Ionic Liquid Coating-Driven Nanoparticle Delivery to the Brain: Applications for NeuroHIV.

Delivering cargo to the central nervous system (CNS) remains a pharmacological challenge. For infectious diseases such as HIV, the CNS acts as a latent reservoir that is inadequately managed by systemic antiretrovirals (ARTs). ARTs thus cannot eradicate HIV, and given CNS infection, patients experience neurological deficits collectively referred to as "neuroHIV". Herein, the development of bioinspired ionic liquid-coated nanoparticles (IL-NPs) for in situ hitchhiking on red blood cells (RBCs) is reported, which enables 48% brain delivery of intracarotid arterial- infused cargo. Moreover, IL choline trans-2-hexenoate (CA2HA 1:2) demonstrates preferential accumulation in parenchymal microglia over endothelial cells post-delivery. This study further demonstrates successful loading of abacavir (ABC), an ART that is challenging to encapsulate, into IL-NPs, and verifies retention of antiviral efficacy in vitro. IL-NPs are not cytotoxic to primary human peripheral blood mononuclear cells (PBMCs) and the CA2HA 1:2 coating itself confers notable anti-viremic capacity. In addition, in vitro cell culture assays show markedly increased uptake of IL-NPs into neural cells compared to bare PLGA nanoparticles. This work debuts bioinspired ionic liquids as promising nanoparticle coatings to assist CNS biodistribution and has the potential to revolutionize the delivery of cargos (i.e., drugs, viral vectors) through compartmental barriers such as the blood-brain-barrier (BBB).

Selective Blood Cell Hitchhiking in Whole Blood with Ionic Liquid-Coated PLGA Nanoparticles to Redirect Biodistribution After Intravenous Injection.

Less than 5% of intravenously-injected nanoparticles (NPs) reach destined sites in the body due to opsonization and immune-based clearance in vascular circulation. By hitchhiking in situ onto specific blood components post-injection, NPs can selectively target tissue sites for unprecedentedly high drug delivery rates. Choline carboxylate ionic liquids (ILs) are biocompatible liquid salts <100X composed of bulky asymmetric cations and anions. This class of ILs has been previously shown to significantly extend circulation time and redirect biodistribution in BALB/c mice post-IV injection via hitchhiking on red blood cell (RBC) membranes. Herein, we synthesized & screened 60 choline carboxylic acid-based ILs to coat PLGA NPs and present the impact of structurally engineering the coordinated anion identity to selectively interface and hitchhike lymphocytes, monocytes, granulocytes, platelets, and RBCs in whole mouse blood for in situ targeted drug delivery. Furthermore, we find this nanoparticle platform to be biocompatible (non-cytotoxic), translate to human whole blood by resisting serum uptake and maintaining modest hitchhiking, and also significantly extend circulation retention over 24 hours in BALB/c healthy adult mice after IV injection. Because of their altered circulation profiles, we additionally observe dramatically different organ accumulation profiles compared to bare PLGA NPs. This study establishes an initial breakthrough platform for a modular and transformative targeting technology to hitchhike onto blood components with high efficacy and safety in the bloodstream post-IV administration.

Selective Near-Infrared Blood Detection Driven by Ionic Liquid-Dye-Albumin Nanointeractions.

Due to its abundance in blood, a great deal of research has been undertaken to develop efficient biosensors for serum albumin and provide insight into the interactions that take place between these biosensing molecules and the protein. Near-infrared (NIR, >700 nm) organic dyes have been shown to be effective biosensors of serum albumin, but their effectiveness is diminished in whole blood. Herein, it is shown that an NIR sulfonate indolizine-donor-based squaraine dye, SO3SQ, can be strengthened as a biosensor of albumin through the addition of biocompatible ionic liquids (ILs). Specifically, the IL choline glycolate (1:1), at a concentration of 160 mM, results in the enhanced fluorescence emission ("switch-on") of the dye in the presence of blood. The origin of the fluorescence enhancement was investigated via methods, including DLS, ITC, and molecular dynamics. Further, fluorescence measurements were conducted to see the impact the dye-IL system had on the fluorescence of the tryptophan residue of human serum albumin (HSA), as well as to determine its apparent association constants in relation to albumin. Circular dichroism (CD) spectroscopy was used to provide evidence that the dye-IL system does not alter the secondary structures of albumin or DNA. Our results suggest that the enhanced fluorescence of the dye in the presence of IL and blood is due to diversification of binding sites in albumin, controlled by the interaction of the IL-dye-albumin complex.

