Radiotherapy management of rectal cancer in the backdrop of the COVID pandemic.
COVID-19 outbreak was declared as a pandemic by the World Health Organization in March 2020. Over the last 3 months, the pandemic has challenged the diagnosis and treatment of all cancer, including rectal cancer. Constraints in resources call for a change in the treatment strategy without compromising efficacy. Delivery of shorter treatment schedules for radiotherapy offers advantages like short overall treatment time, improved throughput on the machine, improved compliance and reduced risk of transmission of COVID 19. Other strategies include delaying surgery, reducing the intensity of chemotherapy and adoption of organ preservation approach. The curative treatment of rectal cancer should not be hindered during the COVID pandemic, and modifications in the multi-modality treatment will help achieve quality care.


Corticothalamic Synaptic Noise as a Mechanism for Selective Attention in Thalamic Neurons.
A reason why the thalamus is more than a passive gateway for sensory signals is that two-third of the synapses of thalamocortical neurons are directly or indirectly related to the activity of corticothalamic axons. While the responses of thalamocortical neurons evoked by sensory stimuli are well characterized, with ON- and OFF-center receptive field structures, the prevalence of synaptic noise resulting from neocortical feedback in intracellularly recorded thalamocortical neurons in vivo has attracted little attention. However, in vitro and modeling experiments point to its critical role for the integration of sensory signals. Here we combine our recent findings in a unified framework suggesting the hypothesis that corticothalamic synaptic activity is adapted to modulate the transfer efficiency of thalamocortical neurons during selective attention at three different levels: First, on ionic channels by interacting with intrinsic membrane properties, second at the neuron level by impacting on the input-output gain, and third even more effectively at the cell assembly level by boosting the information transfer of sensory features encoded in thalamic subnetworks. This top-down population control is achieved by tuning the correlations in subthreshold membrane potential fluctuations and is adapted to modulate the transfer of sensory features encoded by assemblies of thalamocortical relay neurons. We thus propose that cortically-controlled (de-)correlation of subthreshold noise is an efficient and swift dynamic mechanism for selective attention in the thalamus.


The Control of Cell Expansion, Cell Division, and Vascular Development by Brassinosteroids: A Historical Perspective.
Steroid hormones are important signaling molecules in plants and animals. The plant steroid hormone brassinosteroids were first isolated and characterized in the 1970s and have been studied since then for their functions in plant growth. Treatment of plants or plant cells with brassinosteroids revealed they play important roles during diverse developmental processes, including control of cell expansion, cell division, and vascular differentiation. Molecular genetic studies, primarily in Arabidopsis thaliana, but increasingly in many other plants, have identified many genes involved in brassinosteroid biosynthesis and responses. Here we review the roles of brassinosteroids in cell expansion, cell division, and vascular differentiation, comparing the early physiological studies with more recent results of the analysis of mutants in brassinosteroid biosynthesis and signaling genes. A few representative examples of other molecular pathways that share developmental roles with brassinosteroids are described, including pathways that share functional overlap or response components with the brassinosteroid pathway. We conclude by briefly discussing the origin and conservation of brassinosteroid signaling.


RCAS/SCL-TVA animal model allows targeted delivery of polyoma middle T oncogene to vascular endothelial progenitors in vivo and results in hemangioma development.
To recapitulate the generation of cancer stem cells in the context of an intact animal using a retroviral vector capable of in vivo delivery of oncogenes to primitive endothelial and hematopoietic stem cells. Targeting of these progenitors was achieved using transgenic mice in which the avian TVA retroviral receptor was placed under the control of the stem cell leukemia (scl/tal-1) gene promoter and SCL +19 enhancer. Injection of an avian retrovirus encoding polyoma middle T (PyMT), an oncogene that transforms endothelial cells, caused rapid lethality in all SCL-TVA mice but not in control TVA(-) littermates. The infected animals exhibited hemorrhagic foci in several organs. Histopathologic analysis confirmed the presence of hemangiomas and the endothelial origin of the PyMT-transformed cells. Surprisingly, the transformed endothelial cells contained readily detectable numbers of TVA(+) cells. By contrast, normal blood vessels had very few of these cells. The presence of TVA(+) cells in the lesions suggests that the cells originally infected by PyMT retained stem cell characteristics. Further analysis showed that the tumor cells exhibited activation of the phosphatidylinositol 3-kinase/Akt and S6/mammalian target of rapamycin pathways, suggesting a mechanism used by PyMT to transform endothelial progenitors in vivo. We conclude that this experimental system can specifically deliver oncogenes to vascular endothelial progenitors in vivo and cause a fatal neoplastic disease. This animal model should allow the generation of endothelial cancer stem cells in the natural environment of an immunocompetent animal, thereby enabling the recapitulation of genetic alterations that are responsible for the initiation and progression of human malignancies of endothelial origin.


The evolution of health status and chronic conditions in Catalonia, 1994-2006: the paradox of health revisited using the Blinder - Oaxaca decomposition.
The paradox of health refers to the improvement in objective measures of health and the increase in the reported prevalence of chronic conditions. The objective of this paper is to test the paradox of health in Catalonia from 1994 to 2006. Longitudinal cross-sectional study using the Catalonia Health Interview Survey of 1994 and 2006. The approach used was the three-fold Blinder - Oaxaca decomposition, separating the part of the differential in mean visual analogue scale value (VAS) due to group differences in the predictors (prevalence effect), due to differences in the coefficients (severity effect), and an interaction term. Variables included were the VAS value, education level, labour status, marital status, all common chronic conditions over the two cross-sections, and a variable for non-common chronic conditions and other conditions. Sample weights have been applied. Results show that there is an increase in mean VAS for men aged 15-44, and a decrease in mean VAS for women aged 65-74 and 75 and more. The increase in mean VAS for men aged 15-44 could be explained by a decrease in the severity effect, which offsets the increase in the prevalence effect. The decrease in mean VAS for women aged 65-74 and 75 and more could be explained by an increase in the prevalence effect, which does not offset the decrease in the severity effect. The results of the present analysis corroborate the paradox of health hypothesis for the population of Catalonia, and highlight the need to be careful when measuring population health over time, as well as their usefulness to detect population's perceptions.


Robotic radical prostatectomy: operative technique, outcomes, and learning curve.
To report the operative technique, oncologic and therapeutic outcomes, and learning curve from our initial series of over 140 patients treated by robotic radical prostatectomy. Between January 2003 and May 2005, 143 patients with clinically localized prostate cancer underwent a robotic radical prostatectomy. Prospective data collection included patient age, body mass index (BMI), clinical T stage, biopsy Gleason score, and prostate-specific antigen (PSA). Operative outcome measures included operative time, estimated blood loss (EBL), and complications. Post-operative outcomes were length of hospital stay, catheter duration, pathology, margin status, biochemical recurrence, and return of continence. Mean operative time was 241 minutes with an EBL of 274 mL. Five patients (3%) required conversion to open surgery. The average hospitalization was 1.8 days, and Foley catheters were removed after 8.9 days. Twenty-four of 141 men (17%) had a positive surgical margin, with a decrease from 23% in the first half of our experience to 11% in the latter half. Patients with an extracapsular extension had a significantly higher positive surgical margin rate than did those with organ-confined disease (47% vs 15%). Over 40% of the positive margins were located posteriorly. At a mean follow-up of 11 months, 96% of patients had a PSA <0.2 ng/mL. The median time to complete continence was 3.5 months, and over 95% of patients were fully continent at 1 year. Robotic radical prostatectomy is an effective treatment modality for clinically localized prostate cancer. Although a learning curve needs to be overcome, patients experienced benefits in convalescence with early oncologic and functional outcomes comparable to those of the open approach. Longer-term results are needed; however, patient outcomes in our series are encouraging.


Effects of non-native Melilotus albus on pollination and reproduction in two boreal shrubs.
The establishment of abundantly flowered, highly rewarding non-native plant species is expected to have strong consequences for native plants through altered pollination services, particularly in boreal forest where the flowering season is short and the pollinator pool is small. In 18 boreal forest sites, we added flowering Melilotus albus to some sites and left some sites as controls in 2 different years to test if the invasive plant influences the pollination and reproductive success of two co-flowering ericaceous species: Vaccinium vitis-idaea and Rhododendron groenlandicum. We found that M. albus increased the pollinator diversity and tended to increase visitation rates to the focal native plant species compared to control sites. Melilotus albus facilitated greater seed production per berry in V. vitis-idaea when we added 120 plants compared to when we added 40 plants or in control sites. In R. groenlandicum, increasing numbers of M. albus inflorescences lowered conspecific pollen loads and percentage of flowers pollinated; however, no differences in fruit set were detected. The number of M. albus inflorescences had greater importance in explaining R. groenlandicum pollination compared to other environmental variables such as weather and number of native flowers, and had greater importance in lower quality black spruce sites than in mixed deciduous and white spruce sites for explaining the percentage of V. vitis-idaea flowers pollinated. Our data suggest that the identity of new pollinators attracted to the invaded sites, degree of shared pollinators between invasive and native species, and variation in resource limitation among sites are likely determining factors in the reproductive responses of boreal native plants in the presence of an invasive.


Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.
Studies of the pathogenesis and molecular biology of JC virus infection over the last two decades have significantly changed our understanding of progressive multifocal leukoencephalopathy, which can be described as a subacute viral infection of neuroglial cells that probably follows reactivation of latent infection rather than being the consequence of prolonged JC virus replication in the brain. There is now sufficient evidence to suggest that JC virus latency occurs in kidney and B cells. However, JC virus isolates from brain or kidney differ in the regulatory regions of their viral genomes which are controlled by host cell factors for viral gene expression and replication. DNA sequences of noncoding regions of the viral genome display a certain heterogeneity among isolates from brain and kidney. These data suggest that an archetypal strain of JC virus exists whose sequence is altered during replication in different cell types. The JC virus regulatory region likely plays a significant role in establishing viral latency and must be acted upon for reactivation of the virus. A developing hypothesis is that reactivation takes place from latently infected B lymphocytes that are activated as a result of immune suppression. JC virus enters the brain in the activated B cell. Evidence for this mechanism is the detection of JC virus DNA in peripheral blood lymphocytes and infected B cells in the brains of patients with progressive multifocal leukoencephalopathy. Once virus enters the brain, astrocytes as well as oligodendrocytes support JC virus multiplication. Therefore, JC virus infection of neuroglial cells may impair other neuroglial functions besides the production and maintenance of myelin. Consequently our increased understanding of the pathogenesis of progressive multifocal leukoencephalopathy suggests new ways to intervene in JC virus infection with immunomodulation therapies. Perhaps along with trials of nucleoside analogs or interferon administration, this fatal disease, for which no consensus of antiviral therapy exists, may yield to innovative treatment protocols.


