Proteomics of the mediodorsal thalamic nucleus of rats with stress-induced gastric ulcer.
Stress-induced gastric ulcer (SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress (RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. The mediodorsal thalamic nucleus (MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied. To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate molecular mechanisms of SGU. Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by Western blot analysis. A total of 2853 proteins were identified, and these included 65 dysregulated (31 upregulated and 34 downregulated) proteins (fold change ratio ≥ 1.2). Gene Ontology (GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanism through which RWIS gives rise to SGU. Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.


Onychomycosis: A Review.
Onychomycosis is the most common nail infective disorder. It is caused mainly by anthropophilic dermatophytes, in particular by Trichophyton rubrum and T. mentagrophytes var. interdigitale. Yeasts, like Candida albicans and C. parapsilosis, and molds, like Aspergillus spp., represent the second cause of onychomycosis. The clinical suspect of onychomycosis should be confirmed my mycology. Onychoscopy is a new method that can help the physician, as in onychomycosis, it shows a typical fringed proximal margin. Treatment is chosen depending on the modality of nail invasion, fungus species and the number of affected nails. Oral treatments are often limited by drug interactions, while topical antifungal lacquers have less efficacy. A combination of both oral and systemic treatment is often the best choice.


Diaphragmatic injury presenting as delayed hemothorax.
Diaphragmatic injuries are difficult to diagnose if not associated with conditions that require exploration even with the noninvasive and minimally invasive tools available in evaluation of the trauma patient. The diaphragm anatomically and physiologically separates the largest body cavities making it vulnerable to penetrating injuries to the thoracoabdominal region. Its structural and functional importance is reflected in the serious consequences that can result after missed injury. This injury has a highly varied clinical and radiological presentation, and can remain occult. We present a case of diaphragmatic laceration discovered after exploratory thoracotomy for delayed hemothorax.


Interaction of Gram-negative bacteria with cationic proteins: Dependence on the surface characteristics of the bacterial cell.
Gram-negative bacteria can enter the bloodstream and interact with serum cationic proteins. The character of interaction will depend on the surface characteristics of bacterial cells, which are determined by bacterial chemotype and density of lipopolysaccharide (LPS) packing in the cell wall. It was shown that the lysozyme treatment resulted in the increase sensitivity to hypotonic shock. Significant differences to this effect were found between Escherichia coli strain D21 and D21f2 under treatment with physiological protein concentration. On the basis of electrokinetic measurements and studies of the interaction of cells with lysozyme, the hypothesis was formed that the cell wall of the E. coli strain D21f2 contains more LPS and has a higher density of their packing than the cell wall of the E. coli D21 cells. The effect of lysozyme and lactoferrin on the viability of E. coli cells of two different strains was examined. Lysozyme was found to more effectively inhibit the growth of the E. coli D21 bacteria, and lactoferrin suppressed mainly the growth of the E. coli D21f2 bacteria. These results indicate that the differences in LPS core structure of bacterial R-chemotype, which determines surface charge and density of LPS packing, plays an essential role in the mechanisms of interaction of the cationic proteins with the cell wall.


Co-targeting FAK and Gli1 inhibits the tumor-associated macrophages-released CCL22-mediated esophageal squamous cell carcinoma malignancy.
Esophageal squamous cell carcinoma (ESCC) is a frequently seen esophageal tumor type in China. Activation of signaling proteins and relevant molecular mechanisms in ESCC are partially explored, impairing the antitumor efficiency of targeted therapy in ESCC treatment. Tumor-associated macrophages (TAMs)-released C-C motif chemokine 22 (CCL22) can activate intratumoral focal adhesion kinase (FAK), thus promoting the progression of ESCC. Here, we demonstrated that highly secreted CCL22 by TAMs (CCL22-positive TAMs) induced ESCC cell stemness and invasion through facilitating transcriptional activity of intratumoral glioma-associated oncogene 1 (Gli1), a downstream effector for Hedgehog (HH) pathway. Mechanistically, FAK-activated protein kinase B (AKT) mediated Gli1 phosphorylation at its Ser112/Thr115/Ser116 sites and released Gli1 from suppressor of fused homolog, the endogenous inhibitor of Gli1 to activate downstream stemness-associated factors, such as SRY-box transcription factor 2 (SOX2), Nanog homeobox (Nanog), or POU class 5 homeobox (OCT4). Furthermore, inhibition of FAK activity by VS-4718, the FAK inhibitor, enhanced antitumor effect of GDC-0449, the HH inhibitor, both in xenografted models and in vitro assays. Clinically, CCL22/Gli1 axis is used to evaluate ESCC prognosis. Overall, our study establishes the communication of FAK with HH pathway and offers the novel mechanism related to Gli1 activation independent of Smoothened as well as the rationale for the anti-ESCC combination treatment.


Blood transfusions, thrombosis, and mortality in hospitalized patients with cancer.
Anemia is frequent in patients with cancer, but there are concerns regarding treatment with erythropoiesis-stimulating agents. Blood transfusions are commonly used as an alternative, but with little data regarding outcomes. In a retrospective cohort study, we investigated the associations between transfusions and venous thromboembolism, arterial thromboembolism, and mortality in hospitalized patients with cancer using the discharge database of the University HealthSystem Consortium, which included 504 208 hospitalizations of patients with cancer between 1995 and 2003 at 60 US medical centers. Of the patients included, 70 542 (14.0%) received at least 1 red blood cell (RBC) transfusion and 15 237 (3.0%) received at least 1 platelet transfusion. Of patients receiving RBC transfusions, 7.2% developed venous thromboembolism and 5.2% developed arterial thromboembolism, and this was significantly greater than the rates of 3.8% and 3.1%, respectively, for the remaining study population (P < .001). In multivariate analysis, RBC transfusion (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.53-1.67) and platelet transfusion (1.20; 1.11-1.29) were independently associated with an increased risk of venous thromboembolism. Both RBC transfusion (OR, 1.53; 95% CI, 1.46-1.61) and platelet transfusion (1.55; 1.40-1.71) were also associated with arterial thromboembolism (P < .001 for each). Transfusions were also associated with an increased risk of in-hospital mortality (RBCs: OR, 1.34; 95% CI, 1.29-1.38; platelets: 2.40; 2.27-2.52; P < .001). Both RBC and platelet transfusions are associated with increased risks of venous and arterial thrombotic events and mortality in hospitalized patients with cancer. Further investigation is necessary to determine whether this relationship is causal.


Current therapy of varicella zoster virus infection in immunocompromised patients. A comparison of acyclovir and vidarabine.
Both acyclovir and vidarabine are effective treatment for varicella zoster virus (VZV) infection in immunosuppressed patients. To determine which is preferable, therapy with these two agents was compared in a prospective, randomized trial. A total of 22 immunocompromised patients undergoing treatment for hematologic malignancies and presenting with VZV infection within 72 hours of the onset of rash were randomly assigned to receive intravenous acyclovir or vidarabine; 11 patients were randomly assigned to each treatment group. Acyclovir was significantly more effective than vidarabine in preventing complications of VZV infection, and treatment failures requiring a change to the alternate therapy occurred only among those treated with vidarabine. As compared with vidarabine, acyclovir shortened the median period during which results of viral culture specimens were positive and new lesions formed. Acyclovir also shortened the median interval until the first decrease in pain, the crusting of all lesions, and the complete healing of lesions. Acyclovir is more effective than vidarabine in the treatment of VZV infection in severely immunocompromised patients and should be considered the treatment of choice in such cases.


Novel Computational Analysis of Left Atrial Anatomy Improves Prediction of Atrial Fibrillation Recurrence after Ablation.
The left atrium (LA) can change in size and shape due to atrial fibrillation (AF)-induced remodeling. These alterations can be linked to poorer outcomes of AF ablation. In this study, we propose a novel comprehensive computational analysis of LA anatomy to identify what features of LA shape can optimally predict post-ablation AF recurrence. To this end, we construct smooth 3D geometrical models from the segmentation of the LA blood pool captured in pre-procedural MR images. We first apply this methodology to characterize the LA anatomy of 144 AF patients and build a statistical shape model that includes the most salient variations in shape across this cohort. We then perform a discriminant analysis to optimally distinguish between recurrent and non-recurrent patients. From this analysis, we propose a new shape metric called vertical asymmetry, which measures the imbalance of size along the anterior to posterior direction between the superior and inferior left atrial hemispheres. Vertical asymmetry was found, in combination with LA sphericity, to be the best predictor of post-ablation recurrence at both 12 and 24 months (area under the ROC curve: 0.71 and 0.68, respectively) outperforming other shape markers and any of their combinations. We also found that model-derived shape metrics, such as the anterior-posterior radius, were better predictors than equivalent metrics taken directly from MRI or echocardiography, suggesting that the proposed approach leads to a reduction of the impact of data artifacts and noise. This novel methodology contributes to an improved characterization of LA organ remodeling and the reported findings have the potential to improve patient selection and risk stratification for catheter ablations in AF.


Relationship of different domains of physical activity practice with health-related quality of life among community-dwelling older people: a cross-sectional study.
To analyse the association between different domains of physical activity (PA) and health-related domains of health-related quality of life (HRQoL) in older adults, independent of confounding variables. Cross-sectional study. In total, 400 individuals 60 years or above were randomly selected to participate in the study. PA was assessed by a questionnaire in three different domains (work/occupational, sports/gym and leisure time) and total PA. The 36-Item Short Form Health Survey was used to evaluate HRQoL. The variables socioeconomic condition, marital status and presence of health professional-diagnosed comorbidities were self-reported. The mean age of the sample was 71.5 (±8.4) years, of whom 58% (n=232) were female. Male older adults showed higher scores of PA in sports, leisure time and in total PA than female adults. Older adults who were more physically active in the work/occupational domain were associated with better scores in functional capacity (OR=1.73, 95% CI 1.02 to 2.93) and general health perception (OR=1.61, 95% CI 1.02 to 2.56). Those who presented a higher score in the sports/gym domain had better scores in functional capacity, even after adjustment for comorbidities (OR=1.72, 95% CI 1.01 to 2.96). Individuals with higher activity in leisure time were more likely to have better scores in functional capacity (OR=1.75, 95% CI 1.03 to 2.98), body pain (OR=1.74, 95% CI 1.09 to 2.78) and mental health (OR=1.67, 95% CI 1.03 to 2.69). Older adults who were more active in total PA were 77% more likely to have better scores in functional capacity (OR=1.77, 95% CI 1.04 to 3.02). Physically active older adults in the different domains of PA presented better HRQoL parameters, reinforcing the importance of studies analysing PA in different contexts and in countries with low and medium socioeconomic conditions.


