Non-destructive Identification of Individual Leukemia Cells by Optical Trapping Raman Spectroscopy

Currently, a combination of technologies is typically required to assess the malignancy of cancer cells. These methods often lack the specificity and sensitivity necessary for early, accurate diagnosis. Here we demonstrate using clinical samples the application of laser trapping Raman spectroscopy as a novel approach that provides intrinsic biochemical markers for the noninvasive detection of individual cancer cells. The Raman spectra of live, hematopoietic cells provide reliable molecular fingerprints that reflect their biochemical composition and biology. Populations of normal T and B lymphocytes from four healthy individuals, and cells from three leukemia patients were analyzed, and multiple intrinsic Raman markers associated with DNA and protein vibrational modes have been identified that exhibit excellent discriminating power for cancer cell identification. A combination of two multivariate statistical methods, principal component analysis (PCA) and linear discriminant analysis (LDA), was used to confirm the significance of these markers for identifying cancer cells and classifying the data. The results indicate that, on average, 95% of the normal cells and 90% of the patient cells were accurately classified into their respective cell types. We also provide evidence that these markers are unique to cancer cells and not purely a function of differences in their cellular activation

Genetic imaging of the association of oxytocin receptor gene (OXTR) polymorphisms with positive maternal parenting

Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation. Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4-6 years old. Results: In response to child stimuli during functional magnetic resonance imaging (fMRI), hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (SNPs) (rs53576 and rs1042778) in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus. Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods. © 2014 Michalska, Decety, Liu, Chen, Martz, Jacob, Hipwell, Lee, Chronis-Tuscano, Waldman and Lahey

The Grizzly, September 29, 1998

Construction Begins for New Bookstore • Ursinus Students Named Smith Scholars • Econ. Students Apply Classroom Knowledge • Opinion: Terrorist Debate Continues; Ursinus Keeps up With the Times; Students Vote Two Thumbs up for Co-ed Living • Is Home the way you Left it? • Students Spending Weekends Differently • Hugs Help Pottstown Hospital • Family Day \u2798 = Success • Kelley on Photography • Berman Exhibits Not Well Attended • Volleyball Hit With Key Injury • UC Football Gets Terrorized • Men\u27s Soccer Drops Two • Women\u27s Soccer Shuts-Out Dickinson • Who\u27s in Charge Here? • Women\u27s Rugby Overpowered by Lock Haven University • Centennial Conference Newshttps://digitalcommons.ursinus.edu/grizzlynews/1425/thumbnail.jp

CD40L induces multidrug resistance to apoptosis in breast carcinoma and lymphoma cells through caspase independent and dependent pathways

BACKGROUND: CD40L was found to reduce doxorubicin-induced apoptosis in non Hodgkin's lymphoma cell lines through caspase-3 dependent mechanism. Whether this represents a general mechanism for other tumor types is unknown. METHODS: The resistance induced by CD40L against apoptosis induced by a panel of cytotoxic chemotherapeutic drugs in non Hodgkin's lymphoma and breast carcinoma cell lines was investigated. RESULTS: Doxorubicin, cisplatyl, etoposide, vinblastin and paclitaxel increased apoptosis in a dose-dependent manner in breast carcinoma as well as in non Hodgkin's lymphoma cell lines. Co-culture with irradiated L cells expressing CD40L significantly reduced the percentage of apoptotic cells in breast carcinoma and non Hodgkin's lymphoma cell lines treated with these drugs. In breast carcinoma cell lines, these 5 drugs induced an inconsistent increase of caspase-3/7 activity, while in non Hodgkin's lymphoma cell lines all 5 drugs increased caspase-3/7 activity up to 28-fold above baseline. Co-culture with CD40L L cells reduced (-39% to -89%) the activation of caspase-3/7 induced by these agents in all 5 non Hodgkin's lymphoma cell lines, but in none of the 2 breast carcinoma cell lines. Co culture with CD40L L cells also blocked the apoptosis induced by exogenous ceramides in breast carcinoma and non Hodgkin's lymphoma cell lines through a caspase-3-like, 8-like and 9-like dependent pathways. CONCLUSION: These results indicate that CD40L expressed on adjacent non tumoral cells induces multidrug resistance to cytotoxic agents and ceramides in both breast carcinoma and non Hodgkin's lymphoma cell lines, albeit through a caspase independent and dependent pathway respectively

