Limited availability of ZBP1 restricts axonal mRNA localization and nerve regeneration capacity.
Subcellular localization of mRNAs is regulated by RNA-protein interactions. Here, we show that introduction of a reporter mRNA with the 3'UTR of β-actin mRNA competes with endogenous mRNAs for binding to ZBP1 in adult sensory neurons. ZBP1 is needed for axonal localization of β-actin mRNA, and introducing GFP with the 3'UTR of β-actin mRNA depletes axons of endogenous β-actin and GAP-43 mRNAs and attenuates both in vitro and in vivo regrowth of severed axons. Consistent with limited levels of ZBP1 protein in adult neurons, mice heterozygous for the ZBP1 gene are haploinsufficient for axonal transport of β-actin and GAP-43 mRNAs and for regeneration of peripheral nerve. Exogenous ZBP1 can rescue the RNA transport deficits, but the axonal growth deficit is only rescued if the transported mRNAs are locally translated. These data support a direct role for ZBP1 in transport and translation of mRNA cargos in axonal regeneration in vitro and in vivo.


A Comparison of the Use of In Vitro-Transcribed and Native rRNA for the Quantification of Microorganisms in the Environment.
Abstract Nearly full-length, small subunit (SSU) rRNA was transcribed in vitro from clones of SSU rDNA genes. Comparing the use of in vitro-transcribed and native rRNA indicated that, when in vitro-transcribed rRNA was used as a standard for quantitative hybridizations with oligonucleotide probes, the population was consistently underestimated. The population abundance was expressed as a percentage of specific target SSU rRNA (determined with a specific oligonucleotide probe), relative to the total SSU rRNA (measured with a universal probe). Differences in hybridization signals could be related to specific probe target locations and rRNA denaturation conditions, suggesting that higher order structure is important in quantitative membrane hybridizations. Therefore, in vitro-transcribed rRNA cannot always be used for the absolute quantification of microbial populations, but can be employed as a standard to quantify shifts in population abundance over time, and to compare community structure in various environments.


Microwave Hydrothermal Synthesis of Terbium Ions Complexed with Porous Graphene for Effective Absorbent for Organic Dye.
A luminescent terbium ions/reduced graphene oxide complex (Tb-RGO) was successfully and rapidly synthesized by the microwave hydrothermal reaction via the interactions between terbium ions and the active oxygen functional groups of graphene oxide. The as-prepared material was porous stacked by multilayer graphene in all directions. Thus, the resulting product owed the high specific surface area, high adsorption capacity and ultra-fast adsorption rate. Combined with the characteristic photoluminescence derived from terbium ions, the material has potential applications in biosensing and environmental protection.


The Effects of Amine-Carboxyborane Related Derivatives on UMR-106 Bone Metabolism.
The amine-carboxyboranes and related derivatives have been shown to be potent anti-inflammatory and anti-osteoporosis agents. Their action in part appears to be mediated by the modulation of cytokines, e.g. TNFalpha or IL-1. Previous studies have demonstrated that LPS induced macrophages release of TNFalpha maximally at 60 to 90 min. and IL-1 from 5 to 8 hr. The amine-carboxyboranes reduced significantly the release of these cytokines but also blocked TNFalpha high affinity binding to UMR-106 receptor at 90 min. at 10 muM, and IL-1 high affinity binding at 5 hr. at 12.5 muM. In addition, the agents suppressed IL-8 binding to CHO K1 high affinity receptor at 24 hr. at 50 muM and IL-2 binding to HuT-8 receptors at 25 muM at 90 min. and 5 hr. Correlation of metabolic events associated with osteoporosis showed that at 90 min., when TNFalpha receptor binding was reduced by the agents, calcium uptake into UMR-106 cells was reduced at 10 muM as well as the acid and alkaline phosphatases, and the prostaglandin cyclo-oxygenase activities and adhesion of leukocytes and macrophages to UMR-106 cell monolayers. At 5hr. when the agents reduced IL-1 binding to UMR-106 receptors, calcitonin and 1,25-dihydrovitamin D(3) binding was reduced by the agents as was acid and alkaline phosphatase, and 5'-lipoxygenase activities and white blood cell adhesion. At this time calcium uptake and proline incorporation was increased significantly by the agents. At later times e.g. 18-48 hr. calcium uptake was still increased, and NAG activity was inhibited in the presence of the agents. These effects may be related more to the inhibition of other cytokine receptor binding, e.g. IL-8. Thus, many of the observed metabolic effects of amine-carboxyboranes as antiosteoporosis agents can be correlated with their inhibition of cytokine high affinity binding to target cell receptors.


