Spectrum of Surgical Site Infection Pathogens in Chronic Infectious Spondylitis Requiring Revision Surgery: A 5-Year Cohort Study.

Background: Spectrum monitoring of the pathogen in spondylitis patients plays a key role in preventing infectious complications of spinal reconstructions in chronic spondylitis (CS) and in the treatment of surgical site infection (SSI). The aim of this study is to characterize the spectrum of SSI pathogens in CS requiring revision surgery. Methods: The primary cohort encompassed 569 surgical patients with infectious CS. In 99 patients (61 men and 38 women) requiring revision surgical interventions due to SSI, continuous microbiological monitoring of the pathogens was conducted. The average age of the patients was 63 ± 14 years. The vast majority of the patients underwent surgery on a set of multilevel (two or more spinal-motor segments) lesions. Lesions of the lumbar spine were more often noted, and lesions of the thoracic, thoracolumbar, and cervical spine sections were less often noted. This study included all patients operated on within the scope of revision spinal reconstructions in connection with the development of infection of the surgical area over the period from January 2018 to December 2022. Inclusion criteria were etiologically verified spondylitis, age of 18 years or older, and follow-up of 6 months or more. Results: The average rate of revision surgery due to SSI was 17.4%. Germ detection from the material of vertebral localization was noted in 48.3% and pathogen strains were isolated in urine in 60.8%, in decubital ulcers in 23.9%, and in hemoculture in 15.2% of all study patients. Aseptic, deep SSI was detected in 10.1%. Gram-positive, multidrug-resistant, and Gram-negative bacteria with extreme resistance prevailed in the microbiological landscape of late SSI, early, and delayed Gram-positive strains without drug resistance. Conclusions: Infectious etiology of spondylitis is associated with a significantly higher frequency of SSI. In the absence of a positive result from bacteriological examination of the vertebral localization material, it is advisable to conduct blood, decubital ulcer discharge, and urine sampling.

Risk assessment of psychiatric complications in infectious diseases: CALCulation of prognostic indices on example of COVID-19.

Introduction: Factors such as coronavirus neurotropism, which is associated with a massive increase in pro-inflammatory molecules and neuroglial reactivity, along with experiences of intensive therapy wards, fears of pandemic, and social restrictions, are pointed out to contribute to the occurrence of neuropsychiatric conditions. Aim: The aim of this study is to evaluate the role of COVID-19 inflammation-related indices as potential markers predicting psychiatric complications in COVID-19. Methods: A total of 177 individuals were examined, with 117 patients from a temporary infectious disease ward hospitalized due to COVID-19 forming the experimental group and 60 patients from the outpatient department showing signs of acute respiratory viral infection comprising the validation group. The PLR index (platelet-to-lymphocyte ratio) and the CALC index (comorbidity + age + lymphocyte + C-reactive protein) were calculated. Present State Examination 10, Hospital Anxiety and Depression Scale, and Montreal Cognitive Assessment were used to assess psychopathology in the sample. Regression and Receiver operating characteristic (ROC) analysis, establishment of cutoff values for the COVID-19 prognosis indices, contingency tables, and comparison of means were used. Results: The presence of multiple concurrent groups of psychopathological symptoms in the experimental group was associated (R² = 0.28, F = 5.63, p < 0.001) with a decrease in the PLR index and a simultaneous increase in CALC. The Area Under Curve (AUC) for the cutoff value of PLR was 0.384 (unsatisfactory). For CALC, the cutoff value associated with an increased risk of more psychopathological domains was seven points (sensitivity = 79.0%, specificity = 69.4%, AUC = 0.719). Those with CALC > 7 were more likely to have disturbances in orientation (χ² = 13.6; p < 0.001), thinking (χ² = 7.07; p = 0.008), planning ability (χ² = 3.91; p = 0.048). In the validation group, an association (R²McF = 0.0775; p = 0.041) between CALC values exceeding seven points and the concurrent presence of pronounced anxiety, depression, and cognitive impairments was demonstrated (OR = 1.52; p = 0.038; AUC = 0.66). Discussion: In patients with COVID-19, the CALC index may be used for the risk assessment of primary developed mental disturbances in the context of the underlying disease with a diagnostic threshold of seven points.

The Expression of Kisspeptins and Matrix Metalloproteinases in Extragenital Endometriosis.

