Fetal scalp stimulation for assessing fetal well-being during labour.

BACKGROUND: Continuous fetal heart rate monitoring by cardiotocography (CTG) is used in labour for women with complicated pregnancies. Fetal heart rate abnormalities are common and may result in the decision to expedite delivery by caesarean section. Fetal scalp stimulation (FSS) is a second-line test of fetal well-being that may provide reassurance that the labour can continue. OBJECTIVES: To evaluate methods of FSS as second-line tests of intrapartum fetal well-being in cases of non-reassuring CTG. FSS and CTG were compared to CTG alone, and to CTG with fetal blood sampling (FBS). SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (which includes trials from CENTRAL, MEDLINE, Embase, CINAHL, the WHO ICTRP and conference proceedings), ClinicalTrials.gov (18 October 2022), and reference lists of retrieved studies. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) that compared any form of FSS to assess fetal well-being in labour. Quasi-RCTs, cluster-RCTs and studies published in abstract form were also eligible for inclusion, but none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Two trials, involving 377 women, met the inclusion criteria for this review. Both trials were conducted in hospital settings and included women with singleton, term (37+0 weeks or more) pregnancies, a cephalic presentation, and abnormal CTG. Follow-up was until hospital discharge after the birth. A pilot trial of 50 women in a high-income country (Ireland) compared CTG and digital fetal scalp stimulation (dFSS) with CTG and fetal blood sampling (FBS). A single-centre trial of 327 women in a lower middle-income country (India) compared CTG and manual fetal stimulation (abdominal or vaginal scalp stimulation) with CTG alone. The two included studies were at moderate or unclear risk of bias. Both trials provided clear information on allocation concealment but it was not possible to blind participants or health professionals in relation to the intervention. Although objective outcome measures were reported, outcome assessment was not blinded or blinding was unclear. dFSS and CTG versus FBS and CTG There were no perinatal deaths and data were not reported for neurodevelopmental disability at >/= 12 months. The risk of caesarean section (CS) may be lower with dFSS compared to FBS (risk ratio (RR) 0.38, 95% confidence interval (CI) 0.16 to 0.92; 1 pilot trial, 50 women; very low-certainty evidence) but the evidence is very uncertain. There were no cases of neonatal encephalopathy reported. The evidence was also very uncertain between dFSS and FBS for assisted vaginal birth (RR 1.44, 95% CI 0.76 to 2.75; very low-certainty evidence) and for the spontaneous vaginal birth rate (RR 2.33, 95% CI 0.68 to 8.01, very low-certainty evidence). Maternal acceptability of the procedures was not reported. FSS and CTG versus CTG alone Manual stimulation of the fetus was performed either abdominally (92/164) or vaginally (72/164). There were no perinatal deaths and data were not reported for neurodevelopmental disability at >/= 12 months. There may be little differences in the risk of CS on comparing manual fetal stimulation and CTG with CTG alone (RR 0.83, 95% CI 0.59 to 1.18; 1 trial, 327 women; very low-certainty evidence), but again the evidence was very uncertain. There were no cases of neonatal encephalopathy reported. There may be no differences in the risk of assisted vaginal birth (RR 1.43, 95% CI 0.78 to 2.60; very low-certainty evidence) or in the rates of spontaneous vaginal birth (RR 1.01, 95% CI 0.85 to 1.21, very low-certainty evidence), but again the evidence is very uncertain. Maternal acceptability of abdominal stimulation/FSS was not reported although 13 women withdrew consent after randomisation due to concerns about fetal well-being. AUTHORS' CONCLUSIONS: There is very low-certainty evidence available which makes it unclear whether stimulating the fetal scalp is a safe and effective way to confirm fetal well-being in labour. Evidence was downgraded based on limitations in study design and imprecision. Further high-quality studies of adequate sample size are required to evaluate this research question. In order to be generalisable, these trials should be conducted in different settings, including broad clinical criteria at both preterm and term gestational ages, and standardising the method of stimulation. There is an ongoing study (FIRSST) that will be incorporated into this review in a subsequent update.

Peak Serum Chloride and Hyperchloremia in Patients Undergoing Cardiac Surgery Is Not Explained by Chloride-Rich Intravenous Fluid Alone: A Post-Hoc Analysis of the LICRA Trial.

