Evaluation of SARS-CoV-2 interferon gamma release assay in BNT162b2 vaccinated healthcare workers.

To predict protective immunity to SARS-CoV-2, cellular immunity seems to be more sensitive than humoral immunity. Through an Interferon-Gamma (IFN-γ) Release Assay (IGRA), we show that, despite a marked decrease in total antibodies, 94.3% of 123 healthcare workers have a positive cellular response 6 months after inoculation with the 2nd dose of BNT162b2 vaccine. Despite the qualitative relationship found, we did not observe a quantitative correlation between IFN-γ and IgG levels against SARS-CoV-2. Using stimulated whole blood from a subset of participants, we confirmed the specific T-cell response to SARS-CoV-2 by dosing elevated levels of the IL-6, IL-10 and TNF-α. Through a 20-month follow-up, we found that none of the infected participants had severe COVID-19 and that the first positive cases were only 12 months after the 2nd dose inoculation. Future studies are needed to understand if IGRA-SARS-CoV-2 can be a powerful diagnostic tool to predict future COVID-19 severe disease, guiding vaccination policies.

Impact of a daily legume-based meal on blood and anthropometric parameters in a group of omnivorous adults: A pilot study.

This pilot study aimed to assess the impact of substituting a traditional lunch for a vegetarian legume-based meal on blood and anthropometric parameters in a group of omnivorous adults. A one-group comparison, quasi-experimental dietary intervention was designed. A vegetarian legume-based meal was offered for 8 consecutive weeks (weekdays) to non-vegetarian individuals (n = 26), (28 years [P25 = 20.0, P75 = 35.5]; 21.9 kg/m2 [P25 = 21.3, P75 = 24.8]). Sociodemographic data, health status and lifestyle-related information were recorded. Three-day food records were used to collect food intake at baseline and at the end of the intervention. Anthropometric parameters were recorded and fasting blood analyses were performed following standard procedures. Wilcoxon signed-rank test was used for statistical comparisons. A p-value <0.05 was considered statistically significant. Participants showed a median intake of 79.8 g of cooked legumes per meal, meaning 13 (50.0%) subjects met the Portuguese daily legume intake recommendations during the intervention days. There were no statistically significant differences in anthropometric parameters. Transferrin concentration increased after 8 weeks (+12.5 mg/dL; p = 0.001). Total cholesterol concentration reduced after 8 weeks (-6 mg/dL; p = 0.041), as well as low-density lipoprotein (LDL) cholesterol (-7 mg/dL; p = 0.003). Triglycerides (+9 mg/dL; p = 0.046), fasting glucose (+2 mg/dL; p = 0.037) and HbA1c (+0.1 mg/dL; p = 0.010) concentration increased after the 2-month legume-based trial. Results suggest a cholesterol-lowering potential of legume-rich diets. However, unfavourable results regarding the impact on glucose metabolism-related biomarkers and triglyceride levels were observed. The study's limitations in design and sample size emphasise the importance of conducting further research with larger cohorts to attain more conclusive findings.

The Cardiometabolic Impact of Rebaudioside A Exposure during the Reproductive Stage.

The consumption of non-sugar sweeteners (NSS) has increased during pregnancy. The European Food Safety Agency suggested that steviol glycosides, such as Rebaudioside A (RebA), the major sweetener component of stevia, are safe for humans up to a dose of 4 mg/kg body weight/day. However, the World Health Organization recommended in 2023 the restraint of using NSS, including stevia, at any life stage, highlighting the need to study NSS safety in early periods of development. We aimed to study the mitochondrial and cardiometabolic effects of long-term RebA consumption during the reproductive stage of the life cycle. Female rats were exposed to RebA (4 mg steviol equivalents/kg body weight/day) in the drinking water from 4 weeks before mating until weaning. Morphometry, food and water consumption, glucose and lipid homeostasis, heart structure, function, and mitochondrial function were assessed. RebA showed an atrophic effect in the heart, decreasing cardiomyocyte cross-sectional area and myocardial fibrosis without repercussions on cardiac function. Mitochondrial and myofilamentary functions were not altered. Glucose tolerance and insulin sensitivity were not affected, but fasting glycemia and total plasma cholesterol decreased. This work suggests that this RebA dose is safe for female consumption during the reproductive stage, from a cardiometabolic perspective. However, studies on the effects of RebA exposure on the offspring are mandatory.

