Multiresonant Nonlocal Metasurfaces.

Optical metasurfaces supporting localized resonances have become a versatile platform for shaping the wavefront of light, but their low quality (Q-) factor modes inevitably modify the wavefront over extended momentum and frequency space, resulting in limited spectral and angular control. In contrast, periodic nonlocal metasurfaces have been providing great flexibility for both spectral and angular selectivity but with limited spatial control. Here, we introduce multiresonant nonlocal metasurfaces capable of shaping the spatial properties of light using several resonances with widely disparate Q-factors. In contrast to previous designs, the narrowband resonant transmission punctuates a broadband resonant reflection window enabled by a highly symmetric array, achieving simultaneous spectral filtering and wavefront shaping in the transmission mode. Through rationally designed perturbations, we realize nonlocal flat lenses suitable as compact band-pass imaging devices, ideally suited for microscopy. We further employ modified topology optimization to demonstrate high-quality-factor metagratings for extreme wavefront transformations with large efficiency.

Same-day discharge robot-assisted laparoscopic prostatectomy: feasibility, safety and patient experience.

OBJECTIVES: To report a single centre's experience of the feasibility, safety and patient acceptability of same-day discharge robot-assisted laparoscopic prostatectomy (RALP). SUBJECTS/PATIENTS AND METHODS: Between June 2015 and December 2021, a total of 180 pre-selected consecutive patients underwent RALP with the intention to discharge on the same day as surgery. Cases were performed by two surgeons. An enhanced recovery after surgery (ERAS) programme was used. The feasibility of same-day discharge was analysed, along with the complication rate, oncological outcomes, and postoperative patient experience. RESULTS: Of 180 patients, 169 (93.8%) were successfully discharged on the same day as surgery. The median (range) age was 63 ( 44-74) years. The median (range) console time was 97 (61-256) min and blood loss was 200 (20-800) mL. The resection specimen pathology results were: pT2 69.4%, pT3a 24.4% and pT3b 6.5%. With regard to Gleason Grade Group (GGG), 25.9% had GGG 1, 65.7% had GGG 2-3 and 8.4% had GGG 4-5 disease. Positive surgical margins were present in 25 cases (14.7%), 18 (15.5%) of which occurred in pT2 cases, and seven (13.4%) in pT3 cases. There were no early (<90 days) biochemical relapses (defined as prostate-specific antigen level >0.2 ng/mL). The 30-day readmission rate was 3%. A total of 13 early (0-30 days) complications were observed, five of which were Clavien-Dindo grade ≥3, however, none of these would have been avoided had the patient remained in hospital on the first postoperative night. Of 121 consecutive patients, 107 (88%) returned a satisfaction questionnaire, and 92% of responders stated they preferred recovery at home, with 94% stating they felt ready to go home. CONCLUSION: Robot-assisted laparoscopic prostatectomy combined with an ERAS programme allows patients to be safely discharged home on the same day of their surgery. This is a feasible option, well-liked by patients, with morbidity and oncological outcomes similar to non-day-case or 23 h stay RALP.

Loss-of-learning and the post-Covid recovery in low-income countries.

We analyze the medium-term macroeconomic impact of the Covid-19 pandemic and associated lock-down measures on low-income countries. We focus on the impact of the degradation of health and human capital caused by the pandemic and its aftermath, exploring the trade-offs between rebuilding human capital and the recovery of livelihoods and macroeconomic sustainability. A dynamic general equilibrium model is calibrated to reflect the structural characteristics of vulnerable low-income countries and to replicate key dimensions of the Covid-19 shock. We show that absent significant and sustained external financing, the persistence of loss-of-learning effects on labor productivity is likely to make the post-Covid recovery more attenuated and more expensive than many contemporary analysis suggests.

Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS).

