Ultraviolet protection in eye and face protection against biological hazards.

BACKGROUND: In the development of eye and face protection standards against biological hazards, it is important to consider that the eye and face protectors may be used in the outdoor environment, where ultraviolet (UV) exposure from the sun is much higher than indoors. Workers affected include paramedics, ambulance officers and clinical testing personnel. METHODS: Spectral transmittances (280-780 nm) were measured on eight face shields and one goggle of the types used in hospital and clinical environments, three overhead projector sheets and an occupational impact protective goggle. The UV and luminous transmittances were calculated according to the international and two national sunglass standards, and compared with the compliance requirements. RESULTS: All the face shields and goggle lenses were made of variants of the same material. All the samples, including the overhead projector sheets, complied with the requirements of the sunglass standards (for normal conditions, in the case of the American standard). CONCLUSION: Since all the lenses complied with the sunglass standards for UV protection, and there appears to be uniformity in the choice of materials in this product type, there is no need to make provision, as is the case for occupational eye and face protection standards, for protectors that do not provide UV protection. This makes labelling and advice to end users from eyecare and safety professionals much simpler.

Antibiotic adherence in dermatologic surgery: a Multicenter prospective cohort study.

Understanding patient non-adherence to prescribed antibiotics can inform clinical practices, patient counseling, and antibiotic efficacy study design in dermatology. The primary objective was to determine the rate of and reasons for antibiotic non-adherence in the dermatologic surgery setting. The secondary objective was to test the applicability of previously studied survey questions for antibiotic non-adherence screening in the dermatologic surgery setting. Five academic outpatient dermatologic surgery centers across the United States conducted one multicenter prospective cohort study. Dermatologic surgery patients ≥ 18 years of age who were prescribed an antibiotic were included as part of this study. 15.2% (42/276) of patients did not adhere to their antibiotic regimen after dermatologic surgery. Most common reasons for incomplete antibiotic courses included forgotten antibiotics (42.9%,18/42) and side effects (28.6%, 12/42). Previously evaluated questions to identify and predict non-adherence had modest performance in the dermatologic surgery setting (Area under the curve of 0.669 [95% CI (0.583-0.754)]). Antibiotic non-adherence after skin surgery is prevalent and commonly due to reasons that physicians can address with patients.

Non-Invasive Label-free Analysis Pipeline for In Situ Characterization of Differentiation in 3D Brain Organoid Models.

Brain organoids provide a unique opportunity to model organ development in a system similar to human organogenesis in vivo. Brain organoids thus hold great promise for drug screening and disease modeling. Conventional approaches to organoid characterization predominantly rely on molecular analysis methods, which are expensive, time-consuming, labor-intensive, and involve the destruction of the valuable 3D architecture of the organoids. This reliance on end-point assays makes it challenging to assess cellular and subcellular events occurring during organoid development in their 3D context. As a result, the long developmental processes are not monitored nor assessed. The ability to perform non-invasive assays is critical for longitudinally assessing features of organoid development during culture. In this paper, we demonstrate a label-free high-content imaging approach for observing changes in organoid morphology and structural changes occurring at the cellular and subcellular level. Enabled by microfluidic-based culture of 3D cell systems and a novel 3D quantitative phase imaging method, we demonstrate the ability to perform non-destructive high-resolution imaging of the organoid. The highlighted results demonstrated in this paper provide a new approach to performing live, non-destructive monitoring of organoid systems during culture.

Association of household language and vision screening among children in the United States.

The American Academy of Pediatrics recommends annual testing in children beginning at 3 years of age to detect vision problems and prevent amblyopia. However, rates of vision testing in children from non-English primary language (NEPL) households are not well delineated. This study analyzed the 2018-2020 National Survey of Children's Health to examine patterns and predictors of vision testing among children from NEPL households. In this nationally representative cohort of 89,697 children 3-17 years of age, 70.9% of children received vision testing during the previous 12 months. Children from non-English-speaking households were less likely to undergo vision testing (64.3% vs 72.0%; aOR [95% CI] = 0.83 [0.72-0.95], P = 0.008). Decreased vision testing among children from NEPL households was driven by lower rates of testing at school (16.1% vs 21.0%; 0.72 [0.57-0.89], P = 0.009) or from an ophthalmologist or optometrist (49.0% vs 54.0%; 0.72 [0.61-0.85], P = 0.0004), whereas children from NEPL households were more likely to receive vision testing at health clinics (14.4% vs 3.1%; 3.25 [2.40-4.39], P < 0.0001). No differences were observed in rates of testing by a pediatrician (41.1% vs 44.0%; 1.05 [0.89-1.23], P = 0.69). Interventions to improve language services and health literacy are warranted to increase rates of vision testing among children from NEPL households.

