Eating behaviour, and preprandial and postprandial correlations in male broiler and layer chickens.
1. It has been suggested that broiler chickens have a disturbed satiety and hunger mechanism. The satiety mechanism for eating can be expressed as the positive correlation between meal length and the length of the preceding (preprandial) interval; the hunger mechanism for eating as the positive correlation between meal length and the length of the succeeding (postprandial) interval. An experiment was conducted to investigate eating behaviour of male broiler and layer chickens by measuring meal and interval lengths. 2. Eight male broilers and 8 male layer chickens were housed individually and visually isolated in floor pens (1 m2/pen) on wood shavings. From 4 to 7 weeks of age, eating behaviour of each bird was recorded for 3 h in two conditions each week. In the first condition, the birds were not deprived from feed. In the second condition, they were 24-h food deprived and feed was provided just before the observation started. Preprandial and postprandial correlations were calculated based on data of the non-deprived condition. Before and after each observation bird and feeder were weighed to measure weight gain and feed consumption during observation. 3. Under the non-deprived condition, the broilers spent initially more, but at a later age less time on eating. The broilers had fewer meals per hour, consumed more feed per hour, and had longer meal and interval lengths than the layer chickens. After 24-h feed deprivation, the broilers had a longer first meal, consumed more feed per hour and spent more time on eating than the layer chickens. Significant preprandial correlations but no postprandial correlations were found in the broilers. In the layer chickens, both significant preprandial and postprandial correlations were found. This indicates that for regulating eating behaviour, the satiety mechanism dominates the hunger mechanism in broilers, and satiety and hunger mechanisms are equally involved in layer chickens. 4. The typical eating behaviour of broilers and the calculated preprandial and postprandial correlations have given new indications that hunger and satiety mechanisms in broilers have changed compared with layer chickens. In broilers, there is no lower set point, but only an upper set point for controlling eating behaviour, which suggests that broilers eat to their maximal physical capacity.


Segregation into separate rouleaux of erythrocytes from different species. Evidence against the agglomerin hypothesis of rouleaux formation.
Erythrocytes from one species were labelled with fluorescein isothiocyanate and mixed with unlabelled erythrocytes from another species. Albumin polymers were added to generate rouleaux. The species of origin of erythrocytes in rouleaux was determined by fluorescence microscopy. Erythrocytes from different species segregated into independent rouleaux. However, fluorescent and non-fluorescent erythrocytes from one individual were mixed randomly in rouleaux. These results confirm, using a novel experimental approach, previous observations of Sewchand & Canham [(1976) Can. J. Physiol. Pharmacol. 54, 437-442]. Since rouleaugenic agents are not species-specific, under the 'agglomerin' hypothesis of rouleau formation they would be expected to form bridges between cells from different species. It follows that either the agglomerin hypothesis is incorrect, or additional species-specific surface components are involved in the aggregation of agglomerin-cross-bridged cells.


Protein synthesis during fungal spore germination. IV. Transfer ribonucleic acid from germinated and ungerminated spores.
Transfer ribonucleic acid (tRNA) fractions isolated from germinated and ungerminated spores of Botryodiplodia theobromae and Rhizopus stolonifer had acceptor activity for all 20 amino acids commonly found in protein, when tested with an enzyme fraction from germinated spores. Accordingly, it is unlikely that the absence of tRNA for a particular amino acid limits protein synthesis in fungal spores.


Biology, ecology and distribution of the tick, Haemaphysalis longicornis Neumann (Acari: Ixodidae) in New Zealand.
Haemaphysalis longicornis is the only tick in New Zealand that infests livestock. Throughout its range H. longicornis is exposed to and exhibits tolerance to a wide range of environmental conditions, although it flourishes more in moist, warm-temperate environments. This review examines aspects of the biology, physiology and ecology of H. longicornis that determine its distribution and seasonal activity in New Zealand, based on laboratory and field studies. Examples are also drawn from studies outside New Zealand for comparative purposes, especially in the context of seasonal activity as seen in less temperate latitudes. The tick is able to withstand a wide range of temperature, from its developmental threshold of ∼12°C to nearly 40°C at its lethal limit, but its tolerance of dehydration is less wide, especially in the larva and adult, the former especially being the stage that largely determines suitable biotopes for the tick and its present distributional limits. The importance of H. longicornis to the New Zealand livestock industry has recently increased through the establishment and spread of Theileria orientalis Ikeda among dairy and beef cattle, although the tick has always posed production-limiting problems for cattle, deer and to a lesser extent, sheep. The tick's role as a vector of theileriosis and how aspects of the tick's biology affect the spread and maintenance of this disease are discussed. It is proposed that, of available wildlife hosts, the brown hare with its wide-ranging habits, is an important disseminator of ticks. Currently control of ticks is difficult partly because of their wide host range, overlapping activity periods of stadia, and also because the greater part of their annual cycle is spent on pasture. This means that acaricides alone do not satisfactorily reduce tick populations or provide comprehensive protection to stock, so integrated management combining pasture management with good husbandry and chemical prophylaxis is advocated.


PCR amplification and species determination of microsporidia in formalin-fixed feces after immunomagnetic separation.
The term microsporidia is used to describe several species of opportunistic protozoan parasites. Encephalitozoon intestinalis and Enterocytozoon bieneusi have been found in stools of more than 40% of AIDS patients with diarrhea. Diagnosis of infection with these small protozoans has been difficult, and until recently their occurrence has not been well documented. Formalin is widely used to preserve clinical specimens, but due to the nature of the fixation process, subsequent analysis, especially analysis by the PCR, is difficult. This study evaluated methods used to prepare formalin-fixed fecal specimens for PCR amplification of microsporidial DNA. Two methods were devised to allow PCR detection and subsequent identification of microsporidia in formalin-fixed fecal specimens to the species level. One method involved immunomagnetic separation to concentrate microsporidial spores from fecal specimens. In the second method Chelex resin (Bio-Rad, Hercules, Calif.) was used to remove inhibitory substances, followed by a DNA concentration step. Both methods resulted in reproducible, confirmed detection of microsporidia in formalinized fecal specimens and subsequent species determination by PCR sequencing. The detection sensitivity was two in vitro culture-derived spores (Encephalitozoon intestinalis) for the direct PCR. The reproducible detection sensitivity for DNA amplification from formalin-fixed fecal samples was 200 spores for either the Chelex method or the immunomagnetic bead separation method. Thus, we developed two methods for rapid, inexpensive detection of microsporidial spores in formalin-fixed fecal specimens.


Normal caudate glucose metabolism in persons at risk for Huntington's disease.
Glucose metabolism was examined by positron emission tomographic scanning with F-2-fluoro-2-deoxy-D-glucose in 29 persons at risk for Huntington's disease (HD), 28 age-matched controls, nine patients with stage I, and eight patients with stage II symptomatic HD. Absolute caudate metabolic rates and normalized indexes of caudate metabolism for at-risk persons were normal compared with controls. No at-risk person had caudate indexes outside two SDs of the controls' mean. Caudate metabolism in the earliest HD cases was significantly reduced compared with controls and at-risk persons, but within the 99% confidence levels of both groups. Stage II patients had caudate measures that were significantly depressed compared with those of stage I HD patients. Measurement of caudate glucose hypometabolism is unlikely to be sufficiently sensitive to serve as a presymptomatic marker of heterozygote status, although it will provide a sensitive marker for progressive caudate dysfunction in HD.


The role of combined liver/kidney transplantation in end-stage hepato-renal disease.
The study describes the indications and results of combined liver/kidney transplantation in eight patients suffering from end-stage hepato-renal diseases. The causes of primary renal failure were hyperoxaluria type I (2/8), diabetic nephropathy (2/8), glomerulonephritis (2/8), congenital pyelonephritis (1/8), and polycystic kidneys (1/8). Only five of these patients were on chronic dialysis prior to transplantation. The indication for kidney transplantation in the other three patients was low GFR (< 20 mL/min) and the anticipation of further deterioration of the renal function after liver transplantation as a result of cyclosporine toxicity. The end-stage liver diseases were chronic active hepatitis (4/8) and alcoholic cirrhosis (2/8). There was no evidence for liver failure in two patients undergoing combined transplants for primary hyperoxaluria. The 1-year patient survival rate is 75 per cent, and at that time, kidney and liver function were found to be within normal range. In conclusion, excellent long-term patient survival, as well as kidney and liver graft function, can be achieved in patients suffering from complex end-stage disease of both organs who undergo combined liver and kidney transplantation.


[Incidence of sporadic hepatitis E in Ivory Coast based on still problematic serology].
The first well-documented outbreak of viral hepatitis E in Africa was described in 1986 in Côte d'lvoire. Subsequently, no other outbreaks have been observed in the country. Côte d'lvoire therefore offers an excellent opportunity to evaluate the prevalence of sporadic viral hepatitis E in a country where the frequency of non-A, non-B, non-C viral hepatitis appears to be high. The study was carried out in Abidjan, the most populous city, and involved 111 hospitalized patients suffering from non-A, non-B and presumed non-C acute viral hepatitis. Screening for leptospirosis or a toxic etiology was carried out and the risk of including such patients eliminated. Diagnosis of viral hepatitis A was excluded from the absence of IgM anti-HAV antibodies. Patients with HBsAg and anti-HCV antibodies were not included in the study, although co-infection in asymptomatic HBV carriers or subsequent infection in patients who had recovered from a past HCV infection remained possible. There was a risk that some patients with late appearance of anti-HCV antibodies were included since PCR tests could not be performed. Cytomegalovirus or Epstein-Barr virus was not involved, since no specific IgMs against these viruses were detectable. Large discrepancies between the two commercial enzyme-linked immunosorbent assays (ELISAs) available for serological diagnosis of hepatitis E (Abbott and Genelabs) were observed. Among the 53 sera screened using both tests, only 20 gave positive results in both, and all such sera were confirmed using a domestic immunological test involving inhibition of labelled, well-documented anti-HEV-specific human IgG. Immunological confirmation was obtained for only half of the sera with discordant results in the commercial ELISAs. Full agreement between both commercial tests was observed for only 59% of the sera studied. The minimal incidence of sporadic viral hepatitis E among hospitalized patients in Abidjan with an acute hepatitis was estimated to be 27%.


