Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors

Group 1 metabotropic glutamate receptors (mGlu1/5s) are critical to synapse formation and participate in synaptic LTP and LTD in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a transmembrane protein of the clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice. We show that conditional knock-out of TFR1 in PCs does not affect the cytoarchitecture of PCs, but reduces mGlu1 expression at synapses. This regulation by TFR1 acts in concert with that by Rab8 and Rab11, which modulate the internalization and recycling of mGlu1, respectively. TFR1 can bind to Rab proteins and facilitate their expression at synapses. PC ablation of TFR1 inhibits parallel fiber–PC LTD, whereas parallel fiber–LTP and PC intrinsic excitability are not affected. Finally, we demonstrate that PC ablation of TFR1 impairs motor coordination, but does not affect social behaviors in mice. Together, these findings underscore the importance of TFR1 in regulating mGlu1 trafficking and suggest that mGlu1- and mGlu1-dependent parallel fiber–LTD are associated with regulation of motor coordination, but not autistic behaviors.

SIGNIFICANCE STATEMENT Group 1 metabotropic glutamate receptor (mGlu1/5) signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases. Recent work suggests that altered mGlu1 signaling in Purkinje cells (PCs) may be involved in not only motor learning, but also autistic-like behaviors. We find that conditional knock-out of transferrin receptor 1 (TFR1) in PCs reduces synaptic mGlu1 by tethering Rab8 and Rab11 in the cytosol. PC ablation of TFR1 inhibits parallel fiber–PC LTD, whereas parallel fiber–PC LTP and PC intrinsic excitability are intact. Motor coordination is impaired, but social behaviors are normal in TFR1^flox/flox;pCP2-cre mice. Our data reveal a new regulator for trafficking and synaptic expression of mGlu1 and suggest that mGlu1-dependent LTD is associated with motor coordination, but not autistic-like behaviors.

Cortical Regulation of Nociception of the Trigeminal Nucleus Caudalis

Pain perception is strongly influenced by descending pathways from "higher" brain centers that regulate the activity of spinal circuits. In addition to the extensively studied descending system originating from the medulla, the neocortex provides dense anatomical projections that directly target neurons in the spinal cord and the spinal trigeminal nucleus caudalis (SpVc). Evidence exists that these corticotrigeminal pathways may modulate the processing of nociceptive inputs by SpVc, and regulate pain perception. We demonstrate here, with anatomical and optogenetic methods, and using both rats and mice (of both sexes), that corticotrigeminal axons densely innervate SpVc, where they target and directly activate inhibitory and excitatory neurons. Electrophysiological recordings reveal that stimulation of primary somatosensory cortex potently suppresses SpVc responses to noxious stimuli and produces behavioral hypoalgesia. These findings demonstrate that the corticotrigeminal pathway is a potent modulator of nociception and a potential target for interventions to alleviate chronic pain.

SIGNIFICANCE STATEMENT Many chronic pain conditions are resistant to conventional therapy. Promising new approaches to pain management capitalize on the brain's own mechanisms for controlling pain perception. Here we demonstrate that cortical neurons directly innervate the brainstem to drive feedforward inhibition of nociceptive neurons. This corticotrigeminal pathway suppresses the activity of these neurons and produces analgesia. This corticotrigeminal pathway may constitute a therapeutic target for chronic pain.

Gaze-Stabilizing Central Vestibular Neurons Project Asymmetrically to Extraocular Motoneuron Pools

Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate movements. A major challenge is to relate anatomical features of central neural populations, such as asymmetric connectivity, to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically defined population of central vestibular neurons in rhombomeres 5–7 of larval zebrafish. First, we found that neurons within this central population project preferentially to motoneurons that move the eyes downward. Concordantly, when the entire population of asymmetrically projecting neurons was stimulated collectively, only downward eye rotations were observed, demonstrating a functional correlate of the anatomical bias. When these neurons are ablated, fish failed to rotate their eyes following either nose-up or nose-down body tilts. This asymmetrically projecting central population thus participates in both upward and downward gaze stabilization. In addition to projecting to motoneurons, central vestibular neurons also receive direct sensory input from peripheral afferents. To infer whether asymmetric projections can facilitate sensory encoding or motor output, we modeled differentially projecting sets of central vestibular neurons. Whereas motor command strength was independent of projection allocation, asymmetric projections enabled more accurate representation of nose-up stimuli. The model shows how asymmetric connectivity could enhance the representation of imbalance during nose-up postures while preserving gaze stabilization performance. Finally, we found that central vestibular neurons were necessary for a vital behavior requiring maintenance of a nose-up posture: swim bladder inflation. These observations suggest that asymmetric connectivity in the vestibular system facilitates representation of ethologically relevant stimuli without compromising reflexive behavior.

SIGNIFICANCE STATEMENT Interneuron populations use specific anatomical projections to transform sensations into reflexive actions. Here we examined how the anatomical composition of a genetically defined population of balance interneurons in the larval zebrafish relates to the computations it performs. First, we found that the population of interneurons that stabilize gaze preferentially project to motoneurons that move the eyes downward. Next, we discovered through modeling that such projection patterns can enhance the encoding of nose-up sensations without compromising gaze stabilization. Finally, we found that loss of these interneurons impairs a vital behavior, swim bladder inflation, that relies on maintaining a nose-up posture. These observations suggest that anatomical specialization permits neural circuits to represent relevant features of the environment without compromising behavior.

Concerted Interneuron Activity in the Cerebellar Molecular Layer During Rhythmic Oromotor Behaviors

Molecular layer interneurons (MLIs, stellate and basket cells) of the cerebellar cortex are linked together by chemical and electrical synapses and exert a potent feedforward inhibition on Purkinje cells. The functional role of MLIs during specific motor tasks is uncertain. Here, we used two-photon imaging to study the patterns of activity of neighboring individual MLIs in the Crus II region of awake female mice during two types of oromotor activity, licking and bruxing, using specific expression of the genetically encoded calcium indicator protein GCaMP6s. We found that both stellate and basket cells engaged in synchronized waves of calcium activity during licking and bruxing, with high degrees of correlation among the signals collected in individual MLIs. In contrast, no calcium activity was observed during whisking. MLI activity tended to lag behind the onset of sustained licking episodes, indicating a regulatory action of MLIs during licking. Furthermore, during licking, stellate cell activity was anisotropic: the coordination was constant along the direction of parallel fibers (PFs), but fell off with distance along the orthogonal direction. These results suggest a PF drive for Ca²⁺ signals during licking. In contrast, during bruxing, MLI activity was neither clearly organized spatially nor temporally correlated with oromotor activity. In conclusion, MLI activity exhibits a high degree of correlation both in licking and in bruxing, but spatiotemporal patterns of activity display significant differences for the two types of behavior.

SIGNIFICANCE STATEMENT It is known that, during movement, the activity of molecular layer interneurons (MLIs) of the cerebellar cortex is enhanced. However, MLI–MLI interactions are complex because they depend both from excitatory electrical synapses and from potentially inhibitory chemical synapses. Accordingly, the pattern of MLI activity during movement has been unclear. Here, during two oromotor tasks, licking and bruxism, individual neighboring MLIs displayed highly coordinated activity, showing that the positive influences binding MLIs together are predominant. We further find that spatiotemporal patterns differ between licking and bruxing, suggesting that the precise pattern of MLI activity depends on the nature of the motor task.

Parkinson's Disease-Associated LRRK2 Hyperactive Kinase Mutant Disrupts Synaptic Vesicle Trafficking in Ventral Midbrain Neurons

Parkinson's disease (PD) is characterized pathologically by the selective loss of substantia nigra (SN) dopaminergic (DAergic) neurons. Recent evidence has suggested a role of LRRK2, linked to the most frequent familial PD, in regulating synaptic vesicle (SV) trafficking. However, the mechanism whereby LRRK2 mutants contribute to nigral vulnerability remains unclear. Here we show that the most common PD mutation LRRK2 G2019S impairs SV endocytosis in ventral midbrain (MB) neurons, including DA neurons, and the slowed endocytosis can be rescued by inhibition of LRRK2 kinase activity. A similar endocytic defect, however, was not observed in LRRK2 mutant neurons from the neocortex (hereafter, cortical neurons) or the hippocampus, suggesting a brain region-specific vulnerability to the G2019S mutation. Additionally, we found MB-specific impairment of SV endocytosis in neurons carrying heterozygous deletion of SYNJ1 (PARK20), a gene that is associated with recessive Parkinsonism. Combining SYNJ1^+/– and LRRK2 G2019S does not exacerbate SV endocytosis but impairs sustained exocytosis in MB neurons and alters specific motor functions of 1-year-old male mice. Interestingly, we show that LRRK2 directly phosphorylates synaptojanin1 in vitro, resulting in the disruption of endophilin-synaptojanin1 interaction required for SV endocytosis. Our work suggests a merge of LRRK2 and SYNJ1 pathogenic pathways in deregulating SV trafficking in MB neurons as an underlying molecular mechanism of early PD pathogenesis.

SIGNIFICANCE STATEMENT Understanding midbrain dopaminergic (DAergic) neuron-selective vulnerability in PD is essential for the development of targeted therapeutics. We report, for the first time, a nerve terminal impairment in SV trafficking selectively in MB neurons but not cortical neurons caused by two PARK genes: LRRK2 (PARK8) and SYNJ1 (PARK20). We demonstrate that the enhanced kinase activity resulting from the most frequent G2019S mutation in LRRK2 is the key to this impairment. We provide evidence suggesting that LRRK2 G2019S and SYNJ1 loss of function share a similar pathogenic pathway in deregulating DAergic neuron SV endocytosis and that they play additive roles in facilitating each other's pathogenic functions in PD.

