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Imaging madness: schizophrenia, brain images, and scientific communication in psychiatry’s biological revolution
No full textIn the late twentieth century, a period known as the biological revolution in psychiatry, scientific applications to the field expanded rapidly and mental illnesses were increasingly understood as biological entities rather than moral shortcomings or conflicts of the unconscious. Concurrently, both scientific communication and public opinion about mental illness were shifting. My thesis explores this shift with respect to schizophrenia, which has an especially harmful reputation in the media, and places emphasis on the role of neuroimaging figures in shaping both scientific communication and public perception. I examine what information about schizophrenia was being communicated both between scientists and to the general public before and throughout the biological revolution. I contextualize my analysis with a discussion of visual culture and scientific objectivism, and describe how neuroimaging technology fits into these paradigms. Next, I offer a history of visual representations in psychiatry, demonstrating that interest in capturing images of schizophrenia predates the advent of neuroimages. Finally, I evaluate media sources from throughout the biological revolution that reference schizophrenia and neuroimaging technology to show a transformation in what information was communicated to the public. By investigating the contributions of neuroimaging technology in maintaining a biologically-oriented public perspective of schizophrenia throughout the biological revolution, I intend to comment on the nature of scientific communication and its role in creating and upholding public perceptions and social stigma
Identification of novel genes involved in telomere maintenance
No full textMany proteins necessary for telomere maintenance and lengthening have been identified, but there are a host of proteins that have yet to be discovered in these processes. Identifying these telomere genes would be important in better understanding the telomere lengthening process and in understanding telomere mediated diseases such as pulmonary fibrosis. To do this, we created a forward genetic screen using CRISPR-Cas9 and a variant toxic TR sequence, AU5. Any cells with knockouts in genes important in telomere maintenance would be unable to add the AU5 sequence and therefore be able to tolerate the otherwise toxic sequence. We identified several genes that were able to survive the AU5 treatment, some of which were known telomere maintenance genes such as TERT and ACD. Further characterization and analysis of these genes could prove valuable in understanding telomere biology and potentially in understanding telomere mediated disease as well
Learned Intermediary Doctrine in the Time of Direct-to-Consumer Drug Advertising
No full textThe Learned Intermediary Doctrine (LID) is a common law doctrine that shifts a prescription drug manufacturer’s duty to warn from the end-consumer to a “learned intermediary,” such as a physician, physician assistant, or nurse practitioner. The LID was established long before prescription drug manufacturers began advertising directly to consumers. However, though direct-to-consumer advertising (DTCA) has exploded since in the late 1990’s, manufacturers have continued to benefit from the protection against liability that the LID offers. The rise of DTCA has led to shifts in the doctor-patient relationship where the patient plays a far more active role in her prescription drug decision making. This essay endorses the analyses in the West Virginia Supreme Court opinion, State ex. rel. Johnson & Johnson Corp. v. Karl (2007) that show the rationales that underlie the LID no longer ring true for heavily advertised drugs; however, because not all drugs are advertised to the public, it suggests that the Karl decision goes too far in fully rejecting the LID. Instead, it suggests a subjective test to determine case-by-case if an individual plaintiff-patient was harmed by a drug she was influenced to take through its DTCA efforts
Translational Insights into the Pharmacokinetics of Morphine and M3G in Traumatic Brain Injury: Understanding the Implications for Secondary Injury
No full textTraumatic Brain Injury (TBI) is the leading cause of death and disability in both children and adults aged 1 to 44. Despite promising preclinical indications, effective treatments often falter in clinical trials, highlighting the urgent need to understand how pharmacokinetics translate from preclinical models to clinical settings, along with their influence on pharmacodynamics. This translational gap hinders effective interventions in TBI research.
This dissertation aims to bridge this gap by developing methodologies to assess pharmacokinetic changes in TBI. This dissertation specifically focuses on morphine, a commonly administered sedative, and its major metabolite, morphine-3-glucuronide (M3G). Both these analytes, either directly or indirectly, have been linked to increased inflammation and neurotransmitter dysregulation in previous in vitro and rodent studies. By understanding how TBI alters morphine's pharmacokinetics and its impact on secondary injury pathways, this research seeks to enhance treatment outcomes for TBI patients.
Initially, an ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay was developed to measure sedatives in critical care populations. This method enables simultaneous quantification of nine analytes, including midazolam, dexmedetomidine, morphine, hydromorphone, fentanyl and their metabolites, requiring minimal sample preparation and only 10 minutes for analysis with 100μL of plasma.
Furthermore, the assay was utilized in a clinical study involving 71 pediatric critical care patients receiving mechanical ventilation. The assay successfully measured 91% of 364 samples within their quantifiable range. Population pharmacokinetic models for midazolam and morphine were created, with clearance estimates aligning closely with literature values. However, evaluating the effect of TBI alone was challenging due to recruiting patients and the variability from concurrent injuries.
