Compact metamaterial-based single/double-negative/near-zero index resonator for 5G sub-6 GHz wireless applications.

The concept, performance, and analyses of distinctive, miniaturized metamaterial (MTM) unit cell addressing the forthcoming Sub 6 GHz 5G applications are presented in this paper. Two circular split-ring resonators (CSRR) with two parallel rectangular copper elements in front of the design and a slotted square element in the background make up the suggested metamaterial. It has a line segment with tunable features that is positioned in the center of the little ring copper structure. The suggested design offers a significant operating frequency band of 220 MHz together with a resonance of transmission coefficient S21 at 3.5 GHz. Furthermore, in two (z & x) principal axes of wave propagation, wide-range achievement, single/double-negative (S/DNG) refractive index, negative permittivity, and near-zero permeability properties were demonstrated. Through varying central slotted-strip line length, resonance frequencies can be selectively altered. Moreover, the metamaterial has overall dimensions of 9 × 9 mm2 and is composed on a Rogers 5880 RT substrate. In order to create the suggested MTM's equivalent circuit, which shows similar coefficient of transmission (S21), a proposed design's numerical simulation is carried out in the CST micro-wave studio. This simulation is after that put to comparison with manufacturing of the design.

Defect-Free, Few-Atomic-Layer Thin ZnO Nanosheets with Superior Excitonic Properties for Optoelectronic Devices.

Two-dimensional (2D) wide bandgap materials are gaining significant interest for next-generation optoelectronic devices. However, fabricating electronic-grade 2D nanosheets from non-van der Waals (n-vdW) oxide semiconductors poses a great challenge due to their stronger interlayer coupling compared with vdW crystals. This strong coupling typically introduces defects during exfoliation, impairing the optoelectronic properties. Herein, we report the liquid-phase exfoliation of few-atomic-layer thin, defect-free, free-standing ZnO nanosheets. These micron-sized, ultrathin ZnO structures exhibit three different orientations aligned along both the polar c-plane as well as the nonpolar a- and m-planes. The superior crystalline quality of the ZnO nanosheets is validated through comprehensive characterization techniques. This result is supported by density functional theory (DFT) calculations, which reveals that the formation of oxygen vacancies is energetically less favorable in 2D ZnO and that the c-plane loses its polarity upon exfoliation. Unlike bulk ZnO, which is typically dominated by defect-induced emission, the exfoliated nanosheets exhibit a strong, ambient-stable excitonic UV emission. We further demonstrate the utility of solution processing of ZnO nanosheets by their hybrid integration with organic components to produce stable light emitting diodes (LEDs) for display applications.

Mango Leaves (Mangifera indica)-Derived Highly Florescent Green Graphene Quantum Dot Nanoprobes for Enhanced On-Off Dual Detection of Cholesterol and Fe2+ Ions Based on Molecular Logic Operation.

In the present study, we have engineered a molecular logic gate system employing both Fe2+ ions and cholesterol as bioanalytes for innovative detection strategies. We utilized a green-synthesis method employing the mango leaves extract to create fluorescent graphene quantum dots termed "mGQDs". Through techniques like HR-TEM, i.e., high-resolution transmission electron microscopy, Raman spectroscopy, and XPS, i.e., X-ray photoelectron spectroscopy, the successful formation of mGQDs was confirmed. The photoluminescence (PL) characteristics of mGQDs were investigated for potential applications in metal ion detection, specifically Fe2+ traces in water, by using fluorescence techniques. Under 425 nm excitation, mGQDs exhibited emission bands at 495 and 677 nm in their PL spectrum. Fe2+-induced notable quenching of mGQDs' PL intensity decreased by 97% with 2.5 µM Fe2+ ions; however, adding 20 mM cholesterol resulted in a 92% recovery. Detection limits were established through a linear Stern-Volmer (S-V) plot at room temperature, yielding values of 4.07 µM for Fe2+ ions and 1.8 mM for cholesterol. Moreover, mGQDs demonstrated biocompatibility, aqueous solubility, and nontoxicity, facilitating the creation of a rapid nonenzymatic cholesterol detection method. Selectivity and detection studies underscored mGQDs' reliability in cholesterol level monitoring. Additionally, a molecular logic gate system employing Fe2+ metal ions and cholesterol as a bioanalyte was established for detection purposes. Overall, this research introduces an ecofriendly approach to craft mGQDs and highlights their effectiveness in detecting metal ions and cholesterol, suggesting their potential as versatile nanomaterials for diverse analytical and biomedical applications.

