Comprehensive Comparison of Baculoviral and Plasmid Gene Delivery in Mammalian Cells.

(1) Recombinant protein production in mammalian cells is either based on transient transfection processes, often inefficient and underlying high batch-to-batch variability, or on laborious generation of stable cell lines. Alternatively, BacMam, a transduction process using the baculovirus, can be employed. (2) Six transfecting agents were compared to baculovirus transduction in terms of transient and stable protein expression characteristics of the model protein ACE2-eGFP using HEK293-6E, CHO-K1, and Vero cell lines. Furthermore, process optimization such as expression enhancement using sodium butyrate and TSA or baculovirus purification was assessed. (3) Baculovirus transduction efficiency was superior to all transfection agents for all cell lines. Transduced protein expression was moderate, but an 18-fold expression increase was achieved using the enhancer sodium butyrate. Ultracentrifugation of baculovirus from a 3.5 L bioreactor significantly improved the transduction efficiency and protein expression. Stable cell lines were obtained with each baculovirus transduction, yet stable cell line generation after transfection was highly unreliable. (4) This study demonstrated the superiority of the BacMam platform to standard transfections. The baculovirus efficiently transduced an array of cell lines both transiently and stably and achieved the highest efficiency for all tested cell lines. The feasibility of the scale-up of baculovirus production was demonstrated and the possibility of baculovirus purification was successfully explored.

Urbanization reduces gut bacterial microbiome diversity in a specialist ground beetle, Carabus convexus.

Urbanization is rapidly shaping and transforming natural environments, creating networks of modified land types. These urbanization-driven modifications lead to local extinctions of several species, but the surviving ones also face numerous novel selection pressures, including exposure to pollutants, habitat alteration, and shifts in food availability and diversity. Based on the assumption that the environmental pool of microorganisms is reduced in urban habitats due to habitat alteration, biodiversity loss, and pollution, we hypothesized that the diversity of bacterial microbiome in digestive tracts of arthropods would be lower in urban than rural habitats. Investigating the gut bacterial communities of a specialist ground beetle, Carabus convexus, in forested rural versus urban habitats by next generation high-throughput sequencing of the bacterial 16S rRNA gene, we identified 3839 bacterial amplicon sequence variants. The composition of gut bacterial samples did not significantly differ by habitat (rural vs. urban), sex (female vs. male), sampling date (early vs. late spring), or their interaction. The microbiome diversity (evaluated by the Rényi diversity function), however, was higher in rural than urban adults. Our findings demonstrate that urbanization significantly reduced the diversity of the gut bacterial microbiome in C. convexus.

CYP46A1 activation by low-dose efavirenz enhances brain cholesterol metabolism in subjects with early Alzheimer's disease.

BACKGROUND: Efavirenz is an anti-HIV drug, and cytochrome P450 46A1 (CYP46A1) is a CNS-specific enzyme that metabolizes cholesterol to 24-hydroxycholesterol (24HC). We have previously shown that allosteric CYP46A1 activation by low-dose efavirenz in a transgenic mouse model of Alzheimer's disease (AD) enhanced both cholesterol elimination and turnover in the brain and improved animal performance in memory tests. Here, we sought to determine whether CYP46A1 could be similarly activated by a low-dose efavirenz in human subjects.  METHODS: This pilot study enrolled 5 subjects with early AD. Participants were randomized to placebo (n = 1) or two daily efavirenz doses (50 mg and 200 mg, n = 2 for each) for 20 weeks and evaluated for safety and CYP46A1 target engagement (plasma 24HC levels). A longitudinal mixed model was used to ascertain the statistical significance of target engagement. We also measured 24HC in CSF and conducted a unique stable isotope labeling kinetics (SILK) study with deuterated water to directly measure CYP46A1 activity changes in the brain. RESULTS: In subjects receiving efavirenz, there was a statistically significant within-group increase (P ≤ 0.001) in the levels of plasma 24HC from baseline. The levels of 24HC in the CSF of subjects on the 200-mg dose of efavirenz were also increased. Target engagement was further supported by the labeling kinetics of 24HC by deuterated water in the SILK study. There were no serious adverse effects in any subjects. CONCLUSIONS: Our findings suggest efavirenz target engagement in human subjects with early AD. This supports the pursuit of a larger trial for further determination and confirmation of the efavirenz dose that exerts maximal enzyme activation, as well as evaluation of this drug's effects on AD biomarkers and clinical symptomatology. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03706885.

