Medicine by Alexandros G. Sfakianakis

Catalytic reduction of Cr(VI) to less toxic Cr(III) form using metal nanoparticles is one of the novel approaches adopted to deal with Cr toxicity. In this work, we report the fabrication of a facile, reusable, and robust Pd nanoparticles-immobilized catalytic reactor (Pd-NICaR) system using green, environment-friendly gamma radiolytic, and plasma polymerization processes. A room temperature, RF-powered plasma polymerization process was employed to functionalize a polyethylene–polypropylene (PE–PP) non-woven matrix with epoxy group containing monomer 2,3-epoxypropyl methacrylate (EPMA). EPMA-functionalized PE–PP (EPMA-f-PE–PP) substrate was subsequently used as a template for in situ generation and immobilization of Pd NPs via gamma radiolytic route. The samples were characterized using FTIR, SEM, XPS, and XRF techniques. The catalytic efficacy of Pd-NICaR towards Cr(VI) reduction, in the presence of formic acid (FA) as a reductant, was investigated spectrophotometrically, and reaction parameters were optimized at reaction temperature of 50 °C and [FA]/[Cr(VI)] = 680 to achieve catalytic reduction efficiency of 99.7% within 10 min in batch process. The system showed excellent reusability (~ 20 cycles) and storage stability (> 30 days) without substantial loss (~ 11%) of activity. Practical applicability of the robust catalytic system towards Cr(VI) toxicity mitigation was established in continuous flow mode using a fixed-bed column reactor.

Azithromycin Efficacy in Adults with Severe Persistent Uncontrolled Asthma

Publication date: Available online 28 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Roula Altisheh, Tara Carr

A predictive analysis of CO 2 emissions, environmental policy stringency, and economic growth in China

Abstract

This study takes environmental policy stringency and economic activity as the controlling variables and forecasts the CO₂ emissions in China up to 2022. In doing so, an application of corrected grey model with convolution is used over the annual time series data between 1990 and 2012. The simulation results show that (1) between 2012 and 2022, CO₂ emissions in China is expected to increase at an average rate of 17.46% annually, raising the emissions intensity from 7.04 in 2012 to 25.461 metric tons per capita by 2022; (2) stringent environmental policies reduce CO₂ emissions—whereas, GDP tends to increase the emissions intensity in China; (3) stringent environmental policies are found to have a negative impact on GDP in China. Based on the empirical findings, the study also provides some policy suggestions to reduce emissions intensity in China.

Dermatitis de cara y cuello. Respuesta a itraconazol

Publication date: Available online 27 March 2018
Source:Actas Dermo-Sifiliográficas
Author(s): R. Ruiz-Villaverde, D. Sánchez-Cano, D. López-Delgado

Enfermedad de Rosai-Dorfman cutánea: una nueva presentación clínica

Publication date: Available online 28 March 2018
Source:Actas Dermo-Sifiliográficas
Author(s): J.M. Conde, A.Y. Kim, R. de Miguel, C.H. Nousari

Blended shared control utilizing online identification

Abstract

Purpose

Surgical robots are increasingly common, yet routine tasks such as tissue grasping remain potentially harmful with high occurrences of tissue crush injury due to the lack of force feedback from the grasper. This work aims to investigate whether a blended shared control framework which utilizes real-time identification of the object being grasped as part of the feedback may help address the prevalence of tissue crush injury in robotic surgeries.

Methods

This work tests the proposed shared control framework and tissue identification algorithm on a custom surrogate surgical robotic grasping setup. This scheme utilizes identification of the object being grasped as part of the feedback to regulate to a desired force. The blended shared control is arbitrated between human and an implicit force controller based on a computed confidence in the identification of the grasped object. The online identification is performed using least squares based on a nonlinear tissue model. Testing was performed on five silicone tissue surrogates. Twenty grasps were conducted, with half of the grasps performed under manual control and half of the grasps performed with the proposed blended shared control, to test the efficacy of the control scheme.

Results

The identification method resulted in an average of 95% accuracy across all time samples of all tissue grasps using a full leave-grasp-out cross-validation. There was an average convergence time of \(8.1 \pm 6.3\) ms across all training grasps for all tissue surrogates. Additionally, there was a reduction in peak forces induced during grasping for all tissue surrogates when applying blended shared control online.

Conclusion

The blended shared control using online identification more successfully regulated grasping forces to the desired target force when compared with manual control. The preliminary work on this surrogate setup for surgical grasping merits further investigation on real surgical tools and with real human tissues.

Testing the Efficacy of Single-Cell Stimulation in Biasing Presubicular Head Direction Activity

To support navigation, the firing of head direction (HD) neurons must be tightly anchored to the external space. Indeed, inputs from external landmarks can rapidly reset the preferred direction of HD cells. Landmark stimuli have often been simulated as excitatory inputs from "visual cells" (encoding landmark information) to the HD attractor network; when excitatory visual inputs are sufficiently strong, preferred directions switch abruptly to the landmark location. In the present work, we tested whether mimicking such inputs via juxtacellular stimulation would be sufficient for shifting the tuning of individual presubicular HD cells recorded in passively rotated male rats. We recorded 81 HD cells in a cue-rich environment, and evoked spikes trains outside of their preferred direction (distance range, 11–178°). We found that HD tuning was remarkably resistant to activity manipulations. Even strong stimulations, which induced seconds-long spike trains, failed to induce a detectable shift in directional tuning. HD tuning curves before and after stimulation remained highly correlated, indicating that postsynaptic activation alone is insufficient for modifying HD output. Our data are thus consistent with the predicted stability of an HD attractor network when anchored to external landmarks. A small spiking bias at the stimulus direction could only be observed in a visually deprived environment in which both average firing rates and directional tuning were markedly reduced. Based on this evidence, we speculate that, when attractor dynamics become unstable (e.g., under disorientation), the output of HD neurons could be more efficiently controlled by strong biasing stimuli.

SIGNIFICANCE STATEMENT The activity of head direction (HD) cells is thought to provide the mammalian brain with an internal sense of direction. To support navigation, the firing of HD neurons must be anchored to external landmarks, a process thought to be supported by associative plasticity within the HD system. Here, we investigated these plasticity mechanisms by juxtacellular stimulation of single HD neurons in vivo in awake rats. We found that HD coding is strongly resistant to external manipulations of spiking activity. Only in a visually deprived environment was juxtacellular stimulation able to induce a small activity bias in single presubicular neurons. We propose that juxtacellular stimulation can bias HD tuning only when competing anchoring inputs are reduced or not available.

