Exposure assessment to bisphenol A (BPA) in Portuguese children by human biomonitoring

Abstract

Exposure to bisphenol A (BPA) is known to be widespread and available data suggests that BPA can act as an endocrine disruptor. Diet is generally regarded as the dominant BPA exposure source, namely through leaching to food from packaging materials. The aim of this study was to evaluate the exposure of 110 Portuguese children (4–18 years old), divided in two groups: the regular diet group (n = 43) comprised healthy normal weight/underweight children with no dietary control; the healthy diet group (n = 67) comprised children diagnosed for obesity/overweight (without other known associated diseases) that were set on a healthy diet for weight control. First morning urine samples were collected and total urinary BPA was analyzed after enzymatic hydrolysis via on-line HPLC-MS/MS with isotope dilution quantification. Virtually, all the children were exposed to BPA, with 91% of the samples above the LOQ (limit of quantification) of 0.1 μg/L. The median (95th percentile) urinary BPA levels for non-normalized and creatinine-corrected values were 1.89 μg/L (16.0) and 1.92 μg/g creatinine (14.4), respectively. BPA levels in the regular diet group were higher than in the healthy diet group, but differences were not significant. Calculated daily BPA intakes, however, were significantly higher in children of the regular diet group than in children of healthy diet group. Median (95th percentile) daily intakes amounted to 41.6 (467) ng/kg body weight/day in the regular diet group, and 23.2 (197) ng/kg body weight/day in the healthy diet group. Multiple logistic regression analysis revealed that children in the healthy diet group had 33% lower intakes than children in the regular diet group (OR 0.67; 95% CI 0.51–0.89). For both groups, however, urinary BPA levels and daily BPA intakes were within the range reported for other children's populations and were well below health guidance values such as the European Food Safety Authority (EFSA) temporary tolerable daily intake (t-TDI) of 4 μg/kg body weight/day. In addition, lower daily BPA intakes were more likely linked with the inherent dietary approach rather than with high BMI or obesity.

Light-emitting diodes: whether an efficient source of light for indoor plants?

Abstract

Availability of sufficient light for growth optimization of plants in greenhouse environment during winter is a major challenge, as light during winter is significantly lower than that in the summer. The most commonly used artificial light sources (e.g., metal halide lamps, high pressure sodium lamps, and high fluorescent lamps) are of low quality and inefficient. Therefore, better options should be developed for sustaining agricultural food production during low levels of solar radiation. In recent advances, light-emitting diodes (LEDs) have remarkable potential as supplemental source of light for promoting plant growth. LEDs are novel and versatile source of light with cool emitting surface, wavelength specificity, and low electric power requirement. In the present study, we provided a contemporary synthesis of existing evidence along with our hypothetical concepts to clarify how LED approach could be an efficient and cost-effective source of light for plant growth and development especially in closed production system. In comparative analysis of common artificial vs. LED lighting, we revealed that spectral quality of LEDs can have vivid effects on plant morphogenesis and anatomy. We also discussed the influence of different colors of LEDs on growth performance of plants and provided the cost benefit analysis of using LEDs compared with other traditional sources. Overall, we hope that this article will be of great worth in future due to its practical implications as well as research directions.

Circulating microRNAs in patients with hormone receptor-positive, metastatic breast cancer treated with dovitinib

Serial analysis of biomarkers in the circulation of patients undergoing treatment ("liquid biopsies") can provide new insights into drug effects. In particular the analysis of cell-free, circulating nucleic ac...

Vulnerability as a Key Concept in Museum Pedagogy on Difficult Matters

Abstract

In recent years there has been an increasing interest in museum studies in exhibitions on what is termed Difficult Matters (Silvén and Björklund 2006)—such as rape and mass murder—and how such exhibitions may evoke ethical change. This raises the question about the conditions on which such exhibitions can lead to an ethical change. By developing a conceptual framework this article contributes to museum studies on Difficult Matters demonstrating how vulnerability can work as a key concept in a relational pedagogical understanding of the conditions for ethical change. Inspired by feminist ethics the article suggests that there is an "ambivalent potentiality" of the concept of vulnerability (Murphy, in Violence and the philosophical imaginary, State University of New York Press, Albany, 2012) and forwards a double perspective on vulnerability as condition: vulnerability is inherent to the human condition and always situational. From this point of departure vulnerability is fleshed out as a key concept in museum pedagogy via pedagogical thinkers inspired by the philosopher Emmanuel Lévinas' ethics. Concepts like heteronomy, incarnation, Face and Saying/Said are introduced to define vulnerability and the relation between exhibition and visitor is defined as a teaching–learning relation conditioned by vulnerability. Vulnerability is defined as openness to an encounter with the Other as being different, which is conditional of an ethical transformation of existing perceptions of self, others and the world. Finally, inspired by feminist philosophy (Butler, in Precarious life the powers of mourning and violence, Verso, London, 2006) a norm critical is introduced. It is argued that displaying Difficult Matters in order to evoke an ethical transformation museum professionals need consider critically the norms of vulnerability at play in particular situations. On this basis, the concept of vulnerability can serve as a lever for discussions on the pedagogy of exhibitions on Difficult Matters and the ethical responsibility of museum professionals in public museums in this regard.

Clinical Research in Dermatology in Spain

Publication date: Available online 4 October 2017
Source:Actas Dermo-Sifiliográficas (English Edition)
Author(s): P. Dávila Seijo

Environmentally benign antifouling activity and toxic properties of bioactive metabolites from mangrove Excoecaria agallocha L

Abstract

This study was aimed to investigate the antifouling (AF) potentials and toxic properties of methanol extract from leaves of mangrove Excoecaria agallocha. Antimicrofouling activity results inferred that this extract strongly inhibited fouling bacterial and microalgal growth. This extract had also inhibited the settlement of brown mussel Perna indica and larvae of barnacle Balanus amphitrite. Further, EC₅₀ < LC₅₀ and therapeutic ratio > 1 together propagated non-toxic nature of the extract. Mollusk foot adherence assay result showed complete inhibition of foot spreading and loss of attachment of common rocky fouler Patella vulgata to the substrata. Field assay results affirmed that this extract effectively deterred settlement of biofoulers. Purification and GC-MS analysis of bioassay-guided active spot evidenced presence of three major compounds (> 85%) responsible for the promising AF activity. The identified lead compounds subjected to an estimation (BIOWIN™) program developed by United States Environmental Protection Agency (USEPA) predicts that they are biodegradable in nature.

Graphical abstract

HPV-Induced Atypical Pigmented High-grade Dysplasia of the Scrotum

This case report describes a patient with HPV-induced atypical pigmented high-grade dysplasia of the scrotum.

Delay and Disparity in Time to Surgical Treatment for Melanoma

The relationship between patient health insurance status, health care use, and outcomes has been explored in great depth and detail over decades for myriad diseases in the United States. Likewise, health services research has become increasingly relevant within the specialty of dermatology, especially as the emergence of "big data" and advanced analytics continue to transform overall health care delivery.

Treatment of Psychiatric Disorders and Skin-Restricted Lupus Remission

This observational cohort study investigates the association between treatment of psychiatric disorders and skin-restricted lupus remission in a patient cohort over 2.5 years.

Association of Delays in Surgery for Melanoma With Insurance Type

This cohort study investigates whether patients with Medicaid are more likely than patients with Medicare or private insurance to experience delays in surgery for melanoma.

Brentuximab Vedotin for Patients With Refractory Lymphomatoid Papulosis

This phase 2 trial of 12 patients assesses the efficacy and safety of brentuximab vedotin for lymphomatoid papulosis.

Increased GSNOR Expression during Aging Impairs Cognitive Function and Decreases S-Nitrosation of CaMKII{alpha}

As the population ages, an increasing number of people suffer from age-related cognitive impairment. However, the mechanisms underlying this process remain unclear. Here, we found that S-nitrosoglutathione reductase (GSNOR), the key enzyme that metabolizes intracellular nitric oxide (NO) and regulates S-nitrosation, was significantly increased in the hippocampus of both aging humans and mice. Transgenic mice overexpressing GSNOR exclusively in neurons showed cognitive impairment in behavioral tests, including the Morris water maze, fear conditioning, and the Y-maze test. We also found that GSNOR transgenic mice have LTP defects and lower dendrite spine density, whereas GSNOR knock-out mice rescued the age-related cognitive impairment. Analysis of S-nitrosation showed significantly decreased hippocampal CaMKIIα S-nitrosation in naturally aged mice and GSNOR transgenic mice. Consistent with the change in CaMKIIα S-nitrosation, the accumulation of CaMKIIα in the hippocampal synaptosomal fraction, as well as its downstream signaling targets p(S831)-GLUR1, was also significantly decreased. All these effects could be rescued in the GSNOR knock-out mice. We further verified that the S-nitrosation of CaMKIIα was responsible for the CaMKIIα synaptosomal accumulation by mutating CaMKIIα S-nitrosated sites (C280/C289). Upregulation of the NO signaling pathway rescued the cognitive impairment in GSNOR transgenic mice. In summary, our research demonstrates that GSNOR impairs cognitive function in aging and it could serve as a new potential target for the treatment of age-related cognitive impairment. In contrast to the free radical theory of aging, NO signaling deficiency may be the main mediator of age-related cognitive impairment.

SIGNIFICANCE STATEMENT This study indicated that S-nitrosoglutathione reductase (GSNOR), a key protein S-nitrosation metabolic enzyme, is a new potential target in age-related cognitive impairment; and in contrast to the free radical theory of aging, NO signaling deficiency may be the main cause of this process. In addition, increased GSNOR expression during aging decreases S-nitrosation of CaMKIIα and reduces CaMKIIα synaptosomal accumulation. To our knowledge, it is for the first time to show the cellular function regulation of CaMKIIα by GSNOR-dependent S-nitrosation as a new post-translational modification after its phosphorylation was explored. These findings elucidate a novel mechanism of age-related cognitive impairment and may provide a new potential target and strategy for slowing down this process.

Should a Few Null Findings Falsify Prefrontal Theories of Conscious Perception?

Is activity in prefrontal cortex (PFC) critical for conscious perception? Major theories of consciousness make distinct predictions about the role of PFC, providing an opportunity to arbitrate between these views empirically. Here we address three common misconceptions: (1) PFC lesions do not affect subjective perception; (2) PFC activity does not reflect specific perceptual content; and (3) PFC involvement in studies of perceptual awareness is solely driven by the need to make reports required by the experimental tasks rather than subjective experience per se. These claims are incompatible with empirical findings, unless one focuses only on studies using methods with limited sensitivity. The literature highlights PFC's essential role in enabling the subjective experience in perception, contra the objective capacity to perform visual tasks; conflating the two can also be a source of confusion.