Epidemiological Changes in Respiratory Viral Infections in Children: The Influence of the COVID-19 Pandemic.

BACKGROUND: Viruses are the major cause of acute respiratory infections in children, causing important morbimortality. Before the COVID-19 pandemic, in temperate regions, respiratory viruses displayed a typical seasonality in transmission. A disruption in this pattern was observed in several countries during the pandemic, with low prevalence during the typical season, and an interseasonal rise. We evaluated the effects of the COVID-19 pandemic in the epidemiology of non-COVID viral respiratory infections in children, in a tertiary care hospital in Portugal. METHODS: Between March 2020 and August 2022, nasopharyngeal samples from children with respiratory symptoms in the Emergency Department (ED) and the Pediatric Ward were tested for RSV, influenza and other respiratory viruses, by real-time reverse transcriptase PCR (RT-PCR). RESULTS: A seasonal variation was observed from 2018 to 2020, with prevalence increasing in winter (mainly RSV and influenza). In the winter of 2020/21, when measures to mitigate SARS-CoV-2 transmission were stricter, there was a disruption of the seasonal pattern, with unusually low numbers. In the summer of 2021, when measures were being relaxed, there was an atypical rise. In June 2021, RSV was first detected and peaked in October. Influenza (Influenza A H3) was detected for the first time in February 2022, peaking in March/April. CONCLUSIONS: These findings show a disruption of the seasonality of viral respiratory infections in children during the pandemic, with a virtual elimination during the months of usually higher prevalence, and a subsequent out-of-season increase, coinciding with variations in the measures implemented to control the SARS-CoV-2 transmission, and confirming their efficacy.

Dose-response effect of a recreational team handball-based exercise programme on cardiometabolic health and physical fitness in inactive middle-aged-to-elderly males - a randomised controlled trial.

This study aimed at examining the dose-response of a recreational team handball (TH) exercise-based programme on cardiometabolic health and physical fitness in inactive middle-aged-to-elderly males without TH experience. Fifty-four inactive middle-aged-to-elderly men (67.5 ± 4.2 years; stature 168.8 ± 6.2 cm; body mass 78.4 ± 10.7 kg; fat mass 27.1 ± 5.3%; BMI 27.4 ± 2.9 kg/m2; VO2peak 27.3 ± 4.8 mL/min/kg) were randomised into three intervention groups performing 1 (TH1, n = 13), 2 (TH2, n = 15), or 3 (TH3, n = 12) 60-min weekly recreational TH-based training sessions, for 16 weeks, and a control group (CG, n = 14). A time x group interaction was observed for VO2peak, aerobic performance, fasting plasma insulin and body and fat mass (p ≤ 0.043) with TH3 showing the greatest overall effects. Post-intervention differences were observed in aerobic performance (TH3>CG, TH1 and TH2; TH2>CG), body mass (TH3>CG and TH1), fat mass (TH3>CG), VO2peak (TH3>CG) and plasma insulin (TH3>CG) (p ≤ 0.040). In conclusion, recreational TH performed for 60-min thrice and twice per week results in improved aerobic performance for middle-aged-to-elderly men. Moreover, it was observed that three weekly sessions were more effective in providing overall cardiometabolic benefits compared to training with a lower weekly frequency. ClinicalTrials.gov ID: NCT05295511.Trial registration: ClinicalTrials.gov identifier: NCT05295511.Highlights: We observed high intensities and fun levels during recreational TH, organised as formal and small-sided games, for middle-aged-to-elderly men during a 16-week period, independently of the number of weekly training sessions.Marked positive effects on aerobic performance and cardiometabolic health were observed in the intervention group that performed 3 weekly sessions.The study results indicate that recreational TH training with low frequency and volume results in some beneficial effects on cardiometabolic fitness and health for middle-aged-to-elderly men, but future studies with more participants or longer intervention periods are warranted to explore this possibility.

