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Gnetin C for chemoprevention and therapy of prostate cancer
Get PDFProstate cancer is common among aging men. Despite current management, it continues to be associated with a high mortality rate. A need, therefore, exists for improved treatment approaches that target every stage of the disease. In this study, we investigated the efficacy of Gnetin C, a resveratrol dimer found abundantly in melinjo (Gnetum gnemon) seeds, across three different treatment modalities. The first involved a Gnetin C-supplemented diet as a chemopreventive strategy in a high-risk transgenic mouse model which overexpresses MTA1 on a background of Pten heterozygosity (R26MTA1; Pten+/f). The second involved the administration of Gnetin C by intraperitoneal (i.p.) injection as a therapeutic strategy in a more aggressive transgenic mouse model which overexpresses MTA1 on a background of Pten loss (R26MTA1; Ptenf/f). The third involved i.p. Gnetin C administered as monotherapy and combination therapy (with enzalutamide) in a xenograft-generated model for highly aggressive castrate-resistant prostate cancer. Our chemopreventive studies demonstrated that mice fed Gnetin C diets exhibited significantly less PIN foci, cellular proliferation, angiogenesis, and systemic inflammation. Gnetin C-fed mice also exhibited reduced expression of MTA1 with an upregulation of PTEN. We found that mice injected with Gnetin C as a therapeutic strategy exhibited favorable histopathology with fewer PIN foci, reduced proliferation and angiogenesis, and an increase in apoptosis. Serum from these mice showed a reduction in pro-inflammatory cytokines, and prostate tissue expressed less MTA1 . The CRPC xenograft study demonstrated that Gnetin C treatment was associated with favorable histopathology, reduced expression of MTA1, full-length AR, and truncated AR-V7. Results also showed that combination with enzalutamide could offer benefits over monotherapy. Finally, from our pharmacokinetic studies of Gnetin C, we were able to estimate parameters, such as systemic exposure or AUC (809 mcg.h/L), half-life (1.7 h), and clearance (30.9 L/h/kg). Altogether, this data provides evidence for the use of Gnetin C as a novel anticancer agent that can target different stages of prostate cancer in different modes of administration
A Nonconcurrent Multiple Baseline Evaluation of an Independence Intervention to Treat Child Anxiety
Get PDFRates of child and adolescent anxiety have increased markedly over the past decade (Haidt & Twenge 2021; Parodi et al., 2021). Exposure-based cognitive-behavioral therapy is considered the gold standard in the treatment of anxious children (Hofmann et al., 2012). However, many clinicians refrain from using exposure due to concerns about its safety, effectiveness, and ethics (Deacon et al., 2013; Whiteside et al., 2016). We propose a novel treatment approach for child and adolescent anxiety that draws on research in child development (e.g. Daddis, 2011) and is considerably simpler to administer than traditional exposure-based approaches. This new approach is composed of independence activities (IAs), which are defined as child-directed, fun, unstructured, developmentally challenging tasks that are performed without any help from parents. These tasks are purposely topographically unrelated to the stimuli that cause anxiety, in direct contrast to exposure therapy, which is topographically similar to anxiety-causing stimuli. Despite this dissimilarity, IAs target the hypothesized mechanisms involved in the development and maintenance of child anxiety (e.g. parental accommodation and overinvolvement, child avoidance, and unhelpful thinking styles). IAs also target decreasing rates of child independence from parents, which may in and of itself be an important mechanism in the development of child anxiety (Skenazy, 2021). It was hypothesized that treating child anxiety in this way, without requiring exposure exercises, would result in high treatment acceptability from children and parents. This study employed a nonconcurrent multiple baseline design to examine independence activities as an intervention for child anxiety and independence as a mechanism of child anxiety. Small to large improvements in child (behavioral and cognitive) mechanisms involved in the maintenance of child anxiety, measures of child anxiety and avoidance, parent (behavioral and cognitive) mechanisms involved in the maintenance of child anxiety, and untargeted secondary outcomes such as child happiness were observed. Results have valuable theoretical implications for our understanding of the role that parental overinvolvement plays in child anxiety