PURPOSE: The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known. MATERIALS AND METHODS: We queried the U.S. Food and Drug Administration Adverse Event Reporting System, a retrospective, pharmacovigilance database, for cardiovascular adverse event reports in men with prostate cancer receiving gonadotropin releasing hormone (GnRH) agonists, GnRH antagonists, androgen receptor antagonists, and/or androgen synthesis inhibitors from January 2000 to April 2020. RESULTS: Cardiovascular adverse events accounted for 6,231 reports (12.6%) on hormone monotherapy and 1,793 reports (26.1%) on combination therapy. Arterial vascular events were reported most commonly, followed by arrhythmias, heart failure, and venous thromboembolism. Compared to GnRH agonists, GnRH antagonists were associated with fewer cardiovascular adverse event reports as monotherapy (adjusted reporting odds ratio [ROR]=0.70 [95% CI 0.59-0.84], p <0.001) and as combination therapy (ROR=0.47 [0.34-0.67], p <0.0001), driven by reductions in arterial vascular events. Second generation androgen receptor antagonists and abiraterone were associated with more reports of hypertension requiring hospitalization (ROR=1.21 [1.03-1.41], p=0.02 and ROR=1.19 [1.01-1.40], p=0.03, respectively), and more heart failure events when used in combination with GnRH antagonists (ROR=2.79 [1.30-6.01], p=0.009 and ROR=2.57 [1.12-5.86], p=0.03). CONCLUSIONS: In this retrospective analysis of a pharmacovigilance database, arterial vascular events were the most commonly reported cardiovascular adverse events in men on hormone therapy for prostate cancer. GnRH antagonists were associated with fewer reports of overall cardiovascular events and arterial vascular events than GnRH agonists. Additional study is needed to identify optimal strategies to reduce cardiovascular morbidity among men with prostate cancer receiving hormone therapy.

Cardiovascular Toxicities of Androgen Deprivation Therapy.

OPINION STATEMENT: Prostate cancer is the second leading cause of cancer death in men, and cardiovascular disease is the number one cause of death in patients with prostate cancer. Androgen deprivation therapy, the cornerstone of prostate cancer treatment, has been associated with adverse cardiovascular events. Emerging data supports decreased cardiovascular risk of gonadotropin releasing hormone (GnRH) antagonists compared to agonists. Ongoing clinical trials are assessing the relative safety of different modalities of androgen deprivation therapy. Racial disparities in cardiovascular outcomes in prostate cancer patients are starting to be explored. An intriguing inquiry connects androgen deprivation therapy with reduced risk of COVID-19 infection susceptibility and severity. Recognition of the cardiotoxicity of androgen deprivation therapy and aggressive risk factor modification are crucial for optimal patient care.

Dilated Superior Ophthalmic Vein: Clinical and Radiographic Features of 113 Cases.

PURPOSE: Dilated superior ophthalmic vein (SOV) is an uncommon radiographic finding. The authors review the presentation, etiology, radiography, and visual implications of 113 patients with dilated SOV. METHODS: An observational case series and multicenter retrospective chart review were conducted. There were 113 patients with a dilated SOV. Outcome measures included patient demographics, clinical features, radiographic findings, diagnosis, and treatment, and treatment outcomes were assessed. RESULTS: Cases included 75 women (66%) and 38 men (34%) with a mean age of 49 ± 24 years (range, 0.4-90 years). Diagnoses fell under 6 categories: vascular malformation (n = 92, 81%), venous thrombosis (n = 11, 10%), inflammatory (n = 6, 5%), traumatic hemorrhage (n = 2, 2%), lymphoproliferative (n = 1, 1%), and infectious (n = 1, 1%). Imaging modalities utilized included MRI (n = 98, 87%), digital subtraction angiography (n = 77, 68%), CT (n = 29, 26%), and ultrasonography (n = 4, 4%). Disease status at last follow up included no evidence of disease (n = 57, 50%), alive with persistent disease (n = 53, 47%), and expired from disease (n = 3, 3%). Treatment and management was tailored to the underlying disease process with a mean follow up of 18 months (range, 1 day to 180 months). Visual impairment observed at presentation and last follow up across all cases was 26% and 22%, respectively. CONCLUSION: Dilated SOV is a rare radiographic finding resulting from a wide spectrum of etiologies with clinical implications ranging from benign to sight- and life-threatening. Dilated SOV is most often found with dural-cavernous fistula or carotid-cavernous fistula, orbital or facial arteriovenous malformation, and venous thrombosis. Recognition of this finding and management of the underlying condition is critical.