OBJECTIVES: With the exception of 0.9% saline, little is known about factors that may contribute to increased serum chloride concentration (SCl-) in patients undergoing cardiac surgery. For the present study, the authors sought to characterize the association between administered chloride load from intravenous fluid and other perioperative variables, with peak perioperative SCl-. DESIGN: Secondary analysis of data from a previously published controlled clinical trial in which patients were assigned to a chloride-rich or chloride-limited perioperative fluid strategy (NCT02020538). SETTING: Academic medical center. PARTICIPANTS: The study comprised 1,056 adult patients with normal preoperative SCl- undergoing cardiac surgery. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Peak perioperative SCl- and hyperchloremia, defined as peak SCl- >110 mmol/L, were selected as co-primary endpoints. Regression modeling identified factors independently associated with these endpoints. Mean (standard deviation) peak perioperative SCl- was 114 (5) mmol/L, and hyperchloremia occurred in 824 (78.0%) of the cohort. In addition to administered volume of 0.9% saline, multivariate linear and logistic regression modeling consistently associated preoperative SCl- (regression coefficient 0.5; 95% confidence interval [CI] 0.4-0.6 mmol/L; odds ratio 1.60; 95% CI 1.41-1.82 per 1 mmol/L increase) and cardiopulmonary bypass duration (regression coefficient 0.1; 95% CI 0.1-0.2 mmol/L; odds ratio 1.12; 95% CI 1.06-1.19 per 10 minutes) with both co-primary outcomes. Multivariate modeling only explained approximately 50% of variability in peak SCl-. CONCLUSIONS: The present study's data identified an association for both 0.9% saline administration and other nonfluid variables with peak perioperative SCl- and hyperchloremia. Stand-alone strategies to limit administration of chloride-rich intravenous fluid may have limited ability to prevent hyperchloremia in this setting.

Membrane sweeping for induction of labour.

