Impacts of COVID-19 and social isolation on academic staff and students at universities: a cross-sectional study.

BACKGROUND: "The impacts of the Coronavirus Disease 2019 (COVID-19) pandemic and the shutdown it triggered at universities across the world, led to a great degree of social isolation among university staff and students. The aim of this study was to identify the perceived consequences of this on staff and their work and on students and their studies at universities. METHOD: The study used a variety of methods, which involved an on-line survey on the influences of social isolation using a non-probability sampling. More specifically, two techniques were used, namely a convenience sampling (i.e. involving members of the academic community, which are easy to reach by the study team), supported by a snow ball sampling (recruiting respondents among acquaintances of the participants). A total of 711 questionnaires from 41 countries were received. Descriptive statistics were deployed to analyse trends and to identify socio-demographic differences. Inferential statistics were used to assess significant differences among the geographical regions, work areas and other socio-demographic factors related to impacts of social isolation of university staff and students. RESULTS: The study reveals that 90% of the respondents have been affected by the shutdown and unable to perform normal work or studies at their institution for between 1 week to 2 months. While 70% of the respondents perceive negative impacts of COVID 19 on their work or studies, more than 60% of them value the additional time that they have had indoors with families and others. . CONCLUSIONS: While the majority of the respondents agree that they suffered from the lack of social interaction and communication during the social distancing/isolation, there were significant differences in the reactions to the lockdowns between academic staff and students. There are also differences in the degree of influence of some of the problems, when compared across geographical regions. In addition to policy actions that may be deployed, further research on innovative methods of teaching and communication with students is needed in order to allow staff and students to better cope with social isolation in cases of new or recurring pandemics.

The Puzzling Potential of Carbon Nanomaterials: General Properties, Application, and Toxicity.

Being a member of the nanofamily, carbon nanomaterials exhibit specific properties that mostly arise from their small size. They have proved to be very promising for application in the technical and biomedical field. A wide spectrum of use implies the inevitable presence of carbon nanomaterials in the environment, thus potentially endangering their whole nature. Although scientists worldwide have conducted research investigating the impact of these materials, it is evident that there are still significant gaps concerning the knowledge of their mechanisms, as well as the prolonged and chronic exposure and effects. This manuscript summarizes the most prominent representatives of carbon nanomaterial groups, giving a brief review of their general physico-chemical properties, the most common use, and toxicity profiles. Toxicity was presented through genotoxicity and the activation of the cell signaling pathways, both including in vitro and in vivo models, mechanisms, and the consequential outcomes. Moreover, the acute toxicity of fullerenol, as one of the most commonly investigated members, was briefly presented in the final part of this review. Thinking small can greatly help us improve our lives, but also obliges us to deeply and comprehensively investigate all the possible consequences that could arise from our pure-hearted scientific ambitions and work.

Nanoformulations of doxorubicin: how far have we come and where do we go from here?

Nanotechnology, focused on discovery and development of new pharmaceutical products is known as nanopharmacology, and one research area this branch is engaged in are nanopharmaceuticals. The importance of being nano has been particularly emphasized in scientific areas dealing with nanomedicine and nanopharmaceuticals. Nanopharmaceuticals, their routes of administration, obstacles and solutions concerning their improved application and enhanced efficacy have been briefly yet comprehensively described. Cancer is one of the leading causes of death worldwide and evergrowing number of scientific research on the topic only confirms that the needs have not been completed yet and that there is a wide platform for improvement. This is undoubtedly true for nanoformulations of an anticancer drug doxorubicin, where various nanocarrriers were given an important role to reduce the drug toxicity, while the efficacy of the drug was supposed to be retained or preferably enhanced. Therefore, we present an interdisciplinary comprehensive overview of interdisciplinary nature on nanopharmaceuticals based on doxorubicin and its nanoformulations with valuable information concerning trends, obstacles and prospective of nanopharmaceuticals development, mode of activity of sole drug doxorubicin and its nanoformulations based on different nanocarriers, their brief descriptions of biological activity through assessing in vitro and in vivo behavior.

Hepatoprotective effect of fullerenol/doxorubicin nanocomposite in acute treatment of healthy rats.

In our recent studies we have designed fullerenol/doxorubicin nanocomposite (FNP/DOX) as the new drug nanocarrier. This research has demonstrated that this novel nanocomposite has had better implications on the liver tissue in vivo (Wistar rats treated intraperitoneally), than treatment based only on DOX. FNP/DOX has been characterised by DLS, TEM and AFM measurements which have shown that DOX loaded onto FNP did not influence fullerenol nanoparticle's size. FNP/DOX affected oxidative status in blood causing a significant decrease of catalase and SOD activity in comparison to DOX, implicating the reduction in oxidative stress. qRT-PCR results on the mRNA level of antioxidative enzymes (catalase and MnSOD) revealed that the effect of oxidative stress is significantly reduced by the treatment with FNP/DOX (p < .05). The ultrastructural analysis of the liver tissue has revealed that FNP/DOX nanocomposite generated considerably less damage in the liver tissue, than DOX applied at the same dose. Hence, our results have indicated that FNP, within FNP/DOX nanocomposite, exhibits protective effects to the liver tissue of the healthy rats.

