There is limited data on adherence to systemic medications for psoriasis in real-world practice. Using a large US health insurance claims database, we found significantly increased odds of adherence to biologics compared to methotrexate. Dermatologists should consider adherence when choosing systemic treatments for psoriasis patients.
Τετάρτη 4 Ιουλίου 2018
Drug Utilization Patterns and Adherence in Patients on Systemic Medications for the Treatment of Psoriasis: A Retrospective Comparative Cohort Study
Apremilast for moderate hidradenitis suppurativa: results of a randomized controlled trial
Publication date: Available online 3 July 2018
Source:Journal of the American Academy of Dermatology
Author(s): Allard R.J.V. Vossen, M.B.A. van Doorn, Hessel H. van der Zee, Errol P. Prens
BackgroundEffective anti-inflammatory treatments for hidradenitis suppurativa (HS) are limited.ObjectiveTo evaluate the efficacy and short-term safety of apremilast in patients with moderate HS.MethodsTwenty patients with moderate HS were randomised in a 3 : 1 ratio, to receive blinded treatment with apremilast 30 mg twice daily or placebo for 16 weeks. The primary outcome was the Hidradenitis Suppurativa Clinical Response (HiSCR) at week 16. Linear mixed effects modeling (ANCOVA) was used to assess secondary clinical outcomes between treatment groups.ResultsThe HiSCR was met in 8 of 15 (53.3%) patients in the apremilast group and none of 5 patients (0%) in the placebo group (P=0.055) at week 16. Moreover, apremilast-treated patients showed a significantly lower abscess and nodule count (mean difference -2.6; 95% confidence interval -6.0, -0.9; P=0.011), NRS for pain (-2.7; -4.5, -0.9; P=0.009) and itch (-2.8; -5.0, -0.6; P=0.015) over 16 weeks compared with placebo-treated patients. There was no significant difference in the DLQI over time between the two treatment groups (-3.4; -9.0, 2.3; P=0.230). The most frequently reported adverse events in the apremilast-treated patients were mild to moderate headache and gastro-intestinal symptoms, which have not resulted in drop-outs.LimitationsSmall number of patients, relatively short study duration.ConclusionApremilast at a dose of 30 mg twice daily demonstrated clinically meaningful efficacy and was generally well tolerated in patients with moderate HS.
A Phase 2, Randomized Dose-Finding Study of Tapinarof (GSK2894512 Cream) for the Treatment of Atopic Dermatitis
Publication date: Available online 3 July 2018
Source:Journal of the American Academy of Dermatology
Author(s): Johnny Peppers, Amy S. Paller, Tomoko Maeda-Chubachi, Sterling Wu, Kevin Robbins, Kelly Gallagher, John E. Kraus
BackgroundSafe and efficacious topical treatments are needed for atopic dermatitis (AD).ObjectiveWe assessed the safety and efficacy of tapinarof cream (2 concentrations; 2 application frequencies) in patients with AD.MethodsDouble-blind, vehicle-controlled, randomized, 6-arm trial (1:1:1:1:1:1) in patients aged 12-65 years, with body surface area (BSA) involvement ≥5% and ≤35% and Investigator Global Assessment (IGA) ≥3 (moderate-severe) at Baseline. Primary endpoint included IGA score of clear or almost clear (0 or 1), and minimum 2-grade improvement ("treatment success") at Week 12. Secondary analyses: ≥ 75% improvement in Eczema Area Severity Index (EASI 75), reduction of numeric rating scale (NRS) Itch from Baseline, and other prespecified endpoints.ResultsTreatment success rates at Week 12 were: 53% [1% BID]; 46% [1% QD]; 37% [0.5% BID]; 34% [0.5% QD]; 24% [vehicle BID]; 28% [vehicle QD]. The rate (53%) of 1% BID was statistically significantly higher than (24%) vehicle BID. Treatment success was maintained for 4 weeks after end of tapinarof treatment. Treatment-emergent adverse events (TEAE) were higher with tapinarof (93/165; 56%) vs. vehicle (34/82; 41%) and mild-to-moderate in intensity.LimitationsLarge confirmation trials are needed.ConclusionsTapinarof cream is efficacious and well tolerated in adolescent and adult patients with AD.
A Comparison of Skin Cancer Screening and Treatment Costs at a Massachusetts Cancer Center, 2008 versus 2013
Publication date: Available online 3 July 2018
Source:Journal of the American Academy of Dermatology
Author(s): Frederick C. Morgan, Juanita Duran, Belen Fraile, Pritesh S. Karia, Jennifer Y. Lin, Patrick A. Ott, Emily Stamell Ruiz, David M. Wang, Yichen Zhang, Chrysalyne D. Schmults
BackgroundTemporal analyses of skin cancer costs are needed to examine how expenditure differences between diagnoses are changing.ObjectiveTo tabulate the costs of skin cancer-related care (SCRC), including both screening and treatment, at an academic cancer center at two time points.MethodsCost data (insurance and patient payments) at an academic cancer center from 2008 and 2013 were queried for International Classification of Diseases, Ninth Revision (ICD-9) codes pertaining to skin cancer. Screening costs were separated from treatment costs through associated Current Procedure Terminology (CPT) codes.ResultsThe total annual cost of SCRC increased by 64%, the number of patients receiving SCRC increased by 45%, and the mean cost per patient treated increased by 13%. Screening accounted for 17% and 16% of total annual costs in 2008 and 2013, respectively. The mean cost per melanoma patient increased by 84%, which was the largest increase among skin cancer diagnoses. In 2013, the few melanoma patients treated with ipilimumab (n=48, 4% of melanoma patients) accounted for 42% of melanoma treatment costs and 20% of SCRC costs.LimitationsPrescription costs were unavailableConclusionMelanoma costs increased due to the introduction of ipilimumab. Ongoing studies are needed to monitor SCRC cost-effectiveness at a national level.
Chronic Non-Melanoma Skin Cancers and Health Related Impairment: A Case-Control Study
Publication date: Available online 3 July 2018
Source:Journal of the American Academy of Dermatology
Author(s): Adam Sutton, Ashley Crew, Shauna Higgins, Andrew Kwong, Ashley Wysong
Comparative health risk of inhaled exposure to organic solvents, toxic metals, and hexavalent chromium from the use of spray paints in Taiwan
Abstract
The study investigated the exposure of spray painters to organic solvents, toxic metals, and hexavalent chromium over 21 working days in 2017. The results found these concentrations of 12 VOCs to be below the short-term exposure limit (STEL) established by the US Occupational Safety and Health Administration (OSHA). The mass concentration of total particulate matter (PM) exposure to workers was 20.01 ± 10.78 mg/m3, which exceeds OSHA's permissible exposure level of 15 mg/m3. The mean concentration of the total metals for all particle sizes was 109.1 ± 12.0 μg/m3, and those for lead (496,017.0 ng/m3) and iron (252,123.8 ng/m3) were the highest of metal elements. Significantly, the mean concentrations of Pb and As exceeded OSHA's permissible exposure limits (PELs) of 0.05 and 0.01 mg/m3, respectively. The total hexavalent chromium concentration was 1163.01 ng/m3, and the individual particle sizes (PM1−2.5, PM1, and PM0.25) were strongly and positively correlated with the Cr(VI) concentrations for PM2.5. The study determined that approximately 56.14% of the hexavalent chromium inhaled during the spray-painting process was deposited in the upper respiratory system of the head airway region, followed by the alveolar and tracheobronchial regions, with fractions of 11.93 and 0.05%, respectively. Although the mean ratio of hexavalent chromium to total chromium was only 3.6% for all particle sizes, the cancer risk of the total particles in Cr(VI) (1.6 × 10−3) exceeded the acceptable risk value (10−6). The cancer risks of As and Cr(VI) associated with quasi-ultrafine particles, PM0.5–1, PM1–2.5, and PM> 2.5, also exceeded 10−6. Comparison of the carcinogenicity risk of VOCs and metals suggests that the adverse health effect of inhaled particles on spray-painting workers is more serious than that from VOC exposure.
Industry mimetic isomorphism and sustainable development based on the X-STATIS and HJ-biplot methods
Abstract
Based on both neo-institutional theory and comparative institutional analysis, this paper studies the role that mimetic forces play in the patterns and evolution of behavior concerning company sustainability. The panel data is composed of 6600 observations of 600 international large listed companies belonging to 39 different activity sectors for the period 2004–2014. Through employing the multivariate statistical methods HJ-biplot and X-STATIS, which provide a useful visualization of a complex data structure in a low-dimensional space, it can be observed that mimetic forces indicate that firms operating in high-impact sectors—sectors that operate under greater pressure from interest groups—face greater social and environmental risks and have higher corporate social responsibility (CSR) scores than companies from other sectors. The adoption or development of CSR practices depends largely on the type of industry in which the company operates, as stakeholder engagement in different industry sectors has different areas of concern. Therefore, companies operating in more polluting sectors, such as mining, paper, chemicals, or oil, give higher priority to environmental protection and defense of human rights, while other, less polluting companies involved in the communication sector are concerned to a greater extent by social issues, such as business ethics or the rights of their employees. Finally, this paper evidences that firms operating in similar contexts, in industries that face analogous risks and challenges, probably develop common policies and regulations with the aim of mitigating the pressures applied by their major stakeholder groups.
Alcohol Consumption during Adolescence in a Mouse Model of Binge Drinking Alters the Intrinsic Excitability and Function of the Prefrontal Cortex through a Reduction in the Hyperpolarization-Activated Cation Current
Periodic episodes of excessive alcohol consumption ("binge drinking") occur frequently among adolescents, and early binge drinking is associated with an increased risk of alcohol use disorders later in life. The PFC undergoes significant development during adolescence and hence may be especially susceptible to the effects of binge drinking. In humans and in animal models, adolescent alcohol exposure is known to alter PFC neuronal activity and produce deficits in PFC-dependent behaviors, such as decision making, response inhibition, and working memory. Using a voluntary intermittent access to alcohol (IA EtOH) procedure in male mice, we demonstrate that binge-level alcohol consumption during adolescence leads to altered drinking patterns and working memory deficits in young adulthood, two outcomes that suggest medial PFC dysfunction. We recorded from pyramidal neurons (PNs) in the prelimbic subregion of the medial PFC in slices obtained from mice that had IA EtOH and found that they display altered excitability, including a hyperpolarization of the resting membrane potential and reductions in the hyperpolarization-activated cation current (Ih) and in intrinsic persistent activity (a mode of neuronal firing that is dependent on Ih). Many of these effects on intrinsic excitability were sustained following abstinence and observed in mice that showed working memory deficits. In addition, we found that resting membrane potential and the Ih-dependent voltage "sag" in prelimbic PFC PNs are developmentally regulated during adolescence, suggesting that adolescent alcohol exposure may compromise PFC function by arresting the normal developmental trajectory of PN intrinsic excitability.
