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OBJECTIVE: To compare the effectiveness of neurofeedback (NFB) at infra-low and alpha frequencies in the treatment of cognitive impairment in patients with early cerebral small vessel disease (cSVD). MATERIAL AND METHODS: The study included 71 patients (average age 52.8±6.3 years, men 15%, women 85%) with early cSVD and 21 healthy volunteers (average age 53.2±4.8 years, men 29%, women 71%). All participants were assessed for clinical manifestations and cognitive functions, brain MRI, and EEG. cSVD patients were randomized by an envelope method with double-blind placebo control. Three groups of neurofeedback were formed: infra-low waves (n=25), alpha waves (n=22), simulated neurofeedback using EEG (placebo) (n=24). Fifteen sessions of 30 minutes were conducted 2-5 times a week. The cognitive profile and EEG were assessed immediately and 6-8 weeks after completion of the neurofeedback course. RESULTS: Patients with early cSVD had subjective (65%) and moderate (35%) cognitive impairment with predominant deviations in the components of executive brain functions (EBF). Neurofeedback using infra-low waves significantly improved EBF in the components of productivity, switching and inhibition, non-verbal delayed memory immediately after the course, maintaining the effect for at least 6-8 weeks, which was accompanied by an increase in the power (µB2) of the alpha rhythm in the occipital regions. Neurofeedback using alpha waves showed improvement in the Stroop test (interference index) in the delayed period. CONCLUSION: In patients with early cSVD and deterioration of EBF, it is preferable to conduct biofeedback neurotraining at infra-low frequencies to treat cognitive impairment and create a cognitive reserve. An increase in the power of the alpha rhythm in the occipital regions during the course can be considered a prognostic marker of its effectiveness.

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OBJECTIVE: Accurate measurement of arterial blood pressure (BP) is crucial for the diagnosis, monitoring, and treatment of hypertension. This narrative review highlights the challenges associated with conventional (cuff-based) BP measurement and potential solutions. This work covers each method of cuff-based BP measurement, as well as cuffless alternatives, but is primarily focused on ambulatory BP monitoring. RESULTS: Manual BP measurement requires stringent training and standardized protocols which are often difficult to ensure in stressful and time-restricted clinical office blood pressure monitoring (OBPM) scenarios. Home Blood pressure monitoring (HBPM) can identify white-coat and masked hypertension but strongly depends on patient adherence to measurement techniques and procedure. The widespread use of nonvalidated automated HBPM devices raises further concerns about measurement accuracy. Ambulatory blood pressure measurement (ABPM) may be used in addition to OBPM. It is recommended to diagnose white-coat and masked hypertension as well as nocturnal BP and dipping, which are the BP values most predictive for major adverse cardiac events. Nonetheless, ABPM is limited by its non-continuous nature and susceptibility to measurement artefacts. This leads to poor overall reproducibility of ABPM results, especially regarding clinical parameters such as BP variability or dipping patterns. CONCLUSIONS: Cuff-based BP measurement, despite some limitations, is vital for cardiovascular health assessment in clinical practice. Given the wide range of methodological limitations, the paradigm's potential for improvement is not yet fully realized. There are impactful and easily incorporated opportunities for innovation regarding the enhancement of measurement accuracy and reliability as well as the clinical interpretation of the retrieved data. There is a clear need for continued research and technological advancement to improve BP measurement as the premier tool for cardiovascular disease detection and management.

Accurate blood pressure measurement is crucial for diagnosing, monitoring, and treating hypertension and preventing cardiovascular diseases.Manual blood pressure monitoring is common but may not always be reliable due to the stress and time constraints in clinical settings. It also fails to detect white-coat and masked hypertension.Home blood pressure monitoring helps to identify white-coat and masked hypertension but depends on how well patients follow the measurement instructions. Many devices are not validated, raising concerns about their accuracy.Ambulatory blood pressure measurement may be used in addition to office blood pressure measurement because of its better reproducibility and higher predictive value. It is recommended to diagnose white-coat and masked hypertension as well as nocturnal BP and dipping. However, it and can be prone to errors, affecting the reliability of results like BP variability or night-time dipping patterns.Patient's posture, physical activity, and conditions like atrial fibrillation can influence BP readings.Automated BP devices often have limitations in detecting measurement artefacts, underscoring the need for technological improvements.Despite its limitations, cuff-based blood pressure measurement is essential in everyday clinical practice but has unlocked potential for improvement.

