Medicine by Alexandros G. Sfakianakis: 07/25/17

Tuesday, July 25, 2017

Analyses of PDE-regulated phosphoproteomes reveal unique and specific cAMP-signaling modules in T cells [Pharmacology]

Specific functions for different cyclic nucleotide phosphodiesterases (PDEs) have not yet been identified in most cell types. Conventional approaches to study PDE function typically rely on measurements of global cAMP, general increases in cAMP-dependent protein kinase (PKA), or the activity of exchange protein activated by cAMP (EPAC). Although newer approaches...

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Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells [Physiology]

Caffeine, generally known as a stimulant of gastric acid secretion (GAS), is a bitter-tasting compound that activates several taste type 2 bitter receptors (TAS2Rs). TAS2Rs are expressed in the mouth and in several extraoral sites, e.g., in the gastrointestinal tract, in which their functional role still needs to be clarified....

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Loss of mouse cardiomyocyte talin-1 and talin-2 leads to {beta}-1 integrin reduction, costameric instability, and dilated cardiomyopathy [Physiology]

Continuous contraction–relaxation cycles of the heart require strong and stable connections of cardiac myocytes (CMs) with the extracellular matrix (ECM) to preserve sarcolemmal integrity. CM attachment to the ECM is mediated by integrin complexes localized at the muscle adhesion sites termed costameres. The ubiquitously expressed cytoskeletal protein talin (Tln) is...

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Analyses of PDE-regulated phosphoproteomes reveal unique and specific cAMP-signaling modules in T cells [Pharmacology]

Prediction of intracellular exposure bridges the gap between target- and cell-based drug discovery [Pharmacology]

Inadequate target exposure is a major cause of high attrition in drug discovery. Here, we show that a label-free method for quantifying the intracellular bioavailability (Fic) of drug molecules predicts drug access to intracellular targets and hence, pharmacological effect. We determined Fic in multiple cellular assays and cell types representing...

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Synaptic properties of the lemniscal and paralemniscal pathways to the mouse somatosensory thalamus [Neuroscience]

Somatosensory information is thought to arrive in thalamus through two glutamatergic routes called the lemniscal and paralemniscal pathways via the ventral posterior medial (VPm) and posterior medial (POm) nuclei. Here we challenge the view that these pathways functionally represent parallel information routes. Using electrical stimulation and an optogenetic approach in...

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Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages [Neuroscience]

The nonneural cholinergic system of immune cells is pivotal for the maintenance of immunological homeostasis. Here we demonstrate the expression of choline acetyltransferase (ChAT) and cholinergic enzymes in murine natural killer (NK) cells. The capacity for acetylcholine synthesis by NK cells increased markedly under inflammatory conditions such as experimental autoimmune...

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Bifunctionality of a biofilm matrix protein controlled by redox state [Microbiology]

Biofilms are communities of microbial cells that are encapsulated within a self-produced polymeric matrix. The matrix is critical to the success of biofilms in diverse habitats; however, many details of the composition, structure, and function remain enigmatic. Biofilms formed by the Gram-positive bacterium Bacillus subtilis depend on the production of...

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Two dynamin-like proteins stabilize FtsZ rings during Streptomyces sporulation [Microbiology]

During sporulation, the filamentous bacteria Streptomyces undergo a massive cell division event in which the synthesis of ladders of sporulation septa convert multigenomic hyphae into chains of unigenomic spores. This process requires cytokinetic Z-rings formed by the bacterial tubulin homolog FtsZ, and the stabilization of the newly formed Z-rings is...

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Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children [Medical Sciences]

Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum...

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Anti-inflammatory {omega}-3 endocannabinoid epoxides [Biochemistry]

Clinical studies suggest that diets rich in ω-3 polyunsaturated fatty acids (PUFAs) provide beneficial anti-inflammatory effects, in part through their conversion to bioactive metabolites. Here we report on the endogenous production of a previously unknown class of ω-3 PUFA–derived lipid metabolites that originate from the crosstalk between endocannabinoid and cytochrome...

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Tubal Cytology of the Fallopian Tube as a Promising Tool for Ovarian Cancer Early Detection

We explored a tubal cytologic method by sampling the fallopian tube directly post-surgical excision as a tool of ovarian cancer early detection. Here, we present a protocol to collect fallopian tube cells from freshly received surgical specimens.

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Time-lapse Confocal Imaging of Migrating Neurons in Organotypic Slice Culture of Embryonic Mouse Brain Using In Utero Electroporation

This protocol provides instructions for direct observation of radially migrating cortical neurons. In utero electroporation, organotypic slice culture, and time-lapse confocal imaging are combined to directly and dynamically study the effects of overexpression or downregulation of genes of interest in migrating neurons and to analyze their differentiation during development.

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Ultrasound-guided hydrostatic enema for meconium obstruction in extremely low birth weight infants: a preliminary report

Abstract

Meconium obstruction (MO) in extremely low birth weight (ELBW) infants is a challenging disease to treat. We performed ultrasound-guided hydrostatic enema on six ELBW infants diagnosed with MO. We consider this procedure to be safe and effective, and recommend it as a treatment for MO in ELBW infants.

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Cdk9 and Spt5 are specifically required for expression of Herpes simplex virus 1 replication-dependent late genes. [Gene Regulation]

DNA replication greatly enhances expression of the Herpes simplex virus 1 (HSV-1) γ2 late genes by still unknown mechanisms. Here we demonstrate that 5,6-dichloro-1-β--D-ribofuranosylbenzimidazole (DRB), an inhibitor of CDK9, suppresses expression of γ2 late genes with an IC50 of 5 μM, which is at least ten times lower than the IC50 required for inhibition of expression of early genes. The effect of DRB could not be explained by inhibition of DNA replication per se or loading of RNA polymerase II to late promoters and subsequent reduction of transcription. Instead, DRB reduces accumulation of γ2 late mRNA in the cytoplasm. In addition, we show that siRNA mediated knock-down of the transcription factor SPT5, but not NELF-E, also gives rise to a specific inhibition of HSV-1 late gene expression. Finally, addition of DRB reduces co-immunoprecipitation of ICP27 using an anti-SPT5 antibody. Our results suggest that efficient expression of replication-dependent γ2 late genes is, at least in part, regulated by CDK9 dependent co- and/or post-transcriptional events involving SPT5 and ICP27.

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R213I mutation in release factor 2 (RF2) is one step forward for engineering an omnipotent release factor in bacteria Escherichia coli [RNA]

The current understanding of the specificity of the bacterial class I release factors (RFs) in decoding stop codons has evolved beyond a simple tripeptide anticodon model. A recent molecular dynamics study for deciphering the principles for specific stop codon recognition by RFs identified R213 as a crucial residue on Escherichia coli RF2 for discriminating guanine in the third position (G3). Interestingly, R213 is highly conserved in RF2 and substituted by I196 in the corresponding position in RF1. Another similar pair is L126 in RF1 and D143 in RF2, which are also conserved within their respective groups. With the hypothesis that replacement of R213 and D143 with the corresponding RF1 residues will reduce G3 discrimination by RF2, we swapped these residues between E. coli RF1 and RF2 by site-directed mutagenesis and characterized their preference for different codons using a competitive peptide release assay. Among these, the R213I mutant of RF2 showed five-fold improved reading of the RF1-specific UAG codon relative to UAA, the universal stop codon, compared to the WT. In-depth fast kinetic studies revealed that the gain in UAG reading by RF2 R213I is associated with a reduced efficiency of termination on the cognate UAA codon. Our work highlights the notion that stop codon recognition involves complex interactions with multiple residues beyond the SPT/PXT motifs. We propose that R213I mutation in RF2 brings us one step forward towards engineering an omnipotent RF in bacteria, capable of reading all three stop codons.

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Xanthoceraside modulates neurogenesis to ameliorate cognitive impairment in APP/PS1 transgenic mice

Abstract

Neuronal loss is reported to be an important pathological process in Alzheimer's disease (AD). Neurogenesis is a process of generation of new neurons to fill the neuronal loss. Xanthoceraside has been shown to attenuate the cognitive deficits in several AD animal models. However, little is known about the effect of xanthoceraside on neurogenesis in APP/PS1 transgenic mice. Thus, in this study, we investigated whether xanthoceraside can ameliorate learning and memory impairment by promoting NSCs proliferation and neuronal differentiation. The results suggested that xanthoceraside significantly ameliorated the cognitive impairment and induced NSCs proliferation and neuronal differentiation in APP/PS1 transgenic mice. Meanwhile, in vitro study revealed that xanthoceraside increased the size of NSCs and induced NSCs differentiation into neurons compared with amyloid beta-peptide (25–35) (Aβ_25–35) treatment. Furthermore, we found that xanthoceraside significantly increased the expression of Wnt3a and p-GSK3β, decreased the expression of p-β-catenin, and induced nuclear translocation of β-catenin in APP/PS1 transgenic mice. Furthermore, in vitro study found that the effect of xanthoceraside on inducing NSCs proliferation and neuronal differentiation were inhibited by Wnt pathway inhibitor Dickkopf-1 (Dkk-1). Our data demonstrated that xanthoceraside may promote the proliferation and differentiation of NSCs into neurons by up-regulating the Wnt/β-catenin pathway to fill the neuronal loss, thereby improving learning and memory impairment in APP/PS1 transgenic mice.