C8ORF37 Is Required for Photoreceptor Outer Segment Disc Morphogenesis by Maintaining Outer Segment Membrane Protein Homeostasis

C8ORF37 is a causative gene for three different clinical forms of incurable retinal degeneration. However, the completely unknown function of C8ORF37 limits our understanding of the pathogenicity of C8ORF37 mutations. Here, we performed a comprehensive phenotypic characterization of a C8orf37 KO mouse line, generated using CRISPR/Cas9 technology. Both C8orf37 KO male and female mice exhibited progressive and simultaneous degeneration of rod and cone photoreceptors but no non-ocular phenotypes. The major ultrastructural feature of C8orf37 KO photoreceptors was massive disorganization of the outer segment (OS) membrane discs starting from the onset of disc morphogenesis during development. At the molecular level, the amounts of multiple OS-specific membrane proteins, including proteins involved in membrane disc organization, were reduced, although these proteins were targeted normally to the OS. Considering the distribution of C8ORF37 throughout the photoreceptor cell body, the normal structure of the KO photoreceptor connecting cilium, and the absence of defects in other ciliary organs of the KO mice, our findings do not support the previous notion that C8ORF37 was a ciliary protein. Because C8ORF37 is absent in the photoreceptor OS, C8ORF37 may participate in the secretory pathway of OS membrane proteins in the photoreceptor cell body and thus maintain the homeostasis of these proteins. This study established a valid animal model for future therapeutic studies of C8ORF37-associated retinal degeneration. This study also shed new light on the role of C8ORF37 in photoreceptors and on the pathogenic mechanism underlying retinal degeneration caused by C8ORF37 mutations.

SIGNIFICANCE STATEMENT Inherited retinal degeneration is a group of incurable conditions with poorly understood underlying molecular mechanisms. We investigated C8ORF37, a causative gene for three retinal degenerative conditions: retinitis pigmentosa, cone–rod dystrophy, and Bardet–Biedl syndrome. C8ORF37 encodes a protein with no known functional domains and thus its biological function is unpredictable. We knocked out the C8ORF37 ortholog in mice, which resulted in a retinal phenotype similar to that observed in patients. We further demonstrated that C8ORF37 is required for photoreceptor outer segment disc formation and alignment, a process that is critical for photoreceptor function and survival. This study advances our understanding of the pathogenesis of retinal degeneration and establishes a valuable mouse model for future therapeutic development.

A Novel Retrieval-Dependent Memory Process Revealed by the Arrest of ERK1/2 Activation in the Basolateral Amygdala

Fully consolidated fear memories can be maintained or inhibited by retrieval-dependent mechanisms depending on the degree of re-exposure to fear cues. Short exposures promote memory maintenance through reconsolidation, and long exposures promote inhibition through extinction. Little is known about the neural mechanisms by which increasing cue exposure overrides reconsolidation and instead triggers extinction. Using auditory fear conditioning in male rats, we analyzed the role of a molecular mechanism common to reconsolidation and extinction of fear, ERK1/2 activation within the basolateral amygdala (BLA), after intermediate conditioned stimulus (CS) exposure events. We show that an intermediate re-exposure (four CS presentations) failed to activate ERK1/2 in the BLA, suggesting the absence of reconsolidation or extinction mechanisms. Supporting this hypothesis, pharmacologically inhibiting the BLA ERK1/2-dependent signaling pathway in conjunction with four CS presentations had no effect on fear expression, and the NMDA receptor partial agonist d-cycloserine, which enhanced extinction and ERK1/2 activation in partial extinction protocols (seven CSs), had no behavioral or molecular effect when given in association with four CS presentations. These molecular and behavioral data reveal a novel retrieval-dependent memory phase occurring along the transition between conditioned fear maintenance and inhibition. CS-dependent molecular events in the BLA may arrest reconsolidation intracellular signaling mechanism in an extinction-independent manner. These findings are critical for understanding the molecular underpinnings of fear memory persistence after retrieval both in health and disease.

SIGNIFICANCE STATEMENT Consolidated fear memories can be altered by retrieval-dependent mechanisms. Whereas a brief conditioned stimulus (CS) exposure promotes fear memory maintenance through reconsolidation, a prolonged exposure engages extinction and fear inhibition. The nature of this transition and whether an intermediate degree of CS exposure engages reconsolidation or extinction is unknown. We show that an intermediate cue exposure session (four CSs) produces the arrest of ERK1/2 activation in the basolateral amygdala, a common mechanism for reconsolidation and extinction. Amnestic or hypermnestic treatments given in association with four CSs had no behavioral or molecular effects, respectively. This evidence reveals a novel retrieval-dependent memory phase. Intermediate degrees of CS exposure fail to trigger reconsolidation or extinction, leaving the original memory in an insensitive state.

Assembling a Cellular User Manual for the Brain

For many years, efforts to decipher the various cellular components that comprise the CNS were stymied by a lack of technical strategies for isolating and profiling the brain's resident cell types. The advent of transcriptional profiling, combined with powerful new purification schemes, changed this reality and transformed our understanding of the macroglial populations within the brain. Here, we chronicle the historical context and scientific setting for our efforts to transcriptionally profile neurons, astrocytes, and oligodendrocytes, and highlight some of the profound discoveries that were cultivated by these data.

Following a lengthy battle with pancreatic cancer, Ben Barres passed away during the writing of this Progression piece. Among Ben's innumerable contributions to the greater scientific community, his addition of publicly available transcriptome databases of CNS cell types will forever remain a relic of his generous spirit and boundless scientific curiosity. Although he had impressively committed a majority of these enormous gene lists to memory, Ben could oftentimes be spotted at meetings buried in his cell phone on the Barres RNAseq database. Perhaps the only thing he enjoyed more than exploring these data himself, was knowing how useful these contributions had been (and will hopefully continue to be) to his scientific peers.

This Week in The Journal

Understanding the Hierarchical Organization of Large-Scale Networks Based on Temporal Modulations in Patterns of Neural Connectivity

Celecoxib Ameliorates Seizure Susceptibility in Autosomal Dominant Lateral Temporal Epilepsy

Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. It is known that glutamatergic transmission is altered in LGI1 mutant mice, and seizures can be reduced by restoring LGI1 function. Yet, the mechanism underlying ADLTE is unclear. Here, we propose that seizures in male LGI1^–/– mice are due to nonsynaptic epileptiform activity in cortical neurons. We examined the intrinsic excitability of pyramidal neurons in the temporal cortex of male LGI1^–/– mice and found that the voltage-gated K⁺ channel Kv1.2 was significantly downregulated. We also found that cytosolic phospholipase A₂ (cPLA₂)-cyclooxygenase 2 (Cox2) signaling was enhanced in LGI1^–/– mice. Interestingly, Cox2 inhibition effectively restored the dysregulated Kv1.2 and reduced the intrinsic excitability of pyramidal neurons. Moreover, in vivo injection of celecoxib, an FDA-approved nonsteroidal anti-inflammatory drug, rescued the defective Kv1.2 (an ~1.9-fold increase), thereby alleviating the seizure susceptibility and extending the life of LGI1^–/– mice by 5 d. In summary, we conclude that LGI1 deficiency dysregulates cPLA₂-Cox2 signaling to cause hyperexcitability of cortical pyramidal neurons, and celecoxib is a potential agent to manage human ADLTE.