GFP-Mutant Human Tau Transgenic Mice Develop Tauopathy Following CNS Injections of Alzheimer's Brain-Derived Pathological Tau or Synthetic Mutant Human Tau Fibrils

Neurodegenerative proteinopathies characterized by intracellular aggregates of tau proteins, termed tauopathies, include Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau), and related disorders. Pathological tau proteins derived from human AD brains (AD-tau) act as proteopathic seeds that initiate the templated aggregation of soluble tau upon intracerebral injection into tau transgenic (Tg) and wild-type mice, thereby modeling human tau pathology. In this study, we found that aged Tg mice of both sexes expressing human tau proteins harboring a pathogenic P301L MAPT mutation labeled with green fluorescent protein (T40PL-GFP Tg mouse line) exhibited hyperphosphorylated tau mislocalized to the somatodentritic domain of neurons, but these mice did not develop de novo insoluble tau aggregates, which are characteristic of human AD and related tauopathies. However, intracerebral injections of either T40PL preformed fibrils (PFFs) or AD-tau seeds into T40PL-GFP mice induced abundant intraneuronal pathological inclusions of hyperphosphorylated T40PL-GFP. These injections of pathological tau resulted in the propagation of tau pathology from the injection site to neuroanatomically connected brain regions, and these tau inclusions consisted of both T40PL-GFP and WT endogenous mouse tau. Primary neurons cultured from the brains of neonatal T40PL-GFP mice provided an informative in vitro model for examining the uptake and localization of tau PFFs. These findings demonstrate the seeded aggregation of T40PL-GFP in vivo by synthetic PFFs and human AD-tau and the utility of this system to study the neuropathological spread of tau aggregates.

SIGNIFICANCE STATEMENT The stereotypical spread of pathological tau protein aggregates have recently been attributed to the transmission of proteopathic seeds. Despite the extensive use of transgenic mouse models to investigate the propagation of tau pathology in vivo, details of the aggregation process such as the early seeding events leading to new tau pathology have remained elusive. This study validates the use of GFP-labeled tau expressed by neurons in vivo and in vitro as models for investigating mechanisms underlying the seeded transmission of tau pathology as well as tau-focused drug discovery to identify disease-modifying therapies for AD and related tauopathies.

Presynaptic Neuronal Nicotinic Receptors Differentially Shape Select Inputs to Auditory Thalamus and Are Negatively Impacted by Aging

Acetylcholine (ACh) is a potent neuromodulator capable of modifying patterns of acoustic information flow. In auditory cortex, cholinergic systems have been shown to increase salience/gain while suppressing extraneous information. However, the mechanism by which cholinergic circuits shape signal processing in the auditory thalamus (medial geniculate body, MGB) is poorly understood. The present study, in male Fischer Brown Norway rats, seeks to determine the location and function of presynaptic neuronal nicotinic ACh receptors (nAChRs) at the major inputs to MGB and characterize how nAChRs change during aging. In vitro electrophysiological/optogenetic methods were used to examine responses of MGB neurons after activation of nAChRs during a paired-pulse paradigm. Presynaptic nAChR activation increased responses evoked by stimulation of excitatory corticothalamic and inhibitory tectothalamic terminals. Conversely, nAChR activation appeared to have little effect on evoked responses from inhibitory thalamic reticular nucleus and excitatory tectothalamic terminals. In situ hybridization data showed nAChR subunit transcripts in GABAergic inferior colliculus neurons and glutamatergic auditory cortical neurons supporting the present slice findings. Responses to nAChR activation at excitatory corticothalamic and inhibitory tectothalamic inputs were diminished by aging. These findings suggest that cholinergic input to the MGB increases the strength of tectothalamic inhibitory projections, potentially improving the signal-to-noise ratio and signal detection while increasing corticothalamic gain, which may facilitate top-down identification of stimulus identity. These mechanisms appear to be affected negatively by aging, potentially diminishing speech perception in noisy environments. Cholinergic inputs to the MGB appear to maximize sensory processing by adjusting both top-down and bottom-up mechanisms in conditions of attention and arousal.

SIGNIFICANCE STATEMENT The pedunculopontine tegmental nucleus is the source of cholinergic innervation for sensory thalamus and is a critical part of an ascending arousal system that controls the firing mode of thalamic cells based on attentional demand. The present study describes the location and impact of aging on presynaptic neuronal nicotinic acetylcholine receptors (nAChRs) within the circuitry of the auditory thalamus (medial geniculate body, MGB). We show that nAChRs are located on ascending inhibitory and descending excitatory presynaptic inputs onto MGB neurons, likely increasing gain selectively and improving temporal clarity. In addition, we show that aging has a deleterious effect on nAChR efficacy. Cholinergic dysfunction at the level of MGB may affect speech understanding negatively in the elderly population.

The Right Temporoparietal Junction Supports Speech Tracking During Selective Listening: Evidence from Concurrent EEG-fMRI

Listening selectively to one out of several competing speakers in a "cocktail party" situation is a highly demanding task. It relies on a widespread cortical network, including auditory sensory, but also frontal and parietal brain regions involved in controlling auditory attention. Previous work has shown that, during selective listening, ongoing neural activity in auditory sensory areas is dominated by the attended speech stream, whereas competing input is suppressed. The relationship between these attentional modulations in the sensory tracking of the attended speech stream and frontoparietal activity during selective listening is, however, not understood. We studied this question in young, healthy human participants (both sexes) using concurrent EEG-fMRI and a sustained selective listening task, in which one out of two competing speech streams had to be attended selectively. An EEG-based speech envelope reconstruction method was applied to assess the strength of the cortical tracking of the to-be-attended and the to-be-ignored stream during selective listening. Our results show that individual speech envelope reconstruction accuracies obtained for the to-be-attended speech stream were positively correlated with the amplitude of sustained BOLD responses in the right temporoparietal junction, a core region of the ventral attention network. This brain region further showed task-related functional connectivity to secondary auditory cortex and regions of the frontoparietal attention network, including the intraparietal sulcus and the inferior frontal gyrus. This suggests that the right temporoparietal junction is involved in controlling attention during selective listening, allowing for a better cortical tracking of the attended speech stream.

SIGNIFICANCE STATEMENT Listening selectively to one out of several simultaneously talking speakers in a "cocktail party" situation is a highly demanding task. It activates a widespread network of auditory sensory and hierarchically higher frontoparietal brain regions. However, how these different processing levels interact during selective listening is not understood. Here, we investigated this question using fMRI and concurrently acquired scalp EEG. We found that activation levels in the right temporoparietal junction correlate with the sensory representation of a selectively attended speech stream. In addition, this region showed significant functional connectivity to both auditory sensory and other frontoparietal brain areas during selective listening. This suggests that the right temporoparietal junction contributes to controlling selective auditory attention in "cocktail party" situations.

Nerve injury associated with high-intensity focused ultrasound: A case report

Summary

Skin laxity is a common cosmetic concern in middle-aged women. High-intensity focused ultrasound (HIFU) is one of noninvasive modalities that provides safe and effective improvement in skin laxity and tightening with minimal adverse effects. Concerning an extensive use of HIFU for facial rejuvenation, dermatologists should be aware of potential adverse effects of HIFU treatment. We herein present a case of 33-year-old Thai female with facial nerve injury after HIFU treatment for skin laxity.

Treatment of severe drug reactions by hemodialysis

Abstract

Background

Extracorporeal treatments such as hemodialysis and plasma exchange are lifesaving measures in the treatment of drug poisoning. This treatment method generally is not used for severe cutaneous and systemic drug reactions.

Methods

Here, we describe three cases wherein hemodialysis therapy was instrumental in reversing the adverse drug reaction.

Results

In the cases of severe cutaneous drug reactions reviewed, patients presented with linear immunoglobulin A bullous dermatosis, acute generalized exanthematous pustulosis, and toxic epidermal necrolysis. Salvage treatment with hemodialysis therapy drastically influenced the course of disease, resulting in remission.

Conclusions

This novel and highly effective treatment option is not considered in current algorithms for adverse drug reactions. Hence, in addition to the rarity of these reactions, the main limitation of the study is the small number of patients. Hemodialysis can substantially alter the prognosis and, in some cases, be a lifesaving treatment for patients with severe adverse cutaneous drug reaction associated with systemic toxicity.

Rust-colored patches on the lower extremities: lichen aureus

Congenital unilateral reticulate keratotic papules on the lower extremity

Heavy metals in the surface sediments of lakes on the Tibetan Plateau, China

Abstract

Heavy metal contamination has affected many regions in the world, particularly the developing countries of Asia. We investigated 8 heavy metals (Cu, Zn, Cd, Pb, Cr, Co, Ni, and As) in the surface sediments of 18 lakes on the Tibetan Plateau. It was found that the distributions of the heavy metals showed no clear spatial pattern on the plateau. The results indicated that the mean concentrations of these metals in the sediment samples diminished as follows: Cr > As > Zn > Ni > Pb > Cu > Co > Cd. The results of geoaccumulation index (I _geo) and potential ecological risk factor (E ⁱ_r ) assessments showed that the sediments were moderately polluted by Cd and As, which posed much higher risks than the other metals. The values of the potential ecological risk index (RI) showed that lake Bieruoze Co has been severely polluted by heavy metals. Principal component analysis, hierarchical cluster analysis, and Pearson correlation analysis results indicated that the 8 heavy metals in the lake surface sediments of the Tibetan Plateau could be classified into four groups. Group 1 included Cu, Zn, Pb, Co, and Ni which were mainly derived from both natural and traffic sources. Group 2 included Cd which mainly originated from anthropogenic sources like alloying, electroplating, and dyeing industries and was transported to the Tibetan Plateau by atmospheric circulation. Group 3 included Cr and it might mainly generate from parent rocks of watersheds. The last Group (As) was mainly from manufacturing, living, and the striking deterioration of atmospheric environment of the West, Central Asia, and South Asia.

Juvenile xanthogranuloma with angiomatous appearance and a peculiar immunophenotype

Abstract

Juvenile xanthogranuloma is the most common form of non-Langerhans cell histiocytosis in childhood. The clinical differential diagnosis of a solitary juvenile xanthogranuloma includes molluscum contagiosum, Spitz nevus, and melanoma. Lesions larger than 2 cm in diameter may be misdiagnosed as hemangiomas, but this is not typical of smaller juvenile xanthogranuloma. We report a case of solitary juvenile xanthogranuloma in a 10-year-old boy with angiomatous appearance and peculiar immunophenotype.

Discordance of pediatric morphea treatment by pediatric dermatologists

Abstract

Background/Objectives

Studies describing treatment efficacy in pediatric morphea are lacking. Subspecialists have reached no consensus on how to optimally treat pediatric morphea. The objective of the current study was to describe the most common treatment practices of pediatric dermatologists worldwide who care for children with morphea.

