[Sporadic Inclusion Body Myositis and Autoantibodies].
Sporadic inclusion body myositis (sIBM) is a chronically progressing inflammatory myopathy most common in the aged population. Asymmetric muscle weakness and waste of the quadriceps and finger and wrist flexor muscles are characteristic features of sIBM. Histological findings suggest the involvement of a crosstalk of inflammatory and myodegenerative mechanisms in the pathogenesis of sIBM. As an etiological clue to sIBM, identification of autoantibodies against cytosolic 5'-nucleotidase 1A (NT5C1A) in plasma and serum samples from patients with sIBM has been attracting attention. So far, various methods with clinical utility have been established to detect anti-NT5C1A autoantibodies. The measurement of the autoantibodies is useful for the diagnosis of sIBM due to its high specificity. Moreover, the autoantibodies may have pathogenic roles in the development of the disease by stimulating catabolic conditions and/or causing dysfunction in protein degradation of skeletal muscles; however, the molecular mechanisms by which the sarcoplasmic autoantigen is recognized and involved in the degeneration of myofibers remain unclear.


Single molecule nanobioscience.
In recent years, the rapid development and progress of single-molecule detection techniques have opened up a new era of biological research. The advantage of single-molecule studies is that data are not obscured by the ensemble-averaged measurements inherent in classical biochemical experiments. These techniques are shedding light on the dynamic and mechanistic properties of molecular machines, both in vivo and in vitro. This review summarizes the single-molecule experiments that have been designed to investigate molecular motors, enzyme reactions, protein dynamics, DNA transcription and cell signaling.


Evaluation of the feasibility of the electronic tongue as a rapid analytical tool for wine age prediction and quantification of the organic acids and phenolic compounds. The case-study of Madeira wine.
A set of fourteen Madeira wines comprising wines produced from four Vitis vinifera L. varieties (Bual, Malvasia, Verdelho and Tinta Negra Mole) that were 3, 6, 10 and 17 years old was analysed using HPLC and an electronic tongue (ET) multisensor system. Concentrations of 24 organic acids, phenolic and furanic compounds were determined by HPLC. The ET consisting of 26 potentiometric chemical sensors with plasticized PVC and chalcogenide glass membranes was used. Significance of the effects of age and variety on the ET response and wine composition with respect to the organic acids, phenolics and furanic derivatives were evaluated using ANOVA-Simultaneous Component Analysis (ASCA). Significance of the effects was estimated using a permutation test (1000 permutations). It was found that effects of age, grape variety and their interaction were significant for the HPLC data set and only the effect of age was significant for the ET data. Calibration models of the HPLC and ET data with respect to the wine age and of the ET data with respect to the concentration of the organic acids and phenolics were calculated using PLS1 regression. Models were validated using cross-validation. It was possible to predict wine age from HPLC and ET data with the accuracy in cross-validation of 2.6 and 1.8 years respectively. The ET was capable of detecting the following components (mean relative error in cross-validation is shown in the parentheses): tartaric (8%), citric (5%), formic (12%), protocatehuic (5%), vanillic (18%) and sinapic (14%) acids, catechin (6%), vanillin (12%) and trans-resveratrol (5%). The ET capability of predicting Madeira wine age with good accuracy (1.8 years) as well as quantify of some organic acids and phenolic compounds was demonstrated.


Neural systems of second language reading are shaped by native language.
Reading in a second language (L2) is a complex task that entails an interaction between L2 and the native language (L1). To study the underlying mechanisms, we used functional magnetic resonance imaging (fMRI) to visualize Chinese-English bilinguals' brain activity in phonological processing of logographic Chinese and alphabetic English, two written languages with a sharp contrast in phonology and orthography. In Experiment 1, we found that phonological processing of Chinese characters recruits a neural system involving left middle frontal and posterior parietal gyri, cortical regions that are known to contribute to spatial information representation, spatial working memory, and coordination of cognitive resources as a central executive system. We assume that the peak activation of this system is relevant to the unique feature of Chinese that a logographic character has a square configuration that maps onto a monosyllabic unit of speech. Equally important, when our bilingual subjects performed a phonological task on English words, this neural system was most active, whereas brain areas mediating English monolinguals' fine-grained phonemic analysis, as demonstrated by Experiment 2, were only weakly activated. This suggests that our bilingual subjects were applying their L1 system to L2 reading and that the lack of letter-to-sound conversion rules in Chinese led Chinese readers to being less capable of processing English by recourse to an analytic reading system on which English monolinguals rely. Our brain imaging findings lend strongest support to the idea that language experience tunes the cortex.


[Induced hypotension for endoscopic sinus surgery].
The purpose of the present investigation is to examine whether induced hypotension can improve the dryness of the surgical field in endoscopic sinus surgery (ESS). ASA physical status I and II adult patients with chronic sinutitis undergoing ESS were studied. All patients were not premedicated. Anesthesia was induced with propofol and maintained with sevoflurane and fentanyl. The patients were allocated randomly into two groups. In patients of Group C, mean arterial blood pressure (MAP) was maintained around 80 mmHg. In Group H, sodium nitroprusside was infused to maintain controlled hypotension with MAP around 60 mmHg. Blood loss, dryness of the surgical field, volume of fluid infusion and urine output, and surgical as well as anesthetic time were compared. Blood loss and dryness of the surgical field were significantly different between the groups. Volume of infused fluid, urine output, and surgical as well as anesthetic time were not significantly different. Induced hypotension with sodium nitroprusside improved surgical conditions and decreased blood loss in ESS.


Potential mechanisms underlying the acute lung dysfunction and bacterial extrapulmonary dissemination during Burkholderia cenocepacia respiratory infection.
Burkholderia cenocepacia, an opportunistic pathogen that causes lung infections in cystic fibrosis (CF) patients, is associated with rapid and usually fatal lung deterioration due to necrotizing pneumonia and sepsis, a condition known as cepacia syndrome. The key bacterial determinants associated with this poor clinical outcome in CF patients are not clear. In this study, the cytotoxicity and procoagulant activity of B. cenocepacia from the ET-12 lineage, that has been linked to the cepacia syndrome, and four clinical isolates recovered from CF patients with mild clinical courses were analysed in both in vitro and in vivo assays. B. cenocepacia-infected BEAS-2B epithelial respiratory cells were used to investigate the bacterial cytotoxicity assessed by the flow cytometric detection of cell staining with propidium iodide. Bacteria-induced procoagulant activity in cell cultures was assessed by a colorimetric assay and by the flow cytometric detection of tissue factor (TF)-bearing microparticles in cell culture supernatants. Bronchoalveolar lavage fluids (BALF) from intratracheally infected mice were assessed for bacterial proinflammatory and procoagulant activities as well as for bacterial cytotoxicity, by the detection of released lactate dehydrogenase. ET-12 was significantly more cytotoxic to cell cultures but clinical isolates Cl-2, Cl-3 and Cl-4 exhibited also a cytotoxic profile. ET-12 and CI-2 were similarly able to generate a TF-dependent procoagulant environment in cell culture supernatant and to enhance the release of TF-bearing microparticles from infected cells. In the in vivo assay, all bacterial isolates disseminated from the mice lungs, but Cl-2 and Cl-4 exhibited the highest rates of recovery from mice livers. Interestingly, Cl-2 and Cl-4, together with ET-12, exhibited the highest cytotoxicity. All bacteria were similarly capable of generating a procoagulant and inflammatory environment in animal lungs. B. cenocepacia were shown to exhibit cytotoxic and procoagulant activities potentially implicated in bacterial dissemination into the circulation and acute pulmonary decline detected in susceptible CF patients. Improved understanding of the mechanisms accounting for B. cenocepacia-induced clinical decline has the potential to indicate novel therapeutic strategies to be included in the care B. cenocepacia-infected patients.


HER-targeted tyrosine-kinase inhibitors.
Improved understanding of tumor biology has led to the identification of numerous growth factors that are involved in malignant transformation and tumor progression. Many of these factors induce cellular responses through receptors with intrinsic tyrosine kinase (TK) activity. Therefore, inhibiting receptor TK activity is a way to effectively block the tumorigenic effects that arise from these pathways. The HER family of TK receptors is overexpressed or dysregulated in many types of human cancer. As a result these receptors were identified as targets for cancer therapy. Several agents have been developed that reversibly, or irreversibly, inhibit one, two or all of the HER receptors. Tarceva and Iressa are HER1-TK inhibitors that are advanced in development. Clinical data show that these agents as monotherapy have antitumor activity in patients with various types of solid tumor and are well tolerated; encouraging data are also produced when Tarceva or Iressa are combined with chemotherapeutic agents. Other dual or pan-HER, reversible or irreversible, TK inhibitors are being investigated in phase I trials. Early data show that they are generally well tolerated and have provided evidence of antitumor activity. HER-TK inhibitors are exciting agents that are likely to have a substantial impact on the way we treat patients with cancer.


Feed efficiency measures and their relationships with production and meat quality traits in slower growing broilers.
Feed consumption accounts for the major cost of broiler production. Improving the efficiency of feed utilization is a primary goal in breeding strategies, although few studies have focused on slower growing broilers. Here, we recorded the feed intake (FI) during the fast-growing period (d 56 to 76) and measured the live weight, body measurements, carcass characteristics, and intramuscular fat (IMF) content of Chinese yellow broilers. Then, the residual feed intake (RFI) and feed conversion ratio (FCR) were calculated for each individual. Pair-wise phenotypic correlations were subsequently calculated between feed efficiency traits and others. Finally, we separately selected the more efficient individuals based on RFI and FCR values to evaluate the impacts on the traits of FI, growth, carcass characteristics, and meat quality. The results showed higher correlations between FCR and production traits than with RFI, while RFI showed a moderate and positive phenotypic correlation with abdominal fat. FCR was weakly correlated with FI and slightly positively correlated with IMF content. The correlation coefficient between RFI and FI was 0.62, and that between RFI and IMF content was close to zero. Without increasing FI, decreasing FCR could effectively enhance the growth rate and market weight with no adverse effect on meat quality. In contrast, by improving RFI, FI and abdominal fat mass were significantly reduced and thus increased the yield with no unfavorable effects on meat quality. In consideration of consumer preference and overall economical benefits, RFI is a more suitable index to improve feed efficiency in slower growing broilers.


