Quality Assessment of Smartphone Medication Management Apps in France: Systematic Search.

BACKGROUND: Adherence to medication is estimated to be around 50% for chronically ill patients in high-income countries. Improving the effectiveness of adherence interventions could have a far greater impact on population health than any improvement in specific medical treatments. Mobile health (mHealth) is one of the most effective solutions for helping patients improve their medication intake, notably through the use of mobile apps with reminder systems. With more than 327,000 apps available in the mHealth field, it is difficult for health care professionals and patients alike to choose which apps to recommend and use. OBJECTIVE: We aim to carry out a systematic search of medication management smartphone apps available in France that send reminders to patients and assess their quality using a validated scale. METHODS: Mobile apps were identified in October and November 2022 after a systematic keyword search on the 2 main app download platforms: App Store (Apple Inc) and Google Play Store. Inclusion criteria were free availability, date of last update, and availability in French. Next, 2 health care professionals independently evaluated the included apps using the French version of the Mobile App Rating Scale (MARS-F), an objective scoring system validated for assessing the overall quality of apps in the mHealth field. An intraclass correlation coefficient was calculated to determine interrater reliability. RESULTS: In total, 960 apps were identified and 49 were selected (25 from the App Store and 24 from the Google Play Store). Interrater reliability was excellent (intraclass correlation coefficient 0.92; 95% CI 0.87-0.95; P<.001). The average MARS-F score was 3.56 (SD 0.49) for apps on the App Store and 3.51 (SD 0.46) for those on the Google Play Store, with 10 apps scoring above 4 out of 5. Further, 2 apps were tested in at least one randomized controlled trial and showed positive results. The 2 apps with the highest ratings were Mediteo rappel de médicaments (Mediteo GmbH) and TOM rappel medicaments, pilule (Innovation6 GmbH), available on both platforms. Each app's MARS-F score was weakly correlated with user ratings on the App Store and moderately correlated on the Google Play Store. CONCLUSIONS: To our knowledge, this is the first study that used a validated scoring system to evaluate medication management apps that send medication reminders. The quality of the apps was heterogeneous, with only 2 having been studied in a randomized controlled trial with positive results. The evaluation of apps in real-life conditions by patients is necessary to determine their acceptability and effectiveness. Certification of apps is also essential to help health care professionals and patients identify validated apps.

An interplay between cellular growth and atypical fusion defines morphogenesis of a modular glial niche in Drosophila.

Neural stem cells (NSCs) live in an intricate cellular microenvironment supporting their activity, the niche. Whilst shape and function are inseparable, the morphogenetic aspects of niche development are poorly understood. Here, we use the formation of a glial niche to investigate acquisition of architectural complexity. Cortex glia (CG) in Drosophila regulate neurogenesis and build a reticular structure around NSCs. We first show that individual CG cells grow tremendously to ensheath several NSC lineages, employing elaborate proliferative mechanisms which convert these cells into syncytia rich in cytoplasmic bridges. CG syncytia further undergo homotypic cell-cell fusion, using defined cell surface receptors and actin regulators. Cellular exchange is however dynamic in space and time. This atypical cell fusion remodels cellular borders, restructuring the CG syncytia. Ultimately, combined growth and fusion builds the multi-level architecture of the niche, and creates a modular, spatial partition of the NSC population. Our findings provide insights into how a niche forms and organises while developing intimate contacts with a stem cell population.

Zic-Proteins Are Repressors of Dopaminergic Forebrain Fate in Mice and C. elegans.

In the postnatal forebrain regionalized neural stem cells along the ventricular walls produce olfactory bulb (OB) interneurons with varying neurotransmitter phenotypes and positions. To understand the molecular basis of this region-specific variability we analyzed gene expression in the postnatal dorsal and lateral lineages in mice of both sexes from stem cells to neurons. We show that both lineages maintain transcription factor signatures of their embryonic site of origin, the pallium and subpallium. However, additional factors, including Zic1 and Zic2, are postnatally expressed in the dorsal stem cell compartment and maintained in the lineage that generates calretinin-positive GABAergic neurons for the OB. Functionally, we show that Zic1 and Zic2 induce the generation of calretinin-positive neurons while suppressing dopaminergic fate in the postnatal dorsal lineage. We investigated the evolutionary conservation of the dopaminergic repressor function of Zic proteins and show that it is already present in C. elegansSIGNIFICANCE STATEMENT The vertebrate brain generates thousands of different neuron types. In this work we investigate the molecular mechanisms underlying this variability. Using a genomics approach we identify the transcription factor signatures of defined neural stem cells and neuron populations. Based thereon we show that two related transcription factors, Zic1 and Zic2, are essential to control the balance between two defined neuron types in the postnatal brain. We show that this mechanism is conserved in evolutionary very distant species.

Citrulline stimulates muscle protein synthesis in the post-absorptive state in healthy people fed a low-protein diet - A pilot study.

