Pathological Tau Strains from Human Brains Recapitulate the Diversity of Tauopathies in Nontransgenic Mouse Brain

Pathological tau aggregates occur in Alzheimer's disease (AD) and other neurodegenerative tauopathies. It is not clearly understood why tauopathies vary greatly in the neuroanatomical and histopathological patterns of tau aggregation, which contribute to clinical heterogeneity in these disorders. Recent studies have shown that tau aggregates may form distinct structural conformations, known as tau strains. Here, we developed a novel model to test the hypothesis that cell-to-cell transmission of different tau strains occurs in nontransgenic (non-Tg) mice, and to investigate whether there are strain-specific differences in the pattern of tau transmission. By injecting pathological tau extracted from postmortem brains of AD (AD-tau), progressive supranuclear palsy (PSP-tau), and corticobasal degeneration (CBD-tau) patients into different brain regions of female non-Tg mice, we demonstrated the induction and propagation of endogenous mouse tau aggregates. Specifically, we identified differences in tau strain potency between AD-tau, CBD-tau, and PSP-tau in non-Tg mice. Moreover, differences in cell-type specificity of tau aggregate transmission were observed between tau strains such that only PSP-tau and CBD-tau strains induce astroglial and oligodendroglial tau inclusions, recapitulating the diversity of neuropathology in human tauopathies. Furthermore, we demonstrated that the neuronal connectome, but not the tau strain, determines which brain regions develop tau pathology. Finally, CBD-tau- and PSP-tau-injected mice showed spatiotemporal transmission of glial tau pathology, suggesting glial tau transmission contributes to the progression of tauopathies. Together, our data suggest that different tau strains determine seeding potency and cell-type specificity of tau aggregation that underlie the diversity of human tauopathies.

SIGNIFICANCE STATEMENT Tauopathies show great clinical and neuropathological heterogeneity, despite the fact that tau aggregates in each disease. This heterogeneity could be due to tau aggregates forming distinct structural conformations, or strains. We now report the development of a sporadic tauopathy model to study human tau strains by intracerebrally injecting nontransgenic mice with pathological tau enriched from human tauopathy brains. We show human tau strains seed different types and cellular distributions of tau neuropathology in our model that recapitulate the heterogeneity seen in these human diseases.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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Cladribine to Treat Relapsing Forms of Multiple Sclerosis

Abstract

Cladribine is a purine nucleoside analogue that selectively depletes peripheral lymphocytes without a major impact on cells of the innate immune system. An oral formulation of cladribine has been developed to be given as short courses over two annual cycles. Oral cladribine results in the peripheral depletion of lymphocytes that is gradual, occurring over several weeks, and is not associated with a cell lysis syndrome, has a greater impact on B cells than T cells, and is followed by gradual reconstitution of the peripheral lymphocyte counts over several months. Oral cladribine is effective in relapsing forms of multiple sclerosis. As a selective immune reconstitution therapy (SIRT), cladribine acts as a short-term immunosuppressant, relative to other maintenance immunosuppressive therapies that result in long-term immunosuppression. The main safety signal that has emerge relates primarily to herpes zoster infection, which was more common in patients with higher grades of lymphopenia, in particular grade 3 and 4 lymphopenia. Data from the oral cladribine extension trial and safety register, and reanalysis of the pivotal phase III trial has indicated that oral cladribine is unlikely to be associated with an increased short- to intermediate-term risk of malignancy.

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Application of the Milan system for reporting risk stratification in salivary gland cytopathology

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Reply to Application of the Milan system for reporting risk stratification in salivary gland cytopathology

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Process mapping: A cornerstone of quality improvement

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Phenotyping-based treatment improves obstructive sleep apnea symptoms and severity: a pilot study

Abstract

Background

Obstructive sleep apnea is a common disorder characterized by multiple pathogenetic roots. Continuous positive airway pressure (CPAP) is almost always prescribed as the first-line treatment to all patients regardless of the heterogeneous pathophysiology, because it mechanically splints the airways open and reduces the collapsibility of the upper airway. Despite its high efficacy, CPAP is burdened by poor adherence and compliance rates. In this pilot study, we treated OSA patients with composite approaches different than CPAP, tailoring the therapeutic choice on OSA phenotypic traits.

Methods

We used the CPAP dial down technique to assess phenotypic traits in eight OSA patients with BMI<35. According to these traits, patients received personalized therapies for 2-week period, after which we ran a second polygraphy to compare apnea-hypopnea index (AHI) before and after therapy.

Results

Two weeks of combined behavioral and pharmacological therapy induced a significant reduction in mean AHI, which dropped from 26 ± 15 at baseline to 9 ± 7 post-treatment (p = 0.01). Furthermore, there was a significant reduction in mean ODI (p = 0.03) and subjective sleepiness (p = 0.01) documented by Epworth Sleepiness Scale (ESS) from baseline to post-treatment recordings.

Conclusions

Treating OSA patients with a personalized combination of pharmacological and behavioral therapies according to phenotypic traits leads to a significant improvement in AHI, ODI, and subjective sleepiness.

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Probiotics Mix May Curb Atopic Dermatitis Severity, Topical Steroid Use in Young People

An oral probiotic formulation may reduce both atopic dermatitis severity and use of topical steroids to treat it in young people with moderate disease, researchers say.
Reuters Health Information

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The effects of chemoradiotherapy on recurrence and survival in locally advanced rectal cancers with curative total mesorectal excision: a prospective, nonrandomized study

Abstract

Background

There are only two prospective, randomized studies comparing preoperative long-term chemoradiotherapy and postoperative chemoradiotherapy in locally advanced rectal cancer (LARC); however, conflicting results in terms of locoregional recurrence (LR) and survival rates have been reported. This prospective study aims to compare the effects of preoperative versus postoperative chemoradiotherapy on recurrence and survival rates in LARC patients.

Methods

From January 2003 to January 2016, a total of 336 eligible patients who were clinically diagnosed with LARC (T₃–T₄ tm or node-positive disease) were prospectively assigned into preoperative chemoradiotherapy (n = 177) and postoperative chemoradiotherapy (n = 159) groups. The preoperative treatment consisted of 50.4 Gy total dose of radiotherapy (delivered in fractions of 1.8 Gy) and concomitant two cycles chemotherapy of 5-fluorouracil and leucovorin. The patients in the preoperative group underwent curative total mesorectal excision (TME) following long-term chemoradiotherapy. Surgery was performed 8 (range 4–12) median weeks after the completion of the chemoradiotherapy. Similar protocol was administered to the postoperative group 4 weeks after the operation. Four cycles of adjuvant chemotherapy were added to the groups. The primary end points were locoregional recurrences and 5-year cancer-specific, overall, and disease-free survivals.

Results

The mean follow-up period was 60.4 (range 12 to 168) months. Five-year cumulative incidence of locoregional recurrence (LR) was 7.4% in the preoperative group and 13.4% in the postoperative group (p = 0.021). Five-year cancer-specific survival (CSS) was 87.5% in the preoperative group and 80% in the postoperative group (p = 0.022). Overall survival (OS) was 79.8 versus 74.7% (p = 0.064), disease-free survival (DFS) was 75.2 versus 64.8% (p = 0.062), and severe late toxicity was 7.4 versus 13.2% (p = 0.002), respectively. The rate of patient compliance was higher in the preoperative group (p < 0.001).

Conclusions

Preoperative chemoradiotherapy, as compared with postoperative chemoradiotherapy, significantly improved local control, patient compliance, CSS, and late toxicity and suggested a trend toward improved overall and disease-free survival.

