Functional Changes Research Articles

Lipid‐lowering therapy in the treatment of massive hard exudates in type 1 diabetes

Aims/Purpose: Today there is no approved medical therapy for hard macular exudates in diabetes and unfortunately this pathology often leads to significant visual loss. Purpose of our study was to assess whether long‐term lipid‐lowering therapy with fenofibrate could reduce the number and extension of massive macular exudates in Type 1 diabetes patients.Methods: There were 46 (92 eyes) Type 1 diabetes persons (18–42 years) with diabetic maculopathy and massive hard exudates included in this study. HbA1C ranging from 6% to 9%. The mean visual acuity was 0.3 ± 0.1. Patients were divided into two groups: main (22 person) and control (24 person). Exclusion criteria: patients on lipid‐lowering drugs, oral contraceptive pills, hormone replacement therapy, pregnant woman, familial hypercholesterolemia, hypothyroidism, chronic liver and kidney disease. All patients in the main group received fenofibrate 145 mg once a day for 8 months, patients in control group had conventional therapy. All patients had undergone standard ophthalmological examination, fundus photos and OCT scanning on presentation and during follow‐up visits. Patients were followed at 2, 6, 12 and 18 months after the start of the treatment.Results: In the main group anatomic result expressed by the reduction of number and extension of hard exudates, decrease in central retinal thickness was achieved in 77% of patients (17 patients, 34 eyes). Central retinal thickness in the main group decreased from mean 392 mkm to 255 mkm ± 30 mkm. Good functional result was achieved in 64% of patients (28 eyes), where visual acuity increased from 0.3 to 0.5 ± 0.1. This effect was stable for the whole follow‐up period. In the control group 74% of patients had no anatomic neither functional changes. In 15% of patients mean visual acuity slightly improved from 0.3 to 0.4 ± 0.05 with decrease in central retinal thickness from mean 386 mkm to 320 mkm ± 30 mkm due to better compensation of the main disease. In 15% the number and extension of hard exudates increased with further vision deterioration. No fenofibrate side effects were noticed in either group.Conclusions: Fenofibrate in Type 1 diabetic patients diminishes number of macular hard exudates, reduces macular oedema, improves visual acuity with stable effect over the time.

Hematological and Histopathological Study Effect of Molybdate and Sulfate Alone and in Combination Overloaded Intake on Copper Outcome in Mature Male Rats

The object of this study were to evaluate the effect of molybdate and sulfate overload alone or in combination overload intake on copper outcome with regard toxicopathological changes in mature male rats. Twenty eight adult male rats were housed and arbitrarily divided into four equal groups (seven rat/group) and treated as follows for 60 days: control received distilled water, groups T1 received sodium molybdate 50 mg/kg B.W and T2: given orally 500 mg/kg B.W of sodium sulfate and T3 group were given sodium molybdate and sodium sulfate in combination at half dose in comparison with T1 and T2 doses. The blood tests results, which included Red Blood Cell count, hemoglobin concentration and Packed Cell Volume % that conducted a after one month and at the end of the experiment showed a significant reductions in general but were more in T1 group followed by T2 group, while T3 group showed less decline than that recorded in each of T1 and T2 groups. These functional changes were accompanied by structural changes in the hepatic and renal tissues. Histopathological changes following molybdate (50 mg/kg B.W) exposure were manifested by extensive areas of necrosis, hemorrhage, and hyperplasia of bile ductules. Besides focal area of necrosis and suppurative granuloma observed in livers of rats received 500 mg/kg B.W of sodium sulfate, mild infiltrate of mononuclear cell within the hepatic parenchyma, suppurative granuloma and proliferation of kupffer’s cells with hyperplasia of bile ductules seen in liver of rats received combination of them at half dose. While section of kidney from T1 group showed marked fibrous thickening of the capsule, severe cortical hemosiderosis with infiltrate of plasma cell and neutrophils, While in T2 group showed atrophy of glomerular tuft, focal interstitial mononuclear cells infiltration with deposition of hyaline cast. The histological changes revealed that renal damage was also observed in T3 group but at a little degree, depending on the result of this study it can be concluded that molybdate and sulfate alone and in combination succeeded to induce copper deficiency with severe changes in hematological and histopathological parameters in rats.

