Now showing items 41-60 of 3299

    • Diabetes impairs cardioprotective function of endothelial progenitor cell-derived extracellular vesicles via H3K9Ac inhibition

      Center for Translational Medicine (Temple University) (2022-05-21)
      Background and Purpose: Myocardial infarction (MI) in diabetic patients results in higher mortality and morbidity. We and others have previously shown that bone marrow-endothelial progenitor cells (EPCs) promote cardiac neovascularization and attenuate ischemic injury. Lately, small extracellular vesicles (EVs) have emerged as major paracrine effectors mediating the benefits of stem cell therapy. Modest clinical outcomes of autologous cell-based therapies suggest diabetes-induced EPC dysfunction and may also reflect their EV derivatives. Moreover, studies suggest that post-translational histone modifications promote diabetes-induced vascular dysfunctions. Therefore, we tested the hypothesis that diabetic EPC-EVs may lose their post-injury cardiac reparative function by modulating histone modification in endothelial cells (ECs). Methods: We collected EVs from the culture medium of EPCs isolated from non-diabetic (db/+) and diabetic (db/db) mice and examined their effects on recipient ECs and cardiomyocytes in vitro, and their reparative function in permanent ligation of left anterior descending (LAD) coronary artery and ischemia/reperfusion (I/R) myocardial ischemic injuries in vivo. Results: Compared to db/+ EPC-EVs, db/db EPC-EVs promoted EC and cardiomyocyte apoptosis and repressed tube-forming capacity of ECs. In vivo, db/db EPC-EVs depressed cardiac function, reduced capillary density, and increased fibrosis compared to db/+ EPC-EV treatments after MI. Moreover, in the I/R MI model, db/+ EPC-EV-mediated acute cardio-protection was lost with db/db EPC-EVs, and db/db EPC-EVs increased immune cell infiltration, infarct area, and plasma cardiac troponin-I. Mechanistically, histone 3 lysine 9 acetylation (H3K9Ac) was significantly decreased in cardiac ECs treated with db/db EPC-EVs compared to db/+ EPC-EVs. The H3K9Ac chromatin immunoprecipitation sequencing (ChIP-Seq) results further revealed that db/db EPC-EVs reduced H3K9Ac level on angiogenic, cell survival, and proliferative genes in cardiac ECs. We found that the histone deacetylase (HDAC) inhibitor, valproic acid (VPA), partly restored diabetic EPC-EV-impaired H3K9Ac levels, tube formation and viability of ECs, and enhanced cell survival and proliferative genes, Pdgfd and Sox12, expression. Moreover, we observed that VPA treatment improved db/db EPC-mediated post-MI cardiac repair and functions. Conclusions: Our findings unravel that diabetes impairs EPC-EV reparative function in the ischemic heart, at least partially, through HDACs-mediated H3K9Ac downregulation leading to transcriptional suppression of angiogenic, proliferative and cell survival genes in recipient cardiac ECs. Thus, HDAC inhibitors may potentially be used to restore the function of diabetic EPC and other stem cells for autologous cell therapy applications.
    • Baseline Demographics and Severity and Burden of Atopic Dermatitis in Adult Patients Initiating Dupilumab Treatment in a Real-World Registry (PROSE)

      Bagel, Jerry; Nguyen, Tien Q.; Lima, Hermenio; Jain, Neal; Pariser, David M.; Hsu, Sylvia; Yosipovitch, Gil; Zhang, Haixin; Chao, Jingdong; Bansal, Shikha; Chen, Zhen; Richman, Daniel; Korotzer, Andrew; Ardeleanu, Marius; Hsu|0000-0001-7885-3730 (2022-05-20)
      Introduction: Dupilumab was initially approved in 2017 as the first biologic therapy for atopic dermatitis (AD). We characterized adults with AD initiating dupilumab in a real-world setting in the USA/Canada. Methods: PROSE is an ongoing, longitudinal, prospective, observational, multicenter registry of patients with AD initiating dupilumab per country-specific prescribing information. We report baseline data (day of first dupilumab injection) for patients enrolled from April 2018 through July 2019. Results: Among 315 patients (mean age 42.5 years, 55.2% female), the median AD duration was 17.0 years; 65.4% reported a history of type 2 inflammatory comorbidities (e.g., allergic rhinitis, asthma), and 93.3% reported treatment(s) for AD in the previous year, including topical corticosteroids (90.8%), systemic corticosteroids (36.2%), and nonsteroidal systemic therapies (14.0%). In total, 89.2% had an Overall Disease Severity score of 3 (moderate) or 4 (severe). Other mean disease severity scores included the following: Eczema Area and Severity Index 16.9 (range 0–72), body surface area affected 26.8%, Patient-Oriented Eczema Measure 18.5 (range 0–28), Dermatology Life Quality Index 12.7 (range 0–30), and pruritus Numerical Rating Scale score 6.9 (range 0–10). Conclusion: Patients initiating dupilumab have longstanding moderate-to-severe AD with significant disease burden and frequent type 2 comorbidities.
    • A Watershed Moment for Sanctions? Russia, Ukraine, and the Economic Battlefield