BACKGROUND: Induction of labour involves stimulating uterine contractions artificially to promote the onset of labour. There are several pharmacological, surgical and mechanical methods used to induce labour. Membrane sweeping is a mechanical technique whereby a clinician inserts one or two fingers into the cervix and using a continuous circular sweeping motion detaches the inferior pole of the membranes from the lower uterine segment. This produces hormones that encourage effacement and dilatation potentially promoting labour. This review is an update to a review first published in 2005. OBJECTIVES: To assess the effects and safety of membrane sweeping for induction of labour in women at or near term (≥ 36 weeks' gestation). SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (25 February 2019), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (25 February 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing membrane sweeping used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed on a predefined list of labour induction methods. Cluster-randomised trials were eligible, but none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, risk of bias and extracted data. Data were checked for accuracy. Disagreements were resolved by discussion, or by including a third review author. The certainty of the evidence was assessed using the GRADE approach. MAIN RESULTS: We included 44 studies (20 new to this update), reporting data for 6940 women and their infants. We used random-effects throughout. Overall, the risk of bias was assessed as low or unclear risk in most domains across studies. Evidence certainty, assessed using GRADE, was found to be generally low, mainly due to study design, inconsistency and imprecision. Six studies (n = 1284) compared membrane sweeping with more than one intervention and were thus included in more than one comparison. No trials reported on the outcomes uterine hyperstimulation with/without fetal heart rate (FHR) change, uterine rupture or neonatal encephalopathy. Forty studies (6548 participants) compared membrane sweeping with no treatment/sham Women randomised to membrane sweeping may be more likely to experience: · spontaneous onset of labour (average risk ratio (aRR) 1.21, 95% confidence interval (CI) 1.08 to 1.34, 17 studies, 3170 participants, low-certainty evidence). but less likely to experience: · induction (aRR 0.73, 95% CI 0.56 to 0.94, 16 studies, 3224 participants, low-certainty evidence); There may be little to no difference between groups for: · caesareans (aRR 0.94, 95% CI 0.85 to 1.04, 32 studies, 5499 participants, moderate-certainty evidence); · spontaneous vaginal birth (aRR 1.03, 95% CI 0.99 to 1.07, 26 studies, 4538 participants, moderate-certainty evidence); · maternal death or serious morbidity (aRR 0.83, 95% CI 0.57 to 1.20, 17 studies, 2749 participants, low-certainty evidence); · neonatal perinatal death or serious morbidity (aRR 0.83, 95% CI 0.59 to 1.17, 18 studies, 3696 participants, low-certainty evidence). Four studies reported data for 480 women comparing membrane sweeping with vaginal/intracervical prostaglandins There may be little to no difference between groups for the outcomes: · spontaneous onset of labour (aRR, 1.24, 95% CI 0.98 to 1.57, 3 studies, 339 participants, low-certainty evidence); · induction (aRR 0.90, 95% CI 0.56 to 1.45, 2 studies, 157 participants, low-certainty evidence); · caesarean (aRR 0.69, 95% CI 0.44 to 1.09, 3 studies, 339 participants, low-certainty evidence); · spontaneous vaginal birth (aRR 1.12, 95% CI 0.95 to 1.32, 2 studies, 252 participants, low-certainty evidence); · maternal death or serious morbidity (aRR 0.93, 95% CI 0.27 to 3.21, 1 study, 87 participants, low-certainty evidence); · neonatal perinatal death or serious morbidity (aRR 0.40, 95% CI 0.12 to 1.33, 2 studies, 269 participants, low-certainty evidence). One study, reported data for 104 women, comparing membrane sweeping with intravenous oxytocin +/- amniotomy There may be little to no difference between groups for: · spontaneous onset of labour (aRR 1.32, 95% CI 88 to 1.96, 1 study, 69 participants, low-certainty evidence); · induction (aRR 0.51, 95% CI 0.05 to 5.42, 1 study, 69 participants, low-certainty evidence); · caesarean (aRR 0.69, 95% CI 0.12 to 3.85, 1 study, 69 participants, low-certainty evidence); · maternal death or serious morbidity was reported on, but there were no events. Two studies providing data for 160 women compared membrane sweeping with vaginal/oral misoprostol There may be little to no difference between groups for: · caesareans (RR 0.82, 95% CI 0.31 to 2.17, 1 study, 96 participants, low-certainty evidence). One study providing data for 355 women which compared once weekly membrane sweep with twice-weekly membrane sweep and a sham procedure There may be little to no difference between groups for: · induction (RR 1.19, 95% CI 0.76 to 1.85, 1 study, 234 participants, low-certainty); · caesareans (RR 0.93, 95% CI 0.60 to 1.46, 1 study, 234 participants, low-certainty evidence); · spontaneous vaginal birth (RR 1.00, 95% CI 0.86 to 1.17, 1 study, 234 participants, moderate-certainty evidence); · maternal death or serious maternal morbidity (RR 0.78, 95% CI 0.30 to 2.02, 1 study, 234 participants, low-certainty evidence); · neonatal death or serious neonatal perinatal morbidity (RR 2.00, 95% CI 0.18 to 21.76, 1 study, 234 participants, low-certainty evidence); We found no studies that compared membrane sweeping with amniotomy only or mechanical methods. Three studies, providing data for 675 women, reported that women indicated favourably on their experience of membrane sweeping with one study reporting that 88% (n = 312) of women questioned in the postnatal period would choose membrane sweeping in the next pregnancy. Two studies reporting data for 290 women reported that membrane sweeping is more cost-effective than using prostaglandins, although more research should be undertaken in this area. AUTHORS' CONCLUSIONS: Membrane sweeping may be effective in achieving a spontaneous onset of labour, but the evidence for this was of low certainty. When compared to expectant management, it potentially reduces the incidence of formal induction of labour. Questions remain as to whether there is an optimal number of membrane sweeps and timings and gestation of these to facilitate induction of labour.

B Cell-Activating Factor Neutralization Aggravates Atherosclerosis.

