Higher Initial Levels Research Articles

OPTIMIZATION OF BIOLOGICAL THERAPY IN PATIENTS WITH ULCERATIVE COLITIS (CASE REPORT)

Now in Russia registered two biological drugs for the treatment of UC is infliximab and golimumab. The largest experience with the use of infliximab (IFX) shows that, despite the high efficiency, in some patients the IBD (20-30%) will develop acquired secondary loss of response to the drug. The development of secondary loss of anti-cytokine therapy is influenced by the following causes - irregular administration of the drug, monotherapy with monoclonal antibodies, initial high levels of TNF-α and low albumin, the presence of antibodies to the drug, activation of opportunistic infections, and changes in pathogenesis of the disease. The appearance at present in the arsenal of gastroenterologists of golimumab (GLM) has expanded the possibilities of treatment of patients with UC in the case of secondary loss of response to therapy with anti-TNF-α or the development of adverse events on IFX. This clinical case shows that after discontinuation IFX, there is a risk of recurrence of the disease, which according to the literature is 50 %. The example also demonstrated that GLM is well tolerated in patients who develop adverse events on IFX in the form of anaphylaxis. This is because GLM are fully human inhibitor of TNF-α. Golimumab is a new, effective inhibitor of TNF-α, which may help to optimize therapy in UC.

Habituation of dairy heifers to milking routine—Effects on human avoidance distance, behavior, and cardiac activity during milking

The onset of lactation marks a significant turning point in a heifer’s life, and prior experience with the milking routine could have positive effects on animal welfare and productivity. The objectives of this multifarm (n=5) study were to investigate (1) whether prelactation training sessions affected behavior during milking, cardiac activity, human avoidance distance, and milk yield, and (2) whether these responses would be modified by the heifer’s initial level of fear of humans. Trained heifers (TH, n=30) experienced the routine in the milking parlor on at least 10 d prepartum, whereas untrained heifers (UH, n=29) entered the parlor for the first time after calving. Behavior and cardiac activity were recorded on d 1 and 7 after calving, and an avoidance test was carried out on the day of integration into the dairy herd as well as on d 1, 7, and 28 postpartum. Each animal’s initial level of fear of humans was classified as high or low based on the first human avoidance distance measured toward an unknown person. Results showed that TH showed less stepping and kicking during the udder preparation phase in the parlor and UH had higher probabilities to put their ears flat on the head, clamp their tail between the hind legs, and have their eyes wide open throughout the different phases in the milking parlor. Heart rate decreased from d 1 to 7, increased from before to during and to after milking and was slightly elevated in TH compared with UH. Milk yield did not differ between TH and UH. Human avoidance distance was not influenced by training, but distance decreased in heifers with a high initial level of fear of humans across repetitions of the test, whereas heifers with a low initial level of fear of humans had generally short avoidance distances. However, initial level of fear of humans neither determined behavior and heart rate during milking nor milk yield of TH and UH. The results indicate that the training regimen applied in the present study habituated heifers, to some extent, to the milking routine.

Medical treatment of chylothorax and chylous ascites as a late complication of acute necrotizing pancreatitis

s / Pancreatology 15 (2015) S1eS141 S60 Patients&methods:We evaluated 234 patients with first onset of SAP appears in last twenty fourhours. A total of 77 (33%)patientsdied. SIRS score and serum IL-4 concentration were measured in first hour after admission. Results: In 105 patients with SIRS score 3 and higher, initial measured IL-4 levels were significantly higher than in the group of remaining 129 patients. All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial high level IL-4 concentration. The values of C reactive protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-4 concentration and APACHE II score. Conclusion: The combinationof SIRS score on admission and IL-4 serum concentration can be early, predictor of illness severity and outcome in SAP.

BAFF (B cell activating factor) transcript level in peripheral blood of patients with SLE is associated with same-day disease activity as well as global activity over the next year.