Survey of T-2/HT-2 toxins in unprocessed cereals, food and feed coming from Croatia and Bosnia & Herzegovina.

The aim of this study was to investigate into the level of T-2/HT-2 toxins in different unprocessed cereals (n=201), as well as in marketed cereal-based products (n=58), feed components (n=191) and feedstuffs (n=91) coming from Croatia and Bosnia & Herzegovina. The number of positive samples of unprocessed cereals for food production (>LOD) ranged from 30.4% in barley to 68.8% in oat whereas for feed components ranged from 26.9% in wheat to 86.1% in oat. The maximal values found in unprocessed oat and oat-based feed components were 304.2µg/kg and 521.0µg/kg, respectively. As for final products, the highest T-2/HT-2 concentrations were determined in oat flakes (89.4µg/kg) and calf feed (129.3µg/kg). Despite of the increased T-2/HT-2 concentrations found in some of the samples, the obtained values were unanimously lower than the indicative levels given as recommendations above which further investigations should be necessary performed.

Fullerenol/doxorubicin nanocomposite mitigates acute oxidative stress and modulates apoptosis in myocardial tissue.

Fullerenol (C60(OH)24) is present in aqueous solutions in the form of polyanion nanoparticles with particles' size distribution within the range from 15 to 42 nm. In this research it is assumed that these features could enable fullerenol nanoparticles (FNPs) to bind positively charged molecules like doxorubicin (DOX) and serve as drug carriers. Considering this, fullerenol/doxorubicin nanocomposite (FNP/DOX) is formed and characterized by ultra-performance liquid chromatography tandem mass spectrometry, dynamic light scattering, atomic force microscopy and transmission electron microscopy. Measurements have shown that DOX did not significantly affect particle size (23 nm). It is also assumed that FNP/DOX could reduce the acute cardiotoxic effects of DOX in vivo (Wistar rats treated i.p.). In this study, quantitative real time polymerase chain reaction results have shown that treatment with DOX alone caused significant increase in mRNA levels of catalase (p < 0.05) enzyme indicating the presence of oxidative stress. This effect is significantly reduced by the treatment with FNP/DOX (p < 0.05). Furthermore, mRNA levels of antiapoptotic enzyme (Bcl-2) are significantly increased (p < 0.05) in all treated groups, particularly where FNP/DOX was applied, suggesting cell resistance to apoptosis. Moreover, ultrastructural analysis has shown the absence of myelin figures within the mitochondria in the heart tissue with FNP/DOX treatment, indicating reduction of oxidative stress. Hence, our results have implied that FNP/DOX is generally less harmful to the heart compared to DOX.

Citrinin in cereals and feedstuffs coming from Croatia and Bosnia & Herzegovina.

The aim of this study was to investigate the occurrence of citrinin in different cereals (n = 341) and feedstuffs (n = 67) coming from farms and feed factories established in Croatia and Bosnia & Herzegovina. The highest mean citrinin concentration (103 ± 102 µg/kg) was observed in cereals sampled in Bosnia & Herzegovina during 2014, although significantly different levels between the two countries were not observed. Across the cereal samples, the maximal citrinin concentration was determined in wheat (429 µg/kg), while across the feedstuffs, the highest concentration was found in pig feed (63 µg/kg). Despite of the increased citrinin levels found in some samples, especially wheat, the obtained values cannot be compared against the maximum limits, since no such levels are stipulated under the applicable legislation. But, given that data on citrinin are very scarce, they can serve as an indicator of cereal and feed contamination in this part of Europe.

Hepatitis C virus--T-cell responses and viral escape mutations.

Hepatitis C virus (HCV) is a small, enveloped RNA virus and the number of HCV-infected individuals worldwide is estimated to be approximately 170 million. Most HCV infections persist, with up to 80% of all cases leading to chronic hepatitis associated with liver fibrosis, cirrhosis, and hepatocellular carcinoma. HCV-host interactions have a crucial role in viral survival, persistence, pathogenicity of infection, and disease progression. Maintenance of a vigorous, sustained cellular immune response recognizing multiple epitopes is essential for viral clearance. To escape immune surveillance, HCV alters its epitopes so that they are no-longer recognized by T cells and neutralizing antibodies, in addition to interfering with host cell cellular components and signaling pathways. The generation of escape variants is one of the most potent immune evasion strategies utilized by HCV. A large body of evidence suggests that single or multiple mutations within HLA-restricted epitopes contribute to viral immune escape and establishment of viral persistence. Further elucidation of the molecular mechanisms underlying immune escape will aid in the design of novel vaccines and therapeutics for the disease.