Disrupted Hippocampal Theta-Gamma Coupling and Spike-Field Coherence Following Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) often results in persistent learning and memory deficits, likely due to disrupted hippocampal circuitry underlying these processes. Precise temporal control of hippocampal neuronal activity is important for memory encoding and retrieval and is supported by oscillations that dynamically organize single unit firing. Using high-density laminar electrophysiology, we discovered a loss of oscillatory power across CA1 lamina, with a profound, layer-specific reduction in theta-gamma phase amplitude coupling in injured rats. Interneurons from injured animals were less strongly entrained to theta and gamma oscillations, suggesting a mechanism for the loss of coupling, while pyramidal cells were entrained to a later phase of theta. During quiet immobility, we report decreased ripple amplitudes from injured animals during sharp-wave ripple events. These results reveal deficits in information encoding and retrieval schemes essential to cognition that likely underlie TBI-associated learning and memory impairments, and elucidate potential targets for future neuromodulation therapies.

Correlation of inner retinal thickness evaluated by spectral-domain optical coherence tomography and contrast sensitivity in Parkinson disease.

BACKGROUND: To compare inner retinal layer (IRL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) and contrast sensitivity (CS) in patients with Parkinson disease (PD) and in healthy control (HC) subjects. METHODS: Consecutive patients with and without PD were prospectively analyzed using SD-OCT and Pelli-Robson CS testing. SD-OCT IRL (ganglion-cell complex) thickness, consisting of the nerve fiber layer, ganglion cell layer, and inner plexiform layer, was segmented using an RTVue Model-RT100 with an EMM5 scan parameter covering a 5.0 × 5.0 mm cube centered on the fovea. Thickness voxel measurements at 0.25-mm intervals at sequential radial distances from the foveola were acquired horizontally and vertically. SD-OCT thickness raw data files were imported and analyzed within MATLAB (version 7.10.0). A database of CS scores and IRL thickness values by foveal location was constructed and statistically evaluated using JMP 10 (SAS Institute, Inc, Cary, NC). RESULTS: The results were compared between 28 eyes of 14 patients with PD and 28 eyes of 14 HC subjects. Controlling for age, mean CS scores of monocular right and randomized eyes were statistically lower in PD eyes (P < 0.05). IRL was significantly thinner in PD eyes than in HC eyes at several distances from the foveola (P < 0.05). The most numerous and significant thickness differences by diagnosis were located in the superior quadrant at a distance of 1.00-1.75 mm from the foveal center (17 µm; P < 0.01, maximum significant thickness difference and P value). Correlation was demonstrated between monocular CS and IRL thickness by diagnosis at multiple foveal locations for HC eyes as follows: nasal quadrant, 0.75-1.00 mm (P < 0.02); temporal quadrant, 0.50-1.00 mm (P < 0.05); superior quadrant, 1.00 mm (P < 0.05); and inferior quadrant, 1.00 mm (P < 0.03). No significant correlation was found between monocular CS and IRL thickness within PD subjects (P > 0.05 for each foveal location measured). CONCLUSION: CS and foveal IRL thickness are decreased in patients with PD. CS and IRL thickness correlated in HC subjects; however, no such correlation was demonstrated in PD. The functional deficit of dopaminergic interneurons, including amacrine cells, may outstrip the anatomic structural changes in the inner retina of PD patients. Inner retinal atrophic changes may underlie the pathogenesis of CS deficit and IRL thinning in PD.

Intraocular Lens Formula Comparison of Flanged Intrascleral Intraocular Lens Fixation with Double Needle Technique.