Methods

A survey regarding topical treatment practices of pediatric morphea, with representative case-based scenarios, was distributed to pediatric dermatologists and results were tallied.

Results

The survey response rate was 13.4%, with 110 respondents in the final analysis. The majority of respondents agreed on red violaceous rim (99%), increased local warmth (75%), raised borders (69%), and dermal thickening (64%) as signs of disease activity. Respondents had less agreement on sclerotic lesions (41%), scaling (43%), dyspigmentation (19%), and atrophy (13%) as signs of disease activity. Ninety-two percent of respondents used primary therapy or monotherapy with topical medications, including 45% in linear morphea of the limbs and 37% in linear morphea of the head or neck. High-potency topical corticosteroids were most commonly used (80%), although respondents did not agree on specific regimens. Sixteen different treatment regimens were selected as first-line therapy for one case scenario of active disease.

Conclusion

The survey found large variation in how pediatric dermatologists treat pediatric morphea. Consensus treatment guidelines developed by pediatric dermatologists and pediatric rheumatologists are urgently needed regarding the efficacy of therapies for pediatric morphea. Prospective studies of treatment efficacy in pediatric morphea are urgently needed as well.

Morbihan disease treated with Tripterygium wilfordii successfully

Suppression of UVB-mediated Matrix Metalloproteinase Generation by Sorbus commixta Twig Extract in Human Dermal Fibroblasts

Abstract

Sorbus commixta is a traditional oriental medicinal plant that grows in East Asian countries such as Korea, Japan, and China. The twig of S. commixta has been considered valuable for centuries to treat diseases including asthma, cough, and other bronchial disorders. However, the effect of S. commixta twig extract on human skin has not been investigated well. The present study aimed at assessing the anti-photoaging effect of S. commixta twig ethanol extract (STE) on ultraviolet B (UVB)-induced matrix metalloproteinase (MMP) levels and its underlying mechanism in human dermal fibroblasts. In this study, we found that STE (12.5–50 μg/mL) treatment significantly inhibited UVB-induced MMP-1, MMP-2, and MMP-3 expression, concomitant with a downregulation of intracellular ROS generation. These effects might be associated with a STE-induced inhibition of the mitogen-activated protein kinase (MAPK) pathway. Furthermore, STE also downregulated UVB-induced c-Fos expression in a concentration dependent manner, but had no inhibitory effect on c-Jun phosphorylation. Taken together, these results indicate that STE may be an anti-photoaging agent, and that its effect may occur via its inhibition of MMPs expression and MAPK pathway activation.

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Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation

Abstract

Photobiomodulation (PBM) involves the use of red or near-infrared light at low power densities to produce a beneficial effect on cells or tissues. PBM therapy is used to reduce pain, inflammation, edema, and to regenerate damaged tissues such as wounds, bones and tendons. The primary site of light absorption in mammalian cells has been identified as the mitochondria, and more specifically, cytochrome c oxidase (CCO). It is hypothesized that inhibitory nitric oxide can be dissociated from CCO thus restoring electron transport and increasing mitochondrial membrane potential. Another mechanism involves activation of light or heat-gated ion channels. This review will cover the redox signaling that occurs in PBM and examine the difference between healthy and stressed cells, where PBM can have apparently opposite effects. PBM has a marked effect on stem cells, and this is proposed to operate via mitochondrial redox signaling. PBM can act as a pre-conditioning regimen, and can interact with exercise on muscles.

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International Bullous Diseases Group - Consensus on Diagnostic Criteria for Epidermolysis Bullosa Acquisita

Summary

Background

Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests making an international consensus on diagnosis of EBA needed.

Objectives

To obtain an international consensus on the clinical and diagnostic criteria for EBA.

Methods

The international bullous diseases group (IBDG) met three times to discuss the clinical and diagnostic criteria for EBA. For the final voting exercise, 22 experts from 14 different countries voted on 50 different items. When more than 30% disagreed with a proposal, a discussion was held and revoting occurred.

Results

48/50 proposals achieved consensus after discussion. This included 9 diagnostic criteria that are summarized in a flow chart. The IBDG was unable to determine one procedure which would be applicable worldwide.

Limitations

Differential diagnosis of bullous systemic lupus erythematosus has not been addressed.

Conclusion

This first international consensus conference established generally agreed upon clinical and laboratory criteria defining the clinical classification and diagnostic testing for EBA. Holding these voting exercises in person with the possibility of discussion prior to voting has advantages in reaching consensus over Delphi exercises with remote voting.

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Erratum

RNA-sequencing study of peripheral blood mononuclear cells in sporadic Meniere's disease patients: possible contribution of immunologic dysfunction to the development of this disorder

Summary

To date, the pathogenesis of Meniere's disease (MD) remains unclear. This study aims to investigate the possible relationship between potential immune system related genes and sporadic Meniere's disease. The whole RNA-sequencing (RNA-seq) technology was used to analyze the transcriptome of peripheral blood mononuclear cells of 3 MD patients and 3 control individuals. Of 366 differentially expressed genes (DEGs), 154 genes were up-regulated and 212 genes were down-regulated (|log2Foldchange| >1 and p <0.05). Gene ontology (GO) enrichment analysis illustrated that immune relevant factors played a key role in the pathogenesis of MD. Of 366 DEGs, we focused on analyzing the possible immune related genes, among which, the significantly up-regulated genes (GSTM1, TMEM176B, TMEM176A), and down-regulated genes (SLC4A10 and SLC4A1), especially drew our attention. The mRNA expression levels of GSTM1, TMEM176B, TMEM176A, SLC4A1 and SLC4A10 were analyzed by qRT-PCR. The serum concentration of GSTM1, TMEM176B and SLC4A10 proteins were measured by ELISA. Considering the results of qRT-PCR and ELISA, it was noteworthy that GSTM1 exhibited the highest fold change between two groups, which were consistent with the deep sequencing results by RNA-seq. In conclusion, our study first offers a new perspective in MD development on the basis of RNA expression patterns, suggesting that immune factors might be involved in the MD pathogenesis. Remarkably, GSTM1 might be a possible candidate gene for the diagnostic biomarker of MD and provides the basis for further biological and functional investigations. This article is protected by copyright. All rights reserved.

Nasal dermoid sinus cyst in a young girl: A case report

Two cases of severe fever with thrombocytopenia syndrome virus infection

Successful treatment of Raynaud's phenomenon and digital ulcers in systemic sclerosis patients with botulinum toxin B injection: Assessment of peripheral vascular disorder by angiography and dermoscopic image of nail fold capillary

Abstract

We recently identified the efficacy and safety of a botulinum toxin (BTX)-A/B in Raynaud's phenomenon (RP) and digital ulcers (DU) in Japanese patients with systemic sclerosis (SSc). Detailed assessments of peripheral vascular disorder using angiography and dermoscopic images of nail fold capillaries have not been performed previously. This study aimed to evaluate the effect of BTX-B on SSc-associated peripheral vascular disorder. Two SSc patients who suffered with RP and DU were treated with a BTX-B injection, and thereafter the symptoms of RP were improved and DU healed in both patients. Furthermore, angiography showed an increased blood flow to the palm and fingers, and dermoscopic images of nail fold capillary changes showed improvement. These results suggest that a BTX-B injection may increase peripheral blood flow and improve RP and DU in SSc patients.

Nanoflower-like Yttrium-doped ZnO Photocatalyst for the Degradation of Methylene Blue Dye

Abstract

Pure ZnO and Yttrium doped (Y-doped) ZnO at various mol% with flower-like nanostructures are synthesized by a microwave-assisted sol-gel method, followed by investigating the morphologies, crystal structures, optical properties and photocatalytic performances. While the phase formations are detected by X-ray diffraction technique, both scanning and transmission electron microscopy images clearly depict the flower-like morphology of ZnO and Y-doped ZnO samples. Formation of flower petals are from the nanoparticles that grew and connected by orientation attachment process. The flower-like architecture is addressed in terms of an Ostwald ripening mechanism. The UV-Vis absorption studies show enhanced absorption for the Y-doped ZnO whereas the photoluminescence spectra confirm the significance of sample defects in the photocatalytic degradation of organic pollutants. Effects of various experimental parameters such as the amount of photocatalysts, dye concentration and dopant concentration on the dye degradation are also optimized.

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Impact of Ultraviolet Radiation on Expression of Transforming Growth Factor-beta, Smad2, Metalloproteinases, Cathepsin K and Progerin

Abstract

Ultraviolet radiation (UVR) is one of the most important environmental factors involved in photoaging. Exposure to UVR leads to dysregulation of expression of cell-cycle-related proteins which play key role in skin photodegradation that pretends to develop carcinogenesis. This study examines the role of various UVB doses on the expression of transforming growth factor beta (TGF-β), Smad2, cathepsin K, progerin and matrix metalloproteinases (MMPs)-1,-3,-8,-9. A group consisting of 63 healthy individuals underwent one of the following treatments: 1) whole-body exposed to UVB irradiation on each of 10 consecutive days with 0.7 MED, or 2) whole-body irradiation as described followed by a single erythemal UVB dose on a small body area, or 3) irradiated only with a single erythemal UVB dose on small body area, or 4) were not irradiated at all (control group). When we compared all irradiated groups to the control group there was significantly higher expression of TGF-β, MMP-1,-3,-9, and cathepsin K proteins evaluated by western blot method. The results suggest the role of UVB in impairment of proteins expression that is involved in cell cycle's regulation. Changes of the proteins expression involved by acute and chronic UVR confirms its essential role in skin photodestruction. Moreover, obtained result indicates the tendency to occurrence of photoadaptation phenomenon.

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Analysis of Erythemal UVB Dose Received Inside a Car in Valencia, Spain

Abstract

Continuous exposures to ultraviolet radiation can lead to harmful effects on human skin. Professional drivers may spend more than 8 hours per day inside a vehicle. This paper describes an analysis of the UVER (erythemal ultraviolet radiation) received by a driver and passenger inside a vehicle. A 3-door Peugeot 206 was used for the study. VioSpor Blue Line dosimeters (with a response profile close to that of human skin) were used to measure the erythematic dose of UV radiation (able to produce erythema on human skin). Four dosimeters were placed in the driver's position and another four in the passenger's position. Daily irradiance was analyzed for a day in April using PMA radiometers. The measurements were obtained on relatively clear days from February to December 2009 between 9:30 AM and 3 PM. Additionally, a prediction was made of the time required to produce an erythema on the driver's skin. UVER exposure, in some of the driver's positions, exceeds the Exposure Limits given by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Skin protection measures should be taken into account by professional drivers to prevent the harmful effects of UVER radiation.

