Make Your Cake and Eat It: Refueling of Immune Fitness in AML Post Allo-HCT Using Baking Soda.
Although there has been a recent renaissance in the availability of new therapeutic options for patients with acute myeloid leukemia (AML), survival rates remain low coupled with a high incidence of relapse. Enhancing T cell and immune function has become an effective therapeutic approach in hematological malignancies. However, AML cells can modulate the bone marrow microenvironment by changing extracellular nutrient and biochemical availability which can metabolically regulate immune function. Here we review the findings by Uhl et al. showing that T cell metabolism and function can be boosted by treatment with sodium bicarbonate to counteract the metabolic changes induced by lactic acid produced by leukemia cells.


Risperidone-induced priapism: a case report and literature review.
Priapism is a rare pathological condition defined as painful and persistent penile erection that is unrelated to sexual stimulation. It can be classified as ischaemic or non-ischaemic. Many causes have been attributed to ischaemic priapism, including the use of some medications such as antipsychotics. The mechanism of priapism associated with antipsychotics is thought to be related to alpha-adrenergic blockage that is mediated by the alpha receptors in the corpora cavernosa of the penis. In this paper, we describe a case of a patient who suffered from Risperidone-induced priapism, and how this adverse effect was resolved by switching to olanzapine followed by olanzapine pamoate. A literature search on PubMed/Medline up to 2011 was conducted by some doctors from London and found 30 cases of priapism associated with risperidone. Based on this work, we searched PubMed through 2021, using the keywords 'priapism' and 'risperidone' and found a total of 43 cases of priapism involving risperidone. Priapism is not correlated with the dosage of this psychotropic drug, and has also occasionally occurred when risperidone has been used in conjunction with another drug. The question of choosing a replacement antipsychotic after the first one has induced priapism, remains problematic. It would be preferable to switch to a drug with less marked alpha1-blocking properties, but no consensus has been reached as to the best choice of medication. Finally, any prescription of an antipsychotic treatment must be preceded by a careful interrogation in search of risk factors for priapism, and the patient should be made aware of the possible occurrence of this side effect and the need to then seek urgent medical advice.


Correlations of recurrence of gastric cancer in patients after radical surgery with serum gastrointestinal hormones, vascular endothelial growth factors and serum anti-helicobacter pylori IgG antibody.
To study the correlations of the recurrence of gastric cancer in patients after radical surgery with serum gastrointestinal hormones, serum anti-Helicobacter pylori (anti-HP) immunoglobulin G (IgG) antibody and vascular endothelial growth factors (VEGFs). According to whether gastric cancer recurred within five years after surgery, the patients were divided into recurrence group (RE group, gastric cancer recurred within five years after surgery, n=78) and non-recurrence group (NR group, gastric cancer did not recur within five years after surgery, n=69). Differences in lymph node metastasis, gastrointestinal hormones, VEGFs, anti-HP IgG antibody and the tumor-node-metastasis (TNM) stage between RE group and NR group were detected and compared, so as to analyze the correlations of these factors with the recurrence of gastric cancer in patients after radical surgery. The levels of gastrin (GAS) and motilin (MTL) after meals in RE group and NR group were slightly higher than those before meals. The levels of GAS and MTL in RE group were higher than those in NR group in the two periods (p<0.05). Besides, compared with NR group, RE group had lower pepsinogen (PG) I, PG II and PG I/II ratio (PGR), but a higher positive value of anti-HP IgG antibody (p<0.05) and higher levels of VEGF-A, VEGF-C and VEGF-D (p<0.05). Moreover, there were markedly more cases of gastric cancer in stage III, remarkably few cases of gastric cancer in stage I and obviously more cases of lymph node metastasis in RE group than those in NR group (p<0.05). Multivariate analysis showed that gastrointestinal hormones, lymph node metastasis, VEGFs, the TNM stage of gastric cancer and anti-HP IgG antibody were all risk factors for the recurrence of gastric cancer after radical surgery (p<0.05). The recurrence of gastric cancer in patients after radical surgery is related to the TNM stage of gastric cancer, gastrointestinal hormones, VEGFs, lymph node metastasis, anti-HP IgG antibody and other factors.


Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) and alterations in hepatic lipoprotein kinetics are common metabolic complications associated with obesity. Lifestyle modification involving diet-induced weight loss and regular exercise decreases intrahepatic triglyceride (IHTG) content and very low density lipoprotein (VLDL) triglyceride (TG) secretion rate. The aim of this study was to evaluate the weight loss-independent effect of following the physical activity guidelines recommended by the Department of Health and Human Services on IHTG content and VLDL kinetics in obese persons with NAFLD. Eighteen obese people (body mass index [BMI]: 38.1 ± 4.6 kg/m(2)) with NAFLD were randomized to 16 weeks of exercise training (45%-55% VO(2peak) , 30-60 minutes × 5 days/week; n = 12) or observation (control; n = 6). Magnetic resonance spectroscopy and stable isotope tracer infusions in conjunction with compartmental modeling were used to evaluate IHTG content and hepatic VLDL-TG and apolipoprotein B-100 (apoB-100) secretion rates. Exercise training resulted in a 10.3% ± 4.6% decrease in IHTG content (P < 0.05), but did not change total body weight (103.1 ± 4.2 kg before and 102.9 ± 4.2 kg after training) or percent body fat (38.9% ± 2.1% before and 39.2% ± 2.1% after training). Exercise training did not change the hepatic VLDL-TG secretion rate (17.7 ± 3.9 μmol/min before and 16.8 ± 5.4 μmol/min after training) or VLDL-apoB-100 secretion rate (1.5 ± 0.5 nmol/min before and 1.6 ± 0.6 nmol/min after training). Following the Department of Health and Human Services recommended physical activity guidelines has small but beneficial effects on IHTG content, but does not improve hepatic lipoprotein kinetics in obese persons with NAFLD.


Autoimmune encephalopathies.
Over the past 10 years, the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of 11 autoimmune encephalitic disorders, grouped by syndromes and approached from a clinical perspective. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases.


miR-15b induced by platelet-derived growth factor signaling is required for vascular smooth muscle cell proliferation.
The platelet-derived growth factor (PDGF) signaling pathway is essential for inducing a dedifferentiated state of vascular smooth muscle cells (VSMCs). Activation of PDGF inhibits smooth muscle cell (SMC)-specific gene expression and increases the rate of proliferation and migration, leading to dedifferentiation of VSMCs. Recently, microRNAs have been shown to play a critical role in the modulation of the VSMC phenotype in response to extracellular signals. However, little is known about microRNAs regulated by PDGF in VSMCs. Herein, we identify microRNA-15b (miR-15b) as a mediator of VSMC phenotype regulation upon PDGF signaling. We demonstrate that miR-15b is induced by PDGF in pulmonary artery smooth muscle cells and is critical for PDGF-mediated repression of SMC-specific genes. In addition, we show that miR-15b promotes cell proliferation. These results indicate that PDGF signaling regulates SMC-specific gene expression and cell proliferation by modulating the expression of miR-15b to induce a dedifferentiated state in the VSMCs.


Contribution of vaccines to our understanding of pneumococcal disease.
Pneumonia is the leading cause of mortality in children in developing countries and is also the leading infectious cause of death in adults. The most important cause of pneumonia is the Gram-positive bacterial pathogen, Streptococcus pneumoniae, also known as the pneumococcus. It has thus become the leading vaccine-preventable cause of death and is a successful and diverse human pathogen. The development of conjugate pneumococcal vaccines has made possible the prevention of pneumococcal disease in infants, but has also elucidated aspects of pneumococcal biology in a number of ways. Use of the vaccine as a probe has increased our understanding of the burden of pneumococcal disease in children globally. Vaccination has also elucidated the clinical spectrum of vaccine-preventable pneumococcal infections; the identification of a biological niche for multiple pneumococcal serotypes in carriage and the differential invasiveness of pneumococcal serotypes; the impact of pneumococcal transmission among children on disease burden in adults; the role of carriage as a precursor to pneumonia; the plasticity of a naturally transformable pathogen to respond to selective pressure through capsular switching and the accumulation of antibiotic-resistance determinants; and the role of pneumococcal infections in hospitalization and mortality associated with respiratory viral infections, including both seasonal and pandemic influenza. Finally, there has been a recent demonstration that pneumococcal pneumonia in children may be an important cause of hospitalization for those with underlying tuberculosis.


A theoretical study of model lipid monolayers.
Studies of pure phospholipid monolayers or various well defined lipid mixtures have greatly contributed to the current knowledge of the relationship between monolayer composition and its properties and to understand how their physicochemical properties, e.g. refraction, polarization, are controlled by structural variations at the molecular level. Therefore, an attempt was made to investigate model lipid molecules adsorbed on the air/water interface. Semi-empirical (AM1) quantum chemical calculations were performed for several clusters and were compared with experimental data. The optimized acidic molecules show a marked tendency to group forming domains. An increase in the number of surfactant molecules in the cluster leads to a decrease in the effective headgroup area. On the other hand, the area grows with the increase of the degree of ionization. Both relations are in accordance with the experimental trends and the electrostatic theory. The employed theoretical approach proves to be applicable to the study of monolayers, thus providing a reliable description at molecular level of the traditionally phenomenological investigations in the field.


A fast and pragmatic approach for scatter correction in flat-detector CT using elliptic modeling and iterative optimization.
Scattered radiation is a major source of artifacts in flat detector computed tomography (FDCT) due to the increased irradiated volumes. We propose a fast projection-based algorithm for correction of scatter artifacts. The presented algorithm combines a convolution method to determine the spatial distribution of the scatter intensity distribution with an object-size-dependent scaling of the scatter intensity distributions using a priori information generated by Monte Carlo simulations. A projection-based (PBSE) and an image-based (IBSE) strategy for size estimation of the scanned object are presented. Both strategies provide good correction and comparable results; the faster PBSE strategy is recommended. Even with such a fast and simple algorithm that in the PBSE variant does not rely on reconstructed volumes or scatter measurements, it is possible to provide a reasonable scatter correction even for truncated scans. For both simulations and measurements, scatter artifacts were significantly reduced and the algorithm showed stable behavior in the z-direction. For simulated voxelized head, hip and thorax phantoms, a figure of merit Q of 0.82, 0.76 and 0.77 was reached, respectively (Q = 0 for uncorrected, Q = 1 for ideal). For a water phantom with 15 cm diameter, for example, a cupping reduction from 10.8% down to 2.1% was achieved. The performance of the correction method has limitations in the case of measurements using non-ideal detectors, intensity calibration, etc. An iterative approach to overcome most of these limitations was proposed. This approach is based on root finding of a cupping metric and may be useful for other scatter correction methods as well. By this optimization, cupping of the measured water phantom was further reduced down to 0.9%. The algorithm was evaluated on a commercial system including truncated and non-homogeneous clinically relevant objects.