Purpose: To analyze visual outcomes and accuracy of intraocular lens (IOL) calculation formulas in predicting postoperative outcomes in patients undergoing flanged intrascleral IOL fixation. Design: Case Series. Subjects: Twenty-three patients who had undergone secondary IOL placement using flanged intrascleral fixation technique. Methods: Retrospective chart review. Main Outcome Measures: Corrected distance visual acuity (CDVA) and postoperative spherical equivalent based on manifest refraction. Results: Visual acuity improved from 20/577 to 20/58. Overall, the actual refraction was 0.06 D more myopic than predicted. Holladay 2, Sanders Retzlaff Kraff/Theoretical (SRK/T) and Barrett Universal II resulted in mild myopic surprise (-0.55, -0.18 and -0.20 D). Haigis and Hill-RBF (Radial Basis Function) resulted in mild hyperopic surprise (+0.28 and +0.28 D). Hoffer Q and Holladay 1 were the most accurate (-0.02D and -0.08 D). Conclusion: Flanged intrascleral IOL fixation improved vision even in patients with other posterior segment pathologies. The effective lens positioning is likely similar to in-the-bag positioning. Hoffer Q and Holladay 1 formulas with in-the-bag calculations were the most accurate.

Hippocampal interneuronal dysfunction and hyperexcitability in a porcine model of concussion.

Cognitive impairment is a common symptom following mild traumatic brain injury (mTBI or concussion) and can persist for years in some individuals. Hippocampal slice preparations following closed-head, rotational acceleration injury in swine have previously demonstrated reduced axonal function and hippocampal circuitry disruption. However, electrophysiological changes in hippocampal neurons and their subtypes in a large animal mTBI model have not been examined. Using in vivo electrophysiology techniques, we examined laminar oscillatory field potentials and single unit activity in the hippocampal network 7 days post-injury in anesthetized minipigs. Concussion altered the electrophysiological properties of pyramidal cells and interneurons differently in area CA1. While the firing rate, spike width and amplitude of CA1 interneurons were significantly decreased post-mTBI, these parameters were unchanged in CA1 pyramidal neurons. In addition, CA1 pyramidal neurons in TBI animals were less entrained to hippocampal gamma (40-80 Hz) oscillations. Stimulation of the Schaffer collaterals also revealed hyperexcitability across the CA1 lamina post-mTBI. Computational simulations suggest that reported changes in interneuronal physiology may be due to alterations in voltage-gated sodium channels. These data demonstrate that a single concussion can lead to significant neuronal and circuit level changes in the hippocampus, which may contribute to cognitive dysfunction following mTBI.

Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.

TOXOPLASMOSIS RETINOCHOROIDITIS MASQUERADING AS ENDOGENOUS ENDOPHTHALMITIS IN A CASE OF CONGENITAL LONG QT SYNDROME.

PURPOSE: To describe the diagnostic and treatment challenges of a case of presumed acquired macula-involving toxoplasmosis retinochoroiditis. METHODS: Case report of a woman with congenital long QT syndrome presenting with retinochoroiditis after undergoing a cardiac procedure. Laboratory analysis, ocular fluid biopsy, and multimodal imaging were obtained. RESULTS: Ophthalmic examination was significant for decreased vision and a macula-involving chorioretinal lesion concerning for endogenous endophthalmitis. Multimodal imaging showed a focal, full-thickness necrotizing process associated with vitritis, retinal edema, and choroidal thickening. Analysis of peripheral blood revealed elevated serum toxoplasma Immunoglobulin G titers. Blood cultures and a transesophageal echocardiogram were negative for endocarditis. Aqueous and vitreous specimens were negative for an infectious polymerase chain reaction panel, including toxoplasmosis and negative bacterial and fungal cultures. A diagnosis of presumed acquired toxoplasmosis retinochoroiditis was made and treated with a combination of oral and intravitreal antiparasitic medications resulting in healing of the retinochoroiditis. CONCLUSION: To the authors' knowledge, this is the first reported case of acquired toxoplasmosis retinochoroiditis in an immunocompetent patient with congenital long QT syndrome masquerading as endogenous endophthalmitis. The association of congenital long QT syndrome and a recent cardiac procedure with a risk for endogenous endophthalmitis complicated the diagnosis, clinical course, and treatment options. Our case emphasizes the importance of a thorough patient history, comprehensive clinical examination, and supportive multimodal imaging that were used to characterize the infectious process and guide empirical treatment. In addition, laboratory analysis, comanagement with other specialists, and evaluating the response to antitoxoplasma therapy were all instrumental in the eventual diagnosis and treatment of ocular toxoplasmosis in this atypical case.

