In vivo and in vitro induction of class II molecules on canine renal cells and their effect on the mixed lymphocyte kidney cell culture.
Canine renal cortical cells were obtained by collagenase extraction from allogeneic haploidentical, donor-recipient beagle littermate pairs and from unrelated mongrels. Peripheral blood lymphocytes (PBL) of the mongrels, as well as of one member of the beagle pair that exhibited high mixed lymphocyte culture (MLC) reactivity against the other were also stimulated by renal cortical cells derived from both normal and rejected transplanted kidneys in mixed lymphocyte kidney cell culture (MLKC). A moderate autologous MLKC reactivity occurred in response to normal renal cortical cells. However, rejected kidney cortical cells were markedly more stimulatory than normal renal cortical cells in both allogeneic and autologous MLKC reactions. Lymphocytes from donor animals responded more strongly to autologous cortical cells isolated during rejection of the transplant than to cortical cells from normal allogeneic kidneys. Recipient infiltrating lymphocytes and propagated T cell lines extracted from the rejected kidney also responded more strongly than PBL to cortical cells from this kidney. Gradient purification of the stimulating cortical cells resulted in one virtually pure preparation of distal tubular epithelial cells, as demonstrated by immunohistochemical stains and electron microscopy, which caused enhanced stimulation in MLKC. Class II marker analysis of the canine renal cells from rejected kidneys revealed the presence of these molecules on tubular cells that were absent on normal kidney cells. A 16-hr coculture of normal renal cortical cells not exhibiting class II surface markers in the presence of allogeneic or autologous lymphocytes induced the expression of these molecules, associated with an increased stimulatory capacity. This also occurred to a lesser extent with MLC (and MLKC) cell culture media supernatants. However, the low level of class II expression by all the various gradient-purified fractions in the absence of rejection or coculture, and the increased but equivalent expression on all fractions after coculture did not correlate with the preferential stimulatory capacity of the purified distal tubular cell layer. We conclude that two signals are necessary for the MLKC reaction, one involving tissue (kidney)-associated epitopes (the nominal antigen demonstrated in this study to be present in normal distal tubular cells), the other involving class II molecules as costimulatory (amplification) moieties.


[Prevalence of tuberculosis and HIV infections among participants in an intravenous drug user risk-control program].
To determine the prevalence of tuberculosis and HIV infection in addition to the related factors among a population of participants in the risk control program in the town of Lleida. The sample was comprised of the newly-enrolled participants in the program in April-June 1996, among whom a questionnaire was handed out for collecting the data concerning the variables involved: age, gender, results of the tuberculin test, BCG vaccination, knowledge of the serology regarding HIV, former imprisonment and number of years having used heroin. The prevalence of the tuberculosis and HIV infection was calculated to a 95% confidence interval (CI). The relating of these two variables to all other variables in the study was determined by means of the odds ratio (OR) and its 95% CI. One hundred and fifty (150) patients were seen, 45 of whom were newly enrolled participants. Eighty percent (80%) were males, averaging 31.1 years of age. The prevalence of this dual infection was 8.9% (95% CI 2.8-22.1). The prevalence of the tuberculosis infection was 27.3% (95% CI 12.4-43.0), being higher among former prison inmates (OR = 3.4; 95% CI 0.5-27.4). The prevalence of the HIV infection was 36.1% (95% CI 21.3-53.8), being greater among those who had been using heroin for longer than 11 years (OR = 7.3; 95% CI 1.0-65.9). Former imprisonment is the main risk factor for tuberculosis infection. The number of years of heroin use are related to the HIV infection, especially when longer than 11 years. The risk control programs in our country should carry out activities aimed at monitoring tuberculosis and HIV infection.


Sex-specific compensatory growth in the larvae of the greater wax moth Galleria mellonella.
Deficiency of food resources in ontogeny is known to prolong an organism's developmental time and affect body size in adulthood. Yet life-history traits are plastic: an organism can increase its growth rate to compensate for a period of slow growth, a phenomenon known as 'compensatory growth'. We tested whether larvae of the greater wax moth Galleria mellonella can accelerate their growth after a fast of 12, 24 or 72 h. We found that a subgroup of female larvae showed compensatory growth when starved for 12 h. Food deficiency lasting more than 12 h resulted in longer development and lower mass gain. Strength of encapsulation reactions against a foreign body inserted in haemocoel was the weakest in females that showed compensatory growth, whereas the strongest encapsulation was recorded in the males and females that fasted for 24 and 72 h. More specifically, we found sex-biased immune reactions so that females had stronger encapsulation rates than males in one group that fasted for 72 h. Overall, rapidly growing females had a short larval development period and the shortest adult lifespan. These results suggest that highly dynamic trade-offs between the environment, life-history traits and sex lead to plasticity in developmental strategies/growth rates in the greater wax moth.


The Use of Genomics in Conservation Management of the Endangered Visayan Warty Pig (Sus cebifrons).
The list of threatened and endangered species is growing rapidly, due to various anthropogenic causes. Many endangered species are present in captivity and actively managed in breeding programs in which often little is known about the founder individuals. Recent developments in genetic research techniques have made it possible to sequence and study whole genomes. In this study we used the critically endangered Visayan warty pig (Sus cebifrons) as a case study to test the use of genomic information as a tool in conservation management. Two captive populations of S. cebifrons exist, which originated from two different Philippine islands. We found some evidence for a recent split between the two island populations; however all individuals that were sequenced show a similar demographic history. Evidence for both past and recent inbreeding indicated that the founders were at least to some extent related. Together with this, the low level of nucleotide diversity compared to other Sus species potentially poses a threat to the viability of the captive populations. In conclusion, genomic techniques answered some important questions about this critically endangered mammal and can be a valuable toolset to inform future conservation management in other species as well.


Clinical microfluidics for neutrophil genomics and proteomics.
Neutrophils have key roles in modulating the immune response. We present a robust methodology for rapidly isolating neutrophils directly from whole blood with 'on-chip' processing for mRNA and protein isolation for genomics and proteomics. We validate this device with an ex vivo stimulation experiment and by comparison with standard bulk isolation methodologies. Last, we implement this tool as part of a near-patient blood processing system within a multi-center clinical study of the immune response to severe trauma and burn injury. The preliminary results from a small cohort of subjects in our study and healthy controls show a unique time-dependent gene expression pattern clearly demonstrating the ability of this tool to discriminate temporal transcriptional events of neutrophils within a clinical setting.


Intergenerational educational mobility is associated with cardiovascular disease risk behaviours in a cohort of young Australian adults: The Childhood Determinants of Adult Health (CDAH) Study.
Although educational disparity has been linked to single risk behaviours, it has not previously been studied as a predictor of overall lifestyle. We examined if current education, parental education or educational mobility between generations was associated with healthy lifestyles in young Australian adults. In 2004-06, participant and parental education (high [bachelor degree or higher], intermediate [vocational training], low [secondary school only]) were assessed. Educational mobility was defined as: stable high (participant and parent in high group), stable intermediate (participant and parent in intermediate group), stable low (participant and parent in low group), downwardly (lower group than parent) and upwardly (higher group than parent) mobile. We derived a lifestyle score from 10 healthy behaviours (BMI, non-smoking, alcohol consumption, leisure time physical activity and six components of diet). Scores >4 indicated a high healthy lifestyle score. We estimated the likelihood of having a high healthy lifestyle score by education (participant and parent) and educational mobility. Complete data were available for 1973 participants (53% female, age range 26 to 36 years). Those with lower education were less likely to have healthy lifestyles. Parental education was not associated with having a high healthy lifestyle score after adjustment for participant's education. Those who moved upward or downward were as likely to have a high healthy lifestyle score as those in the group they attained. We found clear disparities in health behaviour by participant education and intergenerational educational mobility. People attaining a higher level of education than their parents appeared protected from developing an unhealthy lifestyle suggesting that population-wide improvements in education may be important for health.


Religious affiliation and suicide attempt.
Few studies have investigated the association between religion and suicide either in terms of Durkheim's social integration hypothesis or the hypothesis of the regulative benefits of religion. The relationship between religion and suicide attempts has received even less attention. Depressed inpatients (N=371) who reported belonging to one specific religion or described themselves as having no religious affiliation were compared in terms of their demographic and clinical characteristics. Religiously unaffiliated subjects had significantly more lifetime suicide attempts and more first-degree relatives who committed suicide than subjects who endorsed a religious affiliation. Unaffiliated subjects were younger, less often married, less often had children, and had less contact with family members. Furthermore, subjects with no religious affiliation perceived fewer reasons for living, particularly fewer moral objections to suicide. In terms of clinical characteristics, religiously unaffiliated subjects had more lifetime impulsivity, aggression, and past substance use disorder. No differences in the level of subjective and objective depression, hopelessness, or stressful life events were found. Religious affiliation is associated with less suicidal behavior in depressed inpatients. After other factors were controlled, it was found that greater moral objections to suicide and lower aggression level in religiously affiliated subjects may function as protective factors against suicide attempts. Further study about the influence of religious affiliation on aggressive behavior and how moral objections can reduce the probability of acting on suicidal thoughts may offer new therapeutic strategies in suicide prevention.


Direct evaluation of cyclic contributions to the pi energy of conjugated hydrocarbons from strongly localized zero-order pictures.
This paper presents a new procedure for identifying that part of the pi electronic energy of conjugated hydrocarbons which results from cyclic circulation of electrons around a ring. It first shows that one may calculate perturbatively the ground state energy of the Hückel Hamiltonian from a strongly localized Kekulé-type zero-order wave function. The contributions due to cyclic circulation of the electrons appear explicitly, in terms of the interatomic hopping integral t, at the second order in cyclobutadiene (where it is equal to -t (antiaromatic)) and at third order in benzene, where its value is 0.5t (aromatic). Conjugated isomers of benzene are also considered. The cyclic circulation contributions for an N-membered ring are shown to depend strongly on the molecular graph in which it is embedded. A general expression is found for the cyclic contribution to the pi energy of a ring, the Kekulé graph of which contains N double bonds alternating with N single bonds. It is the energy of the ring, plus the sum of the energies of the N subsystems that result from one double-bond removal, minus the sum of the energies of the N open systems that result from one single-bond cut. This new aromaticity index, ACE(MC), may be seen as the enthalpy of a hyperhomodesmotic chemical equation. In contrast to the index ACE(DC) previously defined from a double cut of the ring, the multiple-cut ACE(MC) exhibits the expected asymptotic disappearance of the cyclic energy as the ring size tends to infinity. In the multiple-cut approach, aromaticity persists in bond-alternating rings, but, in contrast to the total pi energy, the purely cyclic contribution tends to resist distortion. Extension of the approach to charged, branched and heterosubstituted rings are discussed, as well as its ab initio transcription.


