[Recommendations for defining giant cell arteritis fast-track clinics]. / Empfehlungen zur Definition von Riesenzellarteriitis-Fast-Track-Kliniken.

An expert committee recommends defining fast-track clinics (FTC) for the acute diagnostics of giant cell arteritis (GCA) as follows: low-threshold, easy and prompt reachability at least on weekdays, scheduling appointments ideally within 24 h, examination by a specialist with GCA expertise, ≥ 2 experts per FTC, ≥ 50 patients with suspected GCA per year, sonologists with ≥ 300 (≥ 50) temporal and axillary artery examinations, adherence to standard operating procedures, availability of an ≥ 18 (≥ 15) MHz and a lower frequency linear ultrasound probe and collaboration with partners for fast performance of neurological and ophthalmological examinations, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT, possibly CT) and for temporal artery biopsy.

Development of a 3D-printed nuchal translucency model: a pilot study for prenatal ultrasound training.

BACKGROUND: We used two 3D ultrasound volumes of fetal heads at 13 weeks to create live-size 3D-printed phantoms with a view to training or assessment of diagnostic abilities for normal and abnormal nuchal translucency measurements. The phantoms are suitable for use in a water bath, imitating a real-life exam. They were then used to study measurement accuracy and reproducibility in examiners of different skill levels. METHODS: Ultrasound scans of a 13 + 0-week fetus were processed using 3D Slicer software, producing a stereolithography file for 3D printing. The model, crafted in Autodesk Fusion360™, adhered to FMF guidelines for NT dimensions (NT 2.3 mm). Additionally, a model with pathologic NT was designed (NT 4.2 mm). Printing was performed via Formlabs Form 3® printer using High Temp Resin V2. The externally identical looking 3D models were embedded in water-filled condoms for ultrasound examination. Eight specialists of varying expertise levels conducted five NT measurements for each model, classifying them in physiological and abnormal models. RESULTS: Classification of the models in physiological or abnormal NT resulted in a detection rate of 100%. Average measurements for the normal NT model and the increased NT model were 2.27 mm (SD ± 0.38) and 4.165 mm (SD ± 0.51), respectively. The interrater reliability was calculated via the intraclass correlation coefficient (ICC) which yielded a result of 0.883, indicating robust agreement between the raters. Cost-effectiveness analysis demonstrated the economical nature of the 3D printing process. DISCUSSION: This study underscores the potential of 3D printed fetal models for enhancing ultrasound training through high inter-rater reliability, consistency across different expert levels, and cost-effectiveness. Limitations, including population variability and direct translation to clinical outcomes, warrant further exploration. The study contributes to ongoing discussions on integrating innovative technologies into medical education, offering a practical and economical method to acquire, refine and revise diagnostic skills in prenatal ultrasound. Future research should explore broader applications and long-term economic implications, paving the way for transformative advancements in medical training and practice.

Transorbital Ultrasound in the Diagnosis of Giant Cell Arteritis.

OBJECTIVES: The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. METHODS: Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. RESULTS: We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: ß=-1.91; p=0.029; EDV: ß=-0.57; p=0.032) and significantly elevated OND (ß = 0.79; p=0.003) compared with controls. RI did not significantly differ from controls (ß=-0.06, p=0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (p=0.048) and EDV (p=0.040). No association was found with RI (p=0.249), while a positive significant association was noted with OND (p<0.001). CONCLUSIONS: This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.

Assessing sleep-related breathing disorders among newly diagnosed rheumatoid and psoriatic arthritis patients: a cross-sectional study.

