Immunological Trajectories of White Blood Cells from Adolescence to Adulthood: Description and Determinants

Background: The immune system gradually matures early in life in the face of internal and external stimuli. Whether the immune responses are lasting and stable during the course of life is still unclear. Methods: As part of the EPITeen cohort, 1183 adolescents were prospectively evaluated at the ages of 13, 17, 21, 24 and 27. Sociodemographic, behavioral and clinical data were collected by self- and face-to-face-administered questionnaires, along with a physical examination comprising anthropometric measurements and blood sample collections. Mixed-effects models were used to identify individual trajectories of white blood cells (WBC) and finite Gaussian mixture models were used to identify the clusters of individual trajectories. Results: Participants were allocated into six clusters based on the individual trajectories of WBC distribution. Higher Inflammatory Activation Cluster (11.4%) had the highest total WBC count and neutrophils percentage, as well as the lowest percentage of lymphocytes. These participants had significantly higher odds of being overweight [OR = 2.44, 95%CI:1.51-3.92]. Lowest Levels of WBC Cluster (24.1%) had the lowest total WBC count, being characterized by a higher participation on sports [OR = 1.54, 95%CI:1.12-2.13]. Highest Proportion of Eosinophils Cluster (20.1%) had the highest eosinophils percentage and the highest likelihood of having been diagnosed with a chronic disease [OR = 2.11, 95%CI:1.43-3.13], namely "asthma or allergies" [OR = 14.0 (1.73, 112.2]. Lowest Proportion of Eosinophils Cluster (29.1%) had the lowest percentage of eosinophils and basophils, as well as the highest lymphocyte proportion. Participants in the Undefined Cluster (13.8%) showed the highest percentage of monocytes and basophils and were also characterized by significant lower odds of having parents with 7-9 years of schooling [OR = 0.56, (0.32, 0.99]. Conclusions: In this study we identified distinct immunological trajectories of WBC from adolescence to adulthood that were associated with social, clinical and behavioral determinants. These results suggest that these immunological trajectories are defined early in life, being dependent on the exposures.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and by national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) (POCI-01-0145-FEDER-016829), under Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/DTP/04750/2013/PT); and the individual PhD Grant to VC (PD/BD/149264/2019), co-funded by the FCT and the POPH/FSE Program

How the metabolic phenotype in adulthood is affected by long-lasting immunological trajectories since adolescence

A close relationship between immune and metabolic systems has been perceived in the recent past. We aimed to assess whether the immunological trajectories of circulating white blood cells (WBC) started in adolescence, affects the metabolic phenotype in adulthood. We used data from 1183 participants of the population-based EPITeen cohort, evaluated at 13, 17, 21, 24 and 27 years of age. The Immunological trajectories from 13 to 27 years old were identified by mixed-effects models, being their association with metabolic features at 27 years old measured by logistic regression. The Higher Inflammatory Activation trajectory (HIA trajectory) had the highest percentage of individuals with metabolic syndrome, while Lowest Levels of WBC trajectory (LLWBC trajectory) showed the lowest percentage. Participants with HIA trajectory had significantly higher triglycerides, waist circumference, serum uric acid and BMI. After adjustment for sex and sports practice and hs-CRP, the odds of having one or more metabolic features in adulthood was significantly lower in LLWBC trajectory. Individuals with immunological trajectories of WBC linked with a pattern of higher immune activation showed a less favorable metabolic profile, while those with the lowest levels of WBC were less likely to have metabolic risk factors in adulthood. © 2022, The Author(s).This study was financed by national funds through the Foundation for Science and Technology (Portuguese public agency that supports science, technology and innovation, in all scientific domains, under responsibility of the Ministry of Science, Technology and Higher Education), under the Project UIDB/04750/2020 and under the scientific Project PTDC/DTP-EPI/6506/2014 and the doctoral studentship PD/BD/149264/2019 (VC)

Serological response to a single dose of a SARS-CoV-2 mRNA vaccine

The delays in the production and delivery of COVID-19 vaccines and the growing number of fatal infections across the globe raised the question whether it would be more advantageous to vaccinate a larger group of individuals with one dose instead of a smaller one with two doses. Through a group of vaccinated healthcare workers, we describe the qualitative and quantitative serological response to a single dose of the BNT162b2 vaccine. We found that, before the second dose inoculation, 95.3 % (182/191) already had anti-SARS-CoV-2 IgG and, half of them, antibodies concentrations against RBD (the key target of neutralizing antibodies) that reached maximum values for the used evaluation immunoassay. In order to improve the execution of vaccination programs, further studies are needed to assess whether there are individuals for whom a single dose of mRNA vaccine or a delay in the inoculation of the second dose, produce a sufficient immune response. Additionally, follow-up studies will help in understanding post-vaccination immunity, how long it lasts and how it relates to infection and reinfection.This work was supported by FCT Special Support Research4Covid (Project 186)

