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The present article describes a standard instrument for the continuous online determination of retinal vessel diameters, the commercially available retinal vessel analyzer. This report is intended to provide informed guidelines for measuring ocular blood flow with this system. The report describes the principles underlying the method and the instruments currently available, and discusses clinical protocol and the specific parameters measured by the system. Unresolved questions and the possible limitations of the technique are also discussed.
Hintergrund
Die Anwendung und das Verständnis von Statistik sind sehr wichtig für die biomedizinische Forschung und für die klinische Praxis. Dies gilt insbesondere auch zur Abschätzung der Möglichkeiten unterschiedlichster Diagnostik- und Therapieoptionen beim Glaukom. Die scheinbare Komplexität der Statistik, die zum Teil dem „gesunden Menschenverstand“ zu widersprechen scheint, zusammen mit der nur vorsichtigen Akzeptanz der Statistik bei vielen Medizinern können zu bewussten und unbewussten Manipulationen bei der Datendarstellung und -interpretation führen.
Ziel der Arbeit
Ziel ist die verständliche Darstellung einiger typischer Fehler in der medizinisch-statistischen Datenbehandlung.
Material und Methoden
Anhand hypothetischer Beispiele aus der Glaukomdiagnostik erfolgen die Darstellung der Wirkung eines hypotensiven Medikamentes sowie die Beurteilung der Ergebnisse eines diagnostischen Tests. Es werden die typischsten statistischen Einsatzbereiche und Irrtumsquellen ausführlich und verständlich analysiert
Ergebnisse
Mechanismen von Datenmanipulation und falscher Dateninterpretation werden aufgeklärt. Typische Irrtumsquellen bei der statistischen Auswertung und Datendarstellung werden dabei erläutert.
Schlussfolgerungen
Die erläuterten praktischen Beispiele zeigen die Notwendigkeit, die Grundlagen der Statistik zu verstehen und korrekt anwenden zu können. Fehlendes Grundlagenwissen und Halbwissen der medizinischen Statistik können zu folgenschweren Missverständnissen und falschen Entscheidungen in der medizinischen Forschung, aber auch in der klinischen Praxis führen.
Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5–14), in 11 patients 3 months after ictus (group B: day 90 ± 35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels—central retinal arteriolar and venular equivalent—was significantly reduced in the acute phase (p < 0.001) with gradual improvement in group B (p < 0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p < 0.001) and reduced area under the curve (p < 0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p < 0.05). Venous NVC was significantly delayed after SAH compared to group C (A p < 0.001; B p < 0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.
Mit modernen nicht invasiven bildgebenden Verfahren lassen sich anhand der Fundusfotografie bzw. der optischen Verfilmung Aspekte der funktionellen und strukturellen retinalen Gefäßveränderungen objektiv untersuchen. Der Zustand und das Verhalten retinaler Gefäße beeinflussen im prä-, post- und kapillaren Bereich den Blutfluss und strömungsbedingte Stoffwechselverhältnisse passiv und aktiv über den Gefäßdurchmesser. Retinale Gefäße gleichen von Aufbau und Funktion den zerebralen Gefäßen und spiegeln den Zustand der Mikrozirkulation wider. Mithilfe von aus den Gefäßweiten berechneten Biomarkern soll eine Aussage über die Prognose von systemischen vaskulär bedingten Erkrankungen getroffen werden. Die statische retinale Gefäßanalyse befasst sich mit der Untersuchung des Zustandes der prä- und postkapillaren Gefäßdurchmesser der retinalen Mikrozirkulation anhand einer optischen Fundusaufnahme. Bei der dynamischen retinalen Gefäßanalyse wird der Längsschnitt eines retinalen Gefäßes nicht invasiv funktionell und strukturell über einen Zeitraum vor, während und nach einer spezifischen vaskulären Stimulation untersucht. Die genaue Methodologie der Auswertung und die Bezeichnung der Parameter variieren bei unterschiedlichen Ansätzen. Mittels retinaler Gefäßanalyse wurden bislang mehrere klinische Querschnitts- und Interventionsstudien in der Augenheilkunde und anderen Fachgebieten, inkl. Kardiologie, Neurologie, Neurochirurgie, Nephrologie, Gynäkologie, Sportmedizin, Diabetologie, Hypertensiologie usw. durchgeführt. Mit der statischen retinalen Gefäßanalyse steht eine kostengünstige, reproduzierbare, nicht invasive Screeningtechnik zur Verfügung, um eine prognostische Aussage über die Gefäßgesundheit eines individuellen Patienten zu treffen. Die dynamische retinale Gefäßanalyse besitzt ein weiteres diagnostisches Anwendungsspektrum als die statische, da sie das Verhalten retinaler Gefäße zeitkontinuierlich untersucht. Die Evaluation vaskulärer Erkrankungen sowie zerebro- bzw. kardiovaskulärer Morbidität und Mortalität mittels mehrerer methodologischer Modalitäten retinaler Gefäßanalyse mit ihren jeweiligen quantitativen Biomarkern bietet eine zukunftsträchtige diagnostische Perspektive. Die interdisziplinäre klinische Anwendung dieser vaskulären Biomarker gewinnt zunehmend an Bedeutung, sowohl in der Augenheilkunde als auch in anderen Fachgebieten.
