Surgical Management of Radicular Cyst with the Application of a Natural Platelet Concentrate and Ostoden: A Case Report.

The most frequent cystic lesions that affect the jaw are radicular cysts. The current case report describes the surgical management of a radicular cyst in the periapical region of maxillary central and lateral incisors, and highlights the efficacy of natural platelet concentrate [platelet-rich fibrin (PRF)] along with Ostoden bone graft material used for postoperative healing. A 46-year-old male patient presented to the department with swelling in the palatal aspect of the maxillary anterior region. On radiographic examination, a radiolucent periapical lesion was evident in relation to the left maxillary central and lateral incisor. In the maxillary anterior region, root canal therapy was performed, followed by periapical surgery, and PRF with Ostoden bone graft was placed in the surgical site to initiate the healing at a faster rate. The patient was recalled at follow-ups after 7 days, 3, 6, and 9 months. No symptoms such as pain, inflammation, or discomfort were observed during the review period.

A Case Report of Fracture of the Segment of Maxillary Alveolar Process Involving Primary Incisors.

Traumatic dental injuries (TDIs) have significant long-term consequences for the oral cavity's hard and soft tissues. Alveolar process fractures are particularly complicated. This case report describes the management and 12-month follow-up of a segmental maxillary alveolar process fracture involving laterally luxated primary incisors. A case of a 4-year-old boy was reported to the hospital 1 hour after an accidental fall at school, which resulted in a fracture of the maxillary alveolar process. Emergency treatment consisted of fracture reduction and repositioning of the primary incisors, followed by a semirigid splint between maxillary canines. The splints were removed at the end of week 4, and the affected primary incisors remained asymptomatic.

Leucaena leucocephala succinate based polyelectrolyte complexes for colon delivery of synbiotic in management of inflammatory bowel disease.

Polyelectrolyte complexes (PECs) formed by the interaction between oppositely charged polymers have emerged as promising carriers for accomplishing colon-specific release. In this study, we have explored the potential of polyelectrolyte complexes between a succinate derivative of Leucaena leucocephala galactomannan and cationic guar gum for colon delivery of synbiotic. The PECs were prepared using a polyelectrolyte complexation method and characterized. The PECs exhibited excellent stability, with high encapsulation efficiency for both probiotics (95.53 %) and prebiotics (83.33 %). In vitro studies demonstrated enhanced survivability and proliferation of the encapsulated probiotics in the presence of prebiotics (93.29 %). The SEM images revealed a smooth and firm structure with reduced number of pores when both prebiotic and probiotic were encapsulated together. The treatment with synbiotic PECs in acetic acid induced IBD rats significantly relieves colitis symptoms as was evident from colon/body ratio, DAI score and histopathology studies. An increase in the protein and reduced glutathione levels and reduction in superoxide dismutase activity was observed in colitic rats that received synbiotic treatment as compared to colitic rats. Overall, this study highlights the potential of Leucaena leucocephala succinate-cationic guar gum PECs as a promising system for colon-specific synbiotic delivery, with implications for improved gut health and the treatment of various gastrointestinal disorders.

Morpholinodiazenyl chalcone blocks influenza A virus capsid uncoating by perturbing the clathrin-mediated vesicular trafficking pathway.

Influenza A virus (IAV) is a highly contagious respiratory pathogen that significantly threatens global health by causing seasonal epidemics and occasional, unpredictable pandemics. To identify new compounds with therapeutic potential against IAV, we designed and synthesized a series of 4'-morpholinodiazenyl chalcones using the molecular hybridization method, performed a high-content screen against IAV, and found that (E)-1-{4-[(E)-morpholinodiazenyl]phenyl}-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (MC-22) completely neutralized IAV infection. While MC-22 allowed IAV to successfully internalize into the cell and fuse at the acidic late endosomes, it prevented viral capsid uncoating and genome release. Since IAV majorly utilizes clathrin-mediated endocytosis (CME) for cellular entry, we examined whether MC-22 had any effect on CME, using nonviral cargoes that enter cells via clathrin-dependent or -independent pathways. Although MC-22 showed no effect on the uptake of choleratoxin B, a cargo that enters cells majorly via the clathrin-independent pathway, it significantly attenuated the clathrin-dependent internalization of both epidermal growth factor and transferrin. Cell biological analyses revealed a marked increase in the size of early endosomes upon MC-22 treatment, indicating an endosomal trafficking/maturation defect. This study reports the identification of MC-22 as a novel CME-targeting, highly potent IAV entry inhibitor, which is expected to neutralize a broad spectrum of viruses that enter the host cells via CME.

