Cognivitra, a digital solution to support dual-task rehabilitation training

This article focuses on an eHealth application, CogniViTra, to support cognitive and physical training (i.e., dual-task training), which can be done at home with supervision of a health care provider. CogniViTra was designed and implemented to take advantage of an existing Platform of Services supporting a Cognitive Health Ecosystem and comprises several components, including the CogniViTra Box (i.e., the patient terminal equipment), the Virtual Coach to provide assistance, the Game Presentation for the rehabilitation exercises, and the Pose and Gesture Recognition to quantify responses during dual-task training. In terms of validation, a functional prototype was exposed in a highly specialized event related to healthy and active ageing, and key stakeholders were invited to test it and share their insights. Fifty-seven specialists in information-technology-based applications to support healthy and active ageing were involved and the results and indicated that the functional prototype presents good performance in recognizing poses and gestures such as moving the trunk to the left or to the right, and that most of the participants would use or suggest the utilization of CogniViTra. In general, participants considered that CogniViTra is a useful tool and may represent an added value for remote dual-task training.This study has received funding from the European Union under the AAL programme through project CogniViTra (Grant No. AAL-2018-5-115-CP), with national funding support from FCT, ISCIII, and FNR. This presentation reflects the authors’ views, and neither AAL nor the National Funding Agencies are responsible for any use that may be made of the information

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

ATM Limits Incorrect End Utilization during Non-Homologous End Joining of Multiple Chromosome Breaks

Chromosome rearrangements can form when incorrect ends are matched during end joining (EJ) repair of multiple chromosomal double-strand breaks (DSBs). We tested whether the ATM kinase limits chromosome rearrangements via suppressing incorrect end utilization during EJ repair of multiple DSBs. For this, we developed a system for monitoring EJ of two tandem DSBs that can be repaired using correct ends (Proximal-EJ) or incorrect ends (Distal-EJ, which causes loss of the DNA between the DSBs). In this system, two DSBs are induced in a chromosomal reporter by the meganuclease I-SceI. These DSBs are processed into non-cohesive ends by the exonuclease Trex2, which leads to the formation of I-SceI–resistant EJ products during both Proximal-EJ and Distal-EJ. Using this method, we find that genetic or chemical disruption of ATM causes a substantial increase in Distal-EJ, but not Proximal-EJ. We also find that the increase in Distal-EJ caused by ATM disruption is dependent on classical non-homologous end joining (c-NHEJ) factors, specifically DNA-PKcs, Xrcc4, and XLF. We present evidence that Nbs1-deficiency also causes elevated Distal-EJ, but not Proximal-EJ, to a similar degree as ATM-deficiency. In addition, to evaluate the roles of these factors on end processing, we examined Distal-EJ repair junctions. We found that ATM and Xrcc4 limit the length of deletions, whereas Nbs1 and DNA-PKcs promote short deletions. Thus, the regulation of end processing appears distinct from that of end utilization. In summary, we suggest that ATM is important to limit incorrect end utilization during c-NHEJ

Histone H2AX stabilizes broken DNA strands to suppress chromosome breaks and translocations during V(D)J recombination

The H2AX core histone variant is phosphorylated in chromatin around DNA double strand breaks (DSBs) and functions through unknown mechanisms to suppress antigen receptor locus translocations during V(D)J recombination. Formation of chromosomal coding joins and suppression of translocations involves the ataxia telangiectasia mutated and DNA-dependent protein kinase catalytic subunit serine/threonine kinases, each of which phosphorylates H2AX along cleaved antigen receptor loci. Using Abelson transformed pre–B cell lines, we find that H2AX is not required for coding join formation within chromosomal V(D)J recombination substrates. Yet we show that H2AX is phosphorylated along cleaved Igκ DNA strands and prevents their separation in G1 phase cells and their progression into chromosome breaks and translocations after cellular proliferation. We also show that H2AX prevents chromosome breaks emanating from unrepaired RAG endonuclease-generated TCR-α/δ locus coding ends in primary thymocytes. Our data indicate that histone H2AX suppresses translocations during V(D)J recombination by creating chromatin modifications that stabilize disrupted antigen receptor locus DNA strands to prevent their irreversible dissociation. We propose that such H2AX-dependent mechanisms could function at additional chromosomal locations to facilitate the joining of DNA ends generated by other types of DSBs

