Alteration of the Enantioselective Toxicity of Diclofop Acid by Nonylphenol: Effect on Ascorbate-Glutathione Cycle in Microcystis Aeruginosa.
The enantioselective effects of chiral compounds have been the subject of extensive studies in recent years due to their important implications for contaminant behavior and risk as well as the design of drug and pesticide formulations. The potential alterations of enantioselectivity, however, still remain elusive from the available data suggesting the effects of numerous environmental factors and the coexisting achiral and chiral compounds. Herein we studied the effect of nonylphenol (NP), a ubiquitous contaminant and ingredient in pesticide formulation, on the enantioselectivity of diclofop acid (DC) through ascorbate-glutathione (AsA-GSH) cycle in Microcystis aeruginosa. The enantioselectivity of DC in the AsA and GSH antioxidant defense system of M. aeruginosa was affected significantly by the addition of NP. Specifically, although R- DC and S-DC were added with an equal toxic concentration (at their EC50 values), NP addition to the DC treatments altered the enantiomeric ratios of the activities of monodehydroascorbate reductase (MDHAR) and glutathione reductase (GR), key enzymes in the regeneration of AsA and GSH, respectively. NP also modified the enantiomeric ratios of AsA and GSH levels in both the AsA and GSH antioxidant defense systems of M. aeruginosa. Overall, the oxidative damage induced by R-DC was further deteriorated, whereas that induced by S-DC was alleviated after NP addition. These altered enantioselectivities indicate a need to reexamine the risks and biological effects of chiral compounds in the complex environmental matrices containing a multitude of other chemicals, including commercial chiral agricultural chemicals. Chirality 28:475-481, 2016. © 2016 Wiley Periodicals, Inc.


Risk factors for injury in indoor compared with outdoor adolescent soccer.
There are limited data on the epidemiology of indoor soccer injuries. Injury rates and risk factors for injury in adolescent indoor and outdoor soccer in the same cohort of players will be identified and compared. Cohort study (prevalence); Level of evidence, 2. The study population was a random sample of 21 adolescent (ages 13-17 years) outdoor soccer teams (N = 317). The subcohort included players continuing to play in the indoor soccer season (n = 142). The injury definition included any injury occurring in soccer that resulted in medical attention, the inability to complete a session, and/or missing a subsequent session. The overall injury rate found in indoor soccer over 20 weeks was 4.45 injuries per 1000 player hours (95% confidence interval, 3.1-6.19). The overall injury rate found in the 13-week outdoor soccer season among a similar cohort was 5.59 injuries per 1000 player hours (95% confidence interval, 4.42-6.97). The relative risk of injury suggests that there was no significant difference between injury rates by age group or gender in indoor soccer compared with outdoor soccer. The risk of injury in the most elite division of play was greater in outdoor compared with indoor soccer (relative risk, 3.22; 95% confidence interval, 1.8-6.12). The most commonly injured body part in both indoor and outdoor soccer was the ankle, followed by the groin in indoor and the knee in outdoor soccer. There were no significant differences in overall injury rates found by gender or age group for indoor compared with outdoor soccer. Future research should focus on injury prevention strategies to reduce lower extremity injury in indoor and outdoor adolescent soccer.


Cancer biomarker discovery: the entropic hallmark.
It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases.


Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta.
To examine the characteristics and distribution of possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target cells in the human trophectoderm (TE) and placenta. Bioinformatics analysis was performed based on published single-cell transcriptomic datasets of early TE and first- and second-trimester human placentae. We conducted the transcriptomic analysis of 4198 early TE cells, 1260 first-trimester placental cells and 189 extravillous trophoblast cells (EVTs) from 24-week placentae (EVT_24W) using the SMART-Seq2 method. In addition, to confirm the bioinformatic results, we performed immunohistochemical staining of three first-trimester, three second-trimester and three third-trimester placentae from nine women recruited prospectively to this study. We evaluated the expression of the SARS-CoV-2-related molecules angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Via bioinformatic analysis, we identified the existence of ACE2 and TMPRSS2 expression in human TE as well as in first- and second-trimester placentae. In the human TE, 54.4% of TE1 cells, 9.0% of cytotrophoblasts (CTBs), 3.2% of EVTs and 29.5% of syncytiotrophoblasts (STBs) were ACE2-positive. In addition, 90.7% of TE1 cells, 31.5% of CTBs, 22.1% of EVTs and 70.8% of STBs were TMPRSS2-positive. In placental cells, 20.4% of CTBs, 44.1% of STBs, 3.4% of EVTs from 8-week placentae (EVT_8W) and 63% of EVT_24W were ACE2-positive, while 1.6% of CTBs, 26.5% of STBs, 1.9% of EVT_8W and 20.1% of EVT_24W were TMPRSS2-positive. Pathway analysis revealed that EVT_24W cells that were positive for both ACE2 and TMPRSS2 (ACE2 + TMPRSS2-positive) were associated with morphogenesis of branching structure, extracellular matrix interaction, oxygen binding and antioxidant activity. The ACE2 + TMPRSS2-positive TE1 cells were correlated with an increased capacity for viral invasion, epithelial-cell proliferation and cell adhesion. Expression of ACE2 and TMPRSS2 was observed on immunohistochemical staining in first-, second- and third-trimester placentae. ACE2- and TMPRSS2-positive cells are present in the human TE and placenta in all three trimesters of pregnancy, which indicates the possibility that SARS-CoV-2 could spread via the placenta and cause intrauterine fetal infection. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.


Stability properties of pulse vaccination strategy in SEIR epidemic model.
The problem of the applicability of the pulse vaccination strategy (PVS) for the stable eradication of some relevant general class of infectious diseases is analyzed in terms of study of local asymptotic stability (LAS) and global asymptotic stability (GAS) of the periodic eradication solution for the SEIR epidemic model in which is included the PVS. Demographic variations due or not to diseased-related fatalities are also considered. Due to the non-triviality of the Floquet's matrix associate to the studied model, the LAS is studied numerically and in this way it is found a simple approximate (but analytical) sufficient criterion which is an extension of the LAS constraint for the stability of the trivial equilibrium in SEIR model without vaccination. The numerical simulations also seem to suggest that the PVS is slightly more efficient than the continuous vaccination strategy. Analytically, the GAS of the eradication solutions is studied and it is demonstrated that the above criteria for the LAS guarantee also the GAS.


Pomalidomide-Responsive Extramedullary Myeloma Relapsed after Allogeneic Hematopoietic Transplant and Refractory to Multiple Lines of Chemotherapy.
Patients who experience extramedullary relapses (EMR) of multiple myeloma (MM) have an adverse prognosis, also in this era of novel agents like proteasome inhibitors and immunomodulatory drugs. We describe the case of an MM patient with EMR at 2 different sites after allogeneic stem cell transplantation. EMR was refractory to bortezomib, anthracycline, and bendamustine, but the patient achieved long-term complete remission (4 years) with pomalidomide and dexamethasone. This supports the hypothesis that this could be due to the graft-versus-myeloma effect during therapy enhanced by pomalidomide.


Experimental models of anxiety for drug discovery and brain research.
Animal models have been vital to recent advances in experimental neuroscience, including the modeling of common human brain disorders such as anxiety, depression, and schizophrenia. As mice express robust anxiety-like behaviors when exposed to stressors (e.g., novelty, bright light, or social confrontation), these phenotypes have clear utility in testing the effects of psychotropic drugs. Of specific interest is the extent to which mouse models can be used for the screening of new anxiolytic drugs and verification of their possible applications in humans. To address this problem, the present chapter will review different experimental models of mouse anxiety and discuss their utility for testing anxiolytic and anxiogenic drugs. Detailed protocols will be provided for these paradigms, and possible confounds will be addressed accordingly.


Differential Activation of Expression of a Suberization-Associated Anionic Peroxidase Gene in Near-Isogenic Resistant and Susceptible Tomato Lines by Elicitors of Verticillium albo-atratrum.
We tested whether the expression of the suberization-associated anionic peroxidase gene is involved in the timely appearance of the vascular suberized coating involved in the resistance of a tomato line to Verticillium albo-atrum. The mRNA for this peroxidase appeared at a higher level one day earlier in wound-healing fruits of the resistant tomato line than in a near-isogenic susceptible line. Cell cultures from the resistant line, when treated with low levels (nanograms per milliliter) of fungal elicitor, generated the peroxidase mRNA and this apparent activation of the peroxidase gene expression could be detected in minutes, whereas the cells from the susceptible line hardly responded.


Synthesis and aldose reductase-inhibitory activity of imidazopyrroloquinoline esters.
Derivatives of imidazopyrroloquinoline (IPQ) and its esters were synthesized. Some of these compounds potently inhibited aldose reductases of rabbit lens and dog kidney, as well as the human recombinant enzyme, though the coenzyme pyrroloquinoline quinone (PQQ) was a relatively poor inhibitor. The IPQ esters with a methyl substituent at the C-3 carboxyl group were less potent inhibitors than the analogs without esterification at this position. An IPQ ester with the free carboxyl group at C-3 inhibited sorbitol accumulation in rat red blood cells.


Pin-wheel hexagons: a model for anthraquinone ordering on Cu(111).
The 4-state model of anthraquinone molecules ordering in a pin-wheel large-pore honeycomb phase on Cu(111) is proposed and solved by Monte Carlo simulation. The model is defined on a rescaled triangular lattice with the lattice constant a being equal to intermolecular distance in the honeycomb phase. The pin-wheel triangle formations are obtained taking into account the elongated shape of the molecules and anisotropic interactions for main two attractive short range (double and single dimeric) H-bond interactions. The long-range intermolecular interactions, corresponding to repulsive dipole-dipole forces, are assumed to be isotropic. Also, a very small (compared to short-range forces) isotropic attractive long-range interaction at the "characteristic" distance of a pore diameter is employed, and its effect carefully studied. This interaction is crucial for a formation of closed porous ordered systems, pin-wheel hexagons in particular. If each side of a pin-wheel hexagon is formed of n parallel molecules, the distance of this characteristic interaction is a√(3n(2)+1). The phase diagrams including different pin-wheel hexagon phases and a variety of other ordered structures are obtained. By changing the distance of characteristic interaction, different ordering routes into the experimental pin-wheel honeycomb phase are explored. The results obtained imply that classical explanation of the origin of the pin-wheel honeycomb phase in terms of some balance of attractive and repulsive forces cannot be totally discounted yet.