UNCOVERING THE MENTAL WORLD OF CHILDREN: ATTACHMENT QUALITY, MENTALIZATION, AND CHILDREN’S DRAWINGS
Get PDFAlthough we have long been aware of the widespread benefits of drawing for children (Goodenough, 1926), there is much to learn from a clinical perspective about children’s attachment patterns and mentalization capacities in analyzing their drawings. The present study utilized archival data to uncover trends associated with children’s drawing characteristics, attachment qualities, and mentalization capacities. This study further explored the extent to which mentalization mediates the relationship between attachment quality and Formal Elements (FE) scores as well as the relationship between attachment quality and Content scores of children’s drawings. Two samples of 5–12-year-old children and their caregivers were recruited: one child sample from a public elementary school in White Plains, NY (n = 54), and the other child sample recruited consecutively following admission to a child psychiatric inpatient unit in White Plains, NY (n = 45). Each of the 99 children, including both the inpatient and nonpatient samples, completed three drawings: a drawing of family, primary caregiver, and self, totaling 297 drawings. These drawings were coded using the Formal Elements and Content rating scales (Tuman, 1998, 1999a). Attachment quality and mentalization data for these samples were obtained from previous studies, using the Attachment Story-Completion Task (ASCT) and Children’s Apperception Test (CAT). Attachment quality was found to have a significant positive relationship with the Content scores of family drawings within the inpatient sample. Attachment quality was also found to have a significant positive relationship with mentalization in both the nonpatient and inpatient samples. Mentalization was found to have a significant positive relationship with the Content and FE scores of children’s drawings. This relationship held true for Content scores of caregiver drawings and FE scores of family drawings within the nonpatient sample, and for both the Content and FE scores of family drawings within the inpatient sample. In general, drawings appear to hold promise as tools to access both psychiatrically compromised and nonpatient children’s internal working models and mental states. Gender differences and clinical implications are discussed
Is the Relationship Between Adverse Childhood Experiences and Adult Belief in Paranormality Moderated By Locus of Control?
Get PDFResearch has established a relationship between adverse childhood experiences (ACEs) and belief in paranormal phenomena (Lawrence et al., 1994). In the present study, I sought to replicate this finding in more detail by examining seven dimensions of paranormality. Further, the current study investigated whether locus of control moderated the relationship between ACEs and paranormal belief. I hypothesized that ACEs positively correlated with paranormal belief. Further, I hypothesized that the relationship between ACEs and paranormal belief would be moderated by locus of control, such that, the stronger the internal locus of control, the weaker the relationship between ACEs and paranormal belief. Data in this cross-sectional, correlational study was collected using Cloud Research Connect. Participants (N = 101) completed the Adverse Childhood Experiences Survey (ACES), the Rotter’s Locus of Control Scale (LCS), and the Revised Paranormal Belief Scale (RPBS). The data supported the hypothesis that ACEs positively correlated with adult belief in the paranormal. The relationship between ACEs and adult belief in the paranormal was not moderated by locus of control as hypothesized. However, ACEs were positively correlated with external locus of control, supporting findings from other studies, such as Irwin (1993), that individuals with a history of adverse childhood experiences are less likely to believe they hold control over their lives. The current study provided insight into the development of paranormal belief, as well as how ACEs can impact an individual’s view of themselves and the world – each of which is important to understand when providing psychological treatment. Key words: Trauma, Paranormal Beliefs, Supernatural, Adverse Childhood Experiences, Religion, Locus of Control, Cognitions, Cognitive Behavioral Therap
DOES PERCEIVED EMOTIONAL INVALIDATION MODERATE THE RELATION BETWEEN OCCUPATIONAL STRESS AND MENTAL HEALTH OUTCOMES IN LAW ENFORCEMENT OFFICERS?