Hybrid feature selection and classification technique for early prediction and severity of diabetes type 2.

Diabetes prediction is an ongoing study topic in which medical specialists are attempting to forecast the condition with greater precision. Diabetes typically stays lethargic, and on the off chance that patients are determined to have another illness, like harm to the kidney vessels, issues with the retina of the eye, or a heart issue, it can cause metabolic problems and various complexities in the body. Various worldwide learning procedures, including casting a ballot, supporting, and sacking, have been applied in this review. The Engineered Minority Oversampling Procedure (Destroyed), along with the K-overlay cross-approval approach, was utilized to achieve class evening out and approve the discoveries. Pima Indian Diabetes (PID) dataset is accumulated from the UCI Machine Learning (UCI ML) store for this review, and this dataset was picked. A highlighted engineering technique was used to calculate the influence of lifestyle factors. A two-phase classification model has been developed to predict insulin resistance using the Sequential Minimal Optimisation (SMO) and SMOTE approaches together. The SMOTE technique is used to preprocess data in the model's first phase, while SMO classes are used in the second phase. All other categorization techniques were outperformed by bagging decision trees in terms of Misclassification Error rate, Accuracy, Specificity, Precision, Recall, F1 measures, and ROC curve. The model was created using a combined SMOTE and SMO strategy, which achieved 99.07% correction with 0.1 ms of runtime. The suggested system's result is to enhance the classifier's performance in spotting illness early.

Artificial Intelligence-Based Secured Power Grid Protocol for Smart City.

Due to the modern power system's rapid development, more scattered smart grid components are securely linked into the power system by encircling a wide electrical power network with the underpinning communication system. By enabling a wide range of applications, such as distributed energy management, system state forecasting, and cyberattack security, these components generate vast amounts of data that automate and improve the efficiency of the smart grid. Due to traditional computer technologies' inability to handle the massive amount of data that smart grid systems generate, AI-based alternatives have received a lot of interest. Long Short-Term Memory (LSTM) and recurrent Neural Networks (RNN) will be specifically developed in this study to address this issue by incorporating the adaptively time-developing energy system's attributes to enhance the model of the dynamic properties of contemporary Smart Grid (SG) that are impacted by Revised Encoding Scheme (RES) or system reconfiguration to differentiate LSTM changes & real-time threats. More specifically, we provide a federated instructional strategy for consumer sharing of power data to Power Grid (PG) that is supported by edge clouds, protects consumer privacy, and is communication-efficient. They then design two optimization problems for Energy Data Owners (EDO) and energy service operations, as well as a local information assessment method in Federated Learning (FL) by taking non-independent and identically distributed (IID) effects into consideration. The test results revealed that LSTM had a longer training duration, four hidden levels, and higher training loss than other models. The provided method works incredibly well in several situations to identify FDIA. The suggested approach may successfully induce EDOs to employ high-quality local models, increase the payout of the ESP, and decrease task latencies, according to extensive simulations, which are the last points. According to the verification results, every assault sample could be effectively recognized utilizing the current detection methods and the LSTM RNN-based structure created by Smart.

Evaluation of the Denture Impact on the Palatal Rugae: An Original Research.

Introduction: The palatal rugae may alter their shape based on the various physical pressures that they had to endure. This study's objective is to assess the various alterations in the palatal rugae parameters among the complete denture wearers. Materials and Procedures: Forty subjects in all were chosen for the study. The control group interventional groups had an equal number of participants who were further equally distributed based on gender. For all of the participants, mucostatic maxillary alginate imprints were taken, and gypsum castings were created. They were called at the scheduled intervals of 2, 6, and 12 months following the treatment. The models used during those recalls and all of the palatal rugae were examined under a microscope for quantity, length, form, orientation, and unifications. The unpaired t-test was used to statistically examine palatal rugae alterations. Results: Following the wear of the dentures, the experimental group's primary, secondary, and fragmented rugae all gradually shrank in length. In terms of statistics, the alteration solely affected primary rugae and was significant (P < 0.001). After a year of wearing dentures, a minimal change in rugae's form was noticed in the denture groups, but it was statistically not substantial (P > 0.05). Conclusion: Due to the prolonged mechanical stress the dentures placed on the palatal rugae, complete denture users saw a significant reduction in the length of their primary rugae. Rugae number, orientation, and unification were among the other criteria that did not change during the course of the study. Analysis of the palatal rugae may not be useful in identifying people wearing full dentures. However, in forensic investigations, rugae may act as an adjunct to other methods like fingerprints and DNA analysis.