SIGNIFICANCE STATEMENT Binge alcohol drinking during adolescence has negative consequences for the function of the developing PFC. Using a mouse model of voluntary binge drinking during adolescence, we found that this behavior leads to working memory deficits and altered drinking behavior in adulthood. In addition, we found that adolescent drinking is associated with specific changes to the intrinsic excitability of pyramidal neurons in the PFC, reducing the ability of these neurons to generate intrinsic persistent activity, a phenomenon thought to be important for working memory. These findings may help explain why human adolescent binge drinkers show performance deficits on tasks mediated by the PFC.
{alpha}2{delta}-4 Is Required for the Molecular and Structural Organization of Rod and Cone Photoreceptor Synapses
α2-4 is an auxiliary subunit of voltage-gated Cav1.4 L-type channels that regulate the development and mature exocytotic function of the photoreceptor ribbon synapse. In humans, mutations in the CACNA2D4 gene encoding α2-4 cause heterogeneous forms of vision impairment in humans, the underlying pathogenic mechanisms of which remain unclear. To investigate the retinal function of α2-4, we used genome editing to generate an α2-4 knock-out (α2-4 KO) mouse. In male and female α2-4 KO mice, rod spherules lack ribbons and other synaptic hallmarks early in development. Although the molecular organization of cone synapses is less affected than rod synapses, horizontal and cone bipolar processes extend abnormally in the outer nuclear layer in α2-4 KO retina. In reconstructions of α2-4 KO cone pedicles by serial block face scanning electron microscopy, ribbons appear normal, except that less than one-third show the expected triadic organization of processes at ribbon sites. The severity of the synaptic defects in α2-4 KO mice correlates with a progressive loss of Cav1.4 channels, first in terminals of rods and later cones. Despite the absence of b-waves in electroretinograms, visually guided behavior is evident in α2-4 KO mice and better under photopic than scotopic conditions. We conclude that α2-4 plays an essential role in maintaining the structural and functional integrity of rod and cone synapses, the disruption of which may contribute to visual impairment in humans with CACNA2D4 mutations.
SIGNIFICANCE STATEMENT In the retina, visual information is first communicated by the synapse formed between photoreceptors and second-order neurons. The mechanisms that regulate the structural integrity of this synapse are poorly understood. Here we demonstrate a role for α2-4, a subunit of voltage-gated Ca2+ channels, in organizing the structure and function of photoreceptor synapses. We find that presynaptic Ca2+ channels are progressively lost and that rod and cone synapses are disrupted in mice that lack α2-4. Our results suggest that alterations in presynaptic Ca2+ signaling and photoreceptor synapse structure may contribute to vision impairment in humans with mutations in the CACNA2D4 gene encoding α2-4.
Loss of CaMKI Function Disrupts Salt Aversive Learning in C. elegans
The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. Caenorhabditis elegans can learn to avoid sodium chloride when it is paired with starvation. This behavior may help animals avoid areas without food. Although some genes have been implicated in this salt-aversive learning behavior, critical genetic components, and the neural circuit in which they act, remain elusive. Here, we show that the sole worm ortholog of mammalian CaMKI/IV, CMK-1, is essential for salt-aversive learning behavior in C. elegans hermaphrodites. We find that CMK-1 acts in the primary salt-sensing ASE neurons to regulate this behavior. By characterizing the intracellular calcium dynamics in ASE neurons using microfluidics, we find that loss of cmk-1 has subtle effects on sensory-evoked calcium responses in ASE axons and their modulation by salt conditioning. Our study implicates the expression of the conserved CaMKI/CMK-1 in chemosensory neurons as a regulator of behavioral plasticity to environmental salt in C. elegans.
SIGNIFICANCE STATEMENT Like other animals, the nematode Caenorhabditis elegans depends on salt for survival and navigates toward high concentrations of this essential mineral. In addition to its role as an essential nutrient, salt also causes osmotic stress at high concentrations. A growing body of evidence indicates that C. elegans balances the requirement for salt with the danger it presents through a process called salt-aversive learning. We show that this behavior depends on expression of a calcium/calmodulin-dependent kinase, CMK-1, in the ASE salt-sensing neurons. Our study identifies CMK-1 and salt-sensitive chemosensory neurons as key factors in this form of behavioral plasticity.
Deep Neural Networks for Modeling Visual Perceptual Learning
Understanding visual perceptual learning (VPL) has become increasingly more challenging as new phenomena are discovered with novel stimuli and training paradigms. Although existing models aid our knowledge of critical aspects of VPL, the connections shown by these models between behavioral learning and plasticity across different brain areas are typically superficial. Most models explain VPL as readout from simple perceptual representations to decision areas and are not easily adaptable to explain new findings. Here, we show that a well -known instance of deep neural network (DNN), whereas not designed specifically for VPL, provides a computational model of VPL with enough complexity to be studied at many levels of analyses. After learning a Gabor orientation discrimination task, the DNN model reproduced key behavioral results, including increasing specificity with higher task precision, and also suggested that learning precise discriminations could transfer asymmetrically to coarse discriminations when the stimulus conditions varied. Consistent with the behavioral findings, the distribution of plasticity moved toward lower layers when task precision increased and this distribution was also modulated by tasks with different stimulus types. Furthermore, learning in the network units demonstrated close resemblance to extant electrophysiological recordings in monkey visual areas. Altogether, the DNN fulfilled predictions of existing theories regarding specificity and plasticity and reproduced findings of tuning changes in neurons of the primate visual areas. Although the comparisons were mostly qualitative, the DNN provides a new method of studying VPL, can serve as a test bed for theories, and assists in generating predictions for physiological investigations.
SIGNIFICANCE STATEMENT Visual perceptual learning (VPL) has been found to cause changes at multiple stages of the visual hierarchy. We found that training a deep neural network (DNN) on an orientation discrimination task produced behavioral and physiological patterns similar to those found in human and monkey experiments. Unlike existing VPL models, the DNN was pre-trained on natural images to reach high performance in object recognition, but was not designed specifically for VPL; however, it fulfilled predictions of existing theories regarding specificity and plasticity and reproduced findings of tuning changes in neurons of the primate visual areas. When used with care, this unbiased and deep-hierarchical model can provide new ways of studying VPL from behavior to physiology.
Neural Coding of Whisker-Mediated Touch in Primary Somatosensory Cortex Is Altered Following Early Blindness
Sensory systems do not develop and function independently of one another, yet they are typically studied in isolation. Effects of multisensory interactions on the developing neocortex can be revealed by altering the ratios of incoming sensory inputs associated with different modalities. We investigated neural responses in primary somatosensory cortex (S1) of short-tailed opossums (Monodelphis domestica; either sex) after the elimination of visual input through bilateral enucleation very early in development. To assess the influence of tactile experience after vision loss, we also examined naturally occurring patterns of exploratory behavior. In early blind (EB) animals, overall levels of tactile experience were similar to those of sighted controls (SC); locomotor activity was unimpaired and accompanied by whisking. Using extracellular single-unit recording techniques under anesthesia, we found that EB animals exhibited a reduction in the magnitude of neural responses to whisker stimuli in S1, coupled with spatial sharpening of receptive fields, in comparison to SC animals. These alterations manifested as two different effects on sensory processing in S1 of EB animals: the ability of neurons to detect single whisker stimulation was decreased, whereas their ability to discriminate between stimulation of neighboring whiskers was enhanced. The increased selectivity of S1 neurons in EB animals was reflected in improved population decoding performance for whisker stimulus position, particularly along the rostrocaudal axis of the snout, which aligns with the primary axis of natural whisker motion. These findings suggest that a functionally distinct form of somatosensory plasticity occurs when vision is lost early in development.
SIGNIFICANCE STATEMENT After sensory loss, compensatory behavior mediated through the spared senses could be generated entirely through the recruitment of brain areas associated with the deprived sense. Alternatively, functional compensation in spared modalities may be achieved through a combination of plasticity in brain areas corresponding to both spared and deprived sensory modalities. Although activation of neurons in cortex associated with a deprived sense has been described frequently, it is unclear whether this is the only substrate available for compensation or if plasticity within cortical fields corresponding to spared modalities, particularly primary sensory cortices, may also contribute. Here, we demonstrate empirically that early loss of vision alters coding of sensory inputs in primary somatosensory cortex in a manner that supports enhanced tactile discrimination.
Differential Neurotoxicity Related to Tetracycline Transactivator and TDP-43 Expression in Conditional TDP-43 Mouse Model of Frontotemporal Lobar Degeneration
Frontotemporal lobar degeneration (FTLD) is among the most prevalent dementias of early-onset. Pathologically, FTLD presents with tauopathy or TAR DNA-binding protein 43 (TDP-43) proteinopathy. A biallelic mouse model of FTLD was produced on a mix FVB/129SVE background overexpressing wild-type human TDP-43 (hTDP-43) using tetracycline transactivator (tTA), a system widely used in mouse models of neurological disorders. tTA activates hTDP-43, which is placed downstream of the tetracycline response element. The original study on this transgenic mouse found hippocampal degeneration following hTDP-43 expression, but did not account for independent effects of tTA protein. Here, we initially analyzed the neurotoxic effects of tTA in postweaning age mice of either sex using immunostaining and area measurements of select brain regions. We observed tTA-dependent toxicity selectively in the hippocampus affecting the dentate gyrus significantly more than CA fields, whereas hTDP-43-dependent toxicity in bigenic mice occurred in most other cortical regions. Atrophy was associated with inflammation, activation of caspase-3, and loss of neurons. The atrophy associated with tTA expression was rescuable by the tetracycline analog, doxycycline, in the diet. MRI studies corroborated the patterns of atrophy. tTA-induced degeneration was strain-dependent and was rescued by moving the transgene onto a congenic C57BL/6 background. Despite significant hippocampal atrophy, behavioral tests in bigenic mice revealed no hippocampally mediated memory impairment. Significant atrophy in most cortical areas due solely to TDP-43 expression indicates that this mouse model remains useful for providing critical insight into co-occurrence of TDP-43 pathology, neurodegeneration, and behavioral deficits in FTLD.
SIGNIFICANCE STATEMENT The tTA expression system has been widely used in mice to model neurological disorders. The technique allows investigators to reversibly turn on or off disease causing genes. Here, we report on a mouse model that overexpresses human TDP-43 using tTA and attempt to recapitulate features of TDP-43 pathology present in human FTLD. The tTA expression system is problematic, resulting in dramatic degeneration of the hippocampus. Thus, our study adds a note of caution for the use of the tTA system. However, because FTLD is primarily characterized by cortical degeneration and our mouse model shows significant atrophy in most cortical areas due to human TDP-43 overexpression, our animal model remains useful for providing critical insight on this human disease.
