Lysyl oxidase like-1 deficiency in optic nerve head astrocytes elicits reactive astrocytosis and alters functional effects of astrocyte derived exosomes.

Glaucoma is a multifactorial progressive ocular pathology that manifests clinically with damage to the optic nerve (ON) and the retina, ultimately leading to blindness. The optic nerve head (ONH) shows the earliest signs of glaucoma pathology, and therefore, is an attractive target for drug discovery. The goal of this study was to elucidate the effects of reactive astrocytosis on the elastin metabolism pathway in primary rat optic nerve head astrocytes (ONHA), the primary glial cell type in the unmyelinated ONH. Following exposure to static equibiaxial mechanical strain, we observed prototypic molecular and biochemical signatures of reactive astrocytosis that were associated with a decrease in lysyl oxidase like 1 (Loxl1) expression and a concomitant decrease in elastin (Eln) gene expression. We subsequently investigated the role of Loxl1 in reactive astrocytosis by generating primary rat ONHA cultures with ∼50% decreased Loxl1 expression. Our results suggest that reduced Loxl1 expression is sufficient to elicit molecular signatures of elastinopathy in ONHA. Astrocyte derived exosomes (ADE) significantly increased the length of primary neurites of primary neurons in vitro. In contrast, ADE from Loxl1-deficient ONHA were deficient of trophic effects on neurite outgrowth in vitro, positing that Loxl1 dysfunction and the ensuing impaired elastin synthesis during reactive astrocytosis in the ONH may contribute to impaired neuron-glia signaling in glaucoma. Our data support a role of dysregulated Loxl1 function in eliciting reactive astrocytosis in glaucoma subtypes associated with increased IOP, even in the absence of genetic polymorphisms in LOXL1 typically associated with exfoliation glaucoma. This suggests the need for a paradigm shift toward considering lysyl oxidase activity and elastin metabolism and signaling as contributors to an altered secretome of the ONH that may lead to the progression of glaucomatous changes. Future research is needed to investigate cargo of exosomes in the context of reactive astrocytosis and identify the pathways leading to the observed transcriptome changes during reactive astrocytosis.

Asteroid hyalosis-a comprehensive review.

Asteroid hyalosis is a relatively common cause of vitreous opacities, which is possibly associated with diabetes mellitus and hereditary pigmentary retinopathies. We review the history, epidemiology, and biochemistry of asteroid hyalosis, as well as its relationship with ocular and systemic conditions. We describe imaging modalities used for diagnostic evaluations in cases of severe asteroid hyalosis and propose hypotheses regarding its lack of significant effects on vision. We discuss cataract surgery in patients with asteroid hyalosis and the selection of intraocular lenses for implantation.

Song structure and singing activity of two separate humpback whales populations wintering off the coast of Caño Island in Costa Rica.

Central American (CA) and Breeding Stock-G (BSG) humpback whales are known to winter off Caño Island, Costa Rica at different times of the year. To study their singing behavior, autonomous underwater recorders were used to record the whales. Song detection for BSG whales was higher than CA whales, and song structure was distinct for each population. No strong evidence for cross-equatorial connectivity was found. This study provides the first humpback whale song reference for both populations in Costa Rica, which can help advance understanding of CA and BSG whale song rate of change and connectivity with other wintering areas.

Implementation and assessment of a curriculum for bedside ultrasound training.

OBJECTIVES: This study assessed a curriculum for bedside ultrasound (US) and compared outcomes from 2 common training pathways. METHODS: The program consisted of e-learning paired with expert-led hands-on training administered to pulmonary/critical care and cardiology fellows with no prior formal training in bedside US. This "simulation-based learner" group completed a survey of attitudes and confidence before and after training, and knowledge and skills were assessed after training. The surveys and scores of the simulation-based learners were compared to the scores of "experts," who were US-trained emergency physicians, and "apprentice learners," who were intensivist physicians informally trained in bedside US on the job during fellowships. RESULTS: There was a significant difference in the self-reported level of prior training between the groups (simulation-based learners, 2.8; apprentice learners, 3.7; experts, 4.1, on a scale of 1-5 [P= .02]) but no difference in the interest level or perceived importance of bedside US. The study curriculum was successful, as shown by scores that exceeded the comparison groups in the cardiac and pulmonary courses (cardiac: simulation-based learners, 80%; apprentice learners, 73%; experts, 62% [P= .001]; pulmonary: 84%, 75%, and 72%, respectively [P =.02]). The simulation-based learners gained confidence in skills, whereas the comparison groups lost confidence after testing (P < .005); however, the simulation-based learners gained confidence in US subject areas that were not taught (abdomen [P <.002] and miscellaneous [P =.005]). CONCLUSIONS: The simulation-based learner curriculum resulted in comparable or greater knowledge and confidence in each area of US versus the comparison groups. Findings of overgeneralization of confidence highlight the importance of quality assurance and supervision in bedside US training programs.

Prospective analysis of single operator sonographic optic nerve sheath diameter measurement for diagnosis of elevated intracranial pressure.

