Adherence to a lifestyle monitoring system in patients with heart disease: protocol for the care-on prospective observational trial.

BACKGROUND: Lifestyle factors such as physical fitness, dietary habits, mental stress, and sleep quality, are strong predictors of the occurrence, clinical course, and overall treatment outcomes of common cardiovascular diseases. However, these lifestyle factors are rarely monitored, nor used in daily clinical practice and personalized cardiac care. Moreover, non-adherence to long-term self-reporting of these lifestyle factors is common. In the present study, we evaluate adherence to a continuous unobtrusive and patient-friendly lifestyle monitoring system using evidence-based assessment tools. METHODS: In a prospective observational trial (N = 100), the project investigates usability of and adherence to a monitoring system for multiple lifestyle factors relevant to cardiovascular disease, i.e., daily physical activity levels, dietary habits, mental stress, smoking, and sleep quality. Patients with coronary artery disease, valvular disease and arrhythmias undergoing an elective intervention are asked to participate. The monitoring system consists of a secured online platform with a custom-built conversational interface-a chatbot-and a wrist-worn wearable medical device. The wrist-worn device collects continuous objective data on physical activity and the chatbot is used to collect self-report data. Participants collect self-reported lifestyle data via the chatbot for a maximum of 4 days every other week; in the same week physiological data are collected for 7 days for 24 h. Data collection starts one week before the intervention and continues until 1-year after discharge. Via a dashboard, patients can observe their lifestyle measures and adherence to self-reporting, set and track personal goals, and share their lifestyle data with practitioners and relatives. The primary outcome of the trial is adherence to using the integrated platform for self-tracking data. The secondary outcomes include system usability, determinants of adherence and the relation between baseline lifestyle behaviour and long-term patient-relevant outcomes. DISCUSSION: Systematic monitoring during daily life is essential to gain insights into patients' lifestyle behaviour. In this context, adherence to monitoring systems is critical for cardiologists and other care providers to monitor recovery after a cardiac intervention and to detect clinical deterioration. With this project, we will evaluate patients' adherence to lifestyle monitoring technology. This work contributes to the understanding of patient-centered data collection and interpretation, to enable personalized care after cardiac interventions in order to ultimately improve patient-relevant outcomes and reduce health care costs. TRIAL REGISTRATION: Netherlands Trial Registry (NTR) NL9861. Registered 6th of November 2021.

Dark scene elements strongly influence cuttlefish camouflage responses in visually cluttered environments.

This study investigated how cuttlefish (Sepia officinalis) camouflage patterns are influenced by the proportions of different gray-scales present in visually cluttered environments. All experimental substrates comprised spatially random arrays of texture elements (texels) of five gray-scales: Black, Dark gray, Gray, Light gray, and White. The substrates in Experiment 1 were densely packed arrays of square texels that varied over 4 sizes in different conditions. Experiment 2 used substrates in which texels were disks separated on a homogeneous background that was Black, Gray or White in different conditions. In a given condition, the histogram of texel gray-scales was varied across different substrates. For each of 16 cuttlefish pattern response statistics c, the resulting data were used to determine the strength with which variations in the proportions of different gray-scales influenced c. The main finding is that darker-than-average texels (i.e., texels of negative contrast polarity) predominate in controlling cuttlefish pattern responses in the context of cluttered substrates. In Experiment 1, for example, substrates of all four texel-sizes, activation of the cuttlefish "white square" and "white head bar" (two highly salient skin components) is strongly influenced by variations in the proportions of Black and Dark gray (but not Gray, Light gray, or White) texels. It is hypothesized that in the context of high-variance visual input characteristic of cluttered substrates in the cuttlefish natural habitat, elements of negative contrast polarity reliably signal the presence of edges produced by overlapping objects, in the presence of which disruptive pattern responses are likely to achieve effective camouflage.

Ocean deoxygenation and zooplankton: Very small oxygen differences matter.

Oxygen minimum zones (OMZs), large midwater regions of very low oxygen, are expected to expand as a result of climate change. While oxygen is known to be important in structuring midwater ecosystems, a precise and mechanistic understanding of the effects of oxygen on zooplankton is lacking. Zooplankton are important components of midwater food webs and biogeochemical cycles. Here, we show that, in the eastern tropical North Pacific OMZ, previously undescribed submesoscale oxygen variability has a direct effect on the distribution of many major zooplankton groups. Despite extraordinary hypoxia tolerance, many zooplankton live near their physiological limits and respond to slight (≤1%) changes in oxygen. Ocean oxygen loss (deoxygenation) may, thus, elicit major unanticipated changes to midwater ecosystem structure and function.

