Antiviral Effects of Artesunate on Polyomavirus BK Replication in Primary Human Kidney Cells

Polyomavirus BK (BKV) causes polyomavirus-associated nephropathy (PyVAN) and hemorrhagic cystitis (PyVHC) in renal and bone marrow transplant patients, respectively. Antiviral drugs with targeted activity against BKV are lacking. Since the antimalarial drug artesunate was recently demonstrated to have antiviral activity, the possible effects of artesunate on BKV replication in human primary renal proximal tubular epithelial cells (RPTECs), the host cells in PyVAN, were explored. At 2 h postinfection (hpi), RPTECs were treated with artesunate at concentrations ranging from 0.3 to 80 μM. After one viral replication cycle (approximately 72 hpi), the loads of extracellular BKV DNA, reflecting viral progeny production, were reduced in a concentration-dependent manner. Artesunate at 10 μM reduced the extracellular BKV load by 65%; early large T antigen mRNA and protein expression by 30% and 75%, respectively; DNA replication by 73%; and late VP1 mRNA and protein expression by 47% and 64%, respectively. Importantly, the proliferation of RPTECs was also inhibited in a concentration-dependent manner. At 72 hpi, artesunate at 10 μM reduced cellular DNA replication by 68% and total metabolic activity by 47%. Cell impedance and lactate dehydrogenase measurements indicated a cytostatic but not a cytotoxic mechanism. Flow cytometry and 5-ethynyl-2′-deoxyuridine incorporation revealed a decreased number of cells in S phase and suggested cell cycle arrest in G₀ or G₂ phase. Both the antiproliferative and antiviral effects of artesunate at 10 μM were reversible. Thus, artesunate inhibits BKV replication in RPTECs in a concentration-dependent manner by inhibiting BKV gene expression and genome replication. The antiviral mechanism appears to be closely connected to cytostatic effects on the host cell, underscoring the dependence of BKV on host cell proliferative functions.     

The role of sex in health-related quality of life after cardiac surgery: a prospective study

BACKGROUND: To assess health-related quality of life (HRQOL) in patients after cardiac surgery with emphasis on sex differences. DESIGN AND METHODS: Between September 2004 and September 2005, 534 patients (413 males and 121 females) were consecutively included. HRQOL was measured by the short-form 36 (SF-36) before surgery with follow-up 6 and 12 months after surgery. RESULTS: Five hundred and twenty-one patients were alive after 12 months, 462 (89%) and 465 (89.4%) responded after 6 and 12 months, respectively. Female patients had less favorable scores than male patients on most subscales of the SF-36 both before and after surgery. Both male and female patients improved substantially after surgery, but female patients reported significantly less improvement on two of eight subscales of the SF-36; role emotional and bodily pain. CONCLUSION: The study demonstrates that there are sex differences concerning HRQOL both before and after cardiac surgery. A clear overall improvement in HRQOL over the first year after cardiac surgery, more specifically during the first 6 months for both sexes was found.     

Associations Between Adherence to the Physical Activity and Exercise Program Applied in the LAST Study and Functional Recovery After Stroke

ObjectiveTo investigate the associations between participants’ adherence to a physical activity and exercise program after stroke and functional recovery 18 months after inclusion.DesignSecondary analyses of the intervention arm in the multisite randomized controlled trial Life After Stroke (LAST).SettingPrimary health care services in 3 Norwegian municipalities.ParticipantsOf the participants enrolled (N=380), 186 (48.9%) were randomized to the intervention. The study sample comprised community dwelling individuals included 3 months after stroke, with mean age of 71.7 ± 11.9 years and 82 (44.1%) women. According to the National Institutes of Health Stroke Scale, 97.3% were diagnosed as having mild (National Institutes of Health Stroke Scale<8) and 2.7% with moderate (8-16 on the National Institutes of Health Stroke Scale) stroke.InterventionMonthly coaching by physiotherapists encouraging participants to adhere to 30 minutes of daily physical activity and 45-60 minutes of weekly exercise.Main Outcome MeasuresThe primary outcome was Motor Assessment Scale (MAS). Secondary outcome measures were 6-minute walk test, Timed Up and Go (TUG), Berg Balance Scale (BBS), and the physical domains of the Stroke Impact Scale (SIS). Adherence was assessed by combining participants’ training diaries and physiotherapists’ reports.ResultsThe relationship between adherence and functional recovery was analyzed with simple and multiple linear regression models. Adjusted for age, sex, dependency, and cognition, results showed statistically significant associations between adherence and functional outcomes after 18 months, as measured by MAS, TUG, BBS, and SIS (P≤.026).ConclusionsIncreased adherence to physical activity and exercise was associated with improved functional recovery after mild to moderate stroke. This emphasizes the importance of developing adherence-enhancing interventions. Dose-response studies are recommended for future research.     

A pragmatist approach to the hope discourse in health care research

Hope is a central concept in nursing and other fields of health care. However, there is no consensus about the concept of hope. We argue that seeking consensus is futile given the multifaceted and multidimensional nature of the concept, but instead we encourage in‐depth studies of the assumptions behind talk about hope in specific contexts. Our approach to the ‘science of hope’ is inspired by philosophical pragmatism. We argue that hope is a concept that opens different rooms for action in different contexts and that accordingly, all hope interventions are contextually sensitive. Careful attention to how the relative positions and power of nurses and patients influence what can be inferred from their different ways of talking about hope may make hopeful conversations more meaningful in health care relationships.