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Past-year Prescription Drug Monitoring Program Opioid Prescriptions and Self-reported Opioid Use in an Emergency Department Population with Opioid Use Disorder

Abstract

Background

Despite increasing reliance on Prescription Drug Monitoring Programs (PDMPs) as a response to the opioid epidemic, the relationship between aberrant drug-related behaviors captured by the PDMP and opioid use disorder is incompletely understood. How PDMP data should guide Emergency Department (ED) assessment has not been studied.

Study Objective

To evaluate a relationship between PDMP opioid prescription records and self-reported non-medical opioid use of prescription opioids in a cohort of opioid dependent ED patients enrolled in a treatment trial.

Methods

PDMP opioid prescription records during one year prior to study enrollment on 329 adults meeting Diagnostic and Statistical Manual IV criteria for opioid dependence entering a randomized clinical trial (RCT) in a large, urban ED were cross tabulated with data on 30-day non-medical prescription opioid use self-report. The association among these two types of data was assessed by the Goodman and Kruskal's Gamma; a logistic regression was used to explore characteristics of participants who had PDMP record of opioid prescriptions.

Results

During one year prior to study enrollment,118/329 (36%) patients had ≥ 1 opioid prescriptions (range 1-51) in our states' PDMP. Patients who reported ≥15 out of 30 days of non-medical prescription opioid use were more likely to have ≥4 PDMP opioid prescriptions (20/38; 53%) than patients reporting 1-14 days (14/38, 37%) or zero days of non-medical prescription opioid use (4/38,11%); p=0.002. Female gender and having health insurance were significantly more represented in the PDMP (p<0.05 for both).

Conclusion

PDMPs may be helpful in identifying patients with certain aberrant drug-related behavior, but are unable to detect many patients with OUD. The majority of ED patients with OUD were not captured by the PDMP, highlighting the importance of using additional methods such as screening and clinical history to identify OUDs in ED patients and the limitations of PDMPs to detect OUDs.

This article is protected by copyright. All rights reserved.

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The Reply to the letter on the cost-effectiveness of human papillomavirus in Punjab further distorts the scientific record

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Factors affecting compliance with confirmatory colonoscopy after a positive fecal immunochemical test in a national colorectal screening program

BACKGROUND

Screening with the fecal immunochemical test (FIT) is effective in reducing deaths from colorectal cancer (CRC). Since 2004, biennial FIT screening has been available to a target population in Taiwan as a national screening program. The objective of the current study was to identify the factors that influence willingness to undergo a confirmatory colonoscopy after a positive FIT, because related references in the published literature were scarce.

METHODS

A semistructured questionnaire was based on the Health Belief Model (HBM) and a literature review. A stratified, random sampling method was used to recruit participants who had a positive FIT from all cities/counties in Taiwan. Cross-sectional, computer-assisted telephone interviews were conducted in 2012, and the results were analyzed using a logistic regression model that took into account population demographics, core content of the HBM, and HBM-modifying variables.

RESULTS

In total, 2807 respondents were included in the analysis. The completion rate was 50%. Multivariate analyses revealed that higher perceived threat (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 1.31-2.01), higher cues for action (aOR, 2.18; 95% CI, 1.68-1.82), lower perceived barriers (aOR, 0.42; 95% CI, 0.34-0.42) and higher health behavior scores (aOR, 1.30; 95% CI, 1.05-1.60) were associated with a greater willingness to participate in confirmatory colonoscopy. Participants who were older (aOR, 0.74; 95% CI, 0.55-0.98) or unmarried (aOR, 0.72; 95% CI, 0.56-0.92) were less likely to participate in verification.

CONCLUSIONS

The government could improve the screening rate by training case managers to assist in following patients until they complete colonoscopy, subsidizing sedated colonoscopies, and providing health education not only to the general public but also to physicians. Cancer 2017. © 2017 American Cancer Society.

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Physician interpretation of genomic test results and treatment selection

BACKGROUND

Genomic testing is increasingly performed in oncology, but concerns remain regarding the clinician's ability to interpret results. In the current study, the authors sought to determine the agreement between physicians and genomic annotators from the Precision Oncology Decision Support (PODS) team at The University of Texas MD Anderson Cancer Center in Houston regarding actionability and the clinical use of test results.

METHODS

On a prospective protocol, patients underwent clinical genomic testing for hotspot mutations in 46 or 50 genes. Six months after sequencing, physicians received questionnaires for patients who demonstrated a variant in an actionable gene, investigating their perceptions regarding the actionability of alterations and clinical use of these findings. Genomic annotators independently classified these variants as actionable, potentially actionable, unknown, or not actionable.

RESULTS

Physicians completed 250 of 288 questionnaires (87% response rate). Physicians considered 168 of 250 patients (67%) as having an actionable alteration; of these, 165 patients (98%) were considered to have an actionable alteration by the PODS team and 3 were of unknown significance. Physicians were aware of genotype-matched therapy available for 119 patients (71%) and 48 of these 119 patients (40%) received matched therapy. Approximately 46% of patients in whom physicians regarded alterations as not actionable (36 of 79 patients) were classified as having an actionable/potentially actionable mutation by the PODS team. However, many of these were only theoretically actionable due to limited trials and/or therapies (eg, KRAS).

CONCLUSIONS

Physicians are aware of recurrent mutations in actionable genes on "hotspot" panels. As larger genomic panels are used, there may be a growing need for annotation of actionability. Decision support to increase awareness of genomically relevant trials and novel treatment options for recurrent mutations (eg, KRAS) also are needed. Cancer 2017. © 2017 American Cancer Society.

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Reply to Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein-Barr virus in situ assays

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Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein-Barr virus in situ assays

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Slow correction of severe spastic hyperlordosis in an adult by means of magnetically expandable rods

Abstract

Background

We describe a case of severe and progressive lumbar hyperlordosis (160°) in a 28-year-old female university student with cerebral palsy. Her main complaints were abdominal wall pain and increasing inability to sit in her custom wheelchair.

Method

When deciding on our opinion about the most promising treatment strategy, we contemplated slow continued correction by means of percutaneously expandable magnetic rods (MAGEC) after the index surgery as a key component of a satisfactory correction in this severe and rigid curve. After an initial radical release and partial correction, a release and correction procedure was required for the bilateral hip flexion contracture. A final in situ posterior fusion was performed as a second spinal procedure, once the desired final correction at 66° of lumbar lordosis was achieved.

Result

Three years after the completion of surgery, the patient has a stable clinical and radiological result as well as a solid posterior fusion on CT.

Conclusion

This is the first case published in which percutaneous magnetic distraction was successfully used in an adult patient.

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The Protean Neuropsychiatric and Vestibuloauditory Manifestations of Neurosarcoidosis

Background: A rare subset of sarcoidosis, neurosarcoidosis, is reported to occur in 5-7% of sarcoid patients and can manifest in a variety of ways. The most common are facial paralysis and optic neuritis, less commonly causing cochleovestibulopathy, blindness, anosmia, and other cranial nerve (CN) palsies. The sensory deficit may be severe and psychiatric symptoms may result from the effects of the disease or steroid treatment. Although MRI-compatible cochlear implants are now available, concerns about the feasibility of recoverable hearing with cochlear implantation in these patients as well as the practical difficulty of disease monitoring due to implant artifact must be considered. Results: We present 3 recent cases from different institutions. The first is a 39-year-old man with a history of progressively worsening hearing loss, followed by visual loss, delusions, agitation, ataxia, and musical auditory hallucinations, diffuse leptomeningeal enhancement on MRI with a normal serum angiotensin-converting enzyme (ACE) level but elevated cerebrospinal fluid (CSF) ACE levels, suggesting neurosarcoidosis, was treated with corticosteroids, and underwent successful cochlear implantation. The second is a 36-year-old woman with rapid-onset horizontal diplopia, left mixed severe sensorineural hearing loss (SNHL) and tinnitus, diffuse leptomeningeal enhancement on MRI, and progressive palsy of the left CNs IV, VI, VII, IX, X and XI, with altered mental status requiring admission following high-dose intravenous corticosteroids. The third is a 15-year-old boy who presented with sudden, bilateral, profound SNHL, recurrent headaches, and left facial weakness refractory to antivirals, ultimately diagnosed with neurosarcoidosis following an aborted cochlear implantation where diffuse inflammation was found, and histopathology revealed Schaumann bodies; he was treated with methotrexate and later underwent successful cochlear implantation. Conclusions: Neurosarcoidosis is an elusive diagnosis and can cause hearing loss and psychiatric symptoms. Cochlear implantation for patients with severe hearing loss should be considered once the diagnosis is confirmed, as it is possible to achieve a successful level of hearing. Psychiatric symptoms can manifest with the onset of neurosarcoidosis, result from CN deficits, or develop as a side effect from long-term, high-dose corticosteroids, and should be monitored carefully in patients with neurosarcoidosis.
Audiol Neurotol 2017;22:205-217

