Altered event-related potentials and theta oscillations index auditory working memory deficits in healthy aging

Speech comprehension deficits constitute a major issue for an increasingly aged population, as they may lead older individuals to social isolation. Since conversation requires constant monitoring, updating and selecting information, auditory working memory decline, rather than impoverished hearing acuity, has been suggested a core factor. However, in stark contrast to the visual domain, the neurophysiological mechanisms underlying auditory working memory deficits in healthy aging remain poorly understood, especially those related to on-the-fly information processing under increasing load. Therefore, we investigated the behavioral costs and electrophysiological differences associated with healthy aging and working memory load during continuous auditory processing. We recorded EEG activity from 27 younger (∼25 years) and 29 older (∼70 years) participants during their performance on an auditory version of the n-back task with speech syllables and 2 workload levels (1-back; 2-back). Behavioral measures were analyzed as indices of function; event-related potentials as proxies for sensory and cognitive processes; and theta oscillatory power as a reflection of memory and central executive function. Our results show age-related differences in auditory information processing within a latency range that is consistent with a series of impaired functions, from sensory gating to cognitive resource allocation during constant information updating, especially under high load

Determination of the Primary Molecular Target of 1,2,4-Triazole-Ciprofloxacin Hybrids

We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin.This research was supported by the Ministry of Science and Higher Education under Iuventus Plus grant No. IP2014 037473. Tomasz Plech is a recipient of the Fellowship for Young Researchers with Outstanding Scientific Achievements from the Medical University of Lublin (Lublin, Poland)

The role of Toll-like receptors (TLRs) in virus-related cancers: a mini review

The modulation of the host innate immune system is a well-established carcinogenesis feature of several tumors, including human Epstein-Barr (EBV) and Papillomavirus-(HPV) related cancers. These viruses are able to interrupt the initial events of the immune response, including the expression of Toll-like receptors (TLRs), cytokines, and inflammation. The aim of the study is to review current data and summarize knowledge on the TLRs and their role in the development of cancer, especially viral-related cancers (EBV and HPV). Research work shows a correlation between the TLRs polymorphism and the development of oropharyngeal and gastric cancer (GC), especially related to viral infections. Many studies suggest the important role for TLRs in inflammatory, autoimmune disease and human cancers. However, further efforts are necessary to draw a precise conclusion

Waste Polyurethane Foams as Biomass Carriers in the Treatment Process of Domestic Sewage with Increased Ammonium Nitrogen Content

In order to understand the mechanisms of microbial growth on waste polyurethane sponge materials, their effectiveness as biomass carriers in domestic sewage with increased ammonium nitrogen content treatment was assessed. Comparative experiments were carried out in microreactors under steady conditions of batch culture, which allowed for an assessment of different carriers, in the form of flexible foams, rigid foams, and flexible foams placed in full casings. In the studies conducted in continuous cultures, biomass carriers selected in batch culture were used as fillings in the column model. The structure of the microbial community inhabiting the spongy material was determined and the pollutant-removing process from real domestic sewage was assessed. Analyzes using the Illumina sequencing technique allowed for demonstrating that Nitrosomonas and Nitrospira were the predominant nitrifiers in the biomass carrier in the form of waste polyurethane foams (PUF). It was found that anammox bacteria, the presence of which—as unidentified Planctomycetes—was confirmed in the polyurethane sponge material, were also responsible for the high removal of N-NH4+. Burkholderia and Sphingopyxis phyla were identified as the dominant denitrifying bacteria involved in the treatment of domestic sewage with increased content of ammonium nitrogen. The biomass carrier in the form of waste PUF placed additionally in full casings proved to be more beneficial for the proliferation of bacteria involved in nitrification and denitrification processes. On the other hand, waste foams without casings proved to be more suitable for the growth of microorganisms known to perform partial denitrification and may accumulate nitrites (Staphylococcus, Dokdonella). Additionally, the presence of Devosia and Pseudonocardia, which participated in the phosphorus removal process, was found in the waste PUR foams