Generation of functional hepatocytes from human spermatogonial stem cells.
To generate functional human hepatocytes from stem cells and/or extra-hepatic tissues could provide an important source of cells for treating liver diseases. Spermatogonial stem cells (SSCs) have an unlimited plasticity since they can dedifferentiate and transdifferentiate to other cell lineages. However, generation of mature and functional hepatocytes from human SSCs has not yet been achieved. Here we have for the first time reported direct transdifferentiation of human SSCs to mature and functional hepatocytes by three-step induction using the defined condition medium. Human SSCs were first transdifferentiated to hepatic stem cells, as evidenced by their morphology and biopotential nature of co-expressing hepatocyte and cholangiocyte markers but not hallmarks for embryonic stem cells. Hepatic stem cells were further induced to differentiate into mature hepatocytes identified by their morphological traits and strong expression of CK8, CK18, ALB, AAT, TF, TAT, and cytochrome enzymes rather than CK7 or CK19. Significantly, mature hepatocytes derived from human SSCs assumed functional attributes of human hepatocytes, because they could produce albumin, remove ammonia, and uptake and release indocyanine green. Moreover, expression of β-CATENIN, HNF4A, FOXA1 and GATA4 was upregulated during the transdifferentiation of human SSCs to mature hepatocytes. Collectively, human SSCs could directly transdifferentiate to mature and functional hepatocytes. This study could offer an invaluable source of human hepatocytes for curing liver disorders and drug toxicology screening and provide novel insights into mechanisms underlying human liver regeneration.


Nurses Leading Partnership-Driven Transformation to Address the Nursing Shortage.
For various reasons, including the pandemic's toll, many nurses are preparing to exit their roles or leave the profession entirely. Addressing attrition requires health care systems to develop comprehensive workforce strategies to enhance the nursing pipeline. Health care systems must proactively address challenges through innovative workforce solutions using an academic-practice partnership model while incorporating high schools and post-secondary schools. This column will discuss how nurse leaders in a health care system address attrition through academic-practice partnership models, innovative strategies, and outcomes data. [J Contin Educ Nurs. 2023:54(2):53-55.].


Biological Function and Medicinal Research Significance of G-Quadruplex Interactive Proteins.
G-quadruplexes are four-stranded DNA structures formed from G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Accumulating studies have revealed that G-quadruplex structures are formed in vivo and play important roles in biological processes such as DNA replication, transcription, recombination, epigenetic regulation, meiosis, antigenic variation, and maintenance of telomeres stability. Mounting evidence indicates that a variety of proteins are capable of binding selectively and tightly to G-quadruplex and play essential roles in G-quadruplex-mediated regulation processes. Some of these proteins promote the formation or/and stabilization of G-quadruplex, while some other proteins act to unwind G-quadruplex preferentially. From a drug discovery perspective, many of these G-quadruplex binding proteins and/or their complexes with G-quadruplexes are potential drug targets. Here, we present a general summary of reported G-quadruplex binding proteins and their biological functions, with focus on those of medicinal research significance. We elaborated the possibility for some of these G-quadruplex binding proteins and their complexes with G-quadruplexes as potential drug targets.


Bronchial artery chemoembolization combined with radioactive iodine-125 seed implantation in the treatment of advanced nonsmall cell lung cancer.
The aim of this study was to investigate the short-term efficacy and safety of bronchial artery chemoembolization (BACE) combined with radioactive iodine-125 seed implantation in the treatment of nonsmall cell lung cancer (NSCLC). Sixty-two Stage III-IV NSCLC patients were divided into Groups A and B. Thirty cases were treated with BACE combined with radioactive iodine-125 seed implantation in the Group A and 32 cases were treated with BACE alone in the Group B until disease progression. Efficacy, incidence rate of adverse drug reactions, and survival rate were compared between the two groups. The local control rates and effective rates of Groups A and B were 90% and 59.3% and 74% and 40.6%, respectively, with P < 0.05 for each. The progression-free survival of the study group and the control group was 12.6 and 8.2 months, respectively; the median survival time of the Groups A and B was 644 and 544 days, and the difference was statistically significant (P = 0.034). BACE combined with radioactive iodine-125 seed implantation was safe and effective in the treatment of advanced NSCLC, with an efficacy superior to that of single BACE.


Screening and Phenotypical Characterization of Schistosoma mansoni Histone Deacetylase 8 (SmHDAC8) Inhibitors as Multistage Antischistosomal Agents.
Schistosomiasis (also known as bilharzia) is a neglected tropical disease caused by platyhelminths of the genus Schistosoma. The disease is endemic in tropical and subtropical areas of the world where water is infested by the intermediate parasite host, the snail. More than 800 million people live in endemic areas and more than 200 million are infected and require treatment. Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment and transmission control being safe and very effective against adult worms of all the clinically relevant Schistosoma species. Unfortunately, it is ineffective on immature, juvenile worms; therefore, it does not prevent reinfection. Moreover, the risk of development and spread of drug resistance because of the widespread use of a single drug in such a large population represents a serious threat. Therefore, research aimed at identifying novel drugs to be used alone or in combination with PZQ are needed. Schistosoma mansoni histone deacetylase 8 (SmHDAC8) is a class I zinc-dependent HDAC, which is abundantly expressed in all stages of its life cycle, thus representing an interesting target for drug discovery. Through virtual screening and phenotypical characterization of selected hits, we discovered two main chemical classes of compounds characterized by the presence of a hydroxamate-based metal binding group coupled to a spiroindoline or a tricyclic thieno[3,2-b]indole core as capping groups. Some of the compounds of both classes were deeply investigated and showed to impair viability of larval, juvenile, and adult schistosomes, to impact egg production in vitro and/or to induce morphological alterations of the adult schistosome reproductive systems. Noteworthy, all of them inhibit the recombinant form of SmHDAC8 enzyme in vitro. Overall, we identified very interesting scaffolds, paving the way to the development of effective antischistosomal agents.


Children's loneliness, sense of coherence, family climate, and hope: developmental risk and protective factors.
The study examined the contributions of individual and familial variables for the prediction of loneliness as a developmental risk and the sense of coherence as a protective factor. The sample consisted of 287 children from grades 5-6. Their loneliness, sense of coherence, hope, effort, and family climate were assessed. Separate hierarchical multiple regression analyses revealed that family cohesion and children's hope contributed to the explanation of the risk and protective outcomes. Yet, the contribution of the family adaptability was not significant. Cluster analysis of the family climate dimensions (i.e., cohesion and adaptability) was performed to clarify the interactive roles of family adaptability together with family cohesion. The authors identified 4 separate family profiles: Children in the 2 cohesive families' clusters (Cohesive Structured Families and Cohesive Adaptable Families) reported the lowest levels of loneliness and the highest levels of personal strengths. Children within rigid and noncohesive family cluster reported the highest levels of loneliness and the lowest levels of children's sense of coherence. The unique role of the family flexibility within nonsupportive family systems was demonstrated. The results further clarified the unique profiles' characteristics of the different family clusters and their adjustment indexes in terms of loneliness and personal strengths.


Pharmacological responses to dopamine in isolated guinea-pig cardiovascular tissues: mechanisms of action.
The mechanisms responsible for the positive inotropic, positive chronotropic and vasoconstrictor responses to dopamine in isolated guinea-pig cardiovascular tissues have been investigated in the present study. Since dopamine is the immediate precursor of noradrenaline, the role of noradrenaline in the pharmacological responses after addition of dopamine has been assessed. In isolated, contracting right ventricular papillary muscles, dopamine-induced positive inotropy (-log EC50, 4.77 +/- 0.06) was unaltered by incubation with dopamine antagonists (SCH 23390, domperidone), alpha-adrenoceptor antagonists (prazosin, yohimbine), or an inhibitor of uptake1 (cocaine). Practolol (selective beta 1-adrenoceptor antagonist) and ICI 118,551 (selective beta 2-adrenoceptor antagonist) were noncompetitive antagonists to dopamine. Block of vesicular uptake by reserpine antagonized the positive inotropic responses to dopamine (-log EC50, 4.03 +/- 0.05) but not to noradrenaline; these responses were antagonized by both practolol and ICI 118,551. Chemical sympathectomy by 6-hydroxydopamine antagonized the responses to dopamine (-log EC50, 3.76 +/- 0.11) but potentiated the responses to noradrenaline (-log EC50, 7.35 +/- 0.07). Inhibition of monoamine oxidase with pargyline potentiated the responses to dopamine (-log EC50, 6.05 +/- 0.04) and noradrenaline; the potentiation of dopamine responses was unaffected by chemical sympathectomy. Inhibition of dopamine beta-hydroxylase with sodium diethyldithiocarbamate antagonized the inotropic responses to dopamine (-log EC50, 4.36 +/- 0.05) but not to noradrenaline. Similar results were obtained in guinea-pig left atria (positive inotropy) and right atria (positive chronotropy), except that chemical sympathectomy failed to affect the chronotropic responses. In thoracic aortic rings, dopamine contracted vascular smooth muscle by direct partial agonism of alpha 1-adrenoceptors, without involvement of dopamine beta-hydroxylase. Thus, there is antagonism of the cardiac, but not the vascular responses to dopamine by inhibition of dopamine beta-hydroxylase. This shows that the conversion of dopamine to noradrenaline is important in the inotropic and chronotropic responses, but not the vascular responses to dopamine.


Subscale structure for the Positive and Negative Syndrome Scale (PANSS): a proposed solution focused on clinical validity.
Although the items of the Positive and Negative Syndrome Scale (PANSS) are ordinal, continuous data methods are consistently used to analyze them. The current study addresses this issue by applying a categorical method and critically examining the ideas of item inclusion and goodness of fit. Data from 1527 subjects were used to test a proposed solution to the factor structure of the PANSS using a categorical factor analytic method. The model was made more generalizable by setting a minimum level of association between the item and the factor, and the results were then compared to existing solutions. The model was also tested for consistency in a first-episode sample. Use of categorical methods indicated similar results to previous analyses; however, it is demonstrated that the strength of the estimates can be unstable when items are shared across factors. The current study demonstrates that solutions can change substantially when a model is over-fitted, and therefore use of measures of fit as the criterion for an acceptable model can mask important relationships and decrease clinical validity.


