Trapped in the Bell Jar: Mental Illness in College Students

This is a magazine article that explores the rising problem of mental health in college students, focusing on Connecticut. It explores the experiences of three college students dealing with depression and bipolar disorder, a family who lost a child to suicide, and the measures taken by colleges in Connecticut to curb the problem.

The utility of N5 for gene therapy of human cancer

Cancer is a result of defects in the coordination of cell proliferation and programmed cell death. The extent of cell death is physiologically controlled by the activation of a programmed suicide pathway that results in a morphologically recognizable form of death termed apoptosis. Inducing apoptosis in tumor cells by gene therapy provides a potentially effective means to treat human cancers. The p84N5 is a novel nuclear death domain containing protein that has been shown to bind an amino terminal domain of retinoblastoma tumor suppressor gene product (pRb). Expression of N5 can induce apoptosis that is dependent upon its intact death domain and is inhibited by pRb. In many human cancer cells the functions of pRb are either lost through gene mutation or inactivated by different mechanisms. N5 based gene therapy may induce cell death preferentially in tumor cells relative to normal cells. We have demonstrated that N5 gene therapy is less toxic to normal cells than to tumor cells. To test the possibility that N5 could be used in gene therapy of cancer, we have generated a recombinant adenovirus engineered to express N5 and test the effects of viral infection on growth and tumorigenicity of human cancer cells. Adenovirus N5 infection significantly reduced the proliferation and tumorigenicity of breast, ovarian, and osteosarcoma tumor cell lines. Reduced proliferation and tumorigenicity were mediated by an induction of apoptosis as indicated by DNA fragmentation in infected cells. We also test the potential utility of N5 for gene therapy of pancreatic carcinoma that typically respond poorly to conventional treatment. Adenoviral mediated N5 gene transfer inhibits the growth of pancreatic cancer cell lines in vitro. N5 gene transfer also reduces the growth and metastasis of human pancreatic adenocarcinoma in subcutaneous and orthotopic mouse model. Interestingly, the pancreatic adenocarcinoma cells are more sensitive to N5 than they are to p53, suggesting that N5 gene therapy may be effective in tumors resistant to p53. We also test the possibilities of the use of N5 and p53 together on the inhibition of pancreatic cancer cell growth in vitro and vivo. Simultaneous use of N5 and RbΔCDK has been found to exert a greater extent on the inhibition of pancreatic cancer cell growth in vitro and in vivo. ^

Functional studies of insulin-like growth factor binding protein 2 pathway in glioma progression

Comparison of gene expressing profiles between gliomas with different grades revealed frequent overexpression of insulin-like growth factor binding protein 2 (IGFBP2) in glioblastomas (GBM), in which uncontrolled cell proliferation, angiogenesis, invasion and anti-apoptosis are hallmarks. Using the glia-specific gene transfer transgenic mouse and the stable LN229(BP2) GBM cell lines, we found that IGFBP2 by itself cannot transform cells in vitro and in vivo. IGFBP2 had growth inhibitory effects on mouse primary neural progenitors, but overexpression of IGFBP2 had no effect on GBM cells. ^ Although IGFBP2 does not initiate gliomagenesis, using tissue array technology, we observed strong correlation between IGFBP2 overexpression and VEGF up-regulation in human diffuse gliomas. Furthermore, overexpression of IGFBP2 in GBM cells not only enhanced VEGF expression but also increased the malignant potential of U87 MG cells in our angiogenesis xenograft animal model. ^ In parallel to these studies, using established stable SNB19 GBM cells that overexpress IGFBP2, we found that IGFBP2 significantly increased invasion by induction of matrix metalloproteinase-2 (MMP-2) as well as other invasion related genes, providing evidence that IGFBP2 contributes to glioma progression in part by enhancing MMP-2 gene transcription and in turn tumor cell invasion. ^ Finally, we found that primary filial cells infected with an anti-sense IGFBP2 construct have markedly increased sensitivity to γ irradiation and reduced Akt activation. On the other hand, SNB19(BP2) stable lines have consistently increased levels of Akt and NFkB activation, suggesting that one possible mechanism for anti-apoptosic function of IGFBP2 is through the activation of Akt and NFkB. Beside this, what is especially interesting is the finding that Akt protein was cleaved and inactivated during apoptosis by caspases, and IGFBP2 can prevent Akt cleavage, revealing another possible mechanism through it IGFBP2 exhibit strong antiapoptotic effects. Our data showed that IGFBP2 is a specific substrate for caspase-3, raising the possibility that IGFBP2 may inhibit apoptosis by a suicide mechanism. ^ In summary, using cellular, genomics, and molecular approaches, this thesis documented the potential roles of IGFBP2 in glioma progression. Our findings shed light on an important biological aspect of glioma progression and may provide new insights useful for the design of novel mechanism-based therapies for GBM. ^

