Relying on the French territorial offer of thermal spa therapies to build a care pathway for long COVID-19 patients.

BACKGROUND: Work on long COVID-19 has mainly focused on clinical care in hospitals. Thermal spa therapies represent a therapeutic offer outside of health care institutions that are nationally or even internationally attractive. Unlike local care (hospital care, general medicine, para-medical care), their integration in the care pathways of long COVID-19 patients seems little studied. The aim of this article is to determine what place french thermal spa therapies can take in the care pathway of long COVID-19 patients. METHODS: Based on the case of France, we carry out a geographic mapping analysis of the potential care pathways for long COVID-19 patients by cross-referencing, over the period 2020-2022, the available official data on COVID-19 contamination, hospitalisations in intensive care units and the national offer of spa treatments. This first analysis allows us, by using the method for evaluating the attractiveness of an area defined by David Huff, to evaluate the accessibility of each French department to thermal spas. RESULTS: Using dynamic geographical mapping, this study describes two essential criteria for the integration of the thermal spa therapies offer in the care pathways of long COVID-19 patients (attractiveness of spa areas and accessibility to thermal spas) and three fundamental elements for the success of these pathways (continuity of the care pathways; clinical collaborations; adaptation of the financing modalities to each patient). Using a spatial attractiveness method, we make this type of geographical analysis more dynamic by showing the extent to which a thermal spa is accessible to long COVID-19 patients. CONCLUSION: Based on the example of the French spa offer, this study makes it possible to place the care pathways of long COVID-19 patients in a wider area (at least national), rather than limiting them to clinical and local management in a hospital setting. The identification and operationalization of two geographical criteria for integrating a type of treatment such as a spa cure into a care pathway contributes to a finer conceptualization of the construction of healthcare pathways.

Exploring the Therapeutic Potential of Ampelopsis grossedentata Leaf Extract as an Anti-Inflammatory and Antioxidant Agent in Human Immune Cells.

Inflammation is a vital protective response to threats, but it can turn harmful if chronic and uncontrolled. Key elements involve pro-inflammatory cells and signaling pathways, including the secretion of pro-inflammatory cytokines, NF-κB, reactive oxygen species (ROS) production, and the activation of the NLRP3 inflammasome. Ampelopsis grossedentata, or vine tea, contains dihydromyricetin (DHM) and myricetin, which are known for their various health benefits, including anti-inflammatory properties. Therefore, the aim of this study is to assess the impact of an extract of A. grossedentata leaves (50 µg/mL) on inflammation factors such as inflammasome, pro-inflammatory pathways, and macrophage polarization, as well as its antioxidant properties, with a view to combating the development of low-grade inflammation. Ampelopsis grossedentata extract (APG) significantly decreased ROS production and the secretion of pro-inflammatory cytokines (IFNγ, IL-12, IL-2, and IL-17a) in human leukocytes. In addition, APG reduced LPS/IFNγ -induced M1-like macrophage polarization, resulting in a significant decrease in the expression of the pro-inflammatory cytokines TNF-α and IL-6, along with a decrease in the percentage of M1 macrophages and an increase in M0 macrophages. Simultaneously, a significant decrease in NF-κB p65 phosphorylation and in the expression of inflammasome genes (NLRP3, IL-1ß and Caspase 1) was observed. The results suggest that Ampelopsis grossedentata could be a promising option for managing inflammation-related chronic diseases. Further research is needed to optimize dosage and administration methods.

Spatial Distribution and Physicochemical Properties of Respirable Volcanic Ash From the 16-17 August 2006 Tungurahua Eruption (Ecuador), and Alveolar Epithelium Response In-Vitro.