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Erratum to: Chronic Paroxetine Treatment Prevents the Emergence of Abnormal Electroencephalogram Oscillations in Huntington’s Disease Mice

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Response to the reply by C. J. Portier and P. Clausing, concerning our review “Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC”

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Response to the reply by C. J. Portier and P. Clausing, concerning our review “Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC”

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MAIT cells in infectious diseases

Publication date: October 2017
Source:Current Opinion in Immunology, Volume 48
Author(s): Marion Salou, Katarzyna Franciszkiewicz, Olivier Lantz
In humans, MAIT cells represent the most abundant T cell subset reacting against bacteria. Their frequency in the blood is decreased in a large variety of infectious diseases of either bacterial or viral origin. MAIT cells accumulate at the site of bacterial infection and are protective in experimental infection models. Recent epidemiological evidence supports an implication of MAIT cells in protecting against tuberculosis. MAIT cells can be activated either through direct recognition of microbial ligands or by inflammatory cytokines such as IL-12 and IL-18. MAIT cells secrete IFN-γ, IL-17 and/or other effector molecules according to the context of triggering. MAIT cells can kill bacterially infected epithelial cells in vitro. Herein, we summarize and discuss the data suggesting a role for MAIT cells in infectious diseases.

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TNF-receptor superfamily agonists as molecular adjuvants for cancer vaccines

Publication date: August 2017
Source:Current Opinion in Immunology, Volume 47
Author(s): Timothy NJ Bullock
Cancer vaccines have offered unrequited hope as a mechanism for rapidly and potently eliciting a patient's immune system to counter tumors. Initial results from preclinical mouse models have not translated to substantial benefit to patients, suggesting that either the targets or the vaccination approach were inadequate. Recent innovations in antigen identification have spiked renewed interest vaccination technologies. This has coincided with a detailed molecular understanding of the coordinated steps in postactivation support of T cell proliferation, differentiation and survival, leading to the development of novel targets and combinations that are substantially more effective than first and second generation cancer vaccines in preclinical models. Within this cluster of developments, the TNF-receptor superfamily members have emerged as attractive candidates for clinical implementation. Here we review recent developments in the mechanisms of action of TNFRSF agonists, and how their activity is potentiated by integration co-targeting pattern recognition receptors.

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Tuberculosis vaccines — perspectives from the NIH/NIAID Mycobacteria vaccine testing program

Publication date: August 2017
Source:Current Opinion in Immunology, Volume 47
Author(s): Angelo A Izzo
The development of novel vaccine candidates against infections with Mycobacterium tuberculosis has highlighted our limited understanding of immune mechanisms required to kill M. tuberculosis. The induction of a Th1 immunity is vital, but new studies are required to identify other mechanisms that may be necessary. Novel vaccines formulations that invoke effector cells such as innate lymphoid cells may provide an environment that promote effector mechanisms including T cell and B cell mediated immunity. Identifying pathways associated with killing this highly successful infectious agent has become critical to achieving the goal of reducing the global tuberculosis burden.

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A Generalized Model of Hourly Net Ecosystem Exchange (NEE) for Florida Everglades Freshwater Wetlands

Abstract

A generalized model is presented to estimate the diurnal cycle of hourly net ecosystem exchange (NEE) based on a corresponding single reference-time observation from the Florida Everglades freshwater wetlands. The year-round diurnal cycles of NEE for two different (short vs. long hydroperiod) marsh sites were normalized by the corresponding day- and site-specific reference observations of NEE to obtain a common dimensionless cycle. An extended stochastic harmonic analysis (ESHA) was utilized to calibrate and validate the model with hourly eddy-covariance observations of NEE during 2008–13. The model involved five parameters, which exhibited spatiotemporal robustness by collapsing into narrow ranges among different days, years and sites. The daily estimates were averaged over all calibration days to calculate the site-specific ensemble parameter sets. The site-specific ensemble parameters were further averaged over four mid-day reference times (11 A.M. to 2 P.M.) across sites to obtain a generalized ensemble parameter set. Estimated hourly NEE using the site-specific and the generalized parameter sets indicated a good performance of the model (e.g., Nash-Sutcliffe Efficiency, NSE = 0.66–0.89). The model is represented in three standalone formats, including an Excel spreadsheet, to simulate the hourly NEE for the desired Julian days and years from the respective single reference observations.

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Surface-Localized Sealing of Porous Ultralow-k Dielectric Films with Ultrathin (

TOC Graphic

ACS Nano

DOI: 10.1021/acsnano.7b01998

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Discovery and validation of a colorectal cancer classifier in a new blood test with improved performance for high-risk subjects

Abstract

Background

The aim was to improve upon an existing blood-based colorectal cancer (CRC) test directed to high-risk symptomatic patients, by developing a new CRC classifier to be used with a new test embodiment. The new test uses a robust assay format—electrochemiluminescence immunoassays—to quantify protein concentrations. The aim was achieved by building and validating a CRC classifier using concentration measures from a large sample set representing a true intent-to-test (ITT) symptomatic population.

Methods

4435 patient samples were drawn from the Endoscopy II sample set. Samples were collected at seven hospitals across Denmark between 2010 and 2012 from subjects with symptoms of colorectal neoplasia. Colonoscopies revealed the presence or absence of CRC. 27 blood plasma proteins were selected as candidate biomarkers based on previous studies. Multiplexed electrochemiluminescence assays were used to measure the concentrations of these 27 proteins in all 4435 samples. 3066 patients were randomly assigned to the Discovery set, in which machine learning was used to build candidate classifiers. Some classifiers were refined by allowing up to a 25% indeterminate score range. The classifier with the best Discovery set performance was successfully validated in the separate Validation set, consisting of 1336 samples.

Results

The final classifier was a logistic regression using ten predictors: eight proteins (A1AG, CEA, CO9, DPPIV, MIF, PKM2, SAA, TFRC), age, and gender. In validation, the indeterminate rate of the new panel was 23.2%, sensitivity/specificity was 0.80/0.83, PPV was 36.5%, and NPV was 97.1%.

Conclusions

The validated classifier serves as the basis of a new blood-based CRC test for symptomatic patients. The improved performance, resulting from robust concentration measures across a large sample set mirroring the ITT population, renders the new test the best available for this population. Results from a test using this classifier can help assess symptomatic patients' CRC risk, increase their colonoscopy compliance, and manage next steps in their care.

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Response to the reply by C. J. Portier and P. Clausing, concerning our review “Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC”

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Silver delivery approaches in the management of partial thickness burns: a systematic review and indirect treatment comparison

ABSTRACT

Silver-containing products play an important role in the management of burn wound infections. We sought to compare the efficacy of commonly used silver delivery approaches including nanocrystalline silver, silver-impregnated hydrofiber dressing, and silver-impregnated foam dressing as the main products in the management of partial thickness burns. A systematic review was performed by searching PubMed, EMBASE, Cochrane and other databases to identify relevant randomised controlled trials and observational studies. Due to the paucity of direct head-to-head trials an indirect treatment comparison was performed. The use of nanocrystalline silver was associated with a statistically significant reduction in length of stay when compared to silver-impregnated hydrofiber dressing (p=0.027) and a shorter time to healing when compared to silver-impregnated foam dressing (p=0.0328). There were no statistically significant differences in infection rates and surgical procedures between nanocrystalline silver, silver-impregnated hydrofiber dressing and silver-impregnated foam dressing; however, nanocrystalline silver was found to be the most beneficial for all the outcomes, including infection rates and surgical procedures, according to the Monte-Carlo simulation method. In conclusion, current evidence from the published literature suggests that where the clinical and microbiological priority is to get in control of infection quickly it would seem prudent to use the most potent silver delivery system, which is nanocrystalline silver. Nanocrystalline silver may offer both clinical and economic benefits compared to alternative treatments in the management of patients with mixed burns that are at high risk of infection. This article is protected by copyright. All rights reserved.

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Paediatric inflammatory bowel disease: a presenting lesion

A 12-year-old girl was admitted to the paediatric ward with a 5-week history of increasing tiredness. Her mother noted that she looked pale and had began to lose her hair. Her mother described that she had been complaining of a painful 'cyst' in her perineal area which was discharging pus. She also complained of a painful swollen right elbow which had appeared spontaneously in absence of any trauma. On questioning, she revealed that '9 out of 10' of her bowel motions contained dark red blood mixed in with stool.

On examination, the patient appeared lethargic with generalised pallor. Angular stomatitis and aphthous ulcers on the buccal mucosa were noted. Her abdomen was soft, non-tender with no masses palpable. Her perineum was inspected with a chaperone, which revealed a vulva ulcer at the 11 o'clock position with active bleeding. Multiple skin tags were noted in the perianal area. Musculoskeletal examination demonstrated a...

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Introduction of allergenic foods from 3 months of age reduces incidence of food allergy in breastfed infants

Study question

Patients: 1303 exclusively breastfed, well, singleton infants, aged 13–17 weeks recruited from the general population in England and Wales.

Early introduction group: Introduction of six allergenic foods: cow's milk, peanut, hen's egg, sesame, whitefish and wheat. Minimum amounts defined as 3 g once a week of at least five of the foods for 5 weeks between 3 and 6 months of age.

Standard introduction group: Continue to breast feed until 6 months of age, compliance defined as no consumption of allergenic foods including less than 300 mL of formula per day.

Outcomes: Challenge-proven food allergy to one or more of the six early introduction foods at age 1–3 years.

