Reliability of Upper Limb Pin-Prick Stimulation With Electroencephalography: Evoked Potentials, Spectra and Source Localization

In order for electroencephalography (EEG) with sensory stimuli measures to be used in research and neurological clinical practice, demonstration of reliability is needed. However, this is rarely examined. Here we studied the test-retest reliability of the EEG latency and amplitude of evoked potentials and spectra as well as identifying the sources during pin-prick stimulation. We recorded EEG in 23 healthy older adults who underwent a protocol of pin-prick stimulation on the dominant and non-dominant hand. EEG was recorded in a second session with rest intervals of 1 week. For EEG electrodes Fz, Cz, and Pz peak amplitude, latency and frequency spectra for pin-prick evoked potentials was determined and test-retest reliability was assessed. Substantial reliability ICC scores (0.76–0.79) were identified for evoked potential negative-positive amplitude from the left hand at C4 channel and positive peak latency when stimulating the right hand at Cz channel. Frequency spectra showed consistent increase of low-frequency band activity (< 5 Hz) and also in theta and alpha bands in first 0.25 s. Almost perfect reliability scores were found for activity at both low-frequency and theta bands (ICC scores: 0.81–0.98). Sources were identified in the primary somatosensory and motor cortices in relation to the positive peak using s-LORETA analysis. Measuring the frequency response from the pin-prick evoked potentials may allow the reliable assessment of central somatosensory impairment in the clinical setting

Reliability of Upper Limb Pin-Prick Stimulation With Electroencephalography : Evoked Potentials, Spectra and Source Localization

In order for electroencephalography (EEG) with sensory stimuli measures to be used in research and neurological clinical practice, demonstration of reliability is needed. However, this is rarely examined. Here we studied the test-retest reliability of the EEG latency and amplitude of evoked potentials and spectra as well as identifying the sources during pin-prick stimulation. We recorded EEG in 23 healthy older adults who underwent a protocol of pin-prick stimulation on the dominant and non-dominant hand. EEG was recorded in a second session with rest intervals of 1 week. For EEG electrodes Fz, Cz, and Pz peak amplitude, latency and frequency spectra for pin-prick evoked potentials was determined and test-retest reliability was assessed. Substantial reliability ICC scores (0.76-0.79) were identified for evoked potential negative-positive amplitude from the left hand at C4 channel and positive peak latency when stimulating the right hand at Cz channel. Frequency spectra showed consistent increase of low-frequency band activity (< 5 Hz) and also in theta and alpha bands in first 0.25 s. Almost perfect reliability scores were found for activity at both low-frequency and theta bands (ICC scores: 0.81-0.98). Sources were identified in the primary somatosensory and motor cortices in relation to the positive peak using s-LORETA analysis. Measuring the frequency response from the pin-prick evoked potentials may allow the reliable assessment of central somatosensory impairment in the clinical setting

Workers\u2019 exposure to nano-objects with different dimensionalities in R&D laboratories: Measurement strategy and field studies

With the increasing interest in the potential benefits of nanotechnologies, concern is still growing that they may present emerging risks for workers. Various strategies have been developed to assess the exposure to nano-objects and their agglomerates and aggregates (NOAA) in the workplace, integrating different aerosol measurement instruments and taking into account multiple parameters that may influence NOAA toxicity. The present study proposes a multi-metric approach for measuring and sampling NOAA in the workplace, applied to three case studies in laboratories each dedicated to materials with different shapes and dimensionalities: graphene, nanowires, and nanoparticles. The study is part of a larger project with the aim of improving risk management tools in nanomaterials research laboratories. The harmonized methodology proposed by the Organization for Economic Cooperation and Development (OECD) has been applied, including information gathering about materials and processes, measurements with easy-to-use and hand-held real-time devices, air sampling with personal samplers, and off-line analysis using scanning electron microscopy. Significant values beyond which an emission can be attributed to the NOAA production process were identified by comparison of the particle number concentration (PNC) time series and the corresponding background levels in the three laboratories. We explored the relations between background PNC and microclimatic parameters. Morphological and elemental analysis of sampled filters was done to identify possible emission sources of NOAA during the production processes: rare particles, spherical, with average diameter similar to the produced NOAA were identified in the nanoparticles laboratory, so further investigation is recommended to confirm the potential for worker exposure. In conclusion, the information obtained should provide a valuable basis for improving risk management strategies in the laboratory at work

