Now showing items 21-40 of 7505

    • Immigrants Pharmacy Scoping Review Search Strategy

      Hellerslia, Van; Roth, Stephanie (2022-09)
      To identify studies to include or consider for this scoping review, the review team worked with a medical librarian (SR) to develop detailed search strategies for each database. The PRISMA-S extension was followed for search reporting. The medical librarian (SR) developed the search for PubMed (NLM) and translated the search for every database searched. The PubMed (NLM) search strategy was reviewed by the research team to check for accuracy and term relevancy, and all final searches were peer-reviewed by another medical librarian (TN) following the PRESS checklist. The databases included in this search are PubMed (NLM), Embase (Elsevier), Web of Science (Clarivate Analytics), Cochrane Central (Wiley) and CINAHL (EbscoHost) using a combination of keywords and subject headings. A grey literature search included a clinical trials registry (clinicaltrials.gov), the TRIP Pro medical database (tripdatabase.com) and the OAIster websites (https://oaister.on.worldcat.org/discovery). The search was limited from the year 2000 to present. All final searches were performed on June 14, 2022 by the librarian and were fully reported (SR). The full search strategies as reported by the librarian are provided in Appendix(___). A summary of the search results from databases: PubMed (NLM) from inception to 6/14/2022 (483 Results) Embase (Elsevier) from inception to 6/14/2022 (902 Results) Web of Science (Clarivate Analytics) from inception to 6/14/2022 (572 Results) Cochrane Central (Wiley) from inception to 6/14/2022 (81 Results) CINAHL (EbscoHost) from inception to 6/14/2022 (255 Results) The search resulted in 2,360 studies and 749 duplicate studies were found and omitted by the librarian (SR) using the EndNote 20 duplicate identification strategy. This resulted in 1,545 records to screen from databases or registers and 66 records to screen from other methods, resulting in a total of 1,611 records. Studies were screened by title and abstract by two blinded and independent reviewers. If a tiebreaker was needed, a third reviewer was called in. This process was repeated for full text article screening and article selection.
    • Respiratory Properties of Rat Liver Mitochondria Immobilized on an Alkylsilylated Glass Surface

      Arkles, Barry; Brinigar, William S.; Arkles|0000-0003-4580-2579 (1975-11-25)
      Rat liver mitochondria are shown to adhere to the alkylsilylated glass beads in essentially a monolayer. The amount of mitochondria bound to the beads reaches a maximum where the length of the alkyl groups covalently linked to the beads exceeds eight carbons. Mitochondria immobilized on the beads and placed in a flow system exhibit normal: (a) respiratory control, (b) phosphate to oxygen ratio, (c) uncoupling by 2,4-dinitrophenol and carbonylcyanide p-trifluoromethoxyphenylhydrazone, and (d) inhibition by cyanide, azide, rotenone, oligomycin, and antimycin. Reversibility of the effects of 2,4-dinitrophenol, cyanide, and azide was rapid and complete. Inhibition by rotenone, oligomycin was essentially irreversible. Mitochondria have been maintained in a viable state on the beads at 27 degrees for periods up to 4 hours. The use of immobilized organelles appears to offer a new technique for the study of membrane-bound particles whereby substances can be rapidly added and removed while monitoring the composition of solution flowing over the particles.
    • Real-Time Detection of Flu Season Onset: A Novel Approach to Flu Surveillance

      Liu, Jialiang; Suzuki, Sumihiro (2022-03-19)
      The current gold standard for detection of flu season onset in the USA is done retrospectively, where flu season is detected after it has already started. We aimed to create a new surveillance strategy capable of detecting flu season onset prior to its starting. We used an established data generation method that combines Google search volume and historical flu activity data to simulate real-time estimates of flu activity. We then applied a method known as change-point detection to the generated data to determine the point in time that identifies the initial uptick in flu activity which indicates the imminent onset of flu season. Our strategy exhibits a high level of accuracy in predicting the onset of flu season at 86%. Additionally, on average, we detected the onset three weeks prior to the official start of flu season. The results provide evidence to support both the feasibility and efficacy of our strategy to improve the current standard of flu surveillance. The improvement may provide valuable support and lead time for public health officials to take appropriate actions to prevent and control the spread of the flu.
    • Nasopharyngolaryngoscopy as a Triage Tool for Airway Compromise in Angioedema: A Retrospective Cohort Study