Dual Perspectives Companion Paper: Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence, by Melanie Boly, Marcello Massimini, Naotsugu Tsuchiya, Bradley R. Postle, Christof Koch, and Giulio Tononi

Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current

Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC₅₀ <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons.

SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively.

Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence

The role of the frontal cortex in consciousness remains a matter of debate. In this Perspective, we will critically review the clinical and neuroimaging evidence for the involvement of the front versus the back of the cortex in specifying conscious contents and discuss promising research avenues.

Dual Perspectives Companion Paper: Should a Few Null Findings Falsify Prefrontal Theories of Conscious Perception?, by Brian Odegaard, Robert T. Knight, and Hakwan Lau

Neural Architecture of Selective Stopping Strategies: Distinct Brain Activity Patterns Are Associated with Attentional Capture But Not with Outright Stopping

In stimulus-selective stop-signal tasks, the salient stop signal needs attentional processing before genuine response inhibition is completed. Differential prefrontal involvement in attentional capture and response inhibition has been linked to the right inferior frontal junction (IFJ) and ventrolateral prefrontal cortex (VLPFC), respectively. Recently, it has been suggested that stimulus-selective stopping may be accomplished by the following different strategies: individuals may selectively inhibit their response only upon detecting a stop signal (independent discriminate then stop strategy) or unselectively whenever detecting a stop or attentional capture signal (stop then discriminate strategy). Alternatively, the discrimination process of the critical signal (stop vs attentional capture signal) may interact with the go process (dependent discriminate then stop strategy). Those different strategies might differentially involve attention- and stopping-related processes that might be implemented by divergent neural networks. This should lead to divergent activation patterns and, if disregarded, interfere with analyses in neuroimaging studies. To clarify this crucial issue, we studied 87 human participants of both sexes during a stimulus-selective stop-signal task and performed strategy-dependent functional magnetic resonance imaging analyses. We found that, regardless of the strategy applied, outright stopping displayed indistinguishable brain activation patterns. However, during attentional capture different strategies resulted in divergent neural activation patterns with variable activation of right IFJ and bilateral VLPFC. In conclusion, the neural network involved in outright stopping is ubiquitous and independent of strategy, while different strategies impact on attention-related processes and underlying neural network usage. Strategic differences should therefore be taken into account particularly when studying attention-related processes in stimulus-selective stopping.

SIGNIFICANCE STATEMENT Dissociating inhibition from attention has been a major challenge for the cognitive neuroscience of executive functions. Selective stopping tasks have been instrumental in addressing this question. However, recent theoretical, cognitive and behavioral research suggests that different strategies are applied in successful execution of the task. The underlying strategy-dependent neural networks might differ substantially. Here, we show evidence that, regardless of the strategy used, the neural network involved in outright stopping is ubiquitous. However, significant differences can only be found in the attention-related processes underlying those different strategies. Thus, when studying attentional processing of salient stop signals, strategic differences should be considered. In contrast, the neural networks implementing outright stopping seem less or not at all affected by strategic differences.

Stopping Inflammation in Stroke: Role of ST2/IL-33 Signaling

Reward-Related Ventral Striatum Activity Buffers against the Experience of Depressive Symptoms Associated with Sleep Disturbances

Sleep disturbances represent one risk factor for depression. Reward-related brain function, particularly the activity of the ventral striatum (VS), has been identified as a potential buffer against stress-related depression. We were therefore interested in testing whether reward-related VS activity would moderate the effect of sleep disturbances on depression in a large cohort of young adults. Data were available from 1129 university students (mean age 19.71 ± 1.25 years; 637 women) who completed a reward-related functional MRI task to assay VS activity and provided self-reports of sleep using the Pittsburgh Sleep Quality Index and symptoms of depression using a summation of the General Distress/Depression and Anhedonic Depression subscales of the Mood and Anxiety Symptoms Questionnaire-short form. Analyses revealed that as VS activity increased the association between sleep disturbances and depressive symptoms decreased. The interaction between sleep disturbances and VS activity was robust to the inclusion of sex, age, race/ethnicity, past or present clinical disorder, early and recent life stress, and anxiety symptoms, as well as the interactions between VS activity and early or recent life stress as covariates. We provide initial evidence that high reward-related VS activity may buffer against depressive symptoms associated with poor sleep. Our analyses help advance an emerging literature supporting the importance of individual differences in reward-related brain function as a potential biomarker of relative risk for depression.

SIGNIFICANCE STATEMENT Sleep disturbances are a common risk factor for depression. An emerging literature suggests that reward-related activity of the ventral striatum (VS), a brain region critical for motivation and goal-directed behavior, may buffer against the effect of negative experiences on the development of depression. Using data from a large sample of 1129 university students we demonstrate that as reward-related VS activity increases, the link between sleep disturbances and depression decreases. This finding contributes to accumulating research demonstrating that reward-related brain function may be a useful biomarker of relative risk for depression in the context of negative experiences.

Glucosylsphingosine Promotes {alpha}-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease

Glucocerebrosidase 1 (GBA) mutations responsible for Gaucher disease (GD) are the most common genetic risk factor for Parkinson's disease (PD). Although the genetic link between GD and PD is well established, the underlying molecular mechanism(s) are not well understood. We propose that glucosylsphingosine, a sphingolipid accumulating in GD, mediates PD pathology in GBA-associated PD. We show that, whereas GD-related sphingolipids (glucosylceramide, glucosylsphingosine, sphingosine, sphingosine-1-phosphate) promote α-synuclein aggregation in vitro, glucosylsphingosine triggers the formation of oligomeric α-synuclein species capable of templating in human cells and neurons. Using newly generated GD/PD mouse lines of either sex [Gba mutant (N370S, L444P, KO) crossed to α-synuclein transgenics], we show that Gba mutations predispose to PD through a loss-of-function mechanism. We further demonstrate that glucosylsphingosine specifically accumulates in young GD/PD mouse brain. With age, brains exhibit glucosylceramide accumulations colocalized with α-synuclein pathology. These findings indicate that glucosylsphingosine promotes pathological aggregation of α-synuclein, increasing PD risk in GD patients and carriers.

SIGNIFICANCE STATEMENT Parkinson's disease (PD) is a prevalent neurodegenerative disorder in the aging population. Glucocerebrosidase 1 mutations, which cause Gaucher disease, are the most common genetic risk factor for PD, underscoring the importance of delineating the mechanisms underlying mutant GBA-associated PD. We show that lipids accumulating in Gaucher disease, especially glucosylsphingosine, play a key role in PD pathology in the brain. These data indicate that ASAH1 (acid ceramidase 1) and GBA2 (glucocerebrosidase 2) enzymes that mediate glucosylsphingosine production and metabolism are attractive therapeutic targets for treating mutant GBA-associated PD.

Content-Specific Codes of Parametric Vibrotactile Working Memory in Humans

To understand how the brain handles mentally represented information flexibly in the absence of sensory stimulation, working memory (WM) studies have been essential. A seminal finding in monkey research is that neurons in the prefrontal cortex (PFC) retain stimulus-specific information when vibrotactile frequencies were memorized. A direct mapping between monkey studies and human research is still controversial. Although oscillatory signatures, in terms of frequency-dependent parametric beta-band modulation, have been observed recently in human EEG studies, the content specificity of these representations in terms of multivariate pattern analysis has not yet been shown. Here, we used fMRI in combination with multivariate classification techniques to determine which brain regions retain information during WM. In a retro-cue delayed-match-to-sample task, human subjects memorized the frequency of vibrotactile stimulation over a 12 s delay phase. Using an assumption-free whole-brain searchlight approach, we tested with support vector regression which brain regions exhibited multivariate parametric WM codes of the maintained frequencies during the WM delay. Interestingly, our analysis revealed an overlap with regions previously identified in monkeys composed of bilateral premotor cortices, supplementary motor area, and the right inferior frontal gyrus as part of the PFC. Therefore, our results establish a link between the WM codes found in monkeys and those in humans and emphasize the importance of the PFC for information maintenance during WM also in humans.

SIGNIFICANCE STATEMENT Working memory (WM) research in monkeys has identified a network of regions, including prefrontal regions, to code stimulus-specific information when vibrotactile frequencies are memorized. Here, we performed an fMRI study during which human subjects had to memorize vibratory frequencies in parallel to previous monkey research. Using an assumption-free, whole-brain searchlight decoding approach, we identified for the first time regions in the human brain that exhibit multivariate patterns of activity to code the vibratory frequency parametrically during WM. Our results parallel previous monkey findings and show that the supplementary motor area, premotor, and the right prefrontal cortex are involved in vibrotactile WM coding in humans.

KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS

Neurons in the adult mammalian CNS decrease in intrinsic axon growth capacity during development in concert with changes in Krüppel-like transcription factors (KLFs). KLFs regulate axon growth in CNS neurons including retinal ganglion cells (RGCs). Here, we found that knock-down of KLF9, an axon growth suppressor that is normally upregulated 250-fold in RGC development, promotes long-distance optic nerve regeneration in adult rats of both sexes. We identified a novel binding partner, MAPK10/JNK3 kinase, and found that JNK3 (c-Jun N-terminal kinase 3) is critical for KLF9's axon-growth-suppressive activity. Interfering with a JNK3-binding domain or mutating two newly discovered serine phosphorylation acceptor sites, Ser106 and Ser110, effectively abolished KLF9's neurite growth suppression in vitro and promoted axon regeneration in vivo. These findings demonstrate a novel, physiologic role for the interaction of KLF9 and JNK3 in regenerative failure in the optic nerve and suggest new therapeutic strategies to promote axon regeneration in the adult CNS.

SIGNIFICANCE STATEMENT Injured CNS nerves fail to regenerate spontaneously. Promoting intrinsic axon growth capacity has been a major challenge in the field. Here, we demonstrate that knocking down Krüppel-like transcription factor 9 (KLF9) via shRNA promotes long-distance axon regeneration after optic nerve injury and uncover a novel and important KLF9–JNK3 interaction that contributes to axon growth suppression in vitro and regenerative failure in vivo. These studies suggest potential therapeutic approaches to promote axon regeneration in injury and other degenerative diseases in the adult CNS.