Tungurahua volcano (Ecuador) intermittently emitted ash between 1999 and 2016, enduringly affecting the surrounding rural area and its population, but its health impact remains poorly documented. We aim to assess the respiratory health hazard posed by the 16-17 August 2006 most intense eruptive phase of Tungurahua. We mapped the spatial distribution of the health-relevant ash size fractions produced by the eruption in the area impacted by ash fallout. We quantified the mineralogy, composition, surface texture, and morphology of a respirable ash sample isolated by aerodynamic separation. We then assessed the cytotoxicity and pro-inflammatory potential of this respirable ash toward lung tissues in-vitro using A549 alveolar epithelial cells, by electron microscopy and biochemical assays. The eruption produced a high amount of inhalable and respirable ash (12.0-0.04 kg/m2 of sub-10 µm and 5.3-0.02 kg/m2 of sub-4 µm ash deposited). Their abundance and proportion vary greatly across the deposit within the first 20 km from the volcano. The respirable ash is characteristic of an andesitic magma and no crystalline silica is detected. Morphological features and surface textures are complex and highly variable, with few fibers observed. In-vitro experiments show that respirable volcanic ash is internalized by A549 cells and processed in the endosomal pathway, causing little cell damage, but resulting in changes in cell morphology and membrane texture. The ash triggers a weak pro-inflammatory response. These data provide the first understanding of the respirable ash hazard near Tungurahua and the extent to which it varies spatially in a fallout deposit.

Systematic Review of COVID-19-Related Physical Activity-Based Rehabilitations: Benefits to Be Confirmed by More Robust Methodological Approaches.

The first emergency was to receive and treat COVID-19 patients in their acute phase; today, there is a clear need to propose appropriate post-acute rehabilitation programs. The aim of this research was to systematically review the effects of physical activity programs in the recovery of post-COVID-19 patients. The literature search followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, was registered in the PROSPERO database (CRD42022289219), and was conducted between August and December 2021. A total of 35 studies out of the 1528 initially identified were finally included in the analysis. The systematic review clearly showed the health benefits of rehabilitation including physical activity in post-COVID-19 recovery, regardless of exercise modalities. These positive results were even observed using minor muscle re-mobilization for severe cases (i.e., postural changes, few steps-2 times/day) or using low volumes of exercise for mild-to-moderate cases (i.e., 120 min/week). A total of 97% of the 29 studies that performed statistical analyses demonstrated a significant increase in at least one parameter of functional capacity, and 96% of the 26 studies that statistically investigated the effects on the quality of life, mental health, and general state reported improvements. Yet, most of the studies were retrospective, uncontrolled, and enrolled aged people with comorbidities presented in severe forms of COVID-19. Physical activity programs, in addition to their high heterogeneity, remained poorly described in 83% of the studies and were part of a multidisciplinary program for 89% of the studies. Despite promising results, there is today a real need for prospective well-designed studies specifically assessing the effects of physical activity. In addition, it might appear relevant to propose standardized programs further considering the main characteristics of patients such as age, comorbidities, or the severity of COVID-19.

Citrulline protects human retinal pigment epithelium from hydrogen peroxide and iron/ascorbate induced damages.

Oxidative stress plays an important role in the ageing of the retina and in the pathogenesis of retinal diseases such as age-related macular degeneration (ARMD). Hydrogen peroxide is a reactive oxygen species generated by the photo-excited lipofuscin that accumulates during ageing in the retinal pigment epithelium (RPE), and the age-related accumulation of lipofuscin is associated with ARMD. Iron also accumulates with age in the RPE that may contribute to ARMD as an important source of oxidative stress. The aim of this work was to investigate the effects of L-Citrulline (CIT), a naturally occurring amino acid with known antioxidant properties, on oxidative stressed cultured RPE cells. Human RPE (ARPE-19) cells were exposed to hydrogen peroxide (H2 O2 ) or iron/ascorbate (I/A) for 4 h, either in the presence of CIT or after 24 h of pretreatment. Here, we show that supplementation with CIT protects ARPE-19 cells against H2 O2 and I/A. CIT improves cell metabolic activity, decreases ROS production, limits lipid peroxidation, reduces cell death and attenuates IL-8 secretion. Our study evidences that CIT is able to protect human RPE cells from oxidative damage and suggests potential protective effect for the treatment of retinal diseases associated with oxidative stress.

Health management of patients with COVID-19: is there a room for hydrotherapeutic approaches?