Genome-wide identification and analysis of expression profiles of maize mitogen-activated protein kinase kinase kinase.
Mitogen-activated protein kinase (MAPK) cascades are highly conserved signal transduction model in animals, yeast and plants. Plant MAPK cascades have been implicated in development and stress responses. Although MAPKKKs have been investigated in several plant species including Arabidopsis and rice, no systematic analysis has been conducted in maize. In this study, we performed a bioinformatics analysis of the entire maize genome and identified 74 MAPKKK genes. Phylogenetic analyses of MAPKKKs from maize, rice and Arabidopsis have classified them into three subgroups, which included Raf, ZIK and MEKK. Evolutionary relationships within subfamilies were also supported by exon-intron organizations and the conserved protein motifs. Further expression analysis of the MAPKKKs in microarray databases revealed that MAPKKKs were involved in important signaling pathways in maize different organs and developmental stages. Our genomics analysis of maize MAPKKK genes provides important information for evolutionary and functional characterization of this family in maize.


Building Electromagnetic Hot Spots in Living Cells via Target-Triggered Nanoparticle Dimerization.
Electromagnetic hot spots of surface-enhanced Raman scattering have been extensively employed for bioanalysis in solution or on a substrate, but building hot spots in living systems for probing targets of interest has not been achieved yet because of the complex and dynamic physiological environment. Herein, we show that a target-programmed nanoparticle dimerization can be combined with the background-free Raman reporters (alkyne, C≡C; nitrile, C≡N) for multiplexed imaging of microRNAs (miRNAs) in living cells. The in situ formation of plasmonic dimers results in an intense hot spot, thus dramatically enhancing the Raman signals of the reporters residing in the hot spot. More significantly, the reporters exhibit single nonoverlapping peaks in the cellular Raman-silent region (1800-2800 cm-1), thus eliminating spectral unmixing and background interference. A 3D Raman mapping technique was harnessed to monitor the spatial distribution of the dimers and thus the multiple miRNAs in cells. This approach could be extended to probe other biomarkers of interest for monitoring specific pathophysiological events at the live-cell level.


An analysis of the leverage effect of "Internet +" on the economic spillover of sports industry.
Given the unprecedented and profound impact on the traditional sports industry and its economic driving force brought by the "Internet +", the purpose of this study is to explore the driving relationship between the sports industry and local economic development and deconstruct the dynamic regulation mechanism of "Internet +" on the economic spillover of the sports industry. Empirical data collected from China's 11 inter-provincial panel data from 2015-2019 were analyzed through the fixed-effects and threshold models. The study finds that the economic spillover of the sports industry has significantly promoted regional economic development, and the regulation effect of the Internet has complex non-linear characteristics. Only when Internet development exceeds a specific threshold can it develop a benign complementary mechanism with the sports industry. The impact of "Internet +" on the threshold regulation of the sports industry economic spillover has spatial and temporal differentiation characteristics in the three dimensions of Internet hardware level, Internet penetration rate, and Internet application value. The results of this study extend the current study, indicating that it is a practical choice for local governments to develop the economy through the sports industry. Provinces and cities should enhance the Internet penetration rate, expand Internet business applications, and upgrade Internet development to a specific point to maximize the drive of positive spillover. Regional heterogeneity requires differential regulation strategies and more concentration on the middle and western regions.


Molecular pathogenicity of the oral opportunistic pathogen Actinobacillus actinomycetemcomitans.
Periodontitis is mankind's most common chronic inflammatory disease. One severe form of periodontitis is localized aggressive periodontitis (LAP), a condition to which individuals of African origin demonstrate an increased susceptibility. The main causative organism of this disease is Actinobacillus actinomycetemcomitans. A member of the Pasteurellaceae, A. actinomycetemcomitans produces a number of interesting putative virulence factors including (a) an RTX leukotoxin that targets only neutrophils and monocytes and whose action is influenced by a novel type IV secretion system involved in bacterial adhesion; (b) the newly discovered toxin, cytolethal distending toxin (CDT); and (c) a secreted chaperonin 60 with potent leukocyte-activating and bone resorbing activities. This organism also produces a plethora of proteins able to inhibit eukaryotic cell cycle progression and proteins and peptides that can induce distinct forms of proinflammatory cytokine networks. A range of other proteins interacting with the host is currently being uncovered. In addition to these secreted factors, A. actinomycetemcomitans is invasive with an unusual mechanism for entering, and traveling within, eukaryotic cells. This review focuses on recent advances in our understanding of the molecular and cellular pathogenicity of this fascinating oral bacterium.


Micromonospora pattaloongensis sp. nov., isolated from a Thai mangrove forest.
An actinomycete, designated strain TJ2-2(T), was isolated from soil collected from a mangrove forest in Pattaloong Province, Thailand, and was subjected to morphological and chemotaxonomic analysis and phylogenetic investigation based on 16S rRNA gene sequences. The data from these analyses indicated that the novel strain should be classified as a member of the genus Micromonospora and that the closest relative was Micromonospora olivasterospora DSM 43868(T) (98.7 % gene sequence similarity). The DNA-DNA hybridization data and some physiological and biochemical properties indicated that the novel strain could be readily distinguished from its closest phylogenetic relatives. On the basis of these phenotypic and genotypic data, strain TJ2-2(T) represents a novel species of the genus Micromonospora, for which the name Micromonospora pattaloongensis sp. nov. is proposed. The type strain is TJ2-2(T) (=JCM 12833(T)=TISTR 1559(T)).


Establishment of biotrophy by parasitic fungi and reprogramming of host cells for disease resistance.
Parasitic biotrophs such as mildews and rusts evolved specific mechanisms that keep host cells alive during infection. These fungi appear to absorb nutrients mainly by proton-symport-driven transporter proteins that reside in specialized feeding structures. Accumulating evidence suggests that biotrophic fungi both suppress induction of plant defense responses in physical proximity to infection sites and induce specific host genes for the establishment of biotrophy. The peculiarities of biotrophic pathogenesis likely reflect diverse types of plant disease-resistance responses. The cloning of race-specific resistance genes to powdery mildew infection and of genes required for their function provides first insights into molecular mechanisms enabling the host to recognize mildew effector components and suggests candidate mechanisms of resistance signaling. Resistance to powdery mildew fungi that result from mutations in host genes promises to shed light on mechanisms that are required for the establishment of disease susceptibility.


HEALTH, TECHNICAL EFFICIENCY, AND AGRICULTURAL PRODUCTION IN INDIAN DISTRICTS.
We investigate whether better population health may impact economic performance through improvements in technical efficiency in agricultural production. Using district-level data from India, we employ a random-coefficients approach to estimate a Cobb-Douglas production function, computing overall and input-specific technical efficiencies for each district. We then model health (district infant mortality rate) as a determinant of (in)efficiency in a second stage, controlling for a range of other socioeconomic variables. In the preferred specifications, we find that decreases in the infant mortality rate are associated with substantively and statistically significant increases in overall technical efficiency, and that a good portion of this association is likely due to improvements in the efficiency of labor use.


Early anaerobic metabolisms.
Before the advent of oxygenic photosynthesis, the biosphere was driven by anaerobic metabolisms. We catalogue and quantify the source strengths of the most probable electron donors and electron acceptors that would have been available to fuel early-Earth ecosystems. The most active ecosystems were probably driven by the cycling of H2 and Fe2+ through primary production conducted by anoxygenic phototrophs. Interesting and dynamic ecosystems would have also been driven by the microbial cycling of sulphur and nitrogen species, but their activity levels were probably not so great. Despite the diversity of potential early ecosystems, rates of primary production in the early-Earth anaerobic biosphere were probably well below those rates observed in the marine environment. We shift our attention to the Earth environment at 3.8Gyr ago, where the earliest marine sediments are preserved. We calculate, consistent with the carbon isotope record and other considerations of the carbon cycle, that marine rates of primary production at this time were probably an order of magnitude (or more) less than today. We conclude that the flux of reduced species to the Earth surface at this time may have been sufficient to drive anaerobic ecosystems of sufficient activity to be consistent with the carbon isotope record. Conversely, an ecosystem based on oxygenic photosynthesis was also possible with complete removal of the oxygen by reaction with reduced species from the mantle.


Dynamic changes in the T cell receptor repertoire during treatment with radiotherapy combined with an immune checkpoint inhibitor.
Previous studies have indicated a synergistic effect between radiotherapy and immunotherapy. A better understanding of how this combination affects the immune system can help to clarify its role in the treatment of metastatic cancer. We performed T cell receptor (TCR) sequencing on 46 sequentially collected samples from 15 patients with stage IV non-small cell lung cancer, receiving stereotactic body radiotherapy combined with a programmed cell death ligand-1 (PD-L1) inhibitor. TCR repertoire diversity was assessed using Rényi diversity curves and the Shannon diversity index. TCR clones were tracked over time. We found decreasing or stable diversity in the best responders, and an increase in diversity at progression in patients with an initial response. Expansion of TCR clones was more often seen in responders. Several patients also developed new clones of high abundance. This seemed to be more related to radiotherapy than to immune checkpoint blockade. In summary, we observed similar dynamics in the TCR repertoire as have been described with immunotherapy alone. In addition, the occurrence of new unique clones of high abundance after radiotherapy may indicate that radiotherapy functions as a personalized cancer vaccine.