OBJECTIVES: This cross-sectional study aimed to determine the prevalence and risk factors for sleep-related breathing disorders (SRBD) in newly diagnosed, untreated rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients, and to develop a screening algorithm for early detection. METHODS: We evaluated newly diagnosed RA or PsA patients using the Epworth Sleepiness Scale (ESS) questionnaire, cardiorespiratory polygraphy (RPG), and clinical and laboratory assessments. Sleep apnea syndrome (SAS) was diagnosed based on pathological RPG findings excessive daytime sleepiness, defined as ESS score above 10. RESULTS: The study included 39 patients (22 RA, 17 PsA) and 23 controls. In RPG, SRBD was identified in 38.5% of arthritis patients compared to 39.1% of controls (p = 1.00), with male gender (p = .004) and age (p < .001) identified as risk factors. Excessive daytime sleepiness was noted in 36.4% of RA patients, 17.6% of PsA patients, and 21.7% of controls. Of the 24 patients diagnosed with SRBD, 41.6% met the criteria for SAS. SAS prevalence was 31.8% among RA patients, 0% in PsA patients, and 13% in controls. A significant association was observed between excessive daytime sleepiness and SRBD (p = .036). CONCLUSION: Our findings reveal a high prevalence of SRBD in newly diagnosed, untreated RA and PsA patients in ESS and RPG, with excessive daytime sleepiness being a reliable predictor of SRBD. Patients with RA exhibited a higher predisposition to SAS. We therefore suggest incorporating ESS and RPG as screening tools in RA or PsA for early detection and management of SRBD.

Follow-up ultrasound examination in patients with newly diagnosed giant cell arteritis.

OBJECTIVES: Ultrasound is a standard tool to diagnose giant cell arteritis (GCA). Until now, only few studies investigated the role of ultrasound in the follow-up of GCA. The aim of this study was to assess the changes in the intima media thickness (IMT), total number of affected arteries and provisional OMERACT GCA ultrasonography score (OGUS) in a 12-months follow-up period. METHODS: Patients with newly diagnosed GCA were prospectively enrolled. Ultrasound examinations of facial, temporal, carotid, vertebral and axillary arteries were performed at baseline, after three, six, nine and 12 months. Changes of IMT, total number of affected arteries, and OGUS values were evaluated. In a subgroup of patients, exams were conducted weekly in the first 100 days. RESULTS: Fifty patients were enrolled, 36 completed the follow-up. Significant reductions in IMT, total number of affected arteries and OGUS were observed. Eighteen patients presented to weekly exams. The mean IMT of the axillary artery normalized after seven days, while IMT of the common temporal artery normalized after 50 days. The mean OGUS values were below one after six months. There were no differences in IMT changes between GCA patients with or without PMR or between those with and without additional tocilizumab treatment. A relapse occurred in 4 patients. At relapse, mean IMT and OGUS were higher as compared with the preceding assessment. No predictive values indicating a relapse were identified. CONCLUSION: Vascular ultrasound is sensitive to change in GCA. The presence of PMR or treatment with tocilizumab did not affect IMT decrease.

Protective Properties of S-layer Protein 2 from Lactobacillus crispatus 2029 against Candida albicans Infections.

Previously, the protective role of the S-layer protein 2 (Slp2) of the vaginal Lactobacillus crispatus 2029 (LC2029) strain against foodborne pathogens Campylobacter jejuni, Salmonella enterica serovar Enteritidis, and Escherichia coli O157:H was demonstrated. We demonstrate the new roles of the Slp2-positive LC2029 strain and soluble Slp2 against C. albicans infections. We show that LC2029 bacteria can adhere to the surface of the cervical epithelial HeLa cells, prevent their contact with C. albicans, and block yeast transition to a pathogenic hyphal form. Surface-bound Slp2 provides the ability for LC2029 to co-aggregate with various C. albicans strains, including clinical isolates. C. albicans-induced necrotizing epithelial damage is reduced by colonization with the Slp2-positive LC2029 strain. Slp2 inhibits the adhesion of various strains of C. albicans to different human epithelial cells, blocks yeast transition to a pathogenic hyphal form, and prevents the colonization and pathogenic infiltration of mucosal barriers. Only Slp2 and LC2029 bacteria stimulate the production of protective human ß-defensin 3 in various epithelial cells. These findings support the anti-Candida albicans potential of the probiotic LC2029 strain and Slp2 and form the basis for further research on their ability to prevent and manage invasive Candida infections.

Ligilactobacillus salivarius 7247 Strain: Probiotic Properties and Anti-Salmonella Effect with Prebiotics.