With highly variable types of coronavirus disease 2019 (COVID-19) symptoms in both severity and duration, there is today an important need for early, individualized, and multidisciplinary strategies of rehabilitation. Some patients present persistent affections of the respiratory function, digestive system, cardiovascular function, locomotor system, mental health, sleep, nervous system, immune system, taste, smell, metabolism, inflammation, and skin. In this context, we highlight here that hydrothermal centers should be considered today as medically and economically relevant alternatives to face the urgent need for interventions among COVID-19 patients. We raise the potential benefits of hydrotherapy programs already existing which combine alternative medicine with respiratory care, physical activity, nutritional advice, psychological support, and physiotherapy, in relaxing environments and under medical supervision. Beyond the virtues of thermal waters, many studies reported medical benefits of natural mineral waters through compressing, buoyancy, resistance, temperature changes, hydrostatic pressure, inhalations, or drinking. Thermal institutions might offer individualized follow-up helping to unclog hospitals while ensuring the continuity of health care for the different clinical manifestations of COVID-19 in both post-acute and chronic COVID-19 patients. Our present review underlines the need to further explore the medical effectiveness, clinical and territorial feasibility, and medico-economic impacts of the implementation of post-COVID-19 patient management in hydrotherapeutic establishments.

Biofilm-coated microbeads and the mouse ear skin: An innovative model for analysing anti-biofilm immune response in vivo.

Owing to its ability to form biofilms, Staphylococcus aureus is responsible for an increasing number of infections on implantable medical devices. The aim of this study was to develop a mouse model using microbeads coated with S. aureus biofilm to simulate such infections and to analyse the dynamics of anti-biofilm inflammatory responses by intravital imaging. Scanning electron microscopy and flow cytometry were used in vitro to study the ability of an mCherry fluorescent strain of S. aureus to coat silica microbeads. Biofilm-coated microbeads were then inoculated intradermally into the ear tissue of LysM-EGFP transgenic mice (EGFP fluorescent immune cells). General and specific real-time inflammatory responses were studied in ear tissue by confocal microscopy at early (4-6h) and late time points (after 24h) after injection. The displacement properties of immune cells were analysed. The responses were compared with those obtained in control mice injected with only microbeads. In vitro, our protocol was capable of generating reproducible inocula of biofilm-coated microbeads verified by labelling matrix components, observing biofilm ultrastructure and confirmed in vivo and in situ with a matrix specific fluorescent probe. In vivo, a major inflammatory response was observed in the mouse ear pinna at both time points. Real-time observations of cell recruitment at injection sites showed that immune cells had difficulty in accessing biofilm bacteria and highlighted areas of direct interaction. The average speed of cells was lower in infected mice compared to control mice and in tissue areas where direct contact between immune cells and bacteria was observed, the average cell velocity and linearity were decreased in comparison to cells in areas where no bacteria were visible. This model provides an innovative way to analyse specific immune responses against biofilm infections on medical devices. It paves the way for live evaluation of the effectiveness of immunomodulatory therapies combined with antibiotics.

1,2,3-Triazolium-Based Cationic Amphipathic Peptoid Oligomers Mimicking Antimicrobial Helical Peptides.

Amphipathic cationic peptoids (N-substituted glycine oligomers) represent a promising class of antimicrobial peptide mimics. The aim of this study is to explore the potential of the triazolium group as a cationic moiety and helix inducer to develop potent antimicrobial helical peptoids. Herein we report the first solid-phase synthesis of peptoid oligomers incorporating 1,2,3-triazolium-type side chains and their evaluation against Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus. Several triazolium-based oligomers, even of short length, selectively kill bacteria over mammalian cells. SEM visualization of S. aureus cells treated with a dodecamer and a hexamer reveals severe cell membrane damage and suggests that the longer oligomer acts by pore formation.

Transient Abnormalities in Masking Tuning Curve in Early Progressive Hearing Loss Mouse Model.

Damage to cochlear outer hair cells (OHCs) usually affects frequency selectivity in proportion to hearing threshold increase. However, the current clinical heuristics that attributes poor hearing performance despite near-normal auditory sensitivity to auditory neuropathy or "hidden" synaptopathy overlooks possible underlying OHC impairment. Here, we document the part played by OHCs in influencing suprathreshold auditory performance in the presence of noise in a mouse model of progressive hair cell degeneration, the CD1 strain, at postnatal day 18-30 stages when high-frequency auditory thresholds remained near-normal. Nonetheless, total loss of high-frequency distortion product otoacoustic emissions pointed to nonfunctioning basal OHCs. This "discordant profile" came with a huge low-frequency shift of masking tuning curves that plot the level of interfering sound necessary to mask the response to a probe tone, against interfering frequency. Histology revealed intense OHC hair bundle abnormalities in the basal cochlea uncharacteristically associated with OHC survival and preserved coupling with the tectorial membrane. This pattern dismisses the superficial diagnosis of "hidden" neuropathy while underpinning a disorganization of cochlear frequency mapping with optimistic high-frequency auditory thresholds perhaps because responses to high frequencies are apically shifted. The audiometric advantage of frequency transposition is offset by enhanced masking by low-frequency sounds, a finding essential for guiding rehabilitation.