Long-duration monitoring and mass balance of PFAS at a wastewater treatment plant following the release of aqueous film-forming foam concentrate.

Approximately 760 liters (200 gallons) of first-generation, PFOS-dominant, Aqueous Film-Forming Foam (AFFF) concentrate entered the sanitary sewer after an accidental release at the Kalamazoo/Battle Creek International Airport and migrated 11.4 km to the Kalamazoo Water Reclamation Plant. Near-daily sampling of influent, effluent, and biosolids generated a high-frequency, long-duration dataset used to understand the transport and fate of accidental PFAS releases to wastewater treatment plants, identify AFFF concentrate composition, and perform a plant-wide PFOS mass balance. Monitored influent concentrations exhibited sharp PFOS declines after 7 days post-spill, yet effluent discharges remained elevated due to return activated sludge (RAS) recirculation, resulting in the exceedance of Michigan's Surface Water Quality Value for 46 days. Mass balance estimates indicate 1.292 kg PFOS entering the plant and 1.368 kg leaving. Effluent discharge and sorption to biosolids account for 55% and 45% of estimated PFOS outputs, respectively. Identification of AFFF formulation and reasonable agreement between computed influent mass and reported spill volume demonstrates effective isolation of the AFFF spill signal and increases confidence in the mass balance estimates. These findings and related considerations provide critical insight for performing PFAS mass balances and developing operational procedures for accidental spills that minimize PFAS releases to the environment.

Multifocal infantile hemangioma of the eyelid causing amblyopia requiring surgical resection.

Cutaneous vascular lesions in the pediatric population are rare and may represent a variety of localized and systemic diagnoses with diverse treatment protocols. We present a unique case of an infant with multiple cutaneous vascular lesions, initially diagnosed as congenital disseminated pyogenic granuloma based on histopathologic findings and later diagnosed as multifocal infantile hemangioma with extracutaneous hepatic involvement. The largest vascular lesion in our patient was on the left upper eyelid, which failed medical treatment and ultimately required surgical excision to prevent amblyopia progression.

Isolated globe rupture without concomitant eyelid laceration or orbital trauma following facial dog bite injury in a child.

PURPOSE: Facial dog bites often cause periorbital trauma; however, the globe is rarely damaged. Most globe injury following dog bites results from unusual circumstances and typically presents with concomitant periorbital and ocular adnexal injuries. OBSERVATIONS: The case presented is a rare presentation of isolated globe rupture without orbital trauma following facial dog bite in a child without history or evidence of decreased blink reflex, mental deficiency, or substance use. CONCLUSIONS AND IMPORTANCE: Ophthalmic investigation is warranted in all pediatric periorbital dog bite injuries, even in the setting of minimal or absent periorbital trauma. As additional blunt trauma to the globe in the immediate recovery period resulted in a second open globe injury, the critical importance of protective eyewear, activity restriction, and judicious corneal suture removal postoperatively following repair of open globe injury is discussed.

Acute Reconstruction of Periorbital Trauma Resulting in Eyelid Anterior Lamella Loss With Simultaneous Full-thickness Skin Grafting and Amniotic Membrane Grafting: A Case Report.

Complex facial lacerations are frequently encountered in the combat environment. Trauma with soft-tissue loss of the periorbital region offers particular challenges in terms of operative reconstruction. Cicatricial changes in the sub-acute phase can lead to eyelid malposition and lagophthalmos. The authors present a novel technique for acute reconstruction of periorbital trauma with eyelid soft-tissue loss with simultaneous full-thickness skin grafting and amniotic membrane grafting. The technique involves standard preparation of the surgical area of injury and infiltration with local anesthetic. Initially, the area of injury is copiously irrigated, and debridement of any necrotic tissue is accomplished. Amniotic membrane grafting is then performed over the defect. Approximately 2 mm × 2 mm full-thickness skin grafts are procured and distributed over the initial amniotic membrane graft. A second amniotic membrane graft is then secured over the skin graft-amniotic membrane graft complex with cyanoacrylate tissue adhesive. A bolstered suture tarsorrhaphy is performed to minimize tissue trauma during the healing process. The operative and postsurgical outcomes were assessed. The graft site healed well without cicatricial changes or lagophthalmos. Peripheral small papillomatous lesions did develop requiring excision for cosmesis, but ultimately the graft site demonstrated appropriate coverage and healthy re-epithelialization over the previous defect. This case demonstrates the viability of simultaneous full-thickness skin grafting with concomitant amniotic membrane grafting for the acute reconstruction of periorbital trauma with eyelid anterior lamella tissue loss. An excellent cosmetic and functional outcome was attained. By providing acute reconstruction, the risk of damage secondary to cicatricial periorbital changes may be avoided.

