Summary
The extent of analgesia provided by transversus abdominis plane blocks depends upon the site of injection and pattern of spread within the plane. There are currently a number of ...ultrasound‐guided approaches in use, including an anterior oblique‐subcostal approach, a mid‐axillary approach and a more recently proposed posterior approach. We wished to determine whether the site of injection of local anaesthetic into the transversus abdominis plane affects the spread of the local anaesthetic within that plane, by studying the spread of a local anaesthetic and contrast solution in four groups of volunteers. The first group underwent the classical landmark‐based transversus abdominis plane block whereby two different volumes of injectate were studied: 0.3 ml.kg−1 vs 0.6 ml.kg−1. The second group underwent transversus abdominis plane block using the anterior subcostal approach. The third group underwent transversus abdominis plane block using the mid‐axillary approach. The fourth group underwent transversus abdominis plane block using the posterior approach, in which local anaesthetic was deposited close to the antero‐lateral border of the quadratus lumborum. All volunteers subsequently underwent magnetic resonance imaging at 1, 2 and 4 h following each block to determine the spread of local anaesthetic over time. The studies demonstrated that the anterior subcostal and mid‐axillary ultrasound approaches resulted in a predominantly anterior spread of the contrast solution within the transversus abdominis plane and relatively little posterior spread. There was no spread to the paravertebral space with the anterior subcostal approach. The mid‐axillary transversus abdominis plane block gave faint contrast enhancement in the paravertebral space at T12‐L2. In contrast, the posterior approaches, using both landmark and ultrasound identifications, resulted in predominantly posterior spread of contrast around the quadratus lumborum to the paravertebral space from T5 to L1 vertebral levels. We concluded that the pattern of spread of local anaesthetic differs depending on the site of injection into the transversus abdominis plane. This may have important implications for the extent of analgesia produced with each approach.
Maintaining the genetic diversity of populations is important in conservation because it strongly influences the ability to adapt to changing environments. We characterised the genetic structure of ...the endemic and endangered New Zealand (NZ) long-tailed bat (Chalinolobus tuberculatus) in two valleys in Fiordland, NZ. Fiordland is one of the last strongholds of the species, which has drastically declined throughout NZ. C. tuberculatus has suffered from recent habitat fragmentation and episodic predation by exotic mammals over the last 150 years. Gene flow and structuring were measured using nine nuclear microsatellite loci. In addition, the hyper-variable domain HVI of the mitochondrial control region was sequenced to analyse population structure at the maternal level. Our results show that the nine colonies studied have retained high genetic diversity, with moderate signs of genetic bottlenecks. Furthermore, low F ST and F IS values indicated that all colonies are still connected by gene flow and do not show signs of inbreeding. Substantial gene flow among colonies was also demonstrated by Bayesian clustering and PCA analysis. At the mitochondrial level, substantial differentiation between colonies has resulted from strong natal philopatry in females. Overall, our results indicate that genetic diversity is maintained in the Fiordland population of C. tuberculatus despite regular population crashes and habitat fragmentation. Management should ensure that remaining habitat linkages are preserved and further predator-induced population bottlenecks are prevented so that current genetic diversity is maintained in the long-term.
Abstract
We investigated brain wiring in chronic schizophrenia and healthy controls in frontostriatal circuits using diffusion magnetic resonance imaging tractography in a novel way.
We extracted ...diffusion streamlines in 27 chronic schizophrenia and 26 healthy controls connecting 4 frontal subregions to the striatum. We labeled the projection zone striatal surface voxels into 2 subtypes: dominant-input from a single cortical subregion, and, functionally integrative, with mixed-input from diverse cortical subregions.
We showed: 1) a group difference for total striatal surface voxel number (P = .045) driven by fewer mixed-input voxels in the left (P = .007), but not right, hemisphere; 2) a group by hemisphere interaction for the ratio quotient between voxel subtypes (P = .04) with a left (P = .006), but not right, hemisphere increase in schizophrenia, also reflecting fewer mixed-input voxels; and 3) fewer mixed-input voxel counts in schizophrenia (P = .045) driven by differences in left hemisphere limbic (P = .007) and associative (P = .01), but not sensorimotor, striatum.
These results demonstrate a less integrative pattern of frontostriatal structural connectivity in chronic schizophrenia. A diminished integrative pattern yields a less complex input pattern to the striatum from the cortex with less circuit integration at the level of the striatum. Further, as brain wiring occurs during early development, aberrant brain wiring could serve as a developmental biomarker for schizophrenia.