Expression of recombinant streptokinase from streptococcus pyogenes and its reaction with infected human and murine sera.
Streptokinase (SKa) is an antigenic protein which is secreted by Streptococcus pyogenes. Streptokinase induces inflammation by complement activation, which may play a role in post infectious diseases. In the present study, recombinant streptokinase from S. pyogenes was produced and showed that recombinant SKa protein was recognized by infected human sera using Western blot analysis. In this study, the ska gene from S. pyogenes was amplified and cloned into pET32a which is a prokaryotic expression vector. pET32a-ska was transformed to Escherichia coli BL21 (DE3) pLysS and gene expression was induced by IPTG. Protein production was improved by modification of composition of the bacterial culture media and altering the induction time by IPTG. The expressed protein was purified by affinity chromatography using the Ni-NTA resin. The integrity of the product was confirmed by Westernblot analysis using infected mice. Serum reactivity of five infected individuals was further analyzed against the recombinant SKa protein. Data indicated that recombinant SKa protein from S. pyogenes can be recognized by patient and mice sera. The concentration of the purified recombinant protein was 3.2 mg/L of initial culture. The highest amount of the expressed protein after addition of IPTG was obtained in a bacterial culture without glucose with the culture optical density of 0.8 (OD600 = 0.8). Conclusion : Present data shows, recombinant SKa protein has same epitopes with natural form of this antigen. Recombinant SKa also seemed to be a promising antigen for the serologic diagnosis of S. pyogenes infections.


Contra: CD8+ T-cell-mediated suppression without 'suppressor' T cells?
This commentary argues that conventional antiviral cytotoxic T cells act suppressively by eliminating antigen-presenting cells, sometimes including lymphocytes, T or B cells expressing relevant antigens of exogenous or endogenous, most commonly of viral origin. They thereby limit expression of antigens, and by eliminating the antigen-expressing cells stop immune responses. However, to argue that induced T cells (or antibodies) function to eliminate or neutralize antigen is the shortest summary of immunology and neither new nor heretic.


Sweet Selenium: Synthesis and Properties of Selenium-Containing Sugars and Derivatives.
In the last decades, organoselenium compounds gained interest due to their important biological features. However, the lack of solubility, which characterizes most of them, makes their actual clinical exploitability a hard to reach goal. Selenosugars, with their intrinsic polarity, do not suffer from this issue and as a result, they can be conceived as a useful alternative. The aim of this review is to provide basic knowledge of the synthetic aspects of selenosugars, selenonium salts, selenoglycosides, and selenonucleotides. Their biological properties will be briefly detailed. Of course, it will not be a comprehensive dissertation but an analysis of what the authors think is the cream of the crop of this interesting research topic.


Coronary disease prediction using a new atherogenic index.
This report demonstrates the utilization of a new serum factor, Toxicity Preventing Activity (TxPA) in the diagnosis of coronary disease prone individuals. Our laboratory has recently identified TxPA, which offsets the toxicity of very low density lipoproteins (VLDL) upon arterial cells in vitro. In the present study, we measured TxPA activity and serum lipoprotein levels in 73 individuals undergoing coronary angiography. Serum from control subjects demonstrated 270% more TxPA than aged matched individuals with angiographically demonstrable coronary disease (CHD). When TxPA was combined with serum lipoprotein values, a new atherogenic index was generated which further distinguished these individuals with CHD from non-angiographed controls. These results demonstrate that TxPA is a new protective factor in coronary artery disease, and that the new atherogenic index provides for the first time an accurate classification of individuals with coronary artery disease.


The Quantitative Relationship Between ISO 15197 Accuracy Criteria and Mean Absolute Relative Difference (MARD) in the Evaluation of Analytical Performance of Self-Monitoring of Blood Glucose (SMBG) Systems.
The relationship between International Organization for Standardization (ISO) accuracy criteria and mean absolute relative difference (MARD), 2 methods for assessing the accuracy of blood glucose meters, is complex. While lower MARD values are generally better than higher MARD values, it is not possible to define a particular MARD value that ensures a blood glucose meter will satisfy the ISO accuracy criteria. The MARD value that ensures passing the ISO accuracy test can be described only as a probabilistic range. In this work, a Bayesian model is presented to represent the relationship between ISO accuracy criteria and MARD. Under the assumptions made in this work, there is nearly a 100% chance of satisfying ISO 15197:2013 accuracy requirements if the MARD value is between 3.25% and 5.25%.


Ligand-receptor interactions as controlled by wild-type and mutant Thr(370)Lys alpha2B-adrenoceptor-Galpha15 fusion proteins.
Fusion proteins were constructed between either a wild-type or mutant Thr370Lys alpha2B-adrenoceptor (alpha2B AR) and a mouse Galpha15 protein to analyze ligand-receptor interactions at a receptor/Galpha15 protein density ratio of 1. Activation of the wild-type alpha2B AR-Galpha15 fusion protein in CHO-K1 cells by (-)-adrenaline induced a time- and concentration-dependent (pEC50 = 7.37+/-0.13) increase in the intracellular Ca2+ concentration, which could be antagonized by RX 811059 (pK(B) = 7.55+/-0.15). Whereas d-medetomidine and oxymetazoline were as efficacious agonists as (-)-adrenaline, the following ligands displayed partial agonist properties: BRL 44408 < atipamezole < clonidine < UK 14304 < BHT 920. A comparison with the mutant Thr370Lys alpha2B AR-Galpha15 fusion protein displayed similar Ca2+ kinetics and a ligand-mediated receptor activation profile characterized by higher potencies and greater maximal Ca2+ responses for the ligands being investigated, including the putative antagonists dexefaroxan and idazoxan. RX 811059 and RX 821002 remained silent. Similar conclusions could be made on enhancement of the ligands' intrinsic activities by coexpression of the mutant Thr370Lys alpha2B AR with either a Galpha15 or Galphao Cys351Ile protein. The Thr370Lys alpha2B AR-Galpha protein interactions may modify the tertiary structure of the mutant receptor in such a way that some putative alpha2 AR antagonists are capable of stabilizing an active receptor conformation, thereby generating positive efficacy.


Invasive Haemophilus influenzae infections in Germany: impact of non-type b serotypes in the post-vaccine era.
Haemophilus influenzae type b (Hib) vaccination led to a significant decrease in invasive bacterial infections in children. The aim of this study was to assess a potential shift to more non-type b invasive infections in a population with high Hib vaccination coverage and to compare the burden of suffering between children with Hib, capsulated non-b and non-capsulated Hi infections. Cases with confirmed invasive Hi infections were ascertained through two independent nationwide active surveillance systems in 1998-2005. Information on possible predisposing conditions and clinical information was available from 2001 onwards. The total number of reported non-type b Hi cases varied between 10 cases in 1998, 27 in 2000 and 14 in 2005. In each year, non-capsulated serotypes outnumbered capsulated non-type b ones. 192 cases were detected in 2001-2005, more than one half was non-type b and 88% of the non-type b cases were non-capsulated. For cases with Hib/capsulated non-type b infections the most common clinical presentation was meningitis (67% each); 89%/78% had no potential predisposing condition, 75%/72% completely recovered from disease and 6% (each) died. In contrast, meningitis was diagnosed in 34% of the non-capsulated Hi infections, septicaemia in 28% and pneumonia 21%; 62% had no potential predisposing condition, 83% completely recovered and 3% died. There was no increase in non-type b Hi invasive infections during 8 years of active surveillance in Germany. Invasive disease due to non-type b Hi is not confined to children with risk factors. In patients with capsulated non-type b Hi infections the proportion of meningitis cases is similar to Hib, but double as high as in non-capsulated Hi.


Age Is Important for the Early-Stage Detection of Breast Cancer on Both Transcriptomic and Methylomic Biomarkers.
Patients at different ages have different rates of cell development and metabolisms. As a result, age should be an essential part of how a disease diagnosis model is trained and optimized. Unfortunately, most of the existing studies have not taken age into account. This study demonstrated that disease diagnosis models could be improved by merely applying individual models for patients of different age groups. Both transcriptomes and methylomes of the TCGA breast cancer dataset (TCGA-BRCA) were utilized for the analysis procedure of feature selection and classification. Our experimental data strongly suggested that disease diagnosis modeling should integrate patient age into the whole experimental design.


Mechanisms underlying metformin-induced secretion of glucagon-like peptide-1 from the intestinal L cell.
Glucagon-like peptide-1(7-36NH2) (GLP-1) is secreted by the intestinal L cell in response to both nutrient and neural stimulation, resulting in enhanced glucose-dependent insulin secretion. GLP-1 is therefore an attractive therapeutic for the treatment of type 2 diabetes. The antidiabetic drug, metformin, is known to increase circulating GLP-1 levels, although its mechanism of action is unknown. Direct effects of metformin (5-2000 μm) or another AMP kinase activator, aminoimidazole carboxamide ribonucleotide (100-1000 μm) on GLP-1 secretion were assessed in murine human NCI-H716, and rat FRIC L cells. Neither agent stimulated GLP-1 secretion in any model, despite increasing AMP kinase phosphorylation (P < 0.05-0.01). Treatment of rats with metformin (300 mg/kg, per os) or aminoimidazole carboxamide ribonucleotide (250 mg/kg, sc) increased plasma total GLP-1 over 2 h, reaching 37 ± 9 and 29 ± 9 pg/ml (P < 0.001), respectively, compared with basal (7 ± 1 pg/ml). Plasma activity of the GLP-1-degrading enzyme, dipeptidylpeptidase-IV, was not affected by metformin treatment. Pretreatment with the nonspecific muscarinic antagonist, atropine (1 mg/kg, iv), decreased metformin-induced GLP-1 secretion by 55 ± 11% (P < 0.05). Pretreatment with the muscarinic (M) 3 receptor antagonist, 1-1-dimethyl-4-diphenylacetoxypiperidinium iodide (500 μg/kg, iv), also decreased the GLP-1 area under curve, by 48 ± 8% (P < 0.05), whereas the antagonists pirenzepine (M1) and gallamine (M2) had no effect. Furthermore, chronic bilateral subdiaphragmatic vagotomy decreased basal secretion compared with sham-operated animals (7 ± 1 vs. 13 ± 1 pg/ml, P < 0.001) but did not alter the GLP-1 response to metformin. In contrast, pretreatment with the gastrin-releasing peptide antagonist, RC-3095 (100 μg/kg, sc), reduced the GLP-1 response to metformin, by 55 ± 6% (P < 0.01) at 30 min. These studies elucidate the mechanism underlying metformin-induced GLP-1 secretion and highlight the benefits of using metformin with dipeptidylpeptidase-IV inhibitors in patients with type 2 diabetes.


