Dynamics of γ-aminobutyric acid concentration in the human brain in response to short visual stimulation.

OBJECTIVE: To find a possible quantitative relation between activation-induced fast (< 10 s) changes in the γ-aminobutyric acid (GABA) level and the amplitude of a blood oxygen level-dependent contrast (BOLD) response (according to magnetic resonance spectroscopy [MRS] and functional magnetic resonance imaging [fMRI]). MATERIALS AND METHODS: fMRI data and MEGA-PRESS magnetic resonance spectra [echo time (TE)/repetition time (TR) = 68 ms/1500 ms] of an activated area in the visual cortex of 33 subjects were acquired using a 3 T MR scanner. Stimulation was performed by presenting an image of a flickering checkerboard for 3 s, repeated with an interval of 13.5 s. The time course of GABA and creatine (Cr) concentrations and the width and height of resonance lines were obtained with a nominal time resolution of 1.5 s. Changes in the linewidth and height of n-acetylaspartate (NAA) and Cr signals were used to determine the BOLD effect. RESULTS: In response to the activation, the BOLD-corrected GABA + /Cr ratio increased by 5.0% (q = 0.027) and 3.8% (q = 0.048) at 1.6 and 3.1 s, respectively, after the start of the stimulus. Time courses of Cr and NAA signal width and height reached a maximum change at the 6th second (~ 1.2-1.5%, q < 0.05). CONCLUSION: The quick response of the observed GABA concentration to the short stimulus is most likely due to a release of GABA from vesicles followed by its packaging back into vesicles.

Adaptive Phage Therapy for the Prevention of Recurrent Nosocomial Pneumonia: Novel Protocol Description and Case Series.

Nowadays there is a growing interest worldwide in using bacteriophages for therapeutic purposes to combat antibiotic-resistant bacterial strains, driven by the increasing ineffectiveness of drugs against bacterial infections. Despite this fact, no novel commercially available therapeutic phage products have been developed in the last two decades, as it is extremely difficult to register them under the current legal regulations. This paper presents a description of the interaction between a bacteriophage manufacturer and a clinical institution, the specificity of which is the selection of bacteriophages not for an individual patient, but for the entire spectrum of bacteria circulating in the intensive care unit with continuous clinical and microbiological monitoring of efficacy. The study presents the description of three clinical cases of patients who received bacteriophage complex via inhalation for 28 days according to the protocol without antibiotic use throughout the period. No adverse effects were observed and the elimination of multidrug-resistant microorganisms from the bronchoalveolar lavage contents was detected in all patients. A decrease in such inflammatory markers as C-reactive protein (CRP) and procalcitonin was also noted. The obtained results demonstrate the potential of an adaptive phage therapy protocol in intensive care units for reducing the amount of antibiotics used and preserving their efficacy.

Temperature-Dependent Color-Tunable Afterglow in Zirconium-Doped CsCdCl3 Perovskite for Advanced Anti-Counterfeiting and Thermal Distribution Detection.

Persistent luminescence (PersL) materials exhibit thermal-favored optical behavior, enabling their unique applications in security night vision signage, in vivo bioimaging, and optical anti-counterfeiting. Therefore, developing efficient and color-tunable PersL materials is significantly crucial in promoting advanced practical use. In this study, hexagonal Zr4+ -doped CsCdCl3 perovskite is synthesized via a hydrothermal reaction with a tunable photoluminescent (PL) behavior through heterovalent substitution. Moreover, the incorporation of Zr4+ ions result in an extra blue emission band, originating from the enhanced excitonic recombination in D3d octahedrons. Furthermore, the afterglow performances of the samples are dramatically improved, along with the noticeable temperature-dependent PersL as well as the thermo-luminescence with tunable color output. Detailed analysis reveals that the unique temperature-dependent PersL and thermo-luminescence color change are attributed to the presence of multiple luminous centers and abundant traps. Overall, this work facilitates the development of optical intelligence platforms and novel thermal distribution probes with the as-developed halides perovskite for its superior explored PersL characteristic.

