Arc-driven mGRASP highlights CA1 to CA3 synaptic engrams.

Subpopulations of neurons display increased activity during memory encoding and manipulating the activity of these neurons can induce artificial formation or erasure of memories. Thus, these neurons are thought to be cellular engrams. Moreover, correlated activity between pre- and postsynaptic engram neurons is thought to lead to strengthening of their synaptic connections, thus increasing the probability of neural activity patterns occurring during encoding to reoccur at recall. Therefore, synapses between engram neurons can also be considered as a substrate of memory, or a synaptic engram. One can label synaptic engrams by targeting two complementary, non-fluorescent, synapse-targeted GFP fragments separately to the pre- and postsynaptic compartment of engram neurons; the two GFP fragments reconstitute a fluorescent GFP at the synaptic cleft between the engram neurons, thereby highlighting synaptic engrams. In this work we explored a transsynaptic GFP reconstitution system (mGRASP) to label synaptic engrams between hippocampal CA1 and CA3 engram neurons identified by different Immediate-Early Genes: cFos and Arc. We characterized the expression of the cellular and synaptic labels of the mGRASP system upon exposure to a novel environment or learning of a hippocampal-dependent memory task. We found that mGRASP under the control of transgenic ArcCreERT2 labeled synaptic engrams more efficiently than when controlled by viral cFostTA, possibly due to differences in the genetic systems rather than the specific IEG promoters.

Characterization of thoracal fat depots - expression of adipokines and remodeling factors and impact of adipocyte conditioned media in fibroblast scratch assays.

Adipose tissue is not only a connective tissue but also an endocrine organ secreting adipokines like Leptin and Adiponectin, lipokines such as palmitoileic acid and extracellular vesicles. These factors and the expression of matrix remodeling enzymes impact surrounding tissues via paracrine effects. The expression of selected secretion factors and the effect of adipocyte conditioned media from four thoracal adipose tissue origins - subcutaneous, perivascular, pericardial and epicardial adipose tissues - in a fibroblast proliferation/wound healing scratch assay model were investigated. Results were compared directly and according to the type 2 diabetic mellitus (T2DM) status of the patients the tissues are originated from. Adipocyte conditioned media from non-diabetic patients resulted in a significant higher scratch closure rate compared to the media with T2DM background. Linoleic acid incubation in scratch assay resulted in a reduced scratch closure rate. Leptin, Adiponectin and Visfatin/Nampt expression and MMP2, MMP9 and FSTL1 mRNA levels did not vary according to T2DM subgroups directly, leading to the assumption that these factors are not causal for scratch assay effects observed. In contrast significant mRNA expression differences were monitored between the thoracal tissue origins implying variations in the local effects of the different adipose tissue depots.

Effect of chlorhexidine skin disinfection and retrosternal gentamicin sponge on post-sternotomy mediastinitis: results from a prospective controlled registry of 2340 patients.

BACKGROUND: Reducing post-sternotomy mediastinitis (PSM) requires incorporating multiple methods. However, the independent effects of these measures are not well studied. AIM: To evaluate the independent effect of preoperative disinfection using isopropyl alcohol (IPA)-chlorhexidine gluconate (CHG) and the topical application of a retrosternal gentamicin collagen sponge at wound closure on reducing PSM. METHODS: From October 2012 to August 2014, 2340 patients were included in this prospective, controlled registry. Patients were divided into four groups. In groups 1 and 2, the skin was disinfected with IPA, and in groups 3 and 4, the skin was disinfected with IPA-CHG. A retrosternal gentamicin collagen sponge was used in groups 2 and 4. Freedom from PSM up to the 30th postoperative day was the primary endpoint. The secondary endpoint was freedom from any surgical site dehiscence. A stepwise regression model was made to reveal the independent factors associated with lower incidence of PSM. FINDINGS: There were significant differences in outcome among the groups (P < 0.0001). Primary healing was highest in group 4 (91.4%), which showed the lowest rate for mediastinitis (0.9%). Multivariate analysis showed that the use of CHG and a gentamicin sponge was statistically significant (P = 0.026 and 0.013, respectively). The other significant independent factors were valve operation (P = 0.001), body mass index >30 kg/m2 (P = 0.001), preoperative stroke (P = 0.005), and blood transfusion (P = 0.022). CONCLUSION: Preoperative skin disinfection with IPA-CHG is superior to only IPA, and it should be recommended. The addition of a retrosternal gentamicin-releasing sponge further reduces the rate of mediastinitis.

Camera-based photoplethysmography in critical care patients.