Analysis: Intention-to-treat (ITT) analysis and per-protocol analysis (PPA). In PPA, infants who were not compliant with their diet using the above definitions were excluded from the analysis.

Follow-up period: Until 3 years of age.

Main results

When analysed by ITT, there was no significant reduction in allergy in the...

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Add penis bacteria to the list of HIV risk factors

Certain bacteria found on the penis raise the risk of HIV infection, a new study finds.

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Detection of 22 common leukemic fusion genes using a single-step multiplex qRT-PCR-based assay

Fusion genes generated from chromosomal translocation play an important role in hematological malignancies. Detection of fusion genes currently employ use of either conventional RT-PCR methods or fluorescent i...

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GSE99987 Next Generation Sequencing Facilitates Quantitative Analysis of Normoxia and Hypoxia Macrophage Transcriptomes

Contributor : Koichi Murata
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

To test in an unbiased manner for hypoxia effect, we performed a transcriptomic analysis using high throughput RNA sequencing.

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GSE99987 Next Generation Sequencing Facilitates Quantitative Analysis of Normoxia and Hypoxia Macrophage Transcriptomes

Contributor : Koichi Murata
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

To test in an unbiased manner for hypoxia effect, we performed a transcriptomic analysis using high throughput RNA sequencing.

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Long non-coding RNAs in thyroid cancer: Biological functions and clinical significance

Publication date: Available online 24 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Fang Sui, Meiju Ji, Peng Hou
Thyroid cancer is the most common endocrine malignant tumor with rapidly increasing incidence in recent decades. Although the majority of thyroid cancers are relatively indolent, some cases still have a risk of developing into more aggressive and lethal forms of thyroid cancers. Similar to other malignancies, thyroid tumorigenesis is a multistep process involving the accumulation of a large number of genetic and epigenetic alterations. Thus, determination of the mechanisms of tumorigenesis is an urgent need for thyroid cancer treatment. Long noncoding RNAs (lncRNAs) have recently been demonstrated to participate in cancer progression. However, their role and molecular mechanism in thyroid cancer remain largely unclear. In this review, we focus on the dysregulation of lncRNAs in thyroid cancer, summarize the latest findings regarding the functions and mechanism of lncRNAs in thyroid cancer, and discuss their potential clinical significance in diagnosis and prognosis of thyroid cancer.

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The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology

Abstract

The aim of this study was to establish consensus for potential early symptomatic knee osteoarthritis (ESKOA) clinical definition and referral criteria from primary care to rheumatologists, based on available data from literature and a qualitative approach, in order to perform studies on patients fulfilling such criteria and to validate the obtained ESKOA definition. A complex methodological approach was followed including: (1) three focus groups (FG), including expert clinicians, researchers and patients; (2) a systematic literature review (SLR); (3) two discussion groups followed by a Delphi survey. FG and SLR were performed in parallel to inform discussion groups in order to identify relevant constructs to be included in the modified Delphi survey. ESKOA is defined in the presence of: (a) two mandatory symptoms (knee pain in the absence of any recent trauma or injury and very short joint stiffness, lasting for less than 10 min, when starting movement) even in the absence of risk factors, or (b) knee pain, and 1 or 2 risk factors or (c) three or more risk factors in the presence of at least one mandatory symptom, with symptoms lasting less than 6 months. These criteria are applicable in the absence of active inflammatory arthritis, generalized pain, Kellgren-Lawrence grade >0, any recent knee trauma or injury, and age lower than 40 years. Knee pain in the absence of any recent trauma lasting for less than 6 months was considered as the referral criterion to the rheumatologist for the suspicion of ESKOA. This consensus process has identified provisional clinical definition of ESKOA and defined potential referral criterion to rheumatologist, in order to test ESKOA obtained definition in prospective validation studies.

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Association study of estrogen receptor alpha gene polymorphisms with bone mass assessed by quantitative ultrasound in young adults

Abstract

Different genetic variants in estrogen receptor alpha (ESR1) have been shown to influence bone phenotypes including quantitative bone ultrasound in elderly. We aimed to investigate the role of ESR1 polymorphisms in bone mass assessed by calcaneal quantitative ultrasound (QUS) in a population of young adults. The study sample consisted of 466 healthy individuals of Caucasian ancestry (315 females and 152 males) aged 18 and 25 years (median age 20.39 ± 2.70). Six ESR1 polymorphisms (rs302033, rs2982552, rs2982575, rs2504063, rs2234693-PvuII and rs9340799-XbaI) were selected as genetic markers and genotyped. Bone mass in the right calcaneus was estimated with QUS. In the unadjusted analysis, rs2982575 polymorphism was significantly associated with quantitative ultrasound parameter in the whole sample (p = 0.014, β (95% CI) = −0.114 (−1.023, −0.115). However, after adjusting for multiple confounding factors, this association did not remain significant. For the rest of the selected polymorphisms in ESR1, no significant association was observed with calcaneal parameter. Linkage disequilibrium analysis identified a single LD block for the ESR1 gene including PvuII and XbaI SNPs (pair-wise r ² = 0.66). Our results revealed a lack of significant association between ESR1 polymorphisms and calcaneal quantitative ultrasound in a cohort of young adults suggesting that ESR1 gene do not play a major role in the acquisition of bone mass during early adulthood.

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Serum levels of adipokines in patients with idiopathic inflammatory myopathies: a pilot study

Abstract

Adipokines are cytokines not only regulating metabolic and endocrine activities, but also modulating inflammatory and immune responses in several clinical settings, including autoimmunity. This study was aimed to evaluate whether serum adipokine levels may be useful as markers of disease activity in patients with idiopathic inflammatory myopathies (IIM). Adiponectin, leptin, chemokine C–C motif ligand-2 (CCL2), interleukin (IL)-6, and tumor necrosis factor (TNF) were measured in the serum of all participants. For each adipokine, we evaluate the area under the ROC curve (AUC) and its correlation with creatine kinase (CK) levels. Thirteen patients with IIM and 13 age- and gender-matched healthy individuals were studied. In patients, the levels of CK (273 ± 321 versus 54 ± 29 U/L; P < 0.0001), leptin (1994 ± 1355 versus 818 ± 738 pg/mL; P = 0.024), and IL-6 (32.4 ± 24.1 versus 13.9 ± 3.5 pg/mL; P = 0.003) were significantly higher than in controls. As a result, CK (AUC = 0.929, 0.833–1.00; P = 0.0002), leptin (AUC = 0.783, 0.588–0.977; P = 0.025), and IL-6 (AUC = 0.846, 0.680–1.00; P = 0.005) significantly discriminated between patients and controls. Neither CCL2 (3256 ± 4585 versus 1118 ± 399 pg/mL; P = 0.319) nor TNF (85.1 ± 83.3 versus 58.2 ± 16.8 pg/mL; P = 0.809) levels were different. Additionally, only serum levels of CCL2 were significantly correlated with CK titers (Spearman´s rho coefficient 0.620, 0.087–0.877; P = 0.023). The levels of CCL2 are in parallel with CK activity in the serum of patients with IIM, suggesting a potential utility as markers of disease activity. Elevated levels of leptin and IL-6 also support a role for adipokines in IIM.

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Comparison of long-term prognosis and relapse of dermatomyositis complicated with interstitial pneumonia according to autoantibodies: anti-aminoacyl tRNA synthetase antibodies versus anti-melanoma differentiation-associated gene 5 antibody

Abstract

The aim of this study was to investigate long-term prognosis and relapse of dermatomyositis complicated with interstitial pneumonia (DMIP) according to anti-aminoacyl tRNA synthetase (ARS) antibodies and anti-melanoma differentiation-associated gene 5 (MDA5) antibody. This retrospective study comprised 36 patients with DMIP who were divided into the anti-ARS antibody-positive group (ARS+) (n = 12), anti MDA5 antibody-positive group (MDA5+) (n = 11), double-negative group (ARS−/MDA5−) (n = 11), and double-positive group (ARS+/MDA5+) (n = 1). Clinical features, treatment, prognoses, and relapses during the 2 years after initiation of treatment were compared between three groups excluding ARS+/MDA5+ group. Although short-term (24-week) mortality in MDA+ was higher than that in ARS+ or ARS−/MDA5− (P = 0.004), there was no difference in long-term (2-year) mortality between the three groups. Relapse rate in ARS+ was higher than that in MDA5+ and ARS−/MDA5− during the 2 years after initiation of treatment (P = 0.044). There was no difference in serum KL-6 levels at the initiation of treatment between ARS+ and MDA5+, but serum ferritin levels in MDA5+ were significantly higher than those in ARS+ (P = 0.406, 0.042, respectively). Serum KL-6 and ferritin levels at 2 years after initiation of treatment in ARS+ were significantly higher than those in MDA5+ (P = 0.008, 0.034, respectively). We found that in MDA5+ DMIP, acute alveolar inflammation caused a poor prognosis early in the disease course, and in ARS+ DMIP, chronic injury to the alveolar epithelial cells or basement membrane caused long-term recurrence.