Chicken soup really is good for the soul: "comfort food" fulfills the need to belong.
Theories of social surrogacy and embodied cognition assume that cognitive associations with nonhuman stimuli can be affectively charged. In the current research, we examined whether the "comfort" of comfort foods comes from affective associations with relationships. Two experiments support the hypotheses that comfort foods are associated with relationships and alleviate loneliness. Experiment 1 found that the consumption of comfort foods automatically activates relationship-related concepts. Experiment 2 found that comfort foods buffer against belongingness threats in people who already have positive associations with relationships (i.e., are secure in attachment style). Implications for social surrogacy, need to belong, embodied cognition, and eating behavior are discussed.


Behavioral and motor improvement after deep brain stimulation of the globus pallidus externus in a case of Tourette's syndrome.
The objective of our paper is to show the partial decrease of therapeutic effect with battery exhaustion in a previously successfully treated patient with refractory Tourette's syndrome (TS). We present a 47-year-old patient diagnosed with TS based on the TS Study Group Criteria and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Surgery was considered based on refractoriness to conservative management. Presurgical evaluation included magnetic resonance imaging (MRI), positron emission tomography scan, and neuropsychologic, neurologic, and psychiatric tests utilizing Yale Brown Obsessive Compulsive Scale, Yale Global Tics Severity Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Global Assessment of Functioning Scale, and Mini-mental State Examination. Target coordinates were obtained from inversion recovery MRI. Quadripolar deep brain stimulation (DBS) electrodes were implanted bilaterally in the globus pallidus externus (GPe) and connected to the pulse generator in the same procedure. To determine the clinical response to DBS, the scores of the scales obtained preoperatively were compared with those obtained postoperatively. No surgical complications were detected and according to the clinical scales the patient experienced a marked improvement of his symptoms, although he never showed obsessive-compulsive disorder components of any type. The battery was exhausted after two years with the subsequent significant partial loss of therapeutic effect. GPe seems to be a highly promising target of DBS for the treatment of medically refractory TS. After battery exhaustion, the patient experienced a marked partial decrease in the therapeutic effect, which confirms the beneficial action of this method.


Nonlinear relationship of mite allergen exposure to mite sensitization and asthma in a birth cohort.
There is uncertainty about the nature of the relationship between mite allergen exposure during infancy and the expression of allergic diseases in childhood. We sought to explore the relationships between repeated measurements of mite allergen exposure during the first 5 years of life and clinical allergic disease outcomes at age 5 years. In a birth cohort of 516 at-risk children, 13 bed dust samples were collected between birth and 5 years of age and analyzed for mite allergen. At age 5 years, the presence of mite atopy was assessed based on skin prick test results, and clinical assessments for asthma, eczema, and wheeze were conducted. The association of allergen exposure with each clinical outcome was examined by means of logistic regression, with adjustments for potential confounders. The lowest and highest mite exposure quintiles, expressed as mean allergen concentration averaged over 0 to 5 years, were associated with a lower prevalence of mite atopy and of asthma compared with intermediate levels of exposure. These relationships, when determined by using average allergen concentration over 0 to 18 months, were weaker. This study demonstrates a nonlinear relationship between mite allergen exposure and clinical outcomes in this generally high mite allergen environment.


Evaluation of bond strength of metal brackets by a resin to ceramic surfaces.
The purpose of this study was to evaluate the bond strength of three different ceramic brands with two different ceramic surfaces (glazed and deglazed), with and without silane application. Using the three different ceramics (Empress 2, Finesse, and Ceramco II), two metallic brackets were bonded to each sample, one with the adhesive system and the other one with a silane application. The samples were thermocycled, and then the debonding tests were performed with the Instron Universal Testing Machine. All the results were statistically analyzed with a three-way analysis of variance (ANOVA) test. The three-way ANOVA (brand, ceramic surface, with/without silane) indicated significant differences among them (p < 0.05). ANOVA showed that the greatest bond strength value (megapascals, MPa) was for Empress 2 deglazed with the silane application (8.873 MPa), followed by Finesse glazed with the silane application (7.072 MPa). The ceramic surface has a direct effect on adhesion. Therefore, Empress 2 deglazed achieved the greatest value in bond strength. To achieve the ideal values of 6-10 MPa, applying silane to the ceramic surface before bonding the brackets is recommended, even though silane can damage the ceramic surface.


Vibrio mimicus attaches to the intestinal mucosa by outer membrane hemagglutinins specific to polypeptide moieties of glycoproteins.
Vibrio mimicus is the closest organism to Vibrio cholerae. V. mimicus E-33, which is a highly adhesive and enteropathogenic strain, is known to produce three types of hemagglutinins (HAs), i.e., a 31-kDa exocellular metalloprotease (Vm-HA/protease), lipopolysaccharide (Vm-LPSHA), and a 39-kDa major outer membrane protein (Vm-OMPHA). Hemagglutination induced by Vm-LPSHA and Vm-OMPHA was inhibited by glycoproteins, including mucin, fetuin, and asialofetuin, but not by monosaccharides, disaccharides, or N-acetylated saccharides. The inhibitory potential of each glycoprotein for Vm-OMPHA was greatly augmented by treatment with a glycolytic enzyme such as beta-D-galactosidase or beta-D-glucosidase, while pronase treatment achieved complete abolition of the inhibitory potential. The inhibitory ability of the glycoproteins for Vm-LPSHA was also abolished by pronase treatment; however, glycolytic enzyme treatment showed no effect. Hence, the polypeptide portion of glycoproteins may directly associate with Vm-OMPHA and Vm-LPSHA, but the sugar moiety may act as a barrier to interaction with Vm-OMPHA. The glycoproteins as well as Fab antibodies against Vm-OMPHA and Vm-LPSHA eliminated the ability of E-33 cells to agglutinate rabbit erythrocytes and to attach to rabbit intestinal mucosa. Additionally, expression of the hemagglutinating ability by the bacterial cells was accompanied by efficient bacterial adherence to the intestinal mucosa. Finally, the hemagglutinating activity of Vm-OMPHA was markedly increased by incubation with Vm-HA/protease. These results indicate that all three HAs may have significant roles in the glycoprotein-mediated intestinal adherence of V. mimicus E-33.


KBP interacts with SCG10, linking Goldberg-Shprintzen syndrome to microtubule dynamics and neuronal differentiation.
Goldberg-Shprintzen syndrome (GOSHS) is a rare clinical disorder characterized by central and enteric nervous system defects. This syndrome is caused by inactivating mutations in the Kinesin Binding Protein (KBP) gene, which encodes a protein of which the precise function is largely unclear. We show that KBP expression is up-regulated during neuronal development in mouse cortical neurons. Moreover, KBP-depleted PC12 cells were defective in nerve growth factor-induced differentiation and neurite outgrowth, suggesting that KBP is required for cell differentiation and neurite development. To identify KBP interacting proteins, we performed a yeast two-hybrid screen and found that KBP binds almost exclusively to microtubule associated or related proteins, specifically SCG10 and several kinesins. We confirmed these results by validating KBP interaction with one of these proteins: SCG10, a microtubule destabilizing protein. Zebrafish studies further demonstrated an epistatic interaction between KBP and SCG10 in vivo. To investigate the possibility of direct interaction between KBP and microtubules, we undertook co-localization and in vitro binding assays, but found no evidence of direct binding. Thus, our data indicate that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in GOSHS are likely caused by microtubule-related defects.


Antigen-specific helper T cells required for dominant idiotype expression are not H-2 restricted.
Two synergizing antigen-specific helper T (Th) cell populations are required for an optimal TEPC15 (T15)-dominated antiphosphorylcholine (PC) plaque- forming cell response . In these studies, the two Th cell sets are shown to differ in their requirements for recognition of self-major histocompatibility complex (MHC)-encoded determinants by testing the ability of Th cells from F(1) {arrow} parent bone marrow chimeras to collaborate with PC-specific B cells bearing MHC-encoded determinants of either parental haplotypes. Previous studies have shown that one antigen-specific Th cell population is required for T-dependent anti-PC responses and activates PC-specific B cells only if the hapten, PC, is physically linked to the priming antigen. This Th cell, referred to as ThMHC, induces anti-PC responses that are mainly non-T15 in character, and it appears to be identical to the conventional antigen- specific Th cell. In these experiments, using T cells from (A X B)F(1) {arrow} parent A chimeras, ThMHC cells requiring hapten-carrier association provide help for F(1) and parent A B cells but not for B cells from parent B, thus confirming that the activity of the conventional Th cell is H-2 restricted . The second antigen-specific Th cell population, whose function is measured in the presence of the ThMHC cell set, preferentially activates T15-bearing B cells. This Th cell set (ThId) is missing in mice expressing low levels of T15-bearing antibody and can be restored by the addition of antigen-specific T cells from donors expressing high levels of circulating T15 Id. These studies demonstrate that T cells from F(1) {arrow} parent chimeras that express substantial levels of T15-bearing anti-PC antibody could provide ThId cell activity for the selective activation of T15-bearing B cells of F(1) and both parental H-2 types. These results imply that whereas the activity of conventional, ThMHC, cells is clearly H-2 restricted, ThId cells from the same chimeric donors are not required to recognize antigen in association with self-MHC-encoded determinants for successful T-B collaboration .