An emerging expanse: Novel and eco-friendly-biogenic synthesis of E. cardamomum-wrapped TiO2 nanoparticles for environmental and biological applications.

The present research is targeted at E. cardamomum-derived TiO2-photocatalyst synthesis, reporting for the first time. The structural properties observed from the XRD pattern reveal that EC:TiO2 has an anatase phase and crystallite size is assessed by Debye-Scherrer's method (3.56 nm), WH-method (3.30 nm), and Modified-Debye-Scherrer's method (3.27 nm). An optical study by the UV-Vis spectrum shows strong absorption at 313 nm, and the corresponding band gap value is 3.28 eV. The topographical and morphological properties revealed by SEM and HRTEM images, elucidate the formation of multi-shaped particles of nano-size. Further, the phytochemicals on the EC:TiO2 NPs' surface are confirmed by the FTIR spectrum. The photocatalytic activity is well studied under UV light towards Congo Red dye, along with an effect of the dose of catalyst. EC:TiO2 (20 mg) has exhibited high photocatalytic efficiency up to 97% for 150 min of exposure due to the morphological, structural, and optical properties. CR degradation reaction exhibits pseudo-first-order kinetics, displaying a rate constant value of 0.01320 min-1. Reusability investigations reveal that after four photocatalysis cycles, EC:TiO2 has an effective efficiency of >85%. Additionally, EC:TiO2 NPs have been assessed for antibacterial activity and show potential against two bacterial species (S. aureus and P. aeruginosa). Therefore, these research outcomes from the eco-friendly and low-cost synthesis, are promising for the use of EC:TiO2 as a talented photocatalyst towards the removal of crystal violet dye as well as an antibacterial agent against bacterial pathogens.

Endothelial glycocalyx in retina, hyperglycemia, and diabetic retinopathy.

The endothelial glycocalyx (EG) is a meshlike network present on the apical surface of the endothelium. Membrane-bound proteoglycans, the major backbone molecules of the EG, consist of glycosaminoglycans attached to core proteins. In addition to maintaining the integrity of the endothelial barrier, the EG regulates inflammation and perfusion and acts as a mechanosensor. The loss of the EG can cause endothelial dysfunction and drive the progression of vascular diseases including diabetic retinopathy. Therefore, the EG presents a novel therapeutic target for treatment of vascular complications. In this review article, we provide an overview of the structure and function of the EG in the retina. Our particular focus is on hyperglycemia-induced perturbations in the glycocalyx structure in the retina, potential underlying mechanisms, and clinical trials studying protective treatments against degradation of the EG.

Aqueous micellar technology: an alternative beyond organic solvents.

Solvents are the major source of chemical waste from synthetic chemistry labs. Growing attention to more environmentally friendly sustainable processes demands novel technologies to substitute toxic or hazardous solvents. If not always, sometimes, water can be a suitable substitute for organic solvents, if used appropriately. However, the sole use of water as a solvent remains non-practical due to its incompatibility with organic reagents. Nonetheless, over the past few years, new additives have been disclosed to achieve chemistry in water that also include aqueous micelles as nanoreactors. Although one cannot claim micellar catalysis to be a greener technology for every single transformation, it remains the sustainable or greener alternative for many reactions. Literature precedents support that micellar technology has much more potential than just as a reaction medium, i.e., the role of the amphiphile as a ligand obviating phosphine ligands in catalysis, the shielding effect of micelles to protect water-sensitive reaction intermediates in catalysis, and the compartmentalization effect. While compiling the powerful impact of micellar catalysis, this article highlights two diverse recent technologies: (i) the design and employment of the surfactant PS-750-M in selective catalysis; (ii) the use of the semisynthetic HPMC polymer to enable ultrafast reactions in water.

The Endothelial Glycocalyx and Retinal Hemodynamics.