This Week in The Journal

How Human Amygdala and Bed Nucleus of the Stria Terminalis May Drive Distinct Defensive Responses

The ability to adaptively regulate responses to the proximity of potential danger is critical to survival and imbalance in this system may contribute to psychopathology. The bed nucleus of the stria terminalis (BNST) is implicated in defensive responding during uncertain threat anticipation whereas the amygdala may drive responding upon more acute danger. This functional dissociation between the BNST and amygdala is however controversial, and human evidence scarce. Here we used data from two independent functional magnetic resonance imaging studies [n = 108 males and n = 70 (45 females)] to probe how coordination between the BNST and amygdala may regulate responses during shock anticipation and actual shock confrontation. In a subset of participants from Sample 2 (n = 48) we demonstrate that anticipation and confrontation evoke bradycardic and tachycardic responses, respectively. Further, we show that in each sample when going from shock anticipation to the moment of shock confrontation neural activity shifted from a region anatomically consistent with the BNST toward the amygdala. Comparisons of functional connectivity during threat processing showed overlapping yet also consistently divergent functional connectivity profiles for the BNST and amygdala. Finally, childhood maltreatment levels predicted amygdala, but not BNST, hyperactivity during shock anticipation. Our results support an evolutionary conserved, defensive distance-dependent dynamic balance between BNST and amygdala activity. Shifts in this balance may enable shifts in defensive reactions via the demonstrated differential functional connectivity. Our results indicate that early life stress may tip the neural balance toward acute threat responding and via that route predispose for affective disorder.

SIGNIFICANCE STATEMENT Previously proposed differential contributions of the BNST and amygdala to fear and anxiety have been recently debated. Despite the significance of understanding their contributions to defensive reactions, there is a paucity of human studies that directly compared these regions on activity and connectivity during threat processing. We show strong evidence for a dissociable role of the BNST and amygdala in threat processing by demonstrating in two large participant samples that they show a distinct temporal signature of threat responding as well as a discriminable pattern of functional connections and differential sensitivity to early life threat.

Suppression of Striatal Prediction Errors by the Prefrontal Cortex in Placebo Hypoalgesia

Classical learning theories predict extinction after the discontinuation of reinforcement through prediction errors. However, placebo hypoalgesia, although mediated by associative learning, has been shown to be resistant to extinction. We tested the hypothesis that this is mediated by the suppression of prediction error processing through the prefrontal cortex (PFC). We compared pain modulation through treatment cues (placebo hypoalgesia, treatment context) with pain modulation through stimulus intensity cues (stimulus context) during functional magnetic resonance imaging in 48 male and female healthy volunteers. During acquisition, our data show that expectations are correctly learned and that this is associated with prediction error signals in the ventral striatum (VS) in both contexts. However, in the nonreinforced test phase, pain modulation and expectations of pain relief persisted to a larger degree in the treatment context, indicating that the expectations were not correctly updated in the treatment context. Consistently, we observed significantly stronger neural prediction error signals in the VS in the stimulus context compared with the treatment context. A connectivity analysis revealed negative coupling between the anterior PFC and the VS in the treatment context, suggesting that the PFC can suppress the expression of prediction errors in the VS. Consistent with this, a participant's conceptual views and beliefs about treatments influenced the pain modulation only in the treatment context. Our results indicate that in placebo hypoalgesia contextual treatment information engages prefrontal conceptual processes, which can suppress prediction error processing in the VS and lead to reduced updating of treatment expectancies, resulting in less extinction of placebo hypoalgesia.

SIGNIFICANCE STATEMENT In aversive and appetitive reinforcement learning, learned effects show extinction when reinforcement is discontinued. This is thought to be mediated by prediction errors (i.e., the difference between expectations and outcome). Although reinforcement learning has been central in explaining placebo hypoalgesia, placebo hypoalgesic effects show little extinction and persist after the discontinuation of reinforcement. Our results support the idea that conceptual treatment beliefs bias the neural processing of expectations in a treatment context compared with a more stimulus-driven processing of expectations with stimulus intensity cues. We provide evidence that this is associated with the suppression of prediction error processing in the ventral striatum by the prefrontal cortex. This provides a neural basis for persisting effects in reinforcement learning and placebo hypoalgesia.

Overdominant Effect of a CHRNA4 Polymorphism on Cingulo-Opercular Network Activity and Cognitive Control

The nicotinic system plays an important role in cognitive control and is implicated in several neuropsychiatric conditions. However, the contributions of genetic variability in this system to individuals' cognitive control abilities are poorly understood and the brain processes that mediate such genetic contributions remain largely unidentified. In this first large-scale neuroimaging genetics study of the human nicotinic receptor system (two cohorts, males and females, fMRI total N = 1586, behavioral total N = 3650), we investigated a common polymorphism of the high-affinity nicotinic receptor α4β2 (rs1044396 on the CHRNA4 gene) previously implicated in behavioral and nicotine-related studies (albeit with inconsistent major/minor allele impacts). Based on our prior neuroimaging findings, we expected this polymorphism to affect neural activity in the cingulo-opercular (CO) network involved in core cognitive control processes including maintenance of alertness. Consistent across the cohorts, all cortical areas of the CO network showed higher activity in heterozygotes compared with both types of homozygotes during cognitive engagement. This inverted U-shaped relation reflects an overdominant effect; that is, allelic interaction (cumulative evidence p = 1.33 * 10^–5). Furthermore, heterozygotes performed more accurately in behavioral tasks that primarily depend on sustained alertness. No effects were observed for haplotypes of the surrounding CHRNA4 region, supporting a true overdominant effect at rs1044396. As a possible mechanism, we observed that this polymorphism is an expression quantitative trait locus modulating CHRNA4 expression levels. This is the first report of overdominance in the nicotinic system. These findings connect CHRNA4 genotype, CO network activation, and sustained alertness, providing insights into how genetics shapes individuals' cognitive control abilities.

SIGNIFICANCE STATEMENT The nicotinic acetylcholine system plays a central role in neuromodulatory regulation of cognitive control processes and is dysregulated in several neuropsychiatric disorders. Despite this functional importance, no large-scale neuroimaging genetics studies have targeted the contributions of genetic variability in this system to human brain activity. Here, we show the impact of a common polymorphism of the high-affinity nicotinic receptor α4β2 that is consistent across brain activity and behavior in two large human cohorts. We report a hitherto unknown overdominant effect (allelic interaction) at this locus, where the heterozygotes show higher activity in the cingulo-opercular network underlying alertness maintenance and higher behavioral alertness performance than both homozygous groups. This gene–brain–behavior relationship informs about the biological basis of interindividual differences in cognitive control.

Limited Contribution of Primary Motor Cortex in Eye-Hand Coordination: A TMS Study

The ability to track a moving target with the eye is substantially improved when the target is self-moved compared with when it is moved by an external agent. To account for this observation, it has been postulated that the oculomotor system has access to hand efference copy, thereby allowing to predict the motion of the visual target. Along this scheme, we tested the effect of transcranial magnetic stimulation (TMS) over the hand area of the primary motor cortex (M1) when human participants (50% females) are asked to track with their eyes a visual target whose horizontal motion is driven by their grip force. We reasoned that, if the output of M1 is used by the oculomotor system to keep track of the target, on top of inducing short latency disturbance of grip force, single-pulse TMS should also quickly disrupt ongoing eye motion. For comparison purposes, the effect of TMS over M1 was monitored when subjects tracked an externally moved target (while keeping their hand at rest or not). In both cases, results showed no alterations in smooth pursuit, meaning that its velocity was unaffected within the 25–125 ms epoch that followed TMS. Overall, our results imply that the output of M1 has limited contribution in driving the eye motion during our eye-hand coordination task. This study suggests that, if hand motor signals are accessed by the oculomotor system, this is upstream of M1.

SIGNIFICANCE STATEMENT The ability to coordinate eye and hand actions is central in everyday activity. However, the neural mechanisms underlying this coordination remain to be clarified. A leading hypothesis is that the oculomotor system has access to hand motor signals. Here we explored this possibility by means of transcranial magnetic stimulation (TMS) over the hand area of the primary motor cortex (M1) when humans tracked with the eyes a visual target that was moved by the hand. As expected, ongoing hand action was perturbed 25–30 ms after TMS, but our results fail to show any disruption of eye motion, smooth pursuit velocity being unaffected. This work suggests that, if hand motor signals are accessed by the oculomotor system, this is upstream of M1.

Distinct Patterns of Temporal and Directional Connectivity among Intrinsic Networks in the Human Brain

To determine the spatiotemporal relationships among intrinsic networks of the human brain, we recruited seven neurosurgical patients (four males and three females) who were implanted with intracranial depth electrodes. We first identified canonical resting-state networks at the individual subject level using an iterative matching procedure on each subject's resting-state fMRI data. We then introduced single electrical pulses to fMRI pre-identified nodes of the default network (DN), frontoparietal network (FPN), and salience network (SN) while recording evoked responses in other recording sites within the same networks. We found bidirectional signal flow across the three networks, albeit with distinct patterns of evoked responses within different time windows. We used a data-driven clustering approach to show that stimulation of the FPN and SN evoked a rapid (<70 ms) response that was predominantly higher within the SN sites, whereas stimulation of the DN led to sustained responses in later time windows (85–200 ms). Stimulations in the medial temporal lobe components of the DN evoked relatively late effects (>130 ms) in other nodes of the DN, as well as FPN and SN. Our results provide temporal information about the patterns of signal flow between intrinsic networks that provide insights into the spatiotemporal dynamics that are likely to constrain the architecture of the brain networks supporting human cognition and behavior.

SIGNIFICANCE STATEMENT Despite great progress in the functional neuroimaging of the human brain, we still do not know the precise set of rules that define the patterns of temporal organization between large-scale networks of the brain. In this study, we stimulated and then recorded electrical evoked potentials within and between three large-scale networks of the brain, the default network (DN), frontoparietal network (FPN), and salience network (SN), in seven subjects undergoing invasive neurosurgery. Using a data-driven clustering approach, we observed distinct temporal and directional patterns between the three networks, with FPN and SN activity predominant in early windows and DN stimulation affecting the network in later windows. These results provide important temporal information about the interactions between brain networks supporting human cognition and behavior.

Nigral Glutamatergic Neurons Control the Speed of Locomotion

The mesencephalic locomotor region (MLR) plays a crucial role in locomotor control. In vertebrates, stimulation of the MLR at increasing intensities elicits locomotion of growing speed. This effect has been presumed to result from higher brain inputs activating the MLR like a dimmer switch. Here, we show in lampreys (Petromyzon marinus) of either sex that incremental stimulation of a region homologous to the mammalian substantia nigra pars compacta (SNc) evokes increasing activation of MLR cells with a graded increase in the frequency of locomotor movements. Neurons co-storing glutamate and dopamine were found to project from the primal SNc to the MLR. Blockade of glutamatergic transmission largely diminished MLR cell responses and locomotion. Local blockade of D₁ receptors in the MLR decreased locomotor frequency, but did not disrupt the SNc-evoked graded control of locomotion. Our findings revealed the presence of a glutamatergic input to the MLR originating from the primal SNc that evokes graded locomotor movements.