The intergenerational association between parents' problem gambling and impulsivity-hyperactivity/inattention behaviors in children

Despite the well-established association between problem gambling and ADHD core categories of impulsivity-hyperactivity and inattention, the link between parents’ problem gambling and impulsivity-hyperactivity/inattention (IH/I) behaviors in children has not been investigated. This study investigated the association between parents’ problem gambling and children’s IH/I behaviors while controlling for potential confounding variables. A population-based prospective cohort followed-up from kindergarten to age 30, the Quebec Longitudinal Study of Kindergarten Children (QLSKC), provided data over three generations. Among 1358 participants at age 30, parents with a child aged 1 year or older (N=468; Mean age=4.65 years; SD=2.70) were selected. Generalized Linear Models included measures of grandparents’ and parents’ problem gambling, parents’ IH/I behaviors in childhood, and a host of risk factors and comorbidities to predict IH/I in children. Intergenerational bivariate associations were observed between grandparents’ problem gambling, parents’ IH/I in childhood and problem gambling at age 30, and between parents’ IH/I, problem gambling, and children’s IH/I behaviors. Parents’ problem gambling predicted children’s IH/I behaviors above and beyond the effects of covariates such as family and socioeconomic characteristics, alcohol and drug use, depression symptoms and parents’ gambling involvement. Parents’ IH/I behaviors in childhood also predicted children’s IH/I and had a moderating, enhancing effect on parents’ problem gambling association with their offspring’s IH/I behaviors. Problem gambling is a characteristic of parents’ mental health that is distinctively associated with children’s IH/I behaviors, above and beyond parents’ own history of IH/I and of typically related addictive, psychopathological or socioeconomic risk factors and comorbidities

Preschool hyperactivity specifically elevates long-term mental health risks more strongly in males than females: a prospective longitudinal study through to young adulthood

Evidence of continuities between preschool hyperactivity and adult mental health problems highlight the potential value of targeting early identification and intervention strategies. However, specific risk factors are currently unclear. This large-scale prospective longitudinal study aimed to identify which hyperactive preschoolers are at greatest long-term risk of poor mental health. One hundred and seventy children (89 females) rated as hyperactive by their parents and 88 non-hyperactive controls (48 females) were identified from a community sample of 4,215 3 year-olds. Baseline data relating to behavioral/emotional problems and background characteristics were collected. Follow-up mental health and functional impairment outcomes were collected between 14 and 25 years of age. At age 3 years, males and females in the hyperactive group had similarly raised levels of hyperactivity and other behavior problems. In adolescence/young adulthood, these individuals showed elevated symptoms of ADHD, conduct disorder, mood disorder, anxiety and autism, as well as functional impairment. Preschool hyperactivity was strongly predictive of poor adolescent/adult outcomes for males across domains with effects being specifically driven by hyperactivity. For females, the effects of preschool hyperactivity were smaller and dropped to non-significant levels when other preschool problems were taken into account. Environmental risk factors also differed between the sexes, although these may also have been mediated by genetic risk. In conclusion, these results demonstrate marked sex differences in preschool predictors of later adolescent/adult mental health problems. Future research should include a measure of preschool inattention as well hyperactivity. The findings highlight the potential value of tailored approaches to early identification strategies

Bright light therapy versus physical exercise to prevent co-morbid depression and obesity in adolescents and young adults with attention-deficit/hyperactivity disorder: study protocol for a randomized controlled trial