17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury.
A delayed oligodendrocyte cell death after spinal cord injury (SCI) contributes to chronic demyelination of spared axons, leading to a permanent neurological deficit. Therefore, therapeutic approaches to prevent oligodendrocyte cell death after SCI should be considered. Estrogens are well known to have a broad neuroprotective effect, but the protective effect of estrogens on oligodendrocytes after injury is largely unknown. Here, we demonstrated that 17β-estradiol attenuates apoptosis of oligodendrocytes by inhibiting RhoA and c-Jun-N-terminal kinase activation after SCI. Estrogen receptor (ER)-α and -β were expressed in oligodendrocytes of the spinal cord, and 17β-estradiol treatment significantly inhibited oligodendrocyte cell death at 7 d after injury as compared with vehicle (cyclodextrin) control. 17β-Estradiol also attenuated caspase-3 and -9 activation at 7 d and reduced the loss of axons from progressive degeneration. In addition, 17β-estradiol inhibited RhoA and JNK3 activation, which were activated and peaked at 3 and/or 5 d after injury. Furthermore, administration of Rho inhibitor, PEP-1-C3 exoenzyme, inhibited RhoA and JNK3 activation, and decreased phosphorylated c-Jun level at 5 d after injury. Additionally, the attenuation of RhoA and JNK3 activation as well as oligodendrocyte cell death by 17β-estradiol was reversed by ER antagonist, ICI182780. Our results thus indicate that 17β-estradiol treatment improves functional recovery after SCI in part by reducing oligodendrocyte cell death via inhibition of RhoA and JNK3 activation, which were ER dependent. Furthermore, improvement of hindlimb motor function by posttreatment of 17β-estradiol suggests its potential as a therapeutic agent for SCI patients.


Magnetic resonance imaging in symptomatic/cryptogenic partial epilepsies of infants and children.
In order to identify the brain lesions of symptomatic/cryptogenic partial epilepsies (S/CPEs) in infants and children, magnetic resonance imaging (MRI) studies, thorough encephalographic (EEGic) studies, and detailed clinical and neurologic evaluations were obtained in 300 infants and children who were diagnosed to have S/CPEs with onset before the age of 13 years during the past 7 years. The overall detection rate of brain lesions by MRI was 41.7% (125/300). Congenital malformations (18 cases), vascular malformations (9 cases), neurocutaneous syndromes (13 cases), and space-taking lesions (20 cases) constitute a large percentage of SPEs in infants and children. A variety of insults such as infection, ischemia, hemorrhage, trauma and metabolic disorders can result in destructive parenchymal loss lesions including porencephaly, focal atrophy, hemiatrophy, and diffuse brain atrophy (20 cases). Major etiologic factors leading to infarction, encephalomalacia, leukomalacia, included trauma, hvpoxicischemic encephalopathy (HIE), systemic lupus erythematosus (SLE), encephalitis, vasculitis, venous thrombosis, vasculopathies, and heart problems (22 cases). Mesial temporal sclerosis (MTS) could be evidenced in around 20% (18/95) of cases with temporal lobe epilepsy (TLE), which was strongly associated with past histories of febrile seizures and encephalitis complicated by status epileptics. However, cases with porencephaly, global atrophy or delayed myelination of unilateral temporal lobe on MRI were more related to HIE. With the advent of neuroimaging techniques, particularly MRI, a wide variety of underlying pathology can be detected as a cause of symptomatic partial epilepsies in pediatric patients. The occurrence of S/CPE indicates the presence of localized brain dysfunction, and many of the causes are potentially treatable. An orderly and thorough clinical and laboratory investigations, as well as neuroimaging studies should be made to diagnose and treat any underlying conditions.


Chemical Constituents and Insecticidal Activities of Ajania fruticulosa Essential Oil.
The insecticidal activity and chemical constituents of the essential oil from Ajania fruticulosa were investigated. Twelve constituents representing 91.0% of the essential oil were identified, and the main constituents were 1,8-cineole (41.40%), (+)-camphor (32.10%), and myrtenol (8.15%). The essential oil exhibited contact toxicity against Tribolium castaneum and Liposcelis bostrychophila adults with LD50 values of 105.67 μg/adult and 89.85 μg/cm(2) , respectively. The essential oil also showed fumigant toxicity against two species of insect with LC50 values of 11.52 and 0.65 mg/l, respectively. 1,8-Cineole exhibited excellent fumigant toxicity (LC50 = 5.47 mg/l) against T. castaneum. (+)-Camphor showed obvious fumigant toxicity (LC50 = 0.43 mg/l) against L. bostrychophila. Myrtenol showed contact toxicity (LD50 = 29.40 μg/cm(2) ) and fumigant toxicity (LC50 = 0.50 mg/l) against L. bostrychophila. 1,8-Cineole and (+)-camphor showed strong insecticidal activity to some important insects, and they are main constituents of A. fruticulosa essential oil. The two compounds may be related to insecticidal activity of A. fruticulosa essential oil against T. castaneum and L. bostrychophila.


[Progress in researches of biodegradable intravascular stents].
Biodegradable intravascular stents (BIS) become degraded after the short-term need for a stent and thus avoid the potential long-term complications of metal stents. In this paper, the research progress of BIS was reviewed; the materials, fabrication, design, experimental and clinical tests of biodegradable polymeric intravascular stents (BPIS) are introduced.


Replication fork blockage by transcription factor-DNA complexes in Escherichia coli.
All organisms require mechanisms that resuscitate replication forks when they break down, reflecting the complex intracellular environments within which DNA replication occurs. Here we show that as few as three lac repressor-operator complexes block Escherichia coli replication forks in vitro regardless of the topological state of the DNA. Blockage with tandem repressor-operator complexes was also observed in vivo, demonstrating that replisomes have a limited ability to translocate through high affinity protein-DNA complexes. However, cells could tolerate tandem repressor-bound operators within the chromosome that were sufficient to block all forks in vitro. This discrepancy between in vitro and in vivo observations was at least partly explained by the ability of RecA, RecBCD and RecG to abrogate the effects of repressor-operator complexes on cell viability. However, neither RuvABC nor RecF were needed for normal cell growth in the face of such complexes. Holliday junction resolution by RuvABC and facilitated loading of RecA by RecF were not therefore critical for tolerance of protein-DNA blocks. We conclude that there is a trade-off between efficient genome duplication and other aspects of DNA metabolism such as transcriptional control, and that recombination enzymes, either directly or indirectly, provide the means to tolerate such conflicts.


Loss of the response regulator CtrA causes pleiotropic effects on gene expression but does not affect growth phase regulation in Rhodobacter capsulatus.
The purple nonsulfur photosynthetic bacterium Rhodobacter capsulatus has been extensively studied for its metabolic versatility as well as for production of a gene transfer agent called RcGTA. Production of RcGTA is highest in the stationary phase of growth and requires the response regulator protein CtrA. The CtrA protein in Caulobacter crescentus has been thoroughly studied for its role as an essential, master regulator of the cell cycle. Although the CtrA protein in R. capsulatus shares a high degree of sequence similarity with the C. crescentus protein, it is nonessential and clearly plays a different role in this bacterium. We have used transcriptomic and proteomic analyses of wild-type and ctrA mutant cultures to identify the genes dysregulated by the loss of CtrA in R. capsulatus. We have also characterized gene expression differences between the logarithmic and stationary phases of growth. Loss of CtrA has pleiotropic effects, with dysregulation of expression of approximately 6% of genes in the R. capsulatus genome. This includes all flagellar motility genes and a number of other putative regulatory proteins but does not appear to include any genes involved in the cell cycle. Quantitative proteomic data supported 88% of the CtrA transcriptome results. Phylogenetic analysis of CtrA sequences supports the hypothesis of an ancestral ctrA gene within the alphaproteobacteria, with subsequent diversification of function in the major alphaproteobacterial lineages.


5-Methylcytosine-Related Long Noncoding RNAs Are Potential Biomarkers to Predict Overall Survival and Regulate Tumor-Immune Environment in Patients with Bladder Cancer.
The role of 5-methylcytosine-related long noncoding RNAs (m5C-lncRNAs) in bladder cancer (BLCA) remains unclear. Here, we aim to study the prognostic value, gene expression characteristics, and correlation between the m5C-lncRNA risk model and the tumor microenvironment, immune infiltration, and tumor mutations in BLCA. After collecting BLCA patient RNA sequence transcriptome data, clinical information and mutation data from the Cancer Genome Atlas (TCGA) database, 17 m5C-related lncRNAs independently correlated with OS were obtained by Lasso and multivariate Cox regression analysis, and a risk model was constructed. Univariate Cox, multivariate Cox regression analysis, and the C-index curve proved that the risk model was a significant independent prognostic indicator for patients with BLCA. ESTIMATE and CIBERSORT indicated that the higher the number of immune cells and stromal cells in TME, the higher the prognostic risk. We found that in the low-risk group, the expression levels of immune cells that predicted a good prognosis were higher, including plasma cells, regulatory T cells, and CD 8 T cells. There is a negative correlation between TMB and risk score. The TMB of the low-risk group is significantly higher than that of the high-risk group. In conclusion, the m5C-related risk model is crucial to predict the prognosis of patients with BLCA.


Biocatalytic Strategies towards [4+2] Cycloadditions.
Long sought after [4+2] cyclases have sprouted up in numerous biosynthetic pathways in recent years, raising hopes for biocatalytic solutions to cycloaddition catalysis, an important problem in chemical synthesis. In a few cases, detailed pictures of the inner workings of these catalysts have emerged, but intense efforts to gain deeper understanding are underway by means of crystallography and computational modelling. This Minireview aims to shed light on the catalytic strategies that this highly diverse family of enzymes employs to accelerate and direct the course of [4+2] cycloadditions with reference to small-molecule catalysts and designer enzymes. These catalytic strategies include oxidative or reductive triggers and lid-like movements of enzyme domains. A precise understanding of natural cycloaddition catalysts will be instrumental for customizing them for various synthetic applications.


The Powder Diffraction File: present and future.
The International Centre for Diffraction Data (ICDD) produces the Powder Diffraction File (PDF). This paper discusses some of the seminal events in the history of producing this primary reference for powder diffraction. Recent key events that center on collaborative initiatives have led to an enormous jump in entry population for the PDF. Collective efforts to editorialize the PDF are ongoing and provide enormous added value to the file. Recently, the ICDD has created a new series of the PDF, designated PDF-4. These relational database structures are being used to house the PDF of the future. The design and benefits of the PDF-4 are described.