BACKGROUND: Camera-based photoplethysmography (cbPPG) is an optical measurement technique that reveals pulsatile blood flow in cutaneous microcirculation from a distance. cbPPG has been shown to reflect pivotal haemodynamic events like cardiac ejection in healthy subjects. In addition, it provides valuable insight into intrinsic microcirculatory regulation as it yields dynamic, two-dimensional perfusion maps. In this study, we evaluate the feasibility of a clinical cbPPG application in critical care patients. METHODS: A mobile camera set-up to record faces of patients at the bed site was constructed. Videos were made during the immediate recovery after cardiac surgery under standard critical care conditions and were processed offline. Major motion artefacts were detected using an optical flow technique and suitable facial regions were manually annotated. cbPPG signals were highpass filtered and Fourier spectra out of consecutive 10s signal segments calculated for heart rate detection. Signal-to-noise ratios (SNR) of the Fourier spectra were derived as a quality measure. Reference data of vital parameters were synchronously acquired from the bed site monitoring system. RESULTS: Seventy patient videos of an average time of 28.6±2.8 min were analysed. Heart rate (HR) was detected within a±5 bpm range compared to reference in 83% of total recording time. Low SNR and HR detection failure were mostly, but not exclusively, attributed to non-physiological events like patient motion, interventions or sudden changes of illumination. SNR was reduced by low arterial blood pressure, whereas no impact of other perioperative or disease-related parameters was identified. CONCLUSION: Cardiac ejection is detectable by cbPPG under pathophysiologic conditions of cardiovascular disease and perioperative medicine. cbPPG measurements can be seamlessly integrated into the clinical work flow of critical care patients.

Prospective clinical trial on dosage optimizing of tranexamic acid in non-emergency cardiac surgery procedures.

UNLABELLED: After withdrawal of aprotinin in 2008 only tranexamic acid (TxA, Cyclocapron, Pfitzer, Germany) remains available as antihyperfibrinolytic agent in Europe. Dosage (from 1 g to 20 g) and application strategy (single shot i.v., infusion i.v., topical) reflect an indiscriminate use of TXA in cardiac surgery. We use data analysis of three registries to evaluate safety issues and sufficiency of different TxA dosages in our center. METHODS: Registry 1: Single shot ultra-low dose TxA (1 g in priming volume). Registry 2: Single shot medium dose TxA (5 g in priming volume). Registry 3: Single shot medium dose TxA (3 g in priming volume) and continuous, weight-adapted administration during cross clamping. Independence of surgeon's preference was achieved by changing dosage every surgery day regardless of operation schedule. RESULTS: Data analysis was carried out on 1182 consecutive, elective patients (1 g TxA n = 415; 3 g + x g TA n = 367; mean TxA dose 4.4 g ± 1.0 g; 5 g TxA n = 400). Patient characteristics were well matched in all three registries (mean age: 69 ± 9.5y, BMI 28.2 ± 4.7, Creatinin 107.5 ± 52.8 µM), as were performed surgical procedures (excluding organ transplantation). Postoperative data showed no significant differences for blood loss and major adverse events (1 g vs. 3 + g vs. 5 g: blood loss: 894 ± 1479 vs. 903 ± 1282 vs. 1004 ± 1604 ml; stroke: 1.5 vs. 1.6 vs. 1.5%; myocardial infarction 2.7 vs. 3.3 vs. 1.3%; 30d mortality 3.9 vs. 4.2 vs. 4.8%, respectively). Secondary endpoints (de novo dialysis, transfusion requirement, ICU and total treatment time) showed no significant differences between registries. CONCLUSION: Use of 1 g TxA is safe and sufficient for elective patients with on pump cardiac surgery and thus has been established as strategy of choice in our center.

Skin sealant InteguSeal® has no impact on prevention of postoperative mediastinitis after cardiac surgery.

BACKGROUND: Surgical site infections (SSIs) after median sternotomy represent a serious complication and a high potential risk for adverse clinical outcome after cardiac surgery. The antimicrobial skin sealant InteguSeal® was introduced as a novel tool in preventing development of SSI. AIM: This single-centre investigation used two prospective registries to evaluate the prophylactic effect of a cyanoacrylate-based antimicrobial skin sealant (InteguSeal®) on the incidence of postoperative mediastinitis or any other form of chest skin incision SSI after elective cardiac surgery. METHODS: Between October 2010 and April 2011 a total of 998 patients underwent elective cardiac surgical procedures with median sternotomy in our centre. In 496 patients InteguSeal® was included in standard preoperative preparation procedures before chest skin incision (group 1). In 502 patients standard preoperative skin preparation procedures were used without InteguSeal® (group 2). Freedom from mediastinitis and from any other form of SSI within 30 postoperative days were the primary and secondary endpoints, respectively. FINDINGS: A total of 983 patients were eligible for inclusion in per-protocol analysis (488 vs 495 patients). The incidence of postoperative mediastinitis was 2.3% in group 1 vs 3.2% in group 2 (not significant). The incidence of any form of SSI was 10.9% in group 1 vs 11.5% in group 2 (not significant). Perioperative patient characteristics, complexity of surgical procedures performed and length of hospitalization were similar in both groups. CONCLUSION: The use of InteguSeal® has no influence on the incidence of postoperative SSI and mediastinitis after cardiac surgery with median sternotomy.

Perforation of the ascending aorta: a late complication of superior vena cava stenting.

Intravascular stenting of the superior vena cava (SVC) is an established therapy in patients with SVC syndrome. Late complications include re-occlusion, stent infection, migration, and perforation. Affection of the greater thoracic vessels is rare and life-threatening when it occurs. We present a case of ascending aorta laceration as a late complication of SVC stenting. Surgical therapy included excision of the aortic lesion and pericardial patch repair. This case illustrates successful management of a complication after palliative stenting of the SVC.