227 research outputs found
Early human brain development:insights into macroscale connectome wiring
BACKGROUND: Early brain development is closely dictated by distinct neurobiological principles. Here, we aimed to map early trajectories of structural brain wiring in the neonatal brain. METHODS: We investigated structural connectome development in 44 newborns, including 23 preterm infants and 21 full-term neonates scanned between 29 and 45 postmenstrual weeks. Diffusion-weighted imaging data were combined with cortical segmentations derived from T2 data to construct neonatal connectome maps. RESULTS: Projection fibers interconnecting primary cortices and deep gray matter structures were noted to mature faster than connections between higher-order association cortices (fractional anisotropy (FA) F = 58.9, p < 0.001, radial diffusivity (RD) F = 28.8, p < 0.001). Neonatal FA-values resembled adult FA-values more than RD, while RD approximated the adult brain faster (F = 358.4, p < 0.001). Maturational trajectories of RD in neonatal white matter pathways revealed substantial overlap with what is known about the sequence of subcortical white matter myelination from histopathological mappings as recorded by early neuroanatomists (mean RD 68 regions r = 0.45, p = 0.008). CONCLUSION: Employing postnatal neuroimaging we reveal that early maturational trajectories of white matter pathways display discriminative developmental features of the neonatal brain network. These findings provide valuable insight into the early stages of structural connectome development
The Effect of Thiazide Diuretics on Urinary Prostaglandin E2 Excretion and Serum Sodium in the General Population
Context:Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population. Objective:To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2, and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population. Design:Prospective population-based cohort study (Rotterdam Study). Setting:General population. Participants:2178 participants (65% female, age 64 +/- 8 years) Intervention(s):None. Main Outcome:Measure(s) Serum sodium levels. Results:Higher urinary PGE2 excretion was associated with lower serum sodium: difference in serum sodium for each 2-fold higher PGE2 -0.19 mmol/L [95% confidence interval (CI) -0.31 to -0.06], PGEM -0.29 mmol/L (95% CI -0.41 to -0.17). This association was stronger in thiazide users (per 2-fold higher PGE2 -0.73 vs -0.12 mmol/L and PGEM -0.6 vs -0.25 mmol/L, P for interaction <.05 for both). A propensity score matching analysis of thiazide vs non-thiazide users yielded similar results. The SNP rs34550074 was not associated with lower serum sodium or higher urinary PGE2 or PGEM excretion in thiazide or non-thiazide users. Conclusion:Serum sodium is lower in people with higher urinary PGE2 and PGEM excretion, and this association is stronger in thiazide users. This suggests that PGE2-mediated water reabsorption regulates serum sodium, which is relevant for the pathogenesis of hyponatremia in general and thiazide-induced hyponatremia specifically
The Effect of Thiazide Diuretics on Urinary Prostaglandin E2 Excretion and Serum Sodium in the General Population
Context:Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population. Objective:To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2, and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population. Design:Prospective population-based cohort study (Rotterdam Study). Setting:General population. Participants:2178 participants (65% female, age 64 +/- 8 years) Intervention(s):None. Main Outcome:Measure(s) Serum sodium levels. Results:Higher urinary PGE2 excretion was associated with lower serum sodium: difference in serum sodium for each 2-fold higher PGE2 -0.19 mmol/L [95% confidence interval (CI) -0.31 to -0.06], PGEM -0.29 mmol/L (95% CI -0.41 to -0.17). This association was stronger in thiazide users (per 2-fold higher PGE2 -0.73 vs -0.12 mmol/L and PGEM -0.6 vs -0.25 mmol/L, P for interaction <.05 for both). A propensity score matching analysis of thiazide vs non-thiazide users yielded similar results. The SNP rs34550074 was not associated with lower serum sodium or higher urinary PGE2 or PGEM excretion in thiazide or non-thiazide users. Conclusion:Serum sodium is lower in people with higher urinary PGE2 and PGEM excretion, and this association is stronger in thiazide users. This suggests that PGE2-mediated water reabsorption regulates serum sodium, which is relevant for the pathogenesis of hyponatremia in general and thiazide-induced hyponatremia specifically