PURPOSE: Previous studies suggest that the endothelial glycocalyx adds to vascular resistance, inhibits thrombosis, and is critical for regulating homogeneous blood flow and ensuring uniform red blood cell (RBC) distribution. However, these functions and consequences of the glycocalyx have not been examined in the retina. We hypothesize that the endothelial glycocalyx is a critical regulator of retinal hemodynamics and perfusion and decreases the propensity for retinal thrombus formation. METHODS: Hyaluronidase and heparinase, which are endothelial glycocalyx-degrading enzymes, were infused into mice. Fluorescein isothiocyanate-dextran (2000 kDa) was injected to measure lumen diameter, while RBC velocity and distribution were measured using fluorescently labeled RBCs. The diameters and velocities were used to calculate retinal blood flow and shear rates. Mean circulation time was calculated by measuring the difference between arteriolar and venular mean transit times. Rose Bengal dye was infused, followed by illumination with a green light to induce thrombosis. RESULTS: The acute infusion of hyaluronidase and heparinase led to significant increases in both arteriolar (7%) and venular (16%) diameters in the retina, with a tendency towards increased arteriolar velocity. In addition, the degradation caused a significant decrease in the venular shear rate (14%). The enzyme infusion resulted in substantial increases in total retinal blood flow (26%) and retinal microhematocrit but no changes in the mean circulation time through the retina. We also observed an enhanced propensity for retinal thrombus formation with the removal of the glycocalyx. CONCLUSIONS: Our data suggest that acute degradation of the glycocalyx can cause significant changes in retinal hemodynamics, with increases in vessel diameter, blood flow, microhematocrit, pro-thrombotic conditions, and decreases in venular shear rate.

Metal-Micelle Interaction Leading to Spontaneous Formation of Ligand-Free Palladium(0) Nanoparticles: Highly Efficient Catalysis Enabling Biaryl Ketone Formation from Carboxylic Acid Derivatives.

A novel strategy has been developed to spontaneously form ligand-free Pd(0) nanoparticles (NPs) from water- and air-sensitive Pd2dba3 in water. These NPs are thoroughly characterized by IR, NMR, and mass spectrometry, revealing that the metal-micelle binding plays a critical role in their stability and activity. High-resolution transmission electron microscopy supported the ultrasmall nature of NPs, whereas X-ray photoelectron spectroscopy analysis confirmed the zero-oxidation state of Pd. The shielding effect of micelles and enhanced stability of NPs enabled fast cross-couplings of water-sensitive triazine adducts of carboxylic acid to form nonsymmetrical biaryl ketones. These naturally formed NPs are more efficient than new synthetic NPs formed under a hydrogen atmosphere and traditional NPs formed using the air-sensitive Grignard reagent as a reductant. The activity of naturally formed NPs is compared with that of synthetic NPs over 34 substrates, revealing that naturally formed NPs are much more efficient than synthetic NPs.

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity.

The COVID-19 pandemic has spawned global health crisis of unprecedented magnitude, claiming millions of lives and pushing healthcare systems in many countries to the brink. Among several factors that contribute to an increased risk of COVID-19 and progression to exacerbated manifestations, host genetic landscape is increasingly being recognized as a critical determinant of susceptibility/resistance to infection and a prognosticator of clinical outcomes in infected individuals. Recently, several case-control association studies investigated the influence of human gene variants on COVID-19 susceptibility and severity to identify the culpable mutations. However, a comprehensive synthesis of the recent advances in COVID-19 host genetics research was lacking, and the inconsistent findings of the association studies required reliable evaluation of the strength of association with greater statistical power. In this study, we embarked on a systematic search of all possible reports of genetic association with COVID-19 till April 07, 2022, and performed meta-analyses of all the genetic polymorphisms that were examined in at least three studies. After identifying a total of 84 studies that investigated the association of 130 polymorphisms in 61 genes, we performed meta-analyses of all the eligible studies. Seven genetic polymorphisms involving 15,550 cases and 444,007 controls were explored for association with COVID-19 susceptibility, of which, ACE1 I/D rs4646994/rs1799752, APOE rs429358, CCR5 rs333, and IFITM3 rs12252 showed increased risk of infection. Meta-analyses of 11 gene variants involving 6702 patients with severe COVID-19 and 8640 infected individuals with non-severe manifestations revealed statistically significant association of ACE2 rs2285666, ACE2 rs2106809, ACE2 rs2074192, AGTR1 rs5186, and TNFA rs1800629 with COVID-19 severity. Overall, our study presents a synthesis of evidence on all the genetic determinants implicated in COVID-19 to date, and provides evidence of correlation between the above polymorphisms with COVID-19 susceptibility and severity.