ObjectivesQuantitating gene expression is a potential method of developing biomarkers in systemic lupus erythematosus (SLE). Because of the known pathological role of B cell activating factor (BAFF) in SLE, we explored the association between BAFF gene expression and clinical activity in SLE.MethodsA total of 275 patients with SLE completed this phase of a prospective observational study. At entry into the study, the BAFF gene expression levels were determined in peripheral blood RNA. Serum concentration of BAFF protein was also measured. We then determined clinical associations with SLE disease history, SLE activity on the same day and SLE activity over the course of the next year.ResultsElevated BAFF gene expression was associated with a history of more leucopenia and serologically with more autoantibodies (anti-dsDNA, anti-Sm, anti-Ro, anti-La and anti-RNP) and low complement. Patients with higher amounts of BAFF transcript had higher measured levels of clinical disease activity. Initial high levels of BAFF gene expression also predicted increased disease activity over the course of the next year. In contrast, serum concentration of BAFF protein was not strongly associated with same-day global disease activity or with future disease activity.ConclusionsBAFF gene expression level is associated with clinical and serological SLE activity on the same day and predictive of clinical activity over the next year. BAFF gene expression is a better measure and predictor of SLE disease activity than the serum BAFF protein level.

EVALUATING AN ABBREVIATED VERSION OF THE PATHS CURRICULUM IMPLEMENTED BY SCHOOL MENTAL HEALTH CLINICIANS

When evidence-based prevention programs are implemented in schools, adaptations are common. It is important to understand which adaptations can be made while maintaining positive outcomes for students. This preliminary study evaluated an abbreviated version of the Promoting Alternative Thinking Strategies (PATHS) Curriculum implemented by school-based mental health clinicians in preschool/kindergarten classrooms. Results suggest that students (N = 80) demonstrated increases in emotional understanding and prosocial behavior. Children with low initial levels of problem behavior demonstrated large and continual increases in prosocial behavior over the entire course of the intervention, whereas children with high initial levels of problem behavior only demonstrated small gains in prosocial behavior during the first half of the intervention. These preliminary results support the general effectiveness of the adapted intervention, but also suggest the need for additional intervention to produce meaningful and sustained behavioral gains for higher-need students.

Urban–rural transformation in relation to cultivated land conversion in China: Implications for optimizing land use and balanced regional development

The paper aims to investigate land conversion as a result of urban–rural transformation in the Chinese context. Theoretical analysis and empirical study of the Bohai Rim region find strong connections between the land conversion rates and urban–rural transformation intensity in the period 2000–2010. Rapid land conversion normally takes place in counties/districts of low initial level of urban–rural transformation. However, places of high initial socioeconomic level and low transformation intensity would experience slow land conversion. The different land conversion rates in relation to urban–rural transformation intensity are mainly attributed to the China's land quotas distribution system which is subjective and administrative. The study highlights the implementation of land quotas distribution system based on differences to improve the land distribution efficiency and achieve balanced regional development in China.

Relatives of patients with severe brain injury: Growth curve analysis of anxiety and depression the first year after injury

Primary objective: To investigate trajectories and predictors of trajectories of anxiety and depression in relatives of patients with a severe brain injury during the first year after injury.Research design: A prospective longitudinal study with four repeated measurements.Subjects: Ninety relatives of patients with severe brain injury.Methods: The relatives were assessed on the anxiety and depression scales from the Symptom Checklist-90-Revised and latent variable growth curve models were used to model the trajectories. The effects of patient’s age, patient’s Glasgow Coma Score, level of function and consciousness, gender and relationship of the relatives were modelled.Results: Improvement was found in both symptoms of anxiety and depression during the 12-month study period. The analysis revealed different trajectories for symptoms of anxiety and depression, as anxiety had a more rapid improvement. Higher initial level of symptoms of depression was seen in female relatives. Higher initial level of anxiety was associated with younger patient age, lower level of function and consciousness in the patient and the relative being female or the spouse.Conclusion: Future research and interventions should focus not only on specific deficits in the patient, but also on how the emotional state and well-being of the relatives evolve, while trying to adjust and cope with a new life-situation.

A Possible Explanatory Model for the Relationship between Teaching Motivation and Job Satisfaction

This study aims to identify possible correlations that might exist between job satisfaction and motivation of teachers teaching career. It is an empirical research without experimental manipulation, conducted in the 2012-2013 school year, on a sample of 150 subjects, teachers from different schools in Galati, Romania. The partial results obtained show the lack of the correlation between motivation and job satisfaction. In general, teachers require a high initial level of motivation, but in time, job satisfaction tends to decline. We can say that the relationship between motivation and job satisfaction is reversed. The teachers have certain professional expectations, but if these expectations are not achieved, the job satisfaction decreases.