[Selective concurrent suppression of the process of rosette-forming cell accumulation during the immune response].
Repeated injections to mice of normal rabbit immunoglobulins preceding immunization with sheep erythrocytes inhibited the accumulation of rosette-forming cells (RFC) in the spleen, without influencing the proliferation of the antibody-forming cells and hemaggutinin production. Reduction of the RFC under these conditions occurred on account of B-cells whose antigen-binding receptors could be blocked by antibodies against the aggregated mouse immunoglobulins and a complex of polyadenylic-polyuridylic acids. Repeated injections of the competitive antigen enhanced the formation of the immunological memory to the second antigen. The problem of the origin of the immune rosette-forming B-cells and their influence on the formation on the immunological memory is discussed.


Allokutzneria oryzae sp. nov., isolated from rhizospheric soil of Oryza sativa L.
The taxonomic status of a rhizospheric soil actinomycete, designated R8-39(T), was established using a polyphasic approach. The organism had phenotypic and morphological characteristics consistent with its classification in the genus Allokutzneria. Phylogenetic analysis based on an almost complete 16S rRNA gene sequence showed that the strain formed a monophyletic clade with the type strains of members of the genus Allokutzneria. Strain R8-39(T) displayed the highest levels of 16S rRNA gene sequence similarity to Allokutzneria albata DSM 44149(T) (98.8%) and Allokutzneria multivorans YIM 120521(T) (98.3%). However, the DNA-DNA hybridization values between strain R8-39(T) and A. albata and A. multivorans were clearly below the 70% threshold. The organism was found to have chemical characteristics consistent with its classification in the genus Allokutzneria. Whole-cell hydrolysates contained meso-diaminopimelic acid, arabinose, galactose, glucose, mannose, rhamnose and ribose. The main menaquinone was MK-9(H4). No mycolic acid was detected. The G+C content of the genomic DNA was 71.8 mol%. In addition, strain R8-39(T) had a phenotypic profile that readily distinguished it from recognized representatives of the genus Allokutzneria. It is evident from the combined genotypic and phenotypic properties that strain R8-39(T) represents a novel species of the genus Allokutzneria. The proposed name for this species is Allokutzneria oryzae sp. nov.; the type strain is R8-39(T) ( = BCC 60399(T) = NBRC 109649(T)).


Kinetic and hydrodynamic analysis of blood clotting factor V-membrane binding.
The kinetics and hydrodynamic properties of factor V-membrane interaction were characterized. Factor V bound to membranes containing acidic phospholipids with a high collisional efficiency. For membranes of 20% phosphatidyl-serine-80% phosphatidylcholine, an association rate constant of (1.13 +/- 0.10) X 10(8) M-1 s-1 was obtained. These membranes contained about 20 factor V binding sites per vesicle of 3.6 X 10(6) daltons. This association rate represented about a 30% collisional efficiency. Dissociation of factor V was measured by a fluorescence energy transfer method with a dissociation rate constant of 0.0055 s-1 at 10 degrees C. The equilibrium dissociation constant for binding to these membranes at 10 degrees C and 0.14 M ionic strength was 5 X 10(-11) M. Ionic strength, pH, calcium, and charge density in the membrane had large effects on the rate of factor V-membrane dissociation, indicating a strongly ionic interaction between protein and membrane. In contrast, the association rate was nearly insensitive to ionic strength. The membrane-binding properties were relatively unchanged after thrombin digestion of factor V or after long-term protein storage which resulted in loss of procoagulant activity. Other proteins of the prothrombinase reaction greatly decreased the rate of factor Va-membrane dissociation. At protein saturation, factor V increased the hydrodynamic radius of phospholipid vesicles by 11.4 nm. In contrast, factor Va increased the hydrodynamic vesicle radius by only about 5 nm. The mass of membrane-bound protein was comparable for both proteins.


Prediction error and repetition suppression have distinct effects on neural representations of visual information.
Predictive coding theories argue that recent experience establishes expectations in the brain that generate prediction errors when violated. Prediction errors provide a possible explanation for repetition suppression, where evoked neural activity is attenuated across repeated presentations of the same stimulus. The predictive coding account argues repetition suppression arises because repeated stimuli are expected, whereas non-repeated stimuli are unexpected and thus elicit larger neural responses. Here, we employed electroencephalography in humans to test the predictive coding account of repetition suppression by presenting sequences of visual gratings with orientations that were expected either to repeat or change in separate blocks of trials. We applied multivariate forward modelling to determine how orientation selectivity was affected by repetition and prediction. Unexpected stimuli were associated with significantly enhanced orientation selectivity, whereas selectivity was unaffected for repeated stimuli. Our results suggest that repetition suppression and expectation have separable effects on neural representations of visual feature information.


Diversity-oriented synthesis of heterocycles and macrocycles by controlled reactions of oxetanes with α-iminocarbenes.
Using N-sulfonyl triazoles as substrates, compounds as diverse as 2-imino tetrahydrofurans, 13- and 15-membered ring aza-macrocycles can be prepared selectively via formal [1 + 4], [5 + 4 + 4] and [3 + 4 + 4 + 4] condensations of α-imino carbenes and oxetanes under Rh(ii)-catalysis or thermal activation. Spirocyclic N-heterocycles are also accessible by means of Buchwald-Hartwig and Pictet-Spengler cyclizations. By reaction control, substrate selection or further derivatization, a large variety of chemical structures is thus achievable. Finally, using triazoles reacting under thermal activation, interesting mechanistic insight was obtained.


The impact of glucose ingestion and gluco-regulatory control on cognitive performance: a comparison of younger and middle aged adults.
A great deal of research has been devoted to the issue of whether the ingestion of a glucose containing drink facilitates cognitive performance. However, it remains unclear exactly how age and individual differences in gluco-regulatory control mediate a boost in cognitive functioning. The present study investigates these issues further. A repeated measures (25 g vs 50 g glucose vs placebo) counterbalanced, double-blind design was used with 25 younger and middle-aged adults. A battery of memory and non-memory tasks was administered; including tests of episodic and semantic memory, attention and visuospatial functioning. Glucose ingestion largely facilitated performance on tasks with a memory component. Notably, task demands and age (young vs middle-aged) contributed to the magnitude of memory enhancement. This finding suggests an age- and load-specific benefit of glucose intake. In addition, evidence suggests greater facilitation in individuals with good glucose regulation. These data are discussed in relation to the idea that glucose specifically affects neural mechanisms supporting memory functioning (i.e. the hippocampus), which are known to decline in ageing. Importantly, the present investigation adds to the growing body of literature showing the utility of glucose supplementation as memory enhancers.


Family environment and self-esteem development: A longitudinal study from age 10 to 16.
In this study, we examined the effect of family environment on self-esteem development from late childhood (age 10) through adolescence (age 16), using 4-wave longitudinal data from 674 Mexican-origin families living in the United States. To assess family environment, a multi-informant approach was used (i.e., mother, father, and child) to construct latent variables that minimize the influence of response biases. Using cross-lagged panel models (CLPMs) and random intercepts cross-lagged panel models (RI-CLPMs), we tested the prospective effects of parenting behaviors (warmth, hostility, monitoring, and involvement in child's education) and other characteristics of the family environment (quality of parental relationship, positive family values, maternal and paternal depression, economic conditions of the family, and presence of father). In the CLPMs, significant positive effects on children's self-esteem emerged for warmth, monitoring, low maternal depression, economic security (vs. hardship), and presence (vs. absence) of father. With regard to the reciprocal effects, children's self-esteem predicted positive family values (i.e., importance and centrality of the family) of mother and father. In the RI-CLPMs, the pattern of results was similar (in terms of point estimates of the effects); however, only the effects of maternal depression on child self-esteem, and the effect of child self-esteem on family values of father, were statistically significant. In all models, the effects did not differ significantly for boys and girls, or across ages 10 to 16. The findings suggest that multiple features of the family environment shape the development of self-esteem during late childhood and adolescence. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Lateral thalamic infarcts.
A patient with occlusion of the proximal posterior cerebral artery (PCA), a lateral thalamic infarct, and hemisensory loss later developed hemianopia and hemiparesis and had extensive PCA territory infarction in the midbrain, the lateral portion of the thalamus, and the occipital lobe noted at necropsy. Two other patients had lateral thalamic infarcts on computed tomography, normal angiographic findings, and presumed thalamogeniculate artery branch occlusion. There are three clinical syndromes associated with lateral thalamic infarction: (1) hemisensory loss, hemiataxia, and involuntary movements; (2) pure sensory stroke; and (3) sensory-motor stroke. Ataxia, adventitious movements, and sensory loss are due to infarction of the lateral, posterolateral, and posteromedial ventral nuclei caused by occlusion of the PCA proximal to the thalamogeniculate artery branches or by occlusion of large thalamogeniculate arteries. Pure sensory and sensory-motor strokes are due to smaller infarcts in the posterolateral-posteromedial ventral complex and adjacent internal capsule caused by occlusion of penetrating artery branches of the thalamogeniculate arteries.