Intravascular imaging-guided percutaneous coronary intervention for heavily calcified coronary lesions: a systematic review and meta-analysis.

Although multiple randomized clinical trials (RCTs) have shown that intravascular imaging (IVI)-guided percutaneous coronary intervention (PCI) is associated with improved clinical outcomes compared with angiography-guided PCI, its benefits specifically in calcified coronary lesions is unclear due to the small number of patients included in individual trials. We performed a meta-analysis of RCTs to investigate benefits of IVI-guided PCI compared with angiography-guided PCI in heavily calcified coronary lesions. The primary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, target-vessel or target-lesion myocardial infarction, and target-vessel or target lesion revascularization. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated by using a random-effects meta-analysis based on the restricted maximum likelihood method. A search PubMed, EMBASE, and Cochrane Library from their inception to January 2024 identified 4 trials that randomized 1319 patients with angiographically moderate or severe or severe coronary calcification to IVI-guided (n = 702) vs. angiography-guided PCI (n = 617). IVI-guided PCI resulted in a significantly lower odds of MACE (OR 0.57, 95% CI 0.40-0.80) compared with angiography-guided PCI at a weighted median follow-up duration of 27.3 months. There was no evidence of heterogeneity among the studies (I2 = 0.0%), and included trials were judged to be low risk of bias. Compared with angiography-guided PCI, IVI-guided PCI was associated with a significantly lower MACE in angiographically heavily calcified coronary lesions.

Effect of prophylactic corticosteroids on postoperative neurocognitive dysfunction in the adult population: An updated systematic review, meta-analysis, and trial sequential analysis of randomised controlled trials.

Background and Aims: Postoperative neurocognitive dysfunction (PNCD) commonly occurs after surgery and prolongs hospital stays. Both direct noxious stimuli to the central nervous system and systemic inflammation have been implicated. Due to their potent anti-inflammatory effects, corticosteroids have been utilised to attenuate the incidence and severity of PNCD. This systematic review and meta-analysis strived to evaluate the prophylactic role of perioperative corticosteroids for PNCD. Methods: A search was run in pre-defined databases for randomised controlled trials (RCTs) assessing the role of corticosteroids in preventing PNCD. The incidence of PNCD within 1 month was the primary outcome. Secondary outcomes included the use of antipsychotic medications for the treatment, postoperative infection, and hospital length of stay. The results are exhibited as odds ratio (OR) and the mean difference (MD) with 95% confidence interval (CI). Results: Fifteen RCTs comprising 15,398 patients were included. The incidence of PNCD was significantly lower in the corticosteroid group than in the control group, with a pooled OR of 0.75 (95% CI 0.58, 0.96; P = 0.02; I2 = 66%). Trial sequential analysis showed the clinical benefit of corticosteroids in preventing PNCD; however, the requisite information size is still inadequate. The sub-group analysis supported the prophylactic effect of corticosteroids on delirium prevention but not on delayed neurocognitive recovery. Conclusions: Our meta-analysis revealed statistically significant protective effects of corticosteroids on the incidence of PNCD. However, further studies are still needed to confirm the protective role of this commonly used and relatively safe strategy for preventing PNCD.

YouTube as a source of education in perioperative anesthesia for patients and trainees: a systematic review.