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Over the past few decades, researchers have focused on developing new production methods for geopolymers to improve their properties for use in multiple applications as a functional material. This study introduces a new geopolymer system based on wollastonite and metakaolin as precursors. The role of wollastonite was also explored alongside metakaolin in geopolymers. Geopolymers were synthesized by adding wollastonite to metakaolin in different ratios: 0 wt.%, 12.5 wt.%, 25 wt.%, and 50 wt.%. The alkaline activator was then mixed with the powder, wollastonite, and metakaolin to prepare the geopolymers. In addition to mechanical tests, the hardened geopolymers were characterized using XRD, TGA, and SEM techniques. The findings revealed that adding wollastonite in amounts of 0 wt.%-12.5 wt.% did not affect the strength of the geopolymers. Increasing wollastonite between 25 wt.% and 50 wt.% significantly increased the geopolymers' flexural and compressive strength from 3 MPa to 12.3 MPa and from 23 MPa to 54 MPa, respectively. The use of wollastonite as a precursor also led to fundamental changes in the microstructural structure of the geopolymer matrix: a new crystal phase, (Ca5(SiO4)2(OH)2), calciochondrodite was formed, and the Si-Al-Na crystal phase disappeared, leading to significant changes in the amorphous phase.

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The development of drug therapy for the pathological calcification of the aortic valve is still an open issue due to the lack of effective treatment strategies. Currently, the only option for treating this condition is surgical correction and symptom management. The search for models to study the safety and efficacy of anti-calcifying drugs requires them to not only be as close as possible to in vivo conditions, but also to be flexible with regard to the molecular studies that can be applied to them. The ex vivo model has several advantages, including the ability to study the effect of a drug on human cells while preserving the original structure of the valve. This allows for a better understanding of how different cell types interact within the valve, including non-dividing cells. The aim of this study was to develop a reproducible ex vivo calcification model based on valves from patients with calcific aortic stenosis. We aimed to induce spontaneous calcification in valve tissue fragments under osteogenic conditions, and to demonstrate the possibility of significantly suppressing it using a calcification inhibitor. To validate the model, we tested a Notch inhibitor Crenigacestat (LY3039478), which has been previously shown to have an anti-calcifying effect on interstitial cell of the aortic valve. We demonstrate here an approach to testing calcification inhibitors using an ex vivo model of cultured human aortic valve tissue fragments. Thus, we propose that ex vivo models may warrant further investigation for their utility in studying aortic valve disease and performing pre-clinical assessment of drug efficacy.

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OBJECTIVE: Evaluation of the analgesic, opioid-sparing, anti-inflammatory and adverse effects of the diclofenac and orphenadrine (Neodolpasse) fixed combination for analgesia in the postoperative period of surgical cancer patients. MATERIAL AND METHODS: A randomized, single-center, prospective, comparative study evaluated two analgesic regimens in 40 cancer patients undergoing various open cavity surgeries, including extensive combined interventions associated with the resection of 3 or more organs. The study was conducted following the transfer from the ICU to the surgical department during the early activation period, within the first two postoperative days. In the first group N (n=20), "Neodolpasse" (a fixed combination of 75 mg Diclofenac and 30 mg Orphenadrine) was administered as an infusion, twice daily. In the second group K (n=20) analgesia was performed with ketoprofen as an intravenous infusion at a daily dose of 200 mg. Patients in both groups received scheduled prolonged epidural analgesia with 0.2% ropivacaine, and when the severity of pain in a visual analogue scale (VAS) increased to more than 40 mm, so an additional dose of 100 mg tramadol was administered intramuscularly. Daily measurments of blood creatinine level and C-reactive protein were taken, postoperative blood loss was accounted for, as well as postoperative complications according to the Clavien-Dindo classification. RESULTS: The comparative analysis of the indicators of pain syndrome severity showed that the patients in group N exhibited a more pronounced analgesic effect, so on the second postoperative day 30% of patients reported moderate pain (from 50 to 60 mm on the pain scale), on the third day - 15%, and by the fourth day - all 100% of patients experienced pain of low intensity. The additional analgesia with tramadol in group N was required twice less than in the comparison group, and such adverse effects as nausea, drowsiness, and weakness were significantly more common in the ketoprofen group. In both groups, the average blood creatinine level did not exceed permissible values, and the C-reactive protein was elevated at all stages of the study but tended to decrease by the fourth day. The analysis of postoperative complications according to the Clavien-Dindo scale at the time of discharge did not reveal a direct correlation between the occurred complications and the use of NSAIDs. Adverse effects such as anastomotic failure, gastrointestinal complications, or other hemorrhagic manifestations were not recorded. CONCLUSION: The inclusion of Neodolpasse into multimodal analgesic regimens resulted in the most pronounced analgesic and opioid-sparing effects in surgical cancer patients using laparotomy access. Additionally, the application of short courses of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a favorable safety profile.