      Center for Biostatistics and Epidemiology (2022-04-02)
      Background: Airway compromise and respiratory failure are feared complications of angioedema leading to intensive care unit (ICU) admission. However, few of these patients decompensate. There is a paucity of tools that predict airway compromise in patients with angioedema, and it is unclear if automatic triage to the ICU is warranted. We analyzed patients admitted to our tertiary center ICU with angioedema for “airway watch” to find a way to triage those at greatest risk of respiratory decompensation. Methods: We performed a retrospective review of patients with angioedema admitted to our ICU between 2017 and 2020. Data collected included demographics, comorbidities, nasopharyngolaryngoscopy (NPL) findings, need for intubation, and length of stay. Descriptive analysis and subsequent ANOVA or T-test statistical analysis was performed to determine the relationships between individual variables and outcomes. Categorical variables were compared using Pearson's Chi-squared test or Fisher's exact test where applicable. Continuous variables were compared using a Mann-Whitney U test. Results: Of 134 patients admitted to our ICU, 63 (47%) required intubation, primarily in the emergency department (92.1%). Of those who required intubation, 61.9% had abnormal NPL findings in contrast to 25.35% of patients who did not require intubation (p<0.0001). Normal NPL findings had a negative predictive value for requiring intubation of 86.5%. Abnormal NPL findings had a positive predictive value for requiring intubation of 68.4%. Conclusion: While airway compromise is a serious complication of angioedema, there is scant evidence to support triage to the ICU for those not intubated immediately. The majority of patients with angioedema who required intubation had abnormal NPL findings, and the majority of those with normal NPL findings did not require intubation. This suggests that NPL findings in patients with angioedema can help with triage to the ICU.
    • Metabolic Reprogramming in HIV-Associated Neurocognitive Disorders

      Molecular Studies of Neurodegenerative Diseases Lab (Temple University); Fels Cancer Institute for Personalized Medicine (Temple University) (2022-03-28)
      A significant number of patients infected with HIV-1 suffer from HIV-associated neurocognitive disorders (HAND) such as spatial memory impairments and learning disabilities (SMI-LD). SMI-LD is also observed in patients using combination antiretroviral therapy (cART). Our lab has demonstrated that the HIV-1 protein, gp120, promotes SMI-LD by altering mitochondrial functions and energy production. We have investigated cellular processes upstream of the mitochondrial functions and discovered that gp120 causes metabolic reprogramming. Effectively, the addition of gp120 protein to neuronal cells disrupted the glycolysis pathway at the pyruvate level. Looking for the players involved, we found that gp120 promotes increased expression of polypyrimidine tract binding protein 1 (PTBP1), causing the splicing of pyruvate kinase M (PKM) into PKM1 and PKM2. We have also shown that these events lead to the accumulation of advanced glycation end products (AGEs) and prevent the cleavage of pro-brain-derived neurotrophic factor (pro-BDNF) protein into mature brain-derived neurotrophic factor (BDNF). The accumulation of proBDNF results in signaling that increases the expression of the inducible cAMP early repressor (ICER) protein which then occupies the cAMP response element (CRE)-binding sites within the BDNF promoters II and IV, thus altering normal synaptic plasticity. We reversed these events by adding Tepp-46, which stabilizes the tetrameric form of PKM2. Therefore, we concluded that gp120 reprograms cellular metabolism, causing changes linked to disrupted memory in HIV-infected patients and that preventing the disruption of the metabolism presents a potential cure against HAND progression.
    • Omics of endothelial cell dysfunction in sepsis

      Center for Inflammation and Lung Research (Temple University) (2022-05-03)
      During sepsis, defined as life-threatening organ dysfunction due to dysregulated host response to infection, systemic inflammation activates endothelial cells and initiates a multifaceted cascade of pro-inflammatory signaling events, resulting in increased permeability and excessive recruitment of leukocytes. Vascular endothelial cells share many common properties but have organ-specific phenotypes with unique structure and function. Thus, therapies directed against endothelial cell phenotypes are needed to address organ-specific endothelial cell dysfunction. Omics allow for the study of expressed genes, proteins and/or metabolites in biological systems and provide insight on temporal and spatial evolution of signals during normal and diseased conditions. Proteomics quantifies protein expression, identifies protein–protein interactions and can reveal mechanistic changes in endothelial cells that would not be possible to study via reductionist methods alone. In this review, we provide an overview of how sepsis pathophysiology impacts omics with a focus on proteomic analysis of mouse endothelial cells during sepsis/inflammation and its relationship with the more clinically relevant omics of human endothelial cells. We discuss how omics has been used to define septic endotype signatures in different populations with a focus on proteomic analysis in organ-specific microvascular endothelial cells during sepsis or septic-like inflammation. We believe that studies defining septic endotypes based on proteomic expression in endothelial cell phenotypes are urgently needed to complement omic profiling of whole blood and better define sepsis subphenotypes. Lastly, we provide a discussion of how in silico modeling can be used to leverage the large volume of omics data to map response pathways in sepsis.
    • Chronic Exposure to the Combination of Cigarette Smoke and Morphine Decreases CD4+ Regulatory T Cell Numbers by Reprogramming the Treg Cell Transcriptome