BACKGROUND: Online video sharing platforms like YouTube (Google LLC, San Bruno, CA, USA) have become a substantial source of health information. We sought to conduct a systematic review of studies assessing the overall quality of perioperative anesthesia videos on YouTube. METHODS: We searched Embase, MEDLINE, and Ovid for articles published from database inception to 1 May 2023. We included primary studies evaluating YouTube videos as a source of information regarding perioperative anesthesia. We excluded studies not published in English and studies assessing acute or chronic pain. Studies were screened and data were extracted in duplicate by two reviewers. We appraised the quality of studies according to the social media framework published in the literature. We used descriptive statistics to report the results using mean, standard deviation, range, and n/total N (%). RESULTS: Among 8,908 citations, we identified 14 studies that examined 796 videos with 59.7 hr of content and 47.5 million views. Among the 14 studies that evaluated the video content quality, 17 different quality assessment tools were used, only three of which were externally validated (Global Quality Score, modified DISCERN score, and JAMA score). Per global assessment rating of video quality, 11/13 (85%) studies concluded the overall video quality as poor. CONCLUSIONS: Overall, the educational content quality of YouTube videos evaluated in the literature accessible as an educational resource regarding perioperative anesthesia was poor. While these videos are in demand, their impact on patient and trainee education remains unclear. A standardized methodology for evaluating online videos is merited to improve future reporting. A peer-reviewed approach to online open-access videos is needed to support patient and trainee education in anesthesia. STUDY REGISTRATION: Open Science Framework ( https://osf.io/ajse9 ); first posted, 1 May 2023.

RéSUMé: CONTEXTE: Les plateformes de partage de vidéos en ligne comme YouTube (Google LLC, San Bruno, CA, États-Unis) sont devenues une source importante d'informations sur la santé. Nous avons cherché à réaliser une revue systématique des études évaluant la qualité globale des vidéos d'anesthésie périopératoire sur YouTube. MéTHODE: Nous avons recherché des articles dans Embase, MEDLINE et Ovid publiés depuis la création de ces bases de données jusqu'au 1er mai 2023. Nous avons inclus des études primaires évaluant les vidéos YouTube comme source d'information sur l'anesthésie périopératoire. Nous avons exclu les études publiées dans une langue autre que l'anglais et les études évaluant la douleur aiguë ou chronique. Les études ont été examinées et les données ont été extraites en double par deux personnes. Nous avons évalué la qualité des études selon le cadre des médias sociaux publié dans la littérature. Nous avons utilisé des statistiques descriptives pour rapporter les résultats en utilisant la moyenne, l'écart type, la plage et n/total N (%). RéSULTATS: Parmi 8908 citations, nous avons identifié 14 études qui ont examiné 796 vidéos avec 59,7 heures de contenu et 47,5 millions de vues. Parmi les 14 études qui ont évalué la qualité du contenu vidéo, 17 outils d'évaluation de la qualité différents ont été utilisés, dont seulement trois ont été validés en externe (Score Global Quality, score DISCERN modifié et score JAMA). Selon l'évaluation globale de la qualité des vidéos, 11 études sur 13 (85 %) ont conclu que la qualité globale des vidéos était médiocre. CONCLUSION: Dans l'ensemble, la qualité du contenu éducatif des vidéos YouTube évaluées dans la littérature accessible en tant que ressource éducative concernant l'anesthésie périopératoire était médiocre. Bien que ces vidéos soient très demandées, leur impact sur la formation de la patientèle et des stagiaires reste incertain. Une méthodologie normalisée d'évaluation des vidéos en ligne est nécessaire pour améliorer les évaluations futures. Une approche évaluée par les pairs pour les vidéos en libre accès en ligne est nécessaire pour soutenir la formation de la patientèle et des stagiaires en anesthésie. ENREGISTREMENT DE L'éTUDE: Open Science Framework ( https://osf.io/ajse9 ); première publication le 1er mai 2023.

Indications, technical aspects, and outcomes of stent placement in chronic iliofemoral venous obstruction.

