Open Water Swimming: Medical and Water Quality Considerations.

The sport of open water swimming (OWS) has been popularized on a global scale. This population of athletes may experience several unique medical conditions, necessitating a review of medical issues and environmental considerations. Clinicians providing care for OWS athletes should be educated and trained to recognize and manage illnesses and conditions that often occur in an effort to ensure athlete safety. This article focuses on the major medical challenges faced in OWS, including a review of cardiorespiratory conditions and infections, competitor factors, water quality concerns, and risk minimization strategies.

Intravenous anesthetic propofol binds to 5-lipoxygenase and attenuates leukotriene B4 production.

Propofol is an intravenous anesthetic that produces its anesthetic effect, largely via the GABAA receptor in the CNS, and also reduces the N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophil respiratory burst. Because fMLP-stimulated neutrophils produce leukotriene (LT)B4, we examined the effect of propofol on LTB4 production in vivo and in vitro Cecal ligation and puncture surgery was performed in mice, with or without exposure to propofol. Propofol attenuated the production of 5-lipoxygenase (5-LOX)-related arachidonic acid (AA) derivatives in the peritoneal fluid. Also, in the in vitro experiments on fMLP-stimulated neutrophils and 5-LOX-transfected human embryonic kidney cells, propofol attenuated the production of 5-LOX-related AA derivatives. Based on these results, we hypothesized that propofol would directly affect 5-LOX function. Using meta-azi-propofol (AziPm), we photolabeled stable 5-LOX protein, which had been used to solve the X-ray crystallographic structure of 5-LOX, and examined the binding site(s) of propofol on 5-LOX. Two propofol binding pockets were identified near the active site of 5-LOX. Alanine scanning mutagenesis was performed for the residues of 5-LOX in the vicinity of propofol, and we evaluated the functional role of these pockets in LTB4 production. We demonstrated that these pockets were functionally important for 5-LOX activity. These two pockets can be used to explore a novel 5-LOX inhibitor in the future.-Okuno, T., Koutsogiannaki, S., Ohba, M., Chamberlain, M., Bu, W., Lin, F.-Y., Eckenhoff, R. G., Yokomizo T., Yuki, K. Intravenous anesthetic propofol binds to 5-lipoxygenase and attenuates leukotriene B4 production.

Rapidly growing cardiac mass: a rare case of left atrial intramural hematoma complicating coronary artery stenting.

Formation of an intramural left atrial hematoma (ILAH) is a rare complication of coronary artery stenting. Rapid diagnosis with noninvasive multimodality imaging can potentially be lifesaving. We report a case of ILAH that resulted in left ventricular inflow obstruction and pericardial tamponade in a 55-year-old male who presented with hemodynamic instability and worsening dyspnea three weeks after seemingly uncomplicated left circumflex artery stenting. We demonstrate features on transthoracic echocardiography with contrast and cardiac computed tomography that were used for diagnosis and management.

Safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation in the treatment of knee osteoarthritis: A Phase I/IIa randomised controlled trial.

Objectives: To assess the safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation (MAG200) in the treatment of knee osteoarthritis over 12 months. Design: A single-centre, double-blind, ascending dose, randomised controlled trial. 40 participants with moderate knee osteoarthritis were randomised to receive a single intra-articular injection of MAG200 (dose cohorts:10, 20, 50, 100 â€‹× â€‹106 â€‹cells) or placebo. Primary objectives were safety and efficacy according to a compound responder analysis of minimal clinically important difference in pain (numerical pain rating scale [NPRS]) and function (Knee Injury and Osteoarthritis Outcome Score - Function in Daily Living subscale [KOOSADL]) at month 12. Secondary efficacy outcomes included changes from baseline in patient reported outcome measures and evaluation of disease-modification using quantitative MRI. Results: Treatment was well tolerated with no treatment-related serious adverse events. MAG200 cohorts reported a greater proportion of responders than placebo and demonstrated clinical and statistically significant improvement in pain and clinically relevant improvement in all KOOS subscales. MAG200 demonstrated a reproducible treatment effect over placebo, which was clinically relevant for pain in the 10 â€‹× â€‹106 dose cohort (mean difference NPRS:-2.25[95%CI:-4.47,-0.03, p â€‹= â€‹0.0468]) and for function in the 20 â€‹× â€‹106 and 100 â€‹× â€‹106 dose cohorts (mean difference KOOSADL:10.12[95%CI:-1.51,21.76, p â€‹= â€‹0.0863] and 10.81[95%CI:-1.42,23.04, p â€‹= â€‹0.0810] respectively). A trend in disease-modification was observed with improvement in total knee cartilage volume in MAG200 10, 20, and 100 â€‹× â€‹106 dose cohorts, with progression of osteoarthritis in placebo, though this was not statistically significant. No clear dose response was observed. Conclusion: This early-phase study provides supportive safety and efficacy evidence to progress MAG200 to later-stage trial development. Trial registration: ACTRN12617001095358/ACTRN12621000622808.