[LSD score. A new classification system for peristomal skin lesions]. / LSD-Score. Ein neues Klassifikationssystem für peristomale Hautläsionen.

BACKGROUND: Peristomal skin lesions are frequent complications of ostomy; however, there is no generally accepted nomenclature and classification system. OBJECTIVE: An interdisciplinary German expert panel (GESS) composed of ten members, developed an innovative semiquantitative classification system for peristomal skin lesions for further stratification of ostomy therapy. This score is based on criteria which can be assessed by stomal therapists and treating physicians. RESULTS: The new peristomal skin lesion score grades three categories: lesion (L), status of ostomy (S) and disease (D). The L category describes the integrity of the skin as normal (L0), lesion with sustained integrity of skin (L1), integrity destroyed (L2) and local infection (L3). The S category rates the complexity of ostomy therapy as normal (S0), increased (S1) and high but not sufficiently effective (S2). The additional letters for categorization O. R. P. H. E. US describe anatomical pathologies of the stoma itself: ostomy stenosis (O), retraction (R), prolapse (P), hernia (H), edema (E) and unfavorable site (US). A systemic disorder is either absent (D0), irrelevant (D1) or relevant (D2). The LSD score is the basis for a management algorithm. CONCLUSION: The LSD score is comprehensive, standardized and holistic. Its straightforward use by health professionals can improve the consistency of the description of skin lesions and enhance the quality of ostomy therapy.

Variations in HIV-1 pol gene associated with reduced sensitivity to antiretroviral drugs in treatment-naive patients.

OBJECTIVE: Various drugs against the HIV-1 enzymes reverse transcriptase (RT) and protease have been introduced in the last few years: protease inhibitors, nucleoside RT inhibitors (NRTI) and non-NRTI (NNRTI). Several sequence variations associated with reduced drug sensitivity have been described in the HIV-1 pol gene. DESIGN: To analyse the occurrence of mutations associated with drug resistance in treatment-naive individuals. METHODS: RNA was extracted from sera of treatment-naive individuals, who were first diagnosed to be HIV-1 infected between August 1996 and February 1998. The pol region was amplified by RT-PCR and directly sequenced. Data on mutations associated with resistance to antiretroviral drugs were obtained from literature. RESULTS: Fifty protease genes and 53 RT genes from 57 individuals were sequenced. In the RT we analysed 20 amino-acid positions associated with resistance to NRTI and NNRTI. In total, 1054 amino acids at critical positions were analysed and three (0.3%) mutations known to contribute to RTI resistance were detected. In the protease, 16 amino-acid positions associated with resistance to protease inhibitors were analysed. By analysing a total of 768 amino acids at key positions in the protease, 50 (7%) mutations were detected that were associated with reduced drug sensitivity. Thirty-one (61%) patients showed between one and six mutations at the analysed protease amino-acid positions. In eight out of 16 analysed amino-acid positions, up to 44% of all patients carried mutations associated with resistance to protease inhibitors. CONCLUSIONS: Very few pre-existing mutations to RTI were found, suggesting that the transmission of RT-resistant strains is still uncommon. However, about two-thirds of the patients had one or more mutations associated with resistance to protease inhibitors. In addition, at some amino-acid positions up to almost half of the patients carried variations claimed to contribute to protease inhibitor resistance. Most of these mutations are likely to reflect the natural polymorphism of the protease. Their impact on the long-term effect of antiretroviral treatment should be evaluated in future studies.

Kinetics of HIV-1 RNA and resistance-associated mutations after cessation of antiretroviral combination therapy.

OBJECTIVE: To study the kinetics of HIV-1 RNA and drug-induced mutations after cessation of antiretroviral therapy (ART). DESIGN AND METHODS: Successive plasma samples from 26 patients were tested for HIV-1 RNA by PCR and for mutations associated with drug resistance by sequencing of the pol gene. RESULTS: After cessation of ART the phase of undetectable virus (< 50 copies/ml), ranging from 6 to more than 29 days, was followed by a rapid viral increase, which slowed down before a plateau corresponding to pre-treatment levels or higher was reached in most cases (14/19 patients). In one patient virus was still undetectable at 4 weeks. Also, a significantly larger number of primary protease inhibitor (PI)-associated mutations reverted to wild-type, as compared with secondary PI-, and primary reverse transcriptase inhibitor (RTI)-associated mutations. During the rapid viral increase no mutations disappeared, which instead happened during the slower viral increase preceding the viral plateau level. CONCLUSION: After discontinuation of ART large individual variations were found for the time period until HIV-1 became detectable in plasma, possibly due to differences in the HIV-1 specific immunity. The more rapid loss of primary PI mutations suggests that they might cause a more impaired viral fitness than primary RTI mutations. However, the persistence of drug mutations during the initial viral load increase indicates that mutated strains may still replicate efficiently.