      Cardiovascular Research Center (Temple University); Center for Inflammation and Lung Research (Temple University); Center for Metabolic Disease Research (Temple University) (2022-04-20)
      There is a high incidence of tobacco use among intravenous opioid drug users. It is well established that opioids and tobacco smoke induce a degree of immune activation, and recent work suggests that the combination of these drugs promotes further activation of the immune system. Our approach involved the treatment of wild-type mice with cigarette smoke (SM) for a period of eight weeks, and the chronic continuous administration of morphine (M) via mini-pumps for the final four weeks. In an effort to examine the responses of CD4+CD25highCD127low regulatory T (Treg) cells, the major immune suppressive cell type, to the combined chronic administration of SM and M, we determined the frequency of these cells in the spleen, lymph nodes and lungs. Flow cytometric analyses showed that SM and M individually, and the combination (SM + M) have differential effects on the numbers of Treg in the spleen, lymph node, and lung. Either SM or M alone increased Treg cell numbers in the spleen, but SM+M did not. Furthermore, SM + M decreased Treg cell numbers in the lymph node and lung. We then performed RNA-Seq on Treg cells from mice treated with SM, M, or SM + M, and we found that the S + M induced a number of significant changes in the transcriptome, that were not as apparent following treatment with either SM or M alone. This included an activation of TWEAK, PI3K/AKT and OXPHOS pathways and a shift to Th17 immunity. Our results have provided novel insights on tissue Treg cell changes, which we suggest are the result of transcriptomic reprogramming induced by SM, M, and SM + M, respectively. We believe these results may lead to the identification of novel therapeutic targets for suppressing smoke and opioid induced Treg cell impairment.
    • The Effects of Visual Context on Visual-Vestibular Mismatch Revealed by Electrodermal and Postural Response Measures

      Al Sharif, Doaa S.; Tucker, Carole A.; Coffman, Donna L.; Keshner, Emily A. (2022-04-18)
      BACKGROUND: No objective criteria exist for diagnosis and treatment of visual-vestibular mismatch (VVM). OBJECTIVE: To determine whether measures of electrodermal activity (EDA) and trunk acceleration will identify VVM when exposed to visual-vestibular conflict. METHODS: A modified VVM questionnaire identified the presence of VVM (+ VVM) in 13 of 23 young adults (34 ± 8 years old) diagnosed with vestibular migraine. Rod and frame tests and outcome measures for dizziness and mobility were administered. Participants stood on foam while viewing two immersive virtual environments. Trunk acceleration in three planes and electrodermal activity (EDA) were assessed with wearable sensors. Linear mixed effect (LME) models were used to examine magnitude and smoothness of trunk acceleration and tonic and phasic EDA. Welch’s t-test and associations between measures were assessed with a Pearson Correlation Coefficient. Effect sizes of group mean differences were calculated using Cohen’s d test. RESULTS: Greater than 80% of all participants were visually dependent. Outcome measures were significantly poorer in the + VVM group: tonic EDA was lower (t(417)=-4.31,p < 0.001) and phasic EDA higher (t(417) = 4.35, p < 0.001). Postural accelerations varied across groups; LME models indicated a relationship between visual context, postural, and ANS responses in the + VVM group. CONCLUSIONS: Lower tonic EDA with + VVM suggests canal-otolith dysfunction. The positive association between vertical acceleration, tonic EDA, and visual dependence suggests that increased vertical segmental adjustments are used to compensate. Visual context of the spatial environment emerged as an important variable to control when testing or treating VVM.
    • Examining the Influencing Factors of Chronic Hepatitis B Monitoring Behaviors among Asian Americans: Application of the Information-Motivation-Behavioral Model

