Serum Levels of Bupivacaine After Bilateral Ultrasound-Guided Deep Parasternal Intercostal Plane Block in Cardiac Surgery with Median Sternotomy.

OBJECTIVE: To evaluate systemic levels of bupivacaine after bilateral ultrasound-guided deep parasternal intercostal plan (PIP) block in cardiac surgical patients undergoing median sternotomy. DESIGN: Prospective, observational study SETTING: Single institution; academic university hospital PARTICIPANTS: Twenty-eight adult patients undergoing cardiac surgery with median sternotomy received a PIP block with 2.5 mg/kg bupivacaine with or without dexamethasone and dexmedetomidine. MEASUREMENTS: Arterial blood samples were analyzed for total serum bupivacaine concentration at 5, 15, 30, 45, 60, 90, 120, and 150 minutes after placement of PIP. Local anesthetic volume, local anesthetic adjuncts, time to extubation, postoperative pain scores, and opioid consumption were recorded. MAIN RESULTS: The mean peak bupivacaine concentration was 0.60 ± 0.62 µg/mL, and the mean time to maximum concentration (Tmax) was 16.92 ± 12.97 minutes. Two patients (7.1%) had a concentration >2.0 µg/mL within 15 minutes of block placement. The mean Tmax of bupivacaine was significantly greater in patients who did not receive additives compared to those patients who did (22.86 ± 14.77 minutes v 10.0 ± 5.22 minutes; p = .004). The times to extubation and postoperative pain were not improved with additives. CONCLUSIONS: Bilateral PIP placed at the end of cardiac surgery resulted in low systemic bupivacaine levels. The inclusion of additives shortened Tmax without improving outcome.

Hemodynamic Monitoring In The Cardiac Surgical Patient: Comparison of Three Arterial Catheters.

OBJECTIVE: Systemic systolic (SAP) and mean (MAP) arterial pressure monitoring is the cornerstone in hemodynamic management of the cardiac surgical patient, and the radial artery is the most common site of catheter placement. The present study compared 3 different arterial line procedures. It is hypothesized that a 20-G 12.7- cm catheter inserted into the radial artery will be equal to a 20-G 12.7- cm angiocath placed in the brachial artery, and superior to a 20-G 5.00 cm angiocath placed in the radial artery. DESIGN: A prospective randomized control study was performed. SETTING: Single academic university hospital. PARTICIPANTS: Adult patients ≥18 years old undergoing nonemergent cardiac surgery using cardiopulmonary bypass (CPB). INTERVENTIONS: After approval by the Rhode Island Hospital institutional review board, a randomized prospective control study to evaluate 3 different peripheral intraarterial catheter systems was performed: (1) Radial Short (RS): 20-G 5- cm catheter; (2) Radial Long (RL): 20-G 12- cm catheter; and (3) Brachial Long (BL): 20-G 12- cm catheter. MEASUREMENTS AND RESULTS: Gradients between central aortic and peripheral catheters (CA-P) were compared and analyzed before CPB and 2 and 10 minutes after separation from CPB. The placement of femoral arterial lines and administration of vasoactive medications were recorded. After exclusions, 67 BL, 61 RL, and 66 RS patients were compared. Before CPB, CA-P SAP and MAP gradients were not significant among the 3 groups. Two minutes after CPB, the CA-P SAP gradient was significant for the RS group (p = 0.005) and insignificant for BL (p = 0.47) and RL (p = 0.39). Two-group analysis revealed that CA-P SAP gradients are similar between BL and RL (p = 0.84), both of which were superior to RS (p = 0.02 and p = 0.04, respectively). At 10 minutes after CPB, the CA-P SAP gradient for RS remained significant (p = 0.004) and similar to the gradient at 2 minutes. The CA-P SAP gradients increased from 2 to 10 minutes for BL (p = 0.13) and RL (p = 0.06). Two minutes after CPB, the CA-P MAP gradients were significant for the BL (p = 0.003), RL (p < 0.0001), and RS (p < 0.0001) groups. Two-group analysis revealed that the CA-P MAP gradients were lower for the BL group compared with the RL (p = 0.054) and RS (p< 0.05) groups. Ten minutes after CPB, the CA-P MAP gradients in the RL and RS groups remained significant (p < 0.0001) and both greater than the BL group (p = 0.002). A femoral arterial line was placed more frequently in the RS group (8/66 = 12.1%) than in the RL group (3/61 = 4.9%) and the BL group (2/67 = 3.0%). Vasopressin was administered significantly more frequently in the RS group. CONCLUSION: Regarding CA-P SAP gradients, the RL group performed equally to the BL group, both being superior to RS. Regarding CA-P MAP gradients, BL was superior to RL and RS. Clinically, femoral line placement and vasopressin administration were fewer for the BL and RL groups when compared with the RS group. This study demonstrated the benefits of a long (12.7 cm) 20- G angiocath placed in the radial artery.

