was apparent in 41 patients. Other health problems, including cataracts, were not frequent. Serum phenylalanine levels had decreased over the 20 year period. Untreated PKU does not generally cause progressive loss of abilities during adult life.


Neurodevelopmental benefits of antiretroviral therapy in Ugandan children aged 0-6 years with HIV.
Insufficient data on neurodevelopmental benefits of antiretroviral therapy (ART) in children. Prospective study of 329 mothers and children aged 0-6 years to assess neurodevelopment. Results stratified by the maternal (M) and child (C) HIV status (MHIV⁻/CHIV⁻, MHIV⁺/CHIV⁻, and MHIV⁺/CHIV⁺). Gross Motor, Visual Reception, Fine Motor, Receptive, and Expressive Language scores were assessed by Mullen Scales of Early Learning. Global cognitive function was derived from an Early Learning Composite (ELC) score. Standardized weight and height for age z scores were constructed, and the lowest 15% cutoff defined disability. Generalized linear models were used to estimate prevalence rate ratios (PRR) adjusted for the child's age, weight, and height. In HIV-positive children, generalized linear models assessed the impact of ART initiation and duration on neurodevelopment. Compared with MHIV⁻/CHIV⁻ children, HIV-positive children were more likely to have global deficits in all measures of neurodevelopment except gross motor skills, whereas in MHIV⁺/CHIV⁻ children, there was impairment in receptive language [adjusted PRR = 2.67; confidence interval (CI): 1·08 to 6.60] and the ELC (adjusted PRR = 2.94; CI: 1.11 to 7.82). Of the children born to HIV-positive mothers, HIV-positive children did worse than MHIV⁺/CHIV⁻ only in visual reception skills (adjusted PRR = 2.86; CI: 1.23 to 6.65). Of the 116 HIV-positive children, 44% had initiated ART. Compared with ART duration of <12 months, ART durations of 24-60 months were associated with decreased impairments in Fine Motor, Receptive Language, Expressive Language, and ELC scores. Longer duration on ART is associated with reduction of some neurologic impairment and early diagnosis and treatment of HIV-positive children is a priority.


Implementing RapidArc into clinical routine: a comprehensive program from machine QA to TPS validation and patient QA.
With the increased commercial availability of intensity modulated arc therapy (IMAT) comes the need for comprehensive QA programs, covering the different aspects of this newly available technology. This manuscript proposes such a program for the RapidArc (RA) (Varian Medical Systems, Palo Alto) IMAT solution. The program was developed and tested out for a Millennium120 MLC on iX Clinacs and a HighDefinition MLC on a Novalis TX, using a variety of measurement equipment including Gafchromic film, 2D ion chamber arrays (Seven29 and StarCheck, PTW, Freiburg, Germany) with inclinometer and Octavius phantom, the Delta4 systam (ScandiDos, Uppsala, Sweden) and the portal imager (EPID). First, a number of complementary machine QA tests were developed to monitor the correct interplay between the accelerating/decelerating gantry, the variable dose rate and the MLC position, straining the delivery to the maximum allowed limits. Second, a systematic approach to the validation of the dose calculation for RA was adopted, starting with static gantry and RA specific static MLC shapes and gradually moving to dynamic gantry, dynamic MLC shapes. RA plans were then optimized on a series of artificial structures created within the homogeneous Octavius phantom and within a heterogeneous lung phantom. These served the double purpose of testing the behavior of the optimization algorithm (PRO) as well as the precision of the forward dose calculation. Finally, patient QA on a series of clinical cases was performed with different methods. In addition to the well established in-phantom QA, we evaluated the portal dosimetry solution within the Varian approach. For routine machine QA, the "Snooker Cue" test on the EPID proved to be the most sensitive to overall problem detection. It is also the most practical one. The "Twinkle" and "Sunrise" tests were useful to obtain well differentiated information on the individual treatment delivery components. The AAA8.9 dose calculations showed excellent agreement with all corresponding measurements, except in areas where the 2.5 mm fixed fluence resolution was insufficient to accurately model the tongue and groove effect or the dose through nearly closed opposing leafs. Such cases benefited from the increased fluence resolution in AAA10.0. In the clinical RA fields, these effects were smeared out spatially and the impact of the fluence resolution was considerably less pronounced. The RA plans on the artificial structure sets demonstrated some interesting characteristics of the PRO8.9 optimizer, such as a sometimes unexpected dependence on the collimator rotation and a suboptimal coverage of targets within lung tissue. Although the portal dosimetry was successfully validated, we are reluctant to use it as a sole means of patient QA as long as no gantry angle information is embedded. The all-in validation program allows a systematic approach in monitoring the different levels of RA treatments. With the systematic approach comes a better understanding of both the capabilities and the limits of the used solution. The program can be useful for implementation, but also for the validation of major upgrades.