Use-dependent reduction and facilitation of Ca2+ current in guinea-pig myocytes.
1. Action potentials, calcium currents (iCa) and cell contraction have been recorded from single guinea-pig myocytes during periods of stimulation from rest. Voltage clamp was carried out using a single microelectrode. Cell contraction was measured optically. All experiments were performed at 18-22 degrees C. 2. An inverse relationship was observed between cell contraction and action potential duration or iCa. Mixed trains of action potentials and voltage clamp pulses preserved this relationship. Long voltage clamp pulses induced negative 'staircases' of iCa and positive 'staircases' of cell contraction. A facilitation of iCa was observed during repetitive stimulation with clamp pulses of 100 ms duration or less and was accompanied by a decrease in cell contraction. 3. The voltage dependence of inward current staircases was found to depend on Ca2+ entry rather than membrane voltage for long voltage clamp pulses and was not affected by 30 mM-TEA or 50 microM-TTX. Current reduction was greatest at 0 mV (P less than 0.05) when iCa was largest. Changes in cell contraction during pulse trains showed a similar voltage dependence. The time constant of current staircases was only mildly voltage dependent. 4. Interference with normal cellular mechanisms for Ca2+ uptake and release by strontium, 1-5 mM-caffeine and 1 microM-ryanodine increased current staircases and could abolish iCa facilitation with short clamp pulses. 5. Variations in the level of Ca2+-dependent inactivation of iCa can explain many features of the changes in iCa during stimulation after rest. Long clamp pulses (or action potentials) may increase cell Ca2+ loading and inhibit iCa. Short clamp pulses reduce available Ca2+ for cell contraction and this may reflect a lowered myoplasmic Ca2+ level which allows facilitation of iCa.


Renal regulation of plasma total antioxidant capacity.
Hyperuricemia has been labeled both a risk factor and marker for cardiovascular pathology in addition to being associated with gout and kidney disease. Uric acid in vitro acts as a potent antioxidant capable of scavenging hydroxy radicals and peroxynitrite and reacting with nitric oxide. Some clinical studies have provided evidence that, in vivo, uric acid is oxidized under conditions associated with high oxidant stress and may spare other antioxidants such as ascorbic acid. The plasma level of uric acid is controlled by the rates of production and excretion or degradation of uric acid. Under most circumstances, it is the renal clearance of uric acid which primarily determines the plasma concentration. Many factors of exogenous and endogenous origin can influence renal tubular absorption and secretion of uric acid. We suggest that renal urate clearance is not haphazard but regulated by an unknown signal that is issued in response to the level of oxidative stress. Since much cardiovascular pathology is now believed to have an inflammatory component and is associated with enhanced production of free radicals, the accompanying hyperuricemia may be viewed as a compensatory response of potential benefit.


Comparative evaluation of three identification systems for anaerobes.
The accuracy of two new 4-h identification systems for anaerobes, the AN-IDENT (Analytab Products, Plainview, N.Y.) and the RapID ANA (Innovative Diagnostic Systems, Inc., Atlanta, Ga.) was compared with that of the API 20A system (Analytab Products). A total of 132 clinical isolates were tested in each of the three systems. The overall accuracies at the genus and species level for the three systems were: API 20A, 68.9 and 56.8%, respectively; AN-IDENT, 90.2 and 73.5%; and RapID ANA, 93.9 and 81.8%. Improved identification of anaerobes with the AN-IDENT and the RapID ANA systems was observed for isolates of the genus Fusobacterium, Clostridium species other than Clostridium perfringens, non-spore-forming bacilli, and isolates of the genus Peptostreptococcus. Reproducibility studies demonstrated that the results of the individual test reactions in all three identification systems were reproducible when the interpretive guidelines of the manufacturer were followed precisely.


Comparative gene expression analysis of the engulfment and cell motility (ELMO) protein family in the mouse brain.
Engulfment and cell motility (ELMO) proteins bind to Dock180, a guanine nucleotide exchange factor (GEF) of the Rac family, and regulate GEF activity. The resultant ELMO/Dock180/Rac module regulates cytoskeletal reorganization responsible for the engulfment of apoptotic cells, cell migration, and neurite extension. The expression and function of Elmo family proteins in the nervous system, however, are not yet fully understood. Here, we characterize the comparative gene expression profiles of three Elmo family members (Elmo1, Elmo2, and Elmo3) in the brain of C57BL/6J mice, a widely used inbred strain, together with reeler mutant mice to understand gene expression in normal laminated brain areas compared with abnormal areas. Although all three Elmo genes showed widespread mRNA expression over various mouse tissues tested, Elmo1 and Elmo2 were the major types expressed in the brain, and three Elmo genes were up-regulated between the first postnatal week (infant stage) and the third postnatal week (juvenile, weaning stage). In addition, the mRNAs of Elmo genes showed distinct distribution patterns in various brain areas and cell-types; such as neurons including inhibitory interneurons as well as some non-neuronal cells. In the cerebral cortex, the three Elmo genes were widely expressed over many cortical regions, but the predominant areas of Elmo1 and Elmo2 expression tended to be distributed unevenly in the deep (a lower part of the VI) and superficial (II/III) layers, respectively, which also changed depending on the cortical areas and postnatal stages. In the dentate gyrus of the hippocampus, Elmo2 was expressed in dentate granule cells more in the mature stage rather than the immature-differentiating stage. In the thalamus, Elmo1 but not the other members was highly expressed in many nuclei. In the medial habenula, Elmo2 and Elmo3 were expressed at intermediate levels. In the cerebellar cortex, Elmo1 and Elmo2 were expressed in differentiating-mature granule cells and mature granule cells, respectively. In the Purkinje cell layer, Elmo1 and Elmo2 were expressed in Purkinje cells and Bergmann glia, respectively. Disturbed cellular distributions and laminar structures caused by the reeler mutation did not severely change expression in these cell types despite the disturbed cellular distributions and laminar structures, including those of the cerebrum, hippocampus, and cerebellum. Taken together, these results suggested that these three Elmo family members share their functional roles in various brain regions during prenatal-postnatal development.


Direct Synthesis of Controlled-Size Nanospheres inside Nanocavities of Self-Organized Photopolymerizing Soft Oxometalates [PW12 O40 ]n (n=1100-7500).
The unusual self-assembly of {(BMIm)2 (DMIm)[PW12 O40 ]}n (n=1100-7500) (BMIm=1-butyl-3-methylimidazolium, DMIm=3,3'-dimethyl-1,1'-diimidazolium) soft oxometalates (SOMs) with controlled size and a hollow nanocavity was exploited for the photochemical synthesis of polymeric nanospheres within the nanocavity of the SOM. The SOM vesicle has been characterized by using several techniques, including dynamic light scattering (DLS), static light scattering (SLS), attenuated total reflection (ATR) IR spectroscopy, Raman spectroscopy, microscopy, and zeta-potential analysis. The self-assembly and stabilization of this soft-oxometalate vesicle has been shown by means of counter-ion condensation. The immediate implication of such stabilization-the variation of the dielectric constant with the hydrodynamic radius of the vesicle-has been used to synthesize vesicles of controlled size. Such vesicles of varying size have been used as templates for polymerization reactions that produce polymeric spheres of controlled size. Direct evidence shows that the SOM behaves as a model heterogeneous catalytic system. Such surfactant- and initiator-free photochemical synthetic routes for obtaining uniform latex spheres could be used in the making of optical bandgap materials, inverse opals, and paints.


The effect of laser treatment on bonding between zirconia ceramic surface and resin cement.
The purpose of this in-vitro study was to evaluate and compare the effects of different surface treatments and laser irradiation on the shear bond strength of resin cement to zirconia-based ceramic. Forty zirconia core specimens (10-mm diameter, 2-mm thickness) were produced and embedded in the centers of autopolymerizing acrylic resin blocks. Subsequently, specimens were randomly divided into four groups, each containing 10 specimens, for different surface treatment methods. The details of the groups are as follows: Group C, no treatment applied (control); Group SB, bonding surfaces of ceramic disks were airborne particle-abraded with 110-μm alumina oxide particles; Group HF, bonding surfaces of ceramic disks were etched with 9.6% hydrofluoric acid; and Group L, bonding surfaces of ceramic disks were irradiated by a CO₂ laser. A total of 40 composite resin disks were fabricated and cemented with an adhesive resin cement to the specimen surfaces. A universal test machine was used for the shear bond strength test at a crosshead speed of 1 mm/min. The highest shear bond strength values were obtained with Group L (20.99 ± 3.77 MPa) and the lowest values with Group C (13.39 ± 3.10 MPa). Although there was no significant difference between Groups C, HF and SB (P > 0.05), Group L showed a significant difference from all other groups (p < 0.05). All surface treatment methods improved the bond strength between resin cement and the zirconium oxide ceramic surface. CO₂ laser etching may represent an effective method for conditioning zirconia surfaces, enhancing micromechanical retention and improving the bond strength of resin cement on zirconia ceramic.


Dermatology. Positioned for health care reform.
Dermatologic services will of necessity be a fundamental part of any quality, cost-conscious health care system because (1) we treat medically necessary and economically significant diseases, (2) our area of expertise includes a distinct body of medical knowledge over which no other health professional has comparable expertise, and (3) our services are provided in a cost-effective manner.


A short German Physical-Self-Concept Questionnaire for elementary school children (PSCQ-C): Factorial validity and measurement invariance across gender.
Research on children's physical self-concept (PSC) is increasingly recognised as an important field of psychology. However, there is a lack of instruments suitable for younger children at elementary school age. In the present study, a short German 21-item Physical Self-Concept-Questionnaire for children (PSCQ-C) was tested measuring seven specific facets of elementary school children's PSC (strength, endurance, speed, flexibility, coordination, physical appearance, global sport competence). A number of 770 elementary school children aged 8-12 years completed the PSCQ-C. Results showed good psychometric properties and high reliabilities of the seven scales. Confirmatory factor analysis revealed that the presumed 7-factor model fitted the data best compared to a global 1- and 2-factor model. Also, full measurement invariance was strongly established. Correlations among the seven scales were mainly moderate. Gender differences were suggestive of developmental trends that are consistent with prior studies. These results provide support that the PSCQ-C is a confidential instrument with sound psychometric properties measuring seven specific facets of elementary school children's PSC.


