Biological nitrogen fixation by lucerne (Medicago sativa L.) in acid soils

Growth of lucerne( Medicago sativa L.) is poor in soils with values of pH-H2O below 6. This is often due to nitrogen deficiency, resulting from a hampered performance of the symbiosis withRhizobium meliloti. This thesis deals with the factors affecting biological nitrogen fixation by lucerne in acid soils.In a field experiment, lucerne seeds were either inoculated withR.meliloti only,or inoculated and pelleted with lime, before sowing in a sandy soil of pH 5.2. Lime-pelleting significantly improved the establishment of the seedlings. This was caused by earlier nodulation, as evidenced by the formation of crown nodules,i.e.the nodules on the upper 10 mm of the seedling taproot. The number of seedlings carrying crown nodules tripled from 18% to 56%, 26 days after sowing as a result of lime-pelleting. The dry matter yield and nitrogen fixation of the plants at later stages showed a close correlation with crown nodulation.To minimize the problems inherent to field experiments,e.g.costs and labour, besides pots, rhizotrons (small root boxes made of plastic petri dishes) were developed to study the symbiosis under controlable conditions in the laboratory (Chapter 2). Comparative trials showed that crown nodulation in pots was practically similar to that in the field. In rhizotrons, the early root development and nodule formation could continuously be observed. moreover, lime- pelleting resulted in a greater increase of crown nodulation (5% to 90%) during a shorter incubation period (14 days).R.melilotibacteria are notorious for their acid sensitivity. As a consequence the increased crown nodulation by lime-pelleting might be the result of a better proliferation of these bacteria, thus resulting in a higher chance of root infection. To verify this hypothesis, the effect of lime-pelleting on the survival of inoculated R.meliloti around the seed was recorded during a period of 12 days following sowing. In the initial 12 hours a strong increase in rhizobial numbers coincided with the germination of the seed. Little differences in multiplication were measured in the presence or absence of a lime-pellet. To obtain optimal nodulation in this soil, however, lime-pelleting was a prerequisite and at least 10 5cells ofR.meliloti per seed were required. In the absence of lime, only a few plants nodulated, even when the number of rhizobia was increased to 10 7per seed (Chapter 3).The nodulation effect of lime-pelleting could not be explained by a better rhizobial multiplication. The benefit of CaC0 3 can be due to either neutralization of soil acidity and/or to the input of calcium.Tostudy the pH changes in the rhizosphere while leaving the spatial arrangement of the soil intact, the following method was deviced: The soil was covered with a thin layer of agar containing the pH indicator bromocresol purple. To prevent the contamination of agar with soil particles, a nylon gauze was used to keep the soil separated from the agar. Quantitative pH measurements were done by inserting a micro-electrode into the agar after 3 hours of contact with the soil. The validity of the data obtained by this method was investigated by comparing the results with those obtained using standard procedures for pH measurement in a soil-water suspension (Chapter 4).Using the agar-contact method, it was shown that the benefit of lime on the nodulation of lucerne was largely (80%) due to neutralization of acidity, and to a lesser extent (20%) to the supply of calcium. For nodulation, soil-pH measured around lime-pelleted seeds, should at least be 5.8. Untreated roots were also able to induce a pH-increase of 0.6 units at 6 days after sowing (d.a.s.) or later, but only very few plants nodulated. These results, obtained with soil-grown plants, confirm earlier findings with hydroponically grown plants, that nodulation is sensitive for acidity only during the early phase of the process (0 to 3 d.a.s.) (Chapter 5).The soil already contained 1.2 meq of calcium per 100 g. Hence, the contribution of calcium in the lime effect was rather small. When the native calcium was removed with a specific calcium chelator (EGTA). crown nodulation could further be reduced to 12%. However, an additional complication was the acidification that accompanied the chelation of soilcalcium, with soil-pH dropping from 6.1 to 5.2. This problem could be overcome by applying small agar blocks containing the chelator. This technique allowed local application and temporal treatment of the root with EGTA. It was shown that the nodulation could be inhibited by calcium depletion only during the first day (Chapter 6). Obviously, the early phase of the nodulation of lucerne in acid soil is transiently susceptible to low calcium availability, similar to the transient sensitivity to low pH.</TT

