Two-way communication with neural networks in vivo using focused light

Neuronal networks process information in a distributed, spatially heterogeneous manner that transcends the layout of electrodes. In contrast, directed and steerable light offers the potential to engage specific cells on demand. We present a unified framework for adapting microscopes to use light for simultaneous in vivo stimulation and recording of cells at fine spatiotemporal resolutions. We use straightforward optics to lock onto networks in vivo, to steer light to activate circuit elements and to simultaneously record from other cells. We then actualize this 'free' augmentation on both an 'open' two-photon microscope and a leading commercial one. By following this protocol, setup of the system takes a few days, and the result is a noninvasive interface to brain dynamics based on directed light, at a network resolution that was not previously possible and which will further improve with the rapid advance in development of optical reporters and effectors. This protocol is for physiologists who are competent with computers and wish to extend hardware and software to interface more fluidly with neuronal networks.National Institutes of Health (U.S.) (Postdoctoral Fellowship)Simons Foundation (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Predoctoral Fellowship)National Institutes of Health (U.S.)Simons Foundatio

Seizure prediction : ready for a new era

Acknowledgements: The authors acknowledge colleagues in the international seizure prediction group for valuable discussions. L.K. acknowledges funding support from the National Health and Medical Research Council (APP1130468) and the James S. McDonnell Foundation (220020419) and acknowledges the contribution of Dean R. Freestone at the University of Melbourne, Australia, to the creation of Fig. 3.Peer reviewedPostprin

Distinct Campylobacter fetus lineages adapted as livestock pathogens and human pathobionts in the intestinal microbiota

Campylobacter fetus is a venereal pathogen of cattle and sheep, and an opportunistic human pathogen. It is often assumed that C. fetus infection occurs in humans as a zoonosis through food chain transmission. Here we show that mammalian C. fetus consists of distinct evolutionary lineages, primarily associated with either human or bovine hosts. We use whole-genome phylogenetics on 182 strains from 17 countries to provide evidence that C. fetus may have originated in humans around 10,500 years ago and may have "jumped" into cattle during the livestock domestication period. We detect C. fetus genomes in 8% of healthy human fecal metagenomes, where the human-associated lineages are the dominant type (78%). Thus, our work suggests that C. fetus is an unappreciated human intestinal pathobiont likely spread by human to human transmission. This genome-based evolutionary framework will facilitate C. fetus epidemiology research and the development of improved molecular diagnostics and prevention schemes for this neglected pathogen

E-health in heart failure

Aim: The aim of this thesis was to study the effect and the cost-effectiveness of two e-health interventions, of which one included replacement of usual care by e-health, on self-care in heart failure (HF) patients by conducting the e-Vita HF study. In addition, we evaluated the interpretation of the self-care results of the study and their generalizability. Finally, we described the worldwide use of one of the e-health tools studied. Methods: The e-Vita HF study was a three arm randomized controlled trial, with 12 months follow-up. Group 1 received usual care; group 2 usual care plus the heartfailurematters.org website, an information website on HF; and group 3 received the e-health adjusted care pathway with a platform for disease management, including telemonitoring facilities, which replaced routine consultations with HF nurses at the outpatient clinic. Patients were included if they had a confirmed diagnosis of HF for at least 3 months. The primary outcome was self-care as measured by the European Heart Failure Self-care Behavioural scale (EHFScB scale). Secondary outcomes were hospitalisation, mortality and cost-effectiveness. Results: In total, 450 patients participated from 9 Dutch HF outpatient clinics. The mean age was 66.8 (SD 11.0) years, 74.2% were male, and 78.8% classified as NYHA I or II at baseline. After 3 months follow-up, the mean score on the self-care scale was significantly higher in the groups using the website and the adjusted care pathway compared to usual care: 73.5 vs. 70.8 (difference 2.7, 95%CI 0.6 – 6.2), and 78.2 vs. 70.8 (difference 7.4, 95%CI 3.8 – 9.4), respectively. The effect attenuated during follow-up into no differences between the groups after one year. Hospitalisation and mortality did not clearly differ between the groups. Regarding cost-effectiveness, the mean health quality-adjusted life years (QALYs) (range 0-1) were 0.73, 0.74, 0.76 QALY for the usual care, website, and e-health adjusted care pathway group, respectively. The corresponding mean costs per patient were €5,741, €4,865, and €5,111. The comparison between participants and nonparticipants in the e-Vita HF study showed that participants were younger (mean age 66.7 vs 73.4 years, p< .001), more often male (75% vs. 58%, p< .001), and had in general fewer comorbidities. After adjustment, SES was significantly higher in participants compared to nonparticipants. The analysis on interpretation of the self-care results showed that a single threshold of 70 accurately discriminated between patients with adequate and inadequate self-care. Finally, worldwide the annual number of sessions to the e-health tool heartfailurematters.org increased from 416,345 in 2010 to 1,636,368 in 2015. Conclusions: Both the heartfailurematters.org website, and an e-health adjusted care pathway improved self-care in HF patients on the short-term (3 months). Implementing the heartfailurematters.org website in HF outpatient care results in a small increase in health effects while reducing costs. The e-health adjusted care pathway may provide an additional health effect at modest extra costs. The fact that participants of the trial were more healthy and wealthy than nonparticipants limits generalisation to all patients with HF. Finally, the heartfailurematters.org is widely used, with ever increasing visiting numbers

