Long-term treatment of metastatic adenoid cystic carcinoma with sequential brachytherapy and stereotactic body radiotherapy.

Adenoid cystic carcinoma is a malignancy that is difficult to treat and often metastasizes to the lung. Systemic chemotherapies are not effective for this tumor type, thus local therapies are frequently used. Here, we report a case demonstrating the use of extensive ablative interventions in controlling the progression of metastatic adenoid cystic carcinoma. A patient with adenoid cystic carcinoma developed numerous metastases to his lungs and liver. Local ablative therapies including interstitial brachytherapy and SBRT were used to treat approximately 80 different metastases over the course of a decade. Over 850 brachytherapy seeds were implanted in this patient, and the tumor control and patient outcome were good. As of the most recent follow-up in March 2024, the patient has survived for approximately 12 years since his diagnosis of adenoid cystic carcinoma. To our knowledge, this case represents the most brachytherapy treatments reported in a single patient. It highlights the utility of interstitial brachytherapy and SBRT in treating extensive lung and liver metastases.

Factors affecting the development of cystoid macular edema following pars plana vitrectomy with silicone oil placement: a retrospective cohort study.

BACKGROUND: Cystoid macular edema (CME) can develop following silicone oil placement in complex vitreoretinal surgeries, contributing to poor visual outcomes. In this study, we investigated the clinical and surgical characteristics associated with the development of CME following the use of silicone oil (SO) in pars plana vitrectomy (PPV) surgeries. METHODS: We conducted a retrospective chart review of patients who underwent implantation of SO during PPV from 2010 to 2020 by a single surgeon. Patient demographics, type of oil, duration of oil tamponade, retinectomy size, diabetic status, lens status, prior panretinal photocoagulation, visual acuity, and incidence of CME were reviewed. RESULTS: This study included 43 eyes from 40 patients who underwent SO tamponade for retinal detachment (RD) surgery. The mean duration of SO tamponade was 15.7 ± 12.7 months (range: 1-58 months). The most common indication for surgery was diabetic tractional RD (32.7%), followed by traumatic RD (16.3%) and rhegmatogenous RD with proliferative vitreoretinopathy (11.6%). Of the 43 eyes, 18 (41.9%) developed CME for the first time after PPV with SO placement, with 8 (44%) resolving within a year of oil removal. The mean duration for the development of CME was 9 months. A logistic regression model showed that a scleral buckle procedure and poor initial vision were statistically significant factors for predicting the development of CME (ORs: 11.65 and 16.06, respectively). Overall, 91% of the patients had stable or improved vision after surgery. CONCLUSIONS: The use of a scleral buckle procedure and poor initial vision are significant factors for predicting CME following silicone oil tamponade in PPV surgeries, with 41.9% of patients developing CME with an average duration of 9 months. Recognizing such factors can lead to early monitoring and prompt management of CME. MEETING PRESENTATION: Partial analyses were presented at the ASRS 2020 conference. CLINICAL TRIAL NUMBER: Not applicable.

Development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS).

BACKGROUND: Teachers are recognized as 'key agents' for the delivery of physical activity programs and policies in schools. The aim of our study was to develop and evaluate a tool to assess teachers' capability, opportunity, and motivation to deliver school-based physical activity interventions. METHODS: The development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS) involved three phases. In Phase 1, we invited academic experts to participate in a Delphi study to rate, provide recommendations, and achieve consensus on questionnaire items that were based on the Capability, Opportunity, and Motivation Behavior (COM-B) model. Each item was ranked on the degree to which it matched the content of the COM-B model, using a 5-point scale ranging from '1 = Poor match' to '5 = Excellent match'. In Phase 2, we interviewed primary and secondary school teachers using a 'think-aloud' approach to assess their understanding of the items. In Phase 3, teachers (n = 196) completed the COM-PASS to assess structural validity using confirmatory factor analysis (CFA). RESULTS: Thirty-eight academic experts from 14 countries completed three rounds of the Delphi study. In the first round, items had an average rating score of 4.04, in the second round 4.51, and in the third (final) round 4.78. The final tool included 14 items, which related to the six constructs of the COM-B model: physical capability, psychological capability, physical opportunity, social opportunity, reflective motivation, and automatic motivation. In Phase 2, ten teachers shared their interpretation of COM-PASS via a 20-min interview, which resulted in minor changes. In Phase 3, CFA of the 3-factor model (i.e., capability, opportunity, and motivation) revealed an adequate fit to the data (χ2 = 122.6, p < .001, CFI = .945, TLI = .924, RMSEA = .066). The internal consistencies of the three subscale scores were acceptable (i.e., capability: α = .75, opportunity: α = .75, motivation: α = .81). CONCLUSION: COM-PASS is a valid and reliable tool for assessing teachers' capability, opportunity, and motivation to deliver physical activity interventions in schools. Further studies examining additional psychometric properties of the COM-PASS are warranted.