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Erratum to: The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology

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The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5 , STAT4 , IRAK1, and CTGF polymorphisms

Abstract

Pulmonary fibrosis (PF) is one of the leading causes of death in systemic sclerosis (SSc) patients. Although all SSc patients are characterized by autoimmunity, only part of them suffer from PF, suggesting that beside autoimmunity, some additional factors are involved in the initiation of PF in SSc. In this study, we aimed to identify genetic polymorphisms associated with the status of PF in SSc. We performed that an exhaustive search of the PubMed database was performed to identify eligible studies. Then, a comprehensive meta-analysis was performed by comparing PF⁺-SSc and PF⁻-SSc patients to identify genetic polymorphisms associated with the status of PF in SSc. Among eight SSc-associated susceptibility polymorphisms which were applied for meta-analysis, IRF5 rs2004640 polymorphism (OR 1.12; 95% CI 1.02–1.22, P = 1.39 × 10⁻²), STAT4 rs7574865 polymorphism (OR 1.25; 95% CI 1.07–1.47, P = 5.3 × 10⁻³), IRAK1 rs1059702 polymorphism (OR 1.20; 95% CI 1.05–1.37, P = 0.007), and CTGF G-945C polymorphism (OR 1.42; 95% CI 1.18–1.71, P = 0.002) are associated with PF status in SSc, while TNFAIP3 rs5029939, CD226 rs763361, CD247 rs2056626, and IRF5 rs10488631 polymorphisms are not. Since IRF5, STAT4, and IRAK1 are important regulatory factors in the control of innate immune responses and CTGF is involved in the synthesis of extracellular matrix, these results suggest a role of the innate immunity and matrix compounds in the pathogenesis of PF in SSc.

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Periodontal disease in Chinese patients with systemic lupus erythematosus

Abstract

Disease of systemic lupus erythematosus (SLE) and periodontal disease (PD) shares the common multiple characteristics. The aims of the present study were to evaluate the prevalence and severity of periodontal disease in Chinese SLE patients and to determine the association between SLE features and periodontal parameters. A cross-sectional study of 108 SLE patients together with 108 age- and sex-matched healthy controls was made. Periodontal status was conducted by two dentists independently. Sociodemographic characteristics, lifestyle factors, medication use, and clinical parameters were also assessed. The periodontal status was significantly worse in SLE patients compared to controls. In univariate logistic regression, SLE had a significant 2.78-fold [95% confidence interval (CI) 1.60–4.82] increase in odds of periodontitis compared to healthy controls. Adjusted for potential risk factors, patients with SLE had 13.98-fold (95% CI 5.10–38.33) increased odds against controls. In multiple linear regression model, the independent variable negatively and significantly associated with gingival index was education (P = 0.005); conversely, disease activity (P < 0.001) and plaque index (P = 0.002) were positively associated; Age was the only variable independently associated with periodontitis of SLE in multivariate logistic regression (OR 1.348; 95% CI: 1.183–1.536, P < 0.001). Chinese SLE patients were likely to suffer from higher odds of PD. These findings confirmed the importance of early interventions in combination with medical therapy. It is necessary for a close collaboration between dentists and clinicians when treating those patients.

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Pain and fracture-related limitations persist 6 months after a fragility fracture

Abstract

Our objective was to examine the experience of pain after a fracture beyond the conventional healing duration of 6 months. We conducted a phenomenological study in participants who were deemed high risk for future fracture and recruited through an urban fracture clinic in Toronto, Canada. In-depth interviews were conducted with questions addressing the experience of pain, the status of recovery from the fracture, ways in which the fracture affected one's daily activities, and interactions with health care providers. Two researchers coded the transcripts within the phenomenological perspective to develop a structure of the pain experience, promoting rigour through the use of multiple analysts, searching for negative cases, and supporting claims with direct quotations from participants. We interviewed 21 participants who had sustained fractures of the wrist (n = 4), hip (n = 6), vertebrae (n = 2), and multiple or other locations (n = 9). All patients were ambulatory, had a range of socioeconomic status, and lived in the community. Eleven of the 21 participants reported persistent pain at the site of the fracture. Of the 10 participants who reported no pain, four indicated they had ongoing difficulties with range of motion and specific activities and two others described persistent pain from a previous fracture or reliance on a scooter for mobility. Our study demonstrated that over two-thirds of older adults reported fracture-related pain and/or limitations at, or beyond, 6 months post-fracture. We suggest that health care providers ask questions about post-fracture pain and/or limitations when assessing fracture status beyond 6 months.

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Aliens slumbering for billions of years are out there – really?

Trying to explain the Fermi paradox by invoking aliens that sleep for aeons is a speculative idea to be taken with a large pinch of salt, says Geraint Lewis

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Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant with neural tube defects

Folate and vitamin B12 are needed for the proper embryo-fetal development possibly through their interacting role in the one-carbon metabolism. Folate fortification reduces the prevalence of complex birth defects, and more specifically neural tube defects (NTD). GIF and FUT2 are two genes associated with the uptake and blood level of vitamin B12. We evaluated GIF and FUT2 as predictors of severe birth defects, in 181 aborted fetuses compared to 375 healthy newborns. The GIF290C allele frequency was estimated to 0.4% in healthy newborns and to 8.1% in NTD fetuses (odds ratio 17.8 (95% CI: 4.0-77.6)). The frequency of FUT2 rs601338 secretor variant was not different among groups. The GIF 290C heterozygous /FUT2 rs601338 secretor variant combined genotype was reported in 6 of the 37 NTD fetuses, but not in other fetuses and healthy newborns (P<0.0001). This GIF/FUT2 combined genotype has been previously reported in children with congenital GIF deficiency, with respective consequences on B12 binding activity and GIF secretion. In conclusion, a genotype reported in congenital GIF deficiency produces also severe forms of NTD. This suggests that vitamin B12 delivery to neural tissue by the CUBN/GIF pathway could play a role in the neural tube closure mechanisms.

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How earthquake scientists eavesdrop on North Korea’s nuclear blasts

Researchers monitor the power and location of underground nuclear weapons testing by North Korea.

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What's New Online

Publication date: August 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 8

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Creating Images with Impact: Food Photography Tips from MyPlate

Publication date: August 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 8
Author(s): Sarah Chang, Melissa Ciampo, Hannah Mitchell

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Practice Paper of the Academy of Nutrition and Dietetics: Classic and Modified Ketogenic Diets for Treatment of Epilepsy

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Publication date: August 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 8
Author(s): Kelly Roehl, Sarika L. Sewak
Ketogenic diet (KD) therapy is an established form of treatment for both pediatric and adult patients with intractable epilepsy. Ketogenic diet is a term that refers to any diet therapy in which dietary composition would be expected to result in a ketogenic state of human metabolism. While historically considered a last-resort therapy, classic KDs and their modified counterparts, including the modified Atkins diet and low glycemic index treatment, are gaining ground for use across the spectrum of seizure disorders. Registered dietitian nutritionists are often the first line and the most influential team members when it comes to treating those on KD therapy. This paper offers registered dietitian nutritionists insight into the history of KD therapy, an overview of the various diets, and a brief review of the literature with regard to efficacy; provides basic guidelines for practical implementation and coordination of care across multiple health care and community settings; and describes the role of registered dietitian nutritionists in achieving successful KD therapy.

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August 2017 People & Events

Where Can I Find Nutrition Resources for Children and Adolescents Participating in Youth Sports?

Publication date: August 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 8
Author(s): Eleese Cunningham

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Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma

Conditions: Lymphoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Renal Cell Cancer; Recurrent Bladder Carcinoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Renal Cell Carcinoma; Stage III Bladder Cancer; Stage III Lymphoma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Renal Cell Cancer; Stage III Skin Melanoma; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Lymphoma; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Bladder Cancer; Stage IVB Bladder Cancer; Unresectable Head and Neck Squamous Cell Carcinoma; Unresectable Solid Neoplasm
Interventions: Drug: Enzyme Inhibitor Therapy; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Biological: Pembrolizumab
Sponsors: Rutgers, The State University of New Jersey; National Cancer Institute (NCI)
Not yet recruiting - verified July 2017

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Melamine, beyond the kidney: A ubiquitous endocrine disruptor and neurotoxicant?

Publication date: Available online 24 July 2017
Source:Toxicology Letters
Author(s): Ashley L. Bolden, Johanna R. Rochester, Carol F. Kwiatkowski
Melamine is commonly used in a variety of consumer products such as furniture, dining ware, and food utensils. The chemical infamously gained worldwide attention by its illegal addition to a variety of foodstuffs in order to falsify protein content, which led to serious, sometimes fatal, health impacts in children and pets. This resulted in a large amount of published primary studies and reviews of the impacts of melamine exposure on kidney function. However, a growing body of literature suggests that melamine may have impacts beyond renal dysfunction. We conducted a scoping review of this literature which yielded more than 40 studies with human, animal, and in vitro findings. Neurological impacts, reproductive function, and anthropometric outcomes were identified as possible candidates for systematic review based on evidence stream and replication of endpoints. The results of this analysis provide a basis for prioritizing future research on health impacts associated with melamine exposure.

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PKA activity exacerbates hypoxia-induced ROS formation and hypoxic injury in PC-12 cells.

