The implementation of CO₂ huff-n-puff in unconventional oil reservoirs represents a green development technology that integrates oil recovery and carbon storage, emphasizing both efficiency and environmental protection. A rational well selection method is crucial for the success of CO₂ huff-n-puff development. This paper initially identifies eight parameters that influence the effectiveness of CO₂ huff-n-puff development and conducts a systematic analysis of the impact of each factor on development effectiveness. A set of factors for well selection decisions is established with seven successful CO₂ huff-n-puff cases. Subsequently, the influencing factors are classified into positive, inverse, and moderate indicators. By using an exponential formulation, a method for calculating membership degrees is calculated to accurately represent the nonlinearity of each parameter’s influence on development, resulting in a dimensionless fuzzy matrix. Furthermore, with the oil exchange ratio serving as a pivotal parameter reflecting development effectiveness, recalibration of weighting factors is performed in conjunction with the dimensionless fuzzy matrix. The hierarchical order of weighting factors, from primary to secondary, is as follows: porosity, reservoir temperature, water saturation, formation pressure, reservoir thickness, crude oil density, crude oil viscosity, and permeability. The comprehensive decision factor and oil exchange ratio exhibit a positive correlation, affirming the reliability of the weighting factors. Finally, utilizing parameters of the Ordos Basin as a case study, the comprehensive decision factor is calculated, with a value of 0.617, and the oil exchange ratio is predicted as 0.354 t/t, which falls between the Chattanooga and Eagle Ford reservoirs. This approach, which incorporates exponential membership degrees and recalibrated weighting factors derived from actual cases, breaks the limitations of linear membership calculation methods and human factors in expert scoring methods utilized in existing decision-making methodologies. It furnishes oilfield decision-makers with a swifter and more precise well selection method. Full article

Background: This study was designed to assess the diagnostic utility for FIP of cytology, protein measurement and RT-PCR for feline coronaviruses (FCoV) on aqueous humor (AH), since little information is currently available. Methods: AH samples (n = 85) were collected post-mortem from 13 cats with effusive FIP (E-FIP), 15 with non-effusive FIP (NE-FIP) and 16 without FIP, to perform cytology (n = 83) and RT-PCR (n = 66) and to calculate their sensitivity, specificity and positive and negative likelihood ratios (LR+ and LR−). The protein concentration was measured on 80 fluids. Results: The proportion of RT-PCR positive samples did not differ among groups, while positive cytology was more frequent in samples with FIP (p = 0.042) or positive RT-PCR (p = 0.007). Compared with other groups, the protein concentration was higher in samples with NE-FIP (p = 0.017), positive RT-PCR (p = 0.005) or positive cytology (p < 0.001). The specificity of cytology together with RT-PCR, cytology alone, RT-PCR alone and cytological proteinaceous background were 90.0%, 84.6%, 70.0%, 61.5%, and the LRs 3.48, 2.65, 1.83, 1.64, respectively. However, their sensitivities were low (34.8–63.0%) and their LR− high (0.60–0.72). Conclusions: Based on the LR+, cytology and/or RT-PCR may support the diagnosis when the pre-test probability of FIP is high. The concentration of intraocular protein is a promising marker, especially in NE-FIP. Full article

Investigating the neural mechanisms underlying both cooperative and competitive joint actions may have a wide impact in many social contexts of human daily life. An effective pipeline of analysis for hyperscanning data recorded in a naturalistic context with a cooperative and competitive motor task has been missing. We propose an analytical pipeline for this type of joint action data, which was validated on electroencephalographic (EEG) signals recorded in a proof-of-concept study on two dyads playing cooperative and competitive table tennis. Functional connectivity maps were reconstructed using the corrected imaginary part of the phase locking value (ciPLV), an algorithm suitable in case of EEG signals recorded during turn-based competitive joint actions. Hyperbrain, within-, and between-brain functional connectivity maps were calculated in three frequency bands (i.e., theta, alpha, and beta) relevant during complex motor task execution and were characterized with graph theoretical measures and a clustering approach. The results of the proof-of-concept study are in line with recent findings on the main features of the functional networks sustaining cooperation and competition, hence demonstrating that the proposed pipeline is promising tool for the analysis of joint action EEG data recorded during cooperation and competition using a turn-based motor task. Full article