Disrupted cholinergic modulation can underlie abnormal gamma rhythms in schizophrenia and auditory hallucination.
The pathophysiology of auditory hallucination, a common symptom of schizophrenia, has yet been understood, but during auditory hallucination, primary auditory cortex (A1) shows paradoxical responses. When auditory stimuli are absent, A1 becomes hyperactive, while A1 responses to auditory stimuli are reduced. Such activation pattern of A1 responses during auditory hallucination is consistent with aberrant gamma rhythms in schizophrenia observed during auditory tasks, raising the possibility that the pathology underlying abnormal gamma rhythms can account for auditory hallucination. Moreover, A1 receives top-down signals in the gamma frequency band from an adjacent association area (Par2), and cholinergic modulation regulates interactions between A1 and Par2. In this study, we utilized a computational model of A1 to ask if disrupted cholinergic modulation could underlie abnormal gamma rhythms in schizophrenia. Furthermore, based on our simulation results, we propose potential pathology by which A1 can directly contribute to auditory hallucination.


Chiral surface plasmon-enhanced chiral spectroscopy: principles and applications.
In this review, the development context and scientific research results of chiral surface plasmons (SPs) in recent years are classified and described in detail. First, the principle of chiral SPs is introduced through classical and quantum theory. Following this, the classification and properties of different chiral structures, as well as the superchiral near-field, are introduced in detail. Second, we describe the excitation and propagation properties of chiral SPs, which lays a good foundation for the application of chiral SPs and their chiral spectra in various fields. After that, we have summarized the recent research results of chiral SPs and their applications in the areas of biology, two-dimensional materials, topological materials, analytical chemistry, chiral sensing, chiral optical force, and chiral light detection. Chiral SPs are a new type of optical phenomenon that have useful application potential in many fields and are worth exploring.


Socioeconomic differences in the risk profiles of susceptibility and ever use of tobacco among Indian urban youth: a latent class approach.
To empirically determine the socioeconomic differences in risk profiles of susceptibility and ever use of tobacco among adolescents in India and to investigate the association between the risk profiles and the psychosocial factors for tobacco use. Students in 16 private (higher socioeconomic status [SES]; n = 4,489) and 16 government (lower SES; n = 7,153) schools in two large cities in India were surveyed about their tobacco use and related psychosocial factors in 2004. Latent class analysis was used to identify homogenous, mutually exclusive typologies existing within the data. Overall, 3 and 4 latent classes of susceptibility and ever use of tobacco best described students in higher- and lower- SES schools, respectively. Profiles with various combinations of susceptibility and ever use of tobacco were differentially related to psychosocial factors, with lower- SES students being more vulnerable to increased levels of tobacco use than higher- SES students. Acknowledging the multiple dimensions of tobacco use behaviors and identifying constellations of risk behaviors will enable more accurate understanding of etiological processes and will provide information for refining and targeting preventive interventions. Additionally, identifying the socioeconomic differences in susceptibility and ever use risk profiles and their psychosocial correlates will enable policy makers to address these inequities through improved allocation of resources.


Monitoring the long-term spatiotemporal transmission dynamics and ecological surveillance of multidrug-resistant Salmonella enterica serovar Goldcoast: A multicenter genomic epidemiology study.
The emergence of multidrug-resistant Salmonella enterica serovar Goldcoast poses a significant threat to the effective treatment and control of salmonellosis within the ecological environment. Here, we conducted a genomic epidemiological study delineate the global dissemination scenarios of the multidrug-resistant S. Goldcoast originated from 11 countries for over 20 years. The population structure and evolutionary history of multidrug-resistant S. Goldcoast was investigated through phylogenomic and long-term spatiotemporal transmission dynamic analysis. ST358 and ST2529 are the predominant lineages of S. Goldcoast. Multidrug-resistant S. Goldcoast strains have mainly been identified in the ST358 lineage from human and the ST2529 lineage from livestock. ST358 S. Goldcoast was estimated to have emerged in the United Kingdom in 1969, and then spread to China, with both countries serve as centers for the global dissemination of the ST358 lineage. After its emergence and subsequent spread in Chinese clinical and environmental samples, occasional instances of this lineage have been reported in Canada, the United Kingdom, and Ireland. Clonal transmission of ST358 and ST2529 S. Goldcoast have occurred not only on an international and intercontinental scale but also among clinical, environmental and livestock samples. These data indicated that international circulation and local transmission of S. Goldcoast have occurred for over a decade. Continued surveillance of multidrug-resistant S. Goldcoast from a global "one-health" perspective is urgently needed to facilitate monitoring the spread of the antimicrobial resistant high-risk clones.


Hydrogen sulfide gas poisoning in fish garbage room: A report of a fisherman.
We report the case of a fisherman who was exposed to high concentrations of hydrogen sulfide (H2S) gas from the fish garbage room. The patient survived and was discharged with full recovery from the hospital. H2S is a colourless, foul smelling and highly toxic gas next to carbon monoxide, which causes inhalation death. It is a by-product of various industrial processes particularly involves exposure from agriculture, petrochemical industry and organic matter decomposition from sewage processing. It is a by-product of H2S has been referred as the "knock down gas" because inhalation of high concentrations can cause immediate loss of consciousness and death. Although early use of amyl nitrate and hyperbaric oxygen shows some benefit in literature, supportive care remains the mainstay of treatment. Emergency physicians and pre-hospital care personnel are not very familiar with such exposure due to its rarity. This becomes more relevant in the developing world settings where there are rising concerns about the unsafe exposure to hazardous chemicals and its impact on human health. Emergency physicians working in Pakistan should be aware of this entity especially in regard to fishermen presenting to the Emergency Department with such a clinical presentation and its toxic manifestations. This incident also illustrates the need of enforcement of health and safety regulations in the fishing industry.


Elizabethkingia anophelis outer membrane vesicles as a novel vaccine candidate against infection: insights into immune response and potential for passive immunity.
Elizabethkingia anophelis, a Gram-negative pathogen, causes infections such as bacteraemia, pneumonia, and neonatal meningitis. The pathogen resists most antimicrobial classes, making novel approaches urgently needed. In natural settings, Gram-negative bacteria secrete outer membrane vesicles (OMVs) that carry important molecules in the bacterial life cycle. These OMVs are enriched with proteins involved in virulence, survival, and carbohydrate metabolism, making them a promising source for vaccine development against the pathogen. This study investigated the efficacy of imipenem-induced OMVs (iOMVs) as a vaccine candidate against E. anophelis infection in a mouse pneumonia model. Mice immunized with iOMVs were completely protected during lethal-dose challenges. Passive immunization with hyperimmune sera and splenocytes conferred protection against lethal pneumonia. Further investigation is needed to understand the mechanisms underlying the protective effects of iOMV-induced passive immunity, such as the action on specific antibody subclasses or T cell subsets.


From coastal to global: The transnational flow of Ayurveda and its relevance for Indo-African linkages.
Driven by long-standing ties with India, and intertwined with global market interests, a growing influx of materia medica from South Asia is currently emerging in East Africa. To compete at a global level and framed within the language of 'South-South cooperation for mutual benefit', India presents itself as an appropriate exporter of medical products suitable for African clientele. The expansion of India's medical sector into Africa is particularly relevant for Ayurvedic pharmaceuticals. Ayurveda's diaspora into Africa exemplifies the emergence of new health interventions and medical assemblages in a transnationally interconnected world and implies innovative coalitions involved in the complex promotion of local/Global Health industries. By tracking the flow of Ayurvedic pharmaceuticals to East Africa, this paper aims to contribute to the understanding of medical practices as they are configured by the dynamics of global mobility. It interrogates the extent to which the industrialisation of Ayurveda occupies a strategic position in Indo-African discursive practices and the creation of new market opportunities. Moreover, it explores the ways in which South-South alliances between Indian and African actors produce (new) solidarities, but also hierarchies and power imbalances. Special attention will be directed to the political-economic implications of the expansion of transnational markets.


The rapid alteration by tri-iodo-L-thyronine in vivo of both the ADP/O ratio and the apparent H+/O ratio in hypothyroid-rat liver mitochondria.
Mitochondria from the livers of thyroidectomized rats have a lowered ADP/O ratio, which can be restored to normal within 15 min after intravenous injection of a near-physiological dose of tri-iodothyronine. Thyroidectomy lowered the measured delta pH, which appears to be compensated by a rise (not statistically significant) in the membrane potential, so that the protonmotive force is unaltered. A simple simulation technique is described for use in estimating H+/O ratios by the oxygen-pulse technique, which circumvents the problem that this ratio can be seriously underestimated because of re-uptake of protons from the bulk phase by the mitochondria before their expulsion is complete. By this procedure the H+/O ratio of hypothyroid mitochondria is shown to be lowered by the same factor as the ADP/O ratio, and both these ratios are very rapidly restored in parallel by hormone administration. Although these findings could be consistent with a proposal that tri-iodothyronine rapidly modulates by some mechanism the efficiency of the respiratory-chain-linked proton pumps, the kinetic properties of the proton exchange suggest that the bulk-phase protons measured may not reflect faithfully those that drive the ATP synthetase.


Sex determination in the social amoeba Dictyostelium discoideum.
The genetics of sex determination remain mysterious in many organisms, including some that are otherwise well studied. Here we report the discovery and analysis of the mating-type locus of the model organism Dictyostelium discoideum. Three forms of a single genetic locus specify this species' three mating types: two versions of the locus are entirely different in sequence, and the third resembles a composite of the other two. Single, unrelated genes are sufficient to determine two of the mating types, whereas homologs of both these genes are required in the composite type. The key genes encode polypeptides that possess no recognizable similarity to established protein families. Sex determination in the social amoebae thus appears to use regulators that are unrelated to any others currently known.


Georgia plan for education in long-term care.
A successful program for teaching long-term care to students of the Medical College of Georgia is described. Five years of experience have proved its importance in medical education. Such a program could be instituted in community hospitals or in other medical colleges. Improvement in the quality of long-term care is a most pressing need today, and the education of those who will give that care is essential.


