CEACAM1-engineered MSCs have a broad spectrum of immunomodulatory functions and therapeutic potential via cell-to-cell interaction.

Mesenchymal stem cells (MSCs) have garnered attention for their regenerative and immunomodulatory capabilities in clinical trials for various diseases. However, the effectiveness of MSC-based therapies, especially for conditions like graft-versus-host disease (GvHD), remains uncertain. The cytokine interferon (IFN)-γ has been known to enhance the immunosuppressive properties of MSCs through cell-to-cell interactions and soluble factors. In this study, we observed that IFN-γ-treated MSCs upregulated the expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), associated with immune evasion through the inhibition of natural killer (NK) cell cytotoxicity. To co-opt this immunomodulatory function, we generated MSCs overexpressing CEACAM1 and found that CEACAM1-engineered MSCs significantly reduced NK cell activation and cytotoxicity via cell-to-cell interaction, independent of NKG2D ligand regulation. Furthermore, CEACAM1-engineered MSCs effectively inhibited the proliferation and activation of T cells along with the inflammatory responses of monocytes. In a humanized GvHD mouse model, CEACAM1-MSCs, particularly CEACAM1-4S-MSCs, demonstrated therapeutic potential by improving survival and alleviating symptoms. These findings suggest that CEACAM1 expression on MSCs contributes to MSC-mediated regulation of immune responses and that CEACAM1-engineered MSC could have therapeutic potential in conditions involving immune dysregulation.

Wide range of possible trajectories of North Atlantic climate in a warming world.

Decadal variability in the North Atlantic Ocean impacts regional and global climate, yet changes in internal decadal variability under anthropogenic radiative forcing remain largely unexplored. Here we use the Community Earth System Model 2 Large Ensemble under historical and the Shared Socioeconomic Pathway 3-7.0 future radiative forcing scenarios and show that the ensemble spread in northern North Atlantic sea surface temperature (SST) more than doubles during the mid-twenty-first century, highlighting an exceptionally wide range of possible climate states. Furthermore, there are strikingly distinct trajectories in these SSTs, arising from differences in the North Atlantic deep convection among ensemble members starting by 2030. We propose that these are stochastically triggered and subsequently amplified by positive feedbacks involving coupled ocean-atmosphere-sea ice interactions. Freshwater forcing associated with global warming seems necessary for activating these feedbacks, accentuating the impact of external forcing on internal variability. Further investigation on seven additional large ensembles affirms the robustness of our findings. By monitoring these mechanisms in real time and extending dynamical model predictions after positive feedbacks activate, we may achieve skillful long-lead North Atlantic decadal predictions that are effective for multiple decades.

Mapa de evidências - Doenças Crônicas Não Transmissíveis

Este mapa de evidências apresenta estratégias para o cuidado de pessoas com as seguintes Doenças Crônicas Não Transmissíveis (DCNT): Diabetes Mellitus Tipo 2, Hipertensão Arterial sistêmica e Obesidade. A partir de uma ampla busca bibliográfica realizada para o desenvolvimento de 7 revisões rápidas, 93 estudos de revisão foram incluídos no mapa (62 revisões sistemáticas, 31 revisões sistemáticas com meta-análise). Com base na ferramenta AMSTAR2, foi avaliado o nível de confiabilidade para a evidência reportada nestes estudos, resultando em 2 revisões de nível alto, 5 revisões de nível moderado, 10 revisões de nível baixo e 76 revisões de nível criticamente baixo. Todos os estudos foram avaliados, caracterizados, categorizados por uma equipe multiprofissional organizada em pares, composta por pesquisadores que atuam nas áreas de Saúde Coletiva e Políticas Informadas por Evidências. Principais Achados: ● As revisões avaliaram o efeito de 26 intervenções distribuídas em 5 grupos: Teleconsulta/eHealth, Tratamento farmacológico, Automonitoramento/autogerenciamento, Educação, e Serviço de saúde; ● As intervenções foram associadas a 22 desfechos relacionados às DCNT distribuídos em 3 grupos: resultados clínicos, resultados não clínicos e segurança; ● No total foram encontradas 196 associações entre intervenções, desfechos e efeitos nos estudos selecionados. A maior parte das associações foi com intervenções de cuidado assistencial (32 associações) e intervenções combinadas (24 associações); ● Os desfechos que receberam maior número de associações foram: Pressão Arterial (36 associações), Peso corporal (34 associações), Adesão ao tratamento farmacológico (29 associações) e Satisfação do paciente (21 associações).

