Predictors of intraocular pressure reduction after femtosecond laser-assisted cataract surgery versus conventional phacoemulsification surgery: a prospective trial.

PURPOSE: To evaluate the association between postoperative intraocular pressure (IOP) reduction and phacoemulsification parameters in patients who underwent both conventional phacoemulsification surgery (CPS) and femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a prospective multicenter comparative study that enrolled 90 participants who underwent cataract surgery at the University of Maryland Medical System and the Wilmer Eye Institute. Patients underwent FLACS in one eye and CPS in the fellow eye. IOP was measured prior to surgery and monitored through six months postoperatively. Demographic, clinical, biometric, and intraoperative variables including cumulative dissipated energy (CDE), aspiration time, and phacoemulsification time were analyzed for any significant association with postoperative IOP. Postoperative IOP reduction was the primary outcome variable. A secondary goal of the study was to determine differences in postoperative IOP reduction between CPS and FLACS cohorts. RESULTS: In total, 157 non-glaucomatous eyes were included. Using multivariable analysis, we found preoperative IOP to be consistently associated with postoperative IOP reduction in the entire cohort. At the 6-month follow-up visit, there was a 12.4% reduction in IOP (-2.2 ± 3.4 mm Hg) seen, with no statistically significant difference between FLACS and CPS (12.3% ± 19.4% vs 12.5% ± 19.3%, respectively, p = 0.32). FLACS reduced the CDE required for phacoemulsification (6.6 ± 4.4%-seconds vs 8.6 ± 6.9%-seconds, respectively, p < 0.05). CDE was a predictor of IOP response at 6 months, but subgroup analysis revealed that this trend was driven by seven eyes requiring high CDE, and for the majority of eyes, CDE did not influence the size of the decrease. The seven eyes experiencing highest CDE were less likely to show IOP reduction at 6 months. CONCLUSION: Both FLACS and CPS resulted in similar and significant IOP reductions through 6 months after surgery. Preoperative IOP was significantly associated with IOP reduction, and CDE generally did not influence the size of the decrease.

Homonuclear J-Coupling Spectroscopy at Low Magnetic Fields using Spin-Lock Induced Crossing*.

Nuclear magnetic resonance (NMR) spectroscopy usually requires high magnetic fields to create spectral resolution among different proton species. Although proton signals can also be detected at low fields the spectrum exhibits a single line if J-coupling is stronger than chemical shift dispersion. In this work, we demonstrate that the spectra can nevertheless be acquired in this strong-coupling regime using a novel pulse sequence called spin-lock induced crossing (SLIC). This techniques probes energy level crossings induced by a weak spin-locking pulse and produces a unique J-coupling spectrum for most organic molecules. Unlike other forms of low-field J-coupling spectroscopy, our technique does not require the presence of heteronuclei and can be used for most compounds in their native state. We performed SLIC spectroscopy on a number of small molecules at 276 kHz and 20.8 MHZ and show that the simulated SLIC spectra agree well with measurements.

Syphilitic retinitis presentations: punctate inner retinitis and posterior placoid chorioretinitis.

PURPOSE: To describe two distinct presentations of syphilitic fundus features in a series of patients with ocular syphilis. METHODS: This is a retrospective, interventional case series of 22 eyes from 16 serology confirmed cases. Clinical examination, fluorescein angiography, and optical coherence tomography were performed at presentation and following high-dose intravenous penicillin G. RESULTS: In our cohort, the mean age was 47.6 years (range 24-59 years) and 14 patients were male (87.5%), 11 patients were positive for human immunodeficiency virus (68.8%), and 6 had bilateral involvement (37.5%). Mean best-corrected visual acuity improved from 0.99 ± 0.79 logarithm of the minimal angle of resolution (LogMAR) at the time of presentation to 0.29 ± 0.36 LogMAR on final visit (P < 0.01). Posterior segment examinations in eyes with retinitis showed two distinct types (1) discrete, placoid lesions in the macula consistent with acute syphilitic posterior placoid chorioretinitis or (2) punctate inner retinitis with corresponding fluorescein pooling in a segmental pattern. These findings rapidly resolved after antibiotic therapy. CONCLUSION: In the era of resurgence, ocular syphilis may present with two phenotypes of discrete retinal lesions. Recognition of the characteristic ocular features may help make the diagnosis and monitor treatment response.

In vitro simultaneous mapping of the partial pressure of oxygen, pH and inorganic phosphate using electron paramagnetic resonance.