INTRODUCTION: The accurate diagnosis of elevated intracranial pressure (eICP) in the emergent setting is a critical determination that presents significant challenges. Several studies show correlation of sonographic optic nerve sheath diameter (ONSD) to eICP, while others show high inter-observer variability or marginal performance with less experienced sonographers. The objective of our study is to assess the ability of bedside ultrasound measurement of ONSD to identify the presence of eICP when performed by a single experienced sonographer. We hypothesize that ONSD measurement is sensitive and specific for detecting eICP and can be correlated with values obtained by external ventricular device (EVD). METHODS: This was a prospective blinded observational study conducted in a neurocritical care unit of a level 1 trauma center. ONSD measurement was performed on a convenience sample of 27 adult patients who required placement of an invasive intracranial monitor as part of their clinical care. One certified sonographer/physician performed all ultrasounds within 24 hours of placement of EVD. The sonographer was blinded to the ICP recorded by invasive monitor at the time of the scan. A mean ONSD value of ≥5.2 mm was taken as positive. RESULTS: The sonographer performed 27 ocular ultrasounds on individual patients. Six (22%) of these patients had eICP (EVD measurement of >20 mmHg). Spearman rank correlation coefficient of ONSD and ICP was 0.408 (p=0.03), demonstrating a moderate positive correlation. A ROC curve was created to determine the optimal cut off value to distinguish an eICP greater than 20 mmHg. The area under the receiver operator characteristic curve was 0.8712 (95% confidence interval [CI]=0.67 to 0.96). ONSD ≥5.2 mm was a good predictor of eICP (>20 mmHg) with a sensitivity of 83.3% (95% CI=35.9% to 99.6%) and specificity of 100% (95% CI=84.6% to 100%). CONCLUSION: While the study suggests ONSD measurements performed by a single skilled operator may be both sensitive and specific for detecting eICP, confirmation in a much larger sample is needed. Ocular ultrasound may provide additional non-invasive means of assessing eICP.

Cardiac tamponade presenting as refractory asthma.

Asthma has numerous etiologies, and successful treatment requires a proper diagnosis. Changes in weather and exposure to dust can make treatment of asthma difficult. This case exemplifies a diagnostic dilemma associated with bronchospasm; bronchospasm can have an occult cardiac etiology. Diagnosis can be particularly challenging in rural sub-Saharan Africa during the Harmattan, when winds are blowing sands from the Sahara into nearby villages, especially when radiographs are not available. This case is that of a 40-year-old female Ghanaian woman with a lifelong history of asthma. Although she has often had exacerbations of bronchospasm during the dusty Harmattan season, her bronchospasm was now refractory to usual treatments. X-rays were not available at the clinic in the rural city of Tamale, Ghana, and bedside ultrasound was utilized. She was found to have cardiac tamponade with secondary "cardiac asthma." After 750 cc of fluid was aspirated during a bedside pericardiocentesis, her bronchospasm immediately resolved. The cardiac effusion was due to previously unknown renal failure from hyper-tension. The patient was referred for dialysis and 1 year later was well without any recurrence of significant cardiac effusions. Healthcare providers should be wary of atypical non-pulmonary etiologies of bronchospasm, especially in cases where there is an inadequate response to usual treatment. Bedside ultrasound has great utility for the diagnosis of cardiac tamponade.

El asma tiene diversas etiologías y el éxito del tratamiento exige un diagnóstico correcto. Los cambios en las condiciones atmosféricas y la exposición al polvo pueden dificultar su tratamiento. Este caso ejemplifica un dilema diagnóstico asociado con el broncoespasmo, que puede ser de etiología cardíaca oculta. El diagnóstico puede ser especialmente difícil en el África subsahariana rural durante el período del harmatán, cuando el viento sopla llevando arena del desierto del Sáhara a los pueblos cercanos y, especialmente, cuando no es posible realizar radiografías. Este caso es de una mujer ghanesa de 40 años con antecedentes de asma durante toda su vida. Aunque solía sufrir reagudizaciones de broncoespasmo durante la época del harmatán, ahora el trastorno se había vuelto resistente a los tratamientos habituales. En la clínica de la ciudad rural de Tamale (Ghana) no había posibilidad de obtener una radiografía y se utilizó un ultrasonido de cabecera. Se halló que presentaba taponamiento cardíaco con «asma cardíaco¼ secundario. Tras aspirar 750 cc de líquido mediante una pericardiocentesis en la cabecera, su broncoespasmo desapareció de inmediato. El derrame cardíaco se debió a una insuficiencia renal anteriormente desconocida derivada de la hipertensión. Se remitió la paciente para que recibiera diálisis y, 1 año más tarde, se encontraba bien y sin recurrencia de derrames cardíacos de importancia. Los profesionales sanitarios deben sospechar etiologías atípicas no pulmonares del broncoespasmo, especialmente en aquellos casos en los que se produce una respuesta inadecuada al tratamiento habitual. El ultra-sonido de cabecera del paciente resulta de gran utilidad para el diagnóstico de un taponamiento cardíaco.

Applications of a New Handheld Reference Point Indentation Instrument Measuring Bone Material Strength.

A novel, hand-held Reference Point Indentation (RPI) instrument, measures how well the bone of living patients and large animals resists indentation. The results presented here are reported in terms of Bone Material Strength, which is a normalized measure of how well the bone resists indentation, and is inversely related to the indentation distance into the bone. We present examples of the instrument's use in: (1) laboratory experiments on bone, including experiments through a layer of soft tissue, (2) three human clinical trials, two ongoing in Barcelona and at the Mayo Clinic, and one completed in Portland, OR, and (3) two ongoing horse clinical trials, one at Purdue University and another at Alamo Pintado Stables in California. The instrument is capable of measuring consistent values when testing through soft tissue such as skin and periosteum, and does so handheld, an improvement over previous Reference Point Indentation instruments. Measurements conducted on horses showed reproducible results when testing the horse through tissue or on bare bone. In the human clinical trials, reasonable and consistent values were obtained, suggesting the Osteoprobe® is capable of measuring Bone Material Strength in vivo, but larger studies are needed to determine the efficacy of the instrument's use in medical diagnosis.