Publication date: Available online 24 July 2017
Source:Toxicology Letters
Author(s): Evelyne Gozal, Cynthia J. Miller, Maurice Dematteis, Leroy R. Sachleben, Avital Schurr, Madhavi J. Rane
Hypoxia is a primary factor in many pathological conditions. Hypoxic cell death is commonly attributed to metabolic failure and oxidative injury. cAMP-dependent protein kinase A (PKA) is activated in hypoxia and regulates multiple enzymes of the mitochondrial electron transport chain, thus may be implicated in cellular energy depletion and hypoxia-induced cell death.Wild type (WT) PC-12 cells and PKA activity-deficient 123.7 PC-12 cells were exposed to 3, 6, 12 and 24h hypoxia (0.1% or 5% O2). Hypoxia, at 24h 0.1% O2, induced cell death and increased reactive oxygen species (ROS) in WT PC-12 cells. Despite lower ATP levels in normoxic 123.7 cells than in WT cells, hypoxia only decreased ATP levels in WT cells. However, menadione-induced oxidative stress similarly affected both cell types. While mitochondrial COX IV expression remained consistently higher in 123.7 cells, hypoxia decreased COX IV expression in both cell types.N-acetyl cysteine antioxidant treatment blocked hypoxia-induced WT cell death without preventing ATP depletion. Transient PKA catα expression in 123.7 cells partially restored hypoxia-induced ROS but did not alter ATP levels or COX IV expression.We conclude that PKA signaling contributes to hypoxic injury, by regulating oxidative stress rather than by depleting ATP levels. Therapeutic strategies targeting PKA signaling may improve cellular adaptation and recovery in hypoxic pathologies.

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Höhepunkte des ASCO 2017

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Detection of 22 common leukemic fusion genes using a single-step multiplex qRT-PCR-based assay

Abstract

Background

Fusion genes generated from chromosomal translocation play an important role in hematological malignancies. Detection of fusion genes currently employ use of either conventional RT-PCR methods or fluorescent in situ hybridization (FISH), where both methods involve tedious methodologies and require prior characterization of chromosomal translocation events as determined by cytogenetic analysis. In this study, we describe a real-time quantitative reverse transcription PCR (qRT-PCR)-based multi-fusion gene screening method with the capacity to detect 22 fusion genes commonly found in leukemia. This method does not require pre-characterization of gene translocation events, thereby facilitating immediate diagnosis and therapeutic management.

Methods

We performed fluorescent qRT-PCR (F-qRT-PCR) using a commercially-available multi-fusion gene detection kit on a patient cohort of 345 individuals comprising 108 cases diagnosed with acute myeloid leukemia (AML) for initial evaluation; remaining patients within the cohort were assayed for confirmatory diagnosis. Results obtained by F-qRT-PCR were compared alongside patient analysis by cytogenetic characterization.

Results

Gene translocations detected by F-qRT-PCR in AML cases were diagnosed in 69.4% of the patient cohort, which was comparatively similar to 68.5% as diagnosed by cytogenetic analysis, thereby demonstrating 99.1% concordance. Overall gene fusion was detected in 53.7% of the overall patient population by F-qRT-PCR, 52.9% by cytogenetic prediction in leukemia, and 9.1% in non-leukemia patients by both methods. The overall concordance rate was calculated to be 99.0%. Fusion genes were detected by F-qRT-PCR in 97.3% of patients with CML, followed by 69.4% with AML, 33.3% with acute lymphoblastic leukemia (ALL), 9.1% with myelodysplastic syndromes (MDS), and 0% with chronic lymphocytic leukemia (CLL).

Conclusions

We describe the use of a F-qRT-PCR-based multi-fusion gene screening method as an efficient one-step diagnostic procedure as an effective alternative to lengthy conventional diagnostic procedures requiring both cytogenetic analysis followed by targeted quantitative reverse transcription (qRT-PCR) methods, thus allowing timely patient management.

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Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma

Functional movement disorders

Purpose of review: The review highlights the clinical presentation of functional movement disorders (FMDs) and presents current evidence on bedside signs and paraclinical tests to differentiate them from other neurological disorders. Recent findings: FMDs are diagnosed by the presence of positive clinical signs as emphasized in the new Diagnostic and Statistical Manual of Mental Disorders-5 classification criteria. Bedside signs are numerous, and a subset of them has been validated in controlled studies. This review summarizes evidence from the literature on specificity and sensibility of positive clinical signs for FMDs. The value of rule-in paraclinical tests to confirm the diagnosis is also presented. Recent developments in neuroscience with pathophysiological mechanisms and current treatment strategies are also discussed. Summary: FMDs represent a field of neurology that is currently rapidly growing in terms of research. Clinicians should be aware that highly reliable signs exist for the diagnosis and that early multidisciplinary treatment should be offered.

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Imaging plus X: multimodal models of neurodegenerative disease

Purpose of review: This article argues that the time is approaching for data-driven disease modelling to take centre stage in the study and management of neurodegenerative disease. The snowstorm of data now available to the clinician defies qualitative evaluation; the heterogeneity of data types complicates integration through traditional statistical methods; and the large datasets becoming available remain far from the big-data sizes necessary for fully data-driven machine-learning approaches. The recent emergence of data-driven disease progression models provides a balance between imposed knowledge of disease features and patterns learned from data. The resulting models are both predictive of disease progression in individual patients and informative in terms of revealing underlying biological patterns. Recent findings: Largely inspired by observational models, data-driven disease progression models have emerged in the last few years as a feasible means for understanding the development of neurodegenerative diseases. These models have revealed insights into frontotemporal dementia, Huntington's disease, multiple sclerosis, Parkinson's disease and other conditions. For example, event-based models have revealed finer graded understanding of progression patterns; self-modelling regression and differential equation models have provided data-driven biomarker trajectories; spatiotemporal models have shown that brain shape changes, for example of the hippocampus, can occur before detectable neurodegeneration; and network models have provided some support for prion-like mechanistic hypotheses of disease propagation. The most mature results are in sporadic Alzheimer's disease, in large part because of the availability of the Alzheimer's disease neuroimaging initiative dataset. Results generally support the prevailing amyloid-led hypothetical model of Alzheimer's disease, while revealing finer detail and insight into disease progression. Summary: The emerging field of disease progression modelling provides a natural mechanism to integrate different kinds of information, for example from imaging, serum and cerebrospinal fluid markers and cognitive tests, to obtain new insights into progressive diseases. Such insights include fine-grained longitudinal patterns of neurodegeneration, from early stages, and the heterogeneity of these trajectories over the population. More pragmatically, such models enable finer precision in patient staging and stratification, prediction of progression rates and earlier and better identification of at-risk individuals. We argue that this will make disease progression modelling invaluable for recruitment and end-points in future clinical trials, potentially ameliorating the high failure rate in trials of, e.g., Alzheimer's disease therapies. We review the state of the art in these techniques and discuss the future steps required to translate the ideas to front-line application.

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Sleep-related movement disorders and disturbances of motor control

Purpose of review: Review of the literature pertaining to clinical presentation, classification, epidemiology, pathophysiology, diagnosis, and treatment of sleep-related movement disorders and disturbances of motor control. Recent findings: Sleep-related movement disorders and disturbances of motor control are typically characterized by positive motor symptoms and are often associated with sleep disturbances and consequent daytime symptoms (e.g. fatigue, sleepiness). They often represent the first or main manifestation of underlying disorders of the central nervous system, which require specific work-up and treatment. Diverse and often combined cause factors have been identified. Although recent data provide some evidence regarding abnormal activation and/or disinhibition of motor circuits during sleep, for the majority of these disorders the pathogenetic mechanisms remain speculative. The differential diagnosis is sometimes difficult and misdiagnoses are not infrequent. The diagnosis is based on clinical and video-polysomnographic findings. Treatment of sleep-related motor disturbances with few exceptions (e.g. restless legs/limbs syndrome) are based mainly on anecdotal reports or small series. Summary: More state-of-the-art studies on the cause, pathophysiology, and treatment of sleep-related movement disorders and disturbances of motor control are needed.

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Neuroimaging in Parkinson's disease: focus on substantia nigra and nigro-striatal projection

Purpose of review: The diagnosis of Parkinson disease is based on clinical features; however, unmet need is an imaging signature for Parkinson disease and the early differential diagnosis with atypical parkinsonisms. A summary of the molecular imaging and MRI recent evidences for Parkinson disease diagnosis will be presented in this review. Recent findings: The nigro-striatal dysfunction explored by dopamine transporter imaging is not a mandatory diagnostic criterion for Parkinson disease, recent evidence supported its utility as in-vivo proof of degenerative parkinsonisms, and there might be compensatory mechanisms leading to an early overestimation. The visualization of abnormalities in substantia nigra by MRI has been recently described as sensitive and specific tool for Parkinson disease diagnosis, even in preclinical conditions, whereas it is not useful for distinguishing between Parkinson disease and atypical parkinsonisms. The relationship between the nigral anatomical changes, evaluated as structural alterations or neuromelanin signal decrease and the dopaminergic nigro-striatal function needs to be further clarified. Summary: With the hopeful advent of potential neuroprotective drugs for PD, it is crucial to have imaging measures that are able to detect at risk subjects. Moreover it is desirable to increase the knowledge about which measure better predicts the probability and the time of clinical conversion to PD.

