Effect of liberal blood transfusion on clinical outcomes and cost in spine surgery patients.
Blood transfusions in spine surgery are shown to be associated with increased patient morbidity. The association between transfusion performed using a liberal hemoglobin (Hb) trigger-defined as an intraoperative Hb level of ≥10 g/dL, a postoperative level of ≥8 g/dL, or a whole hospital nadir between 8 and 10 g/dL-and perioperative morbidity and cost in spine surgery patients is unknown and thus was investigated in this study. This study aimed to describe the perioperative outcomes and economic cost associated with liberal Hb trigger transfusion among spine surgery patients. This is a retrospective study. The surgical billing database at our institution was queried for inpatients discharged between 2008 and 2015 after the following procedures: atlantoaxial fusion, anterior cervical fusion, posterior cervical fusion, anterior lumbar fusion, posterior lumbar fusion, lateral lumbar fusion, other procedures, and tumor-related surgeries. In total, 6,931 patients were included for analysis. The primary outcome was composite morbidity, which was composed of (1) infection (sepsis, surgical-site infection, Clostridium difficile infection, or drug-resistant infection); (2) thrombotic event (pulmonary embolus, deep venous thrombosis, or disseminated intravascular coagulation); (3) kidney injury; (4) respiratory event; and (5) ischemic event (transient ischemic attack, myocardial infarction, or cerebrovascular accident). Data on intraoperative transfusion were obtained from an automated, prospectively collected anesthesia data management system. Data on postoperative hospital transfusion were obtained through a Web-based intelligence portal. Based on previous research, we analyzed the data using three definitions of a liberal transfusion trigger in patients who underwent red blood cell transfusion: a liberal intraoperative Hb trigger as a nadir Hb level of 10 g/dL or greater, a liberal postoperative Hb trigger as a nadir Hb level of 8 g/dL or greater, or a whole hospital nadir Hb level of 8-10 g/dL. Variables analyzed included in-hospital morbidity, mortality, length of stay, and total costs associated with a liberal transfusion strategy. Among patients with a whole hospital stay nadir Hb between 8 and 10 g/dL, transfused patients demonstrated a longer in-hospital stay (median [interquartile range], 6 [5-9] vs. 4 [3-6] days; p<.0001) and a higher perioperative morbidity (n=145 [11.5%] vs. n=74 [6.1%], p<.0001) than those not transfused. Even after adjusting for age, gender, race, American Society of Anesthesiologists class, Charlson Comorbidity Index score, estimated blood loss, baseline Hb value, and surgery type, logistic regression analysis revealed that patients with a nadir Hb of 8-10 g/dL who were transfused had an independently higher risk of perioperative morbidity (odds ratio=2.11, 95% confidence interval, 1.44-3.09; p<.0001). Estimated additional costs associated with liberal trigger use, defined as a transfusion occurring in patients with a whole hospital stay nadir Hb of 8-10 g/dL, ranged from $202,675 to $700,151 annually. Transfusion using a liberal trigger is associated with increased morbidity, even after controlling for possible confounders. Our results suggest that modification of transfusion practice may be a potential area for improving patient outcomes and reducing costs.


A population survey of pancreatic islet cell antibodies.
A population study on pancreatic islet cell antibodies (pica) among 3766 people from the town of Busselton, Western Australia showed that such antibodies were infrequent, the 'classical' insulin-dependent diabetes associated islet cell antibody being present in less than 0.01%. Pancreatic islet cell antibodies in this population were not associated with insulin-dependent diabetes mellitus, and ten known insulin-dependent diabetics did not have these antibodies. These results for an unselected population are in sharp contrast with those derived from studies on highly selected hospital patients.


Catalytic activity of cytochrome P450 isozymes purified from rat liver in converting 11-oxo-delta 8-tetrahydrocannabinol to delta 8-tetrahydrocannabinol-11-oic acid.
Cytochrome P450 isozymes purified from rat hepatic microsomes were able to catalyse the oxidation of 11-oxo-delta 8-tetrahydrocannabinol (11-oxo-delta 8-THC) to delta 8-THC-11-oic acid in the presence of NADPH, cytochrome P450 reductase and dilauroylphosphatidylcholine. The catalytic activities (nmol/min/nmol P450) of cytochrome P450s, UT-2 (IIC11), UT-4 (IIA2), UT-5 (IIC13), PB-1, PB-2 (IIC6), PB-4 (IIB1), MC-1 (IA2), MC-5 (IA1) and IF-3 (IIA1), were 0.69, 0.08, 0.07, 0.23, 0.46, 0.02, 0.06, 0.07 and 0.34, respectively, whereas the activities of cytochrome P450s, PB-5 (IIB2) and DM (IIE1), were less than 0.02 nmol/min/nmol P450. Cytochrome P450 IIC11 showed the highest catalytic activity of the cytochromes examined. The mechanism for the oxidation of 11-oxo-delta 8-THC to delta 8-THC-11-oic acid by cytochrome P450 IIC11 was established as being an oxygenation since one atom of oxygen-18 was exclusively incorporated into the carboxylic acid formed under 18O2. The antibody raised to cytochrome P450 IIC11 inhibited by 60% the hepatic microsomal oxidation of 11-oxo-delta 8-THC to delta 8-THC-11-oic acid in male rats. These results indicate that cytochrome P450 IIC11 is a major form of the cytochrome to catalyse the oxidation of 11-oxo-delta 8-THC to delta 8-THC-11-oic acid in the hepatic microsomes of male rats and that the oxidation of aldehyde to carboxylic acid is a catalytic activity common to most isozymes of P450.


Use of a drug-screening service in an inner-city teaching hospital.
Experience in urinary drug screening at St Vincent's Hospital, Melbourne, was evaluated over a period of 12 months after the introduction of a commercially available thin-layer chromatographic system which expanded the capabilities and improved the efficiency of the service. Specimens from 167 patients were screened when either drug overdose, or drug abuse, or poor compliance with prescribed medications was suspected. Screening was also undertaken to aid solution of diagnostic problems by excluding the possibility of drug ingestion. Benzodiazepines, barbiturates, and tricyclic antidepressants represented the drug groups which were most frequently detected. Multiple drug use was common with the mode and median number of drugs taken being two. For 75% of the patients studied, relevant information about drug intake was either unreliable or not obtainable before drug screening. Retrospective examination of the case histories showed that drug screening assisted in arriving at diagnostic or management decisions for at least 66% of the patients.


Gene envY of Escherichia coli K-12 affects thermoregulation of major porin expression.
The temperature-dependent expression of OmpF and OmpC, the major channel-forming proteins of the Escherichia coli K-12 outer membrane, was studied. In wild-type cells, decreasing growth temperatures resulted in increased amounts of OmpF protein and correspondingly decreased quantities of OmpC protein. Bacteria deleted for the 13-min chromosomal region did not exhibit this temperature-dependent fluctuation in porin proteins. Plasmid pML22, which consists of pBR322 containing a 0.5-megadalton E. coli chromosomal DNA insert, complemented the thermoregulatory defect. The regulatory gene was named envY. In minicells, pML22 directed the synthesis of an envelope polypeptide (EnvY) having an apparent molecular weight of 25,000. The EnvY protein was synthesized in minicells in greater amounts at 27 degrees C than at 37 degrees C, and a reducing agent was necessary in the solubilization buffer for its subsequent detection on polyacrylamide gels. The results describe the initial characterization of a regulatory system which, along with proteins of the ompB operon, the cyclic AMP system, and the tolC gene product, is involved in a complex network affecting major porin expression.


Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions.
Disruption of newly identified genes in the pathogen Candida albicans is a vital step in determination of gene function. Several gene disruption methods described previously employ long regions of homology flanking a selectable marker. Here, we describe disruption of C. albicans genes with PCR products that have 50 to 60 bp of homology to a genomic sequence on each end of a selectable marker. We used the method to disrupt two known genes, ARG5 and ADE2, and two sequences newly identified through the Candida genome project, HRM101 and ENX3. HRM101 and ENX3 are homologous to genes in the conserved RIM101 (previously called RIM1) and PacC pathways of Saccharomyces cerevisiae and Aspergillus nidulans. We show that three independent hrm101/hrm101 mutants and two independent enx3/enx3 mutants are defective in filamentation on Spider medium. These observations argue that HRM101 and ENX3 sequences are indeed portions of genes and that the respective gene products have related functions.


The current state of play of research on the social, political and legal dimensions of HIV.
This paper offers a critical overview of social science research presented at the 2014 International AIDS Conference in Melbourne, Australia. In an era of major biomedical advance, the political nature of HIV remains of fundamental importance. No new development can be rolled out successfully without taking into account its social and political context, and consequences. Four main themes ran throughout the conference track on social and political research, law, policy and human rights: first, the importance of work with socially vulnerable groups, now increasingly referred to as "key populations"; second, continued recognition that actions and programs need to be tailored locally and contextually; third, the need for an urgent response to a rapidly growing epidemic of HIV among young people; and fourth, the negative effects of the growing criminalization of minority sexualities and people living with HIV. Lack of stress on human rights and community participation is resulting in poorer policy globally. A new research agenda is needed to respond to these challenges.


Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin increases the activation of aryl hydrocarbon receptor and is associated with the aggressiveness of osteosarcoma MG-63 osteoblast-like cells.
The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activity is modulated by xenobiotics and physiological ligands. Activation of the AhR by environmental xenobiotics may induce a conformational change in AhR and has been implicated in a variety of cellular processes, including inflammation and tumorigenesis. It is unknown whether the activation of AhR serves a role in modulating the progression of osteosarcoma. The osteosarcoma cell line MG-63, was treated with AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD treatment degrades AhR expression through activation of the AhR signaling pathway, however there were no survival differences observed in MG-63 cells. There were concomitant elevations of cyclooxygenase-2 and receptor activator of nuclear factor-κB ligand secretion from MG-63 cells upon TCDD treatment on a protein and mRNA level at 24 and 72 h. In addition, TCDD treatment also increases the production of prostaglandin E2 on MG-63 cells, and induces the expression of chemokine receptor CXCR4. However, CXCL12 production was not altered in MG-63 cells when stimulated with TCDD. The AhR antagonist CH-223191, blocks the effects on TCDD-induced RANKL, COX-2, PGE2 and CXCR4 changes. In conclusion, these findings suggest that AhR signal therapy should be further explored as a therapeutic option for the treatment of osteosarcoma.


