Lightweight of a cross beam for commercial vehicles: Development, testing and validation

Publication date: 5 July 2018
Source:Materials & Design, Volume 149
Author(s): S. Cecchel, D. Ferrario, A. Panvini, G. Cornacchia
Commonly the reduction of weight in transport is applied to passenger cars, while commercial vehicles are still not widely involved due to structural and costs restraints. This research studied a new concept of aluminium cross beam suspension for commercial vehicles that would replace the currently used steel component. The related advantages entail the achievement of an affordable solution, weight reduction of about 50%, environmental benefits, avoidance of painting and excellent recyclability. The use of appropriate materials, a new concept of design and a careful function integration allowed the structural limits to be overcome. The feasibility of this solution was verified through detailed characterisation and testing, composed of an analysis of the most relevant failure modes, with microstructures, hardness tests, tensile tests, fractography, salt spray test and fatigue test bench road simulator with field test data. The validation was successfully completed and the feasibility of the light alloy use for this particular heavy application was demonstrated. Further experiments, based on the development of heat treatments for potential future extension of this application, were conducted with the support of Design Of Experiment methodology. The outputs constitute a useful database of properties.

Graphical abstract

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Densities and Laminar Distributions of Kv3.1b-, PV-, GABA-, and SMI-32-Immunoreactive Neurons in Macaque Area V1

Abstract

The Kv3.1b potassium channel subunit is associated with narrow spike widths and fast-spiking properties. In macaque primary visual cortex (V1), subsets of neurons have previously been found to be Kv3.1b-immunoreactive (ir) but not parvalbumin (PV)-ir or not GABA-ir, suggesting that they may be both fast-spiking and excitatory. This population includes Meynert cells, the large layer 5/6 pyramidal neurons that are also labeled by the neurofilament antibody SMI-32. In the present study, triple immunofluorescence labeling and confocal microscopy were used to measure the distribution of Kv3.1b-ir, non-PV-ir, non-GABA-ir neurons across cortical depth in V1, and to determine whether, like the Meynert cells, other Kv3.1b-ir excitatory neurons were also SMI-32-ir pyramidal neurons. We found that Kv3.1b-ir, non-PV-ir, non-GABA-ir neurons were most prevalent in the M pathway-associated layers 4 Cα and 4B. GABAergic neurons accounted for a smaller fraction (11%) of the total neuronal population across layers 1–6 than has previously been reported. Of Kv3.1b-ir neurons, PV expression reliably indicated GABA expression. Kv3.1b-ir, non-PV-ir neurons varied in SMI-32 coimmunoreactivity. The results suggest the existence of a heterogeneous population of excitatory neurons in macaque V1 with the potential for sustained high firing rates, and these neurons were particularly abundant in layers 4B and 4 Cα.

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Altered Neocortical Gene Expression, Brain Overgrowth and Functional Over-Connectivity in Chd8 Haploinsufficient Mice

Abstract

Truncating CHD8 mutations are amongst the highest confidence risk factors for autism spectrum disorder (ASD) identified to date. Here, we report that Chd8 heterozygous mice display increased brain size, motor delay, hypertelorism, pronounced hypoactivity, and anomalous responses to social stimuli. Whereas gene expression in the neocortex is only mildly affected at midgestation, over 600 genes are differentially expressed in the early postnatal neocortex. Genes involved in cell adhesion and axon guidance are particularly prominent amongst the downregulated transcripts. Resting-state functional MRI identified increased synchronized activity in cortico-hippocampal and auditory-parietal networks in Chd8 heterozygous mutant mice, implicating altered connectivity as a potential mechanism underlying the behavioral phenotypes. Together, these data suggest that altered brain growth and diminished expression of important neurodevelopmental genes that regulate long-range brain wiring are followed by distinctive anomalies in functional brain connectivity in Chd8^+/− mice. Human imaging studies have reported altered functional connectivity in ASD patients, with long-range under-connectivity seemingly more frequent. Our data suggest that CHD8 haploinsufficiency represents a specific subtype of ASD where neuropsychiatric symptoms are underpinned by long-range over-connectivity.

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Movement Decomposition in the Primary Motor Cortex

Abstract

A complex action can be described as the composition of a set of elementary movements. While both kinematic and dynamic elements have been proposed to compose complex actions, the structure of movement decomposition and its neural representation remain unknown. Here, we examined movement decomposition by modeling the temporal dynamics of neural populations in the primary motor cortex of macaque monkeys performing forelimb reaching movements. Using a hidden Markov model, we found that global transitions in the neural population activity are associated with a consistent segmentation of the behavioral output into acceleration and deceleration epochs with directional selectivity. Single cells exhibited modulation of firing rates between the kinematic epochs, with abrupt changes in spiking activity timed with the identified transitions. These results reveal distinct encoding of acceleration and deceleration phases at the level of M1, and point to a specific pattern of movement decomposition that arises from the underlying neural activity. A similar approach can be used to probe the structure of movement decomposition in different brain regions, possibly controlling different temporal scales, to reveal the hierarchical structure of movement composition.

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Association Between Brain Activation and Functional Connectivity

Abstract

The origin of the "resting-state" brain activity recorded with functional magnetic resonance imaging (fMRI) is still uncertain. Here we provide evidence for the neurovascular origins of the amplitude of the low-frequency fluctuations (ALFF) and the local functional connectivity density (lFCD) by comparing them with task-induced blood-oxygen level dependent (BOLD) responses, which are considered a proxy for neuronal activation. Using fMRI data for 2 different tasks (Relational and Social) collected by the Human Connectome Project in 426 healthy adults, we show that ALFF and lFCD have linear associations with the BOLD response. This association was significantly attenuated by a novel task signal regression (TSR) procedure, indicating that task performance enhances lFCD and ALFF in activated regions. We also show that lFCD predicts BOLD activation patterns, as was recently shown for other functional connectivity metrics, which corroborates that resting functional connectivity architecture impacts brain activation responses. Thus, our findings indicate a common source for BOLD responses, ALFF and lFCD, which is consistent with the neurovascular origin of local hemodynamic synchrony presumably reflecting coordinated fluctuations in neuronal activity. This study also supports the development of task-evoked functional connectivity density mapping.

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Microglial Pruning of Synapses in the Prefrontal Cortex During Adolescence

Abstract

Exaggerated synaptic elimination in the prefrontal cortex (PFC) during adolescence has been suggested to contribute to the neuropathological changes of schizophrenia. Recent data indicate that microglia (MG) sculpt synapses during early postnatal development. However, it is not known if MG contribute to the structural maturation of the PFC, which has a protracted postnatal development. We determined if MG are involved in developmentally specific synapse elimination in the PFC, focusing on adolescence. Layer 5 PFC pyramidal cells (PCs) were intracellularly filled with Lucifer Yellow for dendritic spine measurements in postnatal day (P) 24, P30, P35, P39, and P50 rats. In the contralateral PFC we evaluated if MG engulfed presynaptic (glutamatergic) and postsynaptic (dendritic spines) elements. Dendritic spine density increased from P24 to P35, when spine density peaked. There was a significant increase in MG engulfment of spines at P39 relative to earlier ages; this subsided by P50. MG also phagocytosed presynaptic glutamatergic terminals. These data indicate that MG transiently prune synapses of PFC PCs during adolescence, when the symptoms of schizophrenia typically first appear. An increase in MG-mediated synaptic remodeling of PFC PCs may contribute to the structural changes observed in schizophrenia.

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Evidence That Default Network Connectivity During Rest Consolidates Social Information

Abstract

Brain regions engaged during social inference, medial prefrontal cortex (MPFC) and tempoparietal junction (TPJ), are also known to spontaneously engage during rest. While this overlap is well known, the social cognitive function of engaging these regions during rest remains unclear. Building on past research suggesting that new information is committed to memory during rest, we explored whether one function of MPFC and TPJ engagement during rest may be to consolidate new social information. MPFC and TPJ regions significantly increased connectivity during rest after encoding new social information (relative to baseline and post nonsocial encoding rest periods). Moreover, greater connectivity between rTPJ and MPFC, as well as other portions of the default network (vMPFC, anterior temporal lobe, and middle temporal gyrus) during post social encoding rest corresponded with superior social recognition and social associative memory. The tendency to engage MPFC and TPJ during rest may tune people towards social learning.

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Adult-Onset Hearing Impairment Induces Layer-Specific Cortical Reorganization: Evidence of Crossmodal Plasticity and Central Gain Enhancement

Abstract

Adult-onset hearing impairment can lead to hyperactivity in the auditory pathway (i.e., central gain enhancement) as well as increased cortical responsiveness to nonauditory stimuli (i.e., crossmodal plasticity). However, it remained unclear to what extent hearing loss-induced hyperactivity is relayed beyond the auditory cortex, and thus, whether central gain enhancement competes or coexists with crossmodal plasticity throughout the distinct layers of the audiovisual cortex. To that end, we investigated the effects of partial hearing loss on laminar processing in the auditory, visual and audiovisual cortices of adult rats using extracellular electrophysiological recordings performed 2 weeks after loud noise exposure. Current-source density analyses revealed that central gain enhancement was not relayed to the audiovisual cortex (V2L), and was instead restricted to the granular layer of the higher order auditory area, AuD. In contrast, crossmodal plasticity was evident across multiple cortical layers within V2L, and also manifested in AuD. Surprisingly, despite this coexistence of central gain enhancement and crossmodal plasticity, noise exposure did not disrupt the responsiveness of these neighboring cortical regions to combined audiovisual stimuli. Overall, we have shown for the first time that adult-onset hearing impairment causes a complex assortment of intramodal and crossmodal changes across the layers of higher order sensory cortices.

https://ift.tt/2GTQahn

MEG Working Memory N-Back Task Reveals Functional Deficits in Combat-Related Mild Traumatic Brain Injury

Abstract

Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained cognitive impairment in military service members and Veterans. However, the mechanism of persistent cognitive deficits including working memory (WM) dysfunction is not fully understood in mTBI. Few studies of WM deficits in mTBI have taken advantage of the temporal and frequency resolution afforded by electromagnetic measurements. Using magnetoencephalography (MEG) and an N-back WM task, we investigated functional abnormalities in combat-related mTBI. Study participants included 25 symptomatic active-duty service members or Veterans with combat-related mTBI and 20 healthy controls with similar combat experiences. MEG source–magnitude images were obtained for alpha (8–12 Hz), beta (15–30 Hz), gamma (30–90 Hz), and low-frequency (1–7 Hz) bands. Compared with healthy combat controls, mTBI participants showed increased MEG signals across frequency bands in frontal pole (FP), ventromedial prefrontal cortex, orbitofrontal cortex (OFC), and anterior dorsolateral prefrontal cortex (dlPFC), but decreased MEG signals in anterior cingulate cortex. Hyperactivations in FP, OFC, and anterior dlPFC were associated with slower reaction times. MEG activations in lateral FP also negatively correlated with performance on tests of letter sequencing, verbal fluency, and digit symbol coding. The profound hyperactivations from FP suggest that FP is particularly vulnerable to combat-related mTBI.

