How HELP Provided the Pathway to become Age-Friendly

In assessing how the 4Ms framework applies to the Hospital Elder Life Program, we were able to target specific ways to deliver more Age-Friendly care to those enrolled in the program

The effects of computer graphics and mira on aquisition of transformation geometry concepts and development of mental rotation skills in grade eight

The purpose of this study was to investigate: (1) whether the use of the Motions computer program will be more effective in the acquisition of transformation geometry concepts in eighth-grade students than the use of the Mira hands-on manipulative, (2) whether the use of the Motions computer program will be more effective in the development of mental rotation skills in eighth-grade students than the use of the Mira hands-on manipulative, and (3) possible sex differences resulting from the use of the Motions computer program or the use of the Mira, hands-on manipulative in the acquisition of transformation geometry concepts by eighth-grade students. The study included 15 teachers at 15 different junior high schools teaching 560 students. The study sample consisted of 16 classes, eight classes in each of the two experimental groups. There were 14 classes in the testing effect control group. Eight teachers each taught a Motions class and a Mira class. The remaining seven teachers taught two control classes each. The subjects were pretested and posttested with The Card Rotations Test from the Kit of Factor-Referenced Tests and the researcher-designed Transformation Geometry Achievement Test. The subjects were also administered the researcher-designed Computer Experience Questionnaire. During the period of time between the pretests and the posttests, the experimental group subjects studied a three-week series of lessons on transformation geometry concepts. To check for a possible mental rotation testing effect, the control group subjects studied a three-week unit on fractions and decimals. Data were analyzed by analysis of covariance. With regard to mathematics achievement of transformation geometry concepts, the analysis revealed no significant difference between the class means: (1) of the Mira and the Motions groups, (2) of the females in the Mira and the Motions groups, and (3) of the females in either the Mira, or Motions groups and of the males in either the Mira or Motions groups. A significant difference, at the 0.05 level, was found between the mean of the males in the Mira and the Motions groups. With regard to mental rotation ability, the analysis revealed no significant difference between the class means: (1) of the Mira and the Motions groups, (2) of the males in the Mira and the Motions groups, and (3) of the females in the Mira, and of the Motions groups

Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction

Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80–90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity. In the current manuscript, we examined the effect of Ebola structural proteins VP40, GP, NP and VLPs on recipient immune cells, as well as the effect of exosomes containing these proteins on naïve immune cells. We found that VP40-transfected cells packaged VP40 into exosomes, and that these exosomes were capable of inducing apoptosis in recipient immune cells. Additionally, we show that presence of VP40 within parental cells or in exosomes delivered to naïve cells could result in the regulation of RNAi machinery including Dicer, Drosha, and Ago 1, which may play a role in the induction of cell death in recipient immune cells. Exosome biogenesis was regulated by VP40 in transfected cells by increasing levels of ESCRT-II proteins EAP20 and EAP45, and exosomal marker proteins CD63 and Alix. VP40 was phosphorylated by Cdk2/Cyclin complexes at Serine 233 which could be reversed with r-Roscovitine treatment. The level of VP40-containing exosomes could also be regulated by treated cells with FDA-approved Oxytetracycline. Additionally, we utilized novel nanoparticles to safely capture VP40 and other viral proteins from Ebola VLPs spiked into human samples using SDS/reducing agents, thus minimizing the need for BSL-4 conditions for most downstream assays. Collectively, our data indicates that VP40 packaged into exosomes may be responsible for the deregulation and eventual destruction of the T-cell and myeloid arms of the immune system (bystander lymphocyte apoptosis), allowing the virus to replicate to high titers in the immunocompromised host. Moreover, our results suggest that the use of drugs such as Oxytetracycline to modulate the levels of exosomes exiting EBOV-infected cells may be able to prevent the devastation of the adaptive immune system and allow for an improved rate of survival

2017 Clinic Yearbook

The Clinic is the yearbook of the Sidney Kimmel Medical College at Thomas Jefferson University

Pennsylvania Folklife Vol. 25, Folk Festival Supplement

• Quilts, Quilts, Quilts • America\u27s Heritage is Endowed with Contributions of the Pennsylvania Dutch • The Hospitality Tent: H is for Help - That\u27s What it\u27s all About • Pottery: A Folk Art Expressing the Most in Simplest Terms • It Never Rains on our Parade - On the Fourth of July • Vegetable Dyeing at the Kutztown Folk Festival • Festival Focus • Folk Festival Program • Festival Foods: The Original Touch of the Dutch • Ursinus College Studies at the Festival • Behind the Scenes of We Like Our Country, But We Love Our God • Reverse Glass Tinsel Painting • Tin, Tole and Independencehttps://digitalcommons.ursinus.edu/pafolklifemag/1069/thumbnail.jp

Autophagy, EVs, and Infections: A Perfect Question for a Perfect Time

Autophagy, a highly conserved process, serves to maintain cellular homeostasis in response to an extensive variety of internal and external stimuli. The classic, or canonical, pathway of autophagy involves the coordinated degradation and recycling of intracellular components and pathogenic material. Proper regulation of autophagy is critical to maintain cellular health, as alterations in the autophagy pathway have been linked to the progression of a variety of physiological and pathological conditions in humans, namely in aging and in viral infection. In addition to its canonical role as a degradative pathway, a more unconventional and non-degradative role for autophagy has emerged as an area of increasing interest. This process, known as secretory autophagy, is gaining widespread attention as many viruses are believed to use this pathway as a means to release and spread viral particles. Moreover, secretory autophagy has been found to intersect with other intracellular pathways, such as the biogenesis and secretion of extracellular vesicles (EVs). Here, we provide a review of the current landscape surrounding both degradative autophagy and secretory autophagy in relation to both aging and viral infection. We discuss their key features, while describing their interplay with numerous different viruses (i.e. hepatitis B and C viruses, Epstein-Barr virus, SV40, herpesviruses, HIV, chikungunya virus, dengue virus, Zika virus, Ebola virus, HTLV, Rift Valley fever virus, poliovirus, and influenza A virus), and compare secretory autophagy to other pathways of extracellular vesicle release. Lastly, we highlight the need for, and emphasize the importance of, more thorough methods to study the underlying mechanisms of these pathways to better advance our understanding of disease progression