The association of cannabis use with quality of life and psychosocial functioning in psychosis

BACKGROUND: Cannabis use is highly prevalent among people with a psychotic disorder. They often report sociality, coping with unpleasant affect and having positive experiences as important reasons for cannabis use, suggesting that cannabis improves their quality of life (QoL) and psychosocial functioning. However, based on previous studies we hypothesize that cannabis use is negatively associated with long-term subjective QoL and psychosocial functioning in people with a psychotic disorder. METHODS: We included 2994 people with a psychotic disorder (36.4% female), mean age 44.4 (SD 11.9), mean illness duration 17.2 years (SD 11.1), who participated in two yearly routine outcome assessments between 2014 and 2018 (interval 9-15 months) from the naturalistic PHAMOUS cohort study. Linear regression analyses were used to examine whether first assessment cannabis use was associated with QoL (ManSA) and psychosocial functioning (HoNOS). Changes in outcomes between assessments were analyzed with AN(C)OVA, to examine differences between continuers (n = 255), discontinuers (n = 85), starters (n = 83) and non-users (n = 2571). RESULTS: At first assessment, 11.4% was using cannabis. They had lower QoL (B = -2.93, p < 0.001) and worse psychosocial functioning (B = 1.03, p = 0.002) than non-users. After one year, changes in QoL and psychosocial functioning were not significantly different between continuers, starters, discontinuers and non-users. CONCLUSIONS: Cannabis users were less satisfied with their family relations and financial situation and showed more aggressive and disruptive behavior and self-harm than non-users. These differences are likely the result of patients having used cannabis for many years. Starting or discontinuing cannabis did not lead to changes in QoL and psychosocial functioning within one year

The distribution of total vitamin b12 holotranscobalamin and the active vitamin b12 fraction in the first 5 weeks postpartum

Introduction Total vitamin B12 levels decrease significantly during pregnancy and recover to normal values within 8-week postpartum. Holotranscobalamin (holoTC) reflects the active part of vitamin B12 and has been shown to remain constant during pregnancy and postpartum. A mechanism of redistribution of vitamin B12 is suggested, with a shift toward holoTC if there is insufficient total vitamin B12 available. Our objective was to examine vitamin B12 deficiency and the active vitamin B12 fraction in postpartum women. Methods Total vitamin B12 and holoTC were measured in 171 women within 48 hours (T0) and at 5 weeks (T5) postpartum. Vitamin B12 deficiency was defined as total vitamin B12 < 180 pmol/L or holoTC <32 pmol/L. The active vitamin B12 fraction was defined as holoTC/total vitamin B12. Results Without intervention, vitamin B12 deficiency based on both serum total vitamin B12 and holoTC changed from 75% and 60%, to respectively 10% and 6% at T5. The fraction of active vitamin B12 was significant higher in vitamin B12 deficient women at both time points and across time (P < .0001 and P = .002). A high fraction of active vitamin B12 was only present in women with total vitamin B12 deficiency at T0. At T5, no high vitamin B12 fraction was found. Conclusion The changes in total vitamin B12 levels seem to be based on a physiological changes rather than vitamin B12 deficiency. The results of this study confirm the hypothesis that a shift toward the metabolic active vitamin B12 (holoTC) occurs in women with insufficient available total vitamin B12

Inhibition of Trophoblast-Induced Spiral Artery Remodeling Reduces Placental Perfusion in Rat Pregnancy.