SIGNIFICANCE STATEMENT Haploinsufficiency of the leucine-rich glioma inactivated 1 (LGI1) gene is the major pathogenic basis for ADLTE, an inherited syndrome with no cure to date. Existing studies suggest that altered glutamatergic transmission in the hippocampus causes this disease, but the data are paradoxical. We demonstrate that the loss of LGI1 decreases Kv1.2 expression, enhances intrinsic excitability, and thereby causes epilepsy. Interestingly, for the first time, we show that an FDA-approved drug, celecoxib, rescues the Kv1.2 defect and alleviates seizure susceptibility in LGI1^–/– mice, as well as improving their survival. Thus, we suggest that celecoxib is a promising drug for the treatment of ADLTE patients.

Identifying the Unique Role of Notch3 in Adult Neural Stem Cell Maintenance

Electrophysiological Signatures of Spatial Boundaries in the Human Subiculum

Environmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. Although studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. To address this gap in the literature, we analyzed intracranial recordings from the hippocampal formation of surgical epilepsy patients (of both sexes) while they performed a virtual spatial navigation task and compared the power in three frequency bands (1–4, 4–10, and 30–90 Hz) for target locations near and far from the environmental boundaries. Our results suggest that encoding locations near boundaries elicited stronger theta oscillations than for target locations near the center of the environment and that this difference cannot be explained by variables such as trial length, speed, movement, or performance. These findings provide direct evidence of boundary-dependent neural activity localized in humans to the subiculum, the homolog of the hippocampal subregion in which most boundary cells are found in rodents, and indicate that this system can represent attended locations that rather than the position of one's own body.

SIGNIFICANCE STATEMENT Spatial computations using environmental boundaries are an integral part of the brain's spatial mapping system. In rodents, border/boundary cells in the subiculum and entorhinal cortex reveal boundary coding at the single-neuron level. Although there is good reason to believe that such representations also exist in humans, the evidence has thus far been limited to functional neuroimaging studies that broadly implicate the hippocampus in boundary-based navigation. By combining intracranial recordings with high-resolution imaging of hippocampal subregions, we identified a neural marker of boundary representation in the human subiculum.

Neuronal Organization in the Inferior Colliculus Revisited with Cell-Type-Dependent Monosynaptic Tracing

The inferior colliculus (IC) is a critical integration center in the auditory pathway. However, because the inputs to the IC have typically been studied by the use of conventional anterograde and retrograde tracers, the neuronal organization and cell-type-specific connections in the IC are poorly understood. Here, we used monosynaptic rabies tracing and in situ hybridization combined with excitatory and inhibitory Cre transgenic mouse lines of both sexes to characterize the brainwide and cell-type-specific inputs to specific neuron types within the lemniscal IC core and nonlemniscal IC shell. We observed that both excitatory and inhibitory neurons of the IC shell predominantly received ascending inputs rather than descending or core inputs. Correlation and clustering analyses revealed two groups of excitatory neurons in the shell: one received inputs from a combination of ascending nuclei, and the other received inputs from a combination of descending nuclei, neuromodulatory nuclei, and the contralateral IC. In contrast, inhibitory neurons in the core received inputs from the same combination of all nuclei. After normalizing the extrinsic inputs, we found that core inhibitory neurons received a higher proportion of inhibitory inputs from the ventral nucleus of the lateral lemniscus than excitatory neurons. Furthermore, the inhibitory neurons preferentially received inhibitory inputs from the contralateral IC shell. Because IC inhibitory neurons innervate the thalamus and contralateral IC, the inhibitory inputs we uncovered here suggest two long-range disinhibitory circuits. In summary, we found: (1) dominant ascending inputs to the shell, (2) two subpopulations of shell excitatory neurons, and (3) two disinhibitory circuits.

SIGNIFICANCE STATEMENT Sound undergoes extensive processing in the brainstem. The inferior colliculus (IC) core is classically viewed as the integration center for ascending auditory information, whereas the IC shell integrates descending feedback information. Here, we demonstrate that ascending inputs predominated in the IC shell but appeared to be separated from the descending inputs. The presence of inhibitory projection neurons is a unique feature of the auditory ascending pathways, but the connections of these neurons are poorly understood. Interestingly, we also found that inhibitory neurons in the IC core and shell preferentially received inhibitory inputs from ascending nuclei and contralateral IC, respectively. Therefore, our results suggest a bipartite domain in the IC shell and disinhibitory circuits in the IC.

Codeficiency of Lysosomal Mucolipins 3 and 1 in Cochlear Hair Cells Diminishes Outer Hair Cell Longevity and Accelerates Age-Related Hearing Loss

Acquired hearing loss is the predominant neurodegenerative condition associated with aging in humans. Although mutations on several genes are known to cause congenital deafness in newborns, few genes have been implicated in age-related hearing loss (ARHL), perhaps because its cause is likely polygenic. Here, we generated mice lacking lysosomal calcium channel mucolipins 3 and 1 and discovered that both male and female mice suffered a polygenic form of hearing loss. Whereas mucolipin 1 is ubiquitously expressed in all cells, mucolipin 3 is expressed in a small subset of cochlear cells, hair cells (HCs) and marginal cells of the stria vascularis, and very few other cell types. Mice lacking both mucolipins 3 and 1, but not either one alone, experienced hearing loss as early as at 1 month of age. The severity of hearing impairment progressed from high to low frequencies and increased with age. Early onset of ARHL in these mice was accompanied by outer HC (OHC) loss. Adult mice conditionally lacking mucolipins in HCs exhibited comparable auditory phenotypes, thereby revealing that the reason for OHC loss is mucolipin codeficiency in the HCs and not in the stria vascularis. Furthermore, we observed that OHCs lacking mucolipins contained abnormally enlarged lysosomes aggregated at the apical region of the cell, whereas other organelles appeared normal. We also demonstrated that these aberrant lysosomes in OHCs lost their membrane integrity through lysosomal membrane permeabilization, a known cause of cellular toxicity that explains why and how OHCs die, leading to premature ARHL.

SIGNIFICANCE STATEMENT Presbycusis, or age-related hearing loss (ARHL), is a common characteristic of aging in mammals. Although many genes have been identified to cause deafness from birth in both humans and mice, only a few are known to associate with progressive ARHL, the most prevalent form of deafness. We have found that mice lacking two lysosomal channels, mucolipins 3 and 1, suffer accelerated ARHL due to auditory outer hair cell degeneration, the most common cause of hearing loss and neurodegenerative condition in humans. Lysosomes lacking mucolipins undergo organelle membrane permeabilization and promote cytotoxicity with age, revealing a novel mechanism of outer hair cell degeneration and ARHL. These results underscore the importance of lysosomes in hair cell survival and the maintenance of hearing.