Investigation of minor species Candida africana, Candida stellatoidea and Candida dubliniensis in the Candida albicans complex among Yaoundé (Cameroon) HIV-infected patients.
Minor species of the Candida albicans complex may cause overestimation of the epidemiology of C. albicans, and misidentifications could mask their implication in human pathology. Authors determined the occurrence of minor species of the C. albicans complex (C. africana, C. dubliniensis and C. stellatoidea) among Yaoundé HIV-infected patients, Cameroon. Stool, vaginal discharge, urine and oropharyngeal samples were analysed by mycological diagnosis. Isolates were identified by conventional methods and mass spectrometry (MS; carried out by the matrix-assisted laser desorption-ionisation time-of-flight MS protocol). Candida albicans isolates were thereafter submitted to the PCR amplification of the Hwp1 gene. The susceptibility of isolates to antifungal drugs was tested using the Clinical and Laboratory Standards Institute M27-A3 protocol. From 115 C. albicans obtained isolates, neither C. dubliniensis nor C. stellatoidea was observed; two strains of C. africana (422PV and 448PV) were identified by PCR electrophoretic profiles at 700 bp. These two C. africana strains were vaginal isolates. The isolate 448PV was resistant to ketoconazole at the minimal inhibitory concentration of 2 μg ml(-1), and showed reduced susceptibility to amphotericin B at 1 μg ml(-1). This first report on C. africana occurrence in Cameroon brings clues for the understanding of the global epidemiology of this yeast as well as that of minor species of the C. albicans complex.


When Harry met Barry, and other stories: A partner's influence on relationships in back pain care.
This study forms part of a longitudinal investigation of pain, disability and health care use in primary care low back pain consulters. Sixteen purposively sampled patients and their health care professionals were interviewed about experiences with back pain and their therapeutic relationships. This case study draws on the accounts of one patient, his wife, and three health care professionals and explores the role of the informal carer in back pain care. The interview with the patient and his wife highlights the dynamics of a co-constructed narrative of back pain. The joint narrative is fundamentally supportive of the patient's condition, yet his wife's preference for a proactive approach to health care is undermined by the patient's unquestioning respect for health professionals. In addition, the patient's limited expression-of his suffering and his feelings regarding care received-results in less beneficial care where opportunities remain unfulfilled and problems unresolved. His wife's role as narrator of his pain provokes different reactions from health professionals and these are discussed. Analysis reveals a positive and mediating role for informal carers within the provision of health care. However, the construction of the patient's limited expression in opposition to his wife as an 'expert carer' raises issues around these roles in the therapeutic encounter that require further exploration. To use supportive relationships effectively there is a need to better understand the interplay between the patient and carer roles, how these roles are negotiated in the health care consultation, and the possible contradictions that this poses.


Glycogen metabolism in the liver of the developing rat.
1. The total activity of glycogen synthease increased 20-fold from day 17 of gestation to birth at day 22, with a further increase of 18% in the 24h after birth. Active synthase (I) rose 45-fold to a maximum at day 21, fell 40% before birth, and then increased by a similar amount 24h after birth. The fraction of synthase in the active form correlated very well with the deposition of glycogen in the liver. 2. Total phosphorylase had a similar developmental pattern of total synthease with an 18-fold increase from day 17 to day 22. The appearance of active phosphorylase showed a lag-period compared with total phosphorylase and did not increase significantly until day 20. The fraction of phosphorylase in the active form did not correlate at all with glycogen deposition or mobilization. 3. There was a close relationshp between the ratio of phosphorylase a/synthase I and the glycogen content of the liver. An increase or decrease in this ratio would result in glycogenolysis of glycogenesis respectively. 4. It is postulated that a cycle between the two enzymes under basal conditions could exist which permits a continuous turnover of glycogen. Such a system would explain why active phosphorylase is always seen, even under conditions of net glycogen synthesis. The differences in hormone sensitivity of synthase and phosphorylase would also be accounted for as only one enzyme would have to respond acutely to hormonal influences.


Soluble gC1qR is an autocrine signal that induces B1R expression on endothelial cells.
Bradykinin (BK) is one of the most potent vasodilator agonists known and belongs to the kinin family of proinflammatory peptides. BK induces its activity via two G protein-coupled receptors: BK receptor 1 (B1R) and BK receptor 2. Although BK receptor 2 is constitutively expressed on endothelial cells (ECs), B1R is induced by IL-1β. The C1q receptor, receptor for the globular heads of C1q (gC1qR), which plays a role in BK generation, is expressed on activated ECs and is also secreted as soluble gC1qR (sgC1qR). Because sgC1qR can bind to ECs, we hypothesized that it may also serve as an autocrine/paracrine signal for the induction of B1R expression. In this study, we show that gC1qR binds to ECs via a highly conserved domain consisting of residues 174-180, as assessed by solid-phase binding assay and deconvolution fluorescence microscopy. Incubation of ECs (24 h, 37 °C) with sgC1qR resulted in enhancement of B1R expression, whereas incubation with gC1qR lacking aa 174-180 and 154-162 had a diminished effect. Binding of sgC1qR to ECs was through surface-bound fibrinogen and was inhibited by anti-fibrinogen. In summary, our data suggest that, at sites of inflammation, sgC1qR can enhance vascular permeability by upregulation of B1R expression through de novo synthesis, as well as rapid translocation of preformed B1R.


Metabolic disturbances and synovial joint responses in osteoarthritis.
Previously held views that the pathogenesis of idiopathic osteoarthritis (OA) originated in the synovial joint and was not influenced by systemic metabolic disturbances in the patient is inconsistent with recent data demonstrate skewing of the growth hormone/insulin-like growth factor-1 axis in the symptomatic OA patient. In light of this novel information, the role of growth hormone and insulin-like growth factor-1 in the pathogenesis and progression of OA requires further definition. In male patients with OA, the red blood cell sequesters more growth hormone than an aged-matched control group. Thus, this growth hormone "depot" may provide a mechanism for removal of "toxic" levels of growth hormone from the circulation. Storage of "excess" growth hormone in red cells may reduce the inflammatory or otherwise undesirable "toxic" actions of GH. In some patients, serum growth hormones levels may exceed three-times the average value considered normal. These "episodic" variations in growth hormone levels may play a significant role in the elevated levels of serum growth hormone seen in the OA patient. The connection between elevated growth hormone and decreased insulin-like growth factor-1 levels and the defined cartilage anabolic and catabolic pathways defined in in vitro assays of articular cartilage derived from the OA patients remain to be more precisely defined. However, the dampened insulin-like growth factor-1 response in OA coupled with elevated cartilage extracellular matrix degradation (mediated by metalloproteinases) and depressed compensatory biosynthesis (induced and perpetuated by the presence of cytokines such as interleukin-1 and tumor necrosis factor-alpha) may, in fact, act synergistically to suppress normal cartilage repair mechanisms thus resulting in progressive destructive lesions of the cartilage and bone.


A Highly Stabilized Phosphonium Ylide that Forms Supramolecular Dimers in Solution and the Solid State.
This work describes the unexpected formation of an unusual phosphonium ylide when attempting the synthesis of bisphosphonium pyromellitic diimides. Spectroscopic and crystallographic characterization reveals that a combination of π-π and CH⋅⋅⋅O interactions leads to supramolecular homodimerization of the ylide both in solution and in the solid-state. Only strong acids are able to protonate the ylide, which is otherwise inert to Wittig and alkylation reactivity. Taken together, these observations indicate that this compound is one of the most highly stabilized phosphonium ylides discovered to date.


Platelets contribute to postnatal occlusion of the ductus arteriosus.
The ductus arteriosus (DA) is a fetal shunt vessel between the pulmonary artery and the aorta that closes promptly after birth. Failure of postnatal DA closure is a major cause of morbidity and mortality particularly in preterm neonates. The events leading to DA closure are incompletely understood. Here we show that platelets have an essential role in DA closure. Using intravital microscopy of neonatal mice, we observed that platelets are recruited to the luminal aspect of the DA during closure. DA closure is impaired in neonates with malfunctioning platelet adhesion or aggregation or with defective platelet biogenesis. Defective DA closure resulted in a left-to-right shunt with increased pulmonary perfusion, pulmonary vascular remodeling and right ventricular hypertrophy. Our findings indicate that platelets are crucial for DA closure by promoting thrombotic sealing of the constricted DA and by supporting luminal remodeling. A retrospective clinical study revealed that thrombocytopenia is an independent predictor for failure of DA closure in preterm human newborns, indicating that platelets are likely to contribute to DA closure in humans.


Novel lipid-lowering properties of Vaccinium myrtillus L. leaves, a traditional antidiabetic treatment, in several models of rat dyslipidaemia: a comparison with ciprofibrate.
Vaccinium myrtillus L. (blueberry) leaf infusions are traditionally used as a folk medicine treatment of diabetes. To further define this therapeutical action, a dried hydroalcoholic extract of the leaf was administered orally to streptozotocin-diabetic rats for 4 days. Plasma glucose levels were consistently found to drop by about 26% at two different stages of diabetes. Unexpectedly, plasma triglyceride (TG) were also decreased by 39% following treatment. Subsequent to the latter observation, possible lipid-lowering properties of the extract were investigated on other models of hyperlipidaemia and ciprofibrate, a well-established hypolipidaemic drug, was used as a reference compound. Both drug reduced TG levels of rats on hyperlipidaemic diet in a dose-dependent fashion. When administered at single doses over the same experimental period, blueberry and ciprofibrate were effective in lowering TG concentrations in ethanol-treated normolipidaemic animals and in genetically hyperlipidaemic Yoshida rats. Unlike ciprofibrate, however, blueberry failed to prevent the rise in plasma TG elicited by fructose and did not affect free fatty acid levels in any of the above experimental conditions. In rats treated with Triton WR-1339, blueberry feeding induced an hypolipidaemic activity one hour after injection but proved to be ineffective at later time points, thus suggesting that its hypolipidaemic action may reflect improved TG-rich lipoprotein catabolism. In addition, ciprofibrate and the extract were tested for antithrombotic activity using a collagen-triggered model of venous thrombosis in diabetic and Yoshida rats. Only ciprofibrate, however, significantly reduced thrombus formation in diabetics, possibly because of its effects on free fatty acid metabolism, whereas no effect was observed in Yoshida rats. In conclusion, the present findings indicate that active consituent(s) of Vaccinium myrtillus L. leaves may prove potentially useful for treatment of dyslipidaemiae associated with impaired TG-rich lipoprotein clearance.


