Medicine by Alexandros G. Sfakianakis

Constant exposure of the living ecosystems to heavy metals, like cadmium (Cd), induces a detectable change at the biochemical and genetic level. Repeated application of phosphate fertilizers in paddy fields, leads to increase in Cd content of soil. Cd being highly mobile is transported to shoot and grain, thereby entering into the food chain of animal system. In the present study, treatment of 7-day old rice seedlings with 10 μM cadmium chloride resulted in Cd toxicity across the seven non-aromatic and six aromatic rice cultivars and landraces used for the study. Free proline and malondialdehyde content of treated samples were higher in comparison to the untreated samples, which indicated Cd induced tissue damage in plants. Photosynthetic pigment content of treated samples was also found to be much lower in comparison to the untreated samples, which is probably due to peroxidation of membrane, leading to compromised and lower photosynthetic efficiency of treated plants. At the genetic level, Randomly Amplified Polymorphic DNA assay was found to efficiently detect the genetic polymorphisms (caused by alterations in DNA bases) induced by Cd. Production of unique polymorphic bands in Cd-treated plants helps in assessment of the degree of damage Cd imparts on the plant system. Cluster analysis was performed and the rice genotypes were grouped into five distinct clusters, with IR64 and Tulsibhog in two distinct groups. Based on the variability in responses, the 13 rice genotypes were grouped into sensitive and tolerant ones.

Deciphering adverse effects of heavy metals on diverse wheat germplasm on irrigation with urban wastewater of mixed municipal-industrial origin

Abstract

The current study provides one of the first attempts to identify tolerant, moderately sensitive, and highly sensitive wheat genotypes on the basis of heavy metal accumulation, biochemical attributes, and human health risk assessments on urban wastewater (UW) irrigation. Mean heavy metals (Fe, Co, Ni, Cu, Zn, Pb, Cd, Cr, Mn) and macro-nutrients (Na, K, Ca, Mg) levels increased in the roots, stem, and grains of studied genotypes. Except K (stem > root > grain), all metals were accumulated in highest concentrations in roots followed by stem and grains. Principal component analyses (PCA) identified three groups of UW-irrigated genotypes which were confirmed by hierarchical agglomerative cluster analyses (HACA). Wheat genotypes with the lowest metal accumulation were regarded as tolerant, whereas those with maximum accumulation were considered highly sensitive. Tolerant genotypes showed the lowest hazard quotient for heavy metals, i.e., Co, Mn, Cd, Cu, Fe, Pb, and Cr, and hazard index (HI) values (adults, 2.04; children, 2.27) than moderately and highly sensitive genotypes. Higher health risks (HI) associated with moderate (adults 2.26; children 2.53) and highly sensitive (adults 2.52; children 2.82) genotypes revealed maximum uptake of heavy metals. The heatmap showed higher mean biochemical levels of chlorophyll, carotenoids, membrane stability index (MSI%), sugars, proteins, proline, superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in tolerant genotypes than remaining genotypes. With the lowest metal accumulation and advanced biochemical mechanisms to cope with the adverse effects of heavy metals in their plant bodies, tolerant genotypes present a better option for cultivation in areas receiving UW or similar type of wastewater.

Recent progress in perioperative management of patients undergoing esophagectomy for esophageal cancer

Abstract

Esophagectomy remains the mainstay of curative intent treatment for esophageal cancer. Oncologic esophagectomy is a highly invasive surgery and both morbidity and mortality rates still remain high. Recently, it has been revealed that multidisciplinary perioperative management can decrease the postoperative complications after esophagectomy. In this review, we summarized the recent progress in each component of multidisciplinary perioperative care bundle, including oral hygiene, cessation of smoking and alcohol, respiratory training, measurement of physical fitness, swallowing evaluation and rehabilitation, nutritional support, pain control and management of delirium. The accumulation of evidence and the popularization of knowledge will increase safety of esophagectomy and thus improve the outcome of patients with esophageal cancer.

Research on the effect of wall corrosion and rim seal on the withdrawal loss for a floating roof tank

Abstract

Storage tanks are important parts of volatile organic compound (VOC) fugitive emission sources of the petrochemical industry; the floating roof tank is the main oil storage facility at present. Based on the mechanism of withdrawal loss and the type of rim seal, octane and gasoline were taken as the research objects. A model instrument for simulating the oil loading process by the 316 stainless steel and A3 carbon steel as the test piece was designed, and the film thickness was measured by wet film thickness gauge to investigate the influence of the corrosion of the tank wall and rim seal on the withdrawal loss for floating roof tanks. It was found that withdrawal loss was directly proportional to the shell factor, and the oil thickness of the octane and gasoline increased with the strength of the wall corrosion with the same wall material and rim seal. Compared with the untreated test piece, the oil film thickness of the octane/gasoline was increased by 7.04~8.57 μm/13.14~21.93 μm and 5.59~11.49 μm/11.61~25.48 μm under the corrosion of hydrochloric acid for 32 and 75 h, respectively. The oil film thickness of octane and gasoline decreased with the increasing of the rim seal, and the oil film thickness of the octane decreased by 11.97~28.90% and 37.32~73.83% under the resilient-filled seal and the double seal, respectively. The gasoline dropped by 11.97~31.18% and 45.98~75.34% under the resilient-filled seal and the double seal, respectively. In addition, the tank surface roughness reduced the compression of the rim seal on the tank wall, and the effect of scraping decreased. The API withdrawal loss formula for a floating roof tank was recommended to take into account the effect of the rim seal to improve the accuracy of the loss evaluation. Finally, some measures of reducing the withdrawal loss were proposed.

Emerging role of semaphorin-3A in autoimmune diseases

Abstract

Autoimmune diseases (ADs) are featured by the body's immune responses being directed against its own tissues, resulting in prolonged inflammation and subsequent tissue damage. Currently, the exact pathogenesis of ADs remains not fully elucidated. Semaphorin-3A (Sema3A), a secreted member of semaphorin family, is a potent immunoregulator during all immune response stages. Sema3A has wide expression, such as in bone, connective tissue, kidney, neurons, and cartilage. Sema3A can downregulate ADs by suppressing the over-activity of both T-cell and B-cell autoimmunity. Moreover, Sema3A shows the ability to enhance T-cell and B-cell regulatory properties that control ADs, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and systemic sclerosis. However, it can also induce ADs when overexpressed. Together, these data strongly suggest that Sema3A plays a pivotal role in ADs, and it may be a promising treatment target for these diseases. In the present review, we focus on the immunological functions of Sema3A and summarize recent studies on the involvement of Sema3A in the pathogenesis of ADs; the discoveries obtained from recent findings may translate into novel therapeutic agent for ADs.

Collagen XIII Is Required for Neuromuscular Synapse Regeneration and Functional Recovery after Peripheral Nerve Injury

Collagen XIII occurs as both a transmembrane-bound and a shed extracellular protein and is able to regulate the formation and function of neuromuscular synapses. Its absence results in myasthenia: presynaptic and postsynaptic defects at the neuromuscular junction (NMJ), leading to destabilization of the motor nerves, muscle regeneration and atrophy. Mutations in COL13A1 have recently been found to cause congenital myasthenic syndrome, characterized by fatigue and chronic muscle weakness, which may be lethal. We show here that muscle defects in collagen XIII-deficient mice stabilize in adulthood, so that the disease is not progressive until very late. Sciatic nerve crush was performed to examine how the lack of collagen XIII or forced expression of its transmembrane form affects the neuromuscular synapse regeneration and functional recovery following injury. We show that collagen XIII-deficient male mice are unable to achieve complete NMJ regeneration and functional recovery. This is mainly attributable to presynaptic defects that already existed in the absence of collagen XIII before injury. Shedding of the ectodomain is not required, as the transmembrane form of collagen XIII alone fully rescues the phenotype. Thus, collagen XIII could serve as a therapeutic agent in cases of injury-induced PNS regeneration and functional recovery. We conclude that intrinsic alterations at the NMJ in Col13a1^–/– mice contribute to impaired and incomplete NMJ regeneration and functional recovery after peripheral nerve injury. However, such alterations do not progress once they have stabilized in early adulthood, emphasizing the role of collagen XIII in NMJ maturation.

SIGNIFICANCE STATEMENT Collagen XIII is required for gaining and maintaining the normal size, complexity, and functional capacity of neuromuscular synapses. Loss-of-function mutations in COL13A1 cause congenital myasthenic syndrome 19, characterized by postnatally progressive muscle fatigue, which compromises patients' functional capacity. We show here in collagen XIII-deficient mice that the disease stabilizes in adulthood once the NMJs have matured. This study also describes a relevant contribution of the altered NMJ morphology and function to neuromuscular synapses, and PNS regeneration and functional recovery in collagen XIII-deficient mice after peripheral nerve injury. Correlating the animal model data on collagen XIII-associated congenital myasthenic syndrome, it can be speculated that neuromuscular connections in congenital myasthenic syndrome patients are not able to fully regenerate and restore normal functionality if exposed to peripheral nerve injury.

Elucidating the Role of the Ventrolateral Prefrontal Cortex in Economic Decision-Making

The Synaptic Properties of Cells Define the Hallmarks of Interval Timing in a Recurrent Neural Network

Extensive research has described two key features of interval timing. The bias property is associated with accuracy and implies that time is overestimated for short intervals and underestimated for long intervals. The scalar property is linked to precision and states that the variability of interval estimates increases as a function of interval duration. The neural mechanisms behind these properties are not well understood. Here we implemented a recurrent neural network that mimics a cortical ensemble and includes cells that show paired-pulse facilitation and slow inhibitory synaptic currents. The network produces interval selective responses and reproduces both bias and scalar properties when a Bayesian decoder reads its activity. Notably, the interval-selectivity, timing accuracy, and precision of the network showed complex changes as a function of the decay time constants of the modeled synaptic properties and the level of background activity of the cells. These findings suggest that physiological values of the time constants for paired-pulse facilitation and GABAb, as well as the internal state of the network, determine the bias and scalar properties of interval timing.

SIGNIFICANCE STATEMENT Timing is a fundamental element of complex behavior, including music and language. Temporal processing in a wide variety of contexts shows two primary features: time estimates exhibit a shift toward the mean (the bias property) and are more variable for longer intervals (the scalar property). We implemented a recurrent neural network that includes long-lasting synaptic currents, which cannot only produce interval-selective responses but also follow the bias and scalar properties. Interestingly, only physiological values of the time constants for paired-pulse facilitation and GABAb, as well as intermediate background activity within the network can reproduce the two key features of interval timing.

Is There a Role for Pattern Separation during Sleep?