      Chachko, Elena; Heath, J. Benton (2022-05-23)
      Russia's invasion of Ukraine has triggered an unprecedented wave of sanctions targeting every facet of the Russian economy. In the early months of the conflict, the sheer scope, speed, and coordination of this response to Russia's aggression instills hope that economic pressure may yet play a decisive role in this conflict. But the massive scale of the effort is also cause for concern. In particular, it highlights the relative lack of legal constraints governing economic warfare, even in the face of potentially grave harms to third parties and the global economy. While these concerns have provoked no shortage of proposals for reform, the fragmented institutional landscape and a lack of political will are likely to frustrate any attempts at far-reaching transformation.
    • Phenol-Soluble Modulins From Staphylococcus aureus Biofilms Form Complexes With DNA to Drive Autoimmunity

      Center for Microbiology and Immunology (Temple University) (2022-05-11)
      The bacterial amyloid curli, produced by Enterobacteriales including Salmonella species and Escherichia coli, is implicated in the pathogenesis of several complex autoimmune diseases. Curli binds to extracellular DNA, and these complexes drive autoimmunity via production of anti-double-stranded DNA autoantibodies. Here, we investigated immune activation by phenol-soluble modulins (PSMs), the amyloid proteins expressed by Staphylococcus species. We confirmed the amyloid nature of PSMs expressed by S. aureus using a novel specific amyloid stain, (E,E)-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy) styrylbenzene (FSB). Direct interaction of one of the S. aureus PSMs, PSMα3, with oligonucleotides promotes fibrillization of PSM amyloids and complex formation with bacterial DNA. Finally, utilizing a mouse model with an implanted mesh-associated S. aureus biofilm, we demonstrated that exposure to S. aureus biofilms for six weeks caused anti-double-stranded DNA autoantibody production in a PSM-dependent manner. Taken together, these results highlight how the presence of PSM-DNA complexes in S. aureus biofilms can induce autoimmune responses, and suggest an explanation for how bacterial infections trigger autoimmunity.
    • Plateaus, Multiplicities, and Interconnections in Distant Star: Between Complexity and Rhizomes

      Guarín, Daniel (2022-05-12)
      This article analyzes the narrative structure of the novel Distant Star, by Roberto Bolaño, from the theory of complexity and from the philosophical concept of Rhizome. The stories of the novel are understood as plateaus that are connected like rhizomes or that interact in a complex system to give meaning to the work. The article begins with a synthesis of the story, then relates the concepts of complexity and rhizome, and finally presents the plateaus and interconnections created by Bolaño in the novel. It is concluded that Distant Star can be read in a linear way, following the trail of the antagonist; or in a rhizomic way, without beginning or end, but with a variety of plateaus, intertextualities and stories that are slightly connected. Wieder becomes a point without end, and like the novel, a rhizome in the universe of Bolaño's work.
    • A-31 | Benign Acquired Chronic Vena Caval Occlusions: A Case Based Approach