Use of Non-Pharmacological Pain Treatment Modalities Among Veterans with Chronic Pain: Results from a Cross-Sectional Survey.
Despite strong evidence for the effectiveness of non-pharmacological pain treatment modalities (NPMs), little is known about the prevalence or correlates of NPM use. This study examined rates and correlates of NPM use in a sample of veterans who served during recent conflicts. We examined rates and demographic and clinical correlates of self-reported NPM use (operationalized as psychological/behavioral therapies, exercise/movement therapies, and manual therapies). We calculated descriptive statistics and examined bivariate associations and multivariable associations using logistic regression. Participants were 460 veterans endorsing pain lasting ≥ 3 months who completed the baseline survey of the Women Veterans Cohort Study (response rate 7.7%. Outcome was self-reported use of NPMs in the past 12 months. Veterans were 33.76 years old (SD = 10.72), 56.3% female, and 80.2% White. Regarding NPM use, 22.6% reported using psychological/behavioral, 50.9% used exercise/movement and 51.7% used manual therapies. Veterans with a college degree (vs. no degree; OR = 2.51, 95% CI = 1.46, 4.30, p = 0.001) or those with worse mental health symptoms (OR = 2.88, 95% CI = 2.11, 3.93, p < 0.001) were more likely to use psychological/behavioral therapies. Veterans who were female (OR = 0.63, 95% CI = 0.43, 0.93, p = 0.02) or who used non-opioid pain medications (OR = 1.82, 95% CI = 1.146, 2.84, p = 0.009) were more likely to use exercise/movement therapies. Veterans who were non-White (OR = 0.57, 95% CI = 0.5, 0.94, p = 0.03), with greater educational attainment (OR = 2.11, 95% CI = 1.42, 3.15, p < 0.001), or who used non-opioid pain medication (OR = 1.71, 95% CI = 1.09, 2.68, p = 0.02) were more likely to use manual therapies. Results identified demographic and clinical characteristics among different NPMs, which may indicate differences in veteran treatment preferences or provider referral patterns. Further study of provider referral patterns and veteran treatment preferences is needed to inform interventions to increase NPM utilization. Research is also need to identify demographic and clinical correlates of clinical outcomes related to NPM use.


Modern preoperative evaluation in ambulatory surgery - who, where and how?
Ambulatory surgery is increasingly performed in medically complex patients. This dynamic environment requires new approaches to ensure cost-effective, efficient, and ultimately safe preoperative evaluation of the patient. This review investigates recent advances in the assessment of ambulatory patients, with a special focus on patient screening, digital communication, and multidisciplinary team evaluation. Identifying suitable candidates for ambulatory surgery relies on a variety of medical, surgical, and institutional factors. Identification of high-risk patients and optimization of their treatment can be achieved through multidisciplinary protocols specific to the local institution and in line with current guidelines. Virtual assessment may be sufficient for most patients and provide an efficient evaluation strategy and high patient satisfaction. Prescreening can be supported by preoperative nursing teams. The increasing complexity of treatment provided in day surgery offers a unique opportunity to highlight the importance of anesthesiology staff as perioperative caregivers. Preoperative evaluation serves as a central junction to integrate a variety of surgical, medical, and institutional factors to provide safe, satisfactory, and efficient care for patients. Implementing technological innovation to streamline and facilitate this process is paramount.


Squamous and glandular differentiation in urothelial bladder carcinomas. Histopathology, histochemistry and immunohistochemical expression of carcinoembryonic antigen.
This paper reports the immunochemical expression of carcinoembryonic antigen in the squamous, glandular and mixed differentiation areas observed in 190 urothelial urinary bladder carcinomas. The antigen was found to occur in 75% and 81% of all papillary and solid infiltrating carcinomas, respectively. The use of the immunohistochemical determination of CEA in improving the morphological examination of these differentiation areas and their scant presence in the prognosis of urothelial carcinomas involving squamous and/or glandular focal differentiation are discussed.


Role of Lymphotoxin-α Gene Polymorphism in Hepatitis C Virus-Related Chronic Liver Disorders.
Tumor necrosis factor (TNF) family includes lymphotoxin-alpha (LTA) which is a pro-inflammatory cytokine which plays a role in hepatic fibrogenesis. LTA gene polymorphism plays a role in different inflammatory and immunomodulatory diseases. This polymorphism is also suggested to affect chronic hepatitis C (CHC) infection course. To study the contribution of LTA gene polymorphism in different chronic hepatitis C stages and hepatocellular carcinoma risk. Our study included 108 chronic HCV patients grouped according to the disease stage. Group (A): CHC, group (B): liver cirrhosis (LC), group (C): LC with HCC, and group (D): healthy controls. Routine laboratory investigations, polymerase chain reaction (PCR) for quantification of HCV, abdominal ultrasonography, and Liver stiffness measurement (LSM) were done. Child-Turcotte-Pugh, Model for end-stage liver disease (MELD), and Fibrosis index based on 4 (FIB-4) scores were calculated. We used the PCR-restriction fragment length polymorphism technique for lymphotoxin-α genotyping. The A/G genotype was predominant in all groups. In HCC patients, G/G genotype was more frequent (31.8%) than in the LC group (19.4%), CHC group (17.8%), and controls (4.17%). A significant association was found between LTA genotypes and the child classes in HCC (P<0.01) but not in LC patients (P>0.05). HCC patients carrying A/G genotype had higher MELD scores than other genotypes. Multivariate binary logistic regression analysis confirmed that LTA G/G genotype and low platelet count were independent predictors for HCC development in patients with HCV-related LC. Detection of LTA G/G genotype in chronic HCV patients could help to recognize high-risk patients for disease progression and HCC development.


Improved ELISA method for screening human antigen-specific IgE and its application for monitoring specific IgE for novel proteins in genetically modified foods.
For monitoring the occurrence of IgE antibody specific for novel proteins in genetically modified (GM) foods, ELISA is the most convenient method. The levels of IgE specific for recombinant proteins, phosphinothricin-N-acetyltransferase (PAT), CP4-EPSPS, and Cry9C were determined by ELISA using the sera from patients allergic to known allergens. Ovalbumin (OVA) and OVA-positive patient sera were used as positive control. In the ELISA, 20-fold-diluted sera tested were mostly negative for the specific IgE. However, the PAT-specific, but not CP4-EPSPS- or Cry9C-specific IgE in some patients was apparently higher than that of the healthy volunteers. To clarify the binding specificity of the antibody, we pre-incubated the sera with soluble PAT, but the inhibition was marginal, suggesting that the binding was non-specific. Therefore, we used 1M NaCl as a washing buffer to remove IgE non-specifically bound to the coated PAT. This washing step efficiently decreased non-specific binding. In contrast, OVA-specific IgE binding to OVA-coated plate was not affected by the washing. Finally, in this pilot study significant levels of IgE antibodies specific for the three proteins were not detected in the sera of Japanese food-allergy patients.


Effect of intercompartmental water exchange on the apparent myelin water fraction in multiexponential T2 measurements of rat spinal cord.
The myelin water fraction has been used as a quantitative measure of the amount of myelin present in tissue. However, recent work has suggested that intercompartmental exchange of water between myelin and nonmyelin compartments may cause the myelin water fraction to underestimate the true myelin content of tissue. In this work, multiexponential T(2) experiments were performed in vivo within the rat spinal cord, and a wide variation of the myelin water fraction (10-35%) was measured within four rat spinal cord tracts with similar myelin content. A numerical simulation based upon segmented histology images was used to quantitatively account for T(2) variations between tracts. The model predicts that a difference in exchange between the four spinal cord tracts, mediated by a difference in the average axon radius and myelin thickness, is sufficient to account for the variation in myelin water fraction measured in vivo.


Learning of Temporal and Spatial Movement Aspects: A Comparison of Four Types of Haptic Control and Concurrent Visual Feedback.
In literature, the effectiveness of haptics for motor learning is controversially discussed. Haptics is believed to be effective for motor learning in general; however, different types of haptic control enhance different movement aspects. Thus, in dependence on the movement aspects of interest, one type of haptic control may be effective whereas another one is not. Therefore, in the current work, it was investigated if and how different types of haptic controllers affect learning of spatial and temporal movement aspects. In particular, haptic controllers that enforce active participation of the participants were expected to improve spatial aspects. Only haptic controllers that provide feedback about the task's velocity profile were expected to improve temporal aspects. In a study on learning a complex trunk-arm rowing task, the effect of training with four different types of haptic control was investigated: position control, path control, adaptive path control, and reactive path control. A fifth group (control) trained with visual concurrent augmented feedback. As hypothesized, the position controller was most effective for learning of temporal movement aspects, while the path controller was most effective in teaching spatial movement aspects of the rowing task. Visual feedback was also effective for learning temporal and spatial movement aspects.


Are mirror-sensations really synesthetic?
Mirror-sensations, including touch and pain, are often referred to as synesthetic. The term can be challenged, however, because mirror-sensations lack the incongruency and saliency of synesthesia, may involve problems of perspective rather than entangled sensations, and may be easier to generate with suggestion. If mirror-sensations are truly sensations then they might be expected to act like the true sensation and mirror-pain, for example, might inhibit pain at a distance or itch in the same location. These predictions are highly testable.


Short hairpin RNA-mediated inhibition of measles virus replication in vitro.
Rab9 has been identified as a key component for the replication of measles virus (MV). In this study, gene-specific shRNAs were developed to suppress the replication of MV in culture cells by silencing the expression of Rab9 GTPase gene. Rab9 GTPase gene-specific shRNAs were designed and cloned into the expression vector of pSUPER.neo+EGFP. Vero-E6 cells were transfected with the recombinant plasmid via liposome and then infected with MV. The expression of Rab9 GTPase mRNA and protein were assayed by RT-PCR and Western blotting, respectively. ShRNA-mediated inhibition of MV replication was further evaluated by detecting the titer of MV. The results showed that the expression of Rab9 GTPase was dramatically and stably downregulated by the generated shRNAs targeting Rab9 GTPase gene, which contribute to the inhibition of MV replication, indicating these shRNAs could be potentially developed into therapeutic agents for the treatment of MV infection in the future.


Seasonal alterations in host range and fidelity in the polyphagous mirid bug, Apolygus lucorum (Heteroptera: Miridae).
In herbivorous insects, host plant switching is commonly observed and plays an important role in their annual life cycle. However, much remains to be learned about seasonal host switching of various pestiferous arthropods under natural conditions. From 2006 until 2012, we assessed Apolygus lucorum (Meyer-Dür) host plant use in successive spring, summer and winter seasons at one single location (Langfang, China). Data were used to quantify changes in host plant breadth and host fidelity between seasons. Host fidelity of A. lucorum differed between seasons, with 87.9% of spring hosts also used in the summer and 36.1% of summer hosts used in winter. In contrast, as little as 25.6% host plant species were shared between winter and spring. Annual herbaceous plants are most often used for overwintering, while perennial woody plants are relatively important for initial population build-up in the spring. Our study contributes to an improved understanding of evolutionary interactions between A. lucorum and its host plants and lays the groundwork for the design of population management strategies for this important pest in myriad crops.