Leg Ulcer Pathway Acceleration (LUPA) study.

BACKGROUND: Leg ulcers are common, costly, and significantly impair quality of life, but their management is variable and associated with considerable delays in healing. The aim of this study was to design an accelerated leg ulcer care pathway in a community and hospital setting to improve patient outcomes. METHODS: A new referral pathway was developed using a series of healthcare professional and patient interviews, focus groups, and stakeholder workshops. The referral pathway, investigation and treatment protocols were further informed by clinical guidelines to develop the Leg Ulcer Pathway Acceleration care pathway. The outcomes of a consecutive series of patients enrolled in the Leg Ulcer Pathway Acceleration care pathway were compared with the outcomes of patients from a historical leg ulcer cohort from the same community and hospital setting. RESULTS: A total of 110 eligible patients were enrolled and followed prospectively through the Leg Ulcer Pathway Acceleration care pathway. Their outcomes were compared with those of 183 patients with venous leg ulcers identified from existing hospital and community ulcer centres, and acting as the historical control group. The 110 patients in the Leg Ulcer Pathway Acceleration group consisted of 73 (66 per cent) men, had a mean(s.d.) age of 55.7(17.2) years, and had a median initial ulcer duration of 14.5 (i.q.r. 6-30) months. The 183 patients in the historical control group consisted of 119 (65 per cent) men, had a mean(s.d.) age of 56.4(17.2) years, and had a median initial ulcer duration of 13.5 (i.q.r. 6-47) months. Venous disease was treated in 67/110 (61 per cent) and deep venous disease was treated in 33/110 (30 per cent) of patients in the Leg Ulcer Pathway Acceleration cohort. In contrast, only 16/183 (8 per cent) of patients in the control group were treated for superficial venous insufficiency and 4/183 (2 per cent) of patients in the control group were treated for deep venous disease. Ulcer healing rates at 12 months were 80 and 20 per cent in the Leg Ulcer Pathway Acceleration group and the control group respectively (P < 0.001). Adjusted for baseline characteristics, the OR for a healed ulcer at 12 months was 21.21 (95 per cent c.i.. 11.32 to 42.46) (P < 0.001). CONCLUSION: The introduction of an accelerated leg ulcer care pathway significantly improves ulcer healing when compared with historical controls.

The Left Ventricular Outflow Tract Changes in Size and Shape From Pre- to Post-Cardiopulmonary Bypass: Three-Dimensional Transesophageal Echocardiography.