Urban Individuals of Three Rove Beetle Species Are Not More Exploratory or Risk-Taking Than Rural Conspecifics.

Urbanization is creating changes in environmental and habitat conditions, as well as creating disturbance and threats to urban-associated species. Some traits, such as high exploratory and risk-taking behavior, are beneficial to allow colonization of urban habitats and coping with urbanization-derived pressures. In this study the exploratory and risk-taking behavior of rural and urban individuals of three forest-associated rove beetle species were tested during their main reproductive period by five frequently used behavioral measures. Individuals of all studied species were similarly ranked by all behavioral measures, indicating that the studied rove beetles responded consistently in the different contexts. However, the behavior of beetles was consistent over time for all/most studied species only by using two measures of exploratory behavior. These provide evidence for the existence of the exploratory dimension of personality in rove beetles. We found a higher exploratory behavior in males than females in Ocypus nitens which can be explained by the active searching of males for mating partners. There were no urbanization-related differences in the exploratory behavior of individuals, suggesting that behavioral changes (being more exploratory) may not yield additional fitness benefits in these rove beetle species with good dispersal capacity.

Mitophagy Mediates the Beige to White Transition of Human Primary Subcutaneous Adipocytes Ex Vivo.

Brown and beige adipocytes have multilocular lipid droplets, express uncoupling protein (UCP) 1, and promote energy expenditure. In rodents, when the stimulus of browning subsides, parkin-dependent mitophagy is activated and dormant beige adipocytes persist. In humans, however, the molecular events during the beige to white transition have not been studied in detail. In this study, human primary subcutaneous abdominal preadipocytes were differentiated to beige for 14 days, then either the beige culture conditions were applied for an additional 14 days or it was replaced by a white medium. Control white adipocytes were differentiated by their specific cocktail for 28 days. Peroxisome proliferator-activated receptor γ-driven beige differentiation resulted in increased mitochondrial biogenesis, UCP1 expression, fragmentation, and respiration as compared to white. Morphology, UCP1 content, mitochondrial fragmentation, and basal respiration of the adipocytes that underwent transition, along with the induction of mitophagy, were similar to control white adipocytes. However, white converted beige adipocytes had a stronger responsiveness to dibutyril-cAMP, which mimics adrenergic stimulus, than the control white ones. Gene expression patterns showed that the removal of mitochondria in transitioning adipocytes may involve both parkin-dependent and -independent pathways. Preventing the entry of beige adipocytes into white transition can be a feasible way to maintain elevated thermogenesis and energy expenditure.

Are There Personality Differences between Rural vs. Urban-Living Individuals of a Specialist Ground Beetle, Carabus convexus?

The world-wide, rapid urbanization is leading to substantial changes in environmental and habitat conditions. These changes, as well as disturbances accompanying urbanization have considerable effects at various levels of the biological organization on wildlife. Understanding behavioral responses to such changes is essential for identifying which organisms may successfully adapt to the altered conditions. In this study, individuals of a forest specialist ground beetle, Carabus convexus, from rural and urban forest patches were tested for their exploratory and risk-taking behavior. Beetles responded consistently in the different contexts; furthermore, by behaving consistently over time, demonstrated that they had personalities. Agglomerative cluster analysis identified two groups of behavioral traits: the exploratory and the risk-taking dimension of personality. Urban females were significantly more exploratory than urban males which can be an adaptation to find high quality food needed to mature eggs in urban habitats, as well as to select favorable microsites for oviposition. Moreover, urban females and males showed more risk-taking behavior than rural females. Urban beetles with more risk-taking behavior may be better able to cope with frequent urbanization-driven disturbance events.

Differences in Life History Traits in Rural vs. Urban Populations of a Specialist Ground Beetle, Carabus convexus.

