Early-life exposure to inorganic arsenic (iAs) may adversely impact health later in life. To date, evidence of iAs adverse effects on children's neurodevelopment comes mainly from populations highly ...exposed to contaminated water with conflicting results. Little is known about those effects among populations with low iAs exposure from food intake. We investigated the cross-sectional association between exposure to iAs and neurodevelopment scores among children living in Spain whose main route of exposure was diet. Arsenic species concentrations in urine from 400 children was determined, and the sum of urinary iAs, dimethylarsinic acid, and monomethylarsonic acid was used to estimate iAs exposure. The McCarthy Scales of Children's Abilities was used to assess children's neuropsychological development at about 4–5 years of age. The median (interquartile range) of children's sum of urinary iAs, MMA, and DMA was 4.85 (2.74–7.54) μg/L, and in adjusted linear regression analyses the natural logarithm transformed concentrations showed an inverse association with children's motor functions (β, 95% confidence interval; global scores (−2.29, -3.95, −0.63)), gross scores (−1.92, -3.52, −0.31) and fine scores (−1.54, -3.06, −0.03). In stratified analyses by sex, negative associations were observed with the scores in the quantitative index (−2.59, -5.36, 0.17) and working memory function (−2.56, -5.36, 0.24) only in boys. Our study suggests that relatively low iAs exposure may impair children's neuropsychological development and that sex-related differences may be present in susceptibility to iAs related effects; however, our findings should be interpreted with caution given the possibility of residual confounding.
•Relatively low iAs exposure may impair children's neuropsychological development.•Sex-related differences may be present in iAs toxic effect susceptibility.•Early-life iAs exposure from food intake should be minimized.
In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the ...white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model.
BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and non-hydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using
H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (
H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay.
Four days after transplantation, BM-MSC were found undifferentiated and scattered into the astrocyte reaction present in the damaged neocortex white matter. Tissue rejection to the integrated BM-MSC was not detected 4 days after transplantation. Hyh mice transplanted with BM-MSC showed a reduction in the apoptosis in the periventricular neocortex walls, suggesting a neuroprotector effect of the BM-MSC in these conditions. A decrease in the levels of metabolites/osmolytes in the neocortex, such as taurine and neuroexcytotoxic glutamate, also indicated a tissue recovering. Under high TNFα level condition in vitro, BM-MSC showed an upregulation of cytokine and protein secretion that may explain homing, immunomodulation, and vascular permeability, and therefore the tissue recovering.
BM-MSC treatment in severe congenital hydrocephalus is viable and leads to the recovery of the severe neurodegenerative conditions in the neocortex. NMR spectroscopy allows to follow-up the effects of stem cell therapy in hydrocephalus.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method able to modulate neuronal activity after stroke. The aim of this systematic review was to determine if tDCS ...combined with robotic therapy (RT) improves limb function after stroke when compared to RT alone.
A search for randomized controlled trials (RCTs) published prior to July 15, 2021 was performed. The main outcome was function assessed with the Fugl-Meyer motor assessment for upper extremities (FM/ue) and 10-m walking test (10MWT) for the lower limbs. As secondary outcomes, strength was assessed with the Motricity Index (MI) or Medical Research Council scale (MRC), spasticity with the modified Ashworth scale (MAS), functional independence with the Barthel Index (BI), and kinematic parameters.
Ten studies were included for analysis (n = 368 enrolled participants). The results showed a non-significant effect for tDCS combined with RT to improve upper limb function standardized mean difference (SMD) = - 0.12; 95% confidence interval (CI): - 0.35-0.11). However, a positive effect of the combined therapy was observed in the lower limb function (SMD = 0.48; 95% CI: - 0.15-1.12). Significant results favouring tDCS combined with RT were not found in strength (SMD = - 0.15; 95% CI: - 0.4-0.1), spasticity mean difference (MD) = - 0.15; 95% CI: - 0.8-0.5), functional independence (MD = 2.5; 95% CI: - 1.9-6.9) or velocity of movement (SMD = 0.06; 95% CI: - 0.3-0.5) with a "moderate" or "low" recommendation level according to the GRADE guidelines.