Cognitive and neural correlates of the 5-repeat allele of the dopamine D4 receptor gene in a population lacking the 7-repeat allele.
The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD) and substantially exists in Asian populations, which have a lower ADHD prevalence. In this study, we investigated the effect of this allele on microstructural properties of the brain and on its functional activity during externally directed attention-demanding tasks and creative performance in the 765 Asian subjects. For this purpose, we employed diffusion tensor imaging, N-back functional magnetic resonance imaging paradigms, and a test to measure creativity by divergent thinking. The 5-repeat allele was significantly associated with increased originality in the creative performance, increased mean diffusivity (the measure of how the tissue includes water molecules instead of neural and vessel components) in the widespread gray and white matter areas of extensive areas, particularly those where DRD4 is expressed, and reduced task-induced deactivation in the areas that are deactivated during the tasks in the course of both the attention-demanding working memory task and simple sensorimotor task. The observed neural characteristics of 5-repeat allele carriers may lead to an increased risk of ADHD and behavioral deficits. Furthermore, the increased originality of creative thinking observed in the 5-repeat allele carriers may support the notion of the side of adaptivity of the widespread risk allele of psychiatric diseases.


A new genus and species of hyponeoid (Copepoda) from the olfactory sac of a gulper shark Centrophorus sp. (Squaliformes: Centrophoridae) captured off Madagascar.
Greeniedeets buccaneer n. gen., n. sp. (Hyponeoidae, Siphonostomatoida, Copepoda) infects the olfactory sac of a gulper shark, Centrophorus sp. (Centrophoridae, Squaliformes) off Madagascar. The adult female of Greeniedeets buccaneer n. gen., n. sp. is most easily distinguished from other hyponeoids (Hyponeoidae) by its possession of a genital complex that is horseshoe shaped in dorsal view. An amended family diagnosis for Hyponeoidae and diagnostic key to hyponeoids based on adult females are provided.


Evolutionary History of the Glycoside Hydrolase 3 (GH3) Family Based on the Sequenced Genomes of 48 Plants and Identification of Jasmonic Acid-Related GH3 Proteins in Solanum tuberosum.
Glycoside Hydrolase 3 (GH3) is a phytohormone-responsive family of proteins found in many plant species. These proteins contribute to the biological activity of indolacetic acid (IAA), jasmonic acid (JA), and salicylic acid (SA). They also affect plant growth and developmental processes as well as some types of stress. In this study, GH3 genes were identified in 48 plant species, including algae, mosses, ferns, gymnosperms, and angiosperms. No GH3 representative protein was found in algae, but we identified 4 genes in mosses, 19 in ferns, 7 in gymnosperms, and several in angiosperms. The results showed that GH3 proteins are mainly present in seed plants. Phylogenetic analysis of all GH3 proteins showed three separate clades. Group I was related to JA adenylation, group II was related to IAA adenylation, and group III was separated from group II, but its function was not clear. The structure of the GH3 proteins indicated highly conserved sequences in the plant kingdom. The analysis of JA adenylation in relation to gene expression of GH3 in potato (Solanum tuberosum) showed that StGH3.12 greatly responded to methyl jasmonate (MeJA) treatment. The expression levels of StGH3.1, StGH3.11, and StGH3.12 were higher in the potato flowers, and StGH3.11 expression was also higher in the stolon. Our research revealed the evolution of the GH3 family, which is useful for studying the precise function of GH3 proteins related to JA adenylation in S. tuberosum when the plants are developing and under biotic stress.


Core flexibility of a truncated metazoan mitochondrial tRNA.
Secondary and tertiary structures of tRNAs are remarkably preserved from bacteria to humans, the notable exception being the mitochondrial (m) tRNAs of metazoans, which often deviate substantially from the canonical cloverleaf (secondary) or 'L'-shaped (tertiary) structure. Many metazoan mtRNAs lack either the TpsiC (T) or dihydrouridine (D) loops of the canonical cloverleaf, which are known to confer structural rigidity to the folded structure. Thus, the absence of canonical TpsiC-D interactions likely results in greater dispersion of anticodon-acceptor interstem angle than for canonical tRNAs. To test this hypothesis, we have assessed the dispersion of the anticodon-acceptor angle for bovine mtRNA(Ser)(AGY), which lacks the canonical D arm and is thus incapable of forming stabilizing interarm interactions. Using the method of transient electric birefringence (TEB), and by changing the helical torsion angle between a core mtRNA bend and a second bend of known angle/rigidity, we have demonstrated that the core of mtRNA(Ser)(AGY) has substantially greater flexibility than its well-characterized canonical counterpart, yeast cytoplasmic tRNA(Phe). These results suggest that increased flexibility, in addition to a more open interstem angle, would allow both noncanonical and canonical mtRNAs to utilize the same protein synthetic apparatus.


Is the rural population of Puducherry district healthy in terms of the burden of non-communicable diseases? Findings from a cross-sectional analytical survey.
Epidemiological transition remains a key contributor to the rising prevalence of non-communicable diseases (NCDs) across developing nations. Population-specific NCD risk factors estimates derived using World Health Organization (WHO) 'STEP-wise approach' are crucial for devising evidence-based public health interventions to combat NCDs. To estimate the prevalence of behavioral and biological risk factors for NCDs among the rural adult population of Puducherry district in India. STEPS survey was conducted by following all three steps (behavioral, physical measurements and biochemical risk factors) of NCD risk factor assessment. A total of 790 participants were selected from 50 villages through multistage cluster sampling method. STEPS instrument was used to assess behavioral risk factors, physical measurements and biochemical (fasting blood glucose and total cholesterol) risk factors. Tobacco use and alcohol consumption were present among 11.3% (95% Confidence Interval (CI): 9-13.6%) and 19.2% (95% CI: 16.5-22.4%) of the population, respectively. Low physical activity, inadequate intake of fruits and vegetables, overweight and obesity were observed among 29.3% (95% CI: 26.2-32.7%), 89.8% (95% CI: 87.6-92%), 15.6% (95% CI: 13.1-18.3%) and 38.9% (95% CI: 35.4-42.2%), respectively. About 28.2% (95% CI: 25.2-31.6%) had hypertension and 24.4% (95% CI: 20-29%) had diabetes mellitus. Abdominal obesity was twice highly prevalent among women. Tobacco and alcohol use were more common among men, whereas low physical activity, obesity and hypercholesterolemia were higher among women. Public health interventions to promote healthy lifestyle need to be initiated especially to increase physical activity, intake for fruits and vegetables, and quitting of tobacco and alcohol consumption in the rural population of Puducherry.


Modulation of the Pol II CTD Phosphorylation Code by Rac1 and Cdc42 Small GTPases in Cultured Human Cancer Cells and Its Implication for Developing a Synthetic-Lethal Cancer Therapy.
Rho GTPases, including Rho, Cdc42, Rac and ROP subfamilies, are key signaling molecules in RNA polymerase II (Pol II) transcriptional control. Our prior work has shown that plant ROP and yeast Cdc42 GTPases similarly modulate Ser2 and Ser5 phosphorylation status of the C-terminal domain (CTD) of the Pol II largest subunit by regulating CTD phosphatase degradation. Here, we present genetic and pharmacological evidence showing that Cdc42 and Rac1 GTPase signaling modulates a similar CTD Ser2 and Ser5 phosphorylation code in cultured human cancer cells. While siRNA knockdown of Cdc42 and Rac1, respectively, in HeLa cells increased the level of CTD Ser phosphatases RPAP2 and FCP1, they both decreased the level of CTD kinases CDK7 and CDK13. In addition, the protein degradation inhibitor MG132 reversed the effect of THZ1, a CDK7 inhibitor which could decrease the cell number and amount of CDK7 and CDK13, accompanied by a reduction in the level of CTD Ser2 and Ser5 phosphorylation and DOCK4 and DOCK9 (the activators for Rac1 and Cdc42, respectively). Conversely, treatments of Torin1 or serum deprivation, both of which promote protein degradation, could enhance the effect of THZ1, indicating the involvement of protein degradation in controlling CDK7 and CDK13. Our results support an evolutionarily conserved signaling shortcut model linking Rho GTPases to Pol II transcription across three kingdoms, Fungi, Plantae and Animalia, and could lead to the development of a potential synthetic-lethal strategy in controlling cancer cell proliferation or death.


[Action mechanism of Mahuang Xixin Fuzi decoction for mice with influenza based on metabolomics information].
This study aimed to analyze the endogenous metabolite changes in the serum of mice infected with H1N1 virus after intervention by Mahuang-Xixin-Fuzi decoction (MXF) based on metabolomics method, investigate potential biomarkers and related metabolic pathways, and explore the therapeutic mechanism of MXF through metabolomics technology. Thirty-six Kunming (KM) mice were randomly divided into three groups: normal group, model group and MXF group. Influenza virus H1N1 was used by nasal drip to establish influenza mice model. The mice in MXF group were orally administrated with MXF for 6 consecutive days after inoculation, and the other two groups were given with equal volume of saline solution in the same way. Body weight, rectal temperature, morbidity and mortality were recorded daily. Serum samples were collected 24 hours after the last administration for HPLC-TOF-MS analysis. The results showed that as compared with the normal group, the body weight and rectal temperature were decreased in model group, and their lung index and mortality rate were significantly increased (P<0.05); MXF had good therapeutic effects on the abnormity of body weight, rectal temperature, lung index and high mortality rate of mice infected with H1N1 virus. The original data collected from the serum samples were analyzed with R language, MPP, SIMCA-P and other software, and significant changes were found in 14 kinds of endogenous substances from mice serum (P<0.05). As compared with model group, the potential metabolic markers in MXF group recovered to normal levels to a certain degree after being intervened by MXF. Further analysis with MetPA data platform showed that, the pathways involved in 14 metabolites included glucose metabolism, arachidonic acid metabolism, glycerophospholipids and sphingolipids metabolism etc. The metabolomics study and pharmacological experiment showed that MXF might play a role of efficacy by improving glucose metabolism, regulating arachidonic acid metabolism, glycerophospholipid and sphingolipid metabolic pathways.


