Advancing the Measurement of Personal Intelligence with the Test of Personal Intelligence, Version 5 (TOPI 5).
People use their personal intelligence (PI) to understand personality in themselves and others. In Studies 1 and 2 (Ns = 961 and 548), individuals completed the Test of Personal Intelligence, Version 5 (TOPI 5), which is introduced here. The TOPI 5 is an ability assessment with a broader range of content and more challenging items than earlier test versions. In past research, factor analyses indicated that people employ two distinct but highly correlated abilities to problem-solve in this area. These two-factor models, however, exhibited instabilities and limited applicability between the TOPI 4 and 5 in this research (and as reported in the Supplementary Materials). In Study 3, we successfully test the one-factor models of the TOPI with the present data and archival data sets (Narchival = 19,627). We then use the one-factor models to develop a pair of new test forms: one that is compatible with all the TOPI test versions and another, TOPI 5E, that is better at distinguishing among people scoring in the higher range of performance relative to previous measures.


Exploring or avoiding novel food resources? The novelty conflict in an invasive bird.
For an animal invading a novel region, the ability to develop new behaviors should facilitate the use of novel food resources and hence increase its survival in the new environment. However, the need to explore new resources may entail costs such as exposing the animal to unfamiliar predators. These two opposing forces result in an exploration-avoidance conflict, which can be expected to interfere with the acquisition of new resources. However, its consequences should be less dramatic in highly urbanized environments where new food opportunities are common and predation risk is low. We tested this hypothesis experimentally by presenting three foraging tasks to introduced common mynas (Acridotheres tristis) from environments with low and high urbanization levels from Australia. Individuals from the highly urbanized environments, where mynas are both more opportunistic when foraging and less fearful to predators, resolved a technical task faster than those from less urbanized environments. These differences did not reflect innovative 'personalities' and were not confounded by sex, morphology or motivational state. Rather, the principal factors underlying differences in mynas' problem-solving ability were neophobic-neophilic responses, which varied across habitats. Thus, mynas seem to modulate their problem-solving ability according to the benefits and costs of innovating in their particular habitat, which may help us understand the great success of the species in highly urbanized environments.


Derivation of induced pluripotent stem cells in Japanese macaque (Macaca fuscata).
Non-human primates are our closest relatives and are of special interest for ecological, evolutionary and biomedical research. The Japanese macaque (Macaca fuscata) has contributed to the progress of primatology and neurosciences over 60 years. Despite this importance, the molecular and cellular basis of the Japanese macaque remains unexplored since useful cellular tools are lacking. Here we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of the Japanese macaque with Sendai virus or plasmid vectors. The Japanese macaque iPSCs (jm-iPSCs) were established under feeder-free culture conditions, but feeder cells turned out to be essential for their maintenance. The jm-iPSCs formed human iPSC-like flat colonies which were positive for pluripotent antigens including alkaline phosphatase, SSEA4, and TRA-1-81. They also expressed endogenous OCT3/4, SOX2, L-MYC, and KLF4 and other pluripotent marker genes. The potential to differentiate into all three germ layers and neural stem cells was confirmed by embryoid body and neurosphere formation, respectively. The jm-iPSCs will provide a robust in vitro tool for investigating the underlying mechanisms of development and physiology studies with the Japanese macaque.


Serum type I and type III procollagen peptide levels in sarcoidosis.
Type I and type III are the most abundant collagens in the lung. The aim of our study was to compare type I and III procollagen peptides in sera of sarcoid patients. Sixty eight patients with sarcoidosis were studied (19 with newly recognized disease, 7 with relapsing disease, 15 with chronic disease, and 27 in stable remission). Thirty healthy volunteers served as controls. The levels of procollagen I and III peptides were determined by radioimmunoassay. Angiotensin-converting enzyme (ACE) level was evaluated by means of a colorimetric assay. In patients with newly recognized sarcoidosis, both serum procollagen I and III peptide levels were increased with respect to controls (p=0.0014 and p<0.00001, respectively). There was a poor correlation between levels of procollagen I and III (r=0.26), whereas there was a closer correlation between procollagen III and ACE (r=0.69). Procollagen I peptide level did not identify patients in roentgenological stage III. In conclusion, in patients with newly recognized sarcoidosis there is a significant increase in the serum level of procollagen I peptide. However, procollagen I peptide is not a marker of sarcoid patients with fibrosis, ie. stage III disease. Its clinical usefulness seems to be weaker than that of procollagen III peptide.


Partitioning of regulatory sites in Bufo marinus during hypercapnia.
Ureters were cannulated in specimens of Bufo marinus (L.) in order to partition the regulatory contributions of the kidney and skin. The in vivo roles of the kidney, skin and internal calcareous deposits in the response of these animals to chronic hypercapnia were then evaluated. There was no compensatory adjustment by the skin and only a minimal regulatory response by the kidney. Major adjustments which have been attributed to combined skin and urinary tract in previous studies must therefore come from the urinary bladder. Removal of the bladder as a regulatory site in these animals completely eliminated the compensatory elevation of HCO3- in the extracellular fluid. Mobilization of internal calcareous deposits as a source of HCO3- was found to contribute 50% of the compensatory response of these animals during hypercapnia.


Hatching asynchrony aggravates inbreeding depression in a songbird (Serinus canaria): an inbreeding-environment interaction.
Understanding how the intensity of inbreeding depression is influenced by stressful environmental conditions is an important area of enquiry in various fields of biology. In birds, environmental stress during early development is often related to hatching asynchrony; differences in age, and thus size, impose a gradient in conditions ranging from benign (first hatched chick) to harsh (last hatched chick). Here, we compared the effect of hatching order on growth rate in inbred (parents are full siblings) and outbred (parents are unrelated) canary chicks (Serinus canaria). We found that inbreeding depression was more severe under more stressful conditions, being most evident in later hatched chicks. Thus, consideration of inbreeding-environment interactions is of vital importance for our understanding of the biological significance of inbreeding depression and hatching asynchrony. The latter is particularly relevant given that hatching asynchrony is a widespread phenomenon, occurring in many bird species. The exact causes of the observed inbreeding-environment interaction are as yet unknown, but may be related to a decrease in maternal investment in egg contents with laying position (i.e. prehatching environment), or to performance of the chicks during sibling competition and/or their resilience to food shortage (i.e. posthatching environment).


Expression of B cell markers on SR-4987 cells derived from murine bone marrow stroma.
The murine cell line SR-4987 was originated in our laboratory from adherent cells of a long term bone marrow culture. SR-4987 cells do not express p21-ras and c-fms products on membrane whereas secrete M-CSF, evidence a fibroblast-like morphology and are vimentine positive. This line shows a very poor "in vitro" agar clonogenicity which is not modulated by the addition of different cytokines and growth factors (M-CSF, GM-CSF, G-CSF, IL-3, IL-7, alpha-TNF, PDGF, and EGF). On the contrary, a dramatic increase in clonogenicity is observed in the presence of bFGF. The RT-PCR investigation evidences the mRNA encoding for bFGF, IL-7, GM-CSF, and SCF (c-kit ligand). The analysis of CD antigen expression on SR-4987 cell membrane indicates a phenotype (CD5+, CD44+, 45R(B220)+, sIg+, 5'-nucleotidase+) that is consistent with a B cell feature. Our observations suggest that exogenous bFGF might represent an appropriate stimulus for inducing the SR-4987 cells proliferation also in the absence of cell-substrate anchorage. Further, they indicate that SR-4987 cells could represent a particular differentiation stage in which characters of "stromal cell" and "B cell" are coexpressed in agreement with the hypothesis of a common stromal-hematopoietic differentiation.


[Early stages of atherosclerosis. The morphogenesis of lipid spots in the aorta of children].
A comprehensive morphobiochemical study of aortal lipoidosis and a study of the serum lipid content were conducted in children. Fifty aortas from children who had died as a result of accidents and diseases at the age of 4 to 16 and the blood serum from 350 healthy children served as the material for the investigation. The development of aortal lipid spots in children was shown to be associated with lipid accumulation, particularly cholesterin ethers in smooth muscle cells of the intima. Lipid accumulation was accompanied by the proliferation of smooth muscle cells, phenomena of enhanced collagen- and elastin formation in parallel with the destruction of elastic fibers and membranes expressed quantitatively in an increased content of collagen and a decreased content of elastin. Aortal lipid spots were inhomogeneous depending on children age. "Juvenile" and "intermediate" types were singled out. Lipid spots of the "intermediate" type found in children over 10 may be of certain importance in the development of atherosclerotic arterial changes. There was no correlation between the frequency of hypercholesterinemia and the frequency of aortal lipoidosis in children.


Transfusion practice in patients receiving VV ECMO (PROTECMO): a prospective, multicentre, observational study.
In patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO) packed red blood cell (PRBC) transfusion thresholds are usually higher than in other patients who are critically ill. Available guidelines suggest a restrictive approach, but do not provide specific recommendations on the topic. The main aim of this study was, in a short timeframe, to describe the actual values of haemoglobin and the rate and the thresholds for transfusion of PRBC during VV ECMO. PROTECMO was a multicentre, prospective, cohort study done in 41 ECMO centres in Europe, North America, Asia, and Australia. Consecutive adult patients with acute respiratory distress syndrome (ARDS) who were receiving VV ECMO were eligible for inclusion. Patients younger than 18 years, those who were not able to provide informed consent when required, and patients with an ECMO stay of less than 24 h were excluded. Our main aim was to monitor the daily haemoglobin concentration and the value at the point of PRBC transfusion, as well as the rate of transfusions. The practice in different centres was stratified by continent location and case volume per year. Adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for baseline and time varying confounding. Between Dec 1, 2018, and Feb 22, 2021, 604 patients were enrolled (431 [71%] men, 173 [29%] women; mean age 50 years [SD 13·6]; and mean haemoglobin concentration at cannulation 10·9 g/dL [2·4]). Over 7944 ECMO days, mean haemoglobin concentration was 9·1 g/dL (1·2), with lower concentrations in North America and high-volume centres. PRBC were transfused on 2432 (31%) of days on ECMO, and 504 (83%) patients received at least one PRBC unit. Overall, mean pretransfusion haemoglobin concentration was 8·1 g/dL (1·1), but varied according to the clinical rationale for transfusion. In a time-dependent Cox model, haemoglobin concentration of less than 7 g/dL was consistently associated with higher risk of death in the intensive care unit compared with other higher haemoglobin concentrations (hazard ratio [HR] 2·99 [95% CI 1·95-4·60]); PRBC transfusion was associated with lower risk of death only when transfused when haemoglobin concentration was less than 7 g/dL (HR 0·15 [0·03-0·74]), although no significant effect in reducing mortality was reported for transfusions for other haemoglobin classes (7·0-7·9 g/dL, 8·0-9·9 g/dL, or higher than 10 g/dL). During VV ECMO, there was no universally accepted threshold for transfusion, but PRBC transfusion was invariably associated with lower mortality only when done with haemoglobin concentration of less than 7 g/dL. Extracorporeal Life Support Organization.