Validation of the Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) Model.
The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) model uses birth weight (BW), gestational age at birth (GA), and weight gain rate to predict the risk of severe retinopathy of prematurity (ROP). In a model development study, it predicted all infants requiring treatment, while greatly reducing the number of examinations compared with current screening guidelines. To validate the CHOP ROP model in a multicenter cohort that is large enough to obtain a precise estimate of the model's sensitivity for treatment-requiring ROP. This investigation was a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study. The setting was 30 hospitals in the United States and Canada between January 1, 2006, and June 30, 2012. The dates of analysis were September 28 to October 5, 2015. Participants were premature infants at risk for ROP with a known ROP outcome. Sensitivity for Early Treatment of Retinopathy of Prematurity type 1 ROP and potential reduction in the number of infants requiring examinations. In the primary analysis, the CHOP ROP model was applied weekly to predict the risk of ROP. If the risk was above a cut-point level (high risk), examinations were indicated, while low-risk infants received no examinations. In a secondary analysis, low-risk infants received fewer examinations rather than no examinations. Participants included 7483 premature infants at risk for ROP with a known ROP outcome. Their median BW was 1070 g (range, 310-3000 g), and their median GA was 28 weeks (range, 22-35 weeks). Among them, 3575 (47.8%) were female, and their race/ethnicity was 3615 white (48.3%), 2310 black (30.9%), 233 Asian (3.1%), 93 Pacific Islander (1.2%), and 40 American Indian/Alaskan native (0.5%). The original CHOP ROP model correctly predicted 452 of 459 infants who developed type 1 ROP (sensitivity, 98.5%; 95% CI, 96.9%-99.3%), reducing the number of infants requiring examinations by 34.3% if only high-risk infants received examinations. Lowering the cut point to capture all type 1 ROP cases (sensitivity, 100%; 95% CI, 99.2%-100%) resulted in only 6.8% of infants not requiring examinations. However, if low-risk infants were examined at 37 weeks' postmenstrual age and followed up only if ROP was present at that examination, all type 1 ROP cases would be captured, and the number of examinations performed among infants with GA exceeding 27 weeks would be reduced by 28.4%. The CHOP ROP model demonstrated high but not 100% sensitivity and may be better used to reduce examination frequency. The model might be used reliably to guide a modified ROP screening schedule and decrease the number of examinations performed.


Characteristics identification and evolution patterns analyses of road chain conflicts.
Chain conflicts would cause chain-reaction crashes, which might result in elevated fatality rates. Chain conflicts describe a phenomenon wherein evasive actions taken by a following vehicle's driver after a conflict impact nearby vehicles, which occur frequently but are reported less often. To effectively reduce conflict risk, comprehending the evolution patterns of chain conflicts under varied traffic conditions and road segments is crucial, in order to make chain conflicts management strategies. Initially, rear-end or sideswipe conflicts between two vehicles are identified based on vehicle trajectory data captured by an unmanned aerial vehicle group. Subsequently, a chain conflict identification algorithm is proposed, considering the randomness of occurrence time and fluctuation of impact duration, to link individual conflicts. Chain conflict rates exhibit significant variations across different road segments under diverse traffic conditions. Multiple risk and propagation indicators are extracted to unveil latent characteristics of chain conflicts from a high-level perspective. Based on prominent characteristic disparities, three evolution patterns are identified, i.e., Longitudinal Risk Decrease Pattern, Longitudinal Risk Increase Pattern, and Comprehensive High-risk Persistent Pattern. Spatial-temporal high-risk areas associated with each pattern are determined, and transition probabilities between patterns are calculated. The results indicate that these patterns tend to remain stable, with transitions mainly occurring from low-risk to high-risk patterns. Moreover, strategies to reduce conflict risk are proposed based on the characteristics of different patterns. This study holds great significance in understanding chain conflict evolution patterns and preventing chain-reaction crashes.


Supported Internet-Delivered Cognitive Behavioral Therapy Programs for Depression, Anxiety, and Stress in University Students: Open, Non-Randomised Trial of Acceptability, Effectiveness, and Satisfaction.
Many university campuses have limited mental health services that cannot cope with the high demand. One alternative is to use internet-delivered cognitive behavioral therapy (iCBT) as a way of tackling barriers such as lack of availability and scheduling issues. This study aimed to assess feasibility, acceptability, effectiveness, and satisfaction of a supported iCBT intervention offering 3 programs on depression, anxiety, and stress to university students. The design was an open or nonrandomized feasibility trial. Participants were recruited from 3 counseling centers at a large midwestern University in the United States. Those agreeing to take part chose 1 of 3 iCBT programs-Space from Depression, Space from Anxiety, or Space from Stress -all comprised 8 modules of media-rich interactive content. Participants were supported throughout the trial by a trained professional. The Patient Health Questionnaire 9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7) questionnaire, and stress subscale of the Depression Anxiety and Stress Scale (DASS-21) were completed at baseline, 8 weeks, and 3-month follow-up. A Satisfaction With Treatment (SAT) questionnaire was completed at 8 weeks, and qualitative interviews were completed by a subsample of participants at 3 months. A total of 102 participants were recruited, with 52 choosing Space from Anxiety, 31 choosing Space from Depression, and 19 choosing Space from Stress. Mixed-effects models showed a significant decrease in symptoms of depression (F4=6.36, P<.001), anxiety (F4=7.97, P<.001), and stress (F4=8.50, P<.001) over time across all 3 programs. The largest decreases in PHQ-9 scores at 8 weeks were among participants who chose the Space from Depression program (d=0.84); at 3 months, the largest decreases in PHQ-9 scores were among those who chose the Space from Stress program (d=0.74). The largest decreases in GAD-7 scores were among those who chose the Space from Anxiety program (d=0.74 at 8 weeks and d=0.94 at 3 months). The largest decrease in DASS-21 stress subscale scores was among those who chose the Space from Stress program (d=0.49 at 8 weeks and d=1.16 at 3 months). The mean time spent using the platform per session was 27.4 min (SD 33.8), and participants completed 53% (SD 37.6) of the total program content on average. Most (37/53, 69%) participants found the programs helpful or very helpful and liked the convenience and flexibility of the intervention. Qualitative interviews (n=14) indicated the intervention met students' expectations, and they saw it as a valuable complement to face-to-face treatment. The iCBT programs tested in our study appear to be feasible, acceptable, and effective in a university environment. Participants described the benefits of having a flexible, supported Web-based intervention available on campus. Larger trials should be conducted to further test the effectiveness of supported Web-based interventions that give students a choice of program depending on their symptom profile.


Differential effects of repeated treatment with haloperidol and clozapine on dopamine release and metabolism in the striatum and the nucleus accumbens.
The differential effects of haloperidol (HAL) and clozapine (CLOZ) on dopamine (DA) release and metabolism (dihydroxyphenylacetic acid levels) in striatum and nucleus accumbens (accumbens) of freely moving rats were investigated using microdialysis. Chronic HAL (2 mg/kg/day x 21 days in drinking water) decreased basal DA release and metabolism in both regions, and produced tolerance to HAL-induced increase in DA metabolism in striatum. No modification of HAL-induced increases in DA release and metabolism were observed in accumbens. Together with D2 receptor blockade, this may produce decreased dopaminergic neurotransmission in both regions during chronic treatment. Chronic HAL (0.5 mg/kg/day x 21 days in drinking water) also decreased basal DA release and metabolism in both regions which were not reversed by 25 micrograms/kg of (-)-apomorphine, s.c. In marked contrast, chronic CLOZ (20 mg/kg/day x 21 days in drinking water) had no effect on basal DA release and metabolism in either region, whereas it produced tolerance to CLOZ-induced increase in DA release and metabolism in accumbens. Together with weak D2 receptor blockade, this may lead to slightly decreased dopaminergic neurotransmission in accumbens and slightly increased dopaminergic neurotransmission in striatum during chronic CLOZ treatment. These differences may contribute to the clinical differences between the two agents.


Understanding middle-aged and older adults' first associations with the word "cancer": A mixed methods study in England.
Cancer is still widely feared and often associated with death. Fatalistic beliefs adversely affect help-seeking for cancer symptoms and engagement in cancer prevention. This study aims to understand middle-aged and older adults' first association with the word "cancer" and their relationship with sociodemographic factors, cancer fear, and cancer information avoidance. We conducted a cross-sectional survey of 1464 community-based adults aged 50 to 70 living in England in April 2015. First associations with cancer were measured qualitatively and analysed using content analysis. We used binary logistic regression to analyse associations between the most common first association of cancer and sociodemographic characteristics, cancer fear, and cancer information avoidance. Cancer was most commonly associated with "death" (26%). Respondents with lower levels of education, living in the Midlands or North of England where cancer mortality is higher, or with close friends or family members with a cancer history, were more likely to associate cancer with death. Cancer fear was significantly associated with death associations, but cancer information avoidance was not. Despite improved cancer outcomes, middle-aged and older adults often associate cancer with death. Further efforts to decrease fatalistic associations in this age group may be needed.


Role of Condensing Particles in Polymer Confinement: A Model for Virus-Packed "Minichromosomes".
Confined mixtures of a polymer and nonspecifically binding particles (condensers) are studied as models for viruses containing double-stranded DNA (polymer) and condensing proteins (particles). We explore a model in which all interactions between the packed content (polymer and particles) and its confinement are purely repulsive, with only a short-range attraction between the condensers and polymer to simulate binding. In the range of physical parameters applicable to viruses, the model predicts reduction of pressure in the system effected by the condensers, despite the reduction in free volume. Condensers are found to be interspersed throughout the spherical confinement and only partially wrapped in the polymer, which acts as an effective medium for the condenser interactions. Crowding of the viral interior influences the DNA and protein organization, producing a picture inconsistent with a chromatin-like, beads-on-a-string structure. The model predicts an organization of the confined interior compatible with experimental data on unperturbed adenoviruses and polyomaviruses, at the same time providing insight into the role of condensing proteins in the viral infectious cycles of related viral families.


Correction of postoperative eyelid retraction with a simplified levator palpebrae superioris (LPS) muscle recession: analysis of a 10-year experience.
A simplified levator palpebrae superioris (LPS) muscle recession was performed to correct eyelid retraction in 56 eyelids of 48 patients. Improvement of preoperative keratopathy and cosmetically acceptable results were achieved in 93% of the eyelids. Based on preoperative surgical intervention, eyelids were divided into four groups: levator resection, levator aponeurosis advancement, surgery associated with dysthyroid ophthalmopathy, and miscellaneous reconstructive eyelid procedures. For each group the mean preoperative and postoperative eyelid levels, the mean change in eyelid level following surgery, and the mean amount of surgery performed were analyzed statistically with the two-tailed student's t-test. Linear regression was used to analyze the relationship between the change in eyelid level and the amount of levator recession performed. No significant relationship was demonstrated between eyelid retraction and dysthyroid ophthalmopathy or reconstructive eyelid surgery. However, a significant relationship was demonstrated between the amount of recession and the eyelid level change for eyelids retracted following levator resection (P less than .01) and levator aponeurosis surgery (P less than .05). This may indicate that the change in eyelid level following a simplified LPS recession in these two groups is predictable. However, additional prospective studies are required to further assess the clinical applicability and use of this finding.


