•The neonatal brain can generate epileptic high-frequency oscillations (HFOs), though their occurrence is not common.•Neonatal ripples and fast ripples co-occur with ictal and interictal sharp ...transients.•Our data on neonatal HFOs could not yet support their potential value for outcome prediction.
Neonatal seizures are often the first symptom of perinatal brain injury. High-frequency oscillations (HFOs) are promising new biomarkers for epileptogenic tissue and can be found in intracranial and surface EEG. To date, we cannot reliably predict which neonates with seizures will develop childhood epilepsy. We questioned whether epileptic HFOs can be generated by the neonatal brain and potentially predict epilepsy.
We selected 24 surface EEGs sampled at 2048 Hz with 175 seizures from 16 neonates and visually reviewed them for HFOs. Interictal epochs were also reviewed.
We found HFOs in thirteen seizures (7%) from four neonates (25%). 5025 ictal ripples (rate 10 to 1311/min; mean frequency 135 Hz; mean duration 66 ms) and 1427 fast ripples (rate 8 to 356/min; mean frequency 298 Hz; mean duration 25 ms) were marked. Two neonates (13%) showed interictal HFOs (285 ripples and 25 fast ripples). Almost all HFOs co-occurred with sharp transients. We could not find a relationship between neonatal HFOs and outcome yet.
Neonatal HFOs co-occur with ictal and interictal sharp transients.
The neonatal brain can generate epileptic ripples and fast ripples, particularly during seizures, though their occurrence is not common and potential clinical value not evident yet.
This paper reports on an experimental animal study evaluating a method of mandibular reconstruction. After a successful pilot study, 28 goats underwent a continuity resection of the mandibular angle. ...Primary reconstruction was carried out using specially designed osteosynthesis plates and screws. The defect was bridged by the original cortical scaffold, filled with an autogenous bone graft from the iliac crest. To accelerate bone healing, platelet-rich plasma (PRP) was mixed with the particulate bone graft in 14 goats. All goats had uneventful healing. The osteosynthesis plates and screws withstood immediate loading for periods varying from 3 weeks to 3 months. The use of PRP appeared to enhance bone healing considerably.
Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive ...heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log
Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.
Intraoperative imaging enables the surgeon to control the position of the implant during orbital reconstruction. Although it might improve surgical outcome and avoid the need for revision surgery, it ...may also increase the duration of the operation and the exposure to radiation. The goal of this study was to find out whether intraoperative imaging improves the position of the implant in reconstructions of the orbital floor and medial wall. Two surgeons reconstructed complex orbital fractures in 10 cadavers. After the reconstruction a computed tomographic scan was made to confirm the position of the implant and, if required, to make any adjustments. Scans were repeated until the surgeon was satisfied. The ideal position was ascertained by scans that were obtained before and after creation of the fractures. The position of the implant achieved was compared with that of the ideal position of the implant, and improved significantly for yaw (p=0.04) and roll (p=0.03). A mean of 1.6 scans was required for each reconstruction (maximum n=3). The main reason for alteration was the rotation roll. Intraoperative imaging significantly improves the position of the implant in fractures of the orbital floor and medial wall. The surgeon has quality control of its position during the reconstruction to restore the anatomical boundaries.