Blood-Brain Barrier Permeability: Is 5-Hydroxytryptamine Receptor Type 4 a Game Changer?
Serotonin affects many functions in the body, both in the central nervous system (CNS) and the periphery. However, its effect on the blood-brain barrier (BBB) in separating these two worlds has been scarcely investigated. The aim of this work was to characterize the serotonin receptor 5-HT4 in the hCMEC/D3 cell line, in the rat and the human BBB. We also examined the effect of prucalopride, a 5-HT4 receptor agonist, on the permeability of the hCMEC/D3 in an in vitro model of BBB. We then confirmed our observations by in vivo experiments. In this work, we show that the 5-HT4 receptor is expressed by hCMEC/D3 cells and in the capillaries of rat and human brains. Prucalopride increases the BBB permeability by downregulating the expression of the tight junction protein, occludin. This effect is prevented by GR113808, a 5-HT4 receptor antagonist, and is mediated by the Src/ERK1/2 signaling pathway. The canonical G-protein-dependent pathway does not appear to be involved in this phenomenon. Finally, the administration of prucalopride increases the diffusion of Evans blue in the rat brain parenchyma, which is synonymous with BBB permeabilization. All these data indicate that the 5-HT4 receptor contributes to the regulation of BBB permeability.


Archaeal communities in High Arctic wetlands at Spitsbergen, Norway (78 degrees N) as characterized by 16S rRNA gene fingerprinting.
Emissions of the greenhouse gas methane from Arctic wetlands have been studied extensively, though little is known about the ecology and community structure of methanogenic archaea that catalyze the methane production. As part of a project addressing microbial transformations of methane in Arctic wetlands, we studied archaeal communities in two wetlands (Solvatnet and Stuphallet) at Spitsbergen, Norway (78 degrees N) during two summer seasons. Directly extracted peat community DNA and enrichment cultures of methanogenic archaea were analyzed by nested PCR combined with denaturing gradient gel electrophoresis and subsequent sequencing of 16S rRNA gene fragments. Sequences affiliated with Methanomicrobiales, Methanobacteriaceae, Methanosaeta and Group I.3b of the uncultured crenarchaeota were detected at both sites. Sequences affiliated with Methanosarcina were recovered only from the site Solvatnet, while sequences affiliated with the euryarchaeotal clusters Rice Cluster II and Sediment 1 were detected only at the site Stuphallet. The phylogenetic affiliation of the recovered sequences suggested a potential of both hydrogenotrophic and acetoclastic methanogenesis at both sites. At Solvatnet, there were clear temporal trends in the archaeal community structure over the Arctic summer season. The archaeal community composition was significantly affected by factors influencing the activity of the overall bacterial community, as measured by in situ emissions of CO2. Methane emissions at both sites were influenced more by peat temperatures and thaw depth than by the archaeal community structure. Enrichment cultures for methanogenic archaea determined that most of the methanogens detected directly in peat could grow in culture at 10 degrees C. Culture based biases were indicated in later enrichment steps by the abundant growth of a Methanosarcina strain that was not detected directly in peat samples.


Microvascular disturbances, thrombosis, and bleeding in thrombocythemia: current concepts and perspectives.
Although ET is a relatively rare disease and, in general, life expectancy of patients is similar to that of individuals without the disease, hemostatic complications are the major causes of mortality and morbidity in some patients. Hemostatic complications are most likely due to as yet poorly defined abnormalities in platelet-vessel wall interactions. Treatment modalities used in the past include cytoreductive therapy and antiplatelet therapy, although the basis of their use has been, until recently, only retrospective observations and not prospective, randomized clinical trials. The older therapeutic modalities, such as radiophosphorus (32P) and alkylating agents, have been largely abandoned because of their leukemogenic potential. The leukemogenic potential of hydroxyurea, presently the most widely used cytoreductive agent, remains uncertain. Interferon-alpha and anagrelide are promising newer drugs. However, because of the toxicity of these agents, there is a pressing need for prospective, controlled clinical trials to establish the indications for cytoreductive and antiplatelet therapy in different subsets of patients with ET. Ultimately, it can be anticipated that elucidation of the molecular basis of ET will permit specific targeting of therapy to the pathogenetic megakaryopoietic defect(s) in the disease.


How to make sure your older patients are getting enough zinc.
Older patients with inadequate dietary habits tend to be at risk for mild to moderate zinc deficiency. Symptoms that can be of particular concern include slow wound healing, increased risk of infection, and a loss of acuity in taste and smell. The diagnosis of zinc deficiency is based on a review of the patient's eating habits; laboratory testing is not generally useful in the clinical setting. Most older adults can achieve an adequate zinc intake by eating a variety of foods each day, including meat, fish, and poultry. Supplementation is appropriate in cases of known or suspected frank zinc deficiency.


Opioids in the Management of Acute Pediatric Pain: An Update in a Time of Crisis.
Management of acute pain in children is fundamental to our practice. Its myriad benefits include reduced suffering, improved patient satisfaction, more rapid recovery, and a reduced risk of developing postsurgical chronic pain. Although a multimodal analgesic approach is now routinely used, informed and judicious use of opioid receptor agonists remains crucial in this treatment paradigm, as long as the benefits and risks are fully understood. Further, an ongoing public health response to the current opioid crisis is required to help prevent new cases of opioid addiction, identify opioid-addicted individuals, and ensure access to effective opioid addiction treatment, while at the same time continuing to safely meet the needs of patients experiencing pain.


Parenting support and PTSD in children of a war zone.
The protective role of parenting factors on the mental well-being of children exposed to war trauma remains an under-researched area. To establish the relationship between perceived positive parenting support and post-traumatic stress disorder (PTSD) symptoms in children exposed to war trauma. A random sample of 412 children aged 12-16 years was selected from the Gaza Strip and was assessed using the Gaza Traumatic Events Checklist (GTEC), the SCID (DSM-IV) and the Perceived Parenting Support Scale (PPSS). Palestinian children were exposed to different types of war-traumatic events. The number of exposed traumatic events was independently associated with the severity of post-traumatic symptoms scores or the diagnosis of PTSD, while perceived parenting support was found to act as a protective factor in this association. Interventions in war zones need to ensure the minimal possible disruption to communities and family units, and to involve parents in preventive or treatment programmes for children exposed to trauma.


Nicotinic acetylcholine receptors have ligand-specific attachment point patterns.
Employing a panel of synthetic peptides as representative structural elements of the nicotinic acetylcholine receptor from Torpedo electric organ, we recently identified three sequence regions of the receptor (alpha 55-74, alpha 134-153 and alpha 181-200) serving as subsites for the binding of high molecular weight antagonists of acetylcholine (Conti-Tronconi et al. 1990). The relative binding affinities to these subsites of alpha-bungarotoxin and three competitive antibodies varied in a ligand-specific fashion. Employing a set of homologous synthetic peptides differing from alpha 181-200 by the exchange of single amino acid residues along the sequence, we now find that ligand binding crucially depends on the presence of particular amino acids within the subsite while others influence binding only marginally if at all. The existence of ligand-specific attachment points may account for the wide range in binding and kinetic parameters, pharmacological specificity and distinct mean open times of the receptor-integral cation channel observed for cholinergic ligands.


Factors Associated with Intermittent Preventive Treatment of Malaria During Pregnancy in Mali.
Intermittent preventive treatment in pregnancy (IPTp) with 3 or more doses of sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization to prevent malaria in pregnant women living in high-risk areas. According to the 2015 malaria indicator survey in Mali, malaria prevalence is 34.6%. The high risk of malaria among pregnant women and children led the Malian government to provide free SP during antenatal clinics visits. The Malian National Program of Malaria Control recommends at least 3 doses during pregnancy. The proportion of pregnant women taking 3 or more doses of IPTp-SP (IPTp 3+) still remains low. In Mali, only 36.7% of pregnant women with a live birth in the past 2 yr received IPTp 3+. To investigate the factors associated with this low coverage, we carried out a secondary data analysis using the database of the Mali 2015 Malaria Indicator Survey. Multiple logistic regression was used to analyze these factors among 2,382 interviewed women. Taking less than 3 doses was higher among women below 20 yr (adjusted odds ratio [AOR] = 1.43, 95% confidence interval [CI, 1.03; 1.98]); however, media accessibility (listening to radio) (AOR = 0.71, 95% CI [0.53-0.95]) and residing in Segou (AOR = 0.56, 95% CI [0.35-0.90]) seem to favor the opposite after adjusting the potential confusion. Residence, educational level, and wealth index were not statistically associated with taking 3 doses of IPTp-SP. This study identifies that women less than 20 yr of age were significantly associated with taking lower than 3 doses of IPTp-SP.


[Closed loop intestinal obstruction: role of computerized tomography].
The obstruction of a bowel segment at both ends results in a closed loop obstruction. Progression to strangulation frequently occurs if surgical intervention is delayed. The role of plain radiography in the diagnosis of closed loop obstruction and strangulation has been shown to be limited, while the recent literature has demonstrated the growing role of computed tomography (CT). This paper reports our experience in the study of closed loop obstruction by CT. The CT studies of 12 patients with surgically confirmed closed loop obstruction were retrospectively reviewed. The following CT signs were used for the diagnosis: a) fluid-filled distended loops, b) C-shaped incarcerated loop, c) radial distribution of several dilated bowel loops and mesenteric vessels converging toward the point of obstruction, d) triangular or fusiform tapering of the closed loop and/or whirl sign in the site of obstruction. On the basis of these signs, the diagnosis was made in 11 of 12 patients. Only 1 patient, who had a negative CT study, was positive at a subsequent enteroclysis. CT findings of strangulation were associated in 3 cases: slight wall thickening with vascular congestion and mesenteric ascites, confirmed at surgery. Small bowel obstruction can be distinguished into simple and closed loop obstructions. The latter is a more severe condition which is often complicated by strangulation with vascular impairment, edema and intramural and mesenteric hemorrhage. Consequent arterial insufficiency rapidly leads to ischemia, infarction and necrosis. The radiologist plays a role in the early recognition of the closed loop obstruction and of any sign of strangulation. The role of CT in the diagnosis and workup of patients with suspected intestinal occlusion has been analyzed in the literature with reported 63% sensitivity, 78% specificity and 66% accuracy. CT is also capable of revealing the causes of occlusion in 73-95% of cases. The above CT signs, as confirmed in our experience, allow to identify closed loop obstruction and also small bowel strangulation, thus supplying a valuable contribution to diagnosis and accurate preoperative evaluation. We conclude that CT can accurately demonstrate the presence of closed loop obstruction and can be the technique of choice in patients in whom obstruction is associated with clinical signs suggestive of strangulation.


