Inhibition of soluble epoxide hydrolase by natural isothiocyanates.

GOAL: The long-term goal of our research is to develop safe and effective soluble epoxide hydrolase (sEH) inhibitors. The objective of this study is to evaluate the potency and selectivity of six natural isothiocyanates (ITCs) as sEH inhibitors. METHODS: Molecular docking was used to model likely interactions between the ligands and receptors. The sEH inhibitory activity was tested using a validated fluorescence-based assay and PHOME as a substrate. To evaluate their selectivity as sEH inhibitors, the inhibitory potential of the ITCs was determined on microsomal epoxide hydrolase (mEH) and cytochrome P450 (CYP) enzymes in human liver microsomes. Probe substrates such as styrene oxide (mEH substrate) and established substrates for CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 were used in this study. The metabolites of these substrates were analyzed using validated LC-MS/MS and HPLC-UV assays. RESULTS: Molecular Docking revealed significant differences in binding site preference among the ITCs in silico and pointed to important interactions between the ligands and the catalytic residues of the sEH enzyme. In vitro, the ITCs showed varying degrees of sEH inhibition, but sulforaphane (SFN) and phenyl isothiocyanate (PITC) were the most potent inhibitors with IC50 values of 3.65 and 7.5 µM, respectively. mEH was not significantly inhibited by any of the ITCs. Erucin and iberin were the only ITCs that did not inhibit the activity of any of the tested CYP enzymes. CONCLUSION: Our results demonstrate that natural ITCs have the potential to offer safe, selective, and potent sEH inhibition.

Characterization of the Native Disulfide Isomers of the Novel χ-Conotoxin PnID: Implications for Further Increasing Conotoxin Diversity.

χ-Conotoxins are known for their ability to selectively inhibit norepinephrine transporters, an ability that makes them potential leads for treating various neurological disorders, including neuropathic pain. PnID, a peptide isolated from the venom of Conus pennaceus, shares high sequence homology with previously characterized χ-conotoxins. Whereas previously reported χ-conotoxins seem to only have a single native disulfide bonding pattern, PnID has three native isomers due to the formation of different disulfide bond patterns during its maturation in the venom duct. In this study, the disulfide connectivity and three-dimensional structure of these disulfide isomers were explored using regioselective synthesis, chromatographic coelution, and solution-state nuclear magnetic resonance spectroscopy. Of the native isomers, only the isomer with a ribbon disulfide configuration showed pharmacological activity similar to other χ-conotoxins. This isomer inhibited the rat norepinephrine transporter (IC50 = 10 ± 2 µM) and has the most structural similarity to previously characterized χ-conotoxins. In contrast, the globular isoform of PnID showed more than ten times less activity against this transporter and the beaded isoform did not display any measurable biological activity. This study is the first report of the pharmacological and structural characterization of an χ-conotoxin from a species other than Conus marmoreus and is the first report of the existence of natively-formed conotoxin isomers.

Early neonatal mortality is modulated by gestational age, birthweight and fetal heart rate abnormalities in the low resource setting in Tanzania - a five year review 2015-2019.

BACKGROUND: Early Neonatal mortality (ENM) (< 7 days) remains a significant problem in low resource settings. Birth asphyxia (BA), prematurity and presumed infection contribute significantly to ENM. The study objectives were to determine: first, the overall ENM rate as well as yearly ENM rate (ENMR) from 2015 to 2019; second, the influence of decreasing GA (< 37 weeks) and BW (< 2500 g) on ENM; third, the contribution of intrapartum and delivery room factors and in particular fetal heart rate abnormalities (FHRT) to ENM; and fourth, the Fresh Still Birth Rates (FSB) rates over the same time period. METHODS: Retrospective cohort study undertaken in a zonal referral teaching hospital located in Northern Tanzania. Labor and delivery room data were obtained from 2015 to 2019 and included BW, GA, fetal heart rate (FHRT) abnormalities, bag mask ventilation (BMV) during resuscitation, initial temperature, and antenatal steroids use. Abnormal outcome was ENM < 7 days. Analysis included t tests, odds ratios (OR), and multivariate regression analysis. RESULTS: The overall early neonatal mortality rate (ENMR) was 18/1000 livebirths over the 5 years and did not change significantly comparing 2015 to 2019. Comparing year 2018 to 2019, the overall ENMR decreased significantly (OR 0.62; 95% confidence interval (CI) 0.45-0.85) as well as infants ≥37 weeks (OR 0.45) (CI 0.23-0.87) and infants < 37 weeks (OR 0.57) (CI 0.39-0.84). ENMR was significantly higher for newborns < 37 versus ≥37 weeks, OR 10.5 (p < 0.0001) and BW < 2500 versus ≥2500 g OR 9.9. For infants < 1000 g / < 28 weeks, the ENMR was ~ 588/1000 livebirths. Variables associated with ENM included BW - odds of death decreased by 0.55 for every 500 g increase in weight, by 0.89 for every week increase in GA, ENMR increased 6.8-fold with BMV, 2.6-fold with abnormal FHRT, 2.2-fold with no antenatal steroids (ANS), 2.6-fold with moderate hypothermia (all < 0.0001). The overall FSB rate was 14.7/1000 births and decreased significantly in 2019 when compared to 2015 i.e., 11.3 versus 17.3/1000 live births respectively (p = 0.02). CONCLUSION: ENM rates were predominantly modulated by decreasing BW and GA, with smaller/ less mature newborns 10-fold more likely to die. ENM in term newborns was strongly associated with FHRT abnormalities and when coupled with respiratory depression and BMV suggests BA. In smaller newborns, lack of ACS exposure and moderate hypothermia were additional associated factors. A composite perinatal approach is essential to achieve a sustained reduction in ENMR.

