Background: Vitamin D plays a role in bone health, pain signaling, and inflammation. We examined the largely unknown relation of dietary vitamin D intake with pain incidence and pain changes over ...time in older adults. Methods: Data were taken from the Seniors-ENRICA-1 cohort, which included 950 individuals aged ≥60 years. Habitual vitamin D intake was assessed in 2012 with a validated diet history, and pain both in 2012 and 2017 with a scale ranging from 0 (no pain) to 6 (highest pain), according to its severity, frequency, and number of locations. Analyses on pain incidence and pain changes were performed in the 524 participants free of pain at baseline and the overall sample, respectively. Results: Higher dietary vitamin D intake was associated with lower 5-year pain incidence; the multivariable-adjusted odds ratio (95% confidence interval) was 0.88 (0.79,0.99) for every 1-µg/day increase in vitamin D intake, and 0.49 (0.28,0.88) for the highest (>3.52 µg/day) vs. lowest (<1.85 µg/day) tertile. Dietary vitamin D intake (highest vs. lowest tertile) was also associated with 5-year favorable pain changes: the multivariable-adjusted odds ratio of pain worsening vs. no change/pain improvement was 0.55 (0.36,0.86), and the β coefficient for changes in the pain scale was −0.56 (−1.03,−0.09). Similar results were found for pain severity, frequency, and number of pain locations. Conclusions: In an older adult population, where compliance with vitamin D intake recommendations was very low, a slightly increased dietary intake was associated with lower pain incidence and favorable pain changes over 5 years.
Porcine circovirus 2 (PCV-2) poses a significant economic threat for the swine industry, causing a range of diseases collectively referred to as porcine circovirus diseases (PCVDs). Despite PCV-2 ...vaccine effectiveness, the need for monitoring infectious pressure remains. PCV-2 coinfection with other pathogens like porcine reproductive and respiratory syndrome virus (PRRSV) can exacerbate disease severity and lead to PCV-2-systemic disease cases. Monitoring both PRRSV and PCV-2 in co-infected farms is crucial for an effective management and vaccination programs. The present cross-sectional study aimed to determine PCV-2 antibody levels in piglets at weaning and PCV-2 and PRRSV viremia in pooled serum samples at weaning (vaccination age) and at 6 and 9 weeks of age from a Spanish swine integration system in 2020 (48 farms) and in 2022 (28 out of the 48 analysed previously).
The frequency of PCV-2 detection in pools of piglet sera was 2.1% (2020) and 7.1% (2022) at vaccination age but increased at the end of the nursery period (10.4% in 2020 and 39.3% in 2022) in both years. Co-infections between PCV-2 and PRRSV were detected in a significant proportion of PRRSV positive farms (15% in 2020, and 60% in 2022). PCV-2 antibody levels (ELISA S/P ratios) at weaning were lower in PCV-2 qPCR positive farms at different sampling time-points (0.361 in 2020 and 0.378 in 2022) compared to PCV-2 qPCR negative ones (0.587 in 2020 and 0.541 in 2022). The 28 farms tested both years were classified in four different epidemiological scenarios depending on their PCV-2 virological status. Those PCV-2 qPCR negative farms in 2020 that turned to be positive in 2022 had a statistically significant increase of PRRSV RT-qPCR detection and a PCV-2 antibody levels reduction, facts that were not observed in the rest of the scenarios.
This epidemiological study in farms from the same integration system determined the occurrence, in 2020 and in 2022, of PCV-2 and PRRSV infections in piglets during the nursery period by using pooled serum samples.
The incidence of breast cancer increases with age until menopause, and breast cancer is more aggressive in younger women. The existence of epidemiological links between breast cancer and aging ...indicates that both processes share some common mechanisms of development. Oxidative stress is associated with both cancer susceptibility and aging. Here we observed that ERBB2-positive breast cancer, which developed in genetically heterogeneous ERBB2-positive transgenic mice generated by a backcross, is more aggressive in chronologically younger than in older mice (differentiated by the median survival of the cohort that was 79 weeks), similar to what occurs in humans. In this cohort, we estimated the oxidative biological age using a mathematical model that integrated several subphenotypes directly or indirectly related to oxidative stress. The model selected the serum levels of HDL-cholesterol and magnesium and total AKT1 and glutathione concentrations in the liver. The grade of aging was calculated as the difference between the predicted biological age and the chronological age. This comparison permitted the identification of biologically younger and older mice compared with their chronological age. Interestingly, biologically older mice developed more aggressive breast cancer than the biologically younger mice. Genomic regions on chromosomes 2 and 15 linked to the grade of oxidative aging were identified. The levels of expression of Zbp1 located on chromosome 2, a gene related to necroptosis and inflammation, positively correlated with the grade of aging and tumour aggressiveness. Moreover, the pattern of gene expression of genes linked to the inflammation and the response to infection pathways was enriched in the livers of biologically old mice. This study shows part of the complex interactions between breast cancer and aging.
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•Breast cancer developed by genetically heterogeneous mice was more aggressive in chronologically younger than in older mice.•We estimated the biological age integrating subphenotypes related to oxidative stress.•Biologically older mice developed more aggressive breast cancer than the biologically younger mice.•We identified QTLs genomic regions on chromosomes 2 and 15 linked to the grade of oxidative aging.•The pattern of gene expression in the liver of biologically old mice is enriched in inflammation and response to infection pathways.