An optical cloak made of dielectrics.
Invisibility devices have captured the human imagination for many years. Recent theories have proposed schemes for cloaking devices using transformation optics and conformal mapping. Metamaterials, with spatially tailored properties, have provided the necessary medium by enabling precise control over the flow of electromagnetic waves. Using metamaterials, the first microwave cloaking has been achieved but the realization of cloaking at optical frequencies, a key step towards achieving actual invisibility, has remained elusive. Here, we report the first experimental demonstration of optical cloaking. The optical 'carpet' cloak is designed using quasi-conformal mapping to conceal an object that is placed under a curved reflecting surface by imitating the reflection of a flat surface. The cloak consists only of isotropic dielectric materials, which enables broadband and low-loss invisibility at a wavelength range of 1,400-1,800 nm.


National Trends in Oral Antibiotic Prescribing in United States Physician Offices from 2009 to 2016.
Prior studies have found that outpatient antibiotics are commonly prescribed for non-bacterial conditions. It is unclear if national prescribing has changed in recent years given recent public health and antimicrobial stewardship initiatives. This study aimed to describe antibiotic prescribing in United States (U.S.) physician offices. This was a cross-sectional study of all sampled patient visits in the Centers for Disease Control and Prevention's National Ambulatory Medical Care Survey from 2009 to 2016. Antibiotic use was defined as at least one oral antibiotic prescription during the visit as identified by Multum code(s). Patient visits were categorized by U.S. geographic region and season. ICD-9-CM and ICD-10 codes were used to assess diagnoses and categorize antibiotic use as appropriate, possibly appropriate, or inappropriate. Seven billion visits were included for analysis, with 793,415,182 (11.3%) including an antibiotic. Prescribing rates were relatively stable over the study period (102.9-124.9 prescriptions per 1000 visits); however, 2016 had one of the lowest prescribing rates (107.7 per 1000 visits). The most commonly prescribed antibiotic class was macrolides (25 per 1000 visits). The South region and winter season had the highest antibiotic prescribing (118.2 and 129.7 per 1000 visits, respectively). Of patients who received an antibiotic, 55.9%, 35.7%, and 8.4% were classified as inappropriate, possibly appropriate, and appropriate, respectively. The most common conditions in which antibiotics were prescribed inappropriately included those with no indication in any of the predefined diagnosis codes (40.1%), other skin conditions (17.3%), and viral upper respiratory conditions (13.3%). There was no significant reduction in outpatient antibiotic prescribing rates among U.S. outpatients from 2009 to 2016 and prescribing varied by region and season. These data suggest that more than half of antibiotics were prescribed inappropriately, with the majority of antibiotics prescribed with no indication. However, these findings need to be confirmed with robust prospective studies.


Three-dimensional power doppler ultrasound is useful to monitor the response to treatment in a patient with primary papillary serous carcinoma of the peritoneum.
To date, this is the first report to monitor changes of intratumor vascularization and the response to radiation and Cyberknife therapy in a patient with recurrent primary papillary serous carcinoma of the peritoneum by three dimensional (3D) power Doppler ultrasonography (PDUS). Transvaginal 3D PDUS detected a recurrent presacral tumor with abundant intratumor vascularity. Serial examinations of the tumor volume and serum CA-125 level were studied before, during, and 6 mo after therapy. Meanwhile, the intratumor blood flow was measured and expressed as vascularity indices. All of the tumor volume, intratumor vascularity indices and serum CA-125 level decreased progressively following therapy. A remaining lesion with nearly absent intratumor power Doppler signals suggested a scarring lesion posttreatment. Indeed, CT-guided tissue biopsy confirmed fibrotic change. 3D PDUS is useful to monitor the response to treatments and to differentiate residual tumors from lesions of scarring change posttreatment. It provides more accurate posttreatment information than pelvic computed tomography.


Speech-in-noise perception in musicians and non-musicians: A multi-level meta-analysis.
Speech-in-noise perception, the ability to hear a relevant voice within a noisy background, is important for successful communication. Musicians have been reported to perform better than non-musicians on speech-in-noise tasks. This meta-analysis uses a multi-level design to assess the claim that musicians have superior speech-in-noise abilities compared to non-musicians. Across 31 studies and 62 effect sizes, the overall effect of musician status on speech-in-noise ability is significant, with a moderate effect size (g = 0.58), 95% CI [0.42, 0.74]. The overall effect of musician status was not moderated by within-study IQ equivalence, target stimulus, target contextual information, type of background noise, or age. We conclude that musicians show superior speech-in-noise abilities compared to non-musicians, not modified by age, IQ, or speech task parameters. These effects may reflect changes due to music training or predisposed auditory advantages that encourage musicianship.


Postcardiopulmonary bypass lung edema. A preventable complication?
Potential etiologic factors of postcardiopulmonary bypass (post-CPB) lung edema (LE) were investigated (phase 1 study). Further patient treatment was modified according to the results of phase 1 study and the influence that these changes had on the incidence of the complication was assessed (phase 2 study). In phase 1 study, among 100 patients who underwent coronary bypass graft surgery, prolonged assisted ventilation was required for severe LE in 7 cases, and 6 patients had a moderate form of LE. Patients who suffered from severe LE had left and right ventricular dysfunction and normal pulmonary vascular resistance. Three predictors of LE were evidenced by logistic regression analysis: number of bypass grafts completed with internal mammary arteries (p = 0.013), transfusions of blood collected in mobile units (p = 0.014), and the combination of a significant lesion of the left main stem and the right coronary artery at preoperative angiography (p = 0.040). In phase 2 study, a further group of 100 patients was treated differently by improving myocardial protection during surgery, achieving a higher rectal temperature at the end of CPB, and reducing the amount of transfusions. This resulted in only one case of LE (p < 0.001). In conclusion, the cases of post-CPB LE evidenced in our study were related to postoperative ventricular dysfunction and blood transfusions. Any means of improving postoperative hemodynamic stability and reducing the need for transfusions could thus prevent the latter complication.


Electronic and hydrogen bonding effects on the chain-breaking activity of sulfur-containing phenolic antioxidants.
A kinetic and thermodynamic investigation of phenols para-substituted with thiyl (SR), sulfinyl (SOR), and sulfonyl (SO(2)R) groups and ortho-substituted with thiyl groups is reported. The effect of the sulfur substituents on the O-H bond dissociation enthalpy values, BDE(O-H), was measured by means of the EPR radical equilibration technique and the reactivity toward peroxyl radicals, k(inh), of these phenolic antioxidants was determined by inhibited autoxidation studies. An inverse correlation between these two parameters was found. A p-SMe substituent decreased the BDE(O-H) value to a lesser extent than a p-OMe group (-3.6 vs -4.4 kcal/mol), whereas the effect of the same groups in an ortho position showed an opposite trend (-0.85 vs -0.2 kcal/mol). The latter result is explained in terms of the different strength of the intramolecular hydrogen bond between the OH proton and the sulfur or oxygen substituents in ortho derivatives. ESI-MS analysis of the products formed by reacting the sulfides with peroxyl radicals from the azoinitiator AIBN revealed the formation of a complex mixture of products, which may play an important role in determining the overall antioxidant activity of the parent compounds.


Purification and measurement of abscisic Acid and indoleacetic Acid by high performance liquid chromatography.
A procedure was selected for the simultaneous extraction and purification of abscisic acid (ABA) and indoleacetic acid (IAA). Unnecessary steps were eliminated and an accumulation of aqueous phase was avoided. The superior performance of diethyl ether (compared to ethyl acetate) for bulk purification and the superior resolution provided by 250 millimeter columns packed with 5-micrometer spherical particles of strong anion exchanger and octadecylsilane (C18) greatly facilitated the purification of samples. A fixed-wavelength (254 nanometer) ultraviolet detector and a fluorescence detector connected in series on a high performance liquid chromatograph permitted nondestructive monitoring and measurement of ABA and IAA. Derivatization was not necessary for chromatography or for detection. Isocratic elution with simple mobile phases gave sharp peaks. A few simple precautions minimized losses. Recoveries through the entire procedure averaged about 75% for ABA and about 50% for IAA. Purified ABA and IAA fractions were usually free of interfering contaminants. Identities were confirmed by gas chromatography-mass spectrometry.


Objective Measures of Near Viewing and Light Exposure in Schoolchildren during COVID-19.
Wearable sensors provide the opportunity for continuous objective measurement of the visual environment with high resolution. Our findings show that absolute and temporal properties of near viewing and time outdoors vary between myopic and nonmyopic schoolchildren, which are important considerations when studying refractive error pathogenesis. Numerous behavioral factors, including near work, time outdoors, electronic device use, and sleep, have been linked to myopia. The purpose of this study was to assess behaviors using subjective and objective methods in myopic and nonmyopic schoolchildren in the United States. Forty children (aged 14.6 ± 0.4 years) simultaneously wore two sensors for 1 week, a Clouclip for objective measurement of near viewing and light exposure and an Actiwatch for objective measurement of activity and sleep. Parents completed an activity questionnaire for their child. Near-viewing distance, daily duration, short-duration (>1 minute) and long-duration (>30 minutes) near-viewing episodes, light exposure, time outdoors, electronic device use, and sleep duration were analyzed by refractive error group and day of the week. Objectively measured daily near-viewing duration was 6.9 ± 0.3 hours. Myopes spent more time in near + intermediate viewing than nonmyopes (P = .008) and had higher diopter hours (P = .03). Short- and long-duration near-viewing episodes were similar between groups (P < .05 for both). Daily light exposure and time outdoors were significantly lower for myopes (P < .05 for both). Electronic device use (12.0 ± 0.7 hours per day) and sleep duration (8.2 ± 0.2 hours per night) were similar between groups (P > .05 for both). Objective and subjective measures confirm that myopic and nonmyopic schoolchildren exhibit different behaviors. Combining wearable sensors with questionnaires provides a comprehensive description of children's visual environment to better understand factors that contribute to myopia.


The effect of varying cuff position on recording ankle systolic blood pressure.
Ankle brachial pressure index (ABPI) aids the diagnosis of leg ulcer aetiology, although there is potential for patient anxiety or discomfort when the cuff is placed over an ulcerated ankle. This study aimed to ascertain any differences in systolic pressure if the cuff is positioned proximal to the ankle and to determine the feasibility of varying the cuff position to avoid ulcerated areas. The systolic blood pressure in the lower limbs of healthy volunteers (n = 60) was measured with the cuff at two discrete sites on the lower limb. There was a statistical difference in systolic blood pressure readings between the two sites (0-4 mmHg; p = 0.02) and a statistically significant ABPI difference (-0.08 to 0.05; p < 0.002). Blood pressure recording is subject to considerable variation in clinical practice and the ABPI has to vary by more than 0.15 to be clinically significant. Therefore, the differences in systolic pressure between sites and the ABPI calculations are not clinically significant in this study. An additional finding was that some subjects found the upper cuff position uncomfortable during the procedure.