Vigorous physical activity increases fracture risk in children irrespective of bone mass: a prospective study of the independent risk factors for fractures in healthy children.
Low bone mass is a determinant of fractures in healthy children. Small studies provide limited evidence on the association between ethnicity, birth weight, family size, socioeconomic status, dietary calcium intake, or physical activity and fracture incidence. No studies have investigated whether these determinants of fracture risk act through affecting bone mass or through other mechanisms. The aim of this study was to use a population-based birth cohort to confirm which variables are determinants of fracture risk and to further study which of these risk factors act independently of bone mass. Children from the Avon Longitudinal Study of Parents and Children have been followed up from birth to 11 yr of age. Maternal self-reported data have been collected contemporaneously on early life factors, diet, puberty, and physical activity. These were linked to reported fractures between 9 and 11 yr of age. Multivariable logistic regression techniques were used to assess whether these potential determinants were independent of, or worked through, estimated volumetric BMD or estimated bone size relative to body size measured by total body DXA scan at 9.9 yr of age. A total of 2692 children had full data. One hundred ninety-three (7.2%) reported at least one fracture over the 2-yr follow-up period. Children who reported daily or more episodes of vigorous physical activity had double the fracture risk compared with those children who reported less than four episodes per week (OR, 2.06; 95% CI, 1.21-1.76). No other independent determinants of fracture risk in healthy children were found. In conclusion, reported vigorous physical activity is an independent risk factor for childhood fracture risk. However, the interrelationship between physical activity, bone mass, and childhood fracture risk suggests that the higher bone mass associated with increased physical activity does not compensate for the risk caused by increased exposure to injuries.


Obstetric complications of placenta previa percreta.
Placenta previa is related to severe maternal and fetal morbidity. The increasing incidence of cesarean delivery rate causes a marked increase in abnormally invasive placenta over the past decades. The abnormally invasive placenta is becoming the foremost cause of obstetric hemorrhage and postpartum hysterectomy, causing a significant maternal and fetal morbidity and even mortality. Maternal morbidity in such cases also comprise politransfusion, development of disseminated intravascular coagulation, uterine rupture, cystostomy, fistula formation, ureteral stricture, intensive care unit admission, infection, and prolonged hos- pitalization, adult respiratory distress syndrome, renal failure, septicemia and even death. A 38-year-old gravida 3, para 2, was admitted to our hospital at 27 weeks of gestation as an emergency due to vaginal bleeding, previously diagnosed with an anterior placenta previa. Following tocolytic therapy, bleeding stopped. The patient was informed on the diagnosis and the possibility of life-threatening hemorrhage necessitating preterm delivery. She was given corticosteroids to enhance fetal lung maturity. At 28 weeks of gestation, she experienced massive vaginal bleeding, and a decision was made to perform emergency cesarean section. We made a corporeal transverse uterine incision well above the uterovesical fold and tortuous vessels, at the same time avoiding the superior edge of the placenta. The placenta was found to be densely adherent to the lower uterine segment, penetrating through it and infiltrating the posterior wall of the urinary bladder. An attempt to remove the placenta resulted in injury to the bladder wall and the uterine rupture at a previous cesarean scar. The decision was made to perform total abdominal hysterectomy with placenta left in situ. At present, both mother and the baby are well. Anticipation and the surgeon's judgment are leading factors for surgery, from the choice of uterine incision type to the decision to proceeding to hysterectomy in order to reduce maternal morbidity.


Post-harvest proteomics and food security.
To guarantee sufficient food supply for a growing world population, efforts towards improving crop yield and plant resistance should be complemented with efforts to reduce post-harvest losses. Post-harvest losses are substantial and occur at different stages of the food chain in developed and developing countries. In recent years, a substantially increasing interest can be seen in the application of proteomics to understand post-harvest events. In the near future post-harvest proteomics will be poised to move from fundamental research to aiding the reduction of food losses. Proteomics research can help in reducing food losses through (i) identification and validation of gene products associated to specific quality traits supporting marker-assisted crop improvement programmes, (ii) delivering markers of initial quality that allow optimisation of distribution conditions and prediction of remaining shelf-life for decision support systems and (iii) delivering early detection tools of physiological or pathogen-related post-harvest problems. In this manuscript, recent proteomics studies on post-harvest and stress physiology are reviewed and discussed. Perspectives on future directions of post-harvest proteomics studies aiming to reduce food losses are presented.


Uniform diffracted fields from a perfectly conducting cylindrical reflector with modified theory of physical optics.
The uniform diffracted fields are calculated on PEC cylindrical reflector by Modified Theory of Physical Optics (MTPO). It is aimed to convert the noncontinuous solution to a continuous solution by finding a uniform equation which does not contain any expression converging to 0 in the denominator part. Three axioms of MTPO theory are used to construct the integral equations for the perfectly electrically conducting surface application. The "edge-point" technique is used to find the diffracted field, and uniform solution is to be found via "detour parameter(s)." Finally, the obtained results are to be compared with the nonuniform ones, numerically.


Oral cancer risk and molecular markers.
The clinical appearance and, especially, the degree of dysplasia that may be shown by pre-cancerous lesions in the oral cavity suggest a potential for malignisation. An increasing number of studies are seeking new, more specific markers that would help to determine the degree of cell alteration and enable a better understanding of the degree of malignant degeneration of these cells. The present review considers the most recent findings for these markers, grouping them into families: tumour growth markers; markers of tumour suppression and anti-tumour response; angiogenesis markers; markers of tumour invasion and metastatic potential; cell surface markers; intracellular markers; markers derived from arachidonic acid; and enzymatic markers.


Reducing ICU costs with computerized tools.
A significant opportunity for cost savings in health care lies in managing ICU utilization. Computerized tools that collect data about patient severity of illness, monitor ICU utilization, and track patient outcomes have the potential to help hospitals lower costs by changing practice patterns and treating patients in appropriate, less-expensive settings.


Plasmodium falciparum: sensitivity in vivo to chloroquine, pyrimethamine/sulfadoxine and mefloquine in western Myanmar.
In Rakhine State, on the western border of Myanmar, the efficacy of chloroquine (CQ) and pyrimethamine/ sulfadoxine (PS), the current treatments for uncomplicated Plasmodium falciparum malaria in this area, was evaluated in an open comparative study of 289 patients, stratified prospectively into 3 age groups. Chloroquine treatment was associated with more rapid clinical recovery (P = 0.03), but the overall cure rates were worse than for PS treatment; failure to clear parasitaemia or recrudescence within 14 d occurred in 72% (102/141) of cases treated with CQ compared to 47% (69/148) of those who received PS (P < 0.0001, adjusted for age). Failure rates at day 28 increased to 82% (116/141) in the CQ group and 67% (99/148) in the PS group (P = 0.003). The risk of treatment failure was significantly higher in children under 15 years old than in adults for both CQ (relative risk [RR] = 2.6; 95% confidence interval [95% CI] 1.3-5.2) and PS (RR = 2.2; 95% CI 1.4-3.3). Mefloquine (15 mg base/kg) proved to be highly effective as a treatment for CQ and PS resistant P. falciparum; only 2 of 75 patients (3%) had early treatment failures (< or = day 7), and the overall failure rate by day 42 was 7%. There is a very high level of chloroquine and PS resistance in P.falciparum on the western border of Myanmar, but mefloquine was effective in the area.


Safety and Efficacy of Powered Non-Thermal Endoscopic Resection Device for Removal of Colonic Polyps: A Systematic Review and Meta-Analysis.
Endoscopic mucosal resection is a frequently employed method for removing colonic polyps. Nonetheless, the recurrence of these polyps over a healed submucosal base can complicate the extraction of leftover lesions through standard procedures. EndoRotor®, a non-thermal device specifically designed for endoscopic mucosal resection, has recently been assessed for its utility in removing colonic polyps, non-dysplastic Barrett's esophagus, and pancreatic necrosis. We conducted a systematic review and meta-analysis to ascertain the safety and efficacy of EndoRotor® in resecting scared or recurrence colonic polyps. We conducted an exhaustive review of existing literature using databases such as Medline, Embase, Web of Science, and the Cochrane Library until January 2023. Our aim was to find all studies that assessed the safety of non-thermal endoscopic resection devices in removing colonic polyps. The primary outcome we focused on was the rate of technical success. Secondary outcomes that we considered included the frequency of remaining lesions and instances of adverse events. To analyze these data, we used comprehensive meta-analysis software. Our analysis incorporated three studies comprising 54 patients who underwent resection of 60 lesions. The combined technical success rate was 93.9% (95% confidence interval (CI): 77.7-98.6%, I2 = 25.5%). In patients who had another endoscopic examination, 20 were found to have a residual lesion. After the initial session, the combined rate of remaining lesions was 39.8% (95% CI: 15.3-70.8%, I2 = 74.5%). There were eight occurrences of intraoperative bleeding and four instances of bleeding post-procedure. The combined rate of intraoperative bleeding was 13.2% (95% CI: 6.7-24.3%, I2 = 0%), and post-procedure bleeding stood at 8.5% (95% CI: 3.4-19.8%, I2 = 0%). Only one major bleeding event was recorded, and no cases of perforation were reported. Our research indicates that the EndoRotor® effectively removes scarred colonic polyps, though the rate of remaining lesions is significant, potentially necessitating several sessions for a thorough removal. There is a need for broader prospective studies, mainly randomized controlled trials, to further assess EndoRotor®'s efficiency and safety in eliminating colonic polyps.


Osmotic pressure and aqueous humor formation in dogfish.
Comparative chemical analyses show the aqueous humor of smooth dogfish has lower concentrations of urea and trimethylamine oxide than the blood plasma. Freezing-point depression determinations demonstrate that the aqueous humor has a correspondingly lower osmotic pressure. It would appear that water entering the aqueous humor from the plasma is moving against an osmotic gradient.