The role of attention in immediate emotional false memory enhancement.
Two experiments examined the effect of reduced attentional resources on false memory production for emotionally valenced stimuli using the Deese/Roediger-McDermott (DRM) paradigm. Prior research has demonstrated that emotional information is often better remembered than neutral information and that enhanced memory for emotional information is dependent on either automatic or controlled neural processing (Kensinger & Corkin, 2004). Behavioral studies designed to reduce attention resources at encoding have supported neuroimaging findings that indicate high arousal negative stimuli rely more on automatic processing but positive high arousal stimuli rely more on controlled processing. No study has yet examined the attentional resources required to produce emotionally valenced false memories. In Experiment 1, negative, positive, and neutral DRM lists were studied under full or divided attention (DA) conditions, and in Experiment 2, negative and neutral DRM lists were studied under fast (20 ms) or slow (2,000 ms) presentation conditions. Under DA and speeded presentation conditions, higher false memory recognition rates were found for negative compared with positive (Experiment 1) and neutral (Experiments 1 and 2) critical lures. This is the first demonstration of which we are aware that suggests negative false memories are associated with automatic neural processing, whereas positive and nonvalenced neutral false memories are associated with more controlled processing. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Brief communication: the popliteal sesamoid bone (cyamella) in primates.
A study of 246 adult nonhuman primates belonging to 34 genera indicates that a popliteal sesamoid bone is always present in the tendon of the popliteus muscle in Prosimii and Callitrichidae. The bone occurs only variably in Atelidae and Pongo, and is usually absent in Gorilla. The bone is absent, or very rare, in Cebus, Cercopithecidae, Hylobatidae, Pan, and humans. When the bone is present, it articulates with the posterior part of the articular surface of the lateral condyle of the tibia, and lies very close to the head of the fibula, at the angulated part of the popliteal tendon, near the tendomuscular junction. The presence of the popliteal sesamoid bone in primates is a primitive character.


Spatial and temporal variation of phytoplankton in a tropical eutrophic river.
This study aims to evaluate the environmental factors determining of the changes in phytoplankton structure in spatial (upper, middle and lower course) and seasonal (dry and rainy period) scales in a eutrophic river (Almada River, northeastern Brazil). In the study period, total accumulated rainfall was below of the historic average, resulting in flow reduction, mainly in rainy period. High orthophosphate concentration was found at the sampling sites. Phytoplankton chlorophyll a increased from upstream to downstream. Geitlerinema splendidum (S1) and Chlamydomonas sp. (X2) were the most abundant species in the upper course and several species of diatoms (D), Euglenophyceae (W1, W2) and Chlorophyceae (X1) in the middle and lower course. The functional groups were found to be characteristic of lotic ecosystem, shallow, with low light availability, rich in organic matter and eutrophic environments. We conclude that phytoplankton community structure was sensitive to change of the river flow and nutrient availability in spatial and seasonal scale in a tropical river.


Single-crystal studies of peptide prolyl and glycyl 15N shielding tensors.
15N shielding tensors were determined for the central peptide groups in GGV, AGG, and APG by single-crystal NMR. We find that the angle between the downfield component (delta11) and the N-H or the N-C(delta) (pro) bonds is in the range of 20-23 degrees and in accord with previous solid-state NMR measurements. However, AGG, unlike APG or GGV, has a distorted peptide plane, and delta11 lies approximately in the plane of N, C(alpha), and H rather than in the peptide plane defined by heavy atoms. Accurate orientations of delta22 and delta33 were determined, and the usual assumption that delta22 is along the peptide normal was found only in APG which has a highly nonaxial tensor. More generally, delta22 and delta33 are rotated about the delta11 axis (36 degrees in GGV). These results are compared with DFT calculations to gain a structural understanding of the effects of intermolecular interactions on shielding tensor principal components and orientations. Trimeric clusters containing H-bonded neighbors predict the orientations of the principal components within 2-3 degrees, but calculated principal components are less quantitative. Possible reasons for this disagreement are explored.


The Wellcome Foundation lecture, 1982. Opioid peptides and their receptors.
The remarkable feature of the opioid system is the complexity of its ligands and their interactions with the mu-, delta- and kappa-binding sites. The three endogenous opioid precursors give rise to more than ten opioid fragments. The fragments of pro-opiocortin and pro-enkephalin have affinities mainly to the mu- and delta-binding sites and those of pro-dynorphin have a preference for the kappa-binding site. It is important to realize that some of the larger fragments may have pharmacological actions that are of a non-opioid character. As the endogenous opioid peptides bind to more than one of the types of binding sites, it was necessary to obtain synthetic compounds that bind almost exclusively at one site. There are now agonists for which this aim has been achieved but we still require antagonists that are exclusively selective for only one opioid site. The results obtained with opioid peptides or non-peptides having such qualities would be the physiological basis for a correlation of the binding at mu-, delta- and kappa-receptors with their pharmacological effects. Furthermore, since almost all endogenous opioid ligands are degraded by peptidases, it is necessary to synthesize non-toxic inhibitors of those peptidases that play a role in opioid transmission. Related to this problem is the need to develop methods for the study of the release of various endogenous opioid peptides under physiological conditions.


[Remote sensing retrieval of vegetation coverage in arid areas based on multiple endmember spectral unmixing].
Vegetation coverage is an important indicator in the assessment of terrestrial ecosystem and land desertification. By using the data acquired from the novel hyperspectral sensor HIS in Chinese HJ-1 small satellite, the suitable endmember spectrum was extracted by the combination of pixel purity index and endmember average root mean square error. Then, the vegetation coverage (FVC) in Shihezi area of Xinjiang, Northwest China was retrieved by the model of multiple endmember spectral mixture analysis (MESMA). With the comparison of the FVCs retrieved from the linear spectral analysis (LSMA) model and the measurement results, the FVCs retrieved from the MESMA model were evaluated. The results showed that the MESMA model enabled the use of different endmember combinations for different image pixels, and thus, could perform better than the LSMA model in the estimation of regional FVCs. As compared with the LSMA model, the correlation coefficient between the FVCs retrieved from the MESMA model and the measured FVCs increased from 0.766 to 0.838, while the root mean square error decreased from 0.375 to 0.196.


Weekend treatment with 20 and 40 mg omeprazole: effect on intragastric pH, fasting and postprandial serum gastrin, and serum pepsinogens.
Weekend treatment with 20 mg omeprazole reduces ulcer relapse rates but the results may improve with a higher dose regimen. We have evaluated three day weekend treatment with 20 and 40 mg doses of omeprazole in eight healthy subjects in a double blind crossover study. Twenty four hour ambulatory intragastric pH and basal and meal stimulated serum gastrin and serum pepsinogens A and C values were studied. The investigations began on the Friday before the third weekend course of omeprazole and were repeated on alternate days, except Sundays, for two weeks. When compared with values before the study, median 24 hour intragastric pH and basal and meal stimulated gastrin concentrations were significantly (p less than 0.01-0.05), but transiently, raised with both doses of omeprazole. Basal pepsinogen A and C values were significantly (p less than 0.01) increased on all study days, but did not return to their pre-study values before the next weekend dose, except for pepsinogen C in subjects treated with 20 mg omeprazole. A dose dependent effect was found for all parameters studied (p less than 0.05). In conclusion, weekend treatment with 20 and 40 mg omeprazole produces pronounced and dose dependent increases in intragastric pH, basal and meal stimulated serum gastrin, and basal serum pepsinogen A and C without inducing prolonged hypoacidity or hypergastrinaemia. Weekend treatment with 40 mg omeprazole merits further study in the prevention of peptic ulcer relapse.


Tumor necrosis factor alpha and interleukin-1beta regulate the murine manganese superoxide dismutase gene through a complex intronic enhancer involving C/EBP-beta and NF-kappaB.
Manganese superoxide dismutase (MnSOD), a tumor necrosis factor (TNF)-inducible reactive oxygen-scavenging enzyme, protects cells from TNF-mediated apoptosis. To understand how MnSOD is regulated, transient transfections of promoter-reporter gene constructions, in vitro DNA binding assays, and in vivo genomic footprint (IVGF) analysis were carried out on the murine MnSOD gene. The results of this analysis identified a 238-bp region of intron 2 that was responsive to TNF and interleukin-1beta (IL-1). This TNF response element (TNFRE) had the properties of a traditional enhancer element that functioned in an orientation- and position-independent manner. IVGF of the TNFRE revealed TNF- and IL-1-induced factor occupancy of sites that could bind NF-kappaB and C/EBP. The 5' portion of the TNFRE bound C/EBP-beta in vitro and was both necessary and sufficient for TNF responsiveness with the MnSOD promoter or with a heterologous promoter when in an upstream position. The 3' end of the TNFRE bound both NF-kappaB and C/EBP but was not necessary for TNF responsiveness with the MnSOD promoter. However, this 3' portion of the TNFRE was required for the TNFRE to function as a downstream enhancer with a heterologous promoter. These data functionally separate the MnSOD TNFRE into a region responsible for TNF activation and one that mediates induction when it is downstream of a promoter.


Sexual Violence Disclosure in #Notokay: Disclosure Goals, Disclosure-Facilitating Resources, and Overall Disclosure Trajectory.
This study investigated the disclosure goals, disclosure-facilitating resources, and overall disclosure trajectory of 16 women who participated in the 2016 #notokay antisexual violence campaign. Findings indicate that most participants' disclosure goals were approach focused. Factors that facilitated disclosure were social media affordances and psychological, professional, and financial resources. Participants' overall disclosure trajectory was upward, but not linear, and disclosure outcomes included self-growth and awareness of the intersectional nature of violence. The findings suggest that the disclosure processes model can be strengthened by considering goal-relevant resources as a structural or environmental factor that influences the choice of approach versus avoidance goals, and consequently, beneficial or harmful disclosure outcomes. Further, by investigating how participants' #notokay disclosure was situated in their other online and offline disclosure episodes, this study provides a contextualized perspective of online hashtagged disclosures of sexual violence.


