Small Capillaries Research Articles

The Potential Impact of Neuroimaging and Translational Research on the Clinical Management of Lacunar Stroke.

Lacunar infarcts represent one of the most frequent subtypes of ischemic strokes and may represent the first recognizable manifestation of a progressive disease of the small perforating arteries, capillaries, and venules of the brain, defined as cerebral small vessel disease. The pathophysiological mechanisms leading to a perforating artery occlusion are multiple and still not completely defined, due to spatial resolution issues in neuroimaging, sparsity of pathological studies, and lack of valid experimental models. Recent advances in the endovascular treatment of large vessel occlusion may have diverted attention from the management of patients with small vessel occlusions, often excluded from clinical trials of acute therapy and secondary prevention. However, patients with a lacunar stroke benefit from early diagnosis, reperfusion therapy, and secondary prevention measures. In addition, there are new developments in the knowledge of this entity that suggest potential benefits of thrombolysis in an extended time window in selected patients, as well as novel therapeutic approaches targeting different pathophysiological mechanisms involved in small vessel disease. This review offers a comprehensive update in lacunar stroke pathophysiology and clinical perspective for managing lacunar strokes, in light of the latest insights from imaging and translational studies.

Effects of the healing activity of rosemary-of-Chapada (Lippia gracilis Schauer) on cutaneous lesions in rats.

ABSTRACTPurpose:To evaluate the effects of rosemary leaf essential oil-based ointments on the healing of rat skin lesions.Methods:Sixty adult male rats, with dorsal excisional skin wounds made surgically under anesthesia, were divided into three groups (n = 20): Sham group (untreated wounds); control group (CG, wounds treated with vehicle); and essential oil (EO) treated group (wounds treated with essential oil-based ointments), administered topically once daily. Skin wounds were evaluated at 4, 7, 14, and 21 days after EO or vehicle treatments. Lesions were analyzed macroscopically for the contraction degree. Formalin-fixed paraffin-embedded sections of skin wounds were used for histopathological evaluation.Results:Macroscopic evaluation showed wounds edges with thin crust without firmness and yellowish color, along with an improvement in wound contraction in EO group when compared to the other groups. A reduced inflammatory reaction, along with newly formed small diameter capillaries and more organized and elongated collagen fibers, were more frequently observed in EO group than in the other groups. Moreover, blood vessel number and collagen fibers density were significantly higher in EO group.Conclusions:Skin lesion treatment with rosemary leaf essential oil-based ointments accelerates the initial stages of healing, reduces inflammation, and increases angiogenesis, collagen fibers density, and wound contraction in rats.

Cerebral disease of small vessels: morphological, neuropsychological and neurovisualization comparisons

The term "cerebrovascular disease of small vessals" (CDSV) includes neuropathological, clinical and neuroimaging manifestations lesions of small perforating arteries, arterioles, capillaries, venules and small veins. CDSV, according to the pathogenetic classification of L. Pantoni, is divided into 6 types: sporadic non-amyloid microangiopathy (SNAMA); sporadic and hereditary cerebral amyloid angiopathy (CAA); hereditary CDSV (CADASIL, CARASIL, MELAS, Fabry disease, CDSV in mutations of COL4A1 gene and others); CDSV, mediated by inflammation and immune processes; venous collagenosis; other options. In 4 chapters of the review the following are considered: morphological and neuroimaging characteristics of CDSV; cognitive impairment and CDSV: morphological, neuropsychological and neuroimaging comparisons; natural aging of the brain: morphological, neuroimaging and neuropsychological comparisons; the influence of modified risk factors (hypertension, type 2 diabetes mellitus, radiation exposure) on the course of CDSV. Conclusions. Despite the threatening consequences of CDSV, its early clinical and instrumental diagnosis has not attracted proper attention of researchers. The subject of the vast majority of studies were: CDSV of moderate and severe degree, post-stroke conditions; neuroimaging criteria for the prognosis of acute cerebrovascular disease, Alzheimer's disease and dementia in the elderly and senile persons; age differences of CDSV and cognitive impairments (CI) in terms of the overall disease duration, and not in terms of the peculiarities of its manifestation in middle or avanced age. There are objective prerequisites for establishing a methodological framework for early diagnosis of CDSV that takes into account the age of patients and the presence of modifiable risk factors. These include: the existence of consensus on the definition, classification and neuroimaging features of CDSV; availability of effective cognitive scales, which are designed to screen and determine the domain affiliation of non-dementia CD; introduction of new neuroimaging technologies that allow molecular (diffusion) research and obtain images with submillimeter resolution. Two clinical observations serve as convincing evidence of the conclusions reached on the basis of the analysis of the scientific literature.

