Manipulating the Crosstalk between Cancer and Immunosuppressive Cells with Phototherapeutic Gold-Nanohut for Reprogramming Tumor Microenvironment.

Photoimmunotherapy faces challenges due to insufficient intratumoral accumulation of photothermal agents and the reversion of the cancer-immunity cycle during treatment. In this study, an anti-PD-L1-immobilized magnetic gold nanohut, AuNH-2-Ab, with photoresponsive, thermosensitive, and immunomodulatory properties to effectively suppress the growth of primary tumors, elevate immunogenic cell death (ICD) levels, reverse the tumor immune microenvironment (TIME), and consequently inhibit metastases are developed. AuNH-2-Ab achieves high tumor accumulation (9.54% injected dose) following systemic administration, allowing the modulation of hyperthermia dose of over 50 °C in the tumor. By optimizing the hyperthermia dose, AuNH-2-Ab simultaneously target and eliminate cancer cells and tumor-associated macrophages, thereby activating potent antitumor immunity without being compromised by immunosuppressive elements. Hyperthermia/pH induced morphological transformation of AuNH-2-Ab involving the detachment of the surface antibody for in situ PD-L1 inhibition, and exposure of the inner fucoidan layer for natural killer (NK) cell activation. This precision photoimmunotherapy approach reprograms the TIME, significantly prolongs survival in a murine hepatocellular carcinoma model (Hep55.1c), and harnesses the synergistic effects of ICD production and checkpoint inhibitors by utilizing a single nanoplatform.

Management of corneal neovascularization: Current and emerging therapeutic approaches.

Corneal neovascularization (CoNV) is a sight-threatening condition affecting an estimated 1.4 million people per year, and the incidence is expected to rise. It is a complication of corneal pathological diseases such as infective keratitis, chemical burn, corneal limbal stem cell deficiency, mechanical trauma, and immunological rejection after keratoplasties. CoNV occurs due to a disequilibrium in proangiogenic and antiangiogenic mediators, involving a complex system of molecular interactions. Treatment of CoNV is challenging, and no therapy thus far has been curative. Anti-inflammatory agents such as corticosteroids are the mainstay of treatment due to their accessibility and well-studied safety profile. However, they have limited effectiveness and are unable to regress more mature neovascularization. With the advent of advanced imaging modalities and an expanding understanding of its pathogenesis, contemporary treatments targeting a wide array of molecular mechanisms and surgical options are gaining traction. This review aims to summarize evidence regarding conventional and emerging therapeutic options for CoNV.

Comparison of Personal or Indoor PM2.5 Exposure Level to That of Outdoor: Over Four Seasons in Selected Urban, Industrial, and Rural Areas of South Korea: (K-IOP Study).

This study aimed to compare the distribution of indoor, outdoor, and personal PM2.5 (particulate matter ≤ 2.5 µm) hourly concentrations measured simultaneously among 81 nonsmoking elderly participants (65 years or older) living in urban, industrial, or rural areas over 4 seasons (2 weeks per season) from November 2021 to July 2022). PM2.5 measurements were conducted using low-cost sensors with quality control and quality assurance tests. Seasonal outdoor PM2.5 levels were 16.4 (9.1-29.6) µg/m3, 20.5 (13.0-38.0) µg/m3, 18.2 (10.2-31.8) µg/m3, and 9.5 (3.8-18.7) µg/m3 for fall, winter, spring, and summer, respectively. For indoor PM2.5, the median seasonal range was 5.9-7.5 µg/m3, and the median personal PM2.5 exposure concentration was 8.0-9.4 µg/m3. This study provided seasonal distributions of IO (ratio of indoor to outdoor PM2.5 concentration) and PO (ratio of personal to outdoor PM2.5 concentration) using a total of 94,676 paired data points. The median seasonal IO ranged from 0.30 to 0.51 in fall, winter, and spring; its value of summer was 0.70. The median PO by season and study area were close to 1.0 in summer while it ranged 0.5 to 0.7 in other seasons, statistically significantly lower (p < 0.05) than that in summer. Our study has revealed that the real-world exposure level to PM2.5 among our elderly study participants might be lower than what was initially expected based on the outdoor data for most of the time. Further investigation may need to identify the reasons for the discrepancy, personal behavior patterns, and the effectiveness of any indoor air quality control system.