N-Ras induces alterations in Golgi complex architecture and in constitutive protein transport.
Aberrant glycosylation of proteins and lipids is a common feature of many tumor cell types, and is often accompanied by alterations in membrane traffic and an anomalous localization of Golgi-resident proteins and glycans. These observations suggest that the Golgi complex is a key organelle for at least some of the functional changes associated with malignant transformation. To gain insight into this possibility, we have analyzed changes in the structure and function of the Golgi complex induced by the conditional expression of the transforming N-Ras(K61) mutant in the NRK cell line. A remarkable and specific effect associated with this N-Ras-induced transformation was a conspicuous rearrangement of the Golgi complex into a collapsed morphology. Ultrastructural and stereological analyses demonstrated that the Golgi complex was extensively fragmented. The collapse of the Golgi complex was also accompanied by a disruption of the actin cytoskeleton. Functionally, N-Ras-transformed KT8 cells showed an increase in the constitutive protein transport from the trans-Golgi network to the cell surface, and did not induce the appearance of aberrant cell surface glycans. The Golgi complex collapse, the actin disassembly, and the increased constitutive secretion were all partially inhibited by the phospholipase A2 inhibitor 4-bromophenylacyl bromide. The results thus suggest the involvement of the actin cytoskeleton in the shape of the Golgi complex, and intracellular phospholipase A2 in its architecture and secretory function.


Changes in monoamine turnover in the brain of cachectic mice bearing colon-26 tumor cells.
Patients with cancer cachexia often suffer from psychiatric disorders. In the present study, we investigated the changes in monoaminergic activities in the brain in tumor-bearing mice with reference to the development of cachexia. Two clones, clone-5 (noncachectic clone) and clone-20 (cachectic clone), derived from the murine Colon-26 adenocarcinoma cell line (Nippon Roche Research Center), were inoculated subcutaneously at 1 x 10(6) cells/0.2 ml into the right lower back of BALB/c mice. In clone-20 mice, body weight and locomotor activity decreased significantly 10-15 days after tumor inoculation. The levels of noradrenaline, dopamine, and 3,4-dihydroxyphenylacetic acid showed no significant change among the three groups. The noradrenaline turnover rate in clone-20 mice was increased in cerebral cortex, hypothalamus, and midbrain. The 5-hydroxytryptamine turnover rate in clone-20 mice was increased in hippocampus, cerebral cortex, midbrain, and pons-medulla oblongata. In contrast, the dopamine turnover rate in clone-20 mice was decreased markedly in hippocampus, cerebral cortex, striatum, hypothalamus, and cerebellum. There was no significant change in amine turnover between control and clone-5 mice except for dopamine in hippocampus, cerebral cortex, and striatum and 5-hydroxytryptamine in striatum. No significant change in the levels of amino acids in the brain was observed among the three groups of mice. It is concluded that some of the psychiatric disorders from which cancer cachectic patients suffer might be ascribable to changes in monoaminergic activities in the brain.


Hepatitis A virus vaccination in childhood-onset systemic lupus erythematosus.
Vaccination of systemic lupus erythematosus patients with non-live vaccines may decrease vaccine-preventable infections and mortalities. In the present study, we aimed to compare the immunogenicity and safety of inactivated hepatitis A vaccination in childhood-onset systemic lupus erythematosus and healthy subjects. A total of 30 childhood-onset systemic lupus erythematosus and 39 healthy participants who were seronegative for hepatitis A received two doses of the hepatitis A vaccine in a 0- and 6-month schedule. Hepatitis A virus (HAV) IgG antibodies were measured before vaccination and 7 months after the vaccination. Although anti-HAV IgG antibody titers after vaccination were found to be somewhat lower in children with systemic lupus erythematosus than that of the healthy subjects ( p < 0.05), the difference in seroconversion rate was insignificant between childhood-onset systemic lupus erythematosus patients ( n = 24/30, 80%) and healthy controls ( n = 33/39, 84.6%). There was no increase in median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores and anti-ds DNA levels after the vaccination procedure. Seroconversion rates in childhood-onset systemic lupus erythematosus patients were not affected by medication, high disease activity (SLEDAI-2K >6) and anti-ds DNA positivity. None of the patients experienced any flare or adverse reaction throughout the study. According to these results, we conclude that inactivated hepatitis A vaccine is safe and well tolerated in childhood-onset systemic lupus erythematosus patients, with no adverse events or increase in activity. Immunogenicity to the hepatitis A vaccine was adequate, with a seropositivity rate of 80%.


Functional characterization of the transactivation properties of the PDX-1 homeodomain protein.
Pancreas formation is prevented in mice carrying a null mutation in the PDX-1 homeoprotein, demonstrating a key role for this factor in development. PDX-1 can also bind to and activate transcription from cis-acting regulatory sequences in the insulin and somatostatin genes, which are expressed in pancreatic islet beta and delta cells, respectively. In this study, we compared the functional properties of PDX-1 with those of the closely related Xenopus homeoprotein XIHbox8. Analysis of chimeras between PDX-1, XIHbox8, and the DNA-binding domain of the Saccharomyces cerevisiae transcription factor GAL4 revealed that their transactivation domain was contained within the N-terminal region (amino acids 1 to 79). Detailed mutagenesis of this region indicated that transactivation is mediated by three highly conserved sequences, spanning amino acids 13 to 22 (subdomain A), 32 to 38 (subdomain B), and 60 to 73 (subdomain C). These sequences were also required by PDX-1 to synergistically activate insulin enhancer-mediated transcription with another key insulin gene activator, the E2A-encoded basic helix-loop-helix E2-5 and E47 proteins. These results indicated that N-terminal sequences conserved between the mammalian PDX-1 and Xenopus XIHbox8 proteins are important in transcriptional activation. Stable expression of the PDX-1 deltaABC mutant in the insulin- and PDX-1-expressing betaTC3 cell line resulted in a threefold reduction in the rate of endogenous insulin gene transcription. Strikingly, the level of the endogenous PDX-1 protein was reduced to very low levels in these cells. These results suggest that PDX-1 is not absolutely essential for insulin gene expression in betaTC3 cells. We discuss the possible significance of these findings for insulin gene transcription in islet beta cells.


Omega-3 and omega-6 Fatty acids in blood and breast tissue of high-risk women and association with atypical cytomorphology.
The ratio of omega-3 to omega-6 fatty acids, especially the long-chain eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) to arachidonic acid (AA) ratio, is inversely associated with breast cancer risk. We measured the association between cytologic atypia, a biomarker for short-term risk of breast cancer development, and omega-3 and omega-6 fatty acid intake and levels in blood and breast tissue. Blood and benign breast tissue, sampled by random periareolar fine-needle aspiration (RPFNA), was obtained from 70 women at elevated risk for breast cancer. Self-reported dietary intake was assessed by the NCI's Food Frequency Questionnaire. The fatty acid composition of five lipid compartments, red blood cell, plasma and breast phospholipids, and plasma and breast triaclyglycerides (TAG), was analyzed by gas chromatography as weight percent. Median daily intakes of EPA+DHA and total omega-3 fatty acids were 80 mg and 1.1 g, respectively. The median total omega-3:6 intake ratio was 1:10. Compared with women without atypia, those with cytologic atypia had lower total omega-3 fatty acids in red blood cell and plasma phospholipids and lower omega-3:6 ratios in plasma TAGs and breast TAGs (P < 0.05). The EPA+DHA:AA ratio in plasma TAGs was also lower among women with atypia. This is the first report of associations between tissue levels of omega-3 and omega-6 fatty acids and a reversible tissue biomarker of breast cancer risk. RPFNA cytomorphology could serve as a surrogate endpoint for breast cancer prevention trials of omega-3 fatty acid supplementation.


Mood, motives, and gambling in young adults: an examination of within- and between-person variations using experience sampling.
It is well established that young adults are a population at risk for problem gambling and that young adults gamble for various reasons, including positive mood enhancement and negative mood reduction. Although these motives have been identified as important proximal predictors of gambling, the research to date has focused on between-subjects relationships. What is missing is a process-level understanding of the specific within-subjects relations between mood-regulation motives for gambling, mood states, and gambling behaviors. The current study used experience sampling to assess the specific link between gambling motives, mood states, and gambling behavior. Participants were 108 young adults (ages 19-24 years), who completed baseline measures of gambling motives and gambling problems and then reported on their mood states and gambling behavior three times a day for 30 days. Multilevel modeling analyses revealed a significant positive moderating effect for enhancement motives on the relationship between positive mood and amount of time spent gambling and number of drinks consumed while gambling. In addition, problem gambling status was associated with consuming fewer drinks while gambling at higher levels of positive mood, and spending more money than intended at higher levels of negative mood. Unexpectedly, there was only one moderating effect for coping motives on the mood-gambling relationship; low coping motivated gamblers consumed more alcohol while gambling at higher levels of positive mood, whereas high coping motivated gamblers did not change their drinking in response to positive mood. The current findings highlight enhancement motives as risky motives for young adult gambling, particularly in the context of positive mood, and suggest that gambling interventions should include strategies to address positive mood management.


Disease networks. Uncovering disease-disease relationships through the incomplete interactome.
According to the disease module hypothesis, the cellular components associated with a disease segregate in the same neighborhood of the human interactome, the map of biologically relevant molecular interactions. Yet, given the incompleteness of the interactome and the limited knowledge of disease-associated genes, it is not obvious if the available data have sufficient coverage to map out modules associated with each disease. Here we derive mathematical conditions for the identifiability of disease modules and show that the network-based location of each disease module determines its pathobiological relationship to other diseases. For example, diseases with overlapping network modules show significant coexpression patterns, symptom similarity, and comorbidity, whereas diseases residing in separated network neighborhoods are phenotypically distinct. These tools represent an interactome-based platform to predict molecular commonalities between phenotypically related diseases, even if they do not share primary disease genes.