Glial {beta}II Spectrin Contributes to Paranode Formation and Maintenance
Action potential conduction along myelinated axons depends on high densities of voltage-gated Na+ channels at the nodes of Ranvier. Flanking each node, paranodal junctions (paranodes) are formed between axons and Schwann cells in the peripheral nervous system (PNS) or oligodendrocytes in the CNS. Paranodal junctions contribute to both node assembly and maintenance. Despite their importance, the molecular mechanisms responsible for paranode assembly and maintenance remain poorly understood. βII spectrin is expressed in diverse cells and is an essential part of the submembranous cytoskeleton. Here, we show that Schwann cell βII spectrin is highly enriched at paranodes. To elucidate the roles of glial βII spectrin, we generated mutant mice lacking βII spectrin in myelinating glial cells by crossing mice with a floxed allele of Sptbn1 with Cnp-Cre mice, and analyzed both male and female mice. Juvenile (4 weeks) and middle-aged (60 weeks) mutant mice showed reduced grip strength and sciatic nerve conduction slowing, whereas no phenotype was observed between 8 and 24 weeks of age. Consistent with these findings, immunofluorescence microscopy revealed disorganized paranodes in the PNS and CNS of both postnatal day 13 and middle-aged mutant mice, but not in young adult mutant mice. Electron microscopy confirmed partial loss of transverse bands at the paranodal axoglial junction in the middle-aged mutant mice in both the PNS and CNS. These findings demonstrate that a spectrin-based cytoskeleton in myelinating glia contributes to formation and maintenance of paranodal junctions.
SIGNIFICANCE STATEMENT Myelinating glia form paranodal axoglial junctions that flank both sides of the nodes of Ranvier. These junctions contribute to node formation and maintenance and are essential for proper nervous system function. We found that a submembranous spectrin cytoskeleton is highly enriched at paranodes in Schwann cells. Ablation of βII spectrin in myelinating glial cells disrupted the paranodal cell adhesion complex in both peripheral and CNSs, resulting in muscle weakness and sciatic nerve conduction slowing in juvenile and middle-aged mice. Our data show that a spectrin-based submembranous cytoskeleton in myelinating glia plays important roles in paranode formation and maintenance.
Perineuronal Nets in the Deep Cerebellar Nuclei Regulate GABAergic Transmission and Delay Eyeblink Conditioning
Perineuronal nets (PNNs), composed mainly of chondroitin sulfate proteoglycans, are the extracellular matrix that surrounds cell bodies, proximal dendrites, and axon initial segments of adult CNS neurons. PNNs are known to regulate neuronal plasticity, although their physiological roles in cerebellar functions have yet to be elucidated. Here, we investigated the contribution of PNNs to GABAergic transmission from cerebellar Purkinje cells (PCs) to large glutamatergic neurons in the deep cerebellar nuclei (DCN) in male mice by recording IPSCs from cerebellar slices, in which PNNs were depleted with chondroitinase ABC (ChABC). We found that PNN depletion increased the amplitude of evoked IPSCs and enhanced the paired-pulse depression. ChABC treatment also facilitated spontaneous IPSCs and increased the miniature IPSC frequency without changing not only the amplitude but also the density of PC terminals, suggesting that PNN depletion enhances presynaptic GABA release. We also demonstrated that the enhanced GABAergic transmission facilitated rebound firing in large glutamatergic DCN neurons, which is expected to result in the efficient induction of synaptic plasticity at synapses onto DCN neurons. Furthermore, we tested whether PNN depletion affects cerebellar motor learning. Mice having received the enzyme into the interpositus nuclei, which are responsible for delay eyeblink conditioning, exhibited the conditioned response at a significantly higher rate than control mice. Therefore, our results suggest that PNNs of the DCN suppress GABAergic transmission between PCs and large glutamatergic DCN neurons and restrict synaptic plasticity associated with motor learning in the adult cerebellum.
SIGNIFICANCE STATEMENT Perineuronal nets (PNNs) are one of the extracellular matrices of adult CNS neurons and implicated in regulating various brain functions. Here we found that enzymatic PNN depletion in the mouse deep cerebellar nuclei (DCN) reduced the paired-pulse ratio of IPSCs and increased the miniature IPSC frequency without changing the amplitude, suggesting that PNN depletion enhances GABA release from the presynaptic Purkinje cell (PC) terminals. Mice having received the enzyme in the interpositus nuclei exhibited a higher conditioned response rate in delay eyeblink conditioning than control mice. These results suggest that PNNs regulate presynaptic functions of PC terminals in the DCN and functional plasticity of synapses on DCN neurons, which influences the flexibility of adult cerebellar functions.
Neural Prediction Errors Distinguish Perception and Misperception of Speech
Humans use prior expectations to improve perception, especially of sensory signals that are degraded or ambiguous. However, if sensory input deviates from prior expectations, then correct perception depends on adjusting or rejecting prior expectations. Failure to adjust or reject the prior leads to perceptual illusions, especially if there is partial overlap (and thus partial mismatch) between expectations and input. With speech, "slips of the ear" occur when expectations lead to misperception. For instance, an entomologist might be more susceptible to hear "The ants are my friends" for "The answer, my friend" (in the Bob Dylan song Blowing in the Wind). Here, we contrast two mechanisms by which prior expectations may lead to misperception of degraded speech. First, clear representations of the common sounds in the prior and input (i.e., expected sounds) may lead to incorrect confirmation of the prior. Second, insufficient representations of sounds that deviate between prior and input (i.e., prediction errors) could lead to deception. We used crossmodal predictions from written words that partially match degraded speech to compare neural responses when male and female human listeners were deceived into accepting the prior or correctly reject it. Combined behavioral and multivariate representational similarity analysis of fMRI data show that veridical perception of degraded speech is signaled by representations of prediction error in the left superior temporal sulcus. Instead of using top-down processes to support perception of expected sensory input, our findings suggest that the strength of neural prediction error representations distinguishes correct perception and misperception.
SIGNIFICANCE STATEMENT Misperceiving spoken words is an everyday experience, with outcomes that range from shared amusement to serious miscommunication. For hearing-impaired individuals, frequent misperception can lead to social withdrawal and isolation, with severe consequences for wellbeing. In this work, we specify the neural mechanisms by which prior expectations, which are so often helpful for perception, can lead to misperception of degraded sensory signals. Most descriptive theories of illusory perception explain misperception as arising from a clear sensory representation of features or sounds that are in common between prior expectations and sensory input. Our work instead provides support for a complementary proposal: that misperception occurs when there is an insufficient sensory representations of the deviation between expectations and sensory signals.
Neural Network Interactions Modulate CRY-Dependent Photoresponses in Drosophila
Light is one of the chief environmental cues that reset circadian clocks. In Drosophila, CRYPTOCHROME (CRY) mediates acute photic resetting of circadian clocks by promoting the degradation of TIMELESS in a cell-autonomous manner. Thus, even circadian oscillators in peripheral organs can independently perceive light in Drosophila. However, there is substantial evidence for nonautonomous mechanisms of circadian photoreception in the brain. We have previously shown that the morning (M) and evening (E) oscillators are critical light-sensing neurons that cooperate to shift the phase of circadian behavior in response to light input. We show here that light can efficiently phase delay or phase advance circadian locomotor behavior in male Drosophila even when either the M- or the E-oscillators are ablated, suggesting that behavioral phase shifts and their directionality are largely a consequence of the cell-autonomous nature of CRY-dependent photoreception. Our observation that the phase response curves of brain and peripheral oscillators are remarkably similar further supports this idea. Nevertheless, the neural network modulates circadian photoresponses. We show that the M-oscillator neurotransmitter pigment dispersing factor plays a critical role in the coordination between M- and E-oscillators after light exposure, and we uncover a potential role for a subset of dorsal neurons in the control of phase advances. Thus, neural modulation of autonomous light detection might play an important role in the plasticity of circadian behavior.
SIGNIFICANCE STATEMENT Input pathways provide circadian rhythms with the flexibility needed to harmonize their phase with environmental cycles. Light is the chief environmental cue that synchronizes circadian clocks. In Drosophila, the photoreceptor CRYPTOCHROME resets circadian clocks cell-autonomously. However, recent studies indicate that, in the brain, interactions between clock neurons are critical to reset circadian locomotor behavior. We present evidence supporting the idea that the ability of flies to advance or delay their rhythmic behavior in response to light input essentially results from cell-autonomous photoreception. However, because of their networked organization, we find that circadian neurons have to cooperate to reset the phase of circadian behavior in response to photic cues. Our work thus helps to reconcile cell-autonomous and non-cell-autonomous models of circadian entrainment.
Nerve Injury-Induced Chronic Pain Is Associated with Persistent DNA Methylation Reprogramming in Dorsal Root Ganglion
Nerve injury-induced hyperactivity of primary sensory neurons in the dorsal root ganglion (DRG) contributes to chronic pain development, but the underlying epigenetic mechanisms remain poorly understood. Here we determined genome-wide changes in DNA methylation in the nervous system in neuropathic pain. Spinal nerve ligation (SNL), but not paclitaxel treatment, in male Sprague Dawley rats induced a consistent low-level hypomethylation in the CpG sites in the DRG during the acute and chronic phases of neuropathic pain. DNA methylation remodeling in the DRG occurred early after SNL and persisted for at least 3 weeks. SNL caused DNA methylation changes at 8% of CpG sites with prevailing hypomethylation outside of CpG islands, in introns, intergenic regions, and repetitive sequences. In contrast, SNL caused more gains of methylation in the spinal cord and prefrontal cortex. The DNA methylation changes in the injured DRGs recapitulated developmental reprogramming at the neonatal stage. Methylation reprogramming was correlated with increased gene expression variability. A diet deficient in methyl donors induced hypomethylation and pain hypersensitivity. Intrathecal administration of the DNA methyltransferase inhibitor RG108 caused long-lasting pain hypersensitivity. DNA methylation reprogramming in the DRG thus contributes to nerve injury-induced chronic pain. Restoring DNA methylation may represent a new therapeutic approach to treat neuropathic pain.
SIGNIFICANCE STATEMENT Epigenetic mechanisms are critically involved in the transition from acute to chronic pain after nerve injury. However, genome-wide changes in DNA methylation in the nervous system and their roles in neuropathic pain development remain unclear. Here we used digital restriction enzyme analysis of methylation to quantitatively determine genome-wide DNA methylation changes caused by nerve injury. We showed that nerve injury caused DNA methylation changes at 8% of CpG sites with prevailing hypomethylation outside of CpG islands in the dorsal root ganglion. Reducing DNA methylation induced pain hypersensitivity, whereas increasing DNA methylation attenuated neuropathic pain. These findings extend our understanding of the epigenetic mechanism of chronic neuropathic pain and suggest new strategies to treat nerve injury-induced chronic pain.