Eucalyptol, limonene and pinene enteric capsules attenuate airway inflammation and obstruction in lipopolysaccharide-induced chronic bronchitis rat model via TLR4 signaling inhibition.

BACKGROUND: Chronic bronchitis (CB), a type of chronic obstructive pulmonary disease (COPD), poses a significant global health burden owing to its high morbidity and mortality rates. Eucalyptol, limonene and pinene enteric capsules (ELPs) are clinically used as expectorants to treat various respiratory diseases, including CB, but their acting mechanisms remain unclear. In this study, we investigated the anti-CB effects of ELP in a rat model of lipopolysaccharide (LPS)-induced CB. The molecular mechanisms underlying its inhibitory effects on airway inflammation were further explored in LPS-stimulated Beas-2B cells. METHODS: ELP was characterized using gas chromatography. The production of inflammatory mediators in bronchoalveolar lavage fluid (BALF) was determined using an enzyme-linked immunosorbent assay. The expression of MUC5AC, MUC5B, and p-p65 in the lung tissue was measured using immunohistochemical staining. The gene expression of inflammatory mediators was determined using qRT-PCR. The expression levels of the target proteins were detected by western blotting. Nuclear localization of p65 was determined using an immunofluorescence assay. RESULTS: Compared to the CB model rats, ELP-treated rats showed reduced airway resistance, inflammation, and goblet cell hyperplasia. In BALF, ELP decreased the levels of inflammatory mediators, including TNF-α, IL-6, MIP-1α, and CCL5. ELP also suppressed LPS-induced elevation of MUC5AC, MUC5B, and p-p65 in the lung tissue. The metabolic pathway changes caused by LPS challenge were improved by ELP treatment. In LPS-exposed Beas-2B cells, ELP treatment inhibited the expression of TNFA, IL6, CCL5, MCP1, and MIP2A and decreased the phospho-levels of toll-like receptor 4 (TLR4) signaling-related proteins, including p-p38, p-JNK, p-ERK, p-TBK1, p-IKKα/ß, p-IκB, p-p65, and p-c-Jun. ELP also hindered the nuclear translocation of p65, c-Jun, and IRF3. CONCLUSIONS: This study showed that ELP has a potential therapeutic effect in LPS-induced CB rat model, possibly by suppressing TLR4 signaling. These results justify the clinical use of ELP for the treatment of pulmonary inflammatory diseases.

Smaller body size under warming is not due to gill-oxygen limitation in a cold-water salmonid.

Declining body size in fishes and other aquatic ectotherms associated with anthropogenic climate warming has significant implications for future fisheries yields, stock assessments and aquatic ecosystem stability. One proposed mechanism seeking to explain such body-size reductions, known as the gill oxygen limitation (GOL) hypothesis, has recently been used to model future impacts of climate warming on fisheries but has not been robustly empirically tested. We used brook trout (Salvelinus fontinalis), a fast-growing, cold-water salmonid species of broad economic, conservation and ecological value, to examine the GOL hypothesis in a long-term experiment quantifying effects of temperature on growth, resting metabolic rate (RMR), maximum metabolic rate (MMR) and gill surface area (GSA). Despite significantly reduced growth and body size at an elevated temperature, allometric slopes of GSA were not significantly different than 1.0 and were above those for RMR and MMR at both temperature treatments (15°C and 20°C), contrary to GOL expectations. We also found that the effect of temperature on RMR was time-dependent, contradicting the prediction that heightened temperatures increase metabolic rates and reinforcing the importance of longer-term exposures (e.g. >6 months) to fully understand the influence of acclimation on temperature-metabolic rate relationships. Our results indicate that although oxygen limitation may be important in some aspects of temperature-body size relationships and constraints on metabolic supply may contribute to reduced growth in some cases, it is unlikely that GOL is a universal mechanism explaining temperature-body size relationships in aquatic ectotherms. We suggest future research focus on alternative mechanisms underlying temperature-body size relationships, and that projections of climate change impacts on fisheries yields using models based on GOL assumptions be interpreted with caution.