IMG: the Integrated Microbial Genomes database and comparative analysis system.
The Integrated Microbial Genomes (IMG) system serves as a community resource for comparative analysis of publicly available genomes in a comprehensive integrated context. IMG integrates publicly available draft and complete genomes from all three domains of life with a large number of plasmids and viruses. IMG provides tools and viewers for analyzing and reviewing the annotations of genes and genomes in a comparative context. IMG's data content and analytical capabilities have been continuously extended through regular updates since its first release in March 2005. IMG is available at http://img.jgi.doe.gov. Companion IMG systems provide support for expert review of genome annotations (IMG/ER: http://img.jgi.doe.gov/er), teaching courses and training in microbial genome analysis (IMG/EDU: http://img.jgi.doe.gov/edu) and analysis of genomes related to the Human Microbiome Project (IMG/HMP: http://www.hmpdacc-resources.org/img_hmp).


Healthcare Utilization and Advance Care Planning among Older Adults Across Cognitive Levels.
This study examined the impact of advance care planning (ACP) on healthcare utilization among older adults with normal cognition and impaired cognition/dementia. Using datasets from the Health and Retirement Study, we conducted a cross-sectional study on 17,698 participants aged 51 years and older. Our analyses included survey descriptive and logistic regression procedures. ACP measures included a living will and durable power of attorney for healthcare. Healthcare utilization was measured using the days spent in hospitals, hospice care, nursing homes, and home care. Of the participants, 77.8% had normal cognition, and 22% had impaired cognition/dementia. The proportion of impaired cognition/dementia was higher among racially minoritized participants, single/widowed participants, and those who lived alone and were less educated. The results showed that having an ACP measure was associated with longer stays in hospitals, nursing homes, and home healthcare in all participants.


A role for the lysosomal protease cathepsin B in zebrafish follicular apoptosis.
This study presents evidence that cathepsin B, a lysosomal protease, may be involved in the regulation of apoptosis during serum-starvation in teleost follicles. Zebrafish vitellogenic follicles were isolated, incubated under serum-free conditions and homogenized. The follicle extracts demonstrated caspase-3-like activity using the fluorogenic substrate DEVD-AMC, indicating the onset of apoptosis. Cathepsin B activity as measured using the fluorogenic cathepsin B substrate, Z-Arg-Arg-AMC was elevated within the first 6h of incubation in serum-free media and coincided with the onset of apoptosis. This increase in cathepsin B activity was sensitive to the cathepsin B inhibitor, CA-074-ME. Furthermore, adding CA-074-ME to the follicle incubation blocked caspase-3-like activation, suggesting that cathepsin B activity is a positive regulator of the apoptotic cascade during serum-starvation. Interestingly, the increase in cathepsin-B-like activity was not preceded by an increase in cathepsin B mRNA transcription, suggesting that regulation of this enzyme is at a level other than of the gene. These results suggest a regulatory role for cathepsin B during follicular apoptosis in zebrafish ovarian follicles.


Graded Exercise Testing Protocols for the Determination of VO2max: Historical Perspectives, Progress, and Future Considerations.
Graded exercise testing (GXT) is the most widely used assessment to examine the dynamic relationship between exercise and integrated physiological systems. The information from GXT can be applied across the spectrum of sport performance, occupational safety screening, research, and clinical diagnostics. The suitability of GXT to determine a valid maximal oxygen consumption (VO2max) has been under investigation for decades. Although a set of recommended criteria exists to verify attainment of VO2max, the methods that originally established these criteria have been scrutinized. Many studies do not apply identical criteria or fail to consider individual variability in physiological responses. As an alternative to using traditional criteria, recent research efforts have been directed toward using a supramaximal verification protocol performed after a GXT to confirm attainment of VO2max. Furthermore, the emergence of self-paced protocols has provided a simple, yet reliable approach to designing and administering GXT. In order to develop a standardized GXT protocol, additional research should further examine the utility of self-paced protocols used in conjunction with verification protocols to elicit and confirm attainment of VO2max.


[Optimal timing of contrast enhancement in coronary CT angiography using the Bolus-tracking method].
Negative product value for coronary artery disease is 98% to 99%. Therefore, the number of unnecessary cardiac catheterization procedures is reduced as the usefulness of CT systems for examination of the coronary arteries improves. In the bolus-tracking method, in which an ROI is placed in the ascending aorta to trigger scanning, scanning may not be performed at the optimal time of contrast enhancement depending on the patient. In addition to identifying the causes of this problem, we have developed a new method in which ROIs are placed in the right ventricle and left atrium to trigger scanning when the concentrations of contrast medium in the right ventricle and left atrium become equal. The two methods were then compared and evaluated. In the scan method, in which an ROI is placed in the ascending aorta, the reason for non-optimal scan timing is considered to be that the time required for contrast medium injected via an antecubital vein to reach the heart varies depending on the individual patient(approximately 3 times the variation of our method)followed by a delay of approximately 5 seconds between the scan trigger time and the actual scan start time. In the scan method in which scanning is triggered when the concentrations of contrast medium in the right ventricle and left atrium become equal, scanning can be performed at the time of peak enhancement regardless of differences in the time required for the injected contrast medium to reach the target region or differences in the injection rate, demonstrating the usefulness of this method.


Factors Related to Positive Memory Count Among Trauma-Exposed Individuals: A Scoping Review.
To examine the existing knowledge base on trauma experiences and positive memories, we conducted a scoping review of trauma and post-trauma factors related to positive memory count. In July 2019, we searched PubMed, Medline, PsycINFO, Web of Science, Cumulative Index of Nursing and Allied Health Literature, Embase, and PTSDpubs for a combination of words related to "positive memories/experiences," "trauma/posttraumatic stress disorder (PTSD)," and "number/retrieval." Twenty-one articles met inclusion criteria (adult samples, original articles in English, peer-reviewed, included trauma-exposed group or variable of trauma exposure, trauma exposure examined with a trauma measure/methodology, assessed positive memory count, empirical experimental/non-experimental study designs). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, two authors reviewed abstracts, completed a secondary search, and independently extracted data. Our review indicated (1) that depression and PTSD were most researched; (2) no conclusive relationships of positive memory count with several psychopathology (depression, acute stress disorder, eating disorder, and anxiety), cognitive/affective, neurobiological, and demographic factors; (3) trends of potential relationships of positive memory count with PTSD and childhood interpersonal traumas (e.g., sexual and physical abuse); and (4) lower positive memory specificity as a potential counterpart to greater overgeneral positive memory bias. Given variations in sample characteristics and methodology as well as the limited longitudinal research, conclusions are tentative and worthy of further investigations.


Neurotensin prevents intestinal mucosal hypoplasia in rats fed an elemental diet.
Liquid elemental diets are associated with mucosal hypoplasia of both the small intestine and colon. Neurotensin, a tridecapeptide widely distributed in the gut, is trophic for the small intestine of rats fed a normal chow diet. The purpose of this study was to determine whether neurotensin could reverse the hypoplasia of intestinal mucosa that is associated with feeding a liquid elemental diet. Forty male Sprague-Dawley rats were randomized into five groups. Four groups were fed (for seven days) a glutamine-free liquid elemental diet. Subcutaneous injection of saline (control) or neurotensin (33, 100 or 300 micrograms/kg) were given to the groups of rats every 8 hr for seven days. Group five (Chow) received rat chow ad libitum for seven days. Rats were killed on day 8, and the proximal jejunum, distal ileum, and proximal colon removed. Mucosal weight, DNA, RNA, and protein contents were determined. Neurotensin (300 micrograms/kg) increased the cellularity of the small intestinal mucosa and reversed mucosal hypoplasia due to an elemental diet; a more pronounced effect was noted in the jejunum compared to the ileum. Neurotensin (33 and 100 micrograms/kg) increased mucosal DNA content in the jejunum but was not effective in reversing the hypoplasia. Neurotensin had no effect on growth of colonic mucosa. These results suggest that neurotensin may be an important trophic hormone for the small intestine. Administration of neurotensin may alleviate hypoplasia of the small bowel mucosa and maintain functional integrity of the gut during prolonged feeding of an elemental diet.


Congenital microvillus atrophy in a 4-month-old girl.
Congenital microvillus atrophy is a severe generalized enteropathy with ultrastructural abnormalities of the intestinal brush border. It is a rather new clinicopathological entity which needs to be differentiated from other enteropathies within the spectrum of intractable diarrhea of infancy. The presented case was a four-month-old girl with a chronic, intractable diarrhea, beginning at birth. The diagnosis was established only after the electron microscopic examination of small intestinal mucosa which revealed the characteristic features of the disease. Congenital microvillus atrophy is a rare autosomal recessively inherited disorder and bowel transplantation becomes a realistic option of treatment. Therefore, it should be specifically considered in the differential diagnosis of chronic intractable diarrhea of infancy.


Use of two cloprostenol administrations 11.5 days apart efficiently synchronizes oestrus in photostimulated multiparous dairy goats in the non-breeding season.
This study assessed the efficiency of synchronous oestrous induction by light programme followed by two doses of cloprostenol in acyclic Saanen goats of different parity orders. Primiparous (n = 22) and multiparous (n = 33) goats were subjected to 16 hr of light and 8 hr of darkness for 60 days (D0-D60), starting 10 days after the winter solstice. All goats received 120 µg cloprostenol doses on D130 (morning) and D141.5 (afternoon) (11.5 days apart). Oestrus behaviour, ovarian follicular dynamics and serum progesterone (P4) analyses were recorded from D0 to D174 at different intervals. Animals in oestrus after D141.5 were randomly assigned into two groups: assisted natural mating (NM) or artificial insemination (AI; 10-24 hr after oestrus onset with frozen-thawed semen). From D57 to D120, 89.0% of goats presented large follicles (5-8 mm) and P4 concentrations were subluteal from D0 to D120. More multiparous compared to primiparous goats (54.5%, 18/33 vs. 18.2%, 4/22) exhibited oestrus after both injections. More primiparous compared to multiparous goats (54.5%, 12/22 vs. 12.1%, 4/33) did not exhibit oestrus after any injection. A total of 35 goats (64%) were in oestrus after the second prostaglandin injection and were subjected to NM or AI. The conception rate was similar among primiparous (70.0%, 7/10) and multiparous (68.0%, 17/25) goats but the pregnancy rate differed, being 31.8% (7/22) and 51.5% (17/33), respectively. No interaction was found between parity order and P4 concentrations in does that became pregnant or not. Thus, the association between light programme (60 days, starting at the beginning of winter) and two cloprostenol administrations 11.5 days apart (starting 70 days after the end of the light treatment) resulted in sufficient synchronous oestrous response in multiparous acyclic Saanen goats to reach satisfactory fertility levels after both NM and AI.