Get PDFPolice officers are exposed to operational stressors while on duty, including child abuse, domestic violence, car crashes, and homicides (Jetelina et al., 2020). Repeated exposure to these stressors is associated with the development of mental illness (Jetelina et al., 2020). Organizational stressors, including lack of support/validation, demand, job pressure, administrative/organizational pressure, and long working hours, may be an even greater source of stress for police officers (Purba & Demou, 2019). Exposure to such organizational stressors can result in psychological distress, burnout, and suicidal ideation (Purba & Demou, 2019). However, there is a dearth of research on invalidation and the role it plays in the development and maintenance of mental health outcomes among law enforcement officers. It is unclear how invalidation from supervisors, colleagues, and the general public, moderates the relation between occupational stressors and the development of mental health outcomes. The current study is the first attempt to evaluate whether perceived emotional invalidation moderates the relationship between mental health outcomes and occupational stress. Results could inform our understanding of the role emotional invalidation from supervisors, colleagues, and the general public has on the mental health outcomes of law enforcement officers after experiencing occupational stress
Reasoning about religion and the effects of belief bias
Get PDFThe present study compares religious skeptics to believers, assessing both performance and response times on logical reasoning problems (syllogisms). Skepticism make fewer reasoning errors than did believers, while controlling for general cognitive ability, time spent on the problems, and various demographic variables. Comparison of response times indicated that skeptics also spent more time reasoning than did believers. This suggests that slower processing is an important component of analytic problem solving. Implications for using additional processing measures, such as response time, to investigate individual differences in cognitive style are discussed
Characterization of the mycobiome of Rafflesia seeds: Their potential ecological roles and applications in Rafflesia propagation and conservation
Get PDFThe plant microbiome exerts a profound influence on plant health, growth, and life cycle. This ecosystem comprises diverse microbial communities, such as symbiotic endophytes, mycorrhizal fungi, epiphytes, saprophytes, rhizobia, and pathogens, which inhabit parasitic and non-parasitic plants. Rafflesia speciosa, a holoparasitic plant, is a unique and endangered species that depends on its host Tetrastigma spp. for survival. In this study, fungal metagenomics was conducted to characterize the fungal community—the mycobiome within Rafflesia seeds, and a phylogeny was reconstructed. The ecophysiological characteristics of these fungal genera were also researched in the literature, and their primary ecological trait, whether plant mutualist, saprotroph, phytopathogen, mycoparasite, or entomopathogen, was mapped on the phylogeny to explore phylogenetic patterns. The majority of the identified fungal genera were Ascomycete fungi. There was no phylogenetic pattern detected in the ecophysiological traits of Rafflesia seed fungi, suggesting that these traits have evolved repeatedly throughout the fungal phylogeny as ecological adaptations. Characterization of Rafflesia’s seed mycobiome allowed us to gain insights on the potential ecology of these fungi and possible roles and applications in the ex situ propagation and conservation of Rafflesia species
Finding Hope
No full textClimate change, habitat and biodiversity loss, and increasing social inequality have caused many of us, myself included, to feel a deepened sense of anxiety and despair. When our ecosystems are degraded and compromised, so are the health and livelihoods of our communities. By examining our individual actions on a daily basis, we can reduce our carbon footprint and make a positive impact on our city and planet. From the transportation choices we make, the food we eat, the goods we buy, the trash we create, the energy sources we utilize, to how we dispose of our unwanted goods — all of these decisions are in our power. Our choices matter.
In my quilt block, I embroidered questions that focus on ongoing choices I make in my everyday life. I’ve found that making consistent small choices lead to bigger, more impactful choices. Speaking up and getting our families, our neighbors, and our communities to join in taking action is one of the quickest and most effective ways to make a difference. Through these efforts over the past couple of years, I have expanded my community, and found hope.
