To determine the epidemiology of congenital and acquired cytomegalovirus (CMV) infections in preterm infants and to analyze the efficacy of breast milk freezing in decreasing the vertical ...transmission rate of CMV.
During 2013 and 2014, preterm newborns who weighed ≤1500 g and were admitted to 22 Spanish neonatal units were included and screened for CMV infection according to the Spanish Neonatology Society recommendations. Each hospital treated the breast milk according to its own protocols.
Among the 1236 preterm neonates included, 10 had a congenital infection (0.8%) and 49 had an acquired infection (4.0%) (82% demonstrated positive PCR-CMV in breast milk). The neonates who received only frozen milk presented less frequently with acquired infection (1.2%) than those fed fresh milk (5.5%) (RR=0.22; 95% CI 0.05–0.90; P=0.017). The newborns who received bank milk followed by frozen or fresh breast milk more frequently had an acquired infection (2.1% or 2.2%, respectively) than those fed only frozen breast milk.
The incidence of congenital CMV infection in our sample is low, as described in the literature. To reduce acquired CMV infection, freezing breast milk might be an advisable procedure for preterm neonates born from seropositive mothers, either from the beginning of lactation or after a period of bank milk administration.
Aims: To assess the relationship between clinically maternal chorioamnionitis and outcome in preterm very-low-birth weight (VLBW) infants. Methods: An observational case-control study was conducted ...in the neonatology departments of 12 acute care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (≤1500 g) infants who were born to a mother with clinical chorioamnionitis were enrolled. The controls included infants who were born to mothers without chorioamnionitis, matched by gestational age, and immediately born after each index case. At a corrected age of 24 months, a neurological examination and a psychological assessment of the surviving children were performed. Results: Sixty-six of the newborn infants died; therefore, 262 infants from the original sample were available for the study. Follow-up data were obtained at a corrected age of 24 months from a total of 209 children (106 cases and 103 controls, 80% of the original sample size). Seventy children (33.5%) were diagnosed with some type of sequelae. The following conditions were all more prevalent in infants born to mothers with chorioamnionitis in comparison to controls: low development quotient (98.3±12.15 vs. 95.9±15.64; P=0.497), cerebral palsy (4.9% vs. 10.4%; P=0.138), seizures (1.0% vs. 3.8%; P=0.369), and other neurological or sensorial sequelae (32.0% vs. 34.9%; P=0.611). Conclusions: After controlling for gestational age, the study population demonstrated that the neurological outcomes in infants at a corrected age of 24 months was not worsened by chorioamnionitis.
Several studies have shown that evening intake of aspirin has antihypertensive effect in healthy adults, which has not been proven in patients with cardiovascular disease, who mostly take aspirin in ...the morning. We have evaluated the antihypertensive effect of bedtime administration of aspirin in patients with cardiovascular disease already treated for hypertension.
This is a multicenter randomized triple-blind placebo-controlled crossover trial, with hypertensive patients treated with aspirin for secondary prevention. There was a baseline-randomized assignment to 2-month periods of bedtime aspirin (100 mg) first and morning-time aspirin later, or inversely, both periods separated by an open label 2-4 weeks period of morning-time aspirin. At the start and end of each treatment period, a 24-h ambulatory blood pressure monitoring was performed. The main outcome measure was mean 24-h blood pressure. The analyses were performed according to the intention-to-treat principle.
Overall, 225 patients were randomized. No significant differences were observed in ambulatory blood pressure by time of intake of usual low doses of aspirin. The mean SBP/DBP was 123.2/69.9 (95% CI 121.58-124.9/68.86-76.86) with bedtime administration and 122.4/68.8 (95% CI 120.76-124.01/67.85-69.83) with daytime administration (P = 0.3 and P = 0.23 for SBP and DBP, respectively).
Administering aspirin at bedtime rather than in the morning does not modify the 24-h ambulatory blood pressure in hypertensive patients in secondary cardiovascular prevention.The trial was registered with ClinicalTrials.gov (number NCT01741922).
The bioavailability and regulation of iron is essential for central biological functions in mammals. The role of this element in ferroptosis and the dysregulation of its metabolism contribute to ...diseases, ranging from anemia to infections, alterations in the immune system, inflammation and atherosclerosis. In this sense, monocytes and macrophages modulate iron metabolism and splenic function, while at the same time they can worsen the atherosclerotic process in pathological conditions. Since the nucleotide-binding oligomerization domain 1 (NOD1) has been linked to numerous disorders, including inflammatory and cardiovascular diseases, we investigated its role in iron homeostasis. The iron content was measured in various tissues of Apoe-/- and Apoe-/-Nod1-/- mice fed a high-fat diet (HFD) for 4 weeks, under normal or reduced splenic function after ligation of the splenic artery. In the absence of NOD1 the iron levels decreased in spleen, heart and liver regardless the splenic function. This iron decrease was accompanied by an increase in the recruitment of F4/80+-macrophages in the spleen through a CXCR2-dependent signaling, as deduced by the reduced recruitment after administration of a CXCR2 inhibitor. CXCR2 mediates monocyte/macrophage chemotaxis to areas of inflammation and accumulation of leukocytes in the atherosclerotic plaque. Moreover, in the absence of NOD1, inhibition of CXCR2 enhanced atheroma progression. NOD1 activation increased the levels of GPX4 and other iron and ferroptosis regulatory proteins in macrophages. Our findings highlight the preeminent role of NOD1 in iron homeostasis and ferroptosis. These results suggest promising avenues of investigation for the diagnosis and treatment of iron-related diseases directed by NOD1.