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Investigation of the abnormal nasal aerodynamics and trigeminal functions among empty nose syndrome patients

Background

Abnormal nasal aerodynamics or trigeminal functions have been frequently implicated in the symptomology of empty nose syndrome (ENS), yet with limited evidence.

Methods

Individual computed tomography (CT)-based computational fluid dynamics (CFD) was applied to 27 ENS patients to simulate their nasal aerodynamics and compared with 42 healthy controls. Patients' symptoms were confirmed with Empty Nose Syndrome 6-item Questionnaire (ENS6Q), 22-item Sino-Nasal Outcome Test (SNOT-22), and Nasal Obstruction Symptom Evaluation (NOSE) scores. Nasal trigeminal sensitivity was measured with menthol lateralization detection thresholds (LDTs).

Results

ENS patients had significantly lower (∼25.7%) nasal resistance and higher (∼2.8 times) cross-sectional areas compared to healthy controls (both p < 0.001). Despite inferior turbinate reductions, CFD analysis demonstrated that ENS patients had increased airflow concentrated in the middle meatus region (66.5% ± 18.3%) compared to healthy controls (49.9% ± 15.1%, p < 0.0001). Significantly less airflow (25.8% ± 17.6%) and lower peak wall shear stress (WSS) (0.58 ± 0.24 Pa) were found in the inferior meatus (vs healthy: 36.5% ± 15.9%; 1.18 ± 0.81 Pa, both p < 0.05), with the latter significantly correlated with the symptom scores of ENS6Q (r = −0.398, p = 0.003). Item-wise, complaints of "suffocation" and "nose feels too open" were also found to be significantly correlated with peak WSS around the inferior turbinate (r = −0.295, p = 0.031; and r = −0.388, p = 0.004, respectively). These correlations were all negative, indicating that less air-mucosal stimulations resulted in worse symptom scores. ENS patients (n = 12) also had impaired menthol LDT when compared to healthy controls (p < 0.0001).

Conclusion

This is the first CFD examination of nasal aerodynamics in a large cohort of ENS patients. The results indicated that a combination of loss of neural sensitivity and poorer inferior air-mucosal stimulation may potentially lead to ENS symptomology.

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Adaptation and validation of the Turkish version of the Nasal Obstruction Symptom Evaluation scale

Background

The Nasal Obstruction Symptom Evaluation (NOSE) scale is a questionnaire used to assess the quality of life in patients with nasal obstruction. The aim of this study was to validate the Turkish translation of the NOSE questionnaire.

Methods

The NOSE questionnaire was translated into Turkish and then back to English. Fifty patients with septal deviation leading to nasal obstruction and 50 healthy subjects without any nasal complaints and pathologies were recruited into the study. The Cronbach α was used to test internal consistency. The Mann-Whitney U test was used to compare the NOSE scores of the 2 groups. Psychosomatic features (reliability, repeatability, validity, responding) were evaluated by concerning the criteria as test-retest procedure, self consistency, within-score and inter-score correlation and sensitivity of responding between the 2 groups.

Results

There was no statistically significant difference between patients and healthy subjects in terms of age, gender, and body mass index. Test-retest results among control subjects also did not demonstrate significant difference and the Cronbach α value of the NOSE scale was found to be 0.966. There was a positive correlation among every question of the NOSE scale and it was statistically significantly different from the control group. Total scores of the NOSE scale were significantly higher than the control group.

Conclusion

The Turkish version of the NOSE scale is a valid tool for assessing patients with septal deviation and measuring the subjective severity of nasal obstruction.

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The properdin pathway: an “alternative activation pathway” or a “critical amplification loop” for C3 and C5 activation?

Abstract

This review is not intended to cover in detail all aspects of the discovery and evolution of our understanding of the "alternative pathway" of complement activation, there are many excellent reviews that do this (see Fearon (CRC Crit Rev Immunol 1:1–32, 1979), Pangburn and Müller-Eberhard (Springer Semin Immunopathol 7:163–192, 1984)), but instead to give sufficient background for current concepts to be put in context. The prevailing textbook view, of components having a primary role as an alternative "pathway" for C3 activation, is challenged, with an argument developed for the primary role of the system being that of providing a surface-dependent amplification loop for both C3 and C5 activation. Whatever the mechanism by which the initial C3b molecule is generated, deposition onto a surface has the potential to target that surface for elimination. Elimination or escape from initial targeting is determined by a sophisticated and highly regulated amplification loop for C3 activation. This viewpoint of the system is then briefly developed to provide a context for therapeutic treatment of disease caused, at least in part, by dysregulated amplification of C3 activation, and to highlight some of the challenges that such therapies will face and need to address.

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Flavone protects HBE cells from DNA double-strand breaks caused by PM2.5

Abstract

Ambient air particulate matter 2.5 (PM2.5) contains many harmful components that can enter the circulatory system and produce reactive oxygen species (ROS) in body. Oxidative stress and DNA damage induced by ROS may affect any cellular macromolecule and lead to DNA double-strand breaks (DSBs). Flavonoids, widely distributed in some herbs and berries, have been proved having anti-oxidative or anti-cancer efficacy. In this study, we investigated whether Flavone, a kind of flavonoids, can protect human bronchial epithelial cells (HBE) from DSBs caused by PM2.5 and how this function is probably implemented. We found that cells exposed to PM2.5 obviously induced viability inhibition, DNA damage and part of apoptosis. However, Flavone treatment prior to PM2.5 apparently improved cell viability, and mitigated the formation of 8-hydroxy-2-deoxyguanosine, the expression of DNA damage-relative protein and cell apoptosis. Our studies demonstrated that PM2.5 induced oxidative DSBs while Flavone ameliorated the DNA damage and increased cell viability probably through influencing DNA repair mechanism of cells.

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Leptomeningeal metastasis from systemic cancer: Review and update on management

Leptomeningeal metastasis is an uncommon and typically late complication of cancer with a poor prognosis and limited treatment options. Diagnosis is often challenging, with nonspecific presenting symptoms ranging from headache and confusion to focal neurologic deficits, such as cranial nerve palsies. Standard diagnostic evaluation involves a neurologic examination, magnetic resonance imaging of the brain and spine with gadolinium, and cytologic evaluation of the cerebral spinal fluid. Therapy entails a multimodal approach focused on palliation with surgery, radiation, and/or chemotherapy, which may be administered systemically or directly into the cerebral spinal fluid. Limited trial data exist to guide treatment, and current regimens are based primarily on expert opinion. Although newer targeted and immunotherapeutic agents are under investigation and have shown promise, an improved understanding of the biology of leptomeningeal metastasis and treatment resistance as well as additional randomized controlled studies are needed to guide the optimal treatment of this devastating disease. Cancer 2017. © 2017 American Cancer Society.