SIGNIFICANCE STATEMENT The mesencephalic locomotor region (MLR) plays a crucial role in the control of locomotion. It projects downward to reticulospinal neurons that in turn activate the spinal locomotor networks. Increasing the intensity of MLR stimulation produces a growing activation of reticulospinal cells and a progressive increase in the speed of locomotor movements. Since the discovery of the MLR some 50 years ago, it has been presumed that higher brain regions activate the MLR in a graded fashion, but this has not been confirmed yet. Here, using a combination of techniques from cell to behavior, we provide evidence of a new glutamatergic pathway activating the MLR in a graded fashion, and consequently evoking a progressive increase in locomotor output.

Prior Learning of Relevant Nonaversive Information Is a Boundary Condition for Avoidance Memory Reconsolidation in the Rat Hippocampus

Reactivated memories can be modified during reconsolidation, making this process a potential therapeutic target for posttraumatic stress disorder (PTSD), a mental illness characterized by the recurring avoidance of situations that evoke trauma-related fears. However, avoidance memory reconsolidation depends on a set of still loosely defined boundary conditions, limiting the translational value of basic research. In particular, the involvement of the hippocampus in fear-motivated avoidance memory reconsolidation remains controversial. Combining behavioral and electrophysiological analyses in male Wistar rats, we found that previous learning of relevant nonaversive information is essential to elicit the participation of the hippocampus in avoidance memory reconsolidation, which is associated with an increase in theta- and gamma-oscillation power and cross-frequency coupling in dorsal CA1 during reactivation of the avoidance response. Our results indicate that the hippocampus is involved in memory reconsolidation only when reactivation results in contradictory representations regarding the consequences of avoidance and suggest that robust nesting of hippocampal theta–gamma rhythms at the time of retrieval is a specific reconsolidation marker.

SIGNIFICANCE STATEMENT Posttraumatic stress disorder (PTSD) is characterized by maladaptive avoidance responses to stimuli or behaviors that represent or bear resemblance to some aspect of a traumatic experience. Disruption of reconsolidation, the process by which reactivated memories become susceptible to modifications, is a promising approach for treating PTSD patients. However, much of what is known about fear-motivated avoidance memory reconsolidation derives from studies based on fear conditioning instead of avoidance-learning paradigms. Using a step-down inhibitory avoidance task in rats, we found that the hippocampus is involved in memory reconsolidation only when the animals acquired the avoidance response in an environment that they had previously learned as safe and showed that increased theta- and gamma-oscillation coupling during reactivation is an electrophysiological signature of this process.

Reticulospinal Contributions to Gross Hand Function after Human Spinal Cord Injury

Multiple descending motor pathways likely contribute to the recovery of hand motor function following spinal cord injury (SCI). Reticulospinal neurons project to spinal motor neurons controlling hand muscles and extensively sprout into gray matter structures after SCI; therefore, it has been proposed that the reticulospinal tract is one of the descending motor pathways involved in recovery of hand function after injury. To test this hypothesis, we examined the StartReact response, an involuntary release of a planned movement via a startling stimulus that engages the reticulospinal tract, by measuring reaction times from electromyographic activity in an intrinsic finger muscle during three motor tasks requiring different degrees of hand dexterity: index finger abduction, a precision grip, and a power grip. Males and females with and without incomplete chronic cervical SCI were tested. We found that although SCI participants voluntarily responded to all tasks, reaction times were shorter during a startle cue while performing a power grip but not index finger abduction or precision grip. Control subjects had similarly shorter reaction times during a startle cue in all motor tasks. These results provide the first evidence for a contribution of the reticulospinal tract to hand control in humans with SCI during gross finger manipulations and suggest that this contribution is less pronounced during fine dexterous finger movements.

SIGNIFICANCE STATEMENT It has been long proposed that brainstem pathways contribute to the recovery of hand function in humans with spinal cord injury (SCI). Here, we show that individuals with anatomically incomplete chronic cervical SCI responded to a startle stimulus, a test that engages the reticulospinal tract, while performing a power grip but not during index finger abduction or precision grip. Control subjects responded to a startle stimulus similarly across tasks. These observations suggest that reticulospinal outputs after SCI contribute to hand motor tasks involving gross finger movements. Interestingly, this contribution is less pronounced during fine dexterous finger movements.

Memantine and Ketamine Differentially Alter NMDA Receptor Desensitization

Memantine and ketamine are clinically useful NMDA receptor (NMDAR) open channel blockers that inhibit NMDARs with similar potency and kinetics, but display vastly different clinical profiles. This discrepancy has been hypothesized to result from inhibition by memantine and ketamine of overlapping but distinct NMDAR subpopulations. For example, memantine but not ketamine may inhibit extrasynaptic NMDARs more effectively than synaptic NMDARs. However, the basis for preferential NMDAR inhibition depending on subcellular location has not been investigated systematically. We integrated recordings from heterologously expressed single NMDAR subtypes, kinetic modeling, and recordings of synaptically evoked NMDAR responses in acute brain slices to investigate mechanisms by which channel blockers may distinguish NMDAR subpopulations. We found that memantine and ketamine differentially alter NMDAR desensitization and that memantine stabilizes a Ca²⁺-dependent desensitized state. As a result, inhibition by memantine of GluN1/2A receptors in tsA201 cells and of native synaptic NMDARs in cortical pyramidal neurons from mice of either sex increased in conditions that enhanced intracellular Ca²⁺ accumulation. Therefore, differential inhibition by memantine and ketamine based on NMDAR location is likely to result from location dependence of the intensity and duration of NMDAR activation. Modulation of Ca²⁺-dependent NMDAR desensitization is an unexplored mechanism of inhibitory action with the potential to endow drugs with NMDAR selectivity that leads to superior clinical profiles. Our results suggest that designing compounds to target specific receptor states, rather than specific receptor types, may be a viable strategy for future drug development.

SIGNIFICANCE STATEMENT Memantine and ketamine are NMDA receptor (NMDAR) channel-blocking drugs with divergent clinical effects. Understanding mechanistically their differential actions may advance our understanding of nervous system disorders and suggest strategies for the design of more effective drugs. Here, we show that memantine and ketamine have contrasting effects on NMDAR desensitization. Ketamine binding decreases occupancy of desensitized states of the GluN1/2B NMDAR subtype. In contrast, memantine binding increases occupancy of GluN1/2A and native NMDAR desensitized states entered after accumulation of intracellular Ca²⁺, a novel inhibitory mechanism. These properties may contribute to inhibition of distinct NMDAR subpopulations by memantine and ketamine and help to explain their differential clinical effects. Our results suggest stabilization of Ca²⁺-dependent desensitized states as a new strategy for pharmaceutical neuroprotection.

2015–2016 Vaccine Effectiveness of Live Attenuated and Inactivated Influenza Vaccines in Children in the United States

Abstract

Background

In the 2015–2016 season, quadrivalent live attenuated influenza vaccine (LAIV) and both trivalent and quadrivalent inactivated influenza vaccine (IIV) were available in the United States.

Methods

This study, conducted according to a test-negative case-control design, enrolled children aged 2–17 years presenting to outpatient settings with fever and respiratory symptoms for <5 days at 8 sites across the United States between November 30, 2015 and April 15, 2016. A nasal swab was obtained for reverse transcriptase–polymerase chain reaction (RT-PCR) testing for influenza, and influenza vaccination was verified in the medical record or vaccine registry. Influenza vaccine effectiveness (VE) was estimated using a logistic regression model.

Results

Of 1012 children retained for analysis, most children (59%) were unvaccinated, 10% received LAIV, and 31% received IIV. Influenza A (predominantly antigenically similar to the A/California/7/2009 strain) was detected in 14% and influenza B (predominantly a B/Victoria lineage) in 10%. For all influenza, VE was 46% (95% confidence interval [CI], 7–69%) for LAIV and 65% (95% CI, 48–76%) for IIV. VE against influenza A(H1N1)pdm09 was 50% (95% CI, –2% to 75%) for LAIV and 71% (95% CI, 51–82%) for IIV. The odds ratio for vaccine failure with RT-PCR–confirmed A(H1N1)pdm09 was 1.71 (95% CI, 0.78–3.73) in LAIV versus IIV recipients.

Conclusions

LAIV and IIV demonstrated effectiveness against any influenza among children aged 2–17 years in 2015–2016. When compared to all unvaccinated children, VE against influenza A(H1N1)pdm09 was significant for IIV but not LAIV.

ClinicalTrials.gov identifier

NCT01997450

The challenge of vaccine policy-making with imperfect data

influenza vaccinelive-attenuated influenza vaccinevaccine policyglobal healthobservational research

Comparative Epidemiology and Outcomes of HIV, Non-HIV Non-Transplant and Organ Transplant Associated Cryptococcosis: A Population-Based Study

Abstract

In this population-based study in the contemporary era in the United States, the proportion of HIV-negative patients with cryptococcosis is approaching that in HIV-infected patients. Cryptococossis is associated with higher mortality in HIV-negative patients (including organ transplant recipients).

Tuberculin skin test conversions and occupational exposure risk in US healthcare workers

Abstract

Background

Health care workers (HCWs) undergo occupational tuberculosis (TB) screening at regular intervals. However, the risk of contracting TB at the workplace in a setting with a low background TB incidence is unclear. We aimed to evaluate the risk of tuberculin skin test (TST) conversion and the risk of occupational TB infection among HCWs in such a setting.

Methods

We conducted a retrospective cohort study of employees of a large tertiary medical center in the US Midwest who had undergone TST screening during the study period January 1, 1998 to May 31, 2014.

Results

Among 40,142 HCWs who received a TST test, only 123 converted over 16.4 years. Only 9 (7%) of the converters had a suspected TB exposure at the workplace and none developed active TB. The majority of TST converters (66%) had a negative QuantiFERON ^®-TB test at the time of the conversion.

Conclusions

In one of the largest cohorts of HCWs in a low TB incidence setting, we demonstrated an extremely low risk of occupational TB exposure among TST converters and no resulting active TB cases. In this setting, the approach of testing HCWs at baseline and after TB exposure, rather than at regular intervals, should be considered.

Erythrodermic psoriasis peculiarly sparing anti-TNF injection sites in a patient with secondary loss of efficacy

Infliximab-induced acne and acute localized exanthematous pustulosis: Case report

Vismodegib persistence and discontinuation patterns in Greek patients from a real world setting

Abstract

Hedghehog pathway inhibitors have been successfully used for patients with locally advanced basal cell carcinomas. However, these treatments have been associated with various adverse events that may limit patient compliance. In this study, an association of patient and disease characteristics with drug compliance in a real clinical setting was made. 18 patients were included in the study. The average patient age was 78.39 years. The time that patients remained to treatment was, on average, 8.73 months. 72.2% of patients experienced at least one adverse event. At study cut-off, 11 out of 18 patients had discontinued treatment. The most common reason for discontinuation was reported "fatigue" from the treatment due to the type of AEs experienced (37.4%) and patient's choice after complete response achievement (30.8%). Factors that were associated with treatment discontinuation was: number of previous treatments, severity of AEs and patient age.