Acetylene Tunes Microbial Growth During Aerobic Cometabolism of Trichloroethene.

Microbial aerobic cometabolism is a possible treatment approach for large, dilute trichloroethene (TCE) plumes at groundwater contaminated sites. Rapid microbial growth and bioclogging pose a persistent problem in bioremediation schemes. Bioclogging reduces soil porosity and permeability, which negatively affects substrate distribution and contaminant treatment efficacy while also increasing the operation and maintenance costs of bioremediation. In this study, we evaluated the ability of acetylene, an oxygenase enzyme-specific inhibitor, to decrease biomass production while maintaining aerobic TCE cometabolism capacity upon removal of acetylene. We first exposed propane-metabolizing cultures (pure and mixed) to 5% acetylene (v v-1) for 1, 2, 4, and 8 d and we then verified TCE aerobic cometabolic activity. Exposure to acetylene overall decreased biomass production and TCE degradation rates while retaining the TCE degradation capacity. In the mixed culture, exposure to acetylene for 1-8 d showed minimal effects on the composition and relative abundance of TCE cometabolizing bacterial taxa. TCE aerobic cometabolism and incubation conditions exerted more notable effects on microbial ecology than did acetylene. Acetylene appears to be a viable approach to control biomass production that may lessen the likelihood of bioclogging during TCE cometabolism. The findings from this study may lead to advancements in aerobic cometabolism remediation technologies for dilute plumes.

Belzutifan-induced regression of retinal capillary hemangioblastoma: A case-series.

Purpose: To report a series of three patients with von Hippel-Lindau (VHL) disease who demonstrated regression of their retinal hemangioblastomas (RH) using belzutifan in conjunction with photocoagulation therapy. Observations: Patient 1, a 23-year-old female, presented with multiple RHs in her right eye (OD) that were lasered. Her left eye (OS) revealed a large inferotemporal RH that measured approximately 2.1 mm2. Systemic belzutifan was administered. Four months after initiation of treatment, the lesion regressed to 1.4 mm2, but belzutifan was not well-tolerated and was discontinued due to side effects. At the date of belzutifan discontinuation, the lesion measured about 1.1 mm2. Focal laser photocoagulation was applied. The lesion regressed to around 0.6 mm2. Two additional laser treatments were applied one month later. On the most recent follow-up, the lesion was completely fibrosed.Patient 2, a 32-year-old male, presented with one RH OD and two RHs OS. Belzutifan was administered for one month before the patient began experiencing side effects of the medication. Consequently, the dose of belzutifan was decreased. After one month with the lowered dose, laser coagulation was applied to OS. In the most recent follow-up, five months after the initial presentation, the lesions remain less vascularized and reduced in size.Patient 3, is a 44-year-old male with a large RH OD. Following seven months of belzutifan daily, there was a significant reduction in the RH size. Conclusions: Belzutifan, a hypoxia-inducible factor inhibitor, is an FDA-approved medication for VHL disease associated with renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors that do not require immediate surgical resection. Because of the high incidence of VHL-associated RHs, adjuvant laser photocoagulation therapy when belzutifan is suspended or withheld can allow for the regression of large lesions. In this case series, we also propose a reproducible and technically simple method to measure RH lesions size, using Optos fundus imaging.