Identification and characterization of positive regulatory elements in the human glyceraldehyde 3-phosphate dehydrogenase gene promoter.
The gene for glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is expressed at high levels in almost all tissues. However, the molecular mechanism which sustains high-level expression of this house-keeping enzyme is still unknown. Here we show that transcriptional activity is reduced by deletion of the nucleotides from -181 to -144 (relative to the transcriptional start site) in the promoter of human GAPDH gene, both in CHO (derived from Chinese hamster ovary) and HepG2 (derived from human hepatoma) cells. Gel retardation assays revealed that at least two nuclear factors, termed GAPBF1 and GAPBF2, bind to this region. Mutations in the GAPBF1 binding site (-178 to -169) or the GAPBF2 binding site (-168 to -163) reduced this promoter activity in vivo, showing that these two sites contribute to the activity of the GAPDH gene promoter. Since mutations in the region from -162 to -146 also reduced the promoter activity, this region seemed to function as an added cis-element, although we failed to find a factor that interacted specifically with this region in vitro. Accordingly, we propose that there are multiple cis-elements in the region from -181 to -144, each of which contributes to the promoter activity of GAPDH gene; the GAPBF1 binding site has the unique feature of having a stretch of repeated A nucleotides.


Two-Way Alloying and Dealloying of Cadmium in Metalloid Gold Clusters.
The alloying of monometal nanoparticles with a transition element has recently attracted extensive interest; however, the dealloying of alloy nanoparticles has rarely been reported. Two-way alloying and dealloying in metal nanoparticles is not known so far to the best of our knowledge. In this work, for the first time, we successfully achieved two-way alloying and dealloying of cadmium in metalloid gold clusters via an antigalvanic reaction in combination with a quasi-antigalvanic reaction and demonstrated reactant-ion-dependent dealloying as well.


Cerebellar metastasis from clear cell sarcoma of the kidney. A case report with immunohistochemistry.
The aim of this study was to describe a child with a right cerebellar hemisphere metastasis from primary clear cell sarcoma of the kidney without evidence of bone metastases, and to investigate the immunohistochemical features of primary and metastatic tumors. A 12-month old boy was admitted our hospital due to an abdominal mass. Abdominal computed tomography revealed a large right renal tumor. Tumor was removed with nephrectomy. Histopathologic examination of tumor revealed clear cell sarcoma of the kidney. The patient received radiotherapy and chemotherapy in postoperative period. He suffered from gait disturbance and confusion 8 months later. A computed tomography scan revealed a tumor that was enhanced with contrast medium at right cerebellar hemisphere concomitant with ventricular enlargement. After ventriculo-peritoneal shunting procedure, tumor was excised totally and histopathologic diagnosis showed metastasis of clear cell sarcoma of the kidney. Immunohistochemically vimentin, actin, desmin, neuron specific enolase, cytokeratin, P 53, Ki-67 and P-170 were performed using formalin fixed, paraffin embedded sections. Both of the tumors were positive for vimentin and negative for desmin, actin, neuron specific enolase, cytokeratin and P 53. Scattered nuclei were stained by Ki-67 in primary and metastatic cerebellar tumor. Both primary and metastatic tumors were negative for p53 and P-170. The treatment consisted of surgery, radiotherapy and chemotherapy. The patient is alive and well without evidence of recurrence 16 months after second surgery. Clear cell sarcoma of the kidney is most commonly associated with bone metastasis. Cerebellar metastasis of clear cell sarcoma of the kidney is very unusual. To the best of our knowledge, this patient is second case in the English literature. With review of the literature, our immunohistochemical findings support the theory that relapse and metastasis of primary clear cell sarcoma of the kidney are not related with increase of aggressiveness.


Design, synthesis and PASS assisted evaluation of novel 2-substituted benzimidazole derivatives as potent anthelimintics.
Two series of compounds (AB and APB) bearing substituted phenoxy groups at 2-position of benzimidazole nucleus through amino or phenyleneamino were synthesized and evaluated through PASS software for predicting the activity spectrum of each compound. All compounds of both the series were predicted to have potent anthelmintic activity. The activity of each compound was evaluated experimentally at the concentrations of 0.1, 0.2 and 0.5% in terms of mortality time and paralysis time of the helminthes and was found to comply with the PASS predicted activity. In general, all compounds of APB series were more potent than those of AB series probably due to the additional hydrophobic interactions of the spacer phenyl ring in the APB series. The activity of all compounds was found to increase with increasing concentration. The compound with p-chlorophenoxy moiety was the most active from the APB series (mortality time 5.7±0.4 min and paralysis time 3.1±0.3 min) and equipotent to albendazole (mortality time 5.4±0.1 min and paralysis time 2.8±0.2 min) at concentration of 0.2%. The o-chlorophenoxy analogs in both the series were found to be the least active of all. Based on these results, a substituent capable of binding with the receptor through van der Waals and/or electronic interactions at 4-position of the phenoxy ring in the compound is suggested to increase binding interaction leading to potent anthelmintic activity.


Translating research findings to promote peace: moving from "field to forum" with verbatim theatre.
Peace, both personal and global, resides in understanding. Verbatim theatre is introduced as a vehicle for translating research findings to promote understanding and thereby, promote health. By shifting our translation lens from "bench to bedside" to "field to forum," new opportunities arise for moving nursing research-findings to an engaged audience. Stories from Pearl Harbor and Hiroshima survivors were woven into the verbatim performance, With Their Voices Raised. Analysis of audience members' reflections after the performance suggests that verbatim theatre created a connection based in openness, engagement, and trust that informed understanding and raised awareness about peace processes.


The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure.
Although the incidence of Gram-positive sepsis has risen strongly, it is unclear how Gram-positive organisms (without endotoxin) initiate septic shock. We investigated whether two cell wall components from Staphylococcus aureus, peptidoglycan (PepG) and lipoteichoic acid (LTA), can induce the inflammatory response and multiple organ dysfunction syndrome (MODS) associated with septic shock caused by Gram-positive organisms. In cultured macrophages, LTA (10 micrograms/ml), but not PepG (100 micrograms/ml), induces the release of nitric oxide measured as nitrite. PepG, however, caused a 4-fold increase in the production of nitrite elicited by LTA. Furthermore, PepG antibodies inhibited the release of nitrite elicited by killed S. aureus. Administration of both PepG (10 mg/kg; i.v.) and LTA (3 mg/kg; i.v.) in anesthetized rats resulted in the release of tumor necrosis factor alpha and interferon gamma and MODS, as indicated by a decrease in arterial oxygen pressure (lung) and an increase in plasma concentrations of bilirubin and alanine aminotransferase (liver), creatinine and urea (kidney), lipase (pancreas), and creatine kinase (heart or skeletal muscle). There was also the expression of inducible nitric oxide synthase in these organs, circulatory failure, and 50% mortality. These effects were not observed after administration of PepG or LTA alone. Even a high dose of LTA (10 mg/kg) causes only circulatory failure but no MODS. Thus, our results demonstrate that the two bacterial wall components, PepG and LTA, work together to cause systemic inflammation and multiple systems failure associated with Gram-positive organisms.


Ultrasonically assisted evaluation of the impact of atherosclerotic plaque on the pulse pressure wave propagation: a clinical feasibility study.
The purpose of this work was to evaluate ultrasound modality as a non-invasive tool for determination of impact of the degree of the atherosclerotic plaque located in human internal carotid arteries on the values of the parameters of the pulse wave. Specifically, the applicability of the method to such arteries as brachial, common, and internal carotid was examined. The method developed is based on analysis of two characteristic parameters: the value of the mean reflection coefficient modulus |Γ|(a) of the blood pressure wave and time delay Δt between the forward (travelling) and backward (reflected) blood pressure waves. The blood pressure wave was determined from ultrasound measurements of the artery's inner (internal) diameter, using the custom made wall tracking system (WTS) operating at 6.75 MHz. Clinical data were obtained from the carotid arteries measurements of 70 human subjects. These included the control group of 30 healthy individuals along with the patients diagnosed with the stenosis of the internal carotid artery (ICA) ranging from 20% to 99% or with the ICA occlusion. The results indicate that with increasing level of stenosis of the ICA the value of the mean reflection coefficient measured in the common carotid artery, significantly increases from |Γ|(a)=0.45 for healthy individuals to |Γ|(a)=0.61 for patients with stenosis level of 90-99%, or ICA occlusion. Similarly, the time delay Δt decreases from 52 ms to 25 ms for the respective groups. The method described holds promise that it might be clinically useful as a non-invasive tool for localization of distal severe artery narrowing, which can assist in identifying early stages of atherosclerosis especially in regions, which are inaccessible for the ultrasound probe (e.g. carotid sinus or middle cerebral artery).


Risk of substance abuse and dependence among young adult sexual minority groups using a multidimensional measure of sexual orientation.
We examined associations between two definitions of sexual minority status (SMS) and substance abuse and/or dependence among young adults in a national population. A total of 14,152 respondents (7,529 women and 6,623 men) interviewed during wave four of the National Longitudinal Study of Adolescent Health were included in the study (age range: 24-32 years). We used two definitions of SMS based on self-reported attraction, behavior, and identity: 1-indicator SMS (endorsing any dimension) and 3-indicator SMS (endorsing all dimensions). Outcomes included nicotine dependence as well as ≥3 signs of substance dependence, any sign of substance abuse, and lifetime diagnosis of abuse or dependence for alcohol, marijuana, and a composite measure of other drugs. Weighted logistic regression models were fit to estimate the odds of each outcome for each of the sexual minority groups (compared with the heterosexual majority), controlling for sociodemographic covariates. SMS women were more likely than exclusively heterosexual women to experience substance abuse and dependence, regardless of substance or SMS definition. In adjusted models for women, 3-indicator SMS was most strongly associated with abuse/dependence (adjusted odds ratio [AOR] range: 2.74-5.17) except for ≥3 signs of cannabis dependence, where 1-indicator SMS had the strongest association (AOR=3.35). For men, the 1-indicator SMS group had higher odds of nicotine dependence (AOR=1.35) and the 3-indicator SMS group had higher odds of ≥3 signs of alcohol dependence (AOR=1.64). Young adult female sexual minority groups, regardless of how defined, are at a higher risk than their heterosexual peers of developing alcohol, drug, or tobacco abuse and dependence.