Anomalous Trends in Nucleic Acid-Based Electrochemical Biosensors with Nanoporous Gold Electrodes.
Molecular diagnostics have significantly advanced the early detection of diseases, where electrochemical sensing of biomarkers has shown considerable promise. For a nucleic acid-based electrochemical sensor with signal-off behavior, the performance is evaluated by percent signal suppression (% ss), which indicates the change in current after hybridization. The % ss is generally due to more redox molecules (e.g., methylene blue) associating with the probe DNA bases in the single-strand form than the double-strand form upon hybridization with the target nucleic acid. Nanostructured electrodes generally enhance electrochemical sensor performance via several mechanisms, including increased number of capture probes per electrode volume and unique nanoscale transport phenomena. Here, we employ nanoporous gold (np-Au) as a model electrode material to study the influence of probe immobilization solution concentration on sensor performance and the underlying mechanisms. Unlike planar gold (pl-Au) electrodes, where % ss reaches a steady state with increasing concentration of the grafting solution, the % ss displays peak performance at certain grafting solution concentrations followed by rapid deterioration and reversal of the % ss polarity, suggesting an unexpected case of increased charge transfer upon hybridization. Fluorometric assessments of electrochemically desorbed nucleic acids for different electrode morphologies reveal that a significant amount of DNA molecules (unhybridized and hybridized) remain within the nanopores posthybridization. Analysis of electrochemical signals (e.g., square wave voltammogram shape) suggests that the large unbound nucleic acid concentration may be altering the modes of methylene blue interaction with the nucleic acids and charge transfer to the electrode surfaces.


SARS-COV-2 Delta variant displays moderate resistance to neutralizing antibodies and spike protein properties of higher soluble ACE2 sensitivity, enhanced cleavage and fusogenic activity.
The SARS-CoV-2 B.1.617 lineage variants, Kappa (B.1.617.1) and Delta (B.1.617.2, AY) emerged during the second wave of infections in India, but the Delta variants have become dominant worldwide and continue to evolve. The spike proteins of B.1.617.1, B.1.617.2, and AY.1 variants have several substitutions in the receptor binding domain (RBD), including L452R+E484Q, L452R+T478K, and K417N+L452R+T478K, respectively, that could potentially reduce effectiveness of therapeutic antibodies and current vaccines. Here we compared B.1.617 variants, and their single and double RBD substitutions for resistance to neutralization by convalescent sera, mRNA vaccine-elicited sera, and therapeutic neutralizing antibodies using a pseudovirus neutralization assay. Pseudoviruses with the B.1.617.1, B.1.617.2, and AY.1 spike showed a modest 1.5 to 4.4-fold reduction in neutralization titer by convalescent sera and vaccine-elicited sera. In comparison, similar modest reductions were also observed for pseudoviruses with C.37, P.1, R.1, and B.1.526 spikes, but seven- and sixteen-fold reduction for vaccine-elicited and convalescent sera, respectively, was seen for pseudoviruses with the B.1.351 spike. Four of twenty-three therapeutic neutralizing antibodies showed either complete or partial loss of neutralization against B.1.617.2 pseudoviruses due to the L452R substitution, whereas six of twenty-three therapeutic neutralizing antibodies showed either complete or partial loss of neutralization against B.1.617.1 pseudoviruses due to either the E484Q or L452R substitution. Against AY.1 pseudoviruses, the L452R and K417N substitutions accounted for the loss of neutralization by four antibodies and one antibody, respectively, whereas one antibody lost potency that could not be fully accounted for by a single RBD substitution. The modest resistance of B.1.617 variants to vaccine-elicited sera suggest that current mRNA-based vaccines will likely remain effective in protecting against B.1.617 variants, but the therapeutic antibodies need to be carefully selected based on their resistance profiles. Finally, the spike proteins of B.1.617 variants are more efficiently cleaved due to the P681R substitution, and the spike of Delta variants exhibited greater sensitivity to soluble ACE2 neutralization, as well as fusogenic activity, which may contribute to enhanced spread of Delta variants.


[Recent progress of international harmonization of crude drugs and medicinal plants--activity of FHH (The Western Pacific Regional Forum for the Harmonization of Herbal Medicines)].
The Western Pacific Regional Forum for the Harmonization of Herbal Medicines (FHH) was established in 2002. The general proposed objective of the FHH is to promote public health by recognizing and developing standards and technical guidelines that aim to improve the quality, safety and efficacy of herbal medicines. At a sub-committee meeting of FHH nomenclature and standardization held in Tokyo, all the participants recognized the importance of comparing the descriptions of herbal medicines contained in member countries' pharmacopoeias or monograph standards as the first step in the harmonization of nomenclature and standardization. It was agreed to set up five expert working groups (EWG) to carry out the following specific tasks: 1) Nomenclature, 2) Testing Methods in Monographs, 3) List of Chemical Reference Standards (CRS) and Reference of Medicinal Plant Materials (RMPM), 4) List of Analytically Validated Methods, and 5) Information on General Tests. In this review, we report four topics of FHH activities from 2002-2009 as follows: 1) Comparative study on testing methods and specification values for crude drugs used in monographs among four Western Pacific regional countries (Japan, China, Korea and Vietnam), 2) Comparative study on TLC conditions for identification, chemical assay conditions for component quantification used in monographs among the four countries, 3) Comparative study on general testing methods for crude drugs among the four countries, 4) Comparative study on TLC identification for crude drugs used in monographs among the four countries considering harmonization and clean analysis.


Pilot study of the association of the DDAH2 -449G polymorphism with asymmetric dimethylarginine and hemodynamic shock in pediatric sepsis.
Genetic variability in the regulation of the nitric oxide (NO) pathway may influence hemodynamic changes in pediatric sepsis. We sought to determine whether functional polymorphisms in DDAH2, which metabolizes the NO synthase inhibitor asymmetric dimethylarginine (ADMA), are associated with susceptibility to sepsis, plasma ADMA, distinct hemodynamic states, and vasopressor requirements in pediatric septic shock. In a prospective study, blood and buccal swabs were obtained from 82 patients ≤ 18 years (29 with severe sepsis/septic shock plus 27 febrile and 26 healthy controls). Plasma ADMA was measured using tandem mass spectrometry. DDAH2 gene was partially sequenced to determine the -871 6g/7 g insertion/deletion and -449G/C single nucleotide polymorphisms. Shock type ("warm" versus "cold") was characterized by clinical assessment. The -871 7g allele was more common in septic (17%) then febrile (4%) and healthy (8%) patients, though this was not significant after controlling for sex and race (p = 0.96). ADMA did not differ between -871 6g/7 g genotypes. While genotype frequencies also did not vary between groups for the -449G/C SNP (p = 0.75), septic patients with at least one -449G allele had lower ADMA (median, IQR 0.36, 0.30-0.41 µmol/L) than patients with the -449CC genotype (0.55, 0.49-0.64 µmol/L, p = 0.008) and exhibited a higher incidence of "cold" shock (45% versus 0%, p = 0.01). However, after controlling for race, the association with shock type became non-significant (p = 0.32). Neither polymorphism was associated with inotrope score or vasoactive infusion duration. The -449G polymorphism in the DDAH2 gene was associated with both low plasma ADMA and an increased likelihood of presenting with "cold" shock in pediatric sepsis, but not with vasopressor requirement. Race, however, was an important confounder. These results support and justify the need for larger studies in racially homogenous populations to further examine whether genotypic differences in NO metabolism contribute to phenotypic variability in sepsis pathophysiology.


Event-related dynamics of glutamate and BOLD effects measured using functional magnetic resonance spectroscopy (fMRS) at 3T in a repetition suppression paradigm.
Proton MR spectroscopy ((1)H-MRS) complements other brain research methods by providing measures of neurometabolites noninvasively in a localized brain area. Improvements in MR scanner technologies, and data acquisition and analysis methods should allow functional (1)H-MRS (fMRS) to measure neurometabolite concentration changes during task-induced brain activation. The aim of the current study was to further develop event-related fMRS at 3T to investigate glutamate dynamics in response to repetition suppression. A secondary aim was to investigate the relationship between blood-oxygen-level-dependent (BOLD) responses and glutamate dynamics in the same paradigm at the same time. A novel approach of interleaved water-suppressed (metabolite) and unsuppressed (water) fMRS was used to simultaneously detect the event-related dynamics of glutamate and BOLD signal to repetition suppression in the lateral occipital cortex of thirteen (N=13) volunteers. On average, (1)H-MRS-visible glutamate increased after novel visual stimuli presentations by 12% and decreased by 11-13% on repeated compared to novel presentations. The BOLD signal, as measured by water peak amplitude changes, showed significant difference between Task and Rest trials, and, on a GLM based analysis of the time series, demonstrated a significant difference between the novel and repeated trials, however appeared to be decoupled from the glutamate response as no correlation was found between the two. These results are the first demonstration that reductions in neuronal activity typical of repetition suppression effects are reflected by reduced glutamatergic and BOLD measures, that glutamate and BOLD responses may not be coupled as previously thought, and that these changes and relationships can be measured simultaneously using event-related fMRS at 3T.


Clinical challenges in the psychopharmacology of schizophrenia.
Better pharmacological treatments for schizophrenia have elevated the expectations of patients and families and allow a wider range of therapeutic options for clinicians. At the same time, the treatment of schizophrenia has become more complex, and clinical decisions must often be made in the absence of unambiguous empirical guidelines. Under these circumstances, good patient care is based on clinical judgement informed by available clinical research. This issue of the Schizophrenia Bulletin reviews research in areas that represent major clinical challenges in the psychopharmacology of schizophrenia.


Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer's disease-like neuroinflammation and cognitive impairment.
Human genetic association studies point to immune response and lipid metabolism, in addition to amyloid-beta (Aβ) and tau, as major pathways in Alzheimer's disease (AD) etiology. Accumulating evidence suggests that chronic neuroinflammation, mainly mediated by microglia and astrocytes, plays a causative role in neurodegeneration in AD. Our group and others have reported early and dramatic losses of brain sulfatide in AD cases and animal models that are mediated by ApoE in an isoform-dependent manner and accelerated by Aβ accumulation. To date, it remains unclear if changes in specific brain lipids are sufficient to drive AD-related pathology. To study the consequences of CNS sulfatide deficiency and gain insights into the underlying mechanisms, we developed a novel mouse model of adult-onset myelin sulfatide deficiency, i.e., tamoxifen-inducible myelinating glia-specific cerebroside sulfotransferase (CST) conditional knockout mice (CSTfl/fl/Plp1-CreERT), took advantage of constitutive CST knockout mice (CST-/-), and generated CST/ApoE double knockout mice (CST-/-/ApoE-/-), and assessed these mice using a broad range of methodologies including lipidomics, RNA profiling, behavioral testing, PLX3397-mediated microglia depletion, mass spectrometry (MS) imaging, immunofluorescence, electron microscopy, and Western blot. We found that mild central nervous system (CNS) sulfatide losses within myelinating cells are sufficient to activate disease-associated microglia and astrocytes, and to increase the expression of AD risk genes (e.g., Apoe, Trem2, Cd33, and Mmp12), as well as previously established causal regulators of the immune/microglia network in late-onset AD (e.g., Tyrobp, Dock, and Fcerg1), leading to chronic AD-like neuroinflammation and mild cognitive impairment. Notably, neuroinflammation and mild cognitive impairment showed gender differences, being more pronounced in females than males. Subsequent mechanistic studies demonstrated that although CNS sulfatide losses led to ApoE upregulation, genetically-induced myelin sulfatide deficiency led to neuroinflammation independently of ApoE. These results, together with our previous studies (sulfatide deficiency in the context of AD is mediated by ApoE and accelerated by Aβ accumulation) placed both Aβ and ApoE upstream of sulfatide deficiency-induced neuroinflammation, and suggested a positive feedback loop where sulfatide losses may be amplified by increased ApoE expression. We also demonstrated that CNS sulfatide deficiency-induced astrogliosis and ApoE upregulation are not secondary to microgliosis, and that astrogliosis and microgliosis seem to be driven by activation of STAT3 and PU.1/Spi1 transcription factors, respectively. Our results strongly suggest that sulfatide deficiency is an important contributor and driver of neuroinflammation and mild cognitive impairment in AD pathology.


Shear bond strength of composite bonded with three adhesives to Er,Cr:YSGG laser-prepared enamel.
To assess in vitro the shear bond strength of a nanohybrid composite resin bonded with three adhesive systems to enamel surfaces prepared with acid and Er,Cr:YSGG laser etching. Sixty extracted caries- and restoration-free human maxillary central incisors were used. The teeth were sectioned 2 mm below the cementoenamel junction. The crowns were embedded in autopolymerizing acrylic resin with the labial surfaces facing up. The labial surfaces were prepared with 0.5-mm reduction to receive composite veneers. Thirty specimens were etched with Er,Cr:YSGG laser. This group was also divided into three subgroups, and the following three bonding systems were then applied on the laser groups and the other three unlased groups: (1) 37% phosphoric acid etch + Bond 1 primer/adhesive (Pentron); (2) Nano-bond self-etch primer (Pentron) + Nano-bond adhesive (Pentron); and (3) all-in-one adhesive-single dose (Futurabond NR, Voco). All of the groups were restored with a nanohybrid composite resin (Smile, Pentron). Shear bond strength was measured with a Zwick universal test device with a knife-edge loading head. The data were analyzed with two-factor ANOVA. There were no significant differences in shear bond strength between self-etch primer + adhesive and all-in-one adhesive systems for nonetched and laser-etched enamel groups (P > .05). However, bond strength values for the laser-etched + Bond 1 primer/adhesive group (48.00 +/- 13.86 MPa) were significantly higher than the 37% phosphoric acid + Bond 1 primer/adhesive group (38.95 +/- 20.07 MPa) (P < .05). The Er,Cr:YSGG laser-powered hydrokinetic system etched the enamel surface more effectively than 37% phosphoric acid for subsequent attachment of composite material.


Acute myocardial infarction.
Modern management of acute myocardial infarction is built on a clinical evidence base drawn from many studies undertaken over the past three decades. The evolution in clinical practice has substantially reduced mortality and morbidity associated with the condition. Key to this success is the effective integration of antithrombotic therapy combined with timely reperfusion, either primary percutaneous coronary intervention or fibrinolysis for ST-elevation myocardial infarction, and invasive investigation and revascularisation for non-ST-elevation myocardial infarction, underpinned by risk stratification and optimised systems of care. After the development of troponin assays for the detection of myonecrosis, the universal definition and classification of myocardial infarction now indicates the underlying pathophysiology. Additionally, an increasing appreciation of the importance of adverse events, such as bleeding, has emerged. Remaining challenges include the effective translation of this evidence to all patients with myocardial infarction, especially to those not well represented in clinical trials who remain at increased risk of adverse events, such as elderly patients and those with renal failure. On a global level, the epidemic of diabetes and obesity in the developed world and the transition from infectious diseases to cardiovascular disease in the developing world will place an increasing demand on health-care infrastructures required to deliver time-dependent and resource-intensive care. This Seminar discusses the underlying pathophysiology, evolving perspectives on diagnosis, risk stratification, and the invasive and pharmacological management of myocardial infarction.


Chitosan exerts anticancer activity through induction of apoptosis and cell cycle arrest in oral cancer cells.
Chitosan, a multipurpose biomaterial, has been shown to exert effects against several types of cancer including oral cancer. However, the mechanisms underlying the anticancer activities of chitosan on oral squamous cell carcinoma (SCC) cells remain largely unknown. The present study aimed to compare the effects of low-molecular-weight chitosan (LMWC) and cisplatin on oral SCC Ca9-22 and non-cancer keratinocyte HaCaT cell lines. Cell viability and cell cycle profiles were measured by MTT assay and laser scanning cytometry, respectively. Apoptosis was examined by TUNEL assay and electron microscopy, followed by analysis of caspase activity. LMWC exhibited cytotoxic effects on Ca9-22, but not HaCaT cells, whereas cisplatin induced apoptosis in both types of cells. Exposure of Ca9-22 cells to LMWC led to G1/S cell cycle arrest and an increase of TUNEL-positive cells accompanied by an early apoptotic cell morphology and subtle increases of caspase activity. Short-term LMWC exposure was less cytotoxic to HaCaT cells than to Ca9-22 cells, and anticancer activity was exerted through induction of apoptosis and cell cycle arrest, suggesting that LMWC could be a promising natural anticancer agent with fewer side effects on normal cells.


DECA: A Discrete-Valued Data Clustering Algorithm.
This paper presents a new clustering algorithm for analyzing unordered discrete-valued data. This algorithm consists of a cluster initiation phase and a sample regrouping phase. The first phase is based on a data-directed valley detection process utilizing the optimal second-order product approximation of high-order discrete probability distribution, together with a distance measure for discrete-valued data. As for the second phase, it involves the iterative application of the Bayes' decision rule based on subgroup discrete distributions. Since probability is used as its major decision criterion, the proposed method minimizes the disadvantages of yielding solutions sensitive to the arbitrary distance measure adopted. The performance of the proposed algorithm is evaluated by applying it to four different sets of simulated data and a set of clinical data. For performance comparison, the decision-directed algorithm [11] is also applied to the same set of data. These evaluation experiments fully demonstrate the validity and the operational feasibility of the proposed algorithm and its superiority as compared to the decision-directed algorithm.


[Rare cause of a chest pain].
A 42-year-old woman was admitted because of a newly perceived pain localized in the ventral part of the fifth left rib. The physical examination was normal except for a palpable nodular thyroid and pain on palpation of this rib. The patient history contained a serious car accident and severe cigarette abuse. The chest x-ray in "bone technique" showed an osteolysis in the fifth left rib, which was confirmed by computer tomography and bone scan. The high resolution CT scan of the lung revealed a discrete interstitial reticular pattern with minor cystic alterations without lymph node enlargement. Transbronchial biopsy, bronchoalveolar lavage and a malignancy screening did not lead to a diagnosis. Therefore, the patient was submitted to partial rib resection and open lung biopsy. Histological examination revealed a Langerhans cell histiocytosis. The initial therapeutic approach was a strict smoking cessation. The differential diagnosis of a lytic bone lesion in a heavy smoker should include Langerhans cell histiocytosis. On smoking cessation a remission of the disease may be achieved.


Potential pros and cons of external healthcare performance evaluation systems: real-life perspectives on Iranian hospital evaluation and accreditation program.
Performance evaluation is essential to quality improvement in healthcare. The current study has identified the potential pros and cons of external healthcare evaluation programs, utilizing them subsequently to look into the merits of a similar case in a developing country. A mixed method study employing both qualitative and quantitative data collection and analysis techniques was adopted to achieve the study end. Subject Matter Experts (SMEs) and professionals were approached for two-stage process of data collection. Potential advantages included greater attractiveness of high accreditation rank healthcare organizations to their customers/purchasers and boosted morale of their personnel. Downsides, as such, comprised the programs' over-reliance on value judgment of surveyors, routinization and incurring undue cost on the organizations. In addition, the improved, standardized care processes as well as the judgmental nature of program survey were associated, as pros and cons, to the program investigated by the professionals. Besides rendering a tentative assessment of Iranian hospital evaluation program, the study provides those running external performance evaluations with a lens to scrutinize the virtues of their own evaluation systems through identifying the potential advantages and drawbacks of such programs. Moreover, the approach followed could be utilized for performance assessment of similar evaluation programs.


Alcohol-Attributable Calories Consumed as a Result of Binge Drinking: A National Survey of Drinkers in the United States.
Estimate the alcohol-attributed calories associated with respondents' (a) most recent binge drinking episode, and (b) binge drinking across a thirty-day period. Examined responses to a module of the 2008 Behavioral Risk Factor Surveillance System (BRFSS), completed by a 10-state sample in the United States (n = 7,375), in order to estimate the alcohol-attributed calories consumed among binge drinkers. Alcohol-attributed calories were estimated by multiplying number of drinks consumed for each category (beer, wine, liquor drinks, and pre-mixed flavored drinks) collected in the BRFSS by caloric averages based on two data sources. In the past 30 days, respondents averaged 4.13 (SD = 5.84) binge drinking episodes, and consumed an average of 4.15 (SD = 3.55) beers, .67 (SD = 1.56) glasses of wine, 1.49 (SD = 2.53) shots of liquor, and .15 (SD = .79) pre-mixed flavored beverages during their most recent binge drinking episode. The average amount of alcohol-attributed calories consumed during this binge drinking episode was 991.76 (SD = 578.71), with men consuming significantly more calories than females. Dietary guidelines suggest the calories associated with alcoholic beverages should be considered as part of one's limited allotment of calories associated with solid fats and sugars, yet our results highlight alcohol as a major contributor (approximately 1,000 calories) to the proposed daily caloric needs on binge drinking days.