Low-Level ionizing radiation induces selective killing of HIV-1-infected cells with reversal of cytokine induction using mtor inhibitors

HIV-1 infects 39.5 million people worldwide, and cART is effective in preventing viral spread by reducing HIV-1 plasma viral loads to undetectable levels. However, viral reservoirs persist by mechanisms, including the inhibition of autophagy by HIV-1 proteins (i.e., Nef and Tat). HIV-1 reservoirs can be targeted by the “shock and kill” strategy, which utilizes latency-reversing agents (LRAs) to activate latent proviruses and immunotarget the virus-producing cells. Yet, limitations include reduced LRA permeability across anatomical barriers and immune hyper-activation. Ionizing radiation (IR) induces effective viral activation across anatomical barriers. Like other LRAs, IR may cause inflammation and modulate the secretion of extracellular vesicles (EVs). We and others have shown that cells may secrete cytokines and viral proteins in EVs and, therefore, LRAs may contribute to inflammatory EVs. In the present study, we mitigated the effects of IR-induced inflammatory EVs (i.e., TNF-α), through the use of mTOR inhibitors (mTORi; Rapamycin and INK128). Further, mTORi were found to enhance the selective killing of HIV-1-infected myeloid and T-cell reservoirs at the exclusion of uninfected cells, potentially via inhibition of viral transcription/translation and induction of autophagy. Collectively, the proposed regimen using cART, IR, and mTORi presents a novel approach allowing for the targeting of viral reservoirs, prevention of immune hyper-activation, and selectively killing latently infected HIV-1 cells

Risk of venous thromboembolism during and after hospitalisation in patients with inflammatory bowel disease activity

Background: Inflammatory bowel disease (IBD) increases the risk of venous thromboembolism. Aim: To determine when patients are at high risk of thromboembolic events, including after major surgery, and to guide timing of thromboprophylaxis. Methods: Each inflammatory bowel disease patient from Clinical Practice Research Datalink, linked with Hospital Episode Statistics, was matched to up to five non-IBD patients in this cohort study. We examined their risk of thromboembolism in hospital and within six weeks after leaving hospital, with or without undergoing major surgery, and while ambulant. Hazard ratios were estimated using Cox regression, with adjustment for age, sex, body mass index, smoking and history of malignancy or thromboembolism. Results: Overall 23,046 inflammatory bowel disease patients had a thromboembolic risk 1.74 times (95% CI = 1.55–1.96) higher than 106,795 non-IBD patients. Among ambulant patients, the thromboembolic risk was raised during acute (hazard ratio = 3.94, 2.79–5.57) or chronic disease activity (3.97, 2.90–5.45) but their absolute risk remained below 5/1000 person-years. The hazard ratio for thromboembolism among in-patients not undergoing major surgery was 1.13 (0.63–2.02), compared to 2.43 (1.20–4.92) among surgical patients, with a near doubling of absolute risk associated with surgery (59.5/1000 person-years, compared with 31.1 without surgery). The absolute risk remained elevated within six weeks after leaving hospital (18.6/1000 person-years in inflammatory bowel disease patients after surgery). Conclusions: Inflammatory bowel disease patients are at an increased risk of venous thromboembolism. Absolute risks are raised during active disease, when in hospital, and after leaving hospital following major surgery

Viral Immune signatures from cerebrospinal fluid extracellular vesicles and particles in HAM and other chronic neurological diseases

Background and objectivesExtracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral components. As such, EVPs can play not only a direct role in the development and progression of disease but can also be used as biomarkers. Here, we characterized immune signatures of EVPs from the cerebrospinal fluid (CSF) of individuals with HTLV-1-associated myelopathy (HAM), other chronic neurologic diseases, and healthy volunteers (HVs) to determine potential indicators of viral involvement and mechanisms of disease.MethodsWe analyzed the EVPs from the CSF of HVs, individuals with HAM, HTLV-1-infected asymptomatic carriers (ACs), and from patients with a variety of chronic neurologic diseases of both known viral and non-viral etiologies to investigate the surface repertoires of CSF EVPs during disease.ResultsSignificant increases in CD8+ and CD2+ EVPs were found in HAM patient CSF samples compared to other clinical groups (p = 0.0002 and p = 0.0003 compared to HVs, respectively, and p = 0.001 and p = 0.0228 compared to MS, respectively), consistent with the immunopathologically-mediated disease associated with CD8+ T-cells in the central nervous system (CNS) of HAM patients. Furthermore, CD8+ (p < 0.0001), CD2+ (p < 0.0001), CD44+ (p = 0.0176), and CD40+ (p = 0.0413) EVP signals were significantly increased in the CSF from individuals with viral infections compared to those without.DiscussionThese data suggest that CD8+ and CD2+ CSF EVPs may be important as: 1) potential biomarkers and indicators of disease pathways for viral-mediated neurological diseases, particularly HAM, and 2) as possible meditators of the disease process in infected individuals