BACKGROUND: Iliofemoral venous stent placement (IVS) has evolved to a well-established endovascular treatment modality for chronic iliofemoral venous obstruction (CIVO). Dedicated venous stents gained approval from the US Food and Drug Administration in 2019 and solidified IVS as a defined intervention with clear indications, contraindications, risks, benefits, and procedural management principles. This review focuses on the indications, technical aspects and outcomes of stenting for CIVO. Other aspects pertaining to IVS are covered in other articles that are a part of this series. METHODS: This study conducted a literature search limited to English articles. Three search strategies were used, and references were managed in Covidence software. Four investigators screened and evaluated articles independently, excluding meta-analyses, clinical trial protocols, and nonrelevant studies. Eligible studies, focused on clinical outcomes and stent patencies, underwent thorough review. RESULTS: The literature search yielded 1704 studies, with 147 meeting eligibility criteria after screening and evaluation. Exclusions were based on duplicates, irrelevant content, and noniliac vein stent placement. CONCLUSIONS: Successful IVS for CIVO relies on meticulous patient selection, consistent use of intravascular ultrasound examination during procedures and attention to the technical details of IVS.

Direct conversion of lignin-rich black liquor to activated carbon for supercapacitor electrodes.

The escalating industrialization trend underscores the imperative for sustainable waste management practices. The present investigation explores a sustainable methodology for managing the waste generated from the kraft process by directly converting it into activated carbon (BLAC) through a cost-effective hydrothermal-assisted activation method. The research involved a comparative analysis of BLAC with acid-washed black liquor lignin-derived activated carbon (ABLAC) and commercial lignin-derived activated carbon (SALAC). The analysis revealed that BLAC possesses a well-developed micro and mesoporous structure, yielding a significantly higher surface area of 2277.2 m2/g as compared to ABLAC (1260 m2/g) and SALAC (1558.4 m2/g). The presence of inherent alkali in the black liquor is the main factor influencing the surface area of the BLAC. Furthermore, it demonstrated impressive electrochemical performance, showing a specific capacitance value of 871.4 F/g at 1 A/g current density, positioning it as a formidable electrode material for supercapacitor applications. The proposed direct conversion strategy will eliminate the need for high-temperature pre­carbonization and additional lignin extraction, reducing chemical usage and presenting a greener approach.

Long-term Stroke and Mortality Risk in Nonagenarians After Transcatheter Aortic Valve Insertion.

BACKGROUND: Limited data exist on the long-term outcomes of transcatheter aortic valve insertion (TAVI) in nonagenarian patients. This study investigated the relationship between patient baseline comorbidity and frailty on the long-term outcome of the nonagenarian population. METHODS: A retrospective analysis was conducted of 187 consecutive nonagenarian patients who underwent TAVI from 2009 to 2020. Multivariable models were used to analyze the association between baseline patient and frailty variables and mortality, stroke, and repeat hospitalization. Long-term survival was compared with an age- and sex-matched United States population. RESULTS: The median Society of Thoracic Surgeons predicted risk of mortality was 10% (interquartile range, 7%-17%). Frailty was met in 72% of patients based on the 5-meter walk test, 13% based on the Kansas City Cardiomyopathy Questionnaire 12-item instrument score, 12% based on Katz Index of Independence in Activities of Daily Living, and 8% based on serum albumin levels. Procedure-related death occurred in 3 patients (2%) and stroke in 8 (4%). The median duration of follow-up was 3.4 years. Outcomes included death in 150 patients (80%), stroke in 15, and repeat hospitalization in 114. Multivariable analysis identified no association between any of the baseline patient variables with mortality, stroke, repeat hospitalization, or the combined outcomes (all P > .05). The 1- and 5-year survival rates in TAVI-treated nonagenarians were similar to age- and sex-matched controls (P = .27). CONCLUSIONS: Long-term death or stroke is independent of The Society of Thoracic Surgeons predicted risk of mortality and frailty risk variables in this nonagenarian patient population who received TAVI. Furthermore, survival is similar to age- and sex-matched controls.