The Ligilactobacillus salivarius 7247 (LS7247) strain, originally isolated from a healthy woman's intestines and reproductive system, has been studied for its probiotic potential, particularly against Salmonella Enteritidis (SE) and Salmonella Typhimurium (ST) as well as its potential use in synbiotics. LS7247 showed high tolerance to gastric and intestinal stress and effectively adhered to human and animal enterocyte monolayers, essential for realizing its probiotic properties. LS7247 showed high anti-Salmonella activity. Additionally, the cell-free culture supernatant (CFS) of LS7247 exhibited anti-Salmonella activity, with a partial reduction upon neutralization with NaOH (p < 0.05), suggesting the presence of anti-Salmonella factors such as lactic acid (LA) and bacteriocins. LS7247 produced a high concentration of LA, reaching 124.0 ± 2.5 mM after 48 h of cultivation. Unique gene clusters in the genome of LS7247 contribute to the production of Enterolysin A and metalloendopeptidase. Notably, LS7247 carries a plasmid with a gene cluster identical to human intestinal strain L. salivarius UCC118, responsible for class IIb bacteriocin synthesis, and a gene cluster identical to porcine strain L. salivarius P1ACE3, responsible for nisin S synthesis. Co-cultivation of LS7247 with SE and ST pathogens reduced their viability by 1.0-1.5 log, attributed to cell wall damage and ATP leakage caused by the CFS. For the first time, the CFS of LS7247 has been shown to inhibit adhesion of SE and ST to human and animal enterocytes (p < 0.01). The combination of Actigen prebiotic and the CFS of LS7247 demonstrated a significant combined effect in inhibiting the adhesion of SE and ST to human and animal enterocytes (p < 0.001). These findings highlight the potential of using the LS7247 as a preventive strategy and employing probiotics and synbiotics to combat the prevalence of salmonellosis in animals and humans caused by multidrug resistant (MDR) strains of SE and ST pathogens.

Aggregation induced nucleic acids recognition by homodimeric asymmetric monomethyne cyanine fluorochromes in mesenchymal stem cells.

In the light of recent retrovirus pandemics, the issue of discovering new and diverse RNA-specific fluorochromes for research and diagnostics became of acute importance. The great majority of nucleic acid-specific probes either do not stain RNA or cannot distinguish between DNA and RNA. The versatility of polymethine dyes makes them suitable as stains for visualization, analysis, and detection of nucleic acids, proteins, and other biomolecules. We synthesized the asymmetric dicationic homodimeric monomethine cyanine dyes 1,1'-(1,3-phenylenebis(methylene))bis(4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)pyridin-1-ium) bromide (Т1) and 1,1'-(1,3-phenylenebis(methylene))bis(4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium) bromide (M1) and tested their binding specificity, spectral characteristics, membrane penetration in living and fixed cells, cellular toxicity, and stability of fluorescent emission. Mesenchymal cells have diverse phenotypes and extensive proliferation and differentiation properties. We found dyes T1 and M1 to show high photochemical stability in living mesenchymal stem cells from apical papilla (SCAP) with a strong fluorescent signal when bound to nucleic acids. We found M1 to perform better than control fluorochrome (Hoechst 33342) for in vivo DNA visualization. T1, on the other hand, stains granular cellular structures resembling ribosomes in living cells and after permeabilization of the nuclear membrane stains the nucleoli and not the chromatin in the nucleus. This makes T1 suitable for the visualization of structures rich in RNA in living and fixed cells.

Promising Gene Delivery Properties of Polycations Based on 2-(N,N-dimethylamino)ethyl Methacrylate and Polyethylene Glycol Monomethyl Ether Methacrylate Copolymers.

Cationic copolymers based on 2-(N,N-dimethylamino)ethyl methacrylate and polyethylene glycol monomethyl ether (pDMAEMA-co-PEO) with different molecular weights have been synthesized. Their physicochemical properties were studied by NMR spectroscopy, sedimentation, and potentiometric titration. According to the data of potentiometric titration for the synthesized pegylated cationic copolymers, the apparent dissociation constants were determined in the pH range from 4.5 to 8.5. The physicochemical properties of interpolyelectrolyte complexes of these polycations with circular DNA (IPEC DNA) were also studied by dynamic light scattering, electrophoretic mobility, and TEM methods. It has been established that the diameter and electrokinetic potential (ζ-potential) of interpolyelectrolyte complexes can be varied over a wide range (from 200 nm to 1.5 µm and from -25 mV to +30 mV) by changing the ratio of oppositely charged ionizable groups in pegylated cationic copolymers and DNA, as well as by regulating medium pH. The resistance of the IPEC DNA/polycation complex to the action of nucleases was studied by electrophoresis in agarose gel; the cytotoxic effect of the polymers in vitro, and the efficiency of penetration (transfection) of IPEC DNA with PDMAEMA-co-PEO-polycations into eukaryotic cells of a cell line derived from human embryonic kidneys HEK 293 in vitro.