Visualized X-ray Dosimetry for Multienvironment Applications.

X-ray dose detection plays a critical role in various scientific fields, including chemistry, materials, and medicine. However, the current materials used for this purpose face challenges in both immediate and delayed radiation detections. Here, we present a visual X-ray dosimetry method for multienvironment applications, utilizing NaLuF4 nanocrystals (NCs) that undergo a color change from green to red upon X-ray irradiation. By adjustment of the concentrations of Ho3+, the emission color of the NCs can be tuned thanks to the cross-relaxation effects. Furthermore, X-ray irradiation induces generation of trapping centers in NaLuF4:Ho3+ NCs, endowing the generation of mechanoluminescence (ML) behavior upon mechanical stimulation after X-ray irradiation ceases. The ML intensity shows a linear correlation with the X-ray dose, facilitating the detection of delayed radiation. This breakthrough facilitates X-ray dose inspection in flaw detection, nuclear medicine, customs, and civil protection, thereby enhancing opportunities for radiation monitoring and control.

Highly efficient near-infrared solid solution phosphors with excellent thermal stability and tunable spectra for pc-LED light sources toward NIR spectroscopy applications.

Near-infrared (NIR) luminescent materials have attracted wide research interest due to their unique photophysical properties for designing NIR light-emitting diodes (NIR LEDs). Here, a series of Cr3+-activated NIR-emitting solid solution phosphors, Gd1-xLux(Al1-xScx)3(BO3)4:0.01Cr3+ (GLASB:Cr3+) (x = 0 to 0.5), are successfully synthesized via a cosubstitution approach. The GLASB:Cr3+ phosphors reveal extraordinary optical performance with a desirable high IQE of 93.6%, considerable broadened FWHM (from 128 nm to 196 nm) and redshift of 119 nm (747 → 866 nm) as the amount of [Lu3+-Sc3+] ion doping increases. Moreover, their photoluminescent thermal stability is substantially improved, maintaining 105.7% of the initial integral intensity up to 150 °C, namely zero-thermal-quenching. The NIR pc-LED fabricated using the GLASB:Cr3+ phosphor generates an NIR output power of 46 mW and an electro-optical efficiency of 37% at a 120 mA input current. Finally, the characteristic NIR emission of this phosphor can not only be utilized in the fields of night-vision technology and biometric identification, but also exhibits a perfect match with the absorption of the bacteriochlorophyll (BChl) and light-harvesting protein (LHP) of photosynthetic bacteria (PSB), presenting a high application prospect for improving PSB photosynthesis.

Multimode-Responsive Luminescence of Er3+ Single-Activated CaF2 Phosphor for Advanced Information Encryption.

The current optical anticounterfeit strategies that rely on multimode luminescence in response to the photon or thermal stimuli have significant importance in the field of anticounterfeiting and information encryption. However, the dependence on light and heat sources might limit their flexibility in practical applications. In this work, Er3+ single-doped CaF2 phosphors that show multistimuli-responsive luminescence have been successfully prepared. The as-obtained CaF2:Er3+ phosphor exhibits green photoluminescence (PL) and color-tunable up-conversation (UC) luminescence from red to green due to the cross-relaxation of Er3+ ions. Additionally, as-obtained CaF2:Er3+ phosphors also display green mechano-luminescence behavior, which is induced by the contact electrification between the CaF2 particles and PDMS polymers, enabling the phosphor to flexibly respond to mechanical stimuli. Moreover, feasible anticounterfeiting schemes with the capability of multistimuli-responsive and flexible decryption have been constructed, further expanding the application of optical materials in the field of advanced anticounterfeiting and information encryption.

Controlled mechano-luminescence properties of SrGa2O4:Tb3+ co-doping with Dy3+ and Eu3+ ions.