Soluble TNF{alpha} Signaling within the Spinal Cord Contributes to the Development of Autonomic Dysreflexia and Ensuing Vascular and Immune Dysfunction after Spinal Cord Injury

Cardiovascular disease and susceptibility to infection are leading causes of morbidity and mortality for individuals with spinal cord injury (SCI). A major contributor to these is autonomic dysreflexia (AD), an amplified reaction of the autonomic nervous system (hallmarked by severe hypertension) in response to sensory stimuli below the injury. Maladaptive plasticity of the spinal sympathetic reflex circuit below the SCI results in AD intensification over time. Mechanisms underlying this maladaptive plasticity are poorly understood, restricting the identification of treatments. Thus, no preventative treatments are currently available. Neuroinflammation has been implicated in other pathologies associated with hyperexcitable neural circuits. Specifically, the soluble form of TNFα (sTNFα) is known to play a role in neuroplasticity. We hypothesize that persistent expression of sTNFα in spinal cord underlies AD exacerbation. To test this, we intrathecally administered XPro1595, a biologic that renders sTNFα nonfunctional, after complete, high-level SCI in female rats. This dramatically attenuated the intensification of colorectal distension-induced and naturally occurring AD events. This improvement is mediated via decreased sprouting of nociceptive primary afferents and activation of the spinal sympathetic reflex circuit. We also examined peripheral vascular function using ex vivo pressurized arterial preparations and immune function via flow cytometric analysis of splenocytes. Diminishing AD via pharmacological inhibition of sTNFα mitigated ensuing vascular hypersensitivity and immune dysfunction. This is the first demonstration that neuroinflammation-induced sTNFα is critical for altering the spinal sympathetic reflex circuit, elucidating a novel mechanism for AD. Importantly, we identify the first potential pharmacological, prophylactic treatment for this life-threatening syndrome.

SIGNIFICANCE STATEMENT Autonomic dysreflexia (AD), a disorder that develops after spinal cord injury (SCI) and is hallmarked by sudden, extreme hypertension, contributes to cardiovascular disease and susceptibility to infection, respectively, two leading causes of mortality and morbidity in SCI patients. We demonstrate that neuroinflammation-induced expression of soluble TNFα plays a critical role in AD, elucidating a novel underlying mechanism. We found that intrathecal administration after SCI of a biologic that inhibits soluble TNFα signaling dramatically attenuates AD and significantly reduces AD-associated peripheral vascular and immune dysfunction. We identified mechanisms behind diminished plasticity of neuronal populations within the spinal sympathetic reflex circuit. This study is the first to pinpoint a potential pharmacological, prophylactic strategy to attenuate AD and ensuing cardiovascular and immune dysfunction.

Task Division within the Prefrontal Cortex: Distinct Neuron Populations Selectively Control Different Aspects of Aggressive Behavior via the Hypothalamus

An important question in behavioral neurobiology is how particular neuron populations and pathways mediate the overall roles of brain structures. Here we investigated this issue by studying the medial prefrontal cortex (mPFC), an established locus of inhibitory control of aggression. We established in male rats that dominantly distinct mPFC neuron populations project to and produce dense fiber networks with glutamate release sites in the mediobasal hypothalamus (MBH) and lateral hypothalamus (LH; i.e., two executory centers of species-specific and violent bites, respectively). Optogenetic stimulation of mPFC terminals in MBH distinctively increased bite counts in resident/intruder conflicts, whereas the stimulation of similar terminals in LH specifically resulted in violent bites. No other behaviors were affected by stimulations. These findings show that the mPFC controls aggressiveness by behaviorally dedicated neuron populations and pathways, the roles of which may be opposite to those observed in experiments where the role of the whole mPFC (or of its major parts) has been investigated. Overall, our findings suggest that the mPFC organizes into working units that fulfill specific aspects of its wide-ranging roles.

SIGNIFICANCE STATEMENT Aggression control is associated with many cognitive and emotional aspects processed by the prefrontal cortex (PFC). However, how the prefrontal cortex influences quantitative and qualitative aspects of aggressive behavior remains unclear. We demonstrated that dominantly distinct PFC neuron populations project to the mediobasal hypothalamus (MBH) and the lateral hypothalamus (LH; i.e., two executory centers of species-specific and violent bites, respectively). Stimulation of mPFC fibers in MBH distinctively increased bite counts during fighting, whereas stimulation of similar terminals in LH specifically resulted in violent bites. Overall, our results suggest a direct prefrontal control over the hypothalamus, which is involved in the modulation of quantitative and qualitative aspects of aggressive behavior through distinct prefrontohypothalamic projections.

Restoration of Kv7 Channel-Mediated Inhibition Reduces Cued-Reinstatement of Cocaine Seeking

Cocaine addicts display increased sensitivity to drug-associated cues, due in part to changes in the prelimbic prefrontal cortex (PL-PFC). The cellular mechanisms underlying cue-induced reinstatement of cocaine seeking remain unknown. Reinforcement learning for addictive drugs may produce persistent maladaptations in intrinsic excitability within sparse subsets of PFC pyramidal neurons. Using a model of relapse in male rats, we sampled >600 neurons to examine spike frequency adaptation (SFA) and afterhyperpolarizations (AHPs), two systems that attenuate low-frequency inputs to regulate neuronal synchronization. We observed that training to self-administer cocaine or nondrug (sucrose) reinforcers decreased SFA and AHPs in a subpopulation of PL-PFC neurons. Only with cocaine did the resulting hyperexcitability persist through extinction training and increase during reinstatement. In neurons with intact SFA, dopamine enhanced excitability by inhibiting Kv7 potassium channels that mediate SFA. However, dopamine effects were occluded in neurons from cocaine-experienced rats, where SFA and AHPs were reduced. Pharmacological stabilization of Kv7 channels with retigabine restored SFA and Kv7 channel function in neuroadapted cells. When microinjected bilaterally into the PL-PFC 10 min before reinstatement testing, retigabine reduced cue-induced reinstatement of cocaine seeking. Last, using cFos-GFP transgenic rats, we found that the loss of SFA correlated with the expression of cFos-GFP following both extinction and re-exposure to drug-associated cues. Together, these data suggest that cocaine self-administration desensitizes inhibitory Kv7 channels in a subpopulation of PL-PFC neurons. This subpopulation of neurons may represent a persistent neural ensemble responsible for driving drug seeking in response to cues.

SIGNIFICANCE STATEMENT Long after the cessation of drug use, cues associated with cocaine still elicit drug-seeking behavior, in part by activation of the prelimbic prefrontal cortex (PL-PFC). The underlying cellular mechanisms governing these activated neurons remain unclear. Using a rat model of relapse to cocaine seeking, we identified a population of PL-PFC neurons that become hyperexcitable following chronic cocaine self-administration. These neurons show persistent loss of spike frequency adaptation, reduced afterhyperpolarizations, decreased sensitivity to dopamine, and reduced Kv7 channel-mediated inhibition. Stabilization of Kv7 channel function with retigabine normalized neuronal excitability, restored Kv7 channel currents, and reduced drug-seeking behavior when administered into the PL-PFC before reinstatement. These data highlight a persistent adaptation in a subset of PL-PFC neurons that may contribute to relapse vulnerability.

Cell-Type-Specific Shank2 Deletion in Mice Leads to Differential Synaptic and Behavioral Phenotypes

Shank2 is an excitatory postsynaptic scaffolding protein implicated in synaptic regulation and psychiatric disorders including autism spectrum disorders. Conventional Shank2-mutant (Shank2^–/–) mice display several autistic-like behaviors, including social deficits, repetitive behaviors, hyperactivity, and anxiety-like behaviors. However, cell-type-specific contributions to these behaviors have remained largely unclear. Here, we deleted Shank2 in specific cell types and found that male mice lacking Shank2 in excitatory neurons (CaMKII-Cre;Shank2^fl/fl) show social interaction deficits and mild social communication deficits, hyperactivity, and anxiety-like behaviors. In particular, male mice lacking Shank2 in GABAergic inhibitory neurons (Viaat-Cre;Shank2^fl/fl) display social communication deficits, repetitive self-grooming, and mild hyperactivity. These behavioral changes were associated with distinct changes in hippocampal and striatal synaptic transmission in the two mouse lines. These results indicate that cell-type-specific deletions of Shank2 in mice lead to differential synaptic and behavioral abnormalities.

SIGNIFICANCE STATEMENT Shank2 is an abundant excitatory postsynaptic scaffolding protein implicated in the regulation of excitatory synapses and diverse psychiatric disorders including autism spectrum disorders. Previous studies have reported in vivo functions of Shank2 mainly using global Shank2-null mice, but it remains largely unclear how individual cell types contribute to Shank2-dependent regulation of neuronal synapses and behaviors. Here, we have characterized conditional Shank2-mutant mice carrying the Shank2 deletion in excitatory and inhibitory neurons. These mouse lines display distinct alterations of synaptic transmission in the hippocampus and striatum that are associated with differential behavioral abnormalities in social, repetitive, locomotor, and anxiety-like domains.

This Week in The Journal

Targeting of NF-{kappa}B to Dendritic Spines Is Required for Synaptic Signaling and Spine Development

Long-term forms of brain plasticity share a requirement for changes in gene expression induced by neuronal activity. Mechanisms that determine how the distinct and overlapping functions of multiple activity-responsive transcription factors, including nuclear factor B (NF-B), give rise to stimulus-appropriate neuronal responses remain unclear. We report that the p65/RelA subunit of NF-B confers subcellular enrichment at neuronal dendritic spines and engineer a p65 mutant that lacks spine enrichment (p65SE) but retains inherent transcriptional activity equivalent to wild-type p65. Wild-type p65 or p65SE both rescue NF-B-dependent gene expression in p65-deficient murine hippocampal neurons responding to diffuse (PMA/ionomycin) stimulation. In contrast, neurons lacking spine-enriched NF-B are selectively impaired in NF-B-dependent gene expression induced by elevated excitatory synaptic stimulation (bicuculline or glycine). We used the setting of excitatory synaptic activity during development that produces NF-B-dependent growth of dendritic spines to test physiological function of spine-enriched NF-B in an activity-dependent response. Expression of wild-type p65, but not p65SE, is capable of rescuing spine density to normal levels in p65-deficient pyramidal neurons. Collectively, these data reveal that spatial localization in dendritic spines contributes unique capacities to the NF-B transcription factor in synaptic activity-dependent responses.

SIGNIFICANCE STATEMENT Extensive research has established a model in which the regulation of neuronal gene expression enables enduring forms of plasticity and learning. However, mechanisms imparting stimulus specificity to gene regulation, ensuring biologically appropriate responses, remain incompletely understood. NF-B is a potent transcription factor with evolutionarily conserved functions in learning and the growth of excitatory synaptic contacts. Neuronal NF-B is localized in both synapse and somatic compartments, but whether the synaptic pool of NF-B has discrete functions is unknown. This study reveals that NF-B enriched in dendritic spines (the postsynaptic sites of excitatory contacts) is selectively required for NF-B activation by synaptic stimulation and normal dendritic spine development. These results support spatial localization at synapses as a key variable mediating selective stimulus–response coupling.