IMPAcT-RLS2: Indagine nazionale sulla salute e la sicurezza sul lavoro: il ruolo dei Rappresentanti dei Lavoratori per la Sicurezza

L’Indagine IMPAcT-RLS2 si inserisce nel più ampio programma di ricerca INSuLa2, la cui prima edizione, condotta nel 2014 e rivolta a tutti gli attori della prevenzione, ha approfondito aspetti della tutela della salute e sicurezza sul lavoro (SSL) secondo il punto di vista delle varie figure intervistate. La survey indirizzata ai Rappresentanti dei lavoratori per la sicurezza (RLS), focalizzata inizialmente su tre contesti regionali, è stata implementata grazie all’indagine IMPAcT-RLS, realizzata nel 2016, che ha coinvolto un campione di circa 2.100 soggetti, rappresentativo a livello nazionale, per dimensione aziendale e settore di attività economica. L’indagine ha evidenziato l’importanza di disporre di informazioni sempre più approfondite sul ruolo dei RLS e di monitorarne l’andamento nel tempo. Il presente studio ribadisce l’importanza di istituire rilevazioni periodiche e replicabili, finalizzate ad aumentare le conoscenze e la consapevolezza sui sistemi di prevenzione e promuovere interventi sempre più mirati per il miglioramento della tutela della SSL.The IMPAcT-RLS2 survey is part of a larger context of INSuLa2 research program; its first edition was conducted in 2014 and targeted to all prevention professionals, investigating occupational health and safety (OSH) protection issues perceived by the various professionals’ point of view. The survey addressed to Health and Safety Representatives (HS reps.), focused on three regional contexts, was further implemented in 2016 through the IMPAcT-RLS survey, which involved a sample representative at national level, by company size and economic activity sector consisting of about 2,100 subjects. The survey highlighted the importance of having ever more in-depth information on the role of HS reps. and monitoring their evolution over time. This study arises from the need to create periodic and replicable surveys, aimed at increasing knowledge and awareness of prevention systems and promoting increasingly targeted interventions for improving the protection of OS

Reliability of upper limb pin-prick stimulation with electroencephalography : evoked potentials, spectra and source localization

In order for electroencephalography (EEG) with sensory stimuli measures to be used in research and neurological clinical practice, demonstration of reliability is needed. However, this is rarely examined. Here we studied the test-retest reliability of the EEG latency and amplitude of evoked potentials and spectra as well as identifying the sources during pin-prick stimulation.We recorded EEG in 23 healthy older adults who underwent a protocol of pin-prick stimulation on the dominant and non-dominant hand. EEG was recorded in a second session with rest intervals of 1 week. For EEG electrodes Fz, Cz, and Pz peak amplitude, latency and frequency spectra for pin-prick evoked potentials was determined and test-retest reliability was assessed. Substantial reliability ICC scores (0.76–0.79) were identified for evoked potential negative-positive amplitude from the left hand at C4 channel and positive peak latency when stimulating the right hand at Cz channel. Frequency spectra showed consistent increase of low-frequency band activity (< 5 Hz) and also in theta and alpha bands in first 0.25 s. Almost perfect reliability scores were found for activity at both low-frequency and theta bands (ICC scores: 0.81–0.98). Sources were identified in the primary somatosensory and motor cortices in relation to the positive peak using s-LORETA analysis. Measuring the frequency response from the pin-prick evoked potentials may allow the reliable assessment of central somatosensory impairment in the clinical setting.peer-reviewe

Myeloid antigens in childhood lymphoblastic leukemia:clinical data point to regulation of CD66c distinct from other myeloid antigens