Additionally, pharmacokinetics of morphine and M3G post-TBI were investigated using a rat controlled cortical impact (CCI) model to study the effect isolated from other concurrent injuries. The study revealed with morphine administration post injury, there was increased M3G exposure in plasma and brain tissue, and a potential trend with M3G formed from morphine AUC correlating with GFAP expression in the ipsilateral hippocampus.
Moreover, neurotransmitter dynamics during the subacute phase of severe TBI were explored using a rodent LFPI model. Microdialysis revealed elevated baseline glutamate levels and reduced changes during synaptic stimulation post-injury, while GABA levels remained unchanged between injured and sham animals. This characterization was essential to first understand before evaluating changes of neurotransmitters when morphine and M3G are present.
Ultimately, this research aims to elucidate pharmacokinetic changes induced by TBI, particularly with morphine administration, to advance towards more effective interventions for TBI patients. By bridging the translational gap between preclinical evidence and clinical application, this dissertation strives to offer hope for improved outcomes in managing this debilitating condition
Development and Test of PBSA Solvation Models for Drug Design
No full textThe Poisson-Boltzmann Surface Area (PBSA) model was extensively used to predict solvation free energy (SFE) and protein-ligand binding free energies, as well as to study protein folding. In addition, partition coefficient (logP), which is an important physicochemical property that determines the distribution of a drug in vivo, can be derived directly from transfer free energies. Within the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL) 9 challenge, we applied the Poisson-Boltzmann (PB) surface area (SA) approach to predict toluene/water transfer free energy and partition coefficient (logPtol/wat) from SFEs. PB calculation directly adopts our previously optimized boundary definition - a set of general AMBER force field 2 (GAFF2) atom-type based sphere radii for solute atoms. For the non-polar SA model, we newly developed the solvent-related molecular surface tension parameters \gamma and offset b for toluene and cyclohexane targeting experimental SFEs. This approach yielded the highest predictive accuracy in terms of root mean squared error (RMSE) of 1.52 kcal/mol in transfer free energy for 16 small drug molecules among all 18 submissions in SAMPL9 challenge. The re-evaluation of the challenge set using multi-conformation strategies based on molecular dynamic (MD) simulations further reduces the prediction RMSE to 1.33 kcal/mol. At the same time, an additional evaluation of our PBSA method on SAMPL5 cyclohexane/water distribution coefficient (logDcyc/wat) prediction revealed that our model outperformed COSMO-RS, the best submission model with RMSEPBSA = 1.88 versus RMSECOSMO-RS = 2.11 log units. Two external logPtol/wat and logPcyc/wat datasets that contain 110 and 87 data points, respectively, are collected for extra validation and provide in-depth insight of the error source of PBSA method. Finally, to identify the best set of radius parameters which define the solute-solvent boundary, we adopted the following strategies: (1) the nonpolar term is fixed; (2) a genetic algorithm is applied to conquer the couplings between the radius parameters; (3) the new nonpolar term is reoptimized. The above three steps will be repeated until there is no further improvement on the model performance. Encouragingly, the newly tuned radii parameters conjugated with the ABCG2 charge model outperformed many widely used models and our previous results
The Association Between Everyday Discrimination and Sense of Purpose in Life in Midlife Women
No full textMidlife is a transitionary period and presents a variety of challenges including changes in roles in life, increased risk of developing chronic illnesses, and increased anxieties about the future. Women are presented with the additional challenges of menopause and discrimination due to age, gender, and race/ethnicity. Everyday, interpersonal discrimination may impact their sense of purpose in life through internalization of the messages about their value. Having a sense of purpose in life has been associated with various positive health outcomes and behaviors so it is vital to understand factors, such as discrimination, that may have an impact on it. Data from the Study of Women’s Health Across the Nation (SWAN) was used in this analysis due to the study’s vast data on a multiracial/multiethnic cohort of midlife women. The goals of this analysis were to 1) determine the distribution of life engagement scores, which is a measure of purpose in life, for SWAN women, 2) examine the association between baseline everyday discrimination and life engagement at annual follow-up Visit 12, and 3) examine the generalizability of the findings to the entire baseline cohort. Descriptive statistics were computed to examine the distribution of life engagement scores. A cumulative everyday discrimination score was created to be a single measurement that accounts for the various experiences of everyday discrimination. Linear regression was utilized to examine the association between everyday discrimination and life engagement scores. Inverse probability weighting was used to examine the generalizability of the findings. SWAN women overall had a high sense of life engagement, with an average score of 26 out of 30. The linear regression analysis showed that higher baseline everyday discrimination scores were significantly associated with lower life engagement scores (β=-0.11, p <.001). After applying the weights to the descriptive statistics and the regressions, the results remained largely the same. These findings are significant to public health given that reducing discrimination and its effects could improve a person’s sense of purpose in life and in turn could provide positive health benefits for women in midlife