Links between viruses and prokaryotes throughout the water column along a North Atlantic latitudinal transect.
Viruses are an abundant, diverse and dynamic component of marine ecosystems and have a key role in the biogeochemical processes of the ocean by controlling prokaryotic and phytoplankton abundance and diversity. However, most of the studies on virus-prokaryote interactions in marine environments have been performed in nearshore waters. To assess potential variations in the relation between viruses and prokaryotes in different oceanographic provinces, we determined viral and prokaryotic abundance and production throughout the water column along a latitudinal transect in the North Atlantic. Depth-related trends in prokaryotic and viral abundance (both decreasing by one order of magnitude from epi- to abyssopelagic waters), and prokaryotic production (decreasing by three orders of magnitude) were observed along the latitudinal transect. The virus-to-prokaryote ratio (VPR) increased from ~19 in epipelagic to ~53 in the bathy- and abyssopelagic waters. Although the lytic viral production decreased significantly with depth, the lysogenic viral production did not vary with depth. In bathypelagic waters, pronounced differences in prokaryotic and viral abundance were found among different oceanic provinces with lower leucine incorporation rates and higher VPRs in the North Atlantic Gyre province than in the provinces further north and south. The percentage of lysogeny increased from subpolar regions toward the more oligotrophic lower latitudes. Based on the observed trends over this latitudinal transect, we conclude that the viral-host interactions significantly change among different oceanic provinces in response to changes in the biotic and abiotic variables.


Mapping of the Saccharomyces cerevisiae CDC3, CDC25, and CDC42 genes to chromosome XII by chromosome blotting and tetrad analysis.
CDC3, CDC25 and CDC42 were localized to chromosome XII by hybridizing the cloned genes to Southern blots of chromosomes separated by orthogonal-field-alternation gel electrophoresis. Meiotic tetrad analyses further localized these genes to the region distal to the RDN1 locus on the right arm of the chromosome. The STE11 gene, which had previously been mapped to chromosome XII (Chaleff and Tatchell, 1985), was found to be tightly linked to ILV5. The data suggest a map order of CEN12-RDN1-CDC42-(CDC25-CDC3)-(ILV5- STE11)-URA4. Certain oddities of the data set raise the possibility that there may be constraints on the patterns of recombination in this region of chromosome XII.


Rendering a membrane protein soluble in water: a common packing motif in bacterial protein toxins.
The recently determined structures of three different protein toxins by X-ray crystallography has unexpectedly revealed a common membrane-insertion domain. This domain consists of an alpha-helical bundle of between seven and ten helices, some of which are hydrophobic. The three toxins, colicin, insecticidal delta-endotoxin and diphtheria toxin are directed towards different hosts, have different killing mechanisms and bear no sequence homology. The observation of a common membrane-insertion domain has implications for the design of therapeutic agents in combating disease.


