Relevance of Circulating Nucleosomes, HMGB1 and sRAGE for Prostate Cancer Diagnosis

Background/Aim: Evasion from cell death occurs in prostate cancer (PCa). We verified whether serum levels of cell death markers can have diagnostic value in PCa. Patients and Methods: A total of 233 men scheduled for prostate biopsy [prostate specific antigen (PSA) level: 2-10 ng/ml] were enrolled. Serum nucleosomes, nucleosomes containing the H3 histone (H3), high mobility group box 1 (HMGB1), and soluble receptor for advanced glycation end products (sRAGE) were analyzed by enzyme immunoassays. Results: There were no differences (p>0.05) in nucleosomes, H3, and sRAGE levels between patients with and without PCa or clinically significant PCa (csPCa). HMGB1 had lower levels in PCa patients (p=0.023) and was a predictor of PCa (p=0.047), but not of csPCa (p=0.180). Conclusion: In patients with critical PSA levels between 2-10 ng/ml, HMGB1 had some diagnostic value for overall PCa detection, but it was not predictive of csPCa. Nucleosomes, H3 and sRAGE did not discriminate between PCa or csPCa and controls.The Authors received no financial support for the research, authorship, and/or publication of this article

Comparison of Three Assays for Total and Free PSA Using Hybritech and WHO Calibrations

Background/Aim: Lack of interchangeability between prostate-specific antigen (PSA) assays could have a clinical impact. We compared PSA assays from different manufacturers and calibrations. Patients and Methods: A total of 233 men who underwent prostate biopsy (PSA: 2-10 ng/ml; Beckman Coulter Access® Hybritech® as reference) were enrolled. Total (tPSA) and free PSA (fPSA) were also measured using the Roche cobas® and the Abbott Architect® methods. Results: Roche tPSA values were ≈1% higher than Beckman, while Abbott values were ≈5% lower. Roche had the highest diagnostic sensitivity (92%) compared to Beckman Coulter (87%) and Abbott (85%). Roche fPSA was ≈3% lower and Abbott ≈17% higher than that of Beckman. For the percentage of fPSA, Roche had the highest sensitivity (98%). Conclusion: Roche cobas® and Beckman Coulter Access® Hybritech® tPSA were almost interchangeable. While the agreement was acceptable for tPSA, this did not happen with fPSA and greater efforts for harmonization are required

Factors influencing sleep quality of people in an intensive care unit

Introdução: O sono desempenha um papel fundamental na manutenção de uma boa saúde física e mental. As unidades de cuidados intensivos, devido à sua estrutura e funcionalidade, são locais propícios à alteração do padrão de sono dos pacientes aí internados, contribuindo para a sua privação. Todavia, existem factores nestas unidades que influenciam a qualidade do sono destes pacientes e que podem ser minimizados e/ou modificados pelas equipes de saúde multidisciplinares. Objectivo: Identificar quais os factores que influenciam a qualidade do sono da pessoa internada em unidade de cuidados intensivos. Material e método: Pesquisa de revisão sistemática. Para a sua elaboração precedeu-se à leitura de artigos existentes na base de dados EBSCO host entre os anos 2011 a 2016, obtendo-se um total de 84 artigos, tendo sido seleccionados 4 para estudo. Resultados: A privação do sono ocorre frequentemente em unidades de cuidados intensivos e decorre da existência de determinados factores, como a evidência científica demonstra, tais como o ruído, a luminosidade as actividades desempenhadas pelos próprios profissionais de saúde, sobretudo os enfermeiros. Conclusão: Os factores apontados prejudicam a qualidade de sono do paciente, entretanto, são por vezes descurados. É fundamental que as equipes de saúde que atuam nestas unidades desenvolvam protocolos ou bundles sobre a qualidade do sono destes pacientesinfo:eu-repo/semantics/publishedVersio

Therapeutic strategies for IVD regeneration through hyaluronan/SDF-1-based hydrogel and intravenous administration of MSCs

Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation.Funding: This research was funded by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia (IUD/BIM/04293/2019) and by EUROSPINE TRF (2017_05)

Paradoxical effects of Worrisome Thoughts Suppression: the influence of depressive mood

Thought suppression increases the persistence of unwanted idiosyncratic worries thoughts when individuals try to suppress them. The failure of suppression may contribute to the development and maintenance of emotional disorders. Depressive people seem particulary prone to engage in unsuccessful mental control strategies such as thought suppression. Worry has been reported to be elevated in depressed individuals and a dysphoric mood may also contribute for the failure of suppression. No studies examine, however, the suppression of worisome thoughts in individuals with depressive symptoms. To investigate the suppression effects of worrisome thoughts, 46 participants were selected according to the cut-off score of a depressive symptomatology scale and they were divided in two groups (subclinical and nonclinical group). All the individuals took part in an experimental paradigm of thought suppression. The results of the mixed factorial analysis of variance revealed an increased frequency of worrisome thoughts during the suppression phase on depending of the depressive symptoms. These findings confirm that depressive mood can reduce the success of suppression.info:eu-repo/semantics/publishedVersio

Validation of a fluorescence in situ hybridization method using peptide nucleic acid probes for detection of helicobacter pylori clarithromycin resistance in gastric biopsy specimens