DARK WITHOUT PRESSURE IN A CASE OF CHOROIDAL OSTEOMA.

PURPOSE: To report a novel case of dark without pressure in a patient with a choroidal osteoma. To our knowledge, this association has not been previously reported. METHODS: Observational case report. Review of clinical examination and multi-modal imaging findings in a patient with a choroidal osteoma and dark without pressure. RESULTS: A 21-year-old African American woman with no significant past medical history presented with a large, unilateral, juxtapapillary, subretinal, orange-colored, ovoid-shaped lesion with macular involvement. An overlying area of mottled pigmentary changes, fibrosis, and atrophy were present. Adjacent to and surrounding the osteoma was an annular band of hyperpigmented mid-peripheral retina with a sharply demarcated scalloped border that abruptly changed to normal-appearing peripheral retina. Multi-modal imaging including wide-field fluorescein angiography, optical coherence tomography, and ophthalmic B-scan were performed. The funduscopic and imaging findings were consistent with a diagnosis of choroidal osteoma and dark without pressure. CONCLUSION: The examination and imaging findings in this patient suggest a unique association between two relatively uncommon lesions, choroidal osteoma, and dark without pressure. Although these two lesions may simply be coinciding in the same eye, there may be an association with space-occupying lesions causing a change in photoreceptor structure.

Clathrin-nanoparticles deliver BDNF to hippocampus and enhance neurogenesis, synaptogenesis and cognition in HIV/neuroAIDS mouse model.

Brain derived neurotrophic factor (BDNF) promotes the growth, differentiation, maintenance and survival of neurons. These attributes make BDNF a potentially powerful therapeutic agent. However, its charge, instability in blood, and poor blood brain barrier (BBB) penetrability have impeded its development. Here, we show that engineered clathrin triskelia (CT) conjugated to BDNF (BDNF-CT) and delivered intranasally increased hippocampal BDNF concentrations 400-fold above that achieved previously with intranasal BDNF alone. We also show that BDNF-CT targeted Tropomyosin receptor kinase B (TrkB) and increased TrkB expression and downstream signaling in iTat mouse brains. Mice were induced to conditionally express neurotoxic HIV Transactivator-of-Transcription (Tat) protein that decreases BDNF. Down-regulation of BDNF is correlated with increased severity of HIV/neuroAIDS. BDNF-CT enhanced neurorestorative effects in the hippocampus including newborn cell proliferation and survival, granule cell neurogenesis, synaptogenesis and increased dendritic integrity. BDNF-CT exerted cognitive-enhancing effects by reducing Tat-induced learning and memory deficits. These results show that CT bionanoparticles efficiently deliver BDNF to the brain, making them potentially powerful tools in regenerative medicine.

Randomized, Comparative Study of Full- and Half-Dose Fluorescein Angiography.