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S): An update on basic science and clinical perspectives.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, underrecognized, systemic small vessel disease caused by heterozygous C-terminal truncating TREX1 mutations. The disease is characterized by vascular retinopathy, focal neurological complaints, cognitive decline and a wide range of systemic manifestations, including Raynaud's phenomenon, anemia and liver and kidney disease. Eventually, RVCL-S leads to premature death. The underlying pathological finding in RVCL-S is a nonatherosclerotic, amyloid-negative angiopathy involving small arteries and capillaries. However, the exact mechanisms by which the truncated TREX1 protein causes angiopathy remains unknown. Timely recognition of this disease is important to slow down and treat complications of the disorder, but also to prevent unnecessary (invasive) diagnostic or therapeutic procedures. As we move forward, translational research combining basic science advances and clinical findings as well as studies focusing on natural history following RVCL-S patients at different disease stages, will be critical to help elucidate RVCL-S pathophysiology. These studies will also provide the tools to identify appropriate biomarkers and therapeutic agent options for RVCL-S patients.

Evaluation of Cardiovascular Experiment Animal

Abstract: In vivo models of myocardial infarction induced by coronary artery ligation in rats usually suffer from high early mortality and a low rate of induction. This study investigated the time course initiation of chronic myocardial infarction in albino rats and the possibility of reducing early mortality rate due to myocardial infarction by modification of the surgical technique. CAL was carried out by passing the suture through the pericardial layer around the midway of the left anterior descending coronary artery including a small area of the myocardium to avoid mechanical damage to the heart geometry. In addition, the role of endothelin-1 in rat heart with congestive heart failure was critically assessed. Time course initiation experiments were designed by sacrificing the animals at different time intervals and by carrying out physiological, biochemical, histopathological, electron microscopical and immunohistochemical studies. Specific markers of myocardial injury, viz. cardiac troponin-T, high sensitivity C-reactive protein, lactate dehydrogenase and fibrinogen were measured at different time points. Serum marker enzymes and activities of lysosomal hydrolases were found to be elevated on the eighth day post-ligation. Histopathological studies demonstrated focal areas showing fibrovascular tissue containing fibroblasts, collagenous ground substance and numerous small capillaries replacing cardiac muscle fibers. Transmission electron micrographs exhibited mitochondrial changes of well-developed irreversible cardiac injury, viz. swelling, disorganization of cristae, appearance of mitochondrial amorphous matrix densities, and significant distortion of muscle fibers and distinct disruption of the intercalated discs. Immune blotting studies confirmed the presence of alpha 2-macroglobulin which supported the inflammatory response. The severity of the CMI was inferred by the measurement of the level of ET-1 in plasma and left ventricle which was significantly higher in the CMI rats than in the sham-operated rats. Immunohistochemical studies at different time intervals showed that there was a significant immunoexpression of ET-1 on the eighth day post-ligation. This study conclusively showed that ligation of left anterior descending artery minimised mortality and ET-1 was expressed during CMI.

The Clinical Significance of the Neutrophil-to-lymphocyte Ratio in Hemorrhagic Vasculitis Coexisting with Nonalcoholic Steatohepatosis