The spindle and kinetochore-associated complex subunit 3 (SKA3) is a protein essential for proper chromosome segregation during mitosis and thus responsible for maintaining genome stability. Although its involvement in the pathogenesis of various cancer types has been reported, the potential clinicopathological significance of SKA3 in pancreatic ductal adenocarcinoma (PDAC) has not been fully elucidated. Therefore, this study aimed to assess clinicopathological associations and prognostic value of SKA3 in PDAC. For this purpose, in-house immunohistochemical analysis on tissue macroarrays (TMAs), as well as a bioinformatic examination using publicly available RNA-Seq dataset, were performed. It was demonstrated that SKA3 expression at both mRNA and protein levels was significantly elevated in PDAC compared to control tissues. Upregulated mRNA expression constituted an independent unfavorable prognostic factor for the overall survival of PDAC patients, whereas altered SKA3 protein levels were associated with significantly better clinical outcomes. The last observation was particularly clear in the early-stage tumors. These findings render SKA3 a promising prognostic biomarker for patients with pancreatic ductal adenocarcinoma. However, further studies are needed to confirm this conclusion. Full article

Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still controversial. This study aimed to investigate the type of viral mono- and co-infections by also evaluating viral correlations in 3525 respiratory samples from 3525 pediatric in/outpatients screened by the Allplex Respiratory Panel Assays and with a Severe Acute Respiratory Syndrome-COronaVirus 2 (SARS-CoV-2) test available. Overall, viral co-infections were detected in 37.8% of patients and were more frequently observed in specimens from children with lower respiratory tract infections compared to those with upper respiratory tract infections (47.1% vs. 36.0%, p = 0.003). SARS-CoV-2 and influenza A were more commonly detected in mono-infections, whereas human bocavirus showed the highest co-infection rate (87.8% in co-infection). After analyzing viral pairings using Spearman’s correlation test, it was noted that SARS-CoV-2 was negatively associated with all other respiratory viruses, whereas a markedly significant positive correlation (p < 0.001) was observed for five viral pairings (involving adenovirus/human bocavirus/human enterovirus/metapneumoviruses/rhinovirus). The correlation between co-infection and clinical outcome may be linked to the type of virus(es) involved in the co-infection rather than simple co-presence. Further studies dedicated to this important point are needed, since it has obvious implications from a diagnostic and clinical point of view. Full article

Old Corrugated Container (OCC) pulping wastewater has a complex organic composition and high levels of biotoxicity. The presence of dissolved and colloidal substances (DCSs) is a major limiting factor for pulp and paper companies to achieve closed-water recycling. In order to solve this problem, the coupled ozone-catalyzed oxidation and biodegradation (OCB) method was used to treat OCC pulping wastewater in this study. A polyurethane sponge was used as the basic skeleton, loaded with nano TiO₂ and microorganisms, respectively, and then put into a reactor. After an 8-min ozone-catalyzed oxidation reaction, a 10-h biological reaction was carried out. The process was effective in removing organic pollutants such as COD and BOD₅ from OCC paper whitewater. The removal rates of COD and BOD₅ were 81.5% and 85.1%, respectively. By using the polyurethane sponge to construct a microenvironment suitable for microbial growth and metabolism, this study successfully applied and optimized engineered bacteria—white rut fungi (WRF)—in the system to achieve practical degradation of OCC pulping wastewater. Meanwhile, the biocompatibility of different microbial communities on the polyurethane sponge was analyzed by examining the degradation performance of OCC pulping wastewater. The structure of microbial communities loaded on the polyurethane sponge was analyzed to understand the degradation mechanism and microbial reaction behavior. White-rot fungi (Phanerochaete) contributed more to the degradation of OCC wastewater, and new strains adapted to OCC wastewater degradation were generated. Full article

Astrocytes actively participate in neurotransmitter homeostasis by bidirectional communication with neuronal cells, a concept named the tripartite synapse, yet their role in dopamine (DA) homeostasis remains understudied. In the present study, we investigated the kinetic and molecular mechanisms of DA transport in cultured striatal astrocytes of adult rats. Kinetic uptake experiments were performed using radiolabeled [³H]-DA, whereas mRNA expression of the dopamine, norepinephrine, organic cation and plasma membrane monoamine transporters (DAT, NET, OCTs and PMAT) and DA receptors D1 and D2 was determined by qPCR. Additionally, astrocyte cultures were subjected to a 24 h treatment with the DA receptor agonist apomorphine, the DA receptor antagonist haloperidol and the DA precursor L-DOPA. [³H]-DA uptake exhibited temperature, concentration and sodium dependence, with potent inhibition by desipramine, nortriptyline and decynium-22, suggesting the involvement of multiple transporters. qPCR revealed prominent mRNA expression of the NET, the PMAT and OCT1, alongside lower levels of mRNA for OCT2, OCT3 and the DAT. Notably, apomorphine significantly altered NET, PMAT and D1 mRNA expression, while haloperidol and L-DOPA had a modest impact. Our findings demonstrate that striatal astrocytes aid in DA clearance by multiple transporters, which are influenced by dopaminergic drugs. Our study enhances the understanding of regional DA uptake, paving the way for targeted therapeutic interventions in dopaminergic disorders. Full article