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Abstraction in ecology: reductionism and holism as complementary heuristics

Abstract

In addition to their core explanatory and predictive assumptions, scientific models include simplifying assumptions, which function as idealizations, approximations, and abstractions. There are methods to investigate whether simplifying assumptions bias the results of models, such as robustness analyses. However, the equally important issue – the focus of this paper – has received less attention, namely, what are the methodological and epistemic strengths and limitations associated with different simplifying assumptions. I concentrate on one type of simplifying assumption, the use of mega parameters as abstractions in ecological models. First, I argue that there are two kinds of mega parameters qua abstractions, sufficient parameters and aggregative parameters, which have gone unnoticed in the literature. The two are associated with different heuristics, holism and reductionism, which many view as incompatible. Second, I will provide a different analysis of abstractions and the associated heuristics than previous authors. Reductionism and holism and the accompanying abstractions have different methodological and epistemic functions, strengths, and limitations, and the heuristics should be viewed as providing complementary research perspectives of cognitively limited beings. This is then, third, used as a premise to argue for epistemic and methodological pluralism in theoretical ecology. Finally, the presented taxonomy of abstractions is used to comment on the current debate whether mechanistic accounts of explanation are compatible with the use of abstractions. This debate has suffered from an abstract discussion of abstractions. With a better taxonomy of abstractions the debate can be resolved.

Association of oxidative stress and dynamic thiol-disulphide homeostasis with atopic dermatitis severity and chronicity in children: a prospective study

Summary

Background

Oxidative stress (OS) has an important effect on the pathogenesis of atopic dermatitis (AD). Thiols are antioxidants that regulate intracellular redox metabolism and protect keratinocytes against OS damage in the stratum corneum.

Aim

To investigate dynamic thiol-disulphide homeostasis (dTDH) as a novel OS parameter in children with AD, and its relationship with disease severity and chronicity.

Methods

Severity of AD was determined by using the instruments SCORing Atopic Dermatitis (SCORAD) and Eczema Area And Severity Index (EASI) upon enrolment in the study (SCORAD₁ and EASI₁) and after 1 year (SCORAD₂ and EASI₂). Native thiol, total thiol and disulphide levels were measured as novel OS parameters, and the ratios of disulphide/native thiol, disulphide/total thiol and native/total thiol were calculated as dTDH.

Results

In the AD group, the serum disulphide level and the ratios of disulphide/native thiol and disulphide/total thiol were significantly lower than in healthy controls (P = 0.01, P < 0.01 and P < 0.01, respectively). There was no significant association between OS parameters and disease severity (P > 0.05). SCORAD₂ and EASI₂ were positively correlated with disulphide/native thiol ratio (r = 0.29, P < 0.03 and r = 0.35, P < 0.01, respectively), whereas they were negatively correlated with the native/total thiol ratio (r = −0.30, P = 0.02 for both).

Conclusions

Both OS and impaired dTDH were found to be related to childhood AD. None of the OS parameters was associated with AD severity. dTDH is a possible diagnostic tool to predict AD chronicity.

Differential Perturbation of the Protrotropic Equilibrium of a Biological Photosensitizer within Bile Salt Aggregates of Varying Hydrophobicity: A Fluorimetric Investigation

Abstract

The present work reveals the binding interactions of a credible cancer cell photosensitizer, harmane (HM) with some selected bile salt aggregates of dissimilar hydrophobicity viz. sodium deoxycholate (NaDC), sodium cholate (NaC) and sodium taurocholate (NaTC). The explicit variation of the prototropic equilibrium of the photosensitizer both in the ground and excited state has been utilized to scrutinize the interaction phenomena. Differential modulation in the prototropic equilibrium of HM in the aforesaid aggregates has been explained on the basis of the structural dissimilarities of the bile-salt monomers. The contrived hydrophobic surroundings provided by the aggregates have been reflected on the spectroscopic results; especially in the time-resolved fluorescence and the rotational dynamical behavior of the molecule of interest. Slow solvent reorientation time with regard to the lifetime of HM proliferated by the Red Edge Effect in two specific bile-salts namely NaC and NaTC; whereas its absence in NaDC aggregates has also been elucidated on the basis of accessibility of the solvent molecules within the aggregates.

This article is protected by copyright. All rights reserved.

Open-label study assessing the efficacy and tolerability of topical skincare and sun protection products following intense pulsed light treatment

Summary

Background

The visible signs of photodamage can be improved by intense pulsed light (IPL). Active ingredients in cosmeceuticals also have effects on skin quality and pigmentation, and can camouflage post-treatment side effects. Combination therapies utilizing different treatment modalities have been shown to optimize clinical outcomes for skin rejuvenation and patient satisfaction.

Aim

To evaluate the efficacy of a combination of IPL with a daily topical skincare and sunscreen regimen for the treatment of facial photodamage and for the improvement of IPL treatment tolerability.

Patients/Methods

Twenty female subjects with moderate-to-severe facial photodamage, with past history of IPL treatments, received one IPL treatment followed by the use of the topical skincare regimen for 8 weeks. An investigator assessed facial photodamage and hyperpigmentation at baseline, week 4, and week 8, and postprocedure erythema. Subject questionnaires were also administered at each visit.

Results

Compared to baseline, there was a significant improvement in photodamage and hyperpigmentation of bare facial skin. The application of the skincare regimen resulted in a significant reduction in post-IPL erythema, stinging/burning, and itching. The majority of patients were very satisfied or satisfied and felt the treatment regimen improved various aspects of skin quality and the tolerability of the procedure.

Conclusions

The addition of a topical skincare regimen after IPL treatment to the face resulted in significant improvements in facial photodamage and pigmentation, decreased post-treatment side effects, and increased tolerability.

Comparative study of buffered 50% glycolic acid (pH 3.0) + 0.5% salicylic acid solution vs Jessner's solution in patients with acne vulgaris

Summary

Background

Superficial chemical peels are frequently used in acne vulgaris treatment. Although glycolic acid (GA) has been widely used in clinical practice, its pH ranges from 0.08-2.75 and thus should be neutralized after application to avoid burns.

Objective

To evaluate treatment efficacy and safety of chemical peeling using buffered 50% GA (pH 3.0) + 0.5% salicylic acid (SA) solution that does not need to be neutralized in the treatment of acne vulgaris compared to the conventional peeling using Jessner's solution.

Methods

We performed a prospective, randomized, evaluator-blind, split-face clinical trial. Twenty patients were randomized by assigning one side of each patient's face to receive a 50% GA (pH 3.0) + 0.5% SA peel (GA side) and the other side to receive the Jessner's solution (Jessner's solution side). All patients underwent 2 sessions of treatment spaced 2 weeks apart. Lesion count, acne severity, subjective efficacy assessment, and side effects were evaluated.

Results

The total lesion count was significantly reduced for the GA and Jessner's solution sides (P < .001). However, there was no significant difference in the total lesion count, acne severity, or subjective efficacy assessment between the 2 sides (P > .05). The GA side had fewer side effects than the Jessner's solution side.

Conclusion

The results of this study suggest that chemical peeling using the 50% GA (pH 3.0) + 0.5% SA solution can be as effective and convenient as the conventional peeling using Jessner's solution in the treatment of acne vulgaris and may show fewer adverse events than the conventional peeling.

Contact dermatitis caused by Geranium robertianum with erythema multiforme-like reaction

Christmas tree dermatitis caused by colophonium allergy

Leukoderma following allergic contact dermatitis caused by the silicone component silprene-30A/B in swimming goggles

Allergic contact dermatitis caused by acrylic acid used in transcutaneous electrical nervous stimulation

Thank you to reviewers

Allergic contact dermatitis caused by polymethylmethacrylate following intradermal filler injection

Hair colour shampoo dermatitis

Acetophenone azine: a new shoe allergen causing severe foot dermatitis

A case of contact dermatitis syndrome caused by Dermabond®, followed by contact dermatitis caused by false eyelash glue and Aron Alpha® glue: possibility of cross-reactions among cyanoacrylates

Erratum

Acrylate allergy: time to intervene

Allergic contact dermatitis caused by 2-ethyl cyanoacrylate contained in glucose sensor sets in two diabetic adults

Severe stomatitis with a deep buccal ulcer associated with an allergic reaction to methyl methacrylate used for dental treatment

Contact urticaria caused by a silk bed quilt in a young atopic female

Polyhexamethylene biguanide and alkyl glucosides: unexpected allergens in an antimicrobial foam dressing

Re: Protein contact dermatitis caused by lime in a pastry chef (Contact Dermatitis 2015: 73: 54–56)

Immunoglobulin G; structure and functional implications of different subclass modifications in initiation and resolution of allergy

Abstract

IgE and not IgG is usually associated with allergy. IgE lodged on mast cells in skin or gut and basophils in the blood allows for the prolonged duration of allergy through the persistent expression of high affinity IgE receptors. However, many allergic reactions are not dependent on IgE and are generated in the absence of allergen specific and even total IgE. Instead, IgG plasma cells are involved in induction of, and for much of the pathogenesis of, allergic diseases. The pattern of IgG producing plasma cells in atopic children and the tendency for direct or further class switching to IgE are the principle factors responsible for long-lasting sensitization of mast cells in allergic children. Indirect class switching from IgG producing plasma cells has been shown to be the predominant pathway for production of IgE while a Th2 microenvironment, genetic predisposition, and the concentration and nature of allergens together act on IgG plasma cells in the atopic tendency to undergo further immunoglobulin gene recombination. The seminal involvement of IgG in allergy is further indicated by the principal role of IgG4 in the natural resolution of allergy and as the favourable immunological response to immunotherapy. This paper will look at allergy through the role of different antibodies than IgE and give current knowledge of the nature and role of IgG antibodies in the start, maintenance and resolution of allergy.