Hemorrhagic vasculitis (HV) is a systemic disease of widespread inflammation in small vessels, arterioles, small capillaries, and perivascular edema with blood cells infiltration. The pathogenesis of HV are currently not well understood, and insufficient investigators attention is given to this disease. It has been established that patients with HV often have sonographic signs of the liver damage with normal liver tests, which indicates the presence of hepatic steatosis (HS). The ratio of neutrophilic granulocytes to lymphocytes (N/L) is widely used by doctors to determine the activity of the process, but in patients with HV, depending on the presence of HS, it was not evaluated. The objective: to analyze the diagnostic capabilities of the N/L ratio in HV adult patients. Materials and methods. The retrospective analyse of the hospital examination results of 50 patients with HV was performed and included data from 20 men and 30 women aged 45.96±2.04 years. The patients were divided into two groups: the main group – 15 men and 16 women with HS, and the control group – 5 men and 14 women with sonographically and laboratory intact liver, in whom the N/L index was additionally determined. Statistic of the study was performed by use Statistica 6.0 program, correlations were assessed by Pearson method (r); p<0.05 was taken as the significance threshold. Results. In patients with HV, the N/L index was 3.29±0.40. It was slightly higher than in SP (3.48±0.53 vs 2.69±0.34; p>0.05). The N/L index exceeded 3.3 was determined in 38.71% and >3.5 – in 22.6 of HV patients with SP. Such patients had worse structural and functional parameters of the heart. According to the correlation analysis, an increase in the N/L index >3.3–3.5 was associated with hypertrophy and dilatation of the ventricles with stretching of the valves and development of dysfunction, activation of neutrophilic inflammation, and suppression of the immune cellular component. It has been established that an increase in the N/L index can be not only a prognostic sign of gastrointestinal and renal lesions, but also a sign of heart changes – hypertrophy and dilatation with impaired systolic and diastolic functions. Conclusion. The ratio of neutrophilic granulocytes to lymphocytes is a simple and informative indicator of the activity of inflammation which is easily calculated in practice and is associated with the structural and functional changes in heart in patients with hemorrhagic vasculitis and hepatic steatosis.

Novel glass capillary microfluidic devices for the flexible and simple production of multi-cored double emulsions

HypothesisDouble emulsions with many monodispersed internal droplets are required for the fabrication of multicompartment microcapsules and tissue-like synthetic materials. These double emulsions can also help to optically resolve different coalescence mechanisms contributing to double emulsion destabilization. Up to date microfluidic double emulsions are limited to either core–shell droplets or droplets with eight or less inner droplets. By applying a two-step jet break-up within one setup, double emulsion droplets filled with up to several hundred monodispersed inner droplets can be achieved. ExperimentsModular interconnected CNC-milled Lego®-inspired blocks were used to create two separated droplet break-up points within coaxial glass capillaries. Inner droplets were formed by countercurrent flow focusing within a small inner capillary, while outer droplets were formed by co-flow in an outer capillary. The size of inner and outer droplets was independently controlled since the two droplet break-up processes were decoupled. FindingsWith the developed setup W/O/W and O/W/O double emulsions were produced with different surfactants, oils, and viscosity modifiers to encapsulate 25–400 inner droplets in each outer drop with a volume percentage of inner phase between 7% and 50%. From these emulsions monodispersed multicompartment microcapsules were obtained. The report offers insights on the relationship between the coalescence of internal droplets and their release.

Altered Spontaneous Brain Activity Related to Neurologic Dysfunction in Patients With Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) encompasses several diseases affecting the small arteries, arterioles, venules, and capillaries of the brain and refers to several pathological processes and etiologies. Neuroimaging is considered the gold standard for detecting CSVD, which can present diverse features on MRI. Cerebral microbleeds (CMBs) in CSVD have been demonstrated to play a synergistic role in both cerebrovascular and neurodegenerative pathology. Considering previous studies on brain structural abnormalities in CSVD, in the present study, we aimed to explore altered spontaneous brain activity among CSVD patients using amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and regional homogeneity (ReHo) methods based on resting-state functional MRI. In this study, we recruited 24 CSVD patients with CMBs (CSVD-c), 42 CSVD patients without CMBs (CSVD-n) and 36 healthy controls from outpatient clinics in Shandong Provincial Hospital affiliated to Shandong First Medical University between September 2018 and June 2019. All subjects underwent 3-T MRI, including blood oxygen level-dependent (BOLD) and susceptibility-weighted imaging (SWI). Anatomic structures were segmented, ALFF/fALFF values were calculated, and ReHo maps were generated. Further statistical analysis was applied to study the difference in ALFF/fALFF/ReHo among the three groups and the association between ALFF/fALFF/ReHo changes in different brain regions and clinical characteristics. Twenty-four CSVD-c patients (age: 67.54 ± 6.00 years, 10 females), 42 CSVD-n patients (age: 66.33 ± 5.25 years, 22 females) and 36 healthy subjects (age: 64.14 ± 8.57 years, 19 females) were evaluated. Compared with controls, the CSVD-c group showed significantly increased ALFF values in the right insula, putamen and left precuneus; decreased fALFF values in the right precentral gyrus and postcentral gyrus; and increased ReHo values in the left precuneus, fusiform gyrus, right supplementary motor area (SMA), and superior frontal gyrus. Notably, the mean ALFF values of the right insula and putamen were not only significantly related to all clinical parameters but also demonstrated the best performance in Receiver Operating Characteristic (ROC) curve analysis. These findings reveal CSVD-c patients have dysfunctions in the default mode network, sensorimotor network and frontoparietal network, which may implicate the underlying neurophysiological mechanisms of intrinsic brain activity. The correlation between altered spontaneous neuronal activity and clinical parameters provides early useful diagnostic biomarkers for CSVD.