Precise quantification of mixtures of bispecific IgG produced in single host cells by liquid chromatography-Orbitrap high-resolution mass spectrometry.
Bispecific IgG are heterotetramers comprising 2 pairs of heavy and light chains. Co-expression of the 4 component chains in a single host cell typically yields the desired bispecific IgG plus up to 9 additional incorrect chain pairings. Several protein engineering strategies have been reported to facilitate the heterodimerization of antibody heavy chains or cognate pairing of antibody heavy and light chains. These technologies have been used to direct the efficient assembly of bispecific IgG in single host cells and minimize unwanted chain pairings. When purifying bispecific IgGs, the identification and quantification of low levels of closely related IgG contaminants are substantial analytical challenges. Here we have developed a robust high-throughput method for quantitative analysis of bispecific IgG preparations using novel online liquid chromatography in conjunction with an extended mass range Orbitrap-based high-resolution mass spectrometer. A mathematical method was developed to estimate the yields of the 2 isobaric species, namely the desired bispecific IgG and the light chain-scrambled IgG. The analytical methods described herein are anticipated to be broadly applicable to the development of bispecific IgG as drugs and potentially to other complex next-generation biotherapeutics.


Two Hypervirulent Klebsiella pneumoniae Isolates Producing a blaKPC-2 Carbapenemase from a Canadian Patient.
This report describes two hypervirulent Klebsiella pneumoniae isolates that produced K. pneumoniae carbapenemase (KPC), which were identified from a rectal swab and a urine culture upon hospital admission. The patient had recently traveled to Greece, where he was hospitalized. The isolates were sequence type 86 and contained an IncHI1B IncFIBK hypervirulent plasmid and an IncFIIK plasmid harboring KPC.


Observation of Au2H- impurity in pure gold clusters and implications for the anomalous Au-Au distances in gold nanowires.
Au(2)H(-) was recognized and confirmed as a minor contamination to typical photoelectron spectra of Au(2) (-), produced by laser vaporization of a pure Au target using an ultrahigh purity helium carrier gas. The hydrogen source was shown to be from trace H impurities present in the bulk gold target. Carefully designed experiments using H(2)- and D(2)-seeded helium carrier gas were used to study the electronic structure of Au(2)H(-) and Au(2)D(-) using photoelectron spectroscopy and density functional calculations. Well-resolved photoelectron spectra with vibrational resolution were obtained for Au(2)H(-) and Au(2)D(-). Two isomers were observed both experimentally and theoretically. The ground state of Au(2)H(-) turned out to be linear with a terminal H atom [Au-Au-H](-) ((1)A(1),C(infinity v)), whereas a linear [Au-H-Au](-) ((1)A(1),D(infinity h)) structure with a bridging H atom was found to be a minor isomer 0.6 eV higher in energy. Calculated electron detachment energies for both isomers agree well with the experimental spectra, confirming their existence in the cluster beam. The observation and confirmation of H impurity in pure gold clusters and the 3.44 A Au-Au distance in the [Au-H-Au](-) isomer presented in the current work provide indirect experimental evidence that the anomalous 3.6 A Au-Au distances observed in gold nanowires is due to an "invisible" hydrogen impurity atom.


In vitro anti-inflammatory and anti-proliferative activity of sulfolipids from the red alga Porphyridium cruentum.
A sulfoglycolipidic fraction (SF) isolated from the red microalga Porphyridium cruentum was analyzed for fatty acid composition and assayed for ability to inhibit, in vitro, the generation of superoxide anion in primed leucocytes and the proliferation of a panel of human cancer cell-lines. Results demonstrated that SF contained large amounts of palmitic acid (26.1%), arachidonic acid (C20: 4 omega-6, 36.8%), and eicopentaenoic (C20:5 omega-3, 16.6%) acids, and noticeable amounts of 16:1n-9 fatty acid (10.5%). It strongly inhibited both the production of superoxide anion generated by peritoneal leukocytes primed with phorbol myristate acetate (IC(50): 29.5 microg/mL), and the growth of human colon adenocarcinoma DLD-1 and to a lesser extent of human breast adenocarcinoma MCF-7, human prostate adenocarcinoma PC-3, and human malignant melanoma M4 Beu cell-lines, and therefore might have a chemopreventive or chemotherapeutic potential, or both. It was found markedly more cytotoxic than sulfoquinovosyldiacylglycerols from plant used as a standard (STD), due to a stronger ability to inhibit DNA alpha-polymerase (IC(50): 378 microg/mL, vs 1784 microg/mL for STD). After a 48-h continuous treatment, IC(50) values for growth inhibition were in the range of 20-46 microg/mL instead of 94 to >250 microg/mL for STD, and those for inhibition of metabolic activity were in the range of 34-87 microg/mL instead of >250 microg/mL for STD. The higher anti-proliferative effect was observed on colon adenocarcinoma DLD-1 cells, and the weaker effect was observed on breast adenocarcinoma MCF-7.


Separating atrial flutter from atrial fibrillation with apparent electrocardiographic organization using dominant and narrow F-wave spectra.
The purpose of this study was to separate atrial flutter (AFL) with atypical F waves from fibrillation (AF) with "apparent organization." We hypothesized that F-wave spectra should reveal a dominant and narrow peak in AFL, reflecting its single macro-re-entrant wave front, but broad spectra in AF, reflecting multiple wave fronts. We identified 39 patients with electrocardiograms (ECGs) of "AFL/AF" or "coarse AF" from 134 consecutive patients referred for ablation: 21 had AFL (18 atypical, 3 typical), 18 had AF, and all were successfully ablated. Filtered atrial ECGs were created by cross-correlating F waves to successive ECG time points. Dominant peaks between 3 and 10 Hz were identified from power spectra of X (lead V5), Y (aVF), and Z (V1) axes, and for each, we calculated height (relative to two adjacent spectral points) and area ratio to envelopes of bandwidth 0.625, 1.25, 2.5, 3.75, and 5 Hz (range 0 to 1, where higher ratios reflect narrower peaks). Dominant peaks had greater relative height for AFL than AF (three-axis mean: 14.2 +/- 6.4 dB vs. 6.6 +/- 2.1 dB; p < 0.001). Peak area ratios were also higher for AFL than AF for all envelopes (p < 0.001). For the 2.5-Hz envelope, the separation (0.61 +/- 0.14 vs. 0.35 +/- 0.05, respectively; p < 0.001) enabled a ratio > or =0.44 to identify all cases of AFL from AF (p < 0.001). A panel of seven cardiologists blinded to clinical data provided lower diagnostic accuracy (82.1%; p < 0.01). In ambiguous ECGs with atypical F waves, spectral evidence for a solitary activation cycle separates AFL from AF with "apparent organization." This approach might improve bedside ECG diagnosis and shed light on intra-atrial organization of both rhythms.


Case report. CT and ultrasound of gastric and duodenal duplications.
We present the radiological findings of gastric and duodenal duplications in four adults, in whom abdominal ultrasound, endoscopic ultrasound (EUS), and CT were primarily used for diagnosis. The diagnosis was surgically confirmed in all cases. Preoperative diagnosis of duplications was possible with ultrasound in three patients, in whom CT showed a nonspecific cystic structure. Ultrasound demonstrated a pathognomonic multilayered wall appearance suggestive of a digestive origin, including an echogenic inner mucosal layer and a hypoechoic muscular layer, better appreciated using EUS in one patient. In one case, digestive origin was confirmed by direct visualization of a peristaltic activity within the cystic wall after water ingestion. In the last patient, a non-specific heterogeneous mainly solid mass of the esophagogastric junction was found to be an adenocarcinoma arising from a duplication on the histological analysis of the surgical specimen.


Application of atomic Hirshfeld surface analysis to intermetallic systems: is Mn in cubic CeMnNi4 a thermoelectric rattler atom?
The Mn atom in the cubic polymorph of CeMnNi(4) appears to be located in an oversized cage-like structure, and anomalously large atomic displacement parameters (ADPs) for the Mn atom indicate that it is a potential "rattler" atom. Here, multitemperature synchrotron powder X-ray diffraction data measured between 110 and 900 K are used to estimate ADPs for the Mn "guest" atom and the "host" structure atoms in cubic CeMnNi(4). The ADPs are subsequently fitted with Debye and Einstein models, giving Θ(D) = 301(2) K for the "host" structure and Θ(E) = 165(2) K for the Mn atom. This is higher than typical Einstein temperatures for rattlers in thermoelectric skutterudites and clathrates (Θ(E) = 50-80 K), indicating that the Mn atom in cubic CeMnNi(4) is more strongly bonded. In order to probe the chemical interactions of the potential Mn rattler atom, atomic Hirshfeld surface (AHS) analysis is carried out and compared with AHS analysis of well-established guest atom rattlers in archetypical skutterudites, MCoSb(3). Surprisingly, the skutterudite rattlers have more deformed AHSs than the Mn atom in cubic CeMnNi(4). This is related to the highly ionic nature of the skutterudite rattlers, which is not taken into account in the neutral spherical atom approach of the AHS. Additionally, visualization of void spaces in the two materials using the procrystal electron density shows that while the Mn atom is tightly fitting in the CeMnNi(4) structure then the La atom in the skutterudite is truly situated in an oversized cage of the host structure. Overall, we conclude that the Mn atom in cubic CeMnNi(4) cannot be coined a rattler.


Barrier function of microvessels and roles of glial cell line-derived neurotrophic factor in the rat testis.
The expression and localization of glial cell line-derived neurotrophic factor (GDNF) and its receptor GFR alpha1 in the testis were examined, because the blood-testis barrier is a well-known tissue barrier and we previously reported that GDNF reduced the endothelial permeability of the blood-brain barrier (BBB). Five minutes after intravenous injection of Evans blue (molecular weight, 960.6) or fluorescent dextran (molecular weight 10000 and 70000), Evans blue was observed outside microvessels of the testis, whereas the fluorescent dextran was not. Immunohistochemically, GDNF was detected in alpha-smooth muscle actin-positive cells around the seminiferous tubules and in microvessels. On the other hand, GFR alpha1 was detected in endothelial cells in the interstitial space, as well as in spermatocytes. Although occludin was positive in Sertoli cells and endothelium, claudin-5 was localized only in the endothelium of the microvessels. Thus, it became very clear that the microvessels in the testis possessed relatively impermeable tight junctions, and that the alpha-smooth muscle actin-positive cells secreted GDNF, which receptor was expressed in endothelial cells. Because this relation between GDNF and GFR alpha1 is similar to that observed in the BBB, we hypothesize that GDNF is a general regulator of tight junctions of the endothelium forming a blood-tissue barrier in a paracrine fashion.