Polymorphisms in the IL6 gene in Asian Indian families with premature coronary artery disease--the Indian Atherosclerosis Research Study.
Inflammation plays a major role in coronary artery disease (CAD). We investigated the polymorphisms in the interleukin 6 (IL6) gene and their effect on the expression of acute-phase proteins in premature CAD in Asian Indian families. One hundred and ninety affected sibling pairs (ASPs) were genotyped for three tag single nucleotide polymorphisms (SNPs) in the IL6 gene for linkage analysis. We observed suggestive logarithm of odds (LOD) score for one SNP (rs2066992) in a subset of 62 ASPs with the age at onset less than 45 years (LOD score=1.114, p=0.011 in linkage analysis; pi=0.55, p=0.008 in identity by descent; LOD score=1.06, p=0.014 in quantitative trait locus for plasma levels of high sensitivity C-reactive protein, hsCRP). This was followed by sequencing of the promoter region and haplotype analysis in 46 probands and 40 controls. Five out of the eight previously reported promoter SNPs were found to be polymorphic (rs1800797, rs1800796, rs7802307, rs7802308, rs1800795). Two novel sequence variants were also found. One promoter haplotype (GGAAG) was detected with an odds ratio (OR) of 3.676 (p=0.0017, 95% confidence interval [CI]: 1.68-8.045) and population attributable risk of 21.1% (95%CI: 9.2%-31.5%). The plasma levels of both hsCRP and fibrinogen exhibited significant association with these promoter SNP genotypes (p<0.001). In conclusion, IL6 gene polymorphisms appear to be important genetic factors in premature CAD, and in the regulation of key atherogenic markers in Asian Indian families.


Spray-chilling system in the initial cooling process of swine half carcasses.
This research was carried out with the objective of evaluating the effects of using a chilling water sprinkler system during the cooling process of swine carcasses on the quantitative and qualitative parameters of carcass and meat. A total of 220 swine carcasses were divided in a completely randomized experiment and two treatments: (1) CONTROL, no water spraying; (2) SPRAY, with water spraying during cooling. Surface and internal temperature of carcasses throughout the cooling process, initial and final pH, and microbiological analyses of carcass surface were evaluated. Samples of the Longissimus lumborum (LL) were collected for analysis of color, cooking loss (CL), shear force (SF), and drip loss (DL). Data were submitted to analysis of variance through the SAS MIXED procedure adopting the most adequate model with treatments as fixed effects and pertinent random effects for each data set. The use of spray-chilling in the initial cooling process accelerates the surface and internal temperature decrease of swine carcasses, which may be a viable technological resource in swine industry.


Genetically engineered multi-component virus-like particles as veterinary vaccines.
Multiprotein structures can be constructed to mimic virus particles. These engineered particles lack genetic material and are not infectious but they can elicit protective immune responses in animals against challenges with infectious viruses. As a prototype, insect cells were co-infected with two recombinant baculoviruses. One recombinant baculovirus contained an insert of L2 and M5 genes, which encode for outer capsid proteins VP2 and VP5, respectively, from bluetongue virus (BTV) downstream of duplicated copies of the baculovirus (Autographa californica nuclear polyhedrosis virus, AcNPV) polyhedrin promoter. Another recombinant baculovirus expressed two major core proteins (VP3 and VP7) from BTV virions. The co-infected cells synthesized non-infectious, double-shelled, virus-like particles (VLP). The VLP resembled the authentic BTV in size, appearance, and biochemical constitution but they lacked the double-stranded-RNA genome and three minor polypeptides normally contained in the icosahedral inner capsid. The VLP consisted of an outer shell of VP2 and VP5 from US BTV-10 attached to an icosahedral framework formed by the two major core proteins VP3 and BTV-17 and VP7 from US BTV-10. Sheep immunized with VLP expressing BTV capsid proteins produced antibodies that neutralized homologous serotypes of BTV. The assembly of VLP from different proteins simultaneously expressed indicates the potential of this novel approach for producing safe and effective vaccines against several viral agents.


Challenges in designing comparative-effectiveness trials for antidepressants.
Comparative-effectiveness antidepressant trials offer promise to provide empirical evidence for clinicians choosing among interventions. Whether such trials posit superiority or noninferiority (NI) hypotheses, they pose formidable challenges. For instance, if meaningful antidepressant differences are seen in comparative-superiority trials, they will be small. NI hypothesis testing, on the other hand, requires an a priori NI margin and evidence of trial assay sensitivity. Either design demands unusually large samples, which could render such trials infeasible.


Bifid median nerve with a double compartment within the transverse carpal canal.
A case is reported in which the radial half of a bifid median nerve passed through a separate compartment within the transverse carpal canal. During its passage within this compartment this portion of the nerve gave off sensory and motor branches to the thumb. The two branches of the median nerve subsequently rejoined distal to the transverse carpal ligament.