Trap-controlled mechano-luminescence (ML) featuring photon emission under mechanical stimuli provides promising applications such as dynamic imaging of force, integrated optical sensing, information storage, and anti-counterfeiting encryption. However, the corresponding emission with a single color still limits the application of ML materials. Here, a trap-controlled ML phosphor of SrGa2O4:Tb3+ (SGO:Tb3+) with a green-emission is investigated with an adjustable ML color. The relationship between ML and thermoluminescence (TL) is verified by co-doping with Dy3+ and Eu3+ ions for the manipulation of the constructed traps. Accordingly, the as-explored ML phosphor with multicolor output is employed to create encrypted anticounterfeiting patterns, which produces bright and spatially resolvable optical codes under the single-point dynamic pressure of a ballpoint pen. Hence, it provides a new approach to achieve ML with multicolor and gives us an insight into understanding the mechanism of the ML procedure.

100-mJ, 100-W cryogenically cooled Yb:YLF laser.

We present a diode-pumped Yb:YLF laser system generating 100-mJ sub-ps pulses at a 1-kHz repetition rate (100 W average power) by chirped-pulse amplification. The laser consists of a cryogenically cooled 78 K, regenerative, eight-pass booster amplifier seeded by an all-fiber front end. The output pulses are compressed to 980 fs in a single-grating Treacy compressor with a throughput of 89%. The laser will be applied to multi-cycle THz generation and pumping of high average power parametric amplifiers.

High Thermal Stability of Copper-Based Perovskite Scintillators for High-Temperature X-ray Detection.

High-temperature scintillation detectors play a significant role in oil exploration. However, traditional scintillators have limited ability to meet the requirements of practical applications owing to their low thermal stability. In this study, we designed and developed a one-dimensional (1D) Cs5Cu3Cl6I2 scintillator with high thermal stability. In addition, by preparing Cs5Cu3Cl7I, we proved that the Cs5Cu3Cl6I2 scintillator exhibits high thermal stability because the bridges linking the structural units in the 1D chain structure are only formed by I- ions, which improve their structural rigidity. The scintillator has a high steady-state light yield (59,700 photons MeV-1) and exhibits the highest spatial resolution for powder-based scintillation screens (18 lp mm-1) after cyclic treatment within the temperature range of 298-423 K. The Cs5Cu3Cl6I2 scintillator allows the visualization of alloy melting, indicating that it has significant potential for application in high-temperature environments. This study provides a new perspective toward the design of scintillators with high thermal stability.

High-Efficiency ZnS: Cu+, Al3+ Scintillator for X-ray Detection in a Non-Darkroom Environment.

Scintillator is a key component in X-ray detectors that determine the performance of the devices. Nevertheless, due to the interference of the ambient light sources, scintillators are only operated in a darkroom environment currently. In this study, we designed a Cu+ and Al3+ co-doped ZnS scintillator (ZnS: Cu+, Al3+) that introduces donor-acceptor (D-A) pairs for X-ray detection. The prepared scintillator displayed an extremely high steady-state light yield (53,000 photons per MeV) upon X-ray irradiation, which is 5.3 times higher than that of the commercial Bi4Ge3O12 (BGO) scintillator, making it possible in X-ray detection with the interference of ambient light. Furthermore, the prepared material was employed as a scintillator to construct an indirect X-ray detector, which performed a superior spatial resolution (≈10.0 lp/mm) as well as persistent stability under visible light interference, demonstrating the feasibility of the scintillator in practical applications. Therefore, this research presented a convenient and useful strategy to realize X-ray detection in a non-darkroom environment.

Serum Cytokines as Biomarkers in Heart Failure with Preserved Ejection Fraction and Sleep Apnea: A Prospective Cohort Study.