Correction: Javadi et al., "Oscillatory Reinstatement Enhances Declarative Memory"

Elevation of Hippocampal Neurogenesis Induces a Temporally Graded Pattern of Forgetting of Contextual Fear Memories

Throughout life neurons are continuously generated in the subgranular zone of the hippocampus. The subsequent integration of newly generated neurons alters patterns of dentate gyrus input and output connectivity, potentially rendering memories already stored in those circuits harder to access. Consistent with this prediction, we previously showed that increasing hippocampal neurogenesis after training induces forgetting of hippocampus-dependent memories, including contextual fear memory. However, the brain regions supporting contextual fear memories change with time, and this time-dependent memory reorganization might regulate the sensitivity of contextual fear memories to fluctuations in hippocampal neurogenesis. By virally expressing the inhibitory designer receptor exclusively activated by designer drugs, hM4Di, we first confirmed that chemogenetic inhibition of dorsal hippocampal neurons impairs retrieval of recent (day-old) but not remote (month-old) contextual fear memories in male mice. We then contrasted the effects of increasing hippocampal neurogenesis at recent versus remote time points after contextual fear conditioning in male and female mice. Increasing hippocampal neurogenesis immediately following training reduced conditioned freezing when mice were replaced in the context 1 month later. In contrast, when hippocampal neurogenesis was increased time points remote to training, conditioned freezing levels were unaltered when mice were subsequently tested. These temporally graded forgetting effects were observed using both environmental and genetic interventions to increase hippocampal neurogenesis. Our experiments identify memory age as a boundary condition for neurogenesis-mediated forgetting and suggest that, as contextual fear memories mature, they become less sensitive to changes in hippocampal neurogenesis levels because they no longer depend on the hippocampus for their expression.

SIGNIFICANCE STATEMENT New neurons are generated in the hippocampus throughout life. As they integrate into the hippocampus, they remodel neural circuitry, potentially making information stored in those circuits harder to access. Consistent with this, increasing hippocampal neurogenesis after learning induces forgetting of the learnt information. The current study in mice asks whether these forgetting effects depend on the age of the memory. We found that post-training increases in hippocampal neurogenesis only impacted recently acquired, and not remotely acquired, hippocampal memories. These experiments identify memory age as a boundary condition for neurogenesis-mediated forgetting, and suggest remote memories are less sensitive to changes in hippocampal neurogenesis levels because they no longer depend critically on the hippocampus for their expression.

The Encoding of Sound Source Elevation in the Human Auditory Cortex

Spatial hearing is a crucial capacity of the auditory system. While the encoding of horizontal sound direction has been extensively studied, very little is known about the representation of vertical sound direction in the auditory cortex. Using high-resolution fMRI, we measured voxelwise sound elevation tuning curves in human auditory cortex and show that sound elevation is represented by broad tuning functions preferring lower elevations as well as secondary narrow tuning functions preferring individual elevation directions. We changed the ear shape of participants (male and female) with silicone molds for several days. This manipulation reduced or abolished the ability to discriminate sound elevation and flattened cortical tuning curves. Tuning curves recovered their original shape as participants adapted to the modified ears and regained elevation perception over time. These findings suggest that the elevation tuning observed in low-level auditory cortex did not arise from the physical features of the stimuli but is contingent on experience with spectral cues and covaries with the change in perception. One explanation for this observation may be that the tuning in low-level auditory cortex underlies the subjective perception of sound elevation.

SIGNIFICANCE STATEMENT This study addresses two fundamental questions about the brain representation of sensory stimuli: how the vertical spatial axis of auditory space is represented in the auditory cortex and whether low-level sensory cortex represents physical stimulus features or subjective perceptual attributes. Using high-resolution fMRI, we show that vertical sound direction is represented by broad tuning functions preferring lower elevations as well as secondary narrow tuning functions preferring individual elevation directions. In addition, we demonstrate that the shape of these tuning functions is contingent on experience with spectral cues and covaries with the change in perception, which may indicate that the tuning functions in low-level auditory cortex underlie the perceived elevation of a sound source.

Cell-Specific Deletion of PGC-1{alpha} from Medium Spiny Neurons Causes Transcriptional Alterations and Age-Related Motor Impairment

Multiple lines of evidence indicate that a reduction in the expression and function of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is associated with neurodegeneration in diseases such as Huntington's disease (HD). Polymorphisms in the PGC-1α gene modify HD progression and PGC-1α expression is reduced in striatal medium spiny neurons (MSNs) of HD patients and mouse models. However, neither the MSN-specific function of PGC-1α nor the contribution of PGC-1α deficiency to motor dysfunction is known. We identified novel, PGC-1α-dependent transcripts involved in RNA processing, signal transduction, and neuronal morphology and confirmed reductions in these transcripts in male and female mice lacking PGC-1α specifically in MSNs, indicating a cell-autonomous effect in this population. MSN-specific PGC-1α deletion caused reductions in previously identified neuronal and metabolic PGC-1α-dependent genes without causing striatal vacuolizations. Interestingly, these mice exhibited a hypoactivity with age, similar to several HD animal models. However, these newly identified PGC-1α-dependent genes were upregulated with disease severity and age in knock-in HD mouse models independent of changes in PGC-1α transcript, contrary to what would be predicted from a loss-of-function etiological mechanism. These data indicate that PGC-1α is necessary for MSN transcriptional homeostasis and function with age and that, whereas PGC-1α loss in MSNs does not replicate an HD-like phenocopy, its downstream genes are altered in a repeat-length and age-dependent fashion. Understanding the additive effects of PGC-1α gene functional variation and mutant huntingtin on transcription in this cell type may provide insight into the selective vulnerability of MSNs in HD.

SIGNIFICANCE STATEMENT Reductions in peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)-mediated transcription have been implicated in the pathogenesis of Huntington's disease (HD). We show that, although PGC-1α-dependent transcription is necessary to maintain medium spiny neuron (MSN) function with age, its loss is insufficient to cause striatal atrophy in mice. We also highlight a set of genes that can serve as proxies for PGC-1α functional activity in the striatum for target engagement studies. Furthermore, we demonstrate that PGC-1α-dependent genes are upregulated in a dose- and age-dependent fashion in HD mouse models, contrary to what would be predicted from a loss-of-function etiological mechanism. However, given this role for PGC-1α in MSN transcriptional homeostasis, it is important to consider how genetic variation in PGC-1α could contribute to mutant-huntingtin-induced cell death and disease progression.