The effect of background noise and its removal on the analysis of single-cell expression data.
In droplet-based single-cell and single-nucleus RNA-seq experiments, not all reads associated with one cell barcode originate from the encapsulated cell. Such background noise is attributed to spillage from cell-free ambient RNA or barcode swapping events. Here, we characterize this background noise exemplified by three scRNA-seq and two snRNA-seq replicates of mouse kidneys. For each experiment, cells from two mouse subspecies are pooled, allowing to identify cross-genotype contaminating molecules and thus profile background noise. Background noise is highly variable across replicates and cells, making up on average 3-35% of the total counts (UMIs) per cell and we find that noise levels are directly proportional to the specificity and detectability of marker genes. In search of the source of background noise, we find multiple lines of evidence that the majority of background molecules originates from ambient RNA. Finally, we use our genotype-based estimates to evaluate the performance of three methods (CellBender, DecontX, SoupX) that are designed to quantify and remove background noise. We find that CellBender provides the most precise estimates of background noise levels and also yields the highest improvement for marker gene detection. By contrast, clustering and classification of cells are fairly robust towards background noise and only small improvements can be achieved by background removal that may come at the cost of distortions in fine structure. Our findings help to better understand the extent, sources and impact of background noise in single-cell experiments and provide guidance on how to deal with it.


Diagnosis and management of entrapped embolus through a patent foramen ovale.
The diagnosis of impending paradoxical embolus by echocardiography is exceptional and its management remains unclear. Through a personal case, we performed an exhaustive review of the medical literature of this rare finding. Since the first report, only 43 cases have ever been reported. The superiority of transesophageal echocardiography is underlined. The clinical features are complex. The classical simultaneous pulmonary and paradoxical embolism is often absent. Therapeutic options are cardiac surgery, thrombolysis or anticoagulation. The early mortality rate is high (21%). In addition, recurrent embolisms are reported when a medical treatment is chosen. The cumulative results of each possibility are described.


[Diffusion weighted imaging: its diagnostic and differential value for prostate cancer].
To explore the diagnostic and differential value of diffusion weighted imaging (DWI) for prostate cancer. Included in the study were 50 patients with prostatic diseases, including 19 cases of prostate cancer (PCa) and 31 cases of benign prostatic hyperplasia (BPH), and another 16 healthy volunteers were recruited as controls. All underwent DWI sequence on a 1.5T superconducting MRI system with an endorectal coil. The results from DWIs and apparent diffusion coefficient (ADC) maps were treated statistically. The mean ADC value of the prostatic peripheral zone and the prostatic central gland of the 16 healthy volunteers were (170.23 +/- 37.39) x 10(-5) mm2/s and (127.84 +/- 17.93) x 10(-5) mm2/s, while those of the 31 BPH cases and 19 PCa cases were (175.21 +/- 64.86) x 10(-5) mm2/s and (104.23 +/- 26.15) x 10(-5) mm2/s, respectively. There were significant differences in the tissue types between any two groups after the treatment of one-way ANOVA, except between the groups of the peripheral zone and. BPH. PCa shows specific DWI features that could be distinguished from those of the normal prostatic tissues and BPH. Therefore, DWI has an important clinical application value in the diagnosis and differentiation of PCa.


Shelf life extension of pre-baked buns by an ACTIVE PACKAGING ethanol emitter.
The paper reports the influence of an ethanol emitter (Ethicap) on the microbiological condition and the shelf life extension of a bakery product. Pre-baked buns, with a water activity of 0.95, were packaged with different amounts of Ethicap and stored at room temperature. Yeasts and moulds remained largely absent from the core of the pre-baked bun (< 10(2) cfu g(-1)) during storage, independent of the presence of ethanol. The total mesophilic count was low at the beginning of the storage experiment (< 10(2) cfu g(-1)), but increased without ethanol within 1 week to an unacceptable level. In the presence of ethanol, the total mesophilic count stabilizes at a consumable level of 10(5)-10(6) cfu g(-1). The increase of total mesophilic count was caused by growth of a Bacillus spp., probably B. subtilis. Mould growth on the outer surface is limiting for shelf life extension. On the pre-baked buns, the following moulds were present: Penicillium solitum, P. commune, P. corylophilum, Cladosporium sphaerospermum and C. herbarum. These started to grow within 4-6 days. Mould growth can be delayed for 13 days by adding Ethicap. The ethanol probably has to be absorbed by the pre-baked bun to be effective in growth suppression of the Bacillus spp. the moulds. The pre-baked buns absorb most of the ethanol from the package headspace, and the ethanol content of the products is approximately 0.8 weight% after 21 days. This largely exceeds the overall migration limit of 60 mg kg(-1) food (0.006 weight%).


