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One full year following first the event of COVID-19 inside Ghana: epidemiology, problems and also achievements.
DNA double strand breaks (DSBs) are the most threatening type of DNA lesions and must be repaired properly in order to inhibit severe diseases and cell death. There are four major repair pathways for DSBs non-homologous end joining (NHEJ), homologous recombination (HR), single strand annealing (SSA) and alternative end joining (alt-EJ). Cells choose repair pathway depending on the cell cycle phase and the length of 3' end of the DNA when DSBs are generated. Blunt and short regions of the 5' or 3' overhang DNA are repaired by NHEJ, which uses direct ligation or limited resection processing of the broken DNA end. In contrast, HR, SSA and alt-EJ use the resected DNA generated by the MRN (MRE11-RAD50-NBS1) complex and C-terminal binding protein interacting protein (CtIP) activated during the S and G2 phases. Here, we review recent findings on each repair pathway and the choice of repair mechanism and highlight the role of mismatch repair (MMR) protein in HR.Alternariol monomethyl ether (AME), a typical Alternaria toxin, has often been detected in grains. We have measured the general toxicity and genotoxicity of AME with a 28-day multi-endpoint (Pig-a assay + in vivo micronucleus [MN] test + comet assay) platform. Male Sprague-Dawley rats were administered AME (1.84, 3.67, or 7.35 μg/kg body weight/day), N-Ethyl-N-nitrosourea (40 mg/kg body weight/day), or corn oil by gavage for 28 consecutive days. Another group (AME-high-dose + recovery) was maintained for a further 14 days after the end of the AME administration. Hematology and serum biochemistry results suggested that AME might compromise the immune system. The histopathology results indicated that AME can cause liver (inflammatory cell infiltration, steatosis, and edema), kidney (renal glomerular atrophy), and spleen (white pulp atrophy) damage. The genotoxicity results showed that AME can induce gene mutations, chromosome breakage, and DNA damage, but the effects were diminished after the recovery period. According to point-of-departure analysis (BMDL10), the risk to the population of exposure to AME cannot be ignored and further assessment is needed.The study aimed to evaluate the micronucleus (MN) frequency in exfoliated buccal cells (EBCs) of 256 6-8-years-old schoolchildren living in a rural area of Salento peninsula (Southern Italy) with low anthropogenic pressure and with a normal rate of chronic diseases in order to determine the basal level of MN and identify which factors are able to influence it. Information about the personal data, lifestyles and dietary habits of the children were obtained by the administration of a questionnaire to their parents. The buccal micronucleus cytome assay was performed to evaluate the presence of early genotoxic effects among the children. In addition, the level of environmental exposure was assessed by sampling atmospheric particulate fractions near the schools attended by participants. The association between MN frequency and individual or environmental factors was also assessed. The children had a mean MN frequency of 0.27 ± 0.43‰ (95%CI = 0.22-0.33). This frequency was positively associated with vehicular traffic (OR = 2.99; 95%CI = 1.15-7.74) and negatively associated with a high educational level of the mother (OR = 0.41; 95%CI = 0.18-0.95) and physical exercise (OR = 0.56; 95%CI = 0.32-0.57). Data on genotoxic effects in buccal cells found in this study could be considered as the MN level in a pediatric population not exposed to environmental pollution.The comet assay is a simple technique for measurements of low levels of DNA damage and repair in single cells. However, there is variation in background levels of DNA damage in peripheral blood mononuclear cells (PBMCs). This variation has been documented by inter-laboratory ring-trials where identical samples have been analysed in different laboratories using the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay. The coefficient of variation of background levels of Fpg-sensitive sites was 128 % in the first inter-laboratory validation trial called European Standards Committee on Oxidative DNA Damage. The variation was reduced to 44 % by the end of the project. Subsequent ring-trials by the European Comet Assay Validation Group showed similar inter-laboratory variation in Fpg-sensitive sites in PBMCs (45 %). The lowest inter-laboratory variation in Fpg-sensitive sites in PBMCs was 12 % when using calibration to standardize comet assay descriptors. Introduction of standard comet assay procedures was surprisingly unsuccessful as certain laboratories experienced technical problems using unaccustomed assay conditions. This problem was alleviated by using flexible assay standard conditions rather than a standard protocol in a ring-trial by the hCOMET group. The approach reduced technical problems, but the inter-laboratory variation in Fpg-sensitive sites was not reduced. Fedratinib order The ring-trials have not pinpointed specific assay steps as major determinants of the variation in DNA damage levels. It is likely that small differences in several steps cause inter-laboratory variation. Although this variation in reported DNA damage levels causes concern, ring-trials have also shown that the comet assay is a reliable tool in biomonitoring studies.Triple-negative breast cancer (TNBC) treatment has only limited effect, and it causes a significant number of deaths. Histone deacetylase inhibitors (HDACis) are emerging as promising anti-tumor agents in many types of cancers. We thus hypothesized that 2-hexyl-4-pentynoic acid (HPTA), a novel HDACi, could sensitize TNBC to hydroxyurea (HU, a ribonucleotide reductase inhibitor). In the present study, we investigated the effect of HPTA, alone or in combination with HU on cell survival, DNA double-strand breaks (DSBs), key homologous recombination (HR) repair proteins and cell cycle progression in MDA-MB-468 and MDA-MB-231 human TNBC cell lines. HPTA and HU synergistically inhibited the survival of TNBC cell lines and resulted in the accumulation of DNA double-strand breaks (DSBs). HPTA can sensitize TNBC cells to HU by inhibiting replication protein A2 (RPA2) hyperphosphorylation-mediated HR repair, and lessen cell accumulation in S-phase by inhibiting ATR-CHK1 signaling pathway. Taken together, our data suggested that HPTA enhances HU therapeutic effect by blocking the HR repair and regulating cell cycle progression in TNBC.Acrylamide is formed during the heating of food and is also found in cigarette smoke. It is classified by the International Agency for Research on Cancer as a probable human carcinogen (Group 2A). Glycidamide, an epoxide metabolite of acrylamide, is implicated in the mechanism of acrylamide carcinogenicity. Acrylamide causes oxidative DNA damage in target organs. We sought to clarify the mechanism of acrylamide-induced oxidative DNA damage by investigating site-specific DNA damage and reactive oxygen species (ROS) generation by a putative metabolite of acrylamide, acrylohydroxamic acid (AA). Our results, using 32P-5'-end-labeled DNA fragments, indicated that, although AA alone did not damage DNA, AA treated with amidase induced DNA damage in the presence of Cu(II). DNA cleavage occurred preferentially at T and C, and particularly at T in 5'-TG-3' sequences, and the DNA cleavage pattern was similar to that of hydroxylamine. The DNA damage was inhibited by methional, catalase, and Cu(I)-chelator bathocuproine, suggesting that H2O2 and Cu(I) are involved in the mechanism of DNA damage induced by AA treated with amidase. In addition, amidase-treated AA increased 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in calf thymus DNA, an indicator of oxidative DNA damage, in a dose-dependent manner. In conclusion, hydroxylamine, possibly produced from AA treated with amidase, was autoxidized via the Cu(II)/Cu(I) redox cycle and H2O2 generation, suggesting that oxidative DNA damage induced by ROS plays an important role in acrylamide-related carcinogenesis.
This study aimed to investigate how value is defined and measured in existing value assessment frameworks (VAFs) in healthcare.