Computational and AI-driven 3D structural analysis of human papillomavirus (HPV) oncoproteins E5, E6, and E7 reveal significant divergence of HPV E5 between low-risk and high-risk genotypes.

There are over 220 identified genotypes of Human papillomavirus (HPV), and the HPV genome encodes 3 major oncogenes, E5, E6, and E7. Conservation and divergence in protein sequence and function between low-risk versus high-risk oncogenic HPV genotypes has not been fully characterized. Here, we used modern computational and structural folding algorithms to perform a comparative analysis of HPV E5, E6, and E7 between multiple low risk and high risk genotypes. We first identified significantly greater sequence divergence in E5 between low- and high-risk genotypes compared to E6 and E7. Next, we used AlphaFold to model the structure of papillomavirus proteins and complexes with high confidence, including some with no established consensus structure. We observed that HPV E5, but not E6 or E7, had a dramatically different 3D structure between low-risk and high-risk genotypes. To our knowledge, this is the first comparative analysis of HPV proteins using Alphafold artificial intelligence (AI) system. The marked differences in E5 sequence and structure in high-risk HPVs may contribute in important and underappreciated ways to the development of HPV-associated cancers.

Hybrid 23/25-Gauge Direct Perfluorocarbon Liquid-Silicone Oil Exchange.

PURPOSE: To describe a novel technique for direct perfluorocarbon liquid (PFCL)-silicone oil exchange that aims to reduce the inherent risk of intraoperative intraocular pressure spike. METHODS: We use the conventional setup for passive PFCL-silicone exchange, but intentionally create a mismatch between the passive PFCL aspiration and the active silicone injection that favors the PFCL extrusion. This is achieved by converting one port to a large gauge one-23 or 20-gauge. RESULTS: We did not note the occurrence of high intraocular pressure spikes with this technique as noted by disk pallor or attenuated vessels. CONCLUSION: A hybrid 23/25-gauge technique for direct PFCL-silicone oil exchange is safe and reduces the risk of intraoperative intraocular pressure spike.

The Cedar Project: Racism and its impacts on health and wellbeing among young Indigenous people who use drugs in Prince George and Vancouver, BC.

Racism continues to drive health disparities between Indigenous and non-Indigenous peoples in Canada. This study focuses on racism experienced by young Indigenous people who have used drugs in British Columbia (BC), and predictors of interpersonal racism. Cedar Project is a community-governed cohort study involving young Indigenous people who use drugs in Vancouver and Prince George, BC. This cross-sectional study included data collected between August 2015-October 2016. The Measure of Indigenous Racism Experiences (MIRE) scale was used to assess experiences of interpersonal racism across 9 unique settings on a 5-point Likert scale, collapsing responses into three categories (none/low/high). Multinomial logistic regression models were used to examine associations between key variables and interpersonal racism. Among 321 participants, 79% (n = 255) experienced racism in at least one setting. Thirty two percent (n = 102) experienced high interpersonal racism from police, governmental agencies (child 'welfare', health personnel), and in public settings. Ever having a child apprehended (AOR:2.76, 95%CI:1.14-6.65), probable post-traumatic stress (AOR:2.64; 95%CI:1.08-6.46), trying to quit substances (AOR:3.69; 95%CI:1.04-13.06), leaving emergency room without receiving treatment (AOR:3.05; 95%CI:1.22-7.64), and having a traditional language spoken at home while growing up (AOR:2.86; 95%CI:1.90-6.90) were associated with high interpersonal racism. Among women, experiencing high interpersonal racism was more likely if they lived in Prince George (AOR:3.94; 95%CI:1.07-14.50), ever had a child apprehended (AOR:5.09; 95%CI:1.50-17.30), and had probable post-traumatic stress (AOR:5.21; 95%CI:1.43-18.95). Addressing racism experienced by Indigenous peoples requires immediate structural systemic, and interpersonal anti-racist reforms.