Low-Dimensional and Monotonic Preparatory Activity in Mouse Anterior Lateral Motor Cortex

Neurons in multiple brain regions fire trains of action potentials anticipating specific movements, but this "preparatory activity" has not been systematically compared across behavioral tasks. We compared preparatory activity in auditory and tactile delayed-response tasks in male mice. Skilled, directional licking was the motor output. The anterior lateral motor cortex (ALM) is necessary for motor planning in both tasks. Multiple features of ALM preparatory activity during the delay epoch were similar across tasks. First, most neurons showed direction-selective activity and spatially intermingled neurons were selective for either movement direction. Second, many cells showed mixed coding of sensory stimulus and licking direction, with a bias toward licking direction. Third, delay activity was monotonic and low-dimensional. Fourth, pairs of neurons with similar direction selectivity showed high spike-count correlations. Our study forms the foundation to analyze the neural circuit mechanisms underlying preparatory activity in a genetically tractable model organism.

SIGNIFICANCE STATEMENT Short-term memories link events separated in time. Neurons in the frontal cortex fire trains of action potentials anticipating specific movements, often seconds before the movement. This "preparatory activity" has been observed in multiple brain regions, but has rarely been compared systematically across behavioral tasks in the same brain region. To identify common features of preparatory activity, we developed and compared preparatory activity in auditory and tactile delayed-response tasks in mice. The same cortical area is necessary for both tasks. Multiple features of preparatory activity, measured with high-density silicon probes, were similar across tasks. We find that preparatory activity is low-dimensional and monotonic. Our study forms a foundation for analyzing the circuit mechanisms underlying preparatory activity in a genetically tractable model organism.

Intralimb and Interlimb Cutaneous Reflexes during Locomotion in the Intact Cat

When the foot contacts an obstacle during locomotion, cutaneous inputs activate spinal circuits to ensure dynamic balance and forward progression. In quadrupeds, this requires coordinated reflex responses between the four limbs. Here, we investigated the patterns and phasic modulation of cutaneous reflexes in forelimb and hindlimb muscles evoked by inputs from all four limbs. Five female cats were implanted to record muscle activity and to stimulate the superficial peroneal and superficial radial nerves during locomotion. Stimulating these nerves evoked short-, mid-, and longer-latency excitatory and/or inhibitory responses in all four limbs that were phase-dependent. The largest responses were generally observed during the peak activity of the muscle. Cutaneous reflexes during mid-swing were consistent with flexion of the homonymous limb and accompanied by modification of the stance phases of the other three limbs, by coactivating flexors and extensors and/or by delaying push-off. Cutaneous reflexes during mid-stance were consistent with stabilizing the homonymous limb by delaying and then facilitating its push-off and modifying the support phases of the homolateral and diagonal limbs, characterized by coactivating flexors and extensors, reinforcing extensor activity and/or delaying push-off. The shortest latencies of homolateral and diagonal responses were consistent with fast-conducting disynaptic or trisynaptic pathways. Descending homolateral and diagonal pathways from the forelimbs to the hindlimbs had a higher probability of eliciting responses compared with ascending pathways from the hindlimbs to the forelimbs. Thus, in quadrupeds, intralimb and interlimb reflexes activated by cutaneous inputs ensure dynamic coordination of the four limbs, producing a whole-body response.

SIGNIFICANCE STATEMENT The skin contains receptors that, when activated, send inputs to spinal circuits, signaling a perturbation. Rapid responses, or reflexes, in muscles of the contacted limb and opposite homologous limb help maintain balance and forward progression. Here, we investigated reflexes during quadrupedal locomotion in the cat by electrically stimulating cutaneous nerves in each of the four limbs. Functionally, responses appear to modify the trajectory or stabilize the movement of the stimulated limb while modifying the support phase of the other limbs. Reflexes between limbs are mediated by fast-conducting pathways that involve excitatory and inhibitory circuits controlling each limb. The comparatively stronger descending pathways from cervical to lumbar circuits controlling the forelimbs and hindlimbs, respectively, could serve a protective function.

Human Episodic Memory Retrieval Is Accompanied by a Neural Contiguity Effect

Cognitive psychologists have long hypothesized that experiences are encoded in a temporal context that changes gradually over time. When an episodic memory is retrieved, the state of context is recovered—a jump back in time. We recorded from single units in the medial temporal lobe of epilepsy patients performing an item recognition task. The population vector changed gradually over minutes during presentation of the list. When a probe from the list was remembered with high confidence, the population vector reinstated the temporal context of the original presentation of that probe during study, a neural contiguity effect that provides a possible mechanism for behavioral contiguity effects. This pattern was only observed for well remembered probes; old probes that were not well remembered showed an anti-contiguity effect. These results constitute the first direct evidence that recovery of an episodic memory in humans is associated with retrieval of a gradually changing state of temporal context, a neural "jump back in time" that parallels the act of remembering.

SIGNIFICANCE STATEMENT Episodic memory is the ability to relive a specific experience from one's life. For decades, researchers have hypothesized that, unlike other forms of memory that can be described as simple associations between stimuli, episodic memory depends on the recovery of a neural representation of spatiotemporal context. During study of a sequence of stimuli, the brain state of epilepsy patients changed slowly over at least a minute. When the participant remembered a particular event from the list, this gradually changing state was recovered. This provides direct confirmation of the prediction from computational models of episodic memory. The resolution of this point means that the study of episodic memory can focus on the mechanisms by which this representation of spatiotemporal context is maintained and sometimes recovered.

Dual Coding of Frequency Modulation in the Ventral Cochlear Nucleus

Frequency modulation (FM) is a common acoustic feature of natural sounds and is known to play a role in robust sound source recognition. Auditory neurons show precise stimulus-synchronized discharge patterns that may be used for the representation of low-rate FM. However, it remains unclear whether this representation is based on synchronization to slow temporal envelope (ENV) cues resulting from cochlear filtering or phase locking to faster temporal fine structure (TFS) cues. To investigate the plausibility of those encoding schemes, single units of the ventral cochlear nucleus of guinea pigs of either sex were recorded in response to sine FM tones centered at the unit's best frequency (BF). The results show that, in contrast to high-BF units, for modulation depths within the receptive field, low-BF units (<4 kHz) demonstrate good phase locking to TFS. For modulation depths extending beyond the receptive field, the discharge patterns follow the ENV and fluctuate at the modulation rate. The receptive field proved to be a good predictor of the ENV responses for most primary-like and chopper units. The current in vivo data also reveal a high level of diversity in responses across unit types. TFS cues are mainly conveyed by low-frequency and primary-like units and ENV cues by chopper and onset units. The diversity of responses exhibited by cochlear nucleus neurons provides a neural basis for a dual-coding scheme of FM in the brainstem based on both ENV and TFS cues.

SIGNIFICANCE STATEMENT Natural sounds, including speech, convey informative temporal modulations in frequency. Understanding how the auditory system represents those frequency modulations (FM) has important implications as robust sound source recognition depends crucially on the reception of low-rate FM cues. Here, we recorded 115 single-unit responses from the ventral cochlear nucleus in response to FM and provide the first physiological evidence of a dual-coding mechanism of FM via synchronization to temporal envelope cues and phase locking to temporal fine structure cues. We also demonstrate a diversity of neural responses with different coding specializations. These results support the dual-coding scheme proposed by psychophysicists to account for FM sensitivity in humans and provide new insights on how this might be implemented in the early stages of the auditory pathway.

Intracranial Electrophysiology Reveals Reproducible Intrinsic Functional Connectivity within Human Brain Networks

Evidence for intrinsic functional connectivity (FC) within the human brain is largely from neuroimaging studies of hemodynamic activity. Data are lacking from anatomically precise electrophysiological recordings in the most widely studied nodes of human brain networks. Here we used a combination of fMRI and electrocorticography (ECoG) in five human neurosurgical patients with electrodes in the canonical "default" (medial prefrontal and posteromedial cortex), "dorsal attention" (frontal eye fields and superior parietal lobule), and "frontoparietal control" (inferior parietal lobule and dorsolateral prefrontal cortex) networks. In this unique cohort, simultaneous intracranial recordings within these networks were anatomically matched across different individuals. Within each network and for each individual, we found a positive, and reproducible, spatial correlation for FC measures obtained from resting-state fMRI and separately recorded ECoG in the same brains. This relationship was reliably identified for electrophysiological FC based on slow (<1 Hz) fluctuations of high-frequency broadband (70–170 Hz) power, both during wakeful rest and sleep. A similar FC organization was often recovered when using lower-frequency (1–70 Hz) power, but anatomical specificity and consistency were greatest for the high-frequency broadband range. An interfrequency comparison of fluctuations in FC revealed that high and low-frequency ranges often temporally diverged from one another, suggesting that multiple neurophysiological sources may underlie variations in FC. Together, our work offers a generalizable electrophysiological basis for intrinsic FC and its dynamics across individuals, brain networks, and behavioral states.

SIGNIFICANCE STATEMENT The study of human brain networks during wakeful "rest", largely with fMRI, is now a major focus in both cognitive and clinical neuroscience. However, little is known about the neurophysiology of these networks and their dynamics. We studied neural activity during wakeful rest and sleep within neurosurgical patients with directly implanted electrodes. We found that network activity patterns showed striking similarities between fMRI and direct recordings in the same brains. With improved resolution of direct recordings, we also found that networks were best characterized with specific activity frequencies and that different frequencies show different profiles of within-network activity over time. Our work clarifies how networks spontaneously organize themselves across individuals, brain networks, and behavioral states.

Adaptation to Noise in Human Speech Recognition Unrelated to the Medial Olivocochlear Reflex

Sensory systems constantly adapt their responses to the current environment. In hearing, adaptation may facilitate communication in noisy settings, a benefit frequently (but controversially) attributed to the medial olivocochlear reflex (MOCR) enhancing the neural representation of speech. Here, we show that human listeners (N = 14; five male) recognize more words presented monaurally in ipsilateral, contralateral, and bilateral noise when they are given some time to adapt to the noise. This finding challenges models and theories that claim that speech intelligibility in noise is invariant over time. In addition, we show that this adaptation to the noise occurs also for words processed to maintain the slow-amplitude modulations in speech (the envelope) disregarding the faster fluctuations (the temporal fine structure). This demonstrates that noise adaptation reflects an enhancement of amplitude modulation speech cues and is unaffected by temporal fine structure cues. Last, we show that cochlear implant users (N = 7; four male) show normal monaural adaptation to ipsilateral noise. Because the electrical stimulation delivered by cochlear implants is independent from the MOCR, this demonstrates that noise adaptation does not require the MOCR. We argue that noise adaptation probably reflects adaptation of the dynamic range of auditory neurons to the noise level statistics.