Selective internal limiting membrane peeling for prevention of secondary epiretinal membrane after vitrectomy for rhegmatogenous retinal detachment.

PURPOSE: We introduce selective internal limiting membrane (ILM) peeling, a guideline procedure to determine whether to remove the ILM during vitrectomy for rhegmatogenous retinal detachment (RRD). STUDY DESIGN: Retrospective case series METHODS: Patients who underwent pars plana vitrectomy for RRD and were followed up for 12 months or longer were included. When vitreous cortex remnants (VCRs) were detected with triamcinolone acetonide, the ILM was removed; otherwise, the ILM was preserved ("selective ILM peeling"). The factors associated with the presence of VCRs and incidence of secondary epiretinal membrane (ERM) were analyzed. RESULTS: VCRs were detected in 87 of 133 eyes (65.4%) in which the ILM was removed. Younger age, better preoperative visual acuity, and vitreous hemorrhage were negatively correlated with the presence of VCRs. No ERM occurred in the eyes after ILM peeling. Among the eyes with ILM preservation, subclinical ERM was noticed in 4 eyes (8.7%), and 1 eye (2.1%) required additional surgery owing to ERM. ERM occurred more commonly in eyes with the ILM preserved (P = .004). However, no differences in the rate of additional surgeries were found between the 2 groups. CONCLUSION: Selective ILM peeling offers an alternative option to reduce the burden of ILM peeling or additional surgery.

Evidence Map on Aromatherapy Clinical Effectiveness

This map presents overview evidence of the clinical effects of essential oils in humans. The search was conducted in several databases, and 73 systematic review studies were included. Main Findings: This Map collects evidence for interventions with 49 essential oils, 9 fatty vegetable oils or in 66 mixtures (synergies) and one hydrolate, with applications through inhalation, massage, bath, ingestion, or topical. Each intervention was associated with at least one of 55 health outcomes classified into 8 groups: Pain; Metabolic and Physiological Indicators; Noncommunicable Diseases; Mental Health; Infectious Diseases; Women´s Health; Skin Diseases; Well-Being, Vitality and Quality of Life, totaling 420 associations. The effects reported by each study included: positive, potentially positive, no effect, and inconclusive effects. This Map found 333 positive effect for different health outcomes. Highlighting that no negative effect was reported. The essential oil most researched was Lavender (Lavandula angustifolia - 116 associations). The Roses essential oil was the second most researched (Rosa damascena - 24 associations). The interventions with Lavender essential oil demonstrated more relevant effects on Mental Health, especially anxiety disorders. Interventions with Rose essential oil the more relevant effects on outcomes related to Women's Health, especially dysmenorrhea and pain in childbirth.

Accuracy of generative deep learning model for macular anatomy prediction from optical coherence tomography images in macular hole surgery.

This study aims to propose a generative deep learning model (GDLM) based on a variational autoencoder that predicts macular optical coherence tomography (OCT) images following full-thickness macular hole (FTMH) surgery and evaluate its clinical accuracy. Preoperative and 6-month postoperative swept-source OCT data were collected from 150 patients with successfully closed FTMH using 6 × 6 mm2 macular volume scan datasets. Randomly selected and augmented 120,000 training and 5000 validation pairs of OCT images were used to train the GDLM. We assessed the accuracy and F1 score of concordance for neurosensory retinal areas, performed Bland-Altman analysis of foveolar height (FH) and mean foveal thickness (MFT), and predicted postoperative external limiting membrane (ELM) and ellipsoid zone (EZ) restoration accuracy between artificial intelligence (AI)-OCT and ground truth (GT)-OCT images. Accuracy and F1 scores were 94.7% and 0.891, respectively. Average FH (228.2 vs. 233.4 µm, P = 0.587) and MFT (271.4 vs. 273.3 µm, P = 0.819) were similar between AI- and GT-OCT images, within 30.0% differences of 95% limits of agreement. ELM and EZ recovery prediction accuracy was 88.0% and 92.0%, respectively. The proposed GDLM accurately predicted macular OCT images following FTMH surgery, aiding patient and surgeon understanding of postoperative macular features.

Effect of topical bromfenac on intraretinal cystoid lesion in simultaneous cataract and idiopathic epiretinal membrane surgery.