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Two critical brain networks for generation and combination of remote associations

Abstract

Recent functional imaging findings in humans indicate that creativity relies on spontaneous and controlled processes, possibly supported by the default mode and the fronto-parietal control networks, respectively. Here, we examined the ability to generate and combine remote semantic associations, in relation to creative abilities, in patients with focal frontal lesions. Voxel-based lesion-deficit mapping, disconnection-deficit mapping and network-based lesion-deficit approaches revealed critical prefrontal nodes and connections for distinct mechanisms related to creative cognition. Damage to the right medial prefrontal region, or its potential disrupting effect on the default mode network, affected the ability to generate remote ideas, likely by altering the organization of semantic associations. Damage to the left rostrolateral prefrontal region and its connections, or its potential disrupting effect on the left fronto-parietal control network, spared the ability to generate remote ideas but impaired the ability to appropriately combine remote ideas. Hence, the current findings suggest that damage to specific nodes within the default mode and fronto-parietal control networks led to a critical loss of verbal creative abilities by altering distinct cognitive mechanisms.

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Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family

Abstract

The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons for the highly variable clinical penetrance are not known. Exome sequencing identified a heterozygous start loss mutation in SSBP1, encoding the single stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi-generational family transmitting m.1555A>G, associated with mtDNA depletion and multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific manner. This family demonstrates the importance of rare trans-acting genetic nuclear modifiers in the clinical expression of mtDNA disease.

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How to solve the problem of hypersensitivity to asparaginase?

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AML presenting with a preleukemic episode and acquired heterochromia in a child with macrosomia

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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.

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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.

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High-resolution spatiotemporal mapping of PM2.5 concentrations at Mainland China using a combined BME-GWR technique

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Lu Xiao, Yichao Lang, George Christakos
With rapid economic development, industrialization and urbanization, the ambient air PM2.5 has become a major pollutant linked to respiratory, heart and lung diseases. In China, PM2.5 pollution constitutes an extreme environmental and social problem of widespread public concern. In this work we estimate ground-level PM2.5 from satellite-derived aerosol optical depth (AOD), topography data, meteorological data, and pollutant emission using an integrative technique. In particular, Geographically Weighted Regression (GWR) analysis was combined with Bayesian Maximum Entropy (BME) theory to assess the spatiotemporal characteristics of PM2.5 exposure in a large region of China and generate informative PM2.5 space-time predictions (estimates). It was found that, due to its integrative character, the combined BME-GWR method offers certain improvements in the space-time prediction of PM2.5 concentrations over China compared to previous techniques. The combined BME-GWR technique generated realistic maps of space-time PM2.5 distribution, and its performance was superior to that of seven previous studies of satellite-derived PM2.5 concentrations in China in terms of prediction accuracy. The purely spatial GWR model can only be used at a fixed time, whereas the integrative BME-GWR approach accounts for cross space-time dependencies and can predict PM2.5 concentrations in the composite space-time domain. The 10-fold results of BME-GWR modeling (R² = 0.883, RMSE = 11.39 μg/m3) demonstrated a high level of space-time PM2.5 prediction (estimation) accuracy over China, revealing a definite trend of severe PM2.5 levels from the northern coast toward inland China (Nov 2015–Feb 2016). Future work should focus on the addition of higher resolution AOD data, developing better satellite-based prediction models, and related air pollutants for space-time PM2.5 prediction purposes.



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A new modeling approach for assessing the contribution of industrial and traffic emissions to ambient NOx concentrations

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Shimon Chen, Yuval, David M. Broday
The Optimized Dispersion Model (ODM) is uniquely capable of incorporating emission estimates, ambient air quality monitoring data and meteorology to provide reliable high-resolution (in both time and space) air quality estimates using non-linear regression. However, it was so far not capable of describing the effects of emissions from elevated sources. We formulated an additional term to extend the ODM such that these sources can be accounted for, and implemented it in modeling the fine spatiotemporal patterns of ambient NOx concentrations over the coastal plain of Israel. The diurnal and seasonal variation in the contribution of industry to the ambient NOx is presented, as well as its spatial features. Although industrial stacks are responsible for 88% of the NOx emissions in the study area, their contribution to ambient NOx levels is generally about 2% with a maximal upper bound of 27%. Meteorology has a major role in this source allocation, with the highest impact of industry in the summer months, when the wind is blowing inland past the coastal stacks and vertical mixing is substantial. The new Optimized Dispersion Model (ODM) out-performs both Inverse-Distance-Weighing (IDW) interpolation and a previous ODM version in predicting ambient NOx concentrations. The performance of the new model is thoroughly assessed.

Graphical abstract

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Seasonal variability of carbon in humic-like matter of ambient size-segregated water soluble organic aerosols from urban background environment

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Sanja Frka, Irena Grgić, Janja Turšič, Maria I. Gini, Konstantinos Eleftheriadis
Long-term measurements of carbon in HUmic-LIke Substances (HULIS-C) of ambient size-segregated water soluble organic aerosols were performed using a ten-stage low-pressure Berner impactor from December 2014 to November 2015 at an urban background environment in Ljubljana, Slovenia. The mass size distribution patterns of measured species (PM - particulate matter, WSOC - water-soluble organic carbon and HULIS-C) for all seasons were generally tri-modal (primarily accumulation mode) but with significant seasonal variability. HULIS-C was found to have similar distributions as WSOC, with nearly the same mass median aerodynamic diameters (MMADs), except for winter when the HULIS-C size distribution was bimodal. In autumn and winter, the dominant accumulation mode with MMAD at ca. 0.65 μm contributed 83 and 97% to the total HULIS-C concentration, respectively. HULIS-C accounted for a large fraction of WSOC, averaging more than 50% in autumn and 40% in winter. Alternatively, during warmer periods the contributions of ultrafine (27% in summer) and coarse mode (27% in spring) were also substantial. Based on mass size distribution characteristics, HULIS-C was found to be of various sources. In colder seasons, wood burning was confirmed as the most important HULIS source; secondary formation in atmospheric liquid water also contributed significantly, as revealed by the MMADs of the accumulation mode shifting to larger sizes. The distinct difference between the spring and summer ratios of HULIS-C/WSOC in fine particles (ca. 50% in spring, but only 10% in summer) indicated different sources and chemical composition of WSOC in summer (e.g., SOA formation from biogenic volatile organic compounds (BVOCs) via photochemistry). The enlarged amount of HULIS-C in the ultrafine mode in summer suggests that the important contribution was most likely from new particle formation during higher emissions of BVOC due to the vicinity of a mixed deciduous forest; the higher contribution of HULIS-C in the coarse mode demonstrated that beside soil erosion other sources, such as pollen and plant fragments, could also be responsible.

Graphical abstract

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Subsurface watering resulted in reduced soil N2O and CO2 emissions and their global warming potentials than surface watering

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Qi Wei, Junzeng Xu, Shihong Yang, Linxian Liao, Guangqiu Jin, Yawei Li, Fazli Hameed
Water management is an important practice with significant effect on greenhouse gases (GHG) emission from soils. Nitrous oxide (N2O) and carbon dioxide (CO2) emissions and their global warming potentials (GWPs) from subsurface watering soil (SUW) were investigated, with surface watering (SW) as a control. Results indicated that the N2O and CO2 emissions from SUW soils were somewhat different to those from SW soil, with the peak N2O and CO2 fluxes from SUW soil reduced by 28.9% and 19.4%, and appeared 72 h and 168 h later compared with SW. The fluxes of N2O and CO2 from SUW soils were lower than those from SW soil in both pulse and post-pulse periods, and the reduction was significantly (p<0.05) in pulse period. Compare to SW, the cumulative N2O and CO2 emissions and its integrative GWPs from SUW soil decreased by 21.0% (p<0.05), 15.9% and 18.0%, respectively. The contributions of N2O to GWPs were lower than those of CO2 during most of time, except in pulse emission periods, and the proportion of N2O from SUW soil was 1.4% (p>0.1) lower that from SW soil. Moreover, N2O and CO2 fluxes from both watering treatments increased exponentially with increase of soil water-filled pore space (WFPS) and temperature. Our results suggest that watering soil from subsurface could significantly reduce the integrative greenhouse effect caused by N2O and CO2 and is a promising strategy for soil greenhouse gases (GHGs) mitigation. And the pulse period, contributed most to the reduction in emissions of N2O and CO2 from soils between SW and SUW, should be a key period for mitigating GHGs emissions. Response of N2O and CO2 emissions to soil WFPS and temperature illustrated that moisture was the dominant parameters that triggering GHG pulse emissions (especially for N2O), and temperature had a greater effect on the soil microorganism activity than moisture in drier soil. Avoiding moisture and temperature are appropriate for GHG emission at the same time is essential for GHGs mitigation, because peak N2O and CO2 emission were observed only when moisture and temperature are both appropriate.