Classification of Neurons in the Primate Reticular Formation and Changes after Recovery from Pyramidal Tract Lesion
The reticular formation is important in primate motor control, both in health and during recovery after brain damage. Little is known about the different neurons present in the reticular nuclei. Here we recorded extracellular spikes from the reticular formation in five healthy female awake behaving monkeys (193 cells), and in two female monkeys 1 year after recovery from a unilateral pyramidal tract lesion (125 cells). Analysis of spike shape and four measures derived from the interspike interval distribution identified four clusters of neurons in control animals. Cluster 1 cells had a slow firing rate. Cluster 2 cells had narrow spikes and irregular firing, which often included high-frequency bursts. Cluster 3 cells were highly rhythmic and fast firing. Cluster 4 cells showed negative spikes. A separate population of 42 cells was antidromically identified as reticulospinal neurons in five anesthetized female monkeys. The distribution of spike width in these cells closely overlaid the distribution for cluster 2, leading us tentatively to suggest that cluster 2 included neurons with reticulospinal projections. In animals after corticospinal lesion, cells could be identified in all four clusters. The firing rate of cells in clusters 1 and 2 was increased in lesioned animals relative to control animals (by 52% and 60%, respectively); cells in cluster 2 were also more regular and more bursting in the lesioned animals. We suggest that changes in both membrane properties and local circuits within the reticular formation occur following lesioning, potentially increasing reticulospinal output to help compensate for lost corticospinal descending drive.
SIGNIFICANCE STATEMENT This work is the first to subclassify neurons in the reticular formation, providing insights into the local circuitry of this important but little understood structure. The approach developed can be applied to any extracellular recording from this region, allowing future studies to place their data within our current framework of four neural types. Changes in reticular neurons may be important to subserve functional recovery after damage in human patients, such as after stroke or spinal cord injury.
Activating Transcription Factor 4 (ATF4) Regulates Neuronal Activity by Controlling GABABR Trafficking
Activating Transcription Factor 4 (ATF4) has been postulated as a key regulator of learning and memory. We previously reported that specific hippocampal ATF4 downregulation causes deficits in synaptic plasticity and memory and reduction of glutamatergic functionality. Here we extend our studies to address ATF4's role in neuronal excitability. We find that long-term ATF4 knockdown in cultured rat hippocampal neurons significantly increases the frequency of spontaneous action potentials. This effect is associated with decreased functionality of metabotropic GABAB receptors (GABABRs). Knocking down ATF4 results in significant reduction of GABABR-induced GIRK currents and increased mIPSC frequency. Furthermore, reducing ATF4 significantly decreases expression of membrane-exposed, but not total, GABABR 1a and 1b subunits, indicating that ATF4 regulates GABABR trafficking. In contrast, ATF4 knockdown has no effect on surface expression of GABABR2s, several GABABR-coupled ion channels or β2 and 2 GABAARs. Pharmacologic manipulations confirmed the relationship between GABABR functionality and action potential frequency in our cultures. Specifically, the effects of ATF4 downregulation cited above are fully rescued by transcriptionally active, but not by transcriptionally inactive, shRNA-resistant, ATF4. We previously reported that ATF4 promotes stabilization of the actin-regulatory protein Cdc42 by a transcription-dependent mechanism. To test the hypothesis that this action underlies the mechanism by which ATF4 loss affects neuronal firing rates and GABABR trafficking, we downregulated Cdc42 and found that this phenocopies the effects of ATF4 knockdown on these properties. In conclusion, our data favor a model in which ATF4, by regulating Cdc42 expression, affects trafficking of GABABRs, which in turn modulates the excitability properties of neurons.
SIGNIFICANCE STATEMENT GABAB receptors (GABABRs), the metabotropic receptors for the inhibitory neurotransmitter GABA, have crucial roles in controlling the firing rate of neurons. Deficits in trafficking/functionality of GABABRs have been linked to a variety of neurological and psychiatric conditions, including epilepsy, anxiety, depression, schizophrenia, addiction, and pain. Here we show that GABABRs trafficking is influenced by Activating Transcription Factor 4 (ATF4), a protein that has a pivotal role in hippocampal memory processes. We found that ATF4 downregulation in hippocampal neurons reduces membrane-bound GABABR levels and thereby increases intrinsic excitability. These effects are mediated by loss of the small GTPase Cdc42 following ATF4 downregulation. These findings reveal a critical role for ATF4 in regulating the modulation of neuronal excitability by GABABRs.
Oscillatory Encoding of Visual Stimulus Familiarity
Familiarity of the environment changes the way we perceive and encode incoming information. However, the neural substrates underlying this phenomenon are poorly understood. Here we describe a new form of experience-dependent low-frequency oscillations in the primary visual cortex (V1) of awake adult male mice. The oscillations emerged in visually evoked potentials and single-unit activity following repeated visual stimulation. The oscillations were sensitive to the spatial frequency content of a visual stimulus and required the mAChRs for their induction and expression. Finally, ongoing visually evoked (4–8 Hz) oscillations boost the visually evoked potential amplitude of incoming visual stimuli if the stimuli are presented at the high excitability phase of the oscillations. Our results demonstrate that an oscillatory code can be used to encode familiarity and serves as a gate for oncoming sensory inputs.
SIGNIFICANCE STATEMENT Previous experience can influence the processing of incoming sensory information by the brain and alter perception. However, the mechanistic understanding of how this process takes place is lacking. We have discovered that persistent low-frequency oscillations in the primary visual cortex encode information about familiarity and the spatial frequency of the stimulus. These familiarity evoked oscillations influence neuronal responses to the oncoming stimuli in a way that depends on the oscillation phase. Our work demonstrates a new mechanism of visual stimulus feature detection and learning.
Eosinophilic Esophagitis and the Eosinophilic Gastrointestinal Diseases: Approach to diagnosis and management
Publication date: Available online 3 July 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Erin Steinbach, Michelle Hernandez, Evan S. Dellon
The eosinophilic gastrointestinal diseases (EGID) represent disorders of the GI tract that result from the local infiltration and aberrant activity of eosinophils and other immune cells. Eosinophilic esophagitis is the most well-characterized EGID and is defined by the presence of intraepithelial eosinophils in the esophagus (≥15 eosinophils per high powered field) and clinical symptoms associated with esophageal dysfunction. The other EGID are rare and lack strong data regarding pathogenesis and management. The incidence and prevalence of EoE are increasing, and EoE is now a major cause of upper GI morbidity. Management is multidisciplinary, with collaboration between gastroenterologists, allergists, pathologists, and dieticians, and is aimed at amelioration of symptoms and prevention of long-term complications such as esophageal stricture. Treatment options for EoE include proton pump inhibitors, swallowed topical corticosteroids, and elimination diets. Esophageal dilation is used when esophageal strictures or fibrostenotic changes are present. Additional therapies targeting eosinophils and other mediators of Th2 inflammation are under development and are promising. Treatment options for other EGIDs typically involve corticosteroids or dietary elimination.
Recommendations for the Use of Etoposide-Based Therapy and Bone Marrow Transplantation for the Treatment of HLH: Consensus Statements by the HLH Steering Committee of the Histiocyte Society
Publication date: Available online 4 July 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Stephan Ehl, Itziar Astigarraga, Tatiana von Bahr Greenwood, Melissa Hines, AnnaCarin Horne, Eiichi Ishii, Gritta Janka, Michael B. Jordan, Paul La Rosée, Kai Lehmberg, Rafal Machowicz, Kim E. Nichols, Elena Sieni, Zhao Wang, Jan-Inge Henter
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome requiring aggressive immunosuppressive therapy. Following 2 large international studies mainly targeting pediatric patients with familial disease and patients without underlying chronic or malignant disease, the HLH-94 protocol is recommended as the standard of care when using etoposide-based therapy by the Histiocyte Society. However, in clinical practice, etoposide-based therapy has been widely used beyond the study inclusion criteria, including older patients and patients with underlying diseases (secondary HLH). Many questions remain around these extended indications and published reports do not address several practical issues. To tackle these concerns, the HLH Steering Committee of the Histiocyte Society decided to issue guidance for use of the HLH-94 protocol. The group convened in a structured consensus finding process to define recommendations that are based largely on expert opinion backed up by available data from the literature. The recommendations address all main elements of HLH-94 including corticosteroids, cyclosporin, etoposide, intrathecal therapy, and hematopoietic stem cell transplantation (HSCT) and consider various forms of HLH and all age groups. Aspects covered include indications, applications, dosing, side effects, duration of therapy, salvage therapy, and HSCT. These recommendations aim to provide a framework to guide treatment decisions in this severe disease.
The LIFE PERSUADED project approach on phthalates and bisphenol A biomonitoring in Italian mother-child pairs linking exposure and juvenile diseases
Abstract
Phthalates and bisphenol A (BPA), plasticizers used in several products of daily life, are considered as endocrine disrupters, therefore children exposure is particularly relevant. The LIFE PERSUADED project aims to define the following: (a) the evaluation of internal levels of DEHP's metabolites and BPA in Italian children and their mothers, (b) the association of the exposure with puberty development and obesity diseases, and (c) the effects of exposure in juvenile in vivo model. The cross-sectional study has involved 2160 mother-child pairs, including males and females, children and adolescents, from urban and rural areas of North, Center, and South Italy. A structured questionnaire and a food diary are designed to evaluate the association between lifestyle variables potentially related to DEHP/BPA exposure and internal levels, through univariate and multivariate analyses. Two pilot case-control studies are carried out on idiopathic premature thelarche and precocious puberty (30 girls each group, aged 2–7 years) and idiopathic obesity (30 boys and 30 girls, aged 6–10 years), matched to healthy controls. BPA and DEHP's metabolites are analyzed in urine samples from all recruited subjects. Clinical and toxicological biomarkers are evaluated in serum of case-control subjects. Moreover, the toxicity study is carried out in a juvenile rodent model exposed to mixtures of BPA and DEHP at dose levels recorded in children population. The scientific results of LIFE PERSUADED will contribute to risk assessment of BPA and DEHP.