White blood cells in a healthy adolescent population according to social and health characteristics.

BACKGROUND: The immune system constitutes a sensory system both for heritable and non-heritable factors. Among the latter, social and environmental determinants of health may influence and shape the immune system in early life. To study the relationship between leukocytes and determinants of health in adolescence, we assessed total and differential white blood cells (WBC) according to social and environmental determinants of health in a healthy adolescent population. METHODS: As part of the population-based cohort Epidemiological Health Investigation of Teenagers in Porto (EPITeen), 1213 adolescents were evaluated at the age of 13. Total and differential WBC were evaluated through a venous blood sample using an automated blood counter (Sysmex®XE-5000, Hyogo, Japan). Sociodemographic, behavioral, and clinical data were collected through self-administered questionnaires. RESULTS: Participants with better socioeconomic conditions (enrolled at private schools or higher parental education) had significantly lower total WBC levels, and the latter showed a lower percentage of neutrophils and higher percentage of lymphocytes. Those who practiced sports had significantly lower total WBC levels and neutrophil percentage, as well as a significantly higher percentage of eosinophils and lymphocytes. Adolescents with chronic disease, chronic medication, or allergic diseases had a significantly higher percentage of eosinophils and a lower percentage of monocytes. With increasing body mass index and systemic inflammation, we found a significant increase in total WBC levels. CONCLUSION: WBC linked to different immune response patterns are associated with several social and environmental determinants of health in adolescence.

Multicomponent recreational team handball training improves global health status in postmenopausal women at the long term - A randomised controlled trial.

We studied the long-term effects of a multicomponent exercise training protocol (recreational team handball training, RTH) on global health status in inactive postmenopausal women. Participants (n = 45; age 65 ± 6 years, stature 157 ± 6 cm, body mass 66.2 ± 9.4 kg, fat mass 41.4 ± 5.5%, VO2peak 25.7 ± 3.6 mL/min/kg) were randomised into a control group (CG; n = 14) and a multicomponent exercise training group (EXG; n = 31, performing two to three weekly 60-min RTH sessions). Attendance was 2.0 ± 0.4 sessions/week (first 16 weeks) and 1.4 ± 0.5 (following 20 weeks) and mean heart rate (HR) loading was 77 and 79% of maximal HR (p = .002) for the first 16 and the following 20 weeks, respectively. Cardiovascular, bone, metabolic health, body composition and physical fitness markers were evaluated at baseline, and after 16 and 36 weeks. An interaction (p ≤ .046) was shown for the 2-h oral glucose tolerance test, HDL, Yo-Yo intermittent endurance level 1 test (YYIE1) and knee strength, in favour of EXG. At 36 weeks, YYIE1 and knee strength were higher (p ≤ .038) for EXG vs CG. Also, within-group improvements (p ≤ .043) were observed after 36 weeks for EXG in VO2peak, lumbar spine bone mineral density, lumbar spine bone mineral content, P1NP, osteocalcin, total cholesterol, HDL, LDL, body mass, android fat mass, YYIE1, knee strength, handgrip strength and postural balance. At 36 comparatively to 16 weeks, EXG showed an increase (p ≤ .036) in fasting blood glucose, HDL, knee strength and handgrip strength, and a decrease (p ≤ .025) in LDL. Collectively, this multicomponent exercise training (RTH) induces beneficial changes in global health status in postmenopausal women.HighlightsWe evaluated the long-term effects of a recreational team handball-based multicomponent training on broad-spectrum health and physical fitness markers of inactive postmenopausal women.Improvements in VO2peak and aerobic performance achieved after 16 weeks of training were maintained at 36 weeks.The 20-week extension of the training intervention resulted in further improvements in lipid profile markers and physical fitness variables.Recreational team handball could be suggested as an effective and safe strategy to counteract postmenopausal health-related constrains.