BACKGROUND & AIMS: Amino acid (AA) availability is critical to maintain protein homeostasis and reduced protein intake causes a decline in protein synthesis. Citrulline, an amino acid metabolite, has been reported to stimulate muscle protein synthesis in malnourished rats. METHODS: To determine whether citrulline stimulates muscle protein synthesis in healthy adults while on a low-protein diet, we studied 8 healthy participants twice in a cross-over study design. Following a 3-days of low-protein intake, either citrulline or a non-essential AA mixture (NEAA) was given orally as small boluses over the course of 8 h. [ring-(13)C6] phenylalanine and [(15)N] tyrosine were administered as tracers to assess protein metabolism. Fractional synthesis rates (FSR) of muscle proteins were measured using phenylalanine enrichment in muscle tissue fluid as the precursor pool. RESULTS: FSR of mixed muscle protein was higher during the administration of citrulline than during NEAA (NEAA: 0.049 ± 0.005; citrulline: 0.060 ± 0.006; P = 0.03), while muscle mitochondrial protein FSR and whole-body protein turnover were not different between the studies. Citrulline administration increased arginine and ornithine plasma concentrations without any effect on glucose, insulin, C-peptide, and IGF-1 levels. Citrulline administration did not promote mitochondria protein synthesis, transcripts, or citrate synthesis. CONCLUSIONS: Citrulline ingestion enhances mixed muscle protein synthesis in healthy participants on 3-day low-protein intake. This anabolic action of citrulline appears to be independent of insulin action and may offer potential clinical application in conditions involving low amino acid intake.

In vivo bioluminescent imaging of a new model of infectious complications in head-injury rats.

Infectious complications are responsible for 10-25% of mortality in head-injured patients. In the present work we developed a model of infectious complications in head-injury rats using Escherichia coli (E. coli) with a stable copy of the lux operon, and monitored the infection in vivo by optical imaging. Rats were randomized into three groups: AL (healthy rats), HI (head-injury rats), and HI-EC (HI rats+single enteral bolus of E. coli, 1.3×10(9)/rat given 2 days after HI). Infection was evaluated with a camera at 2 and 6 h after E. coli challenge. Blood and organs were sampled to assess biological parameters. HI was associated with body weight loss, muscle atrophy, and plasma amino acid disturbances, in particular glutamine depletion (AL 919±37 versus HI 647±25 and HI-EC 717±20 µmol/L; p<0.05). In the HI-EC rats, the luminescence signal was observed at T+2 (mean [range]: 34,778 cpm [1617-2,918,810]), and was significantly decreased at T+6 (0 cpm [0-847,922]; p<0.05). Bacterial challenge was associated with a specific body weight loss and a decrease in gastrocnemius protein content, in alanine (AL 512±41 versus HI-EC 395±29 µmol/L; p<0.05), and in sulfur plasma amino acids. In conclusion, we propose a controlled model of HI with infectious complications characterized by specific metabolic alterations. Combined with the in vivo monitoring of the infection by bioluminescence, this model offers a valuable tool to evaluate specific strategies for HI patients.

High plasma citrulline and arginine levels ensured by sustained-release citrulline supplementation in rats.

OBJECTIVE: Dietary-supplemented arginine has been shown to have positive effects on cardiovascular disease, but several drawbacks exist and could potentially be avoided by using L-citrulline, since it is recycled to L-arginine. However, citrulline is very rapidly metabolized. We therefore developed a sustained-release form of citrulline and evaluated its metabolic behavior in rats. METHODS: Male Sprague Dawley rats were divided into three groups: receiving "empty microcapsule" (control group), 1 g/kg/d immediate-release citrulline (IR citrulline group), or 1 g/kg/d sustained-release citrulline (SR citrulline group). Citrulline was given each day at 9 a.m. after blood samples for 9 d, and on day 10, blood samples were drawn every 4 h to study the decrease in plasma amino acid concentrations. RESULTS: SR citrulline led to a sustained increase in citrullinemia and argininemia compared to IR citrulline, and on day 6 argininemia was significantly (P < 0.01) higher with SR compared to IR citrulline. Moreover, argininemia was significantly higher in the SR citrulline group than in controls throughout the study and SR citrulline maintained high argininemia and citrullinemia, at least over 12 h. CONCLUSION: This experimental study provides a strong rationale for using this new formulation for atherosclerosis treatment.

Tolerance and efficacy of a new enteral formula specifically designed for elderly persons: an experimental study in the aged rat.

For the first time, a formula was specifically designed for the nutritional support of tube-fed elderly patients (Elderly-Specific Formula [ESF], Nestlé, Switzerland). It was tested against a standard formula (Sondalis Iso [SI], Nestlé Clinical Nutrition, Marne la Vallée, France) in sixteen 22-month-old Sprague Dawley rats fed by total continuous enteral infusion for 7 days. Body weight, stool weight, and nitrogen balance were measured daily. After death, muscle weight, plasma levels of amino acids, tissue protein, and amino acid content were measured. The ESF curbed weight loss, improved cumulative nitrogen balance, and increased jejunum protein content. Plasma levels of threonine, leucine, and isoleucine and the sum of total amino acids were higher in ESF-fed than in SF-fed rats. Threonine and isoleucine content in the soleus and gastrocnemius were higher in ESF-fed rats than SI-fed ones. ESF improved intestinal transit. Thus, in old rats, the ESF favored nutritional status more than a standard formula.