Nicosulfuron Degradation by an Ascomycete Fungus Isolated From Submerged Alnus Leaf Litter.

Nicosulfuron is a selective herbicide belonging to the sulfonylurea family, commonly applied on maize crops. Its worldwide use results in widespread presence as a contaminant in surface streams and ground-waters. In this study, we isolated, for the first time, the Plectosphaerella cucumerina AR1 nicosulfuron-degrading fungal strain, a new record from Alnus leaf litter submerged in freshwater. The degradation of nicosulfuron by P. cucumerina AR1 was achieved by a co-metabolism process and followed a first-order model dissipation. Biodegradation kinetics analysis indicated that, in planktonic lifestyle, nicosulfuron degradation by this strain was glucose concentration dependent, with a maximum specific degradation rate of 1 g/L in glucose. When grown on natural substrata (leaf or wood) as the sole carbon sources, the Plectosphaerella cucumerina AR1 developed as a well-established biofilm in 10 days. After addition of nicosulfuron in the medium, the biofilms became thicker, with rising mycelium, after 10 days for leaves and 21 days for wood. Similar biofilm development was observed in the absence of herbicide. These fungal biofilms still conserve the nicosulfuron degradation capacity, using the same pathway as that observed with planktonic lifestyle as evidenced by LC-MS analyses. This pathway involved first the hydrolysis of the nicosulfuron sulfonylurea bridge, leading to the production of two major metabolites: 2-amino-4,6-dimethoxypyrimidine (ADMP) and 2-(aminosulfonyl)-N,N-dimethyl-3-pyridinecarboxamide (ASDM). One minor metabolite, identified as 2-(1-(4,6-dimethoxy-pyrimidin-2-yl)-ureido)-N,N-dimethyl-nicotinamide (N3), derived from the cleavage of the C-S bond of the sulfonylurea bridge and contraction by elimination of sulfur dioxide. A last metabolite (N4), detected in trace amount, was assigned to 2-(4,6-dimethoxy-pyrimidin-2-yl)-N,N-dimethyl-nicotinamide (N4), resulting from the hydrolysis of the N3 urea function. Although fungal growth was unaffected by nicosulfuron, its laccase activity was significantly impaired regardless of lifestyle. Leaf and wood surfaces being good substrata for biofilm development in rivers, P. cucumerina AR1 strain could thus have potential as an efficient candidate for the development of methods aiming to reduce contamination by nicosulfuron in aquatic environments.

Development and cytotoxic response of two proliferative MDA-MB-231 and non-proliferative SUM1315 three-dimensional cell culture models of triple-negative basal-like breast cancer cell lines.

Triple-Negative Basal-Like tumors, representing 15 to 20% of breast cancers, are very aggressive and with poor prognosis. Targeted therapies have been developed extensively in preclinical and clinical studies to open the way for new treatment strategies. The present study has focused on developing 3D cell cultures from SUM1315 and MDA-MB-231, two triple-negative basal-like (TNBL) breast cancer cell lines, using the liquid overlay technique. Extracellular matrix concentration, cell density, proliferation, cell viability, topology and ultrastructure parameters were determined. The results showed that for both cell lines, the best conditioning regimen for compact and homogeneous spheroid formation was to use 1000 cells per well and 2% Geltrex®. This conditioning regimen highlighted two 3D cell models: non-proliferative SUM1315 spheroids and proliferative MDA-MB-231 spheroids. In both cell lines, the comparison of 2D vs 3D cell culture viability in the presence of increasing concentrations of chemotherapeutic agents i.e. cisplatin, docetaxel and epirubicin, showed that spheroids were clearly less sensitive than monolayer cell cultures. Moreover, a proliferative or non-proliferative 3D cell line property would enable determination of cytotoxic and/or cytostatic drug activity. 3D cell culture could be an excellent tool in addition to the arsenal of techniques currently used in preclinical studies.