Training in Temporal Information Processing Ameliorates Phonetic Identification

Many studies revealed a link between temporal information processing (TIP) in a millisecond range and speech perception. Previous studies indicated a dysfunction in TIP accompanied by deficient phonemic hearing in children with specific language impairment (SLI). In this study we concentrate in SLI on phonetic identification, using the voice-onset-time (VOT) phenomenon in which TIP is built-in. VOT is crucial for speech perception, as stop consonants (like /t/ vs. /d/) may be distinguished by an acoustic difference in time between the onsets of the consonant (stop release burst) and the following vibration of vocal folds (voicing). In healthy subjects two categories (voiced and unvoiced) are determined using VOT task. The present study aimed at verifying whether children with SLI indicate a similar pattern of phonetic identification as their healthy peers and whether the intervention based on TIP results in improved performance on the VOT task. Children aged from 5 to 8 years (n = 47) were assigned into two groups: normal children without any language disability (NC, n = 20), and children with SLI (n = 27). In the latter group participants were randomly classified into two treatment subgroups, i.e., experimental temporal training (EG, n = 14) and control non-temporal training (CG, n = 13). The analyzed indicators of phonetic identification were: (1) the boundary location (α) determined as the VOT value corresponding to 50% voicing/unvoicing distinctions; (2) ranges of voiced/unvoiced categories; (3) the slope of identification curve (β) reflecting the identification correctness; (4) percent of voiced distinctions within the applied VOT spectrum. The results indicated similar α values and similar ranges of voiced/unvoiced categories between SLI and NC. However, β in SLI was significantly higher than that in NC. After the intervention, the significant improvement of β was observed only in EG. They achieved the level of performance comparable to that observed in NC. The training-related improvement in CG was non-significant. Furthermore, only in EG the β values in post-test correlated with measures of TIP as well as with phonemic hearing obtained in our previous studies. These findings provide another evidence that TIP is omnipresent in language communication and reflected not only in phonemic hearing but also in phonetic identification

Training-Induced Changes in Rapid Auditory Processing in Children With Specific Language Impairment: Electrophysiological Indicators

The brain’s ability to recognize acoustic changes occurring in rapid temporal succession is important for speech and successful language development. Children with specific language impairment (SLI) are characterized by deficient dynamics of temporal information processing (TIP) in the millisecond time range accompanied by disordered language development. Furthermore, previous studies have found that intervention based on amelioration of TIP resulted in improvement of both language and other cognitive functions. This study aimed to explain the changes associated with TIP training from the perspective of event-related potentials (ERPs). Thirty-six children aged 5–8 years (26 boys, 10 girls) diagnosed with SLI underwent two types of intense audio-visual computer intervention: experimental TIP training targeted at the millisecond time range (n = 18) or control non-TIP training (n = 18). Paired 50 ms tones of 1000 Hz and 1200 Hz were presented with inter-stimulus intervals (ISIs) of either 50 ms (Short ISI Condition) or 200 ms (Long ISI Condition). Auditory ERPs were measured in a passive oddball paradigm before and after each type of training. The mismatch negativity (MMN) paradigm was applied as an electrophysiological indicator of the brain’s ability to automatically detect violations of regularity in paired tones presented in rapid succession. Moreover, the P3a component was also analyzed. After 24 sessions of temporal training (in the experimental group) MMN amplitude enhancement was observed in both ISI conditions, reflecting increased efficiency in perceiving changes in rapid auditory sequences. In both experimental and control groups, P3a amplitude was enhanced in both ISIs. This may be due to the improvement of involuntary attention shifting to the auditory events involved in each training type. To conclude, temporal training, compared to non-temporal control training, improved the ability to detect changes in a rapid auditory stream in children with SLI

Comparison of TGF-β, IL-10 levels and LMP-1 in gastric and oropharyngeal carcinoma associated with EBV infection