Gene-environment interactions and aging visual function: a classical twin study.

OBJECTIVE: To elucidate the contribution of environmental versus genetic factors to the significant losses in visual function associated with normal aging. DESIGN: A classical twin study. PARTICIPANTS: Forty-two twin pairs (21 monozygotic and 21 dizygotic; age 57-75 years) with normal visual acuity recruited through the Australian Twin Registry. METHODS: Cone function was evaluated by establishing absolute cone contrast thresholds to flicker (4 and 14 Hz) and isoluminant red and blue colors under steady state adaptation. Adaptation dynamics were determined for both cones and rods. Bootstrap resampling was used to return robust intrapair correlations for each parameter. MAIN OUTCOME MEASURES: Psychophysical thresholds and adaptational time constants. RESULTS: The intrapair correlations for all color and flicker thresholds, as well as cone absolute threshold, were significantly higher in monozygotic compared with dizygotic twin pairs (P<0.05). Rod absolute thresholds (P = 0.28) and rod and cone recovery rate (P = 0.83; P = 0.79, respectively) did not show significant differences between monozygotic and dizygotic twins in their intrapair correlations, indicating that steady-state cone thresholds and flicker thresholds have a marked genetic contribution, in contrast with rod thresholds and adaptive processes, which are influenced more by environmental factors over a lifetime. CONCLUSIONS: Genes and the environment contribute differently to important neuronal processes in the retina and the role they may play in the decline in visual function as we age. Consequently, retinal structures involved in rod thresholds and adaptive processes may be responsive to appropriate environmental manipulation. Because the functions tested are commonly impaired in the early stages of age-related macular degeneration, which is known to have a multifactorial etiology, this study supports the view that pathogenic pathways early in the disease may be altered by appropriate environmental intervention. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

The effect of different anesthetics on tumor cytotoxicity by natural killer cells.

A number of retrospective studies have suggested that choice of anesthetic drugs during surgical tumor resection might affect tumor recurrence/metastasis, or outcome of patients. The recent study showed that volatile anesthetics-based general anesthesia was associated with the worse outcomes than intravenous anesthetics-based general anesthesia. However, the underlying mechanism is yet to be determined. Because natural killer (NK) cells are implicated as important immune cells for tumor recurrence/metastasis in the perioperative period, we examined the effect of different anesthetics on NK cell-mediated tumor cytotoxicity. Because adhesion molecule leukocyte function-associated antigen-1 (LFA-1) is functionally important in NK cells and is inhibited by commonly used volatile anesthetics isoflurane and sevoflurane, we hypothesized that these anesthetics would attenuate NK cell-mediated cytotoxicity. Using human NK cell line NK92-MI cells and tumor cell line K562 cells as a model system, we performed cytotoxicity, proliferation, conjugation and degranulation assays. Lytic granule polarization was also assessed. We showed that isoflurane, sevoflurane and LFA-1 inhibitor BIRT377 attenuated cytotoxicity, and reduced conjugation and polarization, but not degranulation of NK cells. Our data suggest that isoflurane and sevoflurane attenuated NK cell-mediated cytotoxicity at least partly by their LFA-1 inhibition in vitro. Whether or not isoflurane and sevoflurane attenuate NK cell-mediated tumor cytotoxicity in patients needs to be determined in the future.