Disease Awareness Among Patients With Age-Related Macular Degeneration: Patterns and Predictors.

Purpose: To examine the prevalence and predictors of patient awareness of their disease in adults with age-related macular degeneration (AMD). Methods: This study analyzed 5553 adults 40 years or older in the 2005-2008 National Health and Nutrition Examination Survey who underwent retinal imaging. AMD was determined based on retinal images. Patient awareness of their AMD was assessed by a self-reported AMD diagnosis. Multivariable logistic regression models were constructed to examine the association of patient awareness of their AMD with sociodemographic characteristics and specific AMD lesion types on retinal imaging. Results: AMD was identified in 425 of the adults surveyed (6.5%) (95% confidence interval [CI], 5.5%-7.5%), including 87.7% (95% CI, 82.9%-92.5%) with early AMD and 12.3% (95% CI, 7.5%-17.1%) with late AMD. Among adults with either type of AMD on retinal imaging, 17.5% (95% CI, 13.1%-22.0%) were aware of their disease, which included 11.6% (95% CI, 8.4%-14.9%) with early AMD and 59.2% (95% CI, 43.1%-75.3%) with late AMD (P < .0001). In the same group, those aged 60 years or older (odds ratio [OR], 33.46; 95% CI, 7.67-146.03) and with a best-corrected visual acuity of 20/40 or worse (OR, 4.63; 95% CI, 2.95-7.26) had higher awareness of their AMD diagnosis, whereas Hispanic (OR, 0.28; 95% CI, 0.09-0.88) vs White adults and those who did not speak English at home (OR, 0.05; 95% CI, 0.01-0.41) had lower awareness of their diagnosis. Conclusions: Fewer than 1 in 5 adults with AMD were aware of their personal diagnosis, including fewer than 3 in 5 adults with late AMD. Older adults and those with worse vision were more likely to know they have AMD, whereas Hispanic adults and those who did not speak English at home were less likely. Efforts to increase patients' awareness of their AMD may improve rates of follow-up and prevent vision loss.

Circulating tumour mutation detection in triple-negative breast cancer as an adjunct to tissue response assessment.

Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. Here we determined the prevalence of actionable mutations detectable in ctDNA using a clinically validated cancer gene panel assay in patients with TNBC, without recurrence at the time of study entry. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at much higher risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in neoadjuvant therapy protocols may be identifiable by combining tissue response and sensitive ctDNA detection.

Associating growth factor secretions and transcriptomes of single cells in nanovials using SEC-seq.

Cells secrete numerous bioactive molecules that are essential for the function of healthy organisms. However, scalable methods are needed to link individual cell secretions to their transcriptional state over time. Here, by developing and using secretion-encoded single-cell sequencing (SEC-seq), which exploits hydrogel particles with subnanolitre cavities (nanovials) to capture individual cells and their secretions, we simultaneously measured the secretion of vascular endothelial growth factor A (VEGF-A) and the transcriptome for thousands of individual mesenchymal stromal cells. Our data indicate that VEGF-A secretion is heterogeneous across the cell population and is poorly correlated with the VEGFA transcript level. The highest VEGF-A secretion occurs in a subpopulation of mesenchymal stromal cells characterized by a unique gene expression signature comprising a surface marker, interleukin-13 receptor subunit alpha 2 (IL13RA2), which allowed the enrichment of this subpopulation. SEC-seq enables the identification of gene signatures linked to specific secretory states, facilitating mechanistic studies, the isolation of secretory subpopulations and the development of means to modulate cellular secretion.

Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling.