BACKGROUND: Atherosclerotic cardiovascular disease (heart attacks and strokes) is the major cause of death globally and is caused by the buildup of a plaque in the arterial wall. Genomic data showed that the B cell-activating factor (BAFF) receptor pathway, which is specifically essential for the survival of conventional B lymphocytes (B-2 cells), is a key driver of coronary heart disease. Deletion or antibody-mediated blockade of BAFF receptor ablates B-2 cells and decreases experimental atherosclerosis. Anti-BAFF immunotherapy is approved for treatment of autoimmune systemic lupus erythematosus, and can therefore be expected to limit their associated cardiovascular risk. However, direct effects of anti-BAFF immunotherapy on atherosclerosis remain unknown. METHODS: To investigate the effect of BAFF neutralization in atherosclerosis, the authors treated Apoe-/- and Ldlr-/- mice with a well-characterized blocking anti-BAFF antibody. Moreover, to investigate the mechanism by which BAFF impacts atherosclerosis, the authors studied atherosclerosis-prone mice that lack the alternative receptor for BAFF: transmembrane activator and calcium modulator and cyclophilin ligand interactor. RESULTS: The authors demonstrate here that anti-BAFF antibody treatment increased atherosclerosis in mice, despite efficient depletion of mature B-2 cells, suggesting a unique mechanism of action. Indeed, myeloid cell-specific deletion of transmembrane activator and calcium modulator and cyclophilin ligand interactor also results in increased atherosclerosis, while B cell-specific transmembrane activator and calcium modulator and cyclophilin ligand interactor deletion had no effect. Mechanistically, BAFF-transmembrane activator and calcium modulator and cyclophilin ligand interactor signaling represses macrophage IRF7-dependent (but not NF-κB-dependent) Toll-like receptor 9 responses including proatherogenic CXCL10 production. CONCLUSIONS: These data identify a novel B cell-independent anti-inflammatory role for BAFF in atherosclerosis and may have important clinical implications.

Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation: A Pilot Randomized Trial.

OBJECTIVES: To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa. DESIGN: Randomized, controlled, unblinded study. SETTING: Two ICUs of two university hospitals. PATIENTS: Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation. INTERVENTIONS: Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s). MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95% CI, 8,601-16,031 U] vs 20,710 U [95% CI, 15,343-27,954 U]; p = 0.004), daily geometric mean activated partial thromboplastin time (48.1 s [95% CI, 43.5-53.2 s] vs 55.5 s [95% CI, 50.4-61.2 s]; p = 0.04), and daily geometric mean anti-Xa (0.11 international units/mL [95% CI, 0.07-0.18] vs 0.27 [95% CI, 0.17-0.42]; p = 0.01). We found similar results when considering only venovenous extracorporeal membrane oxygenation episodes; however, no difference in daily geometric mean activated partial thromboplastin time between groups when considering only venoarterial extracorporeal membrane oxygenation episodes. CONCLUSIONS: Allocating patients on extracorporeal membrane oxygenation to two different anticoagulation protocols led to a significant difference in mean daily activated partial thromboplastin time and anti-Xa levels between groups. When considering subgroups analyses, these results were consistent in patients on venovenous extracorporeal membrane oxygenation. Our results support the feasibility of a larger trial in patients undergoing venovenous extracorporeal membrane oxygenation to compare different anticoagulation protocols; however, this study does not provide evidence on the optimal anticoagulation protocol for patients undergoing extracorporeal membrane oxygenation.

Chemoenzymatic synthesis of enantiopure hydroxy sulfoxides derived from substituted arenes.

Enantiopure ß-hydroxy sulfoxides and catechol sulfoxides were obtained, by chemoenzymatic synthesis, involving dioxygenase-catalysed benzylic hydroxylation or arene cis-dihydroxylation and cis-diol dehydrogenase-catalysed dehydrogenation. Absolute configurations of chiral hydroxy sulfoxides were determined by X-ray crystallography, ECD spectroscopy and stereochemical correlation. The application of a new range of ß-hydroxy sulfoxides as chiral ligands was examined.

Haemorrhage at caesarean section: a framework for prevention and research.

PURPOSE OF REVIEW: Caesarean section rates are increasing across the world. Postpartum haemorrhage is a major cause of morbidity and mortality; major haemorrhage is more common after caesarean delivery. There is a wide range of practice in the prevention and treatment of postpartum haemorrhage at caesarean section. The aim of this review is to summarize current opinion in the management of postpartum haemorrhage at caesarean section. RECENT FINDINGS: Recent large randomized controlled trials have shown a possible effect from the routine use of tranexamic acid and ergometrine. Small randomized controlled trials have shown a possible benefit from using carbetocin. SUMMARY: The impact of postpartum haemorrhage can be reduced by antenatal correction of anaemia. Intraoperative medical management consists of oxytocinon, additional oxytocics +/- tranexamic acid, with at present limited evidence as to the order in which these should be considered. Trials of routine use of cell salvage and tranexamic acid are currently underway.