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Distinct Interplay Between Atrophy and Hypometabolism in Alzheimer’s Versus Semantic Dementia

Abstract

Multimodal neuroimaging analyses offer additional information beyond that provided by each neuroimaging modality. Thus, direct comparisons and correlations between neuroimaging modalities allow revealing disease-specific topographic relationships. Here, we compared the topographic discrepancies between atrophy and hypometabolism in two neurodegenerative diseases characterized by distinct pathological processes, namely Alzheimer's disease (AD) versus semantic dementia (SD), to unravel their specific influence on local and global brain structure–function relationships. We found that intermodality topographic discrepancies clearly distinguished the two patient groups: AD showed marked discrepancies between both alterations, with greater hypometabolism than atrophy in large posterior associative neocortical regions, while SD showed more topographic consistency between atrophy and hypometabolism across brain regions. These findings likely reflect the multiple pathologies versus the relatively unitary pathological process underlying AD versus SD respectively. Our results evidence that multimodal neuroimaging-derived indexes can provide clinically relevant information to discriminate the two diseases, and potentially reveal distinct neuropathological processes.

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Fumaric acid production using renewable resources from biodiesel and cane sugar production processes

Abstract

The microbial production of fumaric acid by Rhizopus arrhizus NRRL 2582 has been evaluated using soybean cake from biodiesel production processes and very high polarity (VHP) sugar from sugarcane mills. Soybean cake was converted into a nutrient-rich hydrolysate via a two-stage bioprocess involving crude enzyme production via solid state fermentations (SSF) of either Aspergillus oryzae or R. arrhizus cultivated on soybean cake followed by enzymatic hydrolysis of soybean cake. The soybean cake hydrolysate produced using crude enzymes derived via SSF of R. arrhizus was supplemented with VHP sugar and evaluated using different initial free amino nitrogen (FAN) concentrations (100, 200, and 400 mg/L) in fed-batch cultures for fumaric acid production. The highest fumaric acid concentration (27.3 g/L) and yield (0.7 g/g of total consumed sugars) were achieved when the initial FAN concentration was 200 mg/L. The combination of VHP sugar with soybean cake hydrolysate derived from crude enzymes produced by SSF of A. oryzae at 200 mg/L initial FAN concentration led to the production of 40 g/L fumaric acid with a yield of 0.86 g/g of total consumed sugars. The utilization of sugarcane molasses led to low fumaric acid production by R. arrhizus, probably due to the presence of various minerals and phenolic compounds. The promising results achieved through the valorization of VHP sugar and soybean cake suggest that a focused study on molasses pretreatment could lead to enhanced fumaric acid production.

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Phthalate esters distribution in coastal mariculture of Hong Kong, China

Abstract

The aim of the study is to evaluate the impact of mariculture on phthalate esters speciation and distribution in sediments and cultured fish in the Hong Kong regions and near mainland China. Concentrations of ∑phthalate esters in mariculture surface sediments (0 to 5 cm) ranged from 0.20 to 54.3 mg/kg dw (mean 10.3 mg/kg dw), with the highest recorded at M2 (20.4 mg/kg dw). Concentrations of phthalate esters were not significantly (p > 0.05) enriched in surface and sediment cores at mariculture sites relative to the reference sediments, 1 to 2 km away in areas without mariculture activities. Among different congeners, only butyl benzyl phthalate (BBP) concentrations demonstrated a significant correlation (R² = 0.40, p < 0.05) with TOC values of sediments. The median concentrations of di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) in the sediments were 1.57 and 6.96 times higher than the environmental risk levels (ERL), which may pose environmental risks. Results of health risk assessments revealed that the cultured fish (snubnose pompano, orange-spotted grouper, and red snapper) were safe for consumption, in terms of phthalate esters. This is the first study to assess the differences of phthalate esters contamination between mariculture and natural coastal sediments.

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In situ co-precipitation preparation of a superparamagnetic graphene oxide/Fe 3 O 4 nanocomposite as an adsorbent for wastewater purification: synthesis, characterization, kinetics, and isotherm studies

Abstract

A superparamagnetic graphene oxide (GO)/Fe₃O₄ nanocomposite (MGO) was prepared by a facile in situ co-precipitation strategy, resulting in a prospective material for the application of graphene oxide in wastewater treatment. MGO was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The prepared adsorbent showed a high adsorption efficiency relevant to the purification of dye-contaminated wastewater and could be readily magnetically separated. The maximum adsorption capacity was ca. 546.45 mg g⁻¹ for the common cationic dye methylene blue (MB) and ca. 628.93 mg g⁻¹ for the anionic dye Congo red (CR). The adsorption processes fit the pseudo-second-order kinetic model well, which revealed that these processes may involve the chemical interaction between adsorbate and adsorbent. The thermodynamic parameters indicated that the adsorption reaction was an endothermic and spontaneous process. Furthermore, the prepared magnetic adsorbent had a wide effective pH range from 5 to 11 and showed good stability after five reuse cycles. The synthetic MGO showed great potential as a promising adsorbent for organic contaminant removal in wastewater treatment.

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Subjective Evaluation of Voice Characteristics of School Aged Children in a Basket Ball Team

Abstract

Voice disorders have been estimated to be present in between 3 and 9% of general population. Sports children have vocal abusive behavior i.e. the extra effort which they put on their voice while playing, leading to voice disorders. It is imperative to find out the voice characteristics of children involved in sports activity. To assess voice characteristics of school aged children, who are active participants in a basket ball team. A group of twenty children (13 males and 7 females) were included in the study. He or she was member of school basket ball team and had participated in many events. The perceptual voice assessment was conducted using GRBAS scale, Buffalo III Voice Profile and Voice Handicap Index (VHI). Findings on GRBAS voice rating scale—In the first parameter i.e. grade 46.7% of the subjects reported slight hoarse component. In the second parameter i.e. Roughness 46.7% of the subjects showed slight roughness component. In another parameter i.e. the asthenia 20% % of the subjects reported slight asthenia component in their voice. In the next parameter i.e. strain in the voice, 26.7% of the subjects showed slight strain component in their voice. Finding on BUFFALO III voice screening profile—In the laryngeal tone, 46.7% of the subjects showed mild hoarse component. Findings on voice handicap index (VHI)—28% of the subjects had functional symptoms of voice problems. 43% of the subjects had some physical symptoms while 28% had affected emotional component. Present study is first of its kind to focus on voice disorders among school going children who are members of a basket ball team. During sport events players tend to scream in order to communicate among their team mates, to show their aggressiveness to their opponents and to show excitement of win or frustration of the lost match leading to various voice problems. There is a high probability of occurrence of voice disorders among children who are active participants of basket ball. Proper counselling of these children is required for preventive measures and to seek voice therapy when required.

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Genetically Diversity of Pseudomonas aeruginosa Isolated from Chronic Suppurative Otitis Media with Respect to Their Antibiotic Sensitivity Pattern

Abstract

Pseudomonas aeruginosa is an important chronic suppurative otitis media (CSOM) pathogen that exhibits multiple resistances to antibiotics with increasing frequency, making patient treatment more difficult. The aim of the study is to ascertain the genetically diversity of this clinically isolated P. aeruginosa with inter simple sequence repeat (ISSR) markers. All 25 P. aeruginosa were isolated from CSOM patients by taking their ear swabs and culturing on blood agar and MacConkey agar. All strains were identified with morphological characters and biochemical testing. The antimicrobial susceptibility testing was carried out according to National Committee for Clinical Laboratory Standards. ISSR was used to study the genetic diversity of P. aeruginosa. Clinically CSOM isolated 25 P. aeruginosa were 88% Ciprofloxacin resistant and similarly resistant to other antibiotics were documented. The study has been made using ISSR marker to find out the genomic relation among the strains/populations of P. aeruginosa. The result was shown that maximum similarity (80%) was between S-11 and S-13 and minimum (28.2%) was between S-4 and S-16 with an average similarity of 53.2%. The dendogram showed a distinct separation in between all the strains/populations of P. aeruginosa. The strains/populations were broken up into two main clusters in which small one bear two strains/populations (S-4 and S-9) and another cluster have another 23 strains/populations. These 23 strains were also separated to form subcluster by having different range of small clades. The genetically diversity of pathogenic P. aeruginosa present in CSOM at our hospital indicates the coexistence different strains due to different antibiotic sensitivity patterns. The conventional culture and sensitivity methods are time consuming whereas in PCR, it will detect within 4–6 h for effective antibiotic. Basing upon the banding pattern with ISSR primers, clinicians can prescribe the effective antibiotics accordingly for CSOM patients in the same day.

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Updates on antibody functions in Mycobacterium tuberculosis infection and their relevance for developing a vaccine against tuberculosis

Publication date: August 2018
Source:Current Opinion in Immunology, Volume 53
Author(s): Jacqueline M Achkar, Rafael Prados-Rosales
A more effective vaccine to control tuberculosis (TB), a major global public health problem, is urgently needed. Current vaccine candidates focus predominantly on eliciting cell-mediated immunity but other arms of the immune system also contribute to protection against TB. We review here recent studies that enhance our current knowledge of antibody-mediated functions against Mycobacterium tuberculosis. These findings, which contribute to the increasing evidence that antibodies have a protective role against TB, include demonstrations that firstly distinct human antibody Fc glycosylation patterns, found in latent M. tuberculosis infection but not in active TB, influence the efficacy of the host to control M. tuberculosis infection, secondly antibody isotype influences human antibody functions, and thirdly that antibodies targeting M. tuberculosis surface antigens are protective. We discuss these findings in the context of TB vaccine development and highlight the need for further research on antibody-mediated immunity in M. tuberculosis infection.



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PM2.5 forecasting using SVR with PSOGSA algorithm based on CEEMD, GRNN and GCA considering meteorological factors

Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Suling Zhu, Xiuyuan Lian, Lin Wei, Jinxing Che, Xiping Shen, Ling Yang, Xuanlin Qiu, Xiaoning Liu, Wenlong Gao, Xiaowei Ren, Juansheng Li
The PM2.5 is the culprit of air pollution, and it leads to respiratory system disease when the fine particles are inhaled. Therefore, it is increasingly significant to develop an effective model for PM2.5 forecasting and warnings that informs people to foresee the air quality. People can reduce outdoor activities and take preventive measures if they know the air quality is bad ahead of time. In addition, reliable forecasting results can remind the relevant departments to control and reduce pollutants discharge. According to our knowledge, the current hybrid forecasting techniques of PM2.5 do not take the meteorological factors into consideration. Actually, meteorological factors affect the concentrations of air pollution, but it is unclear whether meteorological factors are helpful for improving the PM2.5 forecasting results or not. This paper proposes a hybrid model called CEEMD-PSOGSA-SVR-GRNN, based on complementary ensemble empirical mode decomposition (CEEMD), particle swarm optimization and gravitational search algorithm (PSOGSA), support vector regression (SVR), generalized regression neural network (GRNN) and grey correlation analysis (GCA), for the daily PM2.5 concentrations forecasting. The main steps of proposed model are described as follows: the original PM2.5 data decomposition with CEEMD, optimal SVR selection with PSOGCA, meteorological factors selection with GCA, residual revision by GRNN and forecasting results analysis. Three cities (Chongqing, Harbin and Jinan) in China with different characteristics of climate, terrain and pollution sources are selected to verify the effectiveness of proposed model, and CEEMD-PSOGSA-SVR*, EEMD-PSOGSA-SVR, PSOGSA-SVR, CEEMD-PSO-SVR, CEEMD-GSA-SVR, CEEMD-GWO-SVR are considered to be compared models. The experimental results show that the hybrid CEEMD-PSOGSA-SVR-GRNN model outperforms other six compared models. Therefore, the proposed CEEMD-PSOGSA-SVR-GRNN model can be used to develop air quality forecasting and warnings.