Distinct Challenges of Eruptive and Non-Eruptive Calcified Nodules in Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: To provide a summary of prevalence, pathogenesis, and treatment of coronary calcified nodules (CNs). RECENT FINDINGS: CNs are most frequently detected at the sites of hinge motion of severely calcified lesions such as in the middle segment of right coronary artery and left main coronary bifurcation. On histopathology, CNs exhibit two distinctive morphologies: eruptive and non-eruptive. Eruptive CNs, which have a disrupted fibrous cap with adherent thrombi, are biologically active. Non-eruptive CNs, which have an intact fibrous cap without thrombi, are biologically inactive, representing either healed eruptive CNs or protrusion of calcium due to plaque progression. Recent studies using optical coherence tomography (OCT) have shown a difference in the mechanism of stent failure in the two subtypes, demonstrating early reappearance of eruptive CNs in the stent (at ~ 6 months) as a unique mechanism of stent failure that does not seem to be preventable by simply achieving adequate stent expansion. The cause of CN reappearance in stent is not known and could be due to acute or subacute intrusion or continued growth of the CN. Whether modification of CN is needed, the most effective calcium modification modality and effectiveness of stent implantation in eruptive CNs has not been elucidated. In this review, we discuss pathogenesis of CNs and how intravascular imaging can help diagnose and manage patients with CNs. We also discuss medical and transcatheter therapies beyond conventional stent implantation for effective treatment of eruptive CNs that warrant testing in prospective studies.

Prevalence and anatomical factors associated with stent under-expansion in non-severely calcified lesions.

BACKGROUND: Stent underexpansion, typically related to lesion calcification, is the strongest predictor of adverse events after percutaneous coronary intervention (PCI). Although uncommon, underexpansion may also occur in non-severely calcified lesions. AIM: We sought to identify the prevalence and anatomical characteristics of underexpansion in non-severely calcified lesions. METHODS: We included 993 patients who underwent optical coherence tomography-guided PCI of 1051 de novo lesions with maximum calcium arc <180°. Negative remodeling (NR) was the smallest lesion site external elastic lamina diameter that was also smaller than the distal reference. Stent expansion was evaluated using a linear regression model accounting for vessel tapering; underexpansion required both stent expansion <70% and stent area <4.5mm2. RESULTS: Underexpansion was observed in 3.6% of non-heavily calcified lesions (38/1051). Pre-stent maximum calcium arc and thickness were greater in lesions with versus without underexpansion (median 119° vs. 85°, p = 0.002; median 0.95 mm vs. 0.78 mm, p = 0.008). NR was also more common in lesions with underexpansion (44.7% vs. 24.5%, p = 0.007). In the multivariable logistic regression model, larger and thicker eccentric calcium, mid left anterior descending artery (LAD) location, and NR were associated with underexpansion in non-severely calcified lesions. The rate of underexpansion was especially high (30.7%) in lesions exhibiting all three morphologies. Two-year TLF tended to be higher in underexpanded versus non-underexpanded stents (9.7% vs. 3.7%, unadjusted hazard ratio [95% confidence interval] = 3.02 [0.92, 9.58], p = 0.06). CONCLUSION: Although underexpansion in the absence of severe calcium (<180°) is uncommon, mid-LAD lesions with NR and large and thick eccentric calcium were associated with underexpansion.

The Importance of Estimating Excess Deaths Regionally During the COVID-19 Pandemic.

National or statewide estimates of excess deaths have limited value to understanding the impact of the COVID-19 pandemic regionally. We assessed excess deaths in a 9-county geographically defined population that had low rates of COVID-19 and widescale availability of testing early in the pandemic, well-annotated clinical data, and coverage by 2 medical examiner's offices. We compared mortality rates (MRs) per 100,000 person-years in 2020 and 2021 with those in the 2019 reference period and MR ratios (MRRs). In 2020 and 2021, 177 and 219 deaths, respectively, were attributed to COVID-19 (MR = 52 and 66 per 100,000 person-years, respectively). COVID-19 MRs were highest in males, older persons, those living in rural areas, and those with 7 or more chronic conditions. Compared with 2019, we observed a 10% excess death rate in 2020 (MRR = 1.10 [95% CI, 1.04 to 1.15]), with excess deaths in females, older adults, and those with 7 or more chronic conditions. In contrast, we did not observe excess deaths overall in 2021 compared with 2019 (MRR = 1.04 [95% CI, 0.99 to 1.10]). However, those aged 18 to 39 years (MRR = 1.36 [95% CI, 1.03 to 1.80) and those with 0 or 1 chronic condition (MRR = 1.28 [95% CI, 1.05 to 1.56]) or 7 or more chronic conditions (MRR = 1.09 [95% CI, 1.03 to 1.15]) had increased mortality compared with 2019. This work highlights the value of leveraging regional populations that experienced a similar pandemic wave timeline, mitigation strategies, testing availability, and data quality.

