Surgical Relevance of Pediatric Anterior Clinoid Process Maturation for Anterior Skull Base Approaches

BACKGROUND Removal of the anterior clinoid process (ACP) can expand anterior skull base surgical corridors. ACP development and anatomical variations are poorly defined in children. OBJECTIVE To perform a morphometric analysis of the ACP during pediatric maturation. METHODS Measurements of ACP base thickness (ACP-BT), midpoint thickness (ACP-MT), length (ACP-L), length from optic strut to ACP tip (ACP-OS), pneumatization (ACP-pneumo), and the presence of an ossified carotico-clinoid ligament (OCCL) or interclinoid ligament (OIL) were made from high-resolution computed-tomography scans from 60 patients (ages 0-3, 4-7, 8-11 12-15, 16-18, and >18 yr). Data were analyzed by laterality, sex, and age groups using t-tests and linear regression. RESULTS There were no significant differences in ACP parameters by laterality or sex, and no significant growth in ACP-BT or ACP-MT during development. From ages 0-3 yr to adult, mean ACP-L increased 49%, from 7.7 to 11.5 mm. The majority of ACP-L growth occurred in 2 phases between ages 0-3 to 8-11 and ages 16-18 to adult. Conversely, ACP-OS was stable from ages 0-3 to 8-11 but increased by 63% between ages 8-11 to adult. Variations in ACP morphology (OCCL/OIL/ACP-pneumo) were found in 15% (9/60) of scans. OCCL and OIL occurred in patients as young as 3 yrs, whereas ACP-pneumo was not seen in patients younger than 11 yrs. CONCLUSION The ACP demonstrates stable thickness and a complex triphasic elongation and remodeling pattern with development, the understanding of which may facilitate removal in patients <12. Clinically relevant ACP anatomic variations can occur at any age.

Defining echocardiographic reference values of LV volume indices and biventricular strain in obese patients with normal ejection fraction in different cardiac remodeling patterns – a single center study

Background The left ventricle (LV) in obese patients undergoes different patterns of remodeling in order to normalize wall stress. However, little is known about how LV volume indices, LV global longitudinal strain and right ventricular free wall strain (GLS) vary according to the pattern of LV remodeling. Aim To define the echocardiographic reference values of LV volumes and biventricular GLS across the different LV remodeling patterns in obese patients with a preserved ejection fraction. Methods 2393 adult obese patients (1428 females, 965 males) with a normal ejection fraction who underwent echocardiography from January 2008 to December 2018 were selected. They were categorized according to 4 cardiac remodeling groups defined by LV mass index (102g/m2 in males, 88g/m2 in females) and relative ventricular wall thickness (0.42): normal geometry (NG), eccentric hypertrophy (EH), concentric remodeling (CR) and concentric hypertrophy (CH). Obese subjects were further categorized by BMI class (30–35, 35–40, >40 kg/m2). Obese subjects were gender matched to controls with a normal BMI (18.5–25 kg/m2) and normal cardiac geometry. Mean ± SD, One-way Anova and Tukey- Kramer HSD were applied. P<0.05 is considered significant. Results The mean age of controls and obese patients' were 50±16 and 57±13.6 years respectively (P<0.0001). LV GLS for controls compared to obese subjects with NG, EH, CR and CH was −21.1±2 vs. −20.2±1.9, −19.6±2.8, −18.5±2.9, −17.5±3.4 respectively (p<0.0001 for all), and for RV GLS it was −27.9±4 vs −26.7±3.9, −25.1±5, −23.5±5.5, −24.1±5.2 respectively (p<0.01 for all, except for NG where p=0.2). The distribution of LV indices according to cardiac remodeling subtypes is shown in the figure. Indexed end diastolic and end systolic volumes were smaller in NG, CH and CR compared to controls (p<0.001 for each respectively). LV GLS and ejection fraction were higher in females, while indexed LV volumes were higher in males within each remodeling category (P<0.0001). No significant difference in LV GLS or indexed LV volume was seen across BMI categories within each remodeling pattern (P>0.05). Obese subjects with CH had the highest incidence of the cardiovascular risk factors hyperlipidemia, hypertension and history of myocardial infarction or stroke, compared to those with other remodeling patterns (p<0.0001 for each, vs. NG, EH and CR). Conclusion To our knowledge, this is the largest study to define LV volumes and left and right ventricular GLS according to LV remodeling pattern and BMI category. The Lowest GLS was noted in CH. Ejection fraction was similar across the LV remodeling patterns. There were no differences in GLS and LV indexed volumes across BMI categories within each remodeling group. These results can be applied as a reference values for the obese population with a normal LV ejection fraction. Funding Acknowledgement Type of funding source: None