Heart failure with preserved ejection fraction (HFpEF) and obstructive sleep apnea (OSA) frequently co-occur and this comorbidity represents a separate phenotype of HFpEF. While many research attempts are focused on biomarkers of HFpEF, currently, there is a lack of validated biomarkers of HFpEF and OSA. In this study, we aimed to evaluate prognostic significance of several serum cytokines in patients with HFpEF and OSA. The patients with HFpEF and OSA were recruited from the Sleep Apnea Center of Novosibirsk, Russian Federation and followed up for 12 months. The main analyzed outcomes were five-point major adverse cardiovascular events (MACE) and the 6-min walk test (6MWT). The analyzed cytokines were circulating IL-6, IL-10, and VEGF measured at baseline. We recruited 77 male patients with HFpEF and OSA, the data of 71 patients were available for analyses. Patients who developed MACE had four-fold elevated concentrations of serum IL-10. There was no association between baseline cytokine levels and longitudinal changes in 6MWT. Circulating IL-10 levels are positively associated with MACE in men with HFpEF and OSA and thus may be a potential prognostic biomarker in this subgroup of patients. These results should be confirmed in larger studies encompassing both males and females.

Clinical and neurophysiological characteristics of 89 patients with narcolepsy and cataplexy from the Russian Narcolepsy Network.

STUDY OBJECTIVES: The first reports of narcolepsy with cataplexy in Russia were made by Mankovsky (The pathogenesis of narcolepsy (the case of epidemic encephalitis with cataplexy) published in the Sovremennaya psihonevrologia) in 1925. The largest series of patients (n = 110) was reported by A. Vein (doctoral thesis: Hypersomnia Syndrome) in 1964. However, until today, narcolepsy remained relatively unknown in Russia. The aim of this study is to report clinical and polysomnography (PSG)/multiple sleep latency test (MSLT) results in the Russian population and compare them with the European Narcolepsy Network (EU-NN) data (n = 1099) reported. METHODS: Eleven sleep centers from Russia agreed to participate and completed a questionnaire including 58 questions concerning demographic, clinical, PSG, and MSLT data. RESULTS: There were 89 patients with a mean age of 35.6 ± 16.9 years (± here and further indicates standard deviation), 58% males, and 42% females. Narcolepsy started at a mean age of 25.6 ± 14.6 years (range 5-74 years). The mean Epworth Sleepiness Scale score was 18.4 ± 3.5 points (range: 11-24). Sleep paralysis was reported by 59.1%, and hallucinations by 82% of patients. In MSLT, ≥ 2 sleep-onset REM (rapid eye movement) periods (SOREMPs) were found in 81.6%. No center provided human leukocyte antigen (HLA) or cerebral spinal fluid hypocretin data. CONCLUSIONS: Clinical and neurophysiological data from this first study of the Russian Narcolepsy Network suggest a similar profile to the recently reported EU-NN data. The more severe and higher percentage of patients with cataplexy and presenting with both excessive daytime sleepiness and cataplexy may reflect low awareness of narcolepsy in Russia. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; URL: https://clinicaltrials.gov/ct2/show/NCT05375890; Name: Clinical and Neurophysiological Characteristics of Narcolepsy; Identifier: NCT05375890. CITATION: Kuts A, Poluektov M, Zakharov A, et al. Clinical and neurophysiological characteristics of 89 patients with narcolepsy and cataplexy from the Russian Narcolepsy Network. J Clin Sleep Med. 2023;19(2):355-359.

Macromolecular-Suppressed GABA-Edited MR Spectroscopy in the Posterior Cingulate Cortex of Patients With Acute Mild Traumatic Brain Injury.