The induction, the pathology, and the resolution of allergy involve antibodies other than specific IgE to allergens. Allergy depends on the pattern of IgG producing plasma cells in atopic children and the tendency for direct or further class switching from IgG to IgE, resulting in the sensitising of mast cells in allergic children.

Speckled acral hypopigmentation in an adolescent

Abstract

We report a case of speckled acral hypopigmentation in a 12-year-old girl. She presented with asymptomatic hypopigmented macules on the hands and feet. This rare entity is a proposed variant of reticulate acropigmentation and of unknown etiology.

Urticarial vasculitis after meningococcal serogroup B vaccine in a 6-year-old girl

Abstract

The first vaccine that shows significant potential in providing broad coverage against serogroup B meningococcal disease has recently been approved. Because of its newness, potential adverse events need to be reported. Here we report a case of urticarial vasculitis, a rare disease in children, in probable relationship with the novel vaccine.

Erythromelanosis follicularis faciei et colli: A clinicoepidemiologic study

Abstract

We describe 25 cases of erythromelanosis follicularis faciei et colli from India. The male:female ratio was 5.25:1 and the average age of onset was 12.3 years. The cheeks, preauricular area, and submandibular region were the sites most commonly affected. Keratosis pilaris was seen in 22 (88%) of the patients.

IDSA POSITION STATEMENT: Why IDSA Did Not Endorse the Surviving Sepsis Campaign Guidelines

Abstract

IDSA did not endorse the 2016 Surviving Sepsis Campaign Guidelines despite being represented in the working group that drafted the guidelines document. Leadership from IDSA, the Surviving Sepsis Campaign Guidelines, and the Society of Critical Care Medicine had numerous amicable discussions primarily regarding the bolded, rated guidelines recommendations. Our societies had different perspectives, however, regarding the interpretation of the major studies that informed the guidelines' recommendations thus leading us to different conclusions and different perspectives on the recommendations. IDSA consequently elected not to endorse the guidelines. IDSA nonetheless hopes to be able to continue collaborating with the Surviving Sepsis Campaign and the Society of Critical Care Medicine to resolve our differences and to develop further strategies together to prevent sepsis and septic shock as well as reduce death and disability from these conditions both nationally and globally.

A two-centre randomised trial of an additional early dose of measles vaccine: Effects on mortality and measles antibody levels

Abstract

Background

Besides protecting against measles, measles vaccine (MV) may have beneficial non-specific effects. We tested the effect of an additional early MV on mortality and measles antibody levels.

Methods

Children aged 4-7 months in two rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomised 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus-influenzae-type-b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrolment to 3 years of age in Cox proportional hazards models, censoring for subsequent non-trial MV. Subgroups of participants had blood sampled at enrolment, before the 9 months MV and in the second year of life to assess measles antibody level.

Results

Among 8309 children enrolled July 18, 2012-December 3, 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomisation group (hazard ratio=1.05 (95%CI: 0.75-1.46)).At enrolment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By 9 months of age, no measles-unvaccinated/unexposed child had protective levels, while 92% (306/333) of early MV recipients had. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels.

Conclusion

Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at 4-7 months and responded with high antibody levels to early MV.

Rigorous Clinical Trial Design in Public Health Emergencies Is Essential

Abstract

Randomized clinical trials are the most reliable approaches to evaluating the effects of new treatments and vaccines. During the 2014-15 West African Ebola epidemic, many argued that such trials were neither ethical nor feasible in an environment of limited health infrastructure and severe disease with a high fatality rate. Consensus among the numerous organizations providing help to the affected areas was never achieved, resulting in fragmented collaboration, delayed study initiation, and ultimately failure to provide definitive evidence on the efficacy of treatments and vaccines. Randomized trials were in fact approved by local ethics boards and initiated, demonstrating that randomized trials, even in such difficult circumstances, are feasible. Improved planning and collaboration among research and humanitarian organizations, and affected communities, in the interepidemic periods are needed to ensure that questions regarding the efficacy of vaccines and treatments can be definitively answered during future public health emergencies.

Immunogenicity and protection from a single dose of internationally available killed oral cholera vaccine: a systematic review and meta-analysis

Abstract

In addition to improved water supply and sanitation, the two-dose killed oral cholera vaccine (OCV) is an important tool for the prevention and control of cholera. We aimed to document the immunogenicity and protection (efficacy and effectiveness) conferred by a single OCV dose against cholera. The meta-analysis showed an estimated 73% and 77% of individuals seroconverted to the Ogawa and Inaba serotypes, respectively, after an OCV first dose. The estimates of single-dose vaccine protection from available studies are 87% at 2 months decreasing to 33% at 2 years. Current immunologic and clinical data suggest that protection conferred by a single dose of killed OCV may be sufficient to reduce short-term risk in outbreaks or other high-risk settings, which may be especially useful when vaccine supply is limited. However, until more data suggests otherwise, a second dose should be given as soon as circumstances allow to ensure robust protection.

Identification determinant factors on willingness to pay for health services in Iran

A common method used to examine the relationship between internal preferences and caring externalities is willingness to pay (WTP) approach. We aimed to estimate WTP for health status with different severity l...

Deciphering psoriasis. A bioinformatic approach

Psoriasis is an immune-mediated, inflammatory and hyperproliferative disease of the skin and joints. The cause of psoriasis is still unknown. The fundamental feature of the disease is the hyperproliferation of keratinocytes and the recruitment of cells from the immune system in the region of the affected skin, which leads to deregulation of many well-known gene expressions.

Environmental mineralization of caffeine micro-pollutant by Fe-MFI zeolites

Abstract

Environmentally emerging micro-pollutant, caffeine, was mineralized (i.e., full degradation) by the isomorphic incorporation of Fe into silicalite-1 (mordenite framework inverted (MFI) structure zeolite) through a microwave synthesis method. The Fe incorporation conferred mesopore formation that facilitated caffeine access and transport to the MFI zeolite structure. Increasing the Fe content favored the formation of Fe(O)₄ sites within the MFI structure. The catalytic activity for the degradation of caffeine increased as a function of Fe(O)₄ sites via a Fenton-like heterogeneous reaction, otherwise not attainable using Fe-free pure MFI zeolites. Caffeine degradation reached 96% (TOC based) for zeolites containing 2.33% of Fe.

Assessment of pollutions and identification of sources of heavy metals in sediments from west coast of Shenzhen, China

Abstract

The sediment samples were collected from eight sites located in the Pearl River Estuary and the Shenzhen Bay of the west coast of Shenzhen. The distributions of the seven elements Zn, Cr, Hg, Cu, Cd, Pb and As have been analyzed, and their pollution degrees, corresponding potential ecological risks and source identifications have been studied using geo-accumulation index, potential ecological risk index and integrated multivariate statistical methods, respectively. Based on the calculated geo-accumulation indices, the contamination levels of all elements in the Pearl River Estuary are similar to those in the Shenzhen Bay, reflecting that these elements in the study areas have similar sources because of the adequate seawater exchange. The calculated potential ecological risk indices suggest that Cd and Hg are at considerable and moderate risk, respectively. Multivariate statistical analyses further reveal that Zn, Hg, Cd and Pb originated from industrial wastewater, while Cr and Cu are mainly from both industrial wastewater and agricultural sources, and As is mainly from natural source. These research results provide baseline information for both the coastal environment management and the worldwide heavy metal distribution and assessment.

Solid fuel use for cooking and its health effects on the elderly in rural China

Abstract

Indoor air pollution is mainly caused by solid fuel use for cooking in developing countries. Many previous studies focused on its health risks on the children and in specific local area. This paper investigates household energy usage and transition for cooking in rural China and the health effects on the elderly. A national large-scale dataset CHARLS (China Health and Retirement Longitudinal Study) covering 450 villages and communities is employed. Logit regressions were used to quantitatively estimate the effects, after controlling for some factors such as income, demographic, and geographical variables. The results robustly show that compared to non-solid fuels, solid fuel use significantly increases the possibility of chronic lung diseases (30%), exacerbation of chronic lung diseases (95%), seizure of heart disease (1.80 times), and decreases self-evaluated health status of the elderly (1.38 times). Thus, it is urgent to improve clean energy access for cooking in rural China.

Assessment of water resource contamination by pesticides in vegetable-producing areas in Burkina Faso

Abstract

This study proposes a comprehensive approach to investigate water resource contamination by pesticides under the specific climatic and hydrological conditions of the Sudano-Sahelian climate. Samples were collected from traditional wells, boreholes, and a lake in Burkina Faso. A multiresidue analysis was developed for 25 pesticides identified during field surveys. Polar organic chemical integrative samplers (POCIS) were used to confirm trends observed with grab samples. Uptake kinetics of POCIS were assessed by in situ calibration. The proposed use of nonlinear least squares regression proved to be a robust approach for estimating time-weighted average concentration in cases of nonlinear uptake. High sampling rates for triazines in a quasi-stagnant lake were attributed to warm water temperatures (30.8 ± 1.3 °C). The combination of sampling techniques during a 3-year monitoring period allowed for identifying potential interactions between resources, seasonal patterns, and origins of contaminants. Atrazine, azadirachtin, carbofuran, chlorpyrifos, cypermethrin, dieldrin, imidacloprid, and profenofos exceeded 0.1 μg L⁻¹, indicating a potential risk for the consumers. Ecological risk assessment was performed using the Pesticide Tool Index for fish, cladocerans, and benthic invertebrates. Peak concentrations of cypermethrin and chlorpyrifos were systematically associated with hazard to the studied taxa.

Kinetic simulation and prediction of pyrolysis process for non-metallic fraction of waste printed circuit boards by discrete distributed activation energy model compared with isoconversional method

Abstract

Kinetic studies on the pyrolysis process for non-metallic fraction (NMF) of waste printed circuit boards (WPCBs) were conducted using both the isoconversional SKAS method and the discrete distributed activation energy model (discrete DAEM). The pyrolysis process of the NMF sample could be classified into three stages, and a large mass loss was observed from 98 to 570 °C, attributed to thermal degradation of epoxy resins in the NMF sample. The kinetic parameters, including activation energies (E _i), pre-exponential factors (A _i), and contributed fractions (f _i,0), were determined. It indicated that the discrete DAEM could predict the pyrolysis process of the NMF more accurately and completely when compared with the isoconversional SKAS method. In the discrete DAEM, E _i and A _i values were evaluated at 99 equally spaced intervals of conversion. The E _i and A _i (in the form of lnA _i) transformed with reaction progress, ranging from 80.9 to 240.5 kJ/mol and 19.07 to 39.55 s⁻¹, respectively, with the conversion increased from 0.01 to 0.99. The pyrolysis of the NMF of WPCBs could be accurately characterized as 17 dominating reactions from f _i,0 results.