Phytoremediation strategies for heavy metal-contaminated soil by selecting native plants near mining areas in Inner Mongolia.
Phytoremediation technology, as an eco-friendly and cost-effective approach, is widely used to restore soil contaminated by heavy metal(loid)s. However, the adaptability and absorption capacity of plants to multiple elements are the crucial factors affecting the application of phytoremediation in mining areas. In this study, dominant native plant species and their paired soils were collected near a lead-zinc mine in Inner Mongolia, to assess the ecological risk of heavy metal(loid)s and phytoremediation potential. The results showed that Cd and As were the dominant soil pollutants, with levels of 90.91% and 100%, respectively, exceeding the risk intervention values for soil contamination of agricultural land. The rates of Pb, Cu, and Zn exceeding the risk screening values were 69.70%, 60.61%, and 96.97%, respectively. Extremely high ecological risk of heavy metal(loid)s was observed in this area. The ability of native plants accumulating heavy metals varied among species. The bioconcentration factor (BCF) varied from 0.14 to 2.59 for Cd, 0.02 to 0.45 for As, 0.06 to 0.76 for Pb, 0.05 to 2.69 for Cr, 0.15 to 1.00 for Cu, and 0.22 to 4.10 for Zn. Chinese Cinquefoil Herb (Potentilla chinensis Ser.) showed the potential to accumulate multiple toxic elements based on the biomass, shoot content, translocation factor (TF), BCF, and metal extraction rate (MER), while, other species showed the potential to accumulate single toxic element: goosefoot (Chenopodium album L.), Lespedeza daurica (Laxm.) Schindl. and peashrubs (Caragana korshinskii Kom.), Herba Artemisiae Scopariae (Artemisia capillaris Thunb.), alfalfa (Medicago sativa L.), and Moldavian Dragonhead (Dracocephalum moldavica L.) for Cd, As, Cr, Cu, and Zn, respectively. Furthermore, wild leek (Allium ramosum L.), cogongrass (Imperata cylindrica (L.) Beauv.), fringed sagebrush (Artemisia frigida Willd.), and field bindweed (Convolvulus arvensis L.) were selected for phytostabilization of specific elements, considering the heavy metal contents in the roots and low TF values. This study provides a reference for selecting appropriate species for the remediation of heavy metal-contaminated soils in certain mining areas.


Validation of diagnoses on death certificates for male alcoholics in Stockholm.
The mortality and the causes of death have been studied in a cohort consisting of 1548 male alcoholics in Stockholm. During the period 1969-1981 there were 542 cases of death in this population. The mortality rates were triple those for males in Stockholm generally. Using the official causes of death there was a highly significant excess mortality in the following diagnostic groups: Cancer in the upper digestive region, primary hepatic cancer, cirrhosis in the liver, pancreatitis, pneumonia, alcoholism and alcoholic poisoning, suicides and other causes of violent death as well as ischemic heart disease. The underlying and contributing causes of death on the death certificates were reclassified according to ICD-rules using clinical records and autopsy protocols. It was found that the underlying cause of death was incorrect in 21.8% of the cases. Important information was withheld in further 19.8%. After validation there was no longer any excess mortality in ischemic heart disease. The number of alcohol-related diagnoses, i.e. alcoholic cardiomyopathy, cirrhosis and fatty liver with alcoholism and alcoholic intoxication, was much greater. It is concluded that there is a underreporting of alcohol-related diseases and injuries which has a great influence on the reliability of death statistics.