Research into the Bioengineering of a Novel α-Conotoxin from the Milked Venom of Conus obscurus.

The marine cone snail produces one of the fastest prey strikes in the animal kingdom. It injects highly efficacious venom, often causing prey paralysis and death within seconds. Each snail has hundreds of conotoxins, which serve as a source for discovering and utilizing novel analgesic peptide therapeutics. In this study, we discovered, isolated, and synthesized a novel α3/5-conotoxins derived from the milked venom of Conus obscurus (α-conotoxin OI) and identified the presence of α-conotoxin SI-like sequence previously found in the venom of Conus striatus. Five synthetic analogs of the native α-conotoxin OI were generated. These analogs incorporated single residue or double residue mutations. Three synthetic post-translational modifications (PTMs) were synthetically incorporated into these analogs: N-terminal truncation, proline hydroxylation, and tryptophan bromination. The native α-conotoxin OI demonstrated nanomolar potency in Poecilia reticulata and Homosapiens muscle-type nicotinic acetylcholine receptor (nAChR) isoforms. Moreover, the synthetic α-[P9K] conotoxin OI displayed enhanced potency in both bioassays, ranging from a 2.85 (LD50) to 18.4 (IC50) fold increase in comparative bioactivity. The successful incorporation of PTMs, with retention of both potency and nAChR isoform selectivity, ultimately pushes new boundaries of peptide bioengineering and the generation of novel α-conotoxin-like sequences.

Mechanisms of Herb-Drug Interactions Involving Cinnamon and CYP2A6: Focus on Time-Dependent Inhibition by Cinnamaldehyde and 2-Methoxycinnamaldehyde.

Information is scarce regarding pharmacokinetic-based herb-drug interactions (HDI) with trans-cinnamaldehyde (CA) and 2-methoxycinnamaldehyde (MCA), components of cinnamon. Given the presence of cinnamon in food and herbal treatments for various diseases, HDIs involving the CYP2A6 substrates nicotine and letrozole with MCA (KS = 1.58 µM; Hill slope = 1.16) and CA were investigated. The time-dependent inhibition (TDI) by MCA and CA of CYP2A6-mediated nicotine metabolism is a complex process involving multiple mechanisms. Molecular dynamic simulations showed that CYP2A6's active site accommodates two dynamic ligands. The preferred binding orientations for MCA and CA were consistent with the observed metabolism: epoxidation, O-demethylation, and aromatic hydroxylation of MCA and cinnamic acid formation from CA. The percent remaining activity plots for TDI by MCA and CA were curved, and they were analyzed with a numerical method using models of varying complexity. The best-fit models support multiple inactivator binding, inhibitor depletion, and partial inactivation. Deconvoluted mass spectra indicated that MCA and CA modified CYP2A6 apoprotein with mass additions of 156.79 (142.54-171.04) and 132.67 (123.37-141.98), respectively, and it was unaffected by glutathione. Heme degradation was observed in the presence of MCA (48.5% ± 13.4% loss; detected by liquid chromatography-tandem mass spectrometry). In the absence of clinical data, HDI predictions were made for nicotine and letrozole using inhibition parameters from the best-fit TDI models and parameters scaled from rats. Predicted area under the concentration-time curve fold changes were 4.29 (CA-nicotine), 4.92 (CA-letrozole), 4.35 (MCA-nicotine), and 5.00 (MCA-letrozole). These findings suggest that extensive exposure to cinnamon (corresponding to ≈ 275 mg CA) would lead to noteworthy interactions. SIGNIFICANCE STATEMENT: Human exposure to cinnamon is common because of its presence in food and cinnamon-based herbal treatments. Little is known about the risk for cinnamaldehyde and methoxycinnamaldehyde, two components of cinnamon, to interact with drugs that are eliminated by CYP2A6-mediated metabolism. The interactions with CYP2A6 are complex, involving multiple-ligand binding, time-dependent inhibition of nicotine metabolism, heme degradation, and apoprotein modification. An herb-drug interaction prediction suggests that extensive exposure to cinnamon would lead to noteworthy interactions with nicotine.