The Hog1 positive regulated YCT1 Gene Expression under Cadmium tolerance of budding yeast
Abstract
Cadmium is a heavy metal that cause irreversible hazard to the living organisms. Cadmium ion can induces the phosphorylation of MAPKs pathway molecules, such as Hog1 and Slt2, but downstream effectors and potential activation pathway were still unclear. In this study, the RNA-seq data analysis in cadmium-stressed yeast was performed to predict and screen the signal transduction pathway and the potential effect molecules regulated by MAPKs. Based on DEGs and Venn diagram, 31 genes regulated by Hog1p and 2 genes induced by Slt2p, which related to carbohydrate metabolism, oxidative damage, DNA replication stress and detoxification were characterized under Cd exposure yeast. A cysteine-specific transporter (Yct1) modulated by Hog1 was confirmed via RNA-seq result. Meanwhile, we tested the cadmium sensitivity, intracellular cadmium concentrations and β-galactosidase assay, the results indicated that the hypersensitivity of the hog1 mutant to Cd was partly abrogated in YCT1 gene deletion, and induction of YCT1 was dependent on Hog1 and its transcription factors. Yct1p would be epistatic to the Hog1p in Cd tolerance, The investigation of the transcriptome of MAPKs under Cd stress provided valuable information for future molecular studies of cadmium tolerance.pH level has a strong impact on population dynamics of the yeast Yarrowia lipolytica and oil micro-droplets in multiphasic bioreactor
Abstract
The oleaginous yeast Yarrowia lipolytica has the ability to use oils and fats as carbon source, making it a promising cell factory for the design of alternative bioprocesses based on renewable substrates. However, such a multiphasic bioreactor design is rather complex and leads to several constraints when considering emulsification of the oil-in-water mixture, foaming and cell growth/physiology on hydrophobic substrate. This study aims to shed light on the effect of pH changes on the physico-chemical properties of the cultivation medium and on cell physiology. It was indeed observed that at a pH value of 6, cell growth rate and intracellular lipid accumulation were optimized. Additionally, foaming was significantly reduced. In order to avoid over foaming in bioreactor, without impairing cell physiology, the use of alternative processes that can only act on the physical structure of culture medium, seems to be an effective alternative to usual chemical antifoam agents.E. coli strain engineering for the production of advanced biopharmaceutical products
Abstract
Since the emergence of the biopharmaceutical industry in the 1980's, Escherichia coli, has played an important role in the industrial production of recombinant proteins and plasmid DNA for therapeutic use. Currently, advanced biopharmaceutical products, including rationally-designed recombinant proteins and viral-vector gene therapies, offer unprecedented promise for the long-term management, and even cure of disease. As such, E. coli remains an important production host for the biopharmaceutical industry. This review provides insight into the industrially-relevant strain engineering approaches used to enhance both the quantity and quality of these therapeutic products.Effects of solid-state fermentation with three higher fungi on the total phenol contents and antioxidant properties of diverse cereal grains
Abstract
Three culinary-medicinal fungi and mushrooms (Agaricus bisporus AS2796, Helvella lacunosa X1 and Fomitiporia yanbeiensis S.Guo & L.Zhou) were individually inoculated into different cereal grains (wheat, rice, oat, corn, millet, quinoa, buckwheat, soybean, pea and sorghum) and the antioxidant properties of fungus-fermented products after solid-state fermentation (SSF) (0, 7, 14, 21, 28 and 35 days; 25°C) were studied.The results showed that the total phenol contents (TPCs) of the fermented cereals varied with fermentation time and the starter organisms. According to the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity, reducing power, ferrous ion chelating ability and superoxide anion radical scavenging ability of ethanolic extracts from the fungus-fermented products (35 days), it was shown that the antioxidant properties of all the products were significantly stronger than uninoculated grains. It revealed that solid-state fermentation (SSF) on cereal grains by dietary fungi is a biotechnological strategy, which may enhance the antioxidant properties of the substrate. The three medicinal mushroom and fungi-fermented products were relatively effective in the antioxidant properties assayed and might be potential antioxidants for application in food products.Le portfolio de l’interne de chirurgie plastique : un outil d’aide à la formation des internes de chirurgie plastique en France ?
Source:Annales de Chirurgie Plastique Esthétique
Author(s): A. Bout-Roumazeilles, S. Dast, N. Assaf, C. Herlin, R. Sinna
La réforme du troisième cycle des études médicales a modifié le modèle d'apprentissage des internes de chirurgie plastique, en lui amputant une année de formation. La réforme précise qu'un portfolio devra suivre l'interne au cours de sa formation. Jusqu'à présent la formation pratique des internes de chirurgie plastique était exclusivement dévolue au coordonnateur local de la spécialité et aucun contrôle officiel des connaissances n'avait lieu avant l'examen national du DESC. Prenant en compte ces faits nous avons imaginé le portfolio de l'interne de chirurgie plastique qui permettrait de guider l'interne dans sa progression pratique et dans l'acquisition de ses connaissances théoriques. Il permettrait aussi d'homogénéiser la formation nationale de la spécialité et pourrait, à terme, servir de support à une évaluation formelle des compétences pratiques des internes de chirurgie plastique. Dans un premier temps nous faisons un état des lieux de la formation avant l'apparition de la réforme. Puis nous détaillons les changements qui seront apportés par la réforme. Enfin nous décrivons le portfolio en détail, son contenu, son utilisation et son intérêt.A recent reform of the French government has shortened the plastic surgery residency from 5 to 4 years. Until today, the evaluation and validation of the residency was shared between the local coordinator for practical skills and, after the residency, by the French College of Plastic Surgery for theorical knowledges. The new reform suggests to add a portfolio that will follow the resident during his surgical training. Based on the French reform and syllabus of others medical specialities, we designed a surgical portfolio that will help the resident both with his practical progression and his knowledges acquisition. The aim of the portfolio is to get a national unity of the plastic surgery training. As a first step we will describe the actual plastic surgery residency. Then, we will detail what the reform is going to change. At last, we will introduce the surgical portfolio, its content, its use and its goals.
Secondary bladder exstrophy repair with a bilateral gracilis muscle flap in an adult female patient: Case report of an original procedure
Source:Annales de Chirurgie Plastique Esthétique
Author(s): J.-B. Schaff, E. Fontaine, C. Dariane, A. Mejean, L. Lantieri, M. Hivelin
Classical bladder exstrophy (CBE), affecting 1 birth out of 30,000, is characterized by an evaginated bladder plate through a defect in the lower abdominal wall, multiple abdominal wall anomalies including a pubic bone arch dehiscence. Numerous approaches from childhood to adulthood are thus required, depending on the severity of the deformity, including the associated genital anomalies. We report the case of a 19-year-old woman with CBE with a history of three-failed primary closure. We performed a secondary neck closure with a concomitant suspension of the bladder neck and reconstruction of the lower abdominal wall using a bilateral gracilis muscle flap transposition. The early postoperative course was uneventful. The patient was discharged at day ten postoperatively. The upper part of the genital sutures (labia minora) secondary healed in three weeks. Assessment at 2, 6 and 16 months postoperatively, respectively noticed a complete healing with successful sexual intercourses, perceived gracilis contraction by the patient, and finally, recent attempts to get pregnant. Neither urinary infection nor urinary leaks occurred. Bilateral crossed gracilis muscles transfer linking both rectus abdominis muscle in front of the reconstructed bladder neck might benefit to bladder exstrophy patients.
Removal of vanadium from wastewater using surface-modified lignocellulosic material
Abstract
Palm fruit husk, a lignocellulosic material, is an agricultural solid waste. Since raw palm fruit husk does not adsorb V (V), it was subjected to surface modification with a cationic surfactant cetyl trimethyl ammonium bromide (CTAB). The surface-modified palm fruit husk showed adsorption capability for V (V). The maximum adsorption of V (V) takes place at pH 4. Adsorption equilibrium data were fitted to Langmuir, Freundlich, and Dubinin Radushkevich (D-R) isotherm models. Kinetic studies showed that the adsorption data fit second-order kinetic model better than first order. Desorption of V (V) proved that it is feasible to recover V (V) from the spent adsorbent. Effect of coexisting anions like Molybdate, sulfate, nitrate, phosphate, and thiocyanate on the adsorption of V (V) was also studied and the foreign ions compete for the adsorption sites with V (V) anionic species. Quantitative removal of V (V) was achieved from synthetic wastewater.
Predictors for Increased and Reduced Rat and Mouse Allergen Exposure in Laboratory Animal Facilities
Abstract
Introduction
Exposure to rat and mouse allergens during work in laboratory animal facilities represents a risk for being sensitized and developing allergic diseases, and it is important to keep the exposure level as low as possible. The objective of this study was to characterize the personal Mus m 1 and Rat n 1 exposure during work in laboratory animal facilities, and to investigate the effect of identified predictors of increased and reduced exposure. Methods
Mus m 1 and Rat n 1 were analysed in whole day or task-based personal air samples by enhanced sensitivity sandwich enzyme-linked immunosorbent assay. Information about cage-and-rack systems, tasks, and other conditions known to influence the allergen exposure was registered. Predictors for allergen exposure were identified by multiple linear regression analyses. Results
The median allergen exposure was 3.0 ng m−3 Mus m 1 and 0.5 ng m−3 Rat n 1, with large task-dependent variations among the samples. The highest exposed job group were animal technicians. Cage emptying and cage washing in the cage washroom represented the highest exposure, whereas animal experiments in the lab/operation room represented the lowest exposure, with laminar airflow bench being an exposure-reducing determinant. Cage changing was the highest exposed task in the animal room, where individually ventilated cages (IVCs) were predictors of reduced exposure for both Mus m 1 and Rat n 1, whereas cage-rack systems with open shelves and sliding doors were predictors of increased Rat n 1 exposure. Cages of IVC type with positive air pressure (IVC+) as well as open shelves and sliding doors were strong predictors of increased exposure during cage emptying and cage washing. Conclusions
Significant different exposure levels depending on type of work and task imply different risks of sensitization and allergy development. The fact that IVC+ cages have opposite impact on Mus m 1 and Rat n 1 exposure during different tasks may have positive clinical implications when taken into account.Assessment of Infraorbital Hypesthesia Following Orbital Floor and Zygomaticomaxillary Complex Fractures Using a Novel Sensory Grading System
Purpose: Introduction of a novel sensory grading system to assess the incidence and long-term recovery of infraorbital hypesthesia following orbital floor and inferior orbital rim fractures. Methods: Patients who presented for evaluation of orbital floor and/or zygomaticomaxillary complex (ZMC) fractures between January 2015 and April 2016 were analyzed. Two-point subjective infraorbital sensory grading in 5 discrete anatomic areas was performed. Fractures were repaired based on traditional criteria; hypesthesia was not an indication for surgery. The sensory grading system was repeated a mean 21.7 months (range 18–28) after initial fracture. Results: Sixty-two patients (mean 41.8 years) participated in the initial symptom grading, and 42 patients (67.7%) completed the 2-year follow-up. Overall, 20 of 42 patients (47.6%) had some infraorbital hypesthesia. There were fewer with isolated orbital floor fractures versus ZMC fractures (31.8% vs. 68.4%; p = 0.019). Two years postinjury, 9.1% and 40.0% with isolated floor and ZMC fractures, respectively, had persistent sensory disturbance (p = 0.0188). Of patients with sensory disturbance on presentation, 71.4% with isolated floor fractures and 38.5% with ZMC fractures experienced complete sensory recovery (p = 0.1596). Patients with isolated floor fractures had improved recovery after surgery (100% vs. 33.3% recovery; p = 0.0410). Patients with ZMC fractures showed no difference in sensory prognosis between those repaired and observed. Conclusions: In this pilot study, isolated orbital floor fractures carried a good infraorbital sensory prognosis, further improved by surgical repair. Zygomaticomaxillary complex fractures portended a worse long-term sensory outcome, unaffected by management strategy. This study validates the novel sensory grading system in post-fracture analysis. Accepted for publication May 1, 2018. Podium presentation at the American Society of Ophthalmic Plastic and Reconstructive Surgery Fall 2017 Symposium, New Orleans, Louisiana. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Michael K. Yoon, M.D., Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114. E-mail: Michael_Yoon@meei.harvard.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.
