Over the past decade, the American Association for the Surgery of Trauma Acute Care Surgery (ACS) fellowship program has matured to 20 verified programs. As part of an ongoing curricular evaluation, ...we queried the current practice patterns of the graduates of ACS fellowship programs regarding their view on their ACS training. We hypothesized that the majority of ACS fellowship graduates would be practicing ACS in academic Level I trauma centers and that fellowship training was pivotal in their career.
Graduates of American Association for the Surgery of Trauma-certified ACS fellowships completed an online survey that included practice demographics, specific categories of cases delineated by the current ACS curriculum, and perceived impact of training.
Surveys were submitted by 56 of 77 graduates for a completion rate of 73%. The majority of respondents were male (68%) aged 40 years or younger (80%). All but four completed ACS fellowship training in last 5 years (93%), and 83% completed fellowship in the last 3 years. Regarding their current practice, broadly defined ACS predominated (96%) with 2% practicing only trauma surgery and 2% only general surgery. Practice settings were 64% urban, 29% suburban, and 7% rural locations, with 84% of graduates practicing in a hospital-based group. The practitioner's hospital was identified as university/university-affiliated in 53%, community in 38%, and military in 9%, with 91% identified as a teaching hospital; trauma designation was identified as Level I (55%), Level II (39%), and other (6%). The graduates' average current practice mix is 10% elective general surgery, 29% emergency general surgery, 32% trauma, 25% surgical critical care, and 4% other (burn, bariatric, vascular, and thoracic). Only 16% of graduates do not perform elective cases. Case specifics demonstrated 92% of graduates perform vascular cases, 88% perform thoracic cases, and 70% perform complex hepatobiliary. Practice elements that were satisfiers included (1) scope of practice, (2) case mix, (3) percentage emergency general surgery, (4) lifestyle, (5) case complexity (with 3 and 4 tied). Graduates agreed the ACS fellowship training prepared them well for practice and was worth the time invested (both 82%), increased their marketability and self-confidence (80%), and prepared them well for academics (71%) and administration (63%). Of those surveyed, 93% would encourage others to do an ACS fellowship.
Although 93% of graduates practice in urban/suburban areas, there was a mixture of university, university-affiliated, and community institutions and an almost even division of Levels I and II designation. Graduates demonstrate ongoing use of their acquired advanced operative training, particularly in vascular and thoracic surgery. The majority of ACS fellowship graduates were practicing ACS and felt fellowship training was valuable in their career path and that they would recommend it to others.
We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility ...variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.
The role of miR-92a on vascular remodelling after injury is currently unknown. Thus, the aim of the present study was to evaluate the role of miR-92a on rat endothelial and vascular smooth muscle ...cells proliferation and migration in vitro as well as after balloon injury or arterial stenting in vivo. MiR-92a was highly expressed in RAO-ECs and vascular endothelium, but not in RAO-SMCs or medial smooth muscle as assessed by real-time RT-PCR. Importantly, BrdU incorporation and wound healing assay provide evidence that functional inhibition of miR-92a resulted in an increased RAO-ECs proliferation and migration, but had no effect on RAO-SMCs proliferation or migration in vitro. Immunoblotting analysis revealed an increased phosphorylation of ERK1/2, JNK/SAPK as well as eNOS and phospho-eNOS increased expression level in RAO-ECs as a consequence of miR-92a inhibition. Using gain and loss of function experiments, we showed that miR-92a modulates regulation of KLF4 and MKK4 expression level in endothelial cells. Finally, in vivo administration of antagomiR-92a significantly enhanced re-endothelialization in injured carotid arteries and reduced neointimal formation after balloon injury or arterial stenting. These data provide the first evidence that inhibition of miR-92a may represent a novel strategy to improve endothelial regeneration and reduce restenosis after vascular injury.
Magnetic skyrmions are topological spin textures that exhibit classical or quantum quasi-particle
behavior. A substantial amount of research has occurred in this field, both because of their unique
...electromagnetic properties and potential application for future nonvolatile memory storage applications, as well as fundamental questions on their topology and unique magnetic phases. Here, we investigate the fluctuation properties of a magnetic Fe/Gd skyrmion lattice, using short-pulsed xrays. We first measure spontaneous fluctuations of the skyrmion lattice phase and find an inherent,
collective mode showing an underdamped oscillation with a relaxation of a couple of nanoseconds.
Further observations track the response towards the continuous phase transition and a ‘critical-like’
slowing down of fluctuations is observed well before the critical point. These results suggest that
the skyrmion lattice phase never fully freezes into a static crystal. This constant state of fluctuation indicates that the physics of topological magnetic phases may have more in common with high-temperature superconductors with disorder.
The concept of the neurovascular unit emphasizes the importance of cell-cell signaling between neural, glial, and vascular compartments. In neurogenesis, for example, brain endothelial cells play a ...key role by supplying trophic support to neural progenitors. Here, we describe a surprising phenomenon where brain endothelial cells may release trans-differentiation signals that convert astrocytes into neural progenitor cells in male mice after stroke. After oxygen-glucose deprivation, brain endothelial cells release microvesicles containing pro-neural factor Ascl1 that enter into astrocytes to induce their trans-differentiation into neural progenitors. In mouse models of focal cerebral ischemia, Ascl1 is upregulated in endothelium prior to astrocytic conversion into neural progenitor cells. Injecting brain endothelial-derived microvesicles amplifies the process of astrocyte trans-differentiation. Endothelial-specific overexpression of Ascl1 increases the local conversion of astrocytes into neural progenitors and improves behavioral recovery. Our findings describe an unexpected vascular-regulated mechanism of neuroplasticity that may open up therapeutic opportunities for improving outcomes after stroke.