Development and validation of a sensitive and specific LC-MS/MS cocktail assay for CYP450 enzymes: Application to study the effect of catechin on rat hepatic CYP activity.

A sensitive and specific liquid chromatography tandem mass spectrometric (LC-MS/MS) method that enables the simultaneous quantification of probe substrates and metabolites of cytochrome P450 (CYP) enzymes was developed and validated. These substrates (metabolites)-coumarin (7-hydroxycoumarin), tolbutamide (4-hydroxytolbutamide), S-mephenytoin (4-hydroxymephenytoin), dextromethorphan (dextrorphan), and testosterone (6ß-hydroxytestosterone)-were utilized as markers for the activities of the major human CYP enzymes CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. Analytes were separated on Kinetex C18 column (2.1 × 50 mm, 5 µm) using a binary gradient mobile phase of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Metabolites were detected and quantified by MS using multiple reaction monitoring at m/z 163 → 107.2 for 7-hydroxycoumarin, m/z 235 → 150.1 for 4-hydroxymephenytoin, m/z 287 → 171 for 4-hydroxytolbutamide, m/z 258 → 157.1 for dextrorphan, m/z 305 → 269 for 6ß-hydroxytestosterone, and m/z 237 → 194 for the internal standard. The assay exhibited good linearity over a range of 10-500 ng/mL with acceptable accuracy and precision criteria. As a proof of concept, the developed cocktail assay was successfully used to examine the potential impact of catechin on the activity of the major rat liver CYP enzymes.

Therapeutic hypothermia during neonatal transport at Regional Perinatal Centers: active vs. passive cooling.

Background Earlier initiation of therapeutic hypothermia in term infants with hypoxic-ischemic encephalopathy has been shown to improve neurological outcomes. The objective of the study was to compare safety and effectiveness of servo-controlled active vs. passive cooling used during neonatal transport in achieving target core temperature. Methods We undertook a prospective cohort quality improvement study with historic controls of therapeutic hypothermia during transport. Primary outcome measures were analyzed: time to cool after initiation of transport, time to achieve target temperature from birth and temperature on arrival to cooling centers. Safety was assessed by group comparison of vital signs, diagnosis of persistent pulmonary hypertension (PPHN) and coagulation profiles on arrival. Results A total of 65 infants were included in the study. Time to cool after initiation of transport and time to achieve target temperature from birth were statistically significantly shorter in the actively cooled group with time reduction of 24% with P<0.01 and 15.6% with P<0.01, respectively. On arrival to our cooling center, we noted a significance difference in the mean core temperature (active 33.8°C vs. passive 35.4°C, P<0.01). Seven percent (2/30) of infants in the passively cooled group were overcooled (temperature <33°C). Patients in the actively cooled group had significantly lower mean heart rate compared to the passively cooled group. There was no statistically significant difference in diagnosis of PPHN or coagulation profiles on admission. Conclusion Our study indicates that active cooling with a servo-controlled device on neonatal transport is safe and more effective in achieving target temperature compared to passive cooling.

Implicit Physician Biases in Periviability Counseling.