Effect of high glucose on glycosaminoglycans in cultured retinal endothelial cells and rat retina.

INTRODUCTION: The endothelial glycocalyx regulates vascular permeability, inflammation, and coagulation, and acts as a mechanosensor. The loss of glycocalyx can cause endothelial injury and contribute to several microvascular complications and, therefore, may promote diabetic retinopathy. Studies have shown a partial loss of retinal glycocalyx in diabetes, but with few molecular details of the changes in glycosaminoglycan (GAG) composition. Therefore, the purpose of our study was to investigate the effect of hyperglycemia on GAGs of the retinal endothelial glycocalyx. METHODS: GAGs were isolated from rat retinal microvascular endothelial cells (RRMECs), media, and retinas, followed by liquid chromatography-mass spectrometry assays. Quantitative real-time polymerase chain reaction was used to study mRNA transcripts of the enzymes involved in GAG biosynthesis. RESULTS AND CONCLUSIONS: Hyperglycemia significantly increased the shedding of heparan sulfate (HS), chondroitin sulfate (CS), and hyaluronic acid (HA). There were no changes to the levels of HS in RRMEC monolayers grown in high-glucose media, but the levels of CS and HA decreased dramatically. Similarly, while HA decreased in the retinas of diabetic rats, the total GAG and CS levels increased. Hyperglycemia in RRMECs caused a significant increase in the mRNA levels of the enzymes involved in GAG biosynthesis (including EXTL-1,2,3, EXT-1,2, ChSY-1,3, and HAS-2,3), with these increases potentially being compensatory responses to overall glycocalyx loss. Both RRMECs and retinas of diabetic rats exhibited glucose-induced alterations in the disaccharide compositions and sulfation of HS and CS, with the changes in sulfation including N,6-O-sulfation on HS and 4-O-sulfation on CS.

Hyperglycemia-induced effects on glycocalyx components in the retina.

PURPOSE: Diabetic retinopathy is a vision-threatening complication of diabetes characterized by endothelial injury and vascular dysfunction. The loss of the endothelial glycocalyx, a dynamic layer lining all endothelial cells, contributes to several microvascular pathologies, including an increase in vascular permeability, leukocyte plugging, and capillary occlusion, and may drive the progression of retinopathy. Previously, a significant decrease in glycocalyx thickness has been observed in diabetic retinas. However, the effects of diabetes on specific components of the retinal glycocalyx have not yet been studied. Therefore, the aim of our study was to investigate changes in synthesis, expression, and shedding of retinal glycocalyx components induced by hyperglycemia, which could provide a novel therapeutic target for diabetic retinopathy. METHODS: Primary rat retinal microvascular endothelial cells (RRMECs) were grown under normal glucose (5 mM) or high-glucose (25 mM) conditions for 6 days. The mRNA and protein levels of the glycocalyx components were examined using qRT-PCR and Western blot analysis, respectively. Further, mass spectrometry was used to analyze protein intensities of core proteins. In addition, the streptozotocin-induced Type 1 diabetic rat model was used to study changes in the expression of the retinal glycocalyx in vivo. The shedding of the glycocalyx was studied in both culture medium and in plasma using Western blot analysis. RESULTS: A significant increase in the shedding of syndecan-1 and CD44 was observed both in vitro and in vivo under high-glucose conditions. The mRNA levels of syndecan-3 were significantly lower in the RRMECs grown under high glucose conditions, whereas those of syndecan-1, syndecan-2, syndecan-4, glypican-1, glypican-3, and CD44 were significantly higher. The protein expression of syndecan-3 and glypican-1 in RRMECs was reduced considerably following exposure to high glucose, whereas that of syndecan-1 and CD44 increased significantly. In addition, mass spectrometry data also suggests a significant increase in syndecan-4 and a significant decrease in glypican-3 protein levels with high glucose stimulation. In vivo, our data also suggest a significant decrease in the mRNA transcripts of syndecan-3 and an increase in mRNA levels of glypican-1 and CD44 in the retinas of diabetic rats. The diabetic rats exhibited a significant reduction in the retinal expression of syndecan-3 and CD44. However, the expression of syndecan-1 and glypican-1 increased significantly in the diabetic retina. CONCLUSIONS: One of the main findings of our study was the considerable diversity of glucose-induced changes in expression and shedding of various components of endothelial glycocalyx, for example, increased endothelial and retinal syndecan-1, but decreased endothelial and retinal syndecan-3. This indicates that the reported decrease in the retinal glycocalyx in diabetes in not a result of a non-specific shedding mechanism. Moreover, mRNA measurements indicated a similar diversity, with increases in endothelial and/or retinal levels of syndecan-1, glypican-1, and CD44, but a decrease for syndecan-3, with these increases in mRNA potentially a compensatory reaction to the overall loss of glycocalyx.