Mercury (Hg) concentrations in fish in boreal reservoirs have been shown to be increased for up to 3 decades after impoundment. However, the time course of increased concentrations is not well known. ...The purpose of this study was to determine the evolution of Hg concentrations in fish in the boreal reservoirs of northern Manitoba, Canada, and its relationship with severity of flooding. We determined total Hg concentrations in three species of fish for up to 35 years after impoundment in 14 lakes and lake basins. Postimpoundment trends depended on fish species and reservoir. In the benthivorous lake whitefish (Coregonus clupeaformis), Hg concentrations increased after flooding to between 0.2 and 0.4 μg g-¹ wet weight compared with preimpoundment concentrations between 0.06 and 0.14 μg g-¹ and concentrations in natural lakes between 0.03 and 0.06 μg g-¹. Hg concentrations in lake whitefish were usually highest within 6 years after lake impoundment and took 10 to 20 years after impoundment to decrease to background concentrations in most reservoirs. Hg concentrations in predatory northern pike (Esox lucius) and walleye (Sander vitreus) were highest 2 to 8 years after flooding at 0.7 to 2.6 μg g-¹ compared with preimpoundment concentrations of 0.19 to 0.47 μg g-¹ and concentrations in natural lakes of 0.35 to 0.47 μg g-¹. Hg concentrations in these predatory species decreased consistently in subsequent years and required 10 to 23 years to return to background levels. Thus, results demonstrate the effect of trophic level on Hg concentrations (biomagnification). Peak Hg concentrations depended on the amount of flooding (relative increase in lake surface area). Asymptotic concentrations of approximately 0.25 μg g-¹ for lake whitefish and 1.6 μg g-¹ for both walleye and northern pike were reached at approximately 100% flooding. Downstream effects were apparent because many reservoirs downstream of other impoundments had higher Hg concentrations in fish than would be expected on the basis of flooding amount.
We present a kinetic Monte Carlo lattice gas model including top and bridge sites on a square lattice, with pairwise lateral interactions between the adsorbates. In addition to the pairwise lateral ...interactions we include an additional interaction: an adsorbate is forbidden to adsorb on a bridge site formed by two surface atoms when both surface atoms are already forming a bond with an adsorbate. This model is used to reproduce the low and high coverage adsorption behaviour of CO on Pt(100) and Rh(100). The parameter set used to simulate CO on Pt(100) produces the c(2 x 2)-2t ordered structure at 0.50 ML coverage, a one-dimensionally ordered structure similar to the experimentally observed (3 square root(2) x square root(2)) - 2t + 2b structure at 0.67 ML coverage, the c(4 x 2)-4t + 2b ordered structure at 0.75 ML coverage, and the recently reported c(6 x 2)-6t + 4b ordered structure at 0.83 ML coverage. The (5 square root(2) x square root(2)) ordered structure at 0.60 ML coverage is not reproduced by our model. The parameter set used to simulate CO on Rh(100) produces the c(2 x 2)-2t ordered structure at 0.50 ML coverage, a one-dimensionally ordered structure similar to the experimentally observed (4 square root(2) x square root(2)) - 2t + 4b structure at 0.75 ML coverage, and the c(6 x 2)-6t + 4b ordered structure at 0.83 ML coverage. Additionally, the simulated change of top and bridge site occupation as a function of coverage matches the trend in experimental vibrational peak intensities.
Abstract The enzyme alkaline phosphatase (ALP) was recently proposed as an implant coating material in order to improve the biological performance of orthopedic and dental implants. The present study ...evaluated the in vivo bone response to electrosprayed coatings, consisting of ALP, calcium phosphate (CaP) or a combination thereof (composite coating: ALP + CaP) compared to non-coated controls (gritblasted and acid etched). A total of 80 implants ( n = 10) with a gap of 1.0 mm, was implanted intramedullary and bilaterally into the femurs of 80 rats. After 1 and 4 weeks, bone response was evaluated qualitatively (histology) and quantitatively (histomorphometry). The results of this study show that all electrosprayed coatings (ALP, CaP, ALP + CaP) significantly improve osteoconduction compared to non-coated controls after 4 weeks of implantation, without significant differences among these coated groups. Consequently, the results indicate that ALP-coatings improve the osteogenic response to a comparable extent as CaP-coatings or an ALP + CaP composite coating. In conclusion, the current study proofs that ALP-coatings have potential as bone implant coatings, though long-term data remain to be obtained. From a clinical perspective, it was observed that the process of osteoconduction is related to positional determinants, which needs to be taken into account when analyzing data on bone response.