OBJECTIVE: To assess whether neonatologists show implicit racial and/or socioeconomic biases and whether these are predictive of recommendations at extreme periviability. STUDY DESIGN: A nationwide survey using a clinical vignette of a woman in labor at 232/7 weeks of gestation asked physicians how likely they were to recommend intensive vs comfort care. Participants were randomized to 1 of 4 versions of the vignette in which racial and socioeconomic stimuli were varied, followed by 2 implicit association tests (IATs). RESULTS: IATs revealed implicit preferences favoring white (mean IAT score = 0.48, P < .001) and greater socioeconomic status (mean IAT score = 0.73, P < .001). Multivariable linear regression analysis showed that physicians with implicit bias toward greater socioeconomic status were more likely than those without bias to recommend comfort care when presented with a patient of high socioeconomic status (P = .037). No significant effect was seen for implicit racial bias. CONCLUSIONS: Building on previous demonstrations of unconscious racial and socioeconomic biases among physicians and their predictive validity, our results suggest that unconscious socioeconomic bias influences recommendations when counseling at the limits of viability. Physicians who display a negative socioeconomic bias are less likely to recommend resuscitation when counseling women of high socioeconomic status. The influence of implicit socioeconomic bias on recommendations at periviability may influence neonatal healthcare disparities and should be explored in future studies.

From nature to creation: Going around in circles, the art of peptide cyclization.

Cyclic peptides and cyclotides are becoming common identities within the present efforts seen in peptide engineering - as we seek approaches to achieve potent biological activity, pharmacological selectivity, structurally stability and oral bioavailability. Yet this unique family of peptides has faced uncommon hurdles in their discovery, synthesis and bioengineering, retaining to characteristics that truly deviate these from their linear counterparts. In this mini-review we take a board spectrum approach to introduce this novel family of biomolecules and the troubles that they face in their sequence and disulfide connectivity assignment, together highlighting the present combined strategies involved in cyclic peptide/cyclotide synthesis and modification. These efforts have circumvented otherwise impossible hurdles in their manipulation and production that are only now advancing cyclic peptides/cyclotides as research probes and future pharmaceutical templates.

Utility of routine urine CMV PCR and total serum IgM testing of small for gestational age infants: a single center review.

BACKGROUND: Due to the extremely low incidence of TORCH (toxoplasmosis, rubella, CMV, herpes simplex virus) infections, diagnostic testing of all small for gestational age (SGA) infants aimed at TORCH etiologies may incur unnecessary tests and cost. OBJECTIVE: To determine the frequency of urine CMV PCR and total IgM testing among infants with birth weight <10% and the rate of test positivity. To evaluate the frequency of alternative etiologies of SGA in tested infants. METHODS: Retrospective chart review of SGA infants admitted to the neonatal intensive care unit (NICU) at NYU Langone Medical Center between 2007 and 2012. Subjects were classified as being SGA with or without intrauterine growth restriction (IUGR). The IUGR subjects were then further categorized as having either symmetric or asymmetric IUGR utilizing the Fenton growth chart at birth. Initial testing for TORCH infections, which included serum total IgM, CMV PCR and head ultrasound, were reviewed and analyzed. RESULTS: Three hundred and eighty-six (13%) infants from a total of 2953 NICU admissions had a birth weight ≤10th percentile. Of these, 44% were IUGR; 34% being symmetric IUGR and 10% asymmetric. A total of 32% of SGA infants had urine CMV PCR and total IgM tested with no positive results. As expected, significantly higher percentage of symmetric IUGR infants were tested compared to asymmetric IUGR and non-IUGR SGA infants, (64% vs. 47% vs. 19%) P≤0.01. However, 63% of infants with a known cause for IUGR had same testing done aimed at TORCH infections. We calculated additional charges of $64,065 that were incurred by such testing. CONCLUSIONS: The majority of infants in our study who received testing for urine CMV PCR and total IgM aimed at TORCH infections had one or more other known non-infectious etiologies for IUGR. Because the overall yield of such testing is extremely low, we suggest tests for possible TORCH infections may be limited to symmetric IUGR infants without other known etiologies. Improved guidelines testing for TORCH infections can result in reducing hospital charges and unnecessary studies.

t-boc synthesis of huwentoxin-i through native chemical ligation incorporating a trifluoromethanesulfonic acid cleavage strategy.

Tert-butyloxycarbonyl (t-Boc)-based native chemical ligation (NCL) techniques commonly employ hydrogen fluoride (HF) to create the thioester fragment required for the ligation process. Our research aimed to assess the replacement of HF with Trifluoromethanesulfonic acid (TFMSA). Here we examined a 33 amino acid test peptide, Huwentoxin-I (HwTx-I) as a novel candidate for our TFMSA cleavage protocol. Structurally HwTx-I has an X-Cys(16) -Cys(17) -X sequence mid-region, which makes it an ideal candidate for NCL. Experiments determined that the best yields (16.8%) obtained for 50 mg of a thioester support resin were achieved with a TFMSA volume of 100 µL with a 0.5-h incubation on ice, followed by 2.0 h at room temperature. RP-HPLC/UV and mass spectra indicated the appropriate parent mass and retention of the cleaved HwTx-I N-terminal thioester fragment (Ala(1) -Cys(16) ), which was used in preparation for NCL. The resulting chemically ligated HwTx-I was oxidized/folded, purified, and then assessed for pharmacological target selectivity. Native-like HwTx-I produced by this method yielded an EC50 value of 340.5 ± 26.8 nM for Nav 1.2 and an EC50 value of 504.1 ± 81.3 nM for Nav 1.3, this being similar to previous literature results using native material. This article represents the first NCL based synthesis of this potent sodium channel blocker. Our illustrated approach removes potential restrictions in the advancement of NCL as a common peptide laboratory technique with minimal investment, and removes the hazards associated with HF usage. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 737-745, 2016.