SIGNIFICANCE STATEMENT People find it easier to understand speech in noisy environments when they are given some time to adapt to the noise. This benefit is frequently but controversially attributed to the medial olivocochlear efferent reflex enhancing the representation of speech cues in the auditory nerve. Here, we show that the adaptation to noise reflects an enhancement of the slow fluctuations in amplitude over time that are present in speech. In addition, we show that adaptation to noise for cochlear implant users is not statistically different from that for listeners with normal hearing. Because the electrical stimulation delivered by cochlear implants is independent from the medial olivocochlear efferent reflex, this demonstrates that adaptation to noise does not require this reflex.

Erratum: Hood et al., "Endoplasmic Reticulum Stress Contributes to the Loss of Newborn Hippocampal Neurons after Traumatic Brain Injury"

Effects and mechanisms of anionic and nonionic surfactants on biochar removal of chromium

Abstract

This work found that the removal of chromium by a straw-derived biochar was significantly promoted or inhibited by various surfactants. For example, the anionic surfactant sodium dodecyl benzene sulfonate (SDBS) inhibited the removal of Cr(VI) by the biochar but significantly promoted the removal of Cr(III) by the biochar. The nonionic surfactant Triton X-100 (TX-100) promoted the removal of Cr(VI) at low concentrations (< 100 mg L⁻¹) but inhibited the removal at high concentrations. Different mechanisms were found for the two surfactants. As an anionic surfactant, surface-sorbed SDBS changed the surface functional groups of the biochar, making the biochar negative charged and changing the sorption ability of the biochar. For the nonionic TX-100, monomers and micelles in the aqueous phase had a major influence on the sorption of chromium due to the impact on the interfacial tension between the biochar and the solution phase as well as the solution pH. The results suggest that when biochar is used to treat heavy metal wastewater containing coexisting surfactants, the type and concentration of surfactants must be considered as important factors. Under certain surfactant conditions, biochar will enable the simultaneous and efficient removal of heavy metals and surfactants.

Carvedilol for Treatment of Red Vulva Syndrome

This case report describes 2 patients with red vulva syndrome treated with carvedilol.

Effectiveness of Low Doses of Hyaluronidase to Remove Hyaluronic Acid Filler Nodules

This parallel-group, randomized clinical trial assesses the effectiveness and dose-related effect of small quantities of hyaluronidase vs saline to treat hyaluronic acid filler nodules in healthy women.

2018 Update of Hyaluronidase Use in Aesthetic Dermatology

Hyaluronidase has become an essential tool in cosmetic dermatology as an eraser of unwanted hyaluronic acid (HA) filler. The purpose of this Editorial is to update the reader on the evidence supporting the use of hyaluronidase in (1) the emergency treatment of vascular occlusion from accidental injection of HA into a blood vessel and (2) the more common case of removing small amounts of HA that are simply unwanted, which is the purpose of the study published by Alam and colleagues in this issue of JAMA Dermatology.

Sulfur Ointment Treatment of Cutaneous Myiasis Caused by the Tumbu Fly

This case report describes a patient treated with sulfur ointment for cutaneous myiasis caused by the tumbu fly.

Framework for Caring for Older Patients With Skin Disease

This Viewpoint describes principles of geriatric science that allow for more appropriate dermatological care for the US population of patients older than 65 years.

A Man With Infiltrated Plaques on the Pretibial Area

A nondiabetic man in his late 20s presented with mildly itchy, large, ill-defined, erythematous plaques on the pretibial areas of both legs. What is your diagnosis?

A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of β- d -mannuronic acid in rheumatoid arthritis patients

Abstract

Background

Following the potent efficacy of β-d-mannuronic acid (M2000) in phase I/II trial in ankylosing spondylitis patients, the present clinical trial was conducted to evaluate the efficacy, safety, and tolerability of this novel drug in rheumatoid arthritis (RA) patients who had inadequate response to conventional therapy.

Method

The study was a 12-week randomized, controlled, phase I/II clinical trial with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modified American College of Rheumatology (ACR) criteria, with active disease at baseline also inadequate response to conventional therapy, were enrolled in this study. M2000 was administrated at a dose of two capsules (500 mg) per day orally during a period of 12 weeks. The primary endpoint was the proportion of patients fulfilling the ACR 20% improvement criteria after 12 weeks of M2000 therapy. Moreover, the patients were also followed up for safety.

Results

There were no statistically significant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was significantly higher among M2000-treated patients than conventional-treated control, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P = 0.011). 10% of M2000-treated patients and 57.1% of conventional-treated patient's adverse events occurred during this study.

Conclusion

Treatment with M2000 in combination with conventional therapy showed a significantly superior efficacy along with a high safety profile compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA.

Mammakarzinom in der Schwangerschaft

Zusammenfassung

Hintergrund und Ziel der Arbeit

Brustkrebs in der Schwangerschaft ist selten. Die Tendenz ist steigend, was sicher auch dem höheren Alter der Frauen bei Eintreten der Schwangerschaft geschuldet ist. Aufgrund erschwerter und konsekutiv verzögerter Diagnostik zeigen sich vermehrt fortgeschrittene Tumorstadien mit ungünstiger Tumorbiologie, sodass eine multimodale Therapie erforderlich ist. Oft herrscht große Unsicherheit über die bestmögliche Behandlung für Mutter und Kind.

Ergebnisse und Schlussfolgerung

Der folgende Artikel gibt einen Überblick über diagnostische, lokale und systemische Therapieoptionen des schwangerschaftsassoziierten Mammakarzinoms. Insgesamt konnte gezeigt werden, dass nach Abschluss des 1. Trimenons sichere medikamentöse und operative Therapiekonzepte existieren, welche die Prognose der Mutter trotz bestehender Schwangerschaft nicht verschlechtern und die Entwicklung des Feten nicht gefährden. Schwangerschaftsassoziierter Brustkrebs stellt keine zwingende, medizinische Indikation für einen Schwangerschaftsabbruch dar.

Insight into the effects of biochar as adsorbent and microwave receptor from one-step microwave pyrolysis of sewage sludge

Abstract

The effect of biochar, derived from one-step microwave pyrolysis of sewage sludge (OMPSS), on the removal of industrial wastewater (eosin and safranine T) was investigated in this study. Meanwhile, the multiple-reuse potential of biochar as microwave receptor to raise the pyrolysis temperature was also tested during the pyrolysis process. The results showed that OMPSS prepared adsorbents had excellent adsorption performance, achieving the highest removal efficiencies of 97.3 and 95.9% for eosin and safranine T, respectively. Further analysis indicated that this was due to its appropriate porous structure and surface chemistry characteristics, where the S_BET and pore volume of adsorbent AC-1 reached 459 m²/g and 0.23 cm³/g, respectively. The multiple reuses of biochar adsorbents after five times as microwave receptor was feasible, where the pyrolysis temperature could increase sharply from room temperature to 800 °C within 5 min. The mechanism analysis revealed that the limiting stage of adsorption was chemical sorption. This research provided an alternative way for the preparation of functional adsorbent and microwave receptor.

Graphical abstract

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Transgenic up-regulation of Claudin-6 decreases fine diesel particulate matter (DPM)-induced pulmonary inflammation

Abstract

Claudin-6 (Cldn6) is a tetraspanin transmembrane protein that contributes to tight junctional complexes and has been implicated in the maintenance of lung epithelial barriers. In the present study, we tested the hypothesis that genetic up-regulation of Cldn-6 influences inflammation in mice exposed to short-term environmental diesel particulate matter (DPM). Mice were subjected to ten exposures of nebulized DPM (PM2.5) over a period of 20 days via a nose-only inhalation system (Scireq, Montreal, Canada). Using real-time RT-PCR, we discovered that the Cldn6 gene was up-regulated in control mice exposed to DPM and in lung-specific transgenic mice that up-regulate Cldn-6 (Cldn-6 TG). Interestingly, DPM did not further enhance Cldn-6 expression in Cldn-6 TG mice. DPM caused increased cell diapedesis into bronchoalveolar lavage fluid (BALF) from control mice; however, Cldn-6 TG mice had less total cells and PMNs in BALF following DPM exposure. Because Cldn-6 TG mice had diminished cell diapedesis, other inflammatory intermediates were screened to characterize the impact of increased Cldn-6 on inflammatory signaling. Cytokines that mediate inflammatory responses including TNF-α and IL-1β were differentially regulated in Cldn6 TG mice and controls following DPM exposure. These results demonstrate that epithelial barriers organized by Cldn-6 mediate, at least in part, diesel-induced inflammation. Further work may show that Cldn-6 is a key target in understanding pulmonary epithelial gateways exacerbated by environmental pollution.

Traits and causes of environmental loss-related chemical accidents in China based on co-word analysis

Abstract

Chemical accidents are major causes of environmental losses and have been debated due to the potential threat to human beings and environment. Compared with the single statistical analysis, co-word analysis of chemical accidents illustrates significant traits at various levels and presents data into a visual network. This study utilizes a co-word analysis of the keywords extracted from the Web crawling texts of environmental loss-related chemical accidents and uses the Pearson's correlation coefficient to examine the internal attributes. To visualize the keywords of the accidents, this study carries out a multidimensional scaling analysis applying PROXSCAL and centrality identification. The research results show that an enormous environmental cost is exacted, especially given the expected environmental loss-related chemical accidents with geographical features. Meanwhile, each event often brings more than one environmental impact. Large number of chemical substances are released in the form of solid, liquid, and gas, leading to serious results. Eight clusters that represent the traits of these accidents are formed, including "leakage," "poisoning," "explosion," "pipeline crack," "river pollution," "dust pollution," "emission," and "industrial effluent." "Explosion" and "gas" possess a strong correlation with "poisoning," located at the center of visualization map.

Variations in individuals’ exposure to black carbon particles during their daily activities: a screening study in Brazil

Abstract

Black carbon (BC) is a fraction of airborne PM_2.5 emitted by combustion, causing deleterious effects on human health. Due to its abundance in cities, assessing personal exposure to BC is of utmost importance. Personal exposure and dose of six couples with different working routines were determined for 48 h based on 1-min mobile BC measurements and on ambient concentrations monitored simultaneously at home (outdoor) and at a suburban site. Although couples spent on average ~ 10 h together at home, the routine of each individual in other microenvironments led to 3–55% discrepancies in exposure between partners. The location of the residences and background concentrations accounted for the differences in inter-couple exposure. The overall average exposure and dose by gender were not statistically different. The personal exposure and dose calculated with datasets from fixed sites were lower than the calculations using data from mobile measurements, with the largest divergences (between four and nine times) in the transport category. Even though the individuals spent only 7% of the time commuting, this activity contributed to between 17 and 20% of the integrated exposure and inhaled dose, respectively. On average, exposure was highest on bus trips, while pedestrians and bus passengers had lower doses. Open windows elevated the in-car exposure and dose four times compared to settings with closed windows.