Capillary-like Formations of Endothelial Cells in Defined Patterns Generated by Laser Bioprinting.

Bioprinting is seen as a promising technique for tissue engineering, with hopes of one day being able to produce whole organs. However, thick tissue requires a functional vascular network, which naturally contains vessels of various sizes, down to capillaries of ~10 µm in diameter, often spaced less than 200 µm apart. If such thick tissues are to be printed, the vasculature would likely need to be printed at the same time, including the capillaries. While there are many approaches in tissue engineering to produce larger vessels in a defined manner, the small capillaries usually arise only in random patterns by sprouting from the larger vessels or from randomly distributed endothelial cells. Here, we investigated whether the small capillaries could also be printed in predefined patterns. For this purpose, we used a laser-based bioprinting technique that allows for the combination of high resolution and high cell density. Our aim was to achieve the formation of closed tubular structures with lumina by laser-printed endothelial cells along the printed patterns on a surface and in bioprinted tissue. This study shows that such capillaries are directly printable; however, persistence of the printed tubular structures was achieved only in tissue with external stimulation by other cell types.

Transgenic rat models for cerebral amyloid angiopathy type‐1 and ‐2 and related vascular cognitive impairment and dementia (VCID)

Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease commonly found in the elderly population and in patients with Alzheimer's disease and is significant driver of vascular cognitive impairment and dementia (VCID). CAA exists in two forms: type-1 which affects small microvessels and capillaries and type-2 which primarily affects small arteries and arterioles. Our understanding of how these different forms of CAA promote VCID is hampered by reliable preclinical models. Recently, we generated novel transgenic rat models of CAA type-1 and CAA type-2 to investigate the development and pathological consequences of each type of CAA and their impact on VCID. Cohorts of CAA type-1 and CAA type-2 transgenic rats and wild-type rats were aged from three to twenty four months of age. Magnetic resonance imaging (MRI) was performed to determine the effects of progressive CAA pathology on white matter changes and emergence of cerebral microbleeds. Quantitative histological analyses were performed to measure progressive severity of CAA, neuroinflammation and cerebral microbleeds. A battery of behavioral task assessments was performed to reveal the impact of CAA on cognitive performance. CAA type-1 rats developed microvascular CAA starting at ≈3 months of age that became severe at 12 months leading to a moribund state. CAA type-2 rats developed CAA pathology later starting ≈12 months of age and progressed to 24 months. Histological analysis showed CAA type-1 rats exhibited early-onset perivascular neuroinflammation and microvascular pathology including capillary occlusions and microbleeds. In contrast, CAA type-2 rats presented little evidence of perivascular neuroinflammation and less extensive microbleeds. MR imaging showed that CAA type-1 rats presented with white matter loss at ≈6 months of age. Behavioral analysis revealed that CAA type-1 rats displayed a distinct form sensorimotor slowing that was not observed in CAA type-2 rats. CAA type-1 rats recapitulate many of the pathological features of human microvascular CAA including perivascular neuroinflammation and white matter loss and exhibit cognitive changes. In contrast, CAA type-2 rats lack these particular pathological features and did not display cognitive changes. These findings suggest that CAA-associated neuroinflammation and white matter loss may play an important role in VCID.