The partial pressure of oxygen (pO2) and the extracellular pH in the tumour microenvironment are essential parameters for understanding the physiological state of a solid tumour. Also, phosphate-containing metabolites are involved in energy metabolism, and interstitial inorganic phosphate (Pi) is an informative marker for tumour growth. This article describes the simultaneous mapping of pO2, pH and Pi using 750 MHz continuous-wave (CW) electron paramagnetic resonance (EPR) and a multifunctional probe, monophosphonated trityl radical p1TAM-D. The concept was demonstrated by acquiring three-dimensional (3D) maps of pO2, pH and Pi for multiple solution samples. This was made possible by combining a multifunctional radical probe, fast CW-EPR spectral acquisition, four-dimensional (4D) spectral-spatial image reconstruction, and spectral fitting. The experimental results of mapping pO2, pH and Pi suggest that the concept of simultaneous mapping using EPR is potentially applicable for the multifunctional measurements of a mouse tumour model.

Speeding up dynamic spiral chemical shift imaging with incoherent sampling and low-rank matrix completion.

PURPOSE: To improve the temporal and spatial resolution of dynamic 13 C spiral chemical shift imaging via incoherent sampling and low-rank matrix completion (LRMC). METHODS: Spiral CSI data were both simulated and acquired in rats, and undersampling was implemented retrospectively and prospectively by pseudorandomly omitting a fraction of the spiral interleaves. Undersampled data were reconstructed with both LRMC and a conventional inverse nonuniform fast Fourier transform (iNUFFT) and compared with fully sampled data. RESULTS: Two-fold undersampling with LRMC reconstruction enabled a two-fold improvement in temporal or spatial resolution without significant artifacts or spatiotemporal distortion. Conversely, undersampling with iNUFFT reconstruction created strong artifacts that obscured the image. LRMC performed better at time points with strong metabolite signal. CONCLUSION: Incoherent undersampling and LRMC provides a way to increase the spatiotemporal resolution of spiral CSI without degrading data integrity. Magn Reson Med 77:951-960, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Nuclear spin singlet states as a contrast mechanism for NMR spectroscopy.

Nuclear magnetic resonance (NMR) spectra of complex chemical mixtures often contain unresolved or hidden spectral components, especially when strong background signals overlap weaker peaks. In this article we demonstrate a quantum filter utilizing nuclear spin singlet states, which allows undesired NMR spectral background to be removed and target spectral peaks to be uncovered. The quantum filter is implemented by creating a nuclear spin singlet state with spin quantum numbers j = 0, mz = 0 in a target molecule, applying a continuous RF field to both preserve the singlet state and saturate the magnetization of undesired molecules and then mapping the target molecule singlet state back into an NMR observable state so that its spectrum can be read out unambiguously. The preparation of the target singlet state can be carefully controlled with pulse sequence parameters, so that spectral contrast can be achieved between molecules with very similar structures. We name this NMR contrast mechanism 'Suppression of Undesired Chemicals using Contrast-Enhancing Singlet States' (SUCCESS) and we demonstrate it in vitro for three target molecules relevant to neuroscience: aspartate, threonine and glutamine.

Preparation of nuclear spin singlet states using spin-lock induced crossing.

We introduce a broadly applicable technique to create nuclear spin singlet states in organic molecules and other many-atom systems. We employ a novel pulse sequence to produce a spin-lock induced crossing (SLIC) of the spin singlet and triplet energy levels, which enables triplet-singlet polarization transfer and singlet-state preparation. We demonstrate the utility of the SLIC method by producing a long-lived nuclear spin singlet state on two strongly coupled proton pairs in the tripeptide molecule phenylalanine-glycine-glycine dissolved in D(2)O and by using SLIC to measure the J couplings, chemical shift differences, and singlet lifetimes of the proton pairs. We show that SLIC is more efficient at creating nearly equivalent nuclear spin singlet states than previous pulse sequence techniques, especially when triplet-singlet polarization transfer occurs on the same time scale as spin-lattice relaxation.

Minimalist model for force-dependent DNA replication.