Abstract P4-01-12: Circulating tumor cells (CTC) and endothelial cells (CEC) changes in HER2 negative metastatic breast cancer (MBC) patients treated with first line weekly paclitaxel and bevacizumab: Preliminary results of a prospective cohort from the French Breast Cancer

Abstract Background: increased levels of circulating tumor cells (CTC) are associated with worse progression-free survival (PFS) and overall survival (OS) in patients (pts) with MBC (Bidard FC et al, Lancet Oncol 2014). The failure of chemotherapy to reduce CTCs to levels below five CTCs per 7.5 mL whole blood at first follow-up after initiating a new systemic therapy for MBC predicts shorter time to progression and OS. It has been hypothesized that bevacizumab could modify CTC prognostic value due to extravasation or epithelio-mesenchymal transition induction. CEC variations to predict benefit of anti-angiogenic treatment is still controversial. Patients & methods: the French cohort COMET is a prospective study including first line HER2 negative pts receiving weekly paclitaxel and bevacizumab according to EMEA approved combination. The aim of this cohort is to evaluate clinical, biological and radiological parameters associated with pts outcome (CTC, CEC, VEGFA levels, ctDNA, pharmacogenomic polymorphisms, metabolomic parameters, visceral fat assessed by initial CTscan, serum estradiol level, and quality of life). We present here the first planned analysis on 206 patients evaluated for CTC and CEC using the FDA cleared CellSearch method. Results: inclusions started in 09/2012. At time of analysis, 219 patients were included, 211 were evaluable for CTC at baseline (failure rate 4%) and 207 for CEC at baseline (failure rate 5%). Due to short follow-up, 173 pts and 166 pts were evaluable for both CTC and CEC at baseline and first day of second cycle of CT (D1C2) respectively. At baseline, 100/211 (47%) pts had ≥ 5 CTC (median 4 (range 0-30,000) and 30% had no detectable CTC (0 CTC). After one cycle of chemotherapy (D28) 38 pts (22%) had still ≥ 5 CTC: 37 pts with initial high level and only one patient with low CTC at baseline had increased CTC above 5. Median number CEC was 21 (0)-2231) at baseline and 22 (1-881) at D1C2. CEC increased in 16% and decreased in 15% of the cases. CTC & CEC changes after one cycleCTC BaselineCTC at D1C2CEC BaselineCEC at D1C2≥ 5≥ 537 (21%)>20>2065 (39%)≥ 5<545 (26%)>20≤ 2025 (15%)<5≥ 51 (<1%)≤ 20>2027 (16%)<5<590 (52%)≤ 20≤ 2049 (30%)Total173166 CTC number at baseline line and CTC D1C2 were correlated (p<0.01) (Spearman test). There was no correlation between CEC at baseline or at D1C2 with CTC or CTC changes. Final analysis will be completed when 206 couples for both CTC and CEC at baseline and D1C2 will be available. Accrual is still ongoing. Conclusion: this 22% rate of failure to reduce CTC < 5 after one cycle of first line CT in a homogeneously bevacizumab-treated cohort of MBC patients did not differ from previous series. As second lines of chemotherapy do not improve the poor prognosis of this group of patients according to the SWOG 500 study results (Smerage et al, JCO 2014), trials of novel therapeutic agents should be considered at the time of progression. Citation Format: Jean-Yves Pierga, Isabelle Vaucher, Maya Gutierrez, Olivier Tredan, Séverine Guiu, Gilles Romieu, Anthony Goncalves, Marc Debled, Christelle Levy, Jean-Marc Ferrero, Christelle Jouannaud, Elisabeth Luporsi, Marie-Ange Mouret-Reynier, Florence Dalenc, Bernard Asselain, Jerome Lemonnier, Francois-Clement Bidard. Circulating tumor cells (CTC) and endothelial cells (CEC) changes in HER2 negative metastatic breast cancer (MBC) patients treated with first line weekly paclitaxel and bevacizumab: Preliminary results of a prospective cohort from the French Breast Cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-12.