Hemispheric asymmetries in speech perception: sense, nonsense and modulations.
The well-established left hemisphere specialisation for language processing has long been claimed to be based on a low-level auditory specialization for specific acoustic features in speech, particularly regarding 'rapid temporal processing'. A novel analysis/synthesis technique was used to construct a variety of sounds based on simple sentences which could be manipulated in spectro-temporal complexity, and whether they were intelligible or not. All sounds consisted of two noise-excited spectral prominences (based on the lower two formants in the original speech) which could be static or varying in frequency and/or amplitude independently. Dynamically varying both acoustic features based on the same sentence led to intelligible speech but when either or both acoustic features were static, the stimuli were not intelligible. Using the frequency dynamics from one sentence with the amplitude dynamics of another led to unintelligible sounds of comparable spectro-temporal complexity to the intelligible ones. Positron emission tomography (PET) was used to compare which brain regions were active when participants listened to the different sounds. Neural activity to spectral and amplitude modulations sufficient to support speech intelligibility (without actually being intelligible) was seen bilaterally, with a right temporal lobe dominance. A left dominant response was seen only to intelligible sounds. It thus appears that the left hemisphere specialisation for speech is based on the linguistic properties of utterances, not on particular acoustic features.


Determination of Doxepin in human plasma using cloud-point extraction with high-performance liquid chromatography and ultraviolet detection.
A new straightforward method based on cloud-point extraction has been developed, optimized, and validated for the determination of doxepin in human plasma by high-performance liquid chromatography separation and UV detection. The nonionic surfactant Triton X-114 was chosen as the extraction solvent. Chromatography separation was performed on a μBondapakR C18 column (4.6 mm id × 300 mm, 3 μm particle size), which was used for isocratic elution at a detection wavelength of 289 nm. Under the optimum conditions, the linear range of doxepin in human plasma was 0.1-0.9 μg/mL. Also, the detection limit, preconcentration factor, and enrichment factor were 0.08 μg/mL, 50, and 49.0, respectively.


Adolescent drug abuse.
The author reviews general principles for assessing, intervening in, and treating adolescent drug abuse. Assessment involves uncovering the extent of the drug problem and the reasons behind it, including the role of family psychodynamics. In the intervention phase, the clinician should clearly explain the diagnosis to the family and firmly recommend further actions, being prepared to encounter resistance. Treatment should enable the adolescent to become free of acute drug effects, understand the disorder, and become physically and emotionally capable of abstinence. Involvement in mutual self-help groups modeled after Alcoholics Anonymous is helpful in achieving long-term abstinence. The author also discusses trends in adolescent drug abuse, treatment of medical and psychiatric complications of drug use, and strategies for handling violent drug abusers.


Evolutionarily conserved, alternative splicing of reelin during brain development.
Reelin is the protein defective in reeler mutant mice and plays a pivotal role in brain development. However, some uncertainties remain about the relationship between reelin and the reeler phenotype. It is generally believed that reelin, secreted by specific neuronal types such as Cajal-Retzius cells, acts at short distance via the extracellular matrix on target neurons, the response of which requires the Dab1 gene product. However, the pattern of reelin expression in some structures such as olfactory bulb, retina, and spinal cord suggests that the protein might be endowed with different functions. In the present study, we identify two uncommon, evolutionarily conserved splicing events in the 3' part of the transcript that result in different forms of the protein. First, a 6-nucleotide, brain-specific microexon is skipped in about 10% of reelin RNA. In addition, an alternative polyadenylation event involving 10-25% of reelin mRNA results in secretion of a truncated protein lacking the terminal, highly basic stretch. This alternative reelin is generally expressed in the same cells as the major form, but is almost undetectable in retina and spinal cord. Both alternative splicing events are present in mouse, rat, and man, suggesting that the corresponding reelin forms are functionally important.