Exome sequencing for gene discovery in lethal fetal disorders--harnessing the value of extreme phenotypes.
Massively parallel sequencing has revolutionized our understanding of Mendelian disorders, and many novel genes have been discovered to cause disease phenotypes when mutant. At the same time, next-generation sequencing approaches have enabled non-invasive prenatal testing of free fetal DNA in maternal blood. However, little attention has been paid to using whole exome and genome sequencing strategies for gene identification in fetal disorders that are lethal in utero, because they can appear to be sporadic and Mendelian inheritance may be missed. We present challenges and advantages of applying next-generation sequencing approaches to gene discovery in fetal malformation phenotypes and review recent successful discovery approaches. We discuss the implication and significance of recessive inheritance and cross-species phenotyping in fetal lethal conditions. Whole exome sequencing can be used in individual families with undiagnosed lethal congenital anomaly syndromes to discover causal mutations, provided that prior to data analysis, the fetal phenotype can be correlated to a particular developmental pathway in embryogenesis. Cross-species phenotyping allows providing further evidence for causality of discovered variants in genes involved in those extremely rare phenotypes and will increase our knowledge about normal and abnormal human developmental processes. Ultimately, families will benefit from the option of early prenatal diagnosis.


Serum Vascular Endothelial Growth Factor Levels Correlate with Severity of Retinopathy in Diabetic Patients: A Systematic Review and Meta-Analysis.
Investigations regarding serum and plasma vascular endothelial growth factor (VEGF) levels in patients with diabetic retinopathy (DR) are conflicting. This meta-analysis is aimed at determining whether serum and plasma VEGF levels are associated with DR and its severity in diabetic patients. PubMed and EMBASE were used to search for published studies, and serum and plasma VEGF levels were compared among DR, nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and nondiabetic retinopathy (NDR) patients. Standardized mean differences (SMD) and 95% confidence interval (CI) were pooled using a random effects model. A total of 29 studies comprising 1805 DR (or NPDR or PDR) patients and 1699 NDR patients were included. ELISA was used to evaluate serum or plasma VEGF levels in all except for two studies included in this meta-analysis. Overall, serum VEGF levels were significantly higher in DR patients (SMD: 0.74, 95% CI: 0.44-1.03) than those in NDR patients, while plasma VEGF levels were not in the comparison (SMD: 0.40, 95% CI: -0.13-0.92). Similarly, NPDR (SMD: 0.51, 95% CI: 0.22-0.80) and PDR (SMD: 1.32, 95% CI: 0.79-1.85) patients had higher serum VEGF levels compared with NDR patients, but the difference was not significant in plasma samples (SMD: 0.24, 95% CI: -0.47-0.95; SMD: 0.37, 95% CI: -0.30-1.05). In addition, serum VEGF levels were higher in PDR patients than those in NPDR patients (SMD: 0.87, 95% CI: 0.41-1.33), but plasma VEGF levels were not (SMD: -0.00, 95% CI: -0.31-0.31). The subgroup and metaregression analysis revealed that the study location, study design, and publication year of a study have certain influence on heterogeneity between studies in serum or plasma samples. VEGF levels in the serum instead of those in the plasma correlate to the presence and severity of DR in diabetic patients. Further large-scale studies are required to confirm these findings.


Rapid Detection of Mercury Ions Based on Nitrogen-Doped Graphene Quantum Dots Accelerating Formation of Manganese Porphyrin.
Mercuric ion (HgII) is a stable form of mercury pollution with high toxicity and bioaccumulation ability, and its sensitive and visible determination is of great importance. Herein, a simple method to significantly improve the complexation reaction rate between porphyrin and manganous ions (MnII) has been implemented by using the synergistic effect of trace nitrogen-doped graphene quantum dots (NGQDs) and Hg(II). A mechanism is proposed in accordance with a substitution reaction in which the deformed porphyrin nucleus by relatively larger Hg(II) ions is favorable for attacking small divalent metal ions carried by NGQDs from the back. Meanwhile, the formation of metalloporphyrin is accompanied by the absorption red-shift and fluorescence quenching of porphyrins; simultaneously, the fluorescence of NGQDs is gradually enhanced because of the inner filter effect between porphyrins and NGQDs. Thus, the ratiometric fluorescence and colorimetric methods for trace HgII sensing have been proposed on the basis of the distinct absorption/fluorescence spectral changes, which have potential application in complex environmental and biological conditions.


A new paradigm for anion trapping in high capacity and selectivity: crystal-to-crystal transformation of cationic materials.
We describe a new methodology to the selective trapping of priority pollutants that occur inherently as oxo-anions (e.g., perchlorate, chromate, arsenate, pertechnetate, etc.) or organic anions (e.g., salicylate, pharmaceuticals, and their metabolites, which are often chlorinated into potentially more harmful compounds). The typical approach to trapping anions is exchange into cationic hosts such as resins or layered double hydroxides. Both capacity and selectivity are limited by the equilibrium of the process and moreover are often subject to interference, e.g. by carbonate that is always present in water from atmospheric CO(2). Our approach takes advantage of the metastability of our cationically charged materials to instead trap by recrystallization to a new structure. Exceptionally high adsorption capacities for permanganate and perrhenate--studied as models for pertechnetate--were found for a Ag(I)-based cationic extended framework. The exchange capacity reached 292 and 602 mg/g, respectively, over five times the exchange capacity compared to conventional layered double hydroxides. Our cationic material can also selectively trap these and other toxic oxo-anions when nontoxic anions (e.g., nitrate, carbonate) were present in an over 100-fold excess concentration.


Functional connectivity change between posterior cingulate cortex and ventral attention network relates to the impairment of orientation for time in Alzheimer's disease patients.
Alzheimer's disease (AD) patients exhibit various cognitive dysfunctions, including impairment of orientation for time (OT). The brain regions underlying OT impairment remain to be elucidated. A previous single-photon emission computed tomography study has indicated hypoperfusion of the posterior cingulate cortex (PCC) in relation to deterioration of OT. In this study, we investigated whole brain functional connectivity changes of PCC using resting-state functional magnetic resonance imaging. Voxel-based functional connectivity with PCC was analyzed in OT-poor or OT-good AD patients, classified according to the mean OT scores of the Mini-Mental State Examination subscale. The connectivities of dorsal frontal lobe, and lateral parietal and lateral temporal lobes with PCC in the right hemisphere were reduced in the OT-poor AD group compared with the OT-good AD group. A subtraction connectivity map of OT score differences (OT-good minus OT-poor) revealed the right middle temporal gyrus near the temporo-parietal junction as a significantly connected region with PCC. These results suggest that the right posterior part of the middle temporal gyrus may play an important role in OT in conjunction with PCC, and that disconnection between PCC and the right ventral attention network may cause OT disturbance in AD patients.


Myosin-Va restrains the trafficking of Na+/K+-ATPase-containing vesicles in alveolar epithelial cells.
Stimulation of Na(+)/K(+)-ATPase activity in alveolar epithelial cells by cAMP involves its recruitment from intracellular compartments to the plasma membrane. Here, we studied the role of the actin molecular motor myosin-V in this process. We provide evidence that, in alveolar epithelial cells, cAMP promotes Na(+)/K(+)-ATPase recruitment to the plasma membrane by increasing the average speed of Na(+)/K(+)-ATPase-containing vesicles moving to the cell periphery. We found that three isoforms of myosin-V are expressed in alveolar epithelial cells; however, only myosin-Va and Vc colocalized with the Na(+)/K(+)-ATPase in intracellular membrane fractions. Overexpression of dominant-negative myosin-Va or knockdown with specific shRNA increased the average speed and distance traveled by the Na(+)/K(+)-ATPase-containing vesicles, as well as the Na(+)/K(+)-ATPase activity and protein abundance at the plasma membrane to similar levels as those observed with cAMP stimulation. These data show that myosin-Va has a role in restraining Na(+)/K(+)-ATPase-containing vesicles within intracellular pools and that this restrain is released after stimulation by cAMP allowing the recruitment of the Na(+)/K(+)-ATPase to the plasma membrane and thus increased activity.


Thermopower and Unconventional Nernst Effect in the Predicted Type-II Weyl Semimetal WTe2.
WTe2 is one of a series of recently discovered high mobility semimetals, some of whose properties are characteristic of topological Dirac or Weyl metals. One of its most interesting properties is the unsaturated giant magnetoresistance that it exhibits at low temperatures. An important question is the degree to which this property can be ascribed to a conventional semimetallic model in which a highly compensated, high mobility metal exhibits large magnetoresistance. Here, we show that the longitudinal thermopower (Seebeck effect) of semimetallic WTe2 exfoliated flakes exhibits periodic sign changes about zero with increasing magnetic field that indicates distinct electron and hole Landau levels and nearly fully compensated electron and hole carrier densities. However, inconsistent with a conventional semimetallic picture, we find a rapid enhancement of the Nernst effect at low temperatures that is nonlinear in magnetic field, which is consistent with Weyl points in proximity to the Fermi energy. Hence, we demonstrate the role played by the Weyl character of WTe2 in its transport properties.


What is bizarre in bizarre delusions? A critical review.
Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV) treats the presence of bizarre delusions (BD) as the heaviest-weighted clinical criterion of schizophrenia. Although BD play a major role in contemporary diagnostic systems, only a few empirical studies explore this issue. These studies provide highly heterogenous results because they are based on different experimental paradigms, in terms of definition, clinical sample, and number of raters. Here, we first discuss the psychopathological sources of the concept of BD, which were initially described as either nonsensical or incomprehensible. Then, we provide a critical review of contemporary studies on the reliability of BD and their methodological and conceptual limitations. Current approaches have focused intensely on BD's reliability and have defined BD strictly in terms of delusional content--mainly in terms of the physical impossibility or the cultural or historical incomprehensibility of the delusional claims. These approaches have neglected formal features of experience that underlie BD and the crucial issue of the nature and validity of BD. In the discussion, we argue that clinical diagnosis of BD cannot be limited to delusional contents alone and requires taking into account the subjective side of BD (how altered experience manifests itself) as well as the conditions of intersubjective encounter (how BD are expressed to and experienced by the clinician). The notion of "bizarreness" in schizophrenia is not purely theoretical; it has practical relevance for the therapeutic encounter and implications on further empirical research and on diagnostic approaches.


