Search

Osteosarcoma is the most common primary bone cancer, occurring frequently in children and young adults. Patients are treated with surgery and multi‐agent chemotherapy, and despite the introduction of mifamurtide in 2011, there has been little improvement in survival for decades. 3‐dimensional models offer the potential to understand the complexity of the osteosarcoma tumor microenvironment and aid in developing new treatment approaches. An osteosarcoma 3D bone core model was developed using human trabecular bone and the chorioallantoic membrane (CAM), to form a functioning vasculature. A tri‐culture of cells, stromal cells, macrophages, and the Saos‐2 osteosarcoma cell line, were implanted into this model to simulate components of the tumor microenvironment, and mifamurtide was tested in this context. Immunohistochemistry and micro‐CT were performed to assess phenotypic and structural effects of implantation. Successful integration and angiogenesis of the bone cores were observed after incubation on the CAM. The 3D bone model also showed similar characteristics to osteosarcoma patient samples including CD68 and CD105 expression. Incubating bone cores with mifamurtide induced a reduction of cellular markers and an increase in bone volume. This 3D bone core model has the potential to investigate osteosarcoma tumor microenvironment and provides a representative model for evaluation of novel therapies. [ABSTRACT FROM AUTHOR]

OBJECTIVE The primary aims were to provide descriptive data on systemic and ocular complications associated with the treatment of equine keratomycosis. The secondary aims were to determine if complication rates differ between treatment types or are related to surgical and anesthetic factors. METHODS The study was a retrospective evaluation of 126 cases between 2004 and 2020 with confirmed fungal infection and recorded incidence of complications during hospitalization and surgical intervention if pursued. Additional information recorded included the size of the donor graft if utilized, time under general anesthesia, and prescribed medications. Fisher exact and %2 tests were used to evaluatecomplication frequency differences. Logistic regression models determined the effects of donor graft size, anesthesia time, and duration of hospitalization on complication rates. RESULTS Hypercreatininemia followed by colic were the most frequent systemic complications in the medical treatment group. Colic and conjunctival graft dehiscence were the most frequent systemic and ocular complications in all surgery treatment groups, respectively. The frequency of systemic complications did not vary between treatment groups, although colic rates were significantly higher following general anesthesia. All colic cases were resolved with supportive care. Donor graft size, anesthesia time, and duration of hospitalization did not impact complication frequency. The mainstays of medical therapy included topical fluoroquinolones, topical voriconazole, topical atropine, oral NSAIDS, and oral gastroprotectants. CONCLUSIONS Treatment of keratomycosis is associated with a range of complications. Colic remains a significant risk, with increased frequency reported following general anesthesia. CLINICAL RELEVANCE Reporting common complicationsassociated with treatmentaids in decision-making forequinecliniciansand owners. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine clinical outcome, treatment costs, and hospitalization duration in horses treated for keratomycosis and identify ophthalmic examination and diagnostic results associated with these outcomes. METHODS This was a retrospective study of 126 equine keratomycosis cases between 2004 and 2020 with fungal infection confirmed on cytology, culture, and/or histopathology and a minimum of 1-month follow-up. Details of the ophthalmic examination, diagnostic test results, and treatment and cost outcomes were recorded. Outcomes of interest were analyzed by treatment type. The relationship of patient and diagnostic test variables to the outcomes of interest was determined via logistic and linear regression models. RESULTS Globe retention and positive visual outcome occurred in 82.5% and 78.9% of medically and 88.4% and 85.5% of surgically treated cases, respectively. While not statistically significant, there were more positive clinical outcomes with surgery; in recent years, the globe and vision were preserved in 94.7% of cases following penetrating keratoplasty. The choice to pursue surgery was related to lesion depth. Medical treatment was associated with statistically shorter hospitalization times and lower total and hospitalization invoices compared to all surgical treatments. Diagnosis of stromal abscess was associated with higher total invoice and longer hospitalization times compared to ulcerative keratomycosis, although clinical outcomes were similar. CONCLUSIONS Overall positive clinical outcomes were achieved despite the severity of the disease in many cases, highlighting the need for appropriate treatment selection based on clinical presentation. CLINICAL RELEVANCE Expanding knowledge of clinical decision-making, treatment options, and associated clinical and financial outcomes may further improve outcomes for equine keratomycosis patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine whether novel pre- and postsurgical ultrasound biomicroscopy (UBM) measurements of the canine ciliary cleft (CC) are associated with postoperative ocular hypertension (POH) following cataract surgery and to explore the relationship between intraocular pressure and CC UBM measurements. METHODS Following pharmacologic mydriasis, UBM images were obtained from 31 client-owned dogs before elective cataract surgery, immediately postsurgery, and 4 to 6 hours following surgery or while experiencing POH 2 25 mm Hg Presurgery and the pre- to postsurgery change in CC measurements were assessed for association with POH using individual mixed-effects logistic regression models and forward variable selection models. Linear mixed-effects models were used to evaluate the relationship of intraocular pressure to UBM measurements within the same eye across multiple time points. RESULTS Presurgical measurements were not predictive of POH development. An increase in pectinate ligament distance and CC area from presurgical baseline to immediate postsurgical measurement was associated with reduced odds of developing POH, while increasing CC length (from apex to mid point on the pectinate ligament) from pre- to postsurgery and immature cataracts was associated with increased odds of POH. CONCLUSIONS The change in CC morphology following cataract surgery appears more impactful in the development of POH than individual variations in presurgery CC measurements. Several changes in the CC dimensions following surgery appear associated with POH risk. CLINICAL RELEVANCE This understanding of a potential mechanism of POH development opens new avenues for researching preventative measures associated with modifying surgical techniques to influence CC morphology following cataract surgery. [ABSTRACT FROM AUTHOR]