Changes in prevalence of Helicobacter pylori infection in two groups of patients undergoing endoscopy and living in the same region in the Netherlands.
There are few data on the prevalence of Helicobacter pylori in different populations and no data on changes in time. A cross-sectional study was done in a large population of patients undergoing endoscopy in order to relate the presence of H. pylori to ethnic background and to detect changes in time. All consecutive patients over a 10-year period were included and biopsy specimens from the gastric antrum were taken for detection of H. pylori. A large population of immigrants living in the Zaanstreek region was studied separately. In the 10-year period, 14,909 consecutive diagnostic upper GI endoscopies were done in 11,691 consecutive patients. Only the first endoscopy done in a patient was included. Of 11,691 patients available for evaluation, there were 5669 men and 6022 women (mean age 55 years, range 4-99). Of these, 3201 (27.4%) were H. pylori-positive and 4988 (42.7%) were H. pylori-negative. No biopsy specimens were available for the remaining 3501 (29.9%) patients. In the group under study, 1309 (11%) patients were immigrants. H. pylori was present significantly more often in men and in immigrants, where prevalence was 75% versus 33% (P < 0.0001). The prevalence of H. pylori showed a marked decrease in both populations during the period of study. Extrapolating trend lines into the future indicates a prevalence of H. pylori below 10% by the year 2009. Among immigrants, this will be reached in approximately 2027. This study shows differences in prevalence of H. pylori in different populations. We found a decreasing prevalence that can be explained by the lower acquisition rate of the infection. It is important to be aware of the differences in prevalence of H. pylori in a population composed of different ethnicities.


[Recovery and psychomimetic reactions following S-(+)-ketamine].
Ketamine is a racemic mixture containing equal parts of S-(+)-ketamine and R-(-)-ketamine. Their potency relation is approximately 4:1. In early human studies S-(+)-ketamine was presumed to produce the desired anaesthetic effects and R-(-)-ketamine the undesired psychic emergence reactions. Therefore, ketamine was compared in a number of randomised studies in volunteers and patients with racemic ketamine. This review addresses the impact of S-(+)-ketamine on recovery from anaesthesia, incidence and content of vivid dreams, and other side effects. The dose relation applied in the studies was 1:2. With only one exception, the recovery phase was clearly shorter after S-(+)-ketamine compared to racemic ketamine irrespective of its application as a single bolus, a bolus followed by continuous infusion, or an intramuscular injection. However, the incidence of psychic emergence reactions was lower after S-(+)-ketamine in only a single study. In conclusion, S-(+)-ketamine should be always combined with a hypnotic or sedative drug in clinical anaesthesia.


Inactivation of effector caspases through nondegradative polyubiquitylation.
Ubiquitin-mediated inactivation of caspases has long been postulated to contribute to the regulation of apoptosis. However, detailed mechanisms and functional consequences of caspase ubiquitylation have not been demonstrated. Here we show that the Drosophila Inhibitor of Apoptosis 1, DIAP1, blocks effector caspases by targeting them for polyubiquitylation and nonproteasomal inactivation. We demonstrate that the conjugation of ubiquitin to drICE suppresses its catalytic potential in cleaving caspase substrates. Our data suggest that ubiquitin conjugation sterically interferes with substrate entry and reduces the caspase's proteolytic velocity. Disruption of drICE ubiquitylation, either by mutation of DIAP1's E3 activity or drICE's ubiquitin-acceptor lysines, abrogates DIAP1's ability to neutralize drICE and suppress apoptosis in vivo. We also show that DIAP1 rests in an "inactive" conformation that requires caspase-mediated cleavage to subsequently ubiquitylate caspases. Taken together, our findings demonstrate that effector caspases regulate their own inhibition through a negative feedback mechanism involving DIAP1 "activation" and nondegradative polyubiquitylation.


Recommended surgery of Kaposi's sarcoma nodules.
Classic Kaposi's sarcoma [KS] is a chronic, multifocal, vascular proliferation, which commonly presents purplish nodules on the distal extremities of elderly men. Excisional surgery is one of the traditional therapies, but is generally time consuming and costly. To evaluate the safety and efficacy of curettage for the treatment of KS nodules. A single arm, prospective study in patients with at least one KS nodule removed by curettage. Hemostasis was obtained using 130-volume hydrogen peroxide [H2O2] and the wound was left to heal by secondary intention. Follow-up was done after 15 days, 1, 3, 6 and 12 months. Ninety patients [88 male, 2 female] with mean age of 75.8 years were enrolled. Eighty-two of the curetted nodules were localized on the lower limbs, five on the face, and three on the upper limbs. No postoperative complications were encountered, and cosmetic outcome was rated excellent by 87 patients and good by the remaining 3 patients. After 3 months, we noticed only minimal hypo-/hyperpigmentation in 59 cases, while in the remaining 31 patients the scar appeared imperceptible. Recurrence after 12 months was null. Curettage followed by the application of H2O2 is a safe, effective and simple technique for the treatment of KS nodules in elderly patients.


Augmented intracellular glutathione inhibits Fas-triggered apoptosis of activated human neutrophils.
Agonist signals delivered through cell surface Fas induce apoptosis. However, the apoptotic program can be modulated by signals from the environment, and in particular, by signals delivered through adhesion molecules. Because neutrophil functional activity in inflammation is contingent on cell survival, and because circulating neutrophils normally die rapidly through a constitutively expressed apoptotic program, we evaluated Fas-mediated apoptosis in resting and inflammatory human neutrophils. We show that normal neutrophils respond to Fas engagement with accelerated rates of apoptosis, but cross-linking of beta2 integrins or priming with bacterial lipopolysaccharide (LPS) prevents this increase. Adhesion molecule cross-linking results in increased intracellular glutathione (GSH). Augmentation of intracellular GSH with exogenous GSH or N-acetylcysteine is sufficient to reduce the Fas-triggered increase in apoptotic rates. Prevention of the activation induced GSH increase by buthionine sulfoximine, a cell permeable inhibitor of GSH biosynthesis, restored Fas responsiveness in activated neutrophils, an effect that could be blocked with exogenous GSH. Taken together, these data show that Fas-induced signaling for neutrophil apoptosis is blocked in a redox sensitive manner by costimulatory signals delivered through beta2 integrins or activation by LPS, and provide a biologic explanation for sustained neutrophil survival in the inflammatory environment.


Analysis of Herdsmen's Credit Behavior under the Identification Scheme of Emotional and Psychological State.
Herdsmen's access to credit funds plays an important supporting role in promoting the modern economic development of pastoral areas and broadening the channels for herders to increase their income. This paper studies the credit behavior of herdsmen from the perspective of emotional and psychological state identification to analyze the current credit behavior of herdsmen. Firstly, the internal mechanism of herdsmen's credit and emotional and psychological identification research content are analyzed. Secondly, a scheme of emotional and psychological state identification is proposed, and a corresponding survey of herdsmen is carried out according to the scheme. Finally, the Probit and Heckman models are introduced to analyze the credit behavior of herdsmen. The results show that herdsmen with high emotional and psychological scores strongly demand credit. They are likely to have access to credit and have a high level of credit. Herdsmen with low scores of emotional and psychological characteristics have low or no apparent demand for credit, and their credit availability is also low. The herdsmen with high emotional and psychological characteristics have a 71% higher probability of generating credit demand than herdsmen with low openness. Their likelihood of obtaining credit is also 33.47% higher than herdsmen with low emotional and psychological characteristics. They also have easy access to higher loan amounts. The results provide a reference for related research and analysis of herdsman's credit behavior and economic development.


Nutritional knowledge, attitude and practice of Tehranian adults and their relation to serum lipid and lipoproteins: Tehran lipid and glucose study.
The high prevalence of non-communicable diseases and their risk factors among the general urban population of Tehran necessitates an urgent implementation of nutritional interventional programs to curtail these risk factors. This study aimed to provide preliminary data on the knowledge, attitude and practices of urban Tehranian adults regarding nutrition and their relation to major non-communicable disease risk factors and to assess the need for educational interventions. This cross-sectional study was performed within the framework of the second phase of the Tehran Lipid and Glucose Study (TLGS). Subjects were 826 individuals, 369 men and 457 women, aged 20-70 years old, selected randomly from among 15,005 participants in the TLGS. Knowledge, attitude and practices of subjects were assessed by a 'knowledge, attitude and practice' questionnaire; height, weight, waist and hip circumferences were measured, and BMI and waist to hip ratio were calculated. Biochemical data including fasting blood glucose, cholesterol, triglycerides and HDL-cholesterol were measured, based on standard protocols, and LDL-cholesterol was calculated. Associations between nutritional knowledge, attitude, practice, sex, age and educational level, and between knowledge, attitude and practice and BMI, waist to hip ratio and levels of lipid and lipoproteins, were determined. For knowledge 26.5, 52.7 and 20.8%, for attitude, 27.6, 48.9 and 23.5% and for practice, 27.4, 51.7 and 20.9% of individuals had desirable, moderate and weak knowledge scores, respectively. With increases in educational levels, knowledge scores increased (p < 0.001). Attitudes of illiterate and poorly literate groups were weaker than those of other groups (p < 0.001). However, illiterate and poorly literate groups had higher practice scores as compared to middle school and high school graduates (p < 0.001). Mean practice scores of university graduates were higher than high school graduates (p < 0.05). Those aged 30-50 years had higher knowledge scores than older individuals (p < 0.001). LDL- and total cholesterol were correlated to practice scores (p < 0.001, r = 0.23). Subjects with borderline triglyceride levels had better practice scores than normal individuals (p < 0.001). The findings revealed that age, educational level and gender are factors that can influence knowledge, attitude and practices, regarding nutrition. It is vital to develop approaches and implement programs to improve the nutritional practices of the population.