Extracorporeal Life Support Bridge to Ventricular Assist Device: The Double Bridge Strategy.

In patients requiring left ventricular assist device (LVAD) support, it can be difficult to ascertain suitability for long-term mechanical support with LVAD and eventual transplantation. LVAD implantation in a shocked patient is associated with increased morbidity and mortality. Interest is growing in the utilization of extracorporeal life support (ECLS) as a bridge-to-bridge support for these critically unwell patients. Here, we reviewed our experience with ECLS double bridging. We hypothesized that ECLS double bridging would stabilize end-organ dysfunction and reduce ventricular assist device (VAD) implant perioperative mortality. We conducted a retrospective review of prospectively collected data for 58 consecutive patients implanted with a continuous-flow LVAD between January 2010 and December 2013 at The Alfred Hospital, Melbourne, Victoria, Australia. Twenty-three patients required ECLS support pre-LVAD while 35 patients underwent LVAD implantation without an ECLS bridge. Preoperative morbidity in the ECLS bridge group was reflected by increased postoperative intensive care duration, blood loss, blood product use, and postoperative renal failure, but without negative impact upon survival when compared with the no ECLS group. ECLS stabilization improved end-organ function pre-VAD implant with significant improvements in hepatic and renal dysfunction. This series demonstrates that the use of ECLS bridge to VAD stabilizes end-organ dysfunction and reduces VAD implant perioperative mortality from that traditionally reported in these "crash and burn" patients.

MHC Class II-restricted antigen presentation by plasmacytoid dendritic cells drives proatherogenic T cell immunity.

BACKGROUND: Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and are important regulators of immuno-inflammatory diseases. However, their role in atherosclerosis remains elusive. METHODS AND RESULTS: Here, we used genetic approaches to investigate the role of pDCs in atherosclerosis. Selective pDC deficiency in vivo was achieved using CD11c-Cre × Tcf4(-/flox) bone marrow transplanted into Ldlr(-/-) mice. Compared with control Ldlr(-/-) chimeric mice, CD11c-Cre × Tcf4(-/flox) mice had reduced atherosclerosis levels. To begin to understand the mechanisms by which pDCs regulate atherosclerosis, we studied chimeric Ldlr(-/-) mice with selective MHCII deficiency on pDCs. Significantly, these mice also developed reduced atherosclerosis compared with controls without reductions in pDC numbers or changes in conventional DCs. MHCII-deficient pDCs showed defective stimulation of apolipoprotein B100-specific CD4(+) T cells in response to native low-density lipoprotein, whereas production of interferon-α was not affected. Finally, the atheroprotective effect of selective MHCII deficiency in pDCs was associated with significant reductions of proatherogenic T cell-derived interferon-γ and lesional T cell infiltration, and was abrogated in CD4(+) T cell-depleted animals. CONCLUSIONS: This study supports a proatherogenic role for pDCs in murine atherosclerosis and identifies a critical role for MHCII-restricted antigen presentation by pDCs in driving proatherogenic T cell immunity.

Right ventricular failure after implantation of continuous flow left ventricular assist device: analysis of predictors and outcomes.

Postoperative right ventricular failure is a serious complication for up to 50% of patients following LVAD insertion. Predicting RV failure is an important factor for patients as planned BiVAD support has been shown to correlate with better outcomes compared to delayed BiVAD to LVAD conversion. This retrospective study examined prospectively collected data for 101 patients implanted with an LVAD between 2003 and 2013, aiming to establish preoperative predictive factors for RVF post-LVAD insertion, analyze outcomes, and validate existing RVF scoring systems. In our cohort, 63 patients (62.4%) developed RV failure and consequently demonstrated consistently poorer survival throughout the follow-up period (log-rank p = 0.01). Multivariable logistic regression identified two significant variables: cardiac index <2.2 preoperatively despite inotropic support (OR 4.6 [95%CI 1.8-11.8]; p = 0.001) and preoperative tricuspid regurgitation (OR 8.1 [95%CI 1.9-34]; p = 0.004). Patients who developed RV failure had more complicated postoperative courses including longer ICU stay (p < 0.001), higher incidence of transfusions (p = 0.03) and re-intubation (p = 0.001), longer ventilation duration (p < 0.001), and higher incidence of returning to theater (p = 0.0008). This study found that previous validation models had only moderate correlation with our population emphasizing the need for prospective validation of these scores in the current era of continuous flow devices.