H2AX phosphorylation at the sites of DNA double-strand breaks in cultivated mammalian cells and tissues

A sequence variant of histone H2A called H2AX is one of the key components of chromatin involved in DNA damage response induced by different genotoxic stresses. Phosphorylated H2AX (γH2AX) is rapidly concentrated in chromatin domains around DNA double-strand breaks (DSBs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress. γH2AX foci could be easily detected in cell nuclei using immunofluorescence microscopy that allows to use γH2AX as a quantitative marker of DSBs in various applications. H2AX is phosphorylated in situ by ATM, ATR, and DNA-PK kinases that have distinct roles in different pathways of DSB repair. The γH2AX serves as a docking site for the accumulation of DNA repair proteins, and after rejoining of DSBs, it is released from chromatin. The molecular mechanism of γH2AX dephosphorylation is not clear. It is complicated and requires the activity of different proteins including phosphatases and chromatin-remodeling complexes. In this review, we summarize recently published data concerning the mechanisms and kinetics of γH2AX loss in normal cells and tissues as well as in those deficient in ATM, DNA-PK, and DSB repair proteins activity. The results of the latest scientific research of the low-dose irradiation phenomenon are presented including the bystander effect and the adaptive response estimated by γH2AX detection in cells and tissues

Polycyclic Aromatic Hydrocarbons in Air

Policiklički aromatski ugljikovodici (PAU) spojevi su koji se sastoje od dva ili više kondenziranih aromatskih prstenova. Nastaju prilikom nepotpunog izgaranja ili pirolize organskih tvari. Dokazano je da neki PAU imaju kancerogena, a neki mutagena svojstva, pa je stoga potrebno kontinuirano pratiti koncentracije PAU u zraku, vodi i tlu, te pokušati sanirati izvore PAU. PAU s dva ili tri aromatska prstena postojani su u plinovitoj fazi, dok se PAU s više aromatskih prstenova nalaze u zraku uglavnom vezani na čestice. Visoke koncentracije PAU prisutne su u atmosferi urbanih područja, a najviše su zimi kada su pojačane emisije iz kućnih ložišta. U ljetno doba koncentracije su niže jer je većina policikličkih aromatskih ugljikovodika nestabilna na visokim temperaturama, a osim toga dolazi do njihove oksidacije i fotooksidacije. Metode mjerenja PAU u zraku uključuju uzorkovanje prosisavanjem na filterski papir ili kruti adsorbens, ekstrakciju i kromatografsku analizu. U ovom radu prikazani su rezultati mjerenja benzo[a]pirena (BaP) kao glavnog predstavnika PAU na nekim lokacijama u svijetu. Razine BaP u svijetu uspoređene su s rezultatima mjerenja provedenim do sada u Hrvatskoj.Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds consisting of two or more condense aromatic rings. They are products of incomplete combustion or pyrolysis of organic matter. Because some PAHs such as Benzo[a]pyrene (BaP) are proven carcinogens and mutagens, it is necessary to continuously monitor their concentrations in the air, water, and soil. PAHs with two or three aromatic rings are stable in the gas phase, while most PAHs with five or more aromatic rings bond to particles. Higher concentrations of PAHs are present in the atmosphere of urban areas, mostly in the winter, due to heating. In the summer, these concentrations drop because most PAHs are unstable at high temperatures and break down by oxidation and photooxidation. Measurements of PAHs in the air include sampling on the filter paper or solid adsorbent, extraction, and chromatographic analysis. This review presents the measurements of BaP in some locations in the world and compares them with the findings in Croatia

Significance of abnormal 53BP1 expression as a novel molecular pathologic parameter of follicular-shaped B-cell lymphoid lesions in human digestive tract