Unexpected discovery of superoxide radical generation by oxygen vacancies containing biomass derived granular activated carbon.
Herein, we discovered and reported oxygen vacancies in silicon oxycarbide containing granular palm shell activated carbon (Si-PSAC) as a photocatalyst under UV irradiation. A strong correlation between the atomic content of Si1+, oxygen vacancies and photocatalytic performance of Si-PSAC was obtained. Based on the electron paramagnetic resonance and photoluminescence analyses, Si-PSAC under UVA365 irradiation exhibited a higher donor density, better charge transfer and lower electron-hole recombination than that under the other light sources, leading to a higher O2· production efficiency. Si-PSAC exhibited effective removal performance for various anionic dyes and endocrine-disrupting chemicals under UVA365 irradiation. Continuous-flow column tests revealed the life span of Si-PSAC under UVA365 irradiation was extended by more than 16-fold compared to adsorption column. Since the oxygen vacancies can be created from the naturally present Si in the biomass derived Si-PSAC during the activation, this unexpected discovery of O2· production can extend commercially-available Si-PSAC into the full-scale photocatalysis.


Measurement of functional heel pad behaviour in-shoe during gait using orthotic embedded ultrasonography.
The ability to measure the functional behaviour of the plantar heel pad is clinically relevant in dystrophic or pathological heel conditions and may help to inform the design and development of interventions that attempt to restore normal function. In this study we present a novel technique which utilises orthotic heel inserts with an embedded ultrasound (US) transducer to allow the functional, dynamic behaviour of the heel pad to be measured in-shoe during gait. The aim of this study was to demonstrate feasibility of the technique, determine the reproducibility of measurements, and to compare the effects of two orthotic inserts: (i) a flat orthotic heel raise and (ii) a contoured heel cup insert on the behaviour of the heel pad during gait. Dynamic compression of the heel pads of 16 healthy participants was recorded during treadmill walking and combined with plantar pressure measurements to allow stiffness and energy disappation ratio (EDR) to be estimated. Inter-session reliability of the US measurements was found to be excellent (ICC2,1=0.94-0.95), as was inter-rater reliability (ICC2,1=0.89). Use of the heel cup insert significantly reduced the maximum compression of the heel pad (p<0.0001) as well as the overall stiffness of the pad (p<0.001). There was no change in EDR (p=0.949). In-shoe embedded US is a reliable method to establish person-specific functional geometry of plantar soft tissues. Use of a contoured heel cup reduces the compression of the mid portion of the heel pad.


Different potency of bacterial antigens TLR2 and TLR4 ligands in stimulating mature mast cells to cysteinyl leukotriene synthesis.
The aim of study was to compare the potency of different bacterial antigens to induce rat mature mast cell to cysteinyl leukotriene (cysLT) generation. We examined Toll-like receptor (TLR)2 agonists, i.e. lipoteichoic acid (LTA) Staphylococcus faecalis, Streptococcus pyogenes, Bacillus subtilis and Staphylococcus aureus, lipoarabinomannan (LAM) Mycobacterium smegmatis, peptydoglican (PGN) Staphylococcus aureus, as well as TLR4 agonists, i.e. lipopolysaccharide (LPS) Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enteritidis, Pophyromonas gingivalis and Escherichia coli. We also estimated the effect of tumor necrosis factor (TNF)-, interleukin (IL)-6-, CCL5-, and IL-10-priming on mast cell cysLT synthesis following bacterial antigen activation. We found that all bacterial antigens activated mast cells to cysLT generation; however, the extent of cysLT release in response to stimulation varied. Out of the examined antigens LPS P. gingivalis exhibited the highest potency, as it induced cysLT generation acting at a very low concentration (10(-4) ng/mL). Other LPSs affected mast cells at higher (up to 10(5) -fold) concentrations. LTAs were the most effective at concentrations of 5 × 10(2) ng/mL, while LAM and PGN stimulated mast cells to maximal cysLT generation at concentrations as high as 10(5) ng/mL. Anti-TLR2 and anti-TLR4 antibodies, as well as nuclear factor κB (NF-κB) inhibitor significantly diminished cysLT generation in response to bacterial antigen stimulation. Priming with TNF, IL-6 and CCL5 did not affect bacterial antigen-induced cysLT generation, while IL-10-pretreatment caused significant decrease in cysLT synthesis by mast cells. These observations might have a great pathophysiological importance; inasmuch cysLTs strongly influence the development and intensity of inflammation during bacterial infection.


