Aorto-innominate artery bypass for migrated stent.

We report a case of a 64-year-old female who first presented with a transient ischemic attack in 2007 due to an innominate artery stenosis, which indicated an endovascular stent placement. In 2008, she presented with recurrence of symptoms and was diagnosed with in-stent restenosis alongside an unusual occurrence of retrograde migration into the ascending aortic arch. We performed an aorto-innominate bypass through a median sternotomy. The patient was discharged without any complications thereafter, and the graft has shown excellent patency. As of 2019, the patient remains well.

Epigenetic control of exercise training-induced cardiac hypertrophy by miR-208.

Aerobic exercise-induced cardiac hypertrophy (CH) is a physiological response involving accurate orchestration of gene and protein expression of contractile and metabolic components. The microRNAs: miR-208a, miR-208b and miR-499 are each encoded by a myosin gene and thus are also known as 'MyomiRs', regulating several mRNA targets that in turn regulate CH and metabolic pathways. To understand the role of myomiRs in the fine-tuning of cardiac myosin heavy chain (MHC) isoform expression by exercise training-induced physiological hypertrophy, Wistar rats were subjected to two different swim training protocols. We observed that high-volume swim training (T2), improved cardiac diastolic function, induced CH and decreased the expression of miR-208a and miR-208b Consequently, the increased expression of their targets, sex determining region y-related transcription factor 6 (Sox6), Med13, Purß, specificity proteins (Sp)/Krüppel-like transcription factor 3 (SP3) and HP1ß (heterochromatin protein 1ß) was more prominent in T2, thus converging to modulate cardiac metabolic and contractile adaptation by exercise training, with an improvement in the α-MHC/ß-MHC ratio, bypassing the increase in PPARß and histone deacetylase (HDAC) class I and II regulation. Altogether, we conclude that high-volume swim training finely assures physiological cardiac remodelling by epigenetic regulation of myomiRs, because inhibition of miR-208a and miR-208b increases the expression of their target proteins and stimulates the interaction among metabolic, contractile and epigenetic genes.

Inhibition of the function of class IIa HDACs by blocking their interaction with MEF2.

Enzymes that modify the epigenetic status of cells provide attractive targets for therapy in various diseases. The therapeutic development of epigenetic modulators, however, has been largely limited to direct targeting of catalytic active site conserved across multiple members of an enzyme family, which complicates mechanistic studies and drug development. Class IIa histone deacetylases (HDACs) are a group of epigenetic enzymes that depends on interaction with Myocyte Enhancer Factor-2 (MEF2) for their recruitment to specific genomic loci. Targeting this interaction presents an alternative approach to inhibiting this class of HDACs. We have used structural and functional approaches to identify and characterize a group of small molecules that indirectly target class IIa HDACs by blocking their interaction with MEF2 on DNA.Weused X-ray crystallography and (19)F NMRto show that these compounds directly bind to MEF2. We have also shown that the small molecules blocked the recruitment of class IIa HDACs to MEF2-targeted genes to enhance the expression of those targets. These compounds can be used as tools to study MEF2 and class IIa HDACs in vivo and as leads for drug development.

Staffing in a Level 1 Trauma Center: Quantifying Capacity for Preparedness.

OBJECTIVE: We sought to determine who is involved in the care of a trauma patient. METHODS: We recorded hospital personnel involved in 24 adult Priority 1 trauma patient admissions for 12 h or until patient demise. Hospital personnel were delineated by professional background and role. RESULTS: We cataloged 19 males and 5 females with a median age of 50-y-old (interquartile range [IQR], 35.5-67.5). The average number of hospital personnel involved was 79.71 (standard deviation, 17.62; standard error 3.6). A median of 51.2% (IQR, 43.4%-59.8%) of personnel were first involved within hour 1. More personnel were involved in direct versus indirect care (median 54.5 [IQR, 47.5-67.0] vs 25.0 [IQR, 22.0-30.5]; P < 0.0001). Median number of health-care professionals and auxiliary staff were 74.5 (IQR, 63.5-90.5) and 6.0 (IQR, 5.0-7.0), respectively. More personnel were first involved in hospital locations external to the emergency department (median, 53.0 [IQR, 41.5-63.0] vs 27.5 [IQR, 24.0-30.0]; P < 0.0001). No differences existed in total personnel by Injury Severity Score (P = 0.1266), day (P = 0.7270), or time of admission (P = 0.2098). CONCLUSIONS: A large number of hospital personnel with varying job responsibilities respond to severe trauma. These data may guide hospital staffing and disaster preparedness policies.