Several trypanosomatid cyclic nucleotide phosphodiesterases (PDEs) possess a unique, parasite-specific cavity near the ligand-binding region that is referred to as the P-pocket. One of these enzymes, ...Trypanosoma brucei PDE B1 (TbrPDEB1), is considered a drug target for the treatment of African sleeping sickness. Here, we elucidate the molecular determinants of inhibitor binding and reveal that the P-pocket is amenable to directed design. By iterative cycles of design, synthesis, and pharmacological evaluation and by elucidating the structures of inhibitor-bound TbrPDEB1, hPDE4B, and hPDE4D complexes, we have developed 4a,5,8,8a-tetrahydrophthalazinones as the first selective TbrPDEB1 inhibitor series. Two of these, 8 (NPD-008) and 9 (NPD-039), were potent (K i = 100 nM) TbrPDEB1 inhibitors with antitrypanosomal effects (IC50 = 5.5 and 6.7 μM, respectively). Treatment of parasites with 8 caused an increase in intracellular cyclic adenosine monophosphate (cAMP) levels and severe disruption of T. brucei cellular organization, chemically validating trypanosomal PDEs as therapeutic targets in trypanosomiasis.
Vanins are enzymes that convert pantetheine to pantothenic acid (vitamin B5). Insights into the function of vanins have evolved lately, indicating vanin-1 to play a role in inflammation, oxidative ...stress and cell migration. Moreover, vanin-1 has recently gained attention as a novel modulator of hepatic glucose and lipid metabolism. In the present study, we investigated the role of vanin-1 in the development of hepatic steatosis and insulin resistance in animal models of obesity and diabetes. In addition, we evaluated the potency of RR6, a novel pharmacological vanin-1 inhibitor, as an anti-diabetic drug. Increased vanin activity was observed in plasma and liver of high fat diet (HFD)-induced obese mice, as well as ZDF-diabetic rats. Ablation of vanin-1 (Vnn1(-/-) mice) mildly improved glucose tolerance and insulin sensitivity in HFD-fed mice, but had no effects on body weight, hepatic steatosis or circulating lipid levels. Oral administration of RR6 for 8 days completely inhibited plasma vanin activity, but did not affect hepatic glucose production, insulin sensitivity or hepatic steatosis in ZDF-diabetes rats. In conclusion, absence of vanin-1 activity improves insulin sensitivity in HFD-fed animals, yet short-term inhibition of vanin activity may have limited value as an anti-diabetic strategy.
Abstract Objective Delirium is often accompanied by changes in motor activity but the longitudinal expression of these features and etiological and prognostic significance of clinical subtypes ...defined by motor activity is unclear. Methods This is a prospective cohort study of elderly patients undergoing hip fracture surgery. Baseline characteristics were assessed preoperatively. During hospital admission presence of delirium was assessed daily according to CAM criteria. This study compared baseline characteristics and outcomes according to a longitudinal pattern of motor subtype expression (predominantly hyperactive, predominantly hypoactive, predominantly mixed, no motor subtype and variable). Motor subtype categorization was performed with the DRS-R98. We also investigated the longitudinal stability of motor subtypes across the delirium episode. Results 62 patients had experienced in-hospital delirium postoperatively. The full course of the delirium episode could be defined for 42/62 (67.7%) patients. Of the patients with multiple days of delirium only 4/30 (13.3%) patients had a consistent motor subtype profile throughout the delirium episode, while 26/30 (86.7%) patients had a variable course. Of the patients with multiple days of delirium, 5/30 (16.7%) were predominantly hypoactive in profile, 7/30 (23.3%) predominantly hyperactive, 6/30 (20%) predominantly mixed, 1/30 (3.3%) had no motor subtype and 11/30 (36.7%) had a variable profile. Baseline characteristics and outcomes did not differ between the groups. Conclusion The majority of elderly hip fracture patients in this homogenous sample experienced variable expression of motor subtype over the course of their delirium episodes. The subtype categorization according to dominant motor subtype across the delirium episode identified groups with similar characteristics and outcomes.
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