Characterization of the heat shock response in cultured sugarcane cells : I. Physiology of the heat shock response and heat shock protein synthesis.
Effect of heat shock on the growth of cultured sugarcane cells (Saccharum officinarum L.) was measured. Heat shock (HS) treatment at 36 to 38 degrees C (2 hours) induced the development of maximum thermotolerance to otherwise nonpermissive heat stress at 54 degrees C (7 minutes). Optimum thermotolerance was observed 8 hours after heat shock. Development of thermotolerance was initiated by treatments as short as 30 minutes at 36 degrees C. Temperatures below 36 degrees C or above 40 degrees C failed to induce maximum thermotolerance. In vivo labeling revealed that HS at 32 to 34 degrees C induced several high molecular mass heat shock proteins (HSPs). A complex of 18 kilodalton HSPs required at least 36 degrees C treatment for induction. The majority of the HSPs began to accumulate within 10 minutes, whereas the synthesis of low molecular mass peptides in the 18 kilodalton range became evident 30 minutes after initiation of HS. HS above 38 degrees C resulted in progressively decreased HSP synthesis with inhibition first observed for HSPs larger than 50 kilodaltons. Analysis of two-dimensional gels revealed a complex pattern of label incorporation including the synthesis of four major HSPs in the 18 kilodalton range and continued synthesis of constitutive proteins during HS.


A case report of traumatic neuroma of the cervical spinal cord in a dog.
Traumatic neuroma of the cervical spinal cord was diagnosed in a 14-year-old male mixed-breed dog. A gross view showed two intradural extramedullary masses, measuring 1 and 0.6 cm in length and 0.7 and 0.4 cm in diameter, attached to the left side of the spinal cord at the level of the sixth and seventh cervical vertebrae. Microscopically, the cervical spinal masses comprised interlacing fascicles of axons and Schwann cells surrounded by collagenous stroma. Immunohistochemically, the fascicles were stained positively for neurofilament and S-100 proteins. Ultrastructurally, variably sized myelinated fibers and onion bulb-like structures were observed. To our knowledge, this is the first report of a traumatic neuroma in the cervical spinal cord of a dog.


Surgical treatment of falcotentorial meningioma.
Meningiomas arising from the falcotentorial junction are rare. Among our surgical experience of 375 meningiomas, only 4 cases of so-called falcotentorial meningiomas were encountered. We present these four surgical cases. An occipital transtentorial approach was used in three cases, and a combined midline occipital and suboccipital approach in one case. Total tumour excision was impossible in two cases because of engulfing deep venous structures including the great vein of Galen. Postoperative Gamma knife radiosurgery was performed in these two cases. On the other hand, a posteriorly located tumour was relatively easy to remove, and macroscopic total removal was accomplished. In conclusion, precise microvascular anatomical knowledge is indispensable to satisfactorily excise meningiomas in the falcotentorial area without significant morbidity.


[Advances of IL-33/ST2 signaling pathway in allergic rhinitis].
Interleukin-33 that binds to the membrane receptor ST2L, can not only regulate mast cells, eosinophils, and group 2 innate lymphoid cells(ILC2s), but also affect the function of regulatory T cells(Treg) and Follicular helper T cells(Tfh). Interleukin-33 can activate the NF-κB and MAPK signaling pathways of the above cells, then participates in allergic immunity reaction. IL-33/ST2 signaling pathway is closely related to the allergic rhinitis(AR). IL-33 has been used as a new biomarker to evaluate the effect of AR treatment. At the same time, antagonizing IL-33 is also expected to become a new treatment. This article reviewed the latest research of IL-33/ST2 signaling pathway in the field of AR.


[Therapeutic options for a type 2 diabetic patient not well controlled with metformin plus basal insulin].
In a patient with type 2 diabetes not well controlled with a basal insulin - metformin combination, several therapeutic options may be considered: intensifying insulin therapy with different schemes (appropriate titration using a more favourable basal insulin analogue, adding one, two or three rapid-acting insulin analogues, shift to two or three premix insulin injections), adding a dipeptidyl peptidase-4 inhibitor (gliptin) or an inhibitor of sodium-glucose cotransporters type 2 (gliflozin), or combining a glucagon-like peptide-1 receptor agonist with basal insulin. The choice should be made according the individual profile and preference of the patient, in a personalized approach, taking into account the advantages and disadvantages of each therapeutic solution.