Lymphocyte-tropic simian immunodeficiency virus causes persistent infection in the brains of rhesus monkeys.
Molecularly cloned SIVmac239 is the prototypical SIVmac lymphocyte-tropic virus that replicates productively in lymphocytes but poorly in macrophages. In macaques, the virus causes activation and productive infection of T lymphocytes which invade the central nervous system (CNS) early after infection in the animal. However, infected animals develop immunosuppression and AIDS but rarely overt neurological disease. In this study, we examined multiple regions of the brain and spinal cord for the presence of SIV env sequences and histological lesions in five macaques that had been infected with SIVmac239 for 1.7 to 2.25 years. Histopathological examination of the brain revealed no lesions consistent with encephalitis; however, viral DNA was found in all five brains. In one animal the virus caused infection in a widely disseminated pattern from the frontal cortex to the distal end of the spinal cord, whereas in the other four animals infection in the CNS occurred in a nonspecific, focal pattern. Sequence analyses were performed on gp120 sequences isolated from selected regions of the CNS and compared to gp120 sequences isolated from corresponding lymph nodes, a tissue known to support productive replication of SIVmac239. Examination of the viral sequences from the CNS tissue from two animals (macaques 10F and 14F) revealed a low mutation rate when compared to the sequences isolated from the lymph node tissues. The percentage change in the amino acid sequence was approximately 1% for CNS clones versus > or = 3% for clones isolated from the lymph node. The majority of the CNS viral sequences of macaques 10F and 14F had none of the genetic markers shown in a previous study to be associated with macrophage-tropic variants and indeed retained a nucleotide sequence of similar to the original lymphocyte-tropic virus used for inoculation despite almost 2 years of persistent infection in the animals. Construction of chimeric viruses with V1-V5 regions of selected macaque 10F and macaque 14F CNS-gp120 clones confirmed the predicted lymphocyte-tropic nature of these env genes. In contrast, the gp120 sequences isolated from the CNS tissue of one of the other three animals (macaque 13F) had a mutation rate comparable to that observed for the lymph node clones. The CNS clones from this animal had amino acid substitutions that were previously shown to be associated with macrophage tropism. Compared to the chimeric viruses constructed with V1-V5 sequences from macaques 10F and 14F, viruses constructed with the V1-V5 sequences of several macaque 13F brain clones did not yield infectious virus.(ABSTRACT TRUNCATED AT 400 WORDS)


Sustained brain-derived neurotrophic factor up-regulation and sensorimotor gating abnormality induced by postnatal exposure to phencyclidine: comparison with adult treatment.
Brain-derived neurotrophic factor (BDNF) is involved in synaptic development and plasticity, and alterations in BDNF expression or signaling are implicated in drug addiction and psychiatric diseases, such as depression and schizophrenia. In this study, we administered phencyclidine to postnatal and adult rats with different time schedules, and determined the correlations between BDNF expression and the behavioral effects. Both single and repeated phencyclidine injections into adult rats induced BDNF up-regulation in the corticolimbic system and a decrease in prepulse inhibition, both of which were transient. In contrast, subchronic postnatal administration increased BDNF protein and mRNA levels in the hippocampus and entorhinal cortex, which were sustained until 8 weeks of age. In parallel, the postnatal rats treated with phencyclidine developed a persistent decrease in prepulse inhibition at the adult stage. The chronic BDNF increase appeared to contribute to the prepulse inhibition abnormality, as subchronic BDNF infusion into the hippocampus of normal rats mimicked the prepulse inhibition deficits. This study suggests that phencyclidine exposure during brain development induces sustained BDNF up-regulation in the limbic system with a biological link to sensorimotor gating deficits.


Enantioselective capillary electrophoresis provides insight into the phase II metabolism of ketamine and its metabolites in vivo and in vitro.
Glucuronidation catalyzed by uridine-5'-diphospho-glucuronosyl-transferases (UGTs) is the most important reaction in phase II metabolism of drugs and other compounds. O-glucuronidation is more common than N-glucuronidation. The anesthetic, analgesic and antidepressive drug ketamine is metabolized in phase I by cytochrome P450 enzymes to norketamine, hydroxynorketamine (HNK) diastereomers and dehydronorketamine (DHNK). Equine urine samples collected two hours after ketamine injection were treated with β-glucuronidase and analyzed with three enantioselective capillary electrophoresis assays. Concentrations of HNK diastereomers and norketamine were significantly higher in comparison to untreated urine and an increase of ketamine and DHNK levels was found in selected but not all samples. This suggests that O-glucuronides of HNK and N-glucuronides of the other compounds are formed in equines. N-glucuronidation of norketamine was studied in vitro with liver microsomes of different species and the single human enzyme UGT1A4. With equine liver microsomes (ELM) a stereoselective N-glucuronidation of norketamine was found that compares well to the results obtained with urines collected after ketamine administration. No reaction was observed with canine liver microsomes, human liver microsomes and UGT1A4. Incubation of ketamine and DHNK with ELM did not reveal any glucuronidation. Enantioselective CE is suitable to provide insight into the phase II metabolism of ketamine and its metabolites.


Curcumin assists anti-EV71 activity of IFN-α by inhibiting IFNAR1 reduction in SH-SY5Y cells.
Enterovirus 71(EV71) can cause severe hand, foot, and mouth disease (HFMD) with brain tissue involvement. Few effective anti-EV71 drugs are presently available in clinical practice. Interferon-α (IFN-α) was ineffective while Curcumin was effective in restricting EV71 replication in non-neuronal cells. Ubiquitin-proteasome-mediated degradation of interferon-alpha receptor 1 (IFNAR1) protein contributes to IFN-α resistance. Current study aimed to determine synergistic inhibition of EV71 by Curcumin and IFN-α in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were infected with mock-/Curcumin-pre-incubated EV71 or transfected with plasmid containing interferon-stimulated response element (ISRE) or mRNA containing viral internal ribosomal entry site (IRES) following by post-treatment with Curcumin with or without IFN-α. Supernatant IFN-α/β was detected by ELISA. ISRE, IRSE, proteasome and deubiquitinating activity were measured by luciferase assay. EV71 RNA and viral protein or IFNAR1 were determined by qPCR and western blot, respectively. EV71 flailed to completely block IFN-α/β production but inhibited IFN-α signal. Curcumin only slightly inhibited EV71 proliferation without modulating virus attachment and internalization. However, Curcumin addition restored IFN-α-mediated ISRE activity thus significantly inhibiting EV71 replication. Furthermore, EV71 also reduced IFNAR1 protein with proteasome-dependence in SH-SY5Y cells, which can be reversed by Curcumin addition with the evidence that it lowered proteasome activity. These data demonstrate that Curcumin assists anti-EV71 activity of IFN-α by inhibiting IFNAR1 reduction via ubiquitin-proteasome disruption in SH-SY5Y cells.


Imaging Review of Hockey-related Lower Extremity Injuries.
Hockey is a fast-paced contact sport with a high incidence of injuries. Although injuries are more frequent among elite players, recreational hockey injuries are a common issue faced by primary care and emergency physicians. Lower extremity injuries in hockey are particularly important because they account for approximately a third of all injuries and > 60% of all overuse injuries. This pictorial review provides the general and specialty trained radiologist with a knowledge of the patterns of lower extremity injury that occur in ice hockey.


Electroconvulsive treatment in adolescents with pharmacotherapy-refractory depression.
The effectiveness and safety of ECT in pharmacotherapy-refractory depression was examined in 11 hospitalized adolescents (ages 16.3 +/- 1.7 years, 10 females) with a primary DSM-III-R diagnosis of mood disorder, which had failed to respond to three or more adequate trials of antidepressant pharmacotherapy. After a thorough diagnostic evaluation, patients received a course of ECT involving 11.2 +/- 2.0 (range 8-15) administrations. ECT was commenced with bilateral treatment in 2 adolescents and nondominant right electrode placement in 9 patients; 5 of the 9 patients were subsequently changed to bilateral treatment. All 11 patients improved to a clinically significant degree. Significant improvements were noted in scores on the Children Depression Rating Scale-Revised (CDSR-R) and the Global Assessment of Functioning Scale (GAF) (p < 0.05). Euthymia, defined as CDRS-R score < or = 40, was achieved by 64% (7/11) of patients. The Mini-Mental State Examination showed no significant decline in cognitive functioning. Neuropsychological testing completed in 5 subjects both before ECT and 1-5 days after the last treatment, indicated a significant decline in attention, concentration, and long-term memory search. Minor side effects, experienced within the first 12 hours of treatment, were headache (80% of patients) and nausea/vomiting (64%). The potentially serious complication of tardive seizure (after full recovery of consciousness) occurred in 1 adolescent. Prolonged seizures (> 2.5 minutes) were noted in 7 of the 11 patients (9.6% of the 135 ECT administrations). Pending further research on ECT in youth, it is recommended that ECT should only be administered to youth in hospital settings, that all regularly administered psychotropic medications (including antidepressants) be discontinued before ECT and restarted after the final administration of ECT, and that physicians be aware that 12 treatments are usually sufficient, but that 15 treatments may occasionally be necessary for treating depressed adolescents. With the understanding that scientific evaluation of ECT in youth is lacking, it appears that ECT can be an effective and relatively safe treatment for depressed adolescents who have failed to respond to antidepressant pharmacotherapy.


Use of the osteocutaneous free scapular flap on the lower extremities.
Reports on the use of osteocutaneous free scapular flap transfers have focused primarily on mandible reconstruction. Yet the scapula is a nearly straight bone, and it is also useful in the reconstruction of long bones. We would like to report on 23 patients undergoing osteocutaneous free scapular flap transfers to the lower extremities in whom we obtained extremely satisfactory results. These 23 surgical patients included 10 with pseudoarthrosis with osteomyelitis, 3 with pseudoarthrosis due to trauma, and 5 with osteomyelitis of the lower extremities, as well as 5 with other miscellaneous problems. Surgery was successful in all patients. There was a recurrence of osteomyelitis in 2 patients. In 1 patient, the problem was minor and was treated on an outpatient basis. In the other patient, an infection arose in surgical dead space, and a second operation was required. The level of weight bearing achieved with the osteocutaneous free scapular flap is the same as obtained with a vascularized free fibular graft used for the treatment of pseudoarthrosis. We therefore believe that the osteocutaneous free scapular flap is extremely effective in the treatment of chronic and severe lower leg problems.