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Impacts of climate and synoptic fluctuations on dust storm activity over the Middle East

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Soodabeh Namdari, Neamat Karimi, Armin Sorooshian, GholamHasan Mohammadi, Saviz Sehatkashani
Dust events in the Middle East are becoming more frequent and intense in recent years with impacts on air quality, climate, and public health. In this study, the relationship between dust, as determined from Aerosol Optical Depth (AOD) and meteorological parameters (precipitation, temperature, pressure and wind field) are examined using monthly data from 2000 to 2015 for desert areas in two areas, Iraq-Syria and Saudi Arabia. Bivariate regression analysis between monthly temperature data and AOD reveals a high correlation for Saudi Arabia (R = 0.72) and Iraq-Syria (R = 0.64). Although AOD and precipitation are correlated in February, March and April, the relationship is more pronounced on annual timescales. The opposite is true for the relationship between temperature and AOD, which is evident more clearly on monthly time scales, with the highest temperatures and AOD typically between August and September. Precipitation data suggest that long-term reductions in rainfall promoted lower soil moisture and vegetative cover, leading to more intense dust emissions. Superimposed on the latter effect are more short term variations in temperature exacerbating the influence on the dust storm genesis in hot periods such as the late warm season of the year. Case study analysis of March 2012 and March 2014 shows the impact of synoptic systems on dust emissions and transport in the study region. Dust storm activity was more intense in March 2012 as compared to March 2014 due to enhanced atmospheric turbulence intensifying surface winds.



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Visibility in the Netherlands during New Year's fireworks: The role of soot and salty aerosol products

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Harry ten Brink, Bas Henzing, René Otjes, Ernie Weijers
The visibility on New Year's nights in the Netherlands is low during stagnant weather. This is due to the scattering and absorption of light by the aerosol-smoke from the fireworks. We made an assessment of the responsible aerosol-species. The investigation took place during the New Year's night of 2009. Measurements were made at a regional site in the centre of the country away from specific local sources. An Integrating Nephelometer measured the light-scattering by the inherent compounds after removal of water from the aerosol by drying the air. The actual light-scattering was determined in an open-air scatterometer; it was a factor of five higher than the "dry" value. The difference in actual and "dry" light-scattering can only be explained by water–uptake of the salty hygroscopic components of the aerosol. This hypothesis is substantiated by measurements of the composition of the aerosol. The size-dependent concentrations of the salty ionic species were determined on-line with a MARGA-"sizer". These components were for a large part in particles in the size range that most effectively scatter light. The "dry" light-scattering was exerted by the inorganic salt components and the sooty carbonaceous material alike. However, the salty products from the fireworks are hygroscopic and take up water at the high relative humidities occurring that night. This explains the fivefold larger light-scattering by the wet ambient aerosol as compared to that by the dry aerosol in the integrating nephelometer. The visibility, which is the inverse of the open-air scattering, is thus indirectly governed by the salty products of the fireworks due to their uptake of water. Under stagnant weather conditions during New Year's nights in the Netherlands both the aerosol concentrations and the relative humidity are high; this implies that the ionic species govern the low visibilities in general, be it via their uptake of water.



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Early Placement of Ventilation Tubes in Infants with Cleft Lip and Palate: A Systematic Review.

Early Placement of Ventilation Tubes in Infants with Cleft Lip and Palate: A Systematic Review.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817742840

Authors: Felton M, Lee JW, Balumuka DD, Arneja JS, Chadha NK

Abstract
Objective Studies have shown that the majority of cleft lip and palate (CLP) children have middle ear fluid present at the time of lip repair (3-4 months). Despite hearing loss, the majority of children do not undergo ventilation tube treatment if required until the time of palate repair (9-12 months). We aimed to examine the effectiveness and potential complications of early ventilation tube placement prior to palatoplasty in infants with cleft lip and palate. Data Sources Medline (1946-2015), Embase (1980-2015), and EBM Reviews (Cochrane Central Register of Controlled). Review Methods Data sources were searched for publications that described the results of early ventilation tube placement in children with CLP prior to cleft palate repair. Two independent reviewers appraised the selected studies. Results Of 226 studies identified, 6 studies met the inclusion criteria. Early ventilation tube insertion in CLP gave similar speech and audiology outcomes to non-CLP children undergoing ventilation tube insertion and better outcomes than those children with CLP having later ventilation tube insertion at or after the time of palate closure. The main reported side effect was otorrhea, being higher for children with CLP having early ventilation tube insertion (67% vs 33%), with a reduction in otorrhea with increasing age. Larger studies with longer-term outcome reporting are required to fully address the study objectives. Conclusion Published data are limited but appear to support early insertion of ventilation tubes in children with CLP to restore middle ear function and maximize audiologic and speech outcomes.

PMID: 29161200 [PubMed - as supplied by publisher]

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Intranasal Budesonide and Quality of Life in Pediatric Sleep-Disordered Breathing: A Randomized Controlled Trial.

Intranasal Budesonide and Quality of Life in Pediatric Sleep-Disordered Breathing: A Randomized Controlled Trial.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817742597

Authors: Gudnadottir G, Ellegård E, Hellgren J

Abstract
Objective To study the efficacy of budesonide nasal spray on the health-related quality of life and symptoms among children with sleep-disordered breathing. Study Design Randomized, parallel, double-blind, placebo-controlled trial. Setting Tertiary referral center. Subjects and Methods Sixty children (ages, 4-10 years) who were referred because of snoring and/or apneas for >3 months were included between January 2015 and June 2016 and randomized in a double-blind design to treatment with 64 μg/mL of budesonide nasal spray (n = 30) or placebo nasal spray (n = 30) twice daily for 6 weeks. The primary outcome measurement was the change in the mean OSA-18 total score from baseline. Other variables examined were individual OSA-18 domains, a visual analog scale for quality of life, symptoms (snoring, apneas, and nasal obstruction), and adenoid and tonsil size. The trial was investigator initiated and not sponsored by the pharmaceutical industry. Results Fifty-five children completed the trial. An intention-to-treat analysis revealed a significantly greater improvement in the mean OSA-18 total score after treatment with budesonide than placebo (19.5 vs 7.5, P = .0014). Intranasal budesonide also improved 2 OSA-18 domains (sleep disturbance, caregivers' concerns), the visual analog scale score for quality of life, as well as snoring, apneas, and nasal obstruction. No serious adverse events were reported that could be linked to the treatment. Conclusion Among children with sleep-disordered breathing, 6 weeks' treatment with intranasal budesonide significantly improved quality of life and symptoms as compared with placebo nasal spray.

PMID: 29161199 [PubMed - as supplied by publisher]

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Intraoperative Ultrasound in Oral Tongue Cancer Resection: Feasibility Study and Early Outcomes.