Neuroinflammation and Post-Stroke Depression: Focus on the Microglia and Astrocytes.

Post-stroke depression (PSD), a frequent and disabling complication of stroke, has a strong impact on almost thirty percent of stroke survivors. The pathogenesis of PSD is not completely clear so far. Neuroinflammation following stroke is one of underlying mechanisms that involves in the pathophysiology of PSD and plays an important function in the development of depression and is regarded as a sign of depression. During the neuroinflammation after ischemic stroke onset, both astrocytes and microglia undergo a series of morphological and functional changes and play pro-inflammatory or anti-inflammatory effect in the pathological process of stroke. Importantly, astrocytes and microglia exert dual roles in the pathological process of PSD due to the phenotypic transformation. We summarize the latest evidence of neuroinflammation involving in PSD in this review, focus on the phenotypic transformation of microglia and astrocytes following ischemic stroke and reveal the dual roles of both microglia and astrocytes in the PSD via modulating the neuroinflammation.

СТРУКТУРНО-ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ СЕРДЦА У ПАЦИЕНТОВ МОЛОДОГО ВОЗРАСТА С ЖЕЛУДОЧКОВОЙ ЭЛЕКТРОКАРДИОСТИМУЛЯЦИЕЙ В ОТДАЛЕННОМ ПОСЛЕОПЕРАЦИОННОМ ПЕРИОДЕ

Aim. To study the structural and functional state of the heart in young patients with ventricular pacing in the long-term postoperative period. Materials and methods. The study included 60 people aged 18 to 35 years (35 men and 25 women) with AV blocks that required the implantation of a permanent pacemaker (PM). The first group consisted of 30 people with permanent PMs implanted after surgical correction of CHD due to postoperative AV blockage. The second group consisted of 30 people with non-surgical AV block. All patients underwent a general clinical examination, echocardiography, and medical documentation was retrospectively studied. The duration of pacing in group 1 was 15.6 (13.1; 18.0) years, in group 2 - 15.7 (13.9; 18.5) years. All patients of both groups at the time of the study were implanted with two-chamber PMs. The median percentage of ventricular stimulation in both groups was 100%.Results. In the study groups, significant differences were revealed in the anteroposterior size of the left atrium (LA): 36.5 (33.5; 39.5) mm and 33.5 (31.0; 36.0) mm (U = 281.0, p = 0.030), suggesting initial changes in LA geometry in patients of group 1. Signs of LV remodeling (concentric and eccentric hypertrophy and concentric remodeling) were detected in 40% (12 people out of 30) of patients in group 1 and in 10% (3 people out of 30) in group 2 (χ2 = 7.20, p = 0.007). In group 1, LV ejection fraction (EF) in B mode was significantly lower than in group 2 and made up 59.0 (52.0; 63.0) % and 61.5 (56.0; 66.0)% (U = 307.5, p = 0.034), respectively. 40% of patients in group 1 and 17% in group 2 had LVEF < 55% (χ2 = 4.02, p = 0.045). LV diastolic dysfunction was detected in 26% of people in group 1; in group 2, no patients with diastolic dysfunction were identified (F = 0.154, p = 0.005).Conclusion. In patients with long-term ventricular stimulation after surgical correction of congenital heart disease, significant structural and functional changes in the heart were revealed (signs of remodeling of the left heart, systolic and diastolic dysfunction of the left ventricle), which appear to be significant predictors of cardiovascular events, including heart failure and mortality. In patients with non-surgical AV block and long-term ventricular pacing no significant impairment of cardiac function was detected.