A 20 X 10(3)-base mosaic gene identified on the mitochondrial chromosome of Podospora anserina.
By DNA sequencing and hybridization experiments we have localized the genes cob and col on the mitochondrial chromosome of Podospora anserina. The positions we have determined for these two genes are different from those previously attributed to them. The presence in the gene col of at least two introns, belonging respectively to class I and II, has been demonstrated. This gene, with a size of about 20 X 10(3) bases, appears to be the longest known mitochondrial mosaic gene.


Alfred Binet and higher education.
At the beginning of the 20th century, Alfred Binet sought teaching positions at the Collége de France and the Sorbonne. Binet wanted to develop experimental psychology in France, but the strong psychopathological orientation of French psychology blocked his ambition. The 1st part of this article relates the history of the introduction of psychology, via Théodule Ribot, to the Sorbonne and the Collège de France. Ribot's premature retirement from the Collège de France in 1901 triggered a battle that led to Binet's repeated failure to gain access to these institutions of highter education and the success in 1902 of Ribot's students: Pierre Janet at the Collège de France and George Dumas at the Sorbonne.


[Evaluation of the effectiveness of cefazolin++ (Kefzol) in preventing infections in patients after abdominal surgery].
The purpose of the work as an assessment of the effectiveness of cefazolin (Kefzol) in preventing infections in patients after abdominal surgery. The prospective studies included 200 patients, out of whom in 100 patients in the studied group Kefzol was administered prior to and for 24 hours after operation, while in 100 patients in the control group no prevention was used. The percent of infections in the studied group was lower in comparison to the control group (9% vs 25%, p < 0.01). A statistically significant reduction was obtained of wound infection per cent from 19% in the control group to 7% in the studied group, including a reduction from 14.3% to 3.1% after operations on the gall bladder and bile ducts, and from 18.2% to 11.1% after gastroduodenal operations. The per cent of wound infections after appendectomy was 5.9% in the patients from the studied group receiving prophylactically Kefzol with metronidazole, and 20.6% in the patients from the control group. Bacteriological investigations, demonstrated that 87.5% bacterial strains were susceptible to cefazolin. In the authors' opinion cefazolin (Kefzol) is effective in the prevention of purulent complications, and the reduction of the per cent of infections causes lowering of treatment cost.


Acute and chronic effects of innovative antifouling nanostructured biocides on a tropical marine microcrustacean.
This study aimed to investigate the toxicity of innovative antifouling nanostructured biocides DCOIT and silver associated to silica nanocapsules (SiNC) on the tropical microcrustacean Mysidopsis juniae. The toxicity of the tested compounds can be summarized as follows (acute tests): DCOIT > SiNC-Ag > SiNC-DCOIT > SiNC-DCOIT-Ag > SiNC > Ag; (chronic tests): SiNC-Ag > SiNC-DCOIT-Ag > DCOIT > Ag > SiNC, although it was not possible to determine the chronic toxicity of SiNC-DCOIT. In general, our data demonstrated that mysids were more sensitive than most temperate species, and it was possible to conclude that the combination SiNC-DCOIT-Ag showed less acute toxicity in comparison to the isolated active compounds, reinforcing data obtained for species from temperate environments on the potential use of nanomaterial to reduce toxicity to non-target species. However, despite representing less risk to the environment, the compound SiNC-DCOIT-Ag is still very toxic to the non-target tropical mysid.


Influence of atrioventricular synchrony on hemodynamics in patients with normal and low ejection fractions following open heart surgery.
The authors wished to test the hypothesis that atrioventricular synchrony has a relatively greater effect on hemodynamic parameters in postoperative patients with low ejection fractions compared to those with normal ejection fractions. Temporary pacing wires were placed on the right atrium and right ventricle of patients undergoing open heart surgery. Duplicate thermodilution cardiac outputs were determined during atrial pacing and ventricular pacing at 100 beats/min. Mean left atrial and systemic blood pressures were monitored. Thirteen patients with ejection fractions of 45 per cent or less (range 24 to 45%, mean 37.3%) were included in the low ejection fraction group, and 27 patients with ejection fractions of 59 per cent or greater (range 59 to 80%, mean 66.8%) were considered in the normal ejection fraction group. All hemodynamic parameters improved significantly when changing from ventricular pacing to atrial pacing in both the normal ejection fraction group and low ejection fraction group (P less than 0.05). The magnitude of change between the groups showed no significant difference for all parameters except left atrial pressure, which decreased by a greater percentage in the low ejection fraction group with atrial pacing (P less than 0.001). The atrial contribution to hemodynamic enhancement is important in patients with normal and low ejection fraction following open heart surgery. Patients with low ejection fractions do not sustain a relatively greater reduction in cardiac output, stroke volume index, or systemic blood pressure with loss of atrioventricular synchrony when compared to patients with normal ejection fractions.


[Assessment of time to stimulate the function of the type of AAI in the distant observation in patients with sick sinus syndrome].
For the first time in 1966 vestibular stimulation has been applied. This idea is implemented in a patient with sinus node dysfunction and normal AV conduction. The aim of the study was to evaluate the time of AAI stimulation until the first reimplantation of stimulating system and to determine the cause of it. Work is retrospective in nature. The analysis included 251 patients who were subjected to AAI pacemaker implantation in the period from December 1988 to January 2009. The group consisted of 150 women and 101 men. The average age of patients at the time of implantation of 62.0 +/- 13.3 years (17.3 -90.2). The median follow-up was 7.6 +/- 4.8 years (maximum 20.1 years). For each patient, Wenckebach point was above 130/min. Of the 251 patients, 98 were undergoing treatment reimplantation of stimulating system. The median time to stimulate the function of the type of AAI was 8.69 +/- 2.4 years. The main cause was the exhaustion of the battery replacement--91.8% of cases, but sometimes less damage to the electrodes--7.1% of cases. Duration does not depend on the gender of the patient, or to his age at the time of implantation. The most common cause of reimplantation is battery exhausted. AAI stimulation is very effective treatment in the test group of patients.


Effect of ambient winter air pollution on respiratory health of children with chronic respiratory symptoms.
The acute respiratory effects of ambient air pollution were studied in a panel of 73 children with chronic respiratory symptoms in the winter of 1990 to 1991. The participating children were selected from all children aged 6 to 12 yr in Wageningen and Bennekom, two small, nonindustrial towns in the east of the Netherlands. Peak flow was measured twice daily with MiniWright meters. A diary was used to register the occurrence of acute respiratory symptoms and medication use by the children. Exposure to air pollution was characterized by the ambient concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), black smoke (BS), and particulate matter less than 10 microns (PM10). Associations between air pollution concentrations and health outcomes were analyzed using time series analysis. During the study period an air pollution episode occurred, with moderately elevated concentrations of PM10 and SO2. There were 6 days with 24-h average PM10 concentrations in excess of the WHO suggested lowest observed effect level of 110 micrograms/m3. After adjustment for ambient temperature, there were small but statistically significant negative associations of PM10, BS, and SO2 with both morning and evening PEF. There was a consistent positive association between PM10, BS, and SO2 with the prevalence of wheeze and bronchodilator use. Overall, the observed associations suggest a mild to moderate response to these moderately elevated levels of air pollution in a group of potentially sensitive children.


Malaria cases in Switzerland from 2005 to 2015 and recent rise of imported Plasmodium vivax malaria.
Reporting cases of malaria to the Federal Office of Public Health has been mandatory in Switzerland since 1974. We analysed notifications of imported confirmed malaria cases between 2005 and 2015 in Switzerland or Liechtenstein. Data for previously visited countries, nationality and reason for travelling were analysed. In contrast with the impressive drop of malaria cases reported worldwide since 2000, we found that the number of malaria cases imported yearly in Switzerland doubled in 2014 and 2015 compared to the average for the preceding decade. Since 2014, Plasmodium vivax infection represented 36% of all diagnosed malaria cases in Switzerland, compared to 11% in the decade leading to 2013. Most of the vivax malaria patients originated from the Horn of Africa, especially from Eritrea. This rise in cases was a consequence not only of an increase in the number of Eritrean refugees, but also their vivax malaria incidence rate, which jumped from 1-3‰ previously to 12‰ in 2014. This is a trend that is not matched by national statistics in Eritrea. An unreported increased incidence in the country of origin (Eritrea) might be the cause of the rise of Pv cases imported into Switzerland, but infections are also likely to occur along the harsh and long migration journey. This epidemiology highlights the need to register and use primaquine for the treatment of latent-phase P. vivax malaria in Switzerland, a medicine currently neither marketed nor systematically reimbursed. Moreover, general practitioners should be aware of this specific epidemiological situation in order to avoid misdiagnosis of febrile Eritreans even months after they reach Switzerland.


Immune complexes in pregnancy. III. Immune complexes in immune complex-associated conditions.
Seventeen patients during the third trimester of pregnancy with associated immune complex disease and/or immune complex state and their infants' cord blood were investigated for the presence of immune complexes. In comparing maternal levels of immune complex in normal third-trimester pregnancies to the study group, no statistical significant difference was noted. However, levels in cord blood were significantly lower (p less than 0.0025) than levels in paired maternal samples, but were found to correlate significantly (p less than 0.002). On the basis of the immunochemical analysis of selected pairs, the conclusion is that IgG-containing immune complexes may be responsible for this observed correlation and may represent the normal physiologic situation of pregnancy, whereas IgM-containing immune complexes may represent pathologic, and, therefore, abnormal, states. The suggestion is that the presence of such IgM-containing immune complexes may become predictive of fetoplacental compromise.


A clinical technique for prevention of spasm and preservation of endothelium in saphenous vein grafts.
Spasm and endothelial injury during harvesting of saphenous vein grafts can be prevented by a protocol that involves perivenous infiltration with 37 degrees C papaverine hydrochloride solution prior to skin incision, initial distention of the vein with the same warm papaverine solution, storage of the distended vein graft in a cold papaverine solution, and maintenance of the vein in the distended state throughout the operative procedure. This technique preserves endothelial integrity in human reversed saphenous vein grafts.