PURPOSE: To investigate the effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs,) bromfenac on the intraretinal cystic lesions (IRC) when performing simultaneous cataract and idiopathic epiretinal membrane (iERM) surgery. METHODS: This study included patients with iERM who had been followed up for 6 months after vitrectomy, membrane removal, and concurrent cataract surgery. Eyes were treated with topical bromfenac or not. The baseline fluorescein angiography (FA) was obtained to assess the microvascular leakage (ML). Structural changes of macula, including IRC and central macular thickness (CMT) were assessed using optical coherence tomography (OCT). The main outcome measures were changes in IRCs and best-corrected visual acuity (BCVA) regarding FA findings. RESULTS: One hundred eighteen eyes were included. IRC and ML were observed in 51 eyes (43.2%) and 63 eyes (53.4%), respectively. The IRC did not show any association with the ML. Of total, 29 eyes (24.6%) were treated with topical bromfenac (Group A). Compared to Group B, topical bromfenac did not show beneficial effects in aspect of preventions for the newly developed IRC and treatment for pre-existed IRC. Whether the ML existed or not, topical bromfenac did not show any different effect on the changes in BCVA and IRC. CONCLUSION: When performing simultaneous cataract and ERM surgery, topical NSAIDs, bromfenac did not show beneficial effects on the preventions and treatment of IRC in both eyes with and without the ML.

Diagnosis of posterior staphyloma using the radius of steepest curvature among retinal pigment epithelium segmentation line measured by optic coherent tomography.

PURPOSE: To investigate a novel marker to diagnose posterior staphylomas by measuring the radius of the steepest curvature on the retinal pigment epithelium (RPE) segmentation line using optical coherence tomography (OCT). STUDY DESIGN: Retrospective Cross-sectional Study. METHODS: The authors developed a prototype software to measure the radius of curvature on the RPE segmentation line of OCT. Twelve images of 9-mm radial OCT scans were used. The radius of curvature was measured at the steepest area of the RPE segmentation line, and the macular curvature (MC) index was calculated based on its reciprocal. Based on the wide-field fundus findings, the study sample was divided into three groups: definite posterior staphyloma, no posterior staphyloma, and undetermined. The differences of MC index among the groups and the correlation between the MC index, age, and axial length were analyzed. RESULTS: The present study analyzed 268 eyes, with 54 (20.1%) with definite posterior staphyloma, 202 (75.4%) with no posterior staphyloma, and 12 (4.5%) with undetermined disease status. A maximum MC index of 37.5 was observed in the group with no posterior staphyloma, which was less than the minimum MC index of 42.7 observed in the group with definite posterior staphyloma. The MC index had strong correlations with the axial length and age in eyes with high myopia. CONCLUSIONS: Eyes with posterior staphyloma have a steeper curvature than those with radius 8.44 mm, while eyes without posterior staphyloma do not. MC index 40 (radius 8.44 mm) might act as a reference to distinguish between those with and those without posterior staphyloma.

Ocular syphilis masquerading as refractory retinal diseases.

PURPOSE: To report two cases of syphilis masquerading as chronic refractory macular diseases. CASE DESCRIPTIONS: Two patients had been diagnosed with neovascular age-related macular degeneration (neovascular AMD) and diabetic macular edema (DME), respectively. The disease worsened despite repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) and also surgical treatment (in suspected case of DME). Systemic evaluations were positive for syphilis. Intravenous penicillin was started, and the macular diseases improved. The lesions were well controlled afterward. CONCLUSIONS: The current two cases demonstrated that ocular syphilis can masquerade as refractory chronic retinal diseases such as DME and neovascular AMD. Laboratory evaluations for syphilis may be needed, not only for uveitis but also for refractory retinal diseases. Indocyanine green angiography may be helpful to reveal occult syphilis.

Enhancer of zeste homolog 2 (EZH2)-dependent sirtuin-3 determines sensitivity to glucose starvation in radioresistant head and neck cancer cells.

Sirtuin 3 (SIRT3) regulates mitochondrial function as a mitochondrial deacetylase during oxidative stress. However, the specific regulatory mechanism and function of SIRT3 in radioresistant cancer cells are unclear. In this study, we aim to investigate how SIRT3 determines the susceptibility to glucose deprivation and its regulation in p53-based radioresistant head and neck cancer cells. We observed mitochondrial function using two established isogenic radioresistant subclones (HN3R-A [p53 null] and HN3R-B [p53 R282W]) with intratumoral p53 heterogeneity. Cell counting analysis was performed to evaluate cell proliferation and cell death. The correlation between the regulation of SIRT3 and enhancer of zeste homolog 2 (EZH2) was confirmed by immunoblotting and chromatin immunoprecipitation assay. p53-deficient radioresistant cells (HN3R-A) expression reduced SIRT3 levels and increased sensitivity to glucose deprivation due to mitochondrial dysfunction compared to other cells. In these cells, activation of SIRT3 significantly prevented glucose deprivation-induced cell death, whereas the loss of SIRT3 increased the susceptibility to glucose deficiency. We discovered that radiation-induced EZH2 directly binds to the SIRT3 promoter and represses the expression. Conversely, inhibiting EZH2 increased the expression of SIRT3 through epigenetic changes. Our findings indicate that p53-deficient radioresistant cells with enhanced EZH2 exhibit increased sensitivity to glucose deprivation due to SIRT3 suppression. The regulation of SIRT3 by EZH2 plays a critical role in determining the cell response to glucose deficiency in radioresistant cancer cells. Therefore, EZH2-dependent SIRT3 could be used as a predictive biomarker to select treatment options for patients with radiation-resistance.

