Brain development in fetal life and early infancy is critical to determine lifelong performance in various neuropsychological domains. Metabolic pathologies such as overweight, obesity, and ...gestational diabetes in pregnant women are prevalent and increasing risk factors that may adversely affect long-term brain development in their offspring.
The objective of this research was to investigate the influence of maternal metabolic pathologies on the neurodevelopment of the offspring at 6 and 18 months of life.
This was a prospective case-control study of 331 mother- and child pairs from Granada, Spain. The mothers were included during pregnancy into four groups according to their pre-gestational body mass index and their gestational diabetes status; overweight (n:56), obese (n:64), gestational diabetic (n:79), and healthy normal weight controls (n:132). At 6 months and 18 months we assessed the children with the Bayley III scales of neurodevelopment.
At 6 months (n=215), we found significant group differences in cognition composite language, and expressive language. Post hoc test revealed unexpectedly higher scores in the obese group compared to the normal weight group and a similar trend in overweight and diabetic group. The effects on language remained significant after adjusting for confounders with an adjusted odds ratio for a value above median in composite language score of 3.3 (95% CI: 1.1, 10.0; p=0.035) for children of obese mothers. At 18 month (n=197), the offspring born to obese mothers had lost five points in language composite scores and the previous differences in language and cognition was replaced by a suggestive trend of lower gross motor scores in the overweight, obese, and diabetic groups.
Infants of obese mothers had a temporary accelerated development of cognition and language, followed by a rapid deceleration until 18 months of age, particularly of language scores. This novel observation prompts further confirmative studies to explore possible placental and neurodevelopmental mechanisms involved.
Maternal overweight, obesity, and gestational diabetes (GD) have been negatively associated with offspring development. Further knowledge regarding metabolic and nutritional alterations in these ...mother and their offspring are warranted.
In an observational cohort study we included 331 pregnant women from Granada, Spain. The mothers were categorized into four groups according to BMI and their GD status; overweight (n:56), obese (n:64), GD (n:79), and healthy normal weight controls (n:132). We assessed maternal growth and nutritional biomarkers at 24 weeks (n = 269), 34 weeks (n = 310) and at delivery (n = 310) and the perinatal characteristics including cord blood biomarkers.
Obese and GD mothers had significantly lower weight gain during pregnancy and infant birth weight, waist circumference, and placental weight were higher in the obese group, including a significantly increased prevalence of macrosomia. Except for differences in markers of glucose metabolism (glucose, HbA1c, insulin and uric acid) we found at some measures that overweight and/or obese mothers had lower levels of transferrin saturation, hemoglobin, Vitamin B12 and folate and higher levels of C-reactive protein, erythrocyte sedimentation rate, ferritin, and cortisol. GD mothers had similar differences in hemoglobin and C-reactive protein but higher levels of folate. The latter was seen also in cord blood.
We identified several metabolic alterations in overweight, obese and GD mothers compared to controls. Together with the observed differences in infant anthropometrics, these may be important biomarkers in future research regarding the programming of health and disease in children.
The trial was registered at clinicaltrials.gov, identifier ( NCT01634464 ).
This study assessed the long-term effects of triple therapy with prostanoids on patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD), as there is limited ...information on the safety and efficacy of this treatment approach.
A retrospective cohort study was conducted on patients with PAH-CHD who were actively followed up at our centre. All patients were already receiving dual combination therapy at maximum doses. Clinical characteristics, including functional class (FC), 6-minute walking test distance (6MWTD) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, were documented before initiating triple therapy and annually for a 2-year follow-up period.
A total of 60 patients were included in the study, with a median age of 41 years and 68% being women. Of these, 32 had Eisenmenger syndrome, 9 had coincidental shunts, 18 had postoperative PAH and 1 had a significant left-to-right shunt. After 1 year of triple combination initiation, a significant improvement in 6MWTD was observed (406 vs 450; p=0.0027), which was maintained at the 2-year follow-up. FC improved in 79% of patients at 1 year and remained stable in 76% at 2 years. NT-proBNP levels decreased significantly by 2 years, with an average reduction of 199 ng/L. Side effects were experienced by 33.3% of patients but were mostly mild and manageable. Subgroup analysis showed greater benefits in patients without Eisenmenger syndrome and those with pre-tricuspid defects.