Influence of nano-additive on performance and emission characteristics of a diesel engine running on neat neem oil biodiesel
Abstract
This work investigates the experimental study to examine the operation characteristics of a neat neem oil methyl ester (BD100) along with silver oxide nano-particles as a metal-based additive in various mass fractions. Silver oxide nano-particle is mixed into 100% of BD100 at 5 and 10 ppm. The experimental investigation on diesel engine reveals that the addition of silver oxide nano-particles to BD100 resulted in enhancement of brake thermal efficiency (BTE) with a reduction in brake specific fuel consumption (BSFC). The tested emission parameters such as CO, HC, NOx, and smoke were decreased by 12.22, 10.89, 4.24, and 6.61% for BD100+ Ag2O (5 ppm) and 16.47, 14.21, 6.66, and 8.34% for BD100 respectively when compared to BD100. Overall, improvement in ignition characteristics of the engine was finer by adding 5 and 10 ppm of silver oxide nano-particle to BD100 on account of the enhanced surface area to volume ratio.
Maize shoot cell walls under cadmium stress
Abstract
The composition of shoot cell walls of two maize hybrids (Zea mays L.), the sensitive Novania and the tolerant Almansa, both after cadmium treatment was studied. Previous results showed a smaller effect of cadmium on shoot physiological parameters (e.g., elongation, dry mass, photosynthetic pigments content) in both hybrids compared to their roots. Changes in the composition of shoot cell walls were observed. It was ascertained that the amount of hemicelluloses in shoot cell walls decreased and the amount of lignocellulose complex increased in the sensitive hybrid; the opposite was observed in the tolerant Almansa. Dissimilarities in the cell wall structure of shoots, compared to the roots, in both hybrids were observed mainly in higher quantities of total lignin, in hemicelluloses fractions. The lignocellulose complex remained unchanged in the shoots in comparison to the roots. Nevertheless, in both hybrids, the highest Cd2+ amount was found in hemicelluloses. Such modification of the cell walls might affect the amount of binding sites resulting in lower cell wall permeability and subsequently in a lower pollutant influx into the protoplast.
Τρίτη 3 Ιουλίου 2018
Vertebral Compression Fractures in Elderly: How to Recognize and Report
Abstract
Purpose of Review
In elderly patients, when there is no obvious evidence of malignancy on plain radiography, it can be difficult to evaluate benign and malignant vertebral fractures, because these patients are predisposed to senile osteoporosis and malignant disease. The only complaint could be back pain, as both types of fractures have the same symptoms and signs.
Recent Findings
A reliable imaging modality is always required, as appropriate management and early diagnosis of malignant vertebral fractures are important.
Summary
The aim of this study was to highlight the importance of recognizing, through diagnostic techniques, the presence of vertebral fractures, since the majority of vertebral fractures do not come to clinical attention and to determine the parameters that are useful for the early differentiation between benign versus malignant vertebral fractures.
Advanced oxidation of antihypertensives losartan and valsartan by photo-electro-Fenton at near-neutral pH using natural organic acids and a dimensional stable anode-gas diffusion electrode (DSA-GDE) system under light emission diode (LED) lighting
Abstract
In this work photo-electro-Fenton (PEF) processes using a dimensionally stable anode-gas diffusion electrode (DSA-GDE) system under light emission diodes (LED)-type radiation were used in the degradation of the angiotensin-II-receptor antagonists (ARA II), valsartan (VAL), and losartan (LOS), which are used in the treatment of hypertension diseases, and are considered among the emerging contaminants (ECs). Organic acids as citric, tartaric, and oxalic acids were used as complexing agents of iron ions in order to maintain the performance of the Fenton reaction at near-neutral pH value. The results show that at 3.42 mA/cm2 after 90 min of electro-Fenton (EF) treatment, degradation of 70% of VAL and 100% of LOS were observed. Total degradation of VAL and LOS was reached with a PEF process at the same time with mineralization of 30%. When citric and tartaric acids were used instead of oxalic acid, similar results were obtained, i.e., total degradation of both compounds, LOS and VAL, after 90 min of treatment. The degradation performance can be attributed to the increase of the initial dissolved iron in the system, facilitating the Fe3+/Fe2+ turnover in the catalytic photo-Fenton reaction and consequently, hydroxyl radical (•OH) production. In addition, the increased photo-activity of the complexes can be associated with their high capability to complex Fe3+ and to promote ligand-to-metal charge transfer, which is of key importance to feed Fe2+ to the Fenton process. The results show that the system evaluated was more efficient to eliminate sartan family compounds using LED lighting in comparison with traditional UV-A lamps used in this kind of work. Moreover, three transformation products of VAL degradation and two transformation products of LOS degradation were identified by high-resolution mass spectrometry (HRMS) using hybrid quadrupole-time-of-flight (QTOF) MS and, at the end of the PEF system, the several organic compounds accumulated and no mineralized were effectively treated in a subsequent aerobic biological system.
Tamarind seed coat extract restores fluoride-induced hematological and biochemical alterations in rats
Abstract
Fluoride (F−) is becoming an ineluctable environmental pollutant causing deleterious effects in humans. In the present study, we examined whether tamarind seed coat extract (TSCE) is beneficial against the F−-induced systemic toxicity and hematological changes. Wistar rats were randomly grouped as follows: group I served as control; group II intoxicated with sodium fluoride (NaF, 300 ppm) in drinking water; group III was administered through oral intubation with TSCE (100 mg/kg bw); group IV was treated with NaF (300 ppm) in association with TSCE (100 mg/kg bw) for 30 days. The results indicated that F− exposure induced oxidative stress as evidenced by elevated levels of reactive oxygen species and lipid peroxidation in the brain, liver, and kidney. F− administration modulates hematological indices—WBC, RBC, and mean corpuscular volume. Moreover, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acetylcholinesterase, and monoamine oxidase significantly increased on F− exposure. Conversely, δ-aminolevulinic acid dehydratase and glutathione/reduced glutathione ratio were decreased. Activity of antioxidants—superoxide dismutase, catalase, glutathione peroxidase, and vitamin C—was also significantly decreased due to F− administration. Treatment with TSCE effectively mitigated the alterations through its antioxidant potential. The data suggested that the TSCE had beneficial effects in alleviating the F−-induced toxicity and hence can serve as a promising neutraceutical agent.
EXTRACAPSULAR DISSECTION AND LIMITED PAROTIDECTOMY
Parotid surgery has evolved over the last century. Many of the long-held principles have been questioned and consequently modified. The basic tenets of parotid surgery for benign disease have been identifying and preserving the facial nerve and complete excision of the tumor with an adequate cuff of normal tissue. This can be safely accomplished by extracapsular dissection or limited/partial parotidectomy. Extracapsular dissection implies no attempt at finding the facial nerve, while limited or partial parotidectomy includes finding one (or more) branch of the facial nerve and then dissecting that branch in a retrograde fashion.
Neck dissection for salivary gland malignancies
Salivary gland carcinomas are diverse, and their biological behavior and surgical management are also variable and somewhat controversial. Cervical lymph node status is an important prognostic variable for salivary gland malignancies. Neck dissection should be undertaken if there is clinical or radiographic evidence of associated nodal metastasis in the neck. However, indications for elective neck dissections in a clinically N0 neck remains a controversial topic. This article describes indications for elective neck dissection in salivary gland malignancies, provides a detailed review of the neck dissection technique, and discusses postoperative management of these patients.
Sublingual Gland
It is infrequent for surgery to be necessary for the sublingual salivary gland. As such the anatomy of the floor of mouth is not well taught or understood to medical graduates and head and neck surgeons. Three diseases or conditions require surgical management: the ranula, neoplasm and sialolithiasis. In the benign conditions, the lingual nerve and submandibular duct must be identified and preserved to avoid patient morbidity. Malignant salivary gland neoplasms are rare, and hence an inaccurate diagnosis frequently delayed commencement of correct treatment.
A Phase 2, Randomized Dose-Finding Study of Tapinarof (GSK2894512 Cream) for the Treatment of Atopic Dermatitis
Safe and efficacious topical treatments are needed for atopic dermatitis (AD).
Apremilast for moderate hidradenitis suppurativa: results of a randomized controlled trial
Effective anti-inflammatory treatments for hidradenitis suppurativa (HS) are limited.
A Comparison of Skin Cancer Screening and Treatment Costs at a Massachusetts Cancer Center, 2008 versus 2013
Temporal analyses of skin cancer costs are needed to examine how expenditure differences between diagnoses are changing.
Kinetics, mechanism, and global warming potentials of HFO-1234yf initiated by O 3 molecules and NO 3 radicals: insights from quantum study
Abstract
In the present investigation, the oxidation of HFO-1234yf (2,3,3,3-tetrafluoropropene) with O3 molecule and NO3 radical is studied by quantum chemical methods. The possible reaction pathways of the titled molecule with O3 molecule and NO3 radical are analyzed using M06-2X meta-hybrid density functional with the 6-311++G(d,p) basis set. We have further employed a series of single-point energy calculations by using a potentially high-level couple cluster method with single and double excitations, including perturbative corrections ((CCSD(T)) at the same basis set. The addition reaction of HFO-1234yf with O3 molecule is initiated by the formation of primary ozonide complex, which leads to the formation of various carbonyl compounds and Criegee intermediates. The calculated energy barriers and thermochemical parameters inferred that decomposition of C˙H2OO˙ and CF3CFO is slightly more preferred over the formation of CF3C˙FOO˙ and CH2O. Further, the NO3 radical addition at α- and β-sits of CF3CF〓CH2 molecule is analyzed in details. The individual and overall rate constants for each reaction pathways are calculated by using canonical transition state theory over the temperature range of 250–450 K. We have observed that the computed rate constants are in good agreement with the available experimental data. Atmospheric lifetimes and global warming potentials of the HFO-1234yf are also reported in this manuscript.
Underuse of the Sentinel Lymph Node Biopsy for High-Risk SCC of the Skin—Reply
In Reply We read with interest the response by Glazer et al regarding our study on the underuse of sentinel lymph node biopsy (SLNB) for high-risk cutaneous squamous cell carcinoma (cSCC) and noted several important inquiries and comments.
Onychomadesis Following a Fish Pedicure
This case reports describe the occurrence of onychomadesis in a patient following a fish pedicure.