The Multifaceted Role of Oxytocinergic System and OXTR Gene.

The article explores the multifaceted role of the neuropeptide oxytocin in human behavior and its connection to the oxytocin receptor ( OXTR ) gene. Oxytocin, produced in specific brain nuclei, is implicated in emotional, social, and maternal behaviors, stress reduction, uterine contraction during childbirth, and lactation. The OXTR gene, located on chromosome 3, encodes oxytocin receptors found in various body parts, including critical brain regions associated with social behaviors. The article delves into studies on rodents, revealing correlations between OXTR gene expression and pair bonding in the prefrontal cortex and social behavior regulation in the amygdala. The discussion extends to the impact of oxytocin on social support-seeking behavior, focusing on a specific genetic variation, rs53576. The article explores how this genetic variation influences empathy, stress reactivity, and susceptibility to disorders such as autism and social anxiety. Furthermore, the article examines structural and functional changes in the brain associated with OXTR gene variations. It discusses the role of DNA methylation in influencing oxytocin receptor availability, affecting social perception and responsiveness to negative stimuli. The article also highlights the oxytocinergic system's involvement in disorders such as autism and social anxiety, emphasizing the interplay between genetics and environmental factors. The article also touches on the potential therapeutic use of exogenous oxytocin in mitigating symptoms associated with these disorders. In summary, the article underscores the intricate relationship between oxytocin, the OXTR gene, and diverse aspects of human behavior, providing insights into social bonding, perception, and the development of behavioral disorders.

Imperatorin ameliorates kidney injury in diabetic mice by regulating the TGF-β/Smad2/3 signaling axis, epithelial-to-mesenchymal transition, and renal inflammation

Diabetic nephropathy (DN) is a serious concern in patients with diabetes mellitus. Prolonged hyperglycemia induces oxidative damage, chronic inflammation, and build-up of extracellular matrix (ECM) components in the renal cells, leading to kidney structural and functional changes. Imperatorin (IMP) is a naturally occurring furanocoumarin derivative with proven antioxidative and anti-inflammatory properties. We investigated whether IMP could improve DN and employed high glucose (HG)-induced HK-2 cells and high-fat diet-fed streptozotocin (HFD/STZ)-generated DN experimental model in C57BL/6 J mice. In vitro, IMP effectively reduced the HG-activated reactive oxygen species generation, disturbance in the mitochondrial membrane potential (MMP) and epithelial-to-mesenchymal transition (EMT)-related markers, and the transforming growth factor (TGF)-β and collagen 1 expression in HK-2 cells. In vivo, we found an elevation of serum creatinine, kidney histology alterations, and collagen build-up in the kidneys of the DN control group. Also, we found that altered expression of EMT-related markers, upregulation of the TGF-β/Smad2/3 axis, and elevated pro-inflammatory molecules, TNF-α, IL-1β, IL-18 and phospho–NF–kB (p65) in the DN control group. IMP treatment did not significantly reduce the blood glucose level compared to the DN control group. However, IMP treatment effectively improved renal damage by ameliorating kidney histological changes and serum renal injury markers. IMP treatment restored renal antioxidants and exhibited anti-inflammatory effects in the kidneys. Moreover, the abnormal manifestation of EMT-related attributes and elevated levels of TGF-β, phospho-Smad2/3, and collagen 1 were also normalized in the IMP treatment group. Our findings highlight that IMP may be a potential candidate for treating DN.

Pragmatic Approaches to Scalable Prehabilitation

Patients with cancer should ideally undergo proactive screening for muscle wasting, dietary deficiencies, functional changes, and/or psychological needs. Alternatively, a cross-referral strategy may be useful. A multimodal prehabilitation approach can address impairments and optimize function before treatment. Urological prehabilitation has led to improvements in lean body mass, bone density, erectile function, and urinary continence.

Functional changes across marine habitats due to ocean acidification.