Rifle Blast Exacerbating Hearing Loss in a Patient Treated With Teprotumumab for Thyroid Eye Disease.

Teprotumumab is a promising new immunomodulatory therapy for thyroid eye disease. One unique adverse effect observed in clinical trials was hearing impairment; however, all adverse auditory effects in prior clinical trials resolved spontaneously after completion of teprotumumab therapy. The authors present a case of a patient on teprotumumab for thyroid eye disease who experienced sustained hearing loss secondary to shooting a rifle without ear protection. In this case, it is suspected the teprotumumab infusions resulted in increased susceptibility of the inner ear hair cells to noise-induced trauma secondary to IGF-IR inhibition. Specific ear protection protocols may need to be implemented in the future for patients on teprotumumab therapy to prevent sustained hearing loss, especially for susceptible patient populations.

Pain Control Following Photorefractive Keratectomy: A Prospective Clinical Trial Comparing Codeine Versus Oxycodone for the Management of Postoperative Pain.

PURPOSE: To compare the efficacy of oral codeine plus acetaminophen versus oxycodone plus acetaminophen for severe pain control following photorefractive keratectomy (PRK). METHODS: This single-center trial randomized 200 patients to receive codeine 30 mg/acetaminophen 325 mg (codeine group) or oxycodone 5 mg/acetaminophen 325 mg (oxycodone group)every 4 hours as needed for severe pain for 4 days following PRK. Patients recorded postoperative pain, tablet consumption, and tetracaine use. Patients were monitored at postoperative 1 day, 1 week, and 1, 3, and 6 months for visual acuity and follow-up. Study outcomes were mean postoperative pain, treatment and tetracaine use, and visual acuity. RESULTS: Analysis of 197 patients who completed the trial (97 codeine group and 100 oxycodone group) showed mean pain scores were lower in the codeine group throughout the intervention period. Mean pain scores were higher in the oxycodone group than the codeine group on postoperative days 2 and 4 (P = .017 and P = .034, respectively). The oxycodone group consumed more tablets than the codeine group, with a difference on postoperative day 2 (P = .019), and used a greater number of tetracaine drops (P = .015). Repeated measures analysis of variance showed significant improvement in visual acuity in both groups with no difference in visual outcomes (P = .81). CONCLUSIONS: Codeine/acetaminophen is as effective and safe as oxycodone/acetaminophen for pain control following PRK, with no clinical difference in overall pain control and long-term visual outcomes. This implies that treating postoperative pain after PRK with a Schedule III opioid (codeine) is effective and potentially decreases the risk of misuse by a higher regulated Schedule II opioid (oxycodone), lowering the potential for abuse and dependence. [J Refract Surg. 2021;37(9):582-589.].

Bacillus cereus panophthalmitis with delayed dermis fat graft.

Bacillus cereus panophthalmitis secondary to intravenous drug use typically leads to an explosive ocular and/or orbital infection. Though several cases of B. cereus panophthalmitis secondary to intravenous drug use have been reported, no clear consensus exists regarding preferred surgical technique and orbital reconstruction. Additionally, no cases describe delayed dermis fat graft placement following enucleation for such cases. Herein, a case of B. cereus panophthalmitis secondary to intravenous methamphetamine use is presented, where delayed dermis fat graft placement following enucleation and orbital washout provided an excellent functional and cosmetic outcome.

Disseminated Coccidioidomycosis With Orbital Osteomyelitis and Periorbital Abscess.

Coccidioidomycosis osteomyelitis involving the orbital bones is exceedingly rare and is often misdiagnosed initially as other inflammatory or infectious conditions. No clear guidelines currently exist regarding appropriate management. The authors present an atypical presentation of disseminated coccidioidomycosis in an immunocompetent child with frontal bone superotemporal orbital rim osteomyelitis and associated periorbital abscess, successfully managed with surgical debridement through an upper eyelid crease incision.

Pars Plana Vitrectomy following Traumatic Ocular Injury and Initial Globe Repair: A Retrospective Analysis of Clinical Outcomes.