Recreational futsal provides broad-spectrum fitness and health benefits but no blood pressure effects in men with treated hypertension - a randomised controlled trial.

We determined the coadjuvant effect of a recreational futsal (RF) programme versus standard care alone (CON) in men with treated arterial hypertension (TAHT). Thirty-nine men with TAHT were randomised to RF (N = 20; 48 ± 8 years; systolic blood pressure [SBP]: 122 ± 14 mmHg) with 2-3 one-hour sessions/week for 3 months, or to CON (N = 19; 51 ± 6 years; SBP: 126 ± 13 mmHg). Participants were assessed at baseline, at 3 months, and after 1 month of training cessation (4 months). Mean training attendance was 60 ± 23%. At 3-months, there were no between-group differences in BP parameters (SBP: 0.44 mmHg; 95% CI: -5.79, 6.67). However, compared to CON, RF was effective for peak oxygen uptake (2.76 mL.min-1.kg-1; 95% CI: 0.26, 5.26), time to exhaustion (1.15 min; 95% CI: 0.59, 1.69), Yo-Yo IE1 performance (365 m; 95% CI: 175, 556), resting heart rate (RHR; -5 b.min-1; 95% CI: -10, -1), glycated haemoglobin (-0.52 mmol/L; 95% CI: -0.84, -0.19), blood glucose (-0.25 mmol/L; 95% CI: -0.44, -0.06), left femur bone mineral content (1.96 g; 95% CI: 0.29, 3.65), and postural balance (-2.3 falls; 95% CI: -3.9, -0.6). Similar findings were observed after 1-month of training cessation, except for RHR and blood glucose that returned to baseline levels in the RF group. In conclusion, RF provides broad-spectrum fitness and health benefits but no BP effects in men with TAHT.

Association of thyroid function, within the euthyroid range, with cardiovascular risk: The EPIPorto study.

Background: Thyroid hormones are important modulators of cardiovascular function. Both hypothyroidism and hyperthyroidism are known to contribute to an increased cardiovascular risk. It remains uncertain whether thyroid hormones level within the euthyroid range are associated with cardiometabolic risk. We aimed to evaluate the association between thyroid function levels within the euthyroid range and cardiovascular risk in a population-based cohort. Methods: Eight hundred thirty-five subjects aged ≥45 years from the EPIPorto population-based cohort were included. We excluded participants with TSH, free T4 (FT4), or free T3 (FT3) outside of the reference range, or with previous cardiovascular or thyroid disease. The associations between thyroid function, cardiovascular risk factors and the 10-year estimated risk of cardiovascular events (using SCORE2 and SCORE2-OP) were evaluated in linear and logistic regression models, crudely and adjusting for age, sex, BMI, diabetes, and smoking. Results: The mean age of the participants was 61.5 (SD 10.5) years and 38.9% were men. Eleven percent of the participants had diabetes, 47.8% had dyslipidemia, and 54.8% had hypertension. The mean body mass index (BMI) was 27.4 (SD 4.6) kg/m2, and the median (percentile25-75) 10-year risk of cardiovascular events was 5.46% (2.92, 10.11). Participants with higher BMI, larger waist circumference and higher hs-CRP had higher levels of FT3 and FT3/FT4 ratio. Lower FT3/FT4 ratio and higher FT4 levels were associated with higher prevalence of diabetes and more adverse lipid profile. Higher TSH, lower FT3 and lower FT3/FT4 ratio were associated with lower eGFR. Lower FT3, lower FT3/FT4 ratio and higher FT4 were associated with an increased 10-year risk of cardiovascular events. Conclusions: In a population-based study, variations of thyroid function within the euthyroid range were associated with cardiovascular risk factors. On one hand, individuals with higher BMI, larger waist circumference and higher hs-CRP had higher levels of FT3 and FT3/FT4 ratio. On the other hand, a decreased conversion of T4 to T3 (lower FT3, lower FT3/FT4 ratio and/or higher FT4) was associated with a higher prevalence of diabetes, a more adverse lipid profile, a lower eGFR and an increased 10-year risk of cardiovascular events.