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Neuroimaging as a tool to study the sources of phenotypic heterogeneity in Huntington's disease

Purpose of review: Huntington's disease is a neurodegenerative disorder characterized by a triad of motor, cognitive and psychiatric disturbances. There is great variability regarding the prominence and evolution of each type of clinical sign. One possible source of phenotypic heterogeneity could be the more prominent degeneration of specific brain circuits. The scope of this review is to highlight the most recent neuroimaging studies that have analysed the relationship between brain changes and motor, cognitive and psychiatric alterations in Huntington's disease. Recent findings: The results from recent neuroimaging studies are heterogeneous. Although there is a great overlap between the different regions associated with each symptomatic domain, there is some degree of differentiation. For example, the motor network is associated with motor impairment, whereas the ventral striatum is especially involved in emotional deficits related with psychiatric problems. Summary: Motor, cognitive and psychiatric impairments are associated with structural and functional brain biomarkers. However, the specificity of the regions involved remains unknown, because these studies focused on specific regions and symptoms. In order to tease apart the neural substrates that underlie the phenotypic heterogeneity in Huntington's disease, multivariate approaches combining brain and behavioural measures related to all symptomatic domains should be considered in the future.

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New neurosurgical approaches for tremor and Parkinson's disease

Purpose of review: The objective of this review is to gather the newest advances in the surgical treatment of tremor and Parkinson's disease. We will briefly discuss the potential applications of the new technologies of deep brain stimulation (DBS), and we will focus on MRI-guided focused ultrasound (MRgFUS). Recent findings: Novel DBS devices are being progressively adopted, particularly electrodes allowing a longer stimulating surface (suitable for multiple targets stimulation) and current radial steering (to minimize side effects of stimulation). New implantable pulse generators are also able to record neurons and are generating enough knowledge to advance the implementation of adaptive (closed-loop) DBS. Over the last years, 'minimally-invasive' neurosurgical approaches for the treatment of movement disorders have been developed: gamma knife radiosurgery and MRgFUS. Uncontrolled and recent controlled studies have shown the benefits of MRgFUS targeting the thalamus and pallidus for the treatment of tremor and Parkinson's disease. Summary: The initial clinical data are certainly promising and have expanded the current portfolio of neurosurgical treatments of movement disorders. Many issues are yet to be addressed, particularly safety of MRgFUS-and how these new treatments compare with the existing ones.

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Senate Advances Bill Undermining Trump Administration's Energy Research Cuts

The Senate Appropriations Committee moved to sustain funding for energy research and development, breaking with the President and House of Representatives

-- Read more on ScientificAmerican.com

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The light and shade of knowledge recombination: Insights from a general-purpose technology

Publication date: Available online 24 July 2017
Source:Technological Forecasting and Social Change
Author(s): Francesco Paolo Appio, Antonella Martini, Gualtiero Fantoni
This research focuses on a special case of General Purpose Technology: Bioinformatics. It explores whether – and to what extent – Bioinformatics inventions build upon inherently diverse knowledge sources. Precisely, the role of scientific and technological diversity (measured with Shannon-Wiener diversity index) as driver of impactful Bioinformatics inventions (measured at different standard deviations of the forward citations distribution) is investigated. To this purpose, we carried out an analysis of both Non-Patent and Patent references cited into Bioinformatics patented inventions in the period 1976–2014. Results from a series of logistic regression models indicate that different degrees of impact require different degrees of knowledge diversity; at the same time, and importantly for practitioners and scholars, recombining diverse scientific and technological knowledge bases not always lead to impactful inventions. In other terms: the interplay of science and technology is not always the best option to get impactful inventions.

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GSE90752 Mechanisms of transcription factor-mediated direct reprogramming of mouse embryonic stem cells to trophoblast stem-like cells

Contributor : Jonghwan Kim
Series Type : Expression profiling by high throughput sequencing ; Other ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

Direct reprogramming can be achieved by forced expression of transcription factors (TFs). Yet how such TFs mediate repression of initial cell-type-specific genes while activating target cell-type-specific genes is unclear. Here, we achieve embryonic stem (ES) to trophoblast stem (TS)-like cell reprogramming by introducing individual TS-specific "CAG" factors (Cdx2, Arid3a, Gata3). We interrogated their chromosomal target occupancies, modulation of global transcriptome and chromatin accessibility at the initial stage of reprograming. Our findings uncovered a sequential, two-step mechanism of cellular reprogramming in which repression of exiting ES pluripotency is followed by activated conversion to TS cells by CAG factors.

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Prevalence and predictors of conflict in the families of patients with advanced cancer: A nationwide survey of bereaved family members

Abstract

Objectives

Family conflict has several adverse impacts on caregivers. Thus, there is significant value in determining the prevalence and predictors of family conflict, which can enable the health care provider to intervene if family conflict arises during end-of-life care. Accordingly, we aimed to explore the prevalence and predictors of conflict among the families of patients with advanced cancer who died in palliative care units.

Methods

This study was a nationwide multicenter questionnaire survey of bereaved family members of cancer patients who died in Japanese palliative care units participating in evaluation of the quality of end-of-life care.

Results

We sent out 764 questionnaires and 529 questionnaires (69.2%) were returned. As 70 family members refused to participate and we could not identify the answers in one questionnaire, we analyzed a total of 458 responses. The average Outcome-Family Conflict score was 13.5 ± 4.9 (maximum score: 39.5) and 42.2% of family members reported at least one family conflict during end-of-life care. Greater family conflict was significantly associated with younger family age, with family members asserting control over decision-making for patient care, and with communication constraints among family members, although absent family members "coming out of the woodwork" reduced family conflict.

Conclusions

Many families of patients with advanced cancer experienced conflict during end-of-life care. Family members asserting control over decision-making and communication constraints among family members after diagnosis of cancer can predict the occurrence of family conflict. Absent family members "coming out of the woodwork" might reduce family conflict in particular cultures.

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GSE90752 Mechanisms of transcription factor-mediated direct reprogramming of mouse embryonic stem cells to trophoblast stem-like cells

Contributor : Jonghwan Kim
Series Type : Expression profiling by high throughput sequencing ; Other ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

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A novel CCR-2/TLR-2 triggered signaling in murine peritoneal macrophages intensifies bacterial (Staphylococcus aureus) killing by reactive oxygen species through TNF-R1.

Authors: Nandi A, Bishayi B Abstract Macrophages are remarkably versatile in their ability to recognize and respond to a wide range of stimuli by expressing a variety of surface and intracellular receptors and triggering multiple signal transduction pathways. The onset of microbial infection is primarily determined by the initial contacts made by the microbes with the host macrophages. Although there prevail a relationship between the chemokine receptor and Toll like receptors during disease, particularly TLR-2 and CCR-2 signaling interdependence on each other has not been yet investigated during acute staphylococcal infection. Thus, the present study was aimed to trace possible interaction between CCR-2 and TLR-2 in peritoneal macrophages during acute Staphylococcus aureus infecti...

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Nanoliposomes carrying HER2/neu-derived peptide AE36 with CpG-ODN exhibit therapeutic and prophylactic activities in a mice TUBO model of breast cancer.

This study was designed to prepare and characterize nanoliposomal vaccine formulation encapsulating AE36 HER2/neu-derived peptide with or without CpG and evaluate the immunologic and therapeutic responses of that in BALB/c mice model of Her2 overexpressing breast cancer. AE36 was encapsulated in liposomes composed of DOTAP, DOPE and Cholesterol (DDC) or DD with. The formulations could induce both CD8+ and CD4+ responses and stimulate production of cytokines which was detected by Enzyme-linked immunospot assay (ELISpot) kits, cytotoxicity test and intracellular cytokine assay by flow cytometry. The formulation showed both therapeutic and prophylactic effects in BALB/c mice bearing Her2(+) breast cancer. DDC+CpG showed the best effect in prophylactic study and DD +CpG showed the best effect ...

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A 3 °C global RCP8.5 emission trajectory cancels benefits of European emission reductions on air quality

A 3 °C global RCP8.5 emission trajectory cancels benefits of European emission reductions on air quality

Nature Communications, Published online: 25 July 2017; doi:10.1038/s41467-017-00075-9

Current national pledges to reduce greenhouse gas emissions track to a temperature rise of about 3 °C. Here the authors use future projections to show that 3 °C warming under a business as usual scenario would result in large increases in ozone concentrations, off-setting any benefits from mitigation policies.

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Höhepunkte des ASCO 2017

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A 3 °C global RCP8.5 emission trajectory cancels benefits of European emission reductions on air quality

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The Neuroscience of Body Memory: from the Self through the Space to the Others

Publication date: Available online 25 July 2017
Source:Cortex
Author(s): Giuseppe Riva
Our experience of the body is not direct; rather, it is mediated by perceptual information, influenced by internal information, and recalibrated through stored implicit and explicit body representation (body memory). This paper presents an overview of the current investigations related to body memory by bringing together recent studies from neuropsychology, neuroscience, and evolutionary and cognitive psychology. To do so, in the paper, we explore the origin of representations of human body to elucidate their developmental process and, in particular, their relationship with more explicit concepts of self. First, it is suggested that our bodily experience is constructed from early development through the continuous integration of sensory and cultural data from six different representations of the body, i.e., the Sentient Body (Minimal Selfhood), the Spatial Body (Self Location), the Active Body (Agency), the Personal Body (Whole Body Ownership – Me); the Objectified Body (Objectified Self – Mine), and the Social Body (Body Satisfaction – Ideal Me). Then, it is suggested that these six representations can be combined in a coherent supramodal representation, i.e. the "body matrix", through a predictive, multisensory processing activated by central, top–down, attentional processes. From an evolutionary perspective, the main goal of the body matrix is to allow the self to protect and extend its boundaries at both the homeostatic and psychological levels. From one perspective, the self extends its boundaries (peripersonal space) through the enactment and recognition of motor schemas. From another perspective, the body matrix, by defining the boundaries of the body, also defines where the self is present, i.e., in the body that is processed by the body matrix as the most likely to be its one and in the space surrounding it. In the paper we also introduced and discusses the concept of "embodied medicine": the use of advanced technology for altering the body matrix with the goal of improving our health and well-being.