Intraoperative Ultrasound in Oral Tongue Cancer Resection: Feasibility Study and Early Outcomes.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817742856

Authors: Tarabichi O, Kanumuri V, Juliano AF, Faquin WC, Cunnane ME, Varvares MA

Abstract
The current standard of care in oral tongue cancer surgery is complete resection with a target of 5-mm microscopic clearance at all margins on final pathologic review. While current methods of resection are often successful at determining the mucosal margins of the lesion, they may be limited when attempting to achieve an adequate deep margin. A number of previous studies suggested that ultrasound is superior to manual palpation and other imaging modalities (computed tomography, magnetic resonance imaging) at demarcating the margins of tongue lesions. Recent clinical reports of the intraoperative use of this modality have used an invasive method to mark the proposed deep resection margin. In this communication, we report our initial experience with the use of intraoperative ultrasound as an adjunct to oral tongue cancer surgery without the use of an invasive method to mark the deep resection margin.

PMID: 29161194 [PubMed - as supplied by publisher]

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Patient Preferences in Subglottic Stenosis Treatment: A Discrete Choice Experiment.

Patient Preferences in Subglottic Stenosis Treatment: A Discrete Choice Experiment.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817742851

Authors: Naunheim MR, Naunheim ML, Rathi VK, Franco RA, Shrime MG, Song PC

Abstract
Objectives Subglottic stenosis can be addressed with several different surgical techniques, but patient preferences for these treatment modalities are poorly understood. Economic methods are increasingly being used to understand how patients make decisions. The objective of this pilot study was to assess preferences in subglottic stenosis treatment using patient-centric stated preference techniques. Study Design Discrete choice experiment (DCE). Setting Academic research facility. Subjects and Methods A computer-based DCE was administered in a monitored setting to volunteers from the general population. Signs and symptoms of subglottic stenosis were described, and participants were asked to imagine they had subglottic stenosis. Hypothetical treatments were offered, with 5 systematically varied attributes: need for external incision, length of hospital stay, postoperative voice quality, likelihood of repeat procedures, and risk of complication. A conditional logistic model was used to assess the relative attribute importance. Results In total, 162 participants were included. Attributes with the greatest impact on decision making included potential need for repeat procedures (importance 30.2%; P < .001), amount of operative risk (importance 28.1%; P < .001), and postoperative voice quality (importance 27.7%; P < .001), whereas presence of incision (importance 5.0%; P = .001) was less important, and hospital stay was not (importance 9.0%; P = .089). Based on aggregate responses for these attributes, the model demonstrated that most participants (80.4%) would prefer endoscopic surgery for subglottic stenosis as opposed to open tracheal resection (19.6%). Conclusion In this pilot population, most participants preferred voice-sparing, low-risk procedures as treatment for subglottic stenosis, consistent with an endoscopic approach, even if multiple procedures were required.

PMID: 29161192 [PubMed - as supplied by publisher]

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Development of an Attachable Endoscopic Nerve Stimulator for Intraoperative Neuromonitoring during Endoscopic or Robotic Thyroidectomy.

Development of an Attachable Endoscopic Nerve Stimulator for Intraoperative Neuromonitoring during Endoscopic or Robotic Thyroidectomy.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817742841

Authors: Sung ES, Lee JC, Kim SH, Shin SC, Jung DW, Lee BJ

Abstract
We developed a simple attachable endoscopic nerve stimulator that can be connected to monopolar cauterization surgical instruments. This study on porcine models aimed to investigate the feasibility and efficacy of an attachable endoscopic nerve stimulator for intraoperative neuromonitoring (IONM) before application in humans. We evaluated the electromyography (EMG) amplitudes of 8 recurrent laryngeal nerves in 4 pigs with a conventional nerve probe and the attachable endoscopic nerve stimulator. The attachable endoscopic nerve stimulator was feasible and safe in all cases. There was no significant difference in the EMG amplitude of the recurrent laryngeal nerve among instruments ( P = .429). The application of stimulating dissection with an attachable endoscopic nerve stimulator during endoscopic or robotic thyroidectomy with IONM is simple, convenient, and effective. It provides surgeons with real-time feedback of the EMG response during intermittent IONM. We believe that this novel device could be an essential guide and functional navigator for most surgeons, especially for less experienced ones.

PMID: 29161172 [PubMed - as supplied by publisher]

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Incidental Findings on FDG PET/CT in Head and Neck Cancer.

Incidental Findings on FDG PET/CT in Head and Neck Cancer.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817742579

Authors: Britt CJ, Maas AM, Kennedy TA, Hartig GK

Abstract
Objective 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG PET/CT) imaging is common in head and neck cancer and often identifies incidental findings that necessitate additional patient evaluations. Our goal was to assess the frequency and nature of these incidental imaging findings on FDG-PET/CT. Study Design Retrospective cohort study. Setting Tertiary medical center. Subjects and Methods All patients with head and neck cancer who had undergone FDG-PET/CT imaging between January 2014 and June 2015 at our institution were evaluated for incidental findings. Results A total of 293 patients met criteria; more than one-third (n = 103) had at least 1 finding unrelated to their head and neck cancer, for a total of 134 incidental findings. Incidental findings within the head and neck (33.5% of all) excluding the thyroid were most common: 35% incidental findings were concerning for malignancy; of these, 25.5% were malignant with further workup. Recommendations were given by the head and neck radiologist on 72 (53.7%) findings: 74.5% of potentially malignant findings and 42.5% of benign findings had recommendations for follow-up. Significantly more patients with findings described as malignant were given recommendations for follow-up ( P = .0004). Conclusion Incidental findings on FDG-PET/CT are present in more than one-third of patients with head and neck cancer. More than one-third of incidental findings were concerning for malignancy. This study illustrates how the incidental findings discovered on FDG PET/CT frequently necessitate additional evaluations unrelated to the index head and neck cancer. The impact of these additional assessments on the cost and quality of health care warrants future evaluation.

PMID: 29160180 [PubMed - as supplied by publisher]

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Ideal Particle Sizes for Inhaled Steroids Targeting Vocal Granulomas: Preliminary Study Using Computational Fluid Dynamics.

Ideal Particle Sizes for Inhaled Steroids Targeting Vocal Granulomas: Preliminary Study Using Computational Fluid Dynamics.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817742126

Authors: Perkins EL, Basu S, Garcia GJM, Buckmire RA, Shah RN, Kimbell JS

Abstract
Objectives Vocal fold granulomas are benign lesions of the larynx commonly caused by gastroesophageal reflux, intubation, and phonotrauma. Current medical therapy includes inhaled corticosteroids to target inflammation that leads to granuloma formation. Particle sizes of commonly prescribed inhalers range over 1 to 4 µm. The study objective was to use computational fluid dynamics to investigate deposition patterns over a range of particle sizes of inhaled corticosteroids targeting the larynx and vocal fold granulomas. Study Design Retrospective, case-specific computational study. Setting Tertiary academic center. Subjects/Methods A 3-dimensional anatomically realistic computational model of a normal adult airway from mouth to trachea was constructed from 3 computed tomography scans. Virtual granulomas of varying sizes and positions along the vocal fold were incorporated into the base model. Assuming steady-state, inspiratory, turbulent airflow at 30 L/min, computational fluid dynamics was used to simulate respiratory transport and deposition of inhaled corticosteroid particles ranging over 1 to 20 µm. Results Laryngeal deposition in the base model peaked for particle sizes 8 to 10 µm (2.8%-3.5%). Ideal sizes ranged over 6 to 10, 7 to 13, and 7 to 14 µm for small, medium, and large granuloma sizes, respectively. Glottic deposition was maximal at 10.8% for 9-µm-sized particles for the large posterior granuloma, 3 times the normal model (3.5%). Conclusion As the virtual granuloma size increased and the location became more posterior, glottic deposition and ideal particle size generally increased. This preliminary study suggests that inhalers with larger particle sizes, such as fluticasone propionate dry-powder inhaler, may improve laryngeal drug deposition. Most commercially available inhalers have smaller particles than suggested here.