Altered functional connectivity in the brain default-mode network of earthquake survivors persists after 2 years despite recovery from anxiety symptoms.

Although acute impact of traumatic experiences on brain function in disaster survivors is similar to that observed in post-traumatic stress disorders (PTSD), little is known about the long-term impact of this experience. We have used structural and functional magnetic resonance imaging to investigate resting-state functional connectivity and gray and white matter (WM) changes occurring in the brains of healthy Wenchuan earthquake survivors both 3 weeks and 2 years after the disaster. Results show that while functional connectivity changes 3 weeks after the disaster involved both frontal-limbic-striatal and default-mode networks (DMN), at the 2-year follow-up only changes in the latter persisted, despite complete recovery from high initial levels of anxiety. No gray or WM volume changes were found at either time point. Taken together, our findings provide important new evidence that while altered functional connectivity in the frontal-limbic-striatal network may underlie the post-trauma anxiety experienced by survivors, parallel changes in the DMN persist despite the apparent absence of anxiety symptoms. This suggests that long-term changes occur in neural networks involved in core aspects of self-processing, cognitive and emotional functioning in disaster survivors which are independent of anxiety symptoms and which may also confer increased risk of subsequent development of PTSD.

Shelf-life of n-3 PUFA enriched frankfurters formulated with a konjac-based oil bulking agent

Frankfurters with improved-fat content were manufactured following two strategies: a) reduction of fat content by replacing pork backfat with konjac gel (KG); and b) reduction of fat/improvement of fatty acid profiles through partial substitution of pork backfat by an oil combination (olive, linseed and fish oils) stabilized in a -konjac matrix (oil bulking agent) (KG), in an oil-in-water emulsion (OWE), or a combination of both of these (KG and OWE).Their shelf-life characteristics were studied on the basis of nitrite, microbiological, biogenic amine profile and lipid oxidation analyses during chilling storage. Nitrite levels decreased over storage in all samples and were highest (P < 0.05) in the sample with OWE. No clear relationship was observed between microbiota and reformulation. High initial histamine levels were observed in frankfurters containing OWE and/or KG. Over chilling storage, histamine and tyramine increased the most, with the highest levels occurring in the samples containing the oil combination. Initial levels of lipid oxidation were lower in the control sample. The samples containing the oil combination presented similar lipid oxidation patterns over storage, with higher levels in F/OWE. No reformulation-dependent factor that might limit shelf-life was detected during storage.

CLINICOPATHOLOGICAL STUDY OF PROSTATE BIOPSY IN PATIENTS RECEIVING DUTASTERIDE FOR BENIGN PROSTATIC HYPERPLASIA

Dutasteride is a 5-alpha reductase inhibitor used to treat benign prostatic hyperplasia. Dutasteride lowers prostate-specific antigen (PSA) levels, which may lead to delays in the diagnosis and treatment of prostate cancer (PCa). This study investigated patients who underwent prostate biopsy (PBx) while receiving dutasteride to investigate whether this agent affects the diagnosis and treatment of PCa. PBx was performed on six patients receiving dutasteride for > 3 months at our medical institutions between January 2010 and June 2013. No patients underwent PBx before dutasteride administration. We performed PBx both for patients with high initial PSA levels and for those with elevated PSA levels with or without initial PSA decline after dutasteride administration. We also investigated clinicopathological findings. Mean age at the start of administration was 69.5 ± 5.9 years (range, 59-77 years), mean duration of administration was 14.1 ± 7.4 months (range, 4.0-23.5 months), mean prostate volume at the start of administration was 70.4 ± 30.7 ml (range, 18.8-104.6 ml), and mean PSA level at the start of administration was 7.7 ± 3.3 ng/ml (range, 4.9-14.2 ng/ml). PSA density was 0.098 ± 0.045 ng/ml/cm3 (range, 0.042-0.181 ng/ml/cm3), and PSA level at PBx was 5.4 ± 2.7 ng/ml (range, 2.5-10.7 ng/ml). We detected three PCa patients, and clinical stage in each case was cT1cN0M0. Radical retropubic prostatectomy was performed in two cases, and androgen-deprivation therapy was performed in one case. All PCa were detected in the early clinical stage. No delays in detection or treatment of PCa were seen in any cases. Careful observation of PSA levels is simple and useful for detecting PCa in patients under dutasteride administration.