The Complete Mitochondrial Genome of Aleurocanthus camelliae: Insights into Gene Arrangement and Genome Organization within the Family Aleyrodidae.
There are numerous gene rearrangements and transfer RNA gene absences existing in mitochondrial (mt) genomes of Aleyrodidae species. To understand how mt genomes evolved in the family Aleyrodidae, we have sequenced the complete mt genome of Aleurocanthus camelliae and comparatively analyzed all reported whitefly mt genomes. The mt genome of A. camelliae is 15,188 bp long, and consists of 13 protein-coding genes, two rRNA genes, 21 tRNA genes and a putative control region (GenBank: KU761949). The tRNA gene, trnI, has not been observed in this genome. The mt genome has a unique gene order and shares most gene boundaries with Tetraleurodes acaciae. Nineteen of 21 tRNA genes have the conventional cloverleaf shaped secondary structure and two (trnS₁ and trnS₂) lack the dihydrouridine (DHU) arm. Using ARWEN and homologous sequence alignment, we have identified five tRNA genes and revised the annotation for three whitefly mt genomes. This result suggests that most absent genes exist in the genomes and have not been identified, due to be lack of technology and inference sequence. The phylogenetic relationships among 11 whiteflies and Drosophila melanogaster were inferred by maximum likelihood and Bayesian inference methods. Aleurocanthus camelliae and T. acaciae form a sister group, and all three Bemisia tabaci and two Bemisia afer strains gather together. These results are identical to the relationships inferred from gene order. We inferred that gene rearrangement plays an important role in the mt genome evolved from whiteflies.


Synthesis and pharmacological properties of thieno[2',3':4,5]pyrimido [2,1-b][1,3,4]thiadiazine derivatives.
A new series of 2-substituted-7,8-dimethyl-3H,9H-thieno[2',3':4,5]pyrimido[2,1- b][1,3,4]thiadiazin-9-ones 5a-d and 6a,b was synthesized through the hydrazinium(1+) salt of 3-amino-2,3-dihydro-5,6-dimethyl-2-thioxo- thieno[2,3-d]pyrimidin-4(1H)-one, 2. These derivatives and two analogs 10a,b were tested for their analgesic and antiinflammatory properties. The pharmacological results are discussed in comparison with those of related compounds previously tested.


Anemia management in chronic kidney disease: what have we learned after 17 years?
Anemia management remains controversial in patients with chronic kidney disease (CKD). The overwhelming conclusion from retrospective data analyses show a strong correlation between higher hemoglobin values and improved outcomes, including mortality, hospitalization, left ventricular hypertrophy, and quality of life. However, the evidence available from two large prospective trials in CKD comparing hemoglobin values near the current target of 11-12 g/dl with normalization or near normalization were stopped, as there was a trend toward worsening outcomes in the higher hemoglobin groups. This disparity suggests that patients who have or achieve high hemoglobin values on low doses or no erythropoietin may be inherently different from the general CKD population. Therefore targeting to a hemoglobin value above the current recommendation with intermittent erythropoietin seems unwarranted until randomized prospective trials demonstrate both safety and efficacy.


Colloidal self-assembly meets nanofabrication: from two-dimensional colloidal crystals to nanostructure arrays.
Self-assembly of colloidal microspheres or nanospheres is an effective strategy for fabrication of ordered nanostructures. By combination of colloidal self-assembly with nanofabrication techniques, two-dimensional (2D) colloidal crystals have been employed as masks or templates for evaporation, deposition, etching, and imprinting, etc. These methods are defined as "colloidal lithography", which is now recognized as a facile, inexpensive, and repeatable nanofabrication technique. This paper presents an overview of 2D colloidal crystals and nanostructure arrays fabricated by colloidal lithography. First, different methods for fabricating self-assembled 2D colloidal crystals and complex 2D colloidal crystal structures are summarized. After that, according to the nanofabrication strategy employed in colloidal lithography, related works are reviewed as colloidal-crystal-assisted evaporation, deposition, etching, imprinting, and dewetting, respectively.


Familial ossification of the stylohyoid ligament in a three generation family--a new clinical entity displaying autosomal dominant inheritance.
Ossification of the stylohyoid ligament is very common in the Caucasian population. More than 9000 descriptions of apparently isolated case reports on PubMed have been cited over the last 20 years, often associated with an incidental finding on imaging after neck trauma. No cases of familial ossification have been described. We document a family with several affected members, each with an ossified stylohyoid ligament, confirming that ossification may be hereditary in some families and is most likely due to an autosomal dominant gene.


[Effectiveness of neoadjuvant chemoradiotherapy of locally advanced rectal cancer in conjunction with local hyperthermia and metronidazole].
Our study included 36 patients with hard fixed rectal tumors (T3, T4) who had received combined treatment at the Center's Clinics. On irrigoscopic evidence, lesions were more than 10 cm long. Radiotherapy was conducted thrice a week, STD of 4 Gy--TTD of 40 Gy; capecitabine, per os, 650 mg/m2 twice a day, days 1-22; oxaliplatin, 50 mg/m2, intravenously, days 3, 10 and 17; metronidazole in polymer composition, intrarectally, 10 mg/m2, twice, days 12 and 17 of radiotherapy; local hyperthermia (the <<Yakhta-4>> installation), 460 mHz, 41-45 deg. C, 60 min, days 8, 12, 15 and 17. Diarrhea (stage III) was reported in 3 (8.3%); no toxicity (grade IV). Radical surgery was carried out in 35 (97.2%); sphincter-saving operation--20 (55.5%). Therapy-related pathomorphism (grade III-IV) was detected in 15 (42.8%). Combined neoadjuvant chemoradiotherapy plus polyradiomodification featured low toxicity and good tolerability and immediate effect.


Atrazine and estradiol effects on development of Acris blanchardi (Blanchard's cricket frog) exposed in outdoor enclosures.
The herbicide atrazine has been proposed as a potential endocrine disrupting compound (EDC) for amphibians. Using atrazine concentrations below or at those typically found in surface waters (0.5, 5.0, 50 μg/L), we exposed Acris blanchardi (Blanchard's cricket frog) larvae throughout development until metamorphosis (i.e. Gosner stages 26-45). An additional 50 μg/L treatment (50s μg/L) was utilized where supplemented algae was added to control for indirect atrazine effects from reduced food sources. In addition to atrazine, experimental groups also included a negative control and two positive controls, 17β-estradiol (E2) at 2.3 and 25 μg/L. At 60 days post-metamorphosis, A. blanchardi metamorphs were euthanized for analysis of gross and histopathological development. Atrazine did not significantly influence mortality (mean recovery of 54% across treatments), sex ratio, body mass (BM), snout-vent length (SVL), gonad size, nor gonad development of A. blanchardi. Females exposed to 50s μg/L atrazine had 29% less mass, were 10% shorter, and had a 29% lower mean ovary area (mm2 ) as compared to negative controls, suggesting algae enrichment had a significant negative effect. Males exposed to estradiol (25 μg/L) showed an increased level of oviduct development. Ovary area was also significantly influenced by estradiol treatment at 2.3 and 25 μg/L. Overall, estradiol had much less effect than predicted based on other model species (e.g. Xenopus laevis). Development of A. blanchardi, overall, was not affected by long-term exposure to environmentally relevant concentrations of atrazine. However, this species also was largely insensitive to exogenous estradiol in this test system. © 2022 Society of Chemical Industry.


Early predictors of asthma.
A number of recent cohort and cross-sectional studies have contributed substantial knowledge to factors that influence the early development of asthma. Here, we summarize the recent evidence for the role of early life events such as prenatal factors, infections, diet and allergen exposure, and discuss the implications for future preventative strategies.


A physiologically relevant hyperthermia selectively activates constitutive hsp70 in H9c2 cardiac myoblasts and confers oxidative protection.
Whole body hyperthermia (42-43 degrees C for 15-20 min) elicits the formation of heat shock proteins (hsps) and improves cardiac recovery from subsequent ischemia/reperfusion. However, the beneficial effects of this response are compromised by initial tissue injury, which limits its clinical applicability. Using a simplified myocardial model (rat heart-derived H9c2 myoblasts) a hypothesis was tested that chronic, mild hyperthermia is as effective as acute heat shock in inducing the heat shock response. Our results indicate that 39 degrees C pre-conditioning evoked thermotolerance and oxidative resistance, but caused no detectable adverse effects. An improved survival after hydrogen peroxide (H2O2) exposure (40-54 microm for 3 h) was first observed in cells pre-conditioned at 39 degrees C for 24 h. As the duration of thermal pre-incubation increased, cells became more resistant than the control (37 degrees C) to a greater toxicity of H2O2(68 microm). An optimal oxidative protection developed by;4 days at 39 degrees C and this persisted for as long as the cells were incubated at this temperature. Three hsps are known to modulate cellular antioxidant defenses: the constitutive-hsp70 (hsc70), its inducible counterpart (hsp70), and hsp27. The authors found that mild hyperthermia selectively induced only hsc70, which demonstrates a lower temperature threshold for activation of hsc70. The initial protection against the milder H2O2challenge correlated with a homogenous distribution of pre-existing hsc70. The subsequent optimal protection was associated with an identical distribution pattern and a moderate increase of hsc70. These observations suggest that mild hyperthermia induces a beneficial adaptive response, in which hsc70 plays a critical role.


Arabidopsis 22-kilodalton peroxisomal membrane protein. Nucleotide sequence analysis and biochemical characterization.
We sequenced and characterized PMP22 (22-kD peroxisomal membrane protein) from Arabidopsis, which shares 28% to 30% amino acid identity and 55% to 57% similarity to two related mammalian peroxisomal membrane proteins, PMP22 and Mpv17. Subcellular fractionation studies confirmed that the Arabidopsis PMP22 is a genuine peroxisomal membrane protein. Biochemical analyses established that the Arabidopsis PMP22 is an integral membrane protein that is completely embedded in the lipid bilayer. In vitro import assays demonstrated that the protein is inserted into the membrane posttranslationally in the absence of ATP, but that ATP stimulates the assembly into the native state. Arabidopsis PMP22 is expressed in all organs of the mature plant and in tissue-cultured cells. Expression of PMP22 is not associated with a specific peroxisome type, as it is detected in seeds and throughout postgerminative growth as cotyledon peroxisomes undergo conversion from glyoxysomes to leaf-type peroxisomes. Although PMP22 shows increased accumulation during the growth of young seedlings, its expression is not stimulated by light.


