Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Acquiring reading and vocabulary in Dutch and English: the effect of concurrent instruction

To investigate the effect of concurrent instruction in Dutch and English on reading acquisition in both languages, 23 pupils were selected from a school with bilingual education, and 23 from a school with education in Dutch only. The pupils had a Dutch majority language background and were comparable with regard to social-economic status (SES). Reading and vocabulary were measured twice within an interval of 1 year in Grade 2 and 3. The bilingual group performed better on most English and some of the Dutch tests. Controlling for general variables and related skills, instruction in English contributed significantly to the prediction of L2 vocabulary and orthographic awareness at the second measurement. As expected, word reading fluency was easier to acquire in Dutch with its relatively transparent orthography in comparison to English with its deep orthography, but the skills intercorrelated highly. With regard to cross-linguistic transfer, orthographic knowledge and reading comprehension in Dutch were positively influenced by bilingual instruction, but there was no indication of generalization to orthographic awareness or knowledge of a language in which no instruction had been given (German). The results of the present study support the assumption that concurrent instruction in Dutch and English has positive effects on the acquisition of L2 English and L1 Dutch

Dutch home-based pre-reading intervention with children at familial risk of dyslexia

Children (5 and 6 years old, n = 30) at familial risk of dyslexia received a home-based intervention that focused on phoneme awareness and letter knowledge in the year prior to formal reading instruction. The children were compared to a no-training at-risk control group (n = 27), which was selected a year earlier. After training, we found a small effect on a composite score of phoneme awareness (d = 0.29) and a large effect on receptive letter knowledge (d = 0.88). In first grade, however, this did not result in beneficial effects for the experimental group in word reading and spelling. Results are compared to three former intervention studies in The Netherlands and comparable studies from Denmark and Australia

Playwork in prison as a mechanism to support family health and well-being

Objective: The health of the prison population has become an increasing concern, given the disproportionate rates of ill health in this population. Moreover, the challenges faced by prisoners’ families and their children are also becoming more apparent, with prisoners’ children being more likely than other children to experience mental and emotional health problems and more likely to go to prison themselves. Prison visits are an integral part of institutional structures and are a key way by which families stay in contact and mitigate against the negative effects of family separation. This paper focuses particularly on the impact of prison play visits as an alternative to ‘standard’ visiting procedures. Design: Cross-sectional qualitative study. Setting: A male prison in Northern England. Method: Telephone interviews with six prison visitors who had regularly participated in a play visit, plus a focus group with five prisoners. Results: The paper identifies play visits as a useful way to maintain family well-being as they ‘mimic’, albeit temporarily, domestic life. This is reported to be beneficial for future family outcomes and in enabling children to adjust to parental incarceration. Play visits improve levels of intimacy, which is beneficial for the mental and emotional health both of prisoners and their children. Conclusion: The paper argues for a more holistic notion of prisoner health that sees family connections as a key part of supporting health and well-being

The value of haptic feedback in conventional and robot-assisted minimal invasive surgery and virtual reality training: a current review

BACKGROUND: Virtual reality (VR) as surgical training tool has become a state-of-the-art technique in training and teaching skills for minimally invasive surgery (MIS). Although intuitively appealing, the true benefits of haptic (VR training) platforms are unknown. Many questions about haptic feedback in the different areas of surgical skills (training) need to be answered before adding costly haptic feedback in VR simulation for MIS training. This study was designed to review the current status and value of haptic feedback in conventional and robot-assisted MIS and training by using virtual reality simulation. METHODS: A systematic review of the literature was undertaken using PubMed and MEDLINE. The following search terms were used: Haptic feedback OR Haptics OR Force feedback AND/OR Minimal Invasive Surgery AND/OR Minimal Access Surgery AND/OR Robotics AND/OR Robotic Surgery AND/OR Endoscopic Surgery AND/OR Virtual Reality AND/OR Simulation OR Surgical Training/Education. RESULTS: The results were assessed according to level of evidence as reflected by the Oxford Centre of Evidence-based Medicine Levels of Evidence. CONCLUSIONS: In the current literature, no firm consensus exists on the importance of haptic feedback in performing minimally invasive surgery. Although the majority of the results show positive assessment of the benefits of force feedback, results are ambivalent and not unanimous on the subject. Benefits are least disputed when related to surgery using robotics, because there is no haptic feedback in currently used robotics. The addition of haptics is believed to reduce surgical errors resulting from a lack of it, especially in knot tying. Little research has been performed in the area of robot-assisted endoscopic surgical training, but results seem promising. Concerning VR training, results indicate that haptic feedback is important during the early phase of psychomotor skill acquisitio

Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC), including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19).</p> <p>Methods</p> <p>Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS)</p> <p>Results</p> <p>HNTMB displayed high cytotoxicity (IC50 200-400 nM) compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM) or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM). In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM). In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS) while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels.</p> <p>Conclusions</p> <p>The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other solid tumors.</p

Possible Associations of NTRK2 Polymorphisms with Antidepressant Treatment Outcome: Findings from an Extended Tag SNP Approach

Background: Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment. Methods: We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples. Results: In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects ($P_{corr}$ = .018, $P_{corr}$ = .015 and $P_{corr}$ = .004, respectively). We observed an across-gene BDNF-NTRK2 SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients. Conclusions/Limitations: Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies

Early structural and functional defects in synapses and myelinated axons in stratum lacunosum moleculare in two preclinical models for tauopaty

The stratum lacunosum moleculare (SLM) is the connection hub between entorhinal cortex and hippocampus, two brain regions that are most vulnerable in Alzheimer’s disease. We recently identified a specific synaptic deficit of Nectin-3 in transgenic models for tauopathy. Here we defined cognitive impairment and electrophysiological problems in the SLM of Tau.P301L mice, which corroborated the structural defects in synapses and dendritic spines. Reduced diffusion of DiI from the ERC to the hippocampus indicated defective myelinated axonal pathways. Ultrastructurally, myelinated axons in the temporoammonic pathway (TA) that connects ERC to CA1 were damaged in Tau.P301L mice at young age. Unexpectedly, the myelin defects were even more severe in bigenic biGT mice that co-express GSK3β with Tau.P301L in neurons. Combined, our data demonstrate that neuronal expression of protein Tau profoundly affected the functional and structural organization of the entorhinal-hippocampal complex, in particular synapses and myelinated axons in the SLM. White matter pathology deserves further attention in patients suffering from tauopathy and Alzheimer’s disease