According to the 'hygiene hypothesis', the decreasing incidence of infections in western countries and more recently in developing countries is at the origin of the increasing incidence of both ...autoimmune and allergic diseases. The hygiene hypothesis is based upon epidemiological data, particularly migration studies, showing that subjects migrating from a low-incidence to a high-incidence country acquire the immune disorders with a high incidence at the first generation. However, these data and others showing a correlation between high disease incidence and high socio-economic level do not prove a causal link between infections and immune disorders. Proof of principle of the hygiene hypothesis is brought by animal models and to a lesser degree by intervention trials in humans. Underlying mechanisms are multiple and complex. They include decreased consumption of homeostatic factors and immunoregulation, involving various regulatory T cell subsets and Toll-like receptor stimulation. These mechanisms could originate, to some extent, from changes in microbiota caused by changes in lifestyle, particularly in inflammatory bowel diseases. Taken together, these data open new therapeutic perspectives in the prevention of autoimmune and allergic diseases.
Using DNA sequences 5' to open reading frames, we have constructed green fluorescent protein (GFP) fusions and generated spatial and temporal tissue expression profiles for 1,886 specific genes in ...the nematode Caenorhabditis elegans. This effort encompasses about 10% of all genes identified in this organism. GFP-expressing wild-type animals were analyzed at each stage of development from embryo to adult. We have identified 5' DNA regions regulating expression at all developmental stages and in 38 different cell and tissue types in this organism. Among the regulatory regions identified are sequences that regulate expression in all cells, in specific tissues, in combinations of tissues, and in single cells. Most of the genes we have examined in C. elegans have human orthologs. All the images and expression pattern data generated by this project are available at WormAtlas (http://gfpweb.aecom.yu.edu/index) and through WormBase (http://www.wormbase.org).
Anti-angiogenic therapies for cancer such as VEGF neutralizing antibody bevacizumab have limited durability. While mechanisms of resistance remain undefined, it is likely that acquired resistance to ...anti-angiogenic therapy will involve alterations of the tumor microenvironment. We confirmed increased tumor-associated macrophages in bevacizumab-resistant glioblastoma patient specimens and two novel glioblastoma xenograft models of bevacizumab resistance. Microarray analysis suggested downregulated macrophage migration inhibitory factor (MIF) to be the most pertinent mediator of increased macrophages. Bevacizumab-resistant patient glioblastomas and both novel xenograft models of resistance had less MIF than bevacizumab-naive tumors, and harbored more M2/protumoral macrophages that specifically localized to the tumor edge. Xenografts expressing MIF-shRNA grew more rapidly with greater angiogenesis and had macrophages localizing to the tumor edge which were more prevalent and proliferative, and displayed M2 polarization, whereas bevacizumab-resistant xenografts transduced to upregulate MIF exhibited the opposite changes. Bone marrow-derived macrophage were polarized to an M2 phenotype in the presence of condition-media derived from bevacizumab-resistant xenograft-derived cells, while recombinant MIF drove M1 polarization. Media from macrophages exposed to bevacizumab-resistant tumor cell conditioned media increased glioma cell proliferation compared with media from macrophages exposed to bevacizumab-responsive tumor cell media, suggesting that macrophage polarization in bevacizumab-resistant xenografts is the source of their aggressive biology and results from a secreted factor. Two mechanisms of bevacizumab-induced MIF reduction were identified: (1) bevacizumab bound MIF and blocked MIF-induced M1 polarization of macrophages; and (2) VEGF increased glioma MIF production in a VEGFR2-dependent manner, suggesting that bevacizumab-induced VEGF depletion would downregulate MIF. Site-directed biopsies revealed enriched MIF and VEGF at the enhancing edge in bevacizumab-naive patients. This MIF enrichment was lost in bevacizumab-resistant glioblastomas, driving a tumor edge M1-to-M2 transition. Thus, bevacizumab resistance is driven by reduced MIF at the tumor edge causing proliferative expansion of M2 macrophages, which in turn promotes tumor growth.
Gaseous by-products generated by surgical devices – collectively referred to as ‘surgical smoke’ – present the hazard of transmitting infective viruses from patients to surgical teams. However, ...insufficient evidence exists to evaluate and mitigate the risks of SARS-CoV-2 transmission via surgical smoke.
To demonstrate the existence and infectivity of human coronavirus RNA in surgical smoke using a model experiment and to evaluate the possibility of lowering transmission risk by filtration through a surgical mask.
Pelleted HeLa-ACE2-TMPRSS2 cells infected with human coronavirus were incised by electric scalpel and ultrasonic scalpel, separately. A vacuum system was used to obtain surgical smoke in the form of hydrosol. Reverse transcription–quantitative polymerase chain reaction was used to analyse samples for the presence of viral RNA, and infectivity was determined through plaque assay. Furthermore, a surgical mask was placed centrally in the vacuum line to evaluate its ability to filter viral RNA present in the surgical smoke.
In this model, 1/106 to 1/105 of the viral RNA contained in the incision target was detected in the collected surgical smoke. The virus present in the smoke was unable to induce plaque formation in cultured cells. In addition, filtration of surgical smoke through a surgical mask effectively reduced the amount of viral RNA by at least 99.80%.
This study demonstrated that surgical smoke may carry human coronavirus, though viral infectivity was considerably reduced. In clinical settings, surgical mask filtration should provide sufficient additional protection against potential coronavirus, including SARS-CoV-2, infection facilitated by surgical smoke.