Frequency and Distribution of Ophthalmic Surgical Procedures among Patients with Inherited Retinal Diseases.

OBJECTIVE: In this study, we aimed to characterize the frequency and distribution of ocular surgeries in patients with inherited retinal diseases (IRDs) and evaluate associated patient and disease factors. DESIGN: Retrospective cohort. PARTICIPANTS: Subjects aged ≥ 18 years who were followed at the Johns Hopkins Genetic Eye Disease Center. METHODS: We studied a retrospective cohort of patients with an IRD diagnosis to analyze the occurrence of laser and incisional surgeries. Subjects were categorized into 2 groups: central dysfunction (macular/cone/cone-rod dystrophy, "MCCRD group") and panretinal or peripheral dysfunction (retinitis pigmentosa-like, "RP group"). Genetic testing status was recorded. The association of patient and disease factors on the frequency, distribution, and timing of surgeries was analyzed. MAIN OUTCOME MEASURES: Prevalence, prevalence odds ratio (POR), hazard ratio (HR) of ophthalmic procedures by phenotype. RESULTS: A total of 1472 eyes of 736 subjects were evaluated. Among them, 31.3% (n = 230) had undergone ocular surgery, and 78.3% of those (n = 180/230) had a history of more than 1 surgery. A total of 602 surgical procedures were analyzed. Cataract extraction with intraocular lens implantation (CEIOL) was the most common (51.2%), followed by yttrium aluminum garnet capsulotomy, refractive surgery, retinal surgery, and others. Cataract extraction with intraocular lens implantation occurred more frequently in RP than in MCCRD subjects (POR, 2.59; P = 0.002). Retinitis pigmentosa subjects underwent CEIOL at a younger age than patients with MCCRD (HR, 2.11; P < 0.001). CONCLUSIONS: Approximately one-third of patients with IRD had a history of laser or incisional surgery. Cataract extraction with intraocular lens implantation was the most common surgery; its frequency and timing may be associated with the IRD phenotype. This data may inform the design of prospective research. Such efforts may illuminate routine clinical decision-making and contribute to surgical strategy development for cell and gene therapy delivery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Impact of intraoperative haemoadsorption on outcomes of patients undergoing aortic surgery: a single-centre, prospective, observational study.

OBJECTIVES: To investigate the impact of a cytokine haemoadsorption (HA) device (CytoSorb®) on inflammatory markers and patients' outcome during aortic root surgery. METHODS: Prospective, observational study including all-comers with quasi-randomization by strictly alternating inclusion (1:1 basis). Sixty patients undergoing elective aortic surgery were assigned to either HA group (n = 30) with intraoperative HA, or a control (C) group (n = 30). Primary outcomes were: (i) impact of HA on haemodynamic stability and need for vasopressors (vasoactive-inotropic score) and (ii) sequential organ failure assessment (SOFA) score. Secondary parameters included the impact of HA on the course of hyperinflammation using interleukin-6 and procalcitonin, duration of mechanical ventilation, and lengths of intensive care unit and hospital stay. RESULTS: Noradrenaline requirement was significantly reduced in the HA group postoperatively compared to the C group (HA: 0.03 µg/kg/min vs C: 0.08 µg/kg/min, P = 0.004 at 2 h, and HA: 0.02 µg/kg/min vs C: 0.04 µg/kg/min, P = 0.004 at 24 h). This translated into a significantly lower vasoactive-inotropic score in the HA group. SOFA score was less in the HA group at all time points and reached statistical significance 2 h postoperatively (HA: 5.77 vs C: 7.43, P < 0.001). Intraoperative HA significantly reduced interleukin-6 levels (P < 0.05) at all time points, and procalcitonin at 2 h after discontinuation from cardiopulmonary bypass (P = 0.005). The duration of ventilation, intensive care unit and hospital stays were shorter in the HA group compared to the C group. CONCLUSIONS: Intraoperative HA has the potential to mitigate hyperinflammatory response leading to improved haemodynamics after aortic root surgery, thereby shortening the duration of ventilation, and lengths of intensive care unit and hospital stay. However, it must be evaluated in larger cohorts.