Rats harboring the human angiotensinogen and human renin genes develop preeclamptic features in pregnancy. The preeclamptic rats exhibit a deeper trophoblast invasion associated with a reduced resistance index by uterine Doppler. Doxycycline inhibits matrix metalloproteinase activity. We tested the hypothesis that matrix metalloproteinase inhibition reduces trophoblast invasion with subsequent changes in placental perfusion. Preeclamptic and pregnant control Sprague-Dawley rats were treated with doxycycline (30 mg/kg of body weight orally) from gestational day 12 until day 18. Placental perfusion was assessed using a micromarker contrast agent. The animals were euthanized on day 18 of pregnancy; biometric data were acquired, and trophoblast invasion was analyzed. Doxycycline resulted in intrauterine growth retardation and lighter placentas in both groups. Maternal body weight was not affected. As shown earlier, preeclamptic rats exhibited a deeper endovascular trophoblast invasion. However, doxycycline treatment reduced trophoblast invasion in the preeclamptic rats. The physiological spiral artery remodeling, as assessed by the deposition of fibrinoid and α-actin in the spiral artery contour, was significantly reduced by doxycycline. The vascularity index, as assessed by perfusion measurement of the placenta, was reduced after doxycycline treatment in preeclamptic rats. Thus, matrix metalloproteinase inhibition with doxycycline leads to reduced trophoblast invasion and associated reduced placental perfusion. These studies are the first to show that reducing trophoblast-induced vascular remodeling decreases subsequent placental perfusion. Our model allows the study of dysregulated trophoblast invasion and vascular remodeling in vivo to gain important insights into preeclampsia-related mechanisms

Cognitive Performance and Long-Term Social Functioning in Psychotic Disorder:A Three-Year Follow-Up Study

ObjectiveStudies have linked cognitive functioning to everyday social functioning in psychotic disorders, but the nature of the relationships between cognition, social cognition, symptoms, and social functioning remains unestablished. Modelling the contributions of non-social and social cognitive ability in the prediction of social functioning may help in more clearly defining therapeutic targets to improve functioning.MethodIn a sample of 745 patients with a non-affective psychotic disorder, the associations between cognition and social cognition at baseline on the one hand, and self-reported social functioning three years later on the other, were analysed. First, case-control comparisons were conducted; associations were subsequently further explored in patients, investigating the potential mediating role of symptoms. Analyses were repeated in a subsample of 233 patients with recent-onset psychosis.ResultsInformation processing speed and immediate verbal memory were stronger associated with social functioning in patients than in healthy controls. Most cognition variables significantly predicted social functioning at follow-up, whereas social cognition was not associated with social functioning. Symptoms were robustly associated with follow-up social functioning, with negative symptoms fully mediating most associations between cognition and follow-up social functioning. Illness duration did not moderate the strength of the association between cognitive functioning and follow-up social functioning. No associations were found between (social) cognition and follow-up social functioning in patients with recent-onset psychosis.ConclusionsAlthough cognitive functioning is associated with later social functioning in psychotic disorder, its role in explaining social functioning outcome above negative symptoms appears only modest. In recent-onset psychosis, cognition may have a negligible role in predicting later social functioning. Moreover, social cognition tasks may not predict self-reported social functioning.</p

Increased angiogenic factor secretion by decidual natural killer cells from pregnancies with high uterine artery resistance alters trophoblast function.