OBJECTIVES: To compare two-dimensional (2D) and 3D imaging of the left ventricular outflow tract (LVOT) and to evaluate geometric changes pre- to post-cardiopulmonary bypass (CPB). DESIGN: Retrospective review of intraoperative transesophageal echocardiographic examinations. SETTING: Single academic medical center. PARTICIPANTS: The study comprised 69 cardiac surgical patients-27 with aortic valve stenosis (AS) and 42 without AS. INTERVENTIONS: Two-dimensional and 3D analysis of the LVOT pre- and post-CPB. MEASUREMENTS AND MAIN RESULTS: Pre- and post-CPB 2D assessment of LVOT diameter (2D LVOTd) was compared with 3D analysis of the minor (3D LVOTd-min) and major diameters. LVOT areas (LVOTa) were calculated using LVOTd to yield 2D LVOTa and 3D LVOTa-min. These were compared with LVOTa measured by planimetry (3D LVOTa-plan). An ellipticity ratio (ER) (ER = 3D minor/major axes) was calculated. The 2D LVOTd was larger than the 3D LVOTd-min before (2.12 v 2.02 cm respectively (resp); p < 0.001) and after (1.96 v 1.85 cm resp; p = 0.04) CPB. Compared with pre-CPB, there were significant decreases in the 2D LVOTd (p = 0.003) and the 3D LVOTd-min (p < 0.001) post-CPB. Ellipticity increased after CPB (ER 0.80 v 0.75; p = 0.004), and the 2D LVOTa was larger than the 3D LVOTa-min before CPB (3.60 cm2v 3.28 cm2; p < 0.001) and less so after CPB (3.11 cm2v 2.79 cm2; p = 0.053). Compared with pre-CPB, all LVOTa measurements decreased significantly after CPB (p < 0.001). The 3D LVOTa-plan decreased after CPB by approximately 10% (4.05 cm2v 3.61 cm2; p < 0.001). The 2D LVOTa and 3D LVOTa-min underestimated the 3D LVOTa-plan before and after CPB (p < 0.001) by 11% to 14% and 19% to 23%, respectively. When compared with non-AS patients, patients with AS had a smaller LVOTa pre- and post-CPB (p < 0.05). CONCLUSIONS: The LVOT is smaller and more elliptical after CPB. Patients with AS have a smaller LVOT compared with non-AS patients. LVOTa calculated using LVOTd underestimates the 3D LVOTa-plan by as much as 23% depending on patient type and timing of measurement. Accurate assessment of the LVOT requires 3D imaging.

The Mitral Coaptation to Ventricular Septal Space: Two- and Three-Dimensional Transesophageal Echocardiographic Assessment.

OBJECTIVES: To assess the dimensions and changes in the CSEPT (space between the ventricular septum and mitral coaptation point) before and after cardiopulmonary bypass (CPB) and to compare patients with and without aortic valve stenosis (AS) undergoing cardiac surgery. DESIGN: Retrospective review of intraoperative transesophageal echocardiographic examinations. SETTING: Single academic medical center. PARTICIPANTS: The study comprised 91 elective cardiac surgical patients-30 with AS scheduled for aortic valve replacement and 61 without AS (non-AS). INTERVENTIONS: Two- and 3-dimensional (2D and 3D) analysis of the CSEPT before and after CPB. MEASUREMENTS AND MAIN RESULTS: Assessment of the CSEPT distances and areas was performed using 2D and 3D imaging before and after CPB. Two-dimensional measures of CSEPT distances were performed using midesophageal 5-chamber and long-axis windows. Three-dimensional measures were performed offline using multiplanar reconstruction. The CSEPT space was smaller after CPB (p < 0.01). Before and after CPB, the midesophageal 5-chamber and long-axis windows were similar to each other, and both were larger than the pre-CPB 3D CSEPT distance. Patients with AS had smaller before and after CPB distances and areas compared with non-AS patients (p < 0.05). The change in CSEPT area in AS patients was 24%. CONCLUSIONS: The CSEPT space is smaller after CPB and more so for patients with AS undergoing aortic valve replacement. Two-dimensional CEPT distances vary compared with 3D CSEPT distances. Additional study using Doppler analysis will elucidate the added value of 3D assessment of the CSEPT space.

Can the Use of Video-Based Interventions Increase Public Knowledge About Endocrine Surgeons?