"Heating Up and Cooling Down: Relationship Conflict, Emotion Regulation, and Team Processes"

Conceptualizing relationship conflict as a threat to team members, we examined the relationship between relationship conflict and change in critical team processes in thirty-five project teams over a 4-month period. The purpose of our investigation was to test composite team emotion regulation (i.e. cognitive reappraisal vs. suppression) as a moderator of the change in these team processes over time. Using conditional linear growth modeling to test our hypotheses, we found that teams with high initial levels of relationship conflict experience worse interpersonal functioning and coordinate less initially, and continue to demonstrate low levels of these processes over their lifespan. However, the findings showed that this longitudinal pattern is disrupted where teams are higher on collective cognitive reappraisal. Indeed, over time the teams we surveyed that were more likely to reappraise negative events overcame negative process patterns caused by relationship conflict. Some implications of these findings, and directions for future research are discussed.

Are persistent early onset child conduct problems predicted by the trajectories and initial levels of discipline practices?

In the present investigation we focused on 2 broad sets of questions: Do parental overreactivity, laxness, and corporal punishment show evidence of normative change in early to middle childhood? Are persistently elevated child conduct problems (CPs) associated with deviations from normative changes in, as well as high initial levels of, discipline practices? Four hundred fifty-three couples with 3- to 7-year-old children were recruited via random digit dialing and studied at 3 annual assessments. Parents completed questionnaire measures of all study constructs. Normative declines were found in maternal corporal punishment and laxness. Maternal overreactivity showed a normative increase. For fathers, only corporal punishment showed evidence of a normative decline. The declines in mothers' corporal punishment and laxness, and in fathers' corporal punishment, exhibited little variability. In contrast, the trajectories of maternal overreactivity were significantly variable. High-increasing CPs were more common than low-stable CPs in families with greater increases in maternal overreactivity. High-increasing CPs were also more common in families with greater initial maternal overreactivity and corporal punishment. Yet in no case did discipline practices significantly distinguish children on high-increasing versus high-decreasing CPs trajectories. In tests of alternative models, child effects were found for all parenting variables, suggesting reciprocal causation. The findings are discussed relative to etiological models of CPs and implications for preventive intervention.

Hyperferritinemia is associated with short survival time in dogs with multicentric lymphoma.

In the present study, we examined the relationship between serum ferritin concentration before treatment and survival time in dogs with multicentric lymphoma. Eighteen dogs with multicentric lymphoma were enrolled in the study. When the dogs were classified into high and low ferritin groups on the basis of their serum ferritin concentration (3,000 ng/ml cut-off value), the median survival time of dogs with high concentrations (≥3,000 ng/ml, n=7) was 40 days, whereas it was 360 days among dogs with low concentrations (<3,000 ng/ml, n=11). This difference was statistically significant (P=0.001). This finding suggests that the initial high level of serum ferritin indicates short survival time in dogs with multicentric lymphoma. Large-scale research is necessary to confirm this finding.

Effects of Credit Supply on Unemployment and Inequality

The Great Recession, which was preceded by the financial crisis, resulted in higher unemployment and inequality. We propose a simple model where firms producing varieties face labor-market frictions and credit constraints. In the model, tighter credit leads to lower output, lower number of vacancies, and higher directed-search unemployment. Where workers are more productive at higher levels of firm output, lower credit supply increases firm capital intensity, raises inequality by increasing the rental of capital relative to the wage, and has an ambiguous effect on welfare. At initial high levels of labor share in total costs tighter credit lowers welfare. This pattern reverses during an expansionary phase caused by higher credit availability.