Current findings suggest that tDCS combined with RT does not improve upper limb function, strength, spasticity, functional independence or velocity of movement after stroke. However, tDCS may enhance the effects of RT alone for lower limb function. tDCS parameters and the stage or type of stroke injury could be crucial factors that determine the effectiveness of this therapy.
Objective
To report a 15-y, single-center experience in the management and outcomes of ileocolic intussusception (ICI) episodes.
Methods
A retrospective study was performed in patients with ICI ...episodes, who were treated at a single quaternary referral center from 2005 to 2019. Data evaluated included patient demographics, clinical presentation, treatment modalities, hospital stay, complications, and outcomes.
Results
A total of 546 ICI episodes (66.1% males) were included, with a median age at diagnosis of 15 mo. Enema reduction was performed in 478 patients (87.6%), with an overall success rate of 85.8%. Hydrostatic saline enema was the most effective method (89.3%) when compared to pneumatic (80.6%) or barium enema (79.8%), this difference being statistically significant (
p
= 0.031). No associated complications were observed during nonoperative reduction. Surgical treatment was performed in 101 patients, in whom 36 bowel resections were performed. Postoperative complications were reported in 6 patients (5.9%). Hospital stay was significantly longer in patients with operative management (median 5 d vs. 1 d;
p
< 0.001).
Conclusions
Nonoperative management has a high overall success rate and low complication and recurrence rates. Saline enema reduction presents the highest effectiveness, and should be considered the first-line treatment.
This study aimed to evaluate the safety and mid-term efficacy of transcatheter aortic valve replacement (TAVR) in the setting of aortic valve (AV) infective endocarditis (IE) with residual lesion ...despite successful antibiotic treatment.
Patients with AV-IE presenting residual lesion despite successful antibiotic treatment are often rejected for cardiac surgery due to high-risk. The use of TAVR following IE is not recommended.
This was a multicenter retrospective study across 10 centers, gathering baseline, in-hospital, and 1-year follow-up characteristics of patients with healed AV-IE treated with TAVR. Matched comparison according to sex, EuroSCORE, chronic kidney disease, left ventricular function, prosthesis type, and valve-in-valve procedure was performed with a cohort of patients free of prior IE treated with TAVR (46 pairs).
Among 2,920 patients treated with TAVR, 54 (1.8%) presented with prior AV-IE with residual valvular lesion and healed infection. They had a higher rate of multivalvular disease and greater surgical risk scores. A previous valvular prosthesis was more frequent than a native valve (50% vs. 7.5%; p < 0.001). The in-hospital and 1-year mortality rates were 5.6% and 11.1%, respectively, comparable to the control cohort. After matching, the 1-year III to IV aortic regurgitation rate was 27.9% (vs. 10%; p = 0.08) and was independently associated with higher mortality. There was only 1 case of IE relapse (1.8%); however, 18% of patients were complicated with sepsis, and 43% were readmitted due to heart failure.
TAVR is a safe therapeutic alternative for residual valvular lesion after successfully healed AV-IE. At 1-year follow-up, the risk of IE relapse was low and mortality rate did not differ from TAVR patients free of prior IE, but one-fourth presented with significant aortic regurgitation and >50% required re-admission.