BACKGROUND: Mild traumatic brain injury (mTBI) causes a number of molecular and cellular alterations. There is evidence of an imbalance between the main excitatory (glutamate, Glu) and the main inhibitory (gamma-aminobutyric acid [GABA]) neurotransmitters following mTBI. In vivo human GABA-Glu balance studies following mTBI are sparse. PURPOSE: To investigate the effect of acute mTBI on the GABA concentration measured in the posterior cingulate cortex (PCC) of pediatric patients by using the macromolecular (MM)-suppressed GABA J-editing technique. STUDY TYPE: Prospective patient and phantom. PARTICIPANTS: A total of 14 pediatric patients (mean age 16.0 ± 1.7) with acute mTBI (<3 days after trauma; Glasgow Coma Scale 15) and 16 healthy volunteers (mean age 16.9 ± 2.8). Phantom: 524 cm3 sphere containing 10 mM glycine, 10 mM GABA. FIELD STRENGTH/SEQUENCE: A 3 T, MEGA-PRESS pulse sequence. ASSESSMENT: GABA spectra were processed in Gannet software. MM-suppressed GABA editing efficiency was derived from the phantom study. Absolute GABA and glutamate + glutamine (Glx) concentrations were quantified using different types of correction and compared between groups. N-acetyl aspartate (NAA) and choline (Cho) levels relative to tCr were also compared. STATISTICAL TESTS: Shapiro-Wilk test, Mann-Whitney U test, Student t-test, Pearson or Spearman correlations. P < 0.01 was considered statistically significant. RESULTS: The MM-suppressed GABA editing efficiency was 0.63. GABA signal fit error was <16% for all participants. The GABA concentration in the PCC of the mTBI group was significantly different from that in healthy controls: GABA/tCr was higher by 27%, absolute GABA concentration with different types of correction was higher by ≈17%. No significant differences were observed in Glx concentrations (P ≥ 0.32) or in Glx/tCr (P ≥ 0.1), NAA/tCr (P = 0.55), and Cho/tCr levels (P = 0.85). DATA CONCLUSION: We report an increase in the GABA concentration in the PCC region in acute mTBI pediatric patients. This may suggest activation of GABA synthesis and impairment of the GABAergic system after acute mTBI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

A Genome-Wide Association Study Reveals a BDNF-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical Measures.

At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33 × 10-8 calculated with the Yates-corrected χ2 test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWASs of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network, where BDNF is the most significant hub gene. This study indicates that several genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The study also reveals a central role of BDNF in the pathogenesis of AD.

Role of silymarin as antioxidant in clinical management of chronic liver diseases: a narrative review.

Chronic liver disease (CLD), manifested as hepatic injury, is a major cause of global morbidity and mortality. CLD progresses to fibrosis, cirrhosis, and-ultimately-hepatocellular carcinoma (HCC) if left untreated. The different phenotypes of CLD based on their respective clinical features and causative agents include alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), and drug-induced liver injury (DILI). The preferred treatment modality for CLD includes lifestyle modification and diet, along with limited pharmacological agents for symptomatic treatment. Moreover, oxidative stress (OS) is an important pathological mechanism underlying all CLD phenotypes; hence, the use of antioxidants to manage the disease is justified. Based on available clinical evidence, silymarin can be utilized as a hepatoprotective agent, given its potent antioxidant, antifibrotic, and anti-inflammatory properties. The role of silymarin in suppressing OS has been well established, and therefore silymarin is recommended for use in ALD and NAFLD in the guidelines approved by the Russian Medical Scientific Society of Therapists and the Gastroenterology Scientific Society of Russia. However, to discuss the positioning of the original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies, an expert panel of international and Russian medical professionals was convened on 11 November 2020. The panel reviewed approaches for the prevention and treatment of OS, existing guidelines for patient management for CLD, and available evidence on the effectiveness of silymarin in reducing OS, fibrosis, and hepatic inflammation and presented in the form of a narrative review. Key messagesAn expert panel of international and Russian medical professionals reviewed existing guidelines for ALD, NAFLD, MAFLD, and DILI to establish consensus recommendations that oxidative stress is the common pathophysiological mechanism underlying these conditions.The panel also discussed the positioning of original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies.The panel reviewed the effectiveness of 140 mg original silymarin three times a day in reducing oxidative stress in chronic liver diseases such as ALD, NAFLD, MAFLD, and DILI.