The digestive tract is a common site of extranodal malignant lymphomas (MLs) and benign lymphoid lesions (BLs). TP53-binding protein 1 (53BP1) expression has been widely investigated in class switch recombination but rarely in human lymphoid tissues with respect to tumorigenesis. We previously reported that immunofluorescence (IF) analysis of 53BP1 nuclear foci (NF), reflecting DNA double strand breaks, is useful for estimating genomic instability in different tumor types. In this study, we evaluated the potential of IF-based analysis of 53BP1 expression in differentiating MLs from BLs. We examined 231 biopsied tissue samples of primary MLs and BLs in the digestive tract. The 53BP1 immunoreactivity pattern was determined by multicolor IF. Compared to BLs, MLs showed a high frequency of abnormal 53BP1 expression (p < 0.0001). Statistically, abnormal 53BP1 expression is an effective test for distinguishing follicular lymphomas from BLs (specificity 98.6%, sensitivity 86.8%) and for distinguishing small B-cell lymphomas from BLs (specificity 98.3%, sensitivity 77.6%). Furthermore, a high frequency of abnormal 53BP1 expression was associated with “high-risk” MALT lymphomas, which exhibited t(11;18)(q21;21) (p = 0.0145). Collectively, these results suggest that IF-based analysis of 53BP1 expression in biopsy samples is a promising technique for diagnosing MLs in the digestive system

GC-MS analyses and chemometric processing to discriminate the local and long-distance sources of PAHs associated to atmospheric PM2.5

Purpose . This study presents a procedure to differentiate the local and remote sources of particulate-bound polycyclic aromatic hydrocarbons (PAHs). Methods. Data were collected during an extended PM2.5 sampling campaign (2009–2010) carried out for 1 year in Venice-Mestre, Italy, at three stations with different emissive scenarios: urban, industrial, and semirural background. Diagnostic ratios and factor analysis were initially applied to point out the most probable sources. In a second step, the areal distribution of the identified sources was studied by applying the discriminant analysis on factor scores. Third, samples collected in days with similar atmospheric circulation patterns were grouped using a cluster analysis on wind data. Local contributions to PM2.5 and PAHs were then assessed by interpreting cluster results with chemical data. Results. Results evidenced that significantly lower levels of PM2.5 and PAHs were found when faster winds changed air masses, whereas in presence of scarce ventilation, locally emitted pollutants were trapped and concentrations increased. This way, an estimation of pollutant loads due to local sources can be derived from data collected in days with similar wind patterns. Long-range contributions were detected by a cluster analysis on the air mass back-trajectories. Results revealed that PM2.5 concentrations were relatively high when air masses had passed over the Po Valley. However, external sources do not significantly contribute to the PAHs load. Conclusions. The proposed procedure can be applied to other environments with minor modifications, and the obtained information can be useful to design local and national air pollution control strategies

Cognivitra: An Information Technology-Based Solution to Support Cognitive and Physical Training at Home

Objectives: this article focuses on an information technology-based application, the Cognivitra, to support cognitive and physical training (i.e., dual-task training), which can be done at home with supervision of a health care provider. Cognivitra aims to increase the number and duration of training sessions and to overcome restrictions imposed by the availability of human and physical health care resources, and the aim of the study reported by this article was the assessment of the respective functional prototype. Methods: an observational study was conducted to assess the functional prototype using a peer review approach. The prototype was exposed in a highly specialized event related to healthy and active ageing, and key stakeholders were invited to test it and share their insights, including expectation of use, perception of market value, suggestions for improvement and other comments. Results: the observational study was conducted with 57 specialists in information technology-based applications to support healthy and active ageing, with an average age of 41.5 years. The results indicate that most of the participants would use or suggest the utilization of Cognivitra. Moreover, the participants made positive comments and improvement suggestions that focused on the difficulty level, the system response performance, the intuitiveness of icons and instructions, the user interaction, and the exercise duration. Conclusion: in general participants considered that Cognivitra is a useful tool and may represent an added value for remote dual task training. Although the results of this study were very positive and encouraging, improvements should be implemented before starting tests with real users.This project has received funding from the European Union’s under the AAL programme through project CogniViTra (Grant No. AAL-2018-5- 115-CP), with national funding support from FCT, ISCIII and FNR. This presentation reflects the authors’ views and neither AAL nor the National Funding Agencies are responsible for any use that may be made of the information