Pathological video-gaming among youth: A prospective study examining dynamic protective factors

The primary aim of the study was to understand the phenomenon of pathological video-gaming by identifying protective factors for its development, and examining the dynamic interplay between protective factors and pathological video-gaming within a framework of change. The study was a 2-year longitudinal study involving 3034 children and adolescents recruited from 6 elementary and 6 secondary schools. Controlling for initial levels of pathological video-gaming, personal strengths and familial factors such as parent–child connectedness, and warm family environment were found to be protective factors for later pathological gaming. Increases in levels of emotional regulation and family environment warmth were related to decreases in pathological video-gaming. Higher initial levels and increases in pathological video-gaming were related to higher levels of later depressive symptoms, controlling for earlier levels of depressive symptoms. The study adds to the growing evidence that pathological video-gaming has potentially serious mental health consequences, in particular, on depression. For health providers who work with pathological video-gamers, the findings suggest that developing self-regulatory skills such as emotional regulation, and improving the family environment are useful strategies.

IL-23 and TGF-β1 levels as potential predictive biomarkers in treatment of bipolar I disorder with acute manic episode

BackgroundGrowing evidence suggests that immune dysfunction may be involved in the physiopathology of bipolar disorders, with typical first-line treatment using lithium and quetiapine serving to restore pro-inflammation status. This study aimed to explore the relationship between inflammatory cytokines—especially regulatory factors and the effect of combination treatment—with quetiapine and lithium in manic patients. Methods41 patients of bipolar I disorder with manic episode were enrolled and received combination treatment with quetiapine and lithium. Blood sampling and assessments were performed at baseline and after 8-week treatment. YMRS was used to evaluate the severity of manic symptoms at the same time of detecting plasma levels. A control group comprised of 36 age and gender matched healthy volunteers were enrolled, and their blood samples were assessed at the time of enrollment. ResultsTGF-β1 and IL-23 plasma levels in patients were significantly higher than healthy controls at baseline (P<0.05). When comparing remitted patients with non-remitted patients, initial plasma level TGF-β1 was higher (P=0.029) while IL-23 was lower (P=0.035). The plasma levels of TNF-α, TGF-β1, IL-23 and IL-17 significantly decreased after treatment among the patients who achieved response (P<0.05). LimitationsThe relatively small sample size in patients and control groups should be considered as a limitation of the study. ConclusionsThe high initial plasma level of TGF-β1 and low initial plasma level of IL-23 indicated better prognosis during combination treatment with quetiapine and lithium in manic patients. The trend of decreasing plasma levels of TNF-α, TGF-β1, IL-23 and IL-17 indicated therapeutic effect.

Potential Involvement of Physiological TCR Gamma Delta Clones in Immune Surveillance of Preleukemic Cells