BACKGROUND
Information on actual sodium intake and its relationships with blood pressure (BP) and clinical events in South America is limited. The aim of this cohort study was to assess the ...relationship of sodium intake with BP, cardiovascular (CV) events, and mortality in South America.
METHODS
We studied 17,033 individuals, aged 35–70 years, from 4 South American countries (Argentina, Brazil, Chile, and Colombia). Measures of sodium excretion, estimated from morning fasting urine, were used as a surrogate for daily sodium intake. We measured BP and monitored the composite outcome of death and major CV events.
RESULTS
Overall mean sodium excretion was 4.70±1.43g/day. A positive, nonuniform association between sodium and BP was detected, with a significant steeper slope for the relationship at higher sodium excretion levels (P < 0.001 for interaction). With a median follow-up of 4.7 years, the primary composite outcome (all-cause death, myocardial infarction, stroke, or heart failure) occurred in 568 participants (3.4%). Compared with sodium excretion of 5–6g/day (reference group), participants who excreted >7g/day had increased risks of the primary outcome (odds ratio (OR) 1.73; 95% confidence interval (CI) 1.24 to 2.40; P < 0.001), as well as death from any cause (OR 1.87; 95% CI 1.23 to 2.83; P = 0.003) and major CV disease (OR 1.77; 95% CI 1.12 to 2.81; P = 0.014). Sodium excretion of <3g/day was associated with a statistically nonsignificant increased risk of the primary outcome (OR 1.20; 95% CI 0.86 to 1.65; P = 0.26) and death from any cause (OR 1.25; 95% CI 0.81 to 1.93; P = 0.29), and a significant increased risk of major CV disease (OR 1.50; 95% CI 1.01 to 2.24; P = 0.048), as compared to the reference group.
CONCLUSIONS
Our results support a positive, nonuniform association between estimated urinary sodium excretion and BP, and a possible J-shaped pattern of association between sodium excretion over the entire range and clinical outcomes.
Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic ...determination of the two diseases.
Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype.
Common variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5×10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (PIS=1.62×10(-7)) and ABO (PIS=2.6×10(-4)), as well as at HDAC9 (PLAS=2.32×10(-12)), 9p21 (PLAS=3.70×10(-6)), RAI1-PEMT-RASD1 (PLAS=2.69×10(-5)), EDNRA (PLAS=7.29×10(-4)), and CYP17A1-CNNM2-NT5C2 (PLAS=4.9×10(-4)).
Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.
Ophthalmologic features of Vici syndrome Filloux, Francis M; Hoffman, Robert O; Viskochil, David H ...
Journal of pediatric ophthalmology and strabismus,
07/2014, Volume:
51, Issue:
4
Journal Article
Peer reviewed
To report and compile the ophthalmological features critical to diagnosis of Vici syndrome, a rare congenital disorder characterized principally by agenesis of the corpus callosum, cataracts, ...cardiomyopathy, immune defects, and hypopigmentation.
A child with Vici syndrome (OMIM 242840) is reported with emphasis on the ophthalmologic evaluation. Ophthalmologic assessments including fundus examination, visual evoked potentials (VEPs), and ocular coherence tomography are presented. These findings are compared with those identified in other published cases of children with Vici syndrome.
Ophthalmologic findings included bilateral nuclear and anterior polar cataracts, bilateral optic nerve atrophy, and mild fundus hypopigmentation. Evoked potentials recorded across the mid-occipital scalp demonstrated misrouting of optic pathways typical of albinism. Optical coherence tomography exhibited a poorly defined fovea demonstrating a lesser degree of foveal depression also consistent with ocular albinism. Review of reported children with Vici syndrome identifies bilateral cataracts, nystagmus, fundus hypopigmentation, visual impairment, and optic nerve hypoplasia as common ophthalmologic features.
Ophthalmologic findings are critical to the diagnosis of Vici syndrome. Most common are bilateral cataracts and relative fundus hypopigmentation. VEPs can identify misrouting of optic pathways typical of ocular albinism, thereby establishing the diagnosis in challenging cases.
Interest in techniques and applications of the transversus abdominis plane (TAP) block has expanded exponentially since its introduction over ten years ago. The choice of techniques and approaches ...has been assisted with the availability of ultrasound, but the optimal injection for certain surgical incisions are not yet clear. A literature search was performed looking at anatomical and distribution studies, and clinical trials evaluating the effects of TAP blocks in patients undergoing abdominal surgery. Case reports were also included. Clinical and contrast studies indicate that the landmark and ultrasound guided TAP blocks differ in their spread and mode of action. Regardless, both techniques provide effective analgesia for abdominal surgery. Further research is required to compare TAP blocks with epidural analgesia.