The identification of child abuse in Harris County in 1998

Characteristics of child abuse cases are not well known. In this study I collected data on 70 child abuse cases that were reported to Children's Protective Services in Harris County in 1998. The purpose of this study was to determine the factors in Harris County that lead to the identification of physical and sexual abuse. In order to answer the questions of who, what, where and when relative to the discovery of abuse I applied the same questionnaire (see Appendix) to each of 35 Sexual Abuse case reports and to each of 35 Physical Abuse/Neglect case reports. Answers to the first four questions were arranged by frequency distribution to show the predominant reporter, the 10 most common indicators, the most common locale, and the most frequent timing. Tables of the age, sex, and ethnicity of the children indicate the identity of those whose victimization was most reported. In addition the relationship between the form questions and the characteristics of the children was explored. A comparison of Sexual Abuse cases with Physical Abuse/Neglect cases was conducted and the results were analyzed and recorded in the Tables. ^ Child maltreatment often has negative short and long term effects on children's mental health and development. Suicide, violence, delinquency, drug and alcohol abuse and other forms of criminality are frequently child abuse related. Early detection and treatment helps to alleviate the myriad mental and physical ailments that untreated victims present as adults. This translates into medical dollar savings. ^ The long term objectives of my research were to reduce the number of undetected and unreported child abuse cases in Harris County by formulating better educational programs and literature for medical professionals and other personnel who are in contact with children. ^

Coping with advanced cancer: Caregivers and their patients

Background. Being diagnosed with advanced cancer may be one of the most difficult challenges a person faces. To help deal with advanced cancer, patients and caregivers lean towards the coping skills most familiar to them. Depending on the person, one’s coping may either help or perpetuate the problem. ^ Purpose. To identify predictors of negative coping skills among a group patients and caregivers, and to identify the predictors of prolonged grief among a group of providers, 6-months post loss. ^ Methods. Advanced cancer patients and caregivers were interviewed at the time of their enrollment (baseline) and caregivers were interviewed 6 months after the patient’s death (post-loss). Each participant was administered questionnaires regarding demographics, mental health disorders, mental health service use, coping methods, quality of life, and suicide attempts. Patients were asked about their treatment and diagnosis. Other patient-related information was obtained from medical charts. Moreover, caregivers were given an assessment regarding their alcohol and smoking history. ^ Results. Among White patients, positive coping skills were positively correlated with quality of life and negative coping skills were negatively correlated with quality of life. Gender, psychiatric disorders, suicidality, alcohol and smoking history, and treatment and diagnosis, were significantly related to negative coping skills; however this relationship only held for Hispanic patients. Gender and psychiatric disorders demonstrated predictive value for negative coping skills among all patients. On the other hand, psychiatric disorders, major depression, anxiety disorder, suicidality, and alcohol and smoking history, were not significant predictors of which caregivers experienced prolonged grief. ^ Conclusion. There was a significant relationship between quality of life and positive and negative coping skills of patients and negative coping skills for caregivers. Factors such as gender, psychiatric disorders, suicidality, alcohol and smoking history, and treatment and diagnosis demonstrated predictive value for negative coping skills in patients. ^