Synthetic gene networks as blueprint for smart hydrogels.
The rapidly emerging ability to design and construct synthetic gene networks in mammalian cells is based on the availability of mutually compatible genetic switches that enable the time-dependent induction of transgene expression in response to the dose of an externally applied stimulus. As these genetic switches are inherently compatible with mammalian cell physiology, they are as well predestined to control the functionality of cell-free synthetic devices within an overall physiologic background. In this chapter, we describe how a genetic switch that was originally designed for gene therapeutic studies can be applied in materials science to design and construct a biohybrid hydrogel that can be used to release a therapeutic growth factor in response to an externally applied stimulus for controlling cell fate and function in a time- and space-resolved manner.


Angiogenic pathway inhibition of Corydalis yanhusuo and berberine in human umbilical vein endothelial cells.
Corydalis yanhusuo, a well-known traditional Chinese medicine, is widely used in China as an analgesic for patients with terminal cancer. In this study, we want to expose the antiangiogenic effects and the underlying mechanisms of C. yanhusuo and the alkaloids obtained from this plant. The constituents of C. yanhusuo were first investigated for their inhibitory effects on angiogenesis, using several bioassays, including vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) proliferation, migration, invasion, and tube formation. To determine the active antiangiogenic compounds in C. yanhusuo, we studied the antiproliferative activities of several main constituents of C. yanhusuo, which belong to a group of protoberberine alkaloids, on HUVECs and identified berberine as a powerful angiogenesis inhibitor in C. yanhusuo. Both C. yanhusuo extract and its active compound berberine significantly suppressed the VEGF-induced upregulation of matrix metalloproteinase 2 (MMP2) at both mRNA and protein levels. Their functional effects, including the inhibition of MMP2, were shown to be involved VEGF-triggered ERK1/2 pathways. Our findings provide novel insights into the antiangiogenic effects of C. yanhusuo and berberine, and offer scientific evidence for their traditional clinical application as a cancer treatment.


Reentrant transitions in a mixture of small and big particles interacting via soft repulsive potential.
We report an observation of a temperature-controlled reentrant transition in simulations of mixtures of small and big particles interacting via a soft repulsive potential in two dimensions. As temperature increases, the system passes from a fluid mixture, to a crystal of big particles in a fluid of small particles, and back to a fluid mixture. Solidification is driven by entropy gain of small particles which overcomes the free-energy cost of confining big ones. Melting results from enhanced interpenetration of particles at high temperature which reduces the entropic forces that stabilize the crystal.


Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still's disease.
A 17-year-old female patient was referred to the Infectious Diseases Ward because of fever lasting for 14 days. On admission to the hospital the patient was in a generally good state, without any abnormalities on physical examination. Laboratory investigation revealed elevated inflammatory markers. Diagnostic imaging comprising chest X-ray, abdominal ultrasonography, and echocardiography showed no abnormalities. During the hospitalization, there occurred episodes of fever with skin rash and musculoskeletal pain of the lower limbs. Procalcitonin concentrations continued to increase. C-reactive protein concentrations decreased during therapy, starting from 191 mg/l. On the 23rd day of the disease, edema of the feet, ankles, and knees appeared. On the basis of the clinical picture and after excluding other possible causes of fever, the patient was diagnosed with adult onset Still's disease. The procalcitonin concentration was normalized after 5 days of steroid therapy. The patient was discharged under ambulatory rheumatologic supervision.


Low-intensity treadmill exercise and/or bright light promote neurogenesis in adult rat brain.
The hippocampus is a brain region responsible for learning and memory functions. The purpose of this study was to investigate the effects of low-intensity exercise and bright light exposure on neurogenesis and brain-derived neurotrophic factor expression in adult rat hippocampus. Male Sprague-Dawley rats were randomly assigned to control, exercise, light, or exercise + light groups (n = 9 per group). The rats in the exercise group were subjected to treadmill exercise (5 days per week, 30 minutes per day, over a 4-week period), the light group rats were irradiated (5 days per week, 30 minutes per day, 10 000 lx, over a 4-week period), the exercise + light group rats were subjected to treadmill exercise in combination with bright light exposure, and the control group rats remained sedentary over a 4-week period. Compared with the control group, there was a significant increase in neurogenesis in the hippocampal dentate gyrus of rats in the exercise, light, and exercise + light groups. Moreover, the expression level of brain-derived neurotrophic factor in the rat hippocampal dentate gyrus was significantly higher in the exercise group and light group than that in the control group. Interestingly, there was no significant difference in brain-derived neurotrophic factor expression between the control group and exercise + light group. These results indicate that low-intensity treadmill exercise (first 5 minutes at a speed of 2 m/min, second 5 minutes at a speed of 5 m/min, and the last 20 minutes at a speed of 8 m/min) or bright-light exposure therapy induces positive biochemical changes in the brain. In view of these findings, we propose that moderate exercise or exposure to sunlight during childhood can be beneficial for neural development.


Elucidation of chickpea hydration, effect of soaking temperature, and extent of germination on characteristics of malted flour.
Germination is a biochemical process that has been widely used to improve the nutritional quality, functional properties, and bioavailability of the protein. Soaking is the preliminary step for germination. Effect of soaking temperature on germination parameters was studied to select the suitable soaking temperature for germination. The effect of germination time on nutritional, functional, and microstructural properties of chickpea flour was evaluated. The soaking temperature was selected as 30°C depending on the germination percentage, vigor value, and mean germination time. Physico-chemical composition, antioxidant activity, ascorbic acid, total phenolic, and total flavonoid were investigated over 4 days of germination. It was found that protein content increased on dry matter basis, whereas carbohydrate and fat content decreased during germination. Ascorbic acid content was found to increase to about 3.52 times. Antioxidant activity increased from 24.14% to 58.50% after 4 days of germination. Water absorption capacity was found to decrease, whereas oil absorption capacity increased. XRD pattern depicted a decrease in crystallinity due to the degradation of amylopectin and increased amylose content. SEM was used to study the microstructural changes with increase in germination time. DSC studies were also carried out to study the effect of germination on thermal properties of chickpea flour. PRACTICAL APPLICATION: This research work gives an outline of the available literature on the mechanism of hydration and germination process with the associated chemical and biochemical changes in the bioactive components along with the special emphasis on the health benefits. The present work is an effort toward the development of chickpea-based meal-replacement beverages.


Juxtanuclear lymphocytes in histocultures of mammary cancer.
Juxtanuclear lymphocytes in histocultures of mammary cancer. Am J Clin Pathol 71: 64-71, 1979. This is the first report of a special orientation of autochthonous lymphocytes at a juxtanuclear zone of human mammary cancer cells in primary histocultures. The phenomenon, juxtanuclear orientation of lymphocytes, was observed in 99 histocultures from 16 of 45 (35%) successfully explanted cancers. A total of 686 instances of juxtanuclear orientation of lymphocytes was counted, versus 354 instances of random lymphocytic activities; juxtanuclear/random ratios ranged from 0.2 to 5.2. Ratio determinations may be potentially useful for assistance in evaluating prognosis; the preliminary findings are inconclusive but suggest that a ratio of one or more may indicate a more favorable clinical course. The immediate importance of juxtanuclear orientation of lymphocytes is that it offers a new measurement of pathologic lymphocytic activity that should have applications in basic and clinical studies of host responses in general.


A map of brain neuropils and fiber systems in the ant Cardiocondyla obscurior.
A wide spectrum of occupied ecological niches and spectacular morphological adaptations make social insects a prime object for comparative neuroanatomical studies. Eusocial insects have evolved complex societies based on caste polyphenism. A diverse behavioral repertoire of morphologically distinct castes of the same species requires a high degree of plasticity in the central nervous system. We have analyzed the central brain neuropils and fiber tract systems of the worker of the ant Cardiocondyla obscurior, a model for the study of social traits. Our analysis is based on whole mount preparations of adult brains labeled with an antibody against Drosophila-Synapsin, which cross-reacts strongly with synapses in Cardiocondyla. Neuropil compartments stand out as domains with a certain texture and intensity of the anti-Synapsin signal. By contrast, fiber tracts, which are composed of bundles of axons accompanied by glia and are devoid of synapses, appear as channels or sheaths with low anti-Synapsin signal. We have generated a digital 3D atlas of the Cardiocondyla brain neuropil. The atlas provides a reference for future studies of brain polymorphisms in distinct castes, brain development or localization of neurotransmitter systems.


Prevalence, Demographic Profile, and Psychological Aspects of Epilepsy in North-Western India: A Community-Based Observational Study.
This study was undertaken to determine the prevalence of active epilepsy, assess the sociodemographic profile, and psychological aspects of epilepsy in the Jaipur district of Rajasthan, India. We conducted a community-based, cross-sectional observational study covering both rural (n = 165,660) and urban (n = 179,142) populations of Jaipur district using a house-to-house survey. An adapted, pre-designed World Health Organization screening questionnaire was used to identify the cases. Those confirmed by neurologists as true seizures were included in the study. Cases were classified as per the International League against Epilepsy recommendation. Global Mental Health Assessment Tool electronic questionnaire was used to analyze psychological aspects of cases. The caregivers of the patients participated in the knowledge, attitude, and practice (KAP) survey. A total of 380 patients (258 men, 122 women) were identified with active epilepsy. The estimated prevalence of active epilepsy was 1.1/1,000 population and 71% of cases belonged to low socioeconomic classes. Primary treatment gap was documented in 18.8% of cases in our study, 38% of cases were non-compliant to treatment with poorer compliance in those on pol-therapy, 76% had some psychiatric disorder, anxiety and depression being the commonest, and positive family history of epilepsy was found in 4.7%. KAP survey revealed that only 15% of the respondents believed that epilepsy is non-curable, 74% denied its infectious nature, 26% believed that epilepsy occurs due to past sins, and 81% said that they would not marry persons with epilepsy. A relatively low prevalence (1.1/1,000) of active epilepsy and a smaller primary treatment gap (18.8%) was found in our study population. Almost three-fourth of cases had an associated psychological problem, Though caregivers were aware of the nature of disease, majority would not prefer to marry a person suffering from epilepsy.