Resveratrol inhibits angiotensin II‑induced proliferation of A7r5 cells and decreases neointimal hyperplasia by inhibiting the CaMKII‑HDAC4 signaling pathway.
Resveratrol has been reported to inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia following arterial injury; however, the underlying mechanisms remain unclear. The present study was designed to investigate the effects of resveratrol on angiotensin II (AngII)‑induced proliferation of A7r5 cells and explore the molecular mechanisms responsible for the observed effects. Resveratrol inhibited cell proliferation and migration, and decreased the AngII‑induced protein expression of α‑smooth muscle actin (α‑SMA), proliferating cell nuclear antigen (PCNA) and cyclin‑dependent kinase 4 (CDK4). Resveratrol inhibited AngII‑induced activation of intracellular Ca2+/calmodulin‑dependent protein kinase II (CaMKII) and histone deacetylases 4 (HDAC4), as well as blocking AngII‑induced cell cycle progression from the G0/G1 to S‑phase. In vivo, 4‑weeks of resveratrol treatment decreased the neointima area and the neointima/media area ratio in rats following carotid balloon injury. Resveratrol also inhibited the protein expression of total and phosphorylated CaMKII and HDAC4 in the injured arteries. In conclusion, the present study demonstrated that resveratrol attenuated AngII‑induced cell proliferation and neointimal hyperplasia by inhibiting the CaMKII‑HDAC4 signaling pathway. These findings suggest that resveratrol may potentially prevent arterial restenosis.


Participation of Smad2, Smad3, and Smad4 in transforming growth factor beta (TGF-beta)-induced activation of Smad7. THE TGF-beta response element of the promoter requires functional Smad binding element and E-box sequences for transcriptional regulation.
Smad7 has recently been identified as a player that antagonizes transforming growth factor beta (TGF-beta) signals by acting downstream of TGF-beta receptors. TGF-beta rapidly induces expression of Smad7 mRNA in a variety of cell types, suggesting participation in a negative feedback loop to control TGF-beta responses. We have previously described the genomic locus of rat Smad7 including the promoter region. Here we report polymerase chain reaction cloning of the corresponding promoter regions of human and murine Smad7 genes and functional characterization of the rat Smad7 promoter. Using transient transfection experiments of HepG2 cells, we identified the TGF-beta response element within a strongly conserved region, containing a perfect Smad binding element (SBE; GTCTAGAC). Performing electrophoretic mobility shift assay and cotransfection experiments, we were able to delineate DNA-binding complexes and identified Smad3, Smad4, and Smad2. Mutation of the SBE completely abolished TGF-beta inducibility of Smad7 in HepG2 cells, indicating that this sequence is necessary for TGF-beta-induced transcription. Furthermore, a 3-base pair adjacent E-box is additionally essential for TGF-beta-dependent promoter activation and an overlapping AP1 site is also involved. We conclude that regulation of Smad7 transcription by TGF-beta is mediated via a specific constellation of recognition motifs localized around the SBE, which is conserved in human, rat, and murine genes.


Inclusion of Older Adults in the Research and Design of Digital Technology.
Digital technology holds a promise to improve older adults' well-being and promote ageing in place. However, there seems to be a discrepancy between digital technologies that are developed and what older adults actually want and need. Ageing is stereotypically framed as a problem needed to be fixed, and older adults are considered to be frail and incompetent. Not surprisingly, many of the technologies developed for the use of older adults focus on care. The exclusion of older adults from the research and design of digital technology is often based on such negative stereotypes. In this opinion article, we argue that the inclusion rather than exclusion of older adults in the design process and research of digital technology is essential if technology is to fulfill the promise of improving well-being. We emphasize why this is important while also providing guidelines, evidence from the literature, and examples on how to do so. We unequivocally state that designers and researchers should make every effort to ensure the involvement of older adults in the design process and research of digital technology. Based on this paper, we suggest that ageism in the design process of digital technology might play a role as a possible barrier of adopting technology.


Stability of Mixed Lead Halide Perovskite Films Encapsulated in Cyclic Olefin Copolymer at Room and Cryogenic Temperatures.
Lead Mixed Halide Perovskites (LMHPs), CsPbBrI2, have attracted significant interest as promising candidates for wide bandgap absorber layers in tandem solar cells due to their relative stability and red-light emission with a bandgap ∼1.7 eV. However, these materials segregate into Br-rich and I-rich domains upon continuous illumination, affecting their optical properties and compromising the operational stability of devices. Herein, we track the microscopic processes occurring during halide segregation by using combined spectroscopic measurements at room and cryogenic temperatures. We also evaluate a passivation strategy to mitigate the halide migration of Br/I ions in the films by overcoating with cyclic olefin copolymer (COC). Our results explain the correlation between grain size, intensity dependencies, phase segregation, activation energy barrier, and their influence on photoinduced carrier lifetimes. Importantly, COC treatment increases the lifetime charge carriers in mixed halide thin films, improving efficient charge transport in perovskite solar cell applications.


A naturally occurring polyacetylene isolated from carrots promotes health and delays signatures of aging.
To ameliorate or even prevent signatures of aging in ultimately humans, we here report the identification of a previously undescribed polyacetylene contained in the root of carrots (Daucus carota), hereafter named isofalcarintriol, which we reveal as potent promoter of longevity in the nematode C. elegans. We assign the absolute configuration of the compound as (3 S,8 R,9 R,E)-heptadeca-10-en-4,6-diyne-3,8,9-triol, and develop a modular asymmetric synthesis route for all E-isofalcarintriol stereoisomers. At the molecular level, isofalcarintriol affects cellular respiration in mammalian cells, C. elegans, and mice, and interacts with the α-subunit of the mitochondrial ATP synthase to promote mitochondrial biogenesis. Phenotypically, this also results in decreased mammalian cancer cell growth, as well as improved motility and stress resistance in C. elegans, paralleled by reduced protein accumulation in nematodal models of neurodegeneration. In addition, isofalcarintriol supplementation to both wild-type C57BL/6NRj mice on high-fat diet, and aged mice on chow diet results in improved glucose metabolism, increased exercise endurance, and attenuated parameters of frailty at an advanced age. Given these diverse effects on health parameters in both nematodes and mice, isofalcarintriol might become a promising mitohormesis-inducing compound to delay, ameliorate, or prevent aging-associated diseases in humans.


In-Hospital Outcomes and Recurrence of Acute Ischemic Stroke in Patients With Solid Organ Malignancy.
To evaluate the influence of solid organ malignancies on the in-hospital outcomes and recurrent strokes among patients hospitalized with acute ischemic stroke (AIS). Adult hospitalizations with a primary diagnosis of AIS were identified from the Nationwide Readmissions Database 2016-2018. Logistic regression was used to compare the differences in the utilization of acute stroke interventions and clinical outcomes in patients with and without malignancy. Survival analysis was used to evaluate the risk of readmission due to recurrent stroke after discharge. There were 1385840 hospitalizations due to AIS (mean±SD age 70.4±14.0 years, female 50.2%). Of these, 50553 (3.7%) had a concurrent diagnosis of solid organ malignancy. The five most common malignancies included lung cancer (24.6%), prostate cancer (13.2%), breast cancer (9.3%), pancreatic cancer (6.5%), and colorectal cancer (6.2%). After adjustment for baseline differences, patients with malignancy were more likely to have intraparenchymal hemorrhage (IPH) [odds ratio (OR): 1.11, 95% confidence interval (CI): 1.04-1.19], in-hospital mortality (OR: 2.15, 95% CI: 2.04-2.28), and discharge disposition other than to home (OR: 1.70, 95% CI: 1.64-1.75). Patients with malignancy were less likely to receive intravenous thrombolysis (tPA) and were more likely to undergo mechanical thrombectomy (MT). Among the subgroups of patients treated with tPA or MT, the outcomes were comparable between patients with and without malignancy, except patients with lung cancer remained at a higher risk of mortality and adverse disposition despite these acute stroke interventions. Patients with malignancy were at a higher risk of readmission due to recurrent AIS within 1 year of discharge (hazards ratio: 1.18, 95% CI: 1.11-1.25), and this risk was specifically driven by the lung and pancreatic cancers. While patients with malignancy generally have worse in-hospital outcomes as compared to those without, there is considerable variation in these outcomes according to the different cancer types and the use of acute stroke interventions. The use of tPA and MT is generally safe for eligible patients with an underlying malignancy. Patients with lung and pancreatic cancers have a higher early risk of recurrent stroke and might need more intensive surveillance and careful institution of the optimal secondary prevention measures.


Blastokinin and analogous proteins.
The paper is a review of recent work with blastokinin, a uterine-specific protein of rabbit, and includes consideration of patterns of synthesis, induction by progestagens, metal-binding capacity, translation of its RNA message, possible changes in the molecule, and comparison with the "cone" protein of the oviduct. Other uterine proteins have been identified in the rabbit by their enzymatic or hormonal activity and shown to be distinct from blastokinin though present in the uterine lumen at the same time. Proteins which are temporally or chemically analogous to blastokinin in other species are discussed, including the question of whether a blastokinin-like protein occurs in women. Discussion of the comparative significance of such proteins must await a clearer definition of their function.


Association between brain cancer immunogenetic profile and in silico immunogenicities of 11 viruses.
Several viruses including human herpes viruses (HHVs), human polyomavirus JCV, and human papilloma virus (HPV) have been implicated in brain cancer, albeit inconsistently. Since human leukocyte antigen (HLA) is centrally involved in the human immune response to viruses and has been implicated in brain cancer, we evaluated in silico the immunogenicity between 69 Class I HLA alleles with epitopes of proteins of 9 HHVs, JCV, and HPV with respect to a population-based HLA-brain cancer profile. We found that immunogenicity varied widely across HLA alleles with HLA-C alleles exhibiting the highest immunogenicity, and that immunogenicity scores were negatively associated with the population-based HLA-brain cancer profile, particularly for JCV, HHV6A, HHV5, HHV3, HHV8, and HHV7. Consistent with the role of HLA in foreign antigen elimination, the findings suggest that viruses with proteins of high HLA immunogenicity are eliminated more effectively and, consequently, less likely to cause brain cancer; conversely, the absence of highly immunogenic HLA may allow the viral antigens to persist, contributing to cancer.