Molecular footprints reveal the impact of the protective HLA-A*03 allele in hepatitis C virus infection.

BACKGROUND AND AIMS: CD8 T cells are central to the control of hepatitis C virus (HCV) although the key features of a successful CD8 T cell response remain to be defined. In a cohort of Irish women infected by a single source, a strong association between viral clearance and the human lecucocyte (HLA)-A*03 allele has been described, and the aim of this study was to define the protective nature of the associated CD8 T cell response. METHODS: A sequence-led approach was used to identify HLA-A*03-restricted epitopes. We examine the CD8 T cell response associated with this gene and address the likely mechanism underpinning this protective effect in this special cohort, using viral sequencing, T cell assays and analysis of fitness of viral mutants. RESULTS: A strong 'HLA footprint' in a novel NS3 epitope (TVYHGAGTK) was observed. A lysine (K) to arginine (R) substitution at position 9 (K1088R) was seen in a significant number of A*03-positive patients (9/12) compared with the control group (1/33, p=0.0003). Threonine (T) was also substituted with alanine (A) at position 8 (T1087A) more frequently in A*03-positive patients (6/12) compared with controls (2/33, p=0.01), and the double substitution of TK to AR was also observed predominantly in HLA-A*03-positive patients (p=0.004). Epitope-specific CD8 T cell responses were observed in 60% of patients three decades after exposure and the mutants selected in vivo impacted on recognition in vitro. Using HCV replicons matched to the viral sequences, viral fitness was found to be markedly reduced by the K1088R substitution but restored by the second substitution T1087A. CONCLUSIONS: It is proposed that at least part of the protective effect of HLA-A*03 results from targeting of this key epitope in a functional site: the requirement for two mutations to balance fitness and escape provides an initial host advantage. This study highlights the potential protective impact of common HLA-A alleles against persistent viruses, with important implications for HCV vaccine studies.

Hepatitis C virus targets the T cell secretory machinery as a mechanism of immune evasion.

UNLABELLED: T cell activation and the resultant production of interleukin (IL-2) is a central response of the adaptive immune system to pathogens, such as hepatitis C virus (HCV). HCV uses several mechanisms to evade both the innate and adaptive arms of the immune response. Here we demonstrate that liver biopsy specimens from individuals infected with HCV had significantly lower levels of IL-2 compared with those with other inflammatory liver diseases. Cell culture-grown HCV particles inhibited the production of IL-2 by normal peripheral blood mononuclear cells, as did serum from HCV-infected patients. This process was mediated by the interaction of HCV envelope protein E2 with tetraspanin CD81 coreceptor. HCV E2 attenuated IL-2 production at the level of secretion and not transcription by targeting the translocation of protein kinase C beta (PKCß), which is essential for IL-2 secretion, to lipid raft microdomains. The lipid raft disruptor methyl-ß-cyclodextrin reversed HCV E2-mediated inhibition of IL-2 secretion, but not in the presence of a PKCß-selective inhibitor. HCV E2 further inhibited the secretion of other cytokines, including interferon-γ. CONCLUSION: These data suggest that HCV E2-mediated disruption of the association of PKCß with the cellular secretory machinery represents a novel mechanism for HCV to evade the human immune response and to establish persistent infection.

Effect of immune pressure on hepatitis C virus evolution: insights from a single-source outbreak.

UNLABELLED: The host's immune response to hepatitis C virus (HCV) can result in the selection of characteristic mutations (adaptations) that enable the virus to escape this response. The ability of the virus to mutate at these sites is dependent on the incoming virus, the fitness cost incurred by the mutation, and the benefit to the virus in escaping the response. Studies examining viral adaptation in chronic HCV infection have shown that these characteristic immune escape mutations can be observed at the population level as human leukocyte antigen (HLA)-specific viral polymorphisms. We examined 63 individuals with chronic HCV infection who were infected from a single HCV genotype 1b source. Our aim was to determine the extent to which the host's immune pressure affects HCV diversity and the ways in which the sequence of the incoming virus, including preexisting escape mutations, can influence subsequent mutations in recipients and infection outcomes. CONCLUSION: HCV sequences from these individuals revealed 29 significant associations between specific HLA types within the new hosts and variations within their viruses, which likely represent new viral adaptations. These associations did not overlap with previously reported adaptations for genotypes 1a and 3a and possibly reflected a combination of constraint due to the incoming virus and genetic distance between the strains. However, these sites accounted for only a portion of the sites in which viral diversity was observed in the new hosts. Furthermore, preexisting viral adaptations in the incoming (source) virus likely influenced the outcomes in the new hosts.