Increasing interest has been focused on the Epstein-Barr Virus (EBV)-associated cancers, including oropharyngeal cancer (OPC) and gastric cancer (GC). Different cytokines, growth factors and proteins take part in oncogenesis. The aim of our study was to generate a comparison of interleukin 10 (IL-10) and transforming growth factor β (TGF-β) levels, as well as latent membrane protein (LMP-1), Epstein-Barr virus capsid antigen (EBVCA), Epstein-Barr virus nuclear antigen (EBNA) and early antigen (EA) frequency in the serum of patients with GC and OPC. The study involved 50 patients with diagnosed GC and 50 patients with OPC. All studied patients were EBV positive. Fresh-frozen tumor tissue fragments were tested using nested PCR assay for EBV DNA detection. Sera from all individuals were investigated using ELISA tests to detect the presence of EBVCA IgG, EBNA IgG, EA IgG, as well as to determine the levels of IL-10 and TGF-β. The obtained results were subjected to statistical analysis. In patients with GC, the levels of TGF-β and IL-10 were significantly higher than in OPC patients. However, the frequency and level of EBVCA, EBNA and EA in patients with OPC and GC were not significantly different. In contrast, TGF-β and IL-10 levels were significantly higher in EBVaGC, as compared to OPC, suggesting their role in gastric carcinogenesis. The differences in frequency of LMP-1 detection in patients with OPC and GC may suggest different mechanism of oncogenesis. Further studies are required to clarify the role of Epstein-Barr virus in cancer development

Inhibitory effect of N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide on Haemophilus spp. planktonic or biofilm-forming cells

During this study, we have investigated in vitro activity of N-substituted-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide derivatives with N-ethyl, N-(4-metoxyphenyl) and N-cyclohexyl substituents against Gram-negative Haemophilus influenzae and H. parainfluenzae bacteria. A spectrophotometric assay was used in order to determine the bacterial growth and biofilm formation using a microtiter plate to estimate minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC). Among the tested N-substituted pyrazole derivatives, only N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide showed a significant in vitro activity against both planktonic cells of H. parainfluenzae (MIC = 0.49–31.25 μg ml(−1)) and H. influenzae (MIC = 0.24–31.25 μg ml(−1)) as well as biofilm-forming cells of H. parainfluenzae (MBIC = 0.24–31.25 μg ml(−1)) and H. influenzae (MBIC = 0.49 to ≥31.25 μg ml(−1)). The pyrazole compound exerted higher inhibitory effect both on the growth of planktonic cells and biofilm formation by penicillinase-positive and penicillinase-negative isolates of H. parainfluenzae than the activity of commonly used antibiotics such as ampicillin. No cytotoxicity of the tested compound in vitro at concentrations used was found. The tested pyrazole N-ethyl derivative could be considered as a compound for the design of agents active against both pathogenic H. influenzae and opportunistic H. parainfluenzae, showing also anti-biofilm activity. This appears important because biofilms are determinants of bacterial persistence in long-term and recurrent infections recalcitrant to standard therapy

Serum Level of MMP-3 and MMP-9 in Patients with Diabetes Mellitus Type 2 Infected with Epstein-Barr Virus

Diabetes mellitus type 2 (DM2) has recently become one of the most important health problems in the world. Patients with DM2 with long-term glycaemia are more likely to become infected than the healthy population. Matrix metalloproteinases (MMPs) play a key role in tissue remodeling during various physiological processes. However, it has been reported that certain MMPs are overexpressed during the development of various human diseases. In this study, we analyzed the levels of MMP-3 and MMP-9 in the serum of DM2 patients with and without Epstein-Barr virus (EBV) infection. The study included 115 patients with DM2 hospitalized in the Internal Ward of the Masovian Specialist Hospital in Radom, Poland, who were divided into two groups: EBV-positive and EBV-negative. The levels of MMP-3 and MMP-9 were tested in the serum of patients using the ELISA method, while the presence of EBV in saliva was tested by polymerase chain reaction (PCR). The presented studies showed a significant difference in the concentration of both MMPs in diabetic patients additionally infected with EBV compared to the group of non-infected individuals. It seems that MMPs may be useful biomarkers in the diagnosis, prognosis, and monitoring of diabetes associated with EBV infection