Underlying domains of anxiety trait in a Costa Rican sample: preliminary results.
Imprecision of the psychiatric phenotype might partially explain the failure of genetic research to identify genes that contribute to susceptibility of anxiety disorders. Previous research concluded two underlying constructs, worry and rumination, might explain anxiety sub-syndromic symptoms in Costa Rican patients with history of mania. The goal of the current study is to explore the presence of latent constructs for quantitative anxiety in a group of subjects with a wide diagnostic phenotype and non-affected individuals. We conducted an exploratory factor analysis of anxiety trait in 709 subjects. Our sample was comprised by 419 subjects with psychiatric disorders and 290 non-affected individuals. We used principal factors extraction method with squared multiple correlations of the STAI (trait subscale). We found the following preliminary results: a three-factor solution with a good simple structure and statistical adequacy was obtained with a KMO of 0.92 (>0.6) and Bartlett's Test of Sphericity of 5644,44 (p<0.05). The STAI items were grouped into three factors: anxiety-absent, worry and rumination based on the characteristics of the symptoms. Two underlying constructs, worry and rumination may explain anxiety sub-syndromic symptoms in Costa Rican subjects. Our proposed underlying structure of subsyndromal anxiety in individuals should be considered as an important factor in defining better phenotypic characterizations on a broader diagnostic concept. Worry and rumination as a phenotypic characterization may assist in genotyping; however, its predictive value on actual illness outcome still requires more research. The Genome-Wide QTL analysis for anxiety trait in the same sample is ongoing.


Estradiol postconditioning relieves ischemia/reperfusion injury in axial skin flaps of rats, inhibits apoptosis and alters the MKP-1/ERK pathway.
Previous studies have suggested that estradiol can reduce the ischemia/reperfusion (I/R) injury in skin flaps. However, the mechanism, particularly the signal pathways involved in this protective effect are not well established. In the current study, an I/R injury model was established in rats to explore the connection between estradiol protection during I/R injury and extracellular signal‑regulated kinase (ERK) signaling. Healthy male Wistar rats were divided into five groups (n=10): Control group (group I), I/R group (group II), saline group (group III), estradiol group (group IV) and inhibitor (PD‑98059) group (group V). The survival rate of the flap was compared between groups, morphological changes were observed by hematoxylin and eosin staining of sections, and terminal deoxynucleotidyl transferase dUTP nick end labeling was performed to identify apoptotic cells and determine the apoptotic index. To further investigate the mechanism, western blot analysis was performed to assess the protein level of ERK1/2, phospho‑ERK1/2, and mitogen‑activated protein kinase phosphatase 1 (MKP‑1). The results of the present study demonstrated that estradiol therapy can reduce I/R injury and decrease the apoptosis index in an axial skin flap model. The inhibitor of the ERK pathway (PD‑98059) partially abolished the effects of estradiol, which involve the phosphatase enzyme MKP‑1. Taken together, the findings of the present study indicate that estradiol may act by reducing the expression of MKP‑1, mediating the expression/activation changes of the ERK pathway and subsequently reduce the level of apoptosis and the I/R injury the axial flap. Estrogen may be used to mitigate the adverse reaction caused by ischemia‑reperfusion injury and effectively improve the survival rate and survival quality of free skin flap and improve patient prognosis.


Locking compression plates for the treatment of periprosthetic femoral fractures around well-fixed total hip and knee implants.
There are currently few published studies examining the use of locking compression plates for the treatment of periprosthetic femoral fractures. Fifteen total hip or knee arthroplasty patients with 16 Vancouver type B1 and C fractures with an average age of 76 years were fixed and followed clinically and radiographically for 2 years. Fourteen patients achieved radiographic union by 6 months, and 13 patients were ambulatory by 6 months. There were no intraoperative complications. In summary, locking plates offer a viable treatment option for these difficult fractures. We advocate a minimum of 10 cortices of fixation (with unicortical or bicortical screws and cable combinations) above and below the fracture. Bone grafting should be used if the soft tissue envelope is violated with extensive dissection, and cortical struts should be considered in cases of failed hardware and revision fixation.