The Differential Effects of Anesthetics on Bacterial Behaviors.

Volatile anesthetics have been in clinical use for a long period of time and are considered to be promiscuous by presumably interacting with several ion channels in the central nervous system to produce anesthesia. Because ion channels and their existing evolutionary analogues, ion transporters, are very important in various organisms, it is possible that volatile anesthetics may affect some bacteria. In this study, we hypothesized that volatile anesthetics could affect bacterial behaviors. We evaluated the impact of anesthetics on bacterial growth, motility (swimming and gliding) and biofilm formation of four common bacterial pathogens in vitro. We found that commonly used volatile anesthetics isoflurane and sevoflurane affected bacterial motility and biofilm formation without any effect on growth of the common bacterial pathogens studied here. Using available Escherichia coli gene deletion mutants of ion transporters and in silico molecular docking, we suggested that these altered behaviors might be at least partly via the interaction of volatile anesthetics with ion transporters.

Heritability of macular thickness determined by optical coherence tomography.

PURPOSE: To examine whether genetic factors significantly influence macular thickness in healthy older subjects. METHODS: A classic twin study was performed to compare the correlation of macular thickness between monozygotic (MZ) and dizygotic (DZ) twins in a sample of population-based volunteer twins. The study included 109 white twin pairs from 50 to 80 years of age without evidence of manifest eye disease and corrected visual acuity better than 6/7.5. Dilated macular optical coherence tomography (OCT), fundus photography, clinical examination, ocular biometry, a health-dietary questionnaire, and subjective autorefraction were performed on all subjects. RESULTS: Correlation of retinal thickness was significantly greater between MZ twin pairs than DZ pairs in all macular regions. The MZ-to-DZ correlation was 0.88:0.44 for the foveal region, 0.79:0.47 for the inner macular region, and 0.81:0.50 for the outer macular region. With adjustment for significant covariates and model fitting, final heritability estimates of 85%, 81%, and 81%, respectively, were obtained. A significant correlation between foveal thickness and gender was present, with the men having significantly thicker foveae. There was a significant negative correlation between outer macular thickness and axial length. CONCLUSIONS: This study confirms that macular thickness in older healthy subjects, as measured by OCT, may be affected by genetic factors. Factors such as axial length, gender and age, warrant further examination in larger population-based studies, as variables that may influence macular thickness. This finding suggests an inherited basis of macular thickness and may help in the understanding of the factors that govern macular structure and function.

Heritability of refractive error and ocular biometrics: the Genes in Myopia (GEM) twin study.

PURPOSE: A classic twin study was undertaken to assess the contribution of genes and environment to the development of refractive errors and ocular biometrics in a twin population. METHODS: A total of 1224 twins (345 monozygotic [MZ] and 267 dizygotic [DZ] twin pairs) aged between 18 and 88 years were examined. All twins completed a questionnaire consisting of a medical history, education, and zygosity. Objective refraction was measured in all twins, and biometric measurements were obtained using partial coherence interferometry. RESULTS: Intrapair correlations for spherical equivalent and ocular biometrics were significantly higher in the MZ than in the DZ twin pairs (P < 0.05), when refraction was considered as a continuous variable. A significant gender difference in the variation of spherical equivalent and ocular biometrics was found (P < 0.05). A genetic model specifying an additive, dominant, and unique environmental factor that was sex limited was the best fit for all measured variables. Heritability of spherical equivalents of 88% and 75% were found in the men and women, respectively, whereas, that of axial length was 94% and 92%, respectively. Additive genetic effects accounted for a greater proportion of the variance in spherical equivalent, whereas the variance in ocular biometrics, particularly axial length was explained mostly by dominant genetic effects. CONCLUSIONS: Genetic factors, both additive and dominant, play a significant role in refractive error (myopia and hypermetropia) as well as in ocular biometrics, particularly axial length. The sex limitation ADE model (additive genetic, nonadditive genetic, and environmental components) provided the best-fit genetic model for all parameters.