Potential of Vigna radiata (L.) sprouts in the management of inflammation and arthritis in rats: Possible biochemical alterations.
Vigna radiata (Fabaceae) is an important pulse crop widespread throughout the tropics and warm temperature regions. In this study, we evaluated the in vitro anti-inflammatory and in vivo antiarthritic activity of Vigna radiata sprouts in rats. The in vitro anti-inflammatory activity was determined by membrane stabilization and protein denaturation method. Whereas, the antiarthritic activity of the ethanolic extract of the sprouts was evaluated by complete Freund's adjuvant model with diclofenac sodium as the standard drug. Body weights, paw volume, biochemical parameters such as lipid peroxidation, total reduced glutathione, myeloperoxidase and lysosomal enzymes like cathepsin-D, N-acetyl β-D-glucosamindase and β-D-glucuronidase were estimated. Treatment with ethanolic extract of V. radiata exhibited significant membrane stabilization activity and protein denaturation activity, and significantly attenuated the biochemical changes induced by administration of complete Freund's adjuvant. The findings of the present study suggest the possible role of Vigna radiata in the therapeutics of arthritis.


Platelet activation and anti-phospholipid antibodies collaborate in the activation of the complement system on platelets in systemic lupus erythematosus.
Anti-phospholipid (aPL) antibodies are important contributors to development of thrombosis in patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE). The underlying mechanism of aPL antibody-mediated thrombosis is not fully understood but existing data suggest that platelets and the complement system are key components. Complement activation on platelets is seen in SLE patients, especially in patients with aPL antibodies, and has been related to venous thrombosis and stroke. The aim of this study was to investigate if aPL antibodies could support classical pathway activation on platelets in vitro as well as in SLE patients. Furthermore, we investigated if complement deposition on platelets was associated with vascular events, either arterial or venous, when the data had been adjusted for traditional cardiovascular risk factors. Finally, we analyzed if platelet complement deposition, both C1q and C4d, was specific for SLE. We found that aPL antibodies supported C4d deposition on platelets in vitro as well as in SLE patients (p = 0.001 and p<0.05, respectively). Complement deposition on platelets was increased in SLE patients when compared with healthy individuals (p<0.0001). However, high levels of C4d deposition and a pronounced C1q deposition were also seen in patients with rheumatoid arthritis and systemic sclerosis. In SLE, C4d deposition on platelets was associated with platelet activation, complement consumption, disease activity and venous (OR = 5.3, p = 0.02), but not arterial, thrombosis, observations which were independent of traditional cardiovascular risk factors. In conclusion, several mechanisms operate in SLE to amplify platelet complement deposition, of which aPL antibodies and platelet activation were identified as important contributors in this investigation. Complement deposition on platelets was identified as a marker of venous, but not arterial thrombosis, in SLE patients independently of traditional risk factors and aPL antibodies. Further studies are needed to elucidate the role of complement deposition on platelets in development of venous thrombosis.


Epigenetic regulation of early human embryo development.
Studies of mammalian development have advanced our understanding of the genetic, epigenetic, and cellular processes that orchestrate embryogenesis and have uncovered new insights into the unique aspects of human embryogenesis. Recent studies have now produced the first epigenetic maps of early human embryogenesis, stimulating new ideas about epigenetic reprogramming, cell fate control, and the potential mechanisms underpinning developmental plasticity in human embryos. In this review, we discuss these new insights into the epigenetic regulation of early human development and the importance of these processes for safeguarding development. We also highlight unanswered questions and key challenges that remain to be addressed.


Deploying Cationic Cellulose Nanofiber Confinement to Enable High Iodine Loadings Towards High Energy and High-Temperature Zn-I2 Battery.
High iodine loading and high-temperature adaptability of the iodine cathode are prerequisites to achieving high energy density at full battery level and promoting the practical application for the zinc-iodine (Zn-I2) battery. However, it would aggravate the polyiodide shuttle effect when employing high iodine loading and working temperature. Here, a sustainable cationic cellulose nanofiber (cCNF) was employed to confine the active iodine species through strong physiochemical adsorption to enlarge the iodine loading and stabilize it even at high temperatures. The cCNF could accommodate dual-functionality by enlarging the iodine loading and suppressing the polyiodide shuttle effect, owing to the unique framework structure with abundant surface positive charges. As a result, the iodine cathode based on the cCNF could deliver high iodine mass loading of 14.1 mg cm-2 with a specific capacity of 182.7 mAh g-1, high areal capacity of 2.6 mAh cm-2, and stable cycling over 3000 cycles at 2 A g-1, thus enabling a high energy density of 34.8 Wh kg-1 and the maximum power density of 521.2 W kg-1 at a full Zn-I2 battery level. In addition, even at a high temperature of 60 ℃, the Zn-I2 battery could still deliver a stable cycling.


Do infants show knowledge of the familiar size of everyday objects?
The current study aimed to examine the age at which infants exhibit knowledge of the familiar size of common everyday objects. A total of 65 7- and 12-month-old infants were presented with familiar-sized and novel-sized (i.e., larger or smaller than the familiar size) common everyday objects (i.e., pacifiers and sippy cups), which were placed out of their reach. Both 7- and 12-month-olds' first looks were more frequently directed toward physically larger objects irrespective of whether they were familiar- or novel-sized objects. This finding indicates that initial visual orientation is contingent on the magnitude of the absolute physical size of an object. However, when the entire duration of presentation of the objects (i.e., 10 s) was examined, 12-month-olds' mean looking durations were found to be longer for novel-sized objects than for familiar-sized objects. Thus, although infants in both age groups were able to discern the physical sizes of objects, only 12-month-olds could successfully discriminate between the familiar and novel sizes of everyday objects. Notably, 12-month-olds demonstrated knowledge of familiar size even though the test objects were out of their reach and, consequently, unamenable to manual exploration.


Unresponsiveness to glucose in a streptozocin model of diabetes. Inappropriate insulin and glucagon responses to a reduction of glucose concentration.
The neonatal streptozocin (STZ) rat model of NIDDM has been previously found to have a markedly reduced insulin response to an acute increase in glucose concentration. We studied the effect of an acute reduction in glucose concentration on insulin and glucagon secretion in this model and contrasted the results with the effects of epinephrine and somatostatin using the in vitro isolated, perfused pancreas. The reduction in perfusate glucose concentration from 11.1 to 2.8 mM caused a rapid suppression of insulin release in the control rats, but had no inhibitory effect in the STZ group. Epinephrine (55 nM) and somatostatin (110 nM) caused similar decreases in insulin secretion in both groups. The glucose reduction also caused an increase in glucagon release in the controls, but had no effect in the STZ rats. Epinephrine, however, stimulated glucagon secretion in both groups in a similar fashion, and inhibition by somatostatin was also comparable. The baseline insulin and glucagon concentrations were enhanced in a separate series of experiments by the addition of arginine (5 mM) to the perfusate, and while the insulin and glucagon responses to the glucose reduction remained lost, appropriate inhibition of insulin secretion was demonstrated in the STZ rats with epinephrine. These data indicate that A- and B-cells in this rat model of NIDDM are selectively unresponsive to both increases and decreases in glucose concentration, while the responsiveness to nonglucose agents remains intact.


Prevalence of autoimmune thyroid disease and thyroid dysfunction in young Brazilian patients with type 1 diabetes.
Patients with an autoimmune condition are known to be at higher risk of developing other autoimmune disorders. Type 1 diabetes may be associated with additional autoimmune disorders including autoimmune thyroid disease. The aim of this study was to investigate the prevalence of thyroid autoantibodies in a group of children, adolescents, and young adults with type 1 diabetes from northeastern Brazil as well as their significance for the development of thyroid disorders. The study design was cross-sectional and descriptive, analyzing young people with a previous type 1 diabetes diagnosis. Two hundred and fourteen children and adolescents with prior diagnosis of type 1 diabetes were evaluated. Antibodies to thyroperoxidase (anti-TPO) were determined in all patients and thyroid-stimulating hormone (TSH) levels. The anti-TPO antibody test was positive in 54 out of the 214 patients studied, resulting in an overall prevalence of 25.2%. Among the anti-TPO-positive subjects, females were predominant (72%) over males (28%) (p < 0.001). A total of 55.5% patients with positive anti-TPO antibodies had abnormal TSH levels. Clinically significant hypothyroidism was found in 29.6% and subclinical hypothyroidism in 22.2% of patients with positive anti-TPO. Hyperthyroidism was present in only 3% of them. Our results demonstrate the high prevalence of autoimmune thyroiditis in patients with type 1 diabetes and the need for these patients of regular screening to make a precocious diagnosis of thyroid dysfunction.


Targeting dormant tuberculosis bacilli: results for molecules with a novel pyrimidone scaffold.
Our inability to completely control TB has been due in part to the presence of dormant mycobacteria. This also renders drug regimens ineffective and is the prime cause of the appearance of drug-resistant strains. In continuation of our efforts to develop novel antitubercular agents that especially target dormant mycobacteria, a set of 55 new compounds belonging to the pyrimidone class were designed on the basis of CoMFA and CoMSIA studies, and these were synthesized and subsequently tested against both the dormant and virulent BCG strain of M. tuberculosis. Some novel compounds have been identified which selectively inhibit the dormant tuberculosis bacilli with significantly low IC50 values. This study reports the second molecule after TMC-207, having the ability to inhibit tuberculosis bacilli exclusively in its dormant phase. The synthesis was accomplished by a modified multicomponent Biginelli reaction. A classification model was generated using the binary QSAR approach--recursive partitioning (RP) to identify structural characteristics related to the activity. Physicochemical, structural, topological, connectivity indices, and E-state key descriptors were used for generation of the decision tree. The decision tree could provide insights into structure-activity relationships that will guide the design of more potent inhibitors.


SERS Detection of Multiple Antimicrobial-Resistant Pathogens Using Nanosensors.
Successful pathogen detection is crucial for public health as the threat of infectious disease is dramatically increasing globally due to bacteria developing resistance to many antimicrobial drugs. The increase in bacterial infections has led to urgent demands for simpler, faster, and more reliable detection methods to be developed allowing the most appropriate therapy to be provided. Surface enhanced Raman scattering (SERS) is an analytical technique which has gained a great deal of interest for biosensing due to its sensitivity, selectivity, and multiplexing capabilities. A new bionanosensor has been developed for the isolation and detection of multiple bacterial pathogens via magnetic separation and SERS. This novel assay format involves using lectin functionalized magnetic nanoparticles for capture and isolation of bacteria from the sample matrix followed by specifically detecting bacterial pathogens using SERS active nanoparticles functionalized with antibodies which are strain specific. Therefore, the sample is captured using a "magnetic plug" and interrogated with a laser allowing simple and fast optical detection. Three bacterial pathogens (Escherichia coli, Salmonella typhimurium, and methicillin-resistant Staphylococcus aureus) were successfully isolated and detected, with the lowest concentration for each of the strains detected at just 101 colony forming units per mL (CFU/mL). In addition to single pathogen detection, a mixture of all three bacterial strains was isolated and identified within the same sample matrix using SERS with the triplex detection also being confirmed using principal component analysis. Herein, we demonstrate that this multiplexed bionanosensor is capable of providing rapid and sensitive discrimination of bacterial pathogens both individually, and within a multiplex system, offering opportunities for future point of care devices and advancements in biomedical applications.