No-tillage (NT) cropping systems develop distinct soil ecosystems characterized by a diverse soil fauna and slow fungal decomposition. However, nematode community analyses sometimes fail to detect ...these characteristics because the treatment before study or the sampling period is too short or the studies are not comprehensive. Different nematode taxa may occur depending on the geographic region and soil type, thereby affecting the usefulness of nematode analyses for soil biological assessment. However, studies in Asia are scarce. Thus, in this 2-year study, we compared nematode populations, community structures, and soil physicochemical properties between long-term NT and conventional tillage (CT) treatments combined with chemical (CF), organic (OF), or no (NF) fertilizer treatments in a Japanese soybean field. We then examined whether nematode diversity and community indices could detect differences among the treatments in the Japanese andosols. Although the effects of tillage on nematode densities were significant, the overall trend in NT–CT differences was not clear, except for omnivores and
Meloidogyne. The effects of tillage on nematode diversity and community indices were apparent: diversity indices, maturity index (MI) and related indices, structure index, and channel index were higher, whereas enrichment index (EI) was lower in NT because of higher densities of K-strategy taxa, fungal and facultative root feeders, and lower densities of r-strategy bacterial feeders. Fertilizer treatments also affected nematode densities: most feeding groups were less abundant in NF and predatory nematodes were more abundant in OF than in other treatments. OF increased nematode diversity via an increase in microbivorous and predaceous nematodes. However, the effects of fertilizer on most community indices were not apparent. Interactions between tillage and fertilizer effects were significant for
Pratylenchus and total nematode densities, MI, and EI. Among the soil properties differing among treatments, Ca and Mg content, cation exchange capacity, and percent total nitrogen affected nematode community structure. In conclusion, nematode community analyses using index calculations are useful for assessing soil biological properties under different tillage treatments in Japanese andosols, as well as in soil types in other countries. However, index calculations were less sensitive at detecting fertilizer treatment effects, probably because of simultaneous increases in r- and K-strategy nematodes and OF compost that was too decomposed. Other community analyses such as indicator species analysis or diversity evaluations should be used to detect fertilizer effects.
Abstract
Background
Presenteeism is an important factor in workers’ health. However, few studies have examined how variables such as socio-economic status, health status, workplace status and health ...literacy correlate with and affect presenteeism.
Aims
To assess the correlates of presenteeism with a focus on health-related factors, work-related factors and health literacy.
Methods
We conducted a cross-sectional study of 2914 Japanese workers from one company. We used a self-administered questionnaire to assess socio-demographic characteristics, health status, work environment, presenteeism and health literacy.
Results
Forty-one per cent of participants were under 40 years of age and 70% were male. We found that 59% of the participants were at high risk of presenteeism. Presenteeism was associated with sex, age, household income, marital status, health-related factors (i.e. self-rated health status, dietary choices, exercise habits), work-related factors (i.e. workplace support, job demands, job control) and health literacy. Logistic regression analyses indicated that presenteeism was associated with self-rated health status, overtime hours, workplace support, job demands, job control and health literacy after adjusting for sex, age and income.
Conclusions
Health-related factors, work-related factors and health literacy are all associated with presenteeism. Improving the workplace environment, especially factors such as overtime working hours, workplace support, job demands and job control, and increasing health literacy may reduce presenteeism among general office workers.
Although there are some new criteria for human epidermal growth factor receptor 2 (HER2) expression with immunohistochemistry/fluorescence in situ hybridisation (IHC/FISH) in gastric cancer, the ...method is still ambiguous and is somewhat dependent on the subjective qualities of the evaluator.
We used droplet digital polymerase chain reaction (ddPCR) to evaluate HER2 amplification in formalin-fixed and paraffin-embedded (FFPE) samples and cell-free serum circulating tumour DNA (ctDNA) in 25 patients with gastric cancer.
The concordance rate of HER2 amplification examined in FFPE samples with ddPCR and IHC/FISH was 92% (23 out of 25). The concordance rate of FFPE with ctDNA was not high (62.5%); however, patients who were HER2-positive by ctDNA had significantly shorter survival compared with HER2-negative patients.
Our results demonstrated that this ddPCR method was as effective as IHC/FISH and therefore might become a standard method for analysing not only FFPE but also ctDNA.
Duchenne muscular dystrophy (DMD) is the most common form of the progressive muscular dystrophies characterized by defects of the dystrophin gene. Although primarily characterized by degeneration of ...the limb muscles, cardiomyopathy is a major cause of death. Therefore, the development of curative modalities such as gene therapy is imperative. We evaluated the cardiomyopathic features of mdx mice to observe improvements in response to intravenous administration of recombinant adeno-associated virus (AAV) type 9 encoding microdystrophin. The myocardium was extensively transduced with microdystrophin to significantly prevent the development of fibrosis, and expression persisted for the duration of the study. Intraventricular conduction patterns, such as the QRS complex duration and S/R ratio in electrocardiography, were also corrected, indicating that the transduced microdystrophin has a protective effect on the dystrophin-deficient myocardium. Furthermore, BNP and ANP levels were reduced to normal, suggesting the absence of cardiac dysfunction. In aged mice, prevention of ectopic beats as well as echocardiographic amelioration was also demonstrated with improved exercise performance. These findings indicate that AAV-mediated cardiac transduction with microdystrophin might be a promising therapeutic strategy for the treatment of dystrophin-deficient cardiomyopathy.
PDF