Limosilactobacillus fermentum 3872 That Produces Class III Bacteriocin Forms Co-Aggregates with the Antibiotic-Resistant Staphylococcus aureus Strains and Induces Their Lethal Damage.

LF3872 was isolated from the milk of a healthy lactating and breastfeeding woman. Earlier, the genome of LF3872 was sequenced, and a gene encoding unique bacteriocin was discovered. We have shown here that the LF3872 strain produces a novel thermolabile class III bacteriolysin (BLF3872), exhibiting antimicrobial activity against antibiotic-resistant Staphylococcus aureus strains. Sequence analysis revealed the two-domain structural (lysozyme-like domain and peptidase M23 domain) organization of BLF3872. At least 25% residues of this protein are expected to be intrinsically disordered. Furthermore, BLF3872 is predicted to have a very high liquid-liquid phase separation. According to the electron microscopy data, the bacterial cells of LF3872 strain form co-aggregates with the S. aureus 8325-4 bacterial cells. LF3872 produced bacteriolysin BLF3872 that lyses the cells of the S. aureus 8325-4 mastitis-inducing strain. The sensitivity of the antibiotic-resistant S. aureus collection strains and freshly isolated antibiotic-resistant strains was tested using samples from women with lactation mastitis; the human nasopharynx and oral cavity; the oropharynx of pigs; and the cows with a diagnosis of clinical mastitis sensitive to the lytic action of the LF3872 strain producing BLF3872. The co-cultivation of LF3872 strain with various antibiotic-resistant S. aureus strains for 24 h reduced the level of living cells of these pathogens by six log. The LF3872 strain was found to be able to co-aggregate with all studied S. aureus strains. The cell-free culture supernatant of LF3872 (CSLF3872) induced S. aureus cell damage and ATP leakage. The effectiveness of the bacteriolytic action of LF3872 strain did not depend on the origin of the S. aureus strains. The results reported here are important for the creation of new effective drugs against antibiotic-resistant strains of S. aureus circulating in humans and animals.

Ferroelectric Orthorhombic ZrO2 Thin Films Achieved Through Nanosecond Laser Annealing.

A new approach for the stabilization of the ferroelectric orthorhombic ZrO2 films is demonstrated through nanosecond laser annealing (NLA) of as-deposited Si/SiOx /W(14 nm)/ZrO2 (8 nm)/W(22 nm), grown by ion beam sputtering at low temperatures. The NLA process optimization is guided by COMSOL multiphysics simulations. The films annealed under the optimized conditions reveal the presence of the orthorhombic phase, as confirmed by X-ray diffraction, electron backscatter diffraction, and transmission electron microscopy. Macroscopic polarization-electric field hysteresis loops show ferroelectric behavior, with saturation polarization of 12.8 µC cm-2 , remnant polarization of 12.7 µC cm-2 and coercive field of 1.2 MV cm-1 . The films exhibit a wake-up effect that is attributed to the migration of point defects, such as oxygen vacancies, and/or a transition from nonferroelectric (monoclinic and tetragonal phase) to the ferroelectric orthorhombic phase. The capacitors demonstrate a stable polarization with an endurance of 6.0 × 105 cycles, demonstrating the potential of the NLA process for the fabrication of ferroelectric memory devices with high polarization, low coercive field, and high cycling stability.

The role of autoimmunity and autoinflammation in giant cell arteritis: A systematic literature review.

Giant cell arteritis is the most common form of large vessel vasculitis and preferentially involves large and medium-sized arteries in patients over the age of 50. Aggressive wall inflammation, neoangiogenesis and consecutive remodeling processes are the hallmark of the disease. Though etiology is unknown, cellular and humoral immunopathological processes are well understood. Matrix metalloproteinase-9 mediated tissue infiltration occurs through lysis of basal membranes in adventitial vessels. CD4+ cells attain residency in immunoprotected niches, differentiate into vasculitogenic effector cells and enforce further leukotaxis. Signaling pathways involve the NOTCH1-Jagged1 pathway opening vessel infiltration, CD28 mediated T-cell overstimulation, lost PD-1/PD-L1 co-inhibition and JAK/STAT signaling in interferon dependent responses. From a humoral perspective, IL-6 represents a classical cytokine and potential Th-cell differentiator whereas interferon-γ (IFN- γ) has been shown to induce chemokine ligands. Current therapies involve glucocorticoids, tocilizumab and methotrexate application. However, new agents, most notably JAK/STAT inhibitors, PD-1 agonists and MMP-9 blocking substances, are being evaluated in ongoing clinical trials.