INTRODUCTION: Penetrating and perforating ocular trauma are often devastating and may lead to complete visual loss in the traumatized eye and subsequent compromise of the fellow eye. A significant proportion of traumatic injuries are complex, often requiring vitreoretinal intervention to preserve vision. A retrospective analysis at a level 1 trauma center was performed to evaluate the time course, incidence, and outcomes following pars plana vitrectomy (PPV) after traumatic ocular injury and initial globe repair. MATERIALS AND METHODS: Eyes that underwent open globe repair following ocular trauma at Brooke Army Medical Center, between January 1, 2014 and December 30, 2016 were analyzed. Specific factors evaluated include mechanism of injury, defect size and complexity, ocular trauma score, zone of injury, associated orbital trauma, and time from injury to surgical intervention. A subset analysis was conducted specifically on eyes requiring subsequent PPV for vision preservation because of vitreoretinal disease. Surgical outcomes, time to secondary intervention, and complication rates were then assessed. RESULTS: In total, 70 eyes requiring open globe repair were examined, with 43 having undergone PPV. Average and median time to vitrectomy were 18.8 and 8 days, respectively. Eyes that underwent PPV were more likely to have an afferent papillary defect, vitreous hemorrhage, intraocular foreign body, and retinal detachment at the time of initial injury (although the latter two factors were not statistically significant), and were more likely to receive penetrating keratoplasty. Proliferative vitreoretinopathy occurred in 37.2% of eyes that underwent PPV, versus 3.7% of those that did not (P = 0.0013). Timing of PPV (i.e., before or after 14 days) had no statistically significant effect on the rate of PVR (Table I). Eyes that underwent PPV showed an improvement of visual acuity from average 2.5 logMAR following initial injury to 1.5 logMAR 6 months after PPV, equivalent to 18.7 Early Treatment Diabetic Retinopathy Study (ETDRS) letters gained, versus 37.7 ETDRS letters gained in eyes without PPV. Among PPV eyes, early repair (<14 days) was associated with greater improvement in visual acuity. CONCLUSION: Overall, patients requiring PPV following open globe repair generally had more severe injuries and worse 6-month postoperative visual acuity. Patients who underwent more expedited vitrectomy showed greater improvement in visual acuity as measured by ETDRS letters gained.

Amniotic membrane graft in a recurrent re-fusing temporal tarsorrhaphy: a case report.

Amniotic membrane grafts (AMGs) are commonly used to treat a variety of ophthalmologic conditions. Complications exist with permanent tarsorrhaphies, including the risk of re-fusion following tarsorrhaphy separation. We report a novel application of amniotic graft in lieu of skin grafts to protect the exposed marginal surface during the initial re-epithelialization period following release of a permanent tarsorrhaphy. We present a 24-year-old man who sustained an 80% total body surface area burn from a motor vehicle accident 16 months prior to presentation at our Oculoplastic service for evaluation of residual lagophthalmos. His original permanent tarsorrhaphies were removed; however, re-fusion occurred temporally in both sides. During a second attempt, AMGs were secured over the eyelid margins, leading to a successful tarsorrhaphy takedown without re-fusion. Periocular burn injuries present particular challenges, as cicatricial changes continue to evolve and viable skin graft areas diminish with each successive graft. In the setting of recurrent auto-tarsorrhaphy, the AMG has shown to be a viable alternative to standard skin grafting. This case demonstrates excellent results in a skin graft sparing procedure that is effective and efficient. Amniotic membrane grafting reduces morbidity by foregoing skin graft donor sites and can achieve similar functional and cosmetic results to standard skin grafting with reduced overall surgical time. As such, AMGs have the potential to supplant standard skin grafting in cases of recurrent auto-tarsorrhaphy, particularly in the setting of diminished available healthy skin tissue.

Prevalence of Myopia in Newly Enlisted Airmen at Joint Base San Antonio.

PURPOSE: Myopia is the most common type of refractive error and can lead to significant visual impairment. The frequency of myopia has risen considerably, and its worldwide prevalence is expected to continue to increase. Myopia is present in an increasing number of Basic Military Trainees upon entry into the United States Air Force. This study aims to demonstrate the prevalence of myopia in newly enlisted members of the United States Air Force. METHODS: This study is an institutional retrospective analysis of data collected from the United States Air Force candidates entering Basic Military Training from 1 January 2017 to 31 March 2017. A random selection of 767 Air Force Basic Military Trainees were included in the analysis, yielding 1534 total eyes. The primary outcome measure studied is the mean spherical equivalent (MSE) of participants at initial evaluation. A linear regression analysis was performed to identify any associations related to participant demographics. RESULTS: Of participants analyzed, 45% had myopia (<-0.5 D) and 2% high myopia (<-6.0 D) upon entry into the United States Air Force. Myopia was found to be associated with male gender (p = <0.001). CONCLUSION: Myopia is present in a significant proportion of Basic Military Trainees upon entry into the United States Air Force, regardless of age, gender, race, or ethnicity. The prevalence of myopia presented is higher than previous studies, reflecting a continued trend towards increased myopia prevalence worldwide.