Apple intake and cancer risk: a systematic review and meta-analysis of observational studies.
Conflicting results on the association between fruit consumption and cancer risk have been reported. Little is known about the cancer preventive effects of different fruit types. The present meta-analysis investigates whether an association exists between apple intake and cancer risk. Relevant observational studies were identified by literature search (PubMed, Web of Science and Embase). A random-effect model was used to estimate the cancer risk in different anatomical sites. Between-study heterogeneity and publication bias were assessed using adequate statistical tests. Twenty case-control (three on lung, five on colorectal, five on breast, two on oesophageal, three on oral cavity, two on prostate and one each on pancreas, bladder, larynx, ovary, kidney and brain cancer) and twenty-one cohort (seven on lung, two on colorectal, three on breast and one each on oesophageal, pancreas, bladder, kidney, endometrial, head-neck, urothelial and stomach cancer) studies met the inclusion criteria. Comparing the highest v. lowest level of apple consumption, the reduction of lung cancer risk was statistically highly significant in both case-control (OR=0·75; 95% CI 0·63, 0·88; P=0·001, I 2=0 %) and cohort studies (relative risk=0·89; 95% CI 0·84, 0·94; P<0·001, I 2=53 %). Instead, in the case of colorectal (OR=0·66; 95% CI 0·54, 0·81; P<0·001, I 2=55%), breast (OR=0·79; 95% CI 0·73, 0·87; P<0·001, I 2=1 %) and overall digestive tract (OR=0·50; 95% CI 0·36, 0·69; P<0·001, I 2=90 %) cancers a significant preventive effect of apples was found only in case-control studies while prospective studies indicated no effect. No evidence of publication bias could be detected for colorectal, oral cavity, oesophageal and breast cancer. However, some confounding effects may be present and related to the consumption of other fruit which have not been considered as adjusting factors. The present meta-analysis indicates that consumption of apples is associated with a reduced risk of cancer in different anatomical sites.


Psychosocial stressors that precipitate dissociative trance disorder in Singapore.
To study the psychosocial stressors that precipitate dissociative trance disorder (DTD) and to identify predictors of DTD. We conducted semistructured interviews in which detailed information was obtained for 58 cases diagnosed with DTD at a psychiatric hospital in Singapore. A comparison group of 58 patients who received treatment at the same hospital for major depression (MD) were also interviewed, using the same instrument. While 100% of the DTD group described at least one psychosocial stressor, only 80% of the MD group did so. Common stressors for the DTD group include problems with military life (38%), conflicts over religious and cultural issues (38%), and domestic disharmony and marital woes (24%). Conflicts over religious and cultural issues seemed to be important in the precipitation of DTD but not in the precipitation of MD (p < 0.001). Logistic regression reveals that the following are positive predictors for DTD: conflicts over religious and cultural issues; prior exposure to trance states; and being a spiritual healer or his/her assistant. An understanding of the precipitating psychosocial stressors that overwhelmed the patient's coping abilities would have implications for treatment and enable the clinician to devise strategies for intervention and prevention.


Human papilloma virus genotyping, variants and viral load in tumors, squamous intraepithelial lesions, and controls in a north Indian population subset.
A study of human papilloma virus (HPV) types and variants is important for developing preventive protocols and appropriate intervention targets. The presence of HPV types, their variants, and viral load in a population subset from North India was studied. Polymerase chain reaction (PCR) and line blots were used for HPV genotyping; HPV 16 and 18 viral loads were measured using real-time PCR. Variant analysis was done by sequencing of the PCR-amplified E6/E7 regions of HPV 16 and the long control region and E6/E7 regions of HPV 18. The 93.6%, 78.6%, and 10% of tumors, squamous intraepithelial lesions (SILs), and controls were HPV-positive, respectively. The most commonly observed type was HPV 16. Human papilloma virus 73 which is uncommonly observed was seen in 2 tumors. Multiple infections were more common in controls and SILs than tumors. The majority (86.4%) of the HPV 16-positive and all of the HPV 18-positive samples belonged to the European variant class. Five novel nonsynonymous changes were seen in the HPV 16-positive and 2 in HPV 18-positive samples. There was a significant increase in viral loads from controls through SILs to tumors, but no significant differences in viral loads were observed between different stages of cancer. In tumors, a significant increase in HPV 16 viral loads was seen with increasing age. The study shows a similar HPV type and variant distribution to European studies, with some differences in type distribution. Viral load does not appear to be good marker for stage wise progression and intralesional variability may affect its use as a differentiating parameter between high-grade squamous intraepithelial lesion and low-grade squamous intraepithelial lesions.


Exploiting parallel R in the cloud with SPRINT.
Advances in DNA Microarray devices and next-generation massively parallel DNA sequencing platforms have led to an exponential growth in data availability but the arising opportunities require adequate computing resources. High Performance Computing (HPC) in the Cloud offers an affordable way of meeting this need. Bioconductor, a popular tool for high-throughput genomic data analysis, is distributed as add-on modules for the R statistical programming language but R has no native capabilities for exploiting multi-processor architectures. SPRINT is an R package that enables easy access to HPC for genomics researchers. This paper investigates: setting up and running SPRINT-enabled genomic analyses on Amazon's Elastic Compute Cloud (EC2), the advantages of submitting applications to EC2 from different parts of the world and, if resource underutilization can improve application performance. The SPRINT parallel implementations of correlation, permutation testing, partitioning around medoids and the multi-purpose papply have been benchmarked on data sets of various size on Amazon EC2. Jobs have been submitted from both the UK and Thailand to investigate monetary differences. It is possible to obtain good, scalable performance but the level of improvement is dependent upon the nature of the algorithm. Resource underutilization can further improve the time to result. End-user's location impacts on costs due to factors such as local taxation. Although not designed to satisfy HPC requirements, Amazon EC2 and cloud computing in general provides an interesting alternative and provides new possibilities for smaller organisations with limited funds.


A microfluidic device to establish concentration gradients using reagent density differences.
Microfabrication has become widely utilized to generate controlled microenvironments that establish chemical concentration gradients for a variety of engineering and life science applications. To establish microfluidic flow, the majority of existing devices rely upon additional facilities, equipment, and excessive reagent supplies, which together limit device portability as well as constrain device usage to individuals trained in technological disciplines. The current work presents our laboratory-developed bridged μLane system, which is a stand-alone device that runs via conventional pipette loading and can operate for several days without need of external machinery or additional reagent volumes. The bridged μLane is a two-layer polydimethylsiloxane microfluidic device that is able to establish controlled chemical concentration gradients over time by relying solely upon differences in reagent densities. Fluorescently labeled Dextran was used to validate the design and operation of the bridged μLane by evaluating experimentally measured transport properties within the microsystem in conjunction with numerical simulations and established mathematical transport models. Results demonstrate how the bridged μLane system was used to generate spatial concentration gradients that resulted in an experimentally measured Dextran diffusivity of (0.82 ± 0.01) × 10(-6) cm(2)/s.


Effects of alterations in pulmonary function and sleep variables on survival in patients with amyotrophic lateral sclerosis.
Breathing abnormalities and nocturnal hypoventilation occur in patients with amyotrophic lateral sclerosis (ALS). A prospective study was undertaken to determine the relationship of pulmonary function test abnormalities with quality of sleep and survival in 21 patients with ALS. Results of spirometry including determination of maximal respiratory pressures and arterial blood gases were compared with several formal polysomnographic variables and then also with 18-month survival. The patients had mild to moderate pulmonary function deficits, but the quality of sleep was best related to age (mean age, 58.5 years). The results of pulmonary function tests and arterial blood gas measurements did not correlate well with the presence of nocturnal breathing events or survival time, but the maximal inspiratory pressure was 86% sensitive for predicting the presence of a nocturnal oxygen saturation nadir of 80% or less and 100% sensitive for predicting 18-month survival. Although obstructive breathing events occurred, the primary explanation for the decline in nocturnal oxygen saturation was hypoventilation. We conclude that routine pulmonary function tests may be useful for screening for reductions in nocturnal oxygen saturation and also may have prognostic value. Further studies may determine whether treatment of nocturnal hypoventilation will have an effect on survival in patients with ALS who have breathing impairment.


Efficacy and safety of aztreonam-clindamycin versus tobramycin-clindamycin in the treatment of lower respiratory tract infections caused by aerobic gram-negative bacilli.
A total of 80 patients were randomized to receive either aztreonam or tobramycin for the treatment of lower respiratory tract infections caused by gram-negative bacilli; all these patients received clindamycin concomitantly. A total of 53 patients were randomized to receive aztreonam-clindamycin; of these, 46 were clinically evaluable and 39 were bacteriologically evaluable. Of the 46 clinically evaluable patients, 41 were considered cured, 3 failed to be cured, and 2 died during the study period of unrelated causes. Of the 39 bacteriologically evaluable patients, 36 were considered cured, and 3 failed to be cured. There were 26 clinically evaluable patients in the group randomized to receive tobramycin-clindamycin. Of them, 22 patients were considered cured, 3 failed to be cured, and 1 died of unrelated causes during the study period. There were 18 bacteriologically evaluable patients in the tobramycin-clindamycin group; 17 were cured, and 1 failed to be cured. The most common pathogens isolated from the patients were Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. All of the isolated organisms were susceptible to both tested antibiotics, except for a strain of Pseudomonas cepacia resistant to both tested antimicrobial agents and a strain of Enterobacter aerogenes and one of P. aeruginosa that were resistant to aztreonam. Very few adverse reactions related to the antibiotics were seen. These effects, when present, were transient and comparable in both studied groups, except for renal-function tests, which were altered in 7.7% of the patients randomized to receive tobramycin-clindamycin and in none of the patients randomized to receive aztreonam-clindamycin. Aztreonam-clindamycin is safe and effective for the treatment of lower respiratory tract infections caused by aerobic gram-negative bacilli when the organisms are susceptible.