      Temple University. Hospital (2022-05-19)
      Background: Chronic total occlusion (CTO) of the superior vena cava (SVC) and inferior vena cava (IVC) cause a wide range of symptoms in patients due to obstructed outflow, often manifesting as SVC or IVC syndrome. Percutaneous intervention is now the first line therapy, overtaking prior surgical grafting techniques. We report a series of cases with benign acquired chronic vena caval total occlusions treated with endovascular stenting. Methods: This data was collected from a single center, retrospective chart review of the electronic medical record between November 2015 - August 2021. CTOs were identified as those with a duration of symptoms >3 months. Cases with acute thrombosis were excluded. Results: The cohort consisted of seven patients, four were women and ages ranged from 31-66 years. Two patients were on hemodialysis, three patients had pulmonary hypertension and two had chronic thromboembolic pulmonary hypertension (CTEPH). All the etiologies were benign. The procedure utilized hydrophilic wire with support catheters from multiple access sites. All patients were treated with balloon angioplasty and stenting with bare-metal stents. All patients had a technically successful procedure without procedural complications. Conclusions: These cases highlight the complex interventional techniques of CTO revascularization in the SVC and IVC lesions. Large prospective studies examining the technical and clinical success and long-term complications are needed in the future.
    • Diversity of Microbial Eukaryotes Along the West Antarctic Peninsula in Austral Spring

      Grattepanche, Jean-David; Jeffrey, Wade H.; Gast, Rebecca J.; Sanders, Robert W.; Grattepanche|0000-0002-1854-3762 (2022-05-16)
      During a cruise from October to November 2019, along the West Antarctic Peninsula, between 64.32 and 68.37°S, we assessed the diversity and composition of the active microbial eukaryotic community within three size fractions: micro- (> 20 μm), nano- (20–5 μm), and pico-size fractions (5–0.2 μm). The communities and the environmental parameters displayed latitudinal gradients, and we observed a strong similarity in the microbial eukaryotic communities as well as the environmental parameters between the sub-surface and the deep chlorophyll maximum (DCM) depths. Chlorophyll concentrations were low, and the mixed layer was shallow for most of the 17 stations sampled. The richness of the microplankton was higher in Marguerite Bay (our southernmost stations), compared to more northern stations, while the diversity for the nano- and pico-plankton was relatively stable across latitude. The microplankton communities were dominated by autotrophs, mostly diatoms, while mixotrophs (phototrophs-consuming bacteria and kleptoplastidic ciliates, mostly alveolates, and cryptophytes) were the most abundant and active members of the nano- and picoplankton communities. While phototrophy was the dominant trophic mode, heterotrophy (mixotrophy, phagotrophy, and parasitism) tended to increase southward. The samples from Marguerite Bay showed a distinct community with a high diversity of nanoplankton predators, including spirotrich ciliates, and dinoflagellates, while cryptophytes were observed elsewhere. Some lineages were significantly related—either positively or negatively—to ice coverage (e.g., positive for Pelagophyceae, negative for Spirotrichea) and temperature (e.g., positive for Cryptophyceae, negative for Spirotrichea). This suggests that climate changes will have a strong impact on the microbial eukaryotic community.
    • Negative mood induction effects on problem-solving task in women with eating disorders: a multi-method examination

      Temple Eating Disorders Program (Temple University) (2022-05-21)
      Background: The effects of negative affect on problem-solving and its psychophysiological correlates are poorly understood in eating disorder populations. Methods: This study examined respiratory sinus arrhythmia (RSA) and skin conductance responses of women with Binge Eating Disorder (BED: n = 56), Anorexia Nervosa (AN: n = 12), Bulimia Nervosa (BN: n = 32), and 24 healthy controls (HCs) at baseline, and then during: a negative mood induction task, an adapted Means Ends Problem-Solving (MEPS) task, and recovery. The MEPS task included four interpersonal scenarios: (1) binge-eating as a solution to stress, (2) job loss, (3) rejection by friends, and (4) by a significant other. Results: We found that individuals with eating disorders reported less positive mood than HCs and individuals with BN and BED reported more negative mood and greater urges to binge than HCs. After a negative mood induction, women with BED provided significantly less effective problem-solving strategies compared to HCs and women with BN for the binge-eating MEPS scenario. Relative to baseline and the negative mood induction, all participants exhibited significantly higher skin conductance measures throughout the MEPS scenarios and recovery. BED showed significantly lower respiratory sinus arrhythmia (RSA) levels than individuals with BN and HCs throughout the protocol. Conclusions: The multimethod findings suggest individuals with BED are likely to have disorder-specific problem-solving difficulties after a negative mood induction.
    • Beyond the clinical context: the process of losing oneself living with Huntington’s disease