Background and Objectives: mortality and morbidity due to cardiovascular causes are frequently experienced in amputees. Research on the effects of chronic exercise on biomarkers and cardiac damage indicators in these individuals is limited. The aim of this study was to investigate the effects of a core training program on brain natriuretic-related peptide, as well as hematological and biochemical parameters in amputee soccer players. Materials and Methods: The participants were randomly allocated to the following two groups: a core exercise group (CEG) and a control group (CG). While the CG continued routine soccer training, the CEG group was included in a core exercise program different from this group. During the study, routine hemogram parameters of the participants, various biochemical markers, and the concentration of brain natriuretic-related peptide (NT-pro-BNP) were analyzed. Results: after the training period, notable improvements in various hematological parameters were observed in both groups. In the CEG, there were significant enhancements in red blood cell count (RBC), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular hemoglobin (MCH) values. Similarly, the CG also showed substantial improvements in RBC, HCT, mean corpuscular volume (MCV), MCHC, MCH, red cell distribution width-standard deviation (RDW-SD), platelet-to-lymphocyte ratio (PLCR), mean platelet volume (MPV), and platelet distribution width (PDW). Moreover, in the CEG, serum triglycerides (TG) and maximal oxygen uptake (MaxVO₂) exhibited significant increases. Conversely, TG levels decreased in the CG, while high-density lipoprotein (HDL), low-density lipoprotein (LDL), and MaxVO₂ levels demonstrated substantial elevations. Notably, the N-terminal pro-brain natriuretic peptide (BNP) levels did not undergo significant changes in either the CEG or the CG following the core exercise program (p > 0.05). However, in the CEG, a meaningful positive correlation was observed between NT-pro-BNP and creatine kinase (CK) levels before and after the core exercise program. Conclusions: the findings emphasized the potential benefits of core training in enhancing specific physiological aspects, such as erythrocyte-related parameters and lipid metabolism, as well as aerobic capacity. Furthermore, the observed correlation between NT-pro-BNP and CK levels in the CEG provides intriguing insights into the unique physiological adaptations of amputee athletes. Full article

Cardiovascular diseases (CVDs) reflect a huge and diversified condition that influences patient quality of life (QoL) both in the physical and mental aspects, especially in older adults who often present comorbidities and may be affected by cognitive decline. The concept of cognitive reserve (CR), which is built through life course experiences, has widely been considered a protective factor against cognitive decline, while the results of QoL in the field of CVDs are still controversial. In particular, there is a lack of evidence that explicitly explores the effects of CR on the QoL in CVD cases since studies have considered only single CR proxies (e.g., education) or specific cardiovascular conditions. Moreover, none of them have considered the motor reserve (MR), another recent concept that considers the amount of physical activity carried out during a lifespan. Its potential role in preventing age-related diseases has been observed, but more clarification is needed given the importance of the physical component in CVDs. The present state-of-the-art review aims to (i) examine how the literature conceives CR and its proxies in CVDs relating to QoL and (ii) integrate the concept of MR in this framework. Implications for clinical practice will also be discussed. Full article

Metal-coordinated hydrogels are becoming increasingly popular in the biomedical field due to their unique properties. However, the mechanism behind gel forming involving metal ions is not yet fully understood. In this work, terahertz spectroscopy was used to investigate the role of interfacial water in the gelation process of copper ion-coordinated poly(vinyl alcohol) hydrogels. The results showed that the binding of copper ions could alter the interfacial hydration dynamics of the poly(vinyl alcohol) polymers. Combined with the results of differential scanning calorimetry (DSC), we propose a possible hydration layer-mediated mechanism for the formation of cooper ion-coordinated hydrogel during the freeze–thaw cycle. These results highlight the value of terahertz spectroscopy as a sensor for studying the hydration process in hydrogels and provide an important clue for understanding the mechanism of hydrogelation in ion-coordinated hydrogels. Full article