BACKGROUND: Endocrine surgery (ES) is a relatively young subspecialty of general surgery, and prior research has shown low public awareness of these specialists' roles. We hypothesized that a video-based intervention could increase public knowledge of the specialty in an effective and efficient manner. METHODS: Participants were recruited at three public locations (a farmer's market, a public park, and a university hospital) and were given a three-question survey to assess baseline knowledge of ES. They then watched one of two video-based educational interventions and completed an identical postintervention survey. Two surveyors recruited 80 individuals per site, with 40 participants in each intervention group. Participants' sex and age and whether or not they were on clinical staff at the University of Alabama at Birmingham were recorded. RESULTS: A total of 240 participants were recruited; 61.3% female with median age 40 y. Preintervention, only 42.1% of participants could correctly define ES. ES were confused with endocrinologists by 44.6%, which was not different between sites (P = 0.09). Significantly, more participants at all sites could correctly define ES postintervention (67.9% versus 42.1%; P < 0.001). Clinical staff did not perform better than the lay public at any location (P = 0.32). The long video had a significantly greater increase in correct responses compared with the short video overall (32.5% versus 19.1%; P < 0.001) and at each location. CONCLUSIONS: This study confirms the public's general lack of knowledge about ES and their scope of practice. A video-based intervention was successful in improving knowledge of the practice of ES, with a longer, explanatory video being most effective.

Phosphorylation of mammalian mitochondrial EF-Tu by Fyn and c-Src kinases.

Src Family Kinases (SFKs) are tyrosine kinases known to regulate glucose and fatty acid metabolism as well as oxidative phosphorylation (OXPHOS) in mammalian mitochondria. We and others discovered the association of the SFK kinases Fyn and c-Src with mitochondrial translation components. This translational system is responsible for the synthesis of 13 mitochondrial (mt)-encoded subunits of the OXPHOS complexes and is, thus, essential for energy generation. Mitochondrial ribosomal proteins and various translation elongation factors including Tu (EF-Tumt) have been identified as possible Fyn and c-Src kinase targets. However, the phosphorylation of specific residues in EF-Tumt by these kinases and their roles in the regulation of protein synthesis are yet to be explored. In this study, we report the association of EF-Tumt with cSrc kinase and mapping of phosphorylated Tyr (pTyr) residues by these kinases. We determined that a specific Tyr residue in EF-Tumt at position 266 (EF-Tumt-Y266), located in a highly conserved c-Src consensus motif is one of the major phosphorylation sites. The potential role of EF-Tumt-Y266 phosphorylation in regulation of mitochondrial translation investigated by site-directed mutagenesis. Its phosphomimetic to Glu residue (EF-Tumt-E266) inhibited ternary complex (EF-Tumt•GTP•aatRNA) formation and translation in vitro. Our findings along with data mining analysis of the c-Src knock out (KO) mice proteome suggest that the SFKs have possible roles for regulation of mitochondrial protein synthesis and oxidative energy metabolism in animals.

Left Ventricular Septal Avulsion in the Setting of Blunt Cardiac Injury.

A 23-year-old man sustained blunt cardiac injury after a motor vehicle collision resulting in left ventricular septal avulsion, ruptured chordae tendineae, and moderate to severe tricuspid regurgitation that necessitated operative intervention. The patient underwent successful resection of a prolapsed avulsed septal wall segment and concomitant tricuspid valve repair.

Mother abuse: a matter of youth justice, child welfare or domestic violence?

International evidence suggests that in advanced welfare states the abuse of parents, most particularly mothers, by their (most frequently male) adolescent children is increasingly prevalent. In the United Kingdom, however, child-to-mother abuse remains one of the most under-acknowledged and under-researched forms of family violence. Although it is an issue shrouded in silence, stigma, and shame, the authors' work in the youth justice sphere, focusing on interventions to deal with anti-social behaviour, suggests that adolescent violence toward mothers is a topical and prevalent issue. We identify different ways of conceptualizing it in the policy realms of youth justice, child welfare, and domestic violence. The behaviour of both child/young person and mother is constructed in ways which inform the assignment of blame and responsibility. The paper highlights the silence that surrounds the issue in both the policy and wider academic spheres, hiding the failure of service providers to respond to this very destructive form of intimate interpersonal violence.

c-Src kinase impairs the expression of mitochondrial OXPHOS complexes in liver cancer.