A comparison of follow-up recommendations by chest radiologists, general radiologists, and pulmonologists using computer-aided detection to assess radiographs for actionable pulmonary nodules.

OBJECTIVE: The primary objective of our study was to compare the effect of a chest radiography computer-aided detection (CAD) system on the follow-up recommendations of chest radiologists, general radiologists, and pulmonologists. MATERIALS AND METHODS: A chest radiography CAD system (RapidScreen 1.1) that has been approved by the U.S. Food and Drug Administration (FDA) and a second-generation version of the system (OnGuard 3.0) not yet approved by the FDA were applied to single frontal radiographs of 200 patients at high risk for lung cancer. One hundred patients had actionable nodules (mean size, 16.9 mm) and 100 patients did not. Six chest radiologists, six general radiologists, and six pulmonologists independently interpreted each image first without CAD and then with CAD during blinded reading sessions. The frequency with which readers correctly referred patients for follow-up tests was measured. Differential effects based on nodule size, shape, location, density, and subtlety were tested with multiplevariable logistic regression. RESULTS: For patients without actionable lesions, pulmonologists showed an increase in their recommendations for follow-up from 0.46 unaided to 0.52 with CAD (p = 0.001), whereas chest and general radiologists had much lower average rates and were not affected by CAD's false marks (0.26 without CAD vs 0.25 with RapidScreen 1.1 and 0.26 with OnGuard 3.0, p ≥ 0.734). CAD improved all readers' detection of moderately subtle lesions (p = 0.013) but did not significantly increase follow-up rates overall for patients with actionable nodules (0.63 unaided vs 0.63 with RapidScreen 1.1, p = 0.795; and 0.63 unaided vs 0.64 with OnGuard 3.0, p = 0.187). CONCLUSION: The effect of CAD on readers' clinical decisions varies depending on the training of the reader. CAD did not improve the performance of chest or general radiologists. Nonradiologists are particularly vulnerable to CAD's false-positive marks.

Variability of patient and surgical risk factors for infection in a single, urban, academic total joint replacement center.

BACKGROUND: We describe surgeon-specific patient and procedure variability in a single center to determine how much variability exists between surgeons. METHODS: Data was analyzed from 2009 to 2013 at a single center. The total number of primary and revision hip and knee arthroplasty surgeries were quantified for each surgeon. RESULTS: Surgeon caseload varied significantly, with the largest differences observed in primary TKA caseload. The largest patient differences were in regards to percentage of patients with diabetes mellitus amongst primary TKA patients. CONCLUSION: Significant differences in patient characteristics that could significantly impact outcomes after total joint arthroplasty were found amongst surgeons.

Perceived stress and fatigue among students in a doctor of chiropractic training program.

OBJECTIVE: High levels of stress and fatigue are associated with decreased academic success, well-being, and quality of life. The objective of this research was to quantify levels of perceived stress and fatigue among chiropractic students to identify sources of and student coping mechanisms for perceived stress and fatigue and to identify the relationship between students' perceived stress and fatigue. METHODS: A survey comprised of the Perceived Stress Scale, the Undergraduate Sources of Stress Survey, and the Piper Fatigue Scale was administered to chiropractic students in their 2nd, 5th, and 8th trimesters of doctoral study. Data were analyzed by descriptive statistics, 1-way analysis of variance, and linear correlation tests. RESULTS: Students reported having moderate to high levels of stress and fatigue, with higher levels of stress and fatigue seen in women than in men. A nonsignificant difference among stress scores and a significant difference among fatigue scores were observed based on program term. Levels of stress predicted levels of fatigue, and stress was strongly correlated with psychological health, relationships with family members, mood, and need for learning accommodations. Fatigue was strongly correlated with psychological health, academic demands, and conflicts between studies and other activities. CONCLUSION: There are differences in the reporting of perceived stress and fatigue levels in this chiropractic student population based on gender. The correlation between fatigue and stress also suggests that measures that may alleviate one may likely affect the other.

Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455.

Aberrant FGFR4 signaling has been documented abundantly in various human cancers. The majority of FGFR inhibitors display significantly reduced potency toward FGFR4 compared to FGFR1-3. However, LY2874455 has similar inhibition potency for FGFR1-4 with IC50 less than 6.4 nM. To date, there is no published crystal structure of LY2874455 in complex with any kinase. To better understand the pan-FGFR selectivity of LY2874455, we have determined the crystal structure of the FGFR4 kinase domain bound to LY2874455 at a resolution of 2.35 Å. LY2874455, a type I inhibitor for FGFR4, binds to the ATP-binding pocket of FGFR4 in a DFG-in active conformation with three hydrogen bonds and a number of van der Waals contacts. After alignment of the kinase domain sequence of 4 FGFRs, and superposition of the ATP binding pocket of 4 FGFRs, our structural analyses reveal that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly.