Urbanization is increasing worldwide and causes substantial changes in environmental parameters, generating various kinds of stress on arthropods, with several harmful consequences. We examined a forest specialist ground beetle, Carabus convexus, in forested habitats to evaluate the changes in four important life history traits between rural and urban populations. Analyzing beetles from the overwintered cohort in their first breeding season, we found no significant differences in body length or body mass between the rural and urban individuals. Body condition, judged by fat reserve scores, was similarly poor in both habitats, indicating that beetles were not able to accumulate substantial fat reserves at either habitat. Females with ripe eggs in their ovaries were first captured at the same time in both areas. The number of ripe eggs, however, was significantly higher in females of the low-density urban population (6.13 eggs/female) than in those of the high-density rural population (4.14 eggs/female), indicating density-dependent fecundity. Altered environmental and habitat conditions by urbanization, however, seemed to cause high mortality during egg hatching and/or larval development, preventing the growth of the urban population to the level of rural one.

Thermogenic Activation Downregulates High Mitophagy Rate in Human Masked and Mature Beige Adipocytes.

Thermogenic brown and beige adipocytes oxidize metabolic substrates producing heat, mainly by the mitochondrial uncoupling protein UCP1, and can thus counteract obesity. Masked beige adipocytes possess white adipocyte-like morphology, but can be made thermogenic by adrenergic stimuli. We investigated the regulation of mitophagy upon thermogenic activation of human masked and mature beige adipocytes. Human primary abdominal subcutaneous adipose-derived stromal cells (hASCs) and Simpson-Golabi-Behmel syndrome (SGBS) preadipocytes were differentiated to white and beige adipocytes, then their cAMP-induced thermogenic potential was assessed by detecting increased expressions of UCP1, mitochondrial DNA content and respiratory chain complex subunits. cAMP increased the thermogenic potential of white adipocytes similarly to beige ones, indicating the presence of a masked beige population. In unstimulated conditions, a high autophagic flux and mitophagy rates (demonstrated by LC3 punctae and TOM20 co-immunostaining) were observed in white adipocytes, while these were lower in beige adipocytes. Silencing and gene expression experiments showed that the ongoing mitophagy was Parkin-independent. cAMP treatment led to the downregulation of mitophagy through PKA in both types of adipocytes, resulting in more fragmented mitochondria and increased UCP1 levels. Our data indicates that mitophagy is repressed upon encountering a short-term adrenergic stimulus, as a fast regulatory mechanism to provide high mitochondrial content for thermogenesis.

Generation and Analysis of Pluripotent Stem Cell-Derived Cardiomyocytes and Endothelial Cells for High Content Screening Purposes.

Human-induced pluripotent stem cells (hiPSCs) and their differentiated derivatives became a new, promising source for in vitro screening techniques. Cell lines derived from healthy individuals can be applied for drug safety testing, while patient-derived cells provide a platform to model diseases in vitro and can be used as a tool for personalized medicine including specific drug efficacy testing and identification of new pharmacological targets as well as for tailoring pharmacological therapies. Efficient differentiation protocols yielding cardiomyocytes or endothelial cells derived from iPSCs have been developed recently. Phenotypic characterization and gene expression profiling of these derivatives can reveal clues for developmental and pathological questions. Moreover, functional analysis and cell-based assays using automated fluorescence imaging platform and high content analysis characterize cell type-specific profiles of hiPSC-derived cardiomyocytes (hiPSC-CM) and endothelial cells (hiPSC-EC) at the cellular and subcellular levels. This can be utilized in a platform which can provide multiple endpoint profiles of candidate compounds.

Clinical and molecular markers in retinal detachment-From hyperreflective points to stem cells and inflammation.

PURPOSE: Retinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment. METHODS: 12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ± 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin). RESULTS: OCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer-their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo, the SRF doubled their capacity for engulfing dying RPEs. CONCLUSIONS: Fresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina.

Circulating Relaxin-1 Level Is a Surrogate Marker of Myocardial Fibrosis in HFrEF.