[Non-distinctive features on CT scan of fungal sinusitis].
This article was a retrospective analysis on the preoperative CT scan of fungal sinusitis patients. The non-distinctive clinic feature was suggested to improve the accuracy of preoperative diagnosis. A retrospective analysis was made for 176 patients with fungal sinusitis,which were confirmed by postoperative pathologic diagnosis from January 2000 to January 2008. Every patient was performed both CT examination and nasal endoscopy preoperatively. All patients underwent endoscopic sinus surgery and the lesions in sinus were cleared and confirmed fungal infection by pathology. Thirty-five cases fungal infection located in sphenoid sinus, 84 cases in maxillary sinus, 49 cases in both maxillary and ethmoid sinus, 3 cases in all sinus, 5 cases in both ethmoid and sphenoid sinus. There were 179 sinuses in 176 patients were infected. This group totally had 175 cases (179 sides). One hundred and seventy-three cases had unilateral lesion,3 cases had bilateral lesion. The CT scan showed non-distinctive features including uniform dense, uneven dense in the sinus and bone resorption of the inner side bone wall. Five cases in sphenoid sinus lesion were found calcification in CT scan but 8 cases didn't show such features. Among these cases, 5 cases showed uniform dense and 3 cases showed uneven dense. In 84 cases maxillary sinus lesion, there were 12 cases without distinctive change, among these cases,8 cases showed uniform dense, 4 cases showed uneven dense and 5 cases had bone resorption. In 49 cases both ethmoid and maxillary sinus lesion, 13 cases didn't show distinctive change, among these cases, 9 cases showed uniform dense, 4 cases showed uneven dense and 6 cases had bone resorption. Five cases had calcification in the both sphenoid and ethmoid sinus. Totally 81.56% of these patients had calcification feature in the CT scan. The calcification in the lesion of sinus is usually featured as characteristic manifestation of fungal sinusitis. But in clinic, the calcification does not exit in some patients CT scan. When being absent of the featured sign in CT scan, the fungal sinusitis have to be diagnosed by other detecting means,even postoperative pathology.


Dithiocarbamate-capped silver nanoparticles.
Nanometer-sized silver particles were synthesized by using didecylamine dithiocarbamates as the protecting ligands. With control of the initial ligand-metal feed ratios, the core diameter of the resulting particles was found to vary from about 5 to 2.5 nm, as determined by transmission electron microscopic measurements. The core size dispersity was also found to decrease with increasing feed ratio. In UV-visible spectroscopic studies, the particle surface plasmon resonance peak diminished in intensity as the particle core size decreased, whereas in electrochemical measurements, smaller sized particles gave rise to well-defined quantized charging voltammetric features, in contrast to the featureless responses with the larger particles. Such single electron-transfer behaviors were consistent with those observed in STM measurements involving individual nanoparticles. Overall, this study provides an effective approach to the synthesis of stable nanometer-sized silver nanoparticles with interesting electronic and electrochemical properties.


[EFFECTIVENESS COMPARISON OF EXTERNAL FIXATION AND VOLAR LOCKING COMPRESSION PLATE IN TREATMENT OF DISTAL RADIUS FRACTURES OF TYPE C].
To compare the effectiveness of external fixation and volar locking compression plate in the treatment of distal radius fractures of type C. Between March 2012 and March 2013, 122 patients with distal radius fractures of type C were enrolled in the prospective randomized study. Fractures were treated by external fixation in 61 patients (external fixation group) and by open reduction and internal fixation using a volar locking compression plate in 61 patients (plate group). There was no significant difference in age, gender, fracture side, weight, height, body mass index, fracture type, and interval of injury and operation between 2 groups (P > 0.05). The blood loss, operation time, hospitalization days, fracture union time, wrist function, and complications were compared between 2 groups. And the quality of reduction was observed, including volar tilting angle, ulnar deviation, radial height, and articular reduction. The blood loss, operation time, and hospitalization days in plate group were significantly higher than those in external fixation group (P < 0.05). All of the patients in both groups were followed up 12-28 months. Postoperative complications occurred in 4 patients (6.6%) of external fixation group (pin tract infection in 2 cases and radial nerve neuritis in 2 cases) and in 5 patients (8.2%) of plate group (wound infection in 1 case, carpal tunnel syndrome in 2 cases, and tendon rupture in 2 cases), showing no significant difference between 2 groups (P = 0.500). The X-ray films showed fracture healing in all patients of 2 groups; the union time of plate group was significantly longer than that of external fixation group (P < 0.05). At last follow-up, there was no significant difference in ulnar deviation and radial height between 2 groups (P > 0.05), but the volar tilting angle of plate group was significantly larger than that of external fixation group (P < 0.05). There was no significant difference in wrist function and articular reduction between 2 groups (P > 0.05). For distal radius fractures of type C, the use of external fixation or volar locking compression plate can obtain satisfactory clinical outcomes, but the external fixation has the advantages of less invasion, shorter hospitalization days, minor complications, and faster fracture union.


Use of Bayes theorem to correct size-specific sampling bias in growth data.
The bayesian decomposition of posterior distribution was used to develop a likelihood function to correct bias in the estimates of population parameters from data collected randomly with size-specific selectivity. Positive distributions with time as a parameter were used for parametrization of growth data. Numerical illustrations are provided. The alternative applications of the likelihood to estimate selectivity parameters are discussed.


Fallout from government-sponsored radiation research.
On December 28, 1993, Energy Secretary Hazel R. O'Leary publicly appealed to both the executive and legislative branches of the United States Government to consider compensation for individuals who were harmed by their exposure to ionizing radiation while enrolled in government-sponsored studies conducted between 1940 and the early 1970s. The call for compensation was issued three weeks after Secretary O'Leary disclosed that radiation experiments involving humans, sometimes without their consent, had occurred under the auspices of the Atomic Energy Commission (AEC), a forerunner of the Department of Energy (DOE). Secretary O'Leary directed her department to investigate the nature and extent of the experiments, report on their medical and ethical acceptability, and locate the research subjects or their families.


Genomics of Natural Populations of Staphylococcus aureus.
Staphylococcus aureus is a major human pathogen and an important cause of livestock infections. The first S. aureus genomes to be published, 15 years ago, provided the first view of genome structure and gene content. Since then, thousands of genomes from a wide array of strains from different sources have been sequenced. Comparison of these sequences has resulted in broad insights into population structure, bacterial evolution, clone emergence and expansion, and the molecular basis of niche adaptation. Furthermore, this information is now being applied clinically in outbreak investigations to inform infection control measures and to determine appropriate treatment regimens. In this review, we summarize some of the broad insights into S. aureus biology gained from the analysis of genomes and discuss future directions and opportunities in this dynamic field of research.


Nanopores suggest a negligible influence of CpG methylation on nucleosome packaging and stability.
Nucleosomes are the fundamental repeating units of chromatin, and dynamic regulation of their positioning along DNA governs gene accessibility in eukaryotes. Although epigenetic factors have been shown to influence nucleosome structure and dynamics, the impact of DNA methylation on nucleosome packaging remains controversial. Further, all measurements to date have been carried out under zero-force conditions. In this paper, we present the first automated force measurements that probe the impact of CpG DNA methylation on nucleosome stability. In solid-state nanopore force spectroscopy, a nucleosomal DNA tail is captured into a pore and pulled on with a time-varying electrophoretic force until unraveling is detected. This is automatically repeated for hundreds of nucleosomes, yielding statistics of nucleosome lifetime vs electrophoretic force. The force geometry, which is similar to displacement forces exerted by DNA polymerases and helicases, reveals that nucleosome stability is sensitive to DNA sequence yet insensitive to CpG methylation. Our label-free method provides high-throughput data that favorably compares with other force spectroscopy experiments and is suitable for studying a variety of DNA-protein complexes.


A Case of COVID-19 Infection With Delayed Thromboembolic Complication on Warfarin.
Novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented threat to humanity with more than eight million infections and 450,000 deaths reported worldwide so far. The spectrum of the disease varies from mild asymptomatic infection to severe disease with rapid progression to acute respiratory distress syndrome and multiorgan failure. It is associated with a prothrombotic state and hence there is a risk of thromboembolic complications in critically ill patients, even after recovery. However, the duration of prothrombotic risk after recovery is yet to be determined. We present the case of a 78-year-old man with a history of atrial fibrillation on warfarin who had been recently discharged to a nursing home after recovering from COVID-19 pneumonia and presented to the emergency department a month later with worsening shortness of breath and cough. He was found to have worsening respiratory failure with multiple segmental pulmonary emboli, despite being on warfarin, and supratherapeutic international normalized ratio (INR). He required mechanical ventilation and was started on steroids and therapeutic enoxaparin anticoagulation. This case highlights the risk of delayed thromboembolic complications in patients with COVID-19 infection and the need to identify the subgroup of patients with a higher risk of thromboembolism, such as discharges to nursing homes and those in need of oxygen requirement; and those with underlying comorbid conditions that may require anticoagulation for a longer duration. The role of heparin is being increasingly investigated in patients with COVID-19 infection; however, the role of other anticoagulants such as warfarin is yet to be defined.


Sunlight-enhanced calcareous deposition on cathodic stainless steel in natural seawater.
In replicate series of experiments in natural seawater, one in full darkness and the other in a 1:1 diurnal cycle with as little as ~5% of natural solar illumination, sunlight promoted calcareous deposition on cathodic stainless steel surfaces. As exemplified by scanning electron microscopy, the deposit that formed under the natural diurnal cycle, in the presence of photosynthetic biofilms, was composed of finer calcareous crystals that provided more compact and more uniform surface coverage than the one formed in the dark. The light-enhanced deposit also possessed better scale properties, as suggested by X-ray analysis and electrochemical measurements. Sunlight enhancement of calcareous deposition looked all the more conspicuous when day and night regimes were examined independently. These results not only bear important implications for cathodic protection in marine waters, but also provide an intriguing analogy to coral reef calcification.


Neglected basal cell carcinoma in a schizophrenic patient.
Obtaining informed consent from patients with mental disorders can be a complicated and involved process, potentially resulting in decisions contrary to the advice of physicians. We present a schizophrenic patient with an invasive basal cell carcinoma involving the periocular structures and the right orbit. Exenteration was recommended with en bloc resection of the tumor. The ethical and legal committees decided against surgical intervention. Rather, the patient was admitted for medical treatment of his mental illness. A multidisciplinary approach with consultation of a psychiatrist, social worker, and ethical and legal committees is often necessary in the care of patients with mental illness.


