IMPORTANCE: Giant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often ...negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV). OBJECTIVE: To analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years. MAIN OUTCOMES AND MEASURES: Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers. RESULTS: Varicella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk RR = 2.86; 95% CI, 1.75-5.31; P < .001). Extension of our earlier study revealed VZV antigen in 68 of 93 GCA-positive TAs (73%), compared with 11 of 49 normal TAs (22%) (RR = 3.26; 95% CI, 2.03-5.98; P < .001). Compared with normal TAs, VZV antigen was more likely to be present in the adventitia of both GCA-negative TAs (RR = 2.43; 95% CI, 1.82-3.41; P < .001) and GCA-positive TAs (RR = 2.03; 95% CI, 1.52-2.86; P < .001). Varicella-zoster virus antigen was frequently found in perineurial cells expressing claudin-1 around nerve bundles. Of 45 GCA-negative participants whose TAs contained VZV antigen, 1 had histopathological features characteristic of GCA, and 16 (36%) showed adventitial inflammation adjacent to viral antigen; no inflammation was seen in normal TAs. CONCLUSIONS AND RELEVANCE: In patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.
Granulomatous arteritis characterizes the pathology of giant cell arteritis, granulomatous aortitis, and intracerebral varicella zoster virus (VZV) vasculopathy. Because intracerebral VZV ...vasculopathy and giant cell arteritis are strongly associated with productive VZV infection in cerebral and temporal arteries, respectively, we evaluated human aortas for VZV antigen and VZV DNA. Using 3 different anti-VZV antibodies, we identified VZV antigen in 11 of 11 aortas with pathologically verified granulomatous arteritis, in 1 of 1 cases of nongranulomatous arteritis, and in 5 of 18 control aortas (28%) obtained at autopsy. The presence of VZV antigen in granulomatous aortitis was highly significant (P = .0001) as compared to control aortas, in which VZV antigen was never associated with pathology, indicating subclinical reactivation. VZV DNA was found in most aortas containing VZV antigen. The frequent clinical, radiological, and pathological aortic involvement in patients with giant cell arteritis correlates with the significant detection of VZV in granulomatous aortitis.
Varicella zoster virus (VZV), a human neurotropic alphaherpesvirus, becomes latent after primary infection and reactivates to produce zoster. To study VZV latency and reactivation, human trigeminal ...ganglia removed within 24 h after death were mechanically dissociated, randomly distributed into six-well tissue culture plates and incubated with reagents to inactivate nerve growth factor (NGF) or phosphoinositide 3-kinase (PI3-kinase) pathways. At 5 days, VZV DNA increased in control and PI3-kinase inhibitor-treated cultures to the same extent, but was significantly more abundant in anti-NGF-treated cultures (
p
= 0.001). Overall, VZV DNA replication is regulated in part by an NGF pathway that is PI3-kinase-independent.
Peer-to-peer support programs provide unique psychosocial and educational support for breast cancer patients. A Patient Survivor Advocacy (PSA) program was developed by the University of Wisconsin ...Breast Center (UWBC) to provide support for newly diagnosed patients from peers who had completed primary treatment. In this study, we evaluated patient, advocate, and clinician experience with the PSA program. A program matching volunteer peer advocates at least 1 year removed from primary treatment with newly diagnosed patients was developed. Peer advocates were recruited from the practices of UWBC clinicians and received in-person training on six dimensions of peer advocacy. Trained advocates were then paired based on demographic and medical history with new patients referred to the program. Survey assessment tools were distributed to assess peer advocate and patient satisfaction, as well as clinician experience. Forty patients have been matched with seven advocates, with contact largely by email (53 %) or phone (36 %). Patients and peer advocates reported satisfaction with the program. The majority of patients (92.9 %) reported that the program was “helpful” and that they would recommend the PSA program to another woman with breast cancer. All peer advocates (100 %) responded with a sense of achievement in their advocate roles. Clinicians noted challenges in referral to the program. Peer advocates can provide key emotional and psychosocial support to newly diagnosed breast cancer patients. The peer advocate, patient, and clinician feedback collected in this study will inform the future development of this program at our and peer institutions.
Purpose
This purpose of this study is to provide a case study for how the company strives to provide its employees with “new ways of working” through a culture of transformation and advancement.