Background: Xuelian injection (XI), a classic preparation extracted from Saussureae Involucratae Herba, has been clinically used to manage rheumatoid arthritis (RA) for nearly twenty years in China. However, the underlying anti-RA mechanism of XI remains unclear. In this study, complete Freund's adjuvant (CFA)-induced acute arthritic model was used to examine the anti-RA effects of XI in vivo. The molecular mechanisms of this action were further investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: XI and XI freeze dried powder were characterized by UPLC analysis. CD68 and TLR4 expression in the ankle joints was measured by immunohistochemistry. The secretion of inflammatory mediators was detected by ELISA. The expression levels of TLR4 involved components were measured by Western blotting. The localization of transcription factors was measured by immunofluorescence assay. Results: XI treatment ameliorated arthritic symptoms induced by CFA in the ankle joints of rats. The serum levels of inflammatory mediators, including TNF-α, MCP-1, and Rantes were decreased by XI treatment. The elevation of CD68 and TLR4 levels in ankle joints caused by CFA was suppressed by XI treatment. Moreover, XI treatment inhibited the secretion of nitric oxide and prostaglandin E2 in LPS-treated RAW264.7 macrophages. The expression of their enzymes iNOS and COX-2 was also decreased after XI treatment. The production of inflammatory mediators, including TNF-α, IL-6, IL-1ß, MCP-1, MIP-1α, and Rantes was reduced by XI treatment in LPS-stimulated RAW264.7 cells. The phosphorylation of p38, JNK, ERK, TBK1, IKKα/ß, IκB, p65, c-Jun, and IRF3 was reduced after XI treatment. Additionally, the expression levels of nuclear proteins of p65, c-Jun, and IRF3 were inhibited by XI treatment. Conclusions: Taken together, XI possesses potential anti-RA effect and the underlying mechanism may be closely associated with the inhibition of TLR4 signaling. Our findings provide further pharmacological justifications for the clinical use of XI in RA treatment.

Anticipated Versus Unanticipated Incomplete Mohs Micrographic Surgery for Keratinocyte Carcinomas: Impact on Treatment Delays and Final Margin Status.

BACKGROUND: Mohs micrographic surgery may be discontinued with positive margins as an anticipated strategy for multidisciplinary care or as an unanticipated occurrence. Management of primary tumors has not been compared after anticipated versus unanticipated incomplete Mohs micrographic surgery (iMMS). OBJECTIVE: To compare rates and timing of adjuvant surgery after iMMS and final margin status when iMMS is anticipated versus unanticipated. Secondary outcomes were preoperative and intraoperative clinicopathologic factors associated with iMMS. METHODS: Cases of iMMS of keratinocyte carcinomas at a tertiary academic center between 2005 and 2022 were classified as anticipated (preoperative assembly of multidisciplinary teams) or unanticipated (ad hoc management of positive margins). Rate, timing, and final margin status of adjuvant surgery was compared between anticipated and unanticipated iMMS cohorts using χ2/Fisher exact test for categorical variables and t-test for continuous variables. RESULTS: Of 127 iMMS cases, 51.2% (65/127) were anticipated. Anticipated iMMS cases were more likely to undergo additional resection (98.5% vs 72.6%, p < .001), with fewer delays (3.9 vs 13.2 days, p < .001) and higher rates of final margin clearance (84.6% vs 59.7%, p < .001). CONCLUSION: When iMMS is anticipated as part of multidisciplinary care, patients are more likely to undergo additional resection, with fewer delays to next surgery and higher final margin clearance rates.

2D and 3D multiplexed subcellular profiling of nuclear instability in human cancer.

Nuclear atypia, including altered nuclear size, contour, and chromatin organization, is ubiquitous in cancer cells. Atypical primary nuclei and micronuclei can rupture during interphase; however, the frequency, causes, and consequences of nuclear rupture are unknown in most cancers. We demonstrate that nuclear envelope rupture is surprisingly common in many human cancers, particularly glioblastoma. Using highly-multiplexed 2D and super-resolution 3D-imaging of glioblastoma tissues and patient-derived xenografts and cells, we link primary nuclear rupture with reduced lamin A/C and micronuclear rupture with reduced lamin B1. Moreover, ruptured glioblastoma cells activate cGAS-STING-signaling involved in innate immunity. We observe that local patterning of cell states influences tumor spatial organization and is linked to both lamin expression and rupture frequency, with neural-progenitor-cell-like states exhibiting the lowest lamin A/C levels and greatest susceptibility to primary nuclear rupture. Our study reveals that nuclear instability is a core feature of cancer, and links nuclear integrity, cell state, and immune signaling.

