Search

EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.

The COVID-19 pandemic and the resulting "lockdown" have forced many medical schools to shift from traditional "face-to-face" teaching methodologies and embrace full online delivery. Although lectures and tutorials are readily communicated by this approach, the execution of laboratory exercises is much more difficult. To overcome these challenges, face-to-face laboratory sessions were replaced by a blended learning approach in which students were provided instructional material online and then required to conduct the laboratory exercises at home. These laboratory exercises made use of easily accessible household materials and mobile applications. A self-report survey was designed to assess students' perception of their learning experience and attitudes to the home-based laboratory exercises. The survey consisted of 16 questions that students had to respond to using a 5-point Likert scale. Students were also allowed to provide open responses to select questions. Overall, the 80% of students that completed the survey expressed strong satisfaction with their learning experience and were enthusiastic toward home-based laboratory exercises. However, concerns about not being able to complete particular face-to-face exercises that required specialized equipment were expressed. Several students proposed a combined approach going forward. Our results show that home-based laboratory exercises offer a multimodal option that enriches the learning curriculum by engaging students in "hands-on" bespoke practicals using inexpensive household materials.

Vascular Ehlers-Danlos syndrome (vEDS) Is an autosomal-dominant connective tissue disorder caused by heterozygous mutations in the COL3A1 gene, which encodes the pro-a 1 chain of collagen III. Loss of structural integrity of the extracellular matrix is believed to drive the signs and symptoms of this condition, including spontaneous arterial dissection and/or rupture, the major cause of mortality. We created 2 mouse models of vEDS that carry heterozygous mutations in Col3a1 that encode glycine substitutions analogous to those found in patients, and we showed that signaling abnormalities in the PLC/[IP.sub.3]/ PKC/ERK pathway (phospholipase C/inositol 1,4,5-triphosphate/protein kinase C/extracellular signal-regulated kinase) are major mediators of vascular pathology. Treatment with pharmacologic inhibitors of ERK1/2 or PKC[beta] prevented death due to spontaneous aortic rupture. Additionally, we found that pregnancy- and puberty-associated accentuation of vascular risk, also seen in vEDS patients, was rescued by attenuation of oxytocin and androgen signaling, respectively. Taken together, our results provide evidence that targetable signaling abnormalities contribute to the pathogenesis of vEDS, highlighting unanticipated therapeutic opportunities., Introduction Vascular Ehlers-Danlos syndrome (vEDS) (OMIM 130050) is a rare genetic connective tissue disorder. Patients with vEDS present with thin, translucent skin, easy bruising, and a characteristic facial appearance. Most [...]

Background: Transcarotid Artery Revascularization (TCAR) using the ENROUTE system (Silk Road) has been proposed as a safe and effective alternative to both carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TF-CAS). Two large registries (ROADSTER 1 and ROADSTER 2) have shown that TCAR has acceptable/low rates of perioperative stroke/death. This study will analyze the 30-day perioperative and 1-year clinical outcomes from a single-center. Patient population and methods: This is a retrospective analysis of prospectively collected data from SVS/VQI TCAR surveillance project (TSP) of 100 consecutive patients (102 TCAR procedures) done in our institution. These procedures were done for high-risk patients for CEA, which included anatomical (previous CEA, high cervical lesion, neck radiation, stoma, arch type, etc.), physiological (CHF, severe coronary artery disease, COPD on O2 therapy, etc.) and combined anatomical/physiological reasons. These procedures were done by vascular surgeons after receiving the appropriate training. The perioperative stroke, death, and MI rates were analyzed. Kaplan Meyer analysis was used to estimate rate of freedom from stroke/death and the incidence of ≥50% and ≥80% in-stent restenosis at 1 year. Results: 100 consecutive high-risk patients for CEA included: 38% anatomical, 44% physiological, and 18% combined anatomical and physiological reasons. The mean age was 72.5 years (range 52–90 years). Indications for TCAR were 34% for symptomatic lesions (TIA/stroke) and 66% for asymptomatic lesions. Mean ipsilateral treated stenosis was 80.4%. Contralateral ≥50% stenosis/occlusion was present in 31% of patients. Technical success rate was 100%. 92% had pre-stenting PTA and 26% had post-stenting PTA. The mean flow reversal time was 8.5 min (range 3–26 min). The 30-day perioperative stroke rate was 2.9% (1/67, 1.5% for asymptomatic patients), the stroke/death rate was 2.9%, and stroke/death and MI rate was 3.9% (4/102). Other perioperative complications included cranial nerve injury 3/102 (2.9%), carotid artery dissection (2%), and major hematoma (necessitated operation evacuation) (5.9%). Freedom from stroke rates and stroke/death rates at 1 year were: 90% and 89%. Freedom from ≥50% and ≥80% in-stent restenosis rates at 1 year were 82% and 90%, respectively. None of these restenosis were symptomatic except two (2/13). Freedom from reintervention rate at 1 year was 98%. Conclusion: Although the perioperative events were somewhat higher than what has been reported in previous registries, TCAR for patients who are high-risk for CEA has a low perioperative stroke and stroke/death rates with satisfactory outcome at 1 year. Further long-term data is probably needed to verify long-term outcome. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to test whether critical thinking changes over the course of dental education by assessing dental students at the beginning and toward the end of their training. Methods: Dental student participants completed a survey at the beginning of their first year (August 2019) and at the start of their last year of dental school (August 2022). The survey consisted of two instruments designed to measure the disposition and metacognition components of critical thinking. The study used a pretest‐posttest design. Paired t tests were used to determine whether critical thinking scores changed over the 3‐year period. Results: Surveys were completed by 85 of 94 students (90%) on the pretest and 63 of 93 students (68%) on the posttest. Of the 92 students who were members of the class at both testing periods, data were available for 59 students (64%). There were significant mean decreases in disposition and its tolerance for cognitive complexity subscale, as well as in metacognition and its metacognitive strategies subscale (p <.05). There was no significant mean change in either open‐mindedness or metacognitive thinking. Conclusion: Results of this study suggest that some aspects of critical thinking (metacognition and disposition) decrease over the course of dental education. Future research should investigate why this is the case, and explore different instructional methods designed to improve critical thinking. [ABSTRACT FROM AUTHOR]