U.S.-Trained Genetic Counselors’ Perspectives on International Rotations: A Thematic Analysis
No full textA key element of genetic counseling training includes clinical practice through fieldwork placements. Within some training programs, students can pursue fieldwork placements internationally. Although these types of experiences have been shown to promote professional development in other fields, there is limited literature providing information on genetic counseling international rotations. As the genetic counseling field continues to grow and provide services to more diverse patient populations, there is an increasing need to evaluate the globalization of genetic services. Therefore, the purpose of this research study was to explore the impacts and perceived value of completing an international genetic counseling rotation. We conducted a total of nine semi-structured interviews via Zoom with U.S.-trained practicing genetic counselors who participated in an international fieldwork experience in the last ten years (2013-2023) during their training. Through semantic, inductive thematic analysis, five themes were developed: (1) navigating new environments facilitated learning, (2) students’ personal goals and motivations shaped their experiences, (3) feelings of isolation: protective and risk factors, (4) relationships with international site supervisors and providers, and (5) role of genetic counseling training programs in arranging and promoting international rotations. Overall, international rotations prove to be beneficial experiences for genetic counseling professionals. These experiences provide unique opportunities for professional and personal growth. However, genetic counseling international rotations vary in difficulty and impact based on a multitude of factors. Genetic counseling training programs and professional organizations should consider ways to promote and improve these experiences. This study benefits public health by exploring how international rotations contribute to building a skilled workforce that promotes genetic counseling services globally
Improving the Patient Experience Through Operations at UPMC Shadyside
No full textThis essay follows the progress of three completed projects at UPMC Shadyside by Natasha Shah as an Administrative Resident working in Hospital Operations, addressing issues of public health importance. Through streamlining Gastrointestinal (GI) advanced procedures, the GI lab was able to increase the number of patients they were able to see per week. Through opening an Ophthalmology/ General exam room, patients can receive care faster by providing world class treatment for inpatients coming from the Oncology and other inpatient floors. Finally, this report discusses the continuation of the lymphedema clinic and tracking patient satisfaction through their experience with the multi-disciplinary clinic
Periodontal Education Program in a Trauma Affected Community
No full textThe goal of this study was to evaluate an oral health education program that focused on periodontal health and disease in a Trauma Affected Community (TAC) in a Dental Health Professional Shortage Area (DHPSA). The research question was, “Is a periodontally focused oral health education program effective in increasing periodontal knowledge in individuals who are part of a TAC in a DHPSA?” The Neighborhood Resilience Project (NRP) in Pittsburgh, Pennsylvania is a non-profit organization that offers a volunteer-run Free Health Center in a DHPSA and primarily serves a TAC. We administered a pre-presentation assessment to assess baseline knowledge at weekly NRP community events. Then, we gave presentations about periodontal health, periodontal diseases, risk factors, and home care. Gained participant knowledge was evaluated via a post-presentation assessment. 30 paired pre- and post-surveys were used in the analyses. Improvements in knowledge were identified for plaque causing tooth loss, diabetes affecting gum health, and pregnancy affecting gum health. This research is of public health importance because it focuses on a disease that affects nearly half of the adult population and examines an at-risk population to provide a sustainable solution and reproducible model for other TAC organizations. Per our review there is no literature that documents oral health knowledge and status of individuals from trauma affected communities. These results aid in understanding a TAC’s baseline oral health knowledge and can be used to create programs that improve TACs oral health and consequently overall health
“Populist philanthropy”: corruption in social assistance and the Jóvenes Construyendo el Futuro program in Valladolid, Yucatán, Mexico
No full textMexico has a long history in innovating poverty alleviation techniques. However, this history is also mired with instances of corruption that have become in ingrained in the Mexican psyche. These perceptions of past corruption have resurfaced with the 2018 election of Andrés Manuel López Obrador (AMLO) and the creation of new programs such as the Jóvenes Construyendo el Futuro program aimed at combatting youth unemployment. This thesis seeks to add to existing research on perceptions of corruption in Mexico’s social assistance system by replicating a recent study as well as providing greater insight into how Mexicans view the JCF by utilizing the list experiment or item-count technique. I conclude that perceptions of political and organizational corruption are consistent with the original study replicated, and that the higher proportion found in this thesis can be attributed to the makeup on the sample studied. Additionally, I conclude that Mexicans view the issue of corruption as deeply ingrained within the system, and that the disorganization of the JCF program reinforce this perception