Functional cloning and expression of a novel Endo-alpha-1,5-L-arabinanase from a metagenomic library.
A novel endo-alpha-L-arabinanase gene (arn2) was isolated, and expressed in E. coli in active form. The recombinant enzyme (ARN2) had optimum activity at pH 6.0 and 45-50( degrees )C with stability between pH 5.0-8.0 and at temperatures up to 40( degrees )C. The recombinant ARN2 catalyzed internal cleavage of alpha-1,5 glycosidic bonds of CM-arabinan, debranched arabinan, linear arabinan, and sugar beet (native) arabinan at rates of decreasing order, and was inactive on wheat arabinoxylan and p-nitrophenyl-alpha-L-arabinofuranoside. Kinetic analysis showed that branching in the arabinan did not significantly affect the apparent K(m) values, and the difference in the reaction rates was likely due to the chemical step after substrate binding. The enzyme hydrolyzed arabino-oligosaccharides of DP> or =6 to smaller oligomers and mostly arabinotriose. Natural and modified arabinans were cleaved to oligomers of various chain lengths, which were progressively hydrolyzed to yield arabinotriose. The pattern of degradation revealed an endo-acting mechanism with arabinotriose as the end product.


Low prevalence of significant carotid artery disease on ultrasound in patients proceeding to coronary artery bypass surgery.
Cardiothoracic surgery is associated with an increased risk of perioperative stroke. Preoperative carotid ultrasonography can identify significant stenosis, but there is debate about the value of screening. The aims of this study were to (i) determine the prevalence of significant carotid artery disease in screened patients undergoing cardiothoracic surgery and (ii) correlate their ultrasonographic findings with perioperative strokes. Retrospective analysis of 166 patients (118 men, 48 women) who underwent a preoperative carotid ultrasound and coronary artery bypass graft surgery (CABG) from 2004 to 2007. Perioperative strokes were recorded and compared with ultrasonographic and clinical data. A separate cohort of 1423 patients (1064 men, 359 women) who underwent CABG over the same period was also evaluated. Only 11 screened patients (6.6%) had significant (>70%) carotid artery disease and two of these underwent simultaneous carotid endarterectomy. There were five perioperative strokes in screened patients, four of which occurred in individuals with <50% disease. Compared with the non-screened cohort, ultrasound screened patients were older and more likely to have a prior stroke or transient ischaemic attack, hypertension, hypercholesterolaemia, peripheral vascular disease and/or renal impairment than non-screened patients. There was no significant difference in perioperative strokes compared with non-screened patients (3% vs 1.2% respectively, P= NS). There is a low prevalence of significant carotid artery disease in ultrasound screened patients. The risk of perioperative strokes in screened patients is low and not significantly different from non-screened patients.


Global analysis of the genes involved in the thermotolerance mechanism of thermotolerant Acetobacter tropicalis SKU1100.
Acetobacter tropicalis SKU1100 is a thermotolerant acetic acid bacterium that grows even at 42 °C, a much higher temperature than the limit for the growth of mesophilic strains. To elucidate the mechanism underlying the thermotolerance of this strain, we attempted to identify the genes essential for growth at high temperature by transposon (Tn10) mutagenesis followed by gene or genome analysis. Among the 4,000 Tn10-inserted mutants obtained, 32 exhibited a growth phenotype comparable to that of the parent strain at 30 °C but not at higher temperatures. We identified the insertion site of Tn10 on the chromosomes of all the mutant strains by TAIL (Thermal Asymmetric Interlaced)-PCR, and found 24 genes responsible for thermotolerance. The results also revealed a partial overlap between the genes required for thermotolerance and those required for acetic acid resistance. In addition, the origin and role of these thermotolerant genes are discussed.


[How to assess and monitor postoperative artificial nutrition?].
Quantitative and qualitative nutritional requirements depend on the level of energetic expenses. Various formulas, especially the tables by Harris and Benedict allow the estimation of the level of energetic expenses with an approximation of 14%. Corrective factors permit an adjustment of the figures, according to the level of body aggression. In complex cases, indirect calorimetry allows a more accurate appraisal of energetic expenses. This technique provides also indications on the utilisation of each substrate and allows therefore to determine the optimal carbohydrate-lipid ratio for each patient. The assessment of the direct benefit of artificial nutritional support relies on anthropometric techniques and at present on body composition appraisal by determination of its impedance. The changes in muscular strength are difficult to assess. Moreover the time course of body weight is not specific for nutritional status. Therefore other biological indicators such as the nitrogen balance, the concentration of plasma proteins and albumin are more often assessed; proteins with a short half-life depend on the body aggression level. The potassium balance, which is easy to obtain in clinical practice, is a relevant indicator for nitrogen balance and protein synthesis. Clinical monitoring includes the checking of hydratation and its impact on the circulatory, respiratory and renal functions. The tolerance of enteral nutrition is appraised by the quality of gastrointestinal function. Biological monitoring includes the electrolyte balance and various variables of carbohydrate, lipidic and proteic metabolisms. It allows to check the absence of hyperglycaemia, hyperlipidaemia and cholestasis. The daily checking of catheters is part of the monitoring of nutritional support.(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of restorative care training on caregiver job satisfaction.
The job satisfaction of assisted living facility staff was examined as part of an evaluation study of a restorative care training program. Participants completed a job satisfaction survey at registration (before the training) and again at follow-up 3 months after registration (1 month after the conclusion of the training). Researchers examined the effects of training on job satisfaction. Researchers found a high level of job dissatisfaction at registration. At follow-up, responses were more positive on most of the items suggesting a slight but significant change to a more positive attitude toward their jobs. Improving staff job satisfaction in the assisted living environment is an important goal and needs further investigation. Providing staff with inservice training may be one way to help nurse educators achieve that goal.


Characterization of reperfused infarcted myocardium from high-frequency intracardiac ultrasound imaging using homodyned K distribution.
Myocardial changes caused by infarction/reperfusion (contraction band necrosis, hemorrhage, edema, etc.) may result in an increased scatterer density and a variation in scatterer arrangement. This paper, for the first time, models most of the scattering conditions resulting from the interaction of ultrasound and normal/reperfused infarcted myocardium using the homodyned K distribution. Furthermore, this method is used to characterize the change in scatterer density by calculating the effective scatterer number per resolution cell. The reliability and the effects of attenuation and scan conversion on effective scatterer number estimation are discussed. We used in vivo data acquired using high-frequency intracardiac ultrasound imaging (8.5 MHz) from the left and right ventricles of open-chest pigs in an acute infarction/reperfusion model. The results show that the homodyned K distribution describes the statistical distribution of backscattered signal from both normal and abnormal myocardium. A significant increase in scatterer density occurs in the infarcted region after reperfusion compared with the same region at baseline (normal myocardium prior to occlusion). The scatterer density of the normal region does not change significantly after reperfusion. We conclude that the homodyned K distribution may characterize normal and reperfused infarcted myocardium using high-frequency intracardiac ultrasound images.


Validated Impacts of N6-Methyladenosine Methylated mRNAs on Apoptosis and Angiogenesis in Myocardial Infarction Based on MeRIP-Seq Analysis.
Objectives: N6-methyladenosine (m6A) is hypothesized to play a role in the regulation of pathogenesis of myocardial infarction (MI). This study was designed to compare m6A-tagged transcript profiles to identify mRNA-specific changes on pathophysiological variations after MI. Methods: N6-methyladenosine methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were interacted to select m6A-modified mRNAs with samples collected from sham operated and MI rat models. m6A methylation regulated mRNAs were interacted with apoptosis/angiogenesis related genes in GeneCards. Afterwards, MeRIP-quantitative real-time PCR (MeRIP-qRT-PCR) was performed to measure m6A methylation level of hub mRNAs. m6A methylation variation was tested under different oxygen concentration or hypoxic duration in H9c2 cells and HUVECs. In addition, Western blot and qRT-PCR were employed to detect expression of hub mRNAs and relevant protein level. Flow cytometry and Tunel assay were conducted to assess apoptotic level. CCK-8, EdU, and tube formation assay were performed to measure cell proliferation and tube formation ability. Results: Upregulation of Mettl3 was firstly observed in vivo and in vitro, followed by upregulation of m6A methylation level. A total of 567 significantly changed m6A methylation peaks were identified, including 276 upregulated and 291 downregulated peaks. A total of 576 mRNAs were upregulated and 78 were downregulated. According to combined analysis of MeRIP-seq and RNA-seq, we identified 26 significantly hypermethylated and downregulated mRNAs. Based on qRT-PCR and interactive analysis, Hadh, Kcnn1, and Tet1 were preliminarily identified as hub mRNAs associated with apoptosis/angiogenesis. MeRIP-qRT-PCR assay confirmed the results from MeRIP-seq. With the inhibition of Mettl3 in H9c2 cells and HUVECs, downregulated m6A methylation level of total RNA and upregulated expression of hub mRNAs were observed. Increased m6A level was verified in the gradient context in terms of prolonged hypoxic duration and decreased oxygen concentration. Under simulated hypoxia, roles of Kcnn1 and Tet1 in angiogenesis and Hadh, Tet1, and Kcnn1 in apoptosis were further confirmed with our validation experiments. Conclusion: Roles of m6A-modified mRNA transcripts in the context of MI were preliminarily verified. In the context of m6A methylation, three hub mRNAs were validated to impact the process of apoptosis/angiogenesis. Our study provided theoretical basis and innovative targets for treatment of MI and paved the way for future investigations aiming at exploring upstream epigenetic mechanisms of pathogenesis after MI.


Effect of Electrolytic Manganese Residue in Fly Ash-Based Cementitious Material: Hydration Behavior and Microstructure.
Electrolytic manganese residue (EMR) is a solid waste with a main mineralogical composition of gypsum. It is generated in the production of metal manganese by the electrolysis process. In this research, EMR, fly ash, and clinker were blended to make fly ash-based cementitious material (FAC) to investigate the effect of EMR on strength properties, hydration behavior, microstructure, and environmental performance of FAC. XRD, TG, and SEM studied the hydration behavior of FAC. The pore structure and [SiO4] polymerization degree were characterized by MIP and 29Si NMR, respectively. The experimental results indicate that FAC shows excellent mechanical properties when the EMR dosage is 10%. Moderate content of sulfate provided by EMR can promote hydration reaction of FAC, and it shows a denser pore structure and higher [SiO4] polymerization degree in this case. Heavy metal ions derived from EMR can be adsorbed in the hydration products of FAC to obtain better environmental properties. This paper presents an AFt covering model for the case of excessive EMR in FAC, and it importantly provides theoretical support for the recycling of EMR in cementitious materials.