Background: There is very little information on the experiences of transgender and gender diverse (TGD) youth with cancer. Aims: To examine clinical characteristics and care trajectories of TGD youth a history of cancer. Methods: This case series reviewed records of 2790 pediatric gender clinic patients seen between 2007 and 2022 to identify 14 with a history of cancer diagnosis. Demographics, clinical characteristics, disclosure of gender identity to oncology teams, oncology teams' use of correct names and pronouns, documented interprofessional communication between gender health and oncology teams, and course of medical gender affirmation were reviewed. Results: Of 14 TGD youth with a history of cancer, 11 (78.6%) were diagnosed prior to presenting to the gender clinic (mean [SD] = 8.2 [4.7] years), three following initial gender care (mean [SD] = 1.1 [0.2] years). Six (42.9%) patients were engaged in annual survivorship care when presenting, and 8 (57.1%) were seen concurrently by both clinics. Nine (64.3%) patients had documented communication between teams. Three‐quarters of patients who were seen concurrently by both clinics had documented interprofessional communication. Eight (57.1%) patients received gender affirming hormones, after cancer treatment concluded. Conclusion: TGD youth with cancer experiences present for gender affirming care and merit clinical attention. There was variability in (1) patients' and families' disclosure of TGD identities to oncology teams, (2) whether oncology documentation consistently used patients' correct name and pronouns, and (3) whether there was documented interprofessional consultation between teams. There is need for ongoing improvement in research and clinical protocols for TGD youth with cancer. [ABSTRACT FROM AUTHOR]

Hypertension (HTN) impacts almost half of adults, predisposing them to cardiovascular disease and renal damage. Salt-sensitive HTN (SSHTN) and angiotensin II (A2)-induced HTN (A2HTN) both involve immune system activation and renal innate immune cell infiltration. Subpopulations of activated [Cluster of differentiation 38 (CD38)] innate immune cells, such as macrophages and dendritic cells (DCs), play distinct roles in modulating renal function and blood pressure. It is unknown how these cells become CD38+ or which subtypes are pro-hypertensive. When bone marrow-derived monocytes (BMDMs) were grown in granulocyte-macrophage colony stimulating factor (GM-CSF) and treated with salt or A2, CD38+ macrophages and CD38+ DCs increased. The adoptive transfer of GM-CSF-primed BMDMs into mice with either SSHTN or A2HTN increased renal CD38+ macrophages and CD38+ DCs. Flow cytometry revealed increased renal M1 macrophages and type-2 conventional DCs (cDC2s), along with their CD38+ counterparts, in mice with either SSHTN or A2HTN. These results were replicable in vitro. Either salt or A2 treatment of GM-CSF-primed BMDMs significantly increased bone marrow-derived (BMD)-M1 macrophages, CD38+ BMD-M1 macrophages, BMD-cDC2s, and CD38+ BMD-cDC2s. Overall, these data suggest that GM-CSF is necessary for the salt or A2 induction of CD38+ innate immune cells, and that CD38 distinguishes pro-hypertensive immune cells. Further investigation of CD38+ M1 macrophages and CD38+ cDC2s could provide new therapeutic targets for both SSHTN and A2HTN. [ABSTRACT FROM AUTHOR]