Endometriosis is characterized by a condition where endometrial tissue grows outside the uterine cavity. The mechanisms of endometrium growth during endometriosis might be similar to the development of a tumor. The kisspeptin (KISS1) gene was initially discovered as a suppressor of metastasis. Matrix metalloproteinases (MMPs) and their inhibitors are described as factors in the early stages of endometriosis and tumor growth progression. We applied the quantitative polymerase chain reaction and the immunofluorescence method to investigate KISS1, its receptor (KISS1R), MMP-2, and MMP-9 in the eutopic and ectopic endometrium in women with and without endometriosis. We presume that the dysregulation of KISS1 and MMPs might contribute to endometriosis pathogenesis. Samples for the immunofluorescence study were collected from patients with a confirmed diagnosis of endometriosis in stages I-IV, aged 23 to 38 years old (n = 40). The cell line was derived from the endometrium of patients with extragenital endometriosis (n = 7). KISS1 and KISS1R expression are present in the ectopic endometrium of patients with extragenital endometriosis, as opposed to the control group where these proteins were not expressed. There is a decrease in KISS1 and KISS1R values at all stages of endometriosis. MMP-2 and MMP-9 genes express statistically significant increases in stages II, III, and IV of extragenital endometriosis. MMP synthesis increased in the last stages of endometriosis. We suppose that the KISS1/KISS1R system can be used in the future as a suppressive complex to reduce MMP-2 and MMP-9 expression and prevent endometrial cells from invading.

Pullulan-Based Hydrogels in Wound Healing and Skin Tissue Engineering Applications: A Review.

Wound healing is a complex process of overlapping phases with the primary aim of the creation of new tissues and restoring their anatomical functions. Wound dressings are fabricated to protect the wound and accelerate the healing process. Biomaterials used to design dressing of wounds could be natural or synthetic as well as the combination of both materials. Polysaccharide polymers have been used to fabricate wound dressings. The applications of biopolymers, such as chitin, gelatin, pullulan, and chitosan, have greatly expanded in the biomedical field due to their non-toxic, antibacterial, biocompatible, hemostatic, and nonimmunogenic properties. Most of these polymers have been used in the form of foams, films, sponges, and fibers in drug carrier devices, skin tissue scaffolds, and wound dressings. Currently, special focus has been directed towards the fabrication of wound dressings based on synthesized hydrogels using natural polymers. The high-water retention capacity of hydrogels makes them potent candidates for wound dressings as they provide a moist environment in the wound and remove excess wound fluid, thereby accelerating wound healing. The incorporation of pullulan with different, naturally occurring polymers, such as chitosan, in wound dressings is currently attracting much attention due to the antimicrobial, antioxidant and nonimmunogenic properties. Despite the valuable properties of pullulan, it also has some limitations, such as poor mechanical properties and high cost. However, these properties are improved by blending it with different polymers. Additionally, more investigations are required to obtain pullulan derivatives with suitable properties in high quality wound dressings and tissue engineering applications. This review summarizes the properties and wound dressing applications of naturally occurring pullulan, then examines it in combination with other biocompatible polymers, such chitosan and gelatin, and discusses the facile approaches for oxidative modification of pullulan.

Inhibition of JAK1,2 Prevents Fibrotic Remodeling of Pulmonary Vascular Bed and Improves Outcomes in the Rat Model of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism with poor clinical outcomes. Therapeutic approaches to prevention of fibrotic remodeling of the pulmonary vascular bed in CTEPH are limited. In this work, we tested the hypothesis that Janus kinase 1/2 (JAK1/2) inhibition with ruxolitinib might prevent and attenuate CTEPH in a rat model. CTEPH was induced by repeated embolization of the pulmonary artery with partially biodegradable 180 ± 30 µm alginate microspheres. Two weeks after the last injection of microspheres, ruxolitinib was administered orally at doses of 0.86, 2.58, and 4.28 mg/kg per day for 4 weeks. Prednisolone (1.475 mg/kg, i.m.) was used as a reference drug. Ruxolitinib in all doses as well as prednisolone reduced pulmonary vascular wall hypertrophy. Ruxolitinib at a dose of 2.58 mg/kg and prednisolone reduced vascular wall fibrosis. Prednisolone treatment resulted in decreased right ventricular systolic pressure. Pulmonary vascular resistance was lower in the prednisolone and ruxolitinib (4.28 mg/kg) groups in comparison with the placebo group. The plasma level of brain natriuretic peptide was lower in groups receiving ruxolitinib at doses of 2.58 and 4.28 mg/kg versus placebo. This study demonstrated that JAK1/2 inhibitor ruxolitinib dose-dependently reduced pulmonary vascular remodeling, thereby preventing CTEPH formation in rats.