      Center for Asian Health (Temple University) (2022-04-12)
      Background: Compared to non-Hispanic whites, Asian Americans are 60% more likely to die from the disease. Doctor visitation for chronic hepatitis B (CHB) infection every six months is an effective approach to preventing liver cancer. Methods: This study utilized baseline data from an ongoing randomized controlled clinical trial aimed at improving long-term adherence to CHB monitoring/treatment. Guided by the information-motivation-behavioral skills (IMB) model, we examined factors associated with CHB monitoring adherence among Asian Americans with CHB. Multivariable logistic regression was conducted to test the associations. Results: The analysis sample consisted of 382 participants. Multivariable logistic regression showed that HBV knowledge (OR = 1.24, p < 0.01) and CHB-management motivation (OR = 1.06, p < 0.05) are significant predictors of having a doctor’s visit in the past six months. Both factors were positively associated with the likelihood of having had blood tests for HBV in the past six months. Conclusion: We found that greater HBV-related knowledge and CHB-management motivation are significantly associated with performing CHB-monitoring behaviors in the past six months. The findings have critical implications for the development and implementation of evidence-based interventions for CHB monitoring and liver cancer prevention in the Asian American community.
    • Selective Inhibition of Plasmodium falciparum ATPase 6 by Artemisinins and Identification of New Classes of Inhibitors after Expression in Yeast

      Institute for Computational Molecular Science (Temple University) (2022-04-25)
      Treatment failures with artemisinin combination therapies (ACTs) threaten global efforts to eradicate malaria. They highlight the importance of identifying drug targets and new inhibitors and of studying how existing antimalarial classes work. Here, we report the successful development of a heterologous expression-based compound-screening tool. The validated drug target Plasmodium falciparum ATPase 6 (PfATP6) and a mammalian orthologue (sarco/endoplasmic reticulum calcium ATPase 1a [SERCA1a]) were functionally expressed in Saccharomyces cerevisiae, providing a robust, sensitive, and specific screening tool. Whole-cell and in vitro assays consistently demonstrated inhibition and labeling of PfATP6 by artemisinins. Mutations in PfATP6 resulted in fitness costs that were ameliorated in the presence of artemisinin derivatives when studied in the yeast model. As previously hypothesized, PfATP6 is a target of artemisinins. Mammalian SERCA1a can be mutated to become more susceptible to artemisinins. The inexpensive, low-technology yeast screening platform has identified unrelated classes of druggable PfATP6 inhibitors. Resistance to artemisinins may depend on mechanisms that can concomitantly address multitargeting by artemisinins and fitness costs of mutations that reduce artemisinin susceptibility.
    • Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium

      Fels Cancer Institute for Personalized Medicine (Temple University) (2022-04-20)
      Although morphologic progression coupled with expression of specific molecular markers has been characterized along the esophageal squamous differentiation gradient, the molecular heterogeneity within cell types along this trajectory has yet to be classified at the single cell level. To address this knowledge gap, we perform single cell RNA-sequencing of 44,679 murine esophageal epithelial, to identify 11 distinct cell populations as well as pathways alterations along the basal-superficial axis and in each individual population. We evaluate the impact of aging upon esophageal epithelial cell populations and demonstrate age-associated mitochondrial dysfunction. We compare single cell transcriptomic profiles in 3D murine organoids and human esophageal biopsies with that of murine esophageal epithelium. Finally, we employ pseudotemporal trajectory analysis to develop a working model of cell fate determination in murine esophageal epithelium. These studies provide comprehensive molecular perspective on the cellular heterogeneity of murine esophageal epithelium in the context of homeostasis and aging.
    • Systematic Review of Supervised Machine Learning Models in Prediction of Medical Conditions