Explaining Osteomyelitis and Prosthetic Joint Infections (PJI) in terms of Biofilm - A Review.
Osteomyelitis is a chronic infection of bones. Eradication of bone infection is usually with antibiotics and debridement, but it is slow and the infection can recur even after many years. It is now established that osteomyelitis is due to biofilm and a better understanding of the process is required. We review the development of biofilm and apply it to osteomyelitis management. The planktonic microbes' response to adverse conditions is the formation of biofilm. Bacterial infections in planktonic forms cause infections that can be controlled with antibiotics and immunisation, however the same microbe when its phenotype becomes biofilm is more resilient. The understanding of how planktonic bacteria convert to biofilm is one of the aims set out for this article.


Celivarone for maintenance of sinus rhythm and conversion of atrial fibrillation/flutter.
Celivarone, a new noniodinated benzofuran derivative pharmacologically related to dronedarone and amiodarone, has been shown to have antiarrhythmic properties at a molecular level. The purpose of the 2 trials presented here (MAIA and CORYFEE) was to assess celivarone efficacy in the maintenance of sinus rhythm postcardioversion and for the conversion of atrial fibrillation (AF)/atrial flutter (AFL). In the MAIA trial, 673 patients with AF/AFL recently converted to sinus rhythm were randomly assigned to receive 50, 100, 200, or 300 mg once-daily dosing of celivarone; 200 mg daily of amiodarone preceded by a loading dose of 600 mg for 10 days; or placebo. At 3 months' follow up, no significant difference was observed in time to AF/AFL relapse among the various celivarone groups and placebo. However, fewer symptomatic AF/AFL recurrences were observed in the lower-dose celivarone groups (26.6% for celivarone 50 mg [P = 0.022] and 25.2% for celivarone 100 mg [P = 0.018] vs 40.5% for placebo at 90 days). Fewer adverse events were observed with the use of celivarone and placebo than amiodarone. In the CORYFEE study, 150 patients with AF/AFL were randomly assigned to once-daily celivarone dosing of 300 or 600 mg, or placebo, for a 2-day treatment period. There was no significant difference in the rate of spontaneous conversion to sinus rhythm between the treatment and control groups. In these studies, celivarone does not appear to be efficacious in the maintenance of sinus rhythm in AF/AFL patients or for the conversion of AF/AFL patients.


Effects of insecticides, fipronil and imidacloprid, on the growth, survival, and behavior of brown shrimp Farfantepenaeus aztecus.
Increased use of pesticide is causing detrimental effects on non-target species worldwide. In this study, we examined the lethal and sub-lethal effects of fipronil and imidacloprid, two commonly used insecticides, on juvenile brown shrimp (Farfantepenaeus aztecus), one of the most commercially and ecologically important species in the United States. The effects of six concentrations of fipronil (0.0, 0.005, 0.01, 0.1, 1.0, and 3.0 μg/L) and six concentrations of imidacloprid (0.0, 0.5, 1.0, 15.0, 34.5, 320.0 μg/L) were tested in a laboratory. We examined five different endpoints: growth, moulting interval, survivorship, behavioral change, and body color change. Growth of shrimp was reduced significantly under higher concentrations of both insecticides. Under fipronil exposure, shrimp in control showed the shortest inter-moult interval (7.57 ± 2.17 day) compared with other treatments; similarly, in the imidacloprid experiment, moulting increased from 8.43 ± 2.52 day in control to 11.95 ± 4.9 day in 0.5 μg/L treatment. Higher concentrations of fipronil (1.0 and 3.0 μg/L) showed a 0.0% survival rate compared with 100% survival in the control and 0.005 μg/L treatment. Under imidacloprid, survivorship decreased from 100% in the control to 33.33% in the 320.0 μg/L treatment. The 96-h LC50 of fipronil was 0.12 μg/L, which makes brown shrimp one of the most sensitive invertebrates to the pesticide. Changes in behavior and body color were observed under both insecticides after different durations of exposures depending on concentrations. We conclude that, at the corresponding EPA benchmark concentrations, fipronil had more lethal effects than imidacloprid, and imidacloprid had more sub-lethal effects than fipronil. Both effects are of serious concern, and we suggest monitoring is necessary in estuaries.


[Comparative estimation of the effects of continuous and intermittent cyclical microwave radiation on the behavior of rats in the extraordinary situation].
Research has been carried out to investigate the effects of pulsed microwave exposure without pause (7 GHz, 400 pps, 100 microseconds, 70-150 mW/cm2, exposure 10 min) and pulsed interrupted cyclical microwave exposure (5 min exposure--4 min pause--5 min exposure) on learned behaviors of rats in the paradigm of extraordinary situation (the rescue of the life). It was shown that reductions in conditioned behavior after acute pulsed microwave exposure occurred at SAR of 21 W/kg (100 mW/cm2) and after cyclical pulsed microwave exposure at SAR of 28.4 W/kg (135 mW/cm2).


Integration of T-DNA binary vector 'backbone' sequences into the tobacco genome: evidence for multiple complex patterns of integration.
During the process of crown gall tumorigenesis, Agrobacterium tumefaciens transfers part of the tumor-inducing (Ti) plasmid, the T-DNA, to a plant cell where it eventually becomes stably integrated into the plant genome. Directly repeated DNA sequences, called T-DNA borders, define the left and the right ends of the T-DNA. The T-DNA can be physically separated from the remainder of the Ti-plasmid, creating a 'binary vector' system; this system is frequently used to generate transgenic plants. Scientists initially thought that only those sequences located between T-DNA left and right borders transferred to the plant. More recently, however, several reports have appeared describing the integration of the non-T-DNA binary vector 'backbone' sequences into the genome of transgenic plants. In order to investigate this phenomenon, we constructed T-DNA binary vectors containing a nos-nptll gene within the T-DNA and a mas2'-gusA (beta-glucuronidase) gene outside the T-DNA borders. We regenerated kanamycin-resistant transgenic tobacco plants and analyzed these plants for the expression of the vector-localized gusA gene and for the presence of binary vector backbone sequences. Approximately one-fifth of the plants expressed detectable GUS activity. PCR analysis indicated that approximately 75% of the plants contained the gusA gene. Southern blot analysis indicated that the vector backbone sequences could integrate into the tobacco genome linked either to the left or to the right T-DNA border. The vector backbone sequences could also integrate into the plant genome independently of (unlinked to) the T-DNA. Although we could readily detect T-strands containing the T-DNA within the bacterium, we could not detect T-strands containing only the vector backbone sequences or these vector sequences linked to the T-DNA.


Effect of electrode roughness on the capacitive behavior of self-assembled monolayers.
Analytical gold electrodes were polished mechanically and electrochemically and the true area of the electrode surface was measured by quantitative oxidative/reductive cycling of the electrode. A roughness factor for each electrode was determined from the ratio of the true area to the geometric area. The roughness is fully described by a combination of microscopic roughness (up to tens of nanometers) and macroscopic roughness (on the order of hundreds of nanometers) terms. The electrodes were then derivatized with a self-assembled monolayer (SAM) of dodecanethiol or a thioalkane azacrown and characterized by impedance spectroscopy. The behavior of the electrodes was modeled with either a Helmholtz or Randles equivalent circuit (depending on the SAM used) in which the capacitance was replaced with a constant phase element. From the model, an effective capacitance and an alpha factor that quantifies the nonideality of the SAM capacitance was obtained. The effective capacitance divided by the roughness factor yields the capacitance per unit true area, which is only a function of microscopic roughness. The relationship between this capacitance and the alpha factor indicates that microscopic roughness predominantly affects the nonideality of the film while macroscopic roughness predominantly affects the magnitude of the film's capacitance. Understanding the contribution of the electrode topography to the magnitude and ideality of the SAM capacitance is important in the construction of SAM-based capacitive sensors because it predicts the importance of electrode-electrode variations.


Roboviz: A Game-Centered Project for Information Visualization Education.
Due to their pedagogical advantages, large final projects in information visualization courses have become standard practice. Students take on a client-real or simulated-a dataset, and a vague set of goals to create a complete visualization or visual analytics product. Unfortunately, many projects suffer from ambiguous goals, over or under-constrained client expectations, and data constraints that have students spending their time on non-visualization problems (e.g., data cleaning). These are important skills, but are often secondary course objectives, and unforeseen problems can majorly hinder students. We created an alternative for our information visualization course: Roboviz, a real-time game for students to play by building a visualization-focused interface. By designing the game mechanics around four different data types, the project allows students to create a wide array of interactive visualizations. Student teams play against their classmates with the objective to collect the most (good) robots. The flexibility of the strategies encourages variability, a range of approaches, and solving wicked design constraints. We describe the construction of this game and report on student projects over two years. We further show how the game mechanics can be extended or adapted to other game-based projects.