Young women's perceptions of the benefits of childbearing: associations with contraceptive use and pregnancy.
High unintended pregnancy rates, and inconsistencies between reported pregnancy intentions and contraceptive behaviors, have been well documented among young U.S. women. Women's beliefs about the benefits of childbearing and motherhood may be related to the apparent disconnect between pregnancy intentions and reproductive outcomes. Perceived benefits of childbearing and feelings about a potential pregnancy were assessed among 1,377 women aged 15-24 (most of them black or Latina) participating in a longitudinal study in 2005-2008. The women, who were initiating hormonal contraception at public family planning clinics and did not want to become pregnant for one year, were followed for 12 months. Differences in perceived benefits of childbearing by participant characteristics were examined with linear regression, using a new multi-item measure. Cox proportional hazard regression was used to investigate the association of perceived benefits of childbearing with subsequent contraceptive discontinuation and pregnancy. Perceptions of the benefits of childbearing decreased with increasing age (coefficient, -0.04), and white women perceived fewer benefits to childbearing than blacks (-0.2). As women's perception of the benefits of childbearing increased, their one-year pregnancy rates increased, after demographic characteristics and feelings about a potential pregnancy were controlled for (hazard ratio, 1.2). Benefits of childbearing were not associated with contraceptive discontinuation. To better assess pregnancy risk among young women wanting to avoid pregnancy, it may be useful to acknowledge that they hold not only explicit pregnancy desires, but also beliefs about the benefits of childbearing, which may influence sexual behavior and pregnancy.


Treatment of worry and comorbid symptoms within depression, anxiety, and insomnia with a group-based rumination-focused cognitive-behaviour therapy in a primary health care setting: a randomised controlled trial.
Repetitive negative thinking (RNT) has been described as a maintaining transdiagnostic factor for psychopathology within the areas of depression, anxiety and insomnia. We investigated the effects of rumination-focused cognitive-behaviour therapy (RF-CBT) in a group format at a primary health care centre on symptoms of depression, anxiety, insomnia, RNT, and quality of life. The participants presented clinical symptom levels of worry and at least two disorders among anxiety disorders, major depressive disorder, and insomnia disorder. A randomised controlled superiority parallel arm trial was used. 73 participants were included and randomised in pairs to either group-administered RF-CBT or a waiting list condition. The primary outcomes were self-rated worry and transdiagnostic symptoms (depression, anxiety, and insomnia). Intention-to-treat analyses of group differences were conducted using linear mixed models. Adverse side effects and incidents were presented descriptively. Group RF-CBT significantly reduced self-reported insomnia at post-treatment and self-reported insomnia and depression at the 2 month-follow-up, relative to the wait-list control group. There was no significant difference in change in RNT, anxiety, or quality of life. The current study suggests that group-administered RF-CBT may be effective for insomnia and potentially effective for depression symptomatology. However, the study was underpowered to detect small and moderate effects and the results should therefore be interpreted with caution.


The scattering of surface acoustic waves by electrical effects in two-dimensional metal film structures.
A theory is presented for the scattering of surface acoustic waves by electrical effects in thin metal films of arbitrary shape on the surface of a piezoelectric material. A Green's function approach is used, and an expression for the two-dimensional Green's function appropriate to the problem is given. General expressions are obtained for the far-field radiation pattern and for the response of an interdigital transducer to a single scatterer. Expressions for the reflection and velocity perturbation due to periodic arrays of scatterers are also presented. Good agreement is found when the theoretical predictions are compared with a wide range of experimental results on lithium niobate.


Study on tumour cell-derived hybrid exosomes as dasatinib nanocarriers for pancreatic cancer therapy.
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death. Therefore, we intend to explore novel strategies against PDAC. The exosomes-based biomimetic nanoparticle is an appealing candidate served as a drug carrier in cancer treatment, due to its inherit abilities. In the present study, we designed dasatinib-loaded hybrid exosomes by fusing human pancreatic cancer cells derived exosomes with dasatinib-loaded liposomes, followed by characterization for particle size (119.9 ± 6.10 nm) and zeta potential (-11.45 ± 2.24 mV). Major protein analysis from western blot techniques reveal the presence of exosome marker proteins CD9 and CD81. PEGylated hybrid exosomes showed pH-sensitive drug release in acidic condition, benefiting drug delivery to acidic cancer environment. Dasatinib-loaded hybrid exosomes exhibited significantly higher uptake rates and cytotoxicity to parent PDAC cells by two-sample t-test or by one-way ANOVA analysis of variance, as compared to free drug or liposomal formulations. The results from our computational analysis demonstrated that the drug-likeness, ADMET, and protein-ligand binding affinity of dasatinib are verified successfully. Cancer derived hybrid exosomes may serve as a potential therapeutic candidate for pancreatic cancer treatment.


Complications and Adverse Events of Three Magnetic Resonance Imaging-based Target Biopsy Techniques in the Diagnosis of Prostate Cancer Among Men with Prior Negative Biopsies: Results from the FUTURE Trial, a Multicentre Randomised Controlled Trial.
Three techniques of magnetic resonance imaging (MRI)-based targeted biopsy (TB) of the prostate exist. There is no superiority regarding diagnostic efficacy of prostate cancer (PCa) detection. To compare adverse events (AEs) among three TB techniques and to evaluate the effect on urinary and erectile function. Post hoc analysis of a multicentre randomised controlled trial among men with negative systematic biopsy (SB) and suspicion of PCa. In 234 patients, 3-T multiparametric MRI demonstrated PIRADS≥ 3 lesions, and patients were randomised 1:1:1 for TB: transrectal in-bore MRI TB (MRI-TB), transperineal MRI-transrectal ultrasound (TRUS) fusion TB (FUS-TB), and transrectal cognitive TRUS TB (COG-TB). AEs (Clavien-Dindo) were compared using Pearson chi-square test. Univariate logistic regression tests were performed for the number of cores, biopsy approach, and usage of anticoagulants. The participants filled in baseline and 30-d postbiopsy International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) questionnaires. The delta between measurements was compared using one-way analysis of variance. There were significant differences in minor AEs: 53% in MRI-TB, 71% in FUS-TB, and 85% in COG-TB (p < 0.001). The number of cores was associated with AEs (odds ratio [OR] 1.11 per extra biopsy [95% confidence interval {CI} 1.06-1.17, p < 0.001]). Anticoagulants were not associated with bleeding complications (OR 1.24 [95% CI 0.66-2.35, p = 0.5]). Transrectal approach (MRI-TB + COG-TB) increased the risk of any AE (OR 2.54 [95% CI 1.16-5.77, p < 0.05]) and nonsignificantly increased the risk of urinary tract infections (OR 3.69 [95% CI 0.46-168.4, p = 0.3]). Biopsy did not impact urinary (ΔIPSS 0.3, p = 0.1) and erectile function (ΔIIEF-5 -0.4, p = 0.5). The main limitation was that additional SB was performed in FUS-TB and COG-TB, and was omitted in MRI-TB, making comparison difficult. There was a significant difference in minor AEs among groups. An increase in the number of cores increased the overall risk of AEs. A low AE occurrence in MRI-TB was likely caused by the omission of SB. Prostate biopsy did not impact self-reported urinary and erectile functions. In this study, we compared the complication rates of three techniques of magnetic resonance imaging (MRI)-based targeted biopsy of the prostate. We found a significant difference in the occurrence of minor complication rates among three groups in favour of transrectal in-bore MRI targeted biopsy, likely caused by the omission of additional systematic biopsy in this group.


Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans.
Conjugated linoleic acid (CLA) is reported to have weight-reducing and antiatherogenic properties when fed to laboratory animals. However, the effects of CLA on human health and, in particular, the effects of individual CLA isomers are unclear. This study investigated the effects of 3 doses of highly enriched cis-9,trans-11 (0.59, 1.19, and 2.38 g/d) or trans-10,cis-12 (0.63, 1.26, and 2.52 g/d) CLA preparations on body composition, blood lipid profile, and markers of insulin resistance in healthy men. Healthy men consumed 1, 2, and 4 capsules sequentially, containing either 80% cis-9,trans-11 CLA or 80% trans-10,cis-12 CLA for consecutive 8-wk periods. This phase was followed by a 6-wk washout and a crossover to the other isomer. Body composition was not significantly affected by either isomer of CLA. Mean plasma triacylglycerol concentration was higher during supplementation with trans-10,cis-12 CLA than during that with cis-9,trans-11 CLA, although there was no influence of dose. There were significant effects of both isomer and dose on plasma total cholesterol and LDL-cholesterol concentrations but not on HDL-cholesterol concentration. The ratios of LDL to HDL cholesterol and of total to HDL cholesterol were higher during supplementation with trans-10,cis-12 CLA than during that with cis-9,trans-11 CLA. CLA supplementation had no significant effect on plasma insulin concentration, homeostasis model for insulin resistance, or revised quantitative insulin sensitivity check index. Divergent effects of cis-9,trans-11 CLA and trans-10,cis-12 CLA appear on the blood lipid profile in healthy humans: trans-10,cis-12 CLA increases LDL:HDL cholesterol and total:HDL cholesterol, whereas cis-9,trans-11 CLA decreases them.


Phytosynthesis of gold-198 nanoparticles for a potential therapeutic radio-photothermal agent.
We produced spherical gold-198 nanoparticles with an average size of 41 nm, good stability, and high radiochemical purity for a promising single agent of radio-photothermal therapy using Curcuma longa rhizome extract as a reducing and capping agent. The combination of in vitro treatment using gold-198 nanoparticles and irradiation of 980 nm wavelength lasers with a power output of 2 W/cm2 induced hyperthermia temperature and exhibited enhancement of the percentage dead on MDA-MB-123 cancer cells compared to gold-198 nanoparticles alone.


Anti-mycobacterial activity correlates with altered DNA methylation pattern in immune cells from BCG-vaccinated subjects.
The reason for the largely variable protective effect against TB of the vaccine Bacille Calmette-Guerin (BCG) is not understood. In this study, we investigated whether epigenetic mechanisms are involved in the response of immune cells to the BCG vaccine. We isolated peripheral blood mononuclear cells (PBMCs) from BCG-vaccinated subjects and performed global DNA methylation analysis in combination with functional assays representative of innate immunity against Mycobacterium tuberculosis infection. Enhanced containment of replication was observed in monocyte-derived macrophages from a sub-group of BCG-vaccinated individuals (identified as 'responders'). A stable and robust differential DNA methylation pattern in response to BCG could be observed in PBMCs isolated from the responders but not from the non-responders. Gene ontology analysis revealed that promoters with altered DNA methylation pattern were strongly enriched among genes belonging to immune pathways in responders, however no enrichments could be observed in the non-responders. Our findings suggest that BCG-induced epigenetic reprogramming of immune cell function can enhance anti-mycobacterial immunity in macrophages. Understanding why BCG induces this response in responders but not in non-responders could provide clues to improvement of TB vaccine efficacy.