Changes in Flight Altitude of Black-Tailed Gulls According to Temporal and Environmental Differences.

In this study, GPS trackers were attached to black-tailed gulls (Larus crassirostris) breeding on five islands in Republic of Korea during April and May 2021, and their flight frequency, behavioral range, and flight altitude were compared during and after the breeding season. During the breeding season, the flight frequency was lowest on Dongman Island (28.7%), where mudflats were distributed nearby, and the range of activity was narrow. In contrast, it tended to be high on Gungsi Island (52%), where the breeding colony was far from land, resulting in a wider range of activity. Although the flight frequency on Dongman Island increased post-breeding season (42.7%), it decreased on other islands. The mean flight altitude during the breeding season was lowest on Dongman Island and highest on Napdaegi Island. In most breeding areas, the mean flight altitude during the post-breeding season was higher than that during the breeding season. However, the lead flight altitude was lower during the non-breeding season compared to that in the breeding season. The home range expanded after the breeding season, with no significant difference in lead time between the breeding and non-breeding seasons. Our findings reveal that black-tailed gulls exhibit varying home ranges and flight altitudes depending on season and geographical location. As generalists, gulls display flexible responses to environmental changes, indicating that flight behavior adapts to the evolving environment over time and across regions.

Case series of neuroretinitis in Korea.

BACKGROUND: To present the clinical characteristics of neuroretinitis in Korea. METHODS: Twelve patients with neuroretinitis between January 2009 and September 2020 were retrospectively reviewed. Neuroretinitis was diagnosed based on fundus findings, optical coherence tomography, and fluorescein angiography. The serological findings of each patient were reviewed. RESULTS: Fifteen eyes of 12 patients (9 male and 3 female), with a mean age of 46.0 ± 10.7 years were included. Of the nine patients who underwent serological testing for Toxocara antibodies, six (66.6%) were positive. One patient had high titers of Toxoplasma immunoglobulins M and G. One patient diagnosed with dengue fever was suspected to have neuroretinitis in both eyes. There were no related abnormalities in the serological findings in four patients (33.3%) out of 12 patients. There were no suspected cases of cat-scratch disease. The six patients who were positive for Toxocara antibodies were older (mean age: 54.5 ± 9.1 years) than the others (mean age: 37.5 ± 4.4 years, p = 0.004). The four patients without any abnormal serological findings were relatively younger (mean age: 35.7 ± 3.0 years) than the other 8 patients (mean age: 51.1 ± 10.1 years, p = 0.008). CONCLUSIONS: Two-thirds of neuroretinitis patients were seropositive for Toxocara in the current cohort from Koreans. Causative factors in cases of neuroretinitis may vary according to age and region.

Highly efficient genome editing via CRISPR-Cas9 ribonucleoprotein (RNP) delivery in mesenchymal stem cells.

The CRISPR-Cas9 system has significantly advanced regenerative medicine research by enabling genome editing in stem cells. Due to their desirable properties, mesenchymal stem cells (MSCs) have recently emerged as highly promising therapeutic agents, which properties include differentiation ability and cytokine production. While CRISPR-Cas9 technology is applied to develop MSC-based therapeutics, MSCs exhibit inefficient genome editing, and susceptibility to plasmid DNA. In this study, we compared and optimized plasmid DNA and RNP approaches for efficient genome engineering in MSCs. The RNP-mediated approach enabled genome editing with high indel frequency and low cytotoxicity in MSCs. By utilizing Cas9 RNPs, we successfully generated B2M-knockout MSCs, which reduced T-cell differentiation, and improved MSC survival. Furthermore, this approach enhanced the immunomodulatory effect of IFN-r priming. These findings indicate that the RNP-mediated engineering of MSC genomes can achieve high efficiency, and engineered MSCs offer potential as a promising therapeutic strategy. [BMB Reports 2024; 57(1): 60-65].