The possibility of Toxoplasma gondii transmitted from game meat to humans is of public health concern. Here we determined seroprevalence and risk factors associated with T. gondii in large game ...ungulates that cohabit in Sierras de Cazorla, Segura and Las Villas Natural Park (SCSV‐NP) (Southern Spain), a natural park with high human–animal interaction. Antibodies against T. gondii in 328 wild ungulates were assayed by the modified agglutination test (MAT ≥ 1:25). Antibodies were found in 39 (11.9%, 95% CI: 8.4–15.4) wild ungulates, with seroprevalence levels of 20.8% in wild boars (Sus scrofa) (5/24), 19.0% in fallow deer (Dama dama) (12/63), 13.9% in Iberian ibex (Capra pyrenaica hispanica) (14/101), 7.9% in red deer (Cervus elaphus) (6/76), and 3.1% in mouflons (Ovis aries musimon) (2/64). Significantly higher seroprevalence was observed in fallow deer and wild boars compared to mouflons. Animals living close to urban areas (<2 km) had 4.6‐times higher risk compared to those living at >5 km of urban areas. The results indicate high circulation of T. gondii in wild ungulates in SCSV‐NP, which is of animal and public health concern. The increased seroprevalence of T. gondii detected in wildlife ungulates living close to urban areas may increase human infection in those areas if meat from infected animals is consumed raw or undercooked.
Objective: To assess the major clinical factors affecting the quality of anticoagulation and evaluate the predictive value of the SAMe-TT
2
R
2
score to identify patients who will achieve a high ...average time in therapeutic range (T.T.R.) with vitamin K antagonist (V.K.A.) treatment. Research design and methods: This observational, cross-sectional, retrospective and nationwide multicenter study included 1524 patients from the primary care setting with non-valvular atrial fibrillation receiving V.K.A. (≥12 months). We performed a bivariate analysis to identify factors individually associated with the T.T.R. and a multiple regression analysis to identify the independent predictive factors. For the validation of the SAMe-TT
2
R
2
score, the receiver operating characteristic (R.O.C.) curve was calculated and the Hosmer-Lemeshow test was used to test calibration. Results: A total of 94.8% of patients received acenocumarol (4.8% warfarin). A progressive decrease in mean T.T.R. was found when the SAMe-TT
2
R
2
score increased from 0 points (72.1 ± 17.1%) to 4 points (64.1 ± 23.2%), p < 0.001. Other risk scores (CHADS
2
and CHA
2
DS
2
-VASc, HAS-BLED) were also associated with the mean T.T.R. We found a significant association between low T.T.R. and the following clinical factors: female sex, three or more comorbidities, amiodarone treatment, dietary habits, bleeding history and the intake of ≥7 tablets per day besides V.K.A. (p < 0.01). Regarding SAMe-TT
2
R
2
score validation, the R.O.C. curve showed significant capability, although not high, of discriminating good anticoagulation control (T.T.R. ≥65%) with an area under the curve of 0.562 (95% C.I. 0.533-0.592, p < 0.001) which increased, remaining modest, to 0.594 (95% C.I. 0.564-0.624, p < 0.001) when the factors not included in SAMe-TT
2
R
2
score were added. Conclusion: In this cohort, the SAMe-TT
2
R
2
score had a significant, although modest, ability to assess the likelihood of good international normalized ration (I.N.R.) control, and its predictive value might slightly improve by adding other simple clinical factors. Further research is needed to refine the predictive scales.
Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here ...we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2 oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. Our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.
Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients ...admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% 948/3287. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% 610/3287, followed by ventilator-associated tracheobronchitis (VAT) 10.3% 338/3287. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% 266/1252), followed by Klebsiella pneumoniae (19.1% 239/1252) and Staphylococcus aureus (15.5% 194/1,252). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR 95% CI of 1.81 1.40-2.34), while VAT was not associated with increased hospital mortality (OR 95% CI of 1.34 0.98-1.83). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.
Kidney transplant (KT) is the first therapeutic option for most patients with chronic renal failure that requires renal function replacement. The main complication associated with renal graft loss is ...immune rejection. The T regulatory pathways play a key role in this process, and abnormalities in some of these molecules could participate in the graft rejection. In this paper, our group performed an exploratory analysis of the behavior of the coinducible molecules (CD28, CTLA-4, ICOS, PD-1) in patients with KT rejection and control KT patients without rejection. The Mann-Whitney U test, used for 2 groups, showed significant differences (P = .0005), indicating that PD-1 is underexpressed in patients with allograft rejection. No differences were found in CD28+, regulatory T cells (T reg), CTLA-4, and ICOS, so we are proposing that PD-1 is a key player in the immunotolerance phenomenon and its underexpression participates in the rejection process. More research needs to be performed on this topic.
•Kidney transplant has undoubtedly proven to be the best treatment for patients with advanced chronic kidney disease in terms of survival and quality of life.•Kidney transplant immunomodulation is performed by the regulatory T cells; T cell coregulation is one of the most important effects in renal transplant resulting in immunological tolerance.•New evidence in the literature pointed out that activation of T regulatory cells and T coinducible cells is an essential step for the induction of allograft tolerance.•The aim of this this article was to evaluate the T reg coinducible proteins CD28+, CTLA-4, ICOS, and PD-1 in the lymphocytes of patients with KT rejection and compare them with patients with no rejection.•Our first approach suggests that PD-1 underexpression could be a critical step in kidney rejection and leads to the opportunity to explore in detail this pathway in transplant patients.
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