KMT2A-rearranged (KMT2A-R) is an aggressive and chemo-refractory acute leukemia which mostly affects children. Transcriptomics-based characterization and chemical interrogation identified kinases as ...key drivers of survival and drug resistance in KMT2A-R leukemia. In contrast, the contribution and regulation of phosphatases is unknown. In this study we uncover the essential role and underlying mechanisms of SET, the endogenous inhibitor of Ser/Thr phosphatase PP2A, in KMT2A-R-leukemia. Investigation of SET expression in acute myeloid leukemia (AML) samples demonstrated that SET is overexpressed, and elevated expression of SET is correlated with poor prognosis and with the expression of MEIS and HOXA genes in AML patients. Silencing SET specifically abolished the clonogenic ability of KMT2A-R leukemic cells and the transcription of KMT2A targets genes HOXA9 and HOXA10. Subsequent mechanistic investigations showed that SET interacts with both KMT2A wild type and fusion proteins, and it is recruited to the HOXA10 promoter. Pharmacological inhibition of SET by FTY720 disrupted SET-PP2A interaction leading to cell cycle arrest and increased sensitivity to chemotherapy in KMT2A-R-leukemic models. Phospho-proteomic analyses revealed that FTY720 reduced the activity of kinases regulated by PP2A, including ERK1, GSK3β, AURB and PLK1 and led to suppression of MYC, supporting the hypothesis of a feedback loop among PP2A, AURB, PLK1, MYC, and SET. Our findings illustrate that SET is a novel player in KMT2A-R leukemia and they provide evidence that SET antagonism could serve as a novel strategy to treat this aggressive leukemia.
•Sierra de Aitana lateral spreading was numerically back-analysed.•Faults displacements were numerically reproduced along mesh interfaces.•Slope failures are actively and passively controlled by ...tectonic structures.•Rheological parameters controlling mountain front retreat were constrained.
The Eastern Betic Cordillera (Spain) exemplifies at the Sierra de Aitana an impressive case of lateral spreading which involves a mountain anticline ridge dislodged by a post-orogenic extensional tectonic. The deep trenches testify the ongoing gravitational slope deformation featured by a rock mass lateral spreading. The Sierra de Aitana anticline ridge was dislodged along a normal fault zone which generated a scarp with a kilometric lateral continuity. The lateral spreading originated because Eocene limestone overlays Eocene marls, inducing a continuous evolution over time due to visco-plastic deformations and isolating huge prismatic blocks. To quantify the creep-driven stress-strain effects at Sierra de Aitana ridge, the mechanical and rheological parameter values of the involved rocks were quantified through field and laboratory tests which allowed to constrain an engineering-geological model based on equivalent-continuum approach. A stress-strain numerical modelling aimed at back-analysing the sequential morpho-structural evolution of the Sierra de Aitana anticline-ridge was performed by reproducing the retreat of the ridge front and the time succession of faults (re)activations. A time-dependent solution was approached by assuming a time-dependent creep configuration of the modelling and a parametric solution adopted to calibrate rock mass rheology, also taking into account: tectonic displacement due to the Aitana normal fault system by simulating these element as interface in the discretized domain; influence of pre-existing joint sets by assuming a main anisotropy in the elasto-plastic failure solution; admissible variations of the regional stress-field related to compressive and extensional phases and a generalised visco-plastic behaviour representing the ductile marls. The numerical modelling outputs that the lateral spreading mainly evolved as a creep-driven process while stress-release induced by tectonic activity is not sufficient to justify the observed landforms. The obtained results highlight a not negligible role of inherited structural elements for regulating the time evolution of the ongoing gravitational process at the Sierra the Aitana anticline.
Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been ...implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM.
This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing.
The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04).
Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.
Multidisciplinary management of chronic wounds using comprehensive wound centers improves outcomes. With an increasing need for wound providers, little is known about surgeons’ roles in wound ...centers. An online survey of two national surgical organization members covered demographics, wound center characterization, and surgeons’ perspectives of wound centers and wound care. Surgeon perspectives were compared by age, gender, and relationship status. Three hundred sixty-four surgeons responded. Respondents were mostly older than 50 years, male, in practice older than 10 years, and used wound centers. Most respondents reported favorable experiences with wound centers but uncertainty about financial details. Most respondents were interested in formal wound care certification and participation in a wound practice, particularly as a transition to the retirement option for older surgeons. Surgeons are interested in pursuing a career focus in wound care. Further efforts are needed to educate surgeons and create a pathway for surgeons to become wound center directors. In a nationwide survey, surgeon perspectives on wound centers and wound specialization were positive, although financial understanding was limited. The importance of this finding is the support of wound care pathways for surgeons.
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