      Center for Data Analytics and Biomedical Informatics (Temple University) (2022-04-27)
      Machine learning (ML) models for analyzing medical data are critical for both accelerating development of novel diagnostic and treatment strategies and improving the accuracy of medical care delivery. Our objective was to comprehensively review supervised ML models for diagnosis or treatment prediction. Publications indexed in PubMed were reviewed to identify articles utilizing supervised predictive ML models in medicine. Articles published between 01/01/2020–01/01/2022 were included in this review. Initially, PubMed was searched using MeSH major terms, and if more extensive search results were needed, a broader search was applied (titles/abstracts). PubMed indexed 21,268 published articles (MeSH Major topic) describing ML methods implemented in medicine. Of those, 11,726 articles were published within the last 2 years. Most of the published ML models in medicine in the last two years were different types of deep learning models (about 75%). Fifty articles were included in this review. Almost all categories of disease were subjects of ML predictions. Positive and negative factors in each of the scenarios need to be evaluated before the most optimal ML model is selected. Domain knowledge and collaborations between physicians and ML experts can improve the selection and prediction performance of ML models in medicine and facilitate implementation in clinical practice. Predictive ML models could provide recommendations to recruit suitable patients for clinical trials. Prediction ML models may contribute to development of more effective diagnostic and therapeutic choices, founded on evidence-based medicine. A broad range of methodological approaches have been taken toward this goal, and those approaches are presented here with their various advantages and disadvantages. AUTHOR SUMMARY: Over the last decade, there has been rapid development of Machine learning (ML) methods to analyze Big Data in medicine. ML is aimed to make the computer learn from past experiences and make predictions by recognizing patterns in medical data. We performed a comprehensive systematic literature review of recent publications (last two years), indexed in PubMed/MEDLINE that have described either traditional or deep supervised prediction ML models in medicine. We identified 21,268 articles describing ML implementation in medicine. 11,726 articles were published in the last 2 years. We presented the number of publications describing each of the most often ML methods to show current trends in development of these models. Most of the recently published ML models in medicine were deep learning models. We found that the understanding of disease is likely to lead to more accurate prediction. An important dilemma is the selection of optimal ML models for a specific task, considering amount and type of available data. Domain knowledge and collaborations between physicians and ML experts can improve the prediction performance of ML models, which could help clinicians to select the most effective diagnostic and therapeutic choices available and decrease medical errors.
    • Polysubstance Use and Overdose Visualized via Maps: Opioids

      Raffa, Robert B.; Pergolizzi, Joseph V., Jr.; Cukier, Herm (2022-04-29)
      Polysubstance (combinations of substances) abuse and overdose deaths now surpass mono-substance abuse and overdose deaths. Several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several of the Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies, among others, track and provide a valuable source of statistical information about drug (prescription and illicit) (mis)use and overdose. The information is disseminated free to stakeholders and the general public for use. Although the numeric presentations of the data are helpful and adequate for professionals, the non-expert and the visual learner often find visual representation more clear and more compelling. With this in mind, the aim of this study was to present polysubstance use and overdose using visual maps of the available data. This article considers the opioids.
    • Evaluation of a Large-Scale School Wellness Intervention Through the Consolidated Framework for Implementation Research (CFIR): Implications for Dissemination and Sustainability

      McLoughlin, Gabriella; Sweeney, Rachel; Liechty, Laura; Lee, Joey A.; Rosenkranz, Richard R.; Welk, Gregory J.; McLoughlin|0000-0002-7731-2382 (2022-04-28)
      Background: Numerous studies have tested school-based interventions promoting healthy behaviors in youth, but few have integrated dissemination and implementation (D&I) frameworks. Using D&I frameworks can inform if and how an evidence-based intervention is implemented and maintained and provide strategies to address contextual barriers. Such application is necessary to understand how and why interventions are sustained over time. We evaluated a school wellness initiative called SWITCH® (School Wellness Integration Targeting Child Health) to (1) assess implementation outcomes of adoption, fidelity, and penetration, (2) discern implementation determinants through the Consolidated Framework for Implementation Research (CFIR), and (3) examine differences among inexperienced and experienced schools and influential factors to sustainment. Methods: A total of 52 schools from Iowa, United States enrolled in the 2019–2020 iteration of SWITCH (22 inexperienced; 30 experienced). The CFIR guided the adaptation of mixed methods data collection and analysis protocols for school settings. Specific attention was focused on (1) fidelity to core elements; (2) adoption of best practices; and (3) penetration of behavior change practices. Determinants were investigated through in-depth qualitative interviews and readiness surveys with implementation leaders. A systematic process was used to score CFIR domains (between −2 and +2) indicating positive or negative influence. Independent t-tests were conducted to capture differences between samples, followed by a cross-case analysis to compare determinants data. Inductive coding yielded themes related to sustainment of SWITCH beyond formal implementation support. Results: Experienced schools had higher scores on fidelity/compliance (t = −1.86 p = 0.07) and adoption (t = −2.03 p = 0.04). CFIR determinants of innovation source, culture, relative priority, and leadership engagement were positive implementation determinants, whereas tension for change and networks and communications were negative determinants. Distinguishing factors between experienced and inexperienced schools were Readiness for Implementation and Self-efficacy (experienced significantly higher; p < 0.05). Strategies to enhance sustainability were increasing student awareness/advocacy, keeping it simple, and integrating into school culture. Conclusions: Findings provide specific insights related to SWITCH implementation and sustainability but more generalized insights about the type of support needed to help schools implement and sustain school wellness programming. Tailoring implementation support to both inexperienced and experienced settings will ultimately enhance dissemination and sustainability of evidence-based interventions.
    • Administration of Drugs/Gene Products to the Respiratory System: A Historical Perspective of the Use of Inert Liquids