Differential effects of complement activation products c3a and c5a on cardiovascular function in hypertensive pregnant rats.
Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia-induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension. On gestational day (GD) 14, rats underwent sham surgery or vascular clip placement on ovarian arteries and abdominal aorta (RUPP). Rats were treated once daily with the C5a receptor antagonist (C5aRA), PMX51 (acetyl-F-[Orn-P-(D-Cha)-WR]), the C3a receptor antagonist (C3aRA), SB290157 (N(2)-[(2,2-diphenylethoxy)acetyl]-l-arginine), or vehicle from GD 14-18. Both the C3aRA and C5aRA attenuated placental ischemia-induced hypertension without affecting the decreased fetal weight or decreased concentration of free circulating vascular endothelial growth factor (VEGF) also present in this model. The C5aRA, but not the C3aRA, attenuated placental ischemia-induced increase in heart rate and impaired endothelial-dependent relaxation. The C3aRA abrogated the acute pressor response to C3a peptide injection, but it also unexpectedly attenuated the placental ischemia-induced increase in C3a, suggesting nonreceptor-mediated effects. Overall, these results indicate that both C3a and C5a are important products of complement activation that mediate the hypertension regardless of the reduction in free plasma VEGF. The mechanism by which C3a contributes to placental ischemia-induced hypertension appears to be distinct from that of C5a, and management of pregnancy-induced hypertension is likely to require a broad anti-inflammatory approach.


Impact of organic nutrient load on biomass accumulation, feed channel pressure drop increase and permeate flux decline in membrane systems.
The influence of organic nutrient load on biomass accumulation (biofouling) and pressure drop development in membrane filtration systems was investigated. Nutrient load is the product of nutrient concentration and linear flow velocity. Biofouling - excessive growth of microbial biomass in membrane systems - hampers membrane performance. The influence of biodegradable organic nutrient load on biofouling was investigated at varying (i) crossflow velocity, (ii) nutrient concentration, (iii) shear, and (iv) feed spacer thickness. Experimental studies were performed with membrane fouling simulators (MFSs) containing a reverse osmosis (RO) membrane and a 31 mil thick feed spacer, commonly applied in practice in RO and nanofiltration (NF) spiral-wound membrane modules. Numerical modeling studies were done with identical feed spacer geometry differing in thickness (28, 31 and 34 mil). Additionally, experiments were done applying a forward osmosis (FO) membrane with varying spacer thickness (28, 31 and 34 mil), addressing the permeate flux decline and biofilm development. Assessed were the development of feed channel pressure drop (MFS studies), permeate flux (FO studies) and accumulated biomass amount measured by adenosine triphosphate (ATP) and total organic carbon (TOC). Our studies showed that the organic nutrient load determined the accumulated amount of biomass. The same amount of accumulated biomass was found at constant nutrient load irrespective of linear flow velocity, shear, and/or feed spacer thickness. The impact of the same amount of accumulated biomass on feed channel pressure drop and permeate flux was influenced by membrane process design and operational conditions. Reducing the nutrient load by pretreatment slowed-down the biofilm formation. The impact of accumulated biomass on membrane performance was reduced by applying a lower crossflow velocity and/or a thicker and/or a modified geometry feed spacer. The results indicate that cleanings can be delayed but are unavoidable.


Binding site characterization - similarity, promiscuity, and druggability.
The elucidation of non-obvious binding site similarities has provided useful indications for the establishment of polypharmacology, the identification of potential off-targets, or the repurposing of known drugs. The concept underlying all of these approaches is promiscuous binding which can be analyzed from a ligand-based or a binding site-based perspective. Herein, we applied methods for the automated analysis and comparison of protein binding sites to study promiscuous binding on a novel dataset of sites in complex with ligands sharing common shape and physicochemical properties. We show the suitability of this dataset for the benchmarking of novel binding site comparison methods. Our investigations also reveal promising directions for further in-depth analyses of promiscuity and druggability in a pocket-centered manner. Drawbacks concerning binding site similarity assessment and druggability prediction are outlined, enabling researchers to avoid the typical pitfalls of binding site analyses.


Acupuncture for paroxysmal and persistent atrial fibrillation: An effective non-pharmacological tool?
In Traditional Chinese Medicine, stimulation of the Neiguan spot has been utilized to treat palpitations and symptoms related to different cardiovascular diseases. We evaluated whether acupuncture might exert an antiarrhythmic effect on patients with paroxysmal or persistent atrial fibrillation (AF). Two sets of data are reviewed. The first included patients with persistent AF who underwent electrical cardioversion to restore sinus rhythm. The second included patients with symptomatic paroxysmal AF. All subjects had normal ventricular function. Acupuncture treatment consisted of 10 acupuncture sessions on a once a week basis with puncturing of the Neiguan, Shenmen and Xinshu spots. In patients with persistent AF, the recurrence rate after acupuncture treatment was similar to that observed in patients on amiodarone, but significantly smaller than that measured after sham acupuncture treatment or in the absence of any antiarrhythmic drugs. In a small group of patients with paroxysmal AF, acupuncture resulted in a significant reduction in the number and duration of symptomatic AF episodes. In conclusion, we observed that acupuncture of the Neiguan spot was associated with an antiarrhythmic effect, which was evident in patients with both persistent and paroxysmal AF. These preliminary data, observed in 2 small groups of AF patients, need to be validated in a larger population but strongly suggest that acupuncture may be an effective non-invasive and safe antiarrhythmic tool in the management of these patients.


Review: a century of confusion; which bladder for accurate blood pressure measurement?
This paper reviews the literature on a century-old controversy relating to the error that may be introduced to blood pressure (BP) measurement by using a cuff with a bladder of inappropriate dimensions for the arm for which it is intended. The use of cuffs containing inappropriate bladders is a serious source of error which must inevitably lead to incorrect diagnosis in practice, and erroneous conclusions in hypertension research. There is unequivocal evidence that either too narrow or too short a bladder (undercuffing) will cause overestimation of BP and there is growing evidence that too wide or too long a bladder (overcuffing) may cause underestimation of BP. Undercuffing has the effect in clinical practice of overdiagnosing hypertension and overcuffing leads to hypertensive subjects being diagnosed as normotensive. Either eventuality has serious implications for the epidemiology of hypertension and clinical practice. A detailed review of the literature permits a definitive statement on bladder dimensions for a given arm circumference and clearly indicates that substantial error is caused by the use of inappropriate cuffs. On the basis of this review and aware of the advances in cuff design, the features for an 'Adult Cuff', which would be applicable to all adult arms, are proposed in this paper, and it is hoped that manufacturers may take up the challenge of producing such a cuff.


Development of a universal microarray based on the ligation detection reaction and 16S rrna gene polymorphism to target diversity of cyanobacteria.
The cyanobacteria are photosynthetic prokaryotes of significant ecological and biotechnological interest, since they strongly contribute to primary production and are a rich source of bioactive compounds. In eutrophic fresh and brackish waters, their mass occurrences (water blooms) are often toxic and constitute a high potential risk for human health. Therefore, rapid and reliable identification of cyanobacterial species in complex environmental samples is important. Here we describe the development and validation of a microarray for the identification of cyanobacteria in aquatic environments. Our approach is based on the use of a ligation detection reaction coupled to a universal array. Probes were designed for detecting 19 cyanobacterial groups including Anabaena/Aphanizomenon, Calothrix, Cylindrospermopsis, Cylindrospermum, Gloeothece, halotolerants, Leptolyngbya, Palau Lyngbya, Microcystis, Nodularia, Nostoc, Planktothrix, Antarctic Phormidium, Prochlorococcus, Spirulina, Synechococcus, Synechocystis, Trichodesmium, and Woronichinia. These groups were identified based on an alignment of over 300 cyanobacterial 16S rRNA sequences. For validation of the microarrays, 95 samples (24 axenic strains from culture collections, 27 isolated strains, and 44 cloned fragments recovered from environmental samples) were tested. The results demonstrated a high discriminative power and sensitivity to 1 fmol of the PCR-amplified 16S rRNA gene. Accurate identification of target strains was also achieved with unbalanced mixes of PCR amplicons from different cyanobacteria and an environmental sample. Our universal array method shows great potential for rapid and reliable identification of cyanobacteria. It can be easily adapted to future development and could thus be applied both in research and environmental monitoring.


Bayesian gene/species tree reconciliation and orthology analysis using MCMC.
Comparative genomics in general and orthology analysis in particular are becoming increasingly important parts of gene function prediction. Previously, orthology analysis and reconciliation has been performed only with respect to the parsimony model. This discards many plausible solutions and sometimes precludes finding the correct one. In many other areas in bioinformatics probabilistic models have proven to be both more realistic and powerful than parsimony models. For instance, they allow for assessing solution reliability and consideration of alternative solutions in a uniform way. There is also an added benefit in making model assumptions explicit and therefore making model comparisons possible. For orthology analysis, uncertainty has recently been addressed using parsimonious reconciliation combined with bootstrap techniques. However, until now no probabilistic methods have been available. We introduce a probabilistic gene evolution model based on a birth-death process in which a gene tree evolves 'inside' a species tree. Based on this model, we develop a tool with the capacity to perform practical orthology analysis, based on Fitch's original definition, and more generally for reconciling pairs of gene and species trees. Our gene evolution model is biologically sound (Nei et al., 1997) and intuitively attractive. We develop a Bayesian analysis based on MCMC which facilitates approximation of an a posteriori distribution for reconciliations. That is, we can find the most probable reconciliations and estimate the probability of any reconciliation, given the observed gene tree. This also gives a way to estimate the probability that a pair of genes are orthologs. The main algorithmic contribution presented here consists of an algorithm for computing the likelihood of a given reconciliation. To the best of our knowledge, this is the first successful introduction of this type of probabilistic methods, which flourish in phylogeny analysis, into reconciliation and orthology analysis. The MCMC algorithm has been implemented and, although not yet being in its final form, tests show that it performs very well on synthetic as well as biological data. Using standard correspondences, our results carry over to allele trees as well as biogeography.