Harmful algal bloom aerosols and human health.

Harmful algal blooms (HABs) are increasing across many locations globally. Toxins from HABs can be incorporated into aerosols and transported inland, where subsequent exposure and inhalation can induce adverse health effects. However, the relationship between HAB aerosols and health outcomes remains unclear despite the potential for population-level exposures. In this review, we synthesized the current state of knowledge and identified evidence gaps in the relationship between HAB aerosols and human health. Aerosols from Karenia brevis, Ostreopsis sp., and cyanobacteria were linked with respiratory outcomes. However, most works did not directly measure aerosol or toxin concentrations and instead relied on proxy metrics of exposure, such as cell concentrations in nearby waterbodies. Furthermore, the number of studies with epidemiological designs was limited. Significant uncertainties remain regarding the health effects of other HAB species; threshold dose and the dose-response relationship; effects of concurrent exposures to mixtures of toxins and other aerosol sources, such as microplastics and metals; the impact of long-term exposures; and disparities in exposures and associated health effects across potentially vulnerable subpopulations. Additional studies employing multifaceted exposure assessment methods and leveraging large health databases could address such gaps and improve our understanding of the public health burden of HABs.

Impact of Microplastics on the Ocular Surface.

Plastics are synthetic materials made from organic polymers that are ubiquitous in daily living and are especially important in the healthcare setting. However, recent advances have revealed the pervasive nature of microplastics, which are formed by degradation of existing plastic products. Although the impact on human health has yet to be fully characterised, there is increasing evidence that microplastics can trigger inflammatory damage, microbial dysbiosis, and oxidative stress in humans. Although there are limited studies investigating their effect on the ocular surface, studies of microplastics on other organs provide some insights. The prevalence of plastic waste has also triggered public outcry, culminating in the development of legislation aimed at reducing microplastics in commercial products. We present a review outlining the possible sources of microplastics leading to ocular exposure, and analyse the possible mechanisms of ocular surface damage. Finally, we examine the utility and consequences of current legislation surrounding microplastic regulation.

Uveitis and glaucoma: a look at present day surgical options.

PURPOSE OF REVIEW: To review the various surgical options of management of medically refractory glaucoma in uveitic eyes. RECENT FINDINGS: Uveitic glaucoma is particularly challenging to manage. We look at the evidence for various surgical options, or the lack of, in the surgical management of medically refractory glaucoma in uveitis. SUMMARY: Conventional glaucoma filtration surgeries such as trabeculectomy and glaucoma drainage implants were more commonly described first line surgical options in the therapy of medically refractory uveitic glaucoma. However, with the introduction of newer implants and options of minimally invasive glaucoma surgeries, the choice of first line surgeries may now be possibly expanded to include other options. However, more research is required to evaluate the efficacy of the newer surgical options in the management of glaucoma in uveitis patients.

Primary and metastatic paraganglioma of the cranial vault.