An Annular Eruption in a Young Child
A young child had a 6-month history of an asymptomatic expanding erythematous eruption on the lower legs, abdomen, and buttocks; clinical examination was significant for faint, nonscaling annular serpiginous, erythematous plaques. What is your diagnosis?
Prescription to OTC Switch of Metronidazole and Azelaic Acid for Rosacea
This Viewpoint considers the advantages and disadvantages of topical treatments for rosacea, specifically metronidazole and azelaic acid, undergoing review to switch from prescription to over-the-counter availability.
The Future of JAMA Dermatology
I am deeply humbled to be selected to serve as Editor in Chief of JAMA Dermatology. The fundamental role of an editor in chief is to review, select, and publish the articles that best help clinicians practice more safely and effectively. The opportunity to illuminate the aspects of our field that deserve spotlight is a task both daunting and delightful. I am committed to do a deep dive into dermatology to identify what is most significant, what is most fascinating, what is most problematic, and to find opportunities to improve and elevate the practice of dermatologists. My ultimate goal is to ensure that dermatologists deliver the best patient care possible, and I consider it an incredible honor to be able to contribute to the specialty through this work.
Dupilumab Treatment of Very Severe Refractory Atopic Hand Eczema
This case report describes the use of dupilumab to treat a patient with very severe refractory atopic hand eczema.
Underuse of the Sentinel Lymph Node Biopsy for High-Risk SCC of the Skin
To the Editor We read with interest the article by Ahadiat et al regarding the potential underuse of sentinel lymph node biopsy (SLNB) in patients with high-risk cutaneous squamous cell carcinoma (cSCC). Although SLNB may be underused in these patients, we have some inquiries regarding the research methods and generalizability of the data.
Human Papillomavirus Vaccine to Treat Cutaneous Basaloid Squamous Cell Carcinomas
This case report describes a woman with multiple, inoperable cutaneous basaloid squamous cell carcinomas who was treated with 9-valent human papillomavirus vaccine.
Association of Inadequately Controlled Disease With Patient-Reported Disease Burden in Atopic Dermatitis
This cross-sectional study examines the association of atopic dermatitis severity and disease control with the patient-reported disease burden in clinical practice.
Assessment of arsenic removal efficiency by an iron oxide-coated sand filter process
Abstract
Arsenic is among the most dangerous contaminants which can limit groundwater use for drinking water consumption. Among the most diffused As-removal technologies around the world, adsorptive media systems are usually favored for relatively low cost and simplicity of operation. This study examines the performance of a laboratory-scale iron oxide-coated sand (IOCS) column filter, to remove arsenic (arsenate (As[V]) and arsenite (As[III])) from groundwater. This technology could be adopted in small communities, as it showed consistent removal rates of 99% with an easy-to-operate process. Some considerations about the possible introduction of such technology in developing countries are provided, highlighting the general impacts to human health related to high arsenic concentrations in groundwater. This, among other adsorption processes, could be recommended as a sustainable mean of ensuring good drinking water quality in developing regions, reducing human health impacts.
Partitioning of absorbed light energy within photosystem II in barley can be affected by chloroplast movement
Publication date: Available online 2 July 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): J. Semer, M. Štroch, V. Špunda, M. Navrátil
Plants have developed many ways to protect reaction centres of photosystems against overexcitation. One of the mechanisms involves reduction of the leaf absorption cross-section by light-induced chloroplast avoidance reaction. Decrease in the probability of photon absorption by the pigments bound within photosystem II (PSII) complexes leads to the increase in quantum yield of PSII photochemistry (ΦPSII). On the other hand, the decrease of PSII excitation probability causes reduction of chlorophyll a fluorescence intensity which is manifested as the apparent increase of determined quantum yield of regulated light induced non-photochemical quenching (ΦNPQ). Absorption of different light intensity by phototropins led to the different chloroplast distribution within barley leaves, estimated by measurement of the leaf transmittance. Due to a weak blue light used for transmittance measurements, leaves exposed to actinic light with wavelengths longer than 520 nm undergo chloroplast accumulation reaction, in contrast with leaves exposed to light with shorter wavelengths, that showed a different extent of chloroplast avoidance reaction. Based on the ΦNPQ action spectra measured simultaneously with the transmittance, the influence of different chloroplast distribution on ΦNPQ was assessed. The analysis of results showed that decrease in the leaf absorption cross-section due to increasing part of chloroplasts reaching profile position significantly affected the partitioning of excitation energy within PSII and such rearrangement also distorted measured ΦNPQ and cannot be neglected in its interpretation. When the majority of chloroplasts reached profile position the photoprotective effect appeared to be the most prominent for strong blue light that has the highest absorption in the upper leaf layers in comparison with green or red ones.
Tuning the chain length of new pyrene derivatives for site-selective photocleavage of avidin
Publication date: Available online 2 July 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Sudarat Yenjai, Challa V. Kumar, Mayuso Kuno, Teerayuth Liwporncharoenvong, Siritron Samosorn, Apinya Buranaprapuk
Rational design of photoreagents with systematic modifications of their structures can provide valuable information for a better understanding of the protein photocleavage mechanism by these reagents. Variation of the length of the linker connecting the photoactive moiety with the protein anchoring-group allowed us to investigate the control of the protein photocleavage site. A series of new photochemical reagents (PMA-1A, PMA-2A and PMA-3A) with increasing chain lengths is examined in the current study. Using avidin as a model system, we examined the interaction of these probes by UV–Vis, fluorescence spectroscopic methods, photocleavage and computational docking studies. Hypochromism of the absorption spectrum was observed for the binding of these new photochemical reagents with estimated binding constants (Kb) of 6.2 × 105, 6.7 × 105 and 4.6 × 105 M−1, respectively. No significant changes of Stern-Volmer quenching constant (Ksv) with Co(NH3)6Cl3 has been noted and the data indicated that the probes bind near the surface of the protein with sufficient exposure to the solvent. Photoexcitation of the probe-avidin complex, in the presence of Co(NH3)6Cl3, resulted in protein fragmentation, and the cleavage yield decreased with the increase in the linker length, and paralleled with the observed Ksv values. Amino acid sequencing of the photofragments indicated that avidin is cleaved between Thr77 and Val78, as a major cleavage site for all the three photoreagents. This site is proximate to the biotin binding site on avidin, and molecular docking studies indicated that the H-bonding interactions between the polar end-group of the photoreagents and hydrophilic amino acids of avidin were important in positioning the reagent on the protein. The major cleavage site, at residues 77–78, was within 5 Å of the pyrenyl moiety of the probe, and hence, molecular tuning of the linker provided a simple approach to position the photoreagent along the potential photocleavage site.
Graphical abstract
The percentage of patients achieving complete remission of urticaria increases with repeated courses of treatment
Publication date: Available online 2 July 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Andrea Matucci, Francesca Nencini, Oliviero Rossi, Sara Pratesi, Paola Parronchi, Enrico Maggi, Alessandra Vultaggio
Environmental Endocrinology: Insights Into the Diversity of Regulatory Mechanisms in Life Cycles
Abstract
All organisms must time their life cycles appropriately and organize life history stages into temporal sequences that enhance fitness in a changing environment. The endocrine system plays a major regulatory role in transducing information from the environment into morphological, physiological and behavioral responses appropriate for the time of year. The perception, transduction, response pathways via neural and endocrine mechanisms are beginning to be explored and underscore the critical regulatory roles they play. Whereas many conserved mechanisms (evolutionary constraints hypothesis) are emerging, there is a growing realization that there may be alternate pathways unique to populations and individuals (evolutionary flexibility hypothesis). Field investigations (field endocrinology) over the past 45 years have revealed patterns of hormonal responses to environmental changes, physical and social, that could not have been anticipated from laboratory investigations alone. These patterns include differences at population and individual levels that have enabled new insights into acclimation and adaptation to environmental transitions. The number of species studied under natural conditions has grown exponentially in recent years to include all vertebrate classes and some invertebrates as well. These data are now driving evolutionary perspectives and with the advent of comparative genomics a new and exciting era of evolutionary/ecological endocrinology is developing. This paper gives a brief overview of where the field stands now and where it is likely to go in the future especially in relation to the networks of regulatory pathways and how they can be modulated to enable acclimation of individuals as well as populations. One illustrative example, mechanisms underlying modulation of the adrenocortical responses to environmental stress, is the focus of this communication. These "coping" mechanisms will be key for acclimation and adaptation to global change.Application of Box–Behnken design and desirability function in the optimization of Cd(II) removal from aqueous solution using poly(o-phenylenediamine)/hydrous zirconium oxide composite: equilibrium modeling, kinetic and thermodynamic studies
Abstract
In this research work, poly(o-phenylenediamine) was incorporated into the hydrous zirconium oxide matrix to form poly(o-phenylenediamine)/hydrous zirconium oxide composite which is used for the removal of Cd(II) from aqueous solution. The characterization of the material was done based on FTIR, XRD, SEM, and TGA-DTA. The effects of contact time, pH, adsorbent dose, and initial concentration of Cd(II) on the removal of Cd(II) were studied by performing 29 sets of sorption runs using Box–Behnken design combined with response surface methodology (RSM). Various isotherm models were tested to describe the adsorption equilibrium. The adsorption equilibrium data fitted well with Freundlich isotherm model. The maximum adsorption capacity of 66.66 mg g−1 was obtained from Langmuir isotherm. The pseudo-second-order kinetic model described the adsorption kinetics more accurately. Diffusion-based kinetics such as intraparticle diffusion and Bangham's model suggested that both film and intraparticle pore diffusion were involved in the adsorption process. The Elovich model pointed towards the chemisorption. The investigation of desorption and regeneration suggested that the material can be used as an effective sorbent for removal of Cd(II) from aqueous system.
Microbial fuel cell and membrane bioreactor coupling system: recent trends
Abstract
Membrane bioreactor (MBR) and microbial fuel cell (MFC) are new technologies based on microbial process. MBR takes separation process as the core to achieve the high efficient separation and enrichment the beneficiation of microbes during the biological treatment. MFC is a novel technology based on electrochemical process to realize the mutual conversion between biomass energy and electric energy, in order to solve the problems of serious membrane fouling and low efficiency of denitrification in membrane bioreactor, the low power generation efficiency, and unavailability of bioelectric energy of MFC. In recent years, MFC-MBR coupling system emerged. It can effectively mitigate the membrane fouling and reduce the excess sludge production. Simultaneously, the electricity can be used effectively. The new coupling system has good prospects for development. In this paper, we summarized the research progresses of the two kinds of coupling systems in recent years and analyzed the coupling structure and forms. Based on the above, the future development fields of the MFC-MBR coupling system were prospected.