Triple therapy with prostanoids is safe and effective for patients with PAH-CHD, improving FC, 6MWTD and NT-proBNP levels over 2 years. The treatment is particularly beneficial for patients with pre-tricuspid defects and non-Eisenmenger PAH-CHD.
We have modeled the effects of moderate‐sized (30–100 km diameter) impacts on Mars using a one‐dimensional radiative‐convective model. The model computes the evolution of temperature following an ...impact and includes a subsurface model to compute the evolution of the ground temperature; a hydrological cycle to follow the evaporation, condensation, and precipitation of injected and surface‐evaporated water; a radiative transfer code to compute greenhouse warming by CO2, water vapor, and water clouds; and an atmospheric thermodynamics module to compute the latent heating due to cloud formation/dissipation. We have found that parts of the Martian regolith may be kept above freezing for 95 days to decades by the modeled events. However, if we include the radiative effects of water clouds, a sustained greenhouse climate is computed for impactors 50 km in size that could be centuries long. The amount of water precipitated out of the atmosphere from vaporization of impactor, target, and polar caps yields global rainfall totals ranging from 40 to 18 m depending on the size of the impactor and assumed background CO2 atmosphere. We also estimate the surface erosion following precipitation events and find that the total erosion done by all impactors in time is the same order of magnitude as the total erosion estimated to have occurred on early Mars.
Molecular recognition features (MoRFs) are common in intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs). MoRFs are in constant order–disorder structural transitions ...and adopt well-defined structures once they are bound to their targets. Here, we study Escargot (Esg), a transcription factor in Drosophila melanogaster that regulates multiple cellular functions, and consists of a disordered N-terminal domain and a group of zinc fingers at its C-terminal domain. We analyzed the N-terminal domain of Esg with disorder predictors and identified a region of 45 amino acids with high probability to form ordered structures, which we named S2. Through 54 μs of molecular dynamics (MD) simulations using CHARMM36 and implicit solvent (generalized Born/surface area (GBSA)), we characterized the conformational landscape of S2 and found an α-MoRF of ∼16 amino acids stabilized by key contacts within the helix. To test the importance of these contacts in the stability of the α-MoRF, we evaluated the effect of point mutations that would impair these interactions, running 24 μs of MD for each mutation. The mutations had mild effects on the MoRF, and in some cases, led to gain of residual structure through long-range contacts of the α-MoRF and the rest of the S2 region. As this could be an effect of the force field and solvent model we used, we benchmarked our simulation protocol by carrying out 32 μs of MD for the (AAQAA)3 peptide. The results of the benchmark indicate that the global amount of helix in shorter peptides like (AAQAA)3 is reasonably predicted. Careful analysis of the runs of S2 and its mutants suggests that the mutation to hydrophobic residues may have nucleated long-range hydrophobic and aromatic interactions that stabilize the MoRF. Finally, we have identified a set of residues that stabilize an α-MoRF in a region still without functional annotations in Esg.
Both maternal Fe deficiency (ID) and being overweight or obese (Ow/Ob, BMI≥25 kg/m2) may negatively affect offspring brain development. However, the two risk factors correlate and their independent ...effects on infant neurodevelopment are unclear. PREOBE is a prospective observational study that included 331 pregnant Spanish women, of whom 166 had pre-gestational Ow/Ob. Fe status was analysed at 34 weeks and at delivery, and babies were assessed using Bayley III scales of neurodevelopment at 18 months. In confounder-adjusted analyses, maternal ID at 34 weeks was associated with lower composite motor scores at 18 months (mean 113·3 (sd 9·9) v. 117·1 (sd 9·2), P=0·039). Further, the offspring of mothers with ID at delivery had lower cognitive scores (114·0 (sd 9·7) v. 121·5 (sd 10·9), P=0·039) and lower receptive, expressive and composite (99·5 (sd 8·6) v. 107·6 (sd 8·3), P=0·004) language scores. The negative associations between maternal ID at delivery and Bayley scores remained even when adjusting for maternal Ow/Ob and gestational diabetes. Similarly, maternal Ow/Ob correlated with lower gross motor scores in the offspring (12·3 (sd 2·0) v. 13·0 (sd 2·1), P=0·037), a correlation that remained when adjusting for maternal ID. In conclusion, maternal ID and pre-gestational Ow/Ob are both negatively associated with Bayley scores at 18 months, but independently and on different subscales. These results should be taken into account when considering Fe supplementation for pregnant women.
