Quantitative evaluation of vascular morphogenesis during distraction osteogenesis

PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact [email protected] (MSD) --Boston University, Goldman School of Dental Medicine, 2009 (Department of Prosthodontics).Includes bibliography: leaves 53-59.Introduction: Distraction osteogenesis (DO) is a unique surgical method of applied mechanical tension that is applied to an osteotomy and which enhances new bone formation. Osteogenesis that occurs during DO has been shown to be dependent on the formation of blood vessels. Two separate processes contribute to new vessel formation arteriogenesis (large vessel formation) and angiogenesis (small vessel and capillary formation). Methods were developed using contrast enhanced Micro-CT to quantify the simultaneous structural development of vascular and osteogenic tissues during distraction osteogenesis DO and assess the contributions of these two processes during DO induced vascular tissues formation. Materials and Methods: Femur distraction osteogenesis was carried out using a monolateral fixator on male wild type mice (C57BL/6J) over a 3lday period. Contrast enhanced Micro-CT was used for quantify vascular morphogenesis across the time course of DO. Both total and regional analysis of vessel volume, thickness, connectivity, number, separation, and degree of anisotropy within the gap both inside (intraosteal) and outside (extraosteal) of the periosteal boundary, and in proximal, central and distal thirds of the regenerate were determined. Results: Within the total gap region vessel volume was statistically greater at the end of the consolidation period (31 days post surgery) from both the baseline at the end of the latency period (7 days post surgery) and at 7 days after distraction was initiated (14 days post surgery). Total vessel thickness was statistically greater at the end of the active distraction period at 17 days post surgery. Total vessel volume was statistically greater at all times in the extraosteal region while vessel connectivity was greater at all times in the intraosteal region . Analysis of vessel volume in the proximal to distal orientation always showed statistically greater values in the proximal and central regions in both intra and extraosteal regions. Increasing connectivity was seen in the same proximal to distal manner but only in the analysis of the intraosteal regions. Co-registration methods to align images of bone and vessels were developed using image reconstruction software, and showed the feasibility of obtaining simultaneous measurements of both bone and vessel tissues from the same specimens. Conclusion: During the period of active distraction vessel volume increased primarily through increasing vessel thickness while during the period of consolidation total vessel volume and connectivity increased . These data suggest that arteriogenesis occurred primarily during the period of active distraction and preceded angiogenesis that occurred during consolidation phase. Analysis of regional differences in vessel formation suggest that proximal to distal orientation of tensile strain may play a role in providing the signals that direct the spatial orientation of new vessel formation in the DO regenerate. The intense period of angiogenesis and its spatial association with the intraosteal region suggests that biological factors produced during the maturation of bone tissues during consolidation promote angiogenesis

How COVID-19 Pandemic Restrictions Affected Kuwaiti College Students’ Anthropometry, Lifestyle Behaviors, and Dietary Habits

The COVID-19 pandemic and the measures implemented to control it have led to widespread lifestyle changes globally. While previous studies have explored these effects across different age groups, this research focuses uniquely on college students in Kuwait. A cross-sectional study (N = 1259) was conducted among college students using a validated online questionnaire covering various aspects, including demographics, academic performance, self-reported body weight and height, sleep duration, dietary habits, and physical activity. There were equal proportions of individuals reporting decreased, increased, or no change in body weight, BMI, and dietary habits due to COVID-19, with no significant gender differences observed. A higher decrease (44.3%) than increase (29.2%) occurred due to COVID-19 in the proportion of college students engaging in physical activity. Significant differences were found in the students’ responses to most of the eating behavior questions, concerning the changes attributable to the COVID-19 pandemic restrictions. Multivariable analysis showed significant interaction effects for gender by losing above 9 kg during the last 6 months in age (p = 0.037), total physical activity in METs-min/week (p = 0.048), and cake/donuts intake (p = 0.006). Logistic regression analysis, adjusted for age, revealed that a decrease in BMI was associated with an increase in daily vegetable intake (aOR = 1.531, p = 0.031), whereas increases in BMI were associated with an increased intake of sugar-sweetened drinks equal to or above 4 days/week (aOR = 1.551, p = 0.032) and increased chocolates/candy intake equal to or above 4 days/week (aOR = 1.792, p = 0.037). It was concluded that, in response to a major epidemic, such as COVID-19, college students, as a population, are susceptible to significant changes in lifestyle and eating behaviors that can impact their health and well-being. Future risks for college students’ health can be reduced through appropriate lifestyle interventions

Defective cellular trafficking of missense NPR-B mutants is the major mechanism underlying acromesomelic dysplasia-type Maroteaux

Natriuretic peptides (NPs) comprise a family of structurally related but genetically distinct hormones that regulate a variety of physiological processes such as cardiac growth, blood pressure, axonal pathfinding and endochondral ossification leading to the formation of vertebrae and long bones. The biological actions of NPs are mediated by natriuretic peptide receptors (NPRs) A, B and C that are located on the cell surface. Mutations in NPR-B have been shown to cause acromesomelic dysplasia-type Maroteaux (AMDM), a growth disorder in humans and severe dwarfism in mice. We hypothesized that missense mutations of NPR-B associated with AMDM primarily affect NPR-B function by the arrest of receptor trafficking at the endoplasmic reticulum (ER), due to conformational change, rather than an impairment of ligand binding, transmission of signal through the membrane or catalytic activity. Twelve missense mutations found in AMDM patients and cn/cn mice were generated by site-directed mutagenesis and transiently overexpressed in HeLa cells. Confocal microscopy revealed that 11 out of 12 mutants were retained in the ER. Determination of the ligand-dependent cGMP response confirmed that ER-retained NPR-B mutants are non-functional. Meanwhile, the only cell surface-targeted NPR-B missense mutant (D176E) displayed greatly reduced enzymatic activity due to impaired ligand binding. Thus, in the majority of cases of AMDM associated with missense NPR-B mutation, disease appears to result from defects in the targeting of the ER receptor to the plasma membrane