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Ventral lateral parietal cortex and episodic memory retrieval

Publication date: Available online 25 July 2017
Source:Cortex
Author(s): Michael D. Rugg, Danielle R. King
With the advent of functional neuroimaging it quickly became apparent that successful episodic memory retrieval was consistently associated with enhanced activity in ventral lateral parietal cortex, especially the left angular gyrus. Here, we selectively review recent neuropsychological and functional neuroimaging evidence relevant to the question of the functional significance of this activity. We argue that the balance of the evidence suggests that the angular gyrus supports the representation of retrieved episodic information, and that this likely reflects a more general role for the region in representing multi-modal and multi-domain information.

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Deviant Functional Activation and Connectivity of the Right Insula Are Associated With Lack of Awareness of Episodic Memory Impairment in Nonamnesic Alcoholism

Publication date: Available online 25 July 2017
Source:Cortex
Author(s): Anne-Pascale Le Berre, Eva M. Müller-Oehring, Tilman Schulte, Matthew R. Serventi, Adolf Pfefferbaum, Edith V. Sullivan
A disorder of metamemory, expressed as unawareness of mnemonic ability, is typically associated with the profound amnesia of Korsakoff's Syndrome (KS). A similar but less severe type of limited awareness can also occur in non-KS alcoholism and is observed as an impairment in generating Feeling-of-Knowing (FOK) predictions about future recognition performance. We previously found that FOK accuracy was selectively related to volumes of the insula in alcoholics involved in the present study. Unknown, however, are the neural substrates of unawareness of memory impairment in alcoholism. A task-activated fMRI paradigm served to identify neural nodes and networks implicated in inaccurate self-estimation of mnemonic ability in sober alcoholics while they made prospective FOK judgments in an episodic memory paradigm. Lower activation in the right insula correlated with greater overestimations of future memory abilities in alcoholics. Weaker connectivity of the right insula with the left dorsal anterior cingulate cortex, a node of the salience network, and stronger connectivity of the right insula with the right ventromedial prefrontal cortex, a node of the default mode network (DMN), co-occurred in alcoholics relative to the controls. Specifically, alcoholics, who failed to desynchronize insula-vmPFC activity, had greater overestimation of their memory predictions and poorer recognition performance. This study provides novel support that deviant functional activation and connectivity involving the right insula, a hub of the salience network, appears to participate in disrupting metamemory functioning in alcoholics. Compromised FOK performance might result from disturbance of the switching mechanism between brain networks serving self-referential processes (i.e., DMN network) and networks serving externally-driven activities like memory monitoring (i.e., fronto-parietal network). Thus, compromise in insular network coupling could be a neural mechanism underlying anosognosia for subtle mnemonic impairment in nonamnesic alcoholism.

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Motor correlates of phantom limb pain

Publication date: Available online 25 July 2017
Source:Cortex
Author(s): Sanne Kikkert, Melvin Mezue, David Henderson-Slater, Heidi Johansen-Berg, Irene Tracey, Tamar R. Makin
Following amputation, individuals ubiquitously report lingering sensations of their missing limb. While phantom sensations can be innocuous, they are often manifested as painful. Phantom limb pain (PLP) is notorious for being difficult to monitor and treat. A major challenge in PLP management is the difficulty in assessing PLP symptoms, given the physical absence of the affected body part. Here, we offer a means of quantifying chronic PLP by harnessing the known ability of amputees to voluntarily move their phantom limbs. Upper-limb amputees suffering from chronic PLP performed a simple finger-tapping task with their phantom hand. We confirm that amputees suffering from worse chronic PLP had worse motor control over their phantom hand. We further demonstrate that task performance was consistent over weeks and did not relate to transient PLP or non-painful phantom sensations. Finally, we explore the neural basis of these behavioural correlates of PLP. Using neuroimaging, we reveal that slower phantom hand movements were coupled with stronger activity in the cortical sensorimotor phantom hand territory, previously shown to associate with chronic PLP. By demonstrating a specific link between motor control and PLP, our findings open up new avenues for PLP management and improvement of existing PLP treatments.

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Daenerys still waiting on Prior Authorization to Conquer Westeros

Dragonstone, Westeros – Daenerys Targaryen, or the Queen of Dragons, is still waiting on Prior Authorization to conquer Westeros and rule the seven kingdoms. "I put the request in last season and still I haven't heard," Daenerys siad. Initially denied, a peer-to-peer was set up to help expedite the invasion authorization.

Daenerys said during the peer-to-peer talk the other "peer" had zero experience uniting the seven kingdoms much less combat experience.

"So infuriating," Daenerys told reporters. "They are unsure if I can take Kings Landing but did state I could invade Casterly Rock. I never even asked for Casterly Rock!"

Fans, Unsullied, Dothraki, and Daenerys will have to wait for this stinkin' prior authorization to com through.

The post Daenerys still waiting on Prior Authorization to Conquer Westeros appeared first on GomerBlog.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2uxm8Xn

Macrophage phenotype in response to ECM bioscaffolds.

Authors: Huleihel L, Dziki JL, Bartolacci JG, Rausch T, Scarritt ME, Cramer MC, Vorobyov T, LoPresti ST, Swineheart IT, White LJ, Brown BN, Badylak SF Abstract Macrophage presence and phenotype are critical determinants of the healing response following injury. Downregulation of the pro-inflammatory macrophage phenotype has been associated with the therapeutic use of bioscaffolds composed of extracellular matrix (ECM), but phenotypic characterization of macrophages has typically been limited to small number of non-specific cell surface markers or expressed proteins. The present study determined the response of both primary murine bone marrow derived macrophages (BMDM) and a transformed human mononuclear cell line (THP-1 cells) to degradation products of two different, commonly used...

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Brain Sciences, Vol. 7, Pages 93: Selective Serotonin Reuptake Inhibitors for Treating Neurocognitive and Neuropsychiatric Disorders Following Traumatic Brain Injury: An Evaluation of Current Evidence

Brain Sciences, Vol. 7, Pages 93: Selective Serotonin Reuptake Inhibitors for Treating Neurocognitive and Neuropsychiatric Disorders Following Traumatic Brain Injury: An Evaluation of Current Evidence

Brain Sciences doi: 10.3390/brainsci7080093

Authors: John Yue John Burke Pavan Upadhyayula Ethan Winkler Hansen Deng Caitlin Robinson Romain Pirracchio Catherine Suen Sourabh Sharma Adam Ferguson Laura Ngwenya Murray Stein Geoffrey Manley Phiroz Tarapore

The prevalence of neuropsychiatric disorders following traumatic brain injury (TBI) is 20%–50%, and disorders of mood and cognition may remain even after recovery of neurologic function is achieved. Selective serotonin reuptake inhibitors (SSRI) block the reuptake of serotonin in presynaptic cells to lead to increased serotonergic activity in the synaptic cleft, constituting first-line treatment for a variety of neurocognitive and neuropsychiatric disorders. This review investigates the utility of SSRIs in treating post-TBI disorders. In total, 37 unique reports were consolidated from the Cochrane Central Register and PubMed (eight randomized-controlled trials (RCTs), nine open-label studies, 11 case reports, nine review articles). SSRIs are associated with improvement of depressive but not cognitive symptoms. Pooled analysis using the Hamilton Depression Rating Scale demonstrate a significant mean decrease of depression severity following sertraline compared to placebo—a result supported by several other RCTs with similar endpoints. Evidence from smaller studies demonstrates mood improvement following SSRI administration with absent or negative effects on cognitive and functional recovery. Notably, studies on SSRI treatment effects for post-traumatic stress disorder after TBI remain absent, and this represents an important direction of future research. Furthermore, placebo-controlled studies with extended follow-up periods and concurrent biomarker, neuroimaging and behavioral data are necessary to delineate the attributable pharmacological effects of SSRIs in the TBI population.

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Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma

Single-port thoracoscopic lung wedge resection using the Endo GIA Radial Reload

Abstract

The GIA Radial Reload is a surgical stapler with a curved cut line that is perpendicular to the direction of instrument insertion. We used the GIA Radial Reload in three cases of single-port thoracoscopic lung wedge resection. The operations were performed through a 3.0–4.5-cm incision. For the first stapler, we selected the GIA Radial Reload. The orientation of this device's cut line enabled us to easily cut the lung behind the lesion during single-port thoracoscopic surgery.

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Psoriasis: a mixed autoimmune and autoinflammatory disease.

Authors: Liang Y, Sarkar MK, Tsoi LC, Gudjonsson JE Abstract In recent years marked progress has been made in our understanding of the critical biologic and immunologic pathways involved in psoriasis. Genetic studies have demonstrated that susceptibility to psoriasis involves components of both the adaptive and innate immune system and not surprisingly activation of both of these arms of the immune system is found in psoriatic skin. While adaptive immune responses predominate in chronic plaque psoriasis, innate and autoinflammatory responses dominate in pustular forms of psoriasis, with other clinical subtypes extending on a spectrum between plaque and pustular psoriasis. This makes psoriasis a unique disease where both autoimmune and autoinflammatory responses co-exist, with the b...

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The immunopathology of dengue and Zika virus infections.