Smooth muscle hamartoma of the lungs in a Wistar Hannover rat.
Hamartomas are tumor-like masses comprising disorganized normal tissue elements. To date, spontaneous hamartomas have been reported in several organs and tissues in rodents but not in the lungs. Here, we report the first case of a hamartoma in the lungs of a 108-week-old female Wistar Hannover rat. Grossly, a white spot, 7 mm in diameter, was observed on the costal surface of the left lung. Histopathologically, the nodular lesions adjacent to the bronchioles comprised mature smooth muscle cells. The lesion was not encapsulated and spread along the alveolar walls and ducts without compression of the surrounding tissue. In the nodules, elastic fibers enclosed small lumens lined with factor VIII-related antigen-positive endothelial cells. This structure suggested that the nodule mimicked an artery. Moreover, structural abnormalities were observed within the bronchioles and arterioles owing to the increased number of smooth muscle cells in the surrounding tissues. These features suggested that this was a case of tissue malformation rather than a neoplasm, leading to the diagnosis of a smooth muscle hamartoma of the lung.


Thyrotropin effect on the availability of Ni regulatory protein in FRTL-5 rat thyroid cells to ADP-ribosylation by pertussis toxin.
Incubation of FRTL-5 rat thyroid cell membranes with [32P]NAD and pertussis toxin results in the specific ADP-ribosylation of a protein of about 40 kDa. This protein has the same molecular mass of the alpha i subunit of the adenylate cyclase regulatory protein Ni and is distinct from proteins ADP-ribosylated by cholera toxin in the same membranes. Prior treatment of FRTL-5 cells with pertussis toxin results in the ADP-ribosylation of Ni, as indicated by the loss of the toxin substrate in the ADP-ribosylation assay performed with membranes prepared from such cells. Preincubation of FRTL-5 cells with thyrotropin causes the same loss; cholera toxin has no such effect. Pertussis toxin, as do thyrotropin and cholera toxin, increases cAMP levels in FRTL-5 cells. Forskolin together with thyrotropin, cholera toxin or pertussis toxin causes a further increase in cAMP levels. Pertussis toxin and thyrotropin are not additive in their ability to increase adenylate cyclase activity, whereas both substances are additive with cholera toxin. A role of Ni in the thyrotropin regulation of the adenylate cyclase activity in thyroid cells is proposed.


[N-Acetylcysteine: low and high doses in the treatment of chronic obstructive lung diseases in Chernobyl accident liquidators].
To study clinical effectiveness and antioxidant activity of N-acetylcisteine (NAC) in daily doses 600, 1200, 1800 and 2400 mg in Chernobyl wreckers suffering from chronic obstructive pulmonary diseases (COPD). Cough intensity and expectoration, malonic dialdehyde (MD), plasma calcium ions concentrations were studied in patients taking NAC. Cough intensity diminished insignificantly. Expectoration improved significantly only after intake of 1200 mg/day NAC. In higher doses expectoration difficulties appeared again. Five patients received a maintenance dose 200 mg/day as a result of which their expectoration improved. MDA in the above patients was 3.3 times higher than normal level, free calcium ion concentration was 1.7 times higher. Only 1200 mg/day dose of NAC brought MDA level to normal, higher doses made it subnormal. Calcium ions concentration decreased but insignificantly. Maintenance dose 200 mg/day returned MDA and calcium to initial level. For patients with radiation-induced affection of the respiratory tracts NAC dose 1200 mg/day is optimal both clinically and in terms of antioxidant activity.


Identification and cloning of a type III polyketide synthase required for diffusible pigment biosynthesis in Saccharopolyspora erythraea.
The soluble, diffusible red-brown pigment produced by a Saccharopolyspora erythraea "red variant" has been shown to contain glycosylated and polymerized derivatives of 2,5,7-trihydroxy-1,4-naphthoquinone (flaviolin). Flaviolin is a spontaneous oxidation product of 1,3,6,8-tetrahydroxynaphthalene (THN), which is biosynthesized in bacteria by a chalcone synthase-like (CS-like) type III polyketide synthase (PKS). A fragment of the gene responsible for THN biosynthesis in S. erythraea E_8-7 was amplified by polymerase chain reaction (PCR) using degenerate primers based on conserved regions of known plant CS and bacterial CS-like genes. From the isolated fragment, a suicide vector was prepared, which was subsequently used to disrupt the red-brown pigment-producing (rpp) locus in S. erythraea, generating a mutant that displayed an albino phenotype. Chromosomal DNA from the albino mutant was subsequently used in a vector-recapture protocol to isolate a plasmid that contained an insert spanning the entire rpp locus. Sequencing of the insert revealed that the disrupted open reading frame (ORF) encodes a CS-like protein displaying 69% sequence identity to the rppA gene of Streptomyces griseus. The S. griseus rppA gene encodes RppA, the first characterized bacterial CS-like protein, which is sufficient in vitro for the synthesis of THN from malonyl-CoA. The rppA disruption mutant and rppA sequence provided a means by which to address the mechanism of diffusible pigment biosynthesis, as well as to investigate any link between this and the modulation of erythromycin A titre, which has been observed for S. erythraea variants.


Model-aided targeted volatile fatty acid production from food waste using a defined co-culture microbial community.
The production of volatile fatty acids (VFA) is gaining momentum due to their central role in the emerging carboxylate platform. Particularly, the production of the longest VFA (from butyrate to caproate) is desired due to their increased economic value and easier downstream processing. While the use of undefined microbial cultures is usually preferred with organic waste streams, the use of defined microbial co-culture processes could tackle some of their drawbacks such as poor control over the process outcome, which often leads to low selectivity for the desired products. However, the extensive experimentation needed to design a co-culture system hinders the use of this technology. In this work, a workflow based on the combined use of mathematical models and wet experimentation is proposed to accelerate the design of novel bioprocesses. In particular, a co-culture consisting of Pediococcus pentosaceus and Megaphaera cerevisiae is used to target the production of high-value odd- and even‑carbon VFA. An unstructured kinetic model was developed, calibrated and used to design experiments with the goal of increasing the selectivity for the desired VFA, which were experimentally validated. In the case of even‑carbon VFA, the experimental validation showed an increase of 38 % in caproate yield and, in the case of enhanced odd‑carbon VFA experiments, the yield of butyrate and caproate diminished by 62 % and 94 %, respectively, while propionate became one of the main end products and valerate yield value increased from 0.007 to 0.085 gvalearte per gconsumed sugar. The workflow followed in this work proved to be a sound tool for bioprocess design due to its capacity to explore and design new experiments in silico in a fast way and ability to quickly adapt to new scenarios.


Endocytoscopic Observation of Non-Ampullary Mucosal Duodenal Cancer.
Our previous study of duodenal adenoma using an endocytoscopy system (ECS) demonstrated that disappearance of goblet cells and spindle-shaped nuclei with loss of polarity were characteristic features. In addition, round duct openings and finger-like projections were observed in tubular adenoma and villous adenoma, respectively. Here, we retrospectively investigated six cases of histologically proven sporadic non-ampullary mucosal duodenal cancer (NAMDC) using ECS. Immunohistochemistry for CD10, MUC2, MUC5AC, and MUC6 was employed to determine the mucin phenotype in addition to conventional HE histology. Immunohistochemistry revealed one case involving the duodenal bulb that was considered to be the mixed type. The other five cases, located in the second or third portion, were considered to be the intestinal type. Vital staining of the mixed-type case was considered insufficient for ECS observation because of surface mucus. However, all five cases of intestinal-type duodenal cancer demonstrated a villous structure, disappearance of goblet cells and enlarged nuclei with loss of polarity. Tubular structures were admixed in four of those cases. Four cases demonstrated oval-shaped nuclei, and one case had spindle-shaped nuclei. Cases showing spindle-shaped nuclei in most of the lesion were diagnosed histologically as cancer in adenoma where the adenomatous component of the tumor was dominant. Oval-shaped nuclei and nuclear enlargement are the characteristic features of NAMDC revealed by ECS and are included among the histological criteria used for diagnosis. ECS offers the potential to perform real-time histological diagnosis of NAMDC in vivo.


Pain self-management plus nurse-led support in young adults with irritable bowel syndrome: Study protocol for a pilot randomized control trial.
Irritable bowel syndrome (IBS) is a functional gut disorder that typically manifests in early adult years. IBS patients report that pain is the most distressing symptom with the greatest impact on quality of life. Pain-sensitivity genes and the gut microbiome may influence severity of symptoms as well as response to self-management (SM) interventions. Based on current understanding of the science of SM, pain neurophysiology, and the gut-brain axis, our team developed a pain SM intervention to be added to evidence-based self-management instruction to increase the individual's SM knowledge and skills (self-efficacy, self-regulation, and goal-setting). The purpose of this randomized controlled longitudinal pilot study is to examine the feasibility, acceptability, and preliminary effectiveness of the IBS-pain SM intervention on IBS-pain SM behaviors and related health outcomes. A sample of 80 young adults (age 18-29 years old) will be recruited and randomly assigned to the experimental or control group. Both groups will receive 10 electronic video modules focused on IBS-pain SM knowledge and skills. The experimental group also will receive nurse-led one-on-one phone consultations to facilitate monitoring and problem-solving. All participants will be followed over 12 weeks. Primary outcomes will be measured at baseline, 6 weeks, and 12 weeks, including IBS-pain SM behaviors, quality of life, and well-being. The influence of pain-sensitivity genes and the gut microbiome on IBS-pain SM behaviors and health outcomes also will be assessed.