AIM: Primary paragangliomas (PGs) are extra-adrenal neuroendocrine tumours that are extremely rare. Multiple lesions in the central nervous system raise suspicion of a metastatic process. Lack of consensus on their management warrants the categorization of existing literature to evaluate management options. METHODS: A systematic review of the medical literature on paraganglioma within the cranial vault was completed in accordance with PRISMA guidelines using the Medline database. Tumour physical measures, management parameters, and immunohistochemistry of all documented cases of primary and secondary paraganglioma within the cranial vault were descriptively compared. This review was augmented by comparison with our centre's case of a 48-year-old man diagnosed with metastatic PG originating in the cauda equina and seeding in the cerebellum. Histological parameters within the literature was also established. RESULTS: The systematic literature review yielded published 52 papers. Most prevalent primary intracranial PGs (n = 37) were in the sellar region (78%, n = 23) and the cerebellum (21%, n = 6). The highest progression free survival was seen in primary sellar PGs (87.5% by 34.5 months) and cerebellar PGs (100% by 35.7 months) when treated with adjuvant radiotherapy with subtotal resection or gross total resection, respectively. Contrasting, the most frequent intracranial PGs metastases (n = 15) occurred in the cerebellum (36%, n = 6), and the cerebral parenchyma (29%, n = 4). Their recurrence rate was between 4 and 10% and these metastasized PG in the cerebellum are slow growing (8.9 years, range: 3-22 years). Adjuvant radiotherapy with Gross Total Resection resulted in the optimum progression-free survival (100% up to 48 months) for the patient with PGs metastasis to the cerebellum. CONCLUSION: Metastatic PGs tend to be slow-growing and are clinically silent tumours. Diagnosed patients should undergo regular surveillance neuroradiological assessment, regardless of symptomatology, for metastases along the complete neural axis. We recommend operative management with GTR and adjunct RT in these patients.

Incisional surface quality of electron-beam irradiated cornea-extracted lenticule for stromal keratophakia: high nJ-energy vs. low nJ-energy femtosecond laser.

Introduction: Corneal lenticules can be utilized as an additive material for stromal keratophakia. However, following extraction, they must be reimplanted almost immediately or cryopreserved in lenticule banks. Electron-beam (E-beam) irradiated corneas permit room-temperature storage for up to 2 years, enabling keratophakia to be performed on demand. This study aims to compare the performance of high nano Joule (nJ)-energy (VisuMax) and low nJ-energy (FEMTO LDV) femtosecond laser systems on the thickness consistency and surface quality and collagen morphology of lenticules produced from fresh and E-beamed corneas. Methods: A total of 24 lenticules with -6.00 dioptre power were cut in fresh human donor corneas and E-beamed corneas with VisuMax and FEMTO LDV. Before extraction, the thickness of the lenticules was measured with anterior segment-optical coherence tomography (AS-OCT). The incisional surface roughness of extracted lenticules was analyzed using atomic force microscopy (AFM) and scanning electron microscopy (SEM). Multiphoton microscopy was then used to assess the surface collagen morphometry. Results: The E-beamed lenticules that were cut using FEMTO LDV were significantly thicker than the fresh specimens as opposed to those created with VisuMax, which had a similar thickness as the fresh lenticules. On the vertex, they were ∼11% thicker than the fresh lenticules. The surface roughness (Rq) of E-beamed lenticules incised with FEMTO LDV did not differ significantly from the fresh lenticules. This contrasted with the VisuMax-fashioned lenticules, which showed notably smoother surfaces (∼36 and ∼20% lower Rq on anterior and posterior surfaces, respectively) on the E-beamed than the fresh lenticules. The FEMTO LDV induced less cumulative changes to the collagen morphology on the surfaces of both fresh and E-beamed lenticules than the VisuMax. Conclusion: It has been previously demonstrated that the low nJ-energy FEMTO LDV produced a smoother cutting surface compared to high nJ-energy VisuMax in fresh lenticules. Here, we showed that this effect was also seen in the E-beamed lenticules. In addition, lower laser energy conferred fewer changes to the lenticular surface collagen morphology. The smaller disparity in surface cutting quality and collagen disturbances on the E-beamed lenticules could be beneficial for the early visual recovery of patients who undergo stromal keratophakia.

The Intersection of Immigrant and Environmental Health: A Scoping Review of Observational Population Exposure and Epidemiologic Studies.