The prognosis of segmental glomerulonephritis in systemic lupus erythematosus.
Severe segmental glomerulonephritis (Seg GN) (greater than or equal to 50% involvement) in systemic lupus erythematosus (SLE) is classified as diffuse GN (DPGN) in the WHO classification. We tested the validity of the assumption that severe Seg GN and DPGN have the same prognosis by determining the proportion of glomeruli involved by active segmental inflammation in a series of 127 patients and by comparing the prognosis in various categories of Seg GN with patients with DPGN. In Seg GN we found mild involvement (1 to 19%) in 19 patients, moderate involvement (20 to 49%) in 9 patients and severe involvement (greater than or equal to 50%) in 17 patients. There were 28 cases of DPGN. The actuarial five-year survival of patients with mild and moderate Seg GN was 82%. The survival of patients with severe Seg GN and DPGN were 59 and 53%, respectively. The incidence of adverse outcomes, including death, end-stage kidney disease, and deterioration of renal function was similar in patients with severe Seg GN and DPGN, and greater than in patients with mild and moderate Seg GN. Although there was a trend associating increasing glomerular involvement with elevated urinary protein excretion and serum creatinine and decreased serum C3 and C4, the differences were not significant. Cumulative prednisone dose and prednisone given in the first and second years following biopsy were not different in the various categories of Seg GN and DPGN, suggesting that differences in outcome were not related to the amount of prednisone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


In silico exploration for agonists/antagonists of brassinolide.
Brassinolide (BL) is a plant steroid hormone that is necessary for stem elongation and cell division. To date more than 70 steroidal BL-like compounds, which are collectively named as brassinosteroids, have been identified. However, non-steroidal compounds that mimic BL have not been reported yet, which can be used as plant growth regulators. Twenty-two non-steroidal compounds were screened from the database containing about 5 million compound structures using a pharmacophore-based in silico screening method. The crystal structure (PDB: 4LSX) of the BL receptor was used to generate a pharmacophore model required for in silico screening. Among 22 hit compounds, 15 compounds that are thought to be physicochemically acceptable were submitted to the in vivo rice lamina inclination assay. Although no compound showed BL like activity, three compounds were detected as BL antagonist. The most potent compound was an ester derivative of 1,4-diphenlenedimethanol and isoxazole-4-carboxylic acid, and the other two compounds contain 2-phenylfuran and pyrimidin-2(1H)-one moieties bridged by an ethenyl substructure. The 50% effective doses (ED50) for the antagonistic activity were in a range of 0.6-5nmol per plant. The inhibition of the lamina inclination by the most potent agonist was recovered by the co-application of BL in a dose-dependent manner.


Utilitarianism and the evolution of ecological ethics.
R.M. Hare's two-level utilitarianism provides a useful framework for understanding the evolution of codes of professional ethics. From a Harean perspective, the codes reflect both the fact that members of various professions face special kinds of ethically charged situations in the normal course of their work, and the need for people in special roles to acquire various habits of thought and action. This highlights the role of virtue in professional ethics and provides guidance to professional societies when considering modifications to their codes. From a Harean perspective, a professional society should ask both "Are there kinds of situations that members of this profession will normally encounter which members of other professions and/or the general public will not?" and "What habits of thought and action would it be good for individuals encountering such situations to have?"