Refractive errors in twin studies.

It is estimated that 1.6 billion people worldwide have myopia, a refractive error, and this number is expected to increase to approximately 2.5 billion by the year 2020. It is now well established that both the environment and genetics play a role in the development of myopia. However, the exact contribution of each of these components to myopia development has yet to be completely determined. Twin studies (classical twin model) are commonly used to determine the weighting of genetic and environmental components in disease. Over the last century, twin studies have investigated the heritability of refractive errors in different sample populations and have collectively supported a genetic basis to refractive errors. However, different sample populations and methods of data collection have produced a wide range of heritability estimates ranging from .5 to .9. This article will review those twin studies that have investigated refractive error, particularly myopia, as well as biometric measures linked to refractive error, to compare heritability estimates and methodology designs.

Mirror-image congenital esotropia in monozygotic twins.

Monozygotic twins had mirror-image congenital esotropia and discordant refractive errors. One had right congenital esotropia surgically corrected during childhood, and the other had left congenital esotropia surgically corrected at 3 and 6 years old.

Management of submacular hemorrhage with intravitreal injection of tissue plasminogen activator and expansile gas.

PURPOSE: To evaluate the clinical outcome of intravitreal tissue plasminogen activator (tPA) and expansile gas injection as a minimally invasive treatment for submacular hemorrhage (SMH). METHODS: This study was a retrospective clinical case series examining 104 eyes that received an intravitreal injection of 30-100 mcg of tPA and expansile gas (SF6 or C3F8) for SMH. The main outcomes evaluated were visual acuities (VA), anatomic displacement of submacular blood, and surgical complications. RESULTS: : A total of 85, 77, and 81 eyes were available at 1 week, 3 months, and 12 months follow up, respectively. Postoperatively, > or = 2 Snellen lines improvement were achieved in 43/85 eyes (51%) at 1 week, 49/77 eyes (63%) at 3 months, and 52/81 eyes (64%) at 12 months. Postoperative VA improvement was significantly associated with preoperative VA, submacular blood displacement, and the underlying cause of SMH. Diagnostic postoperative angiogram and clinical examination were possible at 8.2 +/- 7.4 weeks and 9.5 +/- 7.4 weeks, respectively. The observed complications included breakthrough vitreous hemorrhage in 8 eyes (8%) and retinal detachment in 3 eyes (3%). CONCLUSIONS: In this retrospective series, intravitreal injection of tPA and expansile gas was shown to be a safe and effective technique that can improve VA in most eyes with SMH and assist in the diagnosis of the underlying cause.

Concordant bilateral Duane's Retraction Syndrome (type 1) in female monozygotic twins.

We report a single case study of concordant bilateral Duane's Retraction Syndrome (DRS) (type 1) in female monozygotic (MZ) twins aged 47 years. The twin pair were recruited through the Australian Twin Registry as part of a twin study on myopia. This twin pair were full term and had a similar birth weight: 2.27 kg and 1.81 kg in twin 1 and twin 2, respectively. There was no report of any other childhood medical conditions in either twin. Both twins had an equal amount of restriction in right and left abduction. Narrowing of the palpebral fissures and globe retraction in right and left adduction was also observed in both twins. To our knowledge this is the first case to report concordant bilateral DRS (type 1) in female MZ twins. The concordance for the presence of DRS and associated clinical signs observed in this MZ twin pair supports a genetic origin to DRS.

Marked discordance for myopia in female monozygotic twins.

Female monozygotic twins aged 54 years discordant for myopia are reported. One twin presented with bilateral high myopia (right eye = -6.00/+0.50 x 5 degrees , left eye = -6.00/+0.50 x 45 degrees ) and her identical twin had no significant refractive error (right eye = -0.50/plano, left eye = -0.50/+0.75 x 40 degrees ). An explanation for the striking refractive discordance seen in this case report is yet to be determined.