Association of Serum 25-Hydroxyvitamin D Concentration with Pulmonary Function in Young Adults

The role of vitamin D on pulmonary function is unclear and is mostly studied in patients, smokers and elderly people. The aim of this paper was to evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] concentration and pulmonary function in young adults. Cross-sectional analysis of 499 individuals that were evaluated at 21 years of age as part of the population-based cohort Epidemiological Health Investigation of Teenagers in Porto (EPITeen). Serum 25(OH)D was categorized according to the Institute of Medicine. Pulmonary function was evaluated using spirometry. Linear regression models were used to estimate the regression coefficients (beta) and its 95% confidence intervals (95% CI), and were adjusted for confounders. Education, smoking, body mass index, and season of evaluation were determinants of serum 25(OH)D concentration. Prevalence of serum 25(OH)D concentration = 50 nmol/L, PEF was significantly lower for those with a concentration of 30 to < 50 nmol/L (beta = -0.576; 95% CI: -0.943, -0.210), and for those with a concentration of <30 nmol/L (beta = - 0.650; 95% CI: -1.155, -0.146). Although only PEF attained statistical significance, the consistent results with the other parameters support the role of serum 25(OH)D to promote better pulmonary function in young adults.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology-FCT (Portuguese Ministry of Science, Technology and Higher Education) (POCI-01-0145-FEDER-016829), under the project Uma abordagem longitudinal a obesidade metabolicamente saudavel: da inflamacao ao perfil de risco cardiovascular (Ref. FCT PTDC/DTP-EPI/6506/2014) and the Unidade de Investigacao em Epidemiologia -Instituto de Saude Publica da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013); and the PhD Grant PD/BD/105824/2014 (Maria Cabral), co-funded by the FCT and the POPH/FSE Program

The Importance of Design in the Development of a Portable and Modular Iot-Based Detection Device for Clinical Applications

The integration of human factors engineering methods within the medical device design and development process has been highlighted by international standards organizations. Such methods are contributing to the development of safer medical devices, more suitable to users' needs. Errors during device operation might hamper effective patient diagnosis and treatment, or eventually lead to injury or death. Thus, the designing process of a medical device is indeed crucial to user experience and safety operation. This paper presents a human-centred design analysis of a novel IoT-based screening prototype (iLoF) based on Artificial Intelligence algorithms built-in in a patented-photonics system developed by a deep tech startup. The influence of the design process during the development of the prototype was addressed, based on a human-centred design methodology and considering the device's application environment. iLoF's prototype on-field applicability was evaluated considering a single case-study carried out at one of the main hospitals in Portugal through interviews to ten healthcare professionals with high experience in laboratorial testing. A benchmark assessment and a comparison matrix along with the market products are also presented to fully understand the technology state and to find new solutions that can influence iLoF's product development. © Published under licence by IOP Publishing Ltd

Relationship between dietary vitamin D and serum 25-hydroxyvitamin D levels in Portuguese adolescents

Objective: To understand the relationship between vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) levels in a sample of Portuguese adolescents. Design: Cross-sectional evaluation carried out in the 2003/2004 school year. Vitamin D intake was assessed by an FFQ and 25(OH)D was measured in a fasting blood sample. Setting: Public and private schools in Porto, Portugal. Subjects: Adolescents aged 13 years (n 521) enrolled at school (EPITeen cohort). Results: Both mean (sd) intake and serum 25(OH)D level were far below the recommended, 4·47 (2·49) µg/d and 16·5 (5·7) ng/ml, respectively. A significant difference in serum level was found according to season, with lower values in winter than summer (14·8 (4·6) v. 17·3 (5·9) ng/ml, P<0·001). Vitamin D intake was weakly correlated with serum 25(OH)D (r=0·056, P=0·203). Conclusions: Dietary vitamin D and serum 25(OH)D levels were positively but weakly correlated and the error was higher among those with higher serum 25(OH)D concentration. Our results support the need for strategies that promote increase of the most important food sources of vitamin D to reduce the high prevalence of low vitamin D status

SARS-CoV-2 seroprevalence in healthcare workers: The experience of a Portuguese COVID-19 front-line hospital during the 1st pandemic wave