Altered neurovascular coupling as measured by optical imaging: a biomarker for Alzheimer’s disease
(2017)
False spectra formation in the differential two-channel scheme of the laser Doppler flowmeter
(2018)
Noise in the differential two-channel scheme of a classic laser Doppler flowmetry (LDF) instrument was studied. Formation of false spectral components in the output signal due to beating of electrical signals in the differential amplifier was found out. The improved block-diagram of the flowmeter was developed allowing to reduce the noise.
Background
Impairment of neurovascular coupling (NVC) was recently reported in the context of subarachnoid hemorrhage and may correlate with disease severity and outcome. However, previous techniques to evaluate NVC required invasive procedures. Retinal vessels may represent an alternative option for non-invasive assessment of NVC.
Methods
A prototype of an adapted retinal vessel analyzer was used to assess retinal vessel diameter in mice. Dynamic vessel analysis (DVA) included an application of monochromatic flicker light impulses in predefined frequencies for evaluating NVC. All retinae were harvested after DVA and electroretinograms were performed.
Results
A total of 104 retinal scans were conducted in 21 male mice (90 scans). Quantitative arterial recordings were feasible only in a minority of animals, showing an emphasized reaction to flicker light impulses (8 mice; 14 scans). A characteristic venous response to flicker light, however, could observed in the majority of animals. Repeated measurements resulted in a significant decrease of baseline venous diameter (7 mice; 7 scans, p < 0.05). Ex-vivo electroretinograms, performed after in-vivo DVA, demonstrated a significant reduction of transretinal signaling in animals with repeated DVA (n = 6, p < 0.001).
Conclusions
To the best of our knowledge, this is the first non-invasive study assessing murine retinal vessel response to flicker light with characteristic changes in NVC. The imaging system can be used for basic research and enables the investigation of retinal vessel dimension and function in control mice and genetically modified animals.
BACKGROUND
Immunosuppression is often considered as an indication for antibiotic prophylaxis to prevent surgical site infections (SSI) while performing skin surgery. However, the data on the risk of developing SSI after dermatologic surgery in immunosuppressed patients are limited.
PATIENTS AND METHODS
All patients of the Department of Dermatology and Allergology at the University Hospital of RWTH Aachen in Aachen, Germany, who underwent hospitalization for a dermatologic surgery between June 2016 and January 2017 (6 months), were followed up after surgery until completion of the wound healing process. The follow-up addressed the occurrence of SSI and the need for systemic antibiotics after the operative procedure. Immunocompromised patients were compared with immunocompetent patients. The investigation was conducted as a retrospective analysis of patient records.
RESULTS
The authors performed 284 dermatologic surgeries in 177 patients. Nineteen percent (54/284) of the skin surgery was performed on immunocompromised patients. The most common indications for surgical treatment were nonmelanoma skin cancer and malignant melanomas. Surgical site infections occurred in 6.7% (19/284) of the cases. In 95% (18/19), systemic antibiotic treatment was needed. Twenty-one percent of all SSI (4/19) were seen in immunosuppressed patients.
CONCLUSION
According to the authors' data, immunosuppression does not represent a significant risk factor for SSI after dermatologic surgery. However, larger prospective studies are needed to make specific recommendations on the use of antibiotic prophylaxis while performing skin surgery in these patients.
The available data on complications after dermatologic surgery have improved over the past years. Particularly, additional risk factors have been identified for surgical site infections (SSI). Purulent surgical sites, older age, involvement of head, neck, and acral regions, and also the involvement of less experienced surgeons have been reported to increase the risk of the SSI after dermatologic surgeries.1 In general, the incidence of SSI after skin surgery is considered to be low.1,2 However, antibiotics in dermatologic surgeries, especially in the perioperative setting, seem to be overused,3,4 particularly regarding developing antibiotic resistances and side effects.
Immunosuppression has been recommended to be taken into consideration as an additional indication for antibiotic prophylaxis to prevent SSI after skin surgery in special cases.5,6 However, these recommendations do not specify the exact dermatologic surgeries, and were not specifically developed for dermatologic surgery patients and treatments, but adopted from other surgical fields.6 According to the survey conducted on American College of Mohs Surgery members in 2012, 13% to 29% of the surgeons administered antibiotic prophylaxis to immunocompromised patients to prevent SSI while performing dermatologic surgery on noninfected skin,3 although this was not recommended by Journal of the American Academy of Dermatology Advisory Statement. Indeed, the data on the risk of developing SSI after dermatologic surgery in immunosuppressed patients are limited. However, it is possible that due to the insufficient evidence on the risk of SSI occurrence in this patient group, dermatologic surgeons tend to overuse perioperative antibiotic prophylaxis.
To make specific recommendations on the use of antibiotic prophylaxis in immunosuppressed patients in the field of skin surgery, more information about the incidence of SSI after dermatologic surgery in these patients is needed. The aim of this study was to fill this data gap by investigating whether there is an increased risk of SSI after skin surgery in immunocompromised patients compared with immunocompetent patients.