Structure of the MADS-box/MEF2 domain of MEF2A bound to DNA and its implication for myocardin recruitment.

Myocyte enhancer factor 2 (MEF2) regulates specific gene expression in diverse developmental programs and adaptive responses. MEF2 recognizes DNA and interacts with transcription cofactors through a highly conserved N-terminal domain referred to as the MADS-box/MEF2 domain. Here we present the crystal structure of the MADS-box/MEF2 domain of MEF2A bound to DNA. In contrast to previous structural studies showing that the MEF2 domain of MEF2A is partially unstructured, the present study reveals that the MEF2 domain participates with the MADS-box in both dimerization and DNA binding as a single domain. The sequence divergence at and immediately following the C-terminal end of the MEF2 domain may allow different MEF2 dimers to recognize different DNA sequences in the flanking regions. The current structure also suggests that the ligand-binding pocket previously observed in the Cabin1-MEF2B-DNA complex and the HDAC9 (histone deacetylase 9)-MEF2B-DNA complex is not induced by cofactor binding but rather preformed by intrinsic folding. However, the structure of the ligand-binding pocket does undergo subtle but significant conformational changes upon cofactor binding. On the basis of these observations, we generated a homology model of MEF2 bound to a myocardin family protein, MASTR, that acts as a potent coactivator of MEF2-dependent gene expression. The model shows excellent shape and chemical complementarity at the binding interface and is consistent with existing mutagenesis data. The apo structure presented here can also serve as a target for virtual screening and soaking studies of small molecules that can modulate the function of MEF2 as research tools and therapeutic leads.

[Suicide ideation among college students in Chongqing.].

OBJECTIVE: To describe the prevalence and risk factors for suicide ideation among college students in Chongqing city. METHODS: Data on suicide ideation and related factors were collected from 9808 college students at 11 colleges randomly selected in Chongqing. A multiple logistic regression model was used to identify risk factors for suicide ideation. RESULTS: 1279 (13.0%) of the 9808 students reported suicide ideation and the constituent ratio of boys and girls was 3:4 while risk factors for suicide ideation were ranked as follows: high frequency of feeling hopeless in prior year (OR = 5.07, 95%CI: 4.27 - 6.02); having psychological problems in recent 1 month that affecting daily lives and learning (2.07, 1.79 - 2.38); relatives having suicide behavior (1.77, 1.52 - 2.08); having had sexual experience (1.95, 1.65 - 2.30); being female (1.66, 1.45 - 1.90) and friends who had had suicide attempts (1.46, 1.28 - 1.67); having diseases in the last 1 month that affecting daily lives and learning (1.29, 1.08 - 1.52). CONCLUSION: The prevalence of suicide ideation among these college students was high that calls the development, implementation and assessment of suicide prevention plans for college students that focusing on the risk factors identified for suicide ideation.

The critical role of pathology in the investigation of bioterrorism-related cutaneous anthrax.

Cutaneous anthrax is a rare zoonotic disease in the United States. The clinical diagnosis traditionally has been established by conventional microbiological methods, such as culture and gram staining. However, these methods often yield negative results when patients have received antibiotics. During the bioterrorism event of 2001, we applied two novel immunohistochemical assays that can detect Bacillus anthracis antigens in skin biopsy samples even after prolonged antibiotic treatment. These assays provided a highly sensitive and specific method for the diagnosis of cutaneous anthrax, and were critical in the early and rapid diagnosis of 8 of 11 cases of cutaneous anthrax during the outbreak investigation. Skin biopsies were obtained from 10 of these 11 cases, and histopathological findings included various degrees of ulceration, hemorrhage, edema, coagulative necrosis, perivascular inflammation, and vasculitis. Serology was also an important investigation tool, but the results required several weeks because of the need to test paired serum specimens. Other tests, including culture, special stains, and polymerase chain reaction assay, were less valuable in the diagnosis and epidemiological investigation of these cutaneous anthrax cases. This report underscores the critical role of pathology in investigating potential bioterrorism events and in guiding epidemiological studies, a role that was clearly demonstrated in 2001 when B. anthracis spores were intentionally released through the United States postal system.