Amelanotic melanoma arising within a lesion of disseminated superficial actinic porokeratosis: An unusual presentation leading to a novel therapeutic approach

Abstract

Disseminated superficial actinic porokeratosis (DSAP) is the most common variant of porokeratosis with a potential for malignant transformation. Its association with malignant melanoma, however, is exceedingly rare. Treatment of DSAP is often ineffective. We report a unique case of amelanotic melanoma arising within a lesion of DSAP. The melanoma was managed surgically, and her DSAP were treated successfully with a novel approach utilizing 5-fluorouracil chemowraps.

Penicillin-binding protein encoded by pbp4 is involved in mediating copper stress in Listeria monocytogenes

Abstract

Listeria monocytogenes raises major food safety and public health concerns due its potential for severe foodborne disease and persistent colonization of food processing facilities. Copper is often employed to control pathogens in agriculture and is increasingly used in healthcare facilities, but mechanisms mediating tolerance of L. monocytogenes to copper remain poorly understood. A mariner-based mutant library of L. monocytogenes 2011L-2858, implicated in the 2011 listeriosis outbreak via whole cantaloupe, was screened for growth at sublethal levels of copper yielding mutant G2B4 with decreased copper tolerance. The transposon was localized in pbp4 (lmo2229 homolog), encoding a penicillin-binding protein (PBP). In addition to reduced copper tolerance, G2B4 exhibited increased susceptibility to β-lactam antibiotics, reduced biofilm formation, and reduced virulence in the Galleria mellonella model. Mutant phenotypes were fully restored upon genetic complementation of G2B4 with intact pbp4. Findings provide the first evidence for the role of a PBP in copper tolerance of L. monocytogenes and suggest that pbp4 may be a suitable target to enable the use of lower levels of copper or enhance effectiveness of levels currently in use. Given the wide distribution of PBPs and their highly conserved nature, this could have profound impacts in regard to ecology and control of L. monocytogenes and other microorganisms.

Plasmids can transfer to Clostridium difficile CD37 and 630Δ erm both by a DNase resistant conjugation-like mechanism and a DNase sensitive mechanism

Abstract

Broad host range conjugative plasmids that replicate in Escherichia coli have been widely used to mobilise smaller replicons, bearing their cognate origin of transfer (oriT) into a variety of organisms that are less tractable genetically, such as Clostridium (Clostridioides) difficile. In this work we demonstrated that the oriT region of pMTL9301 (derived from RK2) is not required for transfer between E. coli and C. difficile strains 630Δerm and CD37 and that this oriT-independent transfer is abolished in the presence of DNase when CD37 is the recipient. Transfer to the 630Δerm strain is DNase resistant even without an obvious oriT, when E. coli CA434 is used as a donor and is sensitive to DNase when E. coli HB101 is the donor.

Microbial organic acid production as carbon dioxide sink

Abstract

Mixed- substrate conversions are an under-regarded option to fix carbon dioxide in significant amounts. In such a conversion carbon dioxide together with one other carbon source like glucose are converted to a single carbon product. With mixed-substrate conversions it is possible to incorporate carbon dioxide into products with higher oxidation states than the co-substrate. Using abundant co-substrates like glucose, glycerol or methanol, it is possible to produce organic acids anaerobically, using CO₂ both as an electron acceptor and as an additional carbon source. Here, we outline the thermodynamic feasibility to produce industrially important organic acids with this approach to provide guidance for future metabolic engineering endeavours.

Keeping education fresh - Not just in microbiology

Abstract

Innovative practice from around the globe, addressing a range of recent educational themes and trends, was published in the FEMS Microbiology Letters virtual Thematic Issue ''Keeping Education Fresh' in October 2017. Its thought-provoking content is reviewed here to more directly facilitate reflections and discussions in the professional community. The focus is on best practice approaches when enhancing student engagement, how to adjust those to the diversity of learners, learning situations and infrastructures, and to a broad range of subjects. The need for authentic learning and to move away from didactic teaching is emphasized. The 'students as researchers' theme is featured e.g. in context of service learning. Creative approaches are presented such as using performing arts, popular culture and gamification. The development of interdisciplinary and intercultural competences, and the exploration of socioscientific themes and philosophical issues are considered. Revisions of curricula and programmes, reflective of educational advancements and sector drivers, are discussed from undergraduate to postgraduate and professional specialist level also in light of problem-based learning, interactive distance and on-campus learning, and even the legacy of Massive Open Online Courses. Such changes always require resources and skills, and carry risks. Yet, innovation is a risk worth taking to keep education fresh.

Metagenomics: novel enzymes from nonculturable microbes

Abstract

In the transition to the post-petroleum economy, there is a growing demand for novel enzymes with high process performances to replace traditional chemistry with a more 'green' approach. To date, microorganisms encompass the richest source of industrial biocatalysts, but the Earth-living microbiota remains largely untapped by using traditional isolation and cultivation methods. Metagenomics, which is culture-independent, represents a powerful tool for discovering novel enzymes from unculturable microorganisms. Herein, we summarize the variety of approaches adopted for mining environmental DNA and, based on a systematic literature review, we provide a comprehensive list of 332 industrially relevant enzymes discovered from metagenomes within the last three years.

Enhanced killing of Escherichia coli using a combination of polyhexamethylene biguanide hydrochloride and 1-bromo-3-chloro-5,5- dimethylimidazolidine-2,4-dione

Abstract

The bactericidal activities of polyhexamethylene biguanide hydrochloride (PHMB), 1-bromo-3-chloro-5,5-dimethylimidazolidine-2,4-dione (BCDMH), and the combination of the two (designated as PB) were compared using Escherichia coli as the test organism. PB exhibited strong bactericidal activity: 10 mg/L PHMB combined with 8 mg/L BCDMH resulted in approximately 5.74 log₁₀ reduction (LR), whereby 320 mg/L PHMB or 20 mg/L BCDMH was about 5.53 and 6.56 LR, respectively. Analyses using scanning electron microscopy, flow cytometry, and atomic absorption spectroscopy indicated that PB, PHMB, and BCDMH disrupted cell membranes and changed membrane structure and permeability, resulting in the leakage of intracellular soluble proteins and ions. PB exerted stronger effects on potassium and magnesium leakage, membrane potential, and permeability than BCDMH did. PB caused less protein leakage than PHMB did. These results suggest that at a relatively low concentration, PB exhibited good bactericidal activity and physiological effect on E. coli.

Body Contouring Surgery and the Maintenance of Weight-Loss Following Roux-En-Y Gastric Bypass: A Retrospective Study

Abstract

Background

Bariatric surgery leads to significant weight loss with reduced morbidity and mortality. However, excess skin as a consequence of weight loss represents a major problem, impacting upon patient's functionality with potential negative effects on weight loss.

Objectives

We evaluated the effect of body-contouring surgery on weight-loss maintenance following bariatric surgery.

Methods

We undertook a retrospective analysis of patients undergoing Roux-en-Y gastric bypass (RYGB) +/- body-contouring surgery (BC). The control group (n = 61) received RYGB, the test group (n = 30) received RYGB+BC 12 to 18 months after bariatric surgery. Each RYGB+BC patient was matched to two control patients for age, sex, glycaemic status, and weight on day of surgery. Per cent weight loss (%WL) was calculated at 3, 6, 12, 24, 36, 48, and 60 months post-RYGB for both groups.

Results

The %WL was similar at 3, 6, and 12 months post-RYGB. At 24 months, %WL was 35.6% in the RYGB+BC group and 30.0% in the RYGB group (P < 0.05). At 36 months, the RYGB+BC group maintained their weight loss (%WL 33.0%), in contrast, the RYGB gained weight (%WL = 27.3%, P < 0.05). This trend continued (RYGB+BC vs RYGB) at 48 months (%WL 30.8% vs 27.0%) and at 60 months (%WL 32.2% vs 22.7%, P < 0.05).

Conclusions

Our results suggest patients who undergo body contouring after bariatric surgery are able to lose significantly more weight and maintain weight loss at five years of follow up compared to those undergoing bariatric surgery alone.

Level of Evidence: 3

Mitteilungen

Zahntraumata

Zusammenfassung

Verletzungen der Zahnhartsubstanz und des Zahnhalteapparates treten häufig bei Unfallverletzungen auf. Seit Mai 2016 liegt eine von der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. (AWMF) veröffentlichte Leitlinie zur Behandlung des dentalen Traumas vor. Die höchste Inzidenz für Frontzahntraumata findet sich bei den 7‑ bis 12-Jährigen. Weitere häufige Ursachen für Zahntraumata sind in den höheren Lebensjahren Freizeitaktivitäten, Gewaltdelikte oder Folge von Stürzen unter Einfluss von Alkohol oder Drogen. Da viele der auftretenden Befunde im Rahmen von Unfällen festgestellt werden, kommt es häufig vor, dass Zahntraumata übersehen werden, da zunächst lebenserhaltende Maßnahmen Vorrang haben. Als Folge werden Maßnahmen zur Rettung ausgeschlagener Zähne zu spät eingeleitet. Anders als Knochenbrüche heilen Verletzungen der Zahnhartsubstanz zumeist nicht aus und erfordern weitere konservierende oder prothetische Maßnahmen.

Reviewers’ list December 2017

Publication date: Available online 3 October 2017
Source:Journal of the American Academy of Dermatology

Lessons of a day hospital: comprehensive assessment of patients with albinism in a European setting

Summary

Albinism is a rare genetic disease, comprising syndromic and non-syndromic forms. We assessed clinical and genetic characteristics in a prospective evaluation of 64 patients (33 children and 31 adults) seen at a specialized day hospital. Causative genetic mutations were found in TYR (23/64, 35.9%), OCA2 (19/64, 29.7%), TYRP1 (1/64, 1.6%), SLC45A2 (12/64, 18.7%), C10orf11 (1/64, 1.6%), HPS1 (3/64, 4.7%), HPS5 (1/64, 1.5%), HPS6 (1/64, 1.6%) and GPR143 (2/64, 3.1%). Causative mutations remained undetermined for 1 patient (1.6%). Heterogeneity for hair and skin phenotype was noted across and within the different genotypes. Skin and hair hypopigmentation did not correlate with visual impairment. The diagnosis of unrecognized syndromic forms and of cases of ocular albinism in this prospective and comprehensive series of patients with albinism in a European setting is remarkable. Photoprotection was overall good but not optimal.