Collaborating constructively for sustainable biotechnology.

Tackling the pressing sustainability needs of society will require the development and application of new technologies. Biotechnology, emboldened by recent advances in synthetic biology, offers to generate sustainable biologically-based routes to chemicals and materials as alternatives to fossil-derived incumbents. Yet, the sustainability potential of biotechnology is not without trade-offs. Here, we probe this capacity for sustainability for the case of bio-based nylon using both deliberative and analytical approaches within a framework of Constructive Sustainability Assessment. We highlight the potential for life cycle CO2 and N2O savings with bio-based processes, but report mixed results in other environmental and social impact categories. Importantly, we demonstrate how this knowledge can be generated collaboratively and constructively within companies at an early stage to anticipate consequences and to inform the modification of designs and applications. Application of the approach demonstrated here provides an avenue for technological actors to better understand and become responsive to the sustainability implications of their products, systems and actions.

Patterns and prognosis of commotio retinae in orbital wall fractures.

PURPOSE: Orbital wall fractures are a significant cause of ocular injury in trauma and are associated with posterior segment pathology. This study aims to characterize patterns and prognosis of commotio retinae following orbital wall fracture. METHODS: This study is a retrospective analysis of 294 orbital wall fractures diagnosed by computed tomography imaging from August 2015 to October 2016 at a Level 1 trauma center. Dilated funduscopic exams were assessed for acute posterior segment pathology, focusing specifically on commotio retinae (N = 38). These were compared with patients with no traumatic retinal findings (N = 253) to indicate statistically significant differences in the mechanism of injury, fracture pattern, subjective symptoms, radiologic and exam findings, and acute interventions. RESULTS: Commotio was most commonly associated with assault (60.5%, p = 0.004) in a younger patient population, whereas normal retinal exams were more likely after falls from standing (24.1%, p = 0.022). Half of all commotio was found inferiorly and most commonly occurred in medial or inferior wall fracture. Patients with commotio were more likely to have motility deficits (29.7%, p = 0.049) with clinical evidence of entrapment (13.2%, p < 0.001), requiring acute operative repair (15.8%, p = 0.005). Inferior wall fracture was associated with 19.4% surgical intervention in commotio as compared with those with normal funduscopic exams (6.1%, p = 0.012). All patients with follow-up had resolution of commotio and best-corrected visual acuity of 20/25 or better. CONCLUSION: Retinal pathology is not infrequent in orbital wall fractures. Inferior wall fracture was associated with 19.4% surgical intervention in commotio as compared to those with normal funduscopic exams (6.1%, p = 0.012). A high index of suspicion and thorough investigation is warranted in evaluating these patients.

Enucleations and Eviscerations for Combat Ocular Trauma Performed During Operations Iraqi and Enduring Freedom: 2001 to 2011.

PURPOSE: To describe the demographics and clinical outcomes of patients who underwent posttraumatic enucleation or evisceration during Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF) from 2001 to 2011. METHODS: The Walter Reed Ocular Trauma Database is a retrospective case series of US Servicemembers and Department of Defense civilians who had combat ocular injuries in OIF and OEF. Data regarding posttraumatic enucleations and eviscerations performed during OIF and OEF were extracted. The main outcomes analyzed were the number of enucleations and eviscerations performed, location of the surgery, laterality, and graft type. The secondary outcome measures included: mechanism of injury and Ocular Trauma Score classification. RESULTS: One hundred nine enucleations and eviscerations were performed on the 890 eyes (12.24%). Sixty-three (57.80%) primary enucleations, 36 (33.03%) secondary enucleations, 5 (4.59%) postretinal detachment repair enucleations, and 5 (4.59%) primary eviscerations were completed. The surgeries were completed at a combat support hospital (57; 52.3%), or Walter Reed Army Medical Center (49; 45.0%). All surgeries were unilateral except in 2 patients. The most common graft type used was silicone (n = 56; 51.38%). Improvised explosive devices caused 76 (69.72%) eye injuries. Ocular Trauma Score were recorded as 56 (51.38%) between 0 and 44, 44 (40.37%) between 45 and 65, and unknown in 9 (8.26%). CONCLUSION: Posttraumatic enucleation or evisceration due to devastating ocular trauma is required in about 15% of ophthalmic patients in modern combat trauma. The psychosocial impact on veterans who have required an enucleation or evisceration from combat trauma has been poorly studied and requires further review.