O-linked-β-D-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation), which is dynamically regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), is a post-translational modification involved in multiple cellular processes. O-GlcNAcylation of proteins can regulate their biological functions via crosstalk with other post-translational modifications, such as phosphorylation, ubiquitination, acetylation, and methylation. Liver diseases are a major cause of death worldwide; yet, key pathological features of the disease, such as inflammation, fibrosis, steatosis, and tumorigenesis, are not fully understood. The dysregulation of O-GlcNAcylation has been shown to be involved in some severe hepatic cellular stress, viral hepatitis, liver fibrosis, nonalcoholic fatty acid liver disease (NAFLD), malignant progression, and drug resistance of hepatocellular carcinoma (HCC) through multiple molecular signaling pathways. Here, we summarize the emerging link between O-GlcNAcylation and hepatic pathological processes and provide information about the development of therapeutic strategies for liver diseases. Full article

Background: Pain and dysfunction persist for most patients following hip-related pain treatment. Additionally, individuals with hip-related pain are typically less physically active than individuals without hip pain, despite evidence that regular physical activity reduces chronic musculoskeletal pain. Poor psychological health is common in patients with hip-related pain and further reinforces low physical activity. Mind–body interventions can improve psychological health and activity levels but have yet to be integrated to provide comprehensive, psychologically informed care for patients with hip-related pain. Thus, we are using the NCCIH intervention development framework to develop Helping Improve PSychological Health (HIPS), a novel, multimodal mind–body intervention to improve physical activity for individuals with hip-related pain and poor psychological health. Methods: We will recruit physical therapists (N = 20) and patients with hip-related pain (N = 20) to participate in 60 min qualitative interviews (focus groups with therapists; one-on-one interviews with patients). Using these data, we will develop the initial HIPS intervention and provider training materials. One physical therapist will be trained to deliver the HIPS intervention to five participants in an open pilot trial. Participants will attend six 30 min HIPS intervention sessions. We will collect quantitative data on satisfaction, improvement, and physical activity, alongside qualitative exit interviews with participants and the physical therapist in order to refine the HIPS intervention and provider training materials. Results: This study has been approved by the MGB IRB. We aim to develop and test the initial feasibility of the HIPS intervention in an open pilot trial. The findings from this project will inform a subsequent feasibility RCT. Full article

Although XLPE cables are widely used in power transmission and distribution systems, their insulating properties are susceptible to degradation due to thermal aging. In order to clarify the influence law of the thermal aging process on the structural and dielectric properties of XLPE cables, this paper investigates the thermal aging characteristics of XLPE cables by using polarization and depolarization current measurement. Results show that when the XLPE cable is aged at 140 °C, the crystallinity of the insulation layer appears to increase and then decrease. With the increase in aging time, micron-sized microvoids appear on the surface of the XLPE. At the same time, the DC conductivity and 0.1 Hz dielectric loss factor of the insulating layer increase with the aging time. The average DC conductivity increased from 2.26 × 10⁻¹⁶ S/m for new cables to 4.47 × 10⁻¹⁶ S/m after aging for 432 h, while the dielectric loss increased from 0.11% to 0.42%. The polarization characteristics of thermal-aged cables were further analyzed using the extended Debye model. Results indicate that the time constant of the third branch of the model increased significantly with increasing aging time. A correspondence between this parameter and the thermal aging time of the cable was established. Thermal aging can damage the crystalline structure of XLPE, so that the number of interfaces between the crystalline and amorphous regions of the material increases, resulting in structural damages and a decline in the dielectric properties of the cable insulation. Full article

In Saccharomyces cerevisiae, the Rpd3L complex includes the histone deacetylase Rpd3 and the DNA binding proteins Ume6 and Ash1 and serves as a transcriptional silencer or enhancer. In S. cerevisiae, the transcription of PDR5, which encodes a major drug efflux pump, and pleiotropic drug resistance (PDR) are hyperactivated by the transcription factor Pdr3 in ρ^0/− cells, which lack mitochondrial DNA. We previously showed that RPD3 and UME6 are required for the activation of PDR5 transcription and PDR in S. cerevisiae ρ⁰ cells. Here, using real-time PCR analysis, we revealed that RPD3 and UME6 are responsible for the activated basal expression of the ABC transporter-encoding genes SNQ2, PDR15, and PDR5 in S. cerevisiae ρ⁰ cells. Furthermore, using real-time PCR analysis and a spot dilution assay, we found that Ume6 increases the basal expression of PDR5 and PDR15 and induces PDR in a manner dependent on RPD3 and PDR3 in ρ⁰ cells. This finding may contribute to the elucidation of the relationships between the molecules required for the activation of ABC transporter genes in S. cerevisiae ρ^0/− cells and in pathogenic Candida species. Full article