Postulates on electromagnetic activity in biological systems and cancer.
A framework of postulates is formulated to define the existence, nature, and function of a coherent state far from thermodynamic equilibrium in biological systems as an essential condition for the existence of life. This state is excited and sustained by energy supply. Mitochondria producing small packets of energy in the form of adenosine and guanosine triphosphate and strong static electric field around them form boundary elements between biochemical-genetic and physical processes. The transformation mechanism of chemical energy into useful work for biological needs and the excitation of the coherent state far from thermodynamic equilibrium are fundamental problems. The exceptional electrical polarity of biological objects and long-range interactions suggest a basic role of the endogenous electromagnetic field generated by living cells. The formulated postulates encompass generation, properties and function of the electromagnetic field connected with biological activity and its pathological deviations. Excited longitudinal polar oscillations in microtubules in eukaryotic cells generate the endogenous electromagnetic field. The metabolic activity of mitochondria connected with water ordering forms conditions for excitation. The electrodynamic field plays an important role in the establishment of coherence, directional transport, organization of morphological structures, interactions, information transfer, and brain activity. An overview of experimental results and physical models supporting the postulates is included. The existence of the endogenous biological electromagnetic field, its generation by microtubules and supporting effects produced by mitochondria have a reasonable experimental foundation. Cancer transformation is a pathological reduction of the coherent energy state far from thermodynamic equilibrium. Malignancy, i.e. local invasion and metastasis, is a direct consequence of mitochondrial dysfunction, disturbed microtubule polar oscillations and the generated electromagnetic field.


The negative testing and negative generation effects are eliminated by delay.
Although retrieval often enhances subsequent memory (the testing effect), a negative testing effect has recently been documented in which prior retrieval harms later recall compared with restudying. The negative testing effect was predicated on the negative generation effect and the item-specific-relational framework. The present experiments examine whether the negative testing effect persists over longer delays, whether the testing manipulation interacts with retention interval, and whether the negative testing and negative generation effects respond similarly to delay. Experiment 1 demonstrated a significant negative testing effect on an immediate free-recall test but not on a delayed test (after a 2-day retention interval). Furthermore, the retrieval condition produced less forgetting than the restudy condition. Under similar conditions (Experiment 2), generation likewise produced a negative effect on an immediate free-recall test but not after a 2-day delay. In addition, the generation condition produced less forgetting over 2 days than did the read condition. The results uncover important similarities between the mnemonic effects of retrieving information from episodic (testing effect) and semantic (generation effect) memory. The pattern of forgetting across delay also has relevance for accounts of the Testing × Retention interaction, a prominent phenomenon in the literature on the testing effect.


Development of mouse testis and epididymis following intrauterine exposure to a static magnetic field.
In order to test if the in utero exposure to static magnetic fields affects testis and epididymis development in mice, females were exposed to 0.5-0.7 T, generated by a permanent magnet, from day 7 of gestation to the day of birth. No significant differences were found between exposed and sham-exposed animals with respect to body weight gain of dam during the gestational period, litter size, body weight of male pups at the day of birth, and body or testis-epididymis weight gain of pups from birth to day 35. Histopathologic evaluation of testis and epididymis of pups of 1, 5, 15, and 35 days of age showed no detectable alterations due to in utero exposure to static magnetic fields.


Asymmetric Total Synthesis of Propindilactone G.
A concise total synthesis of (+)-propindilactone G, a nortriterpenoid isolated from the stems of Schisandra propinqua var. propinqua, has been achieved for the first time. The key steps of the synthesis include an asymmetric Diels-Alder reaction, a Pauson-Khand reaction, a Pd-catalyzed reductive hydrogenolysis reaction, and an oxidative heterocoupling reaction. These reactions enabled the synthesis of (+)-propindilactone G in only 20 steps. As a consequence of our synthetic studies, the structure of (+)-propindilactone G has been revised.