Identification of essential apoptotic genes in Drosophila

Apoptosis is a normal physiological cell suicide process which is essential for tissue homeostasis and normal development of metazoans. Misregulation of apoptosis is associated with many developmental defects and human diseases. The genes involved in the regulation and execution of apoptosis are highly conserved in humans and flies. Caspases are the executioners of cell suicide. Because of the unavailability of specific fly mutants, the developmental function of many caspase genes and genetic relationship between caspases and apoptotic components were undefined in Drosophila. We isolated several mutant alleles of the initiator caspase gene dronc, the effector casase drICE, and the Mediator component Cyclin C from the GMR-hid eyFLP/FRT screens which is designed to isolate mutants of recessive cell death genes in Drosophila melanogaster. Characterization of these mutants defined that they are essential for developmental cell death in Drosophila. dronc is required for most, but not all, cell death in Drosophila. drICE is required for apoptosis in many cells and it shares redundancy with another effector caspase gene, dcp-1, in a subset of cells in Drosophila. The genetic relationship between caspases and other apoptotic components was established through mutant analysis. We found that the pro-apoptotic protein Hid induces transcription of the initiator caspase gene dronc and the GMR-induced dronc transcripts are dependent on activated effector casapses, revealing a novel regulatory mechanism to promote caspase activity in Drosophila. Cyclin C and its kinase partner Cdk8 are required for prompt transcriptional induction of dronc in cell killing contexts. In short, we define the essential pro-apoptoic function of dronc, drICE, and Cyclin C in Drosophila and reveal a novel mechanism for regulation of dronc transcription. In the long run, these studies will help us decipher the complicated regulatory mechanism of cell death in humans. ^

Incidence of fatal gunshot injuries occurring to Galveston County residents between 1979--1981

Fatal gunshot injury deaths and their characteristics were ascertained for the population of Galveston County, Texas, for 1979-81. A total of 147 gunshot deaths occurring to residents of Galveston County were enumerated from death certificates, police and hospital records. Residents accounted for 96.1% of all gunshot deaths occurring in the county. The overall firearms death rate was 25 per 100,000 population. This ranked gunshot mortality as the third leading cause of injury death and the sixth leading cause of death from all causes. Gunshot deaths accounted for 10% of all years of life lost due to premature mortality.^ Firearms accounted for 73% of all homicide deaths. The median age of gunshot homicide victims was 27 years. Gunshot homicide mortality was highest among black males with a rate of 61 per 100,000. Rates of 23 per 100,000 and 12 per 100,000 were observed for Hispanic males and black females respectively. Gunshot homicide cases were characterized by use of "low quality" handguns (76.1%), circumstances involving a "relationship breakup" (38.1%), and alcohol consumption (79.6%). The place of occurrence of gunshot homicide was a residence in over half of all cases. The occupation most frequently associated was fishing and farming. Homicide was the primary motivation for 84% of the cases.^ The descriptive epidemiology of gunshot suicide differed from that of gunshot homicide. Firearms accounted for 64% of all suicide deaths. The median age of gunshot suicide victims was 41 years. Gunshot suicide mortality was highest among white males with a rate of 24 per 100,000. Rates of 14 per 100,000 and 9 per 100,000 were observed for black males and Hispanic females respectively. Gunshot suicide cases were characterized by use of "low quality" handguns (69.4%), circumstances involving a "relationship breakup" (39.1%) and alcohol consumption (63%). The place of occurrence was a residence in 80% of the cases. The occupation most frequently associated was police or security guard.^ Strategies for primary prevention are recommended. The research strategy, based on Haddon's model, is suggested for further investigations. ^

Editorial: Take Me Home, Down Country Roads

Those of us committed to the tenets of Family Preservation must advocate for increased awareness and attention to the needs of children and their families in rural America. "Country roads" and the rural spaces they traverse have been eulogized by many poets and song writers as ideal places to live. But they may not be ideal for everyone. The past few months, it has become all too evident that rural America is not immune to acts of extreme violence by troubled children. Even though almost 1/3 of American youth live in rural areas, they have been "virtually ignored by mental health service planners and providers"(Cutrona, Halvorson, & Russell, 1996, p. 217). Mental health risk factors such as poverty, parental alcohol abuse, and family instability are on the rise in rural areas, and there has been an increase in suicide attempts, family violence, depression, and alcohol abuse (Cutrona, Halvorson, & Russell, 1996; Petti & Leviton, 1986; National Mental Health Association, 1988). Native Americans are especially concerned about the increases in child abuse and neglect, depression, substance abuse, and suicide in their communities.