      Alapati, Deepthi; Shaffer, Thomas; Shaffer|0000-0003-1757-8506 (2022-05-10)
      The present review is a historical perspective of methodology and applications using inert liquids for respiratory support and as a vehicle to deliver biological agents to the respiratory system. As such, the background of using oxygenated inert liquids (considered a drug when used in the lungs) opposed to an oxygen-nitrogen gas mixture for respiratory support is presented. The properties of these inert liquids and the mechanisms of gas exchange and lung function alterations using this technology are described. In addition, published preclinical and clinical trial results are discussed with respect to treatment modalities for respiratory diseases. Finally, this forward-looking review provides a comprehensive overview of potential methods for administration of drugs/gene products to the respiratory system and potential biomedical applications.
    • Provider Perceptions of Availability, Accessibility, and Adequacy of Health and Behavioral Services for Latino Immigrants: A Qualitative Study

      Martinez-Donate, Ana; Dsouza, Nishita; Cuellar, Sieraa; Connor, Gabrielle; Zumaeta-Castillo, Claudia; Lazo-Elizondo, Mariana; Yamasaki, Yoshiaki; Perez, Cristina; Carroll-Scott, Amy; Martinez, Omar; McGuee Hassrick, Elizabeth (2022-05-09)
      Objective: Latino populations in the United States are disproportionately affected by substance use, HIV/AIDS, violence, and mental health issues (SAVAME). A growing body of evidence demonstrates the syndemic nature of SAVAME and the need for integrated strategies to reduce their impact. This study sought to understand the network of SAVAME services for Latino immigrants in a mid-Atlantic city to inform future interventions for SAVAME prevention and mitigation. Methodology: Key informant interviews (N = 30) were conducted with providers working in Latino-serving organizations providing SAVAME services. Interviews were analyzed using thematic coding and grounded theory. Results: Latino-serving providers perceived a large need for, but important limitations in the availability, accessibility, and adequacy of SAVAME services for Latino immigrants. Gaps were seen as especially acute for mental health and substance use services, partly because of insufficient funding for these services. Latino immigrants’ lack of health insurance, immigration status, limited English proficiency (LEP), stigma surrounding SAVAME issues, and limited knowledge of available services were identified as significant barriers preventing access to services. Providers noted that scarcity of well-trained, culturally competent, and ethnically concordant providers reduced the adequacy of SAVAME services for Latino immigrant clients. The small size, low levels of infrastructure, and limited capacity were reported as additional factors limiting the ability of many Latino-serving organizations to adopt a syndemic approach in the prevention and treatment of SAVAME services. Conclusions: The results call for changes in the structure of funding streams and communitywide strategies to foster collaboration across SAVAME providers working with Latino immigrant clients.
    • Policy surveillance for a global analysis of national abortion laws

      Center for Public Health Law Research (Temple University. James E. Beasley School of Law) (2022-05-18)
      Policy surveillance offers a novel and important method for comparing law across jurisdictions. We used policy surveillance to examine abortion laws across the globe. Self-managed abortion, which generally takes place outside formal healthcare settings, is increasing in prevalence and can be safe. We analysed provisions that do not account for the prevalence of self-managed abortion and evidence of its safety. Such provisions require that abortion take place in a formal healthcare setting. We also analysed criminal penalties for non-compliance. Our method included development of a legal framework, an iterative process of refining coding schemes and procedures, and rigorous quality control. We limited our analysis to liberal abortion laws for two reasons. Abortion laws globally trend towards less restrictive. In addition, we aimed to focus on how laws relate to abortion outside a formal healthcare setting specifically and excluded laws that prohibit abortion more broadly. We found that in all countries with liberal national abortion laws, the law permits only healthcare professionals or trained health workers to perform legal abortion and the majority require the abortion to take place in a specified health facility. With policy surveillance methods we can illuminate characteristics of law across many jurisdictions and the need for widespread reform, toward laws that reflect scientific evidence and the way people have abortions.
    • Polysubstance Use and Overdose Visualized via Maps: Amphetamines and Cocaine