Banding the Right Ventricular Assist Device Outflow Conduit: Is It Really Necessary With Current Devices?

Implantable left ventricular assist devices (LVADs) have been adapted clinically for right-sided mechanical circulatory support (RVAD). Previous studies on RVAD support have established the benefits of outflow cannula restriction and rotational speed reduction, and recent literature has focused on assessing either the degree of outflow cannula restriction required to simulate left-sided afterload, or the limitation of RVAD rotational speeds. Anecdotally, the utility of outflow cannula restriction has been questioned, with suggestion that banding may be unnecessary and may be replaced simply by varying the outflow conduit length. Furthermore, many patients have a high pulmonary vascular resistance (PVR) at the time of ventricular assist device (VAD) insertion that reduces with pulmonary vascular bed remodeling. It is therefore important to assess the potential changes in flow through an RVAD as PVR changes. In this in vitro study, we observed the use of dual HeartWare HVAD devices (HeartWare Inc., Framingham, MA, USA) in biventricular support (BiVAD) configuration. We assessed the pumps' ability to maintain hemodynamic stability with and without banding; and with varying outflow cannulae length (20, 40, and 60 cm). Increased length of the outflow conduit was found to produce significantly increased afterload to the device, but this was not found to be necessary to maintain the device within the manufacturer's recommended operational parameters under a simulated normal physiological setting of mild and severe right ventricular (RV) failure. We hypothesize that 40 cm of outflow conduit, laid down along the diaphragm and then up over the RV to reach the pulmonary trunk, will generate sufficient resistance to maintain normal pump function.

Impact of a personal learning plan supported by an induction meeting on academic performance in undergraduate Obstetrics and Gynaecology: a cluster randomised controlled trial.

BACKGROUND: A personal learning plan (PLP) is an approach to assist medical students maximise their learning experience within clinical rotations. The aim of this study was to investigate whether medical students who created a PLP supported by an induction meeting had an improved academic performance within an undergraduate clinical rotation. METHODS: A cluster randomised controlled study was conducted over a full academic year (2012/13). The intervention was the creation of a PLP by medical students supported by an individual 'one-to-one' induction meeting between each student and a faculty member. Randomisation was by unit of rotation in which students completed the program. There were 2 clusters in the intervention group (n = 71 students) and 2 clusters in the control group (n = 72 students). Primary outcome was the overall examination score. Secondary outcomes were student attendance and student evaluation. RESULTS: There was no difference in overall examination score between the intervention group and control group (mean score 56.3 ± 4.8% versus 56.7 ± 5.6%, p = 0.64). The majority of students in the intervention group (n = 51/71, 85%) reported that the PLP and induction meeting enhanced their learning experience. Attendance at the induction meeting was identified as a key element. CONCLUSIONS: The creation of a PLP supported by an induction meeting was rated highly by students as an approach to enhance their learning experience but did not result in an improved academic performance. Further research is required to establish the role of an interim or exit meeting.

Team Objective Structured Bedside Assessment (TOSBA) as formative assessment in undergraduate Obstetrics and Gynaecology: a cohort study.

BACKGROUND: Team Objective Structured Bedside Assessment (TOSBA) is a learning approach in which a team of medical students undertake a set of structured clinical tasks with real patients in order to reach a diagnosis and formulate a management plan and receive immediate feedback on their performance from a facilitator. TOSBA was introduced as formative assessment to an 8-week undergraduate teaching programme in Obstetrics and Gynaecology (O&G) in 2013/14. Each student completed 5 TOSBA sessions during the rotation. The aim of the study was to evaluate TOSBA as a teaching method to provide formative assessment for medical students during their clinical rotation. The research questions were: Does TOSBA improve clinical, communication and/or reasoning skills? Does TOSBA provide quality feedback? METHODS: A prospective cohort study was conducted over a full academic year (2013/14). The study used 2 methods to evaluate TOSBA as a teaching method to provide formative assessment: (1) an online survey of TOSBA at the end of the rotation and (2) a comparison of the student performance in TOSBA with their performance in the final summative examination. RESULTS: During the 2013/14 academic year, 157 students completed the O&G programme and the final summative examination . Each student completed the required 5 TOSBA tasks. The response rate to the student survey was 68 % (n = 107/157). Students reported that TOSBA was a beneficial learning experience with a positive impact on clinical, communication and reasoning skills. Students rated the quality of feedback provided by TOSBA as high. Students identified the observation of the performance and feedback of other students within their TOSBA team as key features. High achieving students performed well in both TOSBA and summative assessments. The majority of students who performed poorly in TOSBA subsequently passed the summative assessments (n = 20/21, 95 %). Conversely, the majority of students who failed the summative assessments had satisfactory scores in TOSBA (n = 6/7, 86 %). CONCLUSIONS: TOSBA has a positive impact on the clinical, communication and reasoning skills of medical students through the provision of high-quality feedback. The use of structured pre-defined tasks, the observation of the performance and feedback of other students and the use of real patients are key elements of TOSBA. Avoiding student complacency and providing accurate feedback from TOSBA are on-going challenges.