Background: Healthcare workers (HCW) are at increased risk of SARS-CoV-2 infection. Here, we describe the SARS-CoV-2 seroprevalence in HCW who work daily at a COVID-19 front-line hospital in Portugal. Methods: To this end, the seroprevalence of 1027 HCW, assessed after the peak of the first pandemic wave, was determined using the following immunoassays: Euroimmun Anti-SARS-CoV-2 ELISA IgG (Euroimmun, Luebeck, Germany), Abbott SARS-CoV-2 IgG (Abbott Laboratories, Chicago), and Elecsys Anti-SARS-CoV–2 Total (Roche Diagnostics, Basel, Switzerland). Results: We found a 2.7% seroprevalence, very close to the one determined in the community (2.9%) for the same period. Conclusions: This low SARS-CoV–2 seroprevalence highlights the effectiveness of infection prevention and control measures implemented very early in the pandemic, namely the use of appropriate personal protective equipment.This research was supported by a grant from FCT Research4-COVID–19 (Project n° 186_596855206 – CertCOV)

Capilia™ TB-Neo assay: a new tool for rapid distinction between tuberculous and non-tuberculous mycobacteria

SETTING: The ability to rapidly distinguish between Mycobacterium tuberculosis complex (MTC) and non-tuberculous mycobacteria (NTM) is critical in clinical practice. OBJECTIVE: To evaluate the usefulness of an immunochromatographic (IC) assay to distinguish between MTC and NTM. DESIGN: We analysed a panel of 145 cultures from 128 patients. The routine molecular identification approaches, such as the AccuProbe™ Mycobacterium tuberculosis complex culture identification test and GenoType(®) Mycobacterium assays, were used as reference methods. RESULTS: Of the 101 positive cultures, 98 were correctly identified using the Capilia™ TB-Neo Assay. Of the three discordant isolates, one was identified as M. bovis bacille Calmette-Guérin (BCG) and two as M. tuberculosis. Although we have not performed the sequencing of these strains, some false-negative results have been described due to mutations in the mpb64 gene or with some M. bovis BCG strains. We did not observe false-positive results or any cross-reaction with 22 NTM strains, 12 non-mycobacterial micro-organisms and 10 negative cultures. CONCLUSION: We report good overall performance (sensitivity 97%, specificity 100%, positive predictive value 100% and negative predictive value 96%) of this rapid assay that is easy to perform and interpret and does not require sample preparation, trained technicians or expensive equipment

BCG Infection after bladder cancer treatment – 3 clinical case reports

Immunotherapy with Bacillus Calmette-Guérin (BCG) to treat non-muscle invasive bladder cancer has become an effective and superior alternative to chemotherapy. Intravesical treatment with BCG appears to be relatively safe; however, occasionally BCG infection complicates such treatment. In the present work we describe three patients in whom BCG infection occurred after intravesical BCG therapy. All patients had positive urine culture forMycobacterium tuberculosis complex, using AccuProbe culture identification and then Genotype Mycobacterium MTBC test identified Mycobacterium bovis BCG. The diagnosis is difficult and microbiologic study is usually negative, so high index of suspicion is essential

Hypothyroidism in a five-year-old boy with rhabdomyolysis and recent history of cardiac tamponade: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cardiac tamponade is a rare manifestation of hypothyroidism, and a less rare cause of pericardial effusion. The accumulation of the pericardial fluid is gradual, and often does not compromise cardiac hemodynamic function. There is a relationship between the severity and chronicity of the disease with the presence of pericardial effusion. There are few cases describing associated pericardial tamponade published in the literature. When a tamponade occurs, a concomitant provocative factor such as a viral pericarditis may be related. Our patient's case appears to be the youngest patient described so far.</p> <p>Case presentation</p> <p>We report the case of a previously healthy five-year-old Hispanic (non-indigenous) boy who developed rhabdomyolysis with a history of a recent pericardial effusion and tamponade two months before that required the placement of a percutaneous pericardial drainage. Pericardial effusion was considered to be viral. Later on readmission, clinical primary hypothyroidism was diagnosed and thought to be associated with the previous cardiac tamponade. He developed rhabdomyolysis, which was considered to be autoimmune and was treated with steroids. The level of creatine phosphate kinase and creatine kinase MB fraction returned to within the reference rangeone week after our patient was started on steroids and three weeks after he was started on thyroid hormones.</p> <p>Conclusions</p> <p>Physicians should consider hypothyroidism as a differential diagnosis in patients with pericardial effusion. Pericardial effusion may progress and cause a cardiac tamponade with hemodynamic instability. The fact that our patient did not have any manifestations of hypothyroidism might have delayed diagnosis.</p