Purpose — to compare the chemical elemental composition of vitreous cavity content taken from cadaveric eyes compared to samples taken from the eyes with terminal stage refractory glaucoma with decompensated intraocular pressure (IOP). Material and methods. The vitreous contents of the eyes from 2 groups were studied. The 1st group included 15 cadaveric eyes; the 2nd group included 15 eyes with refractory glaucoma in the terminal stage of the disease with decompensated IOP in patients with hypertension pain. The vitreal content samples were taken in the course of antiglaucoma surgery aimed at preserving the eye as an organ and involving employment of drainage in the vitreous cavity. The study of virtual contents was carried out on energy dispersive spectrometer Oxford X-Max 50 integrated into scanning electron microscope Zeiss EVO LS10. Results. Increased concentrations of Kalium and Phosphorus were detected in the vitreous content of cadaveric eyes compared with the vitreal content from the eyes with terminal glaucoma with decompensated IOP taken in vivo (K — 0.172/0.093; P — 0.045/0.025 mmol/L). In the vitreous cavity in the eyes with end-stage glaucoma with decompensated IOP, the concentration of Nitrogen was higher in comparison with human cadaver eyes (2.030/1.424 mmol/L). Conclusion. The increased concentrations of Kalium and Phosphorus in the vitreous content of cadaveric eyes is associated with postmortem autolytic processes and with the release of intracellular content in the destruction of cell membranes. The increased Nitrogen concentration in the vitreal contents of the eyes with terminal stage glaucoma with decompensated IOP may be associated with the presence of osmotically active nitrogen-containing compounds in the eyes with increased IOP.
Objective
Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels.
Methods
152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions.
Results
In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained.
Conclusion
This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention.
Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH.
Background
Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians.
Methods
In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204).
Measurements and main results
PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters.
Conclusion
Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.
Purpose Vascular risk factors and ocular perfusion are heatedly discussed in the pathogenesis of glaucoma. The retinal vessel analyzer (RVA, IMEDOS Systems, Germany) allows noninvasive measurement of retinal vessel regulation. Significant differences especially in the veins between healthy subjects and patients suffering from glaucoma were previously reported. In this pilot-study we investigated if localized vascular regulation is altered in glaucoma patients with altitudinal visual field defect asymmetry. Methods 15 eyes of 12 glaucoma patients with advanced altitudinal visual field defect asymmetry were included. The mean defect was calculated for each hemisphere separately (-20.99 ± 10.49 pro- found hemispheric visual field defect vs -7.36 ± 3.97 dB less profound hemisphere). After pupil dilation, RVA measurements of retinal arteries and veins were conducted using the standard protocol. The superior and inferior retinal vessel reactivity were measured consecutively in each eye. Results Significant differences were recorded in venous vessel constriction after flicker light stimulation and overall amplitude of the reaction (p \ 0.04 and p \ 0.02 respectively) in-between the hemispheres spheres. Vessel reaction was higher in the hemisphere corresponding to the more advanced visual field defect. Arterial diameters reacted similarly, failing to reach statistical significance. Conclusion Localized retinal vessel regulation is significantly altered in glaucoma patients with asymmetri altitudinal visual field defects. Veins supplying the hemisphere concordant to a less profound visual field defect show diminished diameter changes. Vascular dysregulation might be particularly important in early glaucoma stages prior to a significant visual field defect.
Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus.
The term ocular rigidity is widely used in clinical ophthalmology. Generally it is assumed as a resistance of the whole eyeball to mechanical deformation and relates to biomechanical properties of the eye and its tissues. Basic principles and formulas for clinical tonometry, tonography and pulsatile ocular blood flow measurements are based on the concept of ocular rigidity. There is evidence for altered ocular rigidity in aging, in several eye diseases and after eye surgery. Unfortunately, there is no consensual view on ocular rigidity: it used to make a quite different sense for different people but still the same name. Foremost there is no clear consent between biomechanical engineers and ophthalmologists on the concept. Moreover ocular rigidity is occasionally characterized using various parameters with their different physical dimensions. In contrast to engineering approach, clinical approach to ocular rigidity claims to characterize the total mechanical response of the eyeball to its deformation without any detailed considerations on eye morphology or material properties of its tissues. Further to the previous chapter this section aims to describe clinical approach to ocular rigidity from the perspective of an engineer in an attempt to straighten out this concept, to show its advantages, disadvantages and various applications.
The paper presents a method for the quantitative assessment of choroidal blood flow using an OCT-A system. The developed technique for processing of OCT-A scans is divided into two stages. At the first stage, the identification of the boundaries in the selected portion was performed. At the second stage, each pixel mark on the selected layer was represented as a volume unit, a voxel, which characterizes the region of moving blood. Three geometric shapes were considered to represent the voxel. On the example of one OCT-A scan, this work presents a quantitative assessment of the blood flow index. A possible modification of two-stage algorithm based on voxel scan processing is presented.
Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and identify corresponding response alterations.
Retinal endothelial function in cardiovascular risk patients: A randomized controlled exercise trial
(2020)
The aim of this study was to investigate, for the first time, the effects of high-intensity interval training (HIIT) on retinal microvascular endothelial function in cardiovascular (CV) risk patients. In the randomized controlled trial, middle-aged and previously sedentary patients with increased CV risk (aged 58 ± 6 years) with ≥ two CV risk factors were randomized into a 12-week HIIT (n = 33) or control group (CG, n = 36) with standard physical activity recommendations. A blinded examiner measured retinal endothelial function by flicker light-induced maximal arteriolar (ADmax) and venular (VDmax) dilatation as well as the area under the arteriolar (AFarea) and venular (VFarea) flicker curve using a retinal vessel analyzer. Standardized assessments of CV risk factors, cardiorespiratory fitness, and retinal endothelial function were performed before and after HIIT. HIIT reduced body mass index, fat mass, and low-density lipoprotein and increased muscle mass and peak oxygen uptake (VO2peak). Both ADmax (pre: 2.7 ± 2.1%, post: 3.0 ± 2.2%, P = .018) and AFarea (pre: 32.6 ± 28.4%*s, post: 37.7 ± 30.6%*s, P = .016) increased after HIIT compared with CG (ADmax, pre: 3.2 ± 1.8%, post: 2.9 ± 1.8%, P = .254; AFarea, pre: 41.6 ± 28.5%*s, post: 37.8 ± 27.0%*s, P = .186). Venular function remained unchanged after HIIT. There was a significant association between ∆-change VO2peak and ∆-changes ADmax and AFarea (P = .026, R² = 0.073; P = .019, R² = 0.081, respectively). 12-weeks of HIIT improved retinal endothelial function in middle-aged patients with increased CV risk independent of the reduction in classical CV risk factors. Exercise has the potential to reverse or at least postpone progression of small vessel disease in older adults with increased CV risk under standard medication. Dynamic retinal vessel analysis seems to be a sensitive tool to detect treatment effects of exercise interventions on retinal microvascular endothelial function in middle-aged individuals with increased CV risk.