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Genitourinary cancer (GUC) represents more than one fifth of all human cancers. This makes the development of approaches to its early diagnosis an important task of modern biomedicine. Circulating microRNAs, short (17-25 nucleotides) non-coding RNA molecules found in human biological fluids and performing a regulatory role in the cell, are considered as promising diagnostic and prognostic biomarkers of cancers, including GUC. In this review we have considered the current state of research aimed at assessing microRNAs as biomarkers of such human GUC types as malignant tumors of the bladder, kidney, prostate, testicles, ovaries, and cervix. A special attention has been paid to studies devoted to the identification of microRNAs in urine as a surrogate "liquid biopsy" that may provide the simplest and cheapest approach to mass non-invasive screening of human GUC. The use of microRNA panels instead of single types of microRNA generally leads to higher sensitivity and specificity of the developed diagnostic tests. However, to date, work on the microRNAs assessment as biomarkers of human GUC is still of a research nature, and the further introduction of diagnostic tests based on microRNAs into practice requires successful clinical trials.

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[This corrects the article DOI: 10.2141/jpsa.2024021.].

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CLINICAL CASE: The 59-year-old patient complained of hearing loss on the left, ear murmur for a long time, periodic pain and discomfort in the left ear, dizziness for 6 months. She was found to have concurrent vestibular schwannoma in the internal auditory canal and temporal bone paraganglioma. Both tumors were removed in one operation. The schwannoma was removed by translabirinth access due to preoperative deafness, while the glomus tumor was removed during this access. Postoperative biopsy showed the presence of two unrelated diseases: paraganglioma (ICD-0 code 8690/3) and schwannoma (ICD-0 code 9560/0).

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Brazil is renowned for its extensive plant biodiversity, with emphasis on Cymbopogon, C. citratus and C. nardus, with broad antimicrobial potential. Candidemias caused by Candida albicans are highly prevalent in immunosuppressed individuals and are associated with infections by biofilms on medical devices. The aim of this study was to evaluate the antimicrobial potential of essential oils C. citratus and C. nardus against C. albicans in planktonic and biofilm forms. Essential oils were obtained by hydrodistillation and chemical composition evaluated by GC-FID and GC-MS. The minimum inhibitory concentration was determined by the broth microdilution method and the synergy effect of essential oils and amphotericin B were evaluated by the checkerboard test. Biofilm activity was determined by the XTT assay. Cytotoxicity assays performed with VERO cells and molecular docking were performed to predict the effect of oil interaction on the SAP-5 enzyme site. The results showed activity of essential oils against planktonic cells and biofilm of C. albicans. Furthermore, the oils had a synergistic effect, and low cytotoxicity. Molecular docking showed interaction between Cadinene, Caryophyllen oxide, Germacrene D with SAP-5. The results indicate that Cymbopogon spp. studied are anti-Candida, with potential for further application in therapy against infections caused by C. albicans.