Introduction: Autoinflammatory Syndromes Special Issue—hidden mysteries in the corners of autoinflammation

This is the 18th year of ongoing research in 'autoinflammation'. Since the genetic and pathogenic characterization of the first autoinflammatory diseases—familial Mediterranean fever (FMF) and TNF-receptor associated periodic syndrome (TRAPS)—further genetic and clinical discoveries have advanced hand in hand with basic discoveries of innate-immune sensors and pathways that link danger-sensing to the production and release of key pro-inflammatory cytokines (1).

The Names Have Been Changed to Protect the . . . Humanity: Person-First Language in Correctional Health Epidemiology

Abstract

After objections surfaced following a call for papers on "Prisoner Health," the editors of Epidemiologic Reviews decided to rename this year's volume "Incarceration and Health." In this commentary, we trace the origins of person-first language and explain why using appropriate terms in correctional health, including correctional health epidemiology, matters. We discuss the potential consequences of person-first language for justice-involved individuals and how inclusive language might affect the social, emotional, and physical well-being of individuals, families, and communities. Future directions may include measuring health outcomes when language is systematically changed. The barriers that thwart successful reentry may wane when dehumanizing language disappears.

Development, Construct Validity, and Predictive Validity of a Continuous Frailty Scale: Results from Two Large U.S. Cohorts

Abstract

Frailty is an age-related clinical syndrome of decreased resilience to stressors. Among numerous assessments of frailty, the frailty phenotype (FP) scale, proposed by Fried and colleagues has been the most widely used one. We aimed to develop a continuous frailty scale that may overcome limitations facing the categorical FP scale and to evaluate its construct validity, predictive validity, and measurement properties. Data were from the Cardiovascular Health Study (N = 4243) and Health and Retirement Study (N = 7600). Frailty was conceptualized as a continuous construct, measured by five measures used in FP scale: gait speed, grip strength, exhaustion, physical activity, and weight loss. We used confirmatory factor analysis to investigate the relationship between five indicators and the latent frailty construct. We examined the association of the continuous frailty scale with mortality and disability. The unidimensional model fit the data satisfactorily; similar factor structure was observed across two cohorts. Gait speed and weight loss were the strongest and weakest indicators, respectively; grip strength, exhaustion, and physical activity had similar strength in measuring frailty. In each cohort, the continuous frailty scale was strongly associated with mortality and disability and persisted to be associated with outcomes among robust and prefrail persons classified by the FP scale.

Defluoridation using novel chemically treated carbonized bone meal: batch and dynamic performance with scale-up studies

Abstract

Novel defluoridating adsorbent was synthesized by chemical treatment of carbonized bone meal using aluminum sulfate and calcium oxide. Precursor for chemical treatment was prepared by partial carbonization of raw bone meal at 550 °C for 4 h. Maximum fluoride removal capacity was 150 mg/g when carbonized bone meal (100 g/L) was treated with aluminum sulfate (500 g/L) and calcium oxide (15 g/L). Morphological analysis revealed formation of a coating layer consisting of aluminum compounds on the precursor surface. This was verified by stretching frequency of aluminum hydroxide (602 cm⁻¹) in the infrared spectra. Presence of hydroxylapatite (2θ = 30° and 2θ = 24°) and aluminum mineral phases (2θ = 44°) in the adsorbent were identified from the X-ray diffractograms. Adsorption capacity decreased from 150 mg/g (30 °C) to 120 mg/g (50 °C) indicating exothermic adsorption. Adsorption experiments under batch kinetic mode were simulated using shrinking core model. Effective fluoride diffusivity in the adsorbent and the mass transfer coefficient were estimated as 5.8 × 10⁻¹² m²/s and 9 × 10⁻⁴ m/s, respectively. Desorption was maximum at basic pH and desorption efficiency was decreased by 31% after third cycle. Dynamic filtration with artificially fluoride-spiked solution showed that the empty bed contact time for a packed column with equal weight of carbonized and chemically treated adsorbent was 4.7 min and number of bed volumes treated (till WHO limit of 1.5 mg/L) was 340 for a column of 3-cm diameter and 18-cm length. The system was successfully tested using contaminated groundwater from an affected area. Fixed-bed column experiments were simulated from the first principles using convective pore diffusion-adsorption model for both synthetic solution and contaminated groundwater. Axial dispersion coefficient was found to be one order of magnitude less than the pore diffusivity indicating dominance of fluoride diffusion within porous network of adsorbent. The developed adsorbent exhibited antibacterial property as well.

Hand eczema in nurses, nursing auxiliaries and cleaners—A cross‐sectional study from a tertiary hospital in western India

Contact Dermatitis, EarlyView.

Bullous reaction to dimethyl N‐cyanodithioiminocarbonate

Contact Dermatitis, EarlyView.

Méningiomes et acétate de cyprotérone : mise au point

Publication date: Available online 25 April 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-L. Schmutz

Hydratation cutanée et produits hydratants

Publication date: Available online 25 April 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): H. Duplan, T. Nocera
Une des fonctions majeures de la peau est de fournir à l'organisme une protection vis-à-vis de son environnement en maintenant une barrière épidermique efficace, non seulement vis-à-vis de l'extérieur, mais aussi vis-à-vis de la perte en eau corporelle. En effet, l'homéostasie hydrique est une condition requise pour un fonctionnement physiologique normal de la peau. Le taux d'hydratation influence non seulement les paramètres macroscopiques apparents, tels que souplesse et douceur cutanée, mais aussi des paramètres moléculaires, les activités enzymatiques et la signalisation cellulaire au sein de l'épiderme. Une part de l'eau corporelle est continuellement perdue, mais ce phénomène ainsi que le maintien d'un gradient hydrique optimal dans la peau est garanti par un ensemble de régulations fines, s'appuyant sur les propriétés fonctionnelles et dynamiques de la couche la plus superficielle de la peau constituée par le stratum corneum. Cet article rassemble les données récemment acquises dans le domaine de l'hydratation cutanée et de la caractérisation de la peau déshydratée ou sèche, que ce soit dans la compréhension des phénomènes de régulation mis en jeu ou dans l'évolution des principales techniques de mesure in situ, et par conséquent dans l'optimisation de la prise en charge.One of the skin's principal functions is to protect the body against its environment by maintaining an effective epidermal barrier, not only against external factors, but also to prevent water loss from the body. Indeed, water homeostasis is vital for the normal physiological functioning of skin. Hydration levels affect not only visible microscopic parameters such as the suppleness and softness of skin, but also molecular parameters, enzyme activities and cellular signalling within the epidermis. The body is continually losing some of its water, but this phenomenon is limited and the optimal hydration gradient in skin is ensured via a set of sophisticated regulatory processes that rely on the functional and dynamic properties of the uppermost level of the skin consisting of the stratum corneum. The present article brings together data recently acquired in the fields of skin hydration and the characterisation of dehydrated or dry skin, whether through study of the regulatory processes involved or as a result of changes in the techniques used for in situ measurement, and thus in optimisation of management.

Angiosarcomes cutanés de la tête et du cou inopérables traités par bevacizumab et paclitaxel

Publication date: Available online 24 April 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): O. Becquart, C. Girard, C. Lesage, B. Guillot

Traitements des patients atteints de mélanome de stade III inopérable ou de stade IV. Société française de dermatologie

Publication date: Available online 25 April 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): B. Guillot, J. Charles, G. Jeudy, D. Cupissol, A. Dupuy, C. Dutriaux, D. Gangloff, N. Magne, X. Mirabel, A. M'Sadek, M. Pracht, C. Sichel, G. Do Outeiro

Non-epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†

Stringent vaccination of cancer patients – is it that important?

Τρίτη 24 Απριλίου 2018

Trends of absorption, scattering and total aerosol optical depths over India and surrounding oceanic regions from satellite observations: role of local production, transport and atmospheric dynamics

Abstract

The study examines trends of scattering, absorption and total aerosol optical depths (SAOD, AAOD and AOD) over India and surrounding oceanic regions and explores role of local production, long-range transport and atmospheric dynamics on observed trends. Long-term satellite observations are used to estimate trends and assess their statistical significance. Significant spatial and seasonal changes are observed in trends of SAOD, AAOD and AOD. AOD is observed to be increasing during post monsoon and winter over most of the land mass and surrounding oceanic regions, whereas decreasing trends over land and increasing trends over oceanic regions are observed in pre-monsoon and summer months. In general, SAOD and AAOD show similar trends (if there is any) as that of AOD over most of the regions in most of the months. Strongest positive trends over land regions are observed in November with trend of AOD greater than 0.01 year⁻¹, especially over Indo-Gangetic Plain (IGP). Increase of AOD over IGP in post monsoon is contributed significantly by absorbing aerosols with rate of increase ~ 0.005 AAOD year⁻¹. AAODs are observed to be increasing over Arabian Sea and Bay of Bengal (BoB) in December also, with rate ~ 0.003 AAOD year⁻¹. Strongest positive trends over Arabian Sea and BoB are observed in June with rate of increase greater than 0.02 AOD year⁻¹, whereas strong negative trends are observed over north-west India in the same period with rate of decrease greater than 0.02 AOD year⁻¹. Over IGP, AOD, AAOD and SAOD show contrasting trends in winter and summer seasons. AAOD exhibits strongest decreasing trend over IGP during April–June. Positive trends of AOD over Arabian Sea and BoB are favoured significantly by changes in circulation dynamics. Atmospheric convergence is observed to be strengthening over these regions in April and June, leading to more accumulation and hence positive trends of AOD. Aerosol transport over to the Arabian Sea is observed to be enhancing and contributing significantly to AOD increase over the Arabian Sea in pre-monsoon and summer months. Enhancement in aerosol transport over to the Arabian Sea is observed in pre-monsoon at higher altitudes above 3 km, whereas it is observed in summer at lower levels. However, decreasing trends of AOD over north-west India and IGP during pre-monsoon and summer are observed to be due to decrease in aerosol transport from the continental regions at the west.