BACKGROUND: Transnational immigration has increased since the 1950s. In countries such as the United States, immigrants now account for >15% of the population. Although differences in health between immigrants and nonimmigrants are well documented, it is unclear how environmental exposures contribute to these disparities. OBJECTIVES: We summarized current knowledge comparing immigrants' and nonimmigrants' exposure to and health effects of environmental exposures. METHODS: We conducted a title and abstract review on articles identified through PubMed and selected those that assessed environmental exposures or health effects separately for immigrants and nonimmigrants. After a full text review, we extracted the main findings from eligible studies and categorized each article as exposure-focused, health-focused, or both. We also noted each study's exposure of interest, study location, exposure and statistical methods, immigrant and comparison groups, and the intersecting socioeconomic characteristics controlled for. RESULTS: We conducted a title and abstract review on 3,705 articles, a full text review on 84, and extracted findings from 50 studies. There were 43 studies that investigated exposure (e.g., metals, organic compounds, fine particulate matter, hazardous air pollutants) disparities, but only 12 studies that assessed health disparities (e.g., mortality, select morbidities). Multiple studies reported higher exposures in immigrants compared with nonimmigrants. Among immigrants, studies sometimes observed exposure disparities by country of origin and time since immigration. Of the 50 studies, 43 were conducted in North America. DISCUSSION: The environmental health of immigrants remains an understudied area, especially outside of North America. Although most identified studies explored potential exposure disparities, few investigated subsequent differences in health effects. Future research should investigate environmental health disparities of immigrants, especially outside North America. Additional research gaps include the role of immigrants' country of origin and time since immigration, as well as the combined effects of immigrant status with intersecting socioeconomic characteristics, such as race/ethnicity, income, and education attainment. https://doi.org/10.1289/EHP9855.

Conditioned Hallucinations and Prior Overweighting Are State-Sensitive Markers of Hallucination Susceptibility.

BACKGROUND: Recent advances in computational psychiatry have identified latent cognitive and perceptual states that predispose to psychotic symptoms. Behavioral data fit to Bayesian models have demonstrated an overreliance on priors (i.e., prior overweighting) during perception in select samples of individuals with hallucinations, corresponding to increased precision of prior expectations over incoming sensory evidence. However, the clinical utility of this observation depends on the extent to which it reflects static symptom risk or current symptom state. METHODS: To determine whether task performance and estimated prior weighting relate to specific elements of symptom expression, a large, heterogeneous, and deeply phenotyped sample of hallucinators (n = 249) and nonhallucinators (n = 209) performed the conditioned hallucination (CH) task. RESULTS: We found that CH rates predicted stable measures of hallucination status (i.e., peak frequency). However, CH rates were more sensitive to hallucination state (i.e., recent frequency), significantly correlating with recent hallucination severity and driven by heightened reliance on past experiences (priors). To further test the sensitivity of CH rate and prior weighting to symptom severity, a subset of participants with hallucinations (n = 40) performed a repeated-measures version of the CH task. Changes in both CH frequency and prior weighting varied with changes in auditory hallucination frequency on follow-up. CONCLUSIONS: These results indicate that CH rate and prior overweighting are state markers of hallucination status, potentially useful in tracking disease development and treatment response.

Effect modification by sex for associations of fine particulate matter (PM2.5) with cardiovascular mortality, hospitalization, and emergency room visits: systematic review and meta-analysis.

Particulate matter with aerodynamic diameter no larger than 2.5 µm (PM2.5) has been linked to cardiovascular diseases (CVDs) but evidence for vulnerability by sex remains unclear. We performed systematic review and meta-analysis to synthesize the state of scientific evidence on whether cardiovascular risks from PM2.5 differ for men compared to women. The databases Pubmed, Scopus, Embase, and GreenFILE were searched for studies published Jan. 1995 to Feb. 2020. Observational studies conducting subgroup analysis by sex for impacts of short-term or long-term exposure to PM2.5 on target CVDs were included. Data were independently extracted in duplicate and pooled with random-effects meta-regression. Risk ratios (RRs) for long-term exposure and percent changes in outcomes for short-term exposure were calculated per 10 µg/m3 PM2.5 increase. Quality of evidence of risk differences by sex was rated following Grading of Recommendations Assessment, Development and Evaluation (GRADE). A total of 12,502 articles were screened, with 61 meeting inclusion criteria. An additional 32 studies were added from citation chaining. RRs of all CVD mortality for long-term PM2.5 for men and women were the same (1.14; 95% CI: 1.09, 1.22) indicating no statistically different risks. Men and women did not have statistically different risks of daily CVD mortality, hospitalizations from all CVD, ischemic heart disease, cardiac arrest, acute myocardial infarction, and heart failure from short-term PM2.5 exposure (difference in % change in risk per 10 µg/m3 PM2.5: 0.04 (95% CI, -0.42 to 0.51); -0.05 (-0.47 to 0.38); 0.17 (-0.90, 1.24); 1.42 (-1.06, 3.97); 1.33 (-0.05, 2.73); and -0.48 (-1.94, 1.01), respectively). Analysis using GRADE found low or very low quality of evidence for sex differences for PM2.5-CVD risks. In conclusion, this meta-analysis and quality of evidence assessment of current observational studies found very limited evidence of the effect modification by sex for effects of PM2.5 on CVD outcomes in adults, which can inform clinical approaches and policies.