Beneficial and Detrimental Effects of Regulatory T Cells in Neurotropic Virus Infections.
Neurotropic viruses infect the central nervous system (CNS) and cause acute or chronic neurologic disabilities. Regulatory T cells (Treg) play a critical role for immune homeostasis, but may inhibit pathogen-specific immunity in infectious disorders. The present review summarizes the current knowledge about Treg in human CNS infections and their animal models. Besides dampening pathogen-induced immunopathology, Treg have the ability to facilitate protective responses by supporting effector T cell trafficking to the infection site and the development of resident memory T cells. Moreover, Treg can reduce virus replication by inducing apoptosis of infected macrophages and attenuate neurotoxic astrogliosis and pro-inflammatory microglial responses. By contrast, detrimental effects of Treg are caused by suppression of antiviral immunity, allowing for virus persistence and latency. Opposing disease outcomes following Treg manipulation in different models might be attributed to differences in technique and timing of intervention, infection route, genetic background, and the host's age. In addition, mouse models of virus-induced demyelination revealed that Treg are able to reduce autoimmunity and immune-mediated CNS damage in a disease phase-dependent manner. Understanding the unique properties of Treg and their complex interplay with effector cells represents a prerequisite for the development of new therapeutic approaches in neurotropic virus infections.


[Problems and complications of the wound closure in cataract operations (author's transl)].
A presentation is given of some complications resulting from wound closure technique following cataract extraction, without postoperative loss of the anterior chamber. Group 1: In 3 cases a filtering bleb developed within the first 10 days postoperatively, due to faulty suture technique. Wound revision was not necessary. Group 2: In 6 cases wound dehiscence only developed after 3 weeks or longer. In 5 of these cases the fistula, and the subsequent dehiscence, occured at the site of a Barraquer silk suture; which appeared to be at least partially responsible for the complication. 2 of these 5 cases required resuturing, the remaining 3 slowly improved spontaneously. In the 6th case, which also required surgical intervention, the fistula was not situated near a suture. Due to the problems encountered with Barraquer silk sutures the same 3 step cataract incision previously employed was closed instead with interrupted Tübinger nylon sutures, the knots being buried whenever possible. The results were analysed in 81 eyes operated upon with this technique. Postoperative astigmatism lay within normal limits. In one case a filtering bleb developed at the site of a suture. Tübinger nylon sutures are now preferred to Barraquer silk sutures due to the better results obtained so far.


In vitro and in vivo anti-tumor activity of miR-221/222 inhibitors in multiple myeloma.
A rising body of evidence suggests that silencing microRNAs (miRNAs) with oncogenic potential may represent a successful therapeutic strategy for human cancer. We investigated the therapeutic activity of miR-221/222 inhibitors against human multiple myeloma (MM) cells. Enforced expression of miR-221/222 inhibitors triggered in vitro anti-proliferative effects and up-regulation of canonic miR-221/222 targets, including p27Kip1, PUMA, PTEN and p57Kip2, in MM cells highly expressing miR-221/222. Conversely, transfection of miR-221/222 mimics increased S-phase and down-regulated p27Kip1 protein expression in MM with low basal miR-221/222 levels. The effects of miR-221/222 inhibitors was also evaluated in MM xenografts in SCID/ NOD mice. Significant anti-tumor activity was achieved in xenografted mice by the treatment with miR-221/222 inhibitors, together with up-regulation of canonic protein targets in tumors retrieved from animals. These findings provide proof of principle that silencing the miR-221/222 cluster exerts significant therapeutic activity in MM cells with high miR-221/222 level of expression, which mostly occurs in TC2 and TC4 MM groups. These findings suggest that MM genotyping may predict the therapeutic response. All together our results support a framework for clinical development of miR-221/222 inhibitors-based therapeutic strategy in this still incurable disease.


Dynamics of spatial summation in primary visual cortex of alert monkeys.
One of the fundamental tasks of the visual cortex is to integrate input from different parts of the retina, parsing an image into contours and surfaces, and then assembling these features into coherent representations of objects. To examine the role of the primary visual cortex in the integration of visual information, we measured the response properties of neurons under different stimulus conditions. Surprisingly, we found that even the most conventional measures of receptive field (RF) size were not fixed, but could vary depending on stimulus contrast and foreground-background relationships. On average, the length of the excitatory RF was 4-fold greater for a low-contrast stimulus than for a stimulus at high contrast. Embedding a high-contrast stimulus in a textured background tended to suppress neuronal responses and produced an enlargement in RF size similar to that observed by decreasing the contrast of an isolated stimulus. The results show that RF dimensions are regulated in a dynamic manner that depends both on local stimulus characteristics, such as contrast, and on global relationships between a stimulus and its surroundings.


Metagenomes of Mediterranean coastal lagoons.
Coastal lagoons, both hypersaline and freshwater, are common, but still understudied ecosystems. We describe, for the first time, using high throughput sequencing, the extant microbiota of two large and representative Mediterranean coastal lagoons, the hypersaline Mar Menor, and the freshwater Albufera de Valencia, both located on the south eastern coast of Spain. We show there are considerable differences in the microbiota of both lagoons, in comparison to other marine and freshwater habitats. Importantly, a novel uncultured sulfur oxidizing Alphaproteobacteria was found to dominate bacterioplankton in the hypersaline Mar Menor. Also, in the latter prokaryotic cyanobacteria were almost exclusively comprised by Synechococcus and no Prochlorococcus was found. Remarkably, the microbial community in the freshwaters of the hypertrophic Albufera was completely in contrast to known freshwater systems, in that there was a near absence of well known and cosmopolitan groups of ultramicrobacteria namely Low GC Actinobacteria and the LD12 lineage of Alphaproteobacteria.


Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome.
Non-invasive respiratory support is increasingly used for the management of respiratory dysfunction in preterm infants. This approach runs the risk of under-treating those with respiratory distress syndrome (RDS), for whom surfactant administration is of paramount importance. Several techniques of minimally invasive surfactant therapy have been described. This review focuses on surfactant administration to spontaneously breathing infants via a thin catheter briefly inserted into the trachea. Primary objectives In non-intubated preterm infants with established RDS or at risk of developing RDS to compare surfactant administration via thin catheter with: 1. intubation and surfactant administration through an endotracheal tube (ETT); or 2. continuation of non-invasive respiratory support without surfactant administration or intubation. Secondary objective 1. To compare different methods of surfactant administration via thin catheter Planned subgroup analyses included gestational age, timing of intervention, and use of sedating pre-medication during the intervention. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 30 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. We included randomised trials comparing surfactant administration via thin catheter (S-TC) with (1) surfactant administration through an ETT (S-ETT), or (2) continuation of non-invasive respiratory support without surfactant administration or intubation. We also included trials comparing different methods/strategies of surfactant administration via thin catheter. We included preterm infants (at < 37 weeks' gestation) with or at risk of RDS. Review authors independently assessed study quality and risk of bias and extracted data. Authors of all studies were contacted regarding study design and/or missing or unpublished data. We used the GRADE approach to assess the certainty of evidence. We included 16 studies (18 publications; 2164 neonates) in this review. These studies compared surfactant administration via thin catheter with surfactant administration through an ETT with early extubation (Intubate, Surfactant, Extubate technique - InSurE) (12 studies) or with delayed extubation (2 studies), or with continuation of continuous positive airway pressure (CPAP) and rescue surfactant administration at pre-specified criteria (1 study), or compared different strategies of surfactant administration via thin catheter (1 study). Two trials reported neurosensory outcomes of of surviving participants at two years of age. Eight studies were of moderate certainty with low risk of bias, and eight studies were of lower certainty with unclear risk of bias. S-TC versus S-ETT in preterm infants with or at risk of RDS Meta-analyses of 14 studies in which S-TC was compared with S-ETT as a control demonstrated a significant decrease in risk of the composite outcome of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.48 to 0.73; risk difference (RD) -0.11, 95% CI -0.15 to -0.07; number needed to treat for an additional beneficial outcome (NNTB) 9, 95% CI 7 to 16; 10 studies; 1324 infants; moderate-certainty evidence); the need for intubation within 72 hours (RR 0.63, 95% CI 0.54 to 0.74; RD -0.14, 95% CI -0.18 to -0.09; NNTB 8, 95% CI; 6 to 12; 12 studies, 1422 infants; moderate-certainty evidence); severe intraventricular haemorrhage (RR 0.63, 95% CI 0.42 to 0.96; RD -0.04, 95% CI -0.08 to -0.00; NNTB 22, 95% CI 12 to 193; 5 studies, 857 infants; low-certainty evidence); death during first hospitalisation (RR 0.63, 95% CI 0.47 to 0.84; RD -0.02, 95% CI -0.10 to 0.06; NNTB 20, 95% CI 12 to 58; 11 studies, 1424 infants; low-certainty evidence); and BPD among survivors (RR 0.57, 95% CI 0.45 to 0.74; RD -0.08, 95% CI -0.11 to -0.04; NNTB 13, 95% CI 9 to 24; 11 studies, 1567 infants; moderate-certainty evidence). There was no significant difference in risk of air leak requiring drainage (RR 0.58, 95% CI 0.33 to 1.02; RD -0.03, 95% CI -0.05 to 0.00; 6 studies, 1036 infants; low-certainty evidence). None of the studies reported on the outcome of death or survival with neurosensory disability. Only one trial compared surfactant delivery via thin catheter with continuation of CPAP, and one trial compared different strategies of surfactant delivery via thin catheter, precluding meta-analysis. Administration of surfactant via thin catheter compared with administration via an ETT is associated with reduced risk of death or BPD, less intubation in the first 72 hours, and reduced incidence of major complications and in-hospital mortality. This procedure had a similar rate of adverse effects as surfactant administration through an ETT. Data suggest that treatment with surfactant via thin catheter may be preferable to surfactant therapy by ETT. Further well-designed studies of adequate size and power, as well as ongoing studies, will help confirm and refine these findings, clarify whether surfactant therapy via thin tracheal catheter provides benefits over continuation of non-invasive respiratory support without surfactant, address uncertainties within important subgroups, and clarify the role of sedation.