Purpose: This study determines whether fluorescein angiography (FA) with a 250-mg dose of fluorescein (half dose) is equal in quality to the standard 500-mg dose of fluorescein (full dose) when using digital ultra-widefield (UWF) technology. Methods: In a randomized, prospective study using a UWF imaging system, FAs performed with half dose were compared with angiograms performed with full dose. Imaging studies were reviewed by 4 reviewers based on 6 characteristics: dye transit, macrovasculature, macula detail, microvasculature, leakage, and overall quality. The scores for macrovasculature, macula detail, microvasculature, and overall quality were converted to a fuzzy rating score to confirm results. Results: Seventy-nine FAs from 67 patients were reviewed for this study, including 12 patients who had both half-dose and full-dose FAs. Of all the factors studied, only microvasculature received a significantly different score between full dose and half dose that was confirmed by the fuzzy rating scale (3.79 vs 3.53; P = .04). Among those eyes that received both full and half dose, there was no significant difference in any of the 6 factors. Conclusions: In a UWF imaging system, aside from looking at fine microvascular abnormalities, the 250-mg dose of fluorescein provided similar results to a 500-mg dose. The images were not significantly different in overall quality.

Traumatic Brain Injury Preserves Firing Rates But Disrupts Laminar Oscillatory Coupling and Neuronal Entrainment in Hippocampal CA1.

While hippocampal-dependent learning and memory are particularly vulnerable to traumatic brain injury (TBI), the functional status of individual hippocampal neurons and their interactions with oscillations are unknown following injury. Using the most common rodent TBI model and laminar recordings in CA1, we found a significant reduction in oscillatory input into the radiatum layer of CA1 after TBI. Surprisingly, CA1 neurons maintained normal firing rates despite attenuated input, but did not maintain appropriate synchronization with this oscillatory input or with local high-frequency oscillations. Normal synchronization between these coordinating oscillations was also impaired. Simultaneous recordings of medial septal neurons known to participate in theta oscillations revealed increased GABAergic/glutamatergic firing rates postinjury under anesthesia, potentially because of a loss of modulating feedback from the hippocampus. These results suggest that TBI leads to a profound disruption of connectivity and oscillatory interactions, potentially disrupting the timing of CA1 neuronal ensembles that underlie aspects of learning and memory.

Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation.

Human brain organoids provide unique platforms for modeling development and diseases by recapitulating the architecture of the embryonic brain. However, current organoid methods are limited by interior hypoxia and cell death due to insufficient surface diffusion, preventing generation of architecture resembling late developmental stages. Here, we report the sliced neocortical organoid (SNO) system, which bypasses the diffusion limit to prevent cell death over long-term cultures. This method leads to sustained neurogenesis and formation of an expanded cortical plate that establishes distinct upper and deep cortical layers for neurons and astrocytes, resembling the third trimester embryonic human neocortex. Using the SNO system, we further identify a critical role of WNT/ß-catenin signaling in regulating human cortical neuron subtype fate specification, which is disrupted by a psychiatric-disorder-associated genetic mutation in patient induced pluripotent stem cell (iPSC)-derived SNOs. These results demonstrate the utility of SNOs for investigating previously inaccessible human-specific, late-stage cortical development and disease-relevant mechanisms.

Guidance for data collection and computational modelling of regulatory networks.

Many model regulatory networks are approaching the depth of characterisation of bacteriophage lambda, wherein the vast majority of individual components and interactions are identified, and research can focus on understanding whole network function and the role of interactions within that broader context. In recent years, the study of the system-wide behaviour of phage lambda's genetic regulatory network has been greatly assisted by the combination of quantitative measurements with theoretical and computational analyses. Such research has demonstrated the value of a number of general principles and guidelines for making use of the interplay between experiments and modelling. In this chapter we discuss these guidelines and provide illustration through reference to case studies from phage lambda biology.In our experience, computational modelling is best facilitated with a large and diverse set of quantitative, in vivo data, preferably obtained from standardised measurements and expressed as absolute units rather than relative units. Isolation of subsets of regulatory networks may render a system amenable to 'bottom-up' modelling, providing a valuable tool to the experimental molecular biologist. Decoupling key components and rendering their concentration or activity an independent experimental variable provide excellent information for model building, though conclusions drawn from isolated and/or decoupled systems should be checked against studies in the full physiological context; discrepancies are informative. The construction of a model makes possible in silico experiments, which are valuable tools for both the data analysis and the design of wet experiments.