Periodontal conditions of teeth adjacent to extraction sites.
The purpose of the present clinical study was to evaluate the effect of tooth extractions on the periodontal conditions of adjacent teeth. 40 patients were selected for the study. Prior to the extractions, baseline data of the adjacent teeth were obtained. Plaque (PII) and gingival indices (GI), pocket probing depths and probing attachment levels were scored. In addition, the alveolar bone height was determined radiographically in relation to the CEJ adjacent to the extraction sites. The contralateral side of the jaw, where no tooth had to be removed, was examined as a control. A limited hygienic phase (scaling and root planing of all surfaces examined) was performed immediately prior to the extractions. Using the same parameters, all sites were reexamined 2-4 months and 6-9 months following the extractions. After the hygienic phase, the teeth adjacent to the extraction sites indicated a decrease in the pocket probing depths by 0.5 to 1.5 mm. In shallow pockets (1-3 mm), this decrease was less pronounced than in moderate to deep pockets (4-9 mm), where it was composed of shrinkage of the gingival tissues and gain of probing attachment. The radiographic level of the bony alveolar crest in relation to the CEJ of the adjacent teeth was not altered by the extraction procedure. The oral hygiene performances of the patients were not influenced during the 9-month observation period. Therefore, neither PII nor GI scores showed relevant improvements.(ABSTRACT TRUNCATED AT 250 WORDS)


Functionally active thrombomodulin is present in human platelets.
We found functionally active thrombomodulin in human platelets (60 +/- 18 molecules per platelet). Protein C appeared not to be activated by thrombin with gel-filtered platelets. However, the activation of protein C by thrombin was accelerated by thrombin-stimulated and washed platelets. This cofactor activity of the platelets was neutralized by the anti-lung thrombomodulin-F(ab')2. From the Triton X-extract of platelets, thrombomodulin was partially purified by diisopropylphosphoryl-thrombin-agarose affinity chromatography. The Mr of the predominant platelet thrombomodulin was 78,000 before and 109,000 after reduction on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, values identical to those of placental thrombomodulin. The specific activity of the cofactor activity, apparent Kd (0.4 nM) for thrombin and Km (0.67 microM) for protein C of platelet thrombomodulin were also identical to those of placenta thrombomodulin. Thrombomodulin may play a role in activation of protein C on the surface of platelets.


[The phenomenon of unawareness of hypoglycemia].
The incidence of hypoglycaemic episodes in patients with type 1 diabetes mellitus (DM1) is frequent. They experience 1-2 symptomatic hypoglycaemias per week. 10-20% of the patients suffer from at least one severe hypoglycaemia per year. The incidence of severe hypoglycaemia in a group of intensely treated patients is about three times as high as compared with standard treatment and 55% of all episodes occur during sleep. Prevention of hypoglycaemia, and restoration of euglycaemia resp. include disappearance of metabolic effects of insulin and activation of glucose contraregulating systems among which there is a certain hierarchy. The phenomenon of unaware hypoglycaemia (FNH) is defined as failure to diagnose autonomous warning symptoms, and their non-appearance before the development of neuroglycopenia. The incidence of FNH in the population with DM1 is frequent. Based on a standardized insulin diffusion test 26% of patients with DM1 suffer from it which means that every fourth patient is affected. In the pathogenesis of FNH various factors and mechanisms were suggested as predisposing. Most probably a defect at the level of the central nervous system is involved caused by: 1. a reduced ability to recognize the decline of the blood sugar level by the CNS (altered function of the hypothalamic glucostat and/or glucose transport across the haematoencephalic barrier), 2. reduced secretion of neurotransmitters, 3. reduced tissue response to adequate neurotransmitter secretion. The theory of etiopathogenesis must explain and define its association with the persistence of diabetes mellitus, strict metabolic control, autonomous neuropathy and repeated episodes of hypopglycaemia. The contemporary hypothesis of the pathogenesis of FNH is the mechanism of repeated frequent hypoglycaemia which leads to general adaptative changes at the level of the CNS by increased glucose transport across the haematoencephalic barrier which leads to reduced hormonal responses and reduction of symptoms. Thus a dangerous circulus vitiosus is created where hypoglycaemia induces unawareness of hypoglycaemia. This condition is at least partly reversible. The presence of FNH should influence the decision of the physician before using an intensified insulin regimen in diabetics.


Selection of a whole-cell biocatalyst for methyl parathion biodegradation.
Whole-cell biocatalyst has the potential to become a cost-effective alternative to conventional enzyme methods for solving ecological and energy issues. However, cytosolic-expressing biocatalyst systems are critically disadvantaged due to the low permeability of the cell membrane. To overcome substrate transport barrier, periplasmic secretion and surface display biocatalysts were developed by expressing signal peptides or anchor proteins in Escherichia coli. In this work, six carriers were compared in regard to whole-cell activity of methyl parathion hydrolase (MPH). Our results indicate that the surface display systems yielded one to three times whole-cell activity than the periplasmic secretion systems. Although periplasmic secretion systems showed generally more stable than surface display systems, surface display appeared more suitable for whole-cell biocatalyst. It should note that the applicability of the DsbA/PhoA/AIDA-I leader to MPH expression is shown here for the first time. In addition, the result provided a useful reference for other whole-cell biocatalyst selection.


Alternating monocular exposure increases the spacing of ocularity domains in area 17 of cats.
Goodhill (1993) has recently suggested that the spacing of ocularity domains in visual cortex is not solely an intrinsic property of cortex, but is determined, at least in part, by the degree of correlation in the activity of the two eyes. In support of this model, Löwel (1994) has shown that strabismus, which decorrelates the activity of the two eyes, increases the spacing of ocular dominance columns in area 17, but not area 18, of the cat. As a further test of Goodhill's model, in this paper we examine the effects of another rearing procedure that decorrelates the activity of the two eyes, namely alternating monocular exposure (AME). Cats were reared either normally (9 cats) or with AME (21 cats). We labeled their ocularity domains by one of three methods: ocular dominance columns by 2-deoxyglucose (14 cats), and ocular dominance patches by transneuronal transport (14 cats), or by injections of tracer into single layers of the lateral geniculate nucleus (LGN; 2 cats). The spacing of ocular dominance was 11% greater in the AME cats than in the normal cats (0.976 vs. 0.877 mm). These results are similar to those previously reported for strabismic cats, although the effect is less striking. We thus confirm that decorrelating the activity of the two eyes increases the spacing of cortical ocularity domains. Our results further suggest that the degree of decorrelation affects the extent of that increase.


Beliefs, attitudes and the practice of breastfeeding among some urban parturient mothers.
Data on knowledge and beliefs on preparation for breastfeeding, feelings toward breastfeeding, and conditions considered possible or not possible for breastfeeding were obtained from 216 women admitted for delivery in a major hospital. Follow-up questionnaires were sent to them 4-5 weeks after discharge to elicit data on details of feeding. Responses received from 91 women were analyzed to determine relationships among beliefs/knowledge, feelings, conditions, and breastfeeding. Results show that knowledge was positively related to conditions considered possible for breastfeeding and to a lesser extent to feelings, while feelings and conditions were not significantly correlated. Knowledge, intention to breastfeed, husband's support, and friends' support differentiated those who breastfeed from nonbreastfeeders. Knowledge, friends' support, and husband's support were associated with length of breastfeeding. Previous experience, intention, and husband's support was found to explain 44% of the variance in breastfeeding duration.


Phylogenetic analysis of Ara+ and Ara- Burkholderia pseudomallei isolates and development of a multiplex PCR procedure for rapid discrimination between the two biotypes.
A Burkholderia pseudomallei-like organism has recently been identified among some soil isolates of B. pseudomallei in an area with endemic melioidosis. This organism is almost identical to B. pseudomallei in terms of morphological and biochemical profiles, except that it differs in ability to assimilate L-arabinose. These Ara+ isolates are also less virulent than the Ara- isolates in animal models. In addition, clinical isolates of B. pseudomallei available to date are almost exclusively Ara-. These features suggested that these two organisms may belong to distinctive species. In this study, the 16S rRNA-encoding genes from five clinical (four Ara- and one Ara+) and nine soil isolates (five Ara- and four Ara+) of B. pseudomallei were sequenced. The nucleotide sequences and phylogenetic analysis indicated that the 16S rRNA-encoding gene of the Ara+ biotype was similar to but distinctively different from that of the Ara- soil isolates, which were identical to the classical clinical isolates of B. pseudomallei. The nucleotide sequence differences in the 16S rRNA-encoding gene appeared to be specific for the Ara+ or Ara- biotypes. The differences were, however, not sufficient for classification into a new species within the genus Burkholderia. A simple and rapid multiplex PCR procedure was developed to discriminate between Ara- and Ara+ B. pseudomallei isolates. This new method could also be incorporated into our previously reported nested PCR system for detecting B. pseudomallei in clinical specimens.


