A transconjunctival surgical technique for dacryocystotomy in dogs with foreign body-induced dacryocystitis.

PURPOSE: The purpose of this study is to describe a simplified, less invasive dacryocystotomy technique that allows for complete inspection of the canine lacrimal sac and to retrospectively evaluate this surgical technique in a larger series of dogs. The anatomical background of the canine nasolacrimal system is described as a basis for the surgical technique. METHODS: Records of dogs from 2003 to 2023 which were diagnosed with dacryocystitis due to presumed foreign body and underwent surgical exploration and removal of foreign bodies within the lacrimal sac using this technique were reviewed. Postoperative treatment and outcome were evaluated. RESULTS: Records of 48 dogs were included. A foreign body was discovered during the surgery or upon retrieval of the catheter in 85% of cases (41/48). An indwelling catheter was placed in 83% of cases (40/48) for a median of 21 days. At the last recheck, the nasolacrimal duct was patent in 87% of the cases (41/47). The median follow-up time was 34 days (3-1255 days). The most commonly affected breeds were Golden retrievers (11) and dachshunds (8). The following complications occurred: two dogs removed or partly removed the catheter themselves (day 7, day 14), and one dog showed marked irritation at the catheter site which had to be removed by day 10. CONCLUSIONS: The transconjunctival dacryocystotomy technique is simple and less invasive than other described techniques with a successful long-term outcome in the majority of cases.

Outer retinal thickness and visibility of the choriocapillaris in four distinct retinal regions imaged with spectral domain optical coherence tomography in dogs and cats.

PURPOSE: To evaluate the outer retinal band thickness and choriocapillaris (CC) visibility in four distinct retinal regions in dogs and cats imaged with spectral domain optical coherence tomography (SD-OCT). To attempt delineation of a fovea-like region in canine and feline SD-OCT scans, aided by the identification of outer retinal thickness differences between retinal regions. METHODS: Spectralis® HRA + OCT SD-OCT scans from healthy, anesthetized dogs (n = 10) and cats (n = 12) were analyzed. Scanlines on which the CC was identifiable were counted and CC visibility was scored. Outer nuclear layer (ONL) thickness and the distances from external limiting membrane (ELM) to retinal pigment epithelium/Bruch's membrane complex (RPE/BM) and ELM to CC were measured in the area centralis (AC), a visually identified fovea-like region, and in regions superior and inferior to the optic nerve head (ONH). Measurements were analyzed using a multilevel regression. RESULTS: The CC was visible in over 90% of scanlines from dogs and cats. The ONL was consistently thinnest in the fovea-like region. The outer retina (ELM-RPE and ELM-CC) was thickest within the AC compared with superior and inferior to the ONH in dogs and cats (p < .001 for all comparisons). CONCLUSIONS: The CC appears a valid, albeit less than ideal outer retinal boundary marker in tapetal species. The AC can be objectively differentiated from the surrounding retina on SD-OCT images of dogs and cats; a fovea-like region was identified in dogs and its presence was suggested in cats. These findings allow targeted imaging and image evaluation of these regions of retinal specialization.

Innovative high-resolution microCT imaging of animal brain vasculature.

Analysis of the angioarchitecture and quantification of the conduit vessels and microvasculature is of paramount importance for understanding the physiological and pathological processes within the central nervous system (CNS). Most of the available in vivo imaging methods lack penetration depth and/or resolution. Some ex vivo methods may provide better resolution, but are mainly destructive, as they are designed for imaging the CNS tissues after their removal from the skull or vertebral column. The removal procedure inevitably alters the in situ relations of the investigated structures and damages the dura mater and leptomeninges. µAngiofil, a polymer-based contrast agent, permits a qualitatively novel postmortem microangio-computed tomography (microangioCT) approach with excellent resolution and, therefore, visualization of the smallest brain capillaries. The datasets obtained empower a rather straightforward quantitative analysis of the vascular tree, including the microvasculature. The µAngiofil has an excellent filling capacity as well as a radio-opacity higher than the one of bone tissue, which allows imaging the cerebral microvasculature even within the intact skull or vertebral column. This permits in situ visualization and thus investigation of the dura mater and leptomeningeal layers as well as their blood supply in their original geometry. Moreover, the methodology introduced here permits correlative approaches, i.e., microangioCT followed by classical histology, immunohistochemistry and even electron microscopy. The experimental approach presented here makes use of common desktop microCT scanners, rendering it a promising everyday tool for the evaluation of the (micro)vasculature of the central nervous system in preclinical and basic research.

