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The assessment of inter-regional functional connectivity (FC) has allowed for the description of the putative mechanism of action of treatments such as deep brain stimulation (DBS) of the nucleus accumbens in patients with obsessive–compulsive disorder (OCD). Nevertheless, the possible FC alterations of other clinically-effective DBS targets have not been explored. Here we evaluated the FC patterns of the subthalamic nucleus (STN) and the bed nucleus of the stria terminalis (BNST) in patients with OCD, as well as their association with symptom severity.
Eighty-six patients with OCD and 104 healthy participants were recruited. A resting-state image was acquired for each participant and a seed-based analysis focused on our two regions of interest was performed using statistical parametric mapping software (SPM8). Between-group differences in FC patterns were assessed with two-sample t test models, while the association between symptom severity and FC patterns was assessed with multiple regression analyses.
In comparison with controls, patients with OCD showed: (1) increased FC between the left STN and the right pre-motor cortex, (2) decreased FC between the right STN and the lenticular nuclei, and (3) increased FC between the left BNST and the right frontopolar cortex. Multiple regression analyses revealed a negative association between clinical severity and FC between the right STN and lenticular nucleus.
This study provides a neurobiological framework to understand the mechanism of action of DBS on the STN and the BNST, which seems to involve brain circuits related with motor response inhibition and anxiety control, respectively.
Prematurity is a risk factor for hypertension, vascular stiffness, nephron deficit and adult onset cardiorenal disease. The vascular tree and kidneys share morphogenic drivers that promote maturation in utero before 36 weeks of gestation. Vascular elastin accrual terminates after birth leaving collagen to promote vascular stiffness. Our objective was to determine if the histomorphometry of the umbilical artery, an extension of the aorta, parallels nephron mass across gestational age groups. From a cohort of 54 newborns, 32 umbilical cord specimens were adequate for evaluation. The umbilical cord was sectioned, stained with trichrome, and digitalized. Muscular and collagenous areas of the umbilical artery were measured in pixels using the Image J 1.48q software. Total kidney volume was measured by ultrasound and factored by body surface area (TKV/BSA). The umbilical artery total area was significantly greater in term v. preterm infants (9.3±1.3 v. 7.0±2.0 mm2; P<0.05) and increased with gestational age; while the percent muscular and collagen areas were independent of gestational age (R2=0.04; P=ns). Percent muscular area correlated positively with TKV/BSA (r=0.53; P=0.002); while an increase in collagen correlated inversely with kidney mass (r=−0.53; P=0.002). In conclusion, an enhanced % muscular area and presumed vascular elasticity was associated with increased renal mass in all infants. Umbilical artery histomorphometry provides a link between the intrauterine environment, vascular and kidney development.
Recent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.
To systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).
Analysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD–ASD (n = 16) and healthy controls (n = 78).
Weighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures.
Our results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors.
From a new compilation of spectral types and photometry (version April '98 on the Web) performed by van der Hucht for the Galactic WR stars, we have estimated the distance using two different luminosity-spectral type calibrations. Both determinations lead to similar results. On the basis of newly determined distances we have performed a quantitative analysis of the spatial density distribution for the WN and WC spectral types as well as for the whole WR sample and compared them to the one depicted by the large star-forming regions delineated by the population of young open clusters (YOCs). WR stars show a clumpy distribution similar to the one shown by the YOCs and the WN and WC spectral classes present different galactic distributions as well. Otherwise, variations of the WC/WN quotient do not show a clear correlation with the galactic metallicity gradient, on the contrary this ratio seems to be constant on regions of about 1 kpc in size and shows significant variations (even by a factor of 8) between the closest star-forming complexes.
The in vitro leishmanicidal activity of a series of imidazole-containing phthalazine derivatives 1–4 was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, and their cytotoxicity on J774·2 macrophage cells was also measured. All compounds tested showed selectivity indexes higher than that of the reference drug glucantime for the three Leishmania species, and the less bulky monoalkylamino substituted derivatives 2 and 4 were clearly more effective than their bisalkylamino substituted counterparts 1 and 3. Both infection rate measures and ultrastructural alterations studies confirmed that 2 and 4 were highly leishmanicidal and induced extensive parasite cell damage. Modifications to the excretion products of parasites treated with 2 and 4 were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds 2 and 4 were potent inhibitors of iron superoxide dismutase enzyme (Fe-SOD) in the three species considered, whereas their impact on human CuZn-SOD was low. Molecular modelling suggests that 2 and 4 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the antioxidant features of the enzyme.
No comprehensive study has yet been conducted to determine the chronostratigraphic distribution of palygorskite in the Tertiary sediments of Iran. Thirty sediment samples of different Tertiary epochs were taken, based on the field observations and geological maps. The clay fraction of samples was then investigated by X-ray diffraction (XRD), transmission and scanning electron microscopy (TEM and SEM), and inductively coupled plasma mass spectrometry (ICP-MS). Results showed that sediments of the Miocene and Pliocene had large amounts of palygorskite whereas no trace of this mineral was found in the sediments from the Palaeocene, Eocene and Oligocene. Geochemical analyses revealed that sediments younger than the Oligocene had greater amounts of soluble Mg and H4SiO4 and a higher pH than those of the Palaeocene and Eocene. The stability diagram of the smectite-palygorskite system suggests that smectite is unstable and transforms to palygorskite in Neogene sediments. The SEM micrographs showed palygorskite as interwoven fibrous mats, coatings, pore-fillings and pore-bridging material in Neogene sediments. This textural evidence suggests a direct chemical precipitation of palygorskite by dissolution of silicates under the alkaline conditions. The results also suggest that geochemical conditions in the Early Tertiary era, represented by deep-sea conditions in central Iran, were not apparently favourable for palygoskite formation until the Late Oligocene.