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

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.

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.

Assessing SARS-CoV-2 Neutralizing Antibodies after BNT162b2 Vaccination and Their Correlation with SARS-CoV-2 IgG Anti-S1, Anti-RBD and Anti-S2 Serological Titers.

The humoral response through neutralizing antibodies (NAbs) is a key component of the immune response to COVID-19. However, the plaque reduction neutralization test (PRNT), the gold standard for determining NAbs, is technically demanding, time-consuming and requires BSL-3 conditions. Correlating the NAbs and total antibodies levels, assessed by generalized and automated serological tests, is crucial. Through a commercial surrogate virus neutralization test (sVNT), we aimed to evaluate the production of SARS-CoV-2 NAbs in a set of vaccinated healthcare workers and to correlate these NAbs with the SARS-CoV-2 IgG anti-S1, anti-RBD and anti-S2 serological titers. We found that 6 months after vaccination, only 74% maintain NAbs for the Wuhan strain/UK variant (V1) and 47% maintain NAbs for the South African and Brazil variants (V2). Through Spearman's correlation, we found the following correlations between the percentage of inhibition of NAbs and the SARS-CoV-2 IgG II Quant (Abbott Laboratories, Chicago, IL, USA) and BioPlex 2200 SARS-CoV-2 IgG Panel (Bio-Rad, Hercules, CA, USA) immunoassays: rho = 0.87 (V1) and rho = 0.73 (V2) for anti-S1 assessed by Abbott assay; rho = 0.77 (V1) and rho = 0.72 (V2) for anti-S1, rho = 0.88 (V1) and rho = 0.82 (V2) for anti-RBD, and rho = 0.68 (V1) and rho = 0.60 (V2) for anti-S2 assessed by BioPlex assay (p < 0.001 for all). In conclusion, we found a strong correlation between this fast, user-friendly, mobile and bio-safe sVNT and the serological immunoassays.

The pro-proliferative effect of insulin in human breast epithelial DMBA-transformed and non-transformed cell lines is PI3K-, mTOR- and GLUT1-dependent.

Type 2 diabetes mellitus (T2DM) is linked to an increased risk of breast cancer. We aimed to investigate how T2DM-associated characteristics (high levels of glucose, insulin, leptin, inflammatory mediators and oxidative stress) influence breast cancer carcinogenesis, in DMBA-treated (MCF-12ADMBA ) and non-treated breast epithelial (MCF-12A) cell lines. Insulin (50 nM) promotes cell proliferation, 3 H-DG uptake and lactic acid production in both cell lines. The stimulatory effects of insulin upon cell proliferation and 3 H-DG uptake were hampered by rapamycin, LY294001 and BAY-876, in both cell lines. In conclusion, hyperinsulinemia, one important characteristic of T2DM, contributes to the initiation of breast cancer by a PI3K- and mTOR-dependent mechanism involving increased GLUT1-mediated glucose uptake. SIGNIFICANCE: The pro-proliferative effect of insulin in human breast epithelial DMBA-transformed and non-transformed cell lines is PI3K-, mTOR- and GLUT1-dependent.

Benefits on Hematological and Biochemical Parameters of a High-Intensity Interval Training Program for a Half-Marathon in Recreational Middle-Aged Women Runners.