[Effect of amphotericin B on the activity of synthetic polyribonucleotide interferon inducers].
The authors investigated the intensity of interferon production and the degree of the associated antiviral resistance induced by double-stranded synthetic polyribonucleotide interferon inducers poly(G) . poly(C), poly(G, I) . poly(C) and poly(G, A) . poly(C) in chick embryo cell cultures, continuous diploid human fibroblasts and in mice in the presence of amphotericin B, a macrolide polyene antibiotic enhancing the permeability of plasma membranes for macromolecules. Amphotericin B was found to increase considerably the interferon-inducing and antiviral activity of the above polyribonucleotide complexes in those cell systems where they induced interferon production and antiviral resistance alone, without the antibiotic, but to a lower degree. Amphotericin B did not contribute to the activity of the complexes in those cell systems where they were inert alone. The importance of permeability of the plasma membrane for interferon induction is discussed, and a conclusion is reached that the inertness of the complexes under study in one cell system and their activity in the others are not associated with differences in the permeability of the plasma membranes of different cells for polyribonucleotide interferon inducers.


Epidermal growth factor receptor. Characterization of a monoclonal antibody specific for the receptor of A431 cells.
A monoclonal antibody to the epidermal growth factor (EGF) receptor of A431 cells was obtained after fusion of immunized BALB/c mouse spleen cells with NS-1 myeloma cells. Specific binding of the antibody to the plasma membrane of A431 cells was demonstrated by indirect immunofluorescence and electron microscopy. The antibody did not react with human KB cells, normal rat kidney cells, or Swiss 3T3 cells. The antibody is an IgG3K; it specifically immunoprecipitated a Mr approximately 170,000 protein from radiolabeled A431 cell extracts. This protein is phosphorylated in a EGF-dependent manner in intact A431 cells and in Triton X-100-solubilized plasma membranes. The specificity of the interaction of the antibody with the Mr = 170,000 protein was confirmed by electrophoretic transfer of A431 cell proteins to nitrocellulose followed by incubation with the antibody and 125I-protein A. When 125I-EGF was covalently cross-linked to its receptor, the 125I-EGF-receptor complex was specifically precipitated by the antibody. The monoclonal antibody did not inhibit the binding of 125I-EGF to its receptor in intact A431 cells and also failed to stimulate the phosphorylation of the Triton X-100-solubilized EGF receptor. The results indicate that the antibody and EGF bind to different sites on the EGF receptor. The antibody will be useful for isolating the EGF receptor in an unactivated form.


[Differential diagnosis of myocarditis, cardiomyopathy and chronic ischemic heart disease].
A total of 108 patients with myocarditis and cardiomyopathies and 25 with chronic coronary disease (CCD) were investigated. The most informative diagnostic criteria were identified for the differentiation between noncoronarogenic myocardial disease (NMD) and CCD. Bicycle ergometry was positive in all CCD patients, whereas in those with NMD it was negative or had to be discontinued because of fatigue. NMD was associated with increased activity of transaminases, LDH and its isonenzymes (first and second fractions) and normal lipid spectrum. In CCD patients, enzyme activity was normal, and hyperlipidemia was detected in 88%. Coxsackie virus B2 was found in 24 of 58 NMD patients and only 3 of 25 patients with CCD. Echocardiography was effective in the diagnosis of cardiomyopathies. The diagnostic value of the patient's medical history is emphasized.


Postglomerular capillary solute flux restricted by shape and charge in the dog.
The permselectivity characteristics of the postglomerular (PG) microcirculation in dog kidney were investigated employing 3H-labeled cationic (DEAE) and anionic sulfated dextrans (dextran-SO4) ranging from 19 to 29 A Stokes-Einstein Radius. With the use of the multiple-indicator dilution (MID) technique, a bolus injection was made into the left renal artery and timed serial samples were obtained from renal venous and urine outflows. The injection solution contained 125I-labeled albumin (plasma reference), [14C]inulin and/or creatinine (glomerular and interstitial references), and a test [3H]dextran probe. A control run was carried out with tracer, then charge interaction was analyzed by repeating the MID run with excess unlabeled compound or after protamine sulfate infusion. After loading, renal vein recovery and mean transit time (t) were unchanged relative to [14C]inulin for [3H]dextran-SO4. But excess DEAE resulted in reduced recovery and decreased t for [3H]DEAE. After protamine sulfate, the renal vein and urine recoveries of [3H]dextran-SO4 decreased and the renal vein t increased. These findings demonstrate saturable anionic binding sites in the PG microcirculation. Under conditions where charge interaction was eliminated, the ratio of renal vein t for 125I-albumin to cationic or anionic dextran was always less than its ratio to neutral dextran, implying a larger apparent volume of distribution. We concluded that PG capillaries also limit solute flux on the basis of shape.


Analyzing multiple-probe microarray: estimation and application of gene expression indexes.
Gene expression index estimation is an essential step in analyzing multiple probe microarray data. Various modeling methods have been proposed in this area. Amidst all, a popular method proposed in Li and Wong (2001) is based on a multiplicative model, which is similar to the additive model discussed in Irizarry et al. (2003a) at the logarithm scale. Along this line, Hu et al. (2006) proposed data transformation to improve expression index estimation based on an ad hoc entropy criteria and naive grid search approach. In this work, we re-examined this problem using a new profile likelihood-based transformation estimation approach that is more statistically elegant and computationally efficient. We demonstrate the applicability of the proposed method using a benchmark Affymetrix U95A spiked-in experiment. Moreover, We introduced a new multivariate expression index and used the empirical study to shows its promise in terms of improving model fitting and power of detecting differential expression over the commonly used univariate expression index. As the other important content of the work, we discussed two generally encountered practical issues in application of gene expression index: normalization and summary statistic used for detecting differential expression. Our empirical study shows somewhat different findings from the MAQC project (MAQC, 2006).


Effects of insulin and work on fructose 2,6-bisphosphate content and phosphofructokinase activity in perfused rat hearts.
The effects of insulin and increased cardiac work on glycolytic rate, metabolite content, and fructose 2,6-bisphosphate (Fru-2,6-P2) content were studied in isolated perfused rat hearts. Steady-state rates of glycolysis increased 5-fold with the addition of insulin to the perfusate or by increasing cardiac pressure-volume work and correlated well in most conditions with changes in substrate concentration (Fru-6-P) and with concentration of the activator, Fru-2,6-P2. There was no correlation with changes in other well known regulators including citrate, ATP, AMP, Pi, or cytosolic phosphorylation potential. Using phosphofructokinase purified from hearts perfused under identical conditions, allosteric kinetic experiments were performed using the metabolite and effector concentrations determined from in vivo experiments. Reaction rates for phosphofructokinase calculated in vitro agreed well with the glycolytic rates measured in vivo and correlated with changes in Fru-6-P but not with other effectors. However, higher Fru-2,6-P2 levels were more effective in maintaining phosphofructokinase activity at high ATP and citrate levels. Kinetic experiments did not indicate a covalent modification of phosphofructokinase. These data indicate that control of cardiac phosphofructokinase and glycolysis may be accomplished by changes in the availability of substrate, Fru-6-P, and activator, Fru-2,6-P2, rather than by citrate, adenine nucleotides, or cytosolic phosphorylation potential as previously suggested.


The role of insightful disclosure in outcomes for women in peer-directed breast cancer groups: a replication study.
This study was stimulated by the recent publication (Health Commun 2006;19(2):133-142) who reported the effects of insightful disclosure on outcomes in' peer-led internet breast cancer support groups. The present study attempted to replicate their hypotheses using the same methods for coding insightful disclosure as well as parallel outcome measures. Four hypotheses are tested; writing a higher percentage of insightful disclosure words will be associated with: (1) fewer BC concerns; (2) reduction in the emotional distress; (3) better physical health; and (4) few functional limitations. New members (N = 77) to BC bulletin boards (BB) were recruited through BB postings and/or e-mails. We asked them to fill out questionnaires measuring depression and quality of life, when they joined the BB, and again six months later. Two questionnaires (CESD and FACTB [Functional Well being, Physical well being, and Breast cancer Concerns]) were administered and repeated six months later. For two of the four outcome measures (Functional Well being and Breast Cancer Concerns), insightful disclosure played a crucial and significant role, the other two showed a trend toward significance (CESD and Physical well being). The three control variables, stages, years of cancer and level of participation all had effects on the outcomes, varying with the type of outcome measure. The findings, in this study, support Shaw et al. hypotheses. In their study, only one outcome measure, reduction of emotional distress was significant.


Genome-wide association study for birth weight in Nellore cattle points to previously described orthologous genes affecting human and bovine height.
Birth weight (BW) is an economically important trait in beef cattle, and is associated with growth- and stature-related traits and calving difficulty. One region of the cattle genome, located on Bos primigenius taurus chromosome 14 (BTA14), has been previously shown to be associated with stature by multiple independent studies, and contains orthologous genes affecting human height. A genome-wide association study (GWAS) for BW in Brazilian Nellore cattle (Bos primigenius indicus) was performed using estimated breeding values (EBVs) of 654 progeny-tested bulls genotyped for over 777,000 single nucleotide polymorphisms (SNPs). The most significant SNP (rs133012258, PGC = 1.34 × 10-9), located at BTA14:25376827, explained 4.62% of the variance in BW EBVs. The surrounding 1 Mb region presented high identity with human, pig and mouse autosomes 8, 4 and 4, respectively, and contains the orthologous height genes PLAG1, CHCHD7, MOS, RPS20, LYN, RDHE2 (SDR16C5) and PENK. The region also overlapped 28 quantitative trait loci (QTLs) previously reported in literature by linkage mapping studies in cattle, including QTLs for birth weight, mature height, carcass weight, stature, pre-weaning average daily gain, calving ease, and gestation length. This study presents the first GWAS applying a high-density SNP panel to identify putative chromosome regions affecting birth weight in Nellore cattle. These results suggest that the QTLs on BTA14 associated with body size in taurine cattle (Bos primigenius taurus) also affect birth weight and size in zebu cattle (Bos primigenius indicus).