Studies on the cardiovascular effects produced by the spinal action of substance P in the rat.
Administration of 6.5-pmol-6.5-nmol doses of substance P (SP) into the spinal subarachnoid space at T-8-T-10 in urethane-anesthetized rats increases both mean arterial pressure (MAP) and heart rate (HR) in a dose-related manner. However, in rats anesthetized with sodium pentobarbital, an increase in MAP is seen only at low doses of SP (6.5-65 pmol), while a biphasic response is obtained at 650 pmol and only a depressor response at 6.5 nmol SP. These responses also are accompanied by a tachycardia. Depending on the spinal cord level, cardiovascular responses of different time course and magnitude are elicited by SP. The amplitude of the increases in MAP and HR produced by SP (6.5 nmol) are: T-8-T-10 greater than T-1-T-3 greater than L-2-L-4 in rats anesthetized with urethane. In rats anesthetized with sodium pentobarbital, the decrease in MAP levels is greatest at T-1-T-3, while it is similar at T-8-T-10 and L-2-L-4 levels. The effects of SP on HR are more complex. The different cardiovascular responses obtained with the two anesthetics are not attributed to the relative depth of anesthesia but may be due to differential effects of the anesthetics on sympathetic nervous activity. The effect of SP on HR can be blocked by propranolol, but it remains unaffected by the surgical removal of the adrenal glands. We conclude that this cardiovascular response is most likely mediated by the postganglionic noradrenergic fibres and that adrenal medullary catecholamines are not essential. Using several inhibitors of endogenous mediators, two components to the spinal action of SP on MAP are made evident. The pressor response can be explained solely by the activation of sympathetic preganglionic fibres in the intermediolateral nucleus of the spinal cord, while the depressor response, in addition, may involve the release of a vasodilatatory substance in the periphery, the action of which persists in the presence of cholinergic, histaminergic, serotonergic, or opioid antagonists. Moreover, the adrenal glands are excluded as a possible source of this substance.


Stability and pre-formulation development of a plant-produced anthrax vaccine candidate.
Second generation anthrax vaccines focus on the use of recombinant protective antigen (rPA) to elicit a strong, toxin neutralizing antibody responses in immunized subjects. The main difference between the rPA vaccines compared to the current licensed vaccine, anthrax vaccine absorbed (AVA), is the rPA vaccines are highly purified preparations of only rPA. These second generation rPA vaccines strive to elicit strong immune responses with substantially fewer doses than AVA while provoking less side effects. Many of the rPA candidates have shown to be effective in pre-clinical studies, but most of the second generation molecules have stability issues which reduce their efficacy over time. These stability issues are evident even under refrigerated conditions and thus emphasis has been directed to stabilizing the rPA molecule and determining an optimized final formulation. Stabilization of vaccines for long-term storage is a major challenge in the product development life cycle. The effort required to identify suitable formulations can be slow and expensive. The ideal storage for stockpiled vaccines would allow the candidate to withstand years of storage at ambient temperatures. The Fraunhofer Center for Molecular Biotechnology is developing a plant-produced rPA vaccine candidate that shows instability when stored under refrigerated conditions in a solution, as is typical for rPA vaccines. Increased stability of our plant-produced rPA vaccine candidate was achieved in a spray dried powder formulation that could eliminate the need for conventional cold chain allowing greater confidence to stockpile vaccine for civilian and military biodefense.


Fluoroless Rapid Mapping and Catheter Ablation of Intra-atrial Reentry Tachycardia in a Patient with Mustard Operation Using the Ensite™ Precision™ Electroanatomic Mapping System.
Catheter ablation of atrial arrhythmias in patients with atrial baffle palliation for dextro-transposition of the great arteries (requiring the Mustard or Senning procedures) can be challenging cases to complete, with long procedure times and high degrees of associated radiation exposure. Many ablation procedures can now be done using the fluoroless technique. The new EnSite™ Precision™ cardiac mapping system (Abbott Laboratories, Chicago, IL, USA) allows for the rapid mapping of arrhythmias and the performance of non-fluoroscopic procedures. This case report describes the use of this system in an adult patient undergoing Mustard operation, to rapidly map and successfully ablate intra-atrial reentry tachycardia with fluoroless technique.


Superresolution imaging of chemical synapses in the brain.
Determination of the molecular architecture of synapses requires nanoscopic image resolution and specific molecular recognition, a task that has so far defied many conventional imaging approaches. Here, we present a superresolution fluorescence imaging method to visualize the molecular architecture of synapses in the brain. Using multicolor, three-dimensional stochastic optical reconstruction microscopy, the distributions of synaptic proteins can be measured with nanometer precision. Furthermore, the wide-field, volumetric imaging method enables high-throughput, quantitative analysis of a large number of synapses from different brain regions. To demonstrate the capabilities of this approach, we have determined the organization of ten protein components of the presynaptic active zone and the postsynaptic density. Variations in synapse morphology, neurotransmitter receptor composition, and receptor distribution were observed both among synapses and across different brain regions. Combination with optogenetics further allowed molecular events associated with synaptic plasticity to be resolved at the single-synapse level.


Comparative Transcriptome Sequencing and Endogenous Phytohormone Content of Annual Grafted Branches of Zelkova schneideriana and Its Dwarf Variety HenTianGao.
Zelkova schneideriana is a fast-growing tree species endemic to China. Recent surveys and reports have highlighted a continued decline in its natural populations; therefore, it is included in the Red List of Threatened Species by The International Union for Conservation of Nature. A new variety "HenTianGao" (H) has been developed with smaller plant height, slow growth, and lower branching points. In this study, we attempted to understand the differences in plant height of Z. schneideriana (J) and its dwarf variety H. We determined the endogenous hormone content in the annual grafted branches of both J and H. J exhibited higher gibberellic acid (GA)-19 and trans-Zeatin (tZ) levels, whereas H had higher levels of indole-3-acetic acid (IAA) catabolite 2-oxindole-3-acetic acid (OxIAA), IAA-Glu conjugate, and jasmonic acid (JA) (and its conjugate JA-Ile). The transcriptome comparison showed differential regulation of 20,944 genes enriched in growth and development, signaling, and metabolism-related pathways. The results show that the differential phytohormone level (IAA, JA, tZ, and GA) was consistent with the expression of the genes associated with their biosynthesis. The differences in relative OxIAA, IAA-Glu, GA19, trans-Zeatin, JA, and JA-Ile levels were linked to changes in respective signaling-related genes. We also observed significant differences in the expression of cell size, number, proliferation, cell wall biosynthesis, and remodeling-related genes in J and H. The differences in relative endogenous hormone levels, expression of biosynthesis, and signaling genes provide a theoretical basis for understanding the plant height differences in Z. schneideriana.


Subcutaneous Lobular Capillary Hemangioma on 68Ga-PSMA PET/CT.
We present a case of a subcutaneous process in the abdominal wall with high prostate-specific membrane antigen (PSMA) activity on Ga-PSMA PET/CT. Histology demonstrated a benign lobular capillary hemangioma with a high vascular density, with highly PSMA-positive endothelial cells. It is well known that PSMA is expressed in different tissue, including neovasculature in various malignant tumors, and the knowledge is rapidly evolving as new discoveries appear.


Characterization of Leukocytes From HIV-ART Patients Using Combined Cytometric Profiles of 72 Cell Markers.
Motivation: Mass cytometry is a technique used to measure the intensity levels of proteins expressed by cells, at a single cell resolution. This technique is essential to characterize the phenotypes and functions of immune cell populations, but is currently limited to the measurement of 40 cell markers that restricts the characterization of complex diseases. However, algorithms and multi-tube cytometry techniques have been designed for combining phenotypic information obtained from different cytometric panels. The characterization of chronic HIV infection represents a good study case for multi-tube mass cytometry as this disease triggers a complex interactions network of more than 70 cell markers. Method: We collected whole blood from non-viremic HIV-infected patients on combined antiretroviral therapies and healthy donors. Leukocytes from each individual were stained using three different mass cytometry panels, which consisted of 35, 32, and 33 cell markers. For each patient and using the CytoBackBone algorithm, we combined phenotypic information from three different antibody panels into a single cytometric profile, reaching a phenotypic resolution of 72 markers. These high-resolution cytometric profiles were analyzed using SPADE and viSNE algorithms to decipher the immune response to HIV. Results: We detected an upregulation of several proteins in HIV-infected patients relative to healthy donors using our profiling of 72 cell markers. Among them, CD11a and CD11b were upregulated in PMNs, monocytes, mDCs, NK cells, and T cells. CD11b was also upregulated on pDCs. Other upregulated proteins included: CD38 on PMNs, monocytes, NK cells, basophils, B cells, and T cells; CD83 on monocytes, mDCs, B cells, and T cells; and TLR2, CD32, and CD64 on PMNs and monocytes. These results were validated using a mass cytometry panel of 25 cells markers. Impacts: We demonstrate here that multi-tube cytometry can be applied to mass cytometry for exploring, at an unprecedented level of details, cell populations impacted by complex diseases. We showed that the monocyte and PMN populations were strongly affected by the HIV infection, as CD11a, CD11b, CD32, CD38, CD64, CD83, CD86, and TLR2 were upregulated in these populations. Overall, these results demonstrate that HIV induced a specific environment that similarly affected multiple immune cells.


Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen.
Aromatase inhibitors (AI) are being evaluated as long-term adjuvant therapies and chemopreventives in breast cancer. However, there are concerns about bone mineral density loss in an estrogen-free environment. Unlike nonsteroidal AIs, the steroidal AI exemestane may exert beneficial effects on bone through its primary metabolite 17-hydroexemestane. We investigated 17-hydroexemestane and observed it bound estrogen receptor alpha (ERalpha) very weakly and androgen receptor (AR) strongly. Next, we evaluated 17-hydroexemestane in MCF-7 and T47D breast cancer cells and attributed dependency of its effects on ER or AR using the antiestrogen fulvestrant or the antiandrogen bicalutamide. 17-Hydroexemestane induced proliferation, stimulated cell cycle progression and regulated transcription at high sub-micromolar and micromolar concentrations through ER in both cell lines, but through AR at low nanomolar concentrations selectively in T47D cells. Responses of each cell type to high and low concentrations of the non-aromatizable synthetic androgen R1881 paralleled those of 17-hydroexemestane. 17-Hydroexemestane down-regulated ERalpha protein levels at high concentrations in a cell type-specific manner similarly as 17beta-estradiol, and increased AR protein accumulation at low concentrations in both cell types similarly as R1881. Computer docking indicated that the 17beta-OH group of 17-hydroexemestane relative to the 17-keto group of exemestane contributed significantly more intermolecular interaction energy toward binding AR than ERalpha. Molecular modeling also indicated that 17-hydroexemestane interacted with ERalpha and AR through selective recognition motifs employed by 17beta-estradiol and R1881, respectively. We conclude that 17-hydroexemestane exerts biological effects as an androgen. These results may have important implications for long-term maintenance of patients with AIs.