Prevalence and characteristics of giant cell arteritis in patients with newly diagnosed polymyalgia rheumatica - a prospective cohort study.

Background: It is known that giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) often occur together. So far, the prevalence of GCA in newly diagnosed PMR patients has not been evaluated in a prospective ultrasound study. Objective: The aim of this study was to assess the prevalence of GCA using vascular ultrasound in patients with newly diagnosed PMR. Design: A consecutive cohort of newly diagnosed PMR patients was prospectively evaluated for the presence of GCA with the use of systematic musculoskeletal and vascular ultrasound examination. Methods: Overall, 60 patients with newly diagnosed PMR were prospectively enrolled. Symptoms and laboratory findings were collected. All patients underwent ultrasound of shoulder and hip joints, and vascular ultrasound evaluating the facial, temporal, carotid, vertebral and axillary arteries. Patients were diagnosed with GCA if they had ultrasound imaging findings of GCA. Patients with PMR (PMR-group) and patients with PMR and GCA (PMR-GCA-group) were compared, and a C-reactive protein (CRP) cut-off value was evaluated. Results: GCA was diagnosed in 28 of 60 PMR patients (46%). The PMR-group consisted of 20 (62.5%) females with a mean age of 69 (±9.9) years, while the PMR-GCA-group consisted of 11 (39.3%) females with a mean age of 74 (±8.4) years. In 13 of 28 patients (46%) in the PMR-GCA-group, GCA was subclinical and only diagnosed by ultrasound. The PMR-GCA-group showed higher values of joint effusion and significantly higher CRP values. A CRP cut-off value of 26.5 mg/litre (reference range 0-5 mg/litre) yielded a sensitivity of 66% with a specificity of 73% for GCA. Conclusion: GCA was found in 46% of newly diagnosed PMR patients; 22% of the patients with PMR had asymptomatic GCA. Joint effusions were higher in the PMR-GCA-group, with significant results for the hip joint. A CRP cut-off value of ⩾26.5 mg/litre in PMR can help in the identification of subclinical GCA.

Short-lived radioactive8Li and8He ions for hadrontherapy: a simulation study.

Purpose.Although charged particle therapy (CPT) for cancer treatment has grown these past years, the use of protons and carbon ions for therapy remains debated compared to x-ray therapy. While a biological advantage of protons is not clearly demonstrated, therapy using carbon ions is often pointed out for its high cost. Furthermore, the nuclear interactions undergone by carbons inside the patient are responsible for an additional dose delivered after the Bragg peak, which deteriorates the ballistic advantage of CPT. Therefore, a renewed interest for lighter ions with higher biological efficiency than protons was recently observed. In this context, helium and lithium ions represent a good compromise between protons and carbons, as they exhibit a higher linear energy transfer (LET) than protons in the Bragg peak and can be accelerated by cyclotrons. The possibility of accelerating radioactive8Li, decaying in 2α-particles, and8He, decaying in8Li byß-decay, is particularly interesting.Methods. This work aims to assess the interest of the use of8Li and8He ions for therapy by Monte Carlo simulations carried out withGeant4.Results. It was calculated that the8Li and8He decay results in an increase of the LET of almost a factor 2 in the Bragg peak compared to stable7Li and4He. This results also in a higher dose deposited in the Bragg peak without an increase of the dose in the plateau region. It was also shown that both8He and8Li can have a potential interest for prompt-gamma monitoring techniques. Finally, the feasibility of accelerating facilities delivering8Li and8He was also discussed.Conclusion. In this study, we demonstrate that both8Li and8He have interesting properties for therapy. Indeed, simulations predict that8Li and8He are a good compromise between proton and12C, both in terms of LET and dose.

Prospective double-blind study on the value of musculoskeletal ultrasound by dermatologists as a screening instrument for psoriatic arthritis.