Src family kinases (SFKs) play a crucial role in the regulation of multiple cellular pathways, including mitochondrial oxidative phosphorylation (OXPHOS). Aberrant activities of one of the most predominant SFKs, c-Src, was identified as a fundamental cause for dysfunctional cell signaling and implicated in cancer development and metastasis, especially in human hepatocellular carcinoma (HCC). Recent work in our laboratory revealed that c-Src is implicated in the regulation of mitochondrial energy metabolism in cancer. In this study, we investigated the effect of c-Src expression on mitochondrial energy metabolism by examining changes in the expression and activities of OXPHOS complexes in liver cancer biopsies and cell lines. An increased expression of c-Src was correlated with an impaired expression of nuclear- and mitochondrial-encoded subunits of OXPHOS complexes I and IV, respectively, in metastatic biopsies and cell lines. Additionally, we observed a similar association between high c-Src and reduced OXPHOS complex expression and activity in mouse embryonic fibroblast (MEF) cell lines. Interestingly, the inhibition of c-Src kinase activity with the SFK inhibitor PP2 and c-Src siRNA stimulated the expression of complex I and IV subunits and increased their enzymatic activities in both cancer and normal cells. Evidence provided in this study reveals that c-Src impairs the expression and function of mitochondrial OXPHOS complexes, resulting in a significant defect in mitochondrial energy metabolism, which can be a contributing factor to the development and progression of liver cancer. Furthermore, our findings strongly suggest that SFK inhibitors should be used in the treatment of HCC and other cancers with aberrant c-Src kinase activity to improve mitochondrial energy metabolism.

'The rollercoaster': A qualitative study of midwifery students' experiences affecting their mental wellbeing.

OBJECTIVE: Midwifery student mental wellbeing is an important consideration for the sustainability of the profession, however it has seldom been the subject of empirical research. Previous studies of the lived experience of midwifery students have focused on the impact of transition experiences and student satisfaction, rather than specifically on mental health and students' views on support for their mental wellbeing. DESIGN: A qualitative descriptive study using semi-structured interviews. SETTING: A midwifery undergraduate programme in one university in the South of England. PARTICIPANTS: 20 BSc midwifery students. FINDINGS: Two inductive themes were developed from our analysis. The theme of 'the rollercoaster' encapsulated students' experience over the length of the course, characterised by multiple culture shocks of being in different worlds, from one clinical placement to the next, from university to clinical placement. This experience was emotionally taxing. The theme of 'being noticed, feeling connected' encapsulated midwifery students' views on what could help them enjoy their training. They wanted to be seen as individuals by at least one educator, they wanted opportunities to connect with their peers and they wanted the support available to them to be consistent. CONCLUSIONS: Listening to students' insights into the lived experience of being a midwifery student can enable midwifery educators to improve the way courses are designed and support structures are put in place. The importance of having consistent contact with peers and educators cannot be underestimated. IMPLICATIONS FOR PRACTICE: The emotional demands of midwifery training must be acknowledged. Educators should identify ways in which they can provide students with consistent individualised support and regular opportunities to meet with their peers.

Experimental characterization of two archaeal inosine 5'-monophosphate cyclohydrolases.

There is variability as to how archaea catalyze the final step of de novo purine biosynthesis to form inosine 5'-monophosphate (IMP) from 5-formamidoimidazole-4-carboxamide ribonucleotide (FAICAR). Although non-archaea almost uniformly use the bifunctional PurH protein, which has an N-terminal IMP cyclohydrolase (PurH2) fused to a C-terminal folate-dependent aminoimidazole-4-carboxamide ribonucleotide (AICAR) formyltransferase (PurH1) domain, a survey of the genomes of archaea reveals use of PurH2 (with or without fusion to PurH1), the "euryarchaeal signature protein" PurO, or an unidentified crenarchaeal IMP cyclohydrolase. In this report, we present the cloning and functional characterization of two representatives of the known IMP cyclohydrolase families. The locus TK0430 in Thermococcus kodakarensis encodes a PurO-type IMP cyclohydrolase with demonstrated activity despite its position in a cluster of apparently redundant biosynthetic genes, the first functional characterization of a PurO from a non-methanogen. Kinetic characterization reveals a Km for FAICAR of 1.56 ± 0.39 µM and a kcat of 0.48 ± 0.04 s-1. The locus AF1811 from Archaeoglobus fulgidus encodes a PurH2-type IMP cyclohydrolase. This Archaeoglobus fulgidus PurH2 has a Km of 7.8 ± 1.8 µM and kcat of 1.32 ± 0.14 s-1, representing the first characterization of an archaeal PurH2 and the first characterization of PurH2 that naturally occurs unfused to an AICAR formyltransferase domain. Each of these two characterized IMP cyclohydrolases converts FAICAR to IMP in vitro, and each cloned gene allows the growth on purine-deficient media of an E. coli purine auxotroph lacking the purH2 gene.