PMID: 29160160 [PubMed - as supplied by publisher]

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Prestin as an Otologic Biomarker of Cisplatin Ototoxicity in a Guinea Pig Model.

Prestin as an Otologic Biomarker of Cisplatin Ototoxicity in a Guinea Pig Model.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817742093

Authors: Naples J, Cox R, Bonaiuto G, Parham AK

Abstract
Objective To evaluate (1) whether changes in serum prestin aid in early detection of cisplatin ototoxicity, (2) the role of diltiazem as an otoprotectant, and (3) whether prestin levels are sensitive to effects of diltiazem. Study Design Experimental animal study. Setting Translational research laboratory. Subjects Twenty female guinea pigs. Methods Two groups of 10 guinea pigs were used. The relationship between serum prestin levels and auditory brainstem response (ABR) thresholds was compared between the groups. All animals had baseline blood draws and ABR thresholds recorded prior to cisplatin administration. Intraperitoneal cisplatin bolus (8 mg/kg) was administered followed by 5 consecutive days of intratympanic (IT) diltiazem (2 mg/kg) or sham IT-saline injection. Serum prestin levels and ABR thresholds were measured at days 1, 2, 3, 7, and 14 postcisplatin. Results In sham, IT-saline-treated animals, mean prestin levels were elevated above baseline on days 1 to 7. The prestin levels were significantly elevated from baseline on day 1 ( P < .001), while significant ABR threshold elevations did not occur until day 2 ( P = .028) for click-evoked ABRs and day 3 ( P = .041) for tones. In diltiazem-treated animals, prestin levels were not elevated above baseline but ABR thresholds were elevated on days 1 to 3. However, the thresholds returned toward baseline on days 7 and 14. Conclusion Changes in serum prestin levels were detectable prior to shifts in ABR thresholds in a guinea pig cisplatin ototoxicity model. These changes did not occur in diltiazem-treated animals. Prestin may serve as a biomarker of cochlear injury that is sensitive to therapeutic interventions in cisplatin ototoxicity.

PMID: 29160156 [PubMed - as supplied by publisher]

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Staging Neck Dissection and Transoral Robotic Surgery Treatment Algorithm in Palatine Tonsil Cancer.

Staging Neck Dissection and Transoral Robotic Surgery Treatment Algorithm in Palatine Tonsil Cancer.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817742615

Authors: Spellman J, Sload R, Kim P, Martin P, Calzada G

Abstract
Objective This study introduces a treatment algorithm based on staging neck dissection to identify patients with palatine tonsil squamous cell carcinoma who can be effectively treated with single-modality transoral robotic surgery while maintaining quality of life. Study Design Retrospective case series. Setting Kaiser Permanente Southern California Medical Group from 2012 to 2017. Subjects and Methods Patients with early-stage (T1/2) palatine tonsil squamous cell carcinoma with clinically and radiographically N0 necks underwent staging neck dissection. Those with pN2/3 disease or extracapsular extension on final pathology were triaged to definitive chemoradiation treatment. Patients with confirmed pN0/1 necks without extracapsular extension were treated definitively with transoral robotic surgery. Results Nineteen patients with cN0 disease underwent selective neck dissection. All were p16 positive. Of these, 14 had pathologically confirmed N0/1 necks without extracapsular extension and were treated with primary surgical resection via transoral robotic surgery. Clear margins were obtained on all patients. There were no significant intra- or postoperative complications. No patients required gastrostomy tube or tracheostomy placement. Mean and median follow-up was 28 months with no recurrences to date. Conclusion Up-front staging neck dissection accurately triages low-risk patients, determining candidates for single-modality definitive treatment with transoral robotic surgery. This approach provides excellent survival outcomes and minimal morbidity and maintains quality of life among appropriately selected patients with palatine tonsil cancer.

PMID: 29160154 [PubMed - as supplied by publisher]

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Voice and Swallowing Dysfunction in Neurofibromatosis 2.

Voice and Swallowing Dysfunction in Neurofibromatosis 2.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817741839

Authors: Best SR, Ahn J, Langmead S, Dhillon V, Hillel AT, Akst LM, Blakeley JO

Abstract
Objective Neurofibromatosis 2 (NF2) is a neuro-oncologic condition that presents with bilateral vestibular schwannomas of the cerebellopontine angle (CPA). Voice and swallowing impairment can occur from direct involvement or compression of the vagus nerve or as the result of surgical excision of CPA tumors. The objectives in this study are to (1) assess the prevalence of voice and swallowing impairments and (2) analyze the effects of vagal dysfunction in patients with NF2. Study Design Cross-sectional. Setting Academic tertiary care center. Subjects and Methods Patients at a neurofibromatosis center were mailed Voice Handicap Index and Sydney Swallow Questionnaire surveys. Stroboscopic, voice, and swallowing evaluations were performed for patients who elected to participate in screening exams. Results There were high rates of self-assessed and objective voice and swallowing handicaps in this population. Fourteen of 40 (35%) patients had a self-assessed voice handicap, and 20 of 40 (50%) patients had a self-assessed swallow handicap. Vocal fold motion impairment (VFMI) was observed in 22 of 31 (71%) patients examined, with 27 of 62 (44%) possible vocal cords affected. Velopharyngeal insufficiency (45%) and piriform sinus pooling or residue (39%) were seen in a significant percentage of patients. There was a significant relationship between vocal cord motion impairment and CPA surgical intervention ipsilateral to the impairment ( P = .002). The presence of VFMI was strongly associated with voice ( P = .002) and swallowing ( P = .01) impact on quality of life. Conclusion Speech and swallowing impairments are highly prevalent in patients with NF2, cause significant impact on quality of life, and are most commonly related to surgical interventions in the CPA region.

PMID: 29160153 [PubMed - as supplied by publisher]

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Electrocardiogram Screening in Children with Congenital Sensorineural Hearing Loss: Prevalence and Follow-up of Abnormalities.

Electrocardiogram Screening in Children with Congenital Sensorineural Hearing Loss: Prevalence and Follow-up of Abnormalities.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817738975

Authors: Farzal Z, Walsh J, Ahmad FI, Roberts J, Ferns SJ, Zdanski ACJ

Abstract
Objective The purpose is to determine the prevalence of electrocardiogram (ECG) abnormalities, including borderline and prolonged QT, among screened children with sensorineural hearing loss (SNHL) and to analyze their subsequent medical workup. Study Design Institutional Review Board-approved case series with chart review. Setting Tertiary academic center. Subjects and Methods Cases from 1996 to 2014 involving pediatric patients (N = 1994) with SNHL were analyzed. Abnormal ECGs were categorized as borderline/prolonged QT or other. A board-certified pediatric cardiologist retrospectively determined the clinical significance of ECG changes. For follow-up analysis, children with heart disease, known syndromes, or inaccessible records were excluded. Results Among 772 children who had ECGs, 215 (27.8%) had abnormal results: 35 (4.5%) with QT abnormalities and 180 (23.3%) with other abnormalities. For children with QT abnormalities meeting inclusion criteria (n = 30), follow-up measures included cardiology referral (46.6%), repeat ECG by ear, nose, and throat (ENT) specialist (20%), clearance by ENT specialist with clinical correlation and/or comparison with old ECGs (20%), and pediatrician follow-up (6.7%). Documentation of further workup by ENT or referral was absent for 6.7%. For children with other ECG changes meeting inclusion criteria (n = 136), abnormalities were documented for 57 (41.9%); normal QT without other abnormality was documented for 18 (13.2%). The most common follow-up referrals were to pediatricians (16.9%) and cardiologists (10.3%). Among patients with clinically significant non-QT abnormalities mandating further evaluation (n = 122), 38 (31.1%) had documented follow-up in medical records. Conclusion There is a high prevalence of ECG abnormalities among children with congenital SNHL. If findings are confirmed by future studies, screening should be considered for congenital unilateral or bilateral SNHL, regardless of severity. We describe a standardized protocol for ECG screening/follow-up.