BACKGROUND: Aberrant expression of myeloid antigens (MyAgs) on acute lymphoblastic leukemia (ALL) cells is a well-documented phenomenon, although its regulating mechanisms are unclear. MyAgs in ALL are interpreted e.g. as hallmarks of early differentiation stage and/or lineage indecisiveness. Granulocytic marker CD66c – Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is aberrantly expressed on ALL with strong correlation to genotype (negative in TEL/AML1 and MLL/AF4, positive in BCR/ABL and hyperdiploid cases). METHODS: In a cohort of 365 consecutively diagnosed Czech B-precursor ALL patients, we analyze distribution of MyAg+ cases and mutual relationship among CD13, CD15, CD33, CD65 and CD66c. The most frequent MyAg (CD66c) is studied further regarding its stability from diagnosis to relapse, prognostic significance and regulation of surface expression. For the latter, flow cytometry, Western blot and quantitative RT-PCR on sorted cells is used. RESULTS: We show CD66c is expressed in 43% patients, which is more frequent than other MyAgs studied. In addition, CD66c expression negatively correlates with CD13 (p < 0.0001), CD33 (p = 0.002) and/or CD65 (p = 0.029). Our data show that different myeloid antigens often differ in biological importance, which may be obscured by combining them into "MyAg positive ALL". We show that unlike other MyAgs, CD66c expression is not shifted from the onset of ALL to relapse (n = 39, time to relapse 0.3–5.3 years). Although opposite has previously been suggested, we show that CEACAM6 transcription is invariably followed by surface expression (by quantitative RT-PCR on sorted cells) and that malignant cells containing CD66c in cytoplasm without surface expression are not found by flow cytometry nor by Western blot in vivo. We report no prognostic significance of CD66c, globally or separately in genotype subsets of B-precursor ALL, nor an association with known risk factors (n = 254). CONCLUSION: In contrast to general notion we show that different MyAgs in lymphoblastic leukemia represent different biological circumstances. We chose the most frequent and tightly genotype-associated MyAg CD66c to show its stabile expression in patients from diagnosis to relapse, which differs from what is known on the other MyAgs. Surface expression of CD66c is regulated at the gene transcription level, in contrast to previous reports

Integrated evaluation of indoor particulate exposure. The viepi project

Despite the progress made in recent years, reliable modeling of indoor air quality is still far from being obtained. This requires better chemical characterization of the pollutants and airflow physics included in forecasting tools, for which field observations conducted simultaneously indoors and outdoors are essential. The project “Integrated Evaluation of Indoor Particulate Exposure” (VIEPI) aimed at evaluating indoor air quality and exposure to particulate matter (PM) of humans in workplaces. VIEPI ran from February 2016 to December 2019 and included both numerical simulations and field campaigns carried out in universities and research environments located in urban and non-urban sites in the metropolitan area of Rome (Italy). VIEPI focused on the role played by micrometeorology and indoor airflow characteristics in determining indoor PM concentration. Short-and long-term study periods captured diurnal, weekly, and seasonal variability of airflow and PM concentration. Chemical characterization of PM10, including the determination of elements, ions, elemental carbon, organic carbon, and bioaerosol, was also carried out. Large differences in the composition of PM10 were detected between inside and outside as well as between different periods of the day and year. Indoor PM composition was related to the presence of people, to the season, and to the ventilation regime