Retrospective analysis of concurrent chemoradiation with the combination of bleomycin, ifosfamide and cisplatin (BIP) for uterine cervical cancer.
Combination chemotherapy consisting of bleomycin, ifosfamide, and ciplatin (BIP) is recognized as one of the most effective chemotherapies for uterine cervical cancer. However, there have been no reports that evaluate concurrent use of radiation with BIP. The objective of this study was to evaluate the toxicity and response of the combination of BIP concurrent with radiation in patients with squamous cell carcinoma of the uterine cervix. Eligibility criteria included patients who underwent radical hysterectomy (Type III hysterectomy) as a primary treatment and revealed lymph node metastases or deep myometrial invasion (stage IB and IIA) and patients who were previously untreated (stage IIB-IV). All of the patients had biopsy-proven squamous cell carcinoma of the uterine cervix. The patients received three courses of BIP chemoradiation, and the response and toxicity were evaluated. From January 2000 to December 2003, 30 patients met study eligibility criteria. All but three patients completed 3 courses of planned chemotherapy. The frequency of severe (grade 3 and 4) toxicity was as follows: anemia, 46.7%; neutrocytopenia, 73.3%; thrombocytopenia, 16.7%; and nausea and vomiting, 23.3%. Among 30 patients, 22 cases were evaluated for response. Complete response was achieved in 16 (72.7%) of patients, with a response rate of 90.9%. In conclusion, BIP chemoradiation seems to be superior to previously reported chemoradiation regimens, and has a potential as an optimal combination chemotherapy concurrent with radiation.


A glutathione S-transferase and a cytochrome P450 may confer cyhalofop-butyl resistance in Leptochloa chinensis (L.) Nees.
Leptochloa chinensis (L.) Nees is a troublesome weed across China in rice fields, and a suspected L. chinensis resistant population (R) that has survived the recommended field dose of cyhalofop-butyl was collected in a rice field of Hunan Province, China. In this study, we aimed to determine the acetyl-CoA carboxylase-inhibiting herbicide resistance profile of this R population and to investigate its mechanisms of resistance to cyhalofop-butyl. Compared with the susceptible population (S), the R population was confirmed to be 18.9-, 3.2-, 4.1-, 3.6- and 5.8- fold resistant to the APP herbicides cyhalofop-butyl, haloxyfop-P-methyl, clodinafop-propargyl, metamifop and fenoxaprop-P-ethyl, respectively. ACCase gene sequencing analysis revealed no known resistance mutations for TSR in the R population. Pretreatment with the glutathione S-transferase (GST) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) and cytochrome P450 (CYP450) inhibitor malathion reversed resistance to cyhalofop-butyl. The GST gene GSTU1 and CYP450 gene CYP707A5 were constitutively upregulated in the R population according to RNA-seq analysis and RT-qPCR verification. The molecular docking results indicated a good affinity of the active site for five APP herbicides with GSTU1 and CYP707A5. This study shows that the GSTU1 and CYP707A5 genes expressed highly in the R population may be responsible for cyhalofop-butyl resistance in L. chinensis.


Review of Viral Encephalitis Cases Seen at a Tertiary Care Center in Turkey: Focus on Herpes Simplex Type 1.
The objective of this study was to determine the incidence of herpes simplex encephalitis (HSE), known as the most common, potentially mortal, and treatable cause of sporadic encephalitis, in a sample Turkish population. The demographic, clinical, laboratory, imaging, electrophysiology, and polymerase chain reaction (PCR) DNA results of patients examined with a pre-diagnosis of encephalitis were retrospectively examined. A total of 68 patients were included in the study. The most common presenting symptom was altered behavior (67.6%), while temporal T2 hyperintensity was determined in the magnetic resonance imaging (MRI) of 27.9% of the patients and electroencephalography (EEG) abnormalities were determined in 66.2% of the patients. Lymphocytic pleocytosis was determined in the cerebrospinal fluid (CSF) in 35 patients. Fifty-seven patients had been diagnosed with viral encephalitis, 3 with bacterial meningitis, 3 with tuberculous meningitis, 2 with sporadic Creutzfeld-Jakob disease, 2 with acute disseminating encephalomyelitis, and 1 with Brucella encephalitis. Seven (10.2%) cases of viral encephalitis were found to be positive for herpes simplex virus (HSV) DNA by PCR. Viral encephalitis is the most common cause of infectious encephalitis; however, other atypical causes should also be noted. Negative PCR results for HSV DNA should not exclude the need for antiviral therapy in patients with a strong pre-diagnosis of HSE because diagnostic modalities, including PCR, may fail in acute settings and HSE remains the sole treatable cause of infectious encephalitis.


Poly[dimethyl-ammonium [tris-(μ(2)-formato-κO:O')cadmate(II)]].
In the coordination polymer, {(C(2)H(8)N)[Cd(CHO(2))(3)]}(n), the Cd(II) atom lies on a special position of site symmetry in an octa-hedron of O atoms. The formate unit bridges the metal atoms, generating a three-dimensional polyanionic framework. The disordered cations occupy the cavities within the framework, and are N-H⋯O hydrogen-bonded to the framework.


Image-based evaluation of tumor response to treatment: where is radiology today?
Oncological patient care requires long term follow-up in order to estimate effectiveness of existing and new treatment choices. Image-based assessment of whole body tumour burden is commonly used for that purpose. The WHO response criteria were established in 1979 proposing bi-dimensional tumor measurements. New RECIST guidelines appeared in 2000 relying on only the longest diameter (uni-dimensional) measurements. Obviously, a change in tumour size is only one potential surrogate for therapy response which not necessarily reflects the biologic activity of the tumour or the effect of particular therapy. Thus, the evaluation of biological, metabolic or molecular properties of a tumor and its changes might be an attractive means to assess the response to therapy sensitively and early.


Extinction requires new RNA and protein synthesis and the soma of the cell right pedal dorsal 1 in Lymnaea stagnalis.
Lymnaea stagnalis were operantly conditioned to not perform aerial respiratory behavior. This learned response was subsequently extinguished. Here, we show that spaced extinction training is more effective than massed extinction training, in addition to the occurrence of spontaneous recovery. We also find evidence of a critical period within the first hour after extinction training in which new RNA and protein synthesis must occur for a memory of extinction training to be established. The memory for extinction training can also be extended using cooling and by preventing aerial respiration from occurring after extinction training. In addition, we demonstrate that memory formation of extinction training requires the soma of the cell right pedal dorsal 1, a cell that we have previously shown to be necessary for long-term memory consolidation and reconsolidation. This finding implies that the events that lead to the formation of extinction memory occur in the same cell that is responsible for long-term memory of operant conditioning. All of these data are consistent with the hypothesis that, during extinction, a new associative memory is being formed and that this new memory covers up, but does not abolish, the "old" memory.


A morphologic and permeability study of luminal smooth muscle cells after arterial injury in the rat.
In the carotid air drying model of arterial endothelial injury in the stressed rat, endothelium does not always regenerate over the zone of intimal thickening; instead, a layer of modified smooth muscle cells appears to form a temporary luminal surface. We examined the properties of these luminal smooth muscle cells in injured right carotid arteries from stressed rats at intervals up to 2 months by light, scanning electron, and transmission electron microscopy. Before perfusion fixation, selected animals were given injections of Evans blue dye, ferritin, or horseradish peroxidase. Unlike adjacent endothelium, the luminal smooth muscle cells most closely resembled neighboring intimal smooth muscle cells, lacked morphologic characteristics of normal endothelium, and did not stain with rabbit antibody to rat factor viii. Unlike normal mature endothelium, this layer did not exclude horseradish peroxidase, Evans blue, or ferritin. These data demonstrate that a nonthrombogenic layer composed of modified smooth muscle cells can appear at the luminal surface of a zone of injury-induced myointimal thickening; however, this layer does not form a permeability barrier to large molecules.


Neural tube defects, micronutrient deficiencies, and Helicobacter pylori: a new hypothesis.
Previous findings for the Texas Neural Tube Defects Project suggested that while maternal access to nutrients is adequate, bioavailability of nutrients to the fetus is compromised in NTD-affected pregnancies. Helicobacter pylori could cause nutrient loss to the fetus. Folate, B12, and ferritin are depleted in H. pylori infection; these same deficiencies are related to NTD risk. Using H. pylori IgG ELISA Test System, we tested for H. pylori serum antibodies in participants in the population-based case-control study component of the Texas Neural Tube Defect Project conducted along the Texas-Mexico border. Case-women had pregnancies affected by NTD (anencephalus, spina bifida, encephalocele) and resided and delivered in one of the 14 Texas-Mexico border counties from 1995 through 2000. Control-women were study area residents delivering normal live births during the same period. Of 225 case- and 378 control-women, 103 cases and 156 controls provided questionnaire and H. pylori antibody data. H. pylori seropositivity was modestly associated with NTD-affected pregnancies (OR 1.4; 95% CI: 0.8-2.4). ORs of 2.0 or greater were seen in women younger than age 25 and with less than 7 years education. Our findings intimate that H. pylori could play a role in NTD causation in certain populations. While results did not provide compelling support for this proposal, subgroup findings prompt us to advocate an evaluation of this hypothesis in developing nations among populations with higher prevalence of H. pylori, marginal nutrient intake, and young childbearing age.


The arteries of brain base in species of Bovini tribe.
Studies were conducted on 78 preparations of head and brain arteries in four species of Bos genus, that is in domestic cattle (N = 59), including 22 foetuses (CRL 36.5-78.5 cm), in banteng (Bos javanicus, N = 3), yak (Bos mutus f. grunniens, N = 2), American bison (Bison bison, N = 4), and European bison (Bison bonasus, N = 10). The comparative analysis permitted to demonstrate a similar pattern of brain base arteries in the studied animals. In the studied species, blood vessels of the arterial circle of the brain were found to form by bifurcation of intracranial segments of inner carotid arteries, which protruded from the paired rostral epidural rete mirabile. In Bovidae arterial circle of the brain was supplied with blood mainly by maxillary artery through the blood vessels of the paired rostral epidural rete mirabile. The unpaired caudal epidural rete mirabile was participating in blood supply to the arterial circle of the brain from vertebral and occipital arteries. It manifested character of a taxonomic trait for species of Bos and Bison genera. Basilar artery in all the examined animals manifested a variable diameter, with preliminary portion markedly narrowed, which prevented its participation in blood supply to the arterial circle of the brain. The results and taxonomic position of the species made the authors to suggest a hypothesis that a similar arterial pattern on the brain base might be present also in other species, not included in this analysis.