Fate of PAHs in the vicinity of aluminum smelter
Abstract
Investigation has been carried out in the vicinity of an aluminum smelter located in the industrialized town of Konin. Concentrations of 14 polycyclic aromatic hydrocarbons (PAHs) were determined in grass, spruce needles, and soil collected in the period of the smelter operation and several years after its closing. Significant changes in the quantity of PAHs and their profiles observed in the two measuring periods, stressing the importance of aluminum production with regard to PAH emission. It was confirmed by very high values of the carcinogenic potential (CP) found for PAHs accumulated in grass and soil when compared to the values found in urban and remote sites. PAH ratio rates used as a tool for identifying emission sources showed a pyrogenic origin of PAHs in both periods; the ratios in the period of the smelter running activity were similar to those found in other studies carried out near aluminum smelters. Grass turned out to be a good biomonitor of PAHs similarly to commonly used leaves of various tree species. The use of four age classes of spruce needles, some of which were subjected to emission from the smelter, showed that such approach could serve as an analysis tool for describing retrospective pollution.
Evaluation of psychiatric hospital wastewater toxicity: what is its impact on aquatic organisms?
Abstract
The primary source of pharmaceuticals to the aquatic environment is the discharge of wastewater effluents. Pharmaceuticals are a large and diverse group of compounds. Among them, psychotropic substances are particularly interesting to study due to their specific known mode of action. The present study was performed to investigate the effects of wastewater effluents from a psychiatric hospital wastewater treatment plant (WWTP) on several aquatic organisms. All the analyzed pharmaceuticals (10 compounds) were detected in WWTP effluents as well as in the receiving river. Although the environmental concentrations were generally at trace levels (ng L−1 to μg L−1), induce toxic effects were observed. This study showed the effects of the WWTP effluents on the oogenesis and/or embryogenesis of amphipod crustacean Gammarus fossarum, Japanese fish medaka Oryzias latipes, mollusk Radix peregra, and planarian Schmidtea polychroa. A decrease of the number of oocytes and produced embryos was observed for G. fossarum and S. polychroa. Similarly, the hatching rate of R. peregra was affected by effluents. In the receiving river, the macroinvertebrate community was affected by the wastewater effluents discharge.
Vertebroplasty in Elderly Patients: A Clinical Effectiveness Analysis
Abstract
Purpose of Review
Minimally invasive vertebral augmentation procedures (VAP) have been first introduced to provide pain relief in patients with osteoporotic vertebral fractures (VF). However, in the last decade scientific literature revealed to be quite controversial about their efficacy. The aim of this review was to analyze clinical evidences from current literature, supported by our own experience.
Recent Findings
Compared to conservative therapies, VAP represent an effective treatment for recent VF and, in elderly patients, reduce mortality and morbidity. Advances in technology have widened the fields of application towards other spine pathologies typical of elderly, such as primary and metastatic tumors.
Summary
In patients with severe pain for recent or un-healed vertebral fracture, VAP are clinically more effective than conservative treatment. Accurate pain assessment and pre-procedural Magnetic Resonance Imaging are highly recommended to obtain optimal patient selection and best treatment results.
Peer Review to Peer Learning in Radiology: Where Have We Been, What Have We Learned and Where Are We Headed?
Abstract
Purpose of review
To review and contrast varying methods of peer assessment driven practice quality improvement programs in radiology with an emphasis on peer review and peer learning.
Recent findings
Review of the literature revealed that the current consensus is that a shift away from the original peer review system toward a peer learning process has the most beneficial effects for organizations seeking to maximally improve performance. This requires altering perceptions towards the peer review process itself, and significant time, effort, and resources.
Summary
The transition to a peer learning process is a necessity to advance the field of radiology into an era of delivering near faultless quality health care.
PET/CT and Bone Scintigraphy: Metabolic Results in Musculoskeletal Lesions
Abstract
Purpose
This review aimed to provide an overview on findings from metabolic imaging modalities such as bone scintigraphy and positron emission tomography–computed tomography (PET/CT) in musculoskeletal lesions. It is conceivable that methods assessing metabolism of bone tumors, combined with the morphological assessment, could enhance the possibility for a personalized therapy with particular emphasis to malignant neoplasms.
Recent Findings
The assessment of bone tumors by conventional scintigaphic and morphological imaging has been recently integrated with the morpho-metabolic appraisal obtained by PET/CT systems. Increasing availability of this diagnostic modality has been shown to stratify properly the patients and the findings correlate well with outcome. Moreover, new tracers are being implemented in the study of musculoskeletal lesions by PET/CT while the new volumetric parameters used to identify the lesions hold great promise.
Summary
Results from PET/CT are associated with tumor grading and histopathology in bone malignant lesions and they could be of value for implementing treatment strategy. Additionally, the metabolic assessment has been demonstrated useful for predicting surgical response and patients' outcome.
Δευτέρα 2 Ιουλίου 2018
A Systematic Review of Full-Shift, Noise Exposure Levels Among Construction Workers: Are We Improving?
Abstract
Context
Construction industry workers are at high risk of occupational noise exposure. Although regulations and guidelines for this industry specify the use of noise controls, workers continue to be exposed to hazardous noise levels. Objectives
The objectives of this study were (i) to collate and describe full-shift noise exposure experienced by construction workers; (ii) to review trends in full-shift exposure over time and between countries; and (iii) to identify any occupational categories within the construction industries that have higher levels of exposure. Results
Of the 1171 studies found using key terms, 25 contained noise exposure measurements that met our inclusion criteria. Sample populations were predominantly from large construction sites and primarily comprised occupations known to engage in noisy workplace activities. Studies spanned over 36 years with all having average full-shift noise exposure over 85 A-weighted decibels (dBA). No time trend in full-shift noise exposure levels for construction workers was observed. Construction workers in the subgroup occupations of mason, sheet metal workers, carpenters, concrete workers, and operating engineers consistently had mean LAeq,8h over the 85 dBA limit. Conclusion
Studies spanning 36 years in 10 countries consistently show construction workers have been exposed to hazardous noise levels. There has been no significant change over time of the average full-shift exposure levels of construction workers, including in all occupational subgroups except iron-workers. Some variability in full-shift measures is due to sampling methods and population characteristics and to a lesser extent, methods used to derive exposure levels.Correction to: Genetic aberrations of the K-ras proto-oncogene in bladder cancer in relation to pesticide exposure
The original publication of this paper contains a mistake. Line 6 in the abstract, line should read "One hundred patients were diagnosed with bladder cancer and two hundred controls attended the outpatient clinic;"
Biofilm architecture on different substrates of an Oculatella subterranea (Cyanobacteria) strain isolated from Pompeii archaeological site (Italy)
Abstract
The Cyanobacterium Oculatella subterranea Zammit, Billi, Albertano inhabits hypogea and stone caves and is a pioneer of different stone substrata. In this study, a strain isolated from the House of Marco Castricio (Archaeological Park of Pompeii, Italy) was identified by a polyphasic approach and used for an in vitro colonization test to verify the influence of the substrate on the biofilm architecture. Fine structure of O. subterranea microbial mats was revealed as well as filaments orientation toward light source. This aim has been achieved through confocal laser scanner microscope microscopy and computer image analysis. Moreover, bioreceptivity of five different substrates, commonly retrieved in archaeological sites of Campania, was assessed for O. subterranea. Our results show that the three-dimensional structure of O. subterranea microbial mats is poorly affected by physical and geochemical features of substrates: in fact, the porous architecture of its biofilm was preserved, independently of the materials. On the other hand, the area/perimeter ratio relative to the O. subterranea growth on tuff, brick, and porphyry showed significant differences, indicating dissimilar levels of bioreceptivity of the three substrates.
Effects of inorganic ions on the photolysis of propranolol in FA solution
Abstract
Photolysis of the widely used beta-blocker propranolol (PRO) was investigated in the presence of fulvic acid (FA) and inorganic ions under simulated solar irradiation. PRO undergoes direct photolysis proceeding mainly via degradation of the triplet excited state, 3PRO*. FA and inorganic ions inhibited photolysis of PRO in the order of FA > Fe3+ > Cl− > Ca2+ > Mg2+ > NO3− > K+. An antagonistic effect between FA and inorganic ions toward the suppression of PRO photolysis was exhibited. The binding behaviors of PRO, FA, and inorganic ions were examined through fluorescence quenching experiments, which showed that inorganic ions affected the binding between FA and PRO through competing for the binding sites of FA or PRO. The correlation analysis demonstrated a positive correlation between the binding constant (KOC) of FA-PRO and the inhibition rate of FA on PRO photolysis. The observed rate constants of photolysis (kobs) have opposite correlations with the concentration of singlet oxygen (1O2). These findings strongly suggest that inorganic ions decrease the inhibition effect of FA on PRO photolysis via restraining the complexation of FA-PRO and production of 1O2.
Réplica a «Factores de riesgo cardiovascular y grosor de la íntima media carotídea en una población colombiana con psoriasis»
Publication date: Available online 2 July 2018
Source:Actas Dermo-Sifiliográficas
Author(s): Á. González-Cantero, J. González-Cantero, A.I. Sánchez-Moya, C. Pérez-Hortet, C. Schoendorff-Ortega
Nevus epidérmicos y síndromes relacionados. Parte 2: Nevus derivados de estructuras anexiales
Publication date: Available online 2 July 2018
Source:Actas Dermo-Sifiliográficas
Author(s): J. Garcias-Ladaria, M. Cuadrado Rosón, M. Pascual-López
Los nevus epidérmicos son hamartomas originados en la epidermis y/o en las estructuras anexiales de la piel que se han clasificado clásicamente partiendo de la morfología. En los últimos años se han descrito variantes nuevas y se han producido avances en el campo de la genética que han permitido caracterizar mejor estas lesiones y comprender su relación con algunas de las manifestaciones extracutáneas a las que se han asociado. En esta segunda parte revisaremos los nevus derivados de estructuras anexiales de la piel y los síndromes que se asocian.Epidermal nevi are hamartomatous lesions derived from the epidermis and/or adnexal structures of the skin; they have traditionally been classified according to their morphology. New variants have been described in recent years and advances in genetics have contributed to better characterization of these lesions and an improved understanding of their relationship with certain extracutaneous manifestations. In the second part of this review article, we will look at nevi derived from the adnexal structures of the skin and associated syndromes.
Graphical abstract
Tratamiento biológico como primera línea en pacientes con psoriasis: una población no estudiada
Publication date: Available online 2 July 2018
Source:Actas Dermo-Sifiliográficas
Author(s): O. Baniandrés Rodríguez
Inhibidores selectivos de la IL-23: los recién llegados al tratamiento de la psoriasis
Publication date: Available online 2 July 2018
Source:Actas Dermo-Sifiliográficas
Author(s): T. Torres
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A Case of Diprosopus Tetraophthalmos: Ocular Findings and Surgical Treatment of Exposure KeratopathyDiprosopus is a rare variation of conjoined twinning. In this report, ophthalmic findings in an infant with diprosopus tetraophthalmos are p...