A Review on Chitosan and Cellulose Hydrogels for Wound Dressings.

Wound management remains a challenging issue around the world, although a lot of wound dressing materials have been produced for the treatment of chronic and acute wounds. Wound healing is a highly dynamic and complex regulatory process that involves four principal integrated phases, including hemostasis, inflammation, proliferation, and remodeling. Chronic non-healing wounds are wounds that heal significantly more slowly, fail to progress to all the phases of the normal wound healing process, and are usually stalled at the inflammatory phase. These wounds cause a lot of challenges to patients, such as severe emotional and physical stress and generate a considerable financial burden on patients and the general public healthcare system. It has been reported that about 1-2% of the global population suffers from chronic non-healing wounds during their lifetime in developed nations. Traditional wound dressings are dry, and therefore cannot provide moist environment for wound healing and do not possess antibacterial properties. Wound dressings that are currently used consist of bandages, films, foams, patches and hydrogels. Currently, hydrogels are gaining much attention as a result of their water-holding capacity, providing a moist wound-healing milieu. Chitosan is a biopolymer that has gained a lot of attention recently in the pharmaceutical industry due to its unique chemical and antibacterial nature. However, with its poor mechanical properties, chitosan is incorporated with other biopolymers, such as the cellulose of desirable biocompatibility, at the same time having the improved mechanical and physical properties of the hydrogels. This review focuses on the study of biopolymers, such as cellulose and chitosan hydrogels, for wound treatment.

Melatonin: Manager of psychosomatic and metabolic disorders in polymorbid cardiovascular pathology.

Objectives: To investigate the relationship between changes in circadian patterns of melatonin and clinical manifestations of polymorbid cardiovascular pathology (PCVP) in young men and to analyze the effectiveness of their complex treatment. Materials and methods: We made the immunohistochemical (IHC) analysis of epiphysis tissues from autopsies of 25 men aged 32-44 with PCVP and metabolic syndrome (MS) who had died as a result of ischemic cardiomyopathy (IC) and 25 persons after the car accident as a control group. Then, 93 young men aged 35-44 with PCVP, metabolic syndrome, and depressive spectrum disorders (DSD) were divided into three groups: (1) standard therapy; (2) standard therapy and psychotherapy sessions; (3) standard therapy in combination with psychotherapeutic and psychophysiological visual and auditory correction sessions. The control group included 24 conditionally healthy male volunteers. Before and after the treatment, we studied the anthropometric status, lipid and carbohydrate metabolism indicators, the level of urinary 6-hydroxymelatonin sulfate, the degree of nocturnal decrease in blood pressure (BP), and the relationship of these indicators with circadian variations of melatonin excretion. Results: Young polymorbid patients who died from IC have a lower expression of melatonin type 1 and 2 receptors. All patients with PCVP showed a decrease in the nocturnal melatonin excretion fraction and a correlation with higher severity of depressive (r = -0.72) and anxiety (r = -0.66) symptoms. Reduced values of the 6-hydroxymelatonin sulfate (6-SM) in the 1st (r = 0.45), 2nd (r = 0.39), and 3rd (r = 0.51) groups before treatment was associated with periods of increased BP. The achievement of melatonin excretion reference values and normalization of biochemical parameters of carbohydrate and lipid metabolism, daily BP profile, and psychophysiological state were noted in all three patients' groups, with a more pronounced effect in group 3. Conclusion: Low nocturnal melatonin excretion levels are associated with greater severity of clinical symptoms and a higher risk of death in patients with PCVP. Therefore, comprehensive therapy may be more effective for correcting this disease.

The Fabrication of Alginate-Carboxymethyl Cellulose-Based Composites and Drug Release Profiles.