OBJECTIVES: This study evaluated musculoskeletal ultrasound (MSUS) use by dermatologists previously trained on a novel handheld, chip-based ultrasound device (HHUD) to screen for early PsA. METHODS: Twelve dermatologists were recruited to screen psoriasis patients for PsA using the novel HHUD in one major hospital in Bonn (Germany) and six private practices in surrounding regions. Patient screening was based on medical history, clinical examination, and the GEPARD questionnaire paired with an MSUS examination of up to three painful joints. All screened patients were then referred to rheumatologists, who determined the final diagnosis. The screening effect of MSUS was assessed according to its sensitivity and specificity before and after its application. RESULTS: Between 1 October 2020 and 26 May 2021, a total of 140 psoriasis patients with arthralgia participated in this study. PsA was diagnosed in 19 (13.6%) cases. Before applying MSUS, dermatologists' screening sensitivity and specificity were recorded as 88.2% and 54.4%, respectively, while after applying MSUS the sensitivity and specificity changed to 70.6% and 90.4%, respectively. MSUS led to a change of PsA suspicion in 46 cases, with PsA no longer being suspected in 45 of them. CONCLUSION: This study was able to demonstrate that PsA screening using MSUS by previously trained dermatologists can lead to more precise PsA detection and potentially decreased rheumatologist referral rates.

Anti-Salmonella Defence and Intestinal Homeostatic Maintenance In Vitro of a Consortium Containing Limosilactobacillus fermentum 3872 and Ligilactobacillus salivarius 7247 Strains in Human, Porcine, and Chicken Enterocytes.

Limosilactobacillus fermentum strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. Ligilactobacillus salivarius strain 7247 (LS7247) was isolated at the same time from the intestines and reproductive system of a healthy woman. The genomes of these strains contain genes responsible for the production of peptidoglycan-degrading enzymes and factors that increase the permeability of the outer membrane of Gram-negative pathogens. In this work, the anti-Salmonella and intestinal homeostatic features of the LF3872 and LS7247 consortium were studied. A multi-drug resistant (MDR) strain of Salmonella enteritidis (SE) was used in the experiments. The consortium effectively inhibited the adhesion of SE to intact and activated human, porcine, and chicken enterocytes and reduced invasion. The consortium had a bactericidal effect on SE in 6 h of co-culturing. A gene expression analysis of SE showed that the cell-free supernatant (CFS) of the consortium inhibited the expression of virulence genes critical for the colonization of human and animal enterocytes. The CFS stimulated the production of an intestinal homeostatic factor-intestinal alkaline phosphatase (IAP)-in Caco-2 and HT-29 enterocytes. The consortium decreased the production of pro-inflammatory cytokines IL-8, TNF-α, and IL-1ß, and TLR4 mRNA expression in human and animal enterocytes. It stimulated the expression of TLR9 in human and porcine enterocytes and stimulated the expression of TLR21 in chicken enterocytes. The consortium also protected the intestinal barrier functions through the increase of transepithelial electrical resistance (TEER) and the inhibition of paracellular permeability in the monolayers of human and animal enterocytes. The results obtained suggest that a LF3872 and LS7247 consortium can be used as an innovative feed additive to reduce the spread of MDR SE among the population and farm animals.

Atmospheric Air Pollution by Stationary Sources in Ulan-Ude (Buryatia, Russia) and Its Impact on Public Health.

For the first time in the territory of the Russian Far East, a study related to the establishment of correlations between air quality and public health in Ulan-Ude (Buryatia, Russia) was carried out. This study is based on the analysis of official medical statistics on morbidity over several years, the data on the composition and volume of emissions of harmful substances into the air from various stationary sources, and laboratory measurements of air pollutants in different locations in Ulan-Ude. This study confirmed that the morbidity of the population in Ulan-Ude has been increasing every year and it is largely influenced by air pollutants, the main of which are benzo(a)pyrene, suspended solids, PM2.5, PM10, and nitrogen dioxide. It was found that the greatest contribution to the unfavorable environmental situation is made by three types of stationary sources: large heating networks, autonomous sources (enterprises and small businesses), and individual households. The main air pollutants whose concentrations exceed the limits are benzo(a)pyrene, formaldehyde, suspended particles PM2.5, PM10, and nitrogen dioxide. A comprehensive assessment of the content of various pollutants in the atmospheric air showed that levels of carcinogenic and non-carcinogenic risks to public health exceeded allowable levels. Priority pollutants in the atmosphere of Ulan-Ude whose concentrations create unacceptable levels of risk to public health are benzo(a)pyrene, suspended solids, nitrogen dioxide, PM2.5, PM10, formaldehyde, and black carbon. The levels of morbidity in Ulan-Ude were higher than the average for Buryatia by the main disease classes: respiratory organs-by 1.19 times, endocrine system-by 1.25 times, circulatory system-by 1.11 times, eye diseases-by 1.06 times, neoplasms-by 1.47 times, congenital anomalies, and deformations and chromosomal aberrations-by 1.63 times. There is an increase in the incidence of risk-related diseases of respiratory organs and the circulatory system. A strong correlation was found between this growth of morbidity and atmospheric air pollution in Ulan-Ude.