Graphical abstract

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TX99 Is a Neutralizing Monoclonal Antibody Against Mouse TIGIT

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Ahead of Print.


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The Eighth Edition of TNM Staging of Lung Cancer: Reference Chart and Diagrams

AbstractLung cancer is the leading cause of cancer‐related mortality in the U.S. TNM staging of lung cancer is implemented to define the extent of disease and consequently assign prognosis and guide treatment. The newest edition of TNM staging of lung cancer has been released recently. In this article, we present the TNM staging of lung cancer in a concise, yet comprehensive, visual format.

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Use of Direct Oral Anticoagulants in Patients with Cancer: Practical Considerations for the Management of Patients with Nausea or Vomiting

AbstractDirect oral anticoagulants (DOACs) have proven efficacy and safety and are approved for use in the prevention and treatment of thromboembolic events in patients with venous thromboembolism (VTE) and those with atrial fibrillation (AF). There is no clear guidance on the use of DOACs in the significant proportion of these patients who have or will develop concomitant cancer. The occurrence of nausea and vomiting in these patients, despite implementation of guideline‐recommended antiemetic strategies, is a particular concern because it may affect oral drug intake and consequently outcomes with anticoagulation therapy.Here, we review recent data on the incidence and management of cancer‐associated nausea and vomiting and the current evidence and guidance relating to the use of DOACs in patients with cancer. On the basis of this evidence, an international working group of experts in the fields of cancer‐associated thrombosis/hemostasis, hematology, and oncology discussed key issues related to the use of DOACs in patients with VTE or AF and cancer who are at risk of nausea and vomiting and developed some consensus recommendations. We present these consensus recommendations, which outline strategies for the use and management of anticoagulants, including DOACs, in patients with VTE or AF and cancer for whom oral drug intake may pose challenges. Guidance is provided on managing patients with gastrointestinal obstruction or nausea and vomiting that is caused by cancer treatments or other cancer‐related factors.The recommendations outlined in this review provide a useful reference for health care professionals and will help to improve the management of anticoagulation in patients with VTE or AF and cancer.Implications for Practice.Direct oral anticoagulants (DOACs) offer several advantages over traditional anticoagulants, including ease of administration and the lack of need for routine monitoring. However, the management of patients with an indication for anticoagulation and concomitant cancer, who are at high risk of thromboembolic events, presents several challenges for administering oral therapies, particularly with regard to the risk of nausea and vomiting. In the absence of robust data from randomized trials and specific guidelines, consensus recommendations were developed for healthcare professionals regarding the use of DOACs in patients with cancer, with a focus on the management of patients who are at risk of nausea and vomiting.

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Osimertinib: A Novel Dermatologic Adverse Event Profile in Patients with Lung Cancer

AbstractDermatologic adverse events (dAEs) are common with the use of epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) therapy. First‐ and second‐generation agents (erlotinib, gefitinib, and afatinib) are frequently associated with acneiform rash, pruritus, xerosis, and paronychia; the incidence and characterization of these dAEs have been well described. However, there is evidence that the dAE profile is different with third‐generation EGFR‐TKIs. Herein, we describe the dAEs associated with third‐generation EGFR‐TKIs and our clinical experience with osimertinib, a third‐generation EGFR‐TKI approved by the U.S. Food and Drug Administration for the treatment of metastatic, EGFR T790M mutation‐positive non‐small cell lung cancer in patients whose disease has progressed on or after EGFR‐TKI therapy. Case summaries of patients from two of our institutions who received osimertinib and were referred to a dermatologist for dAEs are also presented. Overall, the evidence suggests that osimertinib is associated with less severe and less frequent dAEs than first‐ and second‐generation EGFR‐TKIs and that therefore a different approach is warranted. Finally, we outline dAE management approaches for osimertinib in the context of those typically employed with first‐ and second‐generation EGFR‐TKIs.Implications for Practice.Appropriate prevention and management of dermatologic adverse events (dAEs) associated with the use of epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) may help patients to continue therapy and lessen any negative impact on their quality of life. EGFR‐TKIs are frequently associated with acneiform rash, pruritus, xerosis, and paronychia; however, dAEs associated with third‐generation EGFR‐TKIs are lower in frequency and severity. Before therapy, health care providers should discuss the potential osimertinib‐associated dAEs and encourage patients to report their dAEs. Patients should also be educated on prophylactic measures to minimize the severity of dAEs and the importance of adherence to the treatment regimen.

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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Central Nervous System Metastases from Non‐Small Cell Lung Cancer

AbstractCentral nervous system (CNS) metastases are a common complication in patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC), resulting in a poor prognosis and limited treatment options. Treatment of CNS metastases requires a multidisciplinary approach, and the optimal treatment options and sequence of therapies are yet to be established. Many systemic therapies have poor efficacy in the CNS due to the challenges of crossing the blood‐brain barrier (BBB), creating a major unmet need for the development of agents with good BBB‐penetrating biopharmaceutical properties. Although the CNS penetration of first‐ and second‐generation EGFR tyrosine kinase inhibitors (TKIs) is generally low, EGFR‐TKI treatment has been shown to delay time to CNS progression in patients with CNS metastases from EGFR‐mutated disease. However, a major challenge with EGFR‐TKI treatment for patients with NSCLC is the development of acquired resistance, which occurs in most patients treated with a first‐line EGFR‐TKI. Novel EGFR‐TKIs, such as osimertinib, have been specifically designed to address the challenges of acquired resistance and poor BBB permeability and have demonstrated efficacy in the CNS. A rational, iterative drug development process to design agents that could penetrate the BBB could prevent morbidity and mortality associated with CNS disease progression. To ensure a consistent approach to evaluating CNS efficacy, special consideration also needs to be given to clinical trial endpoints.Implications for Practice.Historically, treatment options for patients who develop central nervous system (CNS) metastases have been limited and associated with poor outcomes. The development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has improved outcomes for patients with EGFR‐mutated disease, and emerging data have demonstrated the ability of these drugs to cross the blood‐brain barrier and elicit significant intracranial responses. Recent studies have indicated a role for next‐generation EGFR‐TKIs, such as osimertinib, in the treatment of CNS metastases. In the context of an evolving treatment paradigm, treatment should be individualized to the patient and requires a multidisciplinary approach.

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FDA Approval Summary: Mylotarg for Treatment of Patients with Relapsed or Refractory CD33‐Positive Acute Myeloid Leukemia

AbstractOn September 2, 2017, the U.S. Food and Drug Administration approved gemtuzumab ozogamicin (GO; Mylotarg; Pfizer, New York City, NY) for treatment of relapsed or refractory (R/R) CD33‐positive acute myeloid leukemia (AML) in patients 2 years of age and older. GO is a CD33‐directed antibody drug conjugate linked to the cytotoxic antibiotic calicheamicin. It originally received accelerated approval for treatment of older patients with relapsed CD33‐positive AML in 2000, but it was withdrawn from the market in 2010 when the confirmatory trial failed to demonstrate clinical benefit among safety concerns, such as a higher rate of induction fatalities on the GO combination arm compared with chemotherapy alone. In addition, GO was associated with hepatic veno‐occlusive disease (VOD), which has substantial morbidity and mortality. Pharmacokinetic analyses suggested a lower maximum concentration of GO would result in less VOD without affecting target saturation or efficacy. A meta‐analysis across dose schedules of GO in patients with R/R AML showed that a lower‐dose "fractionated" schedule of 3 mg/m2 days 1, 4, and 7 was associated with less early mortality, hemorrhage, and VOD, without an apparent decrease in complete remission (CR) rate. MyloFrance 1 was a single‐arm study evaluating response rates in patients with relapsed CD33‐positive AML treated with the lower‐dose fractionated GO regimen. The CR rate was 26% (95% confidence interval 16%–40%). Common adverse reactions were fever, infections, nausea, vomiting, constipation, bleeding, increased liver enzymes, and mucositis. There were no cases of VOD. These results supported the approval of GO as monotherapy for R/R CD33‐positive AML using the lower‐dose fractionated regimen.Implications for Practice.Gemtuzumab ozogamicin (GO) 3 mg/m2 days 1, 4, and 7 is an active regimen for induction of remission when used to treat patients with relapsed or refractory CD33‐positive acute myeloid leukemia without curative intent. The risks of hepatic veno‐occlusive disease and early mortality with this regimen appear to be lower than reported previously for GO 9 mg/m2 days 1 and 15. The data were not sufficient to enable conclusions about the safety of GO in children younger than 2 years of age.

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Conserved association of Argonaute 1 and 2 proteins with miRNA and siRNA pathways throughout insect evolution, from cockroaches to flies

Publication date: Available online 12 April 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Mercedes Rubio, Jose Luis Maestro, Maria-Dolors Piulachs, Xavier Belles




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Perioperative management of transcatheter, aortic and mitral, double valve-in-valve implantation during pregnancy through left ventricular apical approach

Suresh Chengode, Rahul Vijaykumar Shabadi, Ram Narayan Rao, Nasser Alkemyani, Hilal Alsabti

Annals of Cardiac Anaesthesia 2018 21(2):185-188

Pregnant women with stenotic degeneration of bioprosthetic cardiac valves may require another valve replacement procedure when their symptoms deteriorate with progression of pregnancy, but fetal mortality is higher with cardiac surgery done on cardiopulmonary bypass. Transcatheter valve-in-valve implantation may help to improve the fetal and maternal outcomes in these situations. Double valve-in-valve implantation is rare and has not been reported in a pregnant patient. We report, for the first time, the case of a pregnant woman with stenotic bioprosthetic valves in the mitral and aortic positions, who underwent a successful concomitant, transcatheter, double valve-in-valve implantation through the left ventricular apical route during the second trimester of her precious pregnancy.

https://ift.tt/2EGHJjJ

Dishonesty in medical research and publication and the remedial measures

Praveen Kumar Neema

Annals of Cardiac Anaesthesia 2018 21(2):111-113



https://ift.tt/2JGn7M9

Absent right superior vena cava and persistent left superior vena cava in a patient with bicuspid aortic valve with aortic stenosis

Kushant Gupta, Vijayakanth Bhuvana, Varun Bansal, Ruma Ray, Arkalgud Sampath Kumar