Altered gravity downregulates aquaporin-1 protein expression in choroid plexus.
Aquaporin-1 (AQP1) is a water channel expressed abundantly at the apical pole of choroidal epithelial cells. The protein expression was quantified by immunocytochemistry and confocal microscopy in adult rats adapted to altered gravity. AQP1 expression was decreased by 64% at the apical pole of choroidal cells in rats dissected 5.5-8 h after a 14-day spaceflight. AQP1 was significantly overexpressed in rats readapted for 2 days to Earth's gravity after an 11-day flight (48% overshoot, when compared with the value measured in control rats). In a ground-based model that simulates some effects of weightlessness and alters choroidal structures and functions, apical AQP1 expression was reduced by 44% in choroid plexus from rats suspended head down for 14 days and by 69% in rats suspended for 28 days. Apical AQP1 was rapidly enhanced in choroid plexus of rats dissected 6 h after a 14-day suspension (57% overshoot, in comparison with control rats) and restored to the control level when rats were dissected 2 days after the end of a 14-day suspension. Decreases in the apical expression of choroidal AQP1 were also noted in rats adapted to hypergravity in the NASA 24-ft centrifuge: AQP1 expression was reduced by 47% and 85% in rats adapted for 14 days to 2 G and 3 G, respectively. AQP1 is downregulated in the apical membrane of choroidal cells in response to altered gravity and is rapidly restored after readaptation to normal gravity. This suggests that water transport, which is partly involved in the choroidal production of cerebrospinal fluid, might be decreased during spaceflight and after chronic hypergravity.


Clinical efficacy of PD-1 inhibitor combined with radiotherapy in a multi-drug resistant patient with liver metastasis from gastric cancer.
A 54-year-old male was diagnosed with extensive liver metastasis and small nodule metastasis in the lungs from gastric adenocarcinoma [Her-2 (-)]. The patient achieved significant partial response (PR) after chemotherapy combined with anti-angiogenesis therapy but developed progressive disease (PD) after 5 months. Then, the chemotherapeutic and anti-angiogenic drugs were replaced. Meanwhile, the delivery route of some chemotherapeutic drugs was changed, and some chemotherapeutic drugs were given via transcatheter arterial chemoembolization (TACE) to achieve PR, and PD developed after 3 months of remission maintenance. During chemotherapy combined with anti-angiogenesis, the application of programmed cell death-1 (PD-1) inhibitor achieved PR again and maintained for 5 months before disease progression. The progression of the lesions in the left lobe of the liver and the hepatic hilar lymph nodes was significant. Hence, chemotherapy was terminated and gamma stereotactic body radiation therapy (SBRT) was performed on left lobe lesions and hilar lymph nodes. The lesions both inside and outside the radiation field regressed significantly, reaching PR and abscopal effects. The immune-related adverse events (irAEs) occurred, including erythema and black and luster hair. The abscopal effects of lesion reduction in the radiation field and the enhancement of the immune function stimulated by radiation are a highlight of the combination of radiation and immunotherapy. In the end, the patient died of gastrointestinal failure, with overall survival of 18 months.


Ion velocity distribution function investigated inside an unstable magnetized plasma exhibiting a rotating nonlinear structure.
The frequent situation where a strongly nonlinear rotating structure develops in a linear magnetized plasma column is investigated experimentally with emphasis on the ion velocity distribution function (IVDF). Most often, a mode m=2 appears exhibiting a large density and potential perturbation with angular frequency slightly above the ion cyclotron frequency. For the first time the spatiotemporal evolution of the IVDF is studied using time-resolved laser induced fluorescence to explore the ion's interaction with the nonlinear wave propagating inside the column and at the origin of plasma transport outside the limiter. The ion fluid exhibits an alternance from azimuthal to radial velocity due to the electric field inside the rotating structure. A fluid model also allows us to locally reconstruct the self-consistent electric field evolution which contradicts all existing theories.


The impact of repeated surgery and adjuvant therapy on survival for patients with recurrent glioblastoma.
Treatment of glioblastoma recurrence can have a palliative aim, after considering risks and potential benefits. The aim of this study is to verify the impact of surgery and of palliative adjuvant treatments on survival after recurrence. From January 2002 to June 2008, we treated 76 consecutive patients with recurrent glioblastoma. Treatment was: 1-surgery alone--17 patients; 2-adjuvant-therapy alone--24 patients; 3-surgery and adjuvant therapy--16 patients; no treatment--19 patients. The impact on median overall-survival (OS-time between recurrence and death/last follow-up) of age, Karnofsky performance scale (KPS), resection extent and adjuvant treatment scheme (Temozolomide alone vs low-dose fractionated radiotherapy vs others) was determined. Survival curves were obtained through the Kaplan-Meier method. Cox proportional-hazards was used for multivariate analyses. Significance was set at p<0.05. Median OS was 7 months. At univariate analysis, patients with a KPS≥70 had a longer OS (9 months vs 5 months--p<0.0001). OS was 6 months for patients treated with surgery alone, 5 months for patients that received no treatment, 8 months for patients treated with chemotherapy alone, 14 months for patients treated with surgery and adjuvant therapy--p=0.01. Patients with a KPS<70 were significantly at risk for death - HR 2.8 - p=0.001. Subgroup analysis showed no significant differences between patients receiving gross total or partial tumor resection and among patients receiving different adjuvant therapy schemes. Major surgical morbidity at tumor recurrence occurred in 16 out of 33 patients (48%). It is fundamental, before deciding to operate patients for recurrence, to carefully consider the impact of surgical morbidity on outcome.


Pseudomonas aeruginosa. IV. IV. Pyocine typing of strains isolated from the blue fox (Alopex lagopus), mink (Mustela vison), and dog (Canis familiaris) and from their environment.
Investigation of a total of 354 Ps. aeruginosa strains by "active" pyocine typing, using Govan & Gillies' indicator strains (21, 24) by which it may be possible to demonstrate the sources and routes of pseudomonas infection revealed that: (1) of the isolated pyocine-producing types 85.5% could be fitted into Govan & Gillies' classification, (2) 11.1% of all strains tested did not produce pyocine, (3) p3 was the only pyocine type isolated from an enzootic of fatal, haemorrhagic pneumonia in experimental minks debilitated by change of environment and inoculation with plasmacytosis (Aleutian disease), (4) types 1--5, 8, 10, 17, 29, and 37 could be isolated from the blue foxes and their farm environment, and (5) types 1--3, 5, 6, 9, 10, 15, 17, 28, 31, and 37 were identified in hospitalized dogs and their hospital environment. Pyocine type p1 was predominant in all groups except that of experimental minks and samples from the room in which they were kept. This type, plus type p3, made up more than half the typed strains of Ps. aeruginosa. The sources of infection comprised: (1) Carriers among the blue foxes and their winter watering troughs. During periods without frost the troughs were not cleaned, but were left containing more or less water contaminated with urine, faeces, hairs, and dust--a well-suited habitat for Ps. aeruginosa. (2) In the case of the experimental minks the infection may have been derived from a dog with pseudomoniasis in the hospital, brought to the experimental room in the course of feeding and cleaning. (3) The infection in the Small Animal Clinic seems to be maintained by frequent admission of patients for treatment, especially of chronic otitis externa/media caused by widely resistant strains of Ps. aeruginosa.


[Software for illustrating a cost-quality balance carried out by clinical laboratory practice].
We have no proper reference indicating the quality of clinical laboratory practice, which should clearly illustrates that better medical tests require more expenses. Japanese Society of Laboratory Medicine was concerned about recent difficult medical economy and issued a committee report proposing a guideline to evaluate the good laboratory practice. According to the guideline, we developed software that illustrate a cost-quality balance carried out by clinical laboratory practice. We encountered a number of controversial problems, for example, how to measure and weight each quality-related factor, how to calculate costs of a laboratory test and how to consider characteristics of a clinical laboratory. Consequently we finished only prototype software within the given period and the budget. In this paper, software implementation of the guideline and the above-mentioned problems are summarized. Aiming to stimulate these discussions, the operative software will be put on the Society's homepage for trial


Interlaced x-ray microplanar beams: a radiosurgery approach with clinical potential.
Studies have shown that x-rays delivered as arrays of parallel microplanar beams (microbeams), 25- to 90-microm thick and spaced 100-300 microm on-center, respectively, spare normal tissues including the central nervous system (CNS) and preferentially damage tumors. However, such thin microbeams can only be produced by synchrotron sources and have other practical limitations to clinical implementation. To approach this problem, we first studied CNS tolerance to much thicker beams. Three of four rats whose spinal cords were exposed transaxially to four 400-Gy, 0.68-mm microbeams, spaced 4 mm, and all four rats irradiated to their brains with large, 170-Gy arrays of such beams spaced 1.36 mm, all observed for 7 months, showed no paralysis or behavioral changes. We then used an interlacing geometry in which two such arrays at a 90-degree angle produced the equivalent of a contiguous beam in the target volume only. By using this approach, we produced 90-, 120-, and 150-Gy 3.4 x 3.4 x 3.4 mm(3) exposures in the rat brain. MRIs performed 6 months later revealed focal damage within the target volume at the 120- and 150-Gy doses but no apparent damage elsewhere at 120 Gy. Monte Carlo calculations indicated a 30-microm dose falloff (80-20%) at the edge of the target, which is much less than the 2- to 5-mm value for conventional radiotherapy and radiosurgery. These findings strongly suggest potential application of interlaced microbeams to treat tumors or to ablate nontumorous abnormalities with minimal damage to surrounding normal tissue.


Ex Vivo Lung Perfusion: A Review of Research and Clinical Practices.
End-stage lung disease is ultimately treated with lung transplantation. However, there is a paucity of organs with an increasing number of patients being diagnosed with end-stage lung disease. Ex vivo lung perfusion has emerged as a potential tool to assess the quality and to recondition marginal donor lungs prior to transplantation with the goal of increasing the donor pool. This technology has shown promise with similar results compared with the conventional technique of cold static preservation in terms of primary graft dysfunction and overall outcomes. This review provides an update on the results and uses of this technology. The review will also summarize clinical studies and techniques in reconditioning and assessing lungs on ex vivo lung perfusion. Last, we discuss how this technology can be applied to fields outside of transplantation such as thoracic oncology and bioengineering.