PMID: 29160150 [PubMed - as supplied by publisher]

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Structural Fat Grafting to Improve Outcomes of Vocal Folds' Fat Augmentation: Long-term Results.

Structural Fat Grafting to Improve Outcomes of Vocal Folds' Fat Augmentation: Long-term Results.

Otolaryngol Head Neck Surg. 2017 Nov 01;:194599817739256

Authors: Cantarella G, Mazzola RF, Gaffuri M, Iofrida E, Biondetti P, Forzenigo LV, Pignataro L, Torretta S

Abstract
Objective Evaluating the long-term outcomes of vocal fold structural fat grafting. Study Design Case series with chart review. Setting University hospital. Subjects and Methods Seventy-nine dysphonic patients (16-82 years; 55 with unilateral laryngeal paralysis and 24 with vocal fold scarring) underwent vocal fold fat injection. Fat was harvested by low-pressure liposuction and then processed by centrifugation. Refined fat aliquots were placed in the vocal fold and paraglottic space in multiple tunnels to enhance graft neovascularization. All patients were followed for 12 months, 15 for 3 years, and 5 for 10 years with videolaryngostroboscopy, maximal phonation time (MPT) measurement, Voice Handicap Index (VHI) questionnaire, and GRBAS (grade, roughness, breathiness, asthenia, strain) perceptual evaluation. Laryngeal computed tomography (CT) and/or magnetic resonance imaging (MRI) studies were performed in 16 patients 3 to 28 months postoperatively; MRI was repeated in 5 cases 12 to 18 months after the first radiological study. Results The voice quality of all patients improved after surgery, and long-term stability was confirmed by MPT, GRBAS, and VHI ( P ranging between .004 and <.001). The results achieved 1 year postoperatively remained stable at 3 and 10 years. Videolaryn-gostroboscopy showed improved glottic closure in all patients despite a limited amount of fat resorption. CT and MRI demonstrated survival of the fat grafts in all of the 16 examined cases. Serial MRI scans showed no change in graft size over time. Conclusions The reported clinical and radiological data demonstrate that fat is an effective filler for permanent vocal fold augmentation if the refined micro-aliquots are placed in multiple tunnels.

PMID: 29160142 [PubMed - as supplied by publisher]

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Developing a bacteriophage cocktail for biocontrol of potato bacterial wilt

Abstract

Bacterial wilt is a devastating disease of potato and can cause an 80% production loss. To control wilt using bacteriophage therapy, we isolated and characterized twelve lytic bacteriophages from different water sources in Kenya and China. Based on the lytic curves of the phages with the pathogen Ralstonia solanacearum, one optimal bacteriophage cocktail, P1, containing six phage isolations was formulated and used for studying wilt prevention and treatment efficiency in potato plants growing in pots. The preliminary tests showed that the phage cocktail was very effective in preventing potato bacterial wilt by injection of the phages into the plants or decontamination of sterilized soil spiked with R. solanacearum. Eighty percent of potato plants could be protected from the bacterial wilt (caused by R. solanacearum reference strain GIM1.74 and field isolates), and the P1 cocktail could kill 98% of live bacteria spiked in the sterilized soil at one week after spraying. However, the treatment efficiencies of P1 depended on the timing of application of the phages, the susceptibility of the plants to the bacterial wilt, as well as the virulence of the bacteria infected, suggesting that it is important to apply the phage therapy as soon as possible once there are early signs of the bacterial wilt. These results provide the basis for the development of bacteriophagebased biocontrol of potato bacterial wilt as an alternative to the use of antibiotics.

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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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Double-blind placebo-controlled trial of the effect of omalizumab on basophils in chronic urticaria patients

Abstract

Background

Omalizumab has been shown to be effective in treating chronic spontaneous urticaria (CSU). The reduction of FcεRI receptor density on the surface of basophils and mast cells is thought to play a major role in its effectiveness. We conducted a double-blind, randomized, placebo-controlled trial to investigate the mode of action of omalizumab in patients with antihistamine-resistant CSU.

Methods

Thirty patients were randomized in a 2:1 ratio to receive either 300 mg omalizumab or placebo. Four monthly applications of omalizumab/placebo were followed up with a visit 2 months after the last injection. The primary endpoint was the FcεRI receptor density change on basophils.

Results

Omalizumab led to a significant reduction of FcεRI receptor density on

basophils as soon as 1 week after the first injection: baseline omalizumab vs. placebo group, 80.31 ± 47.18x10³ vs. 78.29 ± 45.09x10³ receptors/basophil ± SD; 1 week, 72.89 ± 47.79x10³ vs. 27.83 ± 20.87x10³, p=0.001. This effect continued during the treatment phase and persisted for 2 months after the last injection: 93.81 ± 56.50x10³ vs. 21.09 ± 15.23x10³, p=0.002. Values for basophil "releasability" and the basophil activation test (CU-BAT) of patient serum using donor basophils were unchanged despite treatment: CU-BAT, CD63 10.75% (7.35) in the placebo group vs. 8.35% (15.20) in the omalizumab group, p=0.778.

Conclusion

We demonstrated a rapid reduction of FcεRI receptor density on basophils following treatment with omalizumab. Because CU-BAT using well-characterized, omalizumab-naïve donor basophils did not change during the treatment phase, autoreactive serum factors seem to remain unaltered. This points towards a cellular effect of omalizumab on basophils. To predict the omalizumab response time and to monitor disease, FcεRI density and CU-BAT might be promising cellular-based assays.

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ARHGEF19 interacts with BRAF to activate MAPK signaling during the tumorigenesis of non-small cell lung cancer

Abstract

Rho guanine nucleotide exchange factors (RhoGEFs) are proteins that activate Rho GTPases in response to extracellular stimuli and regulate various biologic processes. ARHGEF19, one of RhoGEFs, was reported to activate RhoA in the Wnt-PCP pathway controlling convergent extension in Xenopus gastrulation. The goal of this study was to identify the role and molecular mechanisms of ARHGEF19 in the tumorigenesis of non-small cell lung cancer (NSCLC). ARHGEF19 expression was significantly elevated in NSCLC tissues, and ARHGEF19 levels were significantly associated with lymph node status, distant metastasis and TNM stage; Patients with high ARHGEF19 levels had poor overall survival (OS) and progression-free survival (PFS). Our investigations revealed that ARHGEF19 overexpression promoted the cell proliferation, invasion and metastasis of lung cancer cells, whereas knockdown of this gene inhibited these processes. Mechanistically, ARHGEF19 activated the mitogen-activated protein kinase (MAPK) pathway in a RhoA-independent manner: ARHGEF19 interacted with BRAF and facilitated the phosphorylation of its downstream kinase MEK1/2; both the Dbl homology (DH) and Pleckstrin homology (PH) domains of ARHGEF19 were indispensable for the phosphorylation of MEK1/2. Furthermore, downregulation of miR-29b was likely responsible for the increased expression of ARHGEF19 in lung cancer tissues and, consequently, the abnormal activation of MAPK signaling. These findings suggest that ARHGEF19 upregulation, due to the low expression of miR-29 in NSCLC tissues, may play a crucial role in NSCLC tumorigenesis by activating MAPK signaling. ARHGEF19 could serve as a negative prognostic marker as well as a therapeutic target for NSCLC patients. This article is protected by copyright. All rights reserved.

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ERRATUM

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Issue Information

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