Mitochondrial oxidative phosphorylation is impaired in TALLYHO mice, a new obesity and type 2 diabetes animal model.

Type 2 diabetes has become an epidemic disease largely explained by the dramatic increase in obesity in recent years. Mitochondrial dysfunction is suggested as an underlying factor in obesity and type 2 diabetes. In this study, we evaluated changes in oxidative phosphorylation and mitochondrial biogenesis in a new human obesity and type 2 diabetes model, TALLYHO/Jng mice. We hypothesized that the sequence variants identified in the whole genome analysis of TALLYHO/Jng mice would affect oxidative phosphorylation and contribute to obesity and insulin resistant phenotypes. To test this hypothesis, we investigated differences in the expression and activity of oxidative phosphorylation complexes, including the transcription and translation of nuclear- and mitochondrial-encoded subunits and enzymatic activities, in the liver and kidney of TALLYHO/Jng and C57BL/6 J mice. A significant decrease was observed in the expression of nuclear- and mitochondrial-encoded subunits of complex I and IV, respectively, in TALLYHO/Jng mice, which coincided with significant reductions in their enzymatic activities. Furthermore, sequence variants were identified in oxidative phosphorylation complex subunits, a mitochondrial tRNA synthetase, and mitochondrial ribosomal proteins. Our data suggested that the lower expression and activity of oxidative phosphorylation complexes results in the diminished energy metabolism observed in TALLYHO/Jng mice. Sequence variants identified in mitochondrial proteins accentuated a defect in mitochondrial protein synthesis which also contributes to impaired biogenesis and oxidative phosphorylation in TALLYHO/Jng mice. These results demonstrated that the identification of factors contributing to mitochondrial dysfunction will allow us to improve the disease prognosis and treatment of obesity and type 2 diabetes in humans.

HSP90 Inhibition and Cellular Stress Elicits Phenotypic Plasticity in Hematopoietic Differentiation.

Cancer cells exist in a state of Darwinian selection using mechanisms that produce changes in gene expression through genetic and epigenetic alteration to facilitate their survival. Cellular plasticity, or the ability to alter cellular phenotype, can assist in survival of premalignant cells as they progress to full malignancy by providing another mechanism of adaptation. The connection between cellular stress and the progression of cancer has been established, although the details of the mechanisms have yet to be fully elucidated. The molecular chaperone HSP90 is often upregulated in cancers as they progress, presumably to allow cancer cells to deal with misfolded proteins and cellular stress associated with transformation. The objective of this work is to test the hypothesis that inhibition of HSP90 results in increased cell plasticity in mammalian systems that can confer a greater adaptability to selective pressures. The approach used is a murine in vitro model system of hematopoietic differentiation that utilizes a murine hematopoietic stem cell line, erythroid myeloid lymphoid (EML) clone 1, during their maturation from stem cells to granulocytic progenitors. During the differentiation protocol, 80%-90% of the cells die when placed in medium where the major growth factor is granulocyte-macrophage-colony stimulating factor. Using this selection point model, EML cells exhibit increases in cellular plasticity when they are better able to adapt to this medium and survive. Increases in cellular plasticity were found to occur upon exposure to geldanamycin to inhibit HSP90, when subjected to various forms of cellular stress, or inhibition of histone acetylation. Furthermore, we provide evidence that the cellular plasticity associated with inhibition of HSP90 in this model involves epigenetic mechanisms and is dependent upon high levels of stem cell factor signaling. This work provides evidence for a role of HSP90 and cellular stress in inducing phenotypic plasticity in mammalian systems that has new implications for cellular stress in progression and evolution of cancer.