Potential of compost mixed with tuff and pozzolana in site restoration.
The present research is aimed at evaluating the potential of mixtures made of different percentages of compost (10%, 20% and 30% by volume) and inorganic waste from extraction activities (tuff and pozzolana) for site restorations. The materials alone and the mixtures were characterised from a geotechnical point of view, in order to determine the optimal percentage to be used. In particular, the oedometric test and the direct shear test were performed. Also the environmental quality of the materials was investigated through chemical characterisation and a leaching test. In addition, a lab-scale seeding test was carried out to assess the potential phytotoxicity of the mixture. Finally, at the end of the experimentation the accumulation of heavy metals in the plants was determined and the plants+artificial soil system underwent a shear stress test. The presence of compost in the percentages tested did not reduce the mechanical performances of the inorganic residues, guaranteeing good resistance and stability. In fact, the response to oedometric compression, the compression coefficient and the internal friction angle of the mixtures were quite similar to those obtained for tuff and pozzolana alone. The mixtures selected as optimal from a mechanical point of view (30% by volume of compost and 70% by volume of tuff/pozzolana), did not represent a potential hazard for the environment due to the low content and negligible leachability of heavy metals. In addition, such mixtures can provide a good substrate for revegetation thanks to the high content of organic matter and the absence of phytotoxic effects in the conditions tested.


Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells.
Animal cells have recently been shown to express a range of approximately 22 nucleotide noncoding RNAs termed micro RNAs (miRNAs). Here, we show that the human mir-30 miRNA can be excised from irrelevant, endogenously transcribed mRNAs encompassing the predicted 71 nucleotide mir-30 precursor. Expression of the mir-30 miRNA specifically blocked the translation in human cells of an mRNA containing artificial mir-30 target sites. Similarly, designed miRNAs were also excised from transcripts encompassing artificial miRNA precursors and could inhibit the expression of mRNAs containing a complementary target site. These data indicate that novel miRNAs can be readily produced in vivo and can be designed to specifically inactivate the expression of selected target genes in human cells.


The tuberculosis pandemic today: routes of transmission and new target groups.
Tuberculosis, a disease that has been with us since the dawn of time, shows little sign of disappearing. Declines in death rates observed for several centuries prior to 1960 have been reversed in recent decades. This is in spite of the fact that efficient means of controlling the disease have been available during this period. This article reviews experience in 3 communities: among the Inuit, who live in the region of the North Pole; in the Beijing Municipality in the People's Republic of China; and in a socially isolated community in South Africa. In the first 2 communities, dramatic declines in the burden of disease have been observed: in the Inuit community, this occurred after substantial intervention; in the Beijing Municipality it was done with limited resources. The third community in South Africa illustrates an alarming trend, with tuberculosis being seen in a variety of locations but in the absence of external agents such as HIV infection. Clearly we need to refocus our efforts to control this disease, making use of the new tools that are rapidly becoming available. This must be done without delay, before influences such as HIV infection put the possibility of control completely out of reach.


[Hydration of oocytes in bony fishes].
Data are collected on the hydration of oocytes in bony fishes during maturation stimulated by gonadotropic or steroid hormones in vivo and in vitro. The reasons for hydration, its dynamics, and certain of the mechanisms ensuring income of water and ions into the oocyte are considered.


How peritoneal dialysis has developed in Vietnam.
In Vietnam, continuous ambulatory peritoneal dialysis (CAPD) with a straight line and one bag was first used in 1998. Because the complication rate, mainly as a result of catheter obstruction and peritonitis, was very high (50%), treatment was stopped after the first 10 cases. Use of the modality resumed only in 2001. However, because of skepticism and concern on both the part of physicians and patients about the effectiveness of peritoneal dialysis (PD) and about the infection risk, CAPD developed very slowly. Until late 2004, patient numbers were very limited, and there was only one PD unit in the entire country. Since then, CAPD using Y-set and two-bag system-plus routine omentectomy during catheter insertion and better patient selection and training in bag exchange-has resulted in much better outcomes with fewer complications, and the technique has been developing far faster. This success, together full insurance coverage of both dialysis and erythropoietin since 2005, has led to a steep rise in the number of patients on PD and the number of PD units. As a result, despite the initial difficulty, the number of PD patients increased to nearly 700 in just 3 years (2004 - 2007), while it took more than 20 years before more than 3000 patients were receiving hemodialysis. Automated PD and icodextrin are not yet available in Vietnam.


Dietary Intake of Marine Polyunsaturated n-3 Fatty Acids and Risk of Recurrent Venous Thromboembolism.
Limited knowledge exists on the association between intake of long-chained n-3 polyunsaturated fatty acids (n-3 PUFAs) and risk of recurrence and all-cause mortality in patients with venous thromboembolism (VTE). This article investigates whether intake of marine n-3 PUFAs was associated with risk of recurrence and mortality in patients with incident VTE. A total of 595 patients with incident VTE and available data on n-3 PUFA intake were derived from the Tromsø Study surveys 4 (1994-1995) and 6 (2007-2008). Weekly intake of n-3 PUFAs was categorized as low, medium, and high based on tertiles. Recurrent VTEs and all-cause mortality were registered up to December 31, 2016. Hazard ratios (HRs) were calculated using Cox regression models with the low intake category as reference. There were 98 recurrent VTEs and 227 deaths during follow-up. Overall, we found no association between intake of n-3 PUFAs and risk of recurrent VTE. However, inverse associations were found for high intakes in patients with unprovoked VTE (HR 0.45, 95% confidence interval [CI]: 0.20-1.01), cancer-free patients (HR 0.51, 95% CI: 0.27-0.95), and deep vein thrombosis (DVT) patients (HR 0.49, 95% CI: 0.24-0.97). The inverse associations were more evident when follow-up was restricted to the time after discontinuation of anticoagulant therapy. No association was observed between intake of n-3 PUFAs and mortality after incident VTE. A high dietary intake of marine n-3 PUFAs was associated with lower risk of recurrent VTE after unprovoked index events, DVT, and in cancer-free patients.


Adequacy of follow-up in children diagnosed with urinary tract infections in a pediatric emergency department.
A retrospective chart review was undertaken to determine primary care provider (PCP) notification of patient visits and appropriateness of follow-up in children discharged from an inner city, university-affiliated children's emergency department with the diagnosis of urinary tract infection (UTI). Seventy-five charts met criteria for review, and phone calls were made to the PCP/families to obtain follow-up information. Statistical analysis was performed using the chi2 analysis and Fisher's exact test. The PCP was notified of the patient's diagnosis at the time of the ED visit in 24 cases (32%) and was aware of the ED visit/diagnosis of UTI in a total of 53 (71%). Children were more likely to have a repeat urine culture in follow-up if the PCP was aware of the diagnosis (60%) than if the PCP was not aware (9%) chi2 = 14.496 P < 0.001. Forty-seven children met criteria commonly accepted for radiographic evaluation. Nineteen children, whose PCPs were aware of their diagnosis, met criteria and had studies performed. Children were more likely to receive appropriate radiographic evaluation if their PCPs were aware of their diagnoses of UTI 19/35 (54%) than if their PCPs were unaware of their diagnoses 0/12 (0%). Fisher's exact two-tailed t test P < 0.001. We conclude that failure of PCP notification can impact negatively on appropriate patient follow-up and that, in many cases, PCPs are not following current recommendations in the management of children with UTIs.


Examining Parents' Preferences for Group and Individual Parent Training for Children with ADHD Symptoms.
Parent training (PT) programs have been found to reduce some behavioral impairment associated with children's attention deficit hyperactivity disorder (ADHD) as well as improve parenting competence, but poor uptake and participation by parents are formidable barriers that affect service effectiveness. We used a discrete-choice experiment (DCE) to examine how parent preferences for treatment format (i.e., group vs. individual) might influence their participation in PT. Participants were 445 parents seeking mental health services for children with elevated symptoms of ADHD in Ontario, Canada. Parents completed a DCE composed of 30 choice tasks used to gauge PT format preference. Results showed that 58.7% of parents preferred individual PT; these parents were most interested in interventions that would make them feel more informed about their child's problems and in understanding-as opposed to solving-their child's problems. A minority of parents (19.4%) preferred group PT; these parents were most interested in active, skill-building services that would help them solve their child's problems. About one fifth of parents (21.9%) preferred the Minimal Information alternative (i.e., receiving neither individual or group PT); these parents reported the highest levels of depression and the most severe mental health problems in their child. Results highlight the importance of considering parent preferences for format and suggest that alternative formats to standard PT should be considered for multiply stressed families.


Phosphoglycerate kinase acts as a futile cycle at high temperature.
In (hyper)thermophilic organisms metabolic processes have to be adapted to function optimally at high temperature. We compared the gluconeogenic conversion of 3-phosphoglycerate via 1,3-bisphosphoglycerate to glyceraldehyde-3-phosphate at 30 °C and at 70 °C. At 30 °C it was possible to produce 1,3-bisphosphoglycerate from 3-phosphoglycerate with phosphoglycerate kinase, but at 70 °C, 1,3-bisphosphoglycerate was dephosphorylated rapidly to 3-phosphoglycerate, effectively turning the phosphoglycerate kinase into a futile cycle. When phosphoglycerate kinase was incubated together with glyceraldehyde 3-phosphate dehydrogenase it was possible to convert 3-phosphoglycerate to glyceraldehyde 3-phosphate, both at 30 °C and at 70 °C, however, at 70 °C only low concentrations of product were observed due to thermal instability of glyceraldehyde 3-phosphate. Thus, thermolabile intermediates challenge central metabolic reactions and require special adaptation strategies for life at high temperature.