Stroke can impair mobility, with deficits more pronounced while simultaneously performing multiple activities. In this study, common clinical tests were instrumented with wearable motion sensors to study motor–cognitive interference effects in stroke survivors (SS). A total of 21 SS and 20 healthy controls performed the Timed Up and Go (TUG), Sit-to-Stand (STS), balance, and 10-Meter Walk (10MWT) tests under single and dual-task (counting backward) conditions. Calculated measures included total time and gait measures for TUG, STS, and 10MWT. Balance tests for both open and closed eyes conditions were assessed using sway, measured using the linear acceleration of the thorax, pelvis, and thighs. SS exhibited poorer performance with slower TUG (16.15 s vs. 13.34 s, single-task p < 0.001), greater sway in the eyes open balance test (0.1 m/s² vs. 0.08 m/s², p = 0.035), and slower 10MWT (12.94 s vs. 10.98 s p = 0.01) compared to the controls. Dual tasking increased the TUG time (~14%, p < 0.001), balance thorax sway (~64%, p < 0.001), and 10MWT time (~17%, p < 0.001) in the SS group. Interaction effects were minimal, suggesting similar dual-task costs. The findings demonstrate exaggerated mobility deficits in SS during dual-task clinical testing. Dual-task assessments may be more effective in revealing impairments. Integrating cognitive challenges into evaluation can optimize the identification of fall risks and personalize interventions targeting identified cognitive–motor limitations post stroke. Full article

Barriers to accessing care and misinterpretations of ischemic heart disease symptoms due to lack of awareness contribute to women’s delay in seeking care. Women may delay seeking treatment for up to 3 h or even up to 5 days. They often perceive themselves to be at low risk of cardiovascular disease (CVD) and prioritize family responsibilities or household chores. The causes of this delay are multifactorial and influence the decision-making process, particularly in the pre-hospital phase. The objective of this study protocol is to evaluate prodromal symptoms and identify risk behaviors in women with acute myocardial infarction (AMI). This is a protocol for a multicenter study that will be conducted using the mixed-method methodology using the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (MAPMISS) to evaluate symptoms and semi-structured interviews to investigate behaviors. This study protocol is intended to fill an important knowledge gap on premonitory and acute symptoms of AMI in women in Italy, as well as to understand the causes and mechanisms underlying delays in accessing healthcare services during an acute event such as AMI. The investigation of this issue will facilitate the removal of gender-related inequalities in the diagnosis and treatment of acute myocardial infarction while also fostering dialogue on the barriers to behavior change. Full article

Land and forest fires in peatland areas in Indonesia have a widespread negative impact on surrounding communities. Possible vulnerabilities relate to economic, social, ecological, livelihoods, and environmental vulnerability. This study aimed to assess household vulnerability due to land and forest fires in peatland areas in Ogan Komering Ilir District in South Sumatra and observe changes in peat ecosystems in those areas. The study was conducted in three peatland hydrological units (PHUs)—(1) PHU Sungai Sugihan–Sungai Lumpur; (2) PHU Sungai Sibumbung–Sungai Batok; and (3) PHU Sungai Saleh–Sungai Sugihan—covering 300 households as samples. Primary data were collected through structured interviews and analyzed descriptively. The analysis revealed the following: (1) PHU Sungai Sibumbung–Sungai Batok had the highest score for livelihood vulnerability and climate change but the lowest score for social, economic, and ecological vulnerability; (2) PHU Sungai Saleh–Sungai Sugihan had the highest score for economic and ecological vulnerability but the lowest score for livelihood vulnerability; (3) PHU Sungai Sugihan–Sungai Lumpur had the highest score for social vulnerability but lowest score for climate change vulnerability; and (4) the number of household members, toddlers, and elderly, and all economic indicators except land ownership, contributed relatively similarly to social vulnerability in all PHUs. Full article