The Effect of Vinegar Supplementation on High-Intensity Cycling Performance within Recreationally Trained Individuals.
Background and objectives: To investigate the effects of vinegar ingestion upon high-intensity cycle performance in recreationally trained individuals. Materials and methods: Twenty-two participants consumed one of the following in a randomized order on four separate visits: (1) 29 mL of vinegar along with 451 mL of water, (2) 39 g of sucrose along with 441 mL of water, (3) 29 mL of vinegar and 39 g of sucrose along with 412 mL of water, or (4) 480 mL of water alone. For each of the experimental testing sessions, all participants completed in order: (1) high-intensity cycle test 1, (2) fatiguing cycle test, (3) high-intensity cycle test 2, (4) supplement consumption, (5) 90 min rest period, and (6) high-intensity cycle test 3. Total time to exhaustion (TTE) and average heart rate (HR) for each set of sprints was used in analysis. Results: There was no supplement by time interaction or significant main treatment effect observed (p > 0.05) for either TTE or HR. However, there was a main time effect observed, with TTE (p = 0.0001) being lower for cycle test 2 than both cycle test 1 and cycle test 3, and cycle test 3 being lower than cycle test 1. HR (p = 0.0001) was lower for cycle test 3 than both cycle test 1 and cycle test 2, but HR for cycle test 1 did not differ significantly from HR for cycle test 2. Conclusions: The addition of vinegar or sucrose alone, or in combination, was ineffective in improving cycle sprinting TTE when performing three cycle tests.


[Appendix protrusion from perforation of uterus--the rare complication during abortion].
Point to an extremly rare complication of a curettage during abortion and follow up surgical treatment of this complicated state. In the case of 32 years old woman, multipara, was perforated cervix uteri during the abortion curettage and fat tissue of mesentery was aspirated into canulla. Apendix vermiformis was aspirated into cannula with its protrusion through the neck of the womb during repeated revision. Surgeon made appendectomy lege artis after abdomen revision and looking after haemoperitoneum. Because of serious devastation of right fallopian tube, salpingektomy was performed. Perforation of cervix in the lenght of three cm was sutured. Extensive incomplete rupture continuing from perforation gap was sutured from ligamentum sacrouterinum I.dx to fundus uteri. Intact foetus of 5,5 week of gestation was leaved in toto because of the high risk of the womb wall disruption during repeatedly attempted abortion. In case of the suspection of the uterus injury a revision and interdisciplinary approach to the solution of complications is necessary.


Stable growth in native-dependent multistate population dynamics.
"Users of multistate life tables and projections have recognized that the Markovian assumptions underlying such models are unduly restrictive and should be relaxed whenever data permit. Efforts to include the influences of previous occupancies have included the incorporation of place-of-birth dependence. This paper addresses the stable growth properties of such generalized multistate models. It shows how place-of-birth-specific stable growth measures can be calculated without projection simply by solving the characteristic equation. An example using Canadian data illustrates the argument." (SUMMARY IN FRE)


Inhibition of somatic embryogenesis in orchardgrass by endogenous cytokinins.
Endogenous indoleacetic acid (IAA) and cytokinin concentrations were measured by high performance liquid chromatography in leaf sections of an orchardgrass (Dactylis glomerata L.) genotype which exhibited a high capacity for somatic embryogenesis in vitro and in two genotypes that did not exhibit this capacity. The nonembryogenic genotypes contained 3- to 4-fold higher concentrations of zeatin, zeatin riboside, dihydrozeatin, dihydrozeatin riboside, and total cytokinins than the embryogenic genotype. There were no significant differences in IAA concentrations between genotypes. Cytokinin concentrations between basal and distal sections of embryogenic genotype were not different, but the IAA concentration was significantly greater in basal sections. Somatic embryogenesis was inhibited in the embryogenic genotype by 0.001 micromolar exogenously added zeatin.


Adding a statin to a combination of ACE inhibitor and ARB normalizes proteinuria in experimental diabetes, which translates into full renoprotection.
The capacity of renin-angiotensin system (RAS) inhibitors to delay progression of diabetic nephropathy depends on the time at which therapy is started. A multimodal intervention is required to afford renoprotection in overt diabetic nephropathy. Here we assessed the effects of maximal RAS inhibition by angiotensin-converting enzyme (ACE) inhibitor plus angiotensin II type 1 receptor blocker (ARB) in combination with statin in rats with overt diabetic nephropathy. Uninephrectomized rats made diabetic by streptozotocin were orally treated from 4 (when proteinuria and renal lesions had developed) to 8 mo with vehicle, lisinopril plus candesartan, lisinopril plus candesartan plus rosuvastatin, or rosuvastatin alone. Systolic blood pressure increased in diabetic rats and was significantly lowered by combined therapies. Dual RAS blockade significantly reduced proteinuria compared with vehicle. Addition of statin further lowered proteinuria to control levels. Glomerulosclerosis was ameliorated by RAS inhibitors or statin, and regression was achieved by the addition of statin. Loss of podocytes of diabetic rats was limited by ACE inhibitor plus ARB while normalized by the three drugs. Defective nephrin expression of diabetes was increased by dual RAS blockade or statin and restored by the triple therapy. Tubular damage, interstitial inflammation, and expression of the fibrotic markers transforming growth factor (TGF)-β1 and phosphorylated Smad 2/3 in tubuli were significantly reduced by the triple regimen. These data suggest a strategy to target proteinuria to try to achieve regression of renal disease in diabetic patients who do not fully benefit from RAS inhibition alone.


Effect of piliation on interactions of Haemophilus influenzae type b with human polymorphonuclear leukocytes.
Piliated, adherent (P+) and nonpiliated, nonadherent (P-) strains of Haemophilus influenzae type b (Hib) were compared with respect to their ability to induce polymorphonuclear leukocyte (PMN) chemiluminescence (CL) and superoxide (O2-) generation and their susceptibility to phagocytosis by PMNs. P+ strains opsonized in normal human serum (NHS) induced significantly greater CL than did P- strains (500 X 10(5) +/- 112 X 10(5) versus 242 X 10(5) +/- 65 X 10(5) total counts per 60 min; P less than 0.001) when reacted with normal PMNs. Contributions of immunoglobulin and complement to CL activity in these mixtures were shown by findings of lower overall levels of CL when hypogammaglobulinemic serum or heat-inactivated NHS was used to opsonize either P+ or P- organisms. Results obtained with mixtures of hypogammaglobulinemic plus adsorbed heat-inactivated NHS (with P+ or P- organisms) suggested a role for an antipilus antibody in the enhancement of CL by these strains. NHS-opsonized P+ strains also induced significantly greater (P less than 0.002) O2- generation than did P- strains (2.83 +/- 0.08 versus 1.94 +/- 0.14 nmol of ferricytochrome c reduced per 10 min/10(6) PMN). Comparable ingestion of P+ or P- strains opsonized in NHS by PMNs was demonstrated by a radiolabeled uptake technique and transmission electron microscopy, and primary granule release (beta-glucuronidase) was comparable during ingestion of P+ or P- strains. The basis for the observed enhanced capacity of P+ Hib to stimulate PMN oxidative metabolism as compared with P- organisms is uncertain. Possible clinical implications of these findings deserve further study.


Preparation and photocatalytical performance of TiO2:SiO2 nanocomposites produced by the polymeric precursors method.
Anatase TiO2 is a promising photocatalyst due to its chemical stability, non-toxic characteristics, notable UV light absorption as well as photo-corrosion resistance and oxidative properties. Surface area and TiO2 dispersion quality are important factors that affect photoactivity of TiO2:SiO2 nanocomposites. In order to improve these factors, TiO2 nanoparticles were immobilized on mesoporous silica substrate through the polymeric precursors method, obtaining the nanocomposites in a simple routine. The TiO2 resin was synthesized by the polymeric precursors method and different resin thickness (0.5; 1.0; 2.0; 3.5; 5.0 nm) on silica were synthesized by calcination during 4 hours at 450 degrees C in pH 1.5. The selected pH for immobilization ensured adhesion of TiO2 nanoparticles onto the silica substrate surface. X-Ray Diffraction patterns indicate that all samples were predominantly anatase phase and immobilization improved surface area. Ametryn kinetic evaluation presents better results for SAM 3.5 and SAM 0.5. The results show that difference in TiO2 loading, surface area and crystallinity of samples are factors that influence photocatalytic efficiency.


Monkeypox (Mpox) virus isolation and ultrastructural characterisation from a Brazilian human sample case.
According to the last 2023 Monkeypox (Mpox) Outbreak Global Map from the Centres for Disease Control and Prevention (CDC), more than 100 countries with no Mpox infection report cases. Brazil stands out in this group and is the second country with the highest number of cases in the last outbreak. To contribute to knowledge of the virus infection effects in a cellular model, which is important for diagnosis infections not yet included in a provider´s differential diagnosis and for developing viral inhibition strategies. We describe a virus isolation protocol for a human clinical sample from a patient from Brazil, the viral growth in a cell model through plaque forming units (PFU) assay, reverse transcriptase polymerase chain reaction (RT-PCR) and transmission electron microscopy (TEM). We follow the viral isolation in Vero cell culture from a Mpox positive clinically diagnosed sample and show the infection effects on cellular structures using a TEM. Understanding the impact of viral growth on cellular structures and its replication kinetics may offer better strategies for the development of new drugs with antiviral properties.


Effects of temperature on the coupled activities of the vanadate-sensitive proton pump from maize root microsomes.
The mechanism by which proton transport is coupled to ATP hydrolysis by vanadate-sensitive pumps is poorly understood. The effects of temperature on the activities of the vanadate-sensitive ATPase from maize (Zea mays) roots were assessed to provide insight into the coupling mechanism. The initial rate of proton transport had a bell-shaped dependence on temperature with an optimal range between 20 and 30 degrees C. However, the rate of vanadate-sensitive ATP hydrolysis increased as the temperature was raised from 4 to 43 degrees C. The differential sensitivity of proton transport to temperatures above 30 degrees C was also observed when the ATPase was reconstituted into dioleoylphosphatidylcholine vesicles. Inhibition of proton transport with temperatures above 30 degrees C was associated with higher rates of proton leakage from the membranes. In addition, proton transport was more inhibited than ATP hydrolysis at temperatures below 10 degrees C. Reduced rates of proton transport at lower temperatures were not associated with higher rate of proton conductivity across the membranes. Therefore, the preferential inhibition of proton transport at temperatures below 10 degrees C may reflect an effect of temperature on the coupling between proton transport and ATP hydrolysis within the vanadate-sensitive ATPase.