E-health in heart failure

Aim: The aim of this thesis was to study the effect and the cost-effectiveness of two e-health interventions, of which one included replacement of usual care by e-health, on self-care in heart failure (HF) patients by conducting the e-Vita HF study. In addition, we evaluated the interpretation of the self-care results of the study and their generalizability. Finally, we described the worldwide use of one of the e-health tools studied. Methods: The e-Vita HF study was a three arm randomized controlled trial, with 12 months follow-up. Group 1 received usual care; group 2 usual care plus the heartfailurematters.org website, an information website on HF; and group 3 received the e-health adjusted care pathway with a platform for disease management, including telemonitoring facilities, which replaced routine consultations with HF nurses at the outpatient clinic. Patients were included if they had a confirmed diagnosis of HF for at least 3 months. The primary outcome was self-care as measured by the European Heart Failure Self-care Behavioural scale (EHFScB scale). Secondary outcomes were hospitalisation, mortality and cost-effectiveness. Results: In total, 450 patients participated from 9 Dutch HF outpatient clinics. The mean age was 66.8 (SD 11.0) years, 74.2% were male, and 78.8% classified as NYHA I or II at baseline. After 3 months follow-up, the mean score on the self-care scale was significantly higher in the groups using the website and the adjusted care pathway compared to usual care: 73.5 vs. 70.8 (difference 2.7, 95%CI 0.6 – 6.2), and 78.2 vs. 70.8 (difference 7.4, 95%CI 3.8 – 9.4), respectively. The effect attenuated during follow-up into no differences between the groups after one year. Hospitalisation and mortality did not clearly differ between the groups. Regarding cost-effectiveness, the mean health quality-adjusted life years (QALYs) (range 0-1) were 0.73, 0.74, 0.76 QALY for the usual care, website, and e-health adjusted care pathway group, respectively. The corresponding mean costs per patient were €5,741, €4,865, and €5,111. The comparison between participants and nonparticipants in the e-Vita HF study showed that participants were younger (mean age 66.7 vs 73.4 years, p< .001), more often male (75% vs. 58%, p< .001), and had in general fewer comorbidities. After adjustment, SES was significantly higher in participants compared to nonparticipants. The analysis on interpretation of the self-care results showed that a single threshold of 70 accurately discriminated between patients with adequate and inadequate self-care. Finally, worldwide the annual number of sessions to the e-health tool heartfailurematters.org increased from 416,345 in 2010 to 1,636,368 in 2015. Conclusions: Both the heartfailurematters.org website, and an e-health adjusted care pathway improved self-care in HF patients on the short-term (3 months). Implementing the heartfailurematters.org website in HF outpatient care results in a small increase in health effects while reducing costs. The e-health adjusted care pathway may provide an additional health effect at modest extra costs. The fact that participants of the trial were more healthy and wealthy than nonparticipants limits generalisation to all patients with HF. Finally, the heartfailurematters.org is widely used, with ever increasing visiting numbers

Interpretability of the European Heart Failure Self-care Behaviour scale

Kim P Wagenaar,1 Berna DL Broekhuizen,1 Frans H Rutten,1 Anna Str&ouml;mberg,2 Henk F van Stel,1 Arno W Hoes,1 Tiny Jaarsma2 1Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands; 2Department of Social and Welfare Studies, Link&ouml;ping University, Link&ouml;ping, Sweden Objective: The European Heart Failure Self-care Behaviour scale (EHFScBs) is a valid patient-reported questionnaire to measure self-care behavior of heart failure (HF) patients. We assessed the interpretability of the EHFScBs.Methods: We used data of 1,023 HF patients. Interpretability refers to the clinical meaning of the score and its changes over time. We operationalized interpretability by evaluating distributions of EHFScBs scores across relevant HF subgroups by eyeballing, by testing the risk on hospitalizations and mortality of a plausible threshold, and by determining a clinically relevant minimal important change (MIC). The scale score ranged from 0 to 100, with a higher score meaning better self-care. A threshold of &ge;70 was defined as adequate and &lt;70 as inadequate self-care.Results: The EHFScBs scores were similarly normally distributed among the subgroups with a mean between 57.8 (SD 19.4) and 72.0 (SD 18.0). The 464 HF patients with adequate self-care had significantly less all-cause hospitalizations than the 559 patients with inadequate self-care.Conclusion: The degree of self-care showed to be independent of relevant HF subgroups. A single threshold of 70 accurately discriminated between patients with adequate and inadequate self-care.Practice implications: The threshold of 70 can be used in designing studies and informing health policy makers. Keywords: heart failure, self-care, interpretability, patient-reported outcome, threshold and minimal important chang

Atacamycins A–C, 22-membered antitumor macrolactones produced by Streptomyces sp. C38*

Three new 22-membered macrolactone antibiotics, atacamycins A–C, were produced by Streptomyces sp. C38, a strain isolated from a hyper-arid soil collected from the Atacama Desert in the north of Chile. The metabolites were discovered in our HPLC-diode array screening and isolated from the mycelium by extraction and chromatographic purification steps. The structures were determined by mass spectrometry and NMR experiments. Atacamycins A, B and C exhibited moderate inhibitory activities against the enzyme phosphodiesterase (PDE-4B2), whereas atacamycin A showed a moderate antiproliferative activity against adeno carcinoma and breast carcinoma cells