DIRECT AND INDIRECT ESTIMATES OF NEIGHBORHOOD AND EFFECTIVE POPULATION SIZE IN A TROPICAL PALM, ASTROCARYUM MEXICANUM.
To estimate the relative importance of genetic drift, the effective population size ∗∗∗(Ne ) can be used. Here we present estimates of the effective population size and related measures in Astrocaryum mexicanum, a tropical palm from Los Tuxtlas rain forest, Veracruz, Mexico. Seed and pollen dispersal were measured. Seeds are primarily dispersed by gravity and secondarily dispersed by small mammals. Mean primary and secondary dispersal distances for seeds were found to be small (0.78 m and 2.35 m, respectively). A. mexicanum is beetle pollinated and pollen movements were measured by different methods: a) using fluorescent dyes, b) as the minimum distance between active female and male inflorescences, and c) using rare allozyme alleles as genetic markers. All three estimates of pollen dispersal were similar, with a mean of approximately 20 m. Using the seed and pollen dispersal data, the genetic neighborhood area (A) was estimated to be 2,551 m2 . To obtain the effective population size, three different overlapping generation methods were used to estimate an effective density with demographic data from six permanent plots. The effective density ranged from 0.040 to 0.351 individuals per m2 . The product of effective density and neighborhood area yields a direct estimate of the neighborhood effective population size (Nb ). Nb ranged from 102 to 895 individuals. Indirect estimates of population size and migration rate (Nm) were obtained using Fst for five different allozymic loci for both adults and seeds. We obtained a range of Nm from 1.2 to 19.7 in adults and a range of Nm from 4.0 to 82.6 for seeds. We discuss possible causes of the smaller indirect estimates of Nm relative to the direct and compare our estimates with values from other plant populations. Gene dispersal distances, neighborhood size, and effective population size in A. mexicanum are relatively high, suggesting that natural selection, rather than genetic drift, may play a dominant role in patterning the genetic variation in this tropical palm.


[Comparison of four different methods for respiratory determination of the anaerobic threshold in normal people, and heart- and lung patients].
We analyzed 128 cardiopulmonary exercise tests (CPX), performed in normal subjects (n = 31), in patients with coronary artery disease (n = 41), with chronic heart failure before (n = 14) and after (n = 14) application of oral PDE-inhibitors and in patients with HIV-infection on a bicycle-ergometer in semi-supine position using a ramp-program (dependent on study-population with 15, 20 or 35 Watt/min increases) with respect to the ability to determine the respiratory anaerobic threshold non-invasively, using the main criteria described by Wasserman et al.: the V-slope-method according to Beaver, the increase of the ventilatory equivalent for O2 (VE/VO2), the increase of the end-tidal PO2 (PETO2) and the increase of the respiratory quotient (RQ) during exercise. In the different study-populations we calculated the detection rates of the AT for each criteria separately. The typical changes in the end-tidal PO2 (124/128 = 96.9%) and the V-slope-method (119/128 = 92.9%) were the most reliable parameters to detect the anaerobic threshold. The characteristic changes of the ventilatory equivalent for O2 (VE/VO2) and of the respiratory quotient (RQ) we found in 100/128 (= 78.1%) and in 107/128 (= 83.6%) of the tests respectively. 86/128 tests (67.2%) showed typical changes in all four mentioned criteria. In another 24/128 tests (19.8%) three of four criteria were fulfilled. Therefore, our investigations showed that in 110/128 cases (85.9%) the AT could be determined by typical changes by means of at least three of the four described parameters. In 15/128 (11.7%) tests only two of four criteria were fulfilled.(ABSTRACT TRUNCATED AT 250 WORDS)


PERSPECTIVE: THE PACE OF MODERN LIFE: MEASURING RATES OF CONTEMPORARY MICROEVOLUTION.
We evaluate methods for measuring and specifying rates of microevolution in the wild, with particular regard to studies of contemporary, often deemed "rapid," evolution. A considerable amount of ambiguity and inconsistency persists within the field, and we provide a number of suggestions that should improve study design, inference, and clarity of presentation. (1) Some studies measure change over time within a population (allochronic) and others measure the difference between two populations that had a common ancestor in the past (synchronic). Allochronic studies can be used to estimate rates of "evolution," whereas synchronic studies more appropriately estimate rates of "divergence." Rates of divergence may range from a small fraction to many times the actual evolutionary rates in the component populations. (2) Some studies measure change using individuals captured from the wild, whereas others measure differences after rearing in a common environment. The first type of study can be used to specify "phenotypic" rates and the later "genetic" rates. (3) The most commonly used evolutionary rate metric, the darwin, has a number of theoretical shortcomings. Studies of microevolution would benefit from specifying rates in standard deviations per generation, the haldane. (4) Evolutionary rates are typically specified without an indication of their precision. Readily available methods for specifying confidence intervals and statistical significance (regression, bootstrapping, randomization) should be implemented. (5) Microevolutionists should strive to accumulate time series, which can reveal temporal shifts in the rate of evolution and can be used to identify evolutionary patterns. (6) Evolutionary rates provide a convenient way to compare the tempo of evolution across studies, traits, taxa, and time scales, but such comparisons are subject to varying degrees of confidence. Comparisons across different time scales are particularly tenuous. (7) A number of multivariate rate measures exist, but considerable theoretical development is required before their utility can be determined. We encourage the continued investigation of evolutionary rates because the information they provide is relevant to a wide range of theoretical and practical issues.


Extended Adjuvant Endocrine Therapy in Breast Cancer: Evidence and Update - A Review.
The optimal duration and treatment strategies involving adjuvant endocrine therapy in early breast cancer remained largely undetermined. As data emerge on the various modalities of treatment in both pre- and postmenopausal groups, debates, and discussions continue. Most studies to date focused on the 5-year duration of treatment consisting of mainly tamoxifen. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) study demonstrated that anastrozole is superior to tamoxifen and has become the mainstream treatment in postmenopausal women with early breast cancer, although the duration was arbitrarily set for 5 years, analogous to tamoxifen treatment. Several clinical trials, however, have emerged to support extended endocrine therapy as it becomes clear that the recurrence risk of breast cancer does not decrease beyond the initial 5 years of treatment. The advent of molecular signatures also plays an important role in the breast cancer profiling, and where available should be incorporated in the overall decision-making. Furthermore, side effects and noncompliance pose another issue in achieving an optimal treatment benefit. The decision-making as regards to extended endocrine treatment should therefore focus not only on the cancer biology alone but also include treatment side effects, assessment of risk of recurrence and patients' preference. In this review, we present an overview of the published studies to date as well as ongoing studies on the topic to better refine the options for adjuvant hormonal therapy.


Impact of Semiconducting Perylene Diimide Nanoparticle Size on Lymph Node Mapping and Cancer Imaging.
Semiconducting molecules of perylene diimide (PDI) with strong light absorption properties in the near-infrared region and good biocompatibility have received increasing attention in the field of theranostics, especially as photoacoustic (PA) imaging agents. Herein, we report a series of [64Cu]-labeled PDI nanoparticles (NPs) of different sizes (30, 60, 100, and 200 nm) as dual positron emission tomography (PET) and PA imaging probes and photothermal therapy agents. The precise size control of the PDI NPs can be achieved by adjusting the initial concentration of PDI molecules in the self-assembly process, and the photophysical property of different sized PDI NPs was studied in detail. Furthermore, we systematically investigated the size-dependent accumulation of the PDI NPs in the lymphatic system after local administration and in tumors after intravenous injection by PA and PET imaging. The results revealed that 100 nm is the best size for differentiating popliteal and sciatic LNs since the interval is around 60 min for the NPs to migrate from popliteal LNs to sciatic LNs, which is an ideal time window to facilitate surgical sentinel LN biopsy and pathological examination. Furthermore, different migration times of the different-sized PDI NPs will provide more choices for surgeons to map the specific tumor relevant LNs. PDI NP theranostics can also be applied to imaging-guided cancer therapy. The NPs with a size of 60 nm appear to be the best for tumor imaging and photothermal cancer therapy due to the maximum tumor accumulation efficiency. Thus, our study not only presents organic PDI NP theranostics but also introduces different-sized NPs for multiple bioapplications.


alpha2-Adrenergic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: emerging concepts from new data.
Recent developments in the field of neuroscience have illuminated the understanding of the neural circuits impaired in attention-deficit/hyperactivity disorder (ADHD) and the mechanism of action of treatments used to treat this condition. There is an exciting confluence between emerging studies in basic neurobiology and the genetic, neuroimaging, and neuropsychological analyses of ADHD. The following provides a brief review of this field, explaining how compounds like guanfacine and the traditional stimulant medications can reduce the core symptoms of ADHD by optimizing the neurochemical environment in the prefrontal cortex (PFC). Knowledge of these basic mechanisms may inform our medication choices and facilitate treatment of ADHD and related disorders.


Analysis of open-label trials in torsion dystonia using high dosages of anticholinergics and other drugs.
We reviewed the records of 358 patients with various forms of focal, segmental, and generalized dystonia who had received pharmacotherapy in a systematic order, beginning with anticholinergics. If no benefit was encountered, we then tested clonazepam, baclofen, and other agents sequentially. In each situation the dosage was gradually increased until benefit or troublesome adverse effects were encountered. In this manner we obtained data on the percentage of patients who showed moderate to marked benefit. Anticholinergics were the most beneficial agent, confirming previous reports. Statistical analysis of this response revealed that benefit from anticholinergics was most likely if treatment was begun within 5 years after the onset of dystonia. From this analysis, it appears that delaying treatment beyond 5 years is likely to result in an unsatisfactory response.


[Overlooked primary hyperparathyroidism presented with fractures: case report].
In the present paper, we report a female patient with multiple cystic lesions of bone arising from the primary hyperparathyroidism and pathological femur and contralateral tibia fractures at the level of these cystic lesions (osteitis fibrosa cystica). The patient's history revealed that she was admitted to a medical center with vague symptoms such as sudden onset of dyspepsia, loss of appetite, myalgia, arthralgia, fatigue, and weight loss six years ago but no disease was diagnosed. Loss of appetite and loss of weight continued. She had been walking only by assisted ambulation for the last year. However, primary hyperparathyroidism was overlooked until our examination. The fractures were managed by interlocking nailing and grafting after confirming with biopsy that the fractures were due to osteitis fibrosa cystica. The fractures healed uneventfully. In conclusion, it is essential to evaluate patients with these vague symptoms with full biochemical screening and radiological examination for the early detection of the disease.


Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study.
Once-daily topical brimonidine tartrate (BT) gel 0.5% was shown to be efficacious and safe for the treatment of erythema of rosacea in previous studies including a 4-week treatment phase. In the present 1-year study, we aimed to assess the long-term safety and efficacy of the treatment. Subjects with moderate to severe erythema of rosacea were instructed to apply topical BT gel 0.5% once daily for 12 months. Severity of erythema and adverse events (AEs) were evaluated. Approximately 345 subject years of exposure to BT gel 0.5% was achieved in the study. The incidence of AEs and AEs judged to be related to the study drug was higher at the beginning and decreased over the course of the study. Similar safety profiles were observed between the subjects who had received or not received concomitant therapies for the inflammatory lesions of rosacea. Effect of topical BT gel 0.5% on erythema severity was observed after the first application and the durability of the effect was maintained until the end of the study at month 12, with no tachyphylaxis observed. In conclusion, once-daily topical BT gel 0.5% is safe and consistently effective for the long-term treatment of moderate to severe erythema of rosacea, even in the presence of concomitant therapies for the inflammatory lesions of rosacea.


Gemcitabine associated pseudocellulitis: A missed diagnosis.
We report a case of a 51-year-old male with past medical history significant for cholangiocarcinoma presented with two weeks of worsening bilateral lower extremity swelling and erythema. Patient has been on active chemotherapy for his cholangiocarcinoma with Gemcitabine weekly infusions. Physical exam was significant for bilaterally petechial rash coalescing into ecchymoses over the dorsum of the feet, sparing soles and toes, which dissipated into thinning petechiae more proximally. On labs he did not have any leukocytosis, his platelet count was 50 × 103/µL and basic metabolic panel was benign. Patient was started on Vancomycin for presumed cellulitis. Lower extremity ultrasound Doppler ruled out deep venous thrombosis. Patient did have biopsies bilaterally on his legs, which showed hypersensitivity reaction consistent with the diagnosis of pseudocellulitis. His Vancomycin was discontinued and his symptoms improved. Our case further supports that pseudocellulitis is underrecognized and underreported, potentially leading to unnecessary antibiotic exposure and unnecessary diagnostic work-up as seen unfortunately in our patient. Unnecessary antibiotic exposure is increasing the risk for clostridium difficile and or antibiotic resistance, therefore awareness of this reaction is critical, as to avoid unnecessary antibiotics, and costly diagnostic workups.


A study of the relationship between peak skin dose and cumulative air kerma in interventional neuroradiology and cardiology.
A study of peak skin doses (PSDs) during neuroradiology and cardiology interventional procedures has been carried out using Gafchromic XR-RV2 film. Use of mosaics made from squares held in cling film has allowed doses to the head to be mapped successfully. The displayed cumulative air kerma (CAK) has been calibrated in terms of cumulative entrance surface dose (CESD) and results indicate that this can provide a reliable indicator of the PSD in neuroradiology. Results linking PSD to CESD for interventional cardiology were variable, but CAK is still considered to provide the best option for use as an indicator of potential radiation-induced effects. A CESD exceeding 3 Gy is considered a suitable action level for triggering follow-up of patients in neuroradiology and cardiology for possible skin effects. Application of dose action levels defined in this way would affect 8% of neurological embolisation procedures and 5% of cardiology ablation and multiple stent procedures at the hospitals where the investigations were carried out. A close relationship was observed between CESD and dose-area product (DAP) for particular types of procedure, and DAPs of 200-300 Gy cm(2) could be used as trigger levels where CAK readings were not available. The DAP value would depend on the mean field size and would need to be determined for each application.


Avascular necrosis of bone following renal transplantation.
Assessment of 78 successful renal transplants carried out in Newcastle upon Tyne between October 1967 and March 1973, revealed avascular necrosis of bone (A.N.) in 11 patients (14 percent). Pain and restriction of movement were the cardinal symptoms, while the onset was from five to 35 months after transplantation. In some patients one joint only was affected but in seven patients (64 per cent) A.N. developed in other joints too in an additive and progressive fashion. A time lag was usually noted between the onset of symptoms and radiological proof. These 11 patients with A.N. were compared with two control groups of unaffected renal transplant patients. Taking into account the patients' body weight, the cumulative dose of prednisone received by affected patients during the first three post-transplant months was found to be significantly higher than that for both control groups (P less than 0.05). Patients with A.N. were found to have had an unusually high incidence of early post-transplant surgical complications and the length of their initial stay in hospital was significantly prolonged (P less than 0.02) when compared to both control groups. It is possible that excessive corticosteroid therapy is more deleterious in transplant patients weakened by peri-renal haematomas, urinary extravasations and stormy prolonged post-operative periods. Having emphasized the detrimental effects of excessive anti-rejection corticosteroid therapy it must be mentioned that occasionally patients develop avascular necrosis even after low doses of steroid therapy, while others, receiving high doses of steroid therapy and undergoing a stormy post-operative course, do not develop this complaint. It is suggested that although excessive steroid therapy is positively harmful, avascular necrosis is not an invariable complication and that ofther factors including possibly a genetic predisposition operate to produce avascular necrosis of bone in renal transplant patients.


A pedigree of homozygous familial hyperalphalipoproteinemia.
A new form of familial lipoprotein disorder, homozygous hyperalphalipoproteinemia (HALP) was studied in one pedigree through three generations. The proband was a healthy male, 50 years old, who was checked for a distinctive elevation of plasma high-density lipoprotein cholesterol (HDL-C) in a routine screening examination. An intensive family study revealed that the proband and one of his sisters were homozygotic carriers of familial HALP judging by their extremely high concentration of HDL-C (181 mg/dL and 163 mg/dL, respectively). In the homozygotes, the lipid composition of HDL was found to be normal while the ratio of HDL lipids to apoproteins A-I and A-II tended to be increased. All five children of the two homozygous individuals and two additional first degree relatives were considered to be heterozygous, since their HDL-C values were moderately elevated, with other lipid levels being normal. The family study thus substantiated the hypothesis, as Glueck et al insisted in 1975, that this lipoprotein disorder is inherited by autosomal dominant transmission. Longevity analysis revealed that the decreased family members showed life prolongation of 9.8 years on an average compared with the appropriate control population of the same district. Our report might be the first to demonstrate the homozygous form of this longevity syndrome.


Two-Dimensional Heterostructure as a Platform for Surface-Enhanced Raman Scattering.
Raman enhancement on a flat nonmetallic surface has attracted increasing attention, ever since the discovery of graphene enhanced Raman scattering. Recently, diverse two-dimensional layered materials have been applied as a flat surface for the Raman enhancement, attributed to different mechanisms. Looking beyond these isolated materials, atomic layers can be reassembled to design a heterostructure stacked layer by layer with an arbitrary chosen sequence, which allows the flow of charge carriers between neighboring layers and offers novel functionalities. Here, we demonstrate the heterostructure as a novel Raman enhancement platform. The WSe2 (W) monolayer and graphene (G) were stacked together to form a heterostructure with an area of 10 mm × 10 mm. Heterostructures with different stacked structuress are used as platforms for the enhanced Raman scattering, including G/W, W/G, G/W/G/W, and W/G/G/W. On the surface of the heterostructure, the intensity of the Raman scattering is much stronger compared with isolated layers, using the copper phthalocyanine (CuPc) molecule as a probe. It is found that the Raman enhancement effect on heterostructures depends on stacked methods. Phonon modes of CuPc have the strongest enhancement on G/W. W/G and W/G/G/W have a stronger enhancement than that on the isolated WSe2 monolayer, while lower than the graphene monolayer. The G/W/G/W/substrate demonstrated a comparable Raman enhancement effect than the G/W/substrate. These differences are due to the different interlayer couplings in heterostructures related to electron transition probability rates, which are further proved by first-principle calculations and probe-pump measurements.


GENOTYPIC VARIATION IN LEAF DAMAGE IN PIPER ARIEIANUM (PIPERACEAE) BY A MULTISPECIES ASSEMBLAGE OF HERBIVORES.
The shrub Piper arieianum (Piperaceae) has a diverse herbivore fauna (95 species total) in Costa Rican rain forest. The effect of plant genotype on leaf damage by individual herbivore species and total leaf area removed was studied in P. arieianum through a cloning experiment. Damage patterns were measured over 3.5 years for two plots, four genotypes per plot, in the understory of lowland rain forest. In both plots, there were significant differences among genotypes in total leaf area missing throughout the study period. Rankings of genotypes based on overall damage remained constant over time in plot 1 but changed in plot 2. Certain individual herbivore species caused significantly higher damage in some genotypes than in others; the change in genotype rankings in plot 2 was associated with increased damage to particular genotypes by specific herbivore groups. The genotype most heavily damaged by a given insect species varied depending on the herbivore species; thus, resistance to one herbivore species did not necessarily confer resistance against all species. Those herbivore species causing the greatest proportion of damage for a given plant changed over time. Because total damage resulted from the summation of losses to individual herbivore species, whether an individual plant lost more leaf area than its neighbors depended on the relative abundance of the herbivore species at any one time. Finally, for a portion of the study period in each plot, more heavily damaged clones grew less than lesser damaged clones. Together with previous reports that naturally growing plants differ significantly in damage and that these differences are sufficient to cause fitness differences, the results presented here suggest that the herbivores of P. arieianum represent a selective force for changes in resistance but that this selective force changes both in intensity and quality over time.


Rabies virus infection of primary neuronal cultures and adult mice: failure to demonstrate evidence of excitotoxicity.
Cultures derived from the cerebral cortices and hippocampi of 17-day-old mouse fetuses infected with the CVS strain of rabies virus showed loss of trypan blue exclusion, morphological apoptotic features, and activated caspase 3 expression, indicating apoptosis. The NMDA (N-methyl-D-aspartate acid) antagonists ketamine (125 microM) and MK-801 (60 microM) were found to have no significant neuroprotective effect on CVS-infected neurons, while the caspase inhibitor Ac-Asp-Glu-Val aspartic acid aldehyde (25 microM) exerted a marked neuroprotective effect. Glutamate-stimulated increases in levels of intracellular calcium were reduced in CVS-infected hippocampal neurons. Ketamine (120 mg/kg of body weight/day intraperitoneally) given to CVS-infected adult mice produced no beneficial effects. We have found no supportive evidence that excitotoxicity plays an important role in rabies virus infection.