Interplay of MPP5a with Rab11 synergistically builds epithelial apical polarity and zonula adherens

ABSTRACTAdherens junction remodeling regulated by apical polarity proteins constitutes a major driving force for tissue morphogenesis, although the precise mechanism remains inconclusive. Here, we report that, in zebrafish, the Crumbs complex component MPP5a interacts with small GTPase Rab11 in Golgi to transport cadherin and Crumbs components synergistically to the apical domain, thus establishing apical epithelial polarity and adherens junctions. In contrast, Par complex recruited by MPP5a is incapable of interacting with Rab11 but might assemble cytoskeleton to facilitate cadherin exocytosis. In accordance, dysfunction of MPP5a induces an invasive migration of epithelial cells. This adherens junction remodeling pattern is frequently observed in zebrafish lens epithelial cells and neuroepithelial cells. The data identify an unrecognized MPP5a-Rab11 complex and describe its essential role in guiding apical polarization and zonula adherens formation in epithelial cells.

Sex-Specific Regulation of miR-29b in the Myocardium Under Pressure Overload is Associated with Differential Molecular, Structural and Functional Remodeling Patterns in Mice and Patients with Aortic Stenosis

Pressure overload in patients with aortic stenosis (AS) induces an adverse remodeling of the left ventricle (LV) in a sex-specific manner. We assessed whether a sex-specific miR-29b dysregulation underlies this sex-biased remodeling pattern, as has been described in liver fibrosis. We studied mice with transverse aortic constriction (TAC) and patients with AS. miR-29b was determined in the LV (mice, patients) and plasma (patients). Expression of remodeling-related markers and histological fibrosis were determined in mouse LV. Echocardiographic morpho-functional parameters were evaluated at baseline and post-TAC in mice, and preoperatively and 1 year after aortic valve replacement (AVR) in patients with AS. In mice, miR-29b LV regulation was opposite in TAC-males (down-regulation) and TAC-females (up-regulation). The subsequent changes in miR-29b targets (collagens and GSK-3β) revealed a remodeling pattern that was more fibrotic in males but more hypertrophic in females. Both systolic and diastolic cardiac functions deteriorated more in TAC-females, thus suggesting a detrimental role of miR-29b in females, but was protective in the LV under pressure overload in males. Clinically, miR-29b in controls and patients with AS reproduced most of the sexually dimorphic features observed in mice. In women with AS, the preoperative plasma expression of miR-29b paralleled the severity of hypertrophy and was a significant negative predictor of reverse remodeling after AVR; therefore, it may have potential value as a prognostic biomarker.

Predictor value of the inflammation biomarkers regarding the post-infarction remodeling of myocardium