Once we ourselves begin to make these choices, we can go on to urge our families, communities, political leaders, employers, and the businesses we all patronize to make green, sustainable choices wherever we can.https://digitalcommons.liu.edu/community_usquilt_2023/1005/thumbnail.jp
A Role of Glutathione-Encoding Gene (gshA) in Oxidative Stress and Antibiotic Susceptibility in Multidrug Resistant Pseudomonas aeruginosa: A Possible Drug Target
Get PDFBackground: Pseudomonas aeruginosa is a major causative agent of hospital- and community-acquired infections. Antibacterial treatment of the infections is often difficult due to presence of antibiotic resistant P. aeruginosa. A number of intrinsic and acquired antibiotic resistance mechanisms reported in P. aeruginosa. Recently, scavenging intracellular reactive oxygen species (ROS) has suggested as an intrinsic antibiotic resistance mechanism to all bacterial species since antibiotics induce oxidative stress in the bacterial species. However, this intrinsic resistance mechanism is currently controversial and further clarification requires. Glutathione is a sulfuhydryl (-SH)-containing tri-peptide intracellular antioxidant and serves as a scavenger of the intracellular ROS. Aim: In this study, a mutant P. aeruginosa knocked-out a gene (gshA) encoding glutathione synthetase, a gshA-complemented mutant P. aeruginosa, and their parental wild type (MPAO1) used to understand the role of glutathione in the neutralization of oxidative stress (H2O2) and antibiotic susceptibility. Approaches and Results: Bacterial killing assays showed that the mutant strain (gshA::Tn-Tc) was completely killed at 0.005% of H2O2 while the gshA-complemented and their parental strains were both completely killed at 0.01% of H2O2. Antibiotic susceptibility testing showed that the mutant strain was at least 2-fold more susceptible to all tested antibiotics than that of its parental strain. The gshA-complemented strain fully restored the susceptibility to the same antibiotics as the same levels of the parental strain. Conclusions and Discussion: The results indicate that i) glutathione is associated with neutralization of oxidative stress, ii) antibiotics induce the oxidative stress, and iii) the antibiotic-induced oxidative stress in the mutant strain may have more ROS than its parental strain which results in the increased-susceptibility to antibiotics. Overall, the results suggest that glutathione is one of the intrinsic antibiotic resistance mechanisms and may be a possible drug target to treat the untreatable multidrug resistant P. aeruginosa
Stardust: Toward a Revolutionary Urban Ecology
No full textI wanted my square for the quilt to express what a sustainable urban ecology would look like with human beings and plants and animals coexisting in harmony in a city. Given the role that population density, public transportation, and greater access to education, jobs, and cultural engagement—museums, theater, galleries, and so on—can play in combating climate change, cities are crucial sites for mitigating the worst ecological crisis in human history. I considered various slogans: “Toward a Revolutionary Urban Ecology,” “The Right to the City,” and “Another World Is Possible.” But the actual design of the square dictated something less explicit, more metaphorical.
In designing the square, I placed blocks of fabric that drew my eye in a quilt-like pattern with two of the same pieces catacorner—blue fish in a sea and flowers on a turquoise background; in between are four wavy red rectangles, perhaps rays of light, in vertical and horizontal lines; and a yellow sun in the center. In the lower left hand corner, a woman is leaping, holding a flag; to her right is a blossoming tree; above the tree is a bird, wings spread; and in the center, enveloped by the sun, is the trace of a cityscape.
Instead of the slogans I had initially considered putting on the flag, I embroidered (a bit crudely) the word “stardust,” signifying the origins of life. The word started to mean more to me after reading the Marxist sociologist Erik Olin Wright’s public diary as he was dying from leukemia. He wrote about his time left “in this marvelous form of stardust,” observing that “Atoms don’t have experiences. They’re just stuff. That’s all I really am is stuff. But stuff so complexly organized across several thresholds of stuff-complexity, that it’s able to reflect upon its stuff-ness and what an extraordinary thing it has been to be alive and aware that it’s alive and aware that it’s aware that it’s alive. And from that complexity comes the love and beauty and meaning that constitutes the life I’ve lived.”
This deep knowledge of the stardust from which we came and to which we return in nonhuman form connects us to everything around us on earth and across the universe. But to realize that harmony between nature and humans will mean enacting a revolutionary urban ecology; demanding the right to the city; sustaining the natural world of which we are part and which global capitalism, run amok, is destroying; and making our own history to prove that another world is possible.https://digitalcommons.liu.edu/community_usquilt_2023/1002/thumbnail.jp