[Studies on the occurrence of Listeria monocytogenes in fecal samples of domestic and companion animals].
Listeria (L.) monocytogenes was isolated from 33.3% fecal samples of 138 cattle (29 strains serovar 1/2b, 10 strains serovar 1/2a, 7 strains serovar 4ab), from 8% fecal samples of 100 hens (5 strains serovar 1/2b, 1 strain serovar 1/2a, 4ab and 4b each), from 8% fecal samples of 100 sheep (6 strains serovar 1/2a, 1 strain serovar 1/2b and 4ab each), from 5.9% fecal samples of 34 pigs (2 strains serovar 4ab), from 4.8% fecal samples of 400 horses (7 strains serovar 1/2a, 6 strains serovar 1/2b and 4ab each), from 1.3% fecal samples of 300 dogs (3 strains serovar 1/2b, 1 strain serovar 4ab), from 0.9% fecal samples of 350 pigeons (1 strains serovar 1/2a, 1/2b and 4ab each), from 0.4% fecal samples of 275 cats (1 strain serovar 4b) and from 5 respectively 2 fecal samples of 35 tortoises (3 strains serovar 4ab, 2 strains serovar 4b) respectively 5 amphibia (1 strain serovar 4ab and 4e each). Further 36.9% fecal samples of cattle, 15% fecal samples of hens, 6% fecal samples of horses, 5.9% fecal samples of pigs, 5% fecal samples of sheep, 4% fecal samples of dogs, 2.3% fecal samples of pigeons, 3 fecal samples of 35 tortoises and 1 fecal sample of 260 rabbits contained L. innocua. In further 2% fecal samples of hens, in further 1.5% fecal samples of horses and in further 0.6% fecal samples of pigeons was detected L. seeligeri. 3 fecal samples of horses and 1 fecal sample of dogs, lizards and amphibia each contained L. welshimeri, while in 1 fecal sample of tortoises and in 3 fecal samples of 33 lizards L. ivanovii was detected.


Pathway of ammonium assimilation in Streptomyces venezuelae examined by amino acid analyses and 15N nuclear magnetic resonance spectroscopy.
To obtain information on the route(s) of ammonium assimilation in Streptomyces venezuelae, cell suspensions transferred to fresh medium lacking nitrogen were pulsed with [15N2]ammonium sulphate. Cells and extracellular fluids were examined by nuclear magnetic resonance and amino acid analysis to assess changes in amino acid pools and the disposition of [15N]ammonium. Following addition of [15N]ammonium, glutamate--glutamine pools of low cell density replacement cultures expanded rapidly and became progressively labelled with 15N, whereas the alanine pool size increased much more slowly and became labelled with 15N to a much lesser extent. These results are consistent with the assimilation of ammonium via glutamate dehydrogenase or glutamine synthetase--glutamate synthase rather than alanine dehydrogenase. Under anaerobic conditions, S. venezuelae assimilates ammonium into alanine rather than glutamate--glutamine. Alanine dehydrogenase may thus function as a vehicle to regenerate NAD+ to maintain substrate-level phosphorylation during periods of anaerobiosis.


Bisphosphonate drug holidays: Can we recommend currently?
Bisphosphonates (BP) are the mainstay of treatment for osteoporosis. Subtrochanteric or diaphyseal fractures have been reported with long term use of BP, which raised world-wide debate on two aspects, i.e., for how long the BP is to be given and potential advantages/role of BP drug holidays. BP accumulates in bone with some persistent protective effect after therapy is stopped endorses the concept. Theoretically, a drug holiday may be a considerable option to decrease risks of BP, which continuing the protection from fractures but the level of evidence and data supporting the concept of drug holidays is a week. Hence, no specific recommendations are available on BP drug holidays from major available treatment guidelines on postmenopausal osteoporosis. Hence, before it is recommended it requires more robust research in this field.


Systematic revision of the genus Phaeaphodius Reitter, 1892 (Coleoptera: Scarabaeidae: Aphodiinae).
The genus Phaeaphodius Reitter, 1892 (Coleoptera: Scarabaeidae: Aphodiinae) is revised and considered to consist of 12 species. A key to species and diagnosis of each species are given to fascilitate identification. Lectotypes are designated for A. costalis Gebler, 1848, A. sibiricus Harold, 1863, A. aeger Sharp, 1878, and A. solskyi Harold, 1871. Neotypes are designated for A. alleoni d'Orbigny, 1896, A. fusculus Reitter, 1892, and A. trucantangulus Reitter, 1894. The name Aphodius fusculus Reitter, 1892 is placed in synonymy with Esymus pusillus (Herbst, 1789) (new synonymy).