Human papillomavirus E5 suppresses immunity via inhibition of the immunoproteasome and STING pathway.

The role that human papillomavirus (HPV) oncogenes play in suppressing responses to immunotherapy in cancer deserves further investigation. In particular, the effects of HPV E5 remain poorly understood relative to E6 and E7. Here, we demonstrate that HPV E5 is a negative regulator of anti-viral interferon (IFN) response pathways, antigen processing, and antigen presentation. Using head and neck cancer as a model, we identify that E5 decreases expression and function of the immunoproteasome and that the immunoproteasome, but not the constitutive proteasome, is associated with improved overall survival in patients. Moreover, immunopeptidome analysis reveals that HPV E5 restricts the repertoire of antigens presented on the cell surface, likely contributing to immune escape. Mechanistically, we discover a direct interaction between E5 and stimulator of interferon genes (STING), which suppresses downstream IFN signaling. Taken together, these findings identify a powerful molecular mechanism by which HPV E5 limits immune detection and mediates resistance to immunotherapy.

Science resource inequalities viewed as less wrong when girls are disadvantaged.

In response to some resource inequalities, children give priority to moral concerns. Yet, in others, children show ingroup preferences in their evaluations and resource allocations. The present study built upon this knowledge by investigating children's and young adults' (N = 144; 5-6-year-olds, M age = 5.83, SD age = .97; 9-11-year-olds, M age = 10.74, SD age = .68; and young adults, M age = 19.92, SD age = 1.10) evaluations and allocation decisions in a science inequality context. Participants viewed vignettes in which male and female groups received unequal amounts of science supplies, then evaluated the acceptability of the resource inequalities, allocated new boxes of science supplies between the groups, and provided justifications for their choices. Results revealed both children and young adults evaluated inequalities of science resources less negatively when girls were disadvantaged than when boys were disadvantaged. Further, 5- to 6-year-old participants and male participants rectified science resource inequalities to a greater extent when the inequality disadvantaged boys compared to when it disadvantaged girls. Generally, participants who used moral reasoning to justify their responses negatively evaluated and rectified the resource inequalities, whereas participants who used group-focused reasoning positively evaluated and perpetuated the inequalities, though some age and participant gender findings emerged. Together, these findings reveal subtle gender biases that may contribute to perpetuating gender-based science inequalities both in childhood and adulthood.

Temperature modifies trait-mediated infection outcomes in a Daphnia-fungal parasite system.

One major concern related to climate change is that elevated temperatures will drive increases in parasite outbreaks. Increasing temperature is known to alter host traits and host-parasite interactions, but we know relatively little about how these are connected mechanistically-that is, about how warmer temperatures impact the relationship between epidemiologically relevant host traits and infection outcomes. Here, we used a zooplankton-fungus (Daphnia dentifera-Metschnikowia bicuspidata) disease system to experimentally investigate how temperature impacted physical barriers to infection and cellular immune responses. We found that Daphnia reared at warmer temperatures had more robust physical barriers to infection but decreased cellular immune responses during the initial infection process. Infected hosts at warmer temperatures also suffered greater reductions in fecundity and lifespan. Furthermore, the relationship between a key trait-gut epithelium thickness, a physical barrier-and the likelihood of terminal infection reversed at warmer temperatures. Together, our results highlight the complex ways that temperatures can modulate host-parasite interactions and show that different defense components can have qualitatively different responses to warmer temperatures, highlighting the importance of considering key host traits when predicting disease dynamics in a warmer world. This article is part of the theme issue 'Infectious disease ecology and evolution in a changing world'.

Transgenerational plasticity in a zooplankton in response to elevated temperature and parasitism.