Successful control of a hospital-wide outbreak of OXA-48 producing Enterobacteriaceae in the Netherlands, 2009 to 2011
On 31 May 2011, after notification of Klebsiella pneumoniae(KP)(OXA-48);(CTX-M-15) in two patients, nosocomial transmission was suspected in a Dutch hospital. Hospital-wide infection control measures and an outbreak investigation were initiated. A total of 72,147 patients were categorised into groups based on risk of OXA-48 colonisation or infection, and 7,527 were screened for Enterobacteriaceae(OXA-48) by polymerase chain reaction (PCR). Stored KP isolates (n=408) were retrospectively tested for OXA-48 and CTX-M-1 group extended-spectrum beta-lactamases (ESBL). 285 KP isolates from retrospective and prospective patient screening were genotyped by amplified fragment length polymorphism (AFLP). 41 isolates harbouring different Enterobacteriaceae species were analysed by plasmid multilocus sequence typing (pMLST). No nosocomial transmission of Enterobacteriaceae(OXA-48) was detected after 18 July 2011. Enterobacteriaceae(OXA-48) were found in 118 patients (KP (n=99), Escherichia coli (n=56), >= 1 Enterobacteriaceae(OXA-48) species (n=52)),of whom 21 had clinical infections. 39/41 (95%) of OXA-48 containing plasmids were identical in pMLST. Minimum inhibitory concentrations (MICs) of KPOXA-48 and E. coli(OXA-48) for imipenem and meropenem ranged from = 16 mg/L, and 153/157 (97%) had MIC >0.25mg/L for ertapenem. AFLP identified a cluster of 203 genetically linked isolates (62 KPOXA-48;(CTX-M15); 107 KPCTX-M-15; 34 KPOXA-48). The 'oldest' KPCTX-M-15 and KPOXA-48 clonal types originated from February 2009 and September 2010, respectively. The last presumed outbreak-related KPOXA-48 was detected in April 2012. Uncontrolled transmission of KP (CTX-M-15) evolved into a nosocomial outbreak of KPOXA-48; CTX-M15 with large phenotypical heterogeneity. Although the outbreak was successfully controlled, the contribution of individual containment measures and of the hospital relocating into a new building just before outbreak notification was impossible to quantify
Can Mobile Phone Data Improve Emergency Response to Natural Disasters?
Peter Gething and Andrew Tatem discuss the potential impact of mobile phone positioning data on disaster response and highlight challenges that must be addressed if use of this technology is to develop
Determinants of Life Expectancy and its Prospects under the Role of Economic Misery: A Case of Pakistan
The present study investigates the determinants of life expectancy in the presence of economic misery using Pakistan’s time series data over the period of 1972-2012. The stationary properties of the variables are examined by applying unit root test accommodating structural breaks. The ARDL bounds testing approach to cointegration is applied to examine the long run relationship between the variables. Our findings show that cointegration between the variables is confirmed. Moreover, health spending improves life expectancy. Food supply contributes to life expectancy. A rise in economic misery deteriorates life expectancy. Urbanization enhances life expectancy while illiteracy declines it. The causality analysis reveals that life expectancy is Granger cause of health spending, food supply, economic misery, urbanization and illiteracy. This paper opens up new insights for policy making authorities to consider the role of economic misery while formulating comprehensive economic policy to improve life expectancy in Pakistan
The distinct traits of the UNC13A polymorphism in amyotrophic lateral sclerosis
OBJECTIVE: The rs12608932 single nucleotide polymorphism in UNC13A is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) susceptibility, and may underlie differences in treatment response. We aimed to characterize the clinical, cognitive, behavioral, and neuroimaging phenotype of UNC13A in patients with ALS. METHODS: We included 2,216 patients with ALS without a C9orf72 mutation to identify clinical characteristics associated with the UNC13A polymorphism. A subcohort of 428 patients with ALS was used to study cognitive and behavioral profiles, and 375 patients to study neuroimaging characteristics. Associations were analyzed under an additive genetic model. RESULTS: Genotyping rs12608932 resulted in 854 A/A, 988 A/C, and 374 C/C genotypes. The C allele was associated with a higher age at symptom onset (median years A/A 63.5, A/C 65.6, and C/C 65.5; p < 0.001), more frequent bulbar onset (A/A 29.6%, A/C 31.8%, and C/C 43.1%; p < 0.001), higher incidences of ALS-FTD (A/A 4.3%, A/C 5.2%, and C/C 9.5%; p = 0.003), lower forced vital capacity at diagnosis (median