Temperature variability associations with cardiovascular and respiratory emergency department visits in Dhaka, Bangladesh.

BACKGROUND: Greenhouse gas emissions are changing the Earth's climate, most directly by modifying temperatures and temperature variability (TV). Residents of low- and middle-income countries (LMICs) are likely more adversely affected, due to lack of air conditioning to compensate. To date, there is no local epidemiological evidence documenting the cardio-respiratory health effects of TV in Dhaka, Bangladesh, one of the most climate change vulnerable cities in the world. OBJECTIVES: We assessed short-term TV associations with daily cardiovascular disease (CVD) and respiratory emergency department (ED) visits, as well as effect modification by age and season. METHODS: TV was calculated from the standard deviations of the daily minimum and maximum temperatures over exposure days. Time-series regression modeling was applied to daily ED visits for respiratory and CVD from January 2014 through December 2017. TV effect sizes were estimated after controlling for long-term trends and seasonality, day-of-week, holidays, and daily mean relative humidity and ambient temperature. RESULTS: A 1 °C increase in TV was associated with a 1.00% (95 %CI: 0.05%, 1.96%) increase in CVD ED visits at lag 0-1 days (TV0-1) and a 2.77% (95 %CI: 0.24%, 5.20%) increase in respiratory ED visits at lag 0-7 days (TV0-7). TV-CVD associations were larger in the monsoon and cold seasons. Respiratory ED visit associations varied by age, with older adults more affected by the TV across all seasons. A 1 °C increase in TV at lag 0-7 days (TV0-7) was associated with a 7.45% (95 %CI: 2.33%, 12.57%) increase in respiratory ED visits among patients above 50 years of age. CONCLUSION: This study provided novel and important evidence that cardio-pulmonary health in Dhaka is adversely affected year-round by day-to-day increases in TV, especially among older adults. TV is a key factor that should be considered in evaluating the potential human health impacts of climate change induced temperature changes.

Renal Neoplasms in Young Adults.

Renal cell carcinoma (RCC) is usually diagnosed in older adults (the median age of diagnosis is 64 years). Although less common in patients younger than 45 years, RCCs in young adults differ in clinical manifestation, pathologic diagnosis, and prognosis. RCCs in young adults are typically smaller, are more organ confined, and manifest at lower stages of disease. The proportion of clear cell RCC is lower in young adults, while the prevalence of familial renal neoplastic syndromes is much higher, and genetic testing is routinely recommended. In such syndromic manifestations, benign-appearing renal cysts can harbor malignancy. Radiologists need to be familiar with the differences of RCCs in young adults and apply an altered approach to diagnosis, treatment, and surveillance. For sporadic renal neoplasms, biopsy and active surveillance are less often used in young adults than in older adults. RCCs in young adults are overall associated with better disease-specific survival after surgical treatment, and minimally invasive nephron-sparing treatment options are preferred. However, surveillance schedules, need for biopsy, decision for an initial period of active surveillance, type of surgery (enucleation or wide-margin partial nephrectomy), and utilization of ablative therapy depend on the presence and type of underlying familial renal neoplastic syndrome. In this pictorial review, syndromic, nonsyndromic, and newer RCC entities that are common in young adults are presented. Their associated unique epidemiology, characteristic imaging and pathologic traits, and key aspects of surveillance and management of renal neoplasms in young adults are discussed. The vital role of the informed radiologist in the multidisciplinary management of RCCs in young adults is highlighted. Online supplemental material is available for this article. ©RSNA, 2022.