Comparison of gene expression profiles produced by CAGE, illumina microarray and real time RT-PCR.
Several technologies are currently used for gene expression profiling, such as Real Time RT-PCR, microarray and CAGE (Cap Analysis of Gene Expression). CAGE is a recently developed method for constructing transcriptome maps and it has been successfully applied to analyzing gene expressions in diverse biological studies. The principle of CAGE has been developed to address specific issues such as determination of transcriptional starting sites, the study of promoter regions and identification of new transcripts. Here, we present both quantitative and qualitative comparisons among three major gene expression quantification techniques, namely: CAGE, illumina microarray and Real Time RT-PCR, by showing that the quantitative values of each method are not interchangeable, however, each of them has unique characteristics which render all of them essential and complementary. Understanding the advantages and disadvantages of each technology will be useful in selecting the most appropriate technique for a determined purpose.


[Features of the inhibition of catalase activity by 3-amino-1,2,4-triazole in erythrocytes and liver of rats with streptozotocin diabetes].
Lipid peroxidation was intensified by streptozotocin induced diabetes mellitus in erythrocytes and liver. Activity of antioxidant enzyme superoxide-dismutase was decreased, activity of catalase was increased. Concentration of lipid peroxidation products was decreased after nicotinamide injections. It was investigated liver- and erythrocyte catalase inhibition in the presence of 3-amino-1,2,4-triazole. Effective inhibitor concentration for liver catalase by streptozotocin induced diabetes mellitus was 10 mM, by control-20 mM. Ascorbic acid induced catalase inhibition in the erythrocytes by diabetes mellitus increased by ascorbic acid concentration from 25 to 150 mM. [DHAA]/[AA]-ratio increased from 0.26 by control to 1.6 by diabetes mellitus and decreased to 0.44 after nicotinamide injections.


Mechanism by which renin secretion from perfused rat kidneys is stimulated by isoprenaline and inhibited by high perfusion pressure.
1. Rat kidneys were completely isolated and perfused to determine the ionic mechanism whereby isoprenaline stimulates and high perfusion pressure inhibits renin secretion. 2. Isoprenaline (2.43 microM) stimulated renin secretion, but K-free medium and ouabain also reduced perfusate flow. 3. Removing Ca from the perfusion medium increased renin secretion threefold when perfusion pressure was 100 mmHg and fourfold when pressure was raised to 150 mmHg. Simultaneously raising the perfusion pressure to 150 mmHg and the Ca concentration to 5 mM inhibited renin secretion. Verapamil (50 microM) prevented this inhibition. Raising Ca also caused vasoconstriction at a pressure of 150 mmHg, but verapamil partially prevented the vasoconstriction. 4. High concentration of K (50 mM) in the perfusion medium also stimulated renin secretion when Ca was removed and inhibited secretion when Ca concentration was raised to 5 mM. Verapamil (50 microM) prevented this inhibition. High K induced vasoconstriction in the presence of high Ca, but verapamil partially prevented the constriction. 5. High concentration of K (50 mM) and high perfusion pressure (150 mmHg) stimulated renin secretion in the absence of Ca and 20 mM-Mg potentiated this effect. This suggests that both sets of stimuli activate renin secretion by different cellular mechanisms, but that both act to lower cytoplasmic Ca in the juxtaglomerular cell. This is discussed. 6. High perfusion pressure inhibited renin secretion and reduced perfusate flow when Na was lowered from 145 to 14.5 or 0 mM whether or not Ca was present. 7. K-free medium and ouabain blocked the elevated renin secretion and reduced the high flow stimulated by high perfusion pressure when Ca was removed from the perfusion medium. 8. These observations suggest that isoprenaline stimulates renin secretion by a mechanism coupled to the Na-K pump. These observations are also consistent with the hypothesis that high renal perfusion pressure inhibits renin secretion by promoting Ca movement into the juxtaglomerular cell and stimulates secretion by a mechanism coupled to the Na-K pump. High perfusion pressure also causes renal vasoconstriction by increasing the Ca permeability of the smooth muscle cells in the afferent arteriole.


Clinical manifestations of HIV infection in children at Enugu, Nigeria.
Three-hundred-and-fifty-eight (358) pediatric patients below 16 years of age were screened for suspected human immunodeficiency virus (HIV) infection between October 1989 and September 1996. Eighty-three (23 per cent) were confirmed positive. However, adequate clinical data were obtained retrospectively in only 63 patients. Twenty-three (37 per cent) of the patients presented with features corresponding to WHO case definition of Paediatric Acquired Immunodeficiency syndrome (AIDS) in Africa. Vertical mode of infection was documented in 13 (30 per cent) of them while 30 (68 per cent) were infected through blood transfusion. The main clinical features at presentation were generalised lymphadenopathy (59 per cent), persistent or recurrent fever (51 per cent), progressive weight loss or poor weight gain (51 per cent), chronic diarrhoea (38 per cent), various skin manifestations (37 per cent), persistent cough (32 per cent), and oral candidiasis (19 per cent). Six patients died during the initial admission, while majority were lost to follow-up.


IL-21 Receptor Antagonist Inhibits Differentiation of B Cells toward Plasmablasts upon Alloantigen Stimulation.
Interaction between T follicular helper (Tfh) cells and B cells is complex and involves various pathways, including the production of IL-21 by the Tfh cells. Secretion of IL-21 results in B cell differentiation toward immunoglobulin-producing plasmablasts. In patients after kidney transplantation, the formation of alloantibodies produced by donor antigen-activated B cells are a major cause of organ failure. In this allogeneic response, the role of IL-21-producing Tfh cells that regulate B cell differentiation is unknown. Here, we tested, in an alloantigen-driven setting, whether Tfh cell help signals control B cell differentiation with its dependency on IL-21. Pre-transplantation patient PBMCs were sorted into pure CD4posCXCR5pos Tfh cells and CD19posCD27pos memory B cells and stimulated with donor antigen in the presence or absence of an IL-21 receptor (IL-21R) antagonist (αIL-21R). Donor antigen stimulation initiated expression of the activation markers inducible co-stimulator (ICOS) and programmed death 1 (PD-1) on Tfh cells and a shift toward a mixed Tfh2 and Tfh17 phenotype. The memory B cells underwent class switch recombination and differentiated toward IgM- and IgG-producing plasmablasts. In the presence of αIL-21R, a dose-dependent inhibition of STAT3 phosphorylation was measured in both T and B cells. Blockade of the IL-21R did not have an effect on PD-1 and ICOS expression on Tfh cells but significantly inhibited B cell differentiation. The proportion of plasmablasts decreased by 78% in the presence of αIL-21R. Moreover, secreted IgM and IgG2 levels were significantly lower in the presence of αIL-21R. In conclusion, our results demonstrate that IL-21 produced by alloantigen-activated Tfh cells controls B cell differentiation toward antibody producing plasmablasts. The IL-21R might, therefore, be a useful target in organ transplantation to prevent antigen-driven immune responses leading to graft failure.


[Methods of pedicle hemostasis in laparoscopically-assisted vaginal hysterectomy (VAVH). Evaluation of results].
The objective was to evaluate whether use of different techniques of hemostasia have effect on laparoscopically assisted vaginal hysterectomy (LAVH) morbidity. Was performed a review of 53 LAVH cases, parameters analyzed were type of hemostasia method and surgical complications. There were five patients with transoperative bleeding and two with incidental bladder lesion, that were managed successfully without complications. There were no significant differences between types of hemostasia with respect to transoperative bleeding. There were no mayor surgical complications in the studied patients. As conclusion LAVH allows patients a expedite recovery with low postoperative complications. All the methods used in this work to perform hemostasia in LAVH are safe and effective for patients with habitual hysterectomy indications.


Trauma-Informed Cultural Humility Mental Health Practice: Centering History among African American Women.
Social work has made significant strides in providing mental health services. However, advancement in mental health practices grounded in social work values, such as trauma-informed care and cultural humility mental health practice (CHMHP), is still lacking. One possible reason is that many strategies overlook clients' historical contexts, particularly the collective history held by the community to which the client belongs. By centering "history" in social work practices, clinical social workers can be more equipped to provide high-quality, client-centered services. This article advocates for adopting trauma-informed CHMHP as a critical strategy to elevate history in clinical social work practice and proposes that trauma-informed CHMHP can improve mental health service quality among clients of color who are profoundly disrupted by historical trauma. Specifically, this article proposes that using trauma-informed CHMHP to address historical trauma can enhance mental health treatment outcomes and experiences for African American women. Clinical social workers trained to address these interconnected issues can help reduce disparities in quality treatment access.


Cyclopropenylidene carbene ligands in palladium catalysed coupling reactions: carbene ligand rotation and application to the Stille reaction.
Reaction of [Pd(PPh(3))(4)] with 1,1-dichloro-2,3-diarylcyclopropenes gives complexes of the type cis-[PdCl(2)(PPh(3))(C(3)(Ar)(2))] (Ar = Ph 5, Mes 6). Reaction of [Pd(dba)(2)] with 1,1-dichloro-2,3-diarylcyclopropenes in benzene gave the corresponding binuclear palladium complexes trans-[PdCl(2)(C(3)(Ar)(2))](2) (Ar = Ph 7, p-(OMe)C(6)H(4)8, p-(F)C(6)H(4)9). Alternatively, when the reactions were performed in acetonitrile, the complexes trans-[PdCl(2)(NCMe)(C(3)(Ar)(2))] (Ar = Ph 10, p-(OMe)C(6)H(4)11 and p-(F)C(6)H(4)) 12) were isolated. Addition of phosphine ligands to the binuclear palladium complex 7 or acetonitrile adducts 11 and 12 gave complexes of the type cis-[PdCl(2)(PR(3))(C(3)(Ar)(2))] (Ar = Ph, R = Cy 13, Ar = p-(OMe)C(6)H(4), R = Ph 14, Ar = p-(F)C(6)H(4), R = Ph 15). Crystal structures of complexes 6·3.25CHCl(3), 10, 11·H(2)O and 12-15 are reported. DFT calculations of complexes 10-12 indicate the barrier to rotation about the carbene-palladium bond is very low, suggesting limited double bond character in these species. Complexes 5-9 were tested for catalytic activity in C-C coupling (Mizoroki-Heck, Suzuki-Miyaura and, for the first time, Stille reactions) and C-N coupling (Buchwald-Hartwig amination) showing excellent conversion with moderate to high selectivity.