A Critical Role for the Nucleus Reuniens in Long-Term, But Not Short-Term Associative Recognition Memory Formation

Recognition memory for single items requires the perirhinal cortex (PRH), whereas recognition of an item and its associated location requires a functional interaction among the PRH, hippocampus (HPC), and medial prefrontal cortex (mPFC). Although the precise mechanisms through which these interactions are effected are unknown, the nucleus reuniens (NRe) has bidirectional connections with each regions and thus may play a role in recognition memory. Here we investigated, in male rats, whether specific manipulations of NRe function affected performance of recognition memory for single items, object location, or object-in-place associations. Permanent lesions in the NRe significantly impaired long-term, but not short-term, object-in-place associative recognition memory, whereas single item recognition memory and object location memory were unaffected. Temporary inactivation of the NRe during distinct phases of the object-in-place task revealed its importance in both the encoding and retrieval stages of long-term associative recognition memory. Infusions of specific receptor antagonists showed that encoding was dependent on muscarinic and nicotinic cholinergic neurotransmission, whereas NMDA receptor neurotransmission was not required. Finally, we found that long-term object-in-place memory required protein synthesis within the NRe. These data reveal a specific role for the NRe in long-term associative recognition memory through its interactions with the HPC and mPFC, but not the PRH. The delay-dependent involvement of the NRe suggests that it is not a simple relay station between brain regions, but, rather, during high mnemonic demand, facilitates interactions between the mPFC and HPC, a process that requires both cholinergic neurotransmission and protein synthesis.

SIGNIFICANCE STATEMENT Recognizing an object and its associated location, which is fundamental to our everyday memory, requires specific hippocampal–cortical interactions, potentially facilitated by the nucleus reuniens (NRe) of the thalamus. However, the role of the NRe itself in associative recognition memory is unknown. Here, we reveal the crucial role of the NRe in encoding and retrieval of long-term object-in-place memory, but not for remembrance of an individual object or individual location and such involvement is cholinergic receptor and protein synthesis dependent. This is the first demonstration that the NRe is a key node within an associative recognition memory network and is not just a simple relay for information within the network. Rather, we argue, the NRe actively modulates information processing during long-term associative memory formation.

Doctor, Teacher, and Stethoscope: Neural Representation of Different Types of Semantic Relations

Concepts can be related in many ways. They can belong to the same taxonomic category (e.g., "doctor" and "teacher," both in the category of people) or be associated with the same event context (e.g., "doctor" and "stethoscope," both associated with medical scenarios). How are these two major types of semantic relations coded in the brain? We constructed stimuli from three taxonomic categories (people, manmade objects, and locations) and three thematic categories (school, medicine, and sports) and investigated the neural representations of these two dimensions using representational similarity analyses in human participants (10 men and nine women). In specific regions of interest, the left anterior temporal lobe (ATL) and the left temporoparietal junction (TPJ), we found that, whereas both areas had significant effects of taxonomic information, the taxonomic relations had stronger effects in the ATL than in the TPJ ("doctor" and "teacher" closer in ATL neural activity), with the reverse being true for thematic relations ("doctor" and "stethoscope" closer in TPJ neural activity). A whole-brain searchlight analysis revealed that widely distributed regions, mainly in the left hemisphere, represented the taxonomic dimension. Interestingly, the significant effects of the thematic relations were only observed after the taxonomic differences were controlled for in the left TPJ, the right superior lateral occipital cortex, and other frontal, temporal, and parietal regions. In summary, taxonomic grouping is a primary organizational dimension across distributed brain regions, with thematic grouping further embedded within such taxonomic structures.

SIGNIFICANCE STATEMENT How are concepts organized in the brain? It is well established that concepts belonging to the same taxonomic categories (e.g., "doctor" and "teacher") share neural representations in specific brain regions. How concepts are associated in other manners (e.g., "doctor" and "stethoscope," which are thematically related) remains poorly understood. We used representational similarity analyses to unravel the neural representations of these different types of semantic relations by testing the same set of words that could be differently grouped by taxonomic categories or by thematic categories. We found that widely distributed brain areas primarily represented taxonomic categories, with the thematic categories further embedded within the taxonomic structure.

Positive Allosteric Modulation as a Potential Therapeutic Strategy in Anti-NMDA Receptor Encephalitis

N-methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors important for synaptic plasticity, memory, and neuropsychiatric health. NMDAR hypofunction contributes to multiple disorders, including anti-NMDAR encephalitis (NMDARE), an autoimmune disease of the CNS associated with GluN1 antibody-mediated NMDAR internalization. Here we characterize the functional/pharmacological consequences of exposure to CSF from female human NMDARE patients on NMDAR function, and we characterize the effects of intervention with recently described positive allosteric modulators (PAMs) of NMDARs. Incubation (48 h) of rat hippocampal neurons of both sexes in confirmed NMDARE patient CSF, but not control CSF, attenuated NMDA-induced current. Residual NMDAR function was characterized by lack of change in channel open probability, indiscriminate loss of synaptic and extrasynaptic NMDARs, and indiscriminate loss of GluN2B-containing and GluN2B-lacking NMDARs. NMDARs tagged with N-terminal pHluorin fluorescence demonstrated loss of surface receptors. Thus, function of residual NMDARs following CSF exposure was indistinguishable from baseline, and deficits appear wholly accounted for by receptor loss. Coapplication of CSF and PAMs of NMDARs (SGE-301 or SGE-550, oxysterol-mimetic) for 24 h restored NMDAR function following 24 h incubation in patient CSF. Curiously, restoration of NMDAR function was observed despite washout of PAMs before electrophysiological recordings. Subsequent experiments suggested that residual allosteric potentiation of NMDAR function explained the persistent rescue. Further studies of the pathogenesis of NMDARE and intervention with PAMs may inform new treatments for NMDARE and other disorders associated with NMDAR hypofunction.

SIGNIFICANCE STATEMENT Anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is increasingly recognized as an important cause of sudden-onset psychosis and other neuropsychiatric symptoms. Current treatment leaves unmet medical need. Here we demonstrate cellular evidence that newly identified positive allosteric modulators of NMDAR function may be a viable therapeutic strategy.

Challenge to Promote Change: The Neural Basis of the Contextual Interference Effect in Young and Older Adults

Motor performance deteriorates with age. Hence, studying the effects of different training types on performance improvement is particularly important. Here, we investigated the neural correlates of the contextual interference (CI) effect in 32 young (YA; 16 female) and 28 older (OA; 12 female) human adults. Participants were randomly assigned to either a blocked or a random practice schedule, practiced three variations of a bimanual visuomotor task over 3 d, and were retested 6 d later. Functional magnetic resonance imaging data were acquired during the first and last training days and during retention. Although the overall performance level was lower in OA than YA, the typical CI effects were observed in both age groups, i.e., inferior performance during acquisition but superior performance during retention for random relative to blocked practice. At the neural level, blocked practice showed higher brain activity in motor-related brain regions compared with random practice across both age groups. However, although activity in these regions decreased with blocked practice in both age groups, it was either preserved (YA) or increased (OA) as a function of random practice. In contrast, random compared with blocked practice resulted in greater activations in visual processing regions across age groups. Interestingly, in OA, the more demanding random practice schedule triggered neuroplastic changes in areas of the default mode network, ultimately leading to better long-term retention. Our findings may have substantial implications for the optimization of practice schedules, and rehabilitation settings in particular.