Here, we evaluated a previously established peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) method as a new diagnostic test for Helicobacter pylori clarithromycin resistance detection in paraffin-embedded gastric biopsy specimens. Both a retrospective study and a prospective cohort study were conducted to evaluate the specificity and sensitivity of a PNA-FISH method to determine H. pylori clarithromycin resistance. In the retrospective study (n 30 patients), full agreement between PNA-FISH and PCR-sequencing was observed. Compared to the reference method (culture followed by Etest), the specificity and sensitivity of PNA-FISH were 90.9% (95% confidence interval [CI], 57.1% to 99.5%) and 84.2% (95% CI, 59.5% to 95.8%), respectively. In the prospective cohort (n 93 patients), 21 cases were positive by culture. For the patients harboring clarithromycin- resistant H. pylori, the method showed sensitivity of 80.0% (95% CI, 29.9% to 98.9%) and specificity of 93.8% (95% CI, 67.7% to 99.7%). These values likely represent underestimations, as some of the discrepant results corresponded to patients infected by more than one strain. PNA-FISH appears to be a simple, quick, and accurate method for detecting H. pylori clarithromycin resistance in paraffin-embedded biopsy specimens. It is also the only one of the methods assessed here that allows direct and specific visualization of this microorganism within the biopsy specimens, a characteristic that allowed the observation that cells of different H. pylori strains can subsist in very close proximity in the stomach

Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota

Objective Gastric carcinoma development is triggered by Helicobacter pylori. Chronic H. pylori infection leads to reduced acid secretion, which may allow the growth of a different gastric bacterial community. This change in the microbiome may increase aggression to the gastric mucosa and contribute to malignancy. Our aim was to evaluate the composition of the gastric microbiota in chronic gastritis and in gastric carcinoma. Design The gastric microbiota was retrospectively investigated in 54 patients with gastric carcinoma and 81 patients with chronic gastritis by 16S rRNA gene profiling, using next-generation sequencing. Differences in microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Associations between the most relevant taxa and clinical diagnosis were validated by real-time quantitative PCR. Predictive functional profiling of microbial communities was obtained with PICRUSt. Results The gastric carcinoma microbiota was characterised by reduced microbial diversity, by decreased abundance of Helicobacter and by the enrichment of other bacterial genera, mostly represented by intestinal commensals. The combination of these taxa into a microbial dysbiosis index revealed that dysbiosis has excellent capacity to discriminate between gastritis and gastric carcinoma. Analysis of the functional features of the microbiota was compatible with the presence of a nitrosating microbial community in carcinoma. The major observations were confirmed in validation cohorts from different geographic origins. Conclusions Detailed analysis of the gastric microbiota revealed for the first time that patients with gastric carcinoma exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of patients with chronic gastritis.This research was supported by a Worldwide Cancer Research grant to CF and JCM (Reference 16-1352). RMF, JPM and IPR have fellowships from Fundacao para a Ciencia e a Tecnologia (FCT; SFRH/BPD/84084/2012, PD/BD/114014/2015 and SFRH/BD/110803/2015, respectively) through Programa Operacional Capital Humano (POCH) and the European Union. JPM's fellowship is in the framework of FCT's PhD Programme BiotechHealth (Ref PD/0016/2012). i3S-Instituto de Investigacao e Inovacao em Saude is funded by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through Fundacao para a Ciencia e a Tecnologia (FCT)/Ministerio da Ciencia, Tecnologia e Inovacao (POCI-01-0145-FEDER-007274)

Gap modification of atomically thin boron nitride by phonon mediated interactions

A theory is presented for the modification of bandgaps in atomically thin boron nitride (BN) by attractive interactions mediated through phonons in a polarizable substrate, or in the BN plane. Gap equations are solved, and gap enhancements are found to range up to 70% for dimensionless electron-phonon coupling \lambda=1, indicating that a proportion of the measured BN bandgap may have a phonon origin

Impact of host DNA and sequencing depth on the taxonomic resolution of whole metagenome sequencing for microbiome analysis

The amount of host DNA poses a major challenge to metagenome analysis. However, there is no guidance on the levels of host DNA, nor on the depth of sequencing needed to acquire meaningful information from whole metagenome sequencing (WMS). Here, we evaluated the impact of a wide range of amounts of host DNA and sequencing depths on microbiome taxonomic profiling using WMS. Synthetic samples with increasing levels of host DNA were created by spiking DNA of a mock bacterial community, with DNA from a mouse-derived cell line. Taxonomic analysis revealed that increasing proportions of host DNA led to decreased sensitivity in detecting very low and low abundant species. Reduction of sequencing depth had major impact on the sensitivity of WMS for profiling samples with 90% host DNA, increasing the number of undetected species. Finally, analysis of simulated datasets with fixed depth of 10 million reads confirmed that microbiome profiling becomes more inaccurate as the level of host DNA increases in a sample. In conclusion, samples with high amounts of host DNA coupled with reduced sequencing depths, decrease WMS coverage for characterization of the microbiome. This study highlights the importance of carefully considering these aspects in the design of WMS experiments to maximize microbiome analyses.This work was supported by European Regional Development Funds (ERDF) funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by FCT – Fundação para a Ciência e a Tecnologia (POCI-01-0145-FEDER-032532). JP-M and IP-R have fellowships from FCT (PD/BD/114014/2015 and SFRH/BD/110803/2015, respectively) through Programa Operacional Capital Humano (POCH) and the European Social Fund. JP-M’s have fellowship from the framework of FCT’s Ph.D. Program Biotech Health (Ref. PD/0016/2012)