In experiments using optical or magnetic tweezers, investigators have monitored the rate at which polymerase enzymes catalyze DNA replication when the template strand is subjected to a stretching force. For T7, Klenow, and Sequenase polymerases, the replication rate increases modestly at low tension and then decreases markedly at higher tension. Molecular-dynamics (MD) simulations using x-ray structure data for the open and closed complexes of the Taq enzyme with DNA revealed that the dependence of replication rate on tension could be accounted for in terms of the induced enthalpy changes for the two DNA segments adjacent to the site of the added nucleotide. Here, we present a simple, minimalist two-segment local model (M2L) derived from some striking features seen in the MD simulations. The model predicts the tension dependence of the replication rate using only structural data and a critical tension, f(∗), without recourse to MD simulations. At f(∗), the outermost DNA segment undergoes a large angular reorientation in the open conformation of the enzyme. We give a generic plot for the M2L model, apply it to family A and B polymerases and HIV reverse transcriptase, and discuss factors that may govern the f(∗) flip parameter.

Homonuclear J-coupling spectroscopy using J-synchronized echo detection.

In the strong coupling regime with J-coupling much larger than chemical shift differences, J-coupling spectroscopy enables spectral identification of molecules even when conventional NMR fails. While this classically required the presence of a heteronucleus, we recently showed that J-coupling spectra can be acquired in many homonuclear systems using spin-lock induced crossing (SLIC). Here, we present an alternative method using a spin echo train in lieu of a spin-locking SLIC pulse, which has a number of advantages. In particular, spin echo acquisition within the pulse train enables simultaneous collection of time and frequency data. The resulting 2D spectrum can be used to study dynamic spin evolution, and the time domain data can be averaged to create a 1D J-coupling spectrum with increased signal-to-noise ratio.

NMR of 31P nuclear spin singlet states in organic diphosphates.

31P NMR and MRI are commonly used to study organophosphates that are central to cellular energy metabolism. In some molecules of interest, such as adenosine diphosphate (ADP) and nicotinamide adenine dinucleotide (NAD), pairs of coupled 31P nuclei in the diphosphate moiety should enable the creation of nuclear spin singlet states, which may be long-lived and can be selectively detected via quantum filters. Here, we show that 31P singlet states can be created on ADP and NAD, but their lifetimes are shorter than T1 and are strongly sensitive to pH. Nevertheless, the singlet states were used with a quantum filter to successfully isolate the 31P NMR spectra of those molecules from the adenosine triphosphate (ATP) background signal.

Survey of musculoskeletal disorders among US ophthalmologists.

PURPOSE: To characterize the prevalence of work-related musculoskeletal disorders (MSD), symptoms, and risk factors among ophthalmologists. METHODS: An online survey was distributed to ophthalmologist members of the Maryland Society of Eye Physicians and Surgeons. The survey consisted of 34 questions on respondent demographics, practice characteristics, pain, and effects of MSD on their practice patterns. Participants were excluded if they were not ophthalmologists or if they had MSD symptoms prior to the start of their ophthalmology career. Demographics and practice patterns were compared for those with or without MSD symptoms using the Welch t test and the Fisher exact test. RESULTS: The survey was completed by 127 of 250 active members (response rate, 51%). Of the 127, 85 (66%) reported experiencing work-related pain, with an average pain level of 4/10. With regard to mean age, height, weight, years in practice, number of patients seen weekly, and hours worked weekly, there was no difference between respondents reporting pain and those without. Those reporting MSD symptoms spent significantly more time in surgery than those who did not (mean of 7.9 vs 5.3 hours/week [P < 0.01]). Fourteen percent of respondents reported plans to retire early due to their symptoms. CONCLUSIONS: A majority of respondents experienced work-related MSD symptoms, which was associated with time spent in surgery. Modifications to the workplace environment focusing on ergonomics, particularly in the operating room, may benefit ophthalmologists.

Large-scale synthesis of a monophosphonated tetrathiatriarylmethyl spin probe for concurrent in vivo measurement of pO2, pH and inorganic phosphate by EPR.

Low-field electron paramagnetic resonance spectroscopy paired with pTAM, a mono-phosphonated triarylmethyl radical, is an unmatched technique for concurrent and non-invasive measurement of oxygen concentration, pH, and inorganic phosphate concentration for in vivo investigations. However, the prior reported synthesis is limited by its low yield and poor scalability, making wide-spread application of pTAM unfeasible. Here, we report a new strategy for the synthesis of pTAM with significantly greater yields demonstrated on a large scale. We also present a standalone application with user-friendly interface for automatic spectrum fitting and extraction of pO2, pH, and [Pi] values. Finally, we confirm that pTAM remains in the extracellular space and has low cytotoxicity appropriate for local injection.