[Nurse practitioners as key actors in pulmonary rehabilitation for chronic obstructive pulmonary disease]. / L'infirmier en pratique avancée, un acteur-clé dans le développement de la réadaptation respiratoire chez le patient atteint de BPCO.

INTRODUCTION: While pulmonary rehabilitation is registered in the COPD management guidelines with a high level of evidence, it is not adequately performed in accordance with patients' needs. Advanced nurse practitioners (IPA, in French) provide expertise enabling improved access and enhanced implementation of rehabilitation programs. Based on foreign experience, the present study has been designed to propose avenues for the development of more effective practices in France. METHODS: Using Google Scholar and Pubmed databases, a search algorithm was used to identify international publications from 2003 to 2022 dealing with the role of nurse practitioners (IP, in French) in respiratory rehabilitation for COPD patients. RESULTS: Fourteen articles, mainly from English-speaking countries, were analysed. The involvement of nurse practitioners in pulmonary rehabilitation is very broad-based, their main missions being initial disease assessment, therapeutic education, improved professional sensitivity and patient follow-up at all stages of a rehabilitation program. CONCLUSION: Nurse practitioners have a major role in the implementation of pulmonary rehabilitation programs for COPD patients. Their involvement at different levels can improve access and success of programs over time.

Limosilactobacillus fermentum Strain 3872: Antibacterial and Immunoregulatory Properties and Synergy with Prebiotics against Socially Significant Antibiotic-Resistant Infections of Animals and Humans.

Limosilactobacillus fermentum strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. The high-quality genome sequencing of LF3872 was performed, and a gene encoding a unique bacteriocin was discovered. It was established that the bacteriocin produced by LF3872 (BLF3872) belongs to the family of cell-wall-degrading proteins that cause cell lysis. The antibacterial properties of LF3872 were studied using test cultures of antibiotic-resistant Gram-positive and Gram-negative pathogens. Gram-positive pathogens (Staphylococcus aureus strain 8325-4 and S. aureus strain IIE CI-SA 1246) were highly sensitive to the bacteriolytic action of LF3872. Gram-negative pathogens (Escherichia coli, Salmonella strains, and Campylobacter jejuni strains) were more resistant to the bacteriolytic action of LF3872 compared to Gram-positive pathogens. LF3872 is a strong co-aggregator of Gram-negative pathogens. The cell-free culture supernatant of LF3872 (CSLF3872) induced cell damage in the Gram-positive and Gram-negative test cultures and ATP leakage. In the in vitro experiments, it was found that LF3872 and Actigen prebiotic (Alltech Inc., Nicholasville, KY, USA) exhibited synergistic anti-adhesive activity against Gram-negative pathogens. LF3872 has immunoregulatory properties: it inhibited the lipopolysaccharide-induced production of proinflammatory cytokines IL-8, IL-1ß, and TNF-α in a monolayer of Caco-2 cells; inhibited the production of IL-12 and stimulated the production of IL-10 in immature human dendritic cells; and stimulated the production of TGF-ß, IFN-γ, and IgA in the immunocompetent cells of intestinal Peyer's patches (PPs) in mice. These results indicate the possibility of creating a synbiotic based on LF3872 and a prebiotic derived from Saccharomyces cerevisiae cell wall components. Such innovative drugs and biologically active additives are necessary for the implementation of a strategy to reduce the spread of antibiotic-resistant strains of socially significant animal and human infections.