SIGNIFICANCE STATEMENT In aging societies, it is critically important to understand how motor skills can be maintained or enhanced in older adults, with the ultimate goal to prolong functional independence. Here, we demonstrated that a more challenging random as opposed to a blocked practice environment temporarily reduced performance during the acquisition phase but resulted in lasting benefits for skill retention. In older adults, learning success was critically dependent on reduction of activation in areas of the default mode network, pointing to plastic functional changes in brain regions that are vulnerable to aging effects. The random practice context led to increased economy of brain activity and better skill retention. This provides new perspectives for reversing the negative consequences of aging.

Nigrostriatal and Mesolimbic D2/3 Receptor Expression in Parkinson's Disease Patients with Compulsive Reward-Driven Behaviors

The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D_2/3 receptor expression are described in drug-seeking and addiction disorders. Parkinson's disease (PD) patients are frequently prescribed D₂-like dopamine agonist (DAgonist) therapy for motor symptoms, yet a proportion develop clinically significant behavioral addictions characterized by impulsive and compulsive behaviors (ICBs). Until now, changes in D_2/3 receptor binding in both striatal and extrastriatal regions have not been concurrently quantified in this population. We identified 35 human PD patients (both male and female) receiving DAgonist therapy, with (n = 17) and without (n = 18) ICBs, matched for age, disease duration, disease severity, and dose of dopamine therapy. In the off-dopamine state, all completed PET imaging with [¹⁸F]fallypride, a high affinity D₂-like receptor ligand that can measure striatal and extrastriatal D_2/3 nondisplaceable binding potential (BP_ND). Striatal differences between ICB+/ICB– patients localized to the ventral striatum and putamen, where ICB+ subjects had reduced BP_ND. In this group, self-reported severity of ICB symptoms positively correlated with midbrain D_2/3 receptor BP_ND. Group differences in regional D_2/3 BP_ND relationships were also notable: ICB+ (but not ICB–) patients expressed positive correlations between midbrain and caudate, putamen, globus pallidus, and amygdala BP_NDs. These findings support the hypothesis that compulsive behaviors in PD are associated with reduced ventral and dorsal striatal D_2/3 expression, similar to changes in comparable behavioral disorders. The data also suggest that relatively preserved ventral midbrain dopaminergic projections throughout nigrostriatal and mesolimbic networks are characteristic of ICB+ patients, and may account for differential DAgonist therapeutic response.

SIGNIFICANCE STATEMENT The biologic determinants of compulsive reward-based behaviors have broad clinical relevance, from addiction to neurodegenerative disorders. Here, we address biomolecular distinctions in Parkinson's disease patients with impulsive compulsive behaviors (ICBs). This is the first study to image a large cohort of ICB+ patients using positron emission tomography with [18F]fallypride, allowing quantification of D_2/3 receptors throughout the mesocorticolimbic network. We demonstrate widespread differences in dopaminergic networks, including (1) D2-like receptor distinctions in the ventral striatum and putamen, and (2) a preservation of widespread dopaminergic projections emerging from the midbrain, which is associated with the severity of compulsive behaviors. This clearly illustrates the roles of D_2/3 receptors and medication effects in maladaptive behaviors, and localizes them specifically to nigrostriatal and extrastriatal regions.

Depression Screening in Dermatology—Think Isotretinoin

To the Editor We applaud McDonald et al for publishing "The PHQ-2 in Dermatology—Standardized Screening for Depression and Suicidal Ideation." The importance of this work cannot be overemphasized. We agree that dermatologists are uniquely situated to identify psychiatric concerns related to skin disease, and the PHQ-2 (Patient Health Questionnaire-2) is a great screening tool for this. Since we published on the use of the PHQ-2 in the context of isotretinoin, we have had positive feedback on its use and wish to reemphasize the importance in association with the article by McDonald et al. Additionally, we believe that their algorithmic approach warrants an expansion.

Rechallenge With Nivolumab After Vemurafenib Treatment of Initially Nivolumab-Resistant Advanced Melanoma

This case report describes a patient with advanced melanoma initially resistant to nivolumab therapy, treated with vemurafenib, and then rechallenged with nivolumab after development of vemurafenib-related adverse effects.

Paucity of Lesbian, Gay, Bisexual, and Transgender Health-Related Content in the Basic Dermatology Curriculum

This cross-sectional study examines the extent to which an online dermatology curriculum for medical students incorporated lesbian, gay, bisexual, and transgender health-related content.

Hair Loss Associated With Cucurbit Poisoning

This case report describes a patient experiencing hair loss following cucurbit poisoning.

Drug Discontinuation, Effectiveness, and Safety in Clinical Trial Eligible vs Ineligible Patients

This observational study examines whether drug discontinuation, effectiveness, and rates of serious adverse events differ in patients with psoriasis being treated with biologics who have been categorized as eligible or ineligible for clinical trials.

Solitary Asymptomatic Tumor in the Axilla

A woman in her 60s presented with a solitary, indolent, erythematous plaque in the right axilla and also reported a slowly growing subcutaneous node with progressive infiltration of the overlying skin. What is your diagnosis?

Dysplasie unguéale isolée non syndromique des doigts : mutations homozygotes du gène SLC25A16

Publication date: Available online 28 March 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): O. Dereure

Plus d’arrêts de l’aprémilast en vie réelle que dans les essais cliniques

Publication date: Available online 28 March 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-L. Schmutz

Quantification of Human Microbiome Stability Over Six Months: Implications for Epidemiologic Studies

Abstract

Temporal variation in microbiome measurements can reduce power. Quantification of this variation is essential for designing chronic disease studies. We analyzed 16S rRNA profiles in paired specimens separated by six months from three studies. We evaluated temporal stability by calculating intraclass correlation coefficients (ICCs). Sample sizes to detect microbiome differences between equal numbers of cases and controls for a nested case-control design were calculated based on estimated ICCs. Across body sites, 12 phylum-level ICCs were greater than 0.5. Similarly, 11 alpha-diversity ICCs were greater than 0.5. Fecal beta diversity estimates had ICCs over 0.5. For a single collection with most microbiome metrics, detecting an odds ratio (OR) of 2.0 would require 300–500 cases when matching one case to one control at P = 0.05. Two or three sequential specimens reduce the number of required subjects by 40%–50% for low-ICC metrics. Relative abundances of major phyla and alpha diversity metrics have low temporal stability. Thus, detecting associations of moderate effect size with these metrics will require large sample sizes. As beta-diversity for feces is reasonably stable over time, smaller sample sizes can detect associations with community composition. Sequential pre-diagnostic specimens from thousands of prospectively ascertained cases are required to detect modest disease associations with particular microbiome metrics.