Treatment options for the management of exercise-induced asthma and bronchoconstriction.
Treatment for exercise-induced bronchospasm and exercise-induced asthma includes both pharmacologic and nonpharmacologic options. Pharmacologic agents that have been proven to be effective for treating these conditions include short- and long-acting β2-adrenoceptor agonists, mast cell-stabilizing agents, anticholinergics, leukotriene receptor antagonists, and inhaled corticosteroids (ICS). When selecting the most appropriate medication, factors to consider include the effectiveness of each, the duration of action, frequency of administration, potential side effects, and tolerance level. Long-acting β2-adrenoceptor agonists should not be used without ICS. Nonpharmacologic treatments include physical conditioning, incorporating a warm-up before and a cool-down period after exercise, performing nasal breathing, avoiding cold weather or environmental allergens, using a face mask or other aid to warm and humidify inhaled air, and modifying dietary intake. The data to support nonpharmacologic treatments are limited; however, they are routinely recommended because of the low risk associated with their use. This article highlights the advantages and limitations of each treatment option.


On the tempo of childbearing in England and Wales.
Abstract The paper describes a computerized model developed to simulate the fertility of a hypothetical marriage cohort in a closed population. The model was applied to England and Wales fertility data of marriage cohorts of the years 1951 to 1970. For each of these cohorts, the computer was programmed to construct five series of tables showing birth-order probabilities, family size frequency distribution, mean length of intervals between marriage and successive births, parity progression ratios and mean family sizes of fertile women. The results showed that the fertility of the cohorts of women who married between the middle 1950s and the early 1960s was character ized by a declining trend in the frequency of childlessness and by a dramatic increase in the proportion of marriages with two or more children. Since 1964 or so, there has been a downward trend in duration-specific birth-order probabilities. The analysis suggests that the recent drop in fertility may well prove to be the effect of an upward shift in the timing of births as well as a fall in completed fertility.


Virological and immunological factors associated with HIV-1 differential disease progression in HLA-B 58:01-positive individuals.
Molecular epidemiology studies have identified HLA-B 58:01 as a protective HIV allele. However, not all B 58:01-expressing persons exhibit slow HIV disease progression. We followed six HLA-B 58:01-positive, HIV subtype C-infected individuals for up to 31 months from the onset of infection and observed substantial variability in their clinical progression despite comparable total breadths of T cell responses. We therefore investigated additional immunological and virological factors that could explain their different disease trajectories. Cytotoxic T-lymphocyte (CTL) responses during acute infection predominantly targeted the TW10 and KF9 epitopes in p24(Gag) and Nef, respectively. Failure to target the TW10 epitope in one B 58:01-positive individual was associated with low CD4(+) counts and rapid disease progression. Among those targeting TW10, escape mutations arose within 2 to 15 weeks of infection. Rapid escape was associated with preexisting compensatory mutations in the transmitted viruses, which were present at a high frequency (69%) in the study population. At 1 year postinfection, B 58:01-positive individuals who targeted and developed escape mutations in the TW10 epitope (n = 5) retained significantly higher CD4(+) counts (P = 0.04), but not lower viral loads, than non-B 58:01-positive individuals (n = 17). The high population-level frequency of these compensatory mutations may be limiting the protective effect of the B 58:01 allele.


The 1993 Medical Device Technology sterilization survey.
The 1993 Medical Device Technology survey on sterilization is the second in a series of annual surveys that examines the use of sterilization techniques within the European medical device industry. By conducting this study each year, a database will be established and maintained on the various ways in which the sterilization of medical devices is achieved. In the longer term this will indicate changes in the market for sterilization equipment and services and will identify future trends in this very important segment of the medical device industry. Such information will be passed on to the readers of Medical Device Technology in forthcoming issues of the magazine.


The effect of polyunsaturated phosphatidylcholine on lipid synthesis in ethanol-intoxicated cultured rat hepatocytes.
Rat liver cells in primary culture have been used to study the influence of ethanol and of a polyunsaturated phosphatidylcholine preparation from soybean lecithin on glycerol incorporation into lipids. Ethanol decreases the incorporation of glycerol into choline and ethanolamine phosphoglycerides and increases that into diglyceride, either when added to the incubation medium or when administered to rats prior to hepatocyte preparation. The addition of the polyunsaturated lipid material (EPL) is able to counteract the effect of ethanol modifying the labeling of glycerol in favour of phospholipids.


Relationship between dental occlusion and posture.
The purpose of this study is to show the effects of dental occlusion on postural position. Thirty subjects were divided into two groups: an experimental group who wore mandibular orthopedic repositioning appliances (MORA) and a control group who wore no oral device. All of the subjects underwent the same Fukuda-Unterberger experimental stepping test to check their postural attitude. Any deviation of the subject during the test from his initial position was analyzed. The results seemed to confirm that altering dental occlusion by wearing an oral appliance could induce some fluctuations in dynamic postural attitude. The phenomenon occurs after prolonged wearing of a MORA. Feedback effects are gradual after removing the mandibular splint.


Navigating the Role of Smartwatches in Cardiac Fitness Monitoring: Insights From Physicians and the Evolving Landscape.
Alongside the advancement of technology, wearable devices like smartwatches have widely been used for monitoring heartbeat, SpO2, EKG, and pacemaker activity. However, the global question is- can they be as effective as our standard diagnostic tests- electrocardiogram and echocardiography? Reported in the studies, smartwatches to the gold standard Holter monitoring for recognizing irregular pulse showed good sensitivity (98.2%), specificity (98.1%), and accuracy (98.1%). Smartwatches can be good enough for helping people get long-term monitoring of cardiac fitness and early diagnosis of atrial fibrillation but physicians shouldn't completely rely on them and perform standard investigations once the patient with symptoms visits them. We are also concerned that there must be certain rules and regulations for FDA approval of smartwatches to maintain standard criteria before they are released in the market.


Bond-Selective Imaging of Cells by Mid-Infrared Photothermal Microscopy in High Wavenumber Region.
Using a visible beam to probe the thermal effect induced by infrared absorption, mid-infrared photothermal (MIP) microscopy allows bond-selective chemical imaging at submicron spatial resolution. Current MIP microscopes cannot reach the high wavenumber region due to the limited tunability of the existing quantum cascade laser source. We extend the spectral range of MIP microscopy by difference frequency generation (DFG) from two chirped femtosecond pulses. Flexible wavelength tuning in both C-D and C-H regions was achieved with mid-infrared power up to 22.1 mW and spectral width of 29.3 cm-1. Distribution of fatty acid in live human lung cancer cells was revealed by MIP imaging of the C-D bond at 2192 cm-1.


Effect of catalyst preparation conditions on the hydrodesulfurization of thiophene over Co-Mo/gamma-Al2O3.
The purpose of this research was to study the effects of preparation conditions on the catalytic properties of the Co-Mo/gamma-Al2O3 catalyst. The work included catalyst preparations and reactions. In the preparations, cobalt-impregnated Mo/gamma-Al2O3 (designated as IcIM) was found to have a promoting effect on the hydrodesulfurization (HDS) of thiophene. Activity and stability of IcIM was higher than that of Mo/gamma-Al2O3. Conversely, when cobalt was added onto Mo/gamma-Al2O3 by the mechanical mixing method, no promoting effect was observed. Mo/gamma-Al2O3 was also prepared using the two different methods (incipient impregnation or mechanical mixing). The differently prepared Mo/gamma-Al203 resulted in no obvious difference in activity of IcIM. It was further found that Co-Mo/gamma-Al2O3 activity initially increased appreciably with Mo content and leveled off at Mo contents above 9 wt.%. The catalyst exhibited a maximum activity at Co/Mo ratio 0.3. The order in which metal species were added had a great influence on the activity of the Co-Mo/gamma-Al2O3 catalyst. Higher activity was obtained when Co was added into Mo/gamma-Al2O3 as opposed to Mo added into Co/gamma-Al2O3.


Chromomycosis in Zaire.
Biopsy specimens from 17 Zairians with chromomycosis are described. Patients ranged in age from 20 to 50 years, with a mean of 37.2 (+/- 10.2). Chromomycosis was suspected clinically in only 3 of the 17 patients. In 14 patients the lesions were on the lower limbs and in 3 on the arms. The lesions were chronic, in one patient persisting for 9 years. The diagnosis was established in each patient by finding typical thick-walled brown fungi within the lesions. Some fungi were in abscesses, others were in histiocytes or giant cells. The fungi and the inflammatory reaction were concentrated in the upper dermis. Acanthosis, hyperkeratosis, and parakeratosis were constant features and pseudoepitheliomatous hyperplasia (PEH) was a feature in 10 patients. Transepithelial elimination (TEE) of fungi was a conspicuous feature in eight specimens. Microscopic features suggested TEE in an additional three. PEH and TEE were associated in all specimens. In patients with TEE, the diagnosis may be confirmed quickly by smearing surface scrapings and finding the characteristic brown fungi.


The endocannabinoid system and energy metabolism.
Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors [cannabinoid receptor type 1 (CB1) and CB2] participate in the physiological modulation of many central and peripheral functions. The ability of the endocannabinoid system to control appetite, food intake and energy balance has recently received considerable attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptors and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control several metabolic functions by acting on peripheral tissues such as adipocytes, hepatocytes, the gastrointestinal tract, the skeletal muscles and the endocrine pancreas. The relevance of the system is further strengthened by the notion that visceral obesity seems to be a condition in which an overactivation of the endocannabinoid system occurs, and therefore drugs interfering with this overactivation by blocking CB1 receptors are considered as potentially valuable candidates for the treatment of obesity and related cardiometabolic risk factors.


LncRNA SNHG1 Regulates the Progression of Esophageal Squamous Cell Cancer by the miR-204/HOXC8 Axis.
Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) has been reported to be aberrantly expressed and plays an important role in human cancers, including esophageal squamous cell cancer. However, the regulatory mechanism underlying SNHG1 in the progression of esophageal squamous cell cancer is poorly defined. Fifty-three esophageal squamous cell cancer patients were recruited and overall survival was analyzed. EC9706 and KYSE150 cells were cultured for study in vitro. The expression levels of SNHG1, microRNA (miR)-204 and homeobox c8 (HOXC8) were detected by quantitative real-time polymerase chain reaction and Western blot. Cell cycle distribution, apoptosis, migration and invasion were determined by flow cytometry and transwell assays, respectively. The target interaction among SNHG1, miR-204 and HOXC8 was validated by luciferase reporter assay and RNA immunoprecipitation. Xenograft model was established to investigate the role of SNHG1 in vivo. High expression of SNHG1 was exhibited in esophageal squamous cell cancer and indicated poor outcomes of patients. SNHG1 silence led to cell cycle arrest at G0-G1 phase, inhibition of migration and invasion and increase of apoptosis. miR-204 was validated to sponge by SNHG1 and target HOXC8 in esophageal squamous cell cancer cells. miR-204 knockdown or HOXC8 restoration reversed the inhibitive role of SNHG1 silence in the progression of esophageal squamous cell cancer cells. Furthermore, inhibiting SNHG1 decreased xenograft tumor growth by regulating miR-204 and HOXC8. SNHG1 knockdown suppresses migration and invasion but induces apoptosis of esophageal squamous cell cancer cells by increasing miR-204 and decreasing HOXC8.