      Bio3Science Research Network (Temple University) (2022-05-07)
      Background: People with Huntington's disease (HD) have increased functional and cognitive dependence. While numerous clinical, genetic, and therapeutic management studies have been carried out, few studies have investigated the disease from the personal experience and the context of people living with HD. To better serve these patients, our purpose is to understand, from the perspective of the patient and their families, how people with HD cope with their daily lives outside the clinical setting. Methods: Thirty-three affected or at-risk people participated in this study. Participants were interviewed at their homes on distinct occasions during a family visit. We analyzed the data using Grounded Theory, which allowed us to understand how people live with the disease on their own terms. Results: Living with HD is a process that begins with acceptance or denial that one is at risk for the disease or, growing awareness of the condition due to motor, behavioral, and cognitive changes, and, finally, loss of autonomy with physical dependence on another person, and loss of sense of self and family. Conclusion: While the daily life of patients before disease onset was characterized by physical and mental/cognitive independence, with HD they become increasingly trapped in their bodies, and their complications are due to the lack of effective curable therapy.
    • Direct anabolic metabolism of three-carbon propionate to a six-carbon metabolite occurs in vivo across tissues and species

      Center for Metabolic Disease Research (Temple University) (2022-06-07)
      Anabolic metabolism of carbon in mammals is mediated via the one- and two-carbon carriers S-adenosyl methionine and acetyl-coenzyme A. In contrast, anabolic metabolism of three-carbon units via propionate has not been shown to extensively occur. Mammals are primarily thought to oxidize the three-carbon short chain fatty acid propionate by shunting propionyl-CoA to succinyl-CoA for entry into the TCA cycle. Here, we found that this may not be absolute as, in mammals, one nonoxidative fate of propionyl-CoA is to condense to two three-carbon units into a six-carbon trans-2-methyl-2-pentenoyl-CoA (2M2PE-CoA). We confirmed this reaction pathway using purified protein extracts provided limited substrates and verified the product via LC-MS using a synthetic standard. In whole-body in vivo stable isotope tracing following infusion of 13C-labeled valine at steady state, 2M2PE-CoA was found to form via propionyl-CoA in multiple murine tissues, including heart, kidney, and to a lesser degree, in brown adipose tissue, liver, and tibialis anterior muscle. Using ex vivo isotope tracing, we found that 2M2PE-CoA also formed in human myocardial tissue incubated with propionate to a limited extent. While the complete enzymology of this pathway remains to be elucidated, these results confirm the in vivo existence of at least one anabolic three- to six-carbon reaction conserved in humans and mice that utilizes propionate.
    • Friction in clay-bearing faults increases with the ionic radius of interlayer cations

      Sakuma, Hiroshi; Lockner, David A.; Solum, John; Davatzes, Nicholas C. (2022-05-16)
      Smectite can dramatically reduce the strength of crustal faults and may cause creep on natural faults without great earthquakes; however, the frictional mechanism remains unexplained. Here, our shear experiments reveal systematic increase in shear strength with the increase of the ionic radius of interlayer cations among lithium-, sodium-, potassium-, rubidium-, and cesium-montmorillonites, a smectite commonly found in faults. Using density-functional-theory calculations, we find that relatively small sodium ions fit in the ditrigonal cavities on the montmorillonite surfaces, resulting in weakening of interlayer repulsion during sliding. On the other hand, relatively large potassium ions do not fit in the ditrigonal cavities, resulting in a larger resistance to sliding due to electrostatic repulsion between potassium ions. Calculated shear strength is consistent with our shear experiments by considering the partial dehydration of the frictional contact area. These results provide the basis for developing a quantitative model of smectite-bearing fault rheology.
    • Why Plasmodium vivax and Plasmodium falciparum are so different? A tale of two clades and their species diversities