Analysis of fatal outcomes from influenza A(H1N1)pdm09 in Mongolia.
While influenza A(H1N1)pdm09 usually causes mild illness in the majority of people, there have been reports of severe cases and deaths. As there is no documented evidence on fatal outcomes from influenza in Mongolia previously, we aimed to describe the epidemiology of fatal influenza A(H1N1)pdm09 cases to provide recommendations to assist the national influenza prevention and control strategy. We selected influenza A(H1N1)pdm09-confirmed deaths in hospitals between 12 October 2009 and 31 January 2010 in Mongolia from the national influenza surveillance system. The mortality rate and case fatality rate (CFR) of influenza A(H1N1)pdm09-hospitalized deaths were calculated. Using country prevalence of pregnancy and chronic diseases, we calculated the relative risk of death from influenza A(H1N1)pdm09. There were 29 deaths with a mortality rate of 1.0 per 100 000 population during the study period, which was highest in children under five and the middle-aged population. Crude CFR was 2.2%. Of all fatal cases, 62% had at least one underlying condition. Most (62%) were provided antivirals, although none received these within 48 hours of symptom onset. Prevalence for pregnancy, cardiovascular and chronic liver diseases was five to 50 times higher in fatal cases compared to country prevalence. Mortality and crude CFR in our study was higher than in other studies. However, due to the diagnostic policy change during the epidemic, this estimate is likely to have overestimated actual case fatalities. Pregnancy, cardiovascular and chronic liver diseases were suggestive risk factors for death from influenza A(H1N1)pdm09. Strengthening hospital-based influenza surveillance is important in predicting severity of an epidemic and responding to influenza epidemics in a timely and appropriate manner.


Growth of primary hippocampal neuronal tissue on an aragonite crystalline biomatrix.
Tissue-like structures of hippocampal neurons were established in a crystalline three-dimensional (3D) aragonite biomatrix obtained from the exoskeleton of the coral Porites lutea. Cultures were maintained in vitro for up to 5 weeks. Cell viability and regeneration of neuronal properties were studied by immunocytochemical methods, light microscopy image analysis techniques, and scanning electron microscopy. Some portions of the cell population acquired the morphological characteristics of hippocampal pyramidal or granule neurons with axons and dendrites extending in a 3D manner along the surfaces of the crystalline biomatrix. The neurons usually grew on a sheet of glial cells. Within the pore void areas, multiple layers of neurons were formed, many of the neurons growing with no attachment to the crystalline surfaces. The neurons developed mature synaptic connections, with presynaptic sites expressing the synaptic vesicle protein 2 and postsynaptic sites having the shape of dendritic spines and expressing type 1 glutamate receptors, as these cells do under conventional culture conditions. The findings of the present study suggest that neuronal networks growing in a strong 3D aragonite support may find application as tissue replacement material for the central nervous system.


[The indirect solid-phase method of immunoenzyme analysis, its accuracy and sources of error].
The study of the accuracy of the enzyme-linked immunosorbent assay has revealed that the accuracy of this assay is low. The influence of instruments (dispensers, photometers, plates) on the accuracy of the assay has been studied. As shown in this study, the main sources are titration procedures and differences in the adsorption and optical properties of available plates, those manufactured in the USSR giving greater errors.


Ion jelly conductive properties using dicyanamide-based ionic liquids.
The thermal behavior and transport properties of several ion jellys (IJs), a composite that results from the combination of gelatin with an ionic liquid (IL), were investigated by dielectric relaxation spectroscopy (DRS), differential scanning calorimetry (DSC), and pulsed field gradient nuclear magnetic resonance spectroscopy (PFG NMR). Four different ILs containing the dicyanamide anion were used: 1-butyl-3-methylimidazolium dicyanamide (BMIMDCA), 1-ethyl-3-methylimidazolium dicyanamide (EMIMDCA), 1-butyl-1-methylpyrrolidinium dicyanamide (BMPyrDCA), and 1-butylpyridinium dicyanamide (BPyDCA); the bulk ILs were also investigated for comparison. A glass transition was detected by DSC for all materials, ILs and IJs, allowing them to be classified as glass formers. Additionally, an increase in the glass transition temperature upon dehydration was observed with a greater extent for IJs, attributed to a greater hindrance imposed by the gelatin matrix after water removal, rendering the IL less mobile. While crystallization is observed for some ILs with negligible water content, it was never detected for any IJ upon thermal cycling, which persist always as fully amorphous materials. From DRS measurements, conductivity and diffusion coefficients for both cations (D+) and anions (D-) were extracted. D+ values obtained by DRS reveal excellent agreement with those obtained from PFG NMR direct measurements, obeying the same VFTH equation over a large temperature range (ΔT ≈ 150 K) within which D+ varies around 10 decades. At temperatures close to room temperature, the IJs exhibit D values comparable to the most hydrated (9%) ILs. The IJ derived from EMIMDCA possesses the highest conductivity and diffusion coefficient, respectively, ∼10(-2) S·cm(-1) and ∼10(-10) m(2)·s(-1). For BMPyrDCA the relaxational behavior was analyzed through the complex permittivity and modulus formalism allowing the assignment of the detected secondary relaxation to a Johari-Goldstein process. Besides the relevant information on the more fundamental nature providing physicochemical details on ILs behavior, new doorways are opened for practical applications by using IJ as a strategy to produce novel and stable electrolytes for different electrochemical devices.


Review of policies to increase fruit and vegetable consumption and physical activity in 49 low- and middle-income countries.
Inadequate physical activity (PA) and consumption of fruits and vegetables (FV) are known risk factors for non-communicable diseases (NCDs). Consequently, the World Health Organization (WHO) encourages the development of policies to increase PA and FV consumption. We reviewed available policies between 2004 and 2013 to increase FV consumption and PA from a convenience sample of 49 LMICs. Information on national policies were obtained from government ministries involved with the formulation of nutrition and PA policies, WHO databases and from PubMed and Scopus. Of the 49 countries, 57% had policies to increase FV consumption, and 76% had policies to promote PA. Policy reviews indicated strategies that focus on schools, communities, the general public, the environment, the economy, mass media and WHO recommendations. Of the 28 countries with FV policies, 18% had formulated policies that met the WHO recommendations for daily intake of FV. Likewise, of the 37 countries with PA policies, 24% had policies that promoted the WHO recommendations for daily PA. Greater progress has been made in developing policies to increase PA compared to policies to increase FV consumption in low- and middle-income countries. However, most countries are still lagging behind in developing policies to meet the WHO recommendations.


The Me in Memory: The Role of the Self in Autobiographical Memory Development.
This article tests the hypothesis that self-development plays a role in the offset of childhood amnesia; assessing the importance of both the capacity to anchor a memory to the self-concept, and the strength of the self-concept as an anchor. This research demonstrates for the first time that the volume of 3- to 6-year old's specific autobiographical memories is predicted by both the volume of their self-knowledge, and their capacity for self-source monitoring within self-referencing paradigms (N = 186). Moreover, there is a bidirectional relation between self and memory, such that autobiographical memory mediates the link between self-source monitoring and self-knowledge. These predictive relations suggest that the self-memory system is active in early childhood.


Influence of long-range forces and capillarity on the function of underwater superoleophobic wrinkled surfaces.
Underwater superoleophobic surfaces can be considered a particular type of lubricant-infused surface, that have anti-fouling properties by virtue of a trapped water layer that repels oils. However, as their function relies on a water layer being trapped in the surface roughness, it is crucial to understand the factors that determine the layer stability. In this work, the forces that are responsible for the stability of thin liquid films within structured surfaces were quantified, and the conclusions were tested against the performance of wrinkled surfaces as underwater superoleophobic coatings. Here, the system studied was a family of wrinkled surfaces made of hydrophilic poly(4-vinylpyridine) (P4VP), whereby the wrinkle width could be controllably tuned in the range 90 nm to 8000 nm. The van der Waals free energy was quantified and the capillary forces trapping water in the surface micro- and nano-wrinkle structure were estimated. P4VP surfaces with micro-scale wrinkles had underwater superoleophobic properties, and low adhesion to different oils with droplet roll-off angle below 6° ± 1°. Despite the van der Waals free energy of the system pointing to the dewetting of a water film under oil on top of a smooth P4VP film, the wrinkled structure is sufficient to induce a Cassie state with a trapped water layer. The micro-scale wrinkles (average width 4-12 μm) were found to be particularly effective in the trapping of the water in a Cassie non-adhesive state. The P4VP wrinkled surfaces are superamphiphobic, as when they were first infused with oil, and then exposed to a droplet of water under oil, they exhibited superhydrophobic behavior. The P4VP wrinkles have the additional useful feature of being transparent underwater, which makes them useful candidates for the protection of underwater cameras and sensors.


Prospects of human malaria and Bancroftian filariasis infections in the Lower Rufiji Basin, Tanzania II. Bancroftian filariasis.
Surveys for human bancroftian filariasis infections were conducted in the Lower Rufiji Basin, Tanzania, before and after the long rains in 1981. A multipurpose water resources development project has been planned in the area. A microfilarial rate of 18.1%, a mean microfilarial count of 80 microfilariae per 100 microliters blood were observed. Generally, males showed higher microfilarial rates than their female counterparts. All microfilariae were identified as Wuchereria bancrofti. A prevalence rate of 0.4% was recorded for leg elephantiasis. None of the cases were seen in individuals below 20 years of age. Only two cases of elephantiasis of the breasts were seen and no cases of elephantiasis of the arms were encountered. Rates for scrotal elephantiasis and hydrocoeles in males were 8.7% and 11.5% respectively, and enlargement of the inguinal and/or femoral lymph glands was common and the onset of this manifestation is early.