Omega-3 fatty acids modulate neonatal cytokine response to endotoxin.

Neonatal immune response is characterized by an uncompensated pro-inflammatory response that can lead to inflammation-related morbidity and increased susceptibility to infection. We investigated the effects of long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) pre-treatment on cytokine secretion to low-concentration endotoxin (lipopolysaccharide, LPS) in THP-1 monocytes and neonatal cord blood (CB) from healthy full-term infants. Pre-treatment of THP-1 cells, with either n-3 PUFA at 25 or 100 µM significantly reduced IL-6, IL-10, and IL-12 secretion while DHA, but not EPA, reduced TNF-α response to LPS. DHA inhibition was stronger compared to EPA and effective at the low concentration. The same concentrations of n-3 PUFAs inhibited IL-12 but not IL-10 cytokine response in whole CB from 9 infants pre-treated for 24 h. To assess clinical relevance for acute response to LPS, the effects of low-concentration DHA at 25 µM or 12.5 µM were assessed before and after LPS exposure of isolated CB mononuclear cells from 20 infants for 1 h. When added before or after LPS, physiologic DHA treatment produced significant concentration-dependent inhibition of TNF-α, IL-6, IL-1ß, and IL-8 secretion. The results demonstrate prophylactic and therapeutic modulation of neonatal cytokine response to LPS and provide proof-of-concept that low-concentration administration of n-3 PUFA could attenuate or resolve neonatal inflammatory response.

Incorporation of post-translational modified amino acids as an approach to increase both chemical and biological diversity of conotoxins and conopeptides.

Bioactive peptides from Conus venom contain a natural abundance of post-translational modifications that affect their chemical diversity, structural stability, and neuroactive properties. These modifications have continually presented hurdles in their identification and characterization. Early endeavors in their analysis relied on classical biochemical techniques that have led to the progressive development and use of novel proteomic-based approaches. The critical importance of these post-translationally modified amino acids and their specific assignment cannot be understated, having impact on their folding, pharmacological selectivity, and potency. Such modifications at an amino acid level may also provide additional insight into the advancement of conopeptide drugs in the quest for precise pharmacological targeting. To achieve this end, a concerted effort between the classical and novel approaches is needed to completely elucidate the role of post-translational modifications in conopeptide structure and dynamics. This paper provides a reflection in the advancements observed in dealing with numerous and multiple post-translationally modified amino acids within conotoxins and conopeptides and provides a summary of the current techniques used in their identification.

Conotoxins and their regulatory considerations.

Venom derived peptides from marine cone snails, conotoxins, have demonstrated unique pharmacological targeting properties that have been pivotal in advancing medical research. The awareness of their true toxic origins and potent pharmacological nature is emphasized by their 'select agent' classification by the US Centers for Disease Control and Prevention. We briefly introduce the biochemical and pharmacological aspects of conotoxins, highlighting current advancements into their biological engineering, and provide details to the present regulations that govern their use in research.

Dural tears in spine surgery.

Dural tears are among the most commonly seen complications in spine surgery. Most studies in the literature indicate that long-term outcomes are not negatively affected, provided that the tears are diagnosed early and managed appropriately. Direct suture repair remains the preferred method for the management of durotomy caused by or found during surgery. However, recent literature reports encouraging results with sutureless repair. Understanding dural anatomy, dural healing, and cerebrospinal fluid dynamics is helpful in choosing among the available management options for dural tear.

Prevention, identification, and treatment of inadequate decompression of the cervical spine.