Salt-sensitive hypertension (SSHTN) is associated with M1 macrophage polarization and inflammatory responses, leading to inflammation-associated lymphangiogenesis and functional impairment across multiple organs, including kidneys and gonads. However, it remains unclear whether promoting M2 macrophage polarization can alleviate the hypertension, inflammation, and end organ damage in mice with salt sensitive hypertension (SSHTN). Male and female mice were made hypertensive by administering nitro-L-arginine methyl ester hydrochloride (L-NAME; 0.5 mg/ml) for 2 weeks in the drinking water, followed by a 2-week interval without any treatments, and a subsequent high salt diet for 3 weeks (SSHTN). AVE0991 (AVE) was intraperitoneally administered concurrently with the high salt diet. Control mice were provided standard diet and tap water. AVE treatment significantly attenuated BP and inflammation in mice with SSHTN. Notably, AVE promoted M2 macrophage polarization, decreased pro-inflammatory immune cell populations, and improved function in renal and gonadal tissues of mice with SSHTN. Additionally, AVE decreased lymphangiogenesis in the kidneys and testes of male SSHTN mice and the ovaries of female SSHTN mice. These findings highlight the effectiveness of AVE in mitigating SSHTN-induced elevated BP, inflammation, and end organ damage by promoting M2 macrophage polarization and suppressing pro-inflammatory immune responses. Targeting macrophage polarization emerges as a promising therapeutic approach for alleviating inflammation and organ damage in SSHTN. Further studies are warranted to elucidate the precise mechanisms underlying AVE-mediated effects and to assess its clinical potential in managing SSHTN. [ABSTRACT FROM AUTHOR]

We reported that salt-sensitive hypertension (SSHTN) is associated with increased pro-inflammatory immune cells, inflammation, and inflammation-associated lymphangiogenesis in the kidneys and gonads of male and female mice. However, it is unknown whether these adverse end organ effects result from increased blood pressure (BP), elevated levels of salt, or both. We hypothesized that pharmaceutically lowering BP would not fully alleviate the renal and gonadal immune cell accumulation, inflammation, and lymphangiogenesis associated with SSHTN. SSHTN was induced in male and female C57BL6/J mice by administering nitro-L-arginine methyl ester hydrochloride (L-NAME; 0.5 mg/ml) in their drinking water for 2 weeks, followed by a 2-week washout period. Subsequently, the mice received a 3-week 4% high salt diet (SSHTN). The treatment group underwent the same SSHTN induction protocol but received hydralazine (HYD; 250 mg/L) in their drinking water during the diet phase (SSHTN+HYD). Control mice received tap water and a standard diet for 7 weeks. In addition to decreasing systolic BP, HYD treatment generally decreased pro-inflammatory immune cells and inflammation in the kidneys and gonads of SSHTN mice. Furthermore, the decrease in BP partially alleviated elevated renal and gonadal lymphatics and improved renal and gonadal function in mice with SSHTN. These data demonstrate that high systemic pressure and salt differentially act on end organ immune cells, contributing to the broader understanding of how BP and salt intake collectively shape immune responses and highlight implications for targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Author(s): Markus Einzinger [sup.1] , Tony Wu [sup.1] , Julia F. Kompalla [sup.1] , Hannah L. Smith [sup.2] , Collin F. Perkinson [sup.1] , Lea Nienhaus [sup.1] , Sarah Wieghold [...], Silicon dominates contemporary solar cell technologies.sup.1. But when absorbing photons, silicon (like other semiconductors) wastes energy in excess of its bandgap.sup.2. Reducing these thermalization losses and enabling better sensitivity to light is possible by sensitizing the silicon solar cell using singlet exciton fission, in which two excited states with triplet spin character (triplet excitons) are generated from a photoexcited state of higher energy with singlet spin character (a singlet exciton).sup.3-5. Singlet exciton fission in the molecular semiconductor tetracene is known to generate triplet excitons that are energetically matched to the silicon bandgap.sup.6-8. When the triplet excitons are transferred to silicon they create additional electron-hole pairs, promising to increase cell efficiencies from the single-junction limit of 29 per cent to as high as 35 per cent.sup.9. Here we reduce the thickness of the protective hafnium oxynitride layer at the surface of a silicon solar cell to just eight angstroms, using electric-field-effect passivation to enable the efficient energy transfer of the triplet excitons formed in the tetracene. The maximum combined yield of the fission in tetracene and the energy transfer to silicon is around 133 per cent, establishing the potential of singlet exciton fission to increase the efficiencies of silicon solar cells and reduce the cost of the energy that they generate. A silicon and tetracene solar cell employing singlet fission uses an eight-angstrom-thick hafnium oxynitride interlayer to promote efficient triplet transfer, increasing the efficiency of the cell.