Global environmental change drives diversity loss and shifts in community structure. A key challenge is to better understand the impacts on ecosystem function and to connect species and trait diversity of assemblages with ecosystem properties that are in turn linked to ecosystem functioning. Here we quantify shifts in species composition and trait diversity associated with ocean acidification (OA) by using field measurements at marine CO2 vent systems spanning four reef habitats across different depths in a temperate coastal ecosystem. We find that both species and trait diversity decreased, and that ecosystem properties (understood as the interplay between species, traits, and ecosystem function) shifted with acidification. Furthermore, shifts in trait categories such as autotrophs, filter feeders, herbivores, and habitat-forming species were habitat-specific, indicating that OA may produce divergent responses across habitats and depths. Combined, these findings reveal the importance of connecting species and trait diversity of marine benthic habitats with key ecosystem properties to anticipate the impacts of global environmental change. Our results also generate new insights on the predicted general and habitat-specific ecological consequences of OA.

Changes in the structure and function of the visual pathway in subjects at high risk for the development of Alzheimer's disease: 27 months of follow‐up

Aims/Purpose: In addition to advanced age, two of the most important risk factors for the development of Alzheimer's disease are having a family history of the disease (FH+) and being a carrier of at least one Ɛ4+ allele for the ApoE gene (ApoE Ɛ4+). AD generates changes in the retina and visual function when the disease is established, so the aim of the present work is to know if these changes appear in healthy subjects but with high genetic risk to develop the disease and to analyse if these changes evolve along 27 months of follow‐up.Methods: A retinal thickness analysis by optical coherence tomography and visual function by assessing visual acuity (VA), contrast sensitivity (CS), colour perception, perception digital test and visual field analysis was completed by all participants. For structural findings analysis subjects were divided into (FH+ ApoE Ɛ4+) and (FH‐ ApoE Ɛ4‐) groups and for functional analysis these subgroups were subdivided by ages between 40 and 60 years and subjects over 60 years.Results: After 27 months of follow‐up, the FH+ ApoE Ɛ4+ group experienced changes in the thickness of all retinal layers except the outer layers. In this group, the inner nuclear layer showed progressing changes, but there was no progression in visual function. However, compared to the FH‐ ApoE Ɛ4‐ group at 27 months, the improvement in visual acuity and contrast sensitivity (3 and 12 cpd) observed during the initial visit was maintained.Conclusions: In cognitively healthy individuals at high risk of developing AD structural changes in the retina continue to progress after 27 months, while functional changes detected at the beginning remain stable.

Optic neuritis: a review of diagnostic imaging modalities and effective management approaches

Optic neuritis (ON) is a medical condition characterized by an acute inflammation of the optic nerve, usually caused by multiple sclerosis (MS). However, there are other causes such as infectious diseases, granulomatous disease, paraneoplastic disorders, and demyelination disorders. Usually, the commonest presentation is unilateral painful loss of vision. This study aimed to review the diagnostic imaging modalities and effective management approaches of ON. ON can be diagnosed through different modalities such as magnetic resonance imaging, which is the modality of choice to assess ON, providing crucial insights into the structural and functional changes within the optic nerve. In ON, the retrobulbar intra-orbital segment of the optic nerve often exhibits noticeable characteristics, including swelling and a high T2 signal. In addition, optical coherence tomography is a new, noninvasive tool for direct visualization of the head of the optic nerve that can detect thinner retinal nerve fiber layers diagnosing ON. In treating ON and MS, the main aim is to reduce the recurrence and severity of the attacks to minimize the subsequent disability. The utilization of disease-modifying drugs contributes to delaying the onset of subsequent episodes, reducing the occurrence of MS relapses, and minimizing the formation of demyelinating lesions.