Recently, hydrogels based on natural water-soluble polysaccharides have attracted more and more attention due to their favorable characteristics. The high water-holding capacity, lack of toxicity, and biodegradability of such hydrogels make it possible to develop new materials on their basis for biotechnological, biomedical, pharmacological, and medical purposes. Sodium alginate is a non-toxic natural polysaccharide found in marine algae. It is capable of forming solid gels under the action of polyvalent cations that cross-link polysaccharide chains. Alginate-based products are popular in many industries, including food processing, pharmaceutical, and biomedical applications. Cellulose is the most abundant, renewable, and natural polymer on Earth, and it is used for various industrial and biomedical applications. Carboxymethyl cellulose (CMC) is useful in pharmaceutical, food, and non-food industries such as tablets, ice cream, drinks, toothpaste, and detergents. In this review, various methods for the preparation of the compositions based on sodium alginate and CMC using different crosslinking agents have been collected for the first time. Additionally, the drug release profile from such polymer matrixes was analyzed.

Electrocardiographic Patterns of Depolarization Abnormalities Help to Identify Reduced Left Ventricular Ejection Fraction.

The aim of the study was to investigate the relationship between a decrease in the left ventricular ejection fraction (EF) and traditional ECG signs associated with structural changes of the myocardium (pathological Q wave, ventricular arrhythmias) and relatively new and poorly understood (fragmented QRS complex (fQRS), early repolarization pattern (ERP)) and evaluate their significance for identifying patients with mildly reduced EF (mrEF). The study included 148 patients who were treated and examined at the Almazov Medical Research Center. FQRS, ERP, pathological Q wave, and premature ventricular contractions (PVC) were described in the analysis of the ECG, and the results of echocardiography and statistical data were analyzed: Fisher's test and chi-square, correlation analysis, and ROC analysis. According to the level of EF, patients were divided into three groups: group 1-patients with low EF (lEF) (less than 40%), group 2-patients with mildly reduced EF (mrEF) (40-49%); group 3-patients with preserved EF (pEF) (more than 50%). In the first group (EF), fQRS was registered in 16 (51.6%) patients, in the mrEF in 16 (18.2%). Pathological Q wave was detected in lEF in 20 (65%), in mrEF in 10 (35%), 15 (18%), in pEF in 15 (18%). The fQRS has been found to be more important in identifying patients with mrEF. In lEF in 2 (6.5%) patients, in mrEF in 2 (6.9%), in pEF in 11 (12.5%). There was no relationship between ERP, the amount of PVC, and the presence of ventricular tachycardia with EF. FQRS is significantly more common occurred with a decrease in EF and may be a marker of a mrEF. Thus, fQRS is associated with mrEF and pay close attention in routine clinical practice to identify patients at high risk of developing systolic dysfunction.

fMRI Findings in Cortical Brain Networks Interactions in Migraine Following Repetitive Transcranial Magnetic Stimulation.

Background: Repetitive transcranial magnetic stimulation (rTMS) is one of the high-potential non-pharmacological methods for migraine treatment. The purpose of this study is to define the neuroimaging markers associated with rTMS therapy in patients with migraine based on data from functional MRI (fMRI). Materials and Methods: A total of 19 patients with episodic migraine without aura underwent a 5-day course of rTMS of the fronto-temporo-parietal junction bilaterally, at 10 Hz frequency and 60% of motor threshold response of 900 pulses. Resting-state functional MRI (1.5 T) and a battery of tests were carried out for each patient to clarify their diagnosis, qualitative and quantitative characteristics of pain, and associated affective symptoms. Changes in functional connectivity (FC) in the brain's neural networks before and after the treatment were identified through independent components analysis. Results: Over the course of therapy, we observed an increase in FC of the default mode network within it, with pain system components and with structures of the visual network. We also noted a decrease in FC of the salience network with sensorimotor and visual networks, as well as an increase in FC of the visual network. Besides, we identified 5 patients who did not have a positive response to one rTMS course after the first week of treatment according to the clinical scales results, presumably because of an increasing trend of depressive symptoms and neuroimaging criteria for depressive disorder. Conclusions: Our results show that a 5-day course of rTMS significantly alters the connectivity of brain networks associated with pain and antinociceptive brain systems in about 70% of cases, which may shed light on the neural mechanisms underlying migraine treatment with rTMS.

Isolated Sphenoid Sinusitis: Anatomical Features for Choosing a Method of Treatment, a Case-Control Study.