Beyond Bullying: Transforming the Culture of Peer Abuse

Bullying needs to be understood and positioned as a form of child abuse – peer abuse. For too many people, bullying is a benign term. This article will include information collected from a wide-range of researchers and discussions with over 50,000 students that I have facilitated during the past twenty years. The content will focus on new morbidities related to bullying such as depression and suicide, obesity, eating disorders, food allergies, juvenile diabetes, truancy, and substance and alcohol abuse. Making a cultural change in our society will require identified Change Agents, along with recommendations for collaboration, policies, projects and legislation.

The association between academic achievement and health status among eighth -grade Hispanic students in Houston

This cross-sectional study examines the association between health and academic achievement among Hispanic eighth-grade students in the Houston Independent School District. As part of the district's 3 year Safe Schools/Healthy Students Initiative to enhance comprehensive educational programs, a brief anonymous questionnaire was administered in the classroom to 359 students in two schools during a one-month period in the early part of the 2001 school year. ^ The primary study questions are: Among this sample of Hispanic adolescents, is there a significant association between academic achievement and health status? and in this same population, is there a significant association between health risk behavior and health status? The specific aims of this research are: (1) to describe the association between academic achievement and health status; (2) to describe the association between health risk behaviors and health status; and (3) to describe the relative contribution of health risk behaviors and academic achievement to adolescent health status among this sample of Hispanic adolescents. ^ The survey instrument was a 32-item questionnaire that incorporated: several academic achievement questions measuring usual grades, school-related performance, attendance, student and perceived parental satisfaction with academic achievement, and educational aspirations; two health and quality of life scales measuring adolescent self-reported health; and specific measures of health risk behavior, e.g., frequency of tobacco cigarette smoking, alcohol and other drug use, aggression, and suicidal ideation and behavior that were incorporated from the national Youth Risk Behavior Survey. Questions pertaining to sexual behavior and pregnancy were omitted to comply with school district guidelines. ^ Analysis revealed that strong associations between academic achievement and health status and between health risk behaviors and health status were observed after controlling for the covariates. Eight factors were found to be significantly associated with poor health status: usual grades (low), academic performance (low), academic achievement beliefs (low), classroom and homework performance satisfaction (low), ever drinking alcohol (6 or more times), suicidality (ever thought about, planned for, or sought medical help after attempting suicide), gender (female), and age (15 years and older). (Abstract shortened by UMI.) ^

Structural and functional analysis of p84N5

Normal development and tissue homeostasis requires the carefully orchestrated balance between cell proliferation and cell death. Cell cycle checkpoints control the extent of cell proliferation. Cell death is coordinated through the activation of a cell suicide pathway that results in the morphologically recognizable form of death, apoptosis. Tumorigenesis requires that the balance between these two pathways be disrupted. The tumor suppressor protein Rb has not only been shown to be involved in the enforcement of cell cycle checkpoints, but has also been implicated in playing a role in the regulation of apoptosis. The manner in which Rb enforces cell cycle checkpoints has been well studied; however, its involvement in the regulation of apoptosis is still very unclear. p84N5 is a novel nuclear death domain containing protein that has been shown to interact with the N-terminus of Rb. The fact that it contains a death domain and the fact that it is nuclear localized possibly provides the first known mechanism for apoptotic signaling from the nucleus. The following study tested the hypothesis that the novel exclusively nuclear death domain containing protein p84N5 is an important mediator of programmed cell death and that its apoptotic function is reliant upon its nuclear localization and is regulated by unique functional domains within the p84N5 protein. We identified the p84N5 nuclear localization signal (NLS), eliminated it, and tested the functional significance of nuclear localization by using wild type and mutant sequences fused to EGFP-C1 (Clontech) to create wild type GFPN5 and subsequent mutants. The results of these assays demonstrated exclusive nuclear localization of GFPN5 is required for normal p84N5 induced apoptosis. We further conducted large-scale mutagenesis of the GFPN5 construct to identify a minimal region within p84N5 capable of interacting with Rb. We were able to identify a minimal sequence containing p84N5 amino acids 318 to 464 that was capable of interacting with Rb in co-immunoprecipitation assays. We continued by conducting a structural and functional analysis to identify the region or regions within p84N5 responsible for inducing apoptosis. Point mutations and small-scale deletions within the death domain of p84N5 lessened the effect but did not eliminate p84N5-induced cytotoxicity. Further analysis revealed that the minimal sequence of 318 to 464 of p84N5 was capable of inducing apoptosis to a similar degree as wild-type GFPN5 protein. Since amino acids 318 to 464 of p84N5 are capable of inducing apoptosis and interacting with Rb, we propose possible mechanisms whereby p84N5 may function in a Rb regulated manner. These results demonstrate that p84N5 induced apoptosis is reliant upon its nuclear localization and is regulated by unique functional domains within the p84N5 protein. ^