Cytogenetic Analysis of the Crustacean Pontogammarus robustoides (Amphipoda, Gammaridae) at Increased Water Temperature under Conditions of Microcosm

Adaptive reactions of <i>Pontogammarus robustoides</i>, a representative of the family Gammaridae, were studied at the cellular level at the increase in water temperature to its critical values under conditions of a model ecosystem - a microcosm. A cytogenetic analysis of its embryo cells was carried out and the activity of nucleoli of somatic cells was investigated. It has been shown that normal development of <i>P. robustoides</i> embryo cells was observed within the temperature range from 25.0°C to 27.5°C. The increase in water temperature up to 30.0-30.5°C resulted in such structural and functional changes in its cells as the increase in chromosome aberrations and the increase in the number of micronuclei. At the prolonged exposure to the increased water temperature, these indices approached critical levels. The number of embryo cells with nuclear fragmentation increased, which is evidence of the development of the processes directed to apoptosis. The destruction of embryo cell structures was registered at 32.0°C. The total volume of nucleoli in the somatic cells increased, which can be indicative of the increased synthesis of proteins probably involved in the processes of adaptation. A decrease in water temperature to the initial level of 25.0°C favored recovery of the structural and functional indices of Gammaridae genome. However, a high contribution of cell division disorders was still observed, which was accompanied by a significant decrease in the number of micronuclei.

Эффективность и безопасность разных режимов cахароснижающего лечения у лиц с синдромом раздраженного кишечника в сочетании с сахарным диабетом 2 типа

Among the disorders associated with type 2 diabetes mellitus, intestinal functional changes (irritable bowel syndrome — IBS) are an insufficiently studied problem. The purpose — a prospective study of the efficacy and safety of various hypoglycemic treatment regimens in patients with IBS and type 2 diabetes mellitus. Material and methods The study included 107 patients aged 48.9 ± 9.4 years with type 2 diabetes mellitus and clinical manifestations of IBS, who were divided into 4 groups depending on the prescribed hypoglycemic therapy: patients of group A received metformin, group B — a combination of metformin with saxagliptin, group C — a combination of metformin with liraglutide or exenatide, group D — combination of metformin with dapagliflozin. The duration of the study was not less than 5 months. Results. Treatment in all groups resulted in a significant decrease in the average values of HbA1c, fructosamine, insulin, C-peptide and the HOMA-IR index, an increase in the values of the NOMA-B index, p < 0.05. A more significant absolute and relative decrease in the levels of HbA1c, insulin and HOMA-IR index was observed in groups C and D in comparison with groups A and B. The use of various classes of hypoglycemic drugs in people with IBS and type 2 diabetes mellitus was characterized by satisfactory tolerability and was associated with a significant decrease in clinical manifestations of constipation, diarrhea, abdominal pain, gastroesophageal reflux, and a positive effect on glycemic levels. The criteria for predicting the effectiveness and safety of hypoglycemic treatment in patients with a combination of IBS and type 2 diabetes mellitus were the diabetes duration < 7 years, the values of HOMA-IR <5 and NOMA-B ³ 60, the absence of smoking, the uric acid concentration in blood < 350 mmol/ l, the absence of hypothyroidism and the choice of dapagliflozin as a component of hypoglycemic therapy.

4D printing for biomedical applications.

While three-dimensional (3D) printing excels at fabricating static constructs, it fails to emulate the dynamic behavior of native tissues or the temporal programmability desired for medical devices. Four-dimensional (4D) printing is an advanced additive manufacturing technology capable of fabricating constructs that can undergo pre-programmed changes in shape, property, or functionality when exposed to specific stimuli. In this Perspective, we summarize the advances in materials chemistry, 3D printing strategies, and post-printing methodologies that collectively facilitate the realization of temporal dynamics within 4D-printed soft materials (hydrogels, shape-memory polymers, liquid crystalline elastomers), ceramics, and metals. We also discuss and present insights about the diverse biomedical applications of 4D printing, including tissue engineering and regenerative medicine, drug delivery, in vitro models, and medical devices. Finally, we discuss the current challenges and emphasize the importance of an application-driven design approach to enable the clinical translation and widespread adoption of 4D printing.