Background
For supratentorial craniotomy, surgical access, and closure technique, including placement of subgaleal drains, may vary considerably. The influence of surgical nuances on postoperative complications such as cerebrospinal fluid leakage or impaired wound healing overall remains largely unclear. With this study, we are reporting our experiences and the impact of our clinical routines on outcome in a prospectively collected data set.
Method
We prospectively observed 150 consecutive patients undergoing supratentorial craniotomy and recorded technical variables (type/length of incision, size of craniotomy, technique of dural and skin closure, type of dressing, and placement of subgaleal drains). Outcome variables (subgaleal hematoma/CSF collection, periorbital edema, impairment of wound healing, infection, and need for operative revision) were recorded at time of discharge and at late follow-up.
Results
Early subgaleal fluid collection was observed in 36.7% (2.8% at the late follow-up), and impaired wound healing was recorded in 3.3% of all cases, with an overall need for operative revision of 6.7%. Neither usage of dural sealants, lack of watertight dural closure, and presence of subgaleal drains, nor type of skin closure or dressing influenced outcome. Curved incisions, larger craniotomy, and tumor size, however, were associated with an increase in early CSF or hematoma collection (p < 0.0001, p = 0.001, p < 0.01 resp.), and larger craniotomy size was associated with longer persistence of subgaleal fluid collections (p < 0.05).
Conclusions
Based on our setting, individual surgical nuances such as the type of dural closure and the use of subgaleal drains resulted in a comparable complication rate and outcome. Subgaleal fluid collections were frequently observed after supratentorial procedures, irrespective of the closing technique employed, and resolve spontaneously in the majority of cases without significant sequelae. Our results are limited due to the observational nature in our single-center study and need to be validated by supportive prospective randomized design.
Masked hypertension is known to induce microvascular complications. However, it is unclear whether early microvascular changes are already occurring in young, otherwise healthy adults. We therefore investigated whether retinal microvascular calibers and acute responses to a flicker stimulus are related to masked hypertension. We used the baseline data of 889 participants aged 20–30 years who were taking part in the African Prospective study on the Early Detection and Identification of Cardiovascular Disease and Hypertension. Clinic and 24-h ambulatory blood pressure were measured. The central retinal artery equivalent (CRAE) and central retinal vein equivalent were calculated from fundus images, and retinal vessel dilation was determined in response to flicker light-induced provocation. A smaller CRAE was observed in those with masked hypertension vs. those with normotension (157.1 vs. 161.2 measuring units, P < 0.001). In forward multivariable-adjusted regression analysis, only CRAE was negatively related to masked hypertension [adjusted R² = 0.267, β = −0.097 (95% CI = −0.165; −0.029), P = 0.005], but other retinal microvascular parameters were not associated with masked hypertension. In multivariable logistic regression analyses, masked hypertension [OR = 2.333, (95% CI = 1.316; 4.241), P = 0.004] was associated with a narrower CRAE. In young healthy adults, masked hypertension was associated with retinal arteriolar narrowing, thereby reflecting early microvascular alterations known to predict cardiovascular outcomes in later life.
Purpose
Globally, a detrimental shift in cardiovascular disease risk factors and a higher mortality level are reported in some black populations. The retinal microvasculature provides early insight into the pathogenesis of systemic vascular diseases, but it is unclear whether retinal vessel calibers and acute retinal vessel functional responses differ between young healthy black and white adults.
Methods
We included 112 black and 143 white healthy normotensive adults (20–30 years). Retinal vessel calibers (central retinal artery and vein equivalent (CRAE and CRVE)) were calculated from retinal images and vessel caliber responses to flicker light induced provocation (FLIP) were determined. Additionally, ambulatory blood pressure (BP), anthropometry and blood samples were collected.
Results
The groups displayed similar 24 h BP profiles and anthropometry (all p > .24). Black participants demonstrated a smaller CRAE (158 ± 11 vs. 164 ± 11 MU, p < .001) compared to the white group, whereas CRVE was similar (p = .57). In response to FLIP, artery maximal dilation was greater in the black vs. white group (5.6 ± 2.1 vs. 3.3 ± 1.8%; p < .001).
Conclusions
Already at a young age, healthy black adults showed narrower retinal arteries relative to the white population. Follow-up studies are underway to show if this will be related to increased risk for hypertension development. The reason for the larger vessel dilation responses to FLIP in the black population is unclear and warrants further investigation.