Inadequate decompression is one of the most common reasons for failed spinal surgery. Understanding the common areas where neural impingement occurs in the cervical spine, recognizing these changes on imaging studies, and recognizing the clinical manifestations help provide an intraoperative template for thorough decompression. A thorough preoperative workup assesses sagittal alignment of the cervical spine, determines if instability exists, identifies the location of the compression, and determines the etiology of the compressive lesion. This information guides the surgeon in deciding whether an anterior, a posterior, or a combined anterior and posterior approach will provide the most adequate decompression. It also will help determine whether arthrodesis is needed to provide optimal neurologic recovery. Patients who have had surgery and present with persistent neurologic symptoms, or who do not recover as expected, pose a unique challenge. The surgeon must determine if persistent compression exists, look for evidence of instability, and evaluate for irreversible spinal cord changes. Alternatively, other causes of neurologic changes, unrelated to neurologic impingement, must be ruled out. The initial step in achieving the goal of complete neurologic decompression is a thorough preoperative evaluation for static and dynamic causes of compression. The most important concept regarding inadequate decompression is to avoid it with careful preoperative planning of the index procedure.

Treatment of distal tibia fractures without articular involvement: a systematic review of 1125 fractures.

BACKGROUND: The management of unstable distal tibia fractures remains challenging. The mechanism of injury and the prognosis of these fractures are different from pilon fractures, but their proximity to the ankle makes the surgical treatment more complicated than the treatment tibial midshaft fractures. A variety of treatment methods have been suggested for these injuries, including nonoperative treatment, external fixation, intramedullary nailing, and plate fixation. However, each of these treatment options is associated with certain challenges. Nonoperative treatment may be complicated by loss of reduction and subsequent malunion. Similarly, external fixation of distal tibia fractures may result in insufficient reduction, malunion, and pin tract infection. Intramedullary nailing can be considered the "gold standard" for the treatment of tibial midshaft fractures, but there are concerns about their use in distal tibia fractures. This is because of technical difficulties with distal nail fixation, the risk of nail propagation into the ankle joint, and the discrepancy between the diaphyseal and metaphyseal diameter of the intramedullary canal. Open reduction and internal plate fixation results in extensive soft tissue dissection and may be associated with wound complications and infections. The optimal treatment of unstable distal tibia without articular involvement remains controversial. OBJECTIVES: This study was designed to review the outcomes of different treatment methods for extra-articular distal tibia fractures. The English literature was systematically reviewed and the rates of malunion, nonunion, infection, fixation failure, and secondary surgical procedures were extracted.

Three-dimensional spectral domain optical coherence tomography and light microscopy of an intravitreal parasite.

BACKGROUND: Various imaging modalities play a role in diagnosing parasitic infections of the eye. We describe the spectral domain optical coherence tomography (SD-OCT) findings of an intravitreal parasite with subsequent evaluation by light microscopy. FINDINGS: This is a case report of a 37-year-old Ecuadorian man who presented with uveitic glaucoma and a new floater in his left eye for 1 week's duration. Full ophthalmic examination revealed an intravitreal parasite. Color fundus photography, fluorescein angiography (FA), ocular ultrasonography (US), and SD-OCT were performed. The parasite was removed via 23-gauge pars plana vitrectomy and sent to pathology for evaluation. Color fundus photography and ocular ultrasonography demonstrated an elongated foreign body within the vitreous above the retina. FA demonstrated minimal vascular changes in the vicinity of the parasite. SD-OCT was utilized to visualize the parasite and to create a three-dimensional (3D) image. The parasite was determined to be most consistent with Gnathostoma spp. by morphologic analysis. CONCLUSIONS: This is the first reported case of SD-OCT of an intravitreal parasite with corresponding evaluation by pathology. SD-OCT allows non-invasive, high-resolution visualization and 3D reconstruction of parasitic anatomy which may help establish tomographic criteria for species identification.

Anatomic and radiographic analysis of arthroscopic tack placement into the anteroinferior glenoid.

Tack location within the anteroinferior aspect of the glenoid when performing simulated repairs of anteroinferior capsulolabral avulsions (Bankart lesions) was evaluated anatomically and radiographically. Arthroscopy was performed on six fresh-frozen cadaveric shoulders, and bioabsorbable tacks were placed through an accessory anteroinferior portal coming into the joint just above the subscapularis tendon using an outside-in technique. Tack location was studied after removal of all soft tissues. In addition to their position on the glenoid, the tacks were also evaluated for being partially or completely within bone. The tacks were recannulated with guide pins and anteroposterior, axillary, and en face glenoid radiographs of each specimen were obtained. This study provides quantitative data about the inferior placement limitations of the insertion angle and location of fixation devices within the anteroinferior glenoid through the anteroinferior accessory portal.