(1) Background: half-marathon races are popular among recreational runners, with increases in participation among middle-aged and women. We aimed to determine the effects of two half-marathon training programs on hematological and biochemical markers in middle-aged female recreational runners; (2) Methods: ten women (40 ± 7 years) followed moderate intensity continuous training (MICT), based on running volume below 80% V˙O2max, and another ten women followed high intensity interval training (HIIT) at 80%-100% V˙O2max, with less volume, and combined with eccentric loading exercise. Hematology, plasma osmolality, and plasma markers of metabolic status, muscle damage, inflammatory, and oxidative stress were measured before (S1) and after (S2) training and 24 h after the half-marathon (S3); (3) Results: both training programs had similar moderate effects at S2. However, the acute response at S3 induced different alterations. There was a greater decrease in cholesterol and triglyceride levels in MICT and reductions in markers of damage and inflammation in HIIT. Greater variability in some plasma markers at S3 in MICT suggests that there is inter-individual variability in the response to training; (4) Conclusions: HIIT led to better adaptation to the competition maybe because of the repeated exposure to higher oxygen consumption and eccentric loading exercise.

Iron Related Biomarkers Predict Disease Severity in a Cohort of Portuguese Adult Patients during COVID-19 Acute Infection.

Large variability in COVID-19 clinical progression urges the need to find the most relevant biomarkers to predict patients' outcomes. We evaluated iron metabolism and immune response in 303 patients admitted to the main hospital of the northern region of Portugal with variable clinical pictures, from September to November 2020. One hundred and twenty-seven tested positive for SARS-CoV-2 and 176 tested negative. Iron-related laboratory parameters and cytokines were determined in blood samples collected soon after admission. Demographic data, comorbidities and clinical outcomes were recorded. Patients were assigned into five groups according to severity. Serum iron and transferrin levels at admission were lower in COVID-19-positive than in COVID-19-negative patients. The levels of interleukin (IL)-6 and monocyte chemoattractant protein 1 (MCP-1) were increased in COVID-19-positive patients. The lowest serum iron and transferrin levels at diagnosis were associated with the worst outcomes. Iron levels negatively correlated with IL-6 and higher levels of this cytokine were associated with a worse prognosis. Serum ferritin levels at diagnosis were higher in COVID-19-positive than in COVID-19-negative patients. Serum iron is the simplest laboratory test to be implemented as a predictor of disease progression in COVID-19-positive patients.

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.

Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity.

Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.Trial registration: NCT04370808.

Unveiling the Metabolic Effects of Glycomacropeptide.

For many years, the main nitrogen source for patients with phenylketonuria (PKU) was phenylalanine-free amino acid supplements. Recently, casein glycomacropeptide (GMP) supplements have been prescribed due to its functional and sensorial properties. Nevertheless, many doubts still persist about the metabolic effects of GMP compared to free amino acids (fAA) and intact proteins such as casein (CAS). We endeavour to compare, in rats, the metabolic effects of different nitrogen sources. Twenty-four male Wistar rats were fed equal energy density diets plus CAS (control, n = 8), fAA (n = 8) or GMP (n = 8) for 8 weeks. Food, liquid intake and body weight were measured weekly. Blood biochemical parameters and markers of glycidic metabolism were assessed. Glucagon-like peptide-1 (GLP-1) was analysed by ELISA and immunohistochemistry. Food intake was higher in rats fed CAS compared to fAA or GMP throughout the treatment period. Fluid intake was similar between rats fed fAA and GMP. Body weight was systematically lower in rats fed fAA and GMP compared to those fed CAS, and still, from week 4 onwards, there were differences between fAA and GMP. None of the treatments appeared to induce consistent changes in glycaemia, while insulin levels were significantly higher in GMP. Likewise, the production of GLP-1 was higher in rats fed GMP when compared to fAA. Decreased urea, total protein and triglycerides were seen both in fAA and GMP related to CAS. GMP also reduced albumin and triglycerides in comparison to CAS and fAA, respectively. The chronic consumption of the diets triggers different metabolic responses which may provide clues to further study potential underlying mechanisms.