Annals of Cardiac Anaesthesia 2018 21(2):212-214

Persistent left superior vena cava (LSVC) with absent right SVC (RSVC) is a rare congenital anomaly. If undetected, the condition may pose difficulties in central venous catheter insertion, pacemaker electrode insertion, and cannulation during cardiopulmonary bypass. We describe a case of persistent LSVC with absent RSVC, who was diagnosed to have bicuspid aortic valve with aortic stenosis.

https://ift.tt/2EGeo99

Immediate extubation after cardiac surgery should be part of routine anesthesia practice for selected patients

Thomas M Hemmerling

Annals of Cardiac Anaesthesia 2018 21(2):114-115



https://ift.tt/2JISd5A

Anesthetic challenges of a patient with the communicating bulla coming for nonthoracic surgery

Bernice Theodare, Vinolia Victory Nissy, Raj Sahajanandan, Ramamani Mariappan

Annals of Cardiac Anaesthesia 2018 21(2):200-202

Management of a patient with a giant bulla coming for a nonthoracic surgery is rare, and its anesthetic management is very challenging. It is imperative to isolate only the subsegmental bronchus, in which the bulla communicates to avoid respiratory morbidities such as pneumothorax, emphysema or atelectasis of the surrounding lung parenchyma, and postoperative respiratory failure. Herewith, we want to report the anesthetic challenges of a patient with giant bulla communicating into one of the subsegmental right upper lobe bronchus for splenectomy.

https://ift.tt/2EI23RH

Retraction: Annals of cardiac anesthesia: Beacon journey toward excellence: 2015–2017

Annals of Cardiac Anaesthesia 2018 21(2):221-221



https://ift.tt/2EGefCD

Inverted left atrial appendage during minimally invasive mitral valve repair

Kazuto Miyata, Sayaka Shigematsu

Annals of Cardiac Anaesthesia 2018 21(2):192-194

Inverted left atrial appendage (LAA) is a rare complication in cardiac surgery. The echocardiographic appearance often leads to misdiagnosis of thrombus or some other cardiac mass. Patients misdiagnosed in this way often undergo unnecessary anticoagulation or surgical treatment. Recently, minimally invasive mitral valve surgery (MIMVS) has become more widespread. However, as the incision for MIMVS through the right thoracotomy is very small, the inverted LAA is not within the surgical field of the cardiac surgeon. We present a case of inverted LAA during MIMVS and provide images from transesophageal echocardiography.

https://ift.tt/2v9gWNz

Absent superior vena cava in tetralogy of fallot

Tejas R Shah, Channabasavaraj S Hiremath, Anitha Diwakar, Krishna Manohar Soman Rema

Annals of Cardiac Anaesthesia 2018 21(2):205-207

Absent superior vena cava (SVC) is an asymptomatic congenital systemic venous anomaly which is rarely detected and compatible with normal life. Undiagnosed absent SVC may cause problems during cardiac catheterization or cardiac surgery. We present our surgical experience in a patient with tetralogy of Fallot who had undiagnosed absent SVC.

https://ift.tt/2EH7znM

Assessment of the effect of two regimens of milrinone infusion in pediatric patients undergoing fontan procedure: A randomized study

Rabie Soliman, Adel Ragheb

Annals of Cardiac Anaesthesia 2018 21(2):134-140

Objective: The aim of the study was to compare the effect of two different regimens of milrinone on hemodynamics and oxygen saturation in pediatric patients undergoing Fontan procedure. Design: This was a randomized study. Setting: Cardiac centers. Patients: This study included 116 patients undergoing Fontan procedure. Material and Methods: Group E: Milrinone was started as infusion 0.5 μg/kg/min without a loading dose at the beginning of cardiopulmonary bypass (CPB) followed by infusion 0.5–0.75 μg/kg/min in the pediatric cardiac surgical intensive care unit (PSICU). Group L: Milrinone was started as a loading dose 50 μg/kg over 10 min before weaning from CPB followed by infusion 0.5–0.75 μg/kg/min in the PSICU. Measurements: Heart rate, mean arterial blood pressure, central venous pressure, transpulmonary pressure, cardiac index, pharmacological support, lactate level, urine output, oxygen saturation, ICU, and hospital length of stay. Main Results: There were no changes in the heart rate and mean arterial blood pressure (P > 0.05). The increase in the postoperative central venous pressure, transpulmonary pressure and lactate level was lower in Group E than Group L (P < 0.05). The increase in the postoperative cardiac index, oxygen saturation, and urine output was higher in Group E than Group L (P < 0.05). The requirement for pharmacological support was lower in the Group E (P < 0.05). The ICU and hospital length of stay were shorter in the Group E than Group L (P < 0.05). Conclusion: Early use of milrinone during Fontan procedure facilitated the weaning from CPB, decreased the elevation in the central venous pressure, transpulmonary gradient pressure, and the requirement for pharmacological support. Furthermore, it increased the cardiac index and arterial oxygen saturation.

https://ift.tt/2JGn5Ux

Milrinone: is bolus bad?

Venugopal Kulkarni

Annals of Cardiac Anaesthesia 2018 21(2):141-142



https://ift.tt/2JDajWJ

View point: Retraction is a pain but scientific misconduct is a crime!

Prabhat Tewari

Annals of Cardiac Anaesthesia 2018 21(2):109-110



https://ift.tt/2vfsuyM

Dexmedetomidine versus ketofol sedation for outpatient diagnostic transesophageal echocardiography: A randomized controlled study

S Sruthi, Banashree Mandal, Manoj K Rohit, Goverdhan Datt Puri

Annals of Cardiac Anaesthesia 2018 21(2):143-150

Background: Moderate sedation is required for out-patient transesophageal echocardiography (TEE). Our objective was to compare the effect of Ketofol and dexmedetomidine for outpatient procedural sedation in diagnostic TEE with a hypothesis that Ketofol would be as effective as dexmedetomidine. Patients and Methods: Fifty adult patients of age group 18-60 years with atrial septal defect, rheumatic valvular heart disease undergoing diagnostic TEE in the outpatient echocardiography laboratory were randomized into two groups, group D and group KF. GROUP D: Dexmedetomidine infusion -200 μg in 20 ml normal saline. GROUP KF: Ketofol infusion: (ketamine: propofol, 1mg: 3 mg in 20 ml syringe). Loading dose of drug at 1ml/kg/hour IV till Ramsay sedation score (RSS) ≥ 3 achieved followed by maintenance infusion at 0.05 ml/kg/hour till end of procedure. Results: The primary outcome - time to achieve Ramsay sedation score ≥ 3 was significantly lesser with Ketofol as compared to Dexmedetomidine 260[69] seconds vs 460 [137], (p value<0.05).Conclusion: In out-patient setting, ketofol is favourable over dexmedetomidine for sedation regimen for diagnostic TEE as lesser time is taken to achieve optimal sedation with lesser hemodynamic perturbations, post procedure complications and better cardiologist satisfaction.

https://ift.tt/2JDWU0y

Utility of thromboelastography versus routine coagulation tests for assessment of hypocoagulable state in patients undergoing cardiac bypass surgery

Seema Sharma, Sujeet Kumar, Prabhat Tewari, Shantanu Pande, Manjula Murari

Annals of Cardiac Anaesthesia 2018 21(2):151-157

Introduction: Peri-operative monitoring of coagulation is important to diagnose potential cause of hemorrhage, to manage coagulopathy and guide treatment with blood products in patients undergoing cardiac surgery with cardiopulmonary bypass. This study was done to evaluate usefulness of Thromboelastography (TEG) and routine coagulation tests (RCT) in assessing hemostatic changes and predicting postoperative bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: Fifty adult patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled in this prospective study. Preoperative and post-operative samples were collected for routine coagulation tests and TEG. Regression analysis and test of significance using Pearson's correlation coefficient was performed to assess correlation between routine coagulation tests and corresponding TEG parameters .Regression analysis was done to study relation between blood loss at 24 hours and various coagulation parameters. Results: The Routine coagulation test i.e. PT, INR, APTT showed no significant correlation with corresponding TEG parameters in pre-operative samples. However platelet count significantly correlated (p = 0.004) with MA values in postoperative samples. A significant correlation (p = 0.001) was seen between fibrinogen levels and alpha angles as well as with MA in both baseline preoperative and postoperative samples. TEG parameters R time and MA in postoperative samples were the only parameters that predicted bleeders with fair accuracy. Conclusion: Though the techniques of RCT and TEG are different, a few RCT e.g. platelet count and fibrinogen correlated with corresponding TEG parameters i.e. MA and Alpha angle. TEG parameters (R time and MA in postoperative samples) were able to predict blood loss better than RCT.

https://ift.tt/2JDWQhk

Tricuspid stenosis: A rare and potential complication of ventricular septal occluder device

Ganesh Kumar Munirathinam, Bhupesh Kumar, Anand Kumar Mishra

Annals of Cardiac Anaesthesia 2018 21(2):195-199

Asymmetrical septal occluder device (ASOD) has made percutaneous closure of ventricular septal defect an easy and effective management option. Although there are reports of aortic and tricuspid valvular regurgitation after deployment of ASOD, only few cases of tricuspid stenosis (TS) has been reported so far in the literature. We report a case of malaligned ASOD that occurred after successful device closure resulting in TS along with mild tricuspid and aortic regurgitation requiring surgical retrieval. Transesophageal echocardiography played crucial role in detecting the cause of tricuspid valve dysfunction besides providing continuous monitoring during the procedure. We intend to emphasize the need of echocardiographic evaluation of the tricuspid valvular apparatus and aortic valve during and after the device deployment even after the successful device closure to prevent this rare complication.

https://ift.tt/2HuKDLm

Factors associated with delayed cardiac tamponade after cardiac surgery

Edgar Hernández Leiva, Marisol Carreño, Fernando Rada Bucheli, Alberto Cadena Bonfanti, Juan Pablo Umaña, Rodolfo José Dennis

Annals of Cardiac Anaesthesia 2018 21(2):158-166

Context: Cardiac tamponade (CT) following cardiac surgery is a potentially fatal complication and the cause of surgical reintervention in 0.1%–6% of cases. There are two types of CT: acute, occurring within the first 48 h postoperatively, and subacute or delayed, which occurs more than 48 h postoperatively. The latter does not show specific clinical signs, which makes it more difficult to diagnose. The factors associated with acute CT (aCT) are related to coagulopathy or surgical bleeding, while the variables associated with subacute tamponade have not been well defined. Aims: The primary objective of this study was to identify the factors associated with the development of subacute CT (sCT). Settings and Design: This report describes a case (n = 80) and control (n = 160) study nested in a historic cohort made up of adult patients who underwent any type of urgent or elective cardiac surgery in a tertiary cardiovascular hospital. Methods: The occurrence of sCT was defined as the presence of a compatible clinical picture, pericardial effusion and confirmation of cardiac tamponade during the required emergency intervention at any point between 48 hours and 30 days after surgery. All factors potentially related to the development of sCT were taken into account. Statistical Analysis Used: For the adjusted analysis, a logistical regression was constructed with 55 variables, including pre-, intra-, and post-operative data. Results: The mortality of patients with sCT was 11% versus 0% in the controls. Five variables were identified as independently and significantly associated with the outcome: pre- or post-operative anticoagulation, reintervention in the first 48 h, surgery other than coronary artery bypass graft, and red blood cell transfusion. Conclusions: Our study identified five variables associated with sCT and established that this complication has a high mortality rate. These findings may allow the implementation of standardized follow-up measures for patients identified as higher risk, leading to either early detection or prevention.