Organisms are increasingly facing multiple stressors, which can simultaneously interact to cause unpredictable impacts compared with a single stressor alone. Recent evidence suggests that phenotypic plasticity can allow for rapid responses to altered environments, including biotic and abiotic stressors, both within a generation and across generations (transgenerational plasticity). Parents can potentially "prime" their offspring to better cope with similar stressors or, alternatively, might produce offspring that are less fit because of energetic constraints. At present, it remains unclear exactly how biotic and abiotic stressors jointly mediate the responses of transgenerational plasticity and whether this plasticity is adaptive. Here, we test the effects of biotic and abiotic environmental changes on within- and transgenerational plasticity using a Daphnia-Metschnikowia zooplankton-fungal parasite system. By exposing parents and their offspring consecutively to the single and combined effects of elevated temperature and parasite infection, we showed that transgenerational plasticity induced by temperature and parasite stress influenced host fecundity and lifespan; offsprings of mothers who were exposed to one of the stressors were better able to tolerate elevated temperature, compared with the offspring of mothers who were exposed to neither or both stressors. Yet, the negative effects caused by parasite infection were much stronger, and this greater reduction in host fitness was not mitigated by transgenerational plasticity. We also showed that elevated temperature led to a lower average immune response, and that the relationship between immune response and lifetime fecundity reversed under elevated temperature: the daughters of exposed mothers showed decreased fecundity with increased hemocyte production at ambient temperature but the opposite relationship at elevated temperature. Together, our results highlight the need to address questions at the interface of multiple stressors and transgenerational plasticity and the importance of considering multiple fitness-associated traits when evaluating the adaptive value of transgenerational plasticity under changing environments.

HEMOGLOBIN C TRAIT PRESENTING WITH BILATERAL CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To report a case of bilateral sequential, central retinal vein occlusion (CRVO) in a man with newly diagnosed hemoglobin C trait. METHODS: A 67-year-old man presented with a one-month history of declining visual acuity. He was diagnosed with left CRVO. Bilateral temporal retinal ischemia and arteriovenous anastomoses on fluorescein angiography suggestive of sickle cell retinopathy prompted a systemic work-up. Hemoglobin electrophoresis revealed an underlying hemoglobin C trait. Six-months after his initial presentation, the patient developed symptomatic right CRVO. RESULTS: The initial left CRVO was complicated by optic disc swelling and macular edema. Intravitreal antiangiogenic therapy was initiated and the macular edema resolved. The left eye subsequently developed an epiretinal membrane which was surgically removed. Macular edema in the right eye also resolved after intravitreal antiangiogenic therapy. CONCLUSION: This is the first reported case of bilateral CRVO in a case of hemoglobin C trait. It is possible that erythrocyte inflexibility, caused by hemoglobin C-induced dehydration and crystallization, acted concomitantly with hypertension to produce occlusive microangiopathy. This case highlights the need for further investigation in patients presenting with central retinal vein occlusion, especially when bilateral, or when retinal angiography reveals bilateral pathology.

Rapidly Progressive Bilateral Vitreoretinal Lymphoma.

A 56-year-old male who presented with unilateral localized sub-retinal lesions suspicious for primary vitreoretinal lymphoma (PVRL) developed florid bilateral ocular involvement and was found to have lesions on MRI of the brain in a five-week period despite the absence of vitreous involvement during the entire course of his disease. His ocular lesions were monitored while on systemic treatment and an excellent clinical response was achieved. His central nervous system (CNS) lesions, however, continued to progress despite chemotherapy and whole-brain radiation. He died 12 months from his time of ocular diagnosis. To our knowledge, this case represents the most rapid progression of PVRL reported in the literature - from unilateral, localized lesions in the sub-retinal space to bilateral ocular involvement and identification of CNS involvement in a five-week period. This case highlights the potential for rapid ocular progression of PVRL stressing the need for early diagnosis. Therefore, we recommend prompt vitreous and, if necessary, sub-retinal biopsy in cases of suspected vitreoretinal lymphoma in addition to neuro-imaging. We emphasize the importance of coordination between pathologists, ophthalmologists, and oncologists for prompt, accurate diagnosis. Delay in diagnosis and treatment can result in rapid intraocular progression and central nervous system spread.