Introduction: Relaxin-1 (RLN1) has emerged as a possible therapeutic target in myocardial fibrosis due to its anti-fibrotic effects. Previous randomized clinical trials investigated therapeutic role of exogenous relaxin in patients with acute-on-chronic heart failure (HF) and failed to meet clinical endpoints. Here, we aimed to assess endogenous, circulating RLN1 levels in patients with heart failure with reduced ejection fraction (HFrEF) of ischemic origin. Furthermore, we analyzed relation of RLN1 and left ventricular diastolic function, left and right ventricular fibrosis, and invasive hemodynamic measurements. Unique feature of our study is the availability of ex vivo human myocardial tissue. Methods: Human myocardial samples were available from the Transplantation Biobank of the Heart and Vascular Center at Semmelweis University after local ethical approval and informed consent of all participants (n = 47). Tissue was collected immediately after heart explantations; peripheral blood was collected before induction of anesthesia. Myocardial sections were stained for Masson's trichrome and Picrosirius red staining to quantify fibrosis. Medical records were analyzed (ECG, anthropometry, blood tests, medication, echocardiography, and invasive hemodynamic measurements). Results: Average RLN1 levels in HFrEF population were significantly higher than measured in age and gender matched healthy control human subjects (702 ± 283 pg/ml in HFrEF vs. 44 ± 27 pg/ml in control n = 47). We found a moderate inverse correlation between RLN1 levels and degree of myocardial fibrosis in both ventricles (r = -0.357, p = 0.014 in the right ventricle vs. r = -0.321, p = 0.028 in the left ventricle with Masson's trichrome staining). Parallel, a moderate positive correlation was found in left ventricular diastolic function (echocardiography, E/A wave values) and RLN1 levels (r = 0.456, p = 0.003); a negative correlation with RLN1 levels and left ventricular end-systolic diameter (r = -0.373, p = 0.023), and diastolic pulmonary artery pressure (r = -0.894, p < 0.001). RLN1 levels showed moderate correlation with RLN2 levels (r = 0.453, p = 0.0003). Conclusion: Increased RLN1 levels were accompanied by lower myocardial fibrosis rate, which is a novel finding in our patient population with coronary artery disease and HFrEF. RLN1 can have a biomarker role in ventricular fibrosis; furthermore, it may influence hemodynamic and vasomotor activity via neurohormonal mechanisms of action. Given these valuable findings, RLN1 may be targeted in anti-fibrotic therapeutics and in perioperative care of heart transplantation.

Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium-Role in Dead Cell Clearance and Inflammation.

Inefficient removal of dying retinal pigment epithelial (RPE) cells by professional phagocytes can result in debris formation and development of age-related macular degeneration (AMD). Chronic oxidative stress and inflammation play an important role in AMD pathogenesis. Only a few well-established in vitro phagocytosis assay models exist. We propose human embryonic stem cell-derived-RPE cells as a new model for studying RPE cell removal by professional phagocytes. The characteristics of human embryonic stem cells-derived RPE (hESC-RPE) are similar to native RPEs based on their gene and protein expression profile, integrity, and barrier properties or regarding drug transport. However, no data exist about RPE death modalities and how efficiently dying hESC-RPEs are taken upby macrophages, and whether this process triggers an inflammatory responses. This study demonstrates hESC-RPEs can be induced to undergo anoikis or autophagy-associated cell death due to extracellular matrix detachment or serum deprivation and hydrogen-peroxide co-treatment, respectively, similar to primary human RPEs. Dying hESC-RPEs are efficiently engulfed by macrophages which results in high amounts of IL-6 and IL-8 cytokine release. These findings suggest that the clearance of anoikic and autophagy-associated dying hESC-RPEs can be used as a new model for investigating AMD pathogenesis or for testing the in vivo potential of these cells in stem cell therapy.

Patterns in the distribution and directional asymmetry of fleas living on the northern white-breasted hedgehog Erinaceus roumanicus.

Fleas infecting northern white-breasted hedgehogs, Erinaceus roumanicus (Barrett-Hamilton), collected from 2009-2011 in Budapest (Hungary) were studied. A total of 305 white-breasted hedgehogs were captured and 1,251 fleas were collected. The flea community comprised two species, the hedgehog flea Archaeopsylla erinacei (Bouche, 1835) and the dog flea Ctenocephalides canis (Curtis, 1826), although the latter was only found on three hedgehogs. Fleas were found on half of the host specimens (51%; n = 156) where their distribution was strongly aggregated. The sex ratio of A. erinacei was biased towards females and was correlated with host size. Interestingly, the sex ratio of fleas became more equal on heavier hosts. It had been expected that, under high competition, the sex ratio would be female biased because it is known that female ectoparasites dominate on poorer hosts. The body size of a random sample of 200 fleas (100 female and 100 male) was measured under a microscope. The analyses showed directional asymmetry in two features - the distance between the top of the head and the eye, and head length. In this two body traits the left side was significantly greater than right side in both sexes of A. erinacei. Our data shed light on the complex nature of the flea population infecting northern white-breasted hedgehogs in an urban area.