Spectral Domain Optical Coherence Tomography in Awake Rabbits Allows Identification of the Visual Streak, a Comparison with Histology.

Purpose: To evaluate visual streak (VS) identification on spectral-domain optical coherence tomography (SD-OCT) scans in awake rabbits. To report thickness measurements in the VS and adjacent retina on OCT B-scans and histologic sections and to assess inter-method bias, precision and repeatability between OCT and histology. Methods: Vertical SD-OCT B-scan images through the optic nerve head and VS were acquired from 16 awake, ophthalmologically healthy experimental rabbits. Scans were acquired from both eyes, which were later enucleated and processed for light microscopy. Inner retina, inner nuclear layer, outer nuclear layer, outer retina (OR) and photoreceptor outer segment (PROS) thickness were measured on OCT images and digitalized microscopy slides in- and outside of the VS, and compared using linear mixed effects models. Results: Both SD-OCT and histology allowed retinal layer identification and measurement. On OCT, OR and PROS were thickest in the central VS and thinnest outside the VS. Histology mirrored OCT results for central outer retinal layers but shows discrepancies for other layers likely because of postmortem processing artifacts. The method comparison demonstrated better repeatability for OCT measurements compared with histology. Conclusions: Increased OR and PROS thickness compared with the adjacent retina allowed identification of the VS on SD-OCT in awake rabbits. OCT allows measurements devoid of processing artifacts in contrast to histology. Translational Relevance: SD-OCT is possible in awake rabbits. Easy and reliable identification of the VS may facilitate the positioning and use of rabbits as model species in human macular and generalized retinal disease research.

Combined cSLO-OCT imaging as a tool in preclinical ocular toxicity testing: A comparison to standard in-vivo and pathology methods.

INTRODUCTION: Confocal scanning laser ophthalmoscopy and optical coherence tomography (cSLO-OCT) became available for human and animal ophthalmic examinations in recent years. The purpose of this study was to evaluate lesion detection and localization with cSLO-OCT imaging in an experimental outer retinal toxicity model and to compare cSLO-OCT to standard examination methods (indirect ophthalmoscopy (IO), fundus photography (FP) and central section histopathology). METHODS: A test compound was orally administered to albino rats (n = 4) for four weeks (part A) and to albino (n = 2) and pigmented (n = 2) rats for eight weeks (part B). Control animals received vehicle only. Retinal changes were documented using cSLO-OCT, IO, FP, angiography and histopathology. Retinal thicknesses were compared between groups using a mixed effects model. RESULTS: All compound-treated animals developed progressive multifocal hyperreflective spot changes mostly confined to the retinal pigment epithelium. In study parts A and B, cSLO identified fundus lesions earlier than IO/FP in albino rats. In study part B, cSLO quantified fundus lesions more accurately than IO/FP in albino rats but no difference was seen in pigmented rats. Central section histopathology revealed no abnormalities in three out of four compound-treated animals in part B. Altogether, without cSLO-OCT, present fundus changes would have remained undetected in one of four compound-treated animals in both parts A and B. DISCUSSION: Integration of combined cSLO-OCT imaging into toxicology study design can improve toxicity study readouts and facilitate longitudinal examination of single animals at multiple time points, leading to a reduction of experimental animal numbers.