https://ift.tt/2JDWJSW

Perioperative management of transcatheter, aortic and mitral, double valve-in-valve implantation during pregnancy through left ventricular apical approach

Suresh Chengode, Rahul Vijaykumar Shabadi, Ram Narayan Rao, Nasser Alkemyani, Hilal Alsabti

Annals of Cardiac Anaesthesia 2018 21(2):185-188

Pregnant women with stenotic degeneration of bioprosthetic cardiac valves may require another valve replacement procedure when their symptoms deteriorate with progression of pregnancy, but fetal mortality is higher with cardiac surgery done on cardiopulmonary bypass. Transcatheter valve-in-valve implantation may help to improve the fetal and maternal outcomes in these situations. Double valve-in-valve implantation is rare and has not been reported in a pregnant patient. We report, for the first time, the case of a pregnant woman with stenotic bioprosthetic valves in the mitral and aortic positions, who underwent a successful concomitant, transcatheter, double valve-in-valve implantation through the left ventricular apical route during the second trimester of her precious pregnancy.

https://ift.tt/2EGHJjJ

Dishonesty in medical research and publication and the remedial measures

Praveen Kumar Neema

Annals of Cardiac Anaesthesia 2018 21(2):111-113



https://ift.tt/2JGn7M9

Absent right superior vena cava and persistent left superior vena cava in a patient with bicuspid aortic valve with aortic stenosis

Kushant Gupta, Vijayakanth Bhuvana, Varun Bansal, Ruma Ray, Arkalgud Sampath Kumar

Annals of Cardiac Anaesthesia 2018 21(2):212-214

Persistent left superior vena cava (LSVC) with absent right SVC (RSVC) is a rare congenital anomaly. If undetected, the condition may pose difficulties in central venous catheter insertion, pacemaker electrode insertion, and cannulation during cardiopulmonary bypass. We describe a case of persistent LSVC with absent RSVC, who was diagnosed to have bicuspid aortic valve with aortic stenosis.

https://ift.tt/2EGeo99

Retraction: Annals of cardiac anesthesia: Beacon journey toward excellence: 2015–2017

Annals of Cardiac Anaesthesia 2018 21(2):221-221



https://ift.tt/2EGefCD

Prophylactic preoperative levosimendan for off-pump coronary artery bypass grafting in patients with left ventricular dysfunction: Single-centered randomized prospective study

Pushkar Mahendra Desai, Manjula S Sarkar, Sanjeeta R Umbarkar

Annals of Cardiac Anaesthesia 2018 21(2):123-128

Background: Off-pump coronary artery bypass surgery (OPCAB) is often complicated by hemodynamic instability, especially in patients with prior left ventricular (LV) dysfunction and appropriate choice of inotrope plays a vital role in perioperative management of these patients. Aim and Objective: To study hemodynamic effects and immediate outcome of prophylactic infusion of levosimendan in patients with the LV dysfunction undergoing OPCAB surgery and whether this strategy helps in successful conduct of OPCAB surgery. Materials and Methods: After Institutional Ethics Committee approval, 60 patients posted for elective OPCAB surgery were randomly divided into two groups (n = 30 each). Patients with the LV ejection fraction <30% were included. Study group was started on injection levosimendan (@ 0.1 μg/kg/min) in the previous night before surgery and continued for 24 h including intraoperative period. Hemodynamic monitoring included heart rate, invasive blood pressure, cardiac index (CI), pulmonary capillary wedge pressure (PCWP), pulse oximetry, and arterial blood gases with serum lactates at as T0 (baseline), T1 (15 min after obtuse marginal and/or PDA anastomoses), T2 (at end of surgery), T3 (6 h after surgery in Intensive Care Unit [ICU]), T4 (12 h after surgery), and T5 (24 h after surgery in ICU). Vasopressor was added to maintain mean arterial pressure >60 mmHg. Chi-square/Fisher's exact/Mid P exact test and Student's t-tests were applied for categorical and continuous data. Results: CI was greater and PCWP reduced significantly in Group L during intraoperative and early postoperative period. Serum lactate concentration was lower in patients pretreated with levosimendan. Incidence of postoperative atrial fibrillation (POAF) (36.6 vs. 6.6%; P = 0.01), low cardiac output syndrome (LCOS) (30% vs. 6%; P = 0.02), and acute kidney injury (23.3% vs. 6.7%; P = 0.04) was less in Group L. Three patients (10%) in control group required conversion to cardiopulmonary bypass (CPB) as compared to none in the study group. There was no difference regarding ICU or hospital stay and mortality in both groups. Conclusion: Preoperative levosimendan helps in successful conduct of OPCAB and reduces the incidence of LCOS, POAF, conversion to CPB, and requirement of intra-aortic balloon pump.

https://ift.tt/2JIScyy

Comparison of immediate extubation versus ultrafast tracking strategy in the management of off-pump coronary artery bypass surgery

Amarja Sachin Nagre, Nagesh P Jambures

Annals of Cardiac Anaesthesia 2018 21(2):129-133

Introduction: Ultrafast tracking of anesthesia (UFTA) is practiced routinely, whereas immediate on-table extubation after off-pump coronary artery bypass (OPCAB) grafting surgery has many concerns. The purpose of our study was to evaluate the safety and feasibility of immediate extubation (IE) versus UFTA. Methods: Sixty patients were enrolled who underwent OPCAB surgery. The two groups IE and UFTA had thirty patients each. Inclusion criteria were patients for OPCAB surgery including left main stenosis. Exclusion criteria were patients with Ejection Fraction(EF) <30%, with unstable hemodynamics, on intra-aortic balloon pump (IABP), with renal dysfunction, with associated valvular heart diseases, on inotropes, on temporary pacemaker, with intraoperative conversion to on-pump coronary artery bypass grafting (CABG), who are chronic smokers, and with chronic obstructive pulmonary disease. Statistical analysis was done with Minitab 15 software. Descriptive statistics were summarized as mean, standard deviation, and percentage. Student's t-test was used to determine the significance of normally distributed parametric values. Z-test was used for proportion. Statistical significance was accepted at P < 0.05. Results: OT extubation was found to be safe as no patient had reintubation or respiratory insufficiency. None of the patients in either group had postoperative myocardial infarction, stroke, low cardiac output, mediastinitis, and renal failure. Hypothermia, blood transfusion, atrial fibrillation, and re-exploration did not occur. Intensive Care Unit length of stay was similar in the two groups. Discharge day is statistically significant (P = 0.001), with 5.66 days in the IE group and 6.36 days in the UFTA group. Time spent in the operating room at the end of surgery is statistically significant, with 14.03 min in UFTA group and 33.9 min in IE group. Conclusion: IE appears to be safe and effective in OPCAB patients without any major complications. It can be achieved after fulfilling traditional extubation criteria but is confined to highly selective group of patients.

https://ift.tt/2JI4do0

Absent superior vena cava in tetralogy of fallot

Tejas R Shah, Channabasavaraj S Hiremath, Anitha Diwakar, Krishna Manohar Soman Rema

Annals of Cardiac Anaesthesia 2018 21(2):205-207

Absent superior vena cava (SVC) is an asymptomatic congenital systemic venous anomaly which is rarely detected and compatible with normal life. Undiagnosed absent SVC may cause problems during cardiac catheterization or cardiac surgery. We present our surgical experience in a patient with tetralogy of Fallot who had undiagnosed absent SVC.

https://ift.tt/2EH7znM

Assessment of the effect of two regimens of milrinone infusion in pediatric patients undergoing fontan procedure: A randomized study

Rabie Soliman, Adel Ragheb

Annals of Cardiac Anaesthesia 2018 21(2):134-140

Objective: The aim of the study was to compare the effect of two different regimens of milrinone on hemodynamics and oxygen saturation in pediatric patients undergoing Fontan procedure. Design: This was a randomized study. Setting: Cardiac centers. Patients: This study included 116 patients undergoing Fontan procedure. Material and Methods: Group E: Milrinone was started as infusion 0.5 μg/kg/min without a loading dose at the beginning of cardiopulmonary bypass (CPB) followed by infusion 0.5–0.75 μg/kg/min in the pediatric cardiac surgical intensive care unit (PSICU). Group L: Milrinone was started as a loading dose 50 μg/kg over 10 min before weaning from CPB followed by infusion 0.5–0.75 μg/kg/min in the PSICU. Measurements: Heart rate, mean arterial blood pressure, central venous pressure, transpulmonary pressure, cardiac index, pharmacological support, lactate level, urine output, oxygen saturation, ICU, and hospital length of stay. Main Results: There were no changes in the heart rate and mean arterial blood pressure (P > 0.05). The increase in the postoperative central venous pressure, transpulmonary pressure and lactate level was lower in Group E than Group L (P < 0.05). The increase in the postoperative cardiac index, oxygen saturation, and urine output was higher in Group E than Group L (P < 0.05). The requirement for pharmacological support was lower in the Group E (P < 0.05). The ICU and hospital length of stay were shorter in the Group E than Group L (P < 0.05). Conclusion: Early use of milrinone during Fontan procedure facilitated the weaning from CPB, decreased the elevation in the central venous pressure, transpulmonary gradient pressure, and the requirement for pharmacological support. Furthermore, it increased the cardiac index and arterial oxygen saturation.

https://ift.tt/2JGn5Ux

Milrinone: is bolus bad?

Venugopal Kulkarni

Annals of Cardiac Anaesthesia 2018 21(2):141-142



https://ift.tt/2JDajWJ

View point: Retraction is a pain but scientific misconduct is a crime!