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In 2 clinical cases the neck soft tissues ultrasound in the young and old patients allowed to solve the main diagnostic tasks: to determine the presence of peritonsillar abscess cavities, their sizes and localization; to exclude the fit of large vessels near to abscesses and the presence of abnormal vessels; to conduct differential diagnosis of abscesses from a tumor and allergic angioedema. Ultrasound with external access did not require any special preparation, was easily tolerated by the patient, was informative, but it was difficult to determine the puncture place. Intraoral ultrasound was more difficult to conduct, because the transducer should be small in size to enter the patient's mouth. If the patient had a pronounced trismus, intraoral ultrasound couldn't be done. On the one hand in a case of children use the standard transducer cannot fit in the mouth as well and may be damaged by teeth. But on the other hand, the abscess puncture site can be more easily determined by intraoral examination. Compared to multi-slice computed tomography with contrast, the ultrasound method is cheaper, more accessible, faster, more informative and there is no radiation exposure associated with this method. CONCLUSION: Ultrasound of the peritonsillar region by external and intraoral methods is informative for detecting peritonsillar abscess, especially in difficult diagnostic cases.

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Background: R/S enantiomers of 11-hydroxyeicosatertraenoic acid (11-HETE) are formed from arachidonic acid by enzymatic and non-enzymatic pathways. 11-HETE is predominately formed by the cytochrome P450 1B1 (CYP1B1). The role of CYP1B1 in the development of cardiovascular diseases is well established. Objectives: This study aimed to assess the cellular hypertrophic effect of 11-HETE enantiomers in human RL-14 cardiomyocyte cell line and to examine their association with CYP1B1 levels. Methods: Human fetal ventricular cardiomyocyte, RL-14 cells, were treated with 20 µM (R) or (S) 11-HETE for 24 h. Thereafter, cellular hypertrophic markers and cell size were then determined using real-time polymerase chain reaction (RT-PCR) and phase-contrast imaging, respectively. The mRNA and protein levels of selected CYPs were determined using RT-PCR and Western blot, respectively. In addition, we examined the effect of (R) and (S) 11-HETE on CYP1B1 catalytic activity using human recombinant CYP1B1 and human liver microsomes. Results: Both (R) and (S) 11-HETE induced cellular hypertrophic markers and cell surface area in RL-14 cells. Both enantiomers significantly upregulated CYP1B1, CYP1A1, CYP4F2, and CYP4A11 at the mRNA and protein levels, however, the effect of the S-enantiomer was more pronounced. Furthermore, 11(S)-HETE increased the mRNA and protein levels of CYP2J and CYP4F2, whereas 11(R)-HETE increased only CYP4F2. Only 11(S)-HETE significantly increased the catalytic activity of CYP1B1 in recombinant human CYP1B1, suggesting allosteric activation in an enantioselective manner. Conclusion: Our study provides the first evidence that 11-HETE can induce cellular hypertrophy in RL-14 cells via the increase in CYP1B1 mRNA, protein, and activity levels.

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OBJECTIVE: To study the effectiveness and the quality of life impact of the mobile application Zdorovye.ru in people with subclinical and clinical anxiety disorder (AD). MATERIAL AND METHODS: 200 patients with more than 7 points on the Hospital Anxiety and Depression Scale (HADS) were included. Participants were randomized into two groups: experimental one (EG, n=133) - to receive standard treatment with temgicoluril (Adaptol), 500 mg (Olainfarm JSC, Latvia) and the Zdorovye.ru application; control group (CG, n=52) - standard treatment with temgicoluril (Adaptol). RESULTS: There were a significant decrease in the HADS-A score, PSS-10 score and an increase in the visual analog scale EQ-5D score in both groups after 3 months of treatment (p<0.001). Clinical improvement was noticeable after 1.5 months in EG group: a decrease in HADS-A scores (p=0.001) and in tension and stress on PSS-10 subscales (p<0.001) were noted. This effect was not observed in the CG. After 3 months, all participants noted an improvement in quality of life (p<0.001), without a statistically significant difference between groups (p=0.233). The application left a positive impression on users and doctors - most respondents rated it as useful and clear. CONCLUSION: Taking temgicoluril (Adaptol) for 3 months led to symptoms decrease and the quality of life and well-being improvement in patients with AD. Using the mobile application Zdorovye.ru in conjunction with drug therapy made it possible to achieve a clinical effect earlier, in 1.5 months.