Severe Intraocular Inflammation Following Intravitreal Faricimab.

Importance: Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents. Objective: To provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution. Design, Setting, and Participants: In this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023. Exposure: Faricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab. Main Outcomes and Measures: Visual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging. Results: All 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3. Conclusions and Relevance: In this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.

Influence of different pH milieu on the structure and function of human Aurora kinase B protein (AURK-B): Amalgamation of both spectroscopic and computational approach.

Aurora kinase B (AURK-B) is a serine/threonine kinase protein that plays an essential role in chromosomal separation during the cell cycle event. AURK-B is highly expressed in various types of cancer such as human seminoma, thyroid carcinoma, non-small cell lung carcinoma (NSCLC), oral carcinoma, and gastric cancer. Hence, it is a potential therapeutic target in the treatment of various cancers. The structure of AURK-B in complex with one of its substrate inner centromeric protein (INCENP) is present, but the structural and functional characterization of native AURK-B at different pH environment is still unexplored.This study determines the effect of different pH milieu on the structure and function of AURK-B protein wherein the influence of pH on the protein conformation was probed using Circular dichroism (CD) and fluorescence spectroscopy. The structural studies were further combined with functional activity assay to observe the change in kinase activity at various pH milieu (2.0-11.0). CD and fluorescence spectroscopy experiments dictate that at high acidic conditions (pH 2.0 - 5.0), the secondary and tertiary structures of AURK-B become distorted, leading to diminished activity. The protein, however, was observed to stabilize towards pH 7.0 - 8.0 with minimal structure alteration over the basic pH range (pH 9.0 -11.0). The measured spectroscopic structural features were found to be in-line with obtained experimental kinase activity assays. Further, in-vitro experiments indicate that the enzyme is maximally active at pH 8.0. More ordered conformation and compact structure was observed at this pH (pH 8.0) as compared to other pH values through molecular dynamics simulation studies (MDS). As AURK-B localizes itself in the intracellular compartment, this study may provide a clue about the role of different pH environments in enhancing cancer growth, proliferation, and invasion.

Transpupillary-Guided Trans-Scleral Transplantation of Subretinal Grafts in a Retinal Degeneration Mouse Model.

Transplantation of photoreceptor cells and retinal pigment epithelial (RPE) cells provide a potential therapy for retinal degeneration diseases. Subretinal transplantation of therapeutic donor cells into mouse recipients is challenging due to the limited surgical space allowed by the small volume of the mouse eye. We developed a trans-scleral surgical transplantation platform with direct transpupillary vision guidance to facilitate the subretinal delivery of exogenous cells in mouse recipients. The platform was tested using retinal cell suspensions and three-dimensional retinal sheets collected from rod-rich Rho::EGFP mice and cone-rich OPN1LW-EGFP;NRL-/- mice, respectively. Live/dead assay showed low cell mortality for both forms of donor cells. Retinal grafts were successfully delivered into the subretinal space of a mouse model of retinal degeneration, Rd1/NS, with minimum surgical complications as detected by multimodal confocal scanning laser ophthalmoscope (cSLO) imaging. Two months post-transplantation, histological staining demonstrated evidence of advanced maturation of the retinal grafts into 'adult' rods and cones (by robust Rho::EGFP, S-opsin, and OPN1LW:EGFP expression, respectively) in the subretinal space. Here, we provide a surgical platform that can enable highly accurate subretinal delivery with a low rate of complications in mouse recipients. This technique offers precision and relative ease of skill acquisition. Furthermore, the technique could be used not only for studies of subretinal cell transplantation but also for other intraocular therapeutic studies including gene therapies.