      Institute for Genomics and Evolutionary Medicine (iGEM) (Temple University) (2022-05-03)
      The global malaria burden sometimes obscures that the genus Plasmodium comprises diverse clades with lineages that independently gave origin to the extant human parasites. Indeed, the differences between the human malaria parasites were highlighted in the classical taxonomy by dividing them into two subgenera, the subgenus Plasmodium, which included all the human parasites but Plasmodium falciparum that was placed in its separate subgenus, Laverania. Here, the evolution of Plasmodium in primates will be discussed in terms of their species diversity and some of their distinct phenotypes, putative molecular adaptations, and host–parasite biocenosis. Thus, in addition to a current phylogeny using genome-level data, some specific molecular features will be discussed as examples of how these parasites have diverged. The two subgenera of malaria parasites found in primates, Plasmodium and Laverania, reflect extant monophyletic groups that originated in Africa. However, the subgenus Plasmodium involves species in Southeast Asia that were likely the result of adaptive radiation. Such events led to the Plasmodium vivax lineage. Although the Laverania species, including P. falciparum, has been considered to share “avian characteristics,” molecular traits that were likely in the common ancestor of primate and avian parasites are sometimes kept in the Plasmodium subgenus while being lost in Laverania. Assessing how molecular traits in the primate malaria clades originated is a fundamental science problem that will likely provide new targets for interventions. However, given that the genus Plasmodium is paraphyletic (some descendant groups are in other genera), understanding the evolution of malaria parasites will benefit from studying “non-Plasmodium” Haemosporida.
    • Cancer Stem Cells and Their Possible Implications in Cervical Cancer: A Short Review

      Sbarro Health Organization (SBHO) (Temple University) (2022-05-05)
      Cervical cancer (CC) is the fourth most common type of gynecological malignancy affecting females worldwide. Most CC cases are linked to infection with high-risk human papillomaviruses (HPV). There has been a significant decrease in the incidence and death rate of CC due to effective cervical Pap smear screening and administration of vaccines. However, this is not equally available throughout different societies. The prognosis of patients with advanced or recurrent CC is particularly poor, with a one-year relative survival rate of a maximum of 20%. Increasing evidence suggests that cancer stem cells (CSCs) may play an important role in CC tumorigenesis, metastasis, relapse, and chemo/radio-resistance, thus representing potential targets for a better therapeutic outcome. CSCs are a small subpopulation of tumor cells with self-renewing ability, which can differentiate into heterogeneous tumor cell types, thus creating a progeny of cells constituting the bulk of tumors. Since cervical CSCs (CCSC) are difficult to identify, this has led to the search for different markers (e.g., ABCG2, ITGA6 (CD49f), PROM1 (CD133), KRT17 (CK17), MSI1, POU5F1 (OCT4), and SOX2). Promising therapeutic strategies targeting CSC-signaling pathways and the CSC niche are currently under development. Here, we provide an overview of CC and CCSCs, describing the phenotypes of CCSCs and the potential of targeting CCSCs in the management of CC.
    • Clustering extent‐dependent differential signaling by CLEC‐2 receptors in platelets

      Sol Sherry Thrombosis Research Center (Temple University) (2022-12-22)
      Background: C‐type lectin receptor family members play a role in many cells including platelets, where they are crucial in the separation of lymphatic and blood vessels during development. The C‐type lectin‐like receptor 2 (CLEC‐2) receptor contains the canonical intracellular hemITAM motif through which it signals to activate Syk. Objectives: One proposed hypothesis for signaling cascade is that Syk bridges two receptors through phosphorylated hemITAM motifs. We demonstrated that the phosphorylated hemITAM stimulates PI3 kinase/Btk pathways to activate Syk. To address this controversy, we used a CLEC‐2 selective agonist and studied the role of Btk in platelet activation. Results and Conclusions: Platelet activation and downstream signaling were abolished in murine and human platelets in the presence of the Btk inhibitors ibrutinib or acalabrutinib when a low concentration of a CLEC‐2 antibody was used to crosslink CLEC‐2 receptors. This inhibition was overcome by increasing concentrations of the CLEC‐2 antibody. Similar results were obtained in X‐linked immunodeficient mouse platelets, with an inactivating mutation in Btk or in Lyn null platelets. We conclude that at low crosslinking conditions of CLEC‐2, Btk plays an important role in the activation of Syk, but at higher crosslinking conditions their role becomes less important and other mechanisms take over to activate Syk.
    • People living with moderate-to-severe COPD prefer improvement of daily symptoms over the improvement of exacerbations: a multicountry patient preference study