Endothelial Dysfunction and Hyperhomocysteinemia-Linked Cerebral Small Vessel Disease: Underlying Mechanisms and Treatment Timing.

Cerebral small vessel disease (cSVD)—a common cause of stroke and vascular dementia—is a group of clinical syndromes that affects the brain's small vessels, including arterioles, capillaries, and venules. Its pathogenesis is not fully understood, and effective treatments are limited. Increasing evidence indicates that an elevated total serum homocysteine level is directly and indirectly associated with cSVD, and endothelial dysfunction plays an active role in this association. Hyperhomocysteinemia affects endothelial function through oxidative stress, inflammatory pathways, and epigenetic alterations at an early stage, even before the onset of small vessel injuries and the disease. Therefore, hyperhomocysteinemia is potentially an important therapeutic target for cSVD. However, decreasing the homocysteine level is not sufficiently effective, possibly due to delayed treatment, which underlying reason remains unclear. In this review, we examined endothelial dysfunction to understand the close relationship between hyperhomocysteinemia and cSVD and identify the optimal timing for the therapy.

A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds.

The development of an in vitro system for the study of lung vascular disease is critical to understanding human pathologies. Conventional culture systems fail to fully recapitulate native microenvironmental conditions and are typically limited in their ability to represent human pathophysiology for the study of disease and drug mechanisms. Whole organ decellularization provides a means to developing a construct that recapitulates structural, mechanical, and biological features of a complete vascular structure. Here, we developed a culture protocol to improve endothelial cell coverage in whole lung scaffolds and used single-cell RNA-sequencing analysis to explore the impact of decellularized whole lung scaffolds on endothelial phenotypes and functions in a biomimetic bioreactor system. Intriguingly, we found that the phenotype and functional signals of primary pulmonary microvascular revert back—at least partially—toward native lung endothelium. Additionally, human induced pluripotent stem cell-derived endothelium cultured in decellularized lung systems start to gain various native human endothelial phenotypes. Vascular barrier function was partially restored, while small capillaries remained patent in endothelial cell-repopulated lungs. To evaluate the ability of the engineered endothelium to modulate permeability in response to exogenous stimuli, lipopolysaccharide (LPS) was introduced into repopulated lungs to simulate acute lung injury. After LPS treatment, proinflammatory signals were significantly increased and the vascular barrier was impaired. Taken together, these results demonstrate a novel platform that recapitulates some pulmonary microvascular functions and phenotypes at a whole organ level. This development may help pave the way for using the whole organ engineering approach to model vascular diseases.

Oral Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Clinicopathologic and Immunohistochemical Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents rapid transmission and significant mortality worldwide. It is responsible for coronavirus disease 2019 (COVID-19). The disease presents diverse clinical symptoms, including fever, cough, dyspnea, and pneumonia. However, other manifestations associated with COVID-19 need to be clarified, leading specialists to an early diagnosis and better prognosis. We describe the spectrum of clinicopathologic COVID-19-related oral lesions that can be the first and/or the unique manifestation of the disease. Fourteen patients with a mean age of 58 years (range: 23 to 88 y) with oral lesions were included. All patients were confirmed to be infected with SARS-CoV-2 by reverse transcription polymerase chain reaction testing. Patients demonstrated mild symptoms, including dysgeusia, anosmia, fever, and headache. The lesions were recognized and classified into 2 groups: (1) lesions caused by ischemia and/or hemorrhage and (2) lesions secondary to inflammatory events associated with viral load. The palate was most affected (n=8), followed by the tongue (n=4), and both the lip and palate (n=2). Histologic analysis demonstrated thrombosis of small arteries and capillaries, associated with areas of hemorrhage and chronic inflammatory infiltrate. Immunohistochemistry showed positive staining for spike protein (SARS-CoV and SARS-CoV-2) and angiotensin-converting enzyme 2 in the surface epithelium, salivary glands, inflammatory cells, and endothelial cells. Although the incidence of oral lesions among patients infected with SARS-CoV-2 appears to be uncommon, these findings suggest that the oral mucosa can also be a target organ for SARS-CoV-2.

