CD26/DPPIV and response to hepatitis B vaccination

The prevention of hepatitis B is important, since it is responsible for significant morbidity and mortality around the world. Unfortunately, hepatitis B vaccine does not always induce protective immunity. The lack of immune response to vaccine (non-responders) can depend on individual characteristics. The objective of this study was to correlate the CD26/DPPIV cellular expression and DPPIV serum activity with HBV vaccine response and its possible role as an indicator of immune competence acquisition. We also determined the cellular expression of CD3, CD19, CD56 and CD25 in peripheral blood T lymphocytes. Blood samples were obtained from 28 healthy human volunteers who were enrolled with a vaccination program. There were "responders" (RM = 13) and "non-responders" (NRM = 15), after vaccination. The lymphocyte populations were identified by flow cytometry. DPPIV serum activity was measured fluorimetrically. CD26 expression in responders (55.9 +/- 7.7%) versus in non-responders (51.9 +/- 7.0%) did not show a significant difference. The DPPIV serum activity in responders compared to in non-responder subgroup (59.9 +/- 8.4/50.3 +/- 10.6U/L) showed, however, a significant difference (P < 0.05). The expression of CD3, CD19 and CD56 on peripheral lymphocytes was similar between responders and non-responders. The expression of CD3CD26 (52.2 +/- 8.6%) and CD3CD25 (10.9 +/- 3.8%) in responders versus the expression of CD3CD26 (48.0 +/- 5.7%) and CD3CD25 (8 +/- 4.6%) in non-responders did not show statistically significant difference. CD25 referred as a marker of T lymphocyte activation was increased in responders (15.8 +/- 4.5%) versus in non-responders (10.1 +/- 4.8%), showing a significant difference (P = 0.003). It was, however, impossible to demonstrate an increase in CD3CD25 and CD3CD26 in the responder subgroup. This suggests that different lymphocyte subsets other than T cells are implicated in the response to hepatitis B vaccination

The impact of long dry periods on the aboveground biomass in a tropical forest: 20 years of monitoring

Background Long-term studies of community and population dynamics indicate that abrupt disturbances often catalyse changes in vegetation and carbon stocks. These disturbances include the opening of clearings, rainfall seasonality, and drought, as well as fire and direct human disturbance. Such events may be super-imposed on longer-term trends in disturbance, such as those associated with climate change (heating, drying), as well as resources. Intact neotropical forests have recently experienced increased drought frequency and fire occurrence, on top of pervasive increases in atmospheric CO2 concentrations, but we lack long-term records of responses to such changes especially in the critical transitional areas at the interface of forest and savanna biomes. Here, we present results from 20 years monitoring a valley forest (moist tropical forest outlier) in central Brazil. The forest has experienced multiple drought events and includes plots which have and which have not experienced fire. We focus on how forest structure (stem density and aboveground biomass carbon) and dynamics (stem and biomass mortality and recruitment) have responded to these disturbance regimes. Results Overall, the biomass carbon stock increased due to the growth of the trees already present in the forest, without any increase in the overall number of tree stems. Over time, both recruitment and especially mortality of trees tended to increase, and periods of prolonged drought in particular resulted in increased mortality rates of larger trees. This increased mortality was in turn responsible for a decline in aboveground carbon toward the end of the monitoring period. Conclusion Prolonged droughts influence the mortality of large trees, leading to a decline in aboveground carbon stocks. Here, and in other neotropical forests, recent droughts are capable of shutting down and reversing biomass carbon sinks. These new results add to evidence that anthropogenic climate changes are already adversely impacting tropical forests

InfectionCMA: A Cell MicroArray Approach for Efficient Biomarker Screening in In Vitro Infection Assays

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the scientific community to acquire knowledge in real-time, when total lockdowns and the interruption of flights severely limited access to reagents as the global pandemic became established. This unique reality made researchers aware of the importance of designing efficient in vitro set-ups to evaluate infectious kinetics. Here, we propose a histology-based method to evaluate infection kinetics grounded in cell microarray (CMA) construction, immunocytochemistry and in situ hybridization techniques. We demonstrate that the chip-like organization of the InfectionCMA has several advantages, allowing side-by-side comparisons between diverse cell lines, infection time points, and biomarker expression and cytolocalization evaluation in the same slide. In addition, this methodology has the potential to be easily adapted for drug screening. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding text 1: Funding: The Portuguese Foundation for Science and Technology (FCT) funded this project through the Research4COVID19 projects 109_596696487 and RESEARCH COVID-19 projects Ref. 510. FCT also financed the Ph.D. grant to R.J.P. (SFRH/BD/145217/2019) and M.N. (2020.04720.BD). i3S is supported by FEDER–Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020–Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Inovação in the framework of the project ‘Institute for Research and Innovation in Health Sciences’ (POCI-01-0145-FEDER-007274).; Funding text 2: The Portuguese Foundation for Science and Technology (FCT) funded this project through the Research4COVID19 projects 109_596696487 and RESEARCH COVID-19 projects Ref. 510. FCT also financed the Ph.D. grant to R.J.P. (SFRH/BD/145217/2019) and M.N. (2020.04720.BD). i3S is supported by FEDER?Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020?Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT/Minist?rio da Ci?ncia, Tecnologia e Inova??o in the framework of the project ?Institute for Research and Innovation in Health Sciences? (POCI-01-0145-FEDER-007274)

Hybrid endoscopic thymectomy : combined transesophageal and transthoracic approach in a survival porcine model with cadaver assessment