Transgenerational plasticity alters parasite fitness in changing environments.

Transgenerational plasticity can help organisms respond rapidly to changing environments. Most prior studies of transgenerational plasticity in host­parasite interactions have focused on the host, leaving us with a limited understanding of transgenerational plasticity of parasites. We tested whether exposure to elevated temperatures while spores are developing can modify the ability of those spores to infect new hosts, as well as the growth and virulence of the next generation of parasites in the new host. We exposed Daphnia dentifera to its naturally co-occurring fungal parasite Metschnikowia bicuspidata, rearing the parasite at cooler (20°C) or warmer (24°C) temperatures and then, factorially, using those spores to infect at 20 and 24°C. Infections by parasites reared at warmer past temperatures produced more mature spores, but only when the current infections were at cooler temperatures. Moreover, the percentage of mature spores was impacted by both rearing and current temperatures, and was highest for infections with spores reared in a warmer environment that infected hosts in a cooler environment. In contrast, virulence was influenced only by current temperatures. These results demonstrate transgenerational plasticity of parasites in response to temperature changes, with fitness impacts that are dependent on both past and current environments.

Persistent Subretinal Fluid Following Successful Rhegmatogenous Retinal Detachment Surgery.

PURPOSE: To provide an updated, critical summary of the literature on the topic of persistent subretinal fluid (PSF) following successful rhegmatogenous retinal detachment surgery. METHODS: Narrative literature review. RESULTS: PSF remains an insufficiently studied topic. Incidence rates vary significantly between reports, but pars plana vitrectomy seems associated with lower rates than buckle surgery. Multiple etiologies and risk factors have been proposed, none being conclusive. PSF gradually resolves in most cases which may be a lengthy process, often with no effect on potential final visual acuity. There is concern that some cases with PSF may sustain photoreceptor damage, retinal displacement, or retinal fold formation. There is no current evidence to support any treatment modality over observation in uncomplicated cases of PSF. CONCLUSION: Future large, well-controlled, prospective trials could help elucidate incidence rate, etiological factors, and sequelae of PSF, as well as the value of different interventions in its prevention and management.

Testing the effectiveness of the Developing Inclusive Youth program: A multisite randomized control trial.

The Developing Inclusive Youth program is a classroom-based, individually administered video tool that depicts peer-based social and racial exclusion, combined with teacher-led discussions. A multisite randomized control trial was implemented with 983 participants (502 females; 58.5% White, 41.5% Ethnic/racial minority; Mage  = 9.64 years) in 48 third-, fourth-, and fifth-grade classrooms across six schools. Children in the program were more likely to view interracial and same-race peer exclusion as wrong, associate positive traits with peers of different racial, ethnic, and gender backgrounds, and report play with peers from diverse backgrounds than were children in the control group. Many approaches are necessary to achieve antiracism in schools. This intervention is one component of this goal for developmental science.

Non-arteritic Anterior Ischemic Optic Neuropathy with Macular Star following COVID-19 Vaccination.

PURPOSE: To report a case of non-arteritic anterior ischemic optic neuropathy (NAAION) with macular star after receiving the second dose of SARS-CoV-2 vaccination. METHOD: Case report. OBSERVATION: A 51-year-old male presented with acute visual disturbances one day after the second dose of BNT162b2 mRNA SARS-CoV-2 vaccination. At presentation, best corrected visual acuity (BCVA) was 20/25 right eye (OD) and counting fingers at 3 feet left eye (OS). Anterior segment examination was normal in both eyes. Dilated fundoscopy was unremarkable OD, however, it disclosed optic nerve swelling and subretinal fluid OS. Patient was treated with a gradual tapering dose of oral prednisone over 1 month. At the five-week follow-up visit, optic disc swelling and subretinal fluid resolved with minimal improvement in BCVA to 20/400 OS. CONCLUSION: It is unclear whether COVID-19 vaccination was the triggering agent to the NAAION or just a coincidence, yet ophthalmologists should be aware of such a possible association.