Clearance of blood components and fluid drainage play a crucial role in subarachnoid hemorrhage (SAH) and post hemorrhagic hydrocephalus (PHH). With the involvement of interstitial fluid (ISF) and cerebrospinal fluid (CSF), two pathways for the clearance of fluid and solutes in the brain are proposed. Starting at the level of capillaries, flow of ISF follows along the basement membranes in the walls of cerebral arteries out of the parenchyma to drain into the lymphatics and CSF [1]–[3]. Conversely, it is shown that CSF enters the parenchyma between glial and pial basement membranes of penetrating arteries [4]–[6]. Nevertheless, the involved structures and the contribution of either flow pathway to fluid balance between the subarachnoid space and interstitial space remains controversial. Low frequency oscillations in vascular tone are referred to as vasomotion and corresponding vasomotion waves are modeled as the driving force for flow of ISF out of the parenchyma [7]. Retinal vessel analysis (RVA) allows non-invasive measurement of retinal vessel vasomotion with respect to diameter changes [8]. Thus, the aim of the study is to investigate vasomotion in RVA signals of SAH and PHH patients.
Retinal Vessel Analysis (RVA) in the context of subarachnoid hemorrhage: A proof of concept study
(2016)
Background
Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH.
Methods
In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2–14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling.
Results
Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion.
Conclusion
RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort.
Recognition of subjects with mild cognitive impairment (MCI) by the use of retinal arterial vessels.
(2019)
Lignite biosolubilization and bioconversion by Bacillus sp.: the collation of analytical data
(2021)
The vast metabolic potential of microbes in brown coal (lignite) processing and utilization can greatly contribute to innovative approaches to sustainable production of high-value products from coal. In this study, the multi-faceted and complex coal biosolubilization process by Bacillus sp. RKB 7 isolate from the Kazakhstan coal-mining soil is reported, and the derived products are characterized. Lignite solubilization tests performed for surface and suspension cultures testify to the formation of numerous soluble lignite-derived substances. Almost 24% of crude lignite (5% w/v) was solubilized within 14 days under slightly alkaline conditions (pH 8.2). FTIR analysis revealed various functional groups in the obtained biosolubilization products. Analyses of the lignite-derived humic products by UV-Vis and fluorescence spectrometry as well as elemental analysis yielded compatible results indicating the emerging products had a lower molecular weight and degree of aromaticity. Furthermore, XRD and SEM analyses were used to evaluate the biosolubilization processes from mineralogical and microscopic points of view. The findings not only contribute to a deeper understanding of microbe–mineral interactions in coal environments, but also contribute to knowledge of coal biosolubilization and bioconversion with regard to sustainable production of humic substances. The detailed and comprehensive analyses demonstrate the huge biotechnological potential of Bacillus sp. for agricultural productivity and environmental health.
Molecular-genetic identification of emerged novel invasive pathogens of Asiatic Elm Ulmus pumila L
(2014)
The dwarf elm Ulmus pumila L. (Ulmaceae) is one of indigenous species of flora in Kazakhstan and forms a basis of dendroflora in virtually all settlements of the region. In the past decade, multiple outbreaks of previously unknown diseases of the small-leaved elm have been registered. In our study, by the molecular-genetic analysis it was found that the pathogens responsible for the outbreaks are microfungi belonging to the genus Fusarium – F. solani and F. oxysporum. The nucleotide sequences (ITS regions) isolated from the diseased trees showed very high similarity with the GenBank control numbers EU625403.1 and FJ478128.1 (100.0 and 99.0 % respectively). Oncoming research will focus on the search of natural microbial antagonists of the discovered phytopathogens.
The scope of this study is the measurement of endotoxin adsorption rate for carbonized rice husk. It showed good adsorption properties for LPS. During the batch experiments, several techniques were used and optimized for improving the material’s adsorption behavior. Also, with the results obtained it was possible to differentiate the materials according to their adsorption capacity and kinetic characteristics.
Sampling of dry surfaces for microorganisms is a main component of microbiological safety and is of critical importance in many fields including epidemiology, astrobiology as well as numerous branches of medical and food manufacturing. Aspects of biofilm formation, analysis and removal in aqueous solutions have been thoroughly discussed in literature. In contrast, microbial communities on air-exposed (dry) surfaces have received significantly less attention. Diverse surface sampling methods have been developed in order to address various surfaces and microbial groups, but they notoriously show poor repeatability, low recovery rates and suffer from lack of mutual consistency. Quantitative sampling for viable microorganisms represents a particular challenge, especially on porous and irregular surfaces. Therefore, it is essential to examine in depth the factors involved in microorganisms’ recovery efficiency and accuracy depending on the sampling technique used. Microbial colonization, retention and community composition on different dry surfaces are very complex and rely on numerous physicochemical and biological factors. This study is devoted to analyze and review the (a) physical phenomena and intermolecular forces relevant for microbiological surface sampling; (b) challenges and problems faced by existing sampling methods for viable microorganisms and (c) current directions of engineering and research aimed at improvement of quality and efficiency of microbiological surface sampling.
Suspension depletion approach for exemption of infected Solanum jasminoides cells from pospiviroids
(2018)
Despite numerous studies, viroid elimination from infected plants remains a very challenging task. This study introduces for the first time a novel ‘suspension depletion’ approach for exemption of Solanum jasminoides plants from viroids. The proposed method implies initial establishment of suspension cultures of the infected plant cells. The suspended cells were then physically treated (mild thermotherapy, 33 °C), which presumably delayed the replication of the viroid. The viroid concentration in the treated biomass was monitored weekly using pospiviroid-specific PCR. After 10–12 weeks of continuous treatment, a sufficient decrease in viroid concentration was observed such that the infection became undetectable by PCR. The treated single cells then gave rise to microcolonies on a solid culture medium and the obtained viroid-negative clones were further promoted to regenerate into viroid-free plants. Three years of accumulated experimental data suggests feasibility, broad applicability, and good efficacy of the proposed approach.