Long-term right ventricular support with a centrifugal ventricular assist device placed in the right atrium.

This case series outlines the technique and results of right ventricular assist device (RVAD) support with the off-label use of the centrifugal HeartWare HVAD (HeartWare Inc., Framingham, MA, USA) for long-term support. Four patients in our institution have been implanted with BiVADs, using the Heartware device as the RVAD, and supported for between 117 days and 772 days. Three of the patients have been successfully supported for over 18 months. Three patients have successfully been transplanted and one patient remains on the device, now approaching two years of support. None of the patients have had RVAD device-related complications.

Accumulation of autophagosomes in Semliki Forest virus-infected cells is dependent on expression of the viral glycoproteins.

Autophagy is a cellular process that sequesters cargo in double-membraned vesicles termed autophagosomes and delivers this cargo to lysosomes to be degraded. It is enhanced during nutrient starvation to increase the rate of amino acid turnover. Diverse roles for autophagy have been reported for viral infections, including the assembly of viral replication complexes on autophagic membranes and protection of host cells from cell death. Here, we show that autophagosomes accumulate in Semliki Forest virus (SFV)-infected cells. Despite this, disruption of autophagy had no effect on the viral replication rate or formation of viral replication complexes. Also, viral proteins rarely colocalized with autophagosome markers, suggesting that SFV did not utilize autophagic membranes for its replication. Further, we found that SFV infection, unlike nutrient starvation, did not inactivate the constitutive negative regulator of autophagosome formation, mammalian target of rapamycin, suggesting that SFV-dependent accumulation of autophagosomes was not a result of enhanced autophagosome formation. In starved cells, addition of NH(4)Cl, an inhibitor of lysosomal acidification, caused a dramatic accumulation of starvation-induced autophagosomes, while in SFV-infected cells, NH(4)Cl did not further increase levels of autophagosomes. These results suggest that accumulation of autophagosomes in SFV-infected cells is due to an inhibition of autophagosome degradation rather than enhanced rates of autophagosome formation. Finally, we show that the accumulation of autophagosomes in SFV-infected cells is dependent on the expression of the viral glycoprotein spike complex.

BAFF receptor deficiency reduces the development of atherosclerosis in mice--brief report.

OBJECTIVE: The goal of this study was to assess the role of B-cell activating factor (BAFF) receptor in B-cell regulation of atherosclerosis. METHODS AND RESULTS: Male LDL receptor-deficient mice (Ldlr(-/-)) were lethally irradiated and reconstituted with either wild type or BAFF receptor (BAFF-R)-deficient bone marrow. After 4 weeks of recovery, mice were put on a high-fat diet for 6 or 8 weeks. BAFF-R deficiency in bone marrow cells led to a marked reduction of conventional mature B2 cells but did not affect the B1a cell subtype. This was associated with a significant reduction of dendritic cell activation and T-cell proliferation along with a reduction of IgG antibodies against malondialdehyde-modified low-density lipoprotein. In contrast, serum IgM type antibodies were preserved. Interestingly, BAFF-R deficiency was associated with a significant reduction in atherosclerotic lesion development and reduced numbers of plaque T cells. Selective BAFF-R deficiency on B cells led to a similar reduction in lesion size and T-cell infiltration but in contrast did not affect dendritic cell activation. CONCLUSIONS: BAFF-R deficiency in mice selectively alters mature B2 cell-dependent cellular and humoral immune responses and limits the development of atherosclerosis.