Interspecies Variation of Outer Retina and Choriocapillaris Imaged With Optical Coherence Tomography.

Purpose: The purpose of this study is to assess with spectral-domain optical coherence tomography (OCT) the interspecies variation of outer retinal morphology and identification of choriocapillaris in four research animal species. Methods: Spectralis HRA+OCT images acquired from locations dorsal, central, and ventral to the optic disc in healthy, anesthetized animals were evaluated by two independent readers. First, the number of OCT B-scans on which a choriocapillaris layer could clearly be identified was determined and quantified, and B-scans were correlated with histology. Second, B-scans demonstrating the highest number of discernable individual outer retinal bands (ORBs) were defined as ideal presentation and quantified. Interrater agreement was evaluated. Results: Five-hundred seventy-four B-scans from 96 subjects were evaluated. The choriocapillaris layer was identified in 100.0% of minipig, 70.8% of rabbit, 75.4% of pigmented rat, 77.7% of albino rat, 56.5% of pigmented mouse, and 50.8% of albino mouse OCT scans. The percentage of ideal ORB presentation in B-scans was 11.7% in minipigs, 73.8% in rabbits, and 80.0%, 91.0%, 28.5%, and 62.5% in pigmented rats and mice and albino rats and mice, respectively. The interrater evaluation for both attributes showed substantial to perfect agreement in all species. Conclusions: The choriocapillaris is an easy and valid marker for identification of the outer retinal margin. ORB presentation likely varies due to differences in retinal anatomy and pigmentation between animal species and strains and between anatomic locations. Proper and consistent outer retinal margin and ORB identification are essential for research result reproducibility and translation.

Hematopoietic Stem Cell Transplantation From Haploidentical Donors in Aplasia After Cladribine/Cytarabine Chemotherapy for Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome.

INTRODUCTION: Survival rate of patients with chemorefractory acute myeloid leukemia (AML) or myelodysplastic syndrome with excess blasts (MDS-EB) is poor. Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy in these patients. PATIENTS AND METHODS: We report a retrospective analysis of outcomes of therapy of 24 patients with AML or MDS-EB refractory to high-dose salvage chemotherapy or who had failed previous HCT, who received T-cell-replete HLA haploidentical HCT in aplasia after cladribine/cytarabine-based chemotherapy followed by reduced intensity or myeloablative conditioning. All patients had active disease before commencement of the treatment. RESULTS: Of the patients, 91.7% achieved complete remission (CR), whereas 2 patients (8.2%) died in aplasia. One-year relapse rate was 49.3%. Cumulative incidence of nonrelapse mortality (NRM) was 25.6%. In a subgroup of patients with HCT-comorbidity index score ≤ 3, NRM was 15.4%. Two-year overall survival and relapse-free survival were 30.6% and 22.6%, respectively. Incidence of grade 3 and 4 acute graft versus host disease was 21.3% and 8.3, respectively. CONCLUSION: We found that sequential therapy with HCT in aplasia after cladribine/cytarabine chemotherapy is feasible, results in high CR rates, and has acceptable toxicity profile; however, posttransplant relapse is common in patients treated with active disease.

Mediation pattern of proactive coping and social support on well-being and depression

Proactive coping is a multidimensional and future-looking quality of life strategy that can predict positive outcomes and regulate distress. Recently, social support has been seen as an essential resource for effective coping with stressors. On this basis, a cross-sectional study examining a theoretical model was investigated using a path analysis. It was hypothesized that social support would be associated with proactive coping in the synergistic relationship and in relation to the positive psychological variable of well-being. Moreover, direct relationships between well-being and feelings of depression were expected. In a sample of 482 full-time university students attending public university, the results showed that social support and comparable proactive coping directly contributed to an increase in well-being. Furthermore, well-being was directly related to depression. Besides direct effects, an indirect pathway from social support to well-being was tested confirming the hypothesis that proactive coping functions as a partial mediator between social support and well-being. Generalizability of the findings was tested across gender and age performing multi-group analyses. Furthermore, practical implications, study limitations, and future research are discussed

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"They Think that I Should Defend": Effects of Peer and Teacher Injunctive Norms on Defending Victimized Classmates in Early Adolescents.