Induction and Differentiation of IL-10-Producing Regulatory B Cells from Healthy Blood Donors and Rheumatoid Arthritis Patients.

The most important feature of B cells is the production of Abs upon activation; additionally, B cells produce pro- and anti-inflammatory cytokines in response to certain stimuli. IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) that suppress autoimmune and inflammatory responses. B cells play a crucial role in the development and maintenance of the chronic inflammatory autoimmune disease rheumatoid arthritis (RA); however, controversial data are available on IL-10- producing Bregs in RA. Our aim was to identify the optimal conditions that induce IL-10+ Bregs and, furthermore, to shed light on the signaling pathways that are responsible for their expansion. The results show that dual stimulation by CpG and CD40L for 48 h is optimal for IL-10 induction, and this can be synergistically boosted by IL-21. We identified the CD19+CD27+ memory B cell population as the major source of IL-10+ Bregs. We detected significantly fewer CD19+CD27+IL-10+ cells in RA patients compared with healthy controls, and these were functionally defective in suppressing IFN-γ production by CD4+ T cells in coculture. IL-21 drastically increased the number of IL-10+ Bregs within the CD19+CD27+ and CD19+CD27- populations; furthermore, it induced the appearance of IL-10+Blimp-1+ plasmablasts. Monitoring the phosphorylation of key signaling molecules revealed that activation of ERK, p38, and CREB is indispensable for the induction of IL-10 production, whereas phosphorylation of STAT3 further enhances IL-10 expression in human Bregs. We conclude that CREB and STAT3 are the key transcription factors responsible for the expansion and differentiation of human IL-10-producing Bregs.

Medicaments, Therapies and their Prices in the Inventary of the Family Batthyány 1650-1654. / Patikaszerek, gyógymódok és áraik a Batthyány család inventáriumának irataiból 1650-1654.

Author - after this short introduction and analysis - published below the pharmaceutical bills sent by various pharmacists for Count Adam Batthyány and for his wife Katalin Aurora For- mentini during the period 1650-1654. Based on these bills author identifies the illnesses to be cured, the names of pharmacists and the medicaments made by them, including their prices as well. The carefully written bills recorded the names of the medicaments used both in German and Latin. The prices partly proved to be astonishingly high, so author concludes that services of pharmacists that time were utilized exclusively by the rich. Analysing the bills we can identify the illnesses of the Batthyány family and also those of the Turks imprisoned in their castle, whose curing served the economic interest of the count.

Triamcinolone regulated apopto-phagocytic gene expression patterns in the clearance of dying retinal pigment epithelial cells. A key role of Mertk in the enhanced phagocytosis.

BACKGROUND: The apopto-phagocytic gene expression patterns during clearance of dying cells in the retina and the effect of triamcinolone (TC) upon these processes have relevance to development of age-related macular degeneration (AMD). METHODS: ARPE-19 cells and primary human retinal pigment epithelium (hRPE) were induced to undergo cell death by anoikis and the clearance of these cells by living hRPE/ARPE-19 or human monocyte-derived macrophages (HMDMs) in the presence or absence of TC was quantified by flow cytometry. TaqMan low-density gene expression array determining known markers of phagocytosis and loss-of-function studies on selected apopto-phagocytic genes was carried out in HMDM engulfing anoikic cells. RESULTS: The glucocorticoid TC had a profound phagocytosis-enhancing effect on HMDM engulfing anoikic ARPE-19 or hRPE cells, causing a selective upregulation of the Mer tyrosine kinase (MERTK) receptor, while decreasing the expression of the AXL receptor tyrosine kinase and thrombospondin-1 (THSB-1). The key role of the MERTK could be demonstrated in HMDM engulfing dying cells using gene silencing as well as blocking antibodies. Similar pathways were found upregulated in living ARPE-19 engulfing anoikic ARPE-19 cells. Gas6 treatment enhanced phagocytosis in TC-treated HMDMs. CONCLUSIONS: Specific agonists of the Mertk receptor may have a potential role as phagocytosis enhancers in the retina and serve as future targets for AMD therapy. GENERAL SIGNIFICANCE: The use of Gas6 as enhancer of retinal phagocytosis via the MerTK receptor, alone or in combination with other specific ligands of the tyrosine kinase receptors' family may have a potential role in AMD therapy.

