Aqueous tear assessment in dogs: Impact of cephalic conformation, inter‐test correlations, and test‐retest repeatability

Objective - To characterize diagnostic findings, test‐retest repeatability, and correlations among lacrimal tests in dogs of diverse cephalic conformations. Animal studied - Fifty healthy dogs (25 brachycephalic, 25 nonbrachycephalic). Procedures - A series of diagnostics were performed in each dog, allowing for a 10‐minute interval between tests and repeating each test 24 hours later under similar conditions: corneal tactile sensation (CTS), strip meniscometry test (SMT), phenol red thread test (PRTT), endodontic absorbent paper point tear test (EAPPTT), Schirmer tear test‐1 without (STT‐1) or with nasolacrimal stimulation (NL‐STT1), and Schirmer tear test‐2 (STT‐2). Results - Mean ± SD test values were lower in brachycephalic vs. nonbrachycephalic dogs (except for SMT; 7.4 ± 2.0 mm/5 seconds vs 7.3 ± 2.4 mm/5 seconds), with statistically significant differences noted for CTS (1.8 ± 0.5 cm vs 3.4 ± 0.8 cm), PRTT (37.2 ± 4.0 mm/15 seconds vs 41.1 ± 5.5 mm/15 seconds), STT‐1 (20.1 ± 3.4 mm/min vs 23.3 ± 5.7 mm/min), STT‐2 (13.0 ± 3.4 mm/min vs 16.9 ± 3.9 mm/min), and NL‐STT1 (23.2 ± 3.6 mm/min vs 27.1 ± 5.4 mm/min), and nonsignificant differences for EAPPTT (16.6 ± 2.7 mm/15 seconds vs 17.5 ± 2.9 mm/15 seconds). Nasolacrimal stimulation increased STT‐1 values by 18% on average. Correlations among tests were generally weak to moderate (r \u3c .70) except for a strong correlation between STT‐1 and NL‐STT1 (r = .83, P \u3c .001). Test reliability was good although test‐retest repeatability was generally poor to moderate, as depicted by low intraclass correlation coefficients (ICC ≤ 0.75) and wide 95% limits of agreement, except for CTS (ICC = 0.91). Conclusions - Corneal sensitivity and aqueous tear secretion are lower in brachycephalic dogs. A comprehensive assessment of the ocular surface requires the combination of several diagnostic tests. The nasolacrimal reflex may provide a useful diagnostic and therapeutic tool in dogs

Influence of convolution filtering on coronary plaque attenuation values: observations in an ex vivo model of multislice computed tomography coronary angiography

Attenuation variability (measured in Hounsfield Units, HU) of human coronary plaques using multislice computed tomography (MSCT) was evaluated in an ex vivo model with increasing convolution kernels. MSCT was performed in seven ex vivo left coronary arteries sunk into oil followingthe instillation of saline (1/∞) and a 1/50 solution of contrast material (400 mgI/ml iomeprol). Scan parameters were: slices/collimation, 16/0.75 mm; rotation time, 375 ms. Four convolution kernels were used: b30f-smooth, b36f-medium smooth, b46f-medium and b60f-sharp. An experienced radiologist scored for the presence of plaques and measured the attenuation in lumen, calcified and noncalcified plaques and the surrounding oil. The results were compared by the ANOVA test and correlated with Pearson’s test. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The mean attenuation values were significantly different between the four filters (p < 0.0001) in each structure with both solutions. After clustering for the filter, all of the noncalcified plaque values (20.8 ± 39.1, 14.2 ± 35.8, 14.0 ± 32.0, 3.2 ± 32.4 HU with saline; 74.7 ± 66.6, 68.2 ± 63.3, 66.3 ± 66.5, 48.5 ± 60.0 HU in contrast solution) were significantly different, with the exception of the pair b36f–b46f, for which a moderate-high correlation was generally found. Improved SNRs and CNRs were achieved by b30f and b46f. The use of different convolution filters significantly modifief the attenuation values, while sharper filtering increased the calcified plaque attenuation and reduced the noncalcified plaque attenuation

Prevalence of anatomical variants and coronary anomalies in 543 consecutive patients studied with 64-slice CT coronary angiography

The aim of our study was to assess the prevalence of variants and anomalies of the coronary artery tree in patients who underwent 64-slice computed tomography coronary angiography (CT-CA) for suspected or known coronary artery disease. A total of 543 patients (389 male, mean age 60.5 ± 10.9) were reviewed for coronary artery variants and anomalies including post-processing tools. The majority of segments were identified according to the American Heart Association scheme. The coronary dominance pattern results were: right, 86.6%; left, 9.2%; balanced, 4.2%. The left main coronary artery had a mean length of 112 ± 55 mm. The intermediate branch was present in the 21.9%. A variable number of diagonals (one, 25%; two, 49.7%; more than two, 24%; none, 1.3%) and marginals (one, 35.2%; two, 46.2%; more than two, 18%; none, 0.6%) was visualized. Furthermore, CT-CA may visualize smaller branches such as the conus branch artery (98%), the sinus node artery (91.6%), and the septal branches (93%). Single or associated coronary anomalies occurred in 18.4% of the patients, with the following distribution: 43 anomalies of origin and course, 68 intrinsic anomalies (59 myocardial bridging, nine aneurisms), three fistulas. In conclusion, 64-slice CT-CA provides optimal visualization of the variable and complex anatomy of coronary arteries because of the improved isotropic spatial resolution and flexible post-processing tool

Strategies to Target Tumor Immunosuppression

The tumor microenvironment is currently in the spotlight of cancer immunology research as a key factor impacting tumor development and progression. While antigen-specific immune responses play a crucial role in tumor rejection, the tumor hampers these immune responses by creating an immunosuppressive microenvironment. Recently, major progress has been achieved in the field of cancer immunotherapy, and several groundbreaking clinical trials demonstrated the potency of such therapeutic interventions in patients. Yet, the responses greatly vary among individuals. This calls for the rational design of more efficacious cancer immunotherapeutic interventions that take into consideration the “immune signature” of the tumor. Multimodality treatment regimens that aim to enhance intratumoral homing and activation of antigen-specific immune effector cells, while simultaneously targeting tumor immunosuppression, are pivotal for potent antitumor immunity

Assessment of age-related changes in pediatric gastrointestinal solubility

PurposeCompound solubility serves as a surrogate indicator of oral biopharmaceutical performance. Between infancy and adulthood, marked compositional changes in gastrointestinal (GI) fluids occur. This study serves to assess how developmental changes in GI fluid composition affects compound solubility.MethodsSolubility assessments were conducted in vitro using biorelevant media reflective of age-specific pediatric cohorts (i.e., neonates and infants). Previously published adult media (i.e., FaSSGF, FeSSGF, FaSSIF.v2, and FeSSIF.v2) were employed as references for pediatric media development. Investigations assessing age-specific changes in GI fluid parameters (i.e., pepsin, bile acids, pH, osmolality, etc.) were collected from the literature and served to define the composition of neonatal and infant media. Solubility assessments at 37°C were conducted for seven BCS Class II compounds within the developed pediatric and reference adult media.ResultsFor six of the seven compounds investigated, solubility fell outside an 80–125% range from adult values in at least one of the developed pediatric media. This result indicates a potential for age-related alterations in oral drug performance, especially for compounds whose absorption is delimited by solubility (i.e., BCS Class II).ConclusionDevelopmental changes in GI fluid composition can result in relevant discrepancies in luminal compound solubility between children and adults.<br/