We searched PubMed, Embase, the Cochrane Library, and Centre for Reviews and Dissemination from 2008 to 2019. We also performed backward citation chaining of included studies and previously published systematic reviews. Studies reporting the development of a VAF in healthcare were included. For each included framework, we extracted and compared the context, target users, intended use, methods used to identify value attributes, description of the attributes, and attribute scoring approaches.

Of the 8151 articles screened, 57 VAFs were included. The value attributes included in 55 VAFs were grouped into 9 categories health benefits (n= 53, 96%), affordability (n= 45, 82%), societal impact (n= 42, 76%), burden of disease (n= 36, 65%), quality of evidence (n= 32, 58%), cost-effectiveness (n= 31, 56%), ethics and equity (n= 27, 49%), unmet needs (n= 21, 38%), and innovation (n= 15, 27%). The remaining 2 VAFs used broad attributes or user-defined attributes. Literature review was the main approach to identify value attributes in 36 VAFs. Patient or public was engaged through the development of only 11 VAFs. Weighting has been used to score 29 VAFs, of which 19 used the methods of multicriteria decision analysis.

There are substantial variations in defining and measuring value. A noticeable weakness of existing VAFs is that patient or public engagement was generally very limited or missing in framework development process. Existing VAFs tend to aggregate multiple value attributes into a single index for decision making.
There are substantial variations in defining and measuring value. A noticeable weakness of existing VAFs is that patient or public engagement was generally very limited or missing in framework development process. Existing VAFs tend to aggregate multiple value attributes into a single index for decision making.
This study aimed to assess the effectiveness of virtual reality (VR) in managing different types of pain in different age groups and to provide evidence for the clinical application of new alternative strategy for pain management.

Electronic databases, including the Cochrane Library, PubMed, EMBASE, and the Web of Science, were searched for studies published up to October 2020. Randomized controlled trials that reported on VR for pain management were included.

A total of 31 randomized controlled trials were included. As for the pain intensity, the increase of visual analog scale score in the VR group was 1.62 scores less than that in the control group. In juvenile patients, the VR group had 1.79 scores lower than that in control group. For adult patients, the VR group had 1.34 scores lower than that in control group. As for other pain-related indicators, the VR group had lower levels of anxiety, lower pain unpleasantness, lower pulse rate, and shorter duration of dressing change and spent less time thinking about pain. Nevertheless, there was no statistical difference in pain tolerance. VR can effectively alleviate acute pain. In terms of chronic low back pain and cancer-related pain, there was no statistical difference between VR therapy and standard therapy.

VR is a feasible alternative therapy for both juveniles and adults in pain management, and it has a greater potential for juveniles. VR can effectively alleviate acute pain. Nevertheless, VR showed little effectiveness in increasing pain tolerance, which may explain in part the ineffectiveness of VR therapy in pain management for chronic pain.
VR is a feasible alternative therapy for both juveniles and adults in pain management, and it has a greater potential for juveniles. VR can effectively alleviate acute pain. Nevertheless, VR showed little effectiveness in increasing pain tolerance, which may explain in part the ineffectiveness of VR therapy in pain management for chronic pain.
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