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Sounds produced by dolphins can be grouped into tonal (whistles) and pulsed sounds (e.g., echolocation clicks and burst sounds). Clicks are broadband pulses temporarily spaced to allow echo processing between the sound source and the object. Echolocation is related mainly to prey detection and environmental recognition. Echolocation click trains tend to present a decreasing inter-click interval due to a continuous changing of the target's location when the animal approaches to capture the prey. In addition to foraging and feeding contexts, burst pulsed sounds have been associated with short social communication. Although echolocation clicks are relatively well documented, there is no consensus regarding the broad variety of the burst pulsed signals. The present study analyzed time-frequency characteristics by conducting a clustering and discrimination analysis to classify pulsed sounds. A total of 64 click trains were analyzed from short-beaked common dolphins recorded in the slope region of the western South Atlantic Ocean. Three analyses (time; frequency; and combined time-frequency parameters) were compared through k-means clustering and posterior cluster validation using Random forest analysis. The k-means clustering resulted in four clusters for all groups of analysis. The time parameters were the most accurate among the comparisons, with the first two-dimensional axis corresponding to 87 % (Dim1 = 70.2 % and Dim2 = 17.2 %). The random forest analysis showed that the time-frequency dataset was the best classification of pulsed sounds in D. delphis (Accuracy = 84.6 %; confidence interval CI = 65.1 %-95.6 %; p < 0.01). This result considers the animal an acoustical identity, emphasizing the importance of certain parameters that influence this identity and thus reflecting the energy-cost optimization for sound production.

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OBJECTIVE: To determine whether the psychostimulant lisdexamfetamine improves subjective and objective measures of cognitive functioning among women genetically at-risk for cancer who have undergone risk-reducing salpingo-oophorectomy and report new-onset executive functioning difficulties. METHODS: 69 participants were assigned to a randomized controlled crossover trial with 6-week trials of active medication (lisdexamfetamine) and placebo, separated by a minimum 2-week washout in an intent-to-treat framework (clinical trial registration number: NCT03187353). At trial baseline, midpoint, and endpoint, participants completed a self-report measure of executive functioning (Brown Attention Deficit Disorder Scale). At study baseline and trial endpoint, participants completed sustained attention, attention/working memory, and verbal learning/memory cognitive tasks. Side effects were assessed at 2, 3, 4, and 6 weeks for each trial. RESULTS: From trial baseline to trial endpoint, lisdexamfetamine - relative to placebo - significantly improved total scores on the self-report Brown Attention Deficit Disorder Scale (and scores on four of five subdomains) as well as attention and working memory performance. Significantly more participants endorsed side effects across the lisdexamfetamine trial versus placebo; however, trial completion rates were similar, indicating that lisdexamfetamine was nonetheless well-tolerated. CONCLUSIONS: Lisdexamfetamine improved both subjective and objective measures of attention and working memory and could offer women experiencing cognitive difficulties post-risk-reducing salpingo-oophorectomy an alternative therapeutic option.

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This study focuses on the acoustic classification of delphinid species at the southern continental slope of Brazil. Recordings were collected between 2013 and 2015 using towed arrays and were processed using a classifier to identify the species in the recordings. Using Raven Pro 1.6 software (Cornell Laboratory of Ornithology, Ithaca, NY), we analyzed whistles for species identification. The random forest algorithm in R facilitates classification analysis based on acoustic parameters, including low, high, delta, center, beginning, and ending frequencies, and duration. Evaluation metrics, such as correct and incorrect classification percentages, global accuracy, balanced accuracy, and p-values, were employed. Receiver operating characteristic curves and area-under-the-curve (AUC) values demonstrated well-fitting models (AUC ≥ 0.7) for species definition. Duration and delta frequency emerged as crucial parameters for classification, as indicated by the decrease in mean accuracy. Multivariate dispersion plots visualized the proximity between acoustic and visual match data and exclusively acoustic encounter (EAE) data. The EAE results classified as Delphinus delphis (n = 6), Stenella frontalis (n = 3), and Stenella longirostris (n = 2) provide valuable insights into the presence of these species between approximately 23° and 34° S in Brazil. This study demonstrates the effectiveness of acousting classification in discriminating delphinids through whistle parameters.