Coexisting members of HIV-1 p17 gene quasispecies represent proteins with distinct antigenicity and immunogenicity.

BACKGROUND: Despite the comparatively conserved nature of the HIV-1 gag gene, countless quasispecies of the p17 gene coexist in HIV-1-infected patients. It is not known if the minor genetic differences in quasispecies will affect immune recognition. OBJECTIVE: To characterize the antigenicity and immunogenicity of three different members of HIV-1 p17 quasispecies. METHODS: Three members of HIV-1 p17 gene quasispecies, one from patient A (clone 9; qsA9) and two from patient E (clones 5 and 8; qsE5 and qsE8), were expressed and purified from Escherichia coli. The antigenicity of the p17 proteins was analysed using sera from HIV-1-infected individuals, and the immunogenicity was evaluated using sera and lymphocytes from primed mice of three different haplotypes. RESULTS: The antigenicity of the qsE5 and qsE8 p17 recombinant proteins were distinct when tested for reactivity with human p17 antibodies. The qsE5 and qsE8 p17 were equally immunogenic in H-2d mice, but not in H-2b and H-2k mice. In H-2b mice the qsE8 protein induced higher levels of anti-p17 IgG2a, IgG2b and IgG3 than the qsE5 protein. Corroborating the IgG subclass pattern, H-2b-restricted qsE5-specific T cells produced higher in vitro levels of interferon-gamma, but not of interleukin (IL)-4, IL-5 and IL-6, than qsE8-specific T cells, suggesting a more pronounced T-helper (TH)1-like response. CONCLUSIONS: The p17 gene quasispecies coexisting in the same patient at the same time may represent antigenically and immunogenically distinct proteins despite sequence homologies of above 90%. Subsequently, subtle differences between two p17 protein quasispecies are enough to prime different TH1/TH2 subsets. These findings will have implications for therapeutic HIV-1 immunizations.

Nonsynonymous mutations within the human immunodeficiency virus type 1 p17 gene are clustered to sequences binding to the host human leukocyte antigen class I molecules.

We have analyzed the relation between intrapatient variabilities of the p17 gene and the location of known host p17 cytotoxic T lymphocyte (CTL) epitopes in five patients infected with human immunodeficiency virus type 1 (HIV-1). All patients were typed with respect to the human leukocyte antigen (HLA) class I type. One to seven previously fine-mapped p17 CTL epitopes corresponded to the HLA class I restriction elements of each patient. An average of 28+/-16% of the p17 gene of each patient encoded CTL epitopes corresponding to the HLA restriction elements of the host. Twenty full-length p17 gene clones were sequenced from each patient. The intrapatient homology between the p17 sequences ranged from 96.4 to 98.9%. The interpatient homology between the consensus sequences of each patient ranged from 83.1 to 91.6%. A total of 246 nucleotide differences within the 100 p17 clones was noted. Fifteen (16%) of 96 synonymous substitutions were found within host CTL epitopes, whereas 72 (48%) of 150 nonsynonymous nucleotide changes were found within CTL epitopes corresponding to the HLA restriction elements of the host (p < 0.0001; Fisher's exact test). Subsequently, variable residues indicating the evolution of at least two major p17 species (i.e., >20% of the clones) were determined to be more common at positions contained within these CTL epitopes (p < 0.01). The present data suggest that the evolution of the p17 gene is influenced by contact areas with the host HLA class I molecules.

Initiation of therapy during primary HIV type 1 infection results in a continuous decay of proviral DNA and a highly restricted viral evolution.

A latent pool of HIV-1 is established early in memory CD4+ T lymphocytes and persists during antiretroviral therapy. Also, viral replication may continue in subjects despite undetectable viremia. However, it remains unclear whether this residual replication results in any significant sequence evolution. We were therefore interested in studying the viral evolution and HIV-1 DNA dynamics in subjects with primary infection receiving or not receiving early potent antiretroviral therapy. In 16 subjects, HIV-1 DNA load was monitored from 1 to 23 days, up to 1253 days, after onset of symptoms. Extensive sequential cloning and sequence analysis of the V3 region was performed in four subjects. In the treated subjects a continuous decline in the proviral load was found, corresponding to a half-life of about 6 months. As expected in newly infected individuals the founder virus populations showed high intrasubject sequence similarity. Also, a limited increase in the viral divergence was detected during the first 6 months in three treated subjects. Thereafter, no significant sequence changes were found despite analysis of a large number of clones. Our data thus suggest that early and successful therapy in compliant subjects with primary HIV-1 infection results in a highly restricted viral evolution and a decline in the proviral load close to the decay rate of human memory T lymphocytes.