Prabhat Tewari

Annals of Cardiac Anaesthesia 2018 21(2):109-110



https://ift.tt/2vfsuyM

Mitral valve repair in infective endocarditis during pregnancy

Takahiro Tamura, Shuichi Yokota

Annals of Cardiac Anaesthesia 2018 21(2):189-191

Infective endocarditis (IE) during pregnancy and subsequent cardiac surgery are rare and associated with a high risk of mortality for the mother and fetus. It is difficult to determine the right time for cardiac intervention when IE is diagnosed early in pregnancy. A 33-year-old previously healthy woman in the 11th week of pregnancy was diagnosed with IE and underwent surgical intervention. The cardiopulmonary bypass settings and the anesthetic drugs were carefully chosen. Although she was in good health, while being discharged, the fetus did not survive. Anesthesiologists prioritizing the mother's survival should aim to improve fetal outcomes in such cases.

https://ift.tt/2v9gmiR

Utility of thromboelastography versus routine coagulation tests for assessment of hypocoagulable state in patients undergoing cardiac bypass surgery

Seema Sharma, Sujeet Kumar, Prabhat Tewari, Shantanu Pande, Manjula Murari

Annals of Cardiac Anaesthesia 2018 21(2):151-157

Introduction: Peri-operative monitoring of coagulation is important to diagnose potential cause of hemorrhage, to manage coagulopathy and guide treatment with blood products in patients undergoing cardiac surgery with cardiopulmonary bypass. This study was done to evaluate usefulness of Thromboelastography (TEG) and routine coagulation tests (RCT) in assessing hemostatic changes and predicting postoperative bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: Fifty adult patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled in this prospective study. Preoperative and post-operative samples were collected for routine coagulation tests and TEG. Regression analysis and test of significance using Pearson's correlation coefficient was performed to assess correlation between routine coagulation tests and corresponding TEG parameters .Regression analysis was done to study relation between blood loss at 24 hours and various coagulation parameters. Results: The Routine coagulation test i.e. PT, INR, APTT showed no significant correlation with corresponding TEG parameters in pre-operative samples. However platelet count significantly correlated (p = 0.004) with MA values in postoperative samples. A significant correlation (p = 0.001) was seen between fibrinogen levels and alpha angles as well as with MA in both baseline preoperative and postoperative samples. TEG parameters R time and MA in postoperative samples were the only parameters that predicted bleeders with fair accuracy. Conclusion: Though the techniques of RCT and TEG are different, a few RCT e.g. platelet count and fibrinogen correlated with corresponding TEG parameters i.e. MA and Alpha angle. TEG parameters (R time and MA in postoperative samples) were able to predict blood loss better than RCT.

https://ift.tt/2JDWQhk

Tricuspid stenosis: A rare and potential complication of ventricular septal occluder device

Ganesh Kumar Munirathinam, Bhupesh Kumar, Anand Kumar Mishra

Annals of Cardiac Anaesthesia 2018 21(2):195-199

Asymmetrical septal occluder device (ASOD) has made percutaneous closure of ventricular septal defect an easy and effective management option. Although there are reports of aortic and tricuspid valvular regurgitation after deployment of ASOD, only few cases of tricuspid stenosis (TS) has been reported so far in the literature. We report a case of malaligned ASOD that occurred after successful device closure resulting in TS along with mild tricuspid and aortic regurgitation requiring surgical retrieval. Transesophageal echocardiography played crucial role in detecting the cause of tricuspid valve dysfunction besides providing continuous monitoring during the procedure. We intend to emphasize the need of echocardiographic evaluation of the tricuspid valvular apparatus and aortic valve during and after the device deployment even after the successful device closure to prevent this rare complication.

http://www.annals.in/text.asp?2018/21/2/195/229929

Factors associated with delayed cardiac tamponade after cardiac surgery

Edgar Hernández Leiva, Marisol Carreño, Fernando Rada Bucheli, Alberto Cadena Bonfanti, Juan Pablo Umaña, Rodolfo José Dennis

Annals of Cardiac Anaesthesia 2018 21(2):158-166

Context: Cardiac tamponade (CT) following cardiac surgery is a potentially fatal complication and the cause of surgical reintervention in 0.1%–6% of cases. There are two types of CT: acute, occurring within the first 48 h postoperatively, and subacute or delayed, which occurs more than 48 h postoperatively. The latter does not show specific clinical signs, which makes it more difficult to diagnose. The factors associated with acute CT (aCT) are related to coagulopathy or surgical bleeding, while the variables associated with subacute tamponade have not been well defined. Aims: The primary objective of this study was to identify the factors associated with the development of subacute CT (sCT). Settings and Design: This report describes a case (n = 80) and control (n = 160) study nested in a historic cohort made up of adult patients who underwent any type of urgent or elective cardiac surgery in a tertiary cardiovascular hospital. Methods: The occurrence of sCT was defined as the presence of a compatible clinical picture, pericardial effusion and confirmation of cardiac tamponade during the required emergency intervention at any point between 48 hours and 30 days after surgery. All factors potentially related to the development of sCT were taken into account. Statistical Analysis Used: For the adjusted analysis, a logistical regression was constructed with 55 variables, including pre-, intra-, and post-operative data. Results: The mortality of patients with sCT was 11% versus 0% in the controls. Five variables were identified as independently and significantly associated with the outcome: pre- or post-operative anticoagulation, reintervention in the first 48 h, surgery other than coronary artery bypass graft, and red blood cell transfusion. Conclusions: Our study identified five variables associated with sCT and established that this complication has a high mortality rate. These findings may allow the implementation of standardized follow-up measures for patients identified as higher risk, leading to either early detection or prevention.

https://ift.tt/2JDWJSW

Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer

Publication date: Available online 12 April 2018
Source:Cancer Cell
Author(s): Matthew D. Hellmann, Tavi Nathanson, Hira Rizvi, Benjamin C. Creelan, Francisco Sanchez-Vega, Arun Ahuja, Ai Ni, Jacki B. Novik, Levi M.B. Mangarin, Mohsen Abu-Akeel, Cailian Liu, Jennifer L. Sauter, Natasha Rekhtman, Eliza Chang, Margaret K. Callahan, Jamie E. Chaft, Martin H. Voss, Megan Tenet, Xue-Mei Li, Kelly Covello, Andrea Renninger, Patrik Vitazka, William J. Geese, Hossein Borghaei, Charles M. Rudin, Scott J. Antonia, Charles Swanton, Jeff Hammerbacher, Taha Merghoub, Nicholas McGranahan, Alexandra Snyder, Jedd D. Wolchok
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis. The low response rate in TMB low NSCLCs demonstrates that combination immunotherapy does not overcome the negative predictive impact of low TMB. This study demonstrates the association between TMB and benefit to combination immunotherapy in NSCLC. TMB should be incorporated in future trials examining PD-(L)1 with CTLA-4 blockade in NSCLC.

Teaser

Hellmann et al. examine non-small-cell lung cancers treated with combined PD-1 and CTLA-4 blockade using whole-exome sequencing and find that high tumor mutation burden is the strongest feature associated with improved objective response, durable benefit, and progression-free survival in multivariable analysis.


https://ift.tt/2JEhQVk

Multi-stage Differentiation Defines Melanoma Subtypes with Differential Vulnerability to Drug-Induced Iron-Dependent Oxidative Stress

Publication date: Available online 12 April 2018
Source:Cancer Cell
Author(s): Jennifer Tsoi, Lidia Robert, Kim Paraiso, Carlos Galvan, Katherine M. Sheu, Johnson Lay, Deborah J.L. Wong, Mohammad Atefi, Roksana Shirazi, Xiaoyan Wang, Daniel Braas, Catherine S. Grasso, Nicolaos Palaskas, Antoni Ribas, Thomas G. Graeber
Malignant transformation can result in melanoma cells that resemble different stages of their embryonic development. Our gene expression analysis of human melanoma cell lines and patient tumors revealed that melanoma follows a two-dimensional differentiation trajectory that can be subclassified into four progressive subtypes. This differentiation model is associated with subtype-specific sensitivity to iron-dependent oxidative stress and cell death known as ferroptosis. Receptor tyrosine kinase-mediated resistance to mitogen-activated protein kinase targeted therapies and activation of the inflammatory signaling associated with immune therapy involves transitions along this differentiation trajectory, which lead to increased sensitivity to ferroptosis. Therefore, ferroptosis-inducing drugs present an orthogonal therapeutic approach to target the differentiation plasticity of melanoma cells to increase the efficacy of targeted and immune therapies.

Graphical abstract

Teaser

Tsoi et al. show that melanoma can be categorized into four subtypes following a differentiation trajectory with subtype-specific sensitivity to ferroptosis induction, which presents a therapeutic approach to target the differentiation plasticity to increase the efficacy of targeted and immune therapies.


https://ift.tt/2veO8TU

The Platelet Lifeline to Cancer: Challenges and Opportunities

Publication date: Available online 12 April 2018
Source:Cancer Cell
Author(s): Monika Haemmerle, Rebecca L. Stone, David G. Menter, Vahid Afshar-Kharghan, Anil K. Sood
Besides their function in limiting blood loss and promoting wound healing, experimental evidence has highlighted platelets as active players in all steps of tumorigenesis including tumor growth, tumor cell extravasation, and metastasis. Additionally, thrombocytosis in cancer patients is associated with adverse patient survival. Due to the secretion of large amounts of microparticles and exosomes, platelets are well positioned to coordinate both local and distant tumor-host crosstalk. Here, we present a review of recent discoveries in the field of platelet biology and the role of platelets in cancer progression as well as challenges in targeting platelets for cancer treatment.

Teaser

Besides their function in limiting blood loss and promoting wound healing, experimental evidence has highlighted platelets as active players in all steps of tumorigenesis including tumor growth, tumor cell extravasation, and metastasis. Additionally, thrombocytosis in cancer patients is associated with adverse patient survival. Due to the secretion of large amounts of microparticles and exosomes, platelets are well positioned to coordinate both local and distant tumor-host crosstalk. Here, we present a review of recent discoveries in the field of platelet biology and the role of platelets in cancer progression as well as challenges in targeting platelets for cancer treatment.


https://ift.tt/2EF1mZf

Synaptotagmin 4 Regulates Pancreatic β Cell Maturation by Modulating the Ca2+ Sensitivity of Insulin Secretion Vesicles

Publication date: Available online 12 April 2018
Source:Developmental Cell
Author(s): Chen Huang, Emily M. Walker, Prasanna K. Dadi, Ruiying Hu, Yanwen Xu, Wenjian Zhang, Tiziana Sanavia, Jisoo Mun, Jennifer Liu, Gopika G. Nair, Hwee Yim Angeline Tan, Sui Wang, Mark A. Magnuson, Christian J. Stoeckert, Matthias Hebrok, Maureen Gannon, Weiping Han, Roland Stein, David A. Jacobson, Guoqiang Gu
Islet β cells from newborn mammals exhibit high basal insulin secretion and poor glucose-stimulated insulin secretion (GSIS). Here we show that β cells of newborns secrete more insulin than adults in response to similar intracellular Ca²⁺ concentrations, suggesting differences in the Ca²⁺ sensitivity of insulin secretion. Synaptotagmin 4 (Syt4), a non-Ca²⁺ binding paralog of the β cell Ca²⁺ sensor Syt7, increased by ∼8-fold during β cell maturation. Syt4 ablation increased basal insulin secretion and compromised GSIS. Precocious Syt4 expression repressed basal insulin secretion but also impaired islet morphogenesis and GSIS. Syt4 was localized on insulin granules and Syt4 levels inversely related to the number of readily releasable vesicles. Thus, transcriptional regulation of Syt4 affects insulin secretion; Syt4 expression is regulated in part by Myt transcription factors, which repress Syt4 transcription. Finally, human SYT4 regulated GSIS in EndoC-βH1 cells, a human β cell line. These findings reveal the role that altered Ca²⁺ sensing plays in regulating β cell maturation.