Predominance of Th2 polarization by vitamin D through a STAT6-dependent mechanism.
Vitamin D has several reported immunomodulatory properties including the reduced generation of pro-inflammatory CD4+ T helper 1 (Th1) cells and the increase in levels of the anti-inflammatory Th2 subset. Less clear has been the impact of vitamin D on the pro-inflammatory Th17 subset, and whether and how vitamin D may preferentially drive the polarization of one of the T helper subsets. Using human peripheral blood-derived mononuclear cells and mouse splenocytes and lymph node cells in culture, we examined whether and how vitamin D preferentially skews T cells towards the Th1, Th2 or Th17 subsets. Mice afflicted with the multiple sclerosis-like condition, experimental autoimmune encephalomyelitis (EAE), were examined in vivo for the relevance of the tissue culture-derived results. We report that the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 {1,25(OH)2D3}, consistently generates human and murine Th2 cells in culture, frequently leaving unchanged the levels of Th1/Th17 cytokines. As a result, the ratio of Th2 to Th1 and Th17 is increased by 1,25(OH)2D3. The upregulation of Th2 to Th1 or Th17 subsets by 1,25(OH)2D3 is enabled by an increase of the GATA-3 transcription factor, which itself is promoted upstream by an elevation of the STAT6 transcription factor. In mice, the alleviation of EAE severity by 1,25(OH)2D3 is accompanied by elevation of levels of GATA-3 and STAT6. Significantly, the efficacy of 1,25(OH)2D3 in ameliorating EAE is completely lost in mice genetically deficient for STAT6, which was accompanied by the inability of 1,25(OH)2D3 to raise GATA-3 in STAT6 null lymphocytes. These results of vitamin D promoting a Th2 shift through upstream GATA-3 and STAT6 transcription factors shed mechanistic understanding on the utility of vitamin D in MS.


Dendrimer-entrapped gold nanoparticles modified with folic acid for targeted gene delivery applications.
We report a new use of dendrimer-entrapped gold nanoparticles (Au DENPs) modified with folic acid (FA) as a non-viral vector for targeted gene delivery applications. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers modified with FA via covalent conjugation were used as templates to synthesize gold nanoparticles with an Au salt/dendrimer molar ratio of 25 : 1. The synthesized FA-modified Au DENPs (Au DENPs-FA) were used as a non-viral vector for the delivery of plasmid DNA (pDNA) into a model cancer cell line (HeLa cells) overexpressing high-affinity FA receptors (FAR). The DNA compaction ability of the formed Au DENPs-FA was systematically characterized using a gel retardation assay, zeta potential, and dynamic light scattering. We show that similar to the Au DENPs vector without FA, the Au DENPs-FA vector was able to compact the pDNA encoding enhanced green fluorescent protein (EGFP) at an N/P ratio of 0.5. Transfection results show that the Au DENPs-FA vector enables much higher luciferase and EGFP gene expression in HeLa cells overexpressing FAR than the Au DENPs without FA, demonstrating the role played by FA-mediated targeting for enhanced gene transfection in target cells. With a lower cytotoxicity than that of the Au DENPs without FA proven by a cell viability assay, the developed FA-modified Au DENPs may be used as a promising non-viral vector for safe and targeted gene therapy applications.


Comparison of Molecular, Microscopic, and Culture Methods for Diagnosis of Cutaneous Leishmaniasis.
Cutaneous leishmaniasis (CL) is endemic in the northwest of Isfahan province, Iran. Increase in the incidence of the disease in Kashan has made it necessary to find out the best method for diagnosis and molecular characterization of Leishmania species. In the present study, 130 patients suspected to cutaneous leishmaniosis referred to health care centers of Kashan were examined. Serosity of lesion was collected for smear preparation and cultured in Novy-Nicolle-McNeal medium. DNA was extracted from serosity, and Leishmania species was determined by polymerase chain reaction (PCR) and nested PCR using kinetoplast DNA (kDNA) specific primers. The diagnostic criteria of CL were based on the observation of amastigotes in the smear, promastigotes in culture, presence of expected bands in PCR, or nested PCR. Of 130 specimens, 87 (66.9%), 72 (56.2%), 98 (75.4 %), 96 (73.8%), and 99 (76.2%) were positive for microscopic culture, PCR, nested PCR, and combined PCR and microscopy (proposed method), respectively. Sensitivity, specificity, positive and negative predictive values of PCR were 99%, 100%, 100%, 96.9%, respectively, for microscopy 87.9%, 100%, 100%, 72.1%, for culture 72.7%, 100%, 100%, 53.4 %, and for nested PCR 97%, 100%, 100%, 91.2%, respectively. Based on the results of the study, kDNA-PCR was the most sensitive method for diagnosis of CL.


Perinatal listeric septicemia in a Celebese black ape.
Perinatal listeric septicemia was diagnosed in a still-born Celebese black ape (Macaca niger). The disease was characterized by prominent focal hepatic necrosis and a diffuse, acute, fibrinopurulent placentitis. Small, gram-positive rods were demonstrable in sections of the placenta and in the liver and lungs of the fetus. Listeria monocytogenes 1A was isolated from the liver of the fetus.


Autism spectrum disorder secondary to enterovirus encephalitis.
Millions of children are infected by enteroviruses each year, usually exhibiting only mild symptoms. Nevertheless, these viruses are also associated with severe and life-threatening infections, such as meningitis and encephalitis. We describe a 32-month-old patient with enteroviral encephalitis confirmed by polymerase chain reaction in cerebrospinal fluid, with unfavorable clinical course with marked developmental regression, autistic features, persistent stereotypes and aphasia. She experienced slow clinical improvement, with mild residual neurologic and developmental deficits at follow-up. Viral central nervous system infections in early childhood have been associated with autism spectrum disorders but the underlying mechanisms are still poorly understood. This case report is significant in presenting a case of developmental regression with autistic features and loss of language improving on follow-up. To our knowledge, this is the first published report of enterovirus encephalitis leading to an autism spectrum disorder.


Effects of Brain Parcellation on the Characterization of Topological Deterioration in Alzheimer's Disease.
Alzheimer's disease (AD) causes the progressive deterioration of neural connections, disrupting structural connectivity (SC) networks within the brain. Graph-based analyses of SC networks have shown that topological properties can reveal the course of AD propagation. Different whole-brain parcellation schemes have been developed to define the nodes of these SC networks, although it remains unclear which scheme can best describe the AD-related deterioration of SC networks. In this study, four whole-brain parcellation schemes with different numbers of parcels were used to define SC network nodes. SC networks were constructed based on high angular resolution diffusion imaging (HARDI) tractography for a mixed cohort that includes 20 normal controls (NC), 20 early mild cognitive impairment (EMCI), 20 late mild cognitive impairment (LMCI), and 20 AD patients, from the Alzheimer's Disease Neuroimaging Initiative. Parcellation schemes investigated in this study include the OASIS-TRT-20 (62 regions), AAL (116 regions), HCP-MMP (180 regions), and Gordon-rsfMRI (333 regions), which have all been widely used for the construction of brain structural or functional connectivity networks. Topological characteristics of the SC networks, including the network strength, global efficiency, clustering coefficient, rich-club, characteristic path length, k-core, rich-club coefficient, and modularity, were fully investigated at the network level. Statistical analyses were performed on these metrics using Kruskal-Wallis tests to examine the group differences that were apparent at different stages of AD progression. Results suggest that the HCP-MMP scheme is the most robust and sensitive to AD progression, while the OASIS-TRT-20 scheme is sensitive to group differences in network strength, global efficiency, k-core, and rich-club coefficient at k-levels from 18 and 39. With the exception of the rich-club and modularity coefficients, AAL could not significantly identify group differences on other topological metrics. Further, the Gordon-rsfMRI atlas only significantly differentiates the groups on network strength, characteristic path length, k-core, and rich-club coefficient. Results show that the topological examination of SC networks with different parcellation schemes can provide important complementary AD-related information and thus contribute to a more accurate and earlier diagnosis of AD.


Comparison of iodixanol with iohexol in excretory urography.
We compared the safety and efficacy of iodixanol, a nonionic, dimeric, iodinated contrast agent, with that of iohexol, a monomeric agent, in adult excretory urography. The study used a randomized, double-blind, parallel-comparison design to evaluate image quality, vital signs, laboratory values, and adverse reactions. Seventy-five patients from each of two centers were included. One third received iodixanol at 270 mg I/ml, one third received iodixanol at 320 mg I/ml, and one third received iohexol at 300 mg I/ml. The dose for every patient was 1 ml/kg of body weight. The radiographs were interpreted and evaluated for quality by the primary investigator at each center. There were no important differences among the three groups in terms of demographics. Evaluation of each phase of the radiographic study showed almost uniform good-to-excellent opacification, with no significant differences among the three agents. No significant differences existed for the three groups in terms of vital signs, hematology, blood and urine chemistry, and injection discomfort. There were no deaths or serious reactions during the study, nor was there a statistically significant difference among the number of adverse events for the three agents. Iodixanol at both 270 and 320 mg I/ml proved to be a safe and effective contrast material for intravenous urography. In this study, its profile was essentially indistinguishable from that of iohexol at 300 mg I/ml.


High-speed, high-sensitivity, gated surface profiling with closed-loop optical coherence topography.
We describe and experimentally demonstrate a novel (to our knowledge) surface profiling technique, for which we propose the term closed-loop optical coherence topography. This technique is a scanning beam, servo-locked variation of low-coherence interferometry. It allows for the sub-wavelength-resolution tracking of a weakly scattering macroscopic-scale surface, with the surface profile being directly output by the controlling electronics. The absence of significant real-time computational overhead makes the technique well suited to high-speed tracking. The use of a micrometer-scale coherence gate efficiently suppresses signals arising from structures not associated with the surface. These features make the technique particularly well suited to real-time surface profiling of in vivo, macroscopic biological surfaces.