Structural Studies of a Four-MBT Repeat Protein MBTD1

The Polycomb group (PcG) of proteins is a family of important developmental regulators. The respective members function as large protein complexes involved in establishment and maintenance of transcriptional repression of developmental control genes. MBTD1, Malignant Brain Tumor domain-containing protein 1, is one such PcG protein. MBTD1 contains four MBT repeats.We have determined the crystal structure of MBTD1 (residues 130-566aa covering the 4 MBT repeats) at 2.5 A resolution by X-ray crystallography. The crystal structure of MBTD1 reveals its similarity to another four-MBT-repeat protein L3MBTL2, which binds lower methylated lysine histones. Fluorescence polarization experiments confirmed that MBTD1 preferentially binds mono- and di-methyllysine histone peptides, like L3MBTL1 and L3MBTL2. All known MBT-peptide complex structures characterized to date do not exhibit strong histone peptide sequence selectivity, and use a "cavity insertion recognition mode" to recognize the methylated lysine with the deeply buried methyl-lysine forming extensive interactions with the protein while the peptide residues flanking methyl-lysine forming very few contacts [1]. Nevertheless, our mutagenesis data based on L3MBTL1 suggested that the histone peptides could not bind to MBT repeats in any orientation.The four MBT repeats in MBTD1 exhibits an asymmetric rhomboid architecture. Like other MBT repeat proteins characterized so far, MBTD1 binds mono- or dimethylated lysine histones through one of its four MBT repeats utilizing a semi-aromatic cage.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

H3K9me2/3 Binding of the MBT Domain Protein LIN-61 Is Essential for Caenorhabditis elegans Vulva Development

MBT domain proteins are involved in developmental processes and tumorigenesis. In vitro binding and mutagenesis studies have shown that individual MBT domains within clustered MBT repeat regions bind mono- and dimethylated histone lysine residues with little to no sequence specificity but discriminate against the tri- and unmethylated states. However, the exact function of promiscuous histone methyl-lysine binding in the biology of MBT domain proteins has not been elucidated. Here, we show that the Caenorhabditis elegans four MBT domain protein LIN-61, in contrast to other MBT repeat factors, specifically interacts with histone H3 when methylated on lysine 9, displaying a strong preference for di- and trimethylated states (H3K9me2/3). Although the fourth MBT repeat is implicated in this interaction, H3K9me2/3 binding minimally requires MBT repeats two to four. Further, mutagenesis of residues conserved with other methyl-lysine binding MBT regions in the fourth MBT repeat does not abolish interaction, implicating a distinct binding mode. In vivo, H3K9me2/3 interaction of LIN-61 is required for C. elegans vulva development within the synMuvB pathway. Mutant LIN-61 proteins deficient in H3K9me2/3 binding fail to rescue lin-61 synMuvB function. Also, previously identified point mutant synMuvB alleles are deficient in H3K9me2/3 interaction although these target residues that are outside of the fourth MBT repeat. Interestingly, lin-61 genetically interacts with two other synMuvB genes, hpl-2, an HP1 homologous H3K9me2/3 binding factor, and met-2, a SETDB1 homologous H3K9 methyl transferase (H3K9MT), in determining C. elegans vulva development and fertility. Besides identifying the first sequence specific and di-/trimethylation binding MBT domain protein, our studies imply complex multi-domain regulation of ligand interaction of MBT domains. Our results also introduce a mechanistic link between LIN-61 function and biology, and they establish interplay of the H3K9me2/3 binding proteins, LIN-61 and HPL-2, as well as the H3K9MT MET-2 in distinct developmental pathways

The ETS Family Member TEL Binds to Nuclear Receptors RAR and RXR and Represses Gene Activation

Retinoic acid receptor (RAR) signaling is important for regulating transcriptional activity of genes involved in growth, differentiation, metabolism and reproduction. Defects in RAR signaling have been implicated in cancer. TEL, a member of the ETS family of transcription factors, is a DNA-binding transcriptional repressor. Here, we identify TEL as a transcriptional repressor of RAR signaling by its direct binding to both RAR and its dimerisation partner, the retinoid x receptor (RXR) in a ligand-independent fashion. TEL is found in two isoforms, created by the use of an alternative startcodon at amino acid 43. Although both isoforms bind to RAR and RXR in vitro and in vivo, the shorter form of TEL represses RAR signaling much more efficiently. Binding studies revealed that TEL binds closely to the DNA binding domain of RAR and that both Helix Loop Helix (HLH) and DNA binding domains of TEL are mandatory for interaction. We have shown that repression by TEL does not involve recruitment of histone deacetylases and suggest that polycomb group proteins participate in the process