Vector-borne agents detected in fleas of the northern white-breasted hedgehog.

This is the first large-scale molecular investigation of fleas from a geographically widespread and highly urbanized species, the northern white-breasted hedgehog. In this study, 759 fleas (the majority were Archaeopsylla erinacei) collected from 134 hedgehogs were molecularly analyzed individually or in pools for the presence of three groups of vector-borne pathogens. All flea samples were positive for rickettsiae: In two samples (1.5%) Rickettsia helvetica and in 10% of the others a novel rickettsia genotype were identified. Additionally, Bartonella henselae (the causative agent of cat scratch disease in humans) was demonstrated in one flea (0.7%), and hemoplasmas of the hemofelis group were identified in seven other samples (5.2%). The findings of vector-borne agents not detected before in A. erinacei fleas broaden the range of those diseases of veterinary-medical importance, of which hedgehogs may play a role in the epidemiology.

Using a patient internet portal to prevent adverse drug events: a randomized, controlled trial.

OBJECTIVES: Adverse drug events (ADEs) are common in ambulatory care and may result from poor patient-physician communication about medication-related symptoms. A module was developed within an electronic patient portal that was designed to enhance communication about medication symptoms and, in turn, reduce ADEs and health-care utilization. METHODS: The researchers conducted a randomized, controlled clinical trial of MedCheck, an automated electronic message generated in a patient Internet portal. MedCheck asked intervention patients if they had filled a recent prescription and if they had experienced any problems with the medication. Patients' responses were forwarded automatically to primary care physicians. The study enrolled 375 intervention patients and 363 controls. After 3 months, the investigators reviewed patients' medical records and conducted telephone interviews to identify ADEs and to assess health-care utilization. RESULTS: Among the 375 intervention patients, 184 (49%) responded to at least 1 MedCheck message. Patients reported 52 unfilled prescriptions and 56 medication problems. Patients responded to 72% of messages within 1 day. There was no statistically significant difference between intervention and control groups in the rate of ADEs, preventable or ameliorable ADEs, serious ADEs, or in subjects' health-care utilization. CONCLUSIONS: Internet portals have the potential to enhance patient-physician communication. However, additional development is required to demonstrate that such interventions can improve medication safety or health-care utilization.

Massage therapy for patients with metastatic cancer: a pilot randomized controlled trial.

OBJECTIVES: The study objectives were to determine the feasibility and effects of providing therapeutic massage at home for patients with metastatic cancer. DESIGN: This was a randomized controlled trial. SETTINGS/LOCATION: Patients were enrolled at Oncology Clinics at a large urban academic medical center; massage therapy was provided in patients' homes. SUBJECTS: Subjects were patients with metastatic cancer. INTERVENTIONS: There were three interventions: massage therapy, no-touch intervention, and usual care. OUTCOME MEASURES: Primary outcomes were pain, anxiety, and alertness; secondary outcomes were quality of life and sleep. RESULTS: In this study, it was possible to provide interventions for all patients at home by professional massage therapists. The mean number of massage therapy sessions per patient was 2.8. A significant improvement was found in the quality of life of the patients who received massage therapy after 1-week follow-up, which was not observed in either the No Touch control or the Usual Care control groups, but the difference was not sustained at 1 month. There were trends toward improvement in pain and sleep of the patients after therapeutic massage but not in patients in the control groups. There were no serious adverse events related to the interventions. CONCLUSIONS: The study results showed that it is feasible to provide therapeutic massage at home for patients with advanced cancer, and to randomize patients to a no-touch intervention. Providing therapeutic massage improves the quality of life at the end of life for patients and may be associated with further beneficial effects, such as improvement in pain and sleep quality. Larger randomized controlled trials are needed to substantiate these findings.