Significance

Albinism is a heterogeneous genetic disease with highly variable skin phenotypes. Genetic analyses must be conducted in case of typical ophthalmological alterations, even if a complete hair and skin depigmentation is absent. Syndromic forms must also be carefully looked for, as we found as many as 7.8% of Hermansky-Pudlak syndromes in this European cohort who should benefit of an early diagnosis for an appropriate follow-up.

This article is protected by copyright. All rights reserved.

Leptomeningeal melanoma – a case series in the era of modern systemic therapy

Abstract

Leptomeningeal metastases (LM) occur more often in patients with melanoma than many other cancers, and historically these patients have an extremely poor prognosis, with survival ranging from 8-10 weeks (Harstad, Hess, & Groves, 2008). Landmark trials of BRAF inhibitors (BRAFi) and anti-PD-1 checkpoint inhibitor immunotherapy have shown high response rates and prolonged survival in patients with melanoma, but have tended to exclude patients with central nervous system metastasis, particularly those with leptomeningeal metastases (Larkin, Hodi, & Wolchok, 2015; G. V. Long et al., 2014; Robert et al., 2015). Subsequent trials in those with parenchymal brain metastases have shown these agents have similar and often concordant responses to extracranial metastasis, but the activity in those with leptomeningeal metastases has not been adequately addressed in any prospective trial (Goldberg et al., 2016; Georgina V. Long et al., 2017; G. V. Long et al., 2012; Tawbi et al., 2017).

This article is protected by copyright. All rights reserved.

Tretinoin

Brooke–Spiegler syndrome: focus on reflectance confocal microscopy findings of trichoepithelioma and flat cylindroma

Summary

Brooke–Spiegler syndrome (BSS) is a rare, autosomal dominant disorder characterized by multiple adnexal tumours, especially trichoepitheliomas, cylindromas and occasionally spiradenomas. These lesions usually begin to appear in the second or third decade of life. Malignant transformation of pre-existing tumours may occur. In vivo reflectance-mode confocal microscopy (RCM) is a noninvasive method that can be used to visualize the epidermis and the upper dermis at almost histological resolution. It has been used to evaluate several skin conditions, especially malignant lesions, and has been reported to be useful for differentiating between malignant and benign skin tumours. Only a few studies have reported on the use of confocal microscopy to characterize the features of benign adnexal neoplasms. We present a patient with BSS who presented to our clinic with multiple skin tumours. The possible utility of RCM for identifying adnexal neoplasms is emphasized in this report, which also describes the observed microscopic features.

Periodic facial erythema in a patient with postural orthostatic tachycardia syndrome

Radiation Therapy and Immediate Breast Reconstruction

Patients who undergo breast reconstruction experience higher complication rates if they have had a history of radiotherapy. However, implant-based reconstruction confers significantly higher complication and reconstruction failure rates compared with autologous reconstruction. This article analyses the factors that contribute to the complications of the different breast reconstruction modalities and the strategies described to mitigate these problems.

Erratum to: Comparing the Efficiency of Two Different Extraction Techniques in Removal of Maxillary Third Molars: A Randomized Controlled Trial

Evaluation of Post-surgical Bacteremia with Use of Povidone-Iodine and Chlorhexidine During Mandibular Third Molar Surgery

Abstract

Background

Microorganisms may invade the blood stream by oral routes through surgical procedures like extractions, fractured teeth and periodontal pockets. The incidence of bacteremia is 70–80 % following tooth extraction, sub gingival scaling and intra ligament injection.

Aims and Objectives

Aim of study was to evaluate and compare the efficacy of two topical antimicrobial agents for the prevention of post-surgical bacteremia during mandibular third molar surgery. And objectives were to suggest need of proper topical antimicrobial agents and select proper antibiotics before oral surgical procedures in high risk cardiac patients.

Materials and Methods

Thirty patients with Class 1, Position B mesioangular impacted mandibular third molar were randomly included in study and divided into 3 groups, each group containing 10 patients. Group I; sterile water group, Group II: povidone-iodine (5 %) group, Group III: chlorhexidine (Q, 2 %) group, pre and post-surgical blood samples were collected and Microbiological analyses of the blood samples were done. The organisms were identified by standard method on grams staining and identification of bacterial species by biochemical tests.

Results

The clinical parameters like oral hygiene index simplified and periodontal index of Russel showed that all patients in three groups had fair oral hygiene with simple gingivitis on mean. In some individuals with slightly higher OHIS and PI scores, bacteremia was noted. All the pre surgical blood samples were negative for the growth of bacteria after 7 days of culture. In total 30 patients, 12 subjects had postoperative bacteremia. Out of those 12 patients 6 cases (60 %) of group I showed positive bacterial growth in the post surgical blood sample, while 4 cases in group III and 2 cases (20 %) in group II showed the same.

Conclusion

Use of povidone-iodine and chlorhexidine prior to the oral surgical procedures decreases the incidence of bacteremia as compared to sterile water irrigation. Povidone-iodine significantly reduces the incidence bacteremia and number of organisms compared to chlorhexidine and sterile water.

Pleomorphic Adenoma of Soft Palate: Unusual Occurrence of the Major Tumor in Minor Salivary Gland—A Case Report and Literature Review

Abstract

Salivary gland tumours constitute about less than 4 % of all head and neck tumours. Pleomorphic adenoma, also called benign mixed tumour, is the most common tumour of the salivary glands. About 80–90 % of these tumours occur in the major salivary glands mainly parotid gland and 10 % of them occur in the minor salivary glands. The most common site for pleomorphic adenoma of the minor salivary glands is the palate, followed by the lips and the cheeks. Other rare sites include the floor of the mouth, tongue, tonsil, pharynx, retromolar area and the nasal cavity. Here, we are reporting a case of pleomorphic adenoma of the minor salivary glands of the soft palate in a 36-year-old Indian female. The mass was removed by wide local excision with adequate margins under general anesthesia. There was no recurrence seen after a follow-up period of 1 year.

Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials

Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB).

Paraprotein deposits in the skin

Cutaneous manifestations secondary to paraprotein deposits in the skin include a group of different disorders that although rare, may be the first clinical manifestation of the underlying hematologic dyscrasia. In this article we review the clinical manifestations and histopathologic findings of the processes that result from specific deposition of the paraprotein in different structures of the skin. Paraneoplastic processes frequently associated with hematologic malignancies will not be covered in this review.

Issue Information

Erratum to: Effects-based spatial assessment of contaminated estuarine sediments from Bear Creek, Baltimore Harbor, MD, USA

Abstract

The original publication of this paper contains an error. The correct image of figure 5 is shown in this paper.

Combining multiple biomarkers differentiates between active sJIA, sJIA-MAS, and EBV-HLH

Abstract

Cytokine storm syndromes are a clinically heterogeneous group of conditions resulting from a maladaptive host response to an inflammatory trigger. These syndromes lead to rapid progression of immune-mediated damage to healthy tissues resulting in life-threatening multisystem organ failure. Prompt recognition of disease and medical intervention to limit damage to healthy tissues is essential to prevent cytokine storm morbidity and mortality. However, the diagnosis of cytokine storm syndromes is challenging given the clinical heterogeneity in disease presentations. Therefore, expeditious and readily available tests to diagnose disease and differentiate between the various types of cytokine storm syndromes is of clinical utility. The recently published work of Shimizu and colleagues brings us closer to making this a reality (1). This article is protected by copyright. All rights reserved.

A comparison of TRECs and flow cytometry for naïve T cell quantification

Summary

Assessment of thymic output by measurement of naïve T cells is routinely carried out in clinical diagnostic laboratories, predominantly using flow cytometry with a suitable panel of antibodies. Naïve T cell measurements can also be made using molecular analyses to quantify TRECs (T cell receptor excision circle) levels in sorted cells from the peripheral blood. In this study we have retrospectively compared TRECs levels with CD45RA+CD27+ T cells and also with CD45RA+CD31+ T cells in 134 patient samples at diagnosis or during follow up. Both panels provide naïve T cell measurements that have a strongly positive correlation with TRECs numbers and are suitable for use with enumerating naïve T cell levels in a clinical laboratory. This article is protected by copyright. All rights reserved.

How you can help, without making a difference

Abstract

There are many cases in which people collectively cause some morally significant outcome (such as a harmful or beneficial outcome) but no individual act seems to make a difference. The problem in such cases is that it seems each person can argue, 'it makes no difference whether or not I do X, so I have no reason to do it.' The challenge is to say where this argument goes wrong. My approach begins from the observation that underlying the problem and motivating the typical responses to it is a standard, intuitive assumption. The assumption is that if an act will not make a difference with respect to an outcome, then it cannot play a significant, non-superfluous role in bringing that outcome about. In other words, helping to bring about an outcome requires making a difference. I argue that the key to solving the problem is to reject this assumption. I develop an account of what it is to help to bring about an outcome, where this does not require making a difference, and I use this explain our reasons for action in the problem cases. This account also yields an error theory that explains why the standard assumption is so tempting, even though it is mistaken.

Phenomenal consciousness, collective mentality, and collective moral responsibility

Abstract

Are corporations and other complex groups ever morally responsible in ways that do not reduce to the moral responsibility of their members? Christian List, Phillip Pettit, Kendy Hess, and David Copp have recently defended the idea that they can be. For them, complex groups (sometimes called collectives) can be irreducibly morally responsible because they satisfy the conditions for morally responsible agency; and this view is made more plausible by the claim (made by Theiner) that collectives can have minds. In this paper I give a new argument that they are wrong. Drawing on recent work in the philosophy of mind (what Uriah Kriegel calls "the phenomenal intentionality research program") and moral theory (David Shoemaker's tripartite theory of moral responsibility), I argue that for something to have a mind, it must be phenomenally conscious, and that the fact that collectives lack phenomenal consciousness implies that they are incapable of accountability, an important form of moral responsibility.

Erratum to: The metaphysics of goodness in the ethics of Aristotle

Why realists must reject normative quietism

Abstract

The last two decades have seen a surge of support for normative quietism: most notably, from Dworkin (1996, 2011), Nagel (1996, 1997), Parfit (2011a, b) and Scanlon (1998, 2014). Detractors like Enoch (2011) and McPherson (2011) object that quietism is incompatible with realism about normativity. The resulting debate has stagnated somewhat. In this paper I explore and defend a more promising way of developing that objection: I'll argue that if normative quietism is true, we can create reasons out of thin air, so normative realists must reject normative quietism.