The Impact of COVID-19 on Diverse Older Adults and Health Equity in the United States.
Older adults are most at risk of negative COVID-19 outcomes and consequences. This study applies the World Health Organization's Health Inequity Causal Model to identify different factors that may be driving the higher observed hospitalizations and deaths among older adults of color compared to non-Latinx Whites in the United States. We used multiple data sets, including the US Census American Community Survey and PULSE COVID data, along with published reports, to understand the social context of older adults, including income distributions by race and ethnicity, household composition and potential COVID-19 exposure to older adults by working family members. Our findings point to multiple social determinants of health, beyond individual health risks, which may explain why older adults of color are the most at risk of negative COVID-19 outcomes and consequences. Current health policies do not adequately address disproportionate impact; some even worsen it. This manuscript provides new data and analysis to support the call for equity-focused solutions to this pandemic and health in general in the future, focusing on meeting the needs of our most vulnerable communities.


Coherent Light Sources at the Nanoscale.
This review focuses on coherent light sources at the nanoscale, and specifically on lasers exploiting plasmonic cavities that can beat the diffraction limit of light. Conventional lasers exhibit coherent, intense, and directional emission with cavity sizes much larger than their operating wavelength. Plasmon lasers show ultrasmall mode confinement, support strong light-matter interactions, and represent a class of devices with extremely small sizes. We discuss the differences between plasmon lasers and traditional ones, and we highlight advances in directionality and tunability through innovative cavity designs and new materials. Challenges and future prospects are also discussed.


Mammograms and healthcare access among US Hispanic and non-Hispanic women 40 years and older.
Compared to non-Hispanic women, Hispanic women have disproportional mortality rates due to breast cancer. Mammographic screening detects breast cancer in its early stages and reduces mortality. We examined data obtained from the 2002 Behavioral Risk Factor Surveillance System questionnare using logistic regression analyses to study the relationships between demographic and healthcare factors and mammography use among Hispanic and non-Hispanic White women 40 years and older. Overall, the odds of ever having had a mammogram were similar among Hispanic and non-Hispanic White women (odds ratio = 1.2; 95% confidence interval = 0.9, 1.6), when adjusted for age, employment status, and other demographic variables. Having a personal physician and the type of healthcare facility typically used were associated with mammography use, regardless of Hispanic ethnicity. Although associations between mammography use and demographic factors were similar between ethnic groups, larger proportions of Hispanics had demographic characteristics that were negatively associated with mammography use. Establishing policies and mechanisms to provide all women with regular access to a personal physician or healthcare professional for their preventive and nonemergency healthcare needs may improve mammography use among both Hispanic and non-Hispanic White women. Similarly, reaching out to women who are uninsured and who use facilities other than physicians' offices for their healthcare needs may increase the use of mammography among both ethnic groups.


PRC1-mediated epigenetic programming is required to generate the ovarian reserve.
The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest in oocytes residing in primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies meiotic entry, but the chromatin changes that underpin the generation and preservation of ovarian reserves are poorly defined. We report that the Polycomb Repressive Complex 1 (PRC1) establishes repressive chromatin states in perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby enable the transition to dictyate arrest. PRC1 dysfuction causes depletion of the ovarian reserve and leads to premature ovarian failure. Our study demonstrates a fundamental role for PRC1-mediated gene silencing in female reproductive lifespan, and reveals a critical window of epigenetic programming required to establish ovarian reserve.


Aortic valve replacement for paraprosthetic leak after transcatheter implantation.
Conversion to surgical aortic valve replacement (AVR) has been described as a complication following transcatheter aortic valve implantation. This complication occurs in up to 8% of cases and, to the best of our knowledge, preoperative data and surgical outcomes of such patients have not been properly evaluated. Mild paraprosthetic regurgitation is commonly observed after transcatheter aortic valve implantation and usually leads to a benign clinical course. Unequal distribution of valve calcifications is described as a potential mechanism. We report a case of a perioperative paraprosthetic regurgitation that underwent successful urgent surgical AVR and review the incidence and results of paraprosthetic leaks following transcatheter implantation.


[Valve replacement in case of a partial atrioventricular canal. A propos of 17 cases].
In 17 patients with a partial form of atrioventricular canal, at least one valve was replaced. The mitral valve was the most commonly affected (16 cases), sometimes in association with the tricuspid valve (5 cases) or the aortic valve (1 case); the tricuspid valve alone was replaced in one case. 7 cases were ranked as operative deaths, and the longer term mortality was of 4 cases. The factors leading to this high mortality figure are discussed. The future treatment policy for this condition is discussed.


Electrical switch for smart pH self-adjusting system based on silver nanowire/polyaniline nanocomposite film.
A sensitive pH-triggered electrical switch is demonstrated by using a layer-structured silver nanowire/polyaniline nanocomposite film fabricated via an easy vertical spinning method. The as-prepared nanocomposite film shows the high electrical conductivity of 1.03 × 10(4) S cm(-1) at the Ag-NW areal density of 0.84 mg cm(-2) and a good cycling stability. Particularly, because of the layered structure, the switch achieves a very high contrast ratio of ca. 9 × 10(8), which is 2-6 orders higher than that reported previously. The high electrical conductivity and the high switching ratio make the layer-structured nanocomposite film a sensitive switch candidate for pH-responsive systems. Finally, a smart pH self-adjusting switching system is successfully designed using the as-prepared layer-structured nanocomposite film.


Breast cancer survivorship--intersecting gendered discourses in a 5-year follow-up study.
In this article the authors present a follow-up study of women's interview narratives about life 5 to 7 years after a breast cancer operation. The women had taken part in a study during the 6-month postoperation period. Art therapy contributed to well-being, including strengthening personal boundaries. In the new study, interview analysis informed by critical discursive psychology indicated three problematic discourses that the women still struggled with several years after the operation: the female survivor, the "good woman," and individual responsibility. We concluded that many women with a history of breast cancer need support several years after their medical treatment is finished.


Growth hormone response to growth hormone-releasing hormone and clonidine in young monkeys: correlation with behavioral characteristics.
Blunted growth hormone (GH) release in response to stimulation by a secretagogue has been widely reported in both children and adults with anxiety and depressive disorders. Blunted GH responsiveness appears to be a stable characteristic of an individual, suggesting that it may be useful as a biological marker that would allow early recognition of these disease processes. Another potential biological marker for anxiety disorders is the temperamental construct of behavioral inhibition. Children identified as being behaviorally inhibited early in life are more likely than less inhibited children to suffer from anxiety disorders later in life (Biederman et al. 1993; Hirshfeld et al. 1992). If blunted GH responsiveness to pharmacological challenge and behavioral inhibition are markers of anxiety and depressive disorders, then it would follow that they would coexist in a subset of individuals. However, such prospective studies in clinically normal young children are difficult to perform. Therefore, in this study, we examined GH responsiveness and temperament in a group of 38 young rhesus monkeys (ages 3-6 months). Monkeys received an intravenous dose of 10 microg/kg of growth hormone-releasing hormone (GHRH) and 5 microg/kg of clonidine, combined, to assess GH response to stimulation. Behavioral reactivity in a fearful situation was assessed using the Human Intruder Test developed by Kalin et al. (1991). This test measures response to a potentially threatening stimulus (a human stranger making direct eye contact). Results showed a population distribution of GH response to GHRH and clonidine ranging from 120 ng/mL/90 minutes to 3,000 ng/mL/90 minutes. There was no difference in GH response in males versus females or any significant effect of age on GH response. There was a significant correlation between GH responsiveness and the time spent reacting to the intruder in the Human Intruder Test. Monkeys with lower GH responsiveness reacted less to the intruder (p < 0.01). Additionally, when monkeys were classified based on their reactivity in the Human Intruder Test, behaviorally nonreactive monkeys had significantly lower GH responsiveness than behaviorally reactive monkeys (p < 0.005). These data provide evidence that there are inherent differences in GH responsiveness to stimulation in young rhesus monkeys and that low GH responsiveness is linked to low behavioral reactivity, which may be a form of behavioral inhibition. Further studies will be necessary to determine if the characteristics of low GH responsiveness and low behavioral reactivity predict an increased propensity to develop anxious or depressive behaviors over the course of the life span.


Comparative and functional genomics reveals genetic diversity and determinants of host specificity among reference strains and a large collection of Chinese isolates of the phytopathogen Xanthomonas campestris pv. campestris.
Xanthomonas campestris pathovar campestris (Xcc) is the causal agent of black rot disease of crucifers worldwide. The molecular genetic diversity and host specificity of Xcc are poorly understood. We constructed a microarray based on the complete genome sequence of Xcc strain 8004 and investigated the genetic diversity and host specificity of Xcc by array-based comparative genome hybridization analyses of 18 virulent strains. The results demonstrate that a genetic core comprising 3,405 of the 4,186 coding sequences (CDSs) spotted on the array are conserved and a flexible gene pool with 730 CDSs is absent/highly divergent (AHD). The results also revealed that 258 of the 304 proved/presumed pathogenicity genes are conserved and 46 are AHD. The conserved pathogenicity genes include mainly the genes involved in type I, II and III secretion systems, the quorum sensing system, extracellular enzymes and polysaccharide production, as well as many other proved pathogenicity genes, while the AHD CDSs contain the genes encoding type IV secretion system (T4SS) and type III-effectors. A Xcc T4SS-deletion mutant displayed the same virulence as wild type. Furthermore, three avirulence genes (avrXccC, avrXccE1 and avrBs1) were identified. avrXccC and avrXccE1 conferred avirulence on the hosts mustard cultivar Guangtou and Chinese cabbage cultivar Zhongbai-83, respectively, and avrBs1 conferred hypersensitive response on the nonhost pepper ECW10R. About 80% of the Xcc CDSs, including 258 proved/presumed pathogenicity genes, is conserved in different strains. Xcc T4SS is not involved in pathogenicity. An efficient strategy to identify avr genes determining host specificity from the AHD genes was developed.


Methanogenic degradation of poly(3-hydroxyalkanoates).
Poly(3-hydroxybutyrate) and the copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) were fermented to methane and carbon dioxide within 16 days by an anaerobic sewage sludge consortium. The cultures adapted quickly to metabolize these polymeric compounds, and between 83 and 96% of the substrate carbon was transformed to methane and carbon dioxide.