Functional stasis and changing habitat preferences among mammalian communities from the PETM of the Bighorn Basin, Wyoming

Functional stasis and changing habitat preferences among mammalian communities from the PETM of the Bighorn Basin, Wyoming

A Brazilian Neonatal Unit's Experience with Functional Echocardiography and Diagnostic Findings in Congenital Heart Disease

Introduction: The diagnosis of congenital heart diseases is a challenge for pediatricians due to the diversity of clinical presentations and symptoms, just like several other diseases prevalent in the neonatal period. Often the diagnosis is established during the gestation period, sometimes the hypothesis is formulated by neonatal screening. However, several cases will require clinical suspicion from the pediatrician. Given the possibility of this diagnosis, the evaluation of the infant cardiologist is essential. Unfortunately, this professional is not always readily available. In the intensive care units, health professionals use heart rate, blood pressure, capillary refill, urinary output and acid-base balance for hemodynamic analysis. These data are significant, but nonspecific. Thus, functional echocardiography can improve hemodynamic evaluation with positive impact on diagnosis. Our objective was to conduct a retrospective analysis of hospitalizations in a Brazilian neonatal unit, with the goal of identifying the diagnoses of congenital heart diseases made by a researcher using functional echocardiography, from July 2015 to September 2017, having as inclusion criteria; clinical manifestations of distress or respiratory failure, characterized by tachypnea, signs of dyspnea, need for oxygen therapy or ventilatory support and/or hemodynamic instability, characterized by tachycardia, cyanosis, cold extremities, prolonged capillary filling time, fine pulses and/or hypotension, low urinary output. Results: During the 26 months of the study, 362 neonates were hospitalized. Of these, 223 were included in the research for presenting cardiorespiratory manifestations. We observed three cases of obstructive shock related to cardiac tamponade, 18 cases of congenital heart disease, five cases of hypertrophic myocardiopathy, seven cases of myocardial dysfunction not related to structural heart disease, 46 cases of neonatal persistent pulmonary hypertension and 27 cases of patent ductus arteriosus (six with hemodynamics repercussion). Conclusions: The results showed functional and/or anatomical changes in 105 patients analyzed (46.7%), identified a diversity of structural cardiopathies, improved hemodynamic evaluation with impact on the therapeutic approach. While using functional echocardiography in neonates, clinicians should be aware that undiagnosed critical congenital heart defects can present during this period. They should acknowledge the limitations of skills, and it should not be used as a screening tool for diagnosing or excluding congenital heart defects. A patient with a suspected critical congenital heart defect should be quickly referred to a pediatric cardiologist, even if this implies out-of-hospital patient’s transportation. We assume that the systematic implementation of this technology by the medical team can improve diagnostic accuracy, which can positively impact the therapy used. Keywords: Critical care, neonatology, ultrasonography, echocardiography, point-of-care systems, cardiac tamponade, hypertension pulmonary, heart defectal congenits.

Morphology of Hassall's corpuscles and their microenvironment in neonates with increased thymus weight