Norms have been suggested as important characteristics of the social-ecological context for defending victimized peers, but little is known about the contribution of student perceived injunctive norms (regarding the appropriateness of defending) imposed by peers and teachers. To investigate the role of these norms in defending, a sample of 751 early adolescents (51% female; Mage at Time 1:13 years) was assessed at two time points. Defending, as measured by peer- and self-ratings, decreased slightly over a six-month timespan. Three-level models (with time, students, and classrooms as the levels) indicated that both individual- and classroom-level perceived peer injunctive norms (but not teacher injunctive norms) had positive effects on defending over time regardless of the source of the information on defending (peers or self). These findings support programs that encourage defending through peer norms.

The relationship of obesity to the timing of permanent tooth emergence in Czech children.

BACKGROUND: The aim of this study was to investigate the influence of BMI on the timing of permanent tooth emergence in Czech children. OBJECTIVES: In this cross-sectional study, 1370 Czech children were examined. The age, gender, weight, height, all emerged permanent teeth (except third molars) of each child were all recorded. A tooth is defined as having emerged when at least any part of it has penetrated the gingiva. METHODS: A logistic regression model was used to calculate the median emergence age per tooth for both genders separately and BMI was used as a factor variable to detect statistically significant differences in the times of tooth emergence within pairs of BMI groups. The data were statistically processed using IBM SPSS Statistics 23 (SPSS Inc., Chicago, IL). RESULTS: Statistically significant differences were found for the following permanent teeth (using the FDI two-digit system): 13, 14, 15, 16, 17, 41, 44, 45, 46, 47, 33, 35, 37, 21, 24, 25, 26, 27 for girls and 12, 13, 14, 15, 16, 41, 43, 44, 45, 22, 25, 32, 34, 35, 36 for boys. These teeth were observed to emerge earlier in obese children. A similar correlation (although not statistically significant) was observed between the time of emergence of the remaining teeth and the BMI of the child. CONCLUSION: The data in this research highlight significant differences in emergence times of permanent teeth due to the influence of BMI in Czech children. These findings are important for dental treatment planning.

Altered HLA Class I Profile Associated with Type A/D Nucleophosmin Mutation Points to Possible Anti-Nucleophosmin Immune Response in Acute Myeloid Leukemia.

Nucleophosmin 1 (NPM1) mutations are frequently found in patients with acute myeloid leukemia (AML) and the newly generated sequences were suggested to induce immune response contributing to the relatively favorable outcome of patients in this AML subset. We hypothesized that if an efficient immune response against mutated nucleophosmin can be induced in vivo, the individuals expressing HLA alleles suitable for presenting NPM-derived peptides should be less prone to developing AML associated with NPM1 mutation. We thus compared HLA class I frequencies in a cohort of patients with mutated NPM1 (63 patients, NPMc+), a cohort of patients with wild-type NPM1 (94 patients, NPMwt) and in normal individuals (large datasets available from Allele Frequency Net Database). Several HLA allelic groups were found to be depleted in NPMc+ patients, but not in NPMwt compared to the normal distribution. The decrease was statistically significant for HLA B(*)07, B(*)18, and B(*)40. Furthermore, statistically significant advantage in the overall survival was found for patients with mutated NPM1 expressing at least one of the depleted allelic groups. The majority of the depleted alleles were predicted to bind potent NPM-derived immunopeptides and, importantly, these peptides were often located in the unmutated part of the protein. Our analysis suggests that individuals expressing specific HLA allelic groups are disposed to develop an efficient anti-AML immune response thanks to aberrant cytoplasmic localization of the mutated NPM protein.