Isolated sphenoid sinusitis (ISS) is a group of pathologies characterized by inflammation in one or both sphenoid sinuses. The gold standard for analyzing and diagnosing ISS is computer tomography. Many researchers have discussed the treatment of patients with ISS variants such as fully opacified sinus, mostly with surgery. A retrospective analysis of clinical data of 59 patients (21 male (35%), 38 female (65%)) with ISS, who were treated in the Otorhinolaryngological Department of Pavlov First Saint Petersburg State Medical University between January 2017 and January 2020, was conducted. All patients were in the first stage of the same medical therapy. In cases where there was no recovery, these patients were referred to surgery. For the control group, we analyzed patients without any disorders according to CT-scan examination. After analyzing the obtained clinical and radiological data, we found indicators that were common in patients who did not recover after medical therapy. According to the reverse regression method statistical model, in male patients with a diffuse headache and nasal discharge it was shown that medical therapy was highly effective (more than 78%). The presence of nasal septum deviation and adenoids in male and female patients leads to the highest risk of surgical treatment (83% probability of the logistic model). The detailed analysis of CT-scans and the complaints of patients with ISS can be the key to determining the preferred therapy choice. Not all cases need to have an endoscopic opening of the sphenoid sinus, according to our research.

Hemolytic Activity, Cytotoxicity, and Antimicrobial Effects of Human Albumin- and Polysorbate-80-Coated Silver Nanoparticles.

In this study, we aimed to develop a technique for colloidal silver nanoparticle (AgNP) modification in order to increase their stability in aqueous suspensions. For this purpose, 40-nm spherical AgNPs were modified by the addition of either human albumin or Tween-80 (Polysorbate-80). After detailed characterization of their physicochemical properties, the hemolytic activity of the nonmodified and modified AgNPs was investigated, as well as their cytotoxicity and antimicrobial effects. Both albumin- and Tween-80-coated AgNPs demonstrated excellent stability in 0.9% sodium chloride solution (>12 months) compared to nonmodified AgNPs, characterized by their rapid precipitation. Hemolytic activity of nonmodified and albumin-coated AgNPs was found to be minimal, while Tween-80-modified AgNPs produced significant hemolysis after 1, 2, and 24 h of incubation. In addition, both native and Tween-80-covered AgNPs showed dose-dependent cytotoxic effects on human adipose-tissue-derived mesenchymal stem cells. The albumin-coated AgNPs showed minimal cytotoxicity. The antimicrobial effects of native and albumin-coated AgNPs against S. aureus, K. pneumonia, P. aeruginosa, Corynebacterium spp., and Acinetobacter spp. were statistically significant. We conclude that albumin coating of AgNPs significantly contributes to improve stability, reduce cytotoxicity, and confers potent antimicrobial action.

Study of the Fabrication Technology of Hybrid Microfluidic Biochips for Label-Free Detection of Proteins.

A study of the peculiarities and a comparative analysis of the technologies used for the fabrication of elements of novel hybrid microfluidic biochips for express biomedical analysis have been carried out. The biochips were designed with an incorporated microfluidic system, which enabled an accumulation of the target compounds in a biological fluid to be achieved, thus increasing the biochip system's sensitivity and even implementing a label-free design of the detection unit. The multilevel process of manufacturing a microfluidic system of a given topology for label-free fluorometric detection of protein structures is presented. The technological process included the chemical modification of the working surface of glass substrates by silanization using (3-aminopropyl) trimethoxysilane (APTMS), formation of the microchannels, for which SU-8 technologies and a last generation dry film photoresist were studied and compared. The solid-state phosphor layers were deposited using three methods: drop application; airbrushing; and mechanical spraying onto the adhesive surface. The processes of sealing the system, installing input ports, and packaging using micro-assembly technologies are described. The technological process has been optimized and the biochip was implemented and tested. The presented system can be used to design novel high-performance diagnostic tools that implement the function of express detection of protein markers of diseases and create low-power multimodal, highly intelligent portable analytical decision-making systems in medicine.

Shape anomaly detection under strong measurement noise: An analytical approach to adaptive thresholding.

We suggest an analytical approach to the adaptive thresholding in a shape anomaly detection problem. We find an analytical expression for the distribution of the cosine similarity score between a reference shape and an observational shape hindered by strong measurement noise that depends solely on the noise level and is independent of the particular shape analyzed. The analytical treatment is also confirmed by computer simulations and shows nearly perfect agreement. Using this analytical solution, we suggest an improved shape anomaly detection approach based on adaptive thresholding. We validate the noise robustness of our approach using typical shapes of normal and pathological electrocardiogram cycles hindered by additive white noise. We show explicitly that under high noise levels our approach considerably outperforms the conventional tactic that does not take into account variations in the noise level.