The Editor's Choice

Editorial board

Long-term study of Cr, Ni, Zn, and P distribution in Typha domingensis growing in a constructed wetland

Abstract

The aim of this work was to study Cr, Ni, Zn, and P bioaccumulation in different compartments of Typha domingensis plants and sediment in a free-water surface constructed wetland for the treatment of a metallurgical effluent for 5 years. Removal efficiencies were satisfactory. To increase metal tolerance, its transport from belowground to aboveground tissues is reduced, being metal concentrations in the roots and rhizomes significantly higher than in the aerial and submerged parts of leaves. Regarding belowground tissues, metals were retained in the roots, while P was mainly accumulated in rhizomes. Bioaccumulation factors (BAFs) of Cr and Ni showed values near 1, and BAF of Zn and P were above 1 in several samplings, indicating bioaccumulation in the roots. Translocation factors (TFs) of Cr, Ni, and Zn were below 1, showing a scarce translocation from the roots to the aerial parts of the leaves, while the TF of P were above 1 in many samplings, indicating that this element is necessary for plant metabolism. The study of plant tissues where contaminants are accumulated allows gaining insight into the constructed wetland operation. The high translocation of P in T. domingensis makes this species suitable for its phytoextraction, while the low metal translocation makes T. domingensis suitable for phytostabilization.

Some aspects of the adsorption of glyphosate and its degradation products on montmorillonite

Abstract

The most worldwide used herbicide is glyphosate, phosphonomethylglycine (PMG). Consequently, a significant amount of PMG, its metabolites (sarcosine, SAR, and aminomethylphosphonic acid, AMPA) and the degradation product, methylphosphonic acid (MPA), reaches the soil, which acts as final sink. Because clays are one of the most reactive components of soils, expansive clays such as montmorillonite (Mt) are used to retain agriculture contaminants with some success. In this work, as a preliminary step for the evaluation of the risk that PMG, SAR, AMPA, and MPA occurrence could have on the environment, their adsorption on Mt surface was performed. The adsorption process was analyzed at constant adsorbate concentrations and two pH values to take into account the different protonation states of the amino group. DTA, XRD, zeta potential measurements, and XPS were used to identify the interactions or association mechanisms with the clay surface, the entry of adsorbates into the Mt interlayer, and electric charge changes on the Mt surface, and evaluate the acid-base surface complex constants, respectively. The interlayer thickness in acid media indicated that adsorbates are able to enter the interlayer in planar form. Besides, for the Mt-PMG sample, some PMG molecules could be also inserted as a bilayer or with a tilt angle of 52.4° in the interlayer. However, in alkaline media, the interlayer thickness indicated that the adsorbate arrangement differed from that of acidic media where PMG and MPA could have more than one orientation. The surface complex deprotonation constants were determined for the =NH⁺² ⇆ =NH+H⁺ process, being 3.0, 5.0, and 7.3 for PMG, AMPA, and SAR, respectively.

Relationships Among C-Reactive Protein, Alanine Aminotransferase, and Metabolic Syndrome in Apparently Healthy Chinese Subjects

Metabolic Syndrome and Related Disorders, Ahead of Print.

Gender Differences in the Effects of the Frequency of Physical Activity on the Incidence of Metabolic Syndrome: Results from a Middle-Aged Community Cohort in Taiwan

Metabolic Syndrome and Related Disorders, Ahead of Print.

Bringing big data from social media reviews to quality improvement

Determination of size-segregated elements in diesel-biodiesel blend exhaust emissions

Abstract

This study was based on the determination of metals in particulate matter emitted by a typical diesel engine used by busses and trucks in Brazil. Emissions were sampled using a cascade impactor, and the engine was operated using diesel with 5% (B5), 10% (B10), 15% (B15), and 20% (B20) of biodiesel. The particulate matter was stratified in different sizes, i.e., 18, 5.6, 3.2, 1.8, 1.0, 0.560, 0.320, 0.180, 0.100, and 0.056 μm. Cd, Co, Cr, Cu, Mn, Mo, Ni, Pb, V, and Zn with concentrations within 10 to 1000 ng m⁻³ were determined. The results indicate a trend in the prevalence of lead, nickel, and chromium in coarse particles and nanoparticles in all blends of fuels. By comparing the results of B5, B10, B15, and B20 fuels, we can confirm that the addition of biodiesel to diesel promotes a reduction of emissions, and by comparing the behavior of the concentration of all elements analyzed, emissions by B10 and B15 fuels are similar, while B5 and B20 suffer significant changes during the process of combustion. Multivariate statistical analysis was used, and it indicates possible sources in three clusters, one for Ni, other for Cr-Mn, and the last one for other metals.

Histopathological patterns in dermatitis artefacta

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Psoriasis vulgaris in a patient with pemphigus vulgaris on corticosteroid therapy

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Moderators of angiogenesis in muscle flaps: a non-randomised animal study

Publication date: Available online 23 April 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): K. Bradshaw, M. Wagels
IntroductionA muscle flap can survive a pedicle injury under favourable conditions. In the reconstruction of compound limb injuries, the wound milieu is variable and may affect the rate and manner of neovascularisation. Our aim is to determine the effect of some key clinical variables on neovascularisation in muscle flaps in an animal model.MethodologyPectoralis profundus was raised in 60 rats and covered with skin graft. Fifteen cases were allocated to groups: separation of the flap from the skin inset (S), inflammation by inoculation with Staphylococcus aureus (I), flap elevation with Harmonic Scalpel (H), preservation of the motor nerve (N) and compared to controls (C). Graft-take and wound complications were assessed five days later, as well as perfusion before and after pedicle ligation, using Laser Doppler Flowmetry and neovascularisation using barium angiography.ResultsFlaps with an intact motor nerve had significantly higher graft take than controls (59% vs 29%). Perfusion changed less than controls in all study groups, though the extent of flap necrosis was not significantly different. Only flaps raised with the harmonic scalpel generated more new vessels than controls at the inset (9.6 vs 3.2), particularly at the origin of the muscle (1.10 vs 0.19).ConclusionsAll study groups were less dependant on their pedicle for perfusion than controls. The use of the harmonic scalpel and increased inflammation seem pro-angiogenic, though they do not reduce flap necrosis after simulated pedicle injury. Neovascularisation will preferentially bridge to skin at the inset rather than tissues in the base of the wound. It is likely that flap necrosis is the result of a combination of unfavourable variables rather than one in isolation.

Deciding Staged Battles of the Past: On the Rhetorics of Olaf Müller’s Historical Philosophy of Science

Abstract

Since Plato's massive critique of the Sophists rhetoric's ill repute runs through the history of western philosophy denunciating methods of rhetoric as in large part dishonest persuasion strategies which are at most marginally interested in dealing with truths. This judgement falls way too short insofar as it distorts the historically grown stock labeled "rhetoric" not only in the Aristotelian work. With reference to Olaf Müller's philosophical book (Mehr Licht: Goethe mit Newton im Streit um die Farben, S. Fischer, Frankfurt am Main, 2015) addressing the "controversy" between Goethe and Newton about the nature of light, I will study the different rhetorical models and methods used by Newton and Goethe and also Müller himself. It becomes apparent that even works attempting to decide who was right in the long run do far more than trying to evoke true "representations" of facts or truths in the reader. The specific use of language patterns provides deeper insight into an author's mindset towards the subject area discussed in his work and generally speaking the investigation of the rhetoric of science and philosophy leads to a better understanding of different epistemic cultures both in philosophy and science.

Intestinal microbiome of broiler chickens after use of nanoparticles and metal salts

Abstract

The research included the study of influence of ultrafine particle preparations (nanoparticles of copper, zinc, iron, CuZn alloy) and metal salts (iron pyrophosphate, copper asparginate, zinc asparginate) on the composition of cecal microbiota of broiler chickens. Before adding the studied nanoparticles and metal salts to the diet, cecal microbiota of broiler chickens was represented by 76% Firmicutes taxon and 16% Bacteroidetes. Numerous among them were the bacteria of the taxa Anaerotruncus spp., Lactobacillus spp., Blautia spp., Alistipes spp., and Bacteroides spp.; they constituted 18, 17, 11, and 6%, respectively. A peculiarity of action of the most analyzed metals in nanoform and in the form of salts was a decrease in the number of phylum Firmicutes bacteria and an increase in the number of microorganisms of the phylum Bacteroidetes. The number of bacteria belonging to the families Ruminococcaceae (III, IV, V, VII, and VIII groups), Bacteroidaceae (in all experimental groups), and Lachnospiraceae (I, IV, V, and VII groups) was registered within the taxa of Firmicutes and Bacteroidetes. At the same time, in some experimental groups, the number of bacteria of the family Lachnospiraceae (II, III, and VIII) decreased in the intestine. The data obtained can be used to assess the possibility of using metal nanoparticles in the poultry diet, as a micronutrient preparation, to correct dysbiosis and to improve the utilization of fodder energy.

The dispositional architecture of epistemic reasons

Abstract

Epistemic reasons are meant to provide justification for beliefs. In this paper, I will be concerned with the requirements that have to be met if reasons are to discharge this function. It is widely recognized, however, that only possessed reasons can justify beliefs and actions. But what are the conditions that have to be satisfied in order for one to possess reasons? I shall begin by motivating a particular condition, namely, the 'treating' requirement that has been deemed to be necessary for possessing reasons. In Sect. 1, I explain and criticize some of the existing accounts of the treating requirement for reason-possession. In Sect. 2, I will suggest a dispositional account of reason-possession in which the treating condition features prominently. Section 3 will deal with the some of the consequences of this account for such issues as the structure of epistemic defeat, the immediacy of perceptual justification and logical knowledge.

Occurrence of polybrominated diphenyl ethers in floor and elevated surface house dust from Shanghai, China

Abstract

House dust is the main source of human exposure to flame retardants by ingestion. This study investigated the occurrence of polybrominated diphenyl ethers (PBDEs) in indoor dust from 22 houses in Shanghai, China. House dust was separately collected from the floor and elevated furnishings surface (mostly between 0.5 and 2 m height) for comparison. The concentrations of ∑₂₂ PBDEs ranged from 19.4 to 3280 ng/g (with a geometric mean of 203 ng/g) and from 55.1 to 792 ng/g (with a geometric mean of 166 ng/g) in floor dust (FD) and elevated surface dust (ESD), respectively. BDE-209 was the predominant congener, accounting for about 73.1% of total PBDE burdens. In terms of congener profiles, the comparison of FD and ESD revealed no significant differences except for the ratio of BDE-47/BDE-99. ESD samples displayed a ratio of BDE-47/BDE-99 very similar to commercial penta-BDE products DE-71 while the ratio in FD was exceptionally higher. Significant correlation was found between concentrations of commercial penta-BDE compositions in FD and ESD (p < 0.05). Except for some occasional values, PBDE levels in house dust exhibited temporal stability. Human exposure to PBDEs via dust ingestion was estimated. The highest daily intake of PBDEs was for toddlers by using 95th percentile concentrations of PBDEs via high dust ingestion in FD (23.07 ng/kg bw/day). About 20-fold difference in exposure estimates between toddlers and adults supports that toddlers are facing greater risk from indoor floor dust. Expectedly, this study highlighted the point that residents in Shanghai were exposed to low doses of PBDEs in house dust.