...Design/methodology/approach
To demonstrate how Aflac effectively executes with strong results, Teresa focuses on three specific programs: Aflac’s Career Success Center, Upskilling Employees for the Future and Reverse Mentoring Programs.
Findings
To date, 2,000+ Aflac employees have participated, with 1,300 obtaining promotions or changing their career direction to something more suited to their goals and talents.
Originality/value
The importance of transformation and advancement within a company.
Objectives The aim of this study was to characterize a novel conjugative transposon Tn6009 composed of a Tn916 linked to a Staphylococcus aureus mer operon in representative Gram-positive and ...Gram-negative bacteria isolated in Nigeria and Portugal. Methods Eighty-three Gram-positive and 34 Gram-negative bacteria were screened for the presence of the Tn6009 using DNA–DNA hybridization, PCR, hybridization of PCR products, sequencing and mating experiments by established procedures. Results Forty-three oral and 23 urine Gram-negative and Gram-positive isolates carried the Tn6009. Sequencing was performed to verify the direct linkage between the mer resistance genes and the tet(M) gene. A Nigerian Klebsiella pneumoniae, isolated from a urinary tract infection patient, and one commensal isolate from each of the other Tn6009-positive genera, Serratia liquefaciens, Pseudomonas sp., Enterococcus sp. and Streptococcus sp. isolated from the oral and urine samples of healthy Portuguese children, were able to act as donors and conjugally transfer the Tn6009 to the Enterococcus faecalis JH2-2 recipient, resulting in tetracycline- and mercury-resistant E. faecalis transconjugants. Conclusions This study reports a novel non-composite conjugative transposon Tn6009 containing a Tn916 element linked to an S. aureus mer operon carrying genes coding for inorganic mercury resistance (merA), an organic mercury resistance (merB), a regulatory protein (merR) and a mercury transporter (merT). This transposon was identified in 66 isolates from two Gram-positive and three Gram-negative genera and is the first transposon in the Tn916 family to carry the Gram-positive mer genes directly linked to the tet(M) gene.
Background: Multiple mechanisms regulate cancer-associated telomerase activity at the level of human telomerase reverse transcriptase
(hTERT) transcription which may serve as novel targets for ...anticancer approaches. Materials and Methods: The effects of prolonged
all-trans retinoic acid (ATRA) exposure on hTERT regulation in estrogen receptor-negative SK-BR-3 breast cancer cells were
examined. Results: ATRA had a profound effect on the morphology and proliferation rate of the SK-BR-3 cells. ATRA also hindered
the ability of these cancer cells to grow independently, rendering them more like normal somatic cells. The effect of ATRA
on the decrease of telomerase activity was found to be associated with a rapid decrease in histone H3-lysine 9 acetylation
(H3-K9-Ac) of the hTERT promoter. Extended-exposure to ATRA in these cells also caused the initiation of a putative compensatory
mechanism, counteracting the induced surge in apoptosis. Conclusion: A rapid decrease of H3-K9 acetylation at the hTERT promoter
could be an important mechanism by which ATRA shuts down telomerase activity and mediates its antitumor effects in estrogen
receptor-negative breast cancer cells.
Abstract only Background and Purpose: Education for stroke survivors and their caregivers is an essential part of the plan of care. Often times, only written materials are provided to this population ...which can be difficult due to varying levels of cognitive function and aphasia after a stroke. Our project sought to find a tool that would help to give education in a different format to help decrease our readmission rates. Process: A group of nurses and the stroke committee at SwedishAmerican evaluated several types of education that exists for stroke survivors and their caregivers. It was decided that the educational video “You’ve Had a Stroke, Now What?” contained the information the group that would be most beneficial to this population. Nurses provided a copy of the educational DVD to stroke survivors prior to discharge to take home with them. They also conducted a survey during their follow-up discharge phone calls to ensure that they had the DVD and if they did not a copy was sent to their home. Results: Pre-data showed that our 7 day readmission rates for stroke ranged from 3.13-7.69%. After implementation of providing the stroke education DVD to patients and their families the 7 day readmission rates dropped to 0%. Conclusions: Health disparities, such as stroke, can cause tremendous anxiety and are taxing on not only the stroke survivor, but the caregivers as well. Using the “You’ve Had a Stroke, Now What?” has proven to be a beneficial educational tool that can help to overcome some of the initial anxiety and stress that is often encountered as this population is learning to adapt upon discharge to home from the hospital setting and help to prevent unnecessary readmissions.
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