Enhancing Metabolic Imaging of Energy Metabolism in Traumatic Brain Injury Using Hyperpolarized [1-13C]Pyruvate and Dichloroacetate.

Hyperpolarized magnetic resonance spectroscopic imaging (MRSI) of [1-13C]pyruvate metabolism has previously been used to assess the effects of traumatic brain injury (TBI) in rats. Here, we show that MRSI can be used in conjunction with dichloroacetate to measure the phosphorylation state of pyruvate dehydrogenase (PDH) following mild-to-moderate TBI, and that measurements can be repeated in a longitudinal study to monitor the course of injury progression and recovery. We found that the level of 13C-bicarbonate and the bicarbonate-to-lactate ratio decreased on the injured side of the brain four hours after injury and continued to decrease through day 7. Levels recovered to normal by day 28. Measurements following dichloroacetate administration showed that PDH was inhibited equally by PDH kinase (PDK) on both sides of the brain. Therefore, the decrease in aerobic metabolism is not due to inhibition by PDK.

Metabolic imaging of energy metabolism in traumatic brain injury using hyperpolarized [1-13C]pyruvate.

Traumatic brain injury (TBI) is known to cause perturbations in the energy metabolism of the brain, but current tests of metabolic activity are only indirect markers of energy use or are highly invasive. Here we show that hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) can be used as a direct, non-invasive method for studying the effects of TBI on energy metabolism. Measurements were performed on rats with moderate TBI induced by controlled cortical impact on one cerebral hemisphere. Following injection of hyperpolarized [1-13C]pyruvate, the resulting 13C-bicarbonate signal was found to be 24 ± 6% lower in the injured hemisphere compared with the non-injured hemisphere, while the hyperpolarized bicarbonate-to-lactate ratio was 33 ± 8% lower in the injured hemisphere. In a control group, no significant difference in signal was found between sides of the brain. The results suggest an impairment in mitochondrial pyruvate metabolism, resulting in a decrease in aerobic respiration at the location of injury following TBI.

Probing scalar coupling differences via long-lived singlet states.

We probe small scalar coupling differences via the coherent interactions between two nuclear spin singlet states in organic molecules. We show that the spin-lock induced crossing (SLIC) technique enables the coherent transfer of singlet order between one spin pair and another. The transfer is mediated by the difference in syn and anti vicinal or long-range J couplings among the spins. By measuring the transfer rate, we calculate a J coupling difference of 8±2mHz in phenylalanine-glycine-glycine and 2.57±0.04Hz in glutamate. We also characterize a coherence between two singlet states in glutamate, which may enable the creation of a long-lived quantum memory.

Nanoscale NMR spectroscopy and imaging of multiple nuclear species.

Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) provide non-invasive information about multiple nuclear species in bulk matter, with wide-ranging applications from basic physics and chemistry to biomedical imaging. However, the spatial resolution of conventional NMR and MRI is limited to several micrometres even at large magnetic fields (>1 T), which is inadequate for many frontier scientific applications such as single-molecule NMR spectroscopy and in vivo MRI of individual biological cells. A promising approach for nanoscale NMR and MRI exploits optical measurements of nitrogen-vacancy (NV) colour centres in diamond, which provide a combination of magnetic field sensitivity and nanoscale spatial resolution unmatched by any existing technology, while operating under ambient conditions in a robust, solid-state system. Recently, single, shallow NV centres were used to demonstrate NMR of nanoscale ensembles of proton spins, consisting of a statistical polarization equivalent to ∼100-1,000 spins in uniform samples covering the surface of a bulk diamond chip. Here, we realize nanoscale NMR spectroscopy and MRI of multiple nuclear species ((1)H, (19)F, (31)P) in non-uniform (spatially structured) samples under ambient conditions and at moderate magnetic fields (∼20 mT) using two complementary sensor modalities.

Dependence of nuclear spin singlet lifetimes on RF spin-locking power.

We measure the lifetime of long-lived nuclear spin singlet states as a function of the strength of the RF spin-locking field and present a simple theoretical model that agrees well with our measurements, including the low-RF-power regime. We also measure the lifetime of a long-lived coherence between singlet and triplet states that does not require a spin-locking field for preservation. Our results indicate that for many molecules, singlet states can be created using weak RF spin-locking fields: more than two orders of magnitude lower RF power than in previous studies. Our findings suggest that for many endogenous biomolecules, singlets and related states with enhanced lifetimes might be achievable in vivo with safe levels of RF power.