With the variety of toothbrushes on the market, the question arises, which toothbrush is best suited to maintain oral health? This thematic review focuses first on plaque formation mechanisms and then on the plaque removal effectiveness of ultrasonic toothbrushes and their potential in preventing oral diseases like periodontitis, gingivitis, and caries. We overviewed the physical effects that occurred during brushing and tried to address the question of whether ultrasonic toothbrushes effectively reduced the microbial burden by increasing the hydrodynamic forces. The results of published studies show that electric toothbrushes, which combine ultrasonic and sonic (or acoustic and mechanic) actions, may have the most promising effect on good oral health. Existing ultrasonic/sonic toothbrush models do not significantly differ regarding the removal of dental biofilm and the reduction of gingival inflammation compared with other electrically powered toothbrushes, whereas the manual toothbrushes show a lower effectiveness.
The treatment of septic wounds with curative dressings based on biocomposites containing sage and marigold phytoextracts was effective in in vitro and in vivo experiments. These dressings caused the purification of the wound surface from purulent-necrotic masses three days earlier than in the other experimental groups. The consequence of an increase in incidents of severe course of the wound and the observed tendency to increase the number of adverse effects is the development of long-term recurrent wound processes. To treat purulent wounds, the following tactics were used: The purulent wounds of animals were covered with the examined wound dressing, and then the next day samples were taken, the procedure was performed once in 2 days. To obtain the active nanostructured sorbents such as carbonized rice husks, they are functionalized with biologically active components possessing antimicrobial, anti-inflammatory, antitoxic, immunomodulating, antiallergic and other types of properties.
Activated carbons are known as excellent adsorbents. Their applications include the adsorptive removal of color, odor, taste, undesirable organic and inorganic pollutants from drinking and waste water; air purification in inhabited spaces; purification of many chemicals, pharmaceutical products and many others. This chapter elucidates the role of normal microflora in the maintenance of human health and presents materials on possible clinical displays of microecological infringements and ways of their correction. It presents new developments concerning new probiotics with immobilized Lactobacillus and Bacillus. The chapter considers the mechanisms of the intestine disbacteriosis correction by sorbed probiotics. It demonstrates the advantages and creation prospects of immobilized probiotics developed on the basis of carbonized rice husk. There are great prospects for the development of medical biotechnology due to use of carbon sorbents with a nanostructured surface. Microbial communities form a biocenosis of the biotope and together with the host organism create permanent or temporary ecosystems.
This chapter shows that nanomaterials obtained by high-temperature carbonization of inexpensive plant raw material such as rice husk, grape seeds, and walnut shells can serve as a basis for the production of highly efficient microbial drugs, biodestructors, biosorbents, and biocatalysts, which are promising for the remediation of the ecosystem contaminated with heavy and radioactive metals, oil and oil products. A strong interest in engineering zymology is dictated by the necessity to address the issues of monitoring enzymatic processes, treatment, and diagnosis of a number of common human diseases, environmental pollution, quality control of pharmaceuticals and food. Nanomaterials obtained by high-temperature carbonization of cheap plant raw material such as-rice husks, grape seeds and walnut shells, can serve as a basis for creating of highly effective microbial preparations-biodestructors, biosorbents and biocatalysts, which are promising for the use of contaminated ecosystems, and for restoration of human intestine microecology.
The recent advances in microbiology have shed light on understanding the role of vitamins beyond the nutritional range. Vitamins are critical in contributing to healthy biodiversity and maintaining the proper function of gut microbiota. The sharing of vitamins among bacterial populations promotes stability in community composition and diversity; however, this balance becomes disturbed in various pathologies. Here, we overview and analyze the ability of different vitamins to selectively and specifically induce changes in the intestinal microbial community. Some schemes and regularities become visible, which may provide new insights and avenues for therapeutic management and functional optimization of the gut microbiota.
Vitamin D plays an essential role in calcium and inorganic phosphate (Pi) homeostasis, maintaining their optimal levels to assure adequate bone mineralization. Vitamin D, as calcitriol (1,25(OH)2D), not only increases intestinal calcium and phosphate absorption but also facilitates their renal reabsorption, leading to elevated serum calcium and phosphate levels. The interaction of 1,25(OH)2D with its receptor (VDR) increases the efficiency of intestinal absorption of calcium to 30–40% and phosphate to nearly 80%. Serum phosphate levels can also influence 1,25 (OH)2D and fibroblast growth factor 23 (FGF23) levels, i.e., higher phosphate concentrations suppress vitamin D activation and stimulate parathyroid hormone (PTH) release, while a high FGF23 serum level leads to reduced vitamin D synthesis. In the vitamin D-deficient state, the intestinal calcium absorption decreases and the secretion of PTH increases, which in turn causes the stimulation of 1,25(OH)2D production, resulting in excessive urinary phosphate loss. Maintenance of phosphate homeostasis is essential as hyperphosphatemia is a risk factor of cardiovascular calcification, chronic kidney diseases (CKD), and premature aging, while hypophosphatemia is usually associated with rickets and osteomalacia. This chapter elaborates on the possible interactions between vitamin D and phosphate in health and disease.