      Cook, Nigel S.; Criner, Gerard J.; Burgel, Pierre-Régis; Mycock, Katie; Gardner, Tom; Mellor, Phil; Hallworth, Pam; Sully, Kate; Tatlock, Sophi; Klein, Beyza; Jones, Byron; Le Rouzic, Olivier; Adams, Kip; Phillips, Kirsten; McKevitt, Mike; Toyama, Kazuko; Gutzwiller, Florian S. (2022-05-05)
      Introduction: This patient preference study sought to quantify the preferences of people living with COPD regarding symptom improvement in the UK, USA, France, Australia and Japan. Methods: The inclusion criteria were people living with COPD aged 40 years or older who experienced ≥1 exacerbation in the previous year with daily symptoms of cough and excess mucus production. The study design included: 1) development of an attributes and levels grid through qualitative patient interviews; and 2) implementation of the main online quantitative survey, which included a discrete choice experiment (DCE) to allow assessment of attributes and levels using hypothetical health state profiles. Preference weights (utilities) were derived from the DCE using hierarchical Bayesian analysis. A preference simulator was developed that enabled different health state scenarios to be evaluated based on the predicted patient preferences. Results: 1050 people living with moderate-to-severe COPD completed the survey. All attributes were considered important when patients determined their preferences in the DCE. In a health state preference simulation, two hypothetical health states (comprising attribute levels) with qualitatively equivalent improvements in A) cough and mucus and B) shortness of breath (SOB) resulted in a clear preference for cough and mucus improved profile. When comparing two profiles with C) daily symptoms improved and D) exacerbations improved, there was a clear preference for the daily symptoms improved profile. Conclusions: People living with moderate-to-severe COPD prefer to reduce cough and mucus production together over improvement of SOB and would prefer to reduce combined daily symptoms over an improvement in exacerbations.
    • Cone Beam CT With Flat Panel Detector and Biplane Fluoroscopy-Guided Percutaneous Trigeminal Nerve Rhizotomy Using Three-Dimensional Needle Trajectory Planning

      Cohen, Dylan T.; Bragin, Ilya; Hwang, Roy; Oselkin, Martin (2022-05-31)
      Trigeminal-mediated pain disorders can be devastating for patients refractory to medical therapy. Gasserian ganglion blocks and percutaneous trigeminal rhizotomy have been used with success to treat these patients, however, serious complication risks include facial hematoma, cranial nerve palsy, and stroke. Cone beam CT, combined with fluoroscopy and needle navigation has been shown to decrease needle pass rates, procedure time, radiation exposure, and complications in multiple interventional radiology procedures, but hitherto has not been utilized for Gasserian ganglion interventions. Here, we present two cases of trigeminal-mediated pain successfully treated via cone beam CT combined fluoroscopy and needle navigation.
    • SAR Probing of KX2-391 Provided Analogues With Juxtaposed Activity Profile Against Major Oncogenic Kinases

      Moulder Center for Drug Discovery Research (Temple University) (2022-05-20)
      Tirbanibulin (KX2-391, KX-01), a dual non-ATP (substrate site) Src kinase and tubulin-polymerization inhibitor, demonstrated a universal anti-cancer activity for variety of cancer types. The notion that KX2-391 is a highly selective Src kinase inhibitor have been challenged by recent reports on the activities of this drug against FLT3-ITD mutations in some leukemic cell lines. Therefore, we hypothesized that analogues of KX2-391 may inhibit oncogenic kinases other than Src. A set of 4-aroylaminophenyl-N-benzylacetamides were synthesized and found to be more active against leukemia cell lines compared to solid tumor cell lines. N-(4-(2-(benzylamino)-2-oxoethyl)phenyl)-4-chlorobenzamide (4e) exhibited activities at IC50 0.96 µM, 1.62 µM, 1.90 µM and 4.23 µM against NB4, HL60, MV4-11 and K562 leukemia cell lines, respectively. We found that underlying mechanisms of 4e did not include tubulin polymerization or Src inhibition. Such results interestingly suggested that scaffold-hopping of KX2-391 may change the two main underlying cytotoxic mechanisms (Src and tubulin). Kinase profiling using two methods revealed that 4e significantly reduces the activities of some other potent oncogenic kinases like the MAPK member ERK1/2 (>99%) and it also greatly upregulates the pro-apoptotic c-Jun kinase (84%). This research also underscores the importance of thorough investigation of total kinase activities as part of the structure-activity relationship studies.
    • Previous concussions increase the risk of mental health disability in college athletes