Promoting Resilience in Stress Management for Parents (PRISM-P): An intervention for caregivers of youth with serious illness.
It is well-known that parental stress and coping impacts the well-being of children with serious illness. The current study aimed to evaluate the feasibility and satisfaction of a novel resilience promoting intervention, the Promoting Resilience in Stress Management Intervention for Parents (PRISM-P) among parents of adolescents and young adults with Type 1 diabetes or cancer. Secondary analyses explored the effect of the PRISM-P on parent-reported resilience and distress. The PRISM-P includes 4 short skills-based modules, delivered in either 2 or 4 separate, individual sessions. English-speaking parents of adolescents with cancer or Type 1 diabetes were eligible. Feasibility was conservatively defined as a completion rate of 80%; satisfaction was qualitatively evaluated based upon parent feedback regarding intervention content, timing, and format. Resilience and distress were assessed pre- and postintervention with the Connor Davidson Resilience Scale and the Kessler-6 Psychological Distress Scale. Twelve of 24 caregivers of youth with diabetes (50%) and 13 of 15 caregivers of youth with cancer (87%) agreed to participate. Nine of 12 (75%) and 9 of 13 (64%) completed all PRISM-P modules, respectively. Among those who completed the intervention, qualitative satisfaction was high. Parent-reported resilience and distress scores improved after the intervention. Effect sizes for both groups indicated a moderate intervention effect. Ultimately, the PRISM-P intervention was well accepted and impactful among parents who completed it. However, attrition rates were higher than anticipated, suggesting alternative or less time-intensive formats may be more feasible. (PsycINFO Database Record


Type, prevalence, and significance of core promoter/enhancer II mutations in hepatitis B viruses from immunosuppressed patients with severe liver disease.
Little is known about the functional significance of hepatitis B virus (HBV) sequence heterogeneity. Here we analyzed the type, frequency, and function of mutations in the core promoter/enhancer II region of HBV in immunosuppressed patients. The major HBV population in immunosuppressed patients with severe liver disease had deletions, insertions, and/or base changes in this region. Such mutations were not found in immunosuppressed patients with mild disease. Except for two mutations, all created a hepatocyte nuclear factor 1 (HNF1) binding site or a potential HNF3 binding site. Occasionally, known binding sites for C/EBP and HNF4 were additionally duplicated. Eleven mutated core promoter prototype sequences were functionally tested in the context of a wild-type genome by transfection in Huh7 cells. Despite the diversity of mutations tested, all decreased steady-state levels of pre-C mRNA drastically and increased those of the C mRNA/ pregenomic RNA. This correlated with reduced levels of secreted hepatitis B e antigen and increased intracellular levels of core and Pol proteins and replicative HBV DNA intermediates. The levels of secreted HBV DNA-containing particles were also increased although most of the mutations reduced the levels of pre-S/S mRNA and pre-S1, and pre-S2 proteins as well as secretion of hepatitis B surface antigen. These data reveal a novel class of HBV variants with HNF1 binding sites in the core promoter which are characterized by a defect in hepatitis B e antigen expression, enhanced replication, and altered protein levels, all probably mediated by altered transcription factor binding. The phenotype of these variants and their prevalence only in immunosuppressed patients with severe liver disease may indicate that they play a role in pathogenesis.


A 102-center prospective study of seizure in association with bupropion.
This trial was conducted to determine the incidence of seizures associated with the use of bupropion. A total of 3341 depressed patients from 102 sites were enrolled in this 8-week, prospective, open trial. Following the 8-week treatment phase, patients could elect to enroll in a humanitarian continuation phase of unlimited duration. Dosing was initiated at 225 mg/day and increased to 450 mg/day as tolerated. Investigators carefully monitored seizure occurrences and rated their patients' response to and tolerance of bupropion. A total of 1986 patients (61%) completed the 8-week treatment phase, and 1616 (81%) of these elected to be maintained on bupropion treatment in the humanitarian continuation phase. The observed seizure rate was 0.24% for the treatment phase and 0.40% for the entire study. An 8-week survival analysis performed on patients with a dosing regimen of 300 to 450 mg/day yielded a cumulative rate of 0.36%. Patients, including those previously resistant to antidepressant treatment, responded to and tolerated bupropion well. These rates confirm earlier seizure estimates and fall within accepted parameters for antidepressant drugs. This trial enhances bupropion's position as a valuable alternative for the management of depression.


Near-infrared spectrophotometric monitoring of oxygen distribution to intact brain and skeletal muscle tissues.
During continuous near-infrared optical monitoring of brain cortex and hindlimb skeletal muscles, anesthetized, ventilated cats were exposed either to progressive alveolar hypoxia, or to acute hemorrhage followed in some cases by resuscitation. Hypoxia decreased cytochrome a,a3 oxidation state in muscle more than in brain, while tissue blood volume increased in brain and decreased in muscle. At a PaO2 of 25 torr, cytochrome a,a3 oxidation level in the brain was sufficient to support EEG activity, but the cytochrome a,a,3 oxidation state in resting, innervated hindlimb muscle was near zero. Hemorrhagic hypotension invariably decreased cytochrome a,a3 oxidation state and tissue blood volume more in muscle than in brain, and muscle cytochrome a,a3 was completely reduced at about a 25-ml/kg blood loss. These observations, supported by noninvasively measured changes in near-infrared absorption in the tissues during serial intravascular injections of indocyanine green dye, indicate that different cytochrome responses to hypoxia and oligemia in muscle vs. brain tissue are attributable to different regional circulatory adjustments.


Pre-Analytical and Analytical Variables of Label-Independent Enrichment and Automated Detection of Circulating Tumor Cells in Cancer Patients.
Circulating tumor cells (CTCs) are promising tools for risk prediction and the monitoring of response to therapy in cancer patients. Within the EU/IMI CANCER-ID consortium, we validated CTC enrichment systems for future inclusion into clinical trials. Due to the known heterogeneity of markers expressed on CTCs, we tested the Parsortix® system (ANGLE plc) which enables label-independent CTC enrichment from whole blood based on increased size and deformability of these tumor cells compared to leukocytes. We performed extensive comparisons both with spiked-in blood models (i.e., MDA-MB-468 tumor cell line cells spiked at very low concentration into blood from healthy donors) and validated the protocol on actual clinical samples from breast, lung, and gastrointestinal cancer patients to define optimal conditions for CTC enrichment. Multiple parameters including cassette gap, separation pressure, and cell fixatives were compared in parallel. Also, the compatibility of blood collection tubes with whole genome amplification of isolated tumor cells was demonstrated and we furthermore established a workflow for semi-automated CTC detection using a quantitative cell imager. The established workflow will contribute to supporting the use of size-based CTC enrichment platforms in clinical trials testing the clinical validity and utility of CTCs for personalized medicine.


Characterization of cigar tobaccos by gas chromatographic/mass spectrometric analysis of nonvolatile organic acids: application to the authentication of Cuban cigars.
A reliable method based on gas chromatographic/mass spectrometric (GC/MS) profiling of nonvolatile organic acids is described for the characterization of cigars. The method involves an aqueous extraction of ground tobacco and selective isolation of the acids by simply stirring strong anion exchange (SAX) disks in the aqueous tobacco extract. The acids are then directly silylated on the disk with N-methyl-N-trimethylsilyl-trifluroacetamide (MSTFA) in acetonitrile in an autosampler vial. Elution of the derivatized acids in situ allows the sample to be directly analyzed by GC/MS without further sample handling. Compared to the conventional disk-extraction technique using a vacuum manifold, this method is much less labor intensive, and is desirable for multiple sample analysis. Nicotinic acid, succinic acid, glyceric acid, malic acid, pyroglutamic acid, threonic acid, citric acid, uracil, and an unidentified acid were reproducibly quantified in tobacco samples. Principal component analysis (PCA) of the acid profiles of the filler tobaccos of 18 Cuban cigars and 31 non-Cuban cigars shows separation of the two groups, indicating that the acid profiles are potentially useful in the authentication of Cuban cigars.


Experimental verification of an all-optical dual-hop 10 Gbit/s free-space optics link under turbulence regimes.
This Letter presents original measurement results from an all-optical 10 Gbit/s free-space optics (FSO) relay link involving two FSO links and an all-optical switch. Considering the fact that reported analyses of relay links are dominated by analytical findings, the experimental results represent a vital resource for evaluating the performance of relay FSO links in the presence of atmospheric turbulence. Bit-error-rate (BER) performance of the relay system is tested for single and dual-hop links under several turbulence regimes. Furthermore, results from this measurement are used to ascertain real parameters of the outdoor links and to improve the accuracy of simulation results. Results show that using a dual-hop FSO link against a single FSO link could result in up to four orders of magnitude improvement in BER in the presence of atmospheric turbulence.


Improvement in Hailey-Hailey disease with a combination of low-dose naltrexone and oral magnesium chloride: A case report.
Hailey-Hailey disease is a rare autosomal dominant acantholytic disorder due to mutation in the ATP2C1 gene and presents with flaccid blisters in intertriginous regions. Its chronic and relapsing course may negatively impact patients' quality of life. Multiple medical and interventional treatments have been described with various efficacy. Low-dose naltrexone and oral magnesium chloride represent emerging treatments. Sustained improvement in Hailey-Hailey disease has been reported with the former in case series, while others have shown variable results. Oral magnesium chloride has been reported in four patients with possible results after 2-4 weeks. Two recent cases suggest that the combination of both treatments may have a synergistic effect. Herein, we present a 63-year-old woman with long-standing and recurrent bilateral inguinal Hailey-Hailey disease who significantly improved with low-dose naltrexone and oral magnesium chloride, representing the third case described with this combination.


Ventilation with lower tidal volumes versus traditional tidal volumes in adults for acute lung injury and acute respiratory distress syndrome.
Patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) require mechanical ventilatory support. ALI/ARDS is further complicated by ventilator-induced lung injury. Lung-protective ventilation strategies may lead to improved survival. To assess the effects of ventilation with lower tidal volume (Vt) on morbidity and mortality in adults patients affected by ALI/ARDS. A secondary objective was to determine whether the comparison between low and conventional Vt is different if a plateau airway pressure of greater than 30 to 35 cm H20 was used. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library issue 3, 2002; MEDLINE (1966 to June 2002); EMBASE and CINAHL (1982 to June 2002); intensive care journals and conference proceedings; databases of ongoing research, reference lists and 'grey literature'. Randomized trials comparing ventilation using lower Vt and/or low airway driving pressure (plateau pressure 30 cm H2O or less), resulting in Vt of 7 ml/kg or less versus ventilation that uses Vt in the range of 10 to 15 ml/kg, in adults (16 year-old or greater). Two reviewers independently assessed trial quality and extracted data. Wherever appropriate, results were pooled. Fixed and random effects models were applied. Five trials, involving 1202 patients, were eligible. The test for heterogeneity gave a P-value of 0.12. Ventilation with lower Vt was associated with a decreased mortality at the end of the follow up period for each trial: 216/605 (35.7%) versus 249/597 (41.7%), relative risk (RR) 0.85 (CI 0.74 to 0.98). The effect of the intervention was not statistically significant when a random effects model was used: RR 0.91 (CI 0.72 to 1.14). Mortality at day 28 was significantly reduced by lung-protective ventilation: RR 0.74 (CI 0.61 to 0.88). The comparison between low and conventional Vt was not significantly different if a plateau pressure less than or equal to 31 cm H2O in control group was used: RR 1.13 (CI 0.88 to 1.45). There was insufficient evidence about morbidity and long term outcomes. Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in two trials make the interpretation of the combined results difficult. Mortality is significantly reduced at day 28 and the effects on long term mortality are uncertain, although the possibility of a clinically relevant benefit cannot be excluded. There is no evidence that low Vt ventilation is beneficial in patients where hypercapnia is potentially harmful.


