Severity of Downgaze Palsy in the Context of Disease Duration Could Estimate Survival Duration in Patients With Progressive Supranuclear Palsy.

It is an unmet need to estimate survival duration for patients with progressive supranuclear palsy (PSP). The objective of this study was to identify factors associated with the survival duration in patients with PSP. We followed up 23 patients with probable PSP-RS (Richardson syndrome) or PSP-P (parkinsonism) in our PSP center until death from 2011 to 2019. We prospectively and quantitatively rated their downgaze palsy whenever first noticed in our clinic. This was utilized along with the disease duration, motor function, medication use for parkinsonism, sex, age at onset of PSP, comorbid pulmonary and cardiovascular diseases, and the total survival duration from the onset of PSP to death for prediction analysis. A well-fitted linear regression model and a multivariant Cox model were applied to identify predicting factors for total survival duration. All patients had the specific hummingbird sign on brain MRI for PSP when downgaze palsy was documented. We found that the severity of downgaze palsy and the disease duration at the assessment were consistently correlated with the total survival duration in both models. The total survival duration could be further estimated by a formed regression equation. We conclude that severity and time to develop downgaze palsy could help to estimate the total survival duration in patients with probable PSP-RS and PSP-P, the major forms of PSP, which has significant clinical applications in clinical counseling and trial enrollment.

12. Review of diabetic papillitis.

Diabetic papillitis (used interchangeably with diabetic papillopathy) is a relatively rare ocular manifestation of systemic diabetic disease. Found in both type 1 and type 2 diabetic patients, it manifests as swelling of the optic nerve head in one or both eyes and is considered a diagnosis of exclusion. Signs and symptoms of optic nerve disease are not necessarily present, and there may be spontaneous recovery. The pathogenesis is poorly understood. The following discussion will cover the presentation, diagnosis, treatment, and prognosis of diabetic papillopathy.

Herpes Simplex Virus 2 Meningoencephalitis-Associated Bilateral Optic Neuritis and Radiculitis.

The most common ocular complication of herpes simplex virus (HSV) is acute retinal necrosis. We present a rare case of a patient with HSV-2 meningoencephalitis that developed severe vision-threatening optic neuritis. The patient was treated with steroids and IVIG, which allowed a rapid improvement in her vision.

Eyelid myeloid sarcoma: ominous presentation of acute myelogenous leukemia.

A 19 year-old African American man presented to our clinic for a second opinion about a right upper eyelid mass which had been recalcitrant to treatment for nonspecific orbital inflammation by an outside facility. Examination for systemic causes of the patients eyelid lesion led to a diagnosis of acute myelogenous leukemia (AML) FAB subtype M1. A subsequent biopsy of the eyelid tumor confirmed the diagnosis of a myeloid sarcoma. The patient succumbed to complications from his leukemia within 13 months of presentation. This case report is the first, to our knowledge, of an eyelid myeloid sarcoma as the presenting sign of AML and demonstrates the poor prognosis of this lesion.

Bilateral Optic Disc Swelling Following Anastrozole Therapy.

A 56-year-old female with early-stage breast cancer, stage IA grade 1 endometrial cancer, and stage IC grade 1 ovarian cancer developed sudden-onset visual changes and right inferior visual field defect following anastrozole therapy. Examination revealed severe bilateral optic disc swelling and impaired visual acuity. Laboratory work-up was otherwise unremarkable. Anastrozole was discontinued and over the next month, patient had near-complete resolution of swelling in the right eye and improvement in the left eye. This is the only reported case of optic disc swelling following anastrozole therapy.

Visual aspects of neurologic protein misfolding disorders.

PURPOSE OF REVIEW: This article reviews topics of interest to the ophthalmologist relating to the most common neurologic protein misfolding disorders. RECENT FINDINGS: Many neurodegenerative diseases are pathologically associated with misfolded proteins. These diseases cause a profound impact of disability to the individual and society. Alzheimer's disease costs alone are estimated to be over US$225 billion annually in the USA. The ophthalmologist is often asked to provide an opinion regarding the cause of visual symptoms in patients with these unique disorders. SUMMARY: The categorization of neurodegenerative diseases has evolved based on advances in genetic, molecular and pathological research. In many neurodegenerative diseases, aggregation of a misfolded protein is responsible for the development of pathologic inclusions. When the misfolded protein is tau or synuclein, these diseases are called tauopathies or synucleinopathies, respectively. This article focuses on ophthalmic findings in some of the most common tauopathies and synucleinopathies: Alzheimer's disease, progressive supranuclear palsy, Parkinson's disease, dementia with Lewy bodies and multisystem atrophy.

Optimization of Spin-Unrestricted Density Functional Theory for Redox Properties of Rubredoxin Redox Site Analogues.

Quantum chemical calculations of metal clusters in proteins for redox studies require both computational feasibility as well as accuracies of at least ∼50 mV for redox energies but only ∼0.05 Å for bond lengths. Thus, optimization of spin-unrestricted density functional theory (DFT) methods, especially the hybrid generalized gradient approximation functionals, for energies while maintaining good geometries is essential. Here, different DFT functionals with effective core potential (ECP) and full core basis sets for [Fe(SCH(3))(4)](2-/1-) and [Fe(SCH(3))(3)](1-/0), which are analogs of the iron-sulfur protein rubredoxin, are investigated in comparison to experiment as well as other more computationally intensive electron correlation methods. In particular, redox energies are calibrated against gas-phase photoelectron spectroscopy data so no approximations for the environment are needed. B3LYP gives the best balance of accuracy in energy and geometry compared B97gga1 and BHandH and is better for energies than Møller-Plesset perturbation theory series (MP2, MP3, MP4SDQ) and comparable to coupled cluster [CCSD, CCSD(T)] methods. Of the full core basis sets tested, the 6-31G** basis sets give good geometries, and addition of diffuse functions to only the sulfur significantly improves the energies. Moreover, a basis set with an ECP on only the iron gives a less accurate but still reasonable geometries and energies.