Graphical abstract

Teaser

In immature pancreatic beta cells, high glucose does not prompt an increase in insulin secretion. Huang et al. show that this poor response is due to greater Ca²⁺ sensitivity in immature cells, producing a higher basal secretion rate. Furthermore, Ca²⁺ sensitivity is regulated by synaptotagmin 4, whose levels increase during maturation.


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DNA N6-Adenine Methylation in Arabidopsis thaliana

Publication date: Available online 12 April 2018
Source:Developmental Cell
Author(s): Zhe Liang, Lisha Shen, Xuean Cui, Shengjie Bao, Yuke Geng, Guoliang Yu, Fan Liang, Shang Xie, Tiegang Lu, Xiaofeng Gu, Hao Yu
DNA methylation on N⁶-adenine (6mA) has recently been found to be a potentially epigenetic mark in several unicellular and multicellular eukaryotes. However, its distribution patterns and potential functions in land plants, which are primary producers for most ecosystems, remain largely unknown. Here we report global profiling of 6mA sites at single-nucleotide resolution in the genome of Arabidopsis thaliana at different developmental stages using single-molecule real-time sequencing. 6mA sites are widely distributed across the Arabidopsis genome and enriched over the pericentromeric heterochromatin regions. 6mA occurs more frequently in gene bodies than intergenic regions. Analysis of 6mA methylomes and RNA sequencing data demonstrates that 6mA frequency positively correlates with the gene expression level and the transition from vegetative to reproductive growth in Arabidopsis. Our results uncover 6mA as a DNA mark associated with actively expressed genes in Arabidopsis, suggesting that 6mA serves as a hitherto unknown epigenetic mark in land plants.

Graphical abstract

Teaser

Characterization of DNA methylation in plants has until now focused mainly on 5-methylcytosine (5mC), which is associated with gene repression. Liang et al. now reveal that methylation on N⁶-adenine (6mA) is a dynamic DNA modification that is enriched on gene bodies and associated with actively expressed genes in Arabidopsis.


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Mass cytometry: a powerful tool for dissecting the immune landscape

Yannick Simoni | Melissa Hui Yen Chng | Shamin Li | Michael Fehlings | Evan W Newell

https://ift.tt/2qpd9G6

Obesity induced T cell dysfunction and implications for cancer immunotherapy

Ethan G Aguilar | William J Murphy

https://ift.tt/2GSLpEJ

Reductive decolorization of azo dyes via in situ generation of green tea extract-iron chelate

Abstract

In this study, rapid decolorization of azo dyes was achieved by in situ-generated green tea extract-iron (GTE-Fe) chelate for the first time. When changing reaction conditions from the aerobic condition to the anaerobic condition, the decolorization efficiencies of two azo dyes, i.e., acid orange 7 (AO7) and acid black 1 (AB1), increased from 46.38 and 83.17 to 90.13 and 95.37%, respectively. The recalcitrant AO7 was then selected as the targeting pollutant in subsequent optimization and mechanism studies. Experimental evidences showed that the initial concentrations of AO7, Fe(III), and GTE are the key factors to optimize the decolorization efficiency. Further characterization studies by spectroscopic analysis, including FESEM, FTIR, and XPS, suggested that the major mechanism of AO7 decolorization is the nucleophilic attack of the oxygen in green tea polyphenols (GTP), and this attack could be facilitated by the organometal chelation. This study provided an efficient and environmental friendly strategy to decolorize azo dyes via in situ generation of the GTE-Fe chelate, as well as its mechanistic insights, shedding lights on in situ remediation of azo dye pollution.

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Stochastic convergence of renewable energy consumption in OECD countries: a fractional integration approach

Abstract

In this article, we have examined the hypothesis of convergence of renewable energy consumption in 27 OECD countries. However, instead of relying on classical techniques, which are based on the dichotomy between stationarity I(0) and nonstationarity I(1), we consider a more flexible approach based on fractional integration. We employ both parametric and semiparametric techniques. Using parametric methods, evidence of convergence is found in the cases of Mexico, Switzerland and Sweden along with the USA, Portugal, the Czech Republic, South Korea and Spain, and employing semiparametric approaches, we found evidence of convergence in all these eight countries along with Australia, France, Japan, Greece, Italy and Poland. For the remaining 13 countries, even though the orders of integration of the series are smaller than one in all cases except Germany, the confidence intervals are so wide that we cannot reject the hypothesis of unit roots thus not finding support for the hypothesis of convergence.

https://ift.tt/2GUHckd

Photoactivatable substrates for systematic study of the impact of an extracellular matrix ligand on appearance of leader cells in collective cell migration

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Shimaa A. Abdellatef, Jun Nakanishi
Epithelial cells migrate as multicellular units. The directionality and speed of these units are determined by actively moving leader cells. It is important to understand how external cues affect the appearance of these leader cells in physiological and pathological processes. However, the impact of extracellular matrices (ECMs) is still controversial, because physically-adsorbed ECM proteins are amenable to protein remodeling, and uncontrolled cluster geometry can vary migration phenotypes. Here, we demonstrate a photoactivatable substrate, which we used to study the impact of a cyclic Arg-Gly-Asp (cRGD) ligand on leader cell formation in MDCK cells. This robust platform allowed us to investigate the effect of cRGD density on leader cell formation, in any given cluster geometry, with minimized ECM remodeling. Our results show a biphasic response of leader cell appearance upon reducing the surface cRGD density. The increase, in leader cell appearance, within the higher density range, is not only associated with the weakening of circumferential actomyosin belts, but also reduction of cellular mechanical tension and intercellular junctional E-cadherin. These results indicate that cRGD-mediated cell-ECM interactions positively regulate mechanical and biochemical coupling within cell clusters; both are critical for the coordination of cell collectives and eventual reduction in the appearance of leader cells.

Graphical abstract

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Anesthesia for collagenase clostridium histolyticum injection in patients with dupuytren disease: A cohort analysis.

Procedural pain is one of the most common adverse effects reported by patients with Dupuytren disease treated with collagenase clostridium histolyticum (CCH). The aim of this study was to assess the effectiveness of wrist block prior to CCH injection in reducing procedural pain and analyze its impact on adverse effects. We performed a prospective, single-centre study in which we compared two groups of patients in a consecutive cohort. In the first group (NO-BLOCK), wrist block was only performed before finger extension, while in the second group (BLOCK) it was performed before CCH injection and finger extension.

https://ift.tt/2JGqDpD

Evolution of an evidence based supermicrosurgery simulation training curriculum: a systematic review

BackgroundSupermicrosurgery (SM) involves operating on vessels with calibers from 0.3-0.8 millimeters. Supermicrosurgery requires skills beyond those of conventional microsurgery. Current microsurgery courses do not prepare a junior surgeon for such a challenge. Several models have been developed to assist in the early learning curve, but their true purpose, benefit and validation have not been addressed. This systematic literature review summarizes the existing SM simulation models, and their likely impact on microsurgery training for small-caliber vessel-based procedures is assessed.

https://ift.tt/2JEWQ0C

Flap choice does not affect complication rates or functional outcomes following extremity soft tissue sarcoma reconstruction

Flap reconstruction plays an essential role in facilitating limb preservation in patients with extremity soft tissue sarcoma (ESTS). However, the effect of flap choice on the rates of post-operative complications and functional outcomes has not been clearly established. This study directly compares the outcomes of free and pedicled flap reconstructions in ESTS patients.

https://ift.tt/2va1L6t

Treatment of dopplerable nummular headache with minimally invasive arterectomy under local anesthesia

The objective of the current study is to elucidate the potential role of surgery in the treatment of nummular headache.

https://ift.tt/2JGqket

The ecological competition and grazing reverse the effects of sulfamethoxazole on plankton: a case study on characterizing community-level effect

Abstract

The toxic effects of sulfamethoxazole (SMX) on densities of two algae, Platymonas helgolandica var. tsingtaoensis, Isochrysis galbana, and of a rotifer, Brachionus plicatilis, were tested by the population and community experiments. Two endpoints, the carrying capacity and the densities array of community in steady state (DACS), were used to characterize the toxic effects at a population level and a community one, respectively. The results showed that the carrying capacity of P. helgolandica var. tsingtaoensis and B. plicatilis did not decline significantly in population test when the concentration of SMX was lower than 6.0 mg L⁻¹ and 12.0 mg L⁻¹, respectively. However, I. galbana was sensitive to SMX and had presented toxic effect at 3.0 mg L⁻¹. By extrapolation of toxic effect at a population level to a community one, a derived community-NOEC was 3.0 mg L⁻¹, representing an inference from data of toxic effects at population level. In community experiment, when the customized community was in steady state, the density of I. galbana increased as a whole with SMX concentration in the range of tested concentration (0–144 mg L⁻¹), while that of P. helgolandica var. tsingtaoensis assumed the trend of a reversed "v" in this range. Only the density of B. plicatilis decreased with SMX concentration. With the DACS as endpoint, a NOEC for the customized community was determined to be 6.0 mg L⁻¹. This indicates that interspecific interactions can reverse the toxic effects of SMX on phytoplankton. The DACS was reliable and stable, serving as the endpoints in assessment of the effects of the pollutants on the ecosystems.

https://ift.tt/2IRkq9f

Erratum

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SQ house dust mite sublingual immunotherapy tablet subgroup efficacy and local application site reaction duration

Allergic rhinitis with or without conjunctivitis (AR/C) is common, necessitating evaluation of SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet efficacy in various subgroups.

https://ift.tt/2JHwWcK

Short and long-term management of cases of venom induced anaphylaxis (via) is suboptimal

Venom induced anaphylaxis (VIA) accounts for severe reactions. However, little is known about the short and long-term management of VIA cases.

https://ift.tt/2vbYt2R

Evolving Industry Partnerships and Investments in Cell and Gene Therapies

Publication date: Available online 12 April 2018
Source:Cell Stem Cell
Author(s): Devyn M. Smith, Emily J. Culme-Seymour, Chris Mason
Cell and gene therapies hold the promise of providing significant and durable health gains to patients in many disease states and have recently elicited significant investor and partner interest. We cover the current state of industry partnerships and investments, highlight what makes a partnership advantageous, and discuss implications for stem cell therapies.

Teaser

Cell and gene therapies hold the promise of providing significant and durable health gains to patients in many disease states and have recently elicited significant investor and partner interest. We cover the current state of industry partnerships and investments, highlight what makes a partnership advantageous, and discuss implications for stem cell therapies.


https://ift.tt/2IRgYeN

Myoepithelial Cells of Submucosal Glands Can Function as Reserve Stem Cells to Regenerate Airways after Injury

Publication date: Available online 12 April 2018
Source:Cell Stem Cell
Author(s): Aleksandra Tata, Yoshihiko Kobayashi, Ryan D. Chow, Jasmine Tran, Avani Desai, Abdull J. Massri, Timothy J. McCord, Michael Dee Gunn, Purushothama Rao Tata
Cells demonstrate plasticity following injury, but the extent of this phenomenon and the cellular mechanisms involved remain underexplored. Using single-cell RNA sequencing (scRNA-seq) and lineage tracing, we uncover that myoepithelial cells (MECs) of the submucosal glands (SMGs) proliferate and migrate to repopulate the airway surface epithelium (SE) in multiple injury models. Specifically, SMG-derived cells display multipotency and contribute to basal and luminal cell types of the SMGs and SE. Ex vivo expanded MECs have the potential to repopulate and differentiate into SE cells when grafted onto denuded airway scaffolds. Significantly, we find that SMG-like cells appear on the SE of both extra- and intra-lobular airways of large animal lungs following severe injury. We find that the transcription factor SOX9 is necessary for MEC plasticity in airway regeneration. Because SMGs are abundant and present deep within airways, they may serve as a reserve cell source for enhancing human airway regeneration.