      Raffa, Robert B.; Pergolizzi, Joseph V., Jr.; Cukier, Herm (2022-05)
      Abuse of drug substances and resultant overdose deaths are no longer very straightforward—viz., attributable to a single chemical entity of known purity. The reality is that most overdose deaths involve polysubstance use (i.e., the use of combinations of substances). Further, the combinations are often of unknown purity, and even of unknown composition. Overdose deaths are at all-time highs. The depressing statistics are monitored and reported by several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies (e.g., DEA). The information is disseminated for free for review and use. But it is our observation that although numeric presentation is helpful and adequate for professionals, the non-expert and the visual learner often find a visual representation clearer and compelling. With this in mind, we present the “gestalt” of polysubstance use and overdose using available maps of the data. The previous article in the series considered the opioids. This one considers amphetamines and cocaine, and places the rise in opioid-associated overdose deaths in the context of other abused drugs.
    • Examining the impact of economic abuse on survivors of intimate partner violence: a scoping review

      Johnson, Laura; Chen, Yafan; Stylianou, Amanda; Arnold, Alexandra; Johnson|0000-0002-1882-8186 (2022-05-19)
      Background: Economic abuse is a unique form of intimate partner violence (IPV) and includes behaviors that control a survivor’s ability to acquire, use, and maintain resources. These tactics can result in someone becoming economically dependent on their partner and may limit their ability to leave the relationship and establish independence. The aim of this study was to conduct a scoping review focused on the impact of economic abuse on survivors of IPV. Methods: A total of 14 databases were reviewed, which resulted in 35 peer-reviewed manuscripts for inclusion in the study. Manuscripts were included if they were: written in English, published since the year 2000, focused specifically on the impact of economic abuse perpetrated by an intimate partner, economic abuse was measured as an independent variable, and if economic abuse was looked at separately from other forms of IPV. Both convenience and population-based samples were included in the review. Information was extracted using a data charting form. The data were analyzed using a combination of grouping techniques and constant comparison methods to identify key findings. Results: Studies found significant associations between economic abuse and a range of outcomes, such as mental and physical health, financial impacts, parent-child interactions, and quality of life. The most frequently examined were mental health, followed by financial issues. Conclusions: Limitations of these studies included a lack of longitudinal research and a focus on heterosexual relationships with male-perpetrated violence toward female survivors. Study findings highlight the wide-ranging potential impacts of economic abuse on survivors and the need for additional research to better understand potential outcomes and implement and evaluate interventions to address them.
    • Paclitaxel binds and activates C5aR1: A new potential therapeutic target for the prevention of chemotherapy-induced peripheral neuropathy and hypersensitivity reactions

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2022-05-25)
      Chemotherapy-induced peripheral neuropathy (CIPN) and hypersensitivity reactions (HSRs) are among the most frequent and impairing side effects of the antineoplastic agent paclitaxel. Here, we demonstrated that paclitaxel can bind and activate complement component 5a receptor 1 (C5aR1) and that this binding is crucial in the etiology of paclitaxel-induced CIPN and anaphylaxis. Starting from our previous data demonstrating the role of interleukin (IL)-8 in paclitaxel-induced neuronal toxicity, we searched for proteins that activate IL-8 expression and, by using the Exscalate platform for molecular docking simulations, we predicted the high affinity of C5aR1 with paclitaxel. By in vitro studies, we confirmed the specific and competitive nature of the C5aR1-paclitaxel binding and found that it triggers intracellularly the NFkB/P38 pathway and c-Fos. In F11 neuronal cells and rat dorsal root ganglia, C5aR1 inhibition protected from paclitaxel-induced neuropathological effects, while in paclitaxel-treated mice, the absence (knock-out mice) or the inhibition of C5aR1 significantly ameliorated CIPN symptoms—in terms of cold and mechanical allodynia—and reduced the chronic pathological state in the paw. Finally, we found that C5aR1 inhibition can counteract paclitaxel-induced anaphylactic cytokine release in macrophages in vitro, as well as the onset of HSRs in mice. Altogether these data identified C5aR1 as a key mediator and a new potential pharmacological target for the prevention and treatment of CIPN and HSRs induced by paclitaxel.