Alternative splicing of CEACAM1 by hypoxia-inducible factor-1α enhances tolerance to hepatic ischemia in mice and humans.

Although alternative splicing (AS) drives transcriptional responses and cellular adaptation to environmental stresses, its contributions in organ transplantation have not been appreciated. We have shown that carcinoembryonic antigen-related cell adhesion molecule (Ceacam1; CD66a), a transmembrane biliary glycoprotein expressed in epithelial, endothelial, and immune cells, determines donor liver transplant quality. Here, we studied how AS of Ceacam1 affects ischemia-reperfusion injury (IRI) in mouse and human livers. We found that the short cytoplasmic isoform Ceacam1-S increased during early acute and late resolution phases of warm IRI injury in mice. Transfection of Ceacam1-deficient mouse hepatocytes with adenoviral Ceacam1-S mitigated hypoxia-induced loss of cellular adhesion by repressing the Ask1/p-p38 cell death pathway. Nucleic acid-blocking morpholinos, designed to selectively induce Ceacam1-S, protected hepatocyte cultures against temperature-induced stress in vitro. Luciferase and chromatin immunoprecipitation assays identified direct binding of hypoxia-inducible factor-1α (Hif-1α) to the mouse polypyrimidine tract binding protein 1 (Ptbp1) promoter region. Dimethyloxalylglycine protected mouse livers from warm IR stress and hepatocellular damage by inhibiting prolyl hydroxylase domain-containing protein 1 and promoting AS of Ceacam1-S. Last, analysis of 46 human donor liver grafts revealed that CEACAM1-S positively correlated with pretransplant HIF1A expression. This also correlated with better transplant outcomes, including reduced TIMP1, total bilirubin, proinflammatory MCP1, CXCL10 cytokines, immune activation markers IL17A, and incidence of delayed complications from biliary anastomosis. This translational study identified mouse Hif-1α-controlled AS of Ceacam1, through transcriptional regulation of Ptbp1 promoter region, as a functional underpinning of hepatoprotection against IR stress and tissue damage in liver transplantation.

New therapeutic concepts against ischemia-reperfusion injury in organ transplantation.

INTRODUCTION: Ischemia-reperfusion injury (IRI) involves a positive amplification feedback loop that stimulates innate immune-driven tissue damage associated with organ procurement from deceased donors and during transplantation surgery. As our appreciation of its basic immune mechanisms has improved in recent years, translating putative biomarkers into therapeutic interventions in clinical transplantation remains challenging. AREAS COVERED: This review presents advances in translational/clinical studies targeting immune responses to reactive oxygen species in IRI-stressed solid organ transplants, especially livers. Here we focus on novel concepts to rejuvenate suboptimal donor organs and improve transplant function using pharmacologic and machine perfusion (MP) strategies. Cellular damage induced by cold ischemia/warm reperfusion and the latest mechanistic insights into the microenvironment's role that leads to reperfusion-induced sterile inflammation is critically discussed. EXPERT OPINION: Efforts to improve clinical outcomes and increase the donor organ pool will depend on improving donor management and our better appreciation of the complex mechanisms encompassing organ IRI that govern the innate-adaptive immune interface triggered in the peritransplant period and subsequent allo-Ag challenge. Computational techniques and deep machine learning incorporating the vast cellular and molecular mechanisms will predict which peri-transplant signals and immune interactions are essential for improving access to the long-term function of life-saving transplants.

Swept-source optical coherence tomography angiography metrics of retinal ischaemic perivascular lesions in patients being evaluated for carotid artery stenosis and controls.