Background: The risk for major depression and obesity is increased in adolescents and adults with attention-deficit / hyperactivity disorder (ADHD) and adolescent ADHD predicts adult depression and obesity. Non-pharmacological interventions to treat and prevent these co-morbidities are urgently needed. Bright light therapy (BLT) improves day– night rhythm and is an emerging therapy for major depression. Exercise intervention (EI) reduces obesity and improves depressive symptoms. To date, no randomized controlled trial (RCT) has been performed to establish feasibility and efficacy of these interventions targeting the prevention of co-morbid depression and obesity in ADHD. We hypothesize that the two manualized interventions in combination with mobile health-based monitoring and reinforcement will result in less depressive symptoms and obesity compared to treatment as usual in adolescents and young adults with ADHD. Methods: This trial is a prospective, pilot phase-IIa, parallel-group RCT with three arms (two add-on treatment groups [BLT, EI] and one treatment as usual [TAU] control group). The primary outcome variable is change in the Inventory of Depressive Symptomatology total score (observer-blinded assessment) between baseline and ten weeks of intervention. This variable is analyzed with a mixed model for repeated measures approach investigating the treatment effect with respect to all three groups. A total of 330 participants with ADHD, aged 14 – < 30 years, will be screened at the four study centers. To establish effect sizes, the sample size was planned at the liberal significance level of α = 0.10 (two-sided) and the power of 1-β = 80% in order to find medium effects. Secondary outcomes measures including change in obesity, ADHD symptoms, general psychopathology, health-related quality of life, neurocognitive function, chronotype, and physical fitness are explored after the end of the intervention and at the 12-week follow-up. This is the first pilot RCT on the use of BLT and EI in combination with mobile health-based monitoring and reinforcement targeting the prevention of co-morbid depression and obesity in adolescents and young adults with ADHD. If at least medium effects can be established with regard to the prevention of depressive symptoms and obesity, a larger scale confirmatory phase-III trial may be warranted.The trial is funded by the EU Framework Programme for Research and Innovation, Horizon 2020 (Project no. 667302). Funding period: January 2016–December 2020. This funding source had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Some local funds additionally contributed to carry out this study, especially for the preparation of the interventions: FBO research activity is by the Spanish Ministry of Economy and Competitiveness – MINECO (RYC-2011-09011) and by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Unit of Excellence on Exercise and Health (UCEES)

Attention-deficit hyperactivity disorder and nonsuicidal self-injury in a clinical sample of adolescents: the role of comorbidities and gender.

BACKGROUND: The aim of the present study was to investigate the possible association between attention-deficit hyperactivity disorder (ADHD) and non-suicidal self-injury (NSSI) with special focus on the role of comorbidities and gender in a clinical sample of adolescents with both a dimensional and a categorical approach to psychopathology. METHODS: Using a structured interview, the Mini International Neuropsychiatric Interview Kid and a self-rated questionnaire, the Deliberate Self-Harm Inventory, the authors examined 202 inpatient adolescents (aged: 13-18 years) in the Vadaskert Child and Adolescent Psychiatric Hospital and Outpatient Clinic, Budapest, Hungary. Descriptive statistics, Mann-Whitney U test, chi-square test and mediator model were used. RESULTS: Fifty-two adolescents met full criteria for ADHD and a further 77 showed symptoms of ADHD at the subthreshold level. From the 52 adolescents diagnosed with ADHD, 35 (67.30%) had NSSI, of whom there were significantly more girls than boys, boys: n = 10 (28.60%), girls: n = 25 (71.40%) ((chi(2)(1) = 10.643 p < .001 varphi = .452). Multiple mediation analyses resulted in a moderated mediation model in which the relationship between symptoms of ADHD and the prevalence of current NSSI was fully mediated by the symptoms of comorbid conditions in both sex. Significant mediators were the symptoms of affective and psychotic disorders and suicidality in both sexes and the symptoms of alcohol abuse/dependence disorders in girls. CONCLUSIONS: ADHD symptoms are associated with an increased risk of NSSI in adolescents, especially in the case of girls. Our findings suggest that clinicians should routinely screen for the symptoms of ADHD and comorbidity, with a special focus on the symptoms of affective disorders and alcohol abuse/dependence psychotic symptoms to prevent NSSI