Long-term pathological changes in lungs after COVID-19

World literature is paying increasing attention to the long-term course of COVID-19 and symptoms that appear after the acute coronavirus infection. The symptoms, functional state of the lungs, and the X-ray changes are assessed. Nevertheless, post-COVID lung histology has not been described yet.The aim of this article is to study the long-term pathological changes in the lungs after acute COVID-19. Methods. We analyzed autopsy lung material from 19 deceased who had COVID-19. The average age of the deceased was 68.82 ± 14.6 years. All patients were found to have IgG to SARS-CoV-2. The median time to death following viral interstitial pneumonia was 72 days. Results. The causes of death and thrombotic complications (infarctions of various organs and venous thrombosis) were analyzed. Histological examination revealed thrombosis of small pulmonary arteries and capillaries of interalveolar septa, microinfarctions, hemorrhages, foci of organizing pneumonia, and nonspecific interstitial pneumonia.Conclusion. The first assessment of histological changes in human lungs showed that the most common post-COVID pathologic changes are microcirculation disorders combined with small areas of acute lung damage. The obtained data are essential for understanding the pathogenesis of post-COVID syndrome, necessitate diagnostic of microvasculature disorders using laboratory tests, scintigraphy, and CT imaging, as well as search for the therapeutic strategies.

Cryogel Monoliths for Analyte Enrichment by Capture and Release

A platform based on cryogel monoliths in small capillaries, which allows very strong enrichment of an analyte through a capture and release process, is described. For their preparation, a photoreactive copolymer solution containing capture molecules of interest is filled into a capillary, frozen in, and then photochemically transformed into cryogel monoliths through C,H-insertion cross-linking reactions. As a test example, the platform is used for the preconcentration of dopamine from bovine serum albumin and urine samples through capture and release processes. During capture from a large volume and release into a smaller volume, the platform shows recovery rates up to 97% and allows up to a roughly 630-fold enrichment of the concentration of the analyte. The presented platform could be used as a disposable device for the purification and enrichment of a variety of cis-diol-containing samples.

Cardiovascular comorbidities, inflammation, and cerebral small vessel disease.

Cerebral small vessel disease (cSVD) is the most common cause of vascular cognitive impairment and affects all levels of the brain's vasculature. Features include diverse structural and functional changes affecting small arteries and capillaries that lead to a decline in cerebral perfusion. Due to an ageing population, incidence of cSVD is continually rising. Despite its prevalence and its ability to cause multiple debilitating illnesses, such as stroke and dementia, there are currently no therapeutic strategies for the treatment of cSVD. In the healthy brain, interactions between neuronal, vascular, and inflammatory cells are required for normal functioning. When these interactions are disturbed, chronic pathological inflammation can ensue. The interplay between cSVD and inflammation has attracted much recent interest, and this review discusses chronic cardiovascular diseases, particularly hypertension, and explores how the associated inflammation may impact on the structure and function of the small arteries of the brain in cSVD. Molecular approaches in animal studies are linked to clinical outcomes in patients, and novel hypotheses regarding inflammation and cSVD are proposed that will hopefully stimulate further discussion and study in this important area.

COVID-19 vulnerabilities are intensified by declining human serum albumin levels.

What is the topic of this review? Human serum albumin (HSA) a common factor in COVID‐19 vulnerabilities. What advances does it highlight? Understanding of HSA capacity, and systemic vulnerabilities to COVID‐19. Raising HSA in COVID‐19 patients may alleviate systemic injury caused by diminished native HSA binding. A change in fluid therapy administration into the portal system of the liver is proposed to safely raise HSA levels. The specific nature of the vulnerabilities to COVID‐19 are an intrinsic part of COVID‐19 infection in many patients. This paper proposes that vulnerabilities to COVID‐19 may be intensified by a decrease in human serum albumin (HSA) as a ligand carrier for nutrients. A mechanism for COVID‐19 vulnerabilities is evident from consideration of ligand carriers such as HSA as intermediaries. We hypothesise that low levels of pool HSA binding, caused for whatever reason, affect the performance of albumin as a carrier protein reducing the availability of nutrients. Hypoalbuminaemia (low HSA) has been implicated as an indicator of COVID‐19 and long‐COVID‐19. The levels of HSA directly affect the immune system and vulnerabilities to age, diabetes and obesity in COVID‐19. Any slight reduction in available HSA has profound effects on ligand concentrations in the small capillaries where damage occurs in COVID‐19. The clinical implication is that attempts should be made to return HSA to clinical levels to compensate for the additional ligands caused by infection (SARS‐CoV‐2 virions, antibodies and cellular breakdown products). Therapeutic albumin is usually given peripherally, and usual preparations are unbound to ligands, but we suggest that a clinical trial of HSA therapy via the hepatic portal vein should be considered.