Overexpression of NLRP3, NLRC4 and AIM2 inflammasomes and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in Malassezia folliculitis

Abstract

Background

The activation of NLRP3, NLRC4 and AIM2 inflammasomes is pivotal for innate immunity against some pathogenic fungi, but their role in the pathogenesis of Malassezia folliculitis (MF) remains unclear.

Objectives

To determine expression of four canonical inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2) and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in MF lesion.

Methods

Expression of NLRP1, NLRP3, NLRC4, AIM2, caspase-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB was detected by immunohistochemistry in skin lesion of 23 MF patients and normal skin of 12 healthy subjects. Furthermore, NLRP1, NLRP3, NLRC4, AIM2, caspase-1, and IL-1β mRNA was measured by quantitative real-time PCR (qRT-PCR) in 12 MF cases and 10 controls.

Results

Immunohistochemical analysis revealed that NLRP3, NLRC4, AIM2, Casp-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB expression was upregulated in the epidermis and dermal inflammatory cells of MF lesion compared with control skin (P<0.01-0.05), but NLRP1 expression was not different between both groups (P>0.05). qRT-PCR showed that levels of NLRP3, Casp-1, and IL-1β mRNA were significantly increased (P<0.01-0.05), whereas those of NLRP1, NLRC4, and AIM2 mRNA were slightly augmented compared to control skin (P>0.05).

Conclusions

Our observation suggests that simultaneous activation of NLRP3, NLRC4 and AIM2 inflammasomes may play an important role in the pathogenesis of MF.

This article is protected by copyright. All rights reserved.

Operieren geht über Studieren

Afrikanisches Zeckenstichfieber – Ein unliebsames Souvenir aus Südafrika

S1 guidelines for the diagnosis and treatment of ichthyoses – update

Summary

Ichthyoses are a group of rare genetic skin disorders that pose numerous clinical challenges, in particular with respect to the correct diagnosis and appropriate management. The present update of the German ichthyosis guidelines addresses recent diagnostic advances that have resulted in the Sorèze consensus classification. In this context, we provide an updated diagnostic algorithm, taking into account clinical features as well as the molecular genetic basis of these disorders. Moreover, we highlight current therapeutic approaches such as psychosocial support, balneotherapy, mechanical scale removal, topical therapy, and systemic retinoid therapy. General aspects such as the indication for physical therapy, ergotherapy, or genetic counseling are also discussed. The present update was consented by an interdisciplinary consensus conference that included dermatologists, pediatricians, human geneticists, and natural scientists as well as representatives of the German patient support organization Selbsthilfe Ichthyose e. V.

30 Jahre Ästhetische Dermatologie in Österreich: Historischer Rückblick über die Tätigkeit der ÖGDKA Österreichische Gesellschaft für Dermatologische Kosmetologie und Altersforschung

Kongresskalender 2017

Allergologische und mikrobiologische Gefährdung durch Hautmarkierung bei medizinischen Prozeduren?

In the English version of the original work

Nichtinvasive Diagnostik in der Dermatologie

Zusammenfassung

Neben der Auflichtmikroskopie gibt es bildgebende und biophysikalische Methoden, mit denen Hautveränderungen nichtinvasiv diagnostiziert werden können. Die konfokale Lasermikroskopie ermöglicht eine hochauflösende Darstellung der Epidermis bis zur oberen Dermis. Sie eignet sich insbesondere zur Differenzialdiagnostik melanozytärer Läsionen. Die optische Kohärenztomographie hat eine geringere Auflösung bei besserer Eindringtiefe. Ihre Domäne ist die Diagnostik epithelialer Hauttumoren und insbesondere die Verlaufsbeobachtung unter nichtchirurgischen Therapien. Die elektrische Impedanzspektroskopie liefert keine Bilder der Haut, sondern berechnet einen Score, der durch die zelluläre Irregularität der Haut beeinflusst wird. Die Multispektralanalyse beleuchtet die Haut mit unterschiedlichen Wellenlängen und berechnet ebenfalls einen Score. Beide Methoden eignen sich zur Differenzialdiagnose zwischen dysplastischen Nävi und malignen Melanomen. Weitere bildgebende und biophysikalische Diagnosemethoden befinden sich noch in einem experimentellen Entwicklungsstadium.

Die Methoden ermöglichen eine Verbesserung der nichtinvasiven Diagnostik, indem sie die Sensitivität und Spezifität der klinischen und auflichtmikroskopischen Diagnostik erhöhen, Verlaufsbeobachtungen ermöglichen und Therapieeffekte quantifizieren können. Sie unterstützen die Früherkennung maligner Tumoren und helfen auf der anderen Seite, unnötige Exzisionen benigner Veränderungen zu vermeiden.

Noninvasive diagnosis in dermatology

Summary

In addition to dermoscopy, there are other imaging and biophysical methods for the noninvasive diagnosis of skin lesions. Confocal laser microscopy allows for high-resolution imaging of the epidermis and upper dermis. It is particularly suitable in the differential diagnosis of melanocytic lesions. Optical coherence tomography (OCT) has a lower resolution compared to confocal laser microscopy but a greater depth of penetration. It is primarily used for imaging epithelial skin cancer, especially in the context of monitoring the effectiveness of nonsurgical therapies. Electrical impedance spectroscopy does not yield cutaneous images but rather provides a score based on the cellular irregularity of the skin. Multispectral analysis involves illumination of the skin with different wavelengths and likewise results in the computation of a score. Both methods are used in the differentiation of dysplastic nevi from melanoma. Other diagnostic imaging and biophysical methods are currently still in the developmental stages.

By increasing the sensitivity and specificity of clinical and dermoscopic findings, the aforementioned methods bring about an improvement in noninvasive diagnosis. They allow for skin lesions to be monitored over time and therapeutic effects to be quantified. Finally, they facilitate early diagnosis of skin cancer, and help avoid unnecessary surgery of benign lesions.

Journal-Club

In memoriam Prof. Dr. med. Carl Schirren

S1-Leitlinie zur Diagnostik und Therapie der Ichthyosen – Aktualisierung

Zusammenfassung

Ichthyosen sind seltene genetische Hautkrankheiten, die den Kliniker vor mannigfache Herausforderungen stellen, insbesondere in Bezug auf das Stellen einer zutreffenden Diagnose und einer angemessenen therapeutischen Betreuung. Mit dieser Aktualisierung der deutschen Ichthyosis-Leitlinie berücksichtigen wir jüngste diagnostische Fortschritte, die in die Konsensus-Klassifikation von Sorèze mündeten und erarbeiten einen aktuellen Diagnose-Algorithmus, der sowohl das klinische Bild als auch die Molekulargenetik dieser Erkrankungen berücksichtigt. Darüber hinaus wird der heutige Wissensstand bezüglich therapeutischer Ansätze wie psychosozialer Unterstützung, Balneotherapie, mechanischer Schuppenlösung, topischer Salbentherapie und Systemtherapie mit Retinoiden erläutert und es werden allgemeine Aspekte wie die Indikation für Physiotherapie, Ergotherapie oder die Notwendigkeit einer umfassenden genetischen Beratung diskutiert. Diese Aktualisierung der deutschen Ichthyosis-Leitlinie wurde durch eine interdisziplinär besetzte Leitlinienkonferenz verabschiedet, an der Dermatologen, Kinderärzte, Humangenetiker und Naturwissenschaftler teilnahmen und in die die deutsche Patientenorganisation Selbsthilfe Ichthyose e. V. eingebunden war.

Überlegenheit der okzipitalen Entnahmestelle bei Spalthauttransplantationen in der Dermatochirurgie: Ergebnisse einer prospektiven, randomisierten, kontrollierten Studie

Zusammenfassung

Hintergrund

Spalthauttransplantationen gehören in den klinischen Alltag der Dermatochirurgie. Für okzipital entnommene Spalthauttransplantate liegen bereits retrospektive Beobachtungsstudien vor, die ein gutes operatives Ergebnis hinsichtlich der Ein- und Abheilrate postulieren. Trotzdem werden in der Mehrheit der Fälle in der Dermatochirurgie femorale Entnahmestellen gewählt. Eine randomisierte, kontrollierte Studie zum Vergleich der Entnahmestelle fehlt bisher.

Patienten und Methodik

108 Patienten wurden nach mikrographisch kontrollierter R0-Resektion zur Defektdeckung mittels Spalthauttransplantat in zwei Gruppen randomisiert (Entnahmestelle Hinterkopf vs. Oberschenkel). Verlaufskontrollen wurden am Tag 3, 5, 7, 14, sowie nach einem und drei Monaten durchgeführt. Es erfolgte eine Dokumentation bezüglich Einheilrate des Transplantats, Reepithelisierungsrate an der Entnahmestelle, Schmerzhaftigkeit, kosmetisches Ergebnis, Vancouver Scar Scale (VSS) an der Entnahmestelle und am Transplantat, Patientenzufriedenheit sowie möglicher Komplikationen.

Ergebnisse

Die okzipitale Entnahmestelle zeigte eine signifikant schnellere Reepithelisierungsrate, weniger Schmerzhaftigkeit, weniger Komplikationen, ein besseres kosmetisches Ergebnis und hinterließ nach VSS eine qualitativ hochwertigere Narbe als die Entnahme am Oberschenkel. Hinsichtlich der Einheilrate im Defekt waren okzipital entnommene Transplantate den femoralen an den Tagen drei und fünf signifikant überlegen.

Schlussfolgerungen

Dies ist die erste randomisierte, kontrollierte Studie, die eine signifikante Überlegenheit der okzipitalen gegenüber der femoralen Entnahmestelle hinsichtlich Reepithelisierung, Schmerzen, des optischen Ergebnisses und des VSS zeigt.