Migration Patterns from an Open Illicit Drug Scene and Emergency Department Visits among People Who Use Illicit Drugs in Vancouver, Canada.

BACKGROUND: People who use illicit drugs (PWUD) experience various adverse health outcomes leading to increased healthcare service utilization. PWUD are also a highly mobile population which poses challenges to healthcare delivery. The objective of this study was to identify migration patterns from the Downtown Eastside (DTES), an urban illicit drug scene in Vancouver and to estimate the impact of different migration patterns on two outcomes: a) emergency department (ED) visits and b) ED visits resulting in inpatient admission among PWUD. METHODS: Three prospective cohorts of PWUD in Vancouver were linked with regional ED data. We defined the optimal number of trajectory groups that best represented distinct patterns of migration from Vancouver's DTES using a latent class growth analysis. Then, generalized estimating equations were used to estimate the effect of migration patterns on the two ED outcomes. RESULTS: Four distinct migration trajectory patterns were identified among the 1210 included participants: PWUD who consistently lived in the DTES, those who migrated out of DTES early, those who migrated out of DTES late, and those who frequently revisited the DTES. Participants who frequently revisited the DTES had higher odds of an ED visit (adjusted odds ratio = 1.62; 95% confidence interval: 1.28-2.06). There was no significant association between migration patterns and inpatient admission. CONCLUSIONS: We found that PWUD who frequently revisited the DTES were more likely to have utilized the ED, suggesting that there may be a subgroup of PWUD who are at increased risk of experiencing negative health outcomes.Supplemental data for this article is available online at 10.1080/10826084.2021.1958849.

Targeting the AnxA1/Fpr2/ALX pathway regulates neutrophil function, promoting thromboinflammation resolution in sickle cell disease.

Neutrophils play a crucial role in the intertwined processes of thrombosis and inflammation. An altered neutrophil phenotype may contribute to inadequate resolution, which is known to be a major pathophysiological contributor of thromboinflammatory conditions such as sickle cell disease (SCD). The endogenous protein annexin A1 (AnxA1) facilitates inflammation resolution via formyl peptide receptors (FPRs). We sought to comprehensively elucidate the functional significance of targeting the neutrophil-dependent AnxA1/FPR2/ALX pathway in SCD. Administration of AnxA1 mimetic peptide AnxA1Ac2-26 ameliorated cerebral thrombotic responses in Sickle transgenic mice via regulation of the FPR2/ALX (a fundamental receptor involved in resolution) pathway. We found direct evidence that neutrophils with SCD phenotype play a key role in contributing to thromboinflammation. In addition, AnxA1Ac2-26 regulated activated SCD neutrophils through protein kinase B (Akt) and extracellular signal-regulated kinases (ERK1/2) to enable resolution. We present compelling conceptual evidence that targeting the AnxA1/FPR2/ALX pathway may provide new therapeutic possibilities against thromboinflammatory conditions such as SCD.

Effect of IFN-Y +874 T/A polymorphism on clinical manifestations of dengue: a meta-analysis.