There is a growing body of evidence for the effects of vitamin D on intestinal host-microbiome interactions related to gut dysbiosis and bowel inflammation. This brief review highlights the potential links between vitamin D and gut health, emphasizing the role of vitamin D in microbiological and immunological mechanisms of inflammatory bowel diseases. A comprehensive literature search was carried out in PubMed and Google Scholar using combinations of keywords “vitamin D,” “intestines,” “gut microflora,” “bowel inflammation”. Only articles published in English and related to the study topic are included in the review. We discuss how vitamin D (a) modulates intestinal microbiome function, (b) controls antimicrobial peptide expression, and (c) has a protective effect on epithelial barriers in the gut mucosa. Vitamin D and its nuclear receptor (VDR) regulate intestinal barrier integrity, and control innate and adaptive immunity in the gut. Metabolites from the gut microbiota may also regulate expression of VDR, while vitamin D may influence the gut microbiota and exert anti-inflammatory and immune-modulating effects. The underlying mechanism of vitamin D in the pathogenesis of bowel diseases is not fully understood, but maintaining an optimal vitamin D status appears to be beneficial for gut health. Future studies will shed light on the molecular mechanisms through which vitamin D and VDR interactions affect intestinal mucosal immunity, pathogen invasion, symbiont colonization, and antimicrobial peptide expression.
Heterogeneous Composites on the Basis of Microbial Cells and Nanostructured Carbonized Sorbents
(2012)
The fact that microorganisms prefer to grow on liquid/solid phase surfaces rather than in the surrounding aqueous phase was noticed long time ago [1]. Virtually any surface – animal, mineral, or vegetable – is a subject for microbial colonization and subsequent biofilm formation. It would be adequate to name just a few notorious examples on microbial colonization of contact lenses, ship hulls, petroleum pipelines, rocks in streams and all kinds of biomedical implants. The propensity of microorganisms to become surface-bound is so profound and ubiquitous that it vindicates the advantages for attached forms over their free-ranging counterparts [2]. Indeed, from ecological and evolutionary standpoints, for many microorganisms the surface-bound state means dwelling in nutritionally favorable, non-hostile environments [3]. Therefore, in most of natural and artificial ecosystems surface-associated microorganisms vastly outnumber organisms in suspension and often organize into complex communities with features that differ dramatically from those of free cells [4].
Many important properties of bacterial cellulose (BC), such as moisture absorption capacity, elasticity and tensile strength, largely depend on its structure. This paper presents a study on the effect of the drying method on BC films produced by Medusomyces gisevii using two different procedures: room temperature drying (RT, (24 ± 2 °C, humidity 65 ± 1%, dried until a constant weight was reached) and freeze-drying (FD, treated at − 75 °C for 48 h). BC was synthesized using one of two different carbon sources—either glucose or sucrose. Structural differences in the obtained BC films were evaluated using atomic force microscopy (AFM), scanning electron microscopy (SEM), and X-ray diffraction. Macroscopically, the RT samples appeared semi-transparent and smooth, whereas the FD group exhibited an opaque white color and sponge-like structure. SEM examination showed denser packing of fibrils in FD samples while RT-samples displayed smaller average fiber diameter, lower surface roughness and less porosity. AFM confirmed the SEM observations and showed that the FD material exhibited a more branched structure and a higher surface roughness. The samples cultivated in a glucose-containing nutrient medium, generally displayed a straight and ordered shape of fibrils compared to the sucrose-derived BC, characterized by a rougher and wavier structure. The BC films dried under different conditions showed distinctly different crystallinity degrees, whereas the carbon source in the culture medium was found to have a relatively small effect on the BC crystallinity.
Biocomposite Materials Based on Carbonized Rice Husk in Biomedicine and Environmental Applications
(2020)
This chapter describes the prospects for biomedical and environmental engineering applications of heterogeneous materials based on nanostructured carbonized rice husk. Efforts in engineering enzymology are focused on the following directions: development and optimization of immobilization methods leading to novel biotechnological and biomedical applications; construction of biocomposite materials based on individual enzymes, multi-enzyme complexes and whole cells, targeted on realization of specific industrial processes. Molecular biological and biochemical studies on cell adhesion focus predominantly on identification, isolation and structural analysis of attachment-responsible biological molecules and their genetic determinants. The chapter provides a short overview of applications of the biocomposite materials based of nanostructured carbonized adsorbents. It emphasizes that further studies and better understanding of the interactions between CNS and microbial cells are necessary. The future use of living cells as biocatalysts, especially in the environmental field, needs more systematic investigations of the microbial adsorption phenomenon.
At the present time, one of the most serious environmental problems of Central Asia and South Kazakhstan is the ongoing large-scale deterioration of principal urban tree populations. Several major centers of massive spread of invasive plant pests have been found in urban dendroflora of this region. The degree of damage of seven most wide-spread aboriginal tree species was found to range from 21.4±1.1 to 85.4±1.8%. In particular, the integrity of the native communities of sycamore (Platanus spp.), willow (Salix spp.), poplar (Populus spp.) and elm (Ulmus spp.) is highly endangered. Our taxonomic analysis of the most dangerous tree pests of the region has revealed them as neobiontic xylophilous insects such as Cossus cossus L. (Order: Lepidoptera L.) Monochamus urussovi Fisch., Monochamus sutor L., Acanthocinus aedelis L. and Ñetonia aureate L. (Order: Coleoptera L.). We relate the origin of this threatening trend with the import of industrial wood in the mid 90s of the last century that was associated with high degree of the constructional work in the region. Because of the absence of efficient natural predators of the pest species, the application of microbiological methods of the pest control and limitation is suggested.