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Abstract
In congenital hydrocephalus, cerebrospinal fluid accumulation is associated with increased intracranial pressure (ICP), ischemia/hypoxia, metabolic impairment, neuronal damage, and ...astrocytic reaction. The aim of this study was to identify whether a metabolite profile revealing tissue responses according to the severity of hydrocephalus can be detected. The hyh mutant mouse used for this study exhibits 2 different forms of hydrocephalus, severe and moderate. In a comprehensive investigation into the 2 progressions of hydrocephalus, mice with severe hydrocephalus were found to have higher ICP and astrocytic reaction. Several metabolites from the mouse brain cortex were analyzed with 1H high-resolution magic angle spinning nuclear magnetic resonance (1H HR-MAS NMR) spectroscopy. A differential profile for metabolites including glutamate and glutamine was found to correlate with the severity of hydrocephalus and can be explained due to differential astrocytic reactions, neurodegenerative conditions, and the presence of ischemia. The glutamate transporter EAAT2 and the metabolite taurine were found to be key histopathological markers of affected parenchymata. In conclusion, a differential metabolite profile can be detected according to the severity of hydrocephalus and associated ICP and therefore can be used to monitor the efficacy of experimental therapies.
This randomized double-blind and controlled single-center clinical trial was designed to evaluate the effect of a 6-week intake of a probiotic product (1 capsule/day) vs. a placebo on an oxidative ...stress model of physical exercise (high intensity and duration) in male cyclists (probiotic group,
= 22; placebo,
= 21). This probiotic included three lyophilized strains (
CECT 7347,
CECT 9104, and
CECT 8361). Study variables were urinary isoprostane, serum malondialdehyde (MDA), serum oxidized low-density lipoprotein (Ox-LDL), urinary 8-hydroxy-2'-deoxiguanosine (8-OHdG), serum protein carbonyl, serum glutathione peroxidase (GPx), and serum superoxide dismutase (SOD). At 6 weeks, as compared with baseline, significant differences in 8-OHdG (Δ mean difference -10.9 (95% CI -14.5 to -7.3);
< 0.001), MDA (Δ mean difference -207.6 (95% CI -349.1 to -66.1;
< 0.05), and Ox-LDL (Δ mean difference -122.5 (95% CI -240 to -4.5);
< 0.05) were found in the probiotic group only. Serum GPx did not increase in the probiotic group, whereas the mean difference was significant in the placebo group (477.8 (95% CI 112.5 to 843.2);
< 0.05). These findings suggest an antioxidant effect of this probiotic on underlying interacting oxidative stress mechanisms and their modulation in healthy subjects. The study was registered in ClinicalTrials.gov (NCT03798821).
We have studied a genomic library of introgression lines from the Solanum pimpinellifolium accession TO-937 into the genetic background of the "Moneymaker" cultivar in order to evaluate the ...accession's breeding potential. Overall, no deleterious phenotypes were observed, and the plants and fruits were phenotypically very similar to those of "Moneymaker," which confirms the feasibility of translating the current results into elite breeding programs. We identified chromosomal regions associated with traits that were both vegetative (plant vigor, trichome density) and fruit-related (morphology, organoleptic quality, color). A trichome-density locus was mapped on chromosome 10 that had not previously been associated with insect resistance, which indicates that the increment of trichomes by itself does not confer resistance. A large number of quantitative trait loci (QTLs) have been identified for fruit weight. Interestingly, fruit weight QTLs on chromosomes 1 and 10 showed a magnitude effect similar to that of QTLs previously defined as important in domestication and diversification. Low variability was observed for fruit-shape-related traits. We were, however, able to identify a QTL for shoulder height, although the effects were quite low, thus demonstrating the suitability of the current population for QTL detection. Regarding organoleptic traits, consistent QTLs were detected for soluble solid content (SSC). Interestingly, QTLs on chromosomes 2 and 9 increased SSC but did not affect fruit weight, making them quite promising for introduction in modern cultivars. Three ILs with introgressions on chromosomes 1, 2, and 10 increased the internal fruit color, making them candidates for increasing the color of modern cultivars. Comparing the QTL detection between this IL population and a recombinant inbred line population from the same cross, we found that QTL stability across generations depended on the trait, as it was very high for fruit weight but low for organoleptic traits. This difference in QTL stability may be due to a predominant additive gene action for QTLs involved in fruit weight, whereas epistatic and genetic background interactions are most likely important for the other traits.
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