STUDY QUESTION Are the concentrations of factors secreted by decidual natural killer (dNK) cells from pregnancies at high risk of poor spiral artery remodelling different to those secreted from pregnancies at low risk? SUMMARY ANSWER Expression levels of PLGF, sIL-2R, endostatin and angiogenin were significantly increased by dNK cells from high-risk pregnancies, and angiogenin and endostatin were found to alter trophoblast function. WHAT IS KNOWN ALREADY During early pregnancy, maternal uterine spiral arteries are remodelled from small diameter, low-flow, high-resistance vessels into larger diameter, higher flow vessels, with low-resistance. This change is essential for the developing fetus to obtain sufficient oxygen and nutrients. dNK cells have been implicated in this process. STUDY DESIGN, SIZE, DURATION dNK cells were isolated from first trimester terminations of pregnancies (obtained with local ethical approval) screened for normal- or high-resistance index, indicative of cases least (21%) likely to have developed pre-eclampsia had the pregnancy not been terminated (n = 18 each group). Secreted factors and the effects of these on the trophoblast cell line, SGHPL-4, were assessed in vitro. PARTICIPANTS/MATERIALS, SETTING, METHODS A multiplex assay was used to assess dNK cell-secreted factors. SGHPL-4 cell functions were assessed using time-lapse microscopy, 3D invasion assays, endothelial-like tube formation ability and western blot analysis. MAIN RESULTS AND THE ROLE OF CHANCE The expression levels of PLGF (P < 0.01), sIL-2R (P < 0.01), endostatin (P < 0.05) and angiogenin (P < 0.05) were significantly increased by dNK cells from high-risk pregnancies. Endostatin significantly decreased SGHPL-4 invasion (P < 0.05), SGHPL-4 tube formation (P < 0.05) and SGHPL-4 Aktser473 phosphorylation (P < 0.05). Angiogenin significantly decreased SGHPL-4 invasion (P < 0.05), but increased SGHPL-4 tube formation (P < 0.01) and decreased SGHPL-4 Aktser473 phosphorylation (P < 0.05). LIMITATIONS, REASONS FOR CAUTION The culture of dNK cells and protein concentrations in vitro may not fully represent the in vivo situation. Although SGHPL-4 cells are extravillous trophoblast derived, further studies would be needed to confirm the roles of angiogenin and endostatin in vivo. WIDER IMPLICATIONS OF THE FINDINGS The altered expression of secreted factors of dNK cells may contribute to pregnancy disorders associated with poor spiral artery remodelling. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Wellcome Trust (project reference 091550). R.F. was a recipient of a PhD studentship from the Division of Biomedical Sciences, St. George's, University of London. The authors have no conflict of interests

Symptomatic and Functional Recovery:Does symptom severity affect the recovery of executive functioning in people with psychotic disorders?

Background: Recovery in psychotic disorder patients is a multidimensional concept that can include personal, symptomatic, societal and functional recovery. Here we define Functional Recovery (FR) as recovery or compensation after the loss or impairment of skills in different cognitive functions. Some of the most impaired cognitive functions in psychosis are the executive functions, whose impairment in people with a psychotic disorder can produce problems that are difficult to overcome, partly because treatment often focuses only on Symptomatic Recovery (SR). Although symptom severity may be a risk factor for longstanding impairments of executive functioning, the association is not always found. To date, there has been little research on the association between the 2. MethodThis study is part of the UP’S study, a longitudinal cohort study of patients with a psychotic disorder. The Behaviour Rating Inventory of Executive Functioning Adult version (BRIEF-A) was used to measure FR at baseline and after 1 year. SR was measured using the Positive and Negative Symptom Scale-Remission (PANSS-R), also at baseline and 1 year? At both time points, correlations were computed as cross-sectional analyses. For the longitudinal analysis, the difference scores were used to calculate generalized linear models. Model selection was based on the Wald-Chi square test. Results323 people were included for the baseline assessment of the UP’S study, 163 of whom had completed the T1 follow-up measurement at the time of this study. We found a moderate association between PANSS-R baseline scores and BRIEF-A baseline scores (β=3.76). While there was also an association between the PANSS-R score at baseline and the BRIEF-A difference scores (β=1.67), we found no association between the PANSS-R difference scores and the BRIEF-A differences scores. ConclusionOur finding that less overall symptom severity was associated with 1 year improvement in executive functioning suggests that symptom severity could be a way of improving executive functioning over a year. However, as no link was found within the year between changes in symptoms and changes in executive functioning, it is possible that symptom severity does not have an immediate effect on executive functioning, but that its effect is delayed. This leaves scope for targeted interventions to improve executive functioning, and thus functional recovery

The association between executive functioning and personal recovery in people with psychotic disorders