Graphical abstract

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Bioagents and silicon promoting fast early upland rice growth

Abstract

Upland rice can overcome major challenges through the insertion of silicate fertilization and the presence of plant growth-promoting microorganisms (PGPMs) during its cultivation, as these factors promote an increase in vigor and plant disease resistance. Two consecutive experiments were conducted to evaluate the beneficial effects of silicon fertilization combined with the PGPM, Pseudomonas fluorensces, Burkholderia pyrrocinia, and a pool of Trichoderma asperellum, in upland rice seedlings, cultivar BRS Primavera CL: (a) E1, selecting PGPM type and Si doses for rice growth promotion and leaf blast supression, and (b) E2, evaluating physiological characteristics correlated with mechanisms involved in the higher vegetative growth in highlighted treatments from E1. In E1, 2 Si t ha⁻¹ combined with the application of T. asperellum pool or PGPM mixture increased 54% in root dry matter biomass and 35 and 65% in shoot and root lengths, respectively; it also suppressed 99% of rice blast severity. In E2, shoot and root dry matter biomass and length, photosynthetic rate, water use efficiency, total soluble sugar, and chloroplastidic pigments were superior in BRS Primavera CL seedlings treated with 2 Si t ha⁻¹ and T. asperellum pool or PGPM mixture. Higher salicilic and jasmonic acid levels were found in seedlings treated with Si and T. asperellum pool, individually. These physiological characteristics may explain, in part, the higher vigor of upland rice seedlings promoted by the synergistic effect between silicate fertilization and beneficial microorganisms.

Ameliorative effect of the anticancer agent salinomycin on cadmium-induced hepatotoxicity and renal dysfunction in mice

Abstract

This study presents experimental data on the effects of the tetraethylammonium salt of salinomycinic acid (Sal) on Cd-induced hepatotoxicity and renal dysfunction in Cd-treated mice compared to those of meso-2,3-dimercaptosuccinic acid (DMSA). Forty 60-day-old male ICR mice were randomized into five groups: control group (untreated mice), Cd group (Cd(II) acetate 20 mg/kg body weight provided orally once per day for 14 days), Cd + DMSA group (exposed to Cd(II) acetate as the Cd-exposed group followed by DMSA 20 mg/kg body weight provided orally once per day for 14 days), and Cd + Sal group (exposed to Cd(II) acetate as the Cd-exposed group followed by Sal 20 mg/kg body weight once per day for 14 days). Cd intoxication of mice induced significant liver and kidney injury and a significant elevation of the concentration of Cd in both organs. Treatment of Cd-exposed mice with DMSA or Sal restored the levels of the renal and hepatic functional markers and significantly decreased the concentration of the toxic metal ion in both organs. Administration of Sal improved Cd-induced alterations of the endogenous levels of the essential metal ions. Histological studies revealed that the antibiotic more effectively ameliorated the Cd effect on the liver morphology compared to DMSA. Taken together, the results confirm that the anticancer agent salinomycin is a promising antidote to Cd poisoning.

Seasonal toxicity variation in light-textured soil amended with urban sewage sludge: interaction effect on cadmium, nickel, and phytotoxicity

Abstract

Sewage sludge is increasingly used as an organic amendment to agricultural soils, especially to soils containing little organic matter. However, little is known on the impact of this biowaste on seasonal changes of nickel and cadmium toxicity in a sandy loam soil. Accordingly, the aim of this field-scale study was to evaluate the seasonal phytotoxicity according to Cd, Ni, and dehydrogenase variation in an agricultural soil during two successive annual amendments with increasing amounts of urban sludge (0, 40, 80, and 120 t ha⁻¹ year⁻¹). Sampling was carried out at the end of dry season (EDS) and at the end of wet season (EWS) during 2 years 2012/2013. Sludge application significantly increased the amount of organic matter and dehydrogenase activity in the soil. In order to explain the seasonal variation of Cd and Ni, pH and electrical conductivity were also monitored in this study. The increased rate of sewage sludge addition slightly reduced the pH but soil remained above neutrality. The electrical conductivity which reflects soil salinity was strongly correlated with Cd and Ni content that increased with sludge dose. Salinity and heavy metals were highest at EDS 2013. In addition, soil phytotoxicity testing was performed by the evaluation of lettuce seed germination for 120 h. Although heavy metal content did not generally exceed Tunisian thresholds (3 and 75 mg kg⁻¹ for Cd and Ni, respectively), the seed germination index decreased with sewage sludge dose at all seasons. In general, we observed a significant effect of seasonal variation for all studied parameters. Sewage sludge reuse could be a feasible way to improve soil organic matter but toxicity risks consistently increased with time.

Deposition, acute toxicity, and bioaccumulation of nickel in some freshwater organisms with best-fit functions modeling

Abstract

Although nickel (Ni) frequently enters into water, documents on speciation of the metal and its toxicity to freshwater organisms are scanty. Laboratory experiments, made in this study, with 1.0–5.0 mg/L of Ni revealed that Ni was not quickly removed from water. Application of cubic regression followed by classical optimization technique showed that maximum reduction time (T) of Ni in water ranged between 60 to 65 h. Ninety-six hours of LC₅₀ value of Ni to crustacean Diaptomus forbesi, fish Cyprinus carpio, and worm Branchiura sowerbyi was respectively 5.43, 14.70, and 19.73 mg/L. Normalizing the lethal values and plotting them against time, it was observed that C. carpio was more sensitive than D. forbesi, which was not reflected in the 96-h LC₅₀ values. However, sensitivity of these organisms to Ni was better explained by power regression equation (M = aNi^b), which exhibited that mortality (M) of D. forbesi and B. sowerbyi increased slowly between 24 to 72 h, increasing sharply at 96 h, while mortality of C. carpio increased steadily every 24 till 96 h. Experiment with 1.0 mg/L of Ni in outdoor vats showed that crustacean zooplankton and worms accumulated high concentration of Ni, while only gut and liver tissues of fish C. carpio accumulated trace and moderately high concentration of Ni, respectively. It is assumed that toxicity of Ni to fish is mediated primarily through gill.

Di-(2-ethylhexyl)-phthalate induces glucose metabolic disorder in adolescent rats

Abstract

As a plasticizer, di-(2-ethylhexyl)-phthalate (DEHP) is widely added in various commercial products. Some researchers had suggested that DEHP has adverse effects on the glucose metabolism, but the mechanisms remain unclear. Adolescent Wistar rats were divided into four groups and administered DEHP by gavage at 0, 5, 50, and 500 mg kg⁻¹ d⁻¹ for 28 days. ELISA was used to quantify the serum insulin and leptin levels; RT-PCR, immunohistochemistry, and Western blot were used to detect the mRNA and protein expressions of Janus-activated kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling 3 (SOCS3), leptin receptor (Ob-R), and insulin receptor (IR) in liver and pancreas In comparison to the control group, the DEHP-treated rats showed the following: (1) higher organ coefficient of liver; (2) higher fasting blood glucose levels, higher fasting serum insulin and leptin levels, higher insulin resistance index homeostasis model assessment; (3) lower protein levels of Ob-R and IR in the liver and pancreas; (4) higher protein levels of JAK2 and STAT3 in the liver; and (5) higher protein and mRNA levels of SOCS3 in the liver and pancreas. Exposure to DEHP induced glucose metabolic disorder in the adolescent rats, and the mechanism is that DEHP may interfere with the JAK2/STAT3/SOCS3 pathway, regulated the sensitivity of the insulin receptor and leptin receptor.

It started from scratch

Tribute to Reviewers

Issue Information

New Zealand Dermatological Society Inc. Annual Scientific meeting Queenstown, New Zealand August 2017 Convener: Dr Paul JM Salmon

Dermatology Practice Consolidation Fueled by Private Equity Investment

This Viewpoint discusses the consolidation of dermatology practices facilitated by private equity investment and the potential consequences for the specialty and patients.

Insect cuticular melanins are distinctly different from those of mammalian epidermal melanins

Summary

Melanin from several insect samples were isolated and subjected to chemical degradation and HPLC analysis for melanin markers. Quantification of different melanin markers reveals that insect melanins are significantly different from that of the mammalian epidermal melanins. The eumelanin produced in mammals are derived from the oxidative polymerization of both 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid. The pheomelanin is formed by the oxidative polymerization of cysteinyldopa. Thus dopa is the major precursor for both eumelanin and pheomelanin in mammals. But insect eumelanin appears to be mostly made from 5,6-dihydroxyindole and originate from dopamine. More importantly, our study points out the wide spread occurrence of pheomelanin in many insect species. In addition, cysteinyldopamine and not cysteinyldopa is the major precursor for insect pheomelanin. Thus both eumelanin and pheomelanin in insects differ from higher animals by using dopamine and not dopa as the major precursor.

This article is protected by copyright. All rights reserved.

Phosphorus speciation and release kinetics of swine manure biochar under various pyrolysis temperatures

Abstract

Converting swine manure to biochar is an effective way to recycle valuable nutrients, but there are few reports on its feasibility as a phosphorus (P) source. The objective of this study was to clarify the unique nature, including P speciation, of manure biochar products under various pyrolysis temperatures. We used solution ³¹P nuclear magnetic resonance and P K-edge X-ray adsorption near-edge spectroscopy (P XANES) to characterize P species in swine manure biochar. For every 100 °C increment starting from 300 °C, the P content in manure biochar increased by 2.16 to 3.37 g kg⁻¹. However, above 400 °C, organic P species did not appear anymore, and only inorganic P, including orthophosphate and pyrophosphate, existed. P K-edge XANES spectra further showed all biochar samples had higher percentages of Ca₃ (PO₄)₂ and NaP₂O₇, and lower percentages of FePO₄, AlPO₄, and inositol hexaphosphate compared to manure. Interestingly, percentages of Ca₃(PO₄)₂, FePO₄, and AlPO₄ in MB400 (indicating manure pyrolysed at 400 °C) were comparable with those in MB700 while the percentage of NaP₂O₇ was higher in MB400. Phosphorus release from MB400 maintained a relatively high level at 0.33 g kg⁻¹ during the whole 300-h observation period. These results suggest that with a suitable pyrolysis temperature, it was feasible for manure biochar to be a P source alternative.