Characterization of chromosome 11 breakpoints and the areas of deletion and amplification in patients with newly diagnosed acute myeloid leukemia.

Chromosome 11 abnormalities are found in many hematological malignancies. In acute myeloid leukemia (AML), a proto-oncogene MLL (11q23.3) is frequently altered. However, rearrangements involving other regions of chromosome 11 have been reported. Therefore, we have characterized the chromosome 11 breakpoints and common deleted and amplified areas in the bone marrow or peripheral blood cells of newly diagnosed patients with AML. Using molecular-cytogenetic methods (multicolor fluorescence in situ hybridization (mFISH), multicolor banding (mBAND), microarrays, and FISH with bacterial artificial chromosome (BAC) probes, chromosome 11 abnormalities were delineated in 54 out of 300 (18%) newly diagnosed AML patients. At least 36 different chromosome 11 breakpoints were identified; two were recurrent (11p15.4 in the NUP98 gene and 11q23.3 in the MLL gene), and three were possibly nonrandom: 11p13 (ch11:29.31-31.80 Mb), 11p12 (ch11:36.75-37.49 Mb) and 11q13.2 (68.31-68.52 Mb). One new MLL gene rearrangement is also described. No commonly deleted region of chromosome 11 was identified. However, some regions were affected more often: 11pter-11p15.5 (n = 4; ch11:0-3.52 Mb), 11p14.1-11p13 (n = 4; ch11:28.00-31.00 Mb) and 11p13 (n = 4; ch11:31.00-31.50 Mb). One commonly duplicated (3 copies) region was identified in chromosomal band 11q23.3-11q24 (n = 9; ch11:118.35-125.00 Mb). In all eight cases of 11q amplification (>3 copies), only the 5' part of the MLL gene was affected. This study highlights several chromosome 11 loci that might be important for the leukemogeneic process in AML.

Prognostic impact of DNMT3A mutations in patients with intermediate cytogenetic risk profile acute myeloid leukemia.

OBJECTIVES: Recently, mutations in DNMT3A gene have been described in about 25% acute myeloid leukemia (AML) cases, preferentially in monocytic AML. They were found to predict worse overall survival (OS) of mutated patients. PATIENTS AND METHODS: RT-PCR followed by direct sequencing was used to test the presence of DNMT3A mutations in 226 AML patients with an intermediate-risk (IR) cytogenetics. RESULTS: Sixty-seven patients of 226 (29.6%) carried a mutation in the DNMT3A gene. Occurrence of DNMT3A mutations was associated with female sex (P = 0.027) and with the presence of FLT3/ITD (P = 0.003), but not with particular FAB subtypes. Patients with DNMT3A mutation had higher initial WBC counts than those without it (P = 0.064) only because of higher incidence of FLT3/ITD within these cases. There was no difference between mutated and wild-type groups in reaching complete remission (CR) (P = 0.380). OS was not affected by DNMT3A mutation (P = 0.251), but OS of patients who reached CR was longer in DNMT3A negative cases (P = 0.025). Patients with DNMT3A mutation had a higher relapse rate (P = 0.007). Patients carrying both the DNMT3A mutation and FLT3/ITD relapsed more often than either patients with single DNMT3A mutation (P = 0.044) or patients with FLT3/ITD only (P = 0.058). DNMT3A mutations were associated with higher relapse rate even within the FLT3/ITD-negative group (P = 0.072). After reaching CR, these two genetic factors were independent predictors of relapse at multivariate analysis (P < 0.001). Only three of 30 'double-mutated' (FLT3/ITD+, DNMT3A+) patients are still alive, all of them having undergone hematopoietic stem cell transplant. CONCLUSIONS: We have confirmed the high incidence of DNMT3A mutations in patients with AML with IR cytogenetics. Patients with DNMT3A mutations relapse more often and have inferior OS when only patients achieving CR are analyzed. 'Double-mutated' patients have a very poor prognosis.