[Lymphoblastic lymphomas in children. Their recognizability as T- or B-cell neoplasms in histologic slides (routine sections) (author's transl)].
Sections of lymph node and tumor biopsies from 60 patients (51 children, 9 adults) with lymphoblastic lymphoma (lbL) were examined in a bind trial to determine whether the subtype of lbL can be diagnosed on the basis of morphologic criteria alone The diagnoses made in this trial were correct in 18 of 20 cases (adults and children) that had been classified as T-, B-, or non-T/non-B-lbL by immunologic, cytochemical (DAP IV, or virologic (EBV) analysis. In 48 of the 51 children, the subclassification made in the blind trial agreed with the definitive diagnosis. In addition to the results of the blind trial, the morphologic characteristics of T- and B-lbL are presented and the diagnostic value of cytochemical staining for acid phosphates is discussed.


Is exenatide improving the treatment of type 2 diabetes? Analysis of the individual clinical trials with exenatide.
The obesity epidemic in the developed and developing world is being followed by an epidemic of type 2 diabetes. In type 2 diabetes, subjects cannot manage glucose properly because they do not produce enough insulin, and the peripheral tissues have become resistant to insulin. Glucagon-like peptide 1 (GLP-1) is an intestinal peptide hormone that is secreted in response to food to regulate the postprandial blood glucose concentration. One of the actions of GLP-1 is to stimulate insulin secretion. In subjects with type 2 diabetes, intravenous or subcutaneous GLP-1 stimulated insulin production and decreased blood glucose levels. However, as GLP-1 is rapidly metabolised, it is not suitable for use in most subjects with type 2 diabetes. Exendin-4 is a 39-amino acid peptide that acts as an agonist at the GLP-1 receptor. After subcutaneous administration, synthetic exendin-4 (exenatide) decreased postprandial concentrations of glucose and insulin, and fasting glucose levels in subjects with type 2 diabetes, and the effects lasted several hours. Subsequently, exenatide was been trialled in subjects taking metformin only, a sulfonylurea only, or metformin and a sulfonylurea, and shown to improve glycemic control with few adverse events, initially over 30 weeks, and then extended to 82 weeks. Exenatide may also be as effective as insulin glargine in subjects with type 2 diabetes not adequately controlled with the oral agents. In conclusion, exenatide represents a new and beneficial addition to the medicines used to treat type 2 diabetes.


[Epidemiological study of clinical characteristics of Chinese Han ethnic women with polycystic ovary syndrome].
To carry out an epidemiological study of clinical characteristics of Chinese Han ethnic women with polycystic ovary syndrome (PCOS). According to Revised 2003 European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria, PCOS can be diagnosed with 2 manifestations out of oligo-or anovulation, clinical and/or biochemical signs of hyperandrogenism exclusion of other etiologies and polycystic ovaries. One thousand and twenty-seven women in reproductive age from one area in Jinan city were investigated and the clinical, metabolic characteristics of the PCOS patients were analyzed. (1) A total of 828 questionnaires were collected from 1027 women; the response rate was 80.62%. Eighty-five PCOS patients were diagnosed; PCOS accounted for 97.65% (83/85) in <or= 35 years old population groups; (2) Clinical manifestations were different between PCOS groups and controls in each age stage (P < 0.05); Menstruation, body hair Ferriman-Gallny (F-G) score, acne, ovarian follicle numbers decreased with aging among PCOS groups, and menstruation cycle was longer, testosterone (T), free androgen index (FAI) and ovarian follicle numbers were higher, sex hormone-binding globulin (SHBG) was lower than control groups of the same age respectively (P < 0.01); (3) Homeostasis model assessment-insulin resistance (Homa-IR) index in infertility PCOS group was higher than in fertility group (1.49 +/- 0.73 vs 1.31 +/- 0.66; t = 2.058; P < 0.05); fasting insulin, fasting blood glucose in obesity PCOS group was higher than in non-obesity group (8.50 +/- 3.46 vs 5.7 +/- 2.3, t = 2.984; P < 0.01, 5.45 +/- 0.54 vs 4.88 +/- 0.45, t = 2.891; P < 0.01), in contrast, insulin sensitivity index was lower in obesity PCOS group than in non-obesity group (0.025 +/- 0.015 vs 0.044 +/- 0.026; t = 2.292, P < 0.05). (1) PCOS mainly distributes in <or= 35 years old population; (2) clinical manifestations of oligo-ovulation, clinical and/or biochemical signs of hyperandrogenism, polycystic ovaries of PCOS change with age increase. (3) PCOS with infertility and obesity is usually associated with glucose metabolic changes, especially insulin resistance.


[Nursing care in elderly patients with cardiovascular disease].
Aging is a process that has biological, physiological, psychological, sociological and chronological dimensions and can be defined from different directions. The incidence of cardiovascular diseases such as hypertension, coronary heart disease, heart failure, dysrhythmia and heart valve diseases is increasing with age. Cardiovascular diseases are the most common cause of death in people over 65 years of age. It also causes serious health problems and poses a significant burden on the health care system. Nurses have important responsibilities in the care of the elderly patients with cardiovascular system disease. Appropriate nursing care for elderly patient provides positive contributions to patient care outcomes.


Direct and mediational links between parental bonds and neglect, antisocial personality, reasons for drinking, alcohol use, and alcohol problems.
The self-medication model suggests that some individuals may use alcohol as a means to cope with their negative experiences. Antisocial personality reflects a lack of concern for others and is often linked to alcohol use disorders. The aim of this investigation was to examine potential parental influences to both pathological reasons for drinking and antisocial personality as pathways to alcohol use and problems. Direct and indirect links between parental bond (care, rejection, overprotection, autonomy, and neglect) and antisocial personality, pathological reasons for drinking, alcohol use, and alcoholrelated problems were investigated. A two-group SEM path model with college students (164 female, 240 male) was examined. In general, the overall patterns among male and female respondents were distinct. Among women, perceptions of having a caring mother lowered the likelihood of having antisocial tendencies, and perceptions of being rejected by one's father were directly linked to pathological reasons for drinking. Feeling neglected by one's mother was also directly linked to alcohol-related problems among women. Conversely, feeling neglected by one's father was directly linked to alcohol-related problems among males, suggesting a parent-offspring gender match. For men, antisocial personality mediated the impact of mother rejection and father overprotection on alcohol use. These findings suggest that parental influences regarding vulnerabilities for alcohol use are very complex and that the genders of the respondent and the parent must be considered jointly.


Any port in a storm: Cryptocurrency safe-havens during the COVID-19 pandemic.
Controlling for the polarity and subjectivity of social media data based on the development of the COVID-19 outbreak, we analyse the relationships between the largest cryptocurrencies and such time-varying realisation as to the scale of the economic shock centralised within the rapidly-escalating pandemic. We find evidence of significant growth in both returns and volumes traded, indicating that large cryptocurrencies acted as a store of value during this period of exceptional financial market stress. Further, cryptocurrency returns are found to be significantly influenced by negative sentiment relating to COVID-19. While not only providing diversification benefits for investors, results suggest that these digital assets acted as a safe-haven similar to that of precious metals during historiccrises.


Organophosphorus ester-induced delayed neurotoxicity.
In certain animals, including humans, exposure to some organophosphorus esters causes delayed neurotoxicity (OPIDN). The clinical condition becomes manifest after a delay period, first as ataxia, followed by paralysis. Lesions are characterized by degeneration of axons with subsequent secondary degeneration of myelin in the peripheral and central nervous systems. Recovery is only likely in mild cases, whereas more severe cases show symptoms of an upper motor neuron lesion in the lower limbs. The risk of use of these chemicals is related not only to human sensitivity to this syndrome, but also to the fact that in most disasters involving OPIDN, humans were the prime victims. Therefore, the neurotoxic action of a chemical is of great significance, since pesticides with this property are not recommended for use. Although OPIDN has been recognized for over a half a century, its mechanism of action is still unknown. It is believed, however, that the initial target in OPIDN is the phosphorylation of a neurotoxicity target protein in the nervous system. Study of the relationship between the chemical structure of organophosphorus esters and their neurotoxic potencies suggests that two hydrophobic areas may be present in the vicinity of the active site of the neurotoxicity protein. This article attempts to present an up-to-date overview of OPIDN. Despite the difficulties attributed to experimental variations of the reported studies, I feel that several significant points have come forth from the data.


Prospective examination of pain-related and psychological predictors of CRPS-like phenomena following total knee arthroplasty: a preliminary study.
We hypothesized that preoperative emotional distress and pain intensity would predict the occurrence of signs and symptoms of complex regional pain syndrome (CRPS) following total knee arthroplasty (TKA). Depression (Beck Depression Inventory, BDI), anxiety (State Trait Anxiety Inventory, STAI), pain (McGill Pain Questionnaire-Short Form, MPQ), and signs/symptoms meeting IASP criteria for CRPS were assessed preoperatively, and at 1-, 3-, and 6-months postoperatively in 77 patients undergoing TKA. The prevalence of subjects fulfilling CRPS criteria was 21.0% at 1 month, 13.0% at 3 months, and 12.7% at 6 months postoperative. Higher preoperative scores on the STAI predicted positive CRPS status at 1-month follow-up (P<0.05), with a similar non-significant trend for preoperative BDI scores (P<0.10). Diagnostic sensitivity for the STAI was good (0.73), with moderate specificity (0.56). Neither measure predicted CRPS at later follow-up (P>0.10). Greater preoperative pain intensity predicted positive CRPS status at 3-month (MPQ-Sensory and MPQ-Affective; P<0.01) and 6-month (MPQ-Sensory) follow-up (P<0.01), but not at 1-month (P>0.10). Diagnostic sensitivity was high (0.83-1.00), with moderate specificity (0.53-0.60). Post-TKA patients with CRPS were more depressed at 1-month follow-up (P<0.05) and more anxious at 6-month follow-up (P<0.05) than patients with ongoing non-CRPS pain (all other comparisons non-significant, P>0.10). Overall, results indicate that CRPS-like phenomena occur in a significant number of patients early post-TKA; however, it is not associated with significantly greater complaints of postoperative pain. There appears to be a modest utility for preoperative distress and pain in predicting CRPS signs and symptoms following TKA, although false positive rates are relatively high.