Transformations of 2-line ferrihydrite and its effect on cadmium adsorption

Abstract

In this study, 2LFh was synthesized, and the effects of 2LFh synthesis in the laboratory as well as its synthetic products' mineral crystal phase changes during high temperature aging process caused by Ca²⁺, Mg²⁺, and Cl⁻ were also studied. In addition, the Cd²⁺ adsorption effects of the products above with different pH values and different Cd²⁺ concentrations were studied in this experiment. The results showed that the existence of Ca²⁺ had no significant effect on the synthesis and aging of 2LFh. However, in the presence of Mg²⁺ and Cl⁻, the akaganeite could be found in the synthetic material, and with the increase of the ion concentration, the crystallinity of the formed akaganeite was higher. And akaganeite had a significant inhibitory effect on the aging of 2LFh, causing the Cd²⁺adsorption effect of 2LFh after aging was better than that of pure 2LFh. The adsorption and removal rates of Cd²⁺ in Fh2 series and Fh2-200 series were increased with the increase of initial concentration. With the increase of pH, the adsorption capacity and removal rate were increased, and the removal rate reached nearly 100% when pH value is ranging from 10 to 11. The isothermal adsorption experiment showed that the isothermal adsorption process of Cd²⁺ in Fh2 series and Fh2-200 series was in accordance with the Freundlich model. The affinity coefficient (Kf) of the Freundlich model of Fh2-200 series arranged in descending order is Fh2-200-Mgs> Fh2-200-Cas> Fh2-200s, showing that the Cd²⁺ adsorption capacity of Fh2-200 was relatively weak, while that of Fh2-200-Ca series and Fh2-200-Mg series was relatively strong, which was confirmed by the experimental results.

Fixed-bed operation for manganese removal from water using chitosan/bentonite/MnO composite beads

Abstract

In the present study, a new composite adsorbent, chitosan/bentonite/manganese oxide (CBMnO) beads, cross-linked with tetraethyl-ortho-silicate (TEOS) was applied in a fixed-bed column for the removal of Mn (II) from water. The adsorbent was characterised by scanning electron microscopy (SEM), Fourier transform infra-red (FT-IR), N₂ adsorption-desorption and X-ray photoelectron spectroscopy (XPS) techniques, and moreover the point of zero charge (pH_pzc) was determined. The extend of Mn (II) breakthrough behaviour was investigated by varying bed mass, flow rate and influent concentration, and by using real environmental water samples. The dynamics of the column showed great dependency of breakthrough curves on the process conditions. The breakthrough time (t_b ), bed exhaustion time (t_s ), bed capacity (q_e ) and the overall bed efficiency (R%) increased with an increase in bed mass, but decreased with the increase in both influent flow rate and concentration. Non-linear regression suggested that the Thomas model effectively described the breakthrough curves while large-scale column performance could be estimated by the bed depth service time (BDST) model. Experiments with environmental water revealed that coexisting ions had little impact on Mn (II) removal, and it was possible to achieve 6.0 mg/g breakthrough capacity (q_b ), 4.0 L total treated water and 651 bed volumes processed with an initial concentration of 38.5 mg/L and 5.0 g bed mass. The exhausted bed could be regenerated with 0.001 M nitric acid solution within 1 h, and the sorbent could be reused twice without any significant loss of capacity. The findings advocate that CBMnO composite beads can provide an efficient scavenging pathway for Mn (II) in polluted water.

Enhanced adsorption of uranium by modified red muds: adsorption behavior study

Abstract

Uranium is a hazardous and radioactive element. Effective removal of uranium from wastewater stream requires advanced functional materials and reliable technologies. Red mud is a type of low-cost adsorbent which is widely used in the adsorption process. In the present work, we successfully modified the raw red mud to gain a series of highly efficient sorbents for uranium removal. They are nitric acid dealkalized red mud (DRM), aluminum nitrate modified red mud (ARM), and ferric nitrate modified red mud (FRM). The adsorption efficiencies of uranium(VI) by DRM, ARM, and FRM were 74.50, 95.56, and 98.75% in their optimal immobilization regions, respectively. The chemisorption of uranium dominates the adsorption process of FRM, while as to physical adsorption dominates the adsorption process of ARM and DRM. Both DRM and ARM reached their maximum adsorption capacities at 10 min while that for FRM occurred at 30 min. FRM performed much stronger anti-interference ability to the influence of carbonate and calcium. The outstanding adsorption ability of these modified red muds is mainly due to the enhancement of ion exchange, co-precipitation, and electrostatic attraction by red mud's active components and functional groups.

Identification of phytotoxins in different plant parts of Brassica napus and their influence on mung bean

Abstract

Plants in Brassica genus have been found to possess strong allelopathic potential. They may inhibit seed germination and emergence of subsequent crops following them in a rotation system. Series of laboratory and greenhouse experiments were conducted to determine the allelopathic impacts of Brassica napus L. against mung bean. We studied (1) the effects of aqueous extract (5%) of different plant parts (root, stem, leaf, flower, and whole plant) of B. napus, (2) the effects of leaf and flower extracts of B. napus at 0, 1, 2, 3, and 4% concentrations, and (3) the effect of residues of different B. napus plant parts and decomposition periods (0, 7, 14, and 21 days) on germination and seedling growth of mung bean. Various types of phenolics including quercitin, chlorogenic acid, p-coumeric acid, m-coumaric acid, benzoic acid, caffeic acid, syringic acid, vanillic acid, ferulic acid, cinamic acid, and gallic acid were identified in plant parts of B. napus. Among aqueous extracts of various plant parts, leaf and flower were found to have stronger inhibitory effects on germination and seedling growth traits of mung bean, higher concentrations were more toxic. The decomposition period changed the phtotoxic effect of residues, more inhibitory effect was shown at 14 days decomposition while decomposition for 21 days reduced inhibitory effect. The more total water-soluble phenolic was found in 5% (w/v) aqueous extract and 5% (w/w) residues of B. napus flowers at 14 days of decomposition (89.80 and 10.47 mg L⁻¹), respectively. The strong inhibitory effects of B. napus should be managed when followed in rotation.

Effects of mining activities on evolution of water chemistry in coal-bearing aquifers in karst region of Midwestern Guizhou, China: evidences from δ 13 C of dissolved inorganic carbon and δ 34 S of sulfate

Abstract

The generation of acid mine drainage (AMD) may accelerate watershed erosion and promote the migration of heavy metals, then threaten local ecosystems such as aquatic life and even human health. Previous studies have focused primarily on influence of AMD in surface environment. In order to reveal the acidizing processes in karst high-sulfur coalfield in Southwest China, this study, by contrast, focused on the hydrogeochemical evolution process and acidification mechanism of mine water in Zhijin coalfield, western Guizhou Province. The oxidation of pyrite and other sulfides induced strong acidification of mine water according to the water chemical analysis. As a result, a series of geochemical processes such as dissolution of carbonates and silicates, hydrolysis of metal ions, and degassing of CO₂ complicated water chemical evolution. The dissolution of silicates controlled the chemical composition of mine water, but more carbonates might be dissolved during the acidification of mine water. The sources of sulfate are quite different in water samples collected from the two selected mine. According to sulfur isotope analysis, the dissolution of gypsum is the primary source of sulfate in samples from Hongfa mine, whereas sulfide oxidation contributed a large amount of sulfate to the mine water in Fenghuangshan mine. The dissolution of carbonates should be an important source of DIC in mine water and CO₂ originating from organic mineralization might also have a certain contribution. This study elucidated the groundwater chemical evolution processes in high-sulfur coal-bearing strata and provided a foundation for further study of carbonates erosion and carbon emission during acidification of mine water.

T cells isolated from patients with checkpoint inhibitor resistant-melanoma are functional and can mediate tumor regression

Abstract

Background

The majority of patients with metastatic melanoma obtain only short-term or no benefit at all from checkpoint inhibitor (CPI) immunotherapy. In this study, we investigated whether the immune system of patients progressing following CPI treatment was able to generate functional tumor-specific immune responses.

Materials and methods

Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions which progressed during or after anti-PD-1 and anti-CTLA-4 treatment. Tumor-specific immune responses were assessed with co-culture assays of TILs and autologous tumor cells.

Results

TILs from 23 metastases of individual patients could be assessed for T cell recognition of autologous tumor cells. All metastases were progressive on or following anti-PD-1 (23/23, 100%), and the majority also after anti-CTLA-4 (17/23, 74%). Functional anti-tumor immune responses were detected in 19/23 patients (83%). Both CD8⁺ (in 18/23 patients, 78%) and CD4⁺ (in 16/23 patients, 70%) TILs were able to recognize autologous tumors. A large fraction of CD8⁺ TILs (median 23%, range 1.0-84%) recognized tumor cells. This is similar to the cohorts of unselected patient populations with metastatic melanoma presented in previous studies. The localization of intratumoral immune infiltrates was heterogeneous among samples. In a phase I/II clinical trial, TILs were administered with lymphodepleting chemotherapy, pegIFNα2b and IL-2 to 12 patients with CPI-resistant melanoma. Out of 12 patients who previously failed CPI therapy, treatment with TILs resulted in two partial responses, of which one is ongoing.

Conclusions

Tumor-reactive T cells appear to heavily infiltrate the tumor microenvironment of patients who failed previous CPI treatment. These patients can still respond to an infusion of unselected autologous TILs. Our results warrant further testing of novel immune re-activation strategies in melanoma patients who failed multiple CPI therapy.

The allure of “ALUR”

Further evidence to support judicious use of antibiotics in patients with cancer

Anti-infective Vaccination Strategies in Patients with Hematologic Malignancies or Solid Tumors – Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO)

Abstract

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.