BACKGROUND/AIMS: Retinal microvascular ischaemia may produce localised middle retinal disruption with corresponding scotoma, a phenomenon termed paracentral acute middle maculopathy (PAMM). Small chronic middle retinal atrophic lesions termed retinal ischaemic perivascular lesions (RIPLs) appear qualitatively similar to PAMM lesions and have recently been hypothesised to result specifically from PAMM. However, no studies have quantitatively demonstrated an ischaemic origin of RIPLs. We quantitatively investigated the pathophysiology of RIPLs and their relationship with PAMM with swept-source optical coherence tomography angiography (SS-OCTA). METHODS: A total of 14 controls and 25 patients being evaluated for carotid artery stenosis (CAS) were enrolled. SS-OCTA imaging of each eye was taken. Projection-resolved en face 6 mm × 6 mm superficial capillary plexus (SCP) and deep capillary plexus (DCP) images were quantitatively analysed with two algorithms for changes in vessel linear density (VLD) and vessel tortuosity (VT) at RIPLs relative to both the immediately surrounding macula and the entire macula, as well as between eyes with RIPLs and eyes without RIPLs. RESULTS: All controls and 22 of 25 CAS patients were included in the analysis. RIPLs demonstrated a localised decrease in DCP VLD in CAS patients and controls. RIPLs tended to show a localised decrease in SCP VLD in CAS patients but a localised increase in controls. No changes in VT were found. Eyes with RIPLs had VLD and VT similar to their RIPL-free fellow eyes. CONCLUSION: RIPLs are associated with quantifiable local, but not global, ischaemia, supporting the idea of shared pathophysiology with classic PAMM lesions along a continuum of ischaemia severity.

Characterizing the Accessibility and Content of Surgical and Medical Retina Fellowship Program Websites.

Purpose: To assess the accessibility and content of surgical and medical retina fellowship websites. Methods: The websites of all surgical and medical retina fellowship programs were examined. Each program's website was evaluated based on information available on 10 recruitment and 10 training criteria. The presence of the criteria was summed to calculate a total content score (range, 0-20). Also examined were the differences in website content score by number of fellows, geographic location, and Association of University Professors of Ophthalmology (AUPO) compliance. Results: This study identified 102 surgical and 25 medical retina programs. Overall, 91.2% of surgical and 88.0% of medical retina programs had an accessible website. The surgical retina program website contained a mean of 9.8 of the total criteria, including 4.9 recruitment criteria and 5.2 training criteria, with no significant differences by number of fellows, geography, or AUPO status. Medical retina websites contained a mean of 9.3 total criteria, including 4.5 recruitment criteria and 4.9 training criteria. Website content scores for medical retina programs were associated with geography and AUPO status, which was consistent when stratifyed by recruitment and training criteria. Conclusions: Most surgical and medical retina fellowships have an accessible program website. However, there are opportunities to improve the completeness and consistency of information on these websites. Improved websites can help programs attract well-suited candidates and might address multiple inefficiencies in the application process.

A Cost Comparison Between Mohs Micrographic Surgery and Conventional Excision for the Treatment of Head and Neck Melanomas In Situ and Thin Melanomas.

BACKGROUND: Variation in operative setting and surgical technique exists when treating specialty site melanomas. There are limited data comparing costs among surgical modalities. OBJECTIVE: To evaluate the costs of head and neck melanoma surgery performed with Mohs micrographic surgery or conventional excision in the operating room or office-based settings. METHODS: A retrospective cohort study was performed on patients aged 18 years and older with surgically treated head and neck melanoma in 2 cohorts, an institutional cohort and an insurance claims cohort, for the years 2008-2019. The primary outcome was total cost of care for a surgical encounter, provided in the form of insurance reimbursement data. A generalized linear model was used to adjust for covariates affecting differences between treatment groups. RESULTS: In the institutional and insurance claims cohorts, average adjusted treatment cost was highest in the conventional excision-operating room treatment group, followed by the Mohs surgery and conventional excision-office setting ( p < .001). CONCLUSION: These data demonstrate the important economic role the office-based setting has for head and neck melanoma surgery. This study allows cutaneous oncologic surgeons to better understand the costs of care involved in head and neck melanoma treatment. Cost awareness is important for shared decision-making discussions with patients.