[Epidemiological characteristics of imported malaria in Zhengzhou City from 2016 to 2020].
To analyze the epidemiological characteristics of reported imported malaria cases in Zhengzhou City from 2016 to 2020, so as to provide insights into the management of imported malaria in the city. All data pertaining to cases with definitive diagnosis of malaria in Zhengzhou City from 2016 to 2020 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China, including individual demographic data, and malaria onset, initial diagnosis and definitive diagnosis data. All data were descriptively analyzed. The duration from malaria onset to initial diagnosis, from initial diagnosis to definitive diagnosis and from onset to definitive diagnosis was compared among cases. In addition, the diagnoses of imported malaria cases in which definitive diagnosis was made were compared with the reexaminations by Zhengzhou Municipal Malaria Diagnosis Reference Laboratory. A total of 302 cases with definitive diagnosis of malaria were reported in Zhengzhou City from 2016 to 2020, and all were imported cases, with Plasmodium falciparum malaria as the predominant type (230 cases, 76.2%). There were 293 malaria cases imported from Africa (293 cases, 97.0%), which mainly included Nigeria (48 cases, 15.9%), Angola (40 cases, 13.2%), and the Democratic Republic of the Congo (29 cases, 9.6%). There was no obvious seasonality found in the date of malaria onset and time of reporting malaria. The ratio of male to female malaria cases was 49.3:1, and there were 103 cases (34.1%) with the current residency address in Zhengzhou City, 193 cases (63.9%) with the current residency address in other cities of Henan Province and 6 cases (2.0%) in other provinces of China. There were 271 cases (89.7%) seeking initial diagnosis in medical institutions, and the diagnostic accuracy of malaria was 56.6% (171/302) at initial diagnosis institutions. A total of 122 cases (40.4%) sought medical care on the day of malaria onset, and 252 cases (86.4%) within 3 days; however, only 22 cases (7.3%) were definitively diagnosed on the day of onset, and 162 cases (53.6%) diagnosed within 3 days. There were no significant differences between malaria cases seeking initial diagnosis at medical institutions and disease control and prevention institutions in terms of the duration from malaria onset to initial diagnosis (Z = -1.663, P > 0.05), from initial diagnosis to definitive diagnosis (Z = -0.413, P > 0.05) or from malaria onset to definitive diagnosis (Z = -0.838, P > 0.05). The median duration (interquartile range) from initial diagnosis to definitive diagnosis of malaria was 3.00 (2.00), 3.00 (6.00), 2.00 (4.00) d and 1.00 (1.00) d among cases seeking medical care at township-level and lower, county-, city- and province-level medical institutions, and the median duration from initial diagnosis to definitive diagnosis of malaria was significantly longer among cases seeking medical care at township-level and lower medical institutions than at city (Z = -3.286, P < 0.008 33) and province-level medical institutions (Z = -9.119, P < 0.008 33), while the median duration from initial diagnosis to definitive diagnosis [1.00 (3.00) d vs. 2.00 (4.00) d; Z = -4.099, P < 0.016] and from malaria onset to definitive diagnosis [3.00 (4.00) d vs. 4.00 (5.00) d; Z = -2.868, P < 0.016] among malaria cases with the current residency address in Zhengzhou City was both shorter than in other cities of Henan Province. The diagnostic accuracy was 89.1% (269/302) among malaria cases in which definitive diagnosis was made, and the accuracy of malaria reexaminations was 94.0% (284/302) in Zhengzhou Municipal Malaria Diagnosis Reference Laboratory. P. falciparum malaria was predominant among reported imported malaria cases in Zhengzhou City from 2016 to 2020, and these imported malaria cases were predominantly diagnosed at medical institutions; however, the diagnostic capability of malaria is poor in township-level and lower medical institutions. Strengthening the collaboration between medical institutions and disease control and prevention institutions and improving the diagnostic capability building at medical institutions are recommended to consolidate malaria elimination achivements.


Modification of the Bio-Rad iQ-Check Listeria spp. Kit for the Detection of Listeria Species in Environmental Surfaces.
The Bio-Rad iQ-Check Listeria spp. Kit uses real-time PCR technology for detection of Listeria species in select food matrixes and environmental surfaces. The iQ-Check Listeria spp. method was modified to reduce the enrichment medium volume for environmental sponges from 225 and 100 to 60 mL and to reduce the enrichment time for sponges and swabs from 25 ± 1 to as short as 18 h. The modified method was validated with stainless steel, polystyrene plastic, and sealed concrete using sponges or swabs with two different neutralizing buffers (Letheen Broth and HiCap™ Neutralizing Broth). In addition, the Bio-Rad Free DNA Removal Solution was used for all environmental samples. The iQ-Check Listeria spp. modified method was compared with the reference culture method in the U.S. Department of Agriculture Food Safety and Inspection Service Microbiology Laboratory Guidebook Chapter 8.10 using an unpaired study design. In the method comparison study, the iQ-Check Listeria spp. modified method demonstrated no statistical difference in performance between candidate and reference method results or between presumptive and confirmed results for all environmental surfaces analyzed using HiCap Neutralizing Broth (World Bioproducts LLC) and Letheen broth. The modified iQ-Check Listeria spp. method is an effective method for the detection of Listeria species in environmental surfaces using both types of neutralizing buffer. The method modification was granted based on the data collected.


Myocardial protection by warm blood cardioplegia. A 31P nuclear magnetic resonance spectroscopy study of an isolated perfused rat heart.
A study of the protective efficiency imparted by intermittent warm blood cardioplegia (WBCP) using perfused rat heart model. Hemodynamic parameters were monitored simultaneously with metabolic changes in high-energy phosphates using 31P-NMR spectroscopy. Following 30 min perfusion with Krebs-Henseleit (KH) buffer, all hearts were arrested for one hour (G1 and G2) and than reperfused with KH for 30 minutes. A warm oxygenated crystalloid cardioplegia (WCCP, modified St Thomas' hospital solution) was used for the control group (G1). The second group of hearts (G2) were arrested with oxygenated WBCP (K+ = 15 mM; Hct = 15-20%) and the third group (G3), was subjected to a protocol consisting of 4 periods (10 min each) of WBCP interspersed by 10 min of global ischaemia. The post-arrest percentage recoveries of LVDP, +dP/dt and HR were respectively: 88, 93 and 90 for G1 (n = 8); 97, 100 and 98 for G2 (n = 10); 76, 79 and 91 for G3 (n = 12). The corresponding metabolic recoveries of ATP and PCr were respectively, 85 and 90 for G1; 91 and 98 for G2 and 73 and 85 for G3. The PCr level declined during the arrest period in G1 contrasting with elevated PCr level (> 140%) during the WBCP arrest in G2. After an initial rise to approximately 140%, PCr level gradually decreased during the intermittent WBCP interval (G3). At normothermia, with equal CF rates, continuous WBCP provides better myocardial protection, through an effective oxygen supply, compared with WCCP. During the intermittent periods of ischaemia, certain metabolic and hemodynamic dysfunction occurs.


Human isopentenyl diphosphate: dimethylallyl diphosphate isomerase: overproduction, purification, and characterization.
Isopentenyl diphosphate (IPP):dimethylallyl diphosphate isomerase catalyzes an essential activation step in the isoprenoid biosynthetic pathway. A human cDNA sequence [J. Xuan, J. Kowalski, A.F. Chambers, and D.T. Denhardt (1994) Genomics 20, 129-131] containing a 684-base-pair open reading frame was recently reported that encoded a protein with a significant degree of similarity to two fungal IPP isomerases [F.M. Hahn and C.D. Poulter (1995) J. Biol. Chem. 270, 11298-11303]. The human cDNA sequence was cloned into expression plasmid pFMH12. The encoded protein was overproduced in Escherichia coli and purified to > 90% homogeneity in two steps by ion-exchange and hydrophobic interaction chromatography. The recombinant protein catalyzed the isomerization of IPP to dimethylallyl diphosphate and was maximally active at pH 7.0 in the presence of Mg2+. The Michaelis constant for IPP was 33 microM, similar to the value of 43 microM reported for yeast IPP isomerase; Vmax = 4.1 mumol min-1 mg-1 for recombinant human IPP isomerase, approximately fivefold less than reported for the yeast enzyme [I.P. Street and C.D. Poulter (1990) Biochemistry 29, 7531-7538].


Interaction between calcium intake and menarcheal age on bone mass gain: an eight-year follow-up study from prepuberty to postmenarche.
Both late menarcheal age and low calcium intake (Ca intake) during growth are risk factors for osteoporosis, probably by impairing peak bone mass. We investigated whether lasting gain in areal bone mineral density (aBMD) in response to increased Ca intake varies according to menarcheal age and, conversely, whether Ca intake could influence menarcheal age. In an initial study, 144 prepubertal girls were randomized in a double-blind controlled trial to receive either a Ca supplement (Ca-suppl.) of 850 mg/d or placebo from age 7.9-8.9 yr. Mean aBMD gain determined by dual energy x-ray absorptiometry at six sites (radius metaphysis, radius diaphysis, femoral neck, trochanter, femoral diaphysis, and L2-L4) was significantly (P = 0.004) greater in the Ca-suppl. than in the placebo group (27 vs. 21 mg/cm(2)). In 122 girls followed up, menarcheal age was recorded, and aBMD was determined at 16.4 yr of age. Menarcheal age was lower in the Ca-suppl. than in the placebo group (P = 0.048). Menarcheal age and Ca intake were negatively correlated (r = -0.35; P < 0.001), as were aBMD gains from age 7.9-16.4 yr and menarcheal age at all skeletal sites (range: r = -0.41 to r = -0.22; P < 0.001 to P = 0.016). The positive effect of Ca-suppl. on the mean aBMD gain from baseline remained significantly greater in girls below, but not in those above, the median of menarcheal age (13.0 yr). Early menarcheal age (12.1 +/- 0.5 yr): placebo, 286 +/- 36 mg/cm(2); Ca-suppl., 317 +/- 46 (P = 0.009); late menarcheal age (13.9 +/- 0.5 yr): placebo, 284 +/- 58; Ca-suppl., 276 +/- 50 (P > 0.05). The level of Ca intake during prepuberty may influence the timing of menarche, which, in turn, could influence long-term bone mass gain in response to Ca supplementation. Thus, both determinants of early menarcheal age and high Ca intake may positively interact on bone mineral mass accrual.


Origin of giant ionic currents in carbon nanotube channels.
Fluid flow inside carbon nanotubes is remarkable: transport of water and gases is nearly frictionless, and the small channel size results in selective transport of ions. Very recently, devices have been fabricated in which one narrow single-walled carbon nanotube spans a barrier separating electrolyte reservoirs. Ion current through these devices is about 2 orders of magnitude larger than predicted from the bulk resistivity of the electrolyte. Electroosmosis can drive these large excess currents if the tube both is charged and transports anions or cations preferentially. By building a nanofluidic field-effect transistor with a gate electrode embedded in the fluid barrier, we show that the tube carries a negative charge and the excess current is carried by cations. The magnitude of the excess current and its control by a gate electrode are correctly predicted by the Poisson-Nernst-Planck-Stokes equations.


Probing viral genomic structure: alternative viewpoints and alternative structures for satellite tobacco mosaic virus RNA.
Viral RNA structure prediction is a valuable tool for development of drugs against viral disease. This work discusses different approaches to predicting encapsidated viral RNA and highlights satellite tobacco mosaic virus (STMV) RNA as a model system with excellent crystallography data. Fundamentally important issues for debate include thermodynamic versus kinetic control of virus assembly and the possible consequences of quasi-species in the primary structure on RNA secondary structure prediction of a single structure or an ensemble of structures. Multiple computational tools and chemical reagents are now available for improved viral RNA structure prediction. Two different predicted structures for encapsidated STMV RNA result from differences in three main areas: a different approach and philosophy to studying encapsidated viral RNA, an emphasis on different RNA motifs, and technical differences in computational methods and chemical reagents. The experiments with traditional chemical probing and SHAPE reagents are compared in terms of chemistry, results, and interpretation for STMV RNA as well as other RNA protein assemblies, such as the 5'UTR of HIV and the ribosome. This discussion of the challenges of viral RNA structure prediction will lead to new experiments and improved future predictions for viral RNA.