Forschungspreis der Jörg Wolff-Stiftung – Arnold Rikli-Preis 2017

Fumarsäureester werden Europäer

Ungewöhnlich therapierefraktäre retikuläre Hautveränderungen bei einer jungen Frau

Longitudinale Sehnenspreizung in Kombination mit Unterdrucktherapie zur Therapie freiliegender Achillessehnen

Kutanes elastolytisches T-Zell-Lymphom (Granulomatous Slack Skin) mit Gefäßbeteiligung

In der deutschen Fassung der Originalarbeit

Proliferierende Trichilemmalzyste an der weiblichen Brust

Scalp hypothermia as a preventative measure for chemotherapy-induced alopecia: A review of controlled clinical trials

Abstract

Chemotherapy-induced alopecia (CIA) is a temporary, yet psychologically devastating form of hair loss that affects 65% of patients receiving cancer chemotherapy. In the 1970s, scalp hypothermia was introduced as a preventative measure against the development of CIA. Numerous studies provide evidence for the effectiveness of scalp cooling to prevent CIA, although results varied because of differences in chemotherapy regimen, cooling technique, mode of administration, and patient factors. However, many of the existing studies are uncontrolled or consist of small sample sizes, and data from randomized, randomized studies are limited. To date, no clear guidelines have been established for optimum scalp cooling use as a treatment modality and its efficacy remains unknown. Nonetheless, scalp cooling remains the most widely utilized method for the prevention of CIA, and in December 2015, the United States Food and Drug Administration (FDA) cleared the DigniCap^® scalp cooling system (Dignitana AB, Sweden) for marketing and the Orbis from Paxman^® Coolers Ltd. received clearance in 2017. This literature review is one of the first to provide up-to-date review and side-by-side comparisons of controlled and randomized clinical trials (CCTs and RCTs) evaluating scalp hypothermia for the prevention of CIA. Our analyses of CCTs and RCTs to date show that scalp hypothermia is effective in reducing the occurrence rate of CIA, by 2.7 fold in the CCTs and 3.9 fold in the RCTs. These results suggest that scalp hypothermia represents an effective preventative measure for CIA, and provide guidance for management of anticipated alopecia following chemotherapy and for future investigations.

This article is protected by copyright. All rights reserved.

Nutrient loads in the river mouth of the Río Verde basin in Jalisco, Mexico: how to prevent eutrophication in the future reservoir?

Abstract

Since nutrients are emitted and mobilized in river basins, causing eutrophication of water bodies, it is important to reduce such emissions and subsequent nutrient loads. Due to processes of attenuation, nutrient loads are reduced during their mobilization in river basins. At the mouth of the Río Verde basin in western Mexico, the El Purgatorio dam is being constructed to supply water to the metropolitan area of the second most populated city in the country, Guadalajara. To analyze situations that allow protecting this future dam from eutrophication, nutrient loads in the mouth of the river basin were determined and their reduction scenarios evaluated by using the NEWS2 (Nutrient Export from Watersheds) model. For this, a nutrient emissions inventory was established and used to model nutrient loads, and modeling results were compared to an analysis of water quality data from two different monitoring sites located on the river. The results suggest that 96% of nitrogen and 99% of phosphorus emissions are attenuated in the watershed. Nutrient loads reaching the mouth of the river basin come mainly from wastewater discharges, followed by livestock activities and different land uses, and loads are higher as emissions are located closer to the mouth of the river basin. To achieve and maintain mesotrophic state of water in the future dam, different nutrient emission reduction scenarios were evaluated. According to these results, the reduction of 90% of the phosphorus loads in wastewater emissions or 75% of the phosphorus loads in wastewater emissions and at least 50% in emissions from livestock activities in the river basin are required.

Assessing the protective effect of bentonite against lead toxicity in growing lambs

Abstract

The objective of the present experiment was to investigate the effect of bentonite supplementation in lead (Pb)-exposed lambs on serum Pb, Ca, P, Cu, Zn, and Fe concentrations, blood hematological parameters, and hepatic enzymes. Twenty Zandi male lambs (initial BW, 17.5 ± 1.6 kg) were randomly assigned to one of the four treatments: (1) control (no Pb or bentonite), (2) 15 mg/kg DM Pb as Pb acetate with no bentonite, (3) 15 mg/kg DM Pb as Pb acetate with 1.5% bentonite, and (4) 15 mg/kg DM Pb as Pb acetate with 3% bentonite. The experiment lasted after 90 days. Lead intake resulted in a decrease (P < 0.05) in serum Fe and an increase in serum Pb, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities (P < 0.05). Bentonite supplementation at 1.5 or 3% of DM decreased blood Pb concentration (P < 0.01) in lambs fed diets containing Pb and reduced (P < 0.05) blood concentration of Cu and Zn compared to control group (P < 0.01). However, the hematological parameters were not affected by any of the treatments. Our results showed that the dietary supplementation of bentonite could protect lambs against lead toxicity.

Effects of sulfur on toxicity and bioavailability of Cu for castor ( Ricinus communis L.) in Cu-contaminated soil

Abstract

The biogeochemical cycling of sulfur (S) in soil has an important impact on the bioavailability of heavy metals and affects the utilization of soil polluted by heavy metals. In addition, S-containing compounds are involved in heavy metal detoxification. This study investigated the effects of S on the toxicity and bioavailability of copper (Cu) in castor (Ricinus communis L.) grown in Cu-contaminated mine tailings. The results showed that the application of S reduced the accumulation of Cu in castor and promoted its growth. With the addition of S, the malondialdehyde (MDA) content of castor leaves decreased significantly compared with control plants, indicating the alleviation of oxidative stress. Superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) content decreased significantly with the alleviation of oxidative stress. The sequential extraction of Cu fractions showed that the application of S significantly reduced the reducible Cu fraction, and increased the oxidizable Cu fraction. It also increased the residual Cu fraction in the soil. The transformation of chemical speciation reduced the bioavailability of Cu in soil, which then reduced the accumulation of Cu in castor. Our results demonstrated that S application was effective at promoting castor growth by reducing the bioavailability and uptake of Cu in Cu-contaminated mine tailings.

Prevalence and predictors of sunburn among beachgoers

Summary

Background

Painful sunburns at any age are one of the main risk factors for skin cancer.

Objectives

To determine the prevalence and predictors of sunburn among beachgoers.

Methods

A cross-sectional health survey was conducted at the beach during the summer. Adults > 18 years with an understanding of Spanish were interviewed using a questionnaire about behaviours, attitudes and knowledge related to sun exposure at the beach. A descriptive analysis was performed and a log binomial regression model was used to determine predictors of sunburn.

Results

The survey was completed by 1054 beachgoers, with a mean age of 43.8 (SD: 18.7) years, 61.2% women, skin phototypes i (13.6%), ii (22.3%), iii (34.0%) and iv (30.2%). 46.9% of responders reported at least one painful sunburn during the previous summer. Age, sex, education, skin phototype, midday sun exposure, sun protection habits, attitudes towards tanning and knowledge about skin cancer were identified as independent predictors of sunburn.

Conclusions

It is necessary to develop photoprotection campaigns aimed at beachgoers, particularly in young people, men, those with skin phototypes I-III and secondary or universitary education. Educational strategies should be aimed at discouraging sun exposure at midday, changing attitudes towards tanning and improving knowledge about skin cancer.

This article is protected by copyright. All rights reserved.

Matrix metalloproteinase in acral and non-acral vitiligo

Repigmentation in vitiligo requires activation, proliferation and migration of the melanoblasts and melanocytes into the depigmented epidermis (1). Cell migration involves modifications of the architecture of cells which requires activation of enzymes that are involved in ECM degradation such as matrix metalloproteinases (MMPs). The significant reduction of their expression in vitiliginous skin has been previously demonstrated (2) and thereby incriminated to share in reducing the migration of melanocytes and their precursors.

This article is protected by copyright. All rights reserved.

Epigenetics of Skin Cancer: Interventions by selected bioactive Phytochemicals

Abstract

The prevalence and risk of skin cancer have been increasing over past three decades. Two major types of skin cancer observed in humans are melanoma and non-melanoma. Non-melanoma further subdivided into basal cell carcinoma and squamous cell carcinoma. Melanoma arises from melanocyte which locates at the bottom layer of skin epidermis, which primarily protects the skin from being exposed to external factors. Melanoma is less common among all other types of skin cancers but causes higher mortality. Epigenetic regulation associated with the transcriptional activation and inactivation of genes plays a major role in various disease progression including skin cancer. The major epigenetic changes observed at cellular level include DNA methylation, histone modifications, and miRNA-mediated gene regulation. The aberrant pattern in these epigenetic processes leads to altered expression of several genes involved in cell cycle, cell proliferation, cell motility and apoptosis. Several natural bioactive phytochemicals have been shown to exhibit epigenetic modulatory capability and act as chemopreventive as well as therapeutic agents. In this review, we mainly discuss the major epigenetic modifications observed in melanoma and the epigenetic modulatory role of selected bioactive phytochemicals against the skin cancer.

This article is protected by copyright. All rights reserved.

Air pollution and admissions due to ST elevation myocardial infarction—a time-series study from northwest of Iran

Abstract

We investigated the association between the levels of air pollutants and the number of daily admissions due to ST segment elevation myocardial infarction (STEMI) in a metropolitan in the northwest of Iran. Daily concentrations of common air pollutants were obtained for the greater city of Tabriz for a period of 2 years. These reports included sulfur dioxide (SO2), nitrogen dioxide (NO2), nitric oxide (NO), nitrogen byproducts (NOx), carbon monoxide (CO), ozone (O3), and particulate matters < 10 μm (PM10). The census of admissions for STEMI was retrieved for the same period from hospital registries. The association of daily variations in air pollutant levels and the daily number of STEMI admissions were investigated in a time-series analysis. In the multi-pollutant model adjusting for long-term trend, seasonality, and temperature, a significant association was found for 1-h [NO2] and 24-h [CO]. A marginally significant association was observed for 24-h [NO2] and 8-h [CO]. The 24-h [CO] had the strongest association with the number of admissions with STEMI. Maximum 1-h concentrations of NO2 on the same day and on the prior day as well as 24-h concentrations of CO on the prior day were independently associated with increased number of STEMI admissions. However, daily concentrations of SO2, NO, O3, and PM10 were not associated with the frequency of hospital admissions for STEMI.

Full-thickness skin grafts for lower leg defects coverage: Interest of postoperative immobilization

Publication date: Available online 3 October 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): S. Struk, N. Correia, Y. Guenane, M. Revol, S. Cristofari
IntroductionFull-thickness skin graft is an effective reconstruction method after excision of skin lesions on the lower limb that are not amenable to primary closure. The randomness of graft take is the major drawback of this procedure.ObjectiveThe objective of the study was to evaluate the outcome of full-thickness skin grafts (FTSG), used to repair lower leg defects after excision of skin lesions, after a 5-day immobilization period.Material and methodsAll consecutive patients who underwent FTSG to cover defects below the knee between November 2011 and January 2016 were retrospective reviewed. Graft take was assessed and defined as good (>90% graft take), moderate (between 50% and 90% graft take), or poor (<50% graft take).ResultsSeventy patients were included. Median age was 70 years (range, 18–92 years). The median area of the defect was 12cm². Graft take was good in 64 patients (91.4%), moderate in 3 patients (4.3%), and poor in 3 patients (4.3%) at Day 5. Complications included hematoma (11%), infection (14%) and venous thrombosis (3%).ConclusionFull-thickness skin graft is a reliable method to repair defects on the lower leg after removal of skin lesions. A 5-day immobilization period can improve the graft take. The authors have indicated no significant interest with commercial supporters.

Issue Information

Issue Information