Specific in vitro toxicity of crude and refined petroleum products: II. Estrogen (alpha and beta) and androgen receptor-mediated responses in yeast assays.
The present study is the second in a series aiming at a systematic inventory of specific toxic effects of oils. By employing a recombinant yeast stably transfected with human estrogen receptor-alpha (ERalpha) or -beta (ERbeta) or androgen receptor (AR) and expressing yeast enhanced green fluorescent protein, the (anti-)estrogenicity and (anti-)androgenicity of 11 crude oils and refined products were studied. None of the oils tested had significant estrogenic effects in the ERalpha assay or androgenic effects in the AR assay. However, all oils were capable of inducing estrogenic responses in the ERbeta assay, with several responses being above even the maximal response of the standard 17beta-estradiol (E2). Based on the lowest effect concentrations, the potencies of oils in all the assays were between four and seven orders of magnitude lower than those of the standards E2 or testosterone (T). The potencies of the actual individual petrochemical agonists may, however, be relatively high, considering the complex composition of oils. Additive effects, antagonistic effects, and a synergistic effect were measured in the assays upon coexposure to a fixed concentration of standard (E2 or T) and increasing concentrations of oils. To investigate whether the observed effects were receptor-mediated, coexposures to the synthetic inhibitors ICI 182,780 (ERbeta assay) or flutamide (AR assay), a fixed concentration of standard, and various concentrations of oils were performed. The results suggested that the androgenic effects were receptor mediated, whereas the estrogenic effects may be only partially mediated via the receptor. The present study indicates that oils contain compounds with possible endocrine-disrupting potential, some of them acting via the hormone receptors.


Importance of differential expression of Marek's disease virus gene pp38 for the pathogenesis of Marek's disease.
The role of pp38 in the pathogenesis of Marek's disease (MD) has not been fully elucidated. Previously, we reported the presence of two splice variants (Spl A and Spl B) for pp38. We also reported that the wild-type pp38 (WT), as well as the mutated pp38 (MUT), altered the oxidative phosphorylation pathway in infected cells. To determine whether the different forms of pp38 are important for the pathogenesis of MD, we generated RB-1B-based bacterial artificial chromosome (BAC) clones expressing pp38MUT, pp38Sp1 A, and pp38Spl B. Infectious viruses were recovered from these BAC clones in chick kidney cells (CKC). The Spl A and Spl B viruses had significantly smaller plaque sizes and replicated to a lesser degree in CKC than the WT and MUT viruses. Two in vivo experiments were conducted by inoculating 7-day-old P2a chicks with 1000 plaque-forming units of each virus. In the first experiment, chicks were sacrificed at 4, 8, 11, and 15 days postinfection (PI). WT and MUT viruses had similar viremia levels using virus isolation and quantitative real-time PCR (qPCR) assays, whereas Spl A and Spl B viruses had significantly lower viremia levels than WT and MUT viruses. In the second experiment, we showed that tumor development and MD mortality were similar in the WT- and MUT-infected chickens, with all birds MD positive at 5 wk PI. In contrast, chickens infected with Spl B and Spl A had a significantly lower MD incidence at 11 wk PI, when the experiment was terminated.


Access to Base Adducts of Low-Valent Organotin-Hydride Compounds by Controlled, Stepwise Hydrogen Abstraction from a Tetravalent Organotin Trihydride.
Hydrogen can be selectively removed from organotin trihydrides to generate the corresponding organohydrostannylene intermediates. Depending on the size of the substituent and the mode of generation, the intermediates undergo further reactions. Herein, we report on the formation of a variety of organotin hydrides with tin in the oxidation states Sn(II) , Sn(I) -Sn(III) and Sn(III) -Sn(III) , all accessed by the controlled removal of hydrogen from the tetravalent Ar'Sn(IV) trihydride (Ar'=2,6-dimesitylphenyl, mesityl=2,4,6-trimethylphenyl).