Dengue virus (DENV) is a mosquito-borne RNA virus, which infects nearly 3.97 billion people every year in the tropical and subtropical regions of the world. DENV infections can range from unrecognizable illnesses to a spectrum of clinical manifestations such as dengue fever (DF), and more severe and potentially lethal dengue hemorrhagic fever (DHF). The variability of clinical manifestations induced by DENV can be attributed to a variety of extrinsic and intrinsic factors including virulence of the DENV strains and host genetic factors influencing the immune response. Interferon gamma (IFN-Y) is one of the critical immunomodulators implicated in DENV infection, and recent case-control association studies examined the role of +874 T/A polymorphism (rs2430561) of the IFN-Y gene in dengue clinical outcomes. Since the results of the association studies on DENV infection and IFN-Y +874 T/A polymorphism were inconsistent, we performed a meta-analysis to derive a more precise estimate of the association. Searching the databases until 15 March 2020, we identified five studies with a total of 1412 subjects (582 cases and 830 controls), which were included in this meta-analysis. The pooled odds ratio (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Pooled data indicated significant association of the TT genotype with DENV infection (DI), DF, and DHF in the recessive model TT vs AT+AA: OR (DI) = 1.47, 95% CI (1.10-1.97), P = 0.01; OR (DF) = 1.40, 95% CI (1.00-1.94), P = 0.04, OR (DHF) = 1.73, 95% CI (1.05-2.86), P = 0.03, and the genotype contrast TT vs AT: OR (DI) = 1.70, 95% CI (1.18-2.47); P = 0.005, OR (DF) = 1.72, 95% CI (1.12-2.66), P = 0.014, OR (DHF) = 1.76, 95% CI (1.01-3.06), P = 0.046. The genotype contrast AA vs AT showed significant association with the milder form of dengue (DF), OR (DF) = 1.60, 95% CI (1.07-2.41), P = 0.023, but not with the severe form (DHF). Taken together, this meta-analysis indicated that both the homozygous genotypes conferred risk to dengue, albeit with varied clinical outcomes, and revealed a protective role of the heterozygous genotype against DENV infection.

Retinal Physiology and Circulation: Effect of Diabetes.

In this article, we present a discussion of diabetes and its complications, including the macrovascular and microvascular effects, with the latter of consequence to the retina. We will discuss the anatomy and physiology of the retina, including aspects of metabolism and mechanisms of oxygenation, with the latter accomplished via a combination of the retinal and choroidal blood circulations. Both of these vasculatures are altered in diabetes, with the retinal circulation intimately involved in the pathology of diabetic retinopathy. The later stages of diabetic retinopathy involve poorly controlled angiogenesis that is of great concern, but in our discussion, we will focus more on several alterations in the retinal circulation occurring earlier in the progression of disease, including reductions in blood flow and a possible redistribution of perfusion that may leave some areas of the retina ischemic and hypoxic. Finally, we include in this article a more recent area of investigation regarding the diabetic retinal vasculature, that is, the alterations to the endothelial surface layer that normally plays a vital role in maintaining physiological functions. © 2020 American Physiological Society. Compr Physiol 10:933-974, 2020.

Targeting of Formyl Peptide Receptor 2 for in vivo imaging of acute vascular inflammation.

Inflammatory conditions are associated with a variety of diseases and can significantly contribute to their pathophysiology. Neutrophils are recognised as key players in driving vascular inflammation and promoting inflammation resolution. As a result, neutrophils, and specifically their surface formyl peptide receptors (FPRs), are attractive targets for non-invasive visualization of inflammatory disease states and studying mechanistic details of the process. Methods: A small-molecule Formyl Peptide Receptor 2 (FPR2/ALX)-targeted compound was combined with two rhodamine-derived fluorescent tags to form firstly, a targeted probe (Rho-pip-C1) and secondly a targeted, pH-responsive probe (Rho-NH-C1) for in vivo applications. We tested internalization, toxicity and functional interactions with neutrophils in vitro for both compounds, as well as the fluorescence switching response of Rho-NH-C1 to neutrophil activation. Finally, in vivo imaging (fluorescent intravital microscopy [IVM]) and therapeutic efficacy studies were performed in an inflammatory mouse model. Results: In vitro studies showed that the compounds bound to human neutrophils via FPR2/ALX without causing internalization at relevant concentrations. Additionally, the compounds did not cause toxicity or affect neutrophil functional responses (e.g. chemotaxis or transmigration). In vivo studies using IVM showed Rho-pip-C1 bound to activated neutrophils in a model of vascular inflammation. The pH-sensitive ("switchable") version termed Rho-NH-C1 validated these findings, showing fluorescent activity only in inflammatory conditions. Conclusions: These results indicate a viable design of fluorescent probes that have the ability to detect inflammatory events by targeting activated neutrophils.