To study morphological features of Hassall's corpuscles (HC) and their microenvironment in newborns with increased thymus mass. The study was carried out on autopsy material of children of the first month of life. Based on the thymic index (TI), 2 groups were identified: with normal (conditional norm) and increased TI value (increased thymus weight). The standard method of histological staining and immunohistochemical methods with antibodies to Pan-CK, CK19, CD68, CD3 and p53 were used in the study. The classification proposed by A.G. Beloveshkin (2013) was used to determine the degree of maturity of HC. Nonparametric Mann-Whitney test was used to determine statistically significant differences in the groups. In the group of children with increased thymus weight, the number of HC decreased by 20%. It was found that the proportion of progressive and mature corpuscles in this group was reduced by 2.3 and 1.6 times, respectively, compared to the group of children with normal thymus weight, while the proportion of regressive corpuscles increased almost 2-fold. In the HC microenvironment, there is an increase in the total number of thymocytes, combined with a decrease in the expression of CD68, CD3 and p53 in them. A sharp decrease in CK19-expressing cells in this group is accompanied by a disruption in the formation of reticular structures characteristic of the comparison group. In the thymus with increased mass, the structural and functional organization changes: along with an increase in the total number of thymocytes in the cortical layer and a decrease in the number of macrophages, epithelial cells and HC (with a predominance of regressive corpuscles), disturbances in the processes of maturation, apoptosis and negative selection of lymphocytes occur, which can lead to development of immunogenesis disorders.

Functional and morphological characterization of ocular phenotype in C3H/HeOuJ (Pde6b‐rd1) mice

Aims: C3H/HeOuJ mice (The Jackson Laboratory strain #000635) are homozygous for the retinal degeneration 1 mutation Pde6brd1 (rd1) causing severe visual deficits. The purpose of this study was to characterize the ocular phenotype of male and female mice with the rd1 mutation.Methods: The ophthalmic phenotype of mixed sex rd1 and aged‐matched C57BL/6J wild type (WT) mice (6 females and 4 males for rd1 group, 6 females and 5 males for WT group) was assessed at 3 months of age. Retinal photoreceptor function was quantified using scotopic flash electroretinography (fERG) with six different light intensities: 0.003, 0.01, 0.1, 1, 3 and 10 cd.s/m2 (Celeris, Diagnosys LLC). Retinal morphology was evaluated with spectral domain optical coherence tomography (SD‐OCT) (Envisu R2200, Bioptigen Inc./Leica Microsystems). Retinal thickness was measured from SD‐OCT images using a proprietary convolutional neural network. Optomotor reflex (OMR) was measured as photopic visual acuity and contrast sensitivity at 0.019 and 0.06 cyc/° (OptoDrum Plus, Striatech GmbH). Data were analysed by unpaired t‐test or Mann–Whitney test.Results: At 3 months of age, the rd1 mutation resulted in significant impairment of visual function in both male and female mice compared to age‐matched WT. fERG a and b‐wave amplitudes were decreased by 90% in both sexes (p < 0.001). The rd1 mice had only minimal visual acuity and contrast sensitivity assessed by OMR. Functional decline correlated with structural changes, notably the significant thinning of the retina (p < 0.001).Conclusions: The Pde6brd1 mutation resulted in severe functional and structural changes at 3 months of age. The mice presented significantly decreased but detectable fERG amplitudes, however, they had no functional vision as assessed by OMR. Combining fERG and OMR offers longitudinal in‐life quantification of retinal circuitry and functional vision with great utility for evaluation of novel therapeutic approaches for regeneration of the visual system.

Towards the preclinical diagnosis of diabetic retinopathy and diabetic macular oedema using tear samples

Aims/Purpose: A wide spectrum of molecular‐genetic events, including inflammation (INF), angiogenesis (ANG), apoptosis (AP) and the concurrence of miRNAs and target genes, are involved in diabetic retinopathy (DR) and diabetic macular oedema (DMO). To unravel the complex pathogenesis of DR and DMO, we focus on the microvascular endothelial dysfunction (MVED) pathophysiologic pathways.Methods: Volunteers of both sexes, aged 35–80 years were enrolled and distributed into type 2 diabetics (T2DM), with DR (+DRG; n = 35), without DR (−DRG; n = 35), with DMO (DMOG; n = 28), and controls (CG; n = 40). Sociodemographic and comorbid data, ophthalmologic parameters, and molecular‐genetic variables related to INF, ANG, and AP, assayed in tear samples, were recorded. Statistics were performed by the R Core Team (2022) program.Results: Most of our participants were middle‐aged (mean age was 58 ± 11 years). Differential expression profile in tears was found statistically significant for SOCS6 gene (involved in INF) target of hsa‐miR‐155‐5p, VEGF‐A gene (implicated in ANG) target of hsa‐miR‐15b‐5p, and the BCL2L2 gene (AP effector) target of hsa‐miR‐10a‐5p, in both the +DRG and DMOG, as compared to the −DRG and CG.Conclusions: We confirm that INF, ANG, and AP, regulated by the hsa‐miR‐155‐5p, hsa‐miR‐15b‐5p and hsa‐miR‐10a‐5p, and its respective target genes SOCS6, VEGF‐A, and BCL2L2, expressed in tears, are key players in the development of structural and functional chorioretinal changes associated with MVED in DR/DMO patients. We may propose the above insights as potential diagnostic‐prognostic biomarkers for better managing the diabetic eyes and vision.