Sellar lesions and visual loss: key concepts in neuro-ophthalmology.

The pituitary gland serves an essential role in the activity and regulation of the endocrine system. Mass lesions within the pituitary gland account for approximately 10-15% of intracranial neoplasms. Patients with pituitary adenomas may present with endocrine dysfunction or neuro-ophthalmic pathology, resulting from compression of surrounding structures, most notably the optic chiasm. Visual deficits from chiasmal tumors may manifest as visual field defects, visual loss, diplopia, nystagmus and visual hallucinations. Visual field defects are the most commonly reported presenting visual symptom. The specific visual field defect usually results from the anatomic compression of the tumor upon the optic chiasm. It is important to recognize characteristic visual deficits in the diagnosis and treatment of chiasmal tumors.

Complexation of the carbonate, nitrate, and acetate anions with the uranyl dication: density functional studies with relativistic effective core potentials.

The structures and vibrational frequencies of uranyl carbonates, [UO2(CO3)n](2-2n) and [(UO2)3(CO3)6]6-, uranyl nitrates, [UO2(NO3)n](2-n), and uranyl acetates, [UO2(CH3COO)n](2-n) (n = 1,2,3) have been calculated by using local density functional theory (LDFT). Only bidentate ligand coordination modes to the uranyl dication have been modeled. The calculated structures and frequencies are compared to available experimental data, including IR, Raman, X-ray diffraction, and EXAFS solution and crystal structure data. The energetics of ligand binding have been calculated using the B3LYP hybrid functional. In general, the structural and vibrational results at the LDFT level are in good agreement with experimental results and provide realistic pictures of solution phase and solid-state behavior. For the [UO2(CO3)3]6- anion, calculations suggest that complexity in the CO3(2-) stretching signature upon complexation is due to the formation of C=O and C-O domains, the latter of which can split by as much as 300 cm(-1). Assessment of the binding energies indicate that the [UO2(CO3)2]2- anion is more stable than the [UO2(CO3)3]4- anion due to the accumulation of excess charge, whereas the tri-ligand species are the most stable in the nitrate and acetate anions.

The effects of ultrafiltration on e-aminocaproic acid: an in vitro analysis.

Blood conservation strategies have become a standard of practice in cardiac surgery, with the use of antifibrinolytic agents and ultrafiltration two popular techniques. The purpose of this study was to evaluate the effects of continuous ultrafiltration on e-aminocaproic acid (EACA) utilizing functional coagulation analysis. A fibrinolytic assay was developed to detect EACA using the thromboelastograph (TEG) and urokinase (0.138 units 0.360 mL(-1)). Fresh bovine blood (23 +/- 1% hematocrit) was pumped (100 mL min(-1)) through an ultrafiltrator (HPH 400) at 37 degrees C with a transmembrane pressure of 280 mmHg. EACA (0.065 mg mL(-1)) was circulated for 10 minutes before initiating ultrafiltration. Samples (pre- and postultrafiltrator) were obtained at baseline, 5, and 10 min of ultrafiltration and analyzed via the fibrinolytic assay for EACA determination. TEG profiles significantly decreased from concentrations of 0.065 mg to 0.0325 mg of EACA mL(-1) blood (maximum amplitude MA, 75.4 +/- 4.0 versus 63.3 +/- 2.9, p < .05, TEG index 5.4 +/- 0.7 versus 4.0 +/- 0.3, p < .05). Fibrinolysis at 30 min increased as EACA concentrations declined (0.065 mg, 0% versus 0.032 mg, 16.4 +/- 2.8%, p < .05). During ultrafiltration the MA increased significantly from baseline to 10 min postultrafiltrator (68.2 +/- 3.0 versus 75.8 +/- 10.0, p < .05) and from 5 min pre- to 10 min postultrafiltrator (69.7 +/- 4.2 versus 75.8 +/- 10.0, p < .05). The TEG index showed no significant change, and no fibrinolysis was detected at 30 min from any datapoint during ultrafiltration. In conclusion, this study demonstrates that the antifibrinolytic properties of EACA are maintained during ultrafiltration with a 25% reduction in total circulating volume.

Mitsunobu Reaction of Unbiased Cyclic Allylic Alcohols.

The stereochemical inversion of unbiased allylic alcohols using triphenylphosphine, diethyl azodicarboxylate, and benzoic acid, commonly known as the Mitsunobu reaction, was studied in three different solvents with specific attention toward the product composition. The results generated for the Mitsunobu reaction of (R)-3-deuterio-2-cyclohexen-1-ol and the cis and trans isomers of 1-deuterio-5-methyl-2-cyclohexen-1-ol, 1-deuterio-5-tert-butyl-2-cyclohexen-1-ol, and optically active cis and trans 5-isopropyl-2-methyl-2-cyclohexen-1-ol all gave similar product distributions with respect to inversion and retention at the carbinol center as well-as syn and anti S(N)2' type addition when THF or benzene was used as the solvent (CH(2)Cl(2) gave less selective product distributions). Interestingly, it was found that the quasi-equatorial and quasi-axial nature of the starting allylic alcohol does not appear to affect the product distribution for this reaction, nor does methyl substitution at the central carbon of the allylic alcohol. In all cases, significant amounts (8-28%) of non-S(N)2 type products were detected for these sterically unbiased allylic alcohols; only 72-77% of the product was from S(N)2 type reaction when sterically undemanding (R)-3-deuterio-2-cyclohexen-1-ol was subjected to Mitsunobu conditions.