The mechanisms underlying the evolution and dynamics of preleukemic clone towards the overt disease are largely unknown. We examined this issue in slow onset leukemia (SOL) cases. SOLs represent a rare subgroup of acute lymphoblastic leukemias (ALLs) initially announced by clinical symptoms of fever, infections and anemia several weeks/months prior to ALL diagnosis. These cases can be indicated for bone marrow aspiration, thus providing us with a unique biological material to follow the disease before its own outbreak.We collected 8 B-lineage ALL cases of SOL (incl. 1 hyperdiploid and 2 ETV6/RUNX1+ patients) with 1-3 prediagnostic samples (taken 6 weeks to 15 months prior to diagnosis). Using qPCR, NGS and SNP array we followed the dynamics of the preleukemic clone from the first symptoms to an overt disease. Strikingly, as we have shown previously, instead of an expected slow progression of blast growth, the preleukemic clones appeared to follow a specific pattern in dynamics, with initial high blast levels followed by a steep decrease, only to rise again towards the diagnosis of ALL.Massive parallel sequencing of immunoglobulin/T-cell receptor repertoir provided deeper insight into the immune background of developing leukemias. We discovered significant proportion of several non-malignant T-cell clones bearing specific Vγ9Vδ2 rearrangements. The Vγ9Vδ2 cells showed opposite dynamics than the preleukemic blasts in the prediagnostic phase with initially low levels subsequently growing during the suppression of preleukemic clone followed by a final decrease before the ALL diagnosis. This finding raises a question whether the Vγ9Vδ2 cells can contribute to immune control of (pre-)ALL blasts.The Vγ9Vδ2 cells, a major subset of circulating TCRγδ T-cells, can respond to phosphoantigens such as isopentenyl pyrophosphate (IPP), an intermediate product of the mevalonate pathway, often dysregulated in cancer cells. Vγ9Vδ2 cells are mentioned to play a pivotal role in tumor immune surveillance, which is attributed to their specific ability to exert tumor specific lysis, notably against epithelial carcinomas or some hematopoietic malignancies. However, their involvement in controlling ALL has not been reported yet.To study its ability to kill the ALL blasts, we purified Vγ9Vδ2 cells and expanded them in the presence of IL2 (1000U/ml) or IL2 + IPP (15 μmol). After 10-14 days cultivation, the expression of intracellular granzyme B was measured within the Vγ9Vδ2 subset, reflecting its capacity to lyse the target tumor cells.In a set of independent experiments, expanded Vγ9Vδ2 T-cells were co-cultivated with human ALL cell lines REH (ETV6/RUNX1+) and RS4;11 (MLL/AF4+) in effector: target ratios 10:1 and 1:3. In the subsequent cytotoxic assay, the viability of leukemic cells and the CD107a (LAMP-1, a marker of T-cell degranulation) expression on Vγ9Vδ2 T-cells were assessed.We detected significantly higher levels of dying REH cells after the co-culture with the Vγ9Vδ2 lymphocytes which was more pronounced in IPP-expanded Vγ9Vδ2 (IL2+IPP: median increase 10.7x, range 5.5 to 29.4; IL-2 alone: 3.6x, range 2.2-5.0; both compared to control cells). Interestingly, the cytotoxicity was increased after IPP stimulation although the Vγ9Vδ2 cells displayed a seemingly lower potential to degranulate (median of granzyme B positivity: 23.6% and 30.6% in IL2+IPP and IL2 alone, respectively). The expression of CD107a was more pronounced in the Vγ9Vδ2 cells co-cultivated with REH. Importantly, no significant target lysis was achieved by co-cultivating of IPP-expanded Vg9Vd2 with RS4;11 cells (median increase 2.1x, range 0.9-4.0). This corresponds with our previous data showing that neither the increased level of Vγ9Vδ2 cells nor its divergent dynamics towards the leukemic clone have been observed in the preleukemic samples of patients with MLL+ secondary leukemia, suggesting a potential differential impact of various molecular aberrations on triggering anti-tumor immune response.In conclusion, by following the preleukemic clone during the prediagnostic phase of the disease, we revealed a specific pattern in its dynamics which might result from the activation of protective anti-tumor mechanisms by certain leukemia subtypes. We showed that physiological TCRγδ T-cells might play an active role in immune surveillance in the preleukemic phase of ALL.Support: IGA NT/12428-5, NT/14350-3, GAUK 618212 DisclosuresNo relevant conflicts of interest to declare.

Sex-related online behaviors and adolescents' body and sexual self-perceptions.

This study investigated: (1) the prevalence and development of 2 receptive (sexually explicit Internet material [SEIM] use and sexual information seeking) and 2 interactive (cybersex and general social networking site [SNS] use) online behaviors in adolescence; (2) whether development of these behaviors predict adolescents' body and sexual self-perceptions; and (3) whether parental strategies regarding adolescents' Internet use reduce engagement in sex-related online behaviors. Four-wave longitudinal data among 1132 seventh- to 10th-grade Dutch adolescents (mean age at wave 1: 13.95 years; 52.7% boys) were collected. Developmental trajectories of sex-related online behaviors were estimated by using latent growth curve modeling. Self-perception outcomes at wave 4 and parental strategies predicting online behaviors were investigated by adding regression paths to growth models. Boys occasionally and increasingly used SEIM. Patterns for girls' SEIM use and boys' and girls' sexual information seeking and cybersex were consistently low. SNS use, however, was a common, daily activity for both. Higher initial levels and/or faster increases in sex-related online behaviors generally predicted less physical self-esteem (girls' SNS use only), more body surveillance, and less satisfaction with sexual experience. Private Internet access and less parental rule setting regarding Internet use predicted greater engagement in sex-related online behaviors. Although most sex-related online behaviors are not widespread among youth, adolescents who engage in such behaviors are at increased risk for developing negative body and sexual self-perceptions. Particular attention should be paid to adolescents' SNS use because this behavior is most popular and may, through its interactive characteristics, elicit more critical self-evaluations. Prevention efforts should focus on parents' role in reducing risky sex-related online behaviors.