Glycerol uptake mutants of the hyphal fungus Aspergillus nidulans.
A new class of glycerol non-utilizing mutants, designated glcC, has been isolated. The glcC gene was mapped in linkage group VI and mutants were found to complement the reference strains glcA1 (linkage group V) and glcB33 (linkage group I) in diploids. The new mutants were unable to grow on glycerol. However, in contrast to the glcA and glcB phenotype these mutants did grow well on dihydroxyacetone and D-galacturonate. By in vivo 13C NMR spectroscopy it was shown that the glcC mutant did not take up glycerol but did take up dihydroxyacetone. The latter substrate was converted intracellularly into glycerol which was then catabolized as normal.


Childhood Predictors of Adult Functional Outcomes in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (MTA).
Recent results from the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (ADHD; MTA) have demonstrated impairments in several functioning domains in adults with childhood ADHD. The childhood predictors of these adult functional outcomes are not adequately understood. The objective of the present study was to determine the effects of childhood demographic, clinical, and family factors on adult functional outcomes in individuals with and without childhood ADHD from the MTA cohort. Regressions were used to determine associations of childhood factors (age range 7-10 years) of family income, IQ, comorbidity (internalizing, externalizing, and total number of non-ADHD diagnoses), parenting styles, parental education, number of household members, parental marital problems, parent-child relationships, and ADHD symptom severity with adult outcomes (mean age 25 years) of occupational functioning, educational attainment, emotional functioning, sexual behavior, and justice involvement in participants with (n = 579) and without (n = 258) ADHD. Predictors of adult functional outcomes in ADHD included clinical factors such as baseline ADHD severity, IQ, and comorbidity; demographic factors such as family income, number of household members and parental education; and family factors such as parental monitoring and parental marital problems. Predictors of adult outcomes were generally comparable for children with and without ADHD. Childhood ADHD symptoms, IQ, and household income levels are important predictors of adult functional outcomes. Management of these areas early on, through timely treatments for ADHD symptoms, and providing additional support to children with lower IQ and from households with low incomes, could assist in improving adult functioning.


Synthesis of 11, 12-2H2- and 11, 12-3H2-labeled chenodeoxycholic and lithocholic acids.
Deuterium- and tritium-labeled chenodeoxycholic acid and lithocholic were prepared by catalytic reduction of their respective delta11 derivatives. Structures of the intermediates and their isotopic purity were verified by chemical ionization and electron impact mass spectrometry and by nuclear magnetic resonance spectroscopy. Experimental conditions for reductive deuteration were defined which gave complete reduction of the olefin and a product of high isotopic purity. Conditions for optimal tritiation were developed with which little exchange of protons with the solvent occurred; the product had high specific activity. To test biological stability of the label, the 3H-labeled chenodeoxycholic acid was administered simultaneously with 14C-labeled chenodeoxycholic acid to two healthy subjects and the 3H/14C ratio in bile was determined daily for several days. The ratio remained identical to that administered, suggesting that the 11,12-3Hlabel in chenodeoxycholic acid is stable during enterohepatic cycling and can be used for valid estimates fo bile acid kinetics in many by the isotope dilution technique.


Improvement in baroreflex control of renal sympathetic nerve activity in obese Sprague Dawley rats following immunosuppression.
This investigation explored the hypothesis that in obesity an inflammatory response in the kidney contributed to a renal nerve-dependent blunting of the baroreflex regulation of renal sympathetic nerve activity. Rats received a normal (12% kcal) or high-fat (45% kcal) diet for 8 weeks plus daily injections of vehicle (0.9% NaCl i.p) or tacrolimus (0.25 mg kg-1 day-1 i.p) from weeks 3-8. Following anaesthesia, left renal sympathetic nerve activity was recorded, baroreflex gain curves were generated, by infusing phenylephrine and sodium nitroprusside, and cardiopulmonary baroreceptors challenged by infusing a saline load. The high-fat diet elevated weight gain and adiposity index by 89 and 129% (both, P < 0.001). Mean blood pressure (132 ± 4 vs 103 ± 5 mmHg), fractional noradrenaline excretion and creatinine clearance (5.64 ± 0.55 vs 3.32 ± 0.35 mL min-1 kg-1 ) were 28, 77 and 69% higher (all P < 0.05), but urine flow and fractional sodium excretions were 42 and 72% (both P < 0.001) lower compared to normal rats. Plasma and renal TNF-α and IL-6 concentrations were fourfold to fivefold (P < 0.001) and 22 and 20% higher (both, P < 0.05), in obese rats but normalized following tacrolimus. In obese rats, baroreflex sensitivity was reduced by 80% (P < 0.05) but restored by renal denervation or tacrolimus. Volume expansion reduced renal sympathetic nerve activity by 54% (P < 0.001) in normal and obese rats subjected to renal denervation and tacrolimus, but not in obese rats with an intact renal innervation. Obesity induced a renal inflammation and pointed to this being both the origin of autonomic dysregulation and a potential focus for targeted therapy.


Exploring blood-brain barrier hyperpermeability and potential biomarkers in traumatic brain injury.
Blood-brain barrier breakdown and associated vascular hyperpermeability leads to vasogenic edema in traumatic brain injury (TBI). Tight junctions maintain blood-brain barrier integrity; their disruption in TBI holds significant promise for diagnosis and treatment. A controlled cortical impactor was used for TBI in mouse studies. Blood was collected 1 h after injury and sent for antibody microarray analysis. Twenty human subjects with radiographic evidence of TBI were enrolled and blood collected within 48 h of admission. Control subjects were individuals with nontrauma diagnoses. The subjects were matched by age and gender. Enzyme-linked immunosorbent assays were performed on each TBI and control sample for tight junction-associated proteins (TJPs), inflammatory markers, and S100β. Plasma was used to conduct in vitro monolayer permeability studies with human brain endothelial cells. S100β and the TJP occludin were significantly elevated in TBI plasma in both the murine and human studies. Monolayer permeability studies showed increased hyperpermeability in TBI groups. Plasma from TBI subjects increases microvascular hyperpermeability in vitro. TJPs in the blood may be a potential biomarker for TBI.


[Clinico-pathogenetic correlations in intellectual deficiency in premature infants].
The comparison of 32 immature infants with mental retardation of various degree (based on the results of clinical, immunological and biochemical examinations) with full-term infants with analogous pathology showed in the former group a high incidence (82.8%) of cerebral antibodies to antigens of the homo- and heterological brain in the complement consumption test. Therapeutic measures helped to reduce neuroimmune changes while the presence of antibodies to the homologous brain remained stable. Using data on the excretion of vanillyl amygdalic and homovanillic acids, the authors established alterations in catecholamine catabolism as well as in the activity of serum amine oxidase, which depended on the degree of mental retardation. Changes in individual components of catecholamine metabolism were found to correlate with neuroimmune shifts. The data obtained point to the presence of changes in biogenic amine metabolism and in immunological processes in mentally retarded children, which are very likely to be caused by immaturity at birth.


High dosage of zinc modulates T-cells in a time-dependent manner within porcine gut-associated lymphatic tissue.
Zn serves as a powerful feed additive to reduce post-weaning diarrhoea in pigs. However, the mechanisms responsible for Zn-associated effects on the adaptive immune responses following feeding of a very high dosage of Zn remain elusive. In this study, we examined the T-cell response in gut-associated lymphatic tissues of seventy-two weaned piglets. Piglets received diets with 57 mg Zn/kg (low Zn concentration, LZn), 164 mg Zn/kg (medium Zn concentration, MZn) or 2425 mg Zn/kg (high Zn concentration, HZn) mg Zn/kg feed for 1, 2 or 4 weeks. We observed that feeding the HZn diet for 1 week increased the level of activated T-helper cells (CD4+ and CD8α dim) compared with feeding MZn and LZn (P<0·05). In addition, we observed higher transcript amounts of interferon γ and T-box 21 (TBET) in the HZn group compared with the MZn and LZn groups (P<0·05). A gene set enrichment analysis revealed an over-representation of genes associated with 'cytokine signalling in immune system'. Remarkably, feeding of a very high Zn dosage led to a switch in the immune response after 2 weeks. We detected higher relative cell counts of CD4+CD25high regulatory T-helper cells (P<0·05) and a higher expression of forkhead box P3 (FOXP3) transcripts (P<0·05). After 4 weeks of feeding a high-dosage Zn diet, the relative CD4+ T-cell count (P<0·05) and the relative CD8β + T-cell count (P<0·1) were reduced compared with the MZn group. We hypothesise that after 1 week the cellular T-helper 1 response is switched on and after 2 weeks it is switched off, leading to decreased numbers of T-cells.


Sleepiness and sleep disordered breathing in Prader-Willi syndrome: relationship to genotype, growth hormone therapy, and body composition.
Patients with Prader-Willi syndrome (PWS) suffer from excessive sleepiness and sleep disordered breathing (SDB). We reviewed the polysomnograms (PSGs) and multiple sleep latency tests (MSLTs) in a cohort of PWS patients to determine the relationship of BMI(Z) scores, daytime sleepiness, growth hormone (GH) treatments, and SDB. Attended overnight PSGs were performed for PWS patients referred for concern for SDB between January 2000 and January 2005. Age at time of study, genotype, use and dose of GH, sleepiness scale, normalized body-mass index (BMI(Z)), total sleep time, latency to stage I and REM sleep, sleep stage percentages, apnea-hypopnea index (AHI), central apnea (CA) frequency, oxygen saturation nadir, maximum carbon dioxide tension, periodic limb movement index, presence of snoring, normality of EEG, and, in several patients, mean sleep latency testing were determined. All patients exhibited some form of SDB. There was a positive correlation between the BMI(Z) and AHI. The BMI(Z) was significantly different between GH-treated and -untreated groups, but there was not a significant difference between AHI, CA, oxygen nadir, or maximum carbon dioxide tension of the GH-treated and -untreated groups. There was no significant correlation between the MSLT and the sleepiness scale or AHI. There was also no significant difference between the AHIs of patients with different genetic defects. There should be a low threshold for obtaining PSG to evaluate SDB, but the type and severity of SDB were not predictable based on a sleepiness scale score, BMI(Z), or underlying genetic defect.