High frequency equipment promotes antibacterial effects dependent on intensity and exposure time

mTOR inhibition in glioblastoma: requiem for a dream?

See the article by Chinnaiyan et al, pp. XXX–XXX.

Survival of patients with prior anti-angiogenic therapy

We read with interest the report by Cloughesy et al on the activity of cabozantinib in recurrent glioblastoma (GBM) patients with prior anti-angiogenic therapy.¹ In their subset analysis, they reported overall survival (OS) results using 2 different cabozantinib doses: 4.1 months (95% CI: 1.4–16.7) in the 140 mg group (n = 12); 4.6 (95% CI: 2.9–5.6) in the 100 mg group (n = 58); OS for combined groups was 4.6 months. Of the 70 patients in the analysis, 57 (81%) with prior anti-angiogenic therapy had bevacizumab (BEV). In their discussion, the authors raise the issue of "how best to define a meaningful response (eg, objective response rate, progression-free survival)."¹ We argue, because of the vagaries in interpreting MRIs in patients receiving BEV or other anti-angiogenic agents, the most meaningful endpoint is OS. Relative to this, we suggest literature can provide a valuable benchmark, as the OS outcome for these patients tends to be relatively uniform. Such a review of the literature² exemplifies this argument and compares well with the reported results in the cabozantinib study (ie, group 3 below):

Validation of a new prognostic model to easily predict outcome in renal cell carcinoma: the GRANT score applied to the ASSURE trial population

Ann Oncol 2017; 28: 2747–2753 (doi: 10.1093/annonc/mdx492)

SUPRA: open-source software-defined ultrasound processing for real-time applications

Abstract

Purpose

Research in ultrasound imaging is limited in reproducibility by two factors: First, many existing ultrasound pipelines are protected by intellectual property, rendering exchange of code difficult. Second, most pipelines are implemented in special hardware, resulting in limited flexibility of implemented processing steps on such platforms.

Methods

With SUPRA, we propose an open-source pipeline for fully software-defined ultrasound processing for real-time applications to alleviate these problems. Covering all steps from beamforming to output of B-mode images, SUPRA can help improve the reproducibility of results and make modifications to the image acquisition mode accessible to the research community. We evaluate the pipeline qualitatively, quantitatively, and regarding its run time.

Results

The pipeline shows image quality comparable to a clinical system and backed by point spread function measurements a comparable resolution. Including all processing stages of a usual ultrasound pipeline, the run-time analysis shows that it can be executed in 2D and 3D on consumer GPUs in real time.

Conclusions

Our software ultrasound pipeline opens up the research in image acquisition. Given access to ultrasound data from early stages (raw channel data, radiofrequency data), it simplifies the development in imaging. Furthermore, it tackles the reproducibility of research results, as code can be shared easily and even be executed without dedicated ultrasound hardware.

Effect of humic and fulvic acid transformation on cadmium availability to wheat cultivars in sewage sludge amended soil

Abstract

The high nutrients and organic matter (OM) content of sewage sludge make it an excellent fertilizer to enhance soil fertility and crop production. However, the presence of adsorbed and precipitated forms of heavy metals, especially cadmium (Cd), can be a major problem for such a utilization of sludge. This pot study aims at producing safe food with minimal Cd concentrations from sewage sludge amended soils. Two wheat cultivars (NARC-11 and Shafaq-06) were sown in soil amended with sewage sludge with rates 0, 15 and 30 g kg⁻¹ soil. Application of sewage sludge resulted in enhancement of wheat grain yield while Cd concentrations in wheat grains of both cultivars remained within permissible limits (24.1 to 58.6 μg kg⁻¹ dry weight). Fourier transform infrared (FTIR) spectroscopic analysis revealed more spectral changes in fulvic acids than in humic acids, which showed a higher humification degree, making them chemically and biologically more stable for Cd retention. Sequential extraction data of Cd after NARC-11 harvest exhibited a significant decrease in mobile fractions (exchangeable and reducible fractions were reduced by 3.6 and 5.2%, respectively) and increase in immobile fraction (the oxidizable and residual fractions increased by 7 and 1.8%, respectively). It is concluded that sewage sludge application could be useful for the improvement of wheat production due to formation of stable humate complexes and decrease in Cd availability.

Study on hydrothermal deactivation of Pt/MnO x -CeO 2 for NO x -assisted soot oxidation: redox property, surface nitrates, and oxygen vacancies

Abstract

The study mainly focuses on surface properties to investigate the deactivation factors of Pt/MnO_x -CeO₂ by H₂ temperature-programmed reduction, CO chemical adsorption, NO_x -temperature-programmed desorption (TPD), O₂-TPD, NO temperature-programmed oxidation, SEM, TEM, in situ diffuse reflectance infrared Fourier transform spectra, Raman, and thermogravimetric methods. The results show that there are three main factors to lead to hydrothermal deactivation of the catalyst: redox property, oxygen vacancy, and surface nitrates. The loss of oxygen vacancies decreases the generation and desorption of active oxygen and that of surface nitrates weakens the production of NO₂ and surface peroxides (-O₂⁻). These factors greatly result in the damage of the C-NO₂-O₂ cooperative reaction.

An evaluation of stabilised/solidified contaminated model soil using PC-based and MgO-based binders under semi-dynamic leaching conditions

Abstract

The leaching performance of stabilised/solidified contaminated model soil was studied to investigate the benefit of stabilisation/solidification treatment using novel binders over conventional binders. Different combinations of Portland cement (PC), ground granulated blast-furnace slag (GGBS), pulverised fly ash (PFA), and magnesia (MgO) were used and grouped into PC-based and MgO-based binders. A semi-dynamic leaching test was used, where the cumulative releases of Zn, Cu, Ni, Pb, Ca, and Mg were measured and the effective diffusion coefficients (De) and the leachability indices (LX) were calculated. The effects of different binders and water/cement ratios (w/c) on the migration of different metals after treatment were also discussed. The results showed that w/c ratio has a significant impact on the cumulative leachability of heavy metals. The diffusion coefficients of Pb and Zn are higher than those of Cu and Ni. In addition, mixes (w/c at 0.5:1) showed better performance in immobilising heavy metals than mixes (w/c at 1:1), especially in the case of Cu, Ni, and Pb.