Faraday isolator based on crystalline silicon for 2-µm laser radiation.

The magneto-optical properties of single-crystal silicon were investigated as a function of wavelength and temperature. A bulk free-space traditional Faraday isolator for the radiation with a wavelength of 1940 nm (magnetic field ∼2.8 Т) was implemented. The negative value of the piezo-optical anisotropy ratio of the used material allowed for the development of a Faraday isolator with compensation of thermally induced depolarization without a reciprocal rotator. The potential of single-crystal silicon as a magneto-optical material for Faraday isolators operating at room as well as at cryogenic temperatures in high-power laser radiation was considered. It was shown that single-crystal silicon is highly promising for the development of Faraday devices, including ones for next-generation laser interferometers aimed at detecting gravitational waves.

Thermally induced depolarization in a silicon (c-Si) single crystal.

Single-crystal silicon is one of the most promising materials for producing test masses for the new generation of laser interferometers intended for the detection of gravitational waves. We studied the thermally induced depolarization of radiation in single-crystal silicon with [001] orientation at a wavelength of 1940 nm at room temperature. The value of the piezo-optical anisotropy ratio was found to be ξ = -0.63 ± 0.05 for one manufacturer and ξ = 0.62 ± 0.05 for another. The physical reason for the different signs was not established, and the search for this reason will continue. For the single-crystal silicon with the negative piezo-optical anisotropy ratio, the directions of the special orientations [C] and [P] for which thermally induced depolarization and thermal lens astigmatism vanish, respectively, were determined. When ξ is close to -0.5, the special orientations are close to [111], making this orientation preferable to the other traditionally used orientation, [001].

Integrative Analysis of Multi-Omics and Genetic Approaches-A New Level in Atherosclerotic Cardiovascular Risk Prediction.

Genetics and environmental and lifestyle factors deeply affect cardiovascular diseases, with atherosclerosis as the etiopathological factor (ACVD) and their early recognition can significantly contribute to an efficient prevention and treatment of the disease. Due to the vast number of these factors, only the novel "omic" approaches are surmised. In addition to genomics, which extended the effective therapeutic potential for complex and rarer diseases, the use of "omics" presents a step-forward that can be harnessed for more accurate ACVD prediction and risk assessment in larger populations. The analysis of these data by artificial intelligence (AI)/machine learning (ML) strategies makes is possible to decipher the large amount of data that derives from such techniques, in order to provide an unbiased assessment of pathophysiological correlations and to develop a better understanding of the molecular background of ACVD. The predictive models implementing data from these "omics", are based on consolidated AI best practices for classical ML and deep learning paradigms that employ methods (e.g., Integrative Network Fusion method, using an AI/ML supervised strategy and cross-validation) to validate the reproducibility of the results. Here, we highlight the proposed integrated approach for the prediction and diagnosis of ACVD with the presentation of the key elements of a joint scientific project of the University of Milan and the Almazov National Medical Research Centre.

Thermo-Optical Studies of Laser Ceramics.

A cycle of works on manufacturing and studying laser and magnetooptical ceramics with a focus on their thermo-optical characteristics performed by the research team is analyzed. Original results that have not been published before such as measurements of the Verdet constant in the Zr:TAG, Re:MgAl2O4, and ZnAl2O4 ceramics are also presented.

Thermo-optical properties of terbium sesquioxide (Tb2O3) ceramics at room temperature.

Thermo-optical properties of several (Tb1-xYx)2O3 ceramic samples were investigated in this Letter. The linear absorption and thermal conductivity coefficients, as well as the power dependence of thermally induced phase and polarization distortions of laser radiation, were measured. In addition, the effective thermo-optical constants Peff and Qeff were estimated. Thermo-optical properties of the studied ceramics were compared with those of the widely used terbium gallium garnet. It was shown that the material under consideration is highly promising for Faraday isolators operating at high average power laser radiation.