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BACKGROUND: The prevalence of internalizing psychopathology rises precipitously from early to mid-adolescence, yet the underlying neural phenotypes that give rise to depression and anxiety during this developmental period remain unclear. METHODS: Youth from the Adolescent Brain and Cognitive DevelopmentSM Study (ages 9-10 years at baseline) with a resting-state fMRI scan and mental health data were eligible for inclusion. Internalizing subscale scores from the Brief Problem Monitor - Youth Form were combined across two years of follow-up to generate a cumulative measure of internalizing symptoms. The total sample (n = 6521) was split into a large discovery dataset and a smaller validation dataset. Brain-behavior associations of resting-state functional connectivity (RSFC) with internalizing symptoms were estimated in the discovery dataset. The weighted contributions of each functional connection were aggregated using multivariate statistics to generate a polyneuro risk score (PNRS). The predictive power of the PNRS was evaluated in the validation dataset. RESULTS: The PNRS explained 10.73% of the observed variance in internalizing symptom scores in the validation dataset. Model performance peaked when the top 2% functional connections identified in the discovery dataset (ranked by absolute ß-weight) were retained. The RSFC networks that were implicated most prominently were the default mode, dorsal attention, and cingulo-parietal networks. These findings were significant (p < 1*10-6) as accounted for by permutation testing (n = 7000). CONCLUSIONS: These results suggest that the neural phenotype associated with internalizing symptoms during adolescence is functionally distributed. The PNRS approach is a novel method for capturing relationships between RSFC and behavior.

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We tested whether one of the consequences predicted for alien plant invasion by the mutualism disruption hypothesis was true in the case of the ash-leaved maple Acer negundo L. The study aimed to determine whether the occurrences of mycorrhizal and nonmycorrhizal herbs varied similarly or differently in communities with varying degrees of A. negundo dominance. The analysis included the results of 78 vegetation descriptions carried out in Belarusian Polesia, the Middle Volga region, and the Middle Urals. Communities with or without A. negundo dominance were described in each region. The mycorrhizal status of plant species was determined using the FungalRoot Database. Species that are more likely to form arbuscular mycorrhiza were found to occur less frequently in A. negundo thickets. On the contrary, a higher probability of the nonmycorrhizal status was associated with a lower frequency of detection in A. negundo thickets. Therefore, the occurrence of arbuscular mycorrhizal herbs was found to selectively decrease in communities dominated by A. negundo.

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BACKGROUND: There is a broad interest in deploying deep learning-based classification algorithms to identify individuals with Alzheimer's disease (AD) from healthy controls (HC) based on neuroimaging data, such as T1-weighted Magnetic Resonance Imaging (MRI). The goal of the current study is to investigate whether modern, flexible architectures such as EfficientNet provide any performance boost over more standard architectures. METHODS: MRI data was sourced from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and processed with a minimal preprocessing pipeline. Among the various architectures tested, the minimal 3D convolutional neural network SFCN stood out, composed solely of 3x3x3 convolution, batch normalization, ReLU, and max-pooling. We also examined the influence of scale on performance, testing SFCN versions with trainable parameters ranging from 720 up to 2.9 million. RESULTS: SFCN achieves a test ROC AUC of 96.0% while EfficientNet got an ROC AUC of 94.9 %. SFCN retained high performance down to 720 trainable parameters, achieving an ROC AUC of 91.4%. COMPARISON WITH EXISTING METHODS: The SFCN is compared to DenseNet and EfficientNet as well as the results of other publications in the field. CONCLUSIONS: The results indicate that using the minimal 3D convolutional neural network SFCN with a minimal preprocessing pipeline can achieve competitive performance in AD classification, challenging the necessity of employing more complex architectures with a larger number of parameters. This finding supports the efficiency of simpler deep learning models for neuroimaging-based AD diagnosis, potentially aiding in better understanding and diagnosing Alzheimer's disease.

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Common marmoset (Callithrix jacchus, CM) is a New World primate species that is of interest for preclinical trials of immunobiological products. In this study, we describe the approaches to long-term laboratory breeding and maintenance of CMs. We also establish the reference values of the main complete blood count and serum chemistry parameters evaluated during preclinical trials of immunobiological products and describe the histological characteristics of CM lymphoid organs during the development of post-vaccination immune response. We show that CMs bred in laboratory conditions excluding background infectious pathology are a relevant model that allows for a high degree of reliability in characterizing the safety and immunogenicity profile of antiviral vaccines during preclinical trials.