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•Absence of NOD1 reduces splenic iron content under pro-atherogenic conditions.•Splenic NOD1 regulates iron homeostasis and macrophage metabolism.•Mobilization of CD68+-cells depends on NOD1 and CXCR2 interplay.•NOD1 activation protects against ferroptosis in macrophages.
Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the ...design of cognitive trials.
Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study.
Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005).
We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD.
Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson’s disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS ...burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = −0.52), change from V0 to V2 in PDSS (Parkinson’s Disease Sleep Scale) (β = −0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.
Sex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD.
PD patients who were recruited from the Spanish cohort COPPADIS from ...January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used.
At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24;
= 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11;
= 0.259). Symptoms such as depression (
< 0.0001), fatigue (
< 0.0001), and pain (
< 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (
< 0.0001), speech problems (
< 0.0001), rigidity (
< 0.0001), and hypersexuality (
< 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (
= 0.002). Perception of quality of life was generally worse in females (PDQ-39,
= 0.002; EUROHIS-QOL8,
= 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (
= 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (
= 0.001).
The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.
Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease ...(PwPD) and to compare them with a control group.
PD patients and controls recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. Two visits were conducted: V0 (baseline); V2 (2-year ± 1 month follow-up). SI was defined as a score ≥1 on item nine of the Beck Depression Inventory-II (BDI-II). Regression analyses were conducted to identify factors related to SI.
At baseline, 693 PwPD (60.2% males; 62.59 ± 8.91 years old) and 207 controls (49.8% males; 60.99 ± 8.32 years old) were included. No differences between PwPD and controls were detected in SI frequency at either V0 (5.1% 35/693 vs. 4.3% 9/207; p = 0.421) or at V2 (5.1% 26/508 vs. 4.8% 6/125; p = 0.549). Major depression (MD) and a worse quality of life were associated with SI at both visits in PwPD: V0 (MD, OR = 5.63; p = 0.003; PDQ-39, OR = 1.06; p = 0.021); V2 (MD, OR = 4.75; p = 0.027; EUROHIS-QOL8, OR = 0.22; p = 0.006). A greater increase in the BDI-II total score from V0 to V2 was the only factor predicting SI at V2 (OR = 1.21; p = 0.002) along with an increase in the total number of non-antiparkinsonian drugs (OR = 1.39; p = 0.041).
The frequency of SI (5%) in PwPD was similar to in controls. Depression, a worse quality of life, and a greater comorbidity were related to SI.
In the course of atherogenesis, the spleen plays an important role in the regulation of extramedullary hematopoiesis, and in the control of circulating immune cells, which contributes to plaque ...progression. Here, we have investigated the role of splenic nucleotide-binding oligomerization domain 1 (NOD1) in the recruitment of circulating immune cells, as well as the involvement of this immune organ in extramedullary hematopoiesis in mice fed on a high-fat high-cholesterol diet (HFD). Under HFD conditions, the absence of NOD1 enhances the mobilization of immune cells, mainly neutrophils, from the bone marrow to the blood. To determine the effect of NOD1-dependent mobilization of immune cells under pro-atherogenic conditions,
Apoe
−/−
and
Apoe
−/−
Nod1
−/−
mice fed on HFD for 4 weeks were used. Splenic NOD1 from
Apoe
−/−
mice was activated after feeding HFD as inferred by the phosphorylation of the NOD1 downstream targets RIPK2 and TAK1. Moreover, this activation was accompanied by the release of neutrophil extracellular traps (NETs), as determined by the increase in the expression of peptidyl arginine deiminase 4, and the identification of citrullinated histone H3 in this organ. This formation of NETs was significantly reduced in
Apoe
−/−
Nod1
−/−
mice. Indeed, the presence of Ly6G
+
cells and the lipidic content in the spleen of mice deficient in
Apoe
and
Nod1
was reduced when compared to the
Apoe
−/−
counterparts, which suggests that the mobilization and activation of circulating immune cells are altered in the absence of NOD1. Furthermore, confirming previous studies,
Apoe
−/−
Nod1
−/−
mice showed a reduced atherogenic disease, and diminished recruitment of neutrophils in the spleen, compared to
Apoe
−/−
mice. However, splenic artery ligation reduced the atherogenic burden in
Apoe
−/−
mice an effect that, unexpectedly was lost in
Apoe
−/−
Nod1
−/−
mice. Together, these results suggest that neutrophil accumulation and activity in the spleen are driven in part by NOD1 activation in mice fed on HFD, contributing in this way to regulating atherogenic progression.