Estimation of physicochemical properties of 2-ethylhexyl-4-methoxycinnamate (EHMC) degradation products and their toxicological evaluation

Abstract

The organic UV filters, commonly used in personal protection products, are of concern because of their potential risk to aquatic ecosystems and living organisms. One of UV filters is ethylhexyl-4-methoxycinnamate (EHMC) acid. Studies have shown that, in the presence of oxidizing and chlorinating factors, EHMC forms a series of products with different properties than the substrate. In this study, the toxicities of EHMC and its transformation/degradation products formed under the influence of NaOCl/UV and H₂O₂/UV systems in the water medium were tested using Microtox® bioassay and by observation of mortality of juvenile crustaceans Daphnia magna and Artemia Salina. We have observed that oxidation and chlorination products of EHMC show significantly higher toxicity than EHMC alone. The toxicity of chemicals is related to their physicochemical characteristic such as lipophilicity and substituent groups. With the increase in lipophilicity of products, expressed as log K_OW, the toxicity (EC₅₀) increases. On the basis of physicochemical properties such as vapour pressure (VP), solubility (S), octanol-water partition coefficient (K_OW), bioconcentration factor (BCF) and half-lives, the overall persistence (P_OV) and long-range transport potential (LRTP) of all the products and EHMC were calculated. It was shown that the most persistent and traveling on the long distances in environment are methoxyphenol chloroderivatives, then methoxybenzene chloroderivatives, EHMC chloroderivatives, methoxybenzaldehyde chloroderivatives and methoxycinnamate acid chloroderivatives. These compounds are also characterised by high toxicity.

Concentration effects of the UV filter oxybenzone in Cyperus alternifolius : assessment of tolerance by stress-related response

Abstract

Phytoremediation has been proposed to reduce the load of the sunscreen oxybenzone (OBZ) in the aquatic environment. Despite the proven removal efficiency of this compound, little is known about its influence, particularly oxidative stress on plants. In this study, a short-term incubation of macrophytic Cyperus alternifolius was performed to prove the plant's ability to withstand the stress. Detached shoots were immersed in medium spiked with different concentrations of OBZ (50, 100, and 500 μM) for 2, 4, and 7 days, respectively. Increased formation of O₂⁻ and H₂O₂ in Cyperus treated with OBZ was characterized by intense colorization following histochemical staining. Alterations of enzyme activities involved in the antioxidative defense system indicate an adaptive response of C. alternifolius to this xenobiotic stress. Quantification of lipid peroxidation reveals that no significant membrane damage occurred during incubation with OBZ. Overall, 50 μM OBZ (tenfold higher than the amount frequently detected in the environment) exhibited low toxic effects. Accordingly, this pilot study provides information on the potential use of Cyperus to remove emerging sunscreen contaminants from water bodies.

Eco-toxicology effect on Moina mongolica Daday exposed to Cd 2+ , Pb 2+ , and Hg 2+ by the food chain

Abstract

As one of the most important contaminants, heavy metals can seriously influence human health via the food chain. In this study, the eco-toxicological effects of Cd²⁺, Pb²⁺, and Hg²⁺ on Moina mongolica Daday were investigated by feeding them Chlorella sp. that contained heavy metals. The relative body lengths of the M. mongolica changed rapidly, peaking at 2 days for Hg²⁺, 6 days for Cd²⁺, and 8 days for Pb²⁺. Moreover, grazing and clearance rates of the experimental group were apparently lower than those of the control group after immersion in heavy metals. Additionally, Cd²⁺ and Pd²⁺ in the food significantly influenced the mean lifespan of M. mongolica of the P and F₁ generations. Egg production per brood was also significantly impacted by Cd²⁺ and Pb²⁺ in the food in generation P. Interestingly, Pb²⁺ was the only metal that significantly influenced the reproduction times of F₂, while the reproductive times were significantly influenced by Cd²⁺ for generation P. Moreover, Cd²⁺, Pb²⁺, and Hg²⁺ in the food significantly influenced the fecundity of generation P. Evaluation of the population growth parameters of M. mongolica revealed that the intrinsic rate of increase, net reproduction rate, and finite rate of increase were significantly influenced by Cd²⁺, Pb²⁺, and Hg²⁺ in the food in generation P. Additionally, Hg²⁺ slightly impacted generation time for generation P. Finally, the acute toxicity toward M. mongolica was Hg²⁺ > Cd²⁺ > Pb²⁺. Overall, heavy metals in the food were likely to influence the growth, survival, and population growth of M. mongolica through the food chain.

Τρίτη 27 Μαρτίου 2018

Information architecture for a patient-specific dashboard in head and neck tumor boards

Abstract

Purpose

Overcoming the flaws of current data management conditions in head and neck oncology could enable integrated information systems specifically tailored to the needs of medical experts in a tumor board meeting. Clinical dashboards are a promising method to assist various aspects of the decision-making process in such cognitively demanding scenarios. However, in order to provide extensive and intuitive assistance to the participating physicians, the design and development of such a system have to be user-centric. To accomplish this task, conceptual methods need to be performed prior to the technical development and integration stages.

Methods

We have conducted a qualitative survey including eight clinical experts with different levels of expertise in the field of head and neck oncology. According to the principles of information architecture, the survey focused on the identification and causal interconnection of necessary metrics for information assessment in the tumor board.

Results

Based on the feedback by the clinical experts, we have constructed a detailed map of the required information items for a tumor board dashboard in head and neck oncology. Furthermore, we have identified three distinct groups of metrics (patient, disease and therapy metrics) as well as specific recommendations for their structural and graphical implementation.

Conclusion

By using the information architecture, we were able to gather valuable feedback about the requirements and cognitive processes of the tumor board members. Those insights have helped us to develop a dashboard application that closely adapts to the specified needs and characteristics, and thus is primarily user-centric.

Reverence and Cheng-Zhu Ecology

Abstract

The Cheng-Zhu 程朱 school of Confucianism congealed from the larger Learning of the Way school in the 11th and 12th centuries. In contrast to Buddhist conceptions of human nature, Cheng-Zhu advocates claimed an understanding that gave a significant role to the natural world. Addressing the ecology of the human organism in its relationship with the natural environment revealed a complex moral psychology that characterized human beings. Self-cultivation was indispensable for connecting to our inborn nature that revealed no separation between ourselves and nature. Cultivating the mental state of maintaining reverence (chi jing 持敬) was an indispensable form of self-cultivation. This mental state initially expressed itself in courteous and caring behavior that could be taught to the young; but, when more highly developed, reverent attention was disciplined, focused thinking that revealed the mind of the Way. A new single-mindedness might then be maintained as the master of one's actions. The morally perfected states of being called humaneness and sagehood confirmed that one was in touch with one's inborn connection to nature.

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Τετάρτη 28 Μαρτίου 2018

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Τρίτη 27 Μαρτίου 2018

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