A glyphosate-based pesticide impinges on transcription.

Widely spread chemicals used for human benefits may exert adverse effects on health or the environment, the identification of which are a major challenge. The early development of the sea urchin constitutes an appropriate model for the identification of undesirable cellular and molecular targets of pollutants. The widespread glyphosate-based pesticide affected sea urchin development by impeding the hatching process at millimolar range concentration of glyphosate. Glyphosate, the active herbicide ingredient of Roundup, by itself delayed hatching as judged from the comparable effect of different commercial glyphosate-based pesticides and from the effect of pure glyphosate addition to a threshold concentration of Roundup. The surfactant polyoxyethylene amine (POEA), the major component of commercial Roundup, was found to be highly toxic to the embryos when tested alone and therefore could contribute to the inhibition of hatching. Hatching, a landmark of early development, is a transcription-dependent process. Correlatively, the herbicide inhibited the global transcription, which follows fertilization at the 16-cell stage. Transcription inhibition was dose-dependent in the millimolar glyphosate range concentration. A 1257-bp fragment of the hatching enzyme transcript from Sphaerechinus granularis was cloned and sequenced; its transcription was delayed by 2 h in the pesticide-treated embryos. Because transcription is a fundamental basic biological process, the pesticide may be of health concern by inhalation near herbicide spraying at a concentration 25 times the adverse transcription concentration in the sprayed microdroplets.

Formulated glyphosate activates the DNA-response checkpoint of the cell cycle leading to the prevention of G2/M transition.

A glyphosate containing pesticide impedes at 10 mM glyphosate the G2/M transition as judged from analysis of the first cell cycle of sea urchin development. We show that formulated glyphosate prevented dephosphorylation of Tyr 15 of the cell cycle regulator CDK1/cyclin B in vivo, the end point target of the G2/M cell cycle checkpoint. Formulated glyphosate had no direct effect on the dual specific cdc25 phosphatase activity responsible for Tyr 15 dephosphorylation. At a concentration that efficiently impeded the cell cycle, formulated glyphosate inhibited the synthesis of DNA occurring in S phase of the cell cycle. The extent of the inhibition of DNA synthesis by formulated glyphosate was correlated with the effect on the cell cycle. We conclude that formulated glyphosate's effect on the cell cycle is exerted at the level of the DNA-response checkpoint of S phase. The resulting inhibition of CDK1/cyclin B Tyr 15 dephosphorylation leads to prevention of the G2/M transition and cell cycle progression.

Glyphosate-based pesticides affect cell cycle regulation.

Cell-cycle dysregulation is a hallmark of tumor cells and human cancers. Failure in the cell-cycle checkpoints leads to genomic instability and subsequent development of cancers from the initial affected cell. A worldwide used product Roundup 3plus, based on glyphosate as the active herbicide, was suggested to be of human health concern since it induced cell cycle dysfunction as judged from analysis of the first cell division of sea urchin embryos, a recognized model for cell cycle studies. Several glyphosate-based pesticides from different manufacturers were assayed in comparison with Roundup 3plus for their ability to interfere with the cell cycle regulation. All the tested products, Amega, Cargly, Cosmic, and Roundup Biovert induced cell cycle dysfunction. The threshold concentration for induction of cell cycle dysfunction was evaluated for each product and suggests high risk by inhalation for people in the vicinity of the pesticide handling sprayed at 500 to 4000 times higher dose than the cell-cycle adverse concentration.

Sharp dose- and time-dependent toxicity of mercuric chloride at the cellular level in sea urchin embryos.

Sea urchin embryos ( Sphaerechinus granularis) offer the opportunity to analyse toxicity towards cell division and stages of early development. Mercuric chloride (HgCl(2)) arrested early development at the level of the first cell cycle. The toxic effect occurred in a very sharp concentration range around 7 microM HgCl(2). At sub-toxic concentrations of HgCl(2), the morphology and kinetics of early development were comparable to control embryos. The time-dependence of toxicity was short; a 5-min exposure to the toxic concentration of 10 microM HgCl(2) was sufficient to provoke developmental dysfunction whereas continuous exposure to 5 microM HgCl(2) allowed development to occur normally. The effects on early development over this range of concentrations were specific to HgCl(2) toxicity since other heavy metal chlorides had no effect at 30 microM. Thus, the sea urchin model may provide new clues to the molecular mechanisms of HgCl(2) toxicity.

Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation.

To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin embryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin embryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a subthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/cyclin B regulates universally the M-phase of the cell cycle, we analyzed CDK1/cyclin B activation during the first division of early development. Roundup delayed the activation of CDK1/cyclin B in vivo. Roundup inhibited also the global protein synthetic rate without preventing the accumulation of cyclin B. In summary, Roundup affects cell cycle regulation by delaying activation of the CDK1/cyclin B complex, by synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/cyclin B regulator, our results question the safety of glyphosate and Roundup on human health.