Bacterial cellulose (BC) is a promising material for biomedical applications due to its unique properties such as high mechanical strength and biocompatibility. This article describes the microbiological synthesis, modification, and characterization of the obtained BC-nanocomposites originating from symbiotic consortium Medusomyces gisevii. Two BC-modifications have been obtained: BC-Ag and BC-calcium phosphate (BC-Ca3(PO4)2). Structure and physicochemical properties of the BC and its modifications were investigated by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM), and infrared Fourier spectroscopy as well as by measurements of mechanical and water holding/absorbing capacities. Topographic analysis of the surface revealed multicomponent thick fibrils (150–160 nm in diameter and about 15 µm in length) constituted by 50–60 nm nanofibrils weaved into a left-hand helix. Distinctive features of Ca-phosphate-modified BC samples were (a) the presence of 500–700 nm entanglements and (b) inclusions of Ca3(PO4)2 crystals. The samples impregnated with Ag nanoparticles exhibited numerous roundish inclusions, about 110 nm in diameter. The boundaries between the organic and inorganic phases were very distinct in both cases. The Ag-modified samples also showed a prominent waving pattern in the packing of nanofibrils. The obtained BC gel films possessed water-holding capacity of about 62.35 g/g. However, the dried (to a constant mass) BC-films later exhibited a low water absorption capacity (3.82 g/g). It was found that decellularized BC samples had 2.4 times larger Young’s modulus and 2.2 times greater tensile strength as compared to dehydrated native BC films. We presume that this was caused by molecular compaction of the BC structure.
Humic substances originating from various organic matters can ameliorate soil properties, stimulate plant growth, and improve nutrient uptake. Due to the low calorific heating value, leonardite is rather unsuitable as fuel. However, it may serve as a potential source of humic substances. This study was aimed at characterizing the leonardite-based soil amendments and examining the effect of their application on the soil microbial community, as well as on potato growth and tuber yield. A high yield (71.1%) of humic acid (LHA) from leonardite has been demonstrated. Parental leonardite (PL) and LHA were applied to soil prior to potato cultivation. The 16S rRNA sequencing of soil samples revealed distinct relationships between microbial community composition and the application of leonardite-based soil amendments. Potato tubers were planted in pots in greenhouse conditions. The tubers were harvested at the mature stage for the determination of growth and yield parameters. The results demonstrated that the LHA treatments had a significant effect on increasing potato growth (54.9%) and tuber yield (66.4%) when compared to the control. The findings highlight the importance of amending leonardite-based humic products for maintaining the biogeochemical stability of soils, for keeping their healthy microbial community structure, and for increasing the agronomic productivity of potato plants.
The necessity of e-books as a primary of learning, its opportunities for realization of competence during training biologist and biotechnologist specialists are determined. Definitions and requirements to the e-books, its advantages in comparison with traditional textbooks, and the ways of creation of e-books in the SunRav BookEditor program are considered.
L.setulosus is offered for creation of biopreparation «Setulin», possesing he- mostatic action, the basic reactant of biopreparation is diterpen – lagochirzin. Results under the maintenance and dynamics of diterpen lagochirzin accumula- tion in various parts of L.setulosus are presented: in roots, stalks, leaves, flowers and calyx lobes during the growing season, and also results on conditions of cultivation L.setulosus in the conditions of a typical sierozem are resulted. From the obtained data is visible, that the given species of a plant is endemic. It is established, that dynamics of accumulation of lagochirzin in phytomass accrues from the beginning to the middle of the growing season. The chemical analysis of L.setulosus on a localization of lagochirzin in various organs of a plant, has shown, that the greatest quantity of lagochirzin collects in calyx lobes of the plants. Also it is established, that L.setulosus can be cultivated in the conditions of the typical sierozem, a mineral food is necessary for the given species of plants of Lagochilus genus, except nitric fertilizers. Comparative studying of wild-growing and cultural forms of L.setulosus has shown, that in the cultivated phytomass of plants the maintenance of lagochirzin on 17-20 % higher than in the wild-growing species.
This study describes the development of a new combined polysaccharide-matrix-based technology for the immobilization of Lactobacillus rhamnosus GG (LGG) bacteria in biofilm form. The new composition allows for delivering the bacteria to the digestive tract in a manner that improves their robustness compared with planktonic cells and released biofilm cells. Granules consisting of a polysaccharide matrix with probiotic biofilms (PMPB) with high cell density (>9 log CFU/g) were obtained by immobilization in the optimized nutrient medium. Successful probiotic loading was confirmed by fluorescence microscopy and scanning electron microscopy. The developed prebiotic polysaccharide matrix significantly enhanced LGG viability under acidic (pH 2.0) and bile salt (0.3%) stress conditions. Enzymatic extract of feces, mimicking colon fluid in terms of cellulase activity, was used to evaluate the intestinal release of probiotics. PMPB granules showed the ability to gradually release a large number of viable LGG cells in the model colon fluid. In vivo, the oral administration of PMPB granules in rats resulted in the successful release of probiotics in the colon environment. The biofilm-forming incubation method of immobilization on a complex polysaccharide matrix tested in this study has shown high efficacy and promising potential for the development of innovative biotechnologies.