Closing service system gaps for homeless clients with a dual diagnosis: integrated teams and interagency cooperation.
There is great concern about fragmentation of mental health service delivery, especially for dually diagnosed homeless people, and apprehension that such fragmentation adversely affects service access and outcomes. This study first seeks to articulate two alternative approaches to the integration of psychiatric and substance abuse services, one involving an integrated team model and the other a collaborative relationship between agencies. It then applies this conceptualization to a sample of dually diagnosed homeless people who participated in the ACCESS demonstration. Longitudinal outcome data were obtained through interviews at baseline, 3 months, and 12 months with homeless clients with a dual diagnosis (N = 1074) who received ACT-like case management services through the ACCESS demonstration. A survey of ACCESS case managers was conducted to obtain information on: (i) the proportion of clients who received substance abuse services directly from ACCESS case management teams, and the proportion who received services from other agencies; and (ii) the perceived quality of the relationship (i.e. communication, cooperation and trust) between providers--both within the same teams and between agencies. Hierarchical linear modeling was then used to examine the relationship of these two factors to service use and outcome with mixed-model regression analysis. Significant (p<.05) and positive relationships were observed in 4 of the 20 analyses of the association of service use and measures of communication, cooperation, and trust (either intrateam or inter-agency) while none were significant and negative. At 12 months, receipt of a higher proportion of services from agencies other than the ACCESS team was associated with fewer days homeless, and greater reduction of psychiatric symptoms, contradicting the hypothesis that integrated team care is more effective than interagency collaborations. This study broadens the conceptual framework for addressing service system fragmentation by considering both single team integration and interagency coordination, and by considering both program structure and the quality of relationships between providers. Data from a multi-site outcome study demonstrated suggestive associations between perceptions of communication, cooperation and measures of clinical service use. However, the proportion of clients treated entirely within a single team was associated with poorer housing and psychiatric outcomes. These empirical results must be regarded as illustrative rather than conclusive because of the use of a non-experimental study design, imperfections in the available measures, and the incomplete sampling of case managers. This study suggests that fragmentation of services for dually diagnosed clients may be reduced by improving the interactions within and between agencies providing these services. While primary emphasis has been placed on developing integrated teams, interagency approaches should not be prematurely excluded. Research on approaches to reducing system fragmentation have focused on either global efforts to integrate numerous agencies in a community or highly focused efforts to develop specialized teams. Future research should also focus on the possibility of fostering constructive relationships between selected pairs or subsets of agencies. Research in this area will also benefit from the further development measures of team integration and of both intra-team and inter-agency communication, collaboration, and trust.


Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter.
The value of radical systematic lymphadenectomy for treatment of early-stage bronchial carcinoma is controversial. We performed a prospective randomized study to address this question. Altogether 115 patients with peripheral non-small-cell lung cancers smaller than 2 cm in diameter were enrolled in this study. They were randomly assigned into a lobectomy with lymph node sampling group (sampling group, n = 56) or a lobectomy with radical systematic lymph node dissection group (dissection group, n = 59). Inclusion criteria were based only on preoperative clinical studies. Four tumors were larger than 2 cm postoperatively. One patient had disseminated disease, and two had intrapulmonary metastases discovered at surgery. Two patients had small-cell carcinoma. There were four with pathologic N1 disease and seven with N2 disease in the dissection group and three with N1 and eight with N2 disease in the sampling group. The numbers of local and distant recurrences were two and six, respectively, in the dissection group and two and five in the sampling group. The overall 5-year survival was 81% in the dissection group and 84% in the sampling group. No significant differences in the recurrence rate or survival was seen between the groups. Our results demonstrate that clinically evaluated peripheral non-small-cell carcinomas smaller than 2 cm in diameter do not require radical systematic mediastinal and hilar lymph node dissection.


Echinococcus granulosus in wildlife in and around the Kosciuszko National Park, south-eastern Australia.
To investigate the distribution of Echinococcus granulosus in wild dogs and foxes and hydatidosis in wildlife coexisting with foxes and wild dogs in and around Kosciuszko National Park. Prospective and ad hoc surveys by necropsy of definitive and intermediate hosts. Wild dogs and foxes were trapped at one location in the Kosciuszko National Park and at 7 locations around the periphery of the Park. Feral pigs, macropodid marsupials, wombats, and feral goats were collected at some of the same locations. The animals were humanely killed, their small intestines removed in the field, the contents collected, preserved and examined microscopically. All internal organs of intermediate hosts were examined for hydatid cysts. Unidentified lesions were examined histologically. Echinococcus granulosus tapeworms were found in wild dogs from all locations. Prevalence ranged up to 100% with worm burdens up to 300,000 worms. Prevalence in foxes ranged up to 50% in animals recovered from 5 locations. The worm burdens were usually less than 50 E. granulosus per fox. Hydatid cysts were found in all macropodid species. Prevalence (69%) and cyst fertility (100%) were highest in swamp wallabies (Wallabia bicolour). Prevalence of cysts in feral pigs ranged up to 49%. Less than 22% of the cysts were fertile. No cysts were found in any of the wombats or feral goats. Echinococcus granulosus occurs commonly in wildlife in and around the Kosciuszko National Park. High numbers of fertile cysts in swamp wallabies, a favoured dietary item for wild dogs in this region, suggests swamp wallabies are pivotal in maintaining transmission. Physical contact with wild dogs and foxes or accidental contact with wild canid faeces is a public health risk.


Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in diabetic and healthy subjects.
We hypothesized that molecules active in vascular remodeling (i.e. MMPs and their TIMPs) could be modified in diabetic patients, as indirect markers of the diabetes related generalized abnormality of vascular activity. To test this hypothesis, we measured the plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in type 2 diabetic patients and in healthy subjects. We enrolled 181 diabetic patients and 165 controls. We measured body mass index (BMI), glycosylated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment index (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct) fibrinogen (Fg), high sensitivity C-reactive protein (hs-CRP), and plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. A significant increase (P<0.0001) of BMI, HbA(1c), FPG, FPI, HOMA index, SBP, DBP, TC, LDL-C, Tg, Lp(a), PAI-1, Hct, Fg, and hs-CRP was present in the diabetic group, with a significant decrease (P<0.0001) of HDL-C levels compared to healthy subjects. MMP-2 and MMP-9 levels were significantly higher (P<0.0001) in diabetic patients. Significant TIMP-1, and TIMP-2 increase was also observed (P<0.0001) in the diabetic group. Plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 are increased in diabetic patients which may reflect abnormal extracellular matrix (ECM) metabolism.


Modeling regulatory network topology improves genome-wide analyses of complex human traits.
Genome-wide association studies (GWAS) have cataloged many significant associations between genetic variants and complex traits. However, most of these findings have unclear biological significance, because they often have small effects and occur in non-coding regions. Integration of GWAS with gene regulatory networks addresses both issues by aggregating weak genetic signals within regulatory programs. Here we develop a Bayesian framework that integrates GWAS summary statistics with regulatory networks to infer genetic enrichments and associations simultaneously. Our method improves upon existing approaches by explicitly modeling network topology to assess enrichments, and by automatically leveraging enrichments to identify associations. Applying this method to 18 human traits and 38 regulatory networks shows that genetic signals of complex traits are often enriched in interconnections specific to trait-relevant cell types or tissues. Prioritizing variants within enriched networks identifies known and previously undescribed trait-associated genes revealing biological and therapeutic insights.


Deaths: Leading Causes for 2020.
Objectives-This report presents final 2020 data on the 10 leading causes of death in the United States by age, race and Hispanic origin, and sex. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2020," the National Center for Health Statistics' annual report of final mortality statistics. Methods-Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2020. Causes of death classified by the International Classification of Diseases, 10th Revision (ICD-10) are ranked according to the number of deaths. Cause-of-death statistics are based on the underlying cause of death. Race and Hispanicorigin data are based on the Office of Management and Budget's 1997 standards for reporting race and Hispanic origin. Results-In 2020, many of the 10 leading causes of death changed rank order due to the emergence of COVID-19 as a leading cause of death in the United States. The 10 leading causes of death in 2020 were, in rank order: Diseases of heart; Malignant neoplasms; COVID-19; Accidents (unintentional injuries); Cerebrovascular diseases; Chronic lower respiratory diseases; Alzheimer disease; Diabetes mellitus; Influenza and pneumonia; and Nephritis, nephrotic syndrome and nephrosis. They accounted for 74.1% of all deaths occurring in the United States. Differences in the rankings are evident by age, race and Hispanic origin, and sex. Leading causes of infant death for 2020 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Accidents (unintentional injuries); Newborn affected by maternal complications of pregnancy; Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage.


Hypoglycaemia monitoring in a medical receiving ward.
It has been suggested that current care for diabetes inpatients remains inadequate and that greater attention is required for high quality management. In this project the aspect of hypoglycaemia was studied in a busy medical receiving ward at the Glasgow Royal Infirmary. A large proportion of inpatients have diabetes and episodes of hypoglycaemia experienced by this population can delay discharge and indeed be detrimental to health. Thus it is important from both an organisational and patient perspective to manage this population well. In this project BM machine data was analysed to identify patients who were hypoglycaemic. These patients were then tracked down to study the subsequent management and compared this against recommended guidance. Following this an intervention was made to promote identification, management, documentation, and prevention of hypoglycaemia. This was deliberately a simple intervention involving discussions with staff and provision of basic documented guidance next to every BM machine. In the first phase 17 patients were identified and in a second and third phase 16 patients each time were further identified. Patients in the study were both type 1 and type 2 diabetics. Initial results in phase I were compared to results in phase II and III respectively. This intervention produced significant improvements in management with correct monitoring of low BMs (i.e. upon identification of low BM repeat within 1 hour) improving from 47% to 100% (for Phase II and III). Also, recording of preventative measures of hypoglycaemia improved from 35% to 88% and 94% with an improvement from 24% to 69% and 75% in recording of treatment given if needed. In conclusion, the study successfully demonstrated that simple measures can significantly improve the quality care of inpatient diabetic patients in relation to hypoglycaemia management.