Aim.To study the trait of the changes of circulating level of pro- and antiinflammatory biomarkers as well as metalloproteinase 8 (MMP-8) in the first 7 days after revascularization in patients with acute myocardial infarction with ST segment elevation (STEMI) for assessment of their prognostic value regarding post-infarction remodeling pattern.Material and methods.In 113 patients with STEMI which developed in 5 months after angioplasty adaptive myocardium remodeling (AMR) (n=56) or pathological myocardium remodeling (PMR) (n=57), determined by enzyme-linked immunosorbent assay (ELISA) method daily serum concentration of pro-inflammatory ((high sensitive C reactive protein, interleukins (IL) 1, 6, tumor necrosis factor alpha and monocyte chemoattractant protein 1)), anti-inflammatory biomarkers (IL-4, IL-10, IL-33, IL-1 receptor antagonist and heregulin-1beta) аs well as ММР-8 in the first 7 days after myocardium revascularization. According to clinic-demographic indices both groups were comparable. Obtained data have been compared with results of 20 healthy persons (control group).Results.The dynamics of pro-inflammatory biomarkers did not differ in patients with AMR and PMR after revascularization. It was characterized by a significant biomarker increase at 3-rd day followed by a decline toward 7-th day up to initial level. Among anti-inflammatory biomarkers IL-4 and IL-10 have manifested by a distinct dynamic in concern to myocardial remodeling pattern. In both groups these interleukins decreased after angioplasty, reaching a minimal level at 3-rd day. However, in patients with AMR since 4-th day has been established an increase of serum content of IL-4 and IL-10, their increment being at 7-th day in a range of 52-55% (p<0,05). In patients with PMR the interleukins rise was negligible: 5,7-5,8%. MMP-8 dynamics also has been different in groups and was correlated with dynamics of IL-4 and IL-10. Thus, in patients with AMR its level has fallen since 4-th day up to 7-th day by 46,6%, while in group with PMR metalloproteinase level in this period practically did not change, remaining significantly higher than control by 45-53%.Conclusion.In our study the serum content of main pro-inflammatory biomarkers (hsCRP, IL-1, IL-6, TNF-ɑ) didn’t differ in the first 7 days after revascularization in patients with adaptive and pathological postinfarction remodeling of myocardium, and thus don’t have predictive value concerning the remodeling pattern. Among anti-inflammatory cytokines dynamics of IL-4 and IL-10 differed in dependence on remodeling pattern. Their significant elevation by 52-55% from 4th up to 7th day after angioplasty was established in patients with adaptive myocardium remodeling, while in PMR their level didn’t change during this period that can emphasize their prognostic value. The character of MMP-8 change is pathogenetically correlated with dynamics of IL-4 and IL-10.

Omega3 Fatty Acids Intake Versus Diclofenac in Osteoarthritis Induced in Experimental rats

Background: Osteoarthritis (OA) is a degenerative joint disease, characterized by abnormal remodeling pattern of joints driven by inflammatory mediators within the affected joints. Its symptoms are many like pain, stiffness, and decreased function.Objective: The present study mainly focused on the anti-inflammatory effect of omega 3 fatty acids (F.As) versus diclofenac, non-steroidal anti-inflammatory drug in OA induced in ratsDesign: Intraarticular injection of monosodiumiodoacetate (MIA) 24.6 mg/kg in 0.6 ml saline was used to induce OA. Diclofenacand omega-3 F. These were administered orally, daily for 21 days and after 24 hours of OA induction.Results: Osteoarthritis induction resulted in an increase in serum levels of IL-6 (479.5%), TNF-a(545.5%), and CRP (754.2%) along with IL-10 level decrease (70.3%) as compared to normal group. Diclofenac intake demonstrated significant increase of IL-6 (24.9%), CRP (88.6%), and TNF-a (25.2%) compared to the OA control group. Omega 3 FAs intake showed significant reduction in inflammatory markers along with IL-10 increase, in comparison to OA group. Both treatment demonstrated a significant increase in TIMP2 along with decreased MMP2 and MPO in comparison with OA control. Positive correlation of IL-6 with MPO (r = 0.7, P=0.002), and negative one with IL-10 (r = 0.9, p<0.0001) and TIMP2 (r = -0.5, p<0.008) was observed. Interleukin-10 was negatively correlated with MMP2 (r = - 0.5, p<0.007) and MPO (r = -0.8, p<0.0001).Conclusion: Data derived from biochemical and histopathological results, indicated that omega3 FAs may be expressed as a natural anti-inflammatory agent of a significant potential in OA with evident remarkable effect.Keywords: OA; omega3FAs; diclofenac; MMP2; TIMP2; MPO