Revisiting the question of nucleated versus enucleated erythrocytes in birds and mammals.

Erythrocyte enucleation is thought to have evolved in mammals to support their energetic cost of high metabolic activities. However, birds face similar selection pressure yet possess nucleated erythrocytes. Current hypotheses on the mammalian erythrocyte enucleation claim that the absence of cell organelles allows erythrocytes to 1) pack more hemoglobin into the cells to increase oxygen carrying capacity and 2) decrease erythrocyte size for increased surface area-to-volume ratio, and improved ability to traverse small capillaries. In this article, we first empirically tested current hypotheses using both conventional and phylogenetically informed analysis comparing literature values of mean cell hemoglobin concentration (MCHC) and mean cell volume (MCV) between 181 avian and 194 mammalian species. We found no difference in MCHC levels between birds and mammals using both conventional and phylogenetically corrected analysis. MCV was higher in birds than mammals according to conventional analysis, but the difference was lost when we controlled for phylogeny. These results suggested that avian and mammalian erythrocytes may employ different strategies to solve a common problem. To further investigate existing hypotheses or develop new hypothesis, we need to understand the functions of various organelles in avian erythrocytes. Consequently, we covered potential physiological functions of various cell organelles in avian erythrocytes based on current knowledge, while making explicit comparisons with their mammalian counterparts. Finally, we proposed by taking an integrative and comparative approach, using tools from molecular biology to evolutionary biology, would allow us to better understand the fundamental physiological functions of various components of avian and mammalian erythrocytes.

Optical coherence tomography in the diagnosis of choroidal neovascularization in children

AIM: Report cases of choroidal neovascularization (CNV) in children and describe structural and hemodynamic changes in retina associated with this pathology detected by Optical Coherence Tomography (OCT) and OCT-angiography (OCTA).
 MATERIALS AND METHODS: 6 children (4 girls, 2 boys) aged from 7 to 17 years with CNV associated with pathological myopia, post-traumatic choroid rupture and optic disc abnormalities were examined. The activity of neovascular complexes was evaluated by ophthalmoscopy, OCT, and OCTA. The maximum follow-up period was 4 years.
 RESULTS: 7 cases of CNV were detected. One child had a two-way process. Myopic and posttraumatic membranes were localized sub- and juxtafoveally and were the membranes of type 2. In children with optic disc anomalies of the 1 type membrane and mixed (1st and 2nd) type was located extrafoveally. The decrease in visual acuity was determined by the localization of membranes, the severity of edema, and the severity of dystrophic changes in the retina. On OCT, subretinal fluid and hyperreflective material corresponding to hemorrhages were visualized in the projection of active membranes. OCTA revealed a network of small capillaries with a large number of loops and anastomoses. Intravitreal angiogenesis inhibitors injections were performed in 5 cases. A persistent effect after a single injection was observed in 2 cases. The return of membrane activity in 3 cases allowed us to justify the repeated administration of angiogenesis inhibitors. Along with a decrease in the activity of CNV, progressive dystrophic changes in the pigment epithelium around the membrane were detected.
 CONCLUSIONS: High sensitivity of OCT was demonstrated for early detection of structural and hemodynamic retinal disorders, determining the activity of neovascular complexes, predicting outcomes of the disease, and evaluating the effectiveness of therapeutic measures. The progression of dystrophic changes in the retinal pigment epithelium in response to therapy with angiogenesis inhibitors requires long-term monitoring of children and determining the optimal strategy for treating CNV in children.

Rapid Point of Care Diagnostic Test for the Detection of Rare Metabolic Disorders

Rapid Point of Care Diagnostic Test for the Detection of Rare Metabolic Disorders