Dental chair units (DCUs) use water to cool and irrigate DCU-supplied instruments and tooth surfaces, and provide rinsewater during dental treatment. A complex network of interconnected plastic ...dental unit waterlines (DUWLs) supply water to these instruments. DUWLs are universally prone to microbial biofilm contamination seeded predominantly from microorganisms in supply water. Consequently, DUWL output water invariably becomes contaminated by high densities of microorganisms, principally Gram-negative environmental bacteria including Pseudomonas aeruginosa and Legionella species, but sometimes contain human-derived pathogens such as Staphylococcus aureus. Patients and staff are exposed to microorganisms from DUWL output water and to contaminated aerosols generated by DCU instruments. A wide variety of approaches, many unsuccessful, have been proposed to control DUWL biofilm. More recently, advances in biofilm science, chemical DUWL biofilm treatment agents, DCU design, supply water treatment and development of automated DUWL biofilm control systems have provided effective long-term solutions to DUWL biofilm control.
A key challenge in natural products drug discovery is compound supply. Hundreds of grams of purified material are needed to advance a natural product lead through preclinical development. ...Spliceostatins are polyketide-nonribosomal peptide natural products that bind to the spliceosome, an emerging target in cancer therapy. The wild-type bacterium Burkholderia sp. FERM BP-3421 produces a suite of spliceostatin congeners with varying biological activities and physiological stabilities. Hemiketal compounds such as FR901464 were the first to be described. Due to its improved properties, we were particularly interested in a carboxylic acid precursor analog that was first reported from Burkholderia sp. MSMB 43 and termed thailanstatin A. Inactivation of the iron/α-ketoglutarate-dependent dioxygenase gene fr9P had been shown to block hemiketal biosynthesis. However, a 4-deoxy congener of thailanstatin A was the main product seen in the dioxygenase mutant. We show here that expression of the cytochrome P450 gene fr9R is a metabolic bottle neck, as use of an l-arabinose inducible system led to nearly complete conversion of the 4-deoxy analog to the target molecule. By integrating fermentation media development approaches with biosynthetic engineering, we were able to improve production titers of the target compound >40-fold, going from the starting ~60mg/L to 2.5g/L, and to achieve what is predominantly a single component production profile. These improvements were instrumental in enabling preclinical development of spliceostatin analogs as chemotherapy.
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•Thailanstatin A is an anticancer, bacterial metabolite from the spliceostatin class.•Expression of the cytochrome P450 gene fr9R was shown to be a metabolic bottle neck.•Use of PBAD/araC led to what is predominantly a single component production profile.•Strain engineering and bioprocess development yielded 2.5g/L thailanstatin A.•Pre-clinical development of thailanstatin A as antibody drug conjugates was enabled.
Since the 2008/9 influenza season, the I-MOVE multicentre case-control study measures influenza vaccine effectiveness (VE) against medically-attended influenza-like-illness (ILI) laboratory confirmed ...as influenza. In 2011/12, European studies reported a decline in VE against influenza A(H3N2) within the season. Using combined I-MOVE data from 2010/11 to 2014/15 we studied the effects of time since vaccination on influenza type/subtype-specific VE. We modelled influenza type/subtype-specific VE by time since vaccination using a restricted cubic spline, controlling for potential confounders (age, sex, time of onset, chronic conditions). Over 10,000 ILI cases were included in each analysis of influenza A(H3N2), A(H1N1)pdm09 and B; with 4,759, 3,152 and 3,617 influenza positive cases respectively. VE against influenza A(H3N2) reached 50.6% (95% CI: 30.0-65.1) 38 days after vaccination, declined to 0% (95% CI: -18.1-15.2) from 111 days onwards. At day 54 VE against influenza A(H1N1)pdm09 reached 55.3% (95% CI: 37.9-67.9) and remained between this value and 50.3% (95% CI: 34.8-62.1) until season end. VE against influenza B declined from 70.7% (95% CI: 51.3-82.4) 44 days after vaccination to 21.4% (95% CI: -57.4-60.8) at season end. To assess if vaccination campaign strategies need revising more evidence on VE by time since vaccination is urgently needed.
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