Graphical abstract

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Lighting Van Leeuwenhoek's samples

Abstract

Possible techniques for lighting opaque samples while using Van Leeuwenhoek microscopes have been tested, and the results are presented in relation to published material. The design of the microscope causes the sample to be in shadow with any form of top-lighting. It is therefore suggested that Van Leeuwenhoek's hinted 'particular method of observing' might refer to a different style of microscope as shown in the frontispiece of the sale catalogue for his microscopes, and available at that time for purchase from sellers of optical equipment.

The Editor's Choice

Editorial board

Prefrontal recruitment mitigates risk taking behavior in HIV infected young adults

Abstract

Background

HIV-infected (HIV+) young adults often engage in risk taking behavior. However, the disruptive effects of HIV on the neurobiological underpinnings of risky decision-making are not well understood.

Methods

Risky decision-making, measured via the Iowa Gambling Task (IGT), was compared voxel-wise to resting cerebral blood flow (rCBF) acquired via arterial spin labeling. Separate topographical maps were obtained for HIV uninfected (HIV–; n=62) and HIV+ (n=41) young adults (18-24 years old) and were compared to the full cohort of participants. For the HIV+ group, rCBF was compared to recent and nadir CD4.

Results

IGT performance was supported by rCBF in three distinct brain regions: Region-I, -II, and -III. The relationship between IGT performance and rCBF in HIV+ individuals was most robust in Region-I, ventromedial prefrontal and insular cortices. Region-II contained strong relationships for both HIV– and HIV+. Region-III, dorsolateral prefrontal and posterior cingulate cortices, contained relationships that were strongest for HIV– controls. IGT performance was intact among HIV+ with higher rCBF in either Region-I or Region-III. By contrast, performance was worse among HIV+ individuals with lower rCBF in both Regions-I, and –III when compared to HIV– controls (p=0.01). rCBF in Region-III was reduced in HIV+ compared to HIV– individuals (p=0.04), and positively associated with nadir CD4 (p=0.02).

Conclusions

Recruitment of executive systems (Region-III) mitigates risk taking behavior in HIV+ and HIV– individuals. Recruitment of reward systems (Region-I) mitigates risk taking behavior when Region-III is disrupted due to immunological compromise. Identifying individual recruitment patterns may aid anatomically directed therapeutics or psychosocial interventions.

Reply to Weinbren and Collins

Drying–submergence alternation enhanced crystalline ratio and varied surface properties of iron plaque on rice ( Oryza sativa ) roots

Abstract

Iron plaque (IP) is valuable in nutrient management and contaminant tolerance for rice (Oryza sativa) because it can adsorb various nutrients and toxic ions. Crystalline ratio (CR) can be defined as the proportion of crystalline iron (CI) to total IP to describe IP crystallinity. Although the knowledge on IP has abounded, the information on the relationship among its formation condition, surface properties, and CR remains insufficient. In this study, quartz sand–soil cultivation with rice was conducted to explore the effect of drying–submergence alternation (DSA) on CI, amorphous iron (AI), CR, root oxidizing capacity (ROC), and surface properties of IP with different treatment durations and at different stages. Fourteen-day DSA treatment increased CI to 2.20 times of that after continuous submergence (CS) but decreased AI to 72.3% of that after CS. Correspondingly, CR was raised to 6.89% from 4.08%. Remarkably, CR of IP after DSA ending in submergence and ending in drying was 6.89% and 4.23%, respectively. In addition, ROC after 14-day DSA was enhanced to twice of that after CS. Results from scanning electronic microscope suggested that 14-day DSA induced thinner sheets with finer particles in IP compared to that after CS. Results from X-ray diffraction revealed that IP contained higher proportions of goethite, lepidocrocite, magnetite, and hematite after DSA than those after CS. Variable charge and surface area of IP after DSA were only 26.5% and 32.0% of those after CS, respectively. Together, our results indicated that proper strength DSA promoted ROC and transformation from AI to CI, and consequently increased CR of IP, while it changed its surface properties.

The effect of animal grazing on vegetation and soil and element cycling in nature

Abstract

Appropriate level of bio-components in blood plasma of animals is associated with their concentration in soil and in green fodder. Cycling of elements in nature and their adequate level in animal organisms result in proper functioning of an organism as a whole (Khan et al. 68:279–284, 2007). Therefore, it is important to analyse soil and green fodder for these components. If some deficits are found, it is important to supplement components responsible for e.g. proper growth and development of a young organism, proper reproduction and, consequently, good quality of obtained product, which may affect human health (Minzanova et al. 134:524–533, 2015). The aim of the presented study was to demonstrate the effect of extensive grazing by sheep on vegetation and soil and to analyse the cycling of some elements important for animal health. The effects of vegetation season on the concentration of potassium in soil and differences in the concentration of some elements in soil, green fodder and animal blood were demonstrated.

Patients' preferences for adjuvant sorafenib after resection of renal cell carcinoma in the SORCE trial: what makes it worthwhile?

Abstract

Background

We sought to determine the survival benefits that patients judged sufficient to warrant adjuvant therapy with sorafenib for 1 year, or for 3 years after resection of renal cell carcinoma (RCC) in the SORCE trial.

Methods

SORCE participants from all sites in Australia and New Zealand, and selected sites in the UK, completed a validated preferences questionnaire at months 0, 3, 15 and 42 to elicit the minimum survival benefits they judged sufficient to warrant adjuvant sorafenib for 1 year (versus observation), or for 3 years (versus 1 year). The questionnaires used reference survival times of 5 years and 15 years; and reference survival rates at 5 years of 65% and 85%.

Results

The 233 participants had a median age of 57 years (range 29 to 78) and 71% were male. For 1 year of sorafenib versus no adjuvant therapy, the median benefits in survival times judged sufficient to warrant treatment were an extra 9 months beyond 5 years and an extra 1 year beyond 15 years; the median benefit in survival rates were an extra 4% beyond 65% and an extra 3% beyond 85% at 5 years. For 3 years of sorafenib versus 1 year of sorafenib, the median benefit in survival time judged sufficient to warrant extended treatment was an extra 1 year beyond both 5 years and 15 years. Participants randomly allocated treatment with sorafenib judged larger benefits necessary than those allocated placebo. Participants' preferences were not associated with their baseline characteristics or the interval from randomisation.

Conclusion

Most participants judged an extra year of survival necessary to warrant 1 year of adjuvant sorafenib worthwhile, and an additional year of survival to warrant extending the duration of sorafenib from 1 year to 3 years. Patients' preferences are important in shared-decision-making.SORCE trial clinical trials number = NCT00492258

Removal of lead from aqueous solution using polyacrylonitrile/magnetite nanofibers

Abstract

Lead is known for its toxic and non-biodegradable behavior. The consumption of lead-contaminated water is one of the major threat the world is facing nowadays. In this study, polyacrylonitrile (PAN) and magnetite (Fe₃O₄) composite nanofiber adsorbent was developed for Pb²⁺ removal in batch mode. The synthesis was done by a simple and scalable process of electrospinning followed by chemical precipitation of Fe₃O₄. The nanofibers thus obtained were characterized through FTIR, zeta potential analyzer, and scanning electron microscope (SEM) and were analyzed for their adsorption capability for Pb²⁺ ions. The amount of metal ion adsorbed was influenced by the initial metal ion concentration, the time the adsorbent was in contact, the amount of nanofiber, and the pH of the solution. The experimental data fitted well with pseudo 2nd-order and Langmuir adsorption isotherm model. The nanofibers showed high adsorption capability and could be recommended for Pb²⁺ removal successfully.

Vulvar swelling as the first presentation of Crohn's disease in children—A report of three cases

Abstract

Vulvar swelling is a rare manifestation of metastatic Crohn's disease in children. It often predates gastrointestinal symptoms and can be the first presentation of pediatric Crohn's disease. We report three cases of pediatric Crohn's disease presenting with vulvar swelling. We discuss this rare presentation and its treatment and highlight the importance of recognizing it so that prompt investigation and appropriate management can be initiated.

Bleomycin-induced flagellate erythema after venous malformation sclerosis—Case report and brief review

Abstract

Bleomycin-induced flagellate erythema is a rare but typical skin toxicity of bleomycin. We report the case of a boy with a left foot venous malformation who developed this skin rash after two sessions of bleomycin intralesional injection. We discuss the mechanism and characteristics of this reaction to bleomycin, which is usually benign and self-limited. We conclude that, although rare, flagellate pigmentation can occur when bleomycin is used as a sclerosant in children.

Prevalence of sun protection behaviors in Hispanic youth residing in a high ultraviolet light environment

Abstract

Although rates of late-stage melanoma are rising in Hispanics, particularly those living in high ultraviolet light environments, little is known about the prevalence of sun protective behaviors in Hispanic children. We analyzed baseline data including frequency of sunburn, sun protective behaviors, level of U.S. acculturation, and skin phototype from a cross-sectional survey of 2003 Hispanic elementary school children in Los Angeles, California, who participated in a skin cancer prevention intervention. Although the Hispanic children reported frequently engaging in some sun protective behaviors, they also had a high rate of sunburn (59%) that exceeded previous national estimates for non-Hispanic white children (43%). Fewer U.S.-acculturated children reported more frequent shade-seeking at home (P = .02), along with less shade-seeking at school (P = .001) and more sunscreen use at school (P = .02). The surprisingly high rate of sunburn in Hispanic children suggests that the way in which they are practicing sun protection is not preventing sunburns. Sun safety interventions should be targeted toward Hispanic youth to provide them with practical methods of effective sun protection, in addition to education on the risks of high sun exposure.

New soft tissue filler derived from autologous keratin and fibroblast for neck wrinkles

Summary

Objective

To assess the effectiveness of injection of autologous keratin gel and fibroblast for neck aging as soft tissue filler.