Estimation of radionuclide ingestion: the "PATHWAY" food-chain model.
This paper describes the structure of the dynamic food-chain model PATHWAY and its utility for estimating radionuclide ingestion after fallout deposition from nuclear testing in Nevada. Model input requirements are described and output examples are provided. The basic output of PATHWAY is the time-integrated radionuclide ingestion by humans per unit fallout deposition (Bq per Bq m-2). Output specific to sex, age, life-style (diet), location (agricultural practice), event (calendar date), and radionuclide may be generated. Uncertainties of model predictions, based on "Monte Carlo" simulations using parameter value distributions, are described. Results of a sensitivity analysis, based on a ranking of partial correlation coefficients, are reviewed to illustrate the relative importance of parameters and associated transport pathways. Output data for 131I and 137Cs in milk are compared with predictions from several well known food-chain models. Preliminary efforts to validate PATHWAY results with real data sets are described.


Chemical and Biocatalytic Routes to Arbutin †.
Arbutin (also called β-arbutin) is a natural product occurring in the leaves of a variety of different plants, the bearberries of the Ericaceae and Saxifragaceae families being prominent examples. It is a β-glucoside derived from hydroquinone (HQ; 1,4-dihydroxybenzene). Arbutin has been identified in traditional Chinese folk medicines as having, inter alia, anti-microbial, anti-oxidant, and anti-inflammatory properties that useful in the treatment of different ailments including urinary diseases. Today, it is also used worldwide for the treatment of skin ailments by way of depigmenting, which means that arbutin is a component of many products in the cosmetics and healthcare industries. It is also relevant in the food industry. Hundreds of publications have appeared describing the isolation, structure determination, toxicology, synthesis, and biological properties of arbutin as well as the molecular mechanism of melanogenesis (tyrosinase inhibition). This review covers the most important aspects with special emphasis on the chemical and biocatalytic methods for the production of arbutin.


Expressive writing moderates the relation between intrusive thoughts and depressive symptoms.
The author investigated whether expressive writing enhances emotional adaptation to a stressful event (graduate entrance exams) by reducing event-related intrusive thoughts or by desensitizing people to such thoughts. Participants in the experimental group, who were instructed to write their deepest thoughts and feelings about the exam, exhibited a significant decline in depressive symptoms from 1 month (Time 1) to 3 days (Time 2) before the exam. Participants in the control group, who wrote about a trivial topic, maintained a relatively high level of depressive symptoms over this same period. Expressive writing did not affect the frequency of intrusive thoughts, but it moderated the impact of intrusive thoughts on depressive symptoms. Specifically, intrusive thoughts at Time 1 were positively related to depressive symptoms at Time 2 in the control group and were unrelated to symptoms in the expressive writing group.


Pancreatitis following scoliosis surgery in children and young adults.
Forty-four patients undergoing single-stage surgery for scoliosis were monitored for biochemical and clinical evidence of pancreatitis. Six patients (14%) developed elevation of both serum amylase and lipase levels. Four of these had symptoms or signs suggestive of pancreatitis. Mean intraoperative blood loss was significantly higher in the group with pancreatitis. No significant differences were noted with regard to age, surgical technique, degree of initial or residual deformity, or length of surgery. The patients with pancreatitis required a longer average period of fasting time. Patients with prolonged ileus or abdominal pain after scoliosis surgery should be investigated for possible pancreatitis.


Asymmetric phthalocyanine synthesis by ROMP-capture-release.
Statistical condensation of norbornenyl-tagged phthalonitrile 3 (Pn A) and 4,5-di-4-methoxyphenoxyphthalonitrile 4 (Pn B) followed by ring-opening metathesis polymerization (ROMP) of Pcs AB(3) and B(4) produced asymmetric Pc-appended polymers. Acidic cleavage of the resulting polymers afforded 2,3,9,10,16,17-hexa-(4-methoxyphenoxy)-23-hydroxy Pc 9. A more soluble 2,3,9,10,16,17-hexa-4-pentylphenoxy-23-hydroxy Pc 13 was synthesized by the same strategy and modified with sebacoyl chloride demonstrating that the unmasked hydroxyl site is reactive as a nucleophile.


The medical implications of gastrointestinal vagal afferent pathways in nausea and vomiting.
Nausea and vomiting are biological systems for defense against food poisoning that are also provoked by numerous drugs (e.g., chemotherapy, anesthesia) and chronic diseases (e.g., cancer, diabetic gastroparesis). The sensory pathways that stimulate nausea and vomiting include vestibular, area postrema, and forebrain inputs, but gastrointestinal vagal afferent fibers arguably play the most prominent role as a first-line defense. Vagal sensory neurons detect toxins that enter the gastrointestinal lumen and transmit information to the hindbrain, leading to nausea (an unconditioned stimulus that serves to facilitate the avoidance of offending foods) and vomiting (a mechanism to clear contents from the stomach). Despite the major importance of these systems to human physiology, progress on the biological basis of nausea and vomiting has been slow - partly because laboratory rats and mice, which represent the largest thrust of preclinical biomedical research, lack a vomiting reflex (although they appear to have indices of nausea, e.g., conditioned food aversion). Several established models are a mainstay of preclinical nausea and vomiting research in academia and pharmaceutical companies, including the dog, cat, ferret, and musk shrew. An argument is made for broader testing across species since each model possesses often unique experimental advantages and sensitivity to emetic and antiemetic agents. This review focuses on the state of knowledge on the neural pathways for nausea and vomiting, behavioral indices of nausea used in preclinical models, role of vagal afferent fibers, current antiemetic and antinausea treatments, and potential future directions.


3'-Untranslated regions are important in mRNA localization and translation: lessons from selenium and metallothionein.
There is increasing evidence that 3'-UTRs (3'-untranslated regions) of mRNAs contain regulatory elements that have important roles in post-transcriptional control of gene expression. For example, 3'-UTRs are important in determining mRNA localization and directing selenocysteine insertion during selenoprotein synthesis. Metallothionein mRNA is localized around the nucleus and associated with the cytoskeleton; this is determined by the 3'-UTR. Deletion and mutagenesis studies are defining the nature of the signal. Incorrect mRNA localization prevents subsequent nuclear localization of metallothionein protein and affects its function. Selenium (Se) is incorporated as selenocysteine into approx. 30 mammalian proteins by a mechanism that requires a specific structure within the 3'-UTR of the corresponding mRNAs. When Se supply is low the effect on selenoprotein expression is not uniform but shows differential effects that are tissue- and protein-specific; there is a 'prioritization' of selenoprotein synthesis that is partly influenced by the 3'-UTRs of the different mRNAs. Single-nucleotide polymorphisms in the gene regions corresponding to 3'-UTRs could potentially influence gene regulation. We have discovered a common polymorphism in a part of the glutathione peroxidase 4 gene which corresponds to the 3'-UTR, and our recent results suggest that this single-nucleotide polymorphism has functional and physiological effects, as well as altered frequency in disease.


Procedures for the biochemical enrichment and proteomic analysis of the cytoskeletome.
The cell cytoskeleton is composed of microtubules, intermediate filaments, and actin that provide a rigid support structure important for cell shape. However, it is also a dynamic signaling scaffold that receives and transmits complex mechanosensing stimuli that regulate normal physiological and aberrant pathophysiological processes. Studying cytoskeletal functions in the cytoskeleton's native state is inherently difficult due to its rigid and insoluble nature. This has severely limited detailed proteomic analyses of the complex protein networks that regulate the cytoskeleton. Here, we describe a purification method that enriches for the cytoskeleton and its associated proteins in their native state that is also compatible with current mass spectrometry-based protein detection methods. This method can be used for biochemical, fluorescence, and large-scale proteomic analyses of numerous cell types. Using this approach, 2346 proteins were identified in the cytoskeletal fraction of purified mouse embryonic fibroblasts, of which 635 proteins were either known cytoskeleton proteins or cytoskeleton-interacting proteins. Functional annotation and network analyses using the Ingenuity Knowledge Database of the cytoskeletome revealed important nodes of interconnectivity surrounding well-established regulators of the actin cytoskeleton and focal adhesion complexes. This improved cytoskeleton purification method will aid our understanding of how the cytoskeleton controls normal and diseased cell functions.


The use of free anterolateral thigh flap for reconstructing soft tissue defects of the lower extremities.
The goal of soft tissue reconstruction in the lower extremities is to provide a functional and cosmetically acceptable limb. The anterolateral thigh flap has become one of the most popular options for soft tissue defect reconstruction recently because of the large amount of skin available and the reliable and versatile nature of this material. The purpose of this article is to present our experiences with the free anterolateral thigh flap for the reconstruction of soft tissue defects of the lower extremity. From April 2002 to October 2003, 31 consecutive free anterolateral thigh flaps were used. There were 24 male and 7 female patients, and their ages were between 3 and 78 years. The size of the flaps ranged from 11 to 34 cm long and 6 to 16 cm wide. In 9 patients, the flaps were harvested in a flow-through manner to both reconstruct soft tissue defects and protect and maintain the vascular status of the lower extremities. In these patients, the pedicle was interposed between vascular gaps, either present or created, in the extremity. The patency of distal anastomosis with the course of the distal vessel was confirmed by using conventional Doppler flow monitoring in flow-through flaps. In 4 cases, thinning of the flap was performed. In 3 patients, flaps were used in a neurosensorial fashion. Four flaps required reoperation due to vascular compromises. While 3 of these were salvaged, 1 flap was lost due to recipient arterial problems. Sixteen cases underwent split-thickness skin grafting of the donor site. No infection or hematomas were observed. We conclude that the anterolateral thigh flap is an ideal and versatile material, especially for lower extremity reconstructions, with its functional and cosmetic advantages, and it can be considered a suitable alternative to the most commonly used conventional soft tissue flaps.


A measure of association for assessing prediction accuracy that is a generalization of non-parametric ROC area.
There is a need for a measure of prediction accuracy that generalizes non-parametric receiver operating characteristic (ROC) area to polytomous ordinal patient state. We describe such a measure, prediction probability PK derived from Kim's measure of association. We show that the value of PK equals the value of non-parametric ROC area for dichotomous patient state and is a meaningful generalization of non-parametric ROC area for polytomous state.