Considering the requirements of the actual production scheduling process, the utilization of the genetic programming hyper-heuristic (GPHH) approach to automatically design dispatching rules (DRs) has recently emerged as a popular optimization approach. However, the decision objects and decision environments for routing and sequencing decisions are different in the dynamic flexible job shop scheduling problem (DFJSSP), leading to different required feature information. Traditional algorithms that allow these two types of scheduling decisions to share one common feature set are not conducive to the further optimization of the evolved DRs, but instead introduce redundant and unnecessary search attempts for algorithm optimization. To address this, some related studies have focused on customizing the feature sets for both routing and sequencing decisions through feature selection when solving single-objective problems. While being effective in reducing the search space, the selected feature sets also diminish the diversity of the obtained DRs, ultimately impacting the optimization performance. Consequently, this paper proposes an improved GPHH with dual feature weight sets for the multi-objective energy-efficient DFJSSP, which includes two novel feature weight measures and one novel hybrid population adjustment strategy. Instead of selecting suitable features, the proposed algorithm assigns appropriate weights to the features based on their multi-objective contribution, which could provide directional guidance to the GPHH while ensuring the search space. Experimental results demonstrate that, compared to existing studies, the proposed algorithm can significantly enhance the optimization performance and interpretability of energy-efficient DRs. Full article

Traditional lithium hydroxide production techniques, like lithium sulfate and lithium carbonate causticizing methods, suffer from drawbacks including high specific energy consumption, time-consuming processes, and low recovery rates. The conversion of lithium chloride to lithium hydroxide using bipolar membrane electrodialysis is straightforward; however, the influence of operational parameters on bipolar membrane electrodialysis performance have not been investigated. Herein, the impact of the current density (20 mA/cm²~80 mA/cm²), feed concentration (0.5 M~2.5 M), initial feed pH (2.5, 3.5 and 4.5), and the volume ratio of the feed and base solution (1:1, 2:1 and 3:1) on the current efficiency and specific energy consumption in the bipolar membrane electrodialysis was systematically investigated. The bipolar membrane electrodialysis process showed promising results under optimal conditions with a current density of 50 mA/cm² and an initial lithium chloride concentration of 1.5 M. This process achieved a current efficiency of 75.86% with a specific energy consumption of 3.65 kwh/kg lithium hydroxide while also demonstrating a lithium hydroxide recovery rate exceeding 90% with a purity of about 95%. This work will provide valuable guidance for hands on implementation of bipolar membrane electrodialysis technology in the production of LiOH. Full article

High-entropy alloys (HEAs) are advanced materials characterized by their unique and complex compositions. Characterized by a mixture of five or more elements in roughly equal atomic ratios, these alloys diverge from traditional alloy formulations that typically focus on one or two principal elements. This innovation has paved the way for subsequent studies that have expanded our understanding of HEAs, highlighting the role of high mixing entropy in stabilizing fewer phases than expected by traditional phase prediction methods like Gibbs’s rule. In this review article, we trace the evolution of HEAs, discussing their synthesis, stability, and the influence of crystallographic structures on their properties. Additionally, we highlight the strength–ductility trade-off in HEAs and explore strategies to overcome this challenge. Moreover, we examine the diverse applications of HEAs in extreme conditions and their promise for future advancements in materials science. Full article

(1) Background: Patients affected by Ménière’s disease can experience Tumarkin’s syndrome, which is characterized by postural instability, gait abnormalities, and, occasionally, an abrupt loss of balance known as vestibular drop attack or Tumarkin’s crisis. In this study, semicircular canal plugging is proposed as the definitive treatment for this condition. The outcomes of this type of surgery are discussed. (2) Methods: A total of 9 patients with a confirmed diagnosis of Ménière disease suffering from Tumarkin crisis underwent posterior semicircular canal plugging. These patients were assessed with Video Head Impulse Tests, vestibular evoked myogenic potentials, and Pure Tone Audiometry preoperatively and postoperatively. (3) Results: VHIT showed a postoperative decrease in PSC gain median (Preop. 0.86 and postop. 0.52; p < 0.009). No statistically significant differences were described for the anterior semicircular canal and the lateral semicircular canal. No patient experienced new Tumarkin crisis after the surgical treatment. (4) Conclusions: Our ten years of experience with posterior semicircular canal plugging in Ménière disease patients with Tumarkin’s syndrome has shown that this type of surgical procedure is successful in controlling Tumarkin’s crisis, with high patient satisfaction and little worsening in hearing level. Full article

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin–Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies. Full article