Screening for HIV, hepatitis B and C infection in a population seeking assisted reproduction in an inner London hospital.
The Human Fertilisation and Embryology Authority requires all sperm donors to be screened for human immunodeficiency virus (HIV), hepatitis B and C and their semen quarantined for six months. No guidelines exist for screening prior to in vitro fertilisation or intracytoplasmic sperm injection. We prospectively analysed the prevalence of these viruses in our patients. Screening detected one case of HIV (0.13%), four of hepatitis C (0.5%) and 14 new cases of hepatitis B (1.7%). The prevalence of hepatitis B and HIV in our antenatal population at this time was 1.4% and 0.8%, respectively. Knowledge allows measures to be taken to reduce the risk of transmission to partner, fetus, new born baby, or by cross-contamination during embryo cryostorage and enables couples to make an informed decision regarding proceeding with treatment. Detection of infection in one partner should no longer preclude fertility treatment.


The IL-21 receptor augments Th2 effector function and alternative macrophage activation.
The IL-21 receptor (IL-21R) shows significant homology with the IL-4R, and CD4+ Th2 cells are an important source of IL-21. Here we examined whether the IL-21R regulates the development of Th2 responses in vivo. To do this, we infected IL-21R-/- mice with the Th2-inducing pathogens Schistosoma mansoni and Nippostrongylus brasiliensis and examined the influence of IL-21R deficiency on the development of Th2-dependent pathology. We showed that granulomatous inflammation and liver fibrosis were significantly reduced in S. mansoni-infected IL-21R-/- mice and in IL-21R+/+ mice treated with soluble IL-21R-Fc (sIL-21R-Fc). The impaired granulomatous response was also associated with a marked reduction in Th2 cytokine expression and function, as evidenced by the attenuated IL-4, IL-13, AMCase, Ym1, and FIZZ1 (also referred to as RELMalpha) responses in the tissues. A similarly impaired Th2 response was observed following N. brasiliensis infection. In vitro, IL-21 significantly augmented IL-4Ralpha and IL-13Ralpha1 expression in macrophages, resulting in increased FIZZ1 mRNA and arginase-1 activity following stimulation with IL-4 and IL-13. As such, these data identify the IL-21R as an important amplifier of alternative macrophage activation. Collectively, these results illustrate an essential function for the IL-21R in the development of pathogen-induced Th2 responses, which may have relevance in therapies for both inflammatory and chronic fibrotic diseases.


S-heterocyclic annelated perylene bisimide: synthesis and co-crystal with pyrene.
An S-heterocyclic annelated perylene bisimide (PBI) has been prepared from readily available tetrachloro-PBI by a one-step palladium-catalyzed reaction; when co-crystallized with pyrene it gives a unique columnar arrangement of 1 : 2 complexes.


Apomorphine effect on pain threshold in Parkinson's disease: a clinical and positron emission tomography study.
Patients with Parkinson's disease (PD) frequently experience pain that could be in part due to central modification of nociception. In this randomized controlled double blind study, we compared the effect of apomorphine versus placebo on pain thresholds and pain-induced cerebral activity in 25 patients with PD. Subjective pain threshold (using thermal stimulation, thermotest), objective pain threshold (nociceptive flexion reflex), and cerebral activity (H(2)(15)O PET) during noxious and innocuous stimulations were performed. Neither subjective nor objective pain thresholds nor pain activation profile were modified by apomorphine compared with placebo in 25 PD patients. Apomorphine has no effect on pain processing in PD. We suggest that other monoamine systems than dopaminergic system could be involved.


Epidemiology of listeriosis in Sweden 1958--1974.
In 1958--1974 altogether 110 cases of listeriosis were diagnosed in Sweden by culture. 64 cases were seen in children and adults. Of these, 52 had manifestations of meningoencephalitis and 10 of septicemia. Another 46 cases were seen in pregnant women and/or their neonates. Pregnancy ended in abortions in 8 cases and in stillborns in 3. Out of 37 neonates born alive, 22 had "early disease", mostly granulomatosis infantiseptica, and 8 had "late disease" with meningoencephalitis. The reported frequency of listeriosis in humans showed no correlation with that in animals. With the exception of pregnant women the incidence and mortality showed no difference with sex. Serotypes 1 and 4b prevailed and were equally common. The serotype did not vary with the clinical diagnosis or the outcome. There was no seasonal variation. Cases of all serotypes were uniformly distributed over the country in proportion to the density of its population. Occupational contact with animals was less common. Only in a few cases was there reason to suspect infection from animals. Co-existing disorders predisposed for the disease and often determined its outcome. Neonates with early onset of disease were infected by their mothers, while neonates with late onset of disease were infected from other and often nosocomial sources.


Development of a method for quantifying cognitive ability in the elderly through adaptive test administration.
The field of geriatric medicine has identified a need for an evaluative tool that can rapidly quantify global cognitive ability and accurately monitor change over time in patients with a wide range of impairments. We hypothesized that the development of an adaptive test approach to cognitive measurement would help to meet that need. This study aimed to provide evidence for the interpretability of scores obtained from a novel, adaptive approach to cognitive assessment, called the Geriatric Rapid Adaptive Cognitive Estimate (GRACE) method. An adaptive method for cognitive assessment was developed using data from 185 patients referred for geriatric cognitive assessment, and pilot tested in an additional 137 patients. Correlations between test scores and between rank orders of patients were computed to examine the reliability and validity of cognitive ability scores obtained by (1) administering test questions out of their usual order, (2) administering only a subset of questions, and (3) administering questions adaptively using simplified selection rules based on the most difficult question passed. Cognitive ability scores obtained with the GRACE method correlated highly with the Montreal Cognitive Assessment (MoCA) scores (r = 0.93) and ranked patients similarly in order of ability (r > 0.87). A simplified adaptive testing algorithm for pencil-and-paper assessment demonstrated moderately high correlations with scores obtained from administering the full set of MMSE and MoCA items as well as the MoCA items alone. Scores from the GRACE method can be obtained easily in 5-10 minutes, reducing test burden. The resulting numeric score quantifies cognitive ability, allowing clinicians to compare patients and monitor change in global cognition over time. The adaptive nature of this method allows for evaluation of persons across a broader range of cognitive ability levels than currently available tests.


Effect of Broussonetia papyrifera L. silage on blood biochemical parameters, growth performance, meat amino acids and fatty acids compositions in beef cattle.
The study was conducted to investigate the effects of Broussonetia papyrifera L.(B. papyrifera) silage on growth performance, serum biochemical parameters, meat quality, and meat amino acids and fatty acids compositions in beef cattle. Sixty-four male Angus beef cattle were assigned to 4 groups with 4 pens in each group and 4 beef cattle in each pen, and fed with the total mixed ration supplemented with 0%, 5%, 10%, or 15% B. papyrifera silage for 100 days (control group, 5% group, 10% group and 15% group) separately. Beef cattle had significantly higher final body weight (BW) in 15% group, higher average daily gain (ADG) and dry matter intake (DMI) in 5% group, 10% group and 15% group, and higher feed conversion ratio (FCR) in 10% group and 15% group. Significantly higher blood superoxide dismutase (SOD) concentration was noted in 15% group, higher blood total antioxidant capacity (TAC) in 10% group and 15% group, lower 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) in 15% group. Meat had lower pH in 15% group, higher Commission International DeI'Eclairage (CIE) L* in 5% group, 10% group, and 15% group, and lower drip loss in 15% group. Greater concentration of meat polyunsaturated fatty acids (PUFA) was observed in 10% group and 15% group, and docosahexaenoic acid (DHA) in 15% group. Diet with 15% B. papyrifera silage could improve performance and increase final BW, ADG, DMI, and FCR, enhance the antioxidant functions by decreasing blood 8-OHdG and MDA and increasing blood SOD and TAC, improve the meat quality by lowing pH and drip loss and increasing CIE L*, increase the meat PUFA and DHA concentration. Polyphenols and flavonoids might be the main components responsible for the antioxidant activity and anti-biohydrogenation in the B. papyrifera silage. And B. papyrifera silage could be used as a new feedstuff in beef cattle nutrition.


HIV screening in blood donors: rapid diagnostic test versus enhanced ELISA.
To compare the laboratory performance of a HIV antibody Rapid Diagnostic Test (RDT) [Determine HIV-1/2] with an Enhanced ELISA [GENSCREEN PLUS HIV Ag-Ab] used for HIV screening among blood donors in a hospital-based transfusion centre in North Central Nigeria. The serum of four hundred and forty (440) blood donors of both sexes aged between 18 and 55 years, who fulfilled the conditions to donate blood, were serially tested for HIV using both methods. DetermineTM HIV-1/2 detected 16 (3.6%) while GENSCREEN PLUS HIV Ag-Ab ELISA detected 41 (9.3%) blood donors who were HIV sero-positive. The DetermineTM HIV-1/2 missed 25 (61%) blood donors who were positive with the GENSCREENPLUS HIV Ag-Ab ELISA. The calculated sensitivity and specificity of Determine HIV-1/2 were 39.0% and 100% respectively while the positive predictive value and negative predictive values of Determine HIV-1/2 were 100% and 94.1% respectively. The HIV Antibody RDT (Determine HIV-1/2) has a very low sensitivity and therefore, inadequate in preventing transfusion transmissible HIV (TT-HIV) in a hospital-based blood transfusion service. The National Blood Transfusion Service (NBTS) in Nigeria should be equipped and supported to provide blood products screened with Enhanced ELISA as well as to embark on regular evaluation of all HIV screening assays used in the country in order to prevent counterfeit and sub standard assays and invariably reduce the risk of TT-HIV infection in the country.


Administration of the same dose of epoetin-beta intravenously and subcutaneously to patients with renal anaemia.
Subcutaneous (s.c.) administration of erythropoietin (EPO) is recommended over the intravenous (i.v.) route to reduce doses and costs. Optimal iron treatment is important for the optimal EPO effect. This study investigated whether the haemoglobin (Hb) level of a single patient could be preserved with the same dose of EPO given i.v. as given s.c. One-hundred and forty-five haemodialysis patients with the same weekly EPO dose s.c. for 3 months and a stable Hb (maximum fluctuation of 1 mmol/l) were randomized in a crossover study to group A (4 months i.v. then 4 months s.c. EPO) or group B (4 months s.c. then 4 months i.v. EPO, with unchanged EPO dose). Ferritin had to be 300-800 μg/l or transferrin saturation ≥ 20%. Patients with a fall in Hb >1 mmol/l were withdrawn. Ferritin and transferrin saturation remained within the target range, and mean Hb in the range of 1 mmol/l. Mean EPO doses were unchanged in both groups, and no difference was found between the dropouts due to Hb fall >1 mmol/l in the i.v. and s.c. groups during the first period of the trial. In iron-replete haemodialysis patients the same EPO dose given intravenously is just as effective as given subcutaneously.