Effects of Lactobacillus plantarum PS128 on Depressive Symptoms and Sleep Quality in Self-Reported Insomniacs: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial.
Recent animal studies have supported that Lactobacillus plantarum PS128 (PS128) can reduce the severity of anxiety and depression. However, previous studies did not focus on the sleep quality and mood of humans. This study determines whether PS128 reduces the severity of anxiety and depressive symptoms, regulates autonomic nervous system function, and improves sleep quality. Forty participants between 20 and 40 years of age with self-reported insomnia were randomly assigned to two groups, a PS128 group and a placebo group, in a double-blind trial. Participants took two capsules of either PS128 or a placebo after dinner for 30 days. Study measures included subjective depressive symptoms, anxiety and sleep questionnaires, and miniature-polysomnography recordings at baseline and on the 15th and 30th days of taking capsules. Overall, all outcomes were comparable between the two groups at baseline and within the 30-day period, yet some differences were still found. Compared to the control group, the PS128 group showed significant decreases in Beck Depression Inventory-II scores, fatigue levels, brainwave activity, and awakenings during the deep sleep stage. Their improved depressive symptoms were related to changes in brain waves and sleep maintenance. These findings suggest that daily administration of PS128 may lead to a decrease in depressive symptoms, fatigue level, cortical excitation, and an improvement in sleep quality during the deep sleep stage. Daily consumption of PS128 as a dietary supplement may improve the depressive symptoms and sleep quality of insomniacs, although further investigation is warranted.


The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection.
CD4 T cells that recognize peptide antigen in the context of class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity (CD4 CTL) play a role in chronic as well as acute infections, such as influenza A virus (IAV) infection. In the last couple of decades, techniques to measure the frequency and activity of these cytolytic cells has demonstrated their abundance in infections, such as human immunodeficiency virus, mouse pox, murine gamma herpes virus, cytomegalovirus, Epstein-Barr virus, and influenza among others. We now appreciate a greater role for CD4 CTL as direct effectors in viral infections and antitumor immunity through their ability to acquire perforin-mediated cytolytic activity and contribution to lysis of virally infected targets or tumors. As early as the 1980s, CD4 T cell clones with cytolytic potential were identified after influenza virus infection, yet much of this early work was dependent on in vitro culture and little was known about the physiological relevance of CD4 CTL. Here, we discuss the direct role CD4 CTL play in protection against lethal IAV infection and the factors that drive the generation of perforin-mediated lytic activity in CD4 cells in vivo during IAV infection. While focusing on CD4 CTL generated during IAV infection, we pull comparisons from the literature in other antiviral and antitumor systems. Further, we highlight what is currently known about CD4 CTL secondary and memory responses, as well as vaccination strategies to induce these potent killer cells that provide an extra layer of cell-mediated immune protection against heterosubtypic IAV infection.


Understanding an Urban Park through Big Data.
To meet the needs of park users, planners and designers must know what park users want to do and how they want the park to offer different activities. Big data may help planners and designers gain this knowledge. This study examines how big data collected in an urban park could be used to identify meaningful implications for planning and design. While big data have emerged as a new data source, big data have not become an accepted source of data due to a lack of understanding of big data analytics. By comparing a survey as a traditional data source with big data, this study identifies the strengths and weaknesses of using big data analytics in park planning and design. There are two research questions: (1) what activities do park users want; and (2) how satisfied are users with different activities. The Gyeongui Line Forest Park, which was built on an abandoned railway, was selected as the study site. A total of 177 responses were collected through the onsite survey, and 3703 tweets mentioning the park were collected from Twitter. Results from the survey show that ordinary activities such as walking and taking a rest in the park were the most common. These findings also support existing studies. The results from social media analytics found notable things such as positive tweets about how the railway was turned into a park, and negative tweets about diseases that may occur in the park. Therefore, a survey as traditional data and social media analytics as big data can be complementary methods for the design and planning process.


Infectivity enhancement by HIV-1 Nef is dependent on the pathway of virus entry: implications for HIV-based gene transfer systems.
Retroviruses have been extensively used in the development of gene transfer systems. Recently, there has been a great deal of interest in the use of lentiviruses for gene transfer because they infect nondividing cells. Human immunodeficiency virus (HIV) has been the lentivirus most often used for this purpose, but its genomic complexity and limited tropism present some challenges to the establishment of efficient gene transfer systems. In this paper we present data showing intrinsic differences between the infectivity of wild-type HIV and HIV particles pseudotyped with heterologous envelope glycoproteins. Interestingly, HIV pseudotypes with envelope glycoproteins from the amphotropic murine leukemia virus or the vesicular stomatitis virus (VSV) are 3 and 40 times more infectious than wild-type HIV, respectively. In addition, we show that the reliance on Nef expression for maximal infectivity of HIV particles is dependent on the path of virus entry. The dependence on Nef for higher infectivity is greater for amphotropic pseudotypes and wild-type HIV than for VSV-G pseudotypes. We conclude that VSV-G pseudotypes of HIV vectors are an excellent choice for gene transfer purposes and Nef-mediated viral infectivity enhancement is affected by virus entry pathway.


Relevance of the antioxidant properties of methotrexate and doxycycline to their treatment of cardiovascular disease.
Many medications exhibit clinical benefits that are unrelated to their primary therapeutic uses. In many cases, the mechanisms underpinning these pleotropic effects are unknown. Two commonly prescribed medications that exhibit pleotropic benefits in cardiovascular disease and other diseases associated with chronic inflammation are methotrexate (MTX) and doxycycline (DOX). The vast majority of cardiovascular disease is associated with atherosclerosis. Because atherosclerosis is a chronic inflammatory disease, possible mechanisms by which MTX and DOX reduce inflammation have been investigated. Interestingly, the primary structure of both of these medications contain aromatic phenolic rings, which resemble polyphenols that are known to possess antioxidant activity. Inflammation and oxidative stress are intimately related. Inflammation promotes oxidative stress, which in turn leads to further inflammation; in this way, oxidative stress and inflammation can establish a self-perpetuating cycle. It has been shown that MTX and DOX act as antioxidants and are capable of scavenging free radicals and the reactive oxygen species (ROS) superoxide (O2-). Furthermore, both MTX and DOX inhibit the formation of malondialdehyde acetaldehyde (MAA) adducts, products of oxidative stress and lipid peroxidation. Importantly, MAA-adducts are highly immunogenic and initiate inflammatory responses; thereby, fueling the cycle of inflammation and oxidative stress that results in chronic inflammation. Thus, reducing the formation of MAA-adducts may ameliorate inflammation that leads to ROS production and in this way, break the self-sustaining cycle of oxidative stress and inflammation. It is possible that the under-recognized antioxidant properties of these medications may be a mechanism by which they and other medications provide pleotropic benefit in the treatment of chronic inflammatory disease.


[Dynamics of neurotic depression in children and adolescents].
Seven hundred thirty nine children and adolescents with neurotic depression (293 male, 446 female, aged 1-17 years) have been examined. Depression was mildly expressed in 90.9% of the cases and moderately--in 9.1%. In clinical picture anxious, asthenic, astheno-anxious and anxious-melancholic depression types were present. In neurotic depression in children and adolescents, the initial (the first) and subsequent (the second) stages have been detected. In a case of favorable development of the disease it stops at the initial stage. In a case of poor prognosis (192 patients) the dynamics of disease was distinguished by 3 features: increase of somatization and development of psychosomatic disorders (119 patients), endogenization (45) and formation of pathologic personality changes (28). During treatment clinical variants of disease and its dynamics peculiarities in the every stage are suggested to be taken into account.


Guided self-help interventions for irritable bowel syndrome: a systematic review and meta-analysis.
Although irritable bowel syndrome (IBS) is highly prevalent and is accompanied by high costs for respective healthcare systems, the data on treatment effectiveness are limited. Current treatment methods have limitations in terms of side effects and availability. Guided self-help (GSH) might be an easily accessible and cost-effective treatment alternative. This study is the first systematic review and meta-analysis of GSH interventions for IBS. Using electronic databases (MEDLINE, SCOPUS, PsycINFO, and Web of Science), we performed a systematic search for randomized-controlled trials. Using a random-effect model, we calculated the pooled standardized mean differences (SMDs) of GSH on IBS symptom severity (primary outcome) and quality of life (secondary outcome). We additionally examined the moderating effects of online-based interventions and face-to-face therapist contact by applying mixed models. A systematic literature search identified 10 eligible randomized-controlled trials, including 886 participants. Compared with the control conditions, the effect size was medium for the decrease in IBS symptom severity (SMD=0.72; 95% confidence interval: 0.34-1.08) and large for the increase in patients' quality of life (SMD=0.84; 95% confidence interval: 0.46-1.22). Neither treatment format nor face-to-face contact was a predictor of therapy outcomes in between-group analyses. In contrast, within-group analyses led to the conclusion that online-based interventions are more effective than other self-help formats. GSH is an effective alternative for the treatment of IBS. As GSH methods are easy to implement, it seems sensible to integrate GSH into clinical practice. With respect to the high study heterogeneity, the number of studies included was relatively small.


Oscillatory connectivity as a mechanism of auditory sensory gating and its disruption in schizophrenia.
Although innumerable studies using an auditory sensory gating paradigm have confirmed that individuals with schizophrenia (SZ) show less reduction in brain response to the second in a pair of clicks, this large literature has not yielded consensus on the circuit(s) responsible for gating nor for the gating difference in SZ. Clinically stable adult inpatients (N = 157) and matched community participants (N = 90) participated in a standard auditory sensory gating protocol. Responses to paired clicks were quantified as peak-to-peak amplitude from a response at approximately 50 ms to a response at approximately 100 ms in MEG-derived source waveforms. For bilateral sources in each of four regions near Heschl's gyrus, the gating ratio was computed as the response to the second stimulus divided by the response to the first stimulus. Spectrally resolved Granger causality quantified effective connectivity among regions manifested in alpha-band oscillatory coupling before and during stimulation. Poorer sensory gating localized to A1 in SZ than in controls confirmed previous results, here found in adjacent brain regions as well. Spontaneous, stimulus-independent effective connectivity within the hemisphere from angular gyrus to portions of the superior temporal gyrus was lower in SZ and correlated with gating ratio. Significant involvement of frontal and subcortical brain regions previously proposed as contributing to the auditory gating abnormality was not found. Findings point to endogenous connectivity evident in a sequence of activity from angular gyrus to portions of superior temporal gyrus as a mechanism contributing to normal and abnormal gating in SZ and potentially to sensory and cognitive symptoms.