Haploinsufficiency of Dyrk1A in mice leads to specific alterations in the development and regulation of motor activity.
DYRK1A is a protein kinase proposed to be involved in neurogenesis. Gene-targeting disruption of Dyrk1A in mice leads to decreased body and brain size, with no severe disturbance of behavior. In this study, the authors focused on the motor profile of Dyrk1A(+/-) mice. These mice presented impairment of neuromotor development with decreased activity, suggesting a physiological role of Dyrk1A in the maturation of the neuromotor system. In the adult, a marked hypoactivity and alteration of specific motor parameters were detected. These results are in agreement with the significant expression of Dyrk1A in structures related to motor function and support a role of Dyrk1A in the control of motor function.


Mkh1, a MEK kinase required for cell wall integrity and proper response to osmotic and temperature stress in Schizosaccharomyces pombe.
We have identified a Schizosaccharomyces pombe gene, mkh1, that encodes a MEK kinase (MEKK) homolog. The coding region of mkh1 is contained within a single exon encoding a 1,116-amino-acid protein. The putative catalytic domain of Mkh1 is 54% identical to the catalytic domain of S. cerevisiae Bck1, the most closely related protein. Deletion of mkh1 did not significantly affect cell growth or division under standard conditions. However, mkh1delta cell growth was inhibited by high KCl or NaCl concentrations. mkh1delta cells required a longer time to reenter the cell cycle after prolonged stationary-phase arrest. Also, mkh1delta cells exhibited a round cell shape, while overexpression of Mkh1 resulted in an elongated cell shape. mkh1delta cells exhibited a more dramatic phenotype when grown in nutrient-limiting conditions at high temperature or in hyperosmotic medium. In such conditions, completion of cytokinesis was inhibited, resulting in the growth of pseudohyphal filaments with multiple septa and nuclei. Also, mkh1delta cells were hypersensitive to beta-glucanase treatment. Together these results suggest that Mkh1 regulates cell morphology, cell wall integrity, salt resistance, cell cycle reentry from stationary-phase arrest, and filamentous growth in response to stress. These phenotypes are essentially identical to those exhibited by cells lacking Pmk1/Spm1, a recently identified mitogen-activated protein kinase. Our evidence suggests that Pmk1/Spm1 acts downstream from Mkh1 in a common pathway. Our results also suggest that Mkh1 and Pck2 act independently to maintain cell wall integrity, cell morphology, and salt resistance but act in opposition to regulate filamentous growth.


Safety and Outcome of High-Flow Nasal Oxygen Therapy Outside ICU Setting in Hypoxemic Patients With COVID-19.
High-flow nasal oxygen (HFNO) therapy is frequently applied outside ICU setting in hypoxemic patients with COVID-19. However, safety concerns limit more widespread use. We aimed to assess the safety and clinical outcomes of initiation of HFNO therapy in COVID-19 on non-ICU wards. Prospective observational multicenter pragmatic study. Respiratory wards and ICUs of 10 hospitals in The Netherlands. Adult patients treated with HFNO for COVID-19-associated hypoxemia between December 2020 and July 2021 were included. Patients with treatment limitations were excluded from this analysis. None. Outcomes included intubation and mortality rate, duration of hospital and ICU stay, severity of respiratory failure, and complications. Using propensity-matched analysis, we compared patients who initiated HFNO on the wards versus those in ICU. Six hundred eight patients were included, of whom 379 started HFNO on the ward and 229 in the ICU. The intubation rate in the matched cohort ( n = 214 patients) was 53% and 60% in ward and ICU starters, respectively ( p = 0.41). Mortality rates were comparable between groups (28-d [8% vs 13%], p = 0.28). ICU-free days were significantly higher in ward starters (21 vs 17 d, p < 0.001). No patient died before endotracheal intubation, and the severity of respiratory failure surrounding invasive ventilation and clinical outcomes did not differ between intubated ward and ICU starters (respiratory rate-oxygenation index 3.20 vs 3.38; Pa o2 :F io2 ratio 65 vs 64 mm Hg; prone positioning after intubation 81 vs 78%; mortality rate 17 vs 25% and ventilator-free days at 28 d 15 vs 13 d, all p values > 0.05). In this large cohort of hypoxemic patients with COVID-19, initiation of HFNO outside the ICU was safe, and clinical outcomes were similar to initiation in the ICU. Furthermore, the initiation of HFNO on wards saved time in ICU without excess mortality or complicated course. Our results indicate that HFNO initiation outside ICU should be further explored in other hypoxemic diseases and clinical settings aiming to preserve ICU capacity and healthcare costs.


Predictors and Outcomes of Postcontrast Acute Kidney Injury after Endovascular Renal Artery Intervention.
To determine incidence, predictors, and clinical outcomes of postcontrast acute kidney injury (PC-AKI) following renal artery stent placement for atherosclerotic renal artery stenosis. This retrospective study reviewed 1,052 patients who underwent renal artery stent placement for atherosclerotic renal artery stenosis; 437 patients with follow-up data were included. Mean age was 73.6 years ± 8.3. PC-AKI was defined as absolute serum creatinine increase ≥ 0.3 mg/dL or percentage increase in serum creatinine ≥ 50% within 48 hours of intervention. Logistic regression analysis was performed to identify risk factors for PC-AKI. The cumulative proportion of patients who died or went on to hemodialysis was determined using Kaplan-Meier survival analysis. Mean follow-up was 71.1 months ± 68.4. PC-AKI developed in 26 patients (5.9%). Patients with PC-AKI had significantly higher levels of baseline proteinuria compared with patients without PC-AKI (odds ratio = 1.38; 95% confidence interval, 1.11-1.72; P = .004). Hydration before intervention, chronic kidney disease stage, baseline glomerular filtration rate, statin medications, contrast volume, and iodine load were not associated with higher rates of PC-AKI. Dialysis-free survival and mortality rates were not significantly different between patients with and without PC-AKI (P = .50 and P = .17, respectively). Elevated baseline proteinuria was the only predictor for PC-AKI in patients undergoing renal artery stent placement. Patients who developed PC-AKI were not at greater risk for hemodialysis or death.


Some theory of reference values. I. Stratified (categorized) normal ranges and a method for following an individual's clinical laboratory values.
The conventional population-based normal range has recently been shown to be a generally defective reference criterion for assessing individual laboratory test results. Applying a previously derived formula to published data, we find that the use of age-, sex-specific normal ranges may fail to produce a substantial improvement in sensitivity over nonspecific ranges, even when age-sex differences in mean values are statistically significant. This occurs when the difference in means is not accompanied by a sufficient reduction in the variation among individuals within a given class. Turning therefore to comparison of an individual's current measurement with his own previous value(s), I suggest a simple statistical model that leads to sequential testing of each new observation against an exponentially weighted moving average of previous results. Estimates of biological and analytical components of variance are required. The ability of this method to detect trends in very short series is explored with the aid of computer-simulated laboratory data. A sample of these data is also used to illustrate the application of these estimation and testing procedures by means of a graph.


Sources of natural resistance to plant viruses: status and prospects.
SUMMARY Globally, virus diseases are common in agricultural crops and have a major agronomic impact. They are countered through the deployment of genetic resistance against the virus, or through the use of a range of farming practices based upon the propagation of virus-free plant material and the exclusion of the virus vectors from the growing crop. We review here the current status of our knowledge of natural virus resistance genes, and consider the future prospects for the deployment of these genes against virus infection.


Molecular architecture of the Cryptococcus neoformans capsule.
Many microbes are surrounded by phagocytosis-inhibiting capsules. We took advantage of the large size of the polysaccharide capsule of the pathogenic yeast Cryptococcus neoformans to examine capsular architecture and the relationship between molecular architecture and the interaction of the capsule with potentially opsonic serum proteins. Our experimental design used complementary approaches in which (i) assessment of permeability to macromolecules of different Stokes radii; (ii) determination of the binding of Fab fragments of anticapsular antibodies as a measure of matrix density; (iii) capsular deconstruction by treatment with dimethyl sulphoxide; and (iv) evaluation of capsule plasticity, were used to probe the molecular structure of the capsule. The results showed that the capsule is a matrix with a variable porosity that increases with distance from the cell wall. A high density of the matrix at the capsule interior prevents penetration of large macromolecules to sites near the cell wall. In contrast, the capsular edge that is the interface with phagocytes presents capsular polysaccharide in a very low density that exhibits considerable plasticity and permeability to macromolecules. Notably, the capsule of yeast cells harvested from infected tissue showed a greater matrix density than yeast cells grown in vitro under capsule induction conditions.


Radial Extracorporeal Shock Wave Therapy in an Individual With Primary Trigeminal Neuralgia: A Case Report and Literature Review.
A patient with primary trigeminal neuralgia exhibited pain relief without medication after radial extracorporeal shock wave therapy. The 52-yr-old woman had a 3-yr history of primary trigeminal neuralgia, involving the right maxillary division (V2) and the mandibular division (V3). She became refractory to carbamazepine and exhibited hepatic dysfunction. She hence received 3000 to 6000 impulses of craniofacial radial extracorporeal shock wave therapy to the region centered on the surface projection of the trigeminal ganglion and pain areas at 10 Hz; the intensity ranged from 1.4 to 4.5 bars twice per week for 8 wks. At baseline, and 1, 2, and 5 mos after treatment, the Barrow Neurological Institute scores were IV, IIIa, II, and II, and the visual analog scale scores were 8, 3, 1, and 1, respectively. No complications or adverse effects were observed. The hepatic function returned to normal after the discontinuation of carbamazepine. This case report demonstrates the feasibility of radial extracorporeal shock wave therapy for primary trigeminal neuralgia without complications or adverse effects with careful regulation of the therapy intensity.