Background Recovery in psychotic disorder patients is a multidimensional concept that can include personal, symptomatic, societal, and functional recovery. Little is known about the associations between personal recovery (PR) and functional recovery (FR). FR involves a person’s ability to recover or compensate for impaired cognition, such as executive functions, and the loss of skills. Method In this cross-sectional study (the UP’S study), we used measures of executive functioning and personal recovery to assess a cohort of people with a psychotic disorder. PR was measured using the Recovering Quality of Life (ReQOL) and Individual Recovery Outcomes (I.ROC). FR was assessed using two forms of assessment. The Behavioral Rating Inventory of Executive Functioning Adult version (BRIEF-A) was used for self-rated executive functioning, and the Tower of London (TOL) for performance-based executive functioning. Regression models were calculated between executive functioning (BRIEF-A and TOL) and PR (ReQOL and I.ROC). Model selection was based on the Wald test. Results The study included data on 260 participants. While total scores of BRIEF-A had a small negative association with those of the ReQOL (β = −0.28, P > .001) and the I.ROC (β = −0.41, P > .001), TOL scores were not significantly associated with the ReQOL scores (β = 0.03, P = .76) and the I.ROC scores (β = 0.17, P = 0.17). Conclusion Self-reported EF, which measures the accomplishment of goal pursuit in real life was associated with PR. However, processing efficiency and cognitive control as measured by performance-based EF were not

Evaluation of an adaptive implementation program for cognitive adaptation training for people with severe mental ilness:A cluster-randomized controlled trial

Introduction Cognitive Adaptation Training (CAT) is a psychosocial intervention focusing on reducing the impact of cognitive disorders on daily functioning in people with severe mental illness (SMI). Similar to many evidence based practices (EBP), implementation of CAT in routine care lags behind, despite the established effectiveness of the intervention. This so called ‘science-to-service gap’ is a widespread problem in mental health care. We developed an innovative implementation program to facilitate implementation of CAT and similar interventions in routine care. Objectives The aim of this study is to evaluate the effectiveness of the implementation program and to determine factors that impede or facilitate the implementation process. Methods We conducted a multicenter cluster randomized controlled trial comparing the implementation program to a single training program in four mental health institutions (a total of 21 rehabilitation teams) in The Netherlands. Focus groups, semistructured interviews and questionnaires were used at multiple levels of service delivery (service user, professional, team, organization). Assessments took place before, during and after implementation and at follow-up, adding up to a total duration of 14 months. Data were analyzed using multilevel modeling. Results Data collection is complete and analyses on the effectiveness of the implementation program are ongoing. Preliminary analyses show that team climate (p<.008) and organizational climate (p<.043) significantly predict the attitudes of mental health providers toward EBP. Conclusions This implementation research may provide important information about the implementation of psychosocial interventions in practice and may result in a program that is useful for Cognitive Adaptation Training, and possibly for psychosocial interventions in general

Cognitive-behavior therapy for children and adolescents with anxiety disorders:A meta-analysis of secondary outcomes

Anxiety-focused cognitive-behavioral therapy (CBT) effectively reduces anxiety in children and adolescents. An important remaining question is to what extent anxiety-focused CBT also affects broader outcome domains. Additionally, it remains unclear whether parental involvement in treatment may have impact on domains other than anxiety. A meta-analysis (nstudies = 42, nparticipants = 3239) of the effects of CBT and the moderating role of parental involvement was conducted on the following major secondary outcomes: depressive symptoms, externalizing behaviors, general functioning, and social competence. Randomized controlled trials were included when having a waitlist or active control condition, a youth sample (aged<19) with a primary anxiety disorder diagnosis receiving anxiety-focused CBT and reported secondary outcomes. Controlled effect sizes (Cohen's d) were calculated employing random effect models. CBT had a large effect on general functioning (-1.25[-1.59;0.90], nstudies = 17), a small to moderate effect on depressive symptoms (-0.31[-0.41;-0.22], nstudies = 31) and a small effect on externalizing behaviors (-0.23[-0.38;-0.09], nstudies = 12) from pre-to post-treatment. Effects remained or even further improved at follow-up. Social competence only improved at follow-up (nstudies = 6). Concluding, anxiety-focused CBT has a positive effect on broader outcome domains than just anxiety. Higher parental involvement seemed to have beneficial effects at follow-up, with improvements in general functioning and comorbid symptoms