Materials and methods

Totally 30 volunteers received treatment of autologous keratin and fibroblast for neck wrinkles and 5 of them received hyaluronic acid (HA) treatment as control. Clinical features of the volunteers were collected at 1st, 3rd, 6th, 12th, and 24th months after treatment. The volunteers were independently assessed using Lemperle's methods at different time points.

Results

The neck wrinkles ameliorated observably and no severe complications were reported after treatment. The effect and maintain time of autologous keratin and fibroblast were better than HA control.

Conclusion

Autologous keratin and fibroblast as soft tissue filler is an effective treatment option for neck rejuvenation with long-term efficacy for reversing of skin aging.

Delayed allergic hypersensitivity to hyaluronidase during the treatment of granulomatous hyaluronic acid reactions

Summary

Hyaluronic acid (HA) is now extensively employed for esthetic concerns. In the majority of cases, HA is considered to be safe, but mild-to-severe complications can occur in a few cases. Hyaluronidase is enzymes that degrade HA, also being suggested for the treatment of HA filler-induced complications. However, hyaluronidase has been reported to be a potential cause of allergic responses in some anesthetic and ophthalmic literature. However, there are few reports of allergic reactions to hyaluronidase in cosmetic medicine. We herein report on a 39-year-old Asian woman who developed a delayed allergic hypersensitivity to hyaluronidase in the treatment process of HA-related granulomatous reaction.

Serum homocysteine levels in acne patients

Summary

Objective

This study was designed to investigate serum homocysteine (HCY) levels in acne patients.

Methods

Acne patients (n = 124) and healthy volunteers (n = 70), matched in terms of both age and sex, were enrolled. Serum HCY levels for all subjects were measured by a clinical laboratory.

Results

Serum HCY levels in male and female patients with severe and moderate acne were significantly higher than in the healthy control group (P < .05). The constituent ratio of male and female acne patients with HCY above the normal range (10 mmol/L) was significantly higher than the healthy control group. The severity of acne patients was positively correlated with serum homocysteine concentration, (P < .01).

Conclusion

Hyperhomocysteinemia may be an independent risk factor for acne vulgaris. Detection of serum HCY is important for acne patients.

Severe Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome—beyond skin involvement

Abstract

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but serious dermatologic diseases with many potential multisystem complications. We describe the case of an 8-year-old girl who developed severe SJS/TEN overlap syndrome (25% of her body surface area was affected) complicated by pancreatitis and bronchiolitis obliterans. These rare complications emphasize the need for careful, intensive monitoring of possible complications and an interdisciplinary team approach to provide optimal treatment and follow-up.

Demographic characteristics of teenage boys with horizontal striae distensae of the lower back

Abstract

Background

This study examines the clinical characteristics and demographics of teenage boys with horizontal striae distensae of the lower back in an outpatient setting.

Methods

Retrospective medical chart reviews and telephone survey studies were completed on an outpatient cohort of 12 boys 11 to 17 years of age with a clinical diagnosis of transverse striae distensae of the lower back at a single-center, university-based, pediatric dermatology practice. We evaluated the clinical features of the striae, participant demographic characteristics, and past medical history. A review of the literature concerning risk factors was conducted using PubMed and Google Scholar.

Results

Of the 14 patients we contacted, 12 agreed to participate. The average age of onset for the striae was 14.3 years. All boys were above the 50th percentile in height at the time of onset. Eight (66.7%) reported a significant growth spurt before the appearance of the stretch marks. Most were asymptomatic. None of the boys had a history of unmonitored exogenous steroid use or prior infection with Bartonella henselae or Borrelia burgdorferi. Only one (8.3%) had a chronic medical condition. Eleven (91.7%) had at least one first-degree relative with striae distensae.

Conclusion

Our results indicate that horizontal striae distensae of the lower back in adolescent boys is associated with a rapid growth spurt, tall stature, and family history of striae distensae. There is no association between this type of striae distensae and any chronic medical condition, bacterial infection, or exogenous steroid use. Thus a careful review of systems and counseling without further medical testing is reasonable management.

Juvenile mycosis fungoides with large-cell transformation: Successful treatment with psoralen with ultraviolet A light, interferon-alfa, and localized radiation

Abstract

Mycosis fungoides with large-cell transformation is historically associated with a poor prognosis. Pediatric cases of mycosis fungoides with large-cell transformation are rare, with only three other cases reported in the literature. We present the first case of a child with almost complete remission of his mycosis fungoides with large-cell transformation shortly after administration of psoralen plus ultraviolet A, interferon-alfa, and localized radiation.

New insights into pemphigoid diseases

Abstract

Pemphigus and pemphigoid diseases are organ-specific autoimmune blistering diseases (AIBD), characterized and caused by autoantibodies to structural components of the skin (1). The autoantigens targeted in pemphigus are desmoglein 1 and 3, two proteins of the desmosomal structure, while the autoantigens in pemphigoid diseases (PD) are components of the basal membrane. For example, bullous pemphigoid (BP), the most frequent PD is characterized by autoantibodies against type XVII collagen (COL17, BP180) and BP230, and epidermolysis bullosa acquisita (EBA) is caused by autoantibodies against type VII collagen (COL7).

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Laryngeal candidiasis: our experience from sixty biopsy specimens

Persistent throat symptoms, such as dysphonia, globus and throat pain, are highly prevalent and are a significant cause of morbidity¹. In a number of cases a clear cause of these symptoms is not identified and many patients are treated empirically with lifestyle advice and/or anti-reflux medication².

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Melanoma in Patients with GATA2 Deficiency

Summary

GATA2 deficiency is a recently described genetic disorder affecting hematopoietic stem cells and is associated with immunodeficiency, cutaneous findings, and hematologic malignancy. The risk of non-hematologic malignancies is unclear. To explore the incidence and clinical course of melanoma in GATA2 deficient patients we conducted a retrospective chart review of 71 patients with GATA2 deficiency. We identified two patients with melanoma, including an invasive melanoma presenting as a graft-versus-tumor effect following bone marrow transplantation. Our observations and published studies of melanoma biology suggest an association between decreased GATA2 expression and melanoma progression. These findings suggest that GATA2 deficient patients may have an increased risk of melanoma and should be observed closely for new or changing skin lesions.

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Association of PD-L1 expression with treatment outcomes in patients with BRAF mutation–positive melanoma treated with vemurafenib or cobimetinib combined with vemurafenib

Summary

The prognostic significance of programmed death ligand-1 (PD-L1) on treatment outcomes in patients receiving BRAF with or without MEK inhibitors is not well understood. This retrospective exploratory analysis evaluated the association of tumour PD-L1 expression with progression-free survival (PFS) and overall survival (OS) among 210 patients in the coBRIM trial treated with cobimetinib plus vemurafenib or placebo plus vemurafenib. In the vemurafenib cohort, there was a trend of increased PFS and OS in those with PD-L1⁺ melanoma, with hazard ratios (HRs) (PD-L1⁺ versus PD-L1⁻) of 0.70 (95% CI, 0.46–1.07) and 0.69 (95% CI, 0.42–1.13) for PFS and OS, respectively. However, in patients treated with cobimetinib plus vemurafenib, a similar trend was not observed with HRs (PD-L1⁺ versus PD-L1⁻) of 1.04 (95% CI, 0.66–1.68) and 0.94 (95% CI, 0.57–1.57) for PFS and OS, respectively. The combination cobimetinib plus vemurafenib appears to overcome the poor prognosis associated with low PD-L1 expression.

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Identifying and assessing human activity impacts on groundwater quality through hydrogeochemical anomalies and NO 3 − , NH 4 + , and COD contamination: a case study of the Liujiang River Basin, Hebei Province, P.R. China

Abstract

In the face of rapid economic development and increasing human activity, the deterioration of groundwater quality has seriously affected the safety of the groundwater supply in eastern China. Identifying and assessing the impact of human activities is key to finding solutions to this problem. This study is an effort to scientifically and systematically identify and assess the influence of human activities on groundwater based on irregularities in hydrochemical properties and water contamination, which are considered to directly result from anthropogenic activity. The combination of the hydrochemical anomaly identification (HAI) and the contaminant identification (CI) was proposed to identify the influence of human activities on groundwater quality. And the degree of abnormality was quantified by the background threshold value. The principal component analysis (PCA) and land use map were used to verify the reliability of the identification result. The final result show that the strong influence areas mainly distributed in the south of the basin and the affected indicators contained the major elements and NO₃⁻, NH₄⁺, COD. Impacts from anthropogenic activities can be divided into two types: mine drainage that disrupts natural water–rock interaction processes, agricultural cultivation, and sewage emissions that contribute to nitrate pollution.

Isolation of lead-resistant Arthrobactor strain GQ-9 and its biosorption mechanism

Abstract

In this study, lead-resistant bacterium Arthrobacter sp. GQ-9 with a resistant capability to cadmium, zinc, and copper was isolated from a heavy metal polluted soil. Microcalorimetry analysis was applied to assess the strain's microbial activity under Pb(II) stress and suggested that GQ-9's microbial activities under Pb(II) stress were stronger than a non-resistant strain. Biosorption batch experiments revealed that the optimal condition for adsorption of Pb(II) by GQ-9 was pH 5.5, a biomass dosage of 1.2 g L⁻¹, and an initial Pb(II) concentration of 100 mg L⁻¹ with a maximum biosorption capacity of 17.56 mg g⁻¹.Adsorption-desorption experiments and Fourier transform infrared spectroscopy (FTIR) analysis were applied to elucidate the biosorption mechanisms. Adsorption-desorption analysis showed that GQ-9 cells could sequester 56.60% of the adsorbed Pb(II) ions on the cell wall. FTIR analysis suggested that hydroxyl, carboxyl, amino, nitrile, and sulfhydryl groups and amide I, amide II bands on the GQ-9 cell wall participated in the complexation of Pb(II) ions. The present study illustrates that the lead-resistant bacteria GQ-9 has the potential for further development of an effective and ecofriendly adsorbent for heavy metal bioremediation.

Correction

Etzkorn JR, Sobanko JF, Elenitsas R, et al. Low recurrence rates for in situ and invasive melanomas using Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining: Tissue processing methodology to optimize pathologic staging and margin assessment. J Am Acad Dermatol. 2015;72(5):840-50.