NMR with (13)C, (15)N-doubly-labeled DNA: The shape Antennapedia homeodomain complex with a 14-mer DNA duplex.
Nearly complete (1)H, (13)C and(15) N NMR assignments have been obtained for a doubly labeled 14-base pair DNA duplex in solution both in the free state and complexed with the uniformly (15)N-labeled Antennapedia homeodomain. The DNA was either fully (13)C,(15)N-labeled or contained uniformly (13)C, (15)N-labeled nucleotides only at those positions which form the protein-DNA interface in the previously determined NMR solution structure of the Antennapedia homeodomain-DNA complex. The resonance assignments were obtained in three steps: (i) identification of the deoxyribose spin systems via scalar couplings using 2D and 3D HCCH-COSY and soft-relayed HCCH-COSY; (ii) sequential assignment of the nucleotides via(1) H-(1)H NOEs observed in 3D(13) C-resolved NOESY; and (iii) assignment of the imino and amino groups via (1)H-(1)H NOEs and(15) N-(1)H correlation spectroscopy. The assignment of the duplex in the 17 kDa protein-DNA complex was greatly facilitated by the fact that (1)H signals of the protein were filtered out in (13)C-resolved spectroscopy and by the excellent carbon chemical shift dispersion of the DNA duplex. Comparison of corresponding (13)C chemical shifts of the free and the protein-bound DNA indicates conformational changes in the DNA upon complex formation.


Attachment style predicts cooperation in intuitive but not deliberative response in one-shot public goods game.
Cooperation is an important prosocial behaviour that is of great significance to individuals and society. The social heuristics hypothesis (SHH) systematically explains how cooperation is interactively affected by intuitive and deliberative processes. On the one hand, the intuitive process can be either cooperative or selfish, which is determined by previous experience. On the other hand, the deliberative process could support either a cooperative decision or a selfish decision, depending on which strategy could maximise the current payoff. This research aims to investigate the mechanism of cooperation. Attachment style was selected as a proxy for previous experience to examine whether and how previous life experience shapes intuitive response. Time constraint (Studies 1 and 2) and cognitive load (Study 3) were manipulated to dissociate the intuitive and deliberative processes. In addition, cooperation was assessed by adopting one-shot public goods games. Results showed that attachment avoidance (Studies 1, 2, and 3) and attachment anxiety (Study 3) significantly predicted cooperation in the intuition condition, whereas these associations were insignificant in the deliberation condition (Studies 1, 2, and 3). These findings provide further support for the SHH and shed new light on the mechanism of cooperation.


A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.
Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects-for instance, within a few hours or days-would have an enormous impact on patient care and public health. To determine whether an N-methyl-D-aspartate-receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression. A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009. Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland. Patients Eighteen subjects with DSM-IV bipolar depression (treatment-resistant). Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion. Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores. Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d = 0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d = 0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point. In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist.


Chemosensory stimulation of luteinizing hormone secretion in male Siberian hamsters (Phodopus sungorus).
Male Siberian hamsters (Phodopus sungorus) housed in long days (LD), but not short days (SD) release luteinizing hormone (LH) when exposed to females. This study examined whether this response is specific to a female and identifies the source of a stimulus that induces LH release. Serum concentrations of LH, testosterone (T), follicle stimulating hormone (FSH), and cortisol were examined in all experiments. T concentrations mirrored the LH response; FSH and cortisol were unchanged in response to all stimuli. Exposure to an LD female, irrespective of her reproductive status, but not an SD female, elicited LH release. Exposure to another male did not trigger LH release. Males released LH when allowed physical contact with an anesthetized female, but not when separated from a normally active female, suggesting that tactile or nonvolatile chemosensory stimuli elicit LH release. Urine and secretions collected from the vagina as well as oral, midventral, perineal, and rectal glands, elicited marked behavioral responses in male P. sungorus. Despite these behavioral responses, only feces from females elicited LH release in males. Males released LH in response to feces extracted from the rectum and to cotton swabs that had been rubbed against the rectal mucosa, suggesting that a component of rectal secretions may trigger LH release in male Siberian hamsters. Taken together, these data and previous data from our laboratory indicate that both the production of and the response to a pheromone that triggers the selective release of LH is regulated by day length.


Using the peptide BP100 as a cell-penetrating tool for the chemical engineering of actin filaments within living plant cells.
The delivery of externally applied macromolecules or nanoparticles into living cells still represents a critically limiting step before the full capabilities of chemical engineering can be explored. Molecular transporters such as cell-penetrating peptides, peptoids, and other mimetics can be used to carry cargo across the cellular membrane, but it is still difficult to find suitable sequences that operate efficiently for any particular type of cell. Here we report that BP100 (KKLFKKILKYL-amide), originally designed as an antimicrobial peptide against plant pathogens, can be employed as a fast and efficient cell-penetrating agent to transport fluorescent test cargoes into the cytosol of walled plant cells. The uptake of BP100 proceeds slightly more slowly than the endocytosis of fluorescent dextranes, but BP100 accumulates more efficiently and to much higher levels (by an order of magnitude). The entry of BP100 can be efficiently blocked by latrunculin B; this suggests that actin filaments are essential to the uptake mechanism. To test whether this novel transporter can also be used to deliver functional cargoes, we designed a fusion construct of BP100 with the actin-binding Lifeact peptide (MGVADLIKKFESISKEE). We demonstrated that the short BP100 could transport the attached 17-residue sequence quickly and efficiently into tobacco cells. The Lifeact construct retained its functionality as it successfully labeled the actin bundles that tether the nucleus in the cell center.


Automated tertiary structure prediction with accurate local model quality assessment using the IntFOLD-TS method.
The IntFOLD-TS method was developed according to the guiding principle that the model quality assessment (QA) would be the most critical stage for our template-based modeling pipeline. Thus, the IntFOLD-TS method firstly generates numerous alternate models, using in-house versions of several different sequence-structure alignment methods, which are then ranked in terms of global quality using our top performing QA method-ModFOLDclust2. In addition to the predicted global quality scores, the predictions of local errors are also provided in the resulting coordinate files, using scores that represent the predicted deviation of each residue in the model from the equivalent residue in the native structure. The IntFOLD-TS method was found to generate high quality 3D models for many of the CASP9 targets, whilst also providing highly accurate predictions of their per-residue errors. This important information may help to make the 3D models that are produced by the IntFOLD-TS method more useful for guiding future experimental work.


Tobacco consumption among primary school teachers in Nairobi.
To determine the extent, pattern and the attendant risk factors of cigarette smoking and tobacco consumption among primary school teachers in Nairobi. A descriptive cross-sectional study. The study was carried out among randomly selected Nairobi City Council primary schools in 1996. All the teachers in the selected primary schools were included in the study. Out of 910 teachers contacted, 813 responded (a response rate of 89.3%). A total of 800 teachers completed the questionnaire correctly and are the subject of the present analysis. Fifty per cent of male and three per cent of female teachers were cigarette smokers at the time of the study. The median age for starting to smoke was between 15 and 24 years. At this age, the teachers were secondary school and tertiary college students. It was observed that the age of smoking initiation seems to determine the individual's smoking status later in life. Since 57% of smokers started smoking during their secondary school days, secondary school students seem to be at a higher risk of initiating smoking. It is therefore important to target them for smoking control initiatives before they start the habit. A number of smokers were willing to quit smoking but did not know how to go about it. External assistance is therefore required for them to achieve their wish. It is also important to emphasise the need by the relevant authorities to initiate programmes for anti-smoking education in secondary schools and colleges in the country.


Decrease and altered distribution of human T antigen on chronic lymphatic leukemia cells of T type, suggesting a clonal origin.
B- and T-cell markers were studied in a patient with chronic lymphocytic leukemia and erythroderma. The absence of immunoglobulin, complement receptor, and Fc receptor, and the presence of sheep erythrocyte receptor and T-cell antigen on the membrane of the leukemic cells classified them as thymus derived. Using quantitative microphotometric immunoautoradiography, surface antigen densities were measured at the cellular level with the following results: (1) The density of T-antigenic sites was less on leukemic cells compared to normal T lymphocytes. (2) The T-antigen densities of leukemic lymphocytes varied less from cell to cell forming a homogeneous peak in histograms. (3) An Ig density of normal B lymphocytes was demonstrated on the residual T-antigen-negative cells. The results were qualitatively confirmed by direct immunofluorescence and electron microscopy with peroxidase-labeled antibodies. Furthermore, the surface antigens were quantitative microcomplement fixation test which revealed reduced binding of anti-T-cell antibodies and complement, and no antiglobulin fixation on the leukemic lymphocytes. Since lymphocytes with normal T-antigen concentration could not be found among the leukemic T lymphocytes, a lack of normal T cells was assumed. The findings that there was a decrease and altered distribution of surface markers on chronic lymphatic leukemia cells of the B- and T-cell type are discussed as further arguments referring to their clonal origin.


Endobronchial argon plasma coagulation for treatment of hemoptysis and neoplastic airway obstruction.
To evaluate the usefulness of endobronchial argon plasma coagulation (APC) for the treatment of hemoptysis and neoplastic airway obstruction. Retrospective study. Bronchoscopy unit of a university hospital. A total of 60 patients with bronchogenic carcinoma (n = 43), metastatic tumors affecting the bronchi (n = 14), or benign bronchial disease (n = 3). Indications for intervention were hemoptysis (n = 31), symptomatic airway obstruction (n = 14), and both obstruction and hemoptysis (n = 25). Hemoptysis was stratified as a volume of > 200 mL/d (n = 6), > 50 to 200 mL/d (n = 23), or < or = 50 mL/d but persistence for > 1 week (n = 27). The mean (+/- SD) duration of hemoptysis was 16.5 +/- 16.1 days before intervention. Obstruction sites were the trachea (n = 8), mainstem bronchi (n = 21), and lobar bronchi (n = 30). In 24 cases, the patient had obstructions at multiple sites. The mean size of the pretreatment obstruction was 76 +/- 24.9%. APC, a noncontact form of electrocoagulation, was performed via flexible bronchoscopy. Sixty patients underwent 70 procedures. Conscious sedation without endotracheal intubation was used in all patients except four, who were mechanically ventilated because of underlying respiratory failure. All patients with hemoptysis experienced a resolution of bleeding immediately after APC. Hemoptysis from treated sites did not recur during a mean follow-up duration of 97 +/- 91.9 days. Patients with endoluminal airway lesions had an overall decrease in mean obstruction size to 18.4 +/- 22.1%. All patients with obstructive lesions, except one who died of sepsis, experienced symptom improvement. In these patients, symptom control was maintained during a median follow-up period of 53 days (range, 18 to 321 days). There were no complications related to the procedure. APC is effective for the treatment of endoluminal hemoptysis and airway obstruction. The procedure can be performed in an outpatient setting or at the bedside in the ICUs. APC provides a simpler, lower-risk alternative to other interventional endobronchial techniques.