Ternary Chalcogenide Nanosheets with Ultrahigh Photothermal Conversion Efficiency for Photoacoustic Theranostics.
2D materials (TDMs) have been explored for photonic theranostics. To achieve deep-tissue penetration, near-infrared (NIR) light is essential for photoacoustic (PA) theranostics. However, because the absorption profiles of existing TDMs are generally featureless with no obvious NIR absorption peaks, their PA signals and therapeutic efficacies are limited. This paper herein reports the synthesis and application of ternary chalcogenide nanosheets (Ta2 NiS5 -P) for PA theranostics. In contrast to the current TDMs for such application, Ta2 NiS5 -P has a ternary instead of binary composition. This difference brings in the strong and featured NIR for Ta2 NiS5 -P. To the best of the knowledge, this is the first example using ternary chalcogenide nanosheets for such application; moreover, the photothermal conversion efficiency of Ta2 NiS5 -P is the highest (35%) among all the reported TDMs based on the same calculation method. These advantages allow Ta2 NiS5 -P to passively target, effectively delineate, and completely eradicate the tumor of living mice after systemic administration.


Characterization of oral fibroblasts: An in vitro model for oral fibrosis.
Oral submucous fibrosis (OSMF) is a chronic debilitating condition of the oral mucosa that has been classified as a potentially malignant disorder with a malignant transformation rate of 2%-8%. Several in vitro and in vivo experiments have been performed to formulate a treatment modality for OSMF, yet no ideal in vitro primary oral fibroblast model has been developed. To establish an in vitro primary oral fibroblast model. In vitro laboratory setting. Primary cell culture protocol was performed after obtaining normal oral tissue. Karyotyping was performed to rule out chromosomal abnormalities. Immunofluorescence staining was carried with a panel of fibroblast-specific markers (vimentin, phalloidin, transforming growth factor-β receptor 1 [TGFβR1] and s100a4) and Masson trichrome staining (MTS) to demonstrate the presence of extracellular matrix (ECM) qualitatively. A monolayer of oral fibroblasts was observed on the 9th-day postseeding. No chromosomal abnormality was observed in the patient samples. Positive staining was observed with vimentin, phalloidin, TGFβR1 and s100a4, thereby confirming the cell type. MTS revealed fibroblasts with spindle morphology and scanty ECM. The present study lays down a protocol to design and characterize primary buccal fibroblast cell culture model that would aid researchers in performing in vitro preliminary experiments in areas concerning fibrosis.


Triplet Sensitized Photodenitrogenation of Δ2-1,2,3-Triazolines To Form Aziridines in Solution and in the Crystalline State: Observation of the Triplet 1,3-Alkyl-aminyl Biradical.
Taking advantage of an operationally simple technique to perform transmission pump-probe spectroscopy in crystalline solids, based on the use nanocrystalline suspensions in water, we analyzed the intermediates in the photodenitrogenation of a Δ2-1,2,3-triazoline bearing a benzophenone group that served as an internal triplet sensitizer. Measurements carried out in acetonitrile solution revealed the formation of a transient with a λmax= 570 nm with a lifetime of 70 ns. Measurements in the solid state displayed an analogous blue-shifted transient with a λmax= 510 nm that first grows and then decays with time constants of 63 and 270 ns, respectively. Based on the comparison of the observed transient spectra with the one obtained from an independently generated aminyl radical, we assign it to the corresponding 1,3,-alkyl-aminyl biradical. We conclude that triplet state denitrogenation and the subsequent intersystem crossing-limited product formation are slower in the solid state than in solution.


Producing a socially accountable medical school: AMEE Guide No. 109.
Health systems worldwide are confronted with challenges due to increased demand from their citizens, an aging population, a variety of health risks and limited resources. Key health stakeholders, including academic institutions and medical schools, are urged to develop a common vision for a more efficient and equitable health sector. It is in this environment that Boelen and Heck defined the concept of the "Social Accountability of Medical Schools" - a concept that encourages schools to produce not just highly competent professionals, but professionals who are equipped to respond to the changing challenges of healthcare through re-orientation of their education, research and service commitments, and be capable of demonstrating a positive effect upon the communities they serve. Social Accountability calls on the academic institution to demonstrate an impact on the communities served and thus make a contribution for a just and efficient health service, through mutually beneficial partnerships with other healthcare stakeholders. The purpose of this Guide is to explore the concept of Social Accountability, to explain it in more detail through examples and to identify ways to overcome obstacles to its development. Although in the Guide reference is frequently made to medical schools, the concept is equally applicable to all forms of education allied to healthcare.