Diesel exhaust particles induce polarization state-dependent functional and transcriptional changes in human monocyte-derived macrophages.

Macrophage populations exist on a spectrum between the proinflammatory M1 and proresolution M2 states and have demonstrated the ability to reprogram between them after exposure to opposing polarization stimuli. Particulate matter (PM) has been repeatedly linked to worsening morbidity and mortality following respiratory infections and has been demonstrated to modify macrophage function and polarization. The purpose of this study was to determine whether diesel exhaust particles (DEP), a key component of airborne PM, would demonstrate polarization state-dependent effects on human monocyte-derived macrophages (hMDMs) and whether DEP would modify macrophage reprogramming. CD14+CD16- monocytes were isolated from the blood of healthy human volunteers and differentiated into macrophages with macrophage colony-stimulating factor (M-CSF). Resulting macrophages were left unpolarized or polarized into the proresolution M2 state before being exposed to DEP, M1-polarizing conditions (IFN-γ and LPS), or both and tested for phagocytic function, secretory profile, gene expression patterns, and bioenergetic properties. Contrary to previous reports, we observed a mixed M1/M2 phenotype in reprogrammed M2 cells when considering the broader range of functional readouts. In addition, we determined that DEP exposure dampens phagocytic function in all polarization states while modifying bioenergetic properties in M1 macrophages preferentially. Together, these data suggest that DEP exposure of reprogrammed M2 macrophages results in a highly inflammatory, highly energetic subpopulation of macrophages that may contribute to the poor health outcomes following PM exposure during respiratory infections.NEW & NOTEWORTHY We determined that reprogramming M2 macrophages in the presence of diesel exhaust particles (DEP) results in a highly inflammatory mixed M1/M2 phenotype. We also demonstrated that M1 macrophages are particularly vulnerable to particulate matter (PM) exposure as seen by dampened phagocytic function and modified bioenergetics. Our study suggests that PM causes reprogrammed M2 macrophages to become a highly energetic, highly secretory subpopulation of macrophages that may contribute to negative health outcomes observed in humans after PM exposure.

The functional role of the pulvinar in discriminating between objective and subjective cognitive impairment in major depressive disorder.

Emotionally driven cognitive complaints represent a major diagnostic challenge for clinicians and indicate the importance of objective confirmation of the accuracy of depressive patients' descriptions of their cognitive symptoms. We compared cognitive status and structural and functional brain connectivity changes in the pulvinar and hippocampus between patients with total depression and healthy controls. The depressive group was also classified as "amnestic" or "nonamnestic," based on the members' subjective reports concerning their forgetfulness. We then sought to determine whether these patients would differ in terms of objective neuroimaging and cognitive findings. The right pulvinar exhibited altered connectivity in individuals with depression with objective cognitive impairment, a finding which was not apparent in depressive patients with subjective cognitive impairment. The pulvinar may play a role in depression-related cognitive impairments. Connectivity network changes may differ between objective and subjective cognitive impairment in depression and may play a role in the increased risk of dementia in patients with depression.