Subjective well -being as predictor of mortality, heart disease, and obesity: Prospective evidence from the Alameda County Study

Based on the World Health Organization's (1965) definition of health, understanding of health requires understanding of positive psychological states. Subjective Well-being (SWB) is a major indicator of positive psychological states. Up to date, most studies of SWB have been focused on its distributions and determinants. However, study of its consequences, especially health consequences, is lacking. This dissertation research examined Subjective Well-being, as operationally defined by constructs drawn from the framework of Positive Psychology, and its sub-scores (Positive Feelings and Negative Feelings) as predictors of three major health outcomes—mortality, heart disease, and obesity. The research used prospective data from the Alameda County Study over 29 years (1965–1994), based on a stratified, randomized, representative sample of the general public in Alameda County, California (Baseline N = 6928). ^ Multivariate analyses (Survival analyses using sequential Cox Proportional Hazard models in the cases of mortality and heart disease, and sequential Logistic Regression analyses in the case of obesity) were performed as the main methods to evaluate the associations of the predictors and the health outcomes. The results revealed that SWB reduced risks of all-cause mortality, natural-cause mortality, and cardiovascular mortality. Positive feelings not only had an even stronger protective effect against all-cause, natural-cause and cardiovascular mortality, but also predicted decreased unnatural-cause mortality which includes deaths from suicide, homicide, accidents, mental disorders, drug dependency, as well as alcohol-related liver diseases. These effects were significant even after adjusted for age, gender, education, and various physical health measures, and, in the case of cardiovascular mortality, obesity and health practices (alcohol consumption, smoking, and physical activities). However, these two positive psychological indicators, SWB and positive feelings, did not predict obesity. And negative feelings had no significant effect on any of the health outcomes evaluated, i.e., all-cause mortality, natural- and unnatural-cause mortality, cardiovascular mortality, or obesity, after covariates were controlled. These findings were discussed (1) in comparison with relevant existing studies, (2) in terms of their implications in health research and promotion, (3) in terms of the independence of positive and negative feelings, and (4) from a Positive Psychology perspective and its significance in Public Health research and practice. ^

Situación límite y suicidio en Jaspers

Este ensayo versa sobre las situaciones límites y su relación con el suicidio. Jaspers aborda en su obra principal Filosofía el suicidio dentro del capítulo “Las acciones incondicionadas que rebasan la existencia empírica (Dasein)". Nuestro intento se abocará en cambio en asociar las situaciones límites con aquella resolución de suicidio que rebase ante todo la existencia (Existenz). Este hecho no significa de ningún modo que todo suicidio sea consecución de una resolución originaria o de un despertar existencial. Únicamente nos centraremos en el pensamiento existencial de quienes lo hayan concretado estando en dicha situación.

Antígona y la muerte

La ponencia analiza la muerte de Antígona en la obra de Sófocles. Se propone que su suicidio es un acto consciente de voluntad preanunciado a lo largo de toda la obra y no una medida desesperada. Con ese fin se exploran las posibles motivaciones de Antígona para poner fin a su vida. En el análisis se proponen tres respuestas (no necesariamente excluyentes): -Antígona responde a la ética homérica. Está en lucha con Creón, y su suicidio es su golpe de gracia al poder del rey. -Antígona se siente impulsada hacia la muerte por amor a la muerte misma. -Antígona concibe la muerte como una reunión con Polinices

De Horacio a Lucano : Operatividad poética de la figura del Expiator en la configuración de Catón de Utica

En este trabajo analizamos cómo los Epodos VII y XVI y las Odas III, 3 y IV, 15 de la obra de Horacio, pasando por la descripción del suicidio de Catón que Séneca hace en su tratado De providentia, son utilizados y reformulados por Lucano en Pharsalia para configurar su particular versión de Cato Uticiencis. Lucano subvierte las imágenes e invierte el trayecto poético de la figura del expiator que Horacio desarrolla a lo largo de su obra para logar perturbadora Weltanschauung que permea su poema