percentage A/A 92.0, A/C 90.0, and C/C 86.5; p < 0.001), and a shorter survival (median in months A/A 33.3, A.C 30.7, and C/C 26.6; p < 0.001). UNC13A was associated with lower scores on ALS-specific cognition tests (means A/A 79.5, A/C 78.1, and C/C 76.6; p = 0.037), and more frequent behavioral disturbances (A/A 16.7%, A/C 24.4%, and C/C 27.7%; p = 0.045). Thinner left inferior temporal and right fusiform cortex were associated with the UNC13A single nucleotide polymorphism (SNP; p = 0.045 and p = 0.036). INTERPRETATION: Phenotypical distinctions associated with UNC13A make it an important factor to take into account in clinical trial design, studies on cognition and behavior, and prognostic counseling. ANN NEUROL 2020;88:796-806
Grafted block complex coacervate core micelles and their effect on protein adsorption on silica and polystyrene
We have studied the formation and the stability of grafted block complex coacervate core micelles (C3Ms) in solution and the influence of grafted block C3M coatings on the adsorption of the proteins β-lactoglobulin, bovine serum albumin, and lysozyme. The C3Ms consist of a grafted block copolymer PAA21-b-PAPEO14 (poly(acrylic acid)-b-poly(acrylate methoxy poly(ethylene oxide)), with a negatively charged PAA block and a neutral PAPEO block and a positively charged homopolymer P2MVPI (poly(N-methyl 2-vinyl pyridinium iodide). In solution, these C3Ms partly disintegrate at salt concentrations between 50 and 100 mM NaCl. Adsorption of C3Ms and proteins has been studied with fixed-angle optical reflectometry, at salt concentrations ranging from 1 to 100 mM NaCl. In comparison with the adsorption of PAA21-b-PAPEO14 alone adsorption of C3Ms significantly increases the amount of PAA21-b-PAPEO14 on the surface. This results in a higher surface density of PEO chains. The stability of the C3M coatings and their influence on protein adsorption are determined by the composition and the stability of the C3Ms in solution. A C3M-PAPEO14/P2MVPI43 coating strongly suppresses the adsorption of all proteins on silica and polystyrene. The reduction of protein adsorption is the highest at 100 mM NaCl (>90%). The adsorbed C3M-PAPEO14/P2MVPI43 layer is partly removed from the surface upon exposure to an excess of β-lactoglobulin solution, due to formation of soluble aggregates consisting of β-lactoglobulin and P2MVPI43. In contrast, C3M-PAPEO14/P2MVPI228 which has a fivefold longer cationic block enhances adsorption of the negatively charged proteins on both surfaces at salt concentrations above 1 mM NaCl. A single PAA21-b-PAPEO14 layer causes only a moderate reduction of protein adsorption
Longitudinal Effects of Asymptomatic C9orf72 Carriership on Brain Morphology
Objective: We investigated effects of C9orf72 repeat expansion and gene expression on longitudinal cerebral changes before symptom onset. Methods: We enrolled 79 asymptomatic family members (AFMs) from 9 families with C9orf72 repeat expansion. Twenty-eight AFMs carried the mutation (C9+). Participants had up to 3 magnetic resonance imaging (MRI) scans, after which we compared motor cortex and motor tracts between C9+ and C9− AFMs using mixed effects models, incorporating kinship to correct for familial relations and lessen effects of other genetic factors. We also compared cortical, subcortical, cerebellar, and connectome structural measurements in a hypothesis-free analysis. We correlated regional C9orf72 expression in donor brains with the pattern of cortical thinning in C9+ AFMs using meta-regression. For comparison, we included 42 C9+ and 439 C9− patients with amyotrophic lateral sclerosis (ALS) in this analysis. Results: C9+ AFM motor cortex had less gyrification and was thinner than in C9− AFMs, without differences in motor tracts. Whole brain analysis revealed thinner cortex and less gyrification in parietal, occipital, and temporal regions, smaller thalami and right hippocampus, and affected frontotemporal connections. Thinning of bilateral precentral, precuneus, and left superior parietal cortex was faster in C9+ than in C9− AFMs. Higher C9orf72 expression correlated with thinner cortex in both C9+ AFMs and C9+ ALS patients. Interpretation: In asymptomatic C9orf72 repeat expansion carriers, brain MRI reveals widespread features suggestive of impaired neurodevelopment, along with faster decline of motor and parietal cortex than found in normal aging. C9orf72 expression might play a role in cortical development, and consequently explain the specific brain abnormalities of mutation carriers. ANN NEUROL 2023;93:668–680
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