      Burns, Karlee; Kerod, Karly; McDevitt, Jane; Burns|0000-0003-1139-1564 (2022-05-25)
      Background and Aim: Mental health concerns, particularly anxiety and depression, are leading causes of disability in young adults. Identifying pre-existing conditions that place individuals at-risk for mental health disability may enable health-care providers to increase patient outcomes with early interventions and condition management. Methods: Student-athletes were grouped by self-reported mental health disability status during preseason baseline physicals. During the pre-season baseline assessment, student athletes completed the post-concussion symptom scale, hospital anxiety and disability scale, short-form 12 survey, and health history questionnaire. A logistic regression was performed to examine the predictive value of previous concussion history, anxiety, and/or depression mental health disability status. Results: Student-athletes with a previous concussion had a 46% higher risk for mental health disability. Higher PROM anxiety and depression scores were associated with a 1.29- and 1.19-times higher risk of mental health disability, respectively. Conclusion: The previous concussion history placed collegiate student-athletes at higher risk for mental health disability. Further, student-athletes that had higher anxiety and depression PROM scores were more likely to have self-reported diagnosed mental health disability. Health-care professionals working with collegiate student-athletes can identify pre-existing conditions that may put a studentathlete at higher risk for mental health disability. Relevance for Patients: The present study identifies previous concussion history and prior mental health diagnoses places individuals at higher risk for the future mental health disability. Identification of these individuals during routine health screenings may improve overall health outcomes.
    • Agonist-Promoted Phosphorylation and Internalization of the Kappa Opioid Receptor in Mouse Brains: Lack of Connection With Conditioned Place Aversion

      Center for Substance Abuse Research (Temple University) (2022-05-16)
      Selective kappa opioid receptor (KOR) agonists are promising antipruritic agents and analgesics. However, clinical development of KOR agonists has been limited by side effects, including psychotomimetic effects, dysphoria, and sedation, except for nalfurafine, and recently. CR845 (difelikefalin). Activation of KOR elicits G protein- and β-arrestin-mediated signaling. KOR-induced analgesic and antipruritic effects are mediated by G protein signaling. However, different results have been reported as to whether conditioned place aversion (CPA) induced by KOR agonists is mediated by β-arrestin signaling. In this study, we examined in male mice if there was a connection between agonist-promoted CPA and KOR phosphorylation and internalization, proxies for β-arrestin recruitment in vivo using four KOR agonists. Herein, we demonstrated that at doses producing maximal effective analgesic and antiscratch effects, U50,488H, MOM-SalB, and 42B, but not nalfurafine, promoted KOR phosphorylation at T363 and S369 in mouse brains, as detected by immunoblotting with phospho-KOR-specific antibodies. In addition, at doses producing maximal effective analgesic and antiscratch effects, U50,488H, MOM-SalB, and 42B, but not nalfurafine, caused KOR internalization in the ventral tegmental area of a mutant mouse line expressing a fusion protein of KOR conjugated at the C-terminus with tdTomato (KtdT). We have reported previously that the KOR agonists U50,488H and methoxymethyl salvinorin B (MOM-SalB) cause CPA, whereas nalfurafine and 42B do not, at doses effective for analgesic and antiscratch effects. Taken together, these data reveal a lack of connection between agonist-promoted KOR-mediated CPA with agonist-induced KOR phosphorylation and internalization in male mice.
    • Exploring the Relationships of Two Curriculum-improved Abilities Scales, Professional Development and Quantitative Skills, to Business Student Satisfaction and Employment Preparedness

      Blau, Gary; Goldberg, Daniel; Voss, Kathleen (2022-05-14)
      Despite the pandemic, on-going efforts to evaluate student perceptions of their curricula improving their abilities across different areas needs to be continued. This study examined one business school’s undergraduate curriculum. Twelve individual item goals of this curriculum closely corresponded to what employers look for on college students’ resumes (NACE, 2021). Ninety-three Fall 2021 graduating business seniors filled out a survey asking their perceptions about the business school’s curriculum improving their abilities on these twelve goals. To date, these individual attributes have not been analyzed together in prior studies to produce a smaller set of research scales. A factor analysis of these twelve individual items resulted in keeping nine of these items, creating two new reliable and distinct scales for future research, labeled as Professional Development (5 items) and Quantitative Skills (4 items). Significant positive relationships between these two scales and two outcomes, student satisfaction and employment preparation, were subsequently found. In addition, a new short multi-item, reliable Employment Preparedness scale was developed. After controlling for record-based student demographics (gender, race, state residency) and school-related variables (GPA, transfer student, quantitative/qualitative major), Quantitative Skills accounted for significant variance in both outcomes, while Professional Development accounted for only student satisfaction.