Authors: Culshaw A, Mongkolsapaya J, Screaton GR Abstract A large proportion of the world's population live in areas with dengue virus (DENV) transmission resulting in tens of millions of symptomatic dengue cases each year. Serious complications following DENV infection occur more frequently in those suffering from a second or subsequent infection implicating virus-specific immunity as having a role in pathogenesis. In recent years outbreaks of the related Zika virus (ZIKV) have been associated with birth defects and neurological complications. As DENV and ZIKV share a viral vector sequential infections can occur. Given the sequence homology between the two viruses, the generation of cross-reactive immune responses is highly likely. This review examines the role immunopathogenesis ...

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Germinal center enhancement by extended antigen availability.

Authors: Cirelli KM, Crotty S Abstract Vaccine elicitation of protective antibody responses has proved difficult for a number of important human pathogens, including HIV-1. The amount of somatic hypermutation associated with the development of broadly neutralizing antibodies against HIV has not been achieved using conventional immunization strategies. An underexplored aspect of vaccine design is modulation of antigen kinetics. Immunization strategies with extended antigen availability have recently been shown to enhance humoral responses. In this review, we explore the mechanisms through which sustained antigen availability can enhance germinal center responses and the potency of antibody responses. These potential mechanisms include shifting B cell recognition away from non-neutra...

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Old and new adjuvants.

Authors: McKee AS, Marrack P Abstract Adjuvants have been deliberately added to vaccines since the 1920's when alum was discovered to boost antibody responses, leading to better protection. The first adjuvants were discovered by accident and were used in the safer but less immunogenic subunit vaccines, supposedly by providing an antigen depot to extend antigen presentation. Since that time, much has been discovered about how these adjuvants impact cells at the tissue site to activate innate immune responses, mobilize dendritic cells and drive adaptive immunity. New approaches to vaccine construction for infectious diseases that have so far not been well addressed by conventional vaccines often attempt to induce antibodies, polyfunctional CD4(+) T cells and CD8(+) CTLs. The discover...

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CD8+ T cell programming by cytomegalovirus vectors: applications in prophylactic and therapeutic vaccination.

Authors: Früh K, Picker L Abstract Vectors based on cytomegalovirus (CMV) represent a novel vaccine platform that maintains high frequencies of non-exhausted effector memory T cells in both CMV sero-positive and sero-negative individuals. In non-human primate models, CMV vectored vaccines provide unprecedented protection against simian immunodeficiency virus (SIV). Moreover, CMV vectors can be genetically altered to program highly diverse CD8+ T cell responses that differ in their epitope targeting including conventional, MHC-I restricted CD8+ T cells as well as unconventional CD8+ T cells restricted by MHC class II or non-polymorphic MHC-E. By modifying cytomegaloviral determinants that control unconventional T cell priming it is possible to uniquely tailor the CD8+ T cell respon...

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No pain no gain? Adjuvant effects of alum and monophosphoryl lipid A in pertussis and HPV vaccines.

Authors: Mitchell TC, Casella CR Abstract Development of non-infectious subunit vaccines is hampered by a slow pipeline of new adjuvants to replace or enhance alum in part because expectations of safety are high. Transient vaccine side effects are not clinical priorities because they cause no lasting harm and vaccine development has appropriately been focused on avoidance of serious adverse events. As a result, surprisingly little is known about the extent to which side effects caused by a vaccine's reactogencicity are predictive of successful immunization outcomes. Recent clinical studies of pertussis and human papillomavirus vaccines adjuvanted with alum or the TLR4 agonist monophosphoryl lipid A can be used to advance understanding of the relationship between vaccine side effect...

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Immunological tolerance as a barrier to protective HIV humoral immunity.

Authors: Schroeder KM, Agazio A, Torres RM Abstract HIV-1 infection typically eludes antibody control by our immune system and is not yet prevented by a vaccine. While many viral features contribute to this immune evasion, broadly neutralizing antibodies (bnAbs) against HIV-1 are often autoreactive and it has been suggested that immunological tolerance may restrict a neutralizing antibody response. Indeed, recent Ig knockin mouse studies have shown that bnAb-expressing B cells are largely censored by central tolerance in the bone marrow. However, the contribution of peripheral tolerance in limiting the HIV antibody response by anergic and potentially protective B cells is poorly understood. Studies using mouse models to elucidate how anergic B cells are regulated and can be recruit...

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Behavioral weight-loss treatment plus motivational interviewing versus attention control: lessons learned from a randomized controlled trial

Studies evaluating the benefit of adding motivational interviewing (MI) to behavioral weight-loss programs (BWLPs) have yielded mixed findings.

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Tight intra-operative blood pressure control versus standard care for patients undergoing hip fracture repair – Hip Fracture Intervention Study for Prevention of Hypotension (HIP-HOP) trial: study protocol for a randomised controlled trial

Hypotension during anaesthesia for hip fracture surgery is common. Recent data suggest that there is an association between the lowest intra-operative blood pressure and mortality, even when adjusted for co-mo...

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Lasers reactivate ‘lost’ memories in mice with Alzheimer’s

It was thought that Alzheimer's completely erases memories, but a mouse experiment suggests the condition messes with our ability to recall them instead

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The immune contexture in cancer prognosis and treatment

Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2017.101

Authors: Wolf H. Fridman, Laurence Zitvogel, Catherine Sautès–Fridman & Guido Kroemer

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Pancreatic Cancer: EGFR inhibition is effective against KRAS-wild-type disease

Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2017.119

Author: Peter Sidaway

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Immunotherapy: Reality check for nivolumab in advanced-stage melanoma

Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2017.112

Author: Diana Romero

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Breast cancer: Profiling of ultra-low-risk disease

Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2017.114

Author: David Killock

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Outcomes research: Integrating PROs into the clinic — overall survival benefit or not, it's worth the trouble

Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2017.109

Authors: Elisa Sperti & Massimo Di Maio

In 2016, results of an important randomized trial demonstrated that patients undergoing chemotherapy who reported symptoms electronically have a better quality of life than those receiving usual care. Now, a significant survival improvement for patients in the experimental arm of this study has been reported. The emphasis of this survival benefit is 'culturally' positive, promoting the adoption of patient-reported outcomes in clinical practice.

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GSE87480 Orphan box C/D snoRNAs guide rRNA base acetylations in yeast

Contributors : Sander Granneman ; Rob van Nues
Series Type : Other
Organism : Saccharomyces cerevisiae

Box C/D snoRNAs snR4 and snR45, whose role was unknown, guide 18S rRNA acetylations by Kre33 in yeast. UV-crosslinking (CRAC) was used to determine binding sites of Kre33 on RNA.

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Cognition, culture and utility: plant classification by Paraguayan immigrant farmers in Misiones, Argentina

Abstract

Background

This study was conducted in three rural communities of small farmers of Paraguayan origin living in the province of Misiones, Argentina. These Criollos (Mestizos) hail chiefly from departments located in the east of Paraguay, where the climate and flora have similar characteristics as those in Misiones. These ecological features contribute to the continuation and maintenance of knowledge and practices related to the use of plants.

Methods

Fieldwork was conducted between September 2014 and August 2015. Forty five informants from three rural localities situated along the Parana River participated in an ethno-classification task. For the classification event, photographs of 30 medicinal and edible plants were chosen, specifically those yielding the highest frequency of mention among the members of that community (based on data obtained in the first stage of research in 2014). Variation in local plant classifications was examined and compared using principal component analysis and cluster analysis.

Results

We found that people classify plants according to application or use (primarily medicinal, to a lesser extent as edible). Morphology is rarely taken into account, even for very similar and closely-related species such as varieties of palms. In light of our findings, we highlight a dominant functionality model at work in the process of plant cognition and classification among farmers of Paraguayan origin. Salient cultural beliefs and practices associated with rural Paraguayan plant-based medicine are described. Additionally, the manner by which residents' concepts of plants articulate with local folk epistemology is discussed.

Conclusions

Culturally constructed use patterns ultimately override morphological variables in rural Paraguayans' ethnobotanical classification.

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Childhood interstitial lung diseases in immunocompetent children in Australia and New Zealand: a decade’s experience

Abstract

Background

Childhood interstitial lung disease (chILD) represents a rare heterogeneous group of respiratory disorders. In the absence of randomized controlled clinical trials, global collaborations have utilized case series with an aim to standardising approaches to diagnosis and management. Australasian data are lacking. The aim of this study was to calculate prevalence and report the experience of chILD in Australasia over a decade.

Methods

Paediatric pulmonologists in Australia and New Zealand involved in the care of patients aged 0–18 years with chILD completed a questionnaire on demographics, clinical features and outcomes, over a 10 year period. These data, together with data from the 2 reference genetics laboratories, were used to calculate prevalence.

Results

One hundred fifteen cases were identified equating to a period prevalence (range) of 1.5 (0.8–2.1) cases/million for children aged 0–18years. Clinical data were provided on 106 patients: the <2 year group comprised 66 children, median age (range) 0.50 years (0.01–1.92); the ≥2 year group comprised 40 children, median age 8.2 years (2.0–18.0). Management approach was heterogeneous. Overall, 79% of patients had a good clinical outcome. Mortality rate was 7% in the study population.

Conclusion

chILD is rare in Australasia. This study demonstrates variation in the investigations and management of chILD cases across Australasia, however the general outcome is favorable. Further international collaboration will help finesse the understanding of these disorders.

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