Dupilumab-associated ocular manifestations: A review of clinical presentations and management.

Dupilumab is a first-in-class biologic approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of multiple atopic diseases, including atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. Since gaining traction as an effective treatment modality, multiple reports have highlighted the many ocular side effects associated with dupilumab usage. These range from mild diseases, such as conjunctivitis, dry eyes, and blepharitis, to more severe manifestations such as intraocular inflammation and cicatrizing conjunctivitis. The pathogenesis behind these manifestations remains controversial, but are likely multi-factorial. We review the current evidence surrounding ocular manifestations of dupilumab-associated disease and proposed treatments to provide an overview of this unique disease entity. With increasing usage of dupilumab, formal recommendations regarding the treatment of dupilumab-associated ocular disease are warranted to provide standardized clinical guidance. Furthermore, it is important for health care practitioners to remain abreast with existing literature to counsel and empower patients with the knowledge surrounding contemporary treatments for atopic diseases and their associated sideeffects.

Therapeutic Response Evaluation in Advanced Melanoma Patients Incorporating Plasma cfDNA, LDH, VEGF, PD-L1, and IFN-γ Measurements.

BACKGROUND/AIM: Current treatment strategies for advanced melanoma require serial assessment of disease status in affected patients. In this study, we sought to examine the relationship between radiographic tumour burden and blood borne biomarkers including plasma cfDNA, serum LDH, plasma VEGF, PD-L1 and IFN-γ in advanced melanoma patients receiving immunotherapy. We hypothesized that a combination of these explanatory variables in a suitable regression analysis model may predict changes in tumour burden during patient treatment. MATERIALS AND METHODS: We extracted and quantified circulating cfDNA, LDH, VEGF, PD-L1, and IFN-γ from thirty patients with stage IV melanoma at baseline and at six months. All participating patients were evaluated with paired blood sample collection and CT scan assessments during treatment. RESULTS: Changes in radiographic tumour burden correlated with changes in levels of cfDNA (p≤0.001), LDH (p≤0.001), VEGF (p≤0.001), and PD-L1 (p<0.05) during treatment. Multiple regression analysis consisting of the follow-up to baseline assessment ratios of cfDNA, LDH, VEGF and PD-L1 explained changes in tumour burden (F (4, 23)=32.05, p<0.001); with an R2 of 0.8479 (Y=ß0+ß1*B+ß2*C+ß3*D+ß4*E). CONCLUSION: A quantitative measure of cfDNA, LDH, VEGF and PD-L1 may complement current methods of assessing tumour burden in advanced melanoma patients.

Beware what lurks on the surface - persistent contamination of high-touch surfaces on slit lamps despite regular cleaning.

High-touch surfaces contributing to infection transmission are particularly concerning in the ophthalmology clinic where frequent contact exists between ophthalmologists and various ophthalmic instruments. Areas of surface contamination from an ophthalmologist's contact with the slit lamp environment were identified using ultraviolet fluorescence as a surrogate for pathogen contamination. Ultraviolet fluorescent product was applied on the ophthalmologist's hands after thorough hand washing to indicate the contamination that may be derived from multiple sources in the ophthalmology clinic, such as touching the patient or the patient's folder during eye examinations and transfers. The ophthalmology clinic was run normally, with the ophthalmologist wiping down patient-contact surfaces on the slit lamp and performing thorough hand hygiene after every patient. Using ultraviolet black light, persistence of surface contamination in the slit lamp environment was identified and evaluated across five days. High-touch surfaces of suboptimal disinfection were inclined towards those touched only by the ophthalmologist, for example: joystick and chin-rest adjustment knob, as compared to patient-contact surfaces. Persistent contamination on the same surfaces revealed inefficacy of current hand hygiene and clinical disinfection practices. This poses a significant risk for pathogen transmission and underscores the importance of including these specific clinician high-touch surfaces in existing cleaning protocols.