Objective: The objective of the study was to determine the effect of gentamicin on CD3+ T‐lymphocyte proliferation and cell viability using an in vitro cell culture model as a means of investigating the mechanism of action of low‐dose intravitreal gentamicin injection. Animals Studied: Three adult horses with no evidence of ophthalmic or systemic disease. Procedure: Peripheral blood lymphocytes were treated with gentamicin at concentrations 37.5 μg/mL, 112.5 μg/mL, 187 μg/mL, 375 μg/mL, or 750 μg/mL then stimulated to proliferate with concanavalin A (ConA). 4′,6‐diamidino‐2‐phenylindole (DAPI) and carboxyfluoroscein succinimidyl ester (CSFE) were used as markers of cell viability and cell proliferation, respectively. Following 5‐day culture, live cell counts and CSFE fluorescent intensity data were collected via automated cell count and flow cytometry. The experimental design was duplicated using preservative‐free gentamicin and a proprietary brand formulation. Statistical analysis was performed using two‐way ANOVA with Tukey's multiple comparison test. Results: No statistically significant comparisons in CD3+ T‐lymphocyte live cell counts and geometric mean fluorescent intensity of CSFE were identified between gentamicin concentrations or formulations. Conclusions: Gentamicin had no effect on equine peripheral blood CD3+ T‐lymphocyte cell viability and proliferation in concentrations ranging from "safe" to "retinotoxic" in relation to intravitreal injection volumes. Low‐dose intravitreal gentamicin may not suppress the Th1‐ and Th17‐mediated immune response. [ABSTRACT FROM AUTHOR]

MΦs display remarkable plasticity and the ability to activate diverse responses to a host of intracellular and external stimuli. Despite extensive characterization of M1 MΦs and a broad set of M2 MΦs, comprehensive characterization of functional phenotype and associated metabotype driving this diverse MΦ activation remains. Herein, an ex vivo model was utilized to produce 6 MΦ functional phenotypes. Isolated CD14+ PBMCs were differentiated into resting M0 MΦs, and then polarized into M1 (IFN‐γ/LPS), M2a (IL‐4/IL‐13), M2b (IC/LPS), M2c (IL‐10), and M2d (IL‐6/LIF) MΦs. The MΦs were profiled using a bioanalyte matrix of 4 cell surface markers, ∼50 secreted proteins, ∼800 expressed myeloid genes, and ∼450 identified metabolites relative to M0 MΦs. Signal protein and expressed gene profiles grouped the MΦs into inflammatory (M1 and M2b) and wound resolution (M2a, M2c, and M2d) phenotypes; however, each had a unique metabolic profile. While both M1 and M2b MΦs shared metabotype profiles consistent with an inflammatory signature; key differences were observed in the TCA cycle, FAO, and OXPHOS. Additionally, M2a, M2c, and M2d MΦs all profiled as tissue repair MΦs; however, metabotype differences were observed in multiple pathways including hexosamine, polyamine, and fatty acid metabolism. These metabolic and other key functional distinctions suggest phagocytic and proliferative functions for M2a MΦs, and angiogenesis and ECM assembly capabilities for M2b, M2c, and M2d MΦs. By integrating metabolomics into a systems analysis of MΦ phenotypes, we provide the most comprehensive map of MΦ diversity to date, along with the global metabolic shifts that correlate to MΦ functional plasticity in these phenotypes. [ABSTRACT FROM AUTHOR]