The issue of group learning has become an even greater concern in recent years as more college and university professors have begun to incorporate specific group assignments (i.e., assignments which require that students meet as a group and equally contribute to a final product) into their class requirements. The purpose of the present descriptive report (based upon the 1984 survey by Fiechtner and Davis) is, therefore, to identify some of the reasons for students' negative reactions to group work in the classroom. Hopefully, the information reported here will aid instructors in evaluating the source of any problems they have experienced in using group work and enhance the development of better group-oriented classes and assignments.

Formal orientation sessions are not the only way new employees get to know a college or university. In fact, the informal orientation they receive--from conversations with their co-workers, participation in the campus intranet and exposure to the institution's Web site--may be more influential in shaping their perceptions of the institution. What kinds of messages are employees giving your new hires? Is your intranet the source of toxic messages that new employees do not have the perspective to evaluate? New employee socialization processes may need altering.

In systemic sclerosis (SSc), a common and aetiologically mysterious form of scleroderma (defined as pathological fibrosis of the skin), previously healthy adults acquire fibrosis of the skin and viscera in association with autoantibodies (1). Familial recurrence is extremely rare and causal genes have not been identified. Although the onset of fibrosis in SSc typically correlates with the production of autoantibodies, whether they contribute to disease pathogenesis or simply serve as a marker of disease remains controversial and the mechanism for their induction is largely unknown (2). The study of SSc is hindered by a lack of animal models that recapitulate the aetiology of this complex disease. To gain a foothold in the pathogenesis of pathological skin fibrosis, we studied stiffskin syndrome (SSS), a rare but tractable Mendelian disorder leading to childhood onset of diffuse skin fibrosis with autosomal dominant inheritance and complete penetrance. We showed previously that SSS is caused by heterozygous missense mutations in the gene (FBN1) encoding fibrillin-1, the main constituent of extracellular microfibrils (3). SSS mutations all localize to the only domain in fibrillin-1 that harbours an Arg-Gly-Asp (RGD) motif needed to mediate cell-matrix interactions by binding to cell-surface integrins (3). Here we show that mouse lines harbouring analogous amino acid substitutions in fibrillin-1 recapitulate aggressive skin fibrosis that is prevented by integrin-modulating therapies and reversed by antagonism of the pro-fibrotic cytokine transforming growth factor β (TGF-β). Mutant mice show skin infiltration of pro-inflammatory immune cells including plasmacytoid dendritic cells, T helper cells and plasma cells, and also autoantibody production; these findings are normalized by integrin-modulating therapies or TGF-β antagonism. These results show that alterations in cell-matrix interactions are sufficient to initiate and sustain inflammatory and pro-fibrotic programmes and highlight new therapeutic strategies., Fibrillin-1 contributes to the regulation of TGF-β, a cytokine that has been descriptively linked to many fibrotic diseases, including both SSS and SSc (3,4). TGF-β is secreted from the cell [...]

Escalation of worker's compensation claims led Saint Cloud State University (Minnesota) to implement an injury prevention program including warm-up exercises, worksite inspection, examination of work practices, employee training in safe body mechanics, and flexibility tests. The program is found to be effective in reducing injury and improving morale. (MSE)