BACKGROUND: Video-assisted thoracoscopic surgery thymectomy has been used in the treatment of Myastenia Gravis and thymomas (coexisting or not). In natural orifice transluminal endoscopic surgery, new approaches to the thorax are emerging as alternatives to the classic transthoracic endoscopic surgery. The aim of this study was to assess the feasibility and reliability of hybrid endoscopic thymectomy (HET) using a combined transthoracic and transesophageal approach. METHODS: Twelve consecutive in vivo experiments were undertaken in the porcine model (4 acute and 8 survival). The same procedure was assessed in a human cadaver afterward. For HET, an 11-mm trocar was inserted in the 2nd intercostal space in the left anterior axillary line. A 0° 10-mm thoracoscope with a 5-mm working channel was introduced. Transesophageal access was created through a submucosal tunnel using a flexible gastroscope with a single working channel introduced through the mouth. Using both flexible (gastroscope) and rigid (thoracoscope) instruments, the mediastinum was opened; the thymus was dissected, and the vessels were ligated using electrocautery alone. RESULTS: Submucosal tunnel creation and esophagotomy were performed safely without incidents in all animals. Complete thymectomy was achieved in all experiments. All animals in the survival group lived for 14 days. Thoracoscopic and postmortem examination revealed pleural adhesions on site of the surgical procedure with no signs of infection. Histological analysis of the proximal third of the esophagus revealed complete cicatrization of both mucosal defect and myotomy site. In the human cadaver, we were able to replicate all the procedure even though we were not able to identify the thymus. CONCLUSIONS: Hybrid endoscopic thymectomy is feasible and reliable. HET could be regarded as a possible alternative to classic thoracoscopic approach for patients requiring thymectomy.This project was funded by the FCT Grants project PTDC/SAU-OSM/105578/2008

TERTp mutations and p53 expression in head and neck cutaneous basal cell carcinomas with different aggressive features

Cutaneous basal cell carcinoma (cBCC) is an economic burden to health services, due to its great morbidity and increasing incidence in old people. Infiltrative cBCCs and cBCCs with micronodular pattern are considered as more aggressive. The role of p53 expression and TERTp mutation on cBCC behavior remains to be clarified. We aimed to assess TERTp mutations and p53 expression in relation to the cBCC histological subtype in a cohort of patients referred to an ENT Department of a tertiary Hospital of Northern Portugal. We performed a retrospective clinicopathological and histological review of the head and neck cBCCs followed-up at the otorhinolaryngology department of Trás-os-Montes e Alto Douro hospital (January 2007–June 2018). We assessed TERTp mutations in 142 cBCCs and p53 protein expression, through immunohistochemistry, in 157 cBCCs. We detected TERTp mutations in 43.7% of cBCCs and p53 overexpression in 60.5% of cBCCs. We spotted association of p53 overexpression and TERTp mutation with necrosis. In the infitrative-growth pattern cBCCs, there was no significant association with the clinical and histological features evaluated, except for necrosis. In the indolent-growth cBCCs, we identified a significant association of TERTp mutation status with female sex, necrosis, multiple cBCCs, and p53 positive expression. Our results suggest that TERTp mutation may be useful to identify more aggressive features in the indolent-growth pattern cBCCs (nodular and superficial subtypes). Further studies with larger cohorts are warranted to clarify the relevance of TERTp mutation in cBCCs.This study was supported by FCT, the Portuguese Foundation for Science and Technology through a Ph.D. Grant to SM (SFRH/BD/137802/2018). This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnolo-gia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). Additional funding by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalization—COMPETE2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390: CANCEL STEM and from the FCT, under the project POCI-01-0145-FEDER-031438: The other faces of telomerase: Looking beyond tumour immortalization (PDTC/MED-ONC/31438/2017)

Tracheal adenoid cystic carcinoma masquerading asthma: A case report

BACKGROUND: Tracheal tumors are often misdiagnosed as asthma and are treated with inhaled steroids and bronchodilators without resolution. CASE PRESENTATION: Here, a patient with tracheal adenoid cystic carcinoma who had been previously diagnosed with difficult asthma was reported. The possibility of the presence of localized airway obstruction was raised when the flow-volume curve suggesting fixed airway obstruction, was obtained. CONCLUSION: The presenting case report emphasizes the fact that not all wheezes are asthma. It is critical to bear in mind that if a patient does not respond to appropriate anti-asthma therapy, localized obstructions should be ruled out before establishing the diagnosis of asthma

Serum amyloid A proteins reduce bone mass during mycobacterial infections

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFN gamma- and TNF alpha-dependent manner. IFN gamma produced during infection enhanced macrophage TNF alpha secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.This article is a result of the project HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (NORTE-01-0145-FEDER-000039), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was supported by KOG-202108-00929 from the European Haematology Society, awarded to AG. Work in the MS lab was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028955 (PTDC/SAU-INF/28955/2017). AG and MS are supported by an Individual Scientific Employment contract (CEECIND/00048/2017; CEECIND/00241/2017 respectively). DS acknowledges the Portuguese Foundation for Science and Technology (FCT) for the Post-Doc fellowship (SFRH/BPD/115341/2016). RP, DS and AF have PhD grants (SFRH/BD/145217/2019; SFRH/BD/143536/2019; 2020.05949.BD, respectively) financed by FCT

economic costs and spatial distribution analysis in an Endemic Northeastern City, Brazil

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