This study analyzed how maternal obesity affected fatty acids (FAs) in breast milk and their association with infant growth and cognition to raise awareness about the programming effect of maternal ...health and to promote a healthy prenatal weight. Mother-child pairs (
= 78) were grouped per maternal pre-pregnancy body mass index (BMI): normal-weight (BMI = 18.5-24.99), overweight (BMI = 25-29.99) and obese (BMI > 30). Colostrum and mature milk FAs were determined. Infant anthropometry at 6, 18 and 36 months of age and cognition at 18 were analyzed. Mature milk exhibited lower arachidonic acid (AA) and docosahexaenoic acid (DHA), among others, than colostrum. Breast milk of non-normal weight mothers presented increased saturated FAs and n6:n3 ratio and decreased α-linolenic acid (ALA), DHA and monounsaturated FAs. Infant BMI-for-age at 6 months of age was inversely associated with colostrum n6 (e.g., AA) and n3 (e.g., DHA) FAs and positively associated with n6:n3 ratio. Depending on the maternal weight, infant cognition was positively influenced by breast milk linoleic acid, n6 PUFAs, ALA, DHA and n3 LC-PUFAs, and negatively affected by n6:n3 ratio. In conclusion, this study shows that maternal pre-pregnancy BMI can influence breast milk FAs and infant growth and cognition, endorsing the importance of a healthy weight in future generations.
Midline prostatic cysts are infrequent and mostly asymptomatic. We presented a striking case of a giant midline cyst and detailed its diagnosis, evolution, and treatment. From this case, we offered a ...comparison of congenital intraprostatic midline cysts, namely, Müller's cysts and utricle cysts. A 40-year-old male experienced recurrent urinary retention. A 10 × 11 mm
cyst in the mid-prostatic region was diagnosed through transrectal ultrasound, leading to a transperineal puncture as a minimally invasive intervention. Seven years later, the cyst recurred, manifesting obstructive symptoms such as a weak urinary stream, frequent urination, and residual urine sensation. Laparoscopic surgery was then performed for the confirmed 98 × 13 mm
cystic recurrence. The postoperative course was favourable with no complications. Symptoms were completely resolved, which was maintained over a three-year follow-up period. The therapeutic approach to midline cysts targets symptomatic cases or infertility, ranging from cyst puncture to transurethral endoscopic treatment. Recurrence after minimally invasive interventions is a challenge, with laparoscopic surgery as an alternative post-failed conservative approach. Although total cyst removal risks adjacent structure damage, marsupialisation improves the clinical outcomes. In summary, symptomatic midline prostatic cysts present challenges owing to recurrences after minimally invasive approaches. Enhanced laparoscopic techniques offer a solution, particularly in highly symptomatic cases requiring definitive treatment, as illustrated by this outstanding case report.
Children born to obese mothers are at increased risk for obesity, but the mechanisms behind this association are not fully understood. Our study aimed to investigate differences in the functions ...encoded by the microbiome of infants at 18 months of age when the transition from early infant-feeding to solid family foods is established. To investigate the impact of maternal prepregnancy body mass index on infants’ gut microbiome, faecal samples from infants born to normoweight (
n
= 21) and obese mothers (
n
= 18) were analysed by 16S rRNA gene sequencing and a functional-inference-based microbiome analysis. Our results indicated that
Firmicutes
was significantly enriched in infants born to normoweight mothers whereas
Bacteroidetes
was significantly enriched in infants born to obese women. In both microbiomes, the greatest number of genes (>50%) that were assigned a function encoded for proteins involved in “metabolism” among tier 1 KEGG Orthology (KO) categories. At lower KO functional categories, the microbiome of infants born to normoweight mothers was characterized by a significant enrichment in the abundances of “pentose phosphate pathway” (
p
= 0.037), “lysine biosynthesis” (
p
= 0.043), “glycerolipid metabolism” (
p
= 0.042), and “C5-branched dibasic acid metabolism” (
p
= 0.045). Notably, the microbiome of infants born to obese mothers was significantly enriched in “streptomycin biosynthesis” (
p
= 0.047), “sulphur metabolism” (
p
= 0.041), “taurine and hypotaurine metabolism” (
p
= 0.036), and “lipopolysaccharide biosynthesis” (
p
= 0.043). In summary, our study showed that maternal prepregnancy obesity may imprint a selective gut microbial composition during late infancy with distinct functional performances.
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