The case for ‘successfully’ treating hormone naïve metastatic prostate cancer

Editorial Board

Publication date: March 2018
Source:Annales de Dermatologie et de Vénéréologie, Volume 145, Supplement 3

Éditorial

Publication date: March 2018
Source:Annales de Dermatologie et de Vénéréologie, Volume 145, Supplement 3
Author(s): B. Cribier

High waterborne Mg does not attenuate the toxic effects of Fe, Mn, and Ba on Na + regulation of Amazonian armored catfish tamoatá ( Hoplosternum litoralle )

Abstract

Formation water (FoW) is a by-product from oil and gas production and usually has high concentrations of soluble salts and metals. Calcium (Ca) and magnesium (Mg) have been shown to reduce the toxicity of metals to aquatic animals, and previous study showed that high waterborne Ca exerts mild effect against disturbances on Na⁺ regulation in Amazonian armored catfish tamoatá (Hoplosternum littorale) acutely exposed to high Fe, Mn, and Ba levels. Here, we hypothesized that high Mg levels might also reduce the toxic effects of these metals on Na⁺ regulation of tamoatá. The exposure to 5% FoW promoted an increase in Na⁺ uptake and a rapid accumulation of Na⁺ in all tissues analyzed (kidney<plasma<gills<carcass<liver), besides increasing the branchial activity of both NKA and v-type H⁺-ATPase in fish. High waterborne Mg lowered Na⁺ efflux rates and markedly inhibited Na⁺ uptake, and also reduced both NKA activity and newly Na⁺ accumulation in gills of fish. High Fe levels increased Na⁺ net losses and inhibited Na⁺ uptake in tamoatá. The diffusive Na⁺ losses and the newly accumulated Na⁺ in gills were reduced in fish exposed to high Mn and Ba. High waterborne Ba also inhibited NKA in gills, while both high Mn and Ba inhibited v-type H⁺-ATPase in kidney of tamoatá. High Mg did not lessen the toxic effect of Fe on Na⁺ net fluxes, and reduced even more Na⁺ uptake and the newly Na⁺ accumulation in gills and plasma, and did not prevent the inhibition of both NKA and v-type H⁺-ATPases in kidney. Furthermore, Mg did not attenuate the effect of Mn on inhibition Na⁺ uptake, keeping the activity of v-type H⁺-ATPase in kidney significantly lowered. High Mg levels mildly attenuated the effects of Ba in Na⁺ balance by increasing the new accumulation of Na⁺ in liver, and restore the activity of both NKA and v-type H⁺-ATPase in gills of tamoatá. Overall, high waterborne Mg does not have a strong contribution to, or have only minor effects, in protecting tamoatá against disruptions in Na⁺ regulation mediated by high Fe, Mn, and Ba levels.

Monitoring substrate enables real-time regulation of a protein localization pathway

Abstract

Protein localization machinery supports cell survival and physiology, suggesting the potential importance of its expression regulation. Here, we summarize a remarkable scheme of regulation, which allows real-time feedback regulation of the machinery expression. A class of regulatory nascent polypeptides, called monitoring substrates, undergoes force-sensitive translation arrest. The resulting ribosome stalling on the mRNA then affects mRNA folding to expose the ribosome-binding site of the downstream target gene and up-regulate its translation. The target gene encodes a component of the localization machinery, whose physical action against the monitoring substrate leads to arrest cancellation. Thus, this scheme of feedback loop allows the cell to adjust the amount of the machinery to correlate inversely with the effectiveness of the process at a given moment. The system appears to have emerged late in evolution, in which a narrow range of organisms selected a distinct monitoring substrate-machinery combination. Currently, regulatory systems of SecM-SecA, VemP-SecDF2, and MifM-YidC2 are known to occur in different bacterial species.

Identification of a unique transcriptional architecture for the sigS operon in Staphylococcus aureus.

Abstract

Staphylococcus aureus possess three alternative σ factors, including a lone extracytoplasmic function σ factor, σ^S. Our group previously identified and characterized this element, mapping three sigS promoters, demonstrating its inducibility during stress and virulence inducing conditions, and demonstrating a role for this factor in disease causation. In the present study, we identify a fourth promoter of the sigS operon, termed P4, located in a unique position internal to the sigS coding region. Transcriptional profiling revealed that expression from P4 is dominant to the three upstream promoters, particularly upon exposure to chemical stressors that elicit DNA damage and disrupt cell wall stability; each of which have previously been shown to stimulate sigS expression. Importantly, expression of this fourth promoter, followed by at least one or more of the upstream promoters, is induced during growth in serum and upon phagocytosis by RAW 264.7 murine macrophage-like cells. Finally, we demonstrate that an upstream gene, SACOL1829, bears a large 3' UTR that spans the sigS-SACOL1828 coding region, and may serve to compete with the P4 transcript to inhibit σ^S production. Collectively, these findings reveal a unique operon architecture for the sigS locus that indicates the potential for novel regulatory mechanisms governing its expression.

Bacteria on display- can we, and should we? Artistically exploring the ethics of public engagement with science in Microbiology

Abstract

The field of microbiology presents unique opportunities, and accompanying challenges, for artistic collaborations. On one hand, artistic works enable exploration of the aesthetics and of issues in biomedical science and new technologies, and draw in new, non-scientific audiences. On the other hand, creating art with microbes requires rigorous consideration of health and safety.Artists working in this field, known as Bio Art, tend to want to push the boundaries of what is possible or 'known', and work with new biomedical tools as they become available. However, when an artist's proposed work is raising novel questions where the risks are not fully understood, who should decide if the benefits outweigh the consequences?The reflections of an art-collaborating scientist are related. Also considered is how close working relationships between disciplines can enable new ethical frameworks which consider these decisions, respecting artists' endeavours as a beneficial form of research in its own right, and even learning from the rich perspectives of artists to broaden reflections on the practice of science.

Angio-3, a 10-residue peptide derived from human plasminogen kringle 3, suppresses tumor growth in mice via impeding both angiogenesis and vascular permeability

Abstract

Anti-angiogenesis therapy is an established therapeutic strategy for cancer. The endogenous angiogenic inhibitor angiostatin contains the first 3–4 kringle domains of plasminogen and inhibits both angiogenesis and vascular permeability. We present here a 10-residue peptide, Angio-3, derived from plasminogen kringle 3, which retains the functions of angiostatin in inhibiting both angiogenesis and vascular permeability. NMR studies indicate that Angio-3 holds a solution structure similar to the corresponding region of kringle 3. Mechanistically, Angio-3 inhibited both VEGF- and bFGF-induced angiogenesis by inhibiting EC proliferation and migration while inducing apoptosis. Inhibition of VEGF-induced vascular permeability results from its ability to impede VEGF-induced dissociation of adherens junction and tight junction proteins as well as the formation of actin stress fibers. When administered intravenously, Angio-3 inhibited subcutaneous breast cancer and melanoma growth by suppressing both tumor angiogenesis and intra-tumor vascular permeability. Hence, Angio-3 is a novel dual inhibitor of angiogenesis and vascular permeability. It is valuable as a lead peptide that can be further developed as therapeutics for diseases involving excessive angiogenesis and/or vascular permeability.

Integration of a photocatalytic multi-tube reactor for indoor air purification in HVAC systems: a feasibility study

Abstract

This work is focused on an in-depth experimental characterization of multi-tube reactors for indoor air purification integrated in ventilation systems. Glass tubes were selected as an excellent photocatalyst substrate to meet the challenging requirements of the operating conditions in a ventilation system in which high flow rates are typical. Glass tubes show a low-pressure drop which reduces the energy demand of the ventilator, and additionally, they provide a large exposed surface area to allow interaction between indoor air contaminants and the photocatalyst. Furthermore, the performance of a range of P25-loaded sol-gel coatings was investigated, based on their adhesion properties and photocatalytic activities. Moreover, the UV light transmission and photocatalytic reactor performance under various operating conditions were studied. These results provide vital insights for the further development and scaling up of multi-tube reactors in ventilation systems which can provide a better comfort, improved air quality in indoor environments, and reduced human exposure to harmful pollutants.

Δευτέρα 23 Απριλίου 2018

Ecotoxicology in tropical regions

Miocardiopatía dilatada en una niña con epidermólisis ampollar distrófica recesiva

Publication date: Available online 23 April 2018
Source:Actas Dermo-Sifiliográficas
Author(s): A. Imbernón-Moya, R. Maseda-Pedrero, M. Feito, R. de Lucas

Rosácea papulopustulosa: respuesta al tratamiento con azitromicina oral

Publication date: Available online 23 April 2018
Source:Actas Dermo-Sifiliográficas
Author(s): M. Lova Navarro, P. Sánchez-Pedreño Guillen, A.M. Victoria Martínez, T. Martínez Menchón, R. Corbalán Vélez, J. Frías Iniesta
IntroducciónEl tratamiento de la rosácea papulopustulosa (RPP) ha consistido durante años en el uso de tetraciclinas orales y antibióticos tópicos. Pero no es infrecuente encontrar casos de RPP resistentes al tratamiento convencional. Azitromicina oral ha demostrado ser una opción eficaz para estos pacientes no respondedores.Material y métodoSe realizó un estudio piloto prospectivo con 16 pacientes con RPP no respondedores al tratamiento convencional (doxiciclina oral y metronidazol gel) que recibieron tratamiento con azitromicina oral. En la visita inicial (visita 1) se realizó una valoración basal del estadio clínico de la RPP, según 4 niveles de gravedad progresiva, y se inició tratamiento con azitromicina oral. A las 8 semanas de finalizar el tratamiento (visita 2) se evaluó la respuesta clínica según 3 niveles de mejoría respecto al estadio clínico basal. Posteriormente, para evaluar la eficacia de azitromicina oral a largo plazo, se realizaron visitas periódicas cada 12 semanas.ResultadosTodos los pacientes que recibieron tratamiento con azitromicina oral mejoraron de su RPP. A las 8 semanas de finalizar el tratamiento se objetivó un eritema facial residual débil o nulo, con desaparición completa de las pápulas y/o pústulas en el 87,5% de los pacientes. En cuanto al mantenimiento de la eficacia a largo plazo, únicamente 2 pacientes presentaron una recidiva de lesiones inflamatorias de RPP.ConclusionesLos resultados de nuestro estudio evidencian que azitromicina oral podría ser un fármaco de gran eficacia a corto y largo plazo para el manejo de aquellos casos de RPP resistentes al tratamiento convencional.IntroductionOral tetracyclines and topical antibiotics have been used to treat papulopustular rosacea (PPR) for years, but it is not uncommon to find patients who do not respond to this standard treatment. In such refractory cases, oral azithromycin has proven to be an effective option.Material and methodWe conducted a prospective pilot study of 16 patients with PPR who were treated with oral azithromycin after a lack of response to oral doxycycline and metronidazole gel. At the first visit, the patients were assessed for baseline severity of PPR on a 4-point clinical scale and started on oral azithromycin. At the second visit, response to treatment in terms of improvement from baseline was evaluated on a 3-point scale. Patients were then scheduled for follow-up visits every 12 weeks to assess long-term effectiveness.ResultsAll 16 patients experienced an improvement in their PPR following treatment with oral azithromycin. Eight weeks after completion of treatment, 14 patients (87.5%) showed complete or almost complete recovery (slight or no residual redness and complete clearance of papules and pustules). Only 2 patients experienced a new episode of inflammatory PPR lesions during follow-up.ConclusionsThe findings of this pilot study suggest that oral azithromycin could be a very effective short-term and long-term treatment for RPP resistant to conventional treatment.

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Τετάρτη 25 Απριλίου 2018

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Τρίτη 24 Απριλίου 2018

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Δευτέρα 23 Απριλίου 2018

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