Graphical abstract

Teaser

Airway submucosal glands are reservoirs of mucous and anti-microbial products that provide defense against microbes. Here, Tata and colleagues uncover a hidden reserve multipotent stem cell population in SMGs that can proliferate, migrate, and transdifferentiate to repair surface epithelium following injury through a SOX9-dependent transcriptional program.


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Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium

Publication date: Available online 12 April 2018
Source:Cell Stem Cell
Author(s): Thomas J. Lynch, Preston J. Anderson, Pavana G. Rotti, Scott R. Tyler, Adrianne K. Crooke, Soon H. Choi, Daniel T. Montoro, Carolyn L. Silverman, Weam Shahin, Rui Zhao, Chandler W. Jensen-Cody, Andrea Adamcakova-Dodd, T. Idil Apak Evans, Weiliang Xie, Yulong Zhang, Hongmei Mou, B. Paul Herring, Peter S. Thorne, Jayaraj Rajagopal, Charles Yeaman, Kalpaj R. Parekh, John F. Engelhardt
The mouse trachea is thought to contain two distinct stem cell compartments that contribute to airway repair—basal cells in the surface airway epithelium (SAE) and an unknown submucosal gland (SMG) cell type. Whether a lineage relationship exists between these two stem cell compartments remains unclear. Using lineage tracing of glandular myoepithelial cells (MECs), we demonstrate that MECs can give rise to seven cell types of the SAE and SMGs following severe airway injury. MECs progressively adopted a basal cell phenotype on the SAE and established lasting progenitors capable of further regeneration following reinjury. MECs activate Wnt-regulated transcription factors (Lef-1/TCF7) following injury and Lef-1 induction in cultured MECs promoted transition to a basal cell phenotype. Surprisingly, dose-dependent MEC conditional activation of Lef-1 in vivo promoted self-limited airway regeneration in the absence of injury. Thus, modulating the Lef-1 transcriptional program in MEC-derived progenitors may have regenerative medicine applications for lung diseases.

Graphical abstract

Teaser

Following severe injury to the surface airway epithelium (SAE), Wnt signals activate myoepithelial cells in the submucosal glands (SMGs) to function as reserve stem cells for multipotent basal cells in the SAE and other SMG cell types. Lef-1 activation induces the myoepithelial cell regenerative response and a basal cell-like phenotype.


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Short-term sleep deprivation with exposure to nocturnal light alters mitochondrial bioenergetics in Drosophila

Publication date: Available online 12 April 2018
Source:Free Radical Biology and Medicine
Author(s): Nathane Rosa Rodrigues, Giulianna Echeverria Macedo, Illana Kemmerich Martins, Karen Kich Gomes, Nélson Rodrigues de Carvalho, Thaís Posser, Jeferson Luis Franco
Many studies have shown the effects of sleep deprivation in several aspects of health and disease. However, little is known about how mitochondrial bioenergetics function is affected under this condition. To clarify this, we developed a simple model of short-term sleep deprivation, in which fruit-flies were submitted to a nocturnal light condition and then mitochondrial parameters were assessed by high resolution respirometry (HRR). Exposure of flies to constant light was able to alter sleep patterns, causing locomotor deficits, increasing ROS production and lipid peroxidation, affecting mitochondrial activity, antioxidant defense enzymes and caspase activity. HRR analysis showed that sleep deprivation affected mitochondrial bioenergetics capacity, decreasing respiration at oxidative phosphorylation (OXPHOS) and electron transport system (ETS). In addition, the expression of genes involved in the response to oxidative stress and apoptosis were increased. Thus, our results suggest a connection between sleep deprivation and oxidative stress, pointing to mitochondria as a possible target of this relationship.

Graphical abstract

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An evidence based protocol for managing neonatal middle ear effusions in babies who fail newborn hearing screening

Publication date: Available online 12 April 2018
Source:American Journal of Otolaryngology
Author(s): Brittany C. Weber, Scott M. Whitlock, Kaidi He, Blake S. Kimbrell, Craig S. Derkay
ObjectivesTo evaluate the prevalence of middle ear disease in infants referred for failed newborn hearing screening (NBHS) and to review patient outcomes after intervention in order to propose an evidence-based protocol for management of newborns with otitis media with effusion (OME) who fail NBHS.Methods85 infants with suspected middle ear pathology were retrospectively reviewed after referral for failed NBHS. All subjects underwent a diagnostic microscopic exam with myringotomy with or without placement of a ventilation tube in the presence of a middle ear effusion and had intra-operative auditory brainstem response (ABR) testing or testing at a later date.ResultsAt the initial office visit, a normal middle ear space bilaterally was documented in 5 babies (6%), 29/85 (34%) had an equivocal exam while 51/85 (60%) had at least a unilateral OME. Myringotomy with or without tube placement due to presence of an effusion was performed on 65/85 (76%) neonates. Normal hearing was established in 17/85 (20%) after intervention, avoiding the need for any further audiologic workup. Bilateral or unilateral sensorineural hearing loss (SNHL) or mixed hearing loss was noted in 54/85 (64%) and these children were referred for amplification. Initially observation with follow up outpatient visits was initiated in 27/85 (32%) however, only 3/27 (11%) resolved with watchful waiting and 24/27 (89%) ultimately required at least unilateral tube placement due to OME and 14/24 (59%) were found to have at least a unilateral mixed or SNHL.ConclusionsAn effective initial management plan for children with suspected middle ear pathology and failed NBHS is diagnostic operative microscopy with placement of a ventilation tube in the presence of a MEE along with either intra-operative ABR or close follow-up ABR. This allows for the identification and treatment of babies with a conductive component due to OME, accurate diagnosing of an underlying SNHL component and for prompt aural rehabilitation.



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Effect of Electrode Montage and Head Position on Air-Conducted Ocular Vestibular Evoked Myogenic Potential.

Related Articles

Effect of Electrode Montage and Head Position on Air-Conducted Ocular Vestibular Evoked Myogenic Potential.

Am J Audiol. 2017 Jun 13;26(2):180-188

Authors: Makowiec K, McCaslin DL, Jacobson GP, Hatton K, Lee J

Abstract
Purpose: The purpose of this investigation was to identify the optimal recording parameters for evoking the ocular vestibular evoked myogenic potential (oVEMP) using air-conduction stimuli.
Method: Subjects were 17 otologically and neurologically intact adults (age: M = 24.18 years, SD = 1.91 years). The oVEMP responses were elicited using a 500-Hz tone burst air-conduction stimulus presented at an intensity of 95 dB nHL. The setting was a balance function laboratory that was part of a large tertiary care otology clinic.
Results: The oVEMP electrode montage and body position that yielded the largest oVEMP amplitude was the belly-tendon montage (Sandhu, George, & Rea, 2013), recorded with the subject in the sitting position. The N1 latency recorded with the belly-tendon montage was significantly shorter than that recorded for the infraorbital montage in both the sitting and supine positions.
Conclusion: The belly-tendon recording montage with the subject sitting yields significantly larger oVEMP amplitudes and shorter N1 latencies than do traditional bipolar infraorbital recordings.

PMID: 28520834 [PubMed - indexed for MEDLINE]

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Evidence for the degradation of an emerging pollutant by a mechanism involving iso-energetic charge transfer under visible light

Publication date: 5 October 2018
Source:Applied Catalysis B: Environmental, Volume 233
Author(s): G. Mamba, J. Kiwi, C. Pulgarin, R. Sanjines, S. Giannakis, S. Rtimi
This study presents the first reports for ZnO/CuxO sequentially sputtered leading to stable and uniform films effective accelerated degradation of the emerging pollutant Norfloxacin (NFX) under visible light. The most effective ZnO film was sputtered from a Zn -target for 4 min followed by Cu-sputtering for 30 s on non-thermal resistant polystyrene (PS). The NFX-degradation proceeded more readily on ZnO/CuxO compared to ZnO-films although the conduction band potential energy position of the two semiconductors were iso-energetic. By X-ray photoelectron spectroscopy (XPS), Cu2O was identified as the predominant Cu-oxidation state in the sputtered film. A mechanism for the NFX degradation is suggested in which the holes generated by Cu2O transfer to ZnO in the ZnO(n)/CuO(p) in the hetero-junction. This transfer is favored by the electrostatic interaction between both semiconductors. The catalyst optical properties and surface potential were monitored during NFX degradation. Stable repetitive NFX degradation kinetics was observed under visible light on the sputtered ZnO/CuxO films. The use of appropriate scavengers allowed the identification of the intermediate radical species (ROS). XPS analysis provided the proof for redox catalysis taking place within the time of NFX abatement. The application of ZnO/CuxO films in a photo-reactor for the degradation of emerging pollutants seems feasible due to the low cost of Zn and Cu and the fast kinetics found for NFX degradation.

Graphical abstract

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Atomic layer deposition of Zn(O,S) buffer layers for Cu(In,Ga)Se2 solar cells with KF post-deposition treatment

Publication date: 15 August 2018
Source:Solar Energy Materials and Solar Cells, Volume 183
Author(s): F. Larsson, O. Donzel-Gargand, J. Keller, M. Edoff, T. Törndahl
We investigate the possibility to combine Zn(O,S) buffer layers grown by atomic layer deposition (ALD) with KF post-deposition treated Cu(In,Ga)Se2 (CIGS-KF) in solar cells. It is shown that the beneficial effect on open-circuit voltage from the post-deposition treatment is essentially independent of buffer layer material. However, a wet-chemical surface treatment is required prior to ALD in order to achieve competitive fill factor values. A water rinse is sufficient to create an absorber surface similar to the one formed during a conventional CdS chemical bath deposition process. However, it is observed that CIGS-KF/Zn(O,S) devices made with water-rinsed absorbers systematically result in lower fill factor values than for the corresponding CIGS-KF/CdS references. This effect can be mitigated by decreasing the H2S:H2O precursor ratio during ALD initiation, indicating that the fill factor limitation is linked to the initial Zn(O,S) growth on the modified CIGS-KF surface. The best CIGS-KF/Zn(O,S) devices were fabricated by etching away the KF-modified surface layer prior to ALD, followed by a low-temperature anneal. The thermal treatment step is needed to increase the open-circuit voltage close to the value of the CdS devices. The results presented in this contribution indicate that the main beneficial effects from KF-PDT in our devices are neither associated with the CdS CBD process nor due to the formation of a K-In-Se rich phase on the CIGS surface.

Graphical abstract

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