Accelerated Epigenetic Age in Normal Cognitive Aging of Korean Community-Dwelling Older Adults.
Epigenetic age acceleration has been studied as a promising biomarker of age-related conditions, including cognitive aging. This pilot study aims to explore potential cognitive aging-related biomarkers by investigating the relationship of epigenetic age acceleration and cognitive function and by examining the epigenetic age acceleration differences between successful cognitive aging (SCA) and normal cognitive aging (NCA) among Korean community-dwelling older adults (CDOAs). We used data and blood samples of Korean CDOAs from the Korean Frailty and Aging Cohort Study. The participants were classified into two groups, SCA (above the 50th percentile in all domains of cognitive function) and NCA. The genome-wide DNA methylation profiling array using Illumina Infinium MethylationEPIC BeadChip was used to calculate the following: the DNA methylation age, universal epigenetic age acceleration, intrinsic epigenetic age acceleration (IEAA), and extrinsic epigenetic age acceleration (EEAA). We also used Pearson correlation analysis and independent t-tests to analyze the data. Universal age acceleration correlated with the Frontal Assessment Battery test results (r = -0.42, p = 0.025); the EEAA correlated with the Word List Recognition test results (r = -0.41, p = 0.027). There was a significant difference between SCA and NCA groups in IEAA (p = 0.041, Cohen's d = 0.82) and EEAA (p = 0.042, Cohen's d = 0.78). Epigenetic age acceleration can be used as a biomarker for early detection of cognitive decline in Korean community-dwelling older adults. Large longitudinal studies are warranted.


A dosimeter for assessment of exposures to ELF fields.
There are currently no biological indicators of electromagnetic field exposure to aid investigation of the biological effects of ELF fields, but this hiatus is partly compensated for by the ease with which the external fields can be measured. The subject of this report is a small electronic instrument that can log electric-, magnetic-, and transient-field intensities of individual subjects for a duration of two weeks, thus allowing exposure to be assessed in considerable detail. A preliminary survey conducted with the instrument has shown clear differences in domestic and occupational exposures of specific groups. Simple analytical models can be fitted to the field-exposure data by adjusting a few parameters such as current, intensity, and distance. Such modeling may be increasingly useful as the data base on exposures expands.


An improved generalized AMBER force field (GAFF) for urea.
We describe an improved force field parameter set for the generalized AMBER force field (GAFF) for urea. Quantum chemical computations were used to obtain geometrical and energetic parameters of urea dimers and larger oligomers using AM1 semiempirical MO theory, density functional theory at the B3LYP/6-31G(d,p) level, MP2 and CCSD ab initio calculations with the 6-311++G(d,p), aug-cc-pVDZ, aug-cc-pVTZ, and aug-cc-pVQZ basis sets, and with the CBS-QB3 and CBS-APNO complete basis set methods. Seven different urea dimer structures were optimized at the MP2/aug-cc-pVDZ level to obtain accurate interaction energies. Atomic partial charges were calculated at the MP2/aug-cc-pVDZ level with the restrained electrostatic potential (RESP) fitting approach. The interaction energies computed with these new RESP charges in the force field are consistent with those obtained from CCSD and MP2 calculations. The linear dimer structure calculated using the force field with modified geometrical parameters and the new RESP charge set agrees well with available experimental data.


Male gender, increased blood viscosity, body mass index and triglyceride levels are independently associated with systemic relative hypertension in sickle cell anemia.
Patients with sickle cell anemia (SCA) have usually lower diastolic, systolic and mean blood pressure (BP) than the general population. However, BP values ≥120/70 mmHg considerably increase the risk for acute and chronic complications in SCA. The aim of this study was to identify biological factors associated with relative hypertension in adults with SCA. We compared the hematological, lipid and hemolytic profiles, as well as blood viscosity, between SCA patients with normal BP (<120/70 mmHg, n = 54) and those with relative hypertension (BP≥120/70 mmHg, n = 43). Our results demonstrated that male gender (OR: 3.49; 95%CI 1.20 to 10.16, p<0.05), triglycerides (OR: 9.19; 95% CI 2.29 to 36.95, p<0.01), blood viscosity (OR: 1.35; 95% CI 1.01 to 1.81, p<0.05) and body mass index (OR: 1.37; 95% CI 1.14 to 1.64, p<0.01) were independent risks factors for relative hypertension in SCA. No association was found between the BP status and the positive history of painful vaso-occlusive crisis or acute chest syndrome. An association between triglycerides level and the occurrence of these two major acute complications was detected. Our study suggests that male gender, increased triglycerides level, BMI and blood viscosity could increase the risk for developing relative hypertension in SCA. In addition, our results support a role of moderately elevated triglycerides in the pathophysiology of vaso-occlusive events.


Healthcare resource utilization and costs in patients with newly diagnosed acute myeloid leukemia.
Acute myeloid leukemia (AML) is associated with high disease burden. This analysis estimated HRU and costs among newly diagnosed AML patients in a US commercially insured population. This was a retrospective observational study using the IMS Health PharMetrics Plus and Hospital Charge Detail Master databases. Patients included adults who were newly diagnosed with AML between January 2007 and June 2016 ("study period"). Patients with <12 months of continuous enrollment prior to the index date were excluded, as were those whose first diagnosis was AML in remission/relapse, those diagnosed with acute promyelocytic leukemia, those on Medicare supplemental insurance, or those with a diagnosis of AML in remission/relapse without evidence of treatment during the study period. Patients were stratified by receipt of AML treatment (chemotherapy/hematopoietic cell transplantation [HCT]), and their follow-up was partitioned into initial, remission, and relapsed health states. Mean HRU and costs were tallied by treatment and, for treated patients, by health state and time since entry into health state (≤6 vs >6 months). A total of 9,455 patients met study criteria, including 6,415 (68%) treated and 3,040 (32%) untreated patients, with mean follow-up of 18.3 and 16.4 months, respectively. Mean age was 55 years in treated patients and 60 years in untreated patients. Mean total costs per patient were $386,077 in treated patients and $79,382 in untreated patients. For treated patients, 60% of total costs ($231,867 per patient) were incurred during the initial health state, representing time without remission/relapse. Mean monthly total healthcare costs were $21,055 and $4,854 among treated and untreated patients, respectively. HRU and costs of managing AML patients are substantial. In treated patients, the majority of costs were incurred during the initial treatment period, without claims indicating remission/relapse.


A high-efficiency induction of dopaminergic cells from human umbilical mesenchymal stem cells for the treatment of hemiparkinsonian rats.
The success rate in previous attempts at transforming human umbilical mesenchymal stem cells (HUMSCs) isolated from Wharton's jelly of the umbilical cord into dopaminergic cells was a mere 12.7%. The present study was therefore initiated to establish a more effective procedure for better yield of dopaminergic cells in such transformation for more effective HUMSC-based therapy for parkinsonism. To examine, in vitro, the effects of enhanced Nurr1 expression in HUMSCs on their differentiation, cells were processed through the three-stage differentiation protocol. The capacity of such cells to synthesize and release dopamine was measured by HPLC. The therapeutic effects of Nurr1-overexppressed HUMSCs were examined in 6-hydroxydopamine-lesioned rats by quantification of rotations in response to amphetamine. Enhanced Nurr1 expression in HUMSCs promoted the transformation into dopaminergic cells in vitro through stepwise culturing in sonic hedgehog, fibroblast growth factor-8, and neuron-conditioned medium. The success rate was about 71%, as determined by immunostaining for tyrosine hydroxylase and around 94 nM dopamine synthesis (intracellular and released into the culture medium), as measured by HPLC. Additionally, transplantation of such cells into the striatum of hemiparkinsonian rats resulted in improvement of their behavioral deficits, as indicated by amphetamine-evoked rotation scores. Viability of the transplanted cells lasted for at least 3 months as verified by positive staining for tyrosine hydroxylase. Nurr1, FGF8, Shh, and NCM can synergistically enhance the differentiation of HUMSCs into dopaminergic cells and may pave the way for HUMSC-based treatments for Parkinson's disease.


Economic incentives to use fertilizer on maize under differing agro-ecological conditions in Burkina Faso.
Increasing agricultural productivity while protecting natural resources depends on proper understanding of farmers' incentives to use intensification strategies, including fertilizer. Using a large-scale household dataset collected in rural Burkina Faso, we examined how the response of maize yield to fertilizer, and thus the economic incentives for its use, varied according to agro-ecological conditions. We employed a Control Function Approach with Correlated Random Effects in order to test and control for endogeneity of fertilizer use, measuring agro-ecological conditions at several scales. We investigated the profitability of fertilizer use with value-cost ratios. We found that productivity and marginal effects of fertilizer differ significantly according to agro-ecological conditions. Micro-variation appeared to be more critical than the definition of agro-ecological zone. Burkinabe soils are severely degraded and would benefit from greater application of fertilizer. However, at full market prices, fertilizer use was unprofitable. Though it was profitable with subsidized prices, transaction costs diminish the benefits of the subsidy. Profitability of fertilizer use with maize varied across agro-ecological conditions, even for field plots located in the same agro-ecological zone. Our results confirm that policy makers need to be cautious when generalizing across regions or drawing policy recommendations from a single agro-ecological zone because crop responses and economic incentives vary widely.


Object Category Understanding via Eye Fixations on Freehand Sketches.
The study of eye gaze fixations on photographic images is an active research area. In contrast, the image sub-category of freehand sketches has not received as much attention for such studies. In this paper, we analyze the results of a free-viewing gaze fixation study conducted on 3904 freehand sketches distributed across 160 object categories. Our analysis shows that fixation sequences exhibit marked consistency within a sketch, across sketches of a category and even across suitably grouped sets of categories. This multi-level consistency is remarkable given the variability in depiction and extreme image content sparsity that characterizes hand-drawn object sketches. In this paper, we show that the multi-level consistency in the fixation data can be exploited to 1) predict a test sketch's category given only its fixation sequence and 2) build a computational model which predicts part-labels underlying fixations on objects. We hope that our findings motivate the community to deem sketch-like representations worthy of gaze-based studies vis-a-vis photographic images.