Microplastics and co-pollutant with ciprofloxacin affect interactions between free-floating macrophytes.
Microplastic and antibiotic contamination are considered an increasing environmental problem in aquatic systems, while little is known about the impact of microplastics and co-pollutant with antibiotics on freshwater vascular plants, particularly the effects of interactions between macrophytes. Here, we performed a mesocosm experiment to evaluate the impact of polyethylene-microplastics and their co-pollutants with ciprofloxacin on the growth and physiological characteristics of Spirodela polyrhiza and Lemna minor and the interactions between these two macrophytes. Our results showed that microplastics alone cannot significantly influence fresh weight and specific leaf area of the two test free-floating macrophytes, but the effects on photosynthetic pigments, malondialdehyde, catalase and soluble sugar contents were species-specific. Ciprofloxacin can significant adverse effects on the growth and physiological traits of the two test macrophytes and microplastic mitigated the toxicity of ciprofloxacin on the two free-floating plants to a certain extent. In addition, our studies showed that microplastics and co-pollutants can influence relative yield and competitiveness of S. polyrhiza and L. minor by directly or indirectly influencing their physiology and growth. Therefore our findings suggest that species-specific sensibility to microplastic and its co-pollutant among free-floating macrophytes may influence macrophyte population dynamics and thereby community structure and ecosystem functioning. And microplastics altered other contaminant behaviours and toxicity, and may directly or indirectly influence macrophytes interactions and community structure. The present study is the first experimental study exploring the effects of microplastics alone and with their co-pollutants on interactions between free-floating macrophytes, which can provide basic theoretical guidance for improving the stability of freshwater ecosystems.


Photoaffinity labeling of adenylate cyclase-linked serotonin receptors in Aplysia neurons.
Serotonin stimulated adenylate cyclase in Aplysia neurons with a Kact of 0.7 microM. Under the same conditions, 1-[2-(4-aminophenyl)ethyl]4-(3-trifluoromethylphenyl)piperazine stimulated adenylate cyclase with a Kact of 20 microM. The azido derivative of this compound, 1-[2-(4-azidophenyl)ethyl]4-(3-trifluoromethylphenyl)piperazine, or of serotonin, (4-amino, 3-nitrophenylazido-serotonin), also stimulated the cyclase in the dark, but with lower efficiency (Kact greater than 10(-4) M). Irradiation of the membranes in the presence of 100 microM 1-[2-(4-azidophenyl)ethyl]4-(3-trifluoromethylphenyl)piperazine abolished 75% of the cyclase activity stimulated by 5 microM serotonin. Under the same conditions, 100 microM 4-amino, 3-nitrophenylazido-serotonin did not inhibit serotonin-stimulated adenylate cyclase activity. When [3H]1-[2-(4-azidophenyl)ethyl]4-(3-trifluoromethylphenyl)piperazine (20 microM) was irradiated with membranes for 5 min at 4 degrees C, a dozen peptides were labeled, as revealed by a fluorogram of sodium dodecyl sulfate-polyacrylamide gels. Among them, the labeling of five polypeptides (molecular weights of 45,000, 55,000, 63,000, 80,000, and 94,000) was protected by the presence of 0.2 mM serotonin during photolysis. These peptides may be related to serotonin receptors.


Small bowel endoscopic enteral access.
The use of small bowel access for small intestinal delivery of enteral nutrition is becoming more common. Patients at risk for gastric regurgitation and aspiration, gastric intolerance, and pancreatitis are some of the classic patient groups for which small bowel feedings may be necessary. The endoscopist should have command of all forms of endoscopic small bowel enteral access, including nasojejunal tube placement, percutaneous gastro/jejunostomy, and direct percutaneous jejunostomy. Knowledge of not only the procedure techniques, but also the potential complications, is imperative to achieving good clinical outcomes.


Patterns of Venous Thromboembolism Prophylaxis During Treatment of Acute Leukemia: Results of a North American Web-Based Survey.
Venous thromboembolism (VTE) occurs in 2% to 12% of patients with acute leukemia (AL) despite disease- and therapy-associated thrombocytopenia, and it can be associated with significant morbidity and mortality. Because of the few high-quality studies, there are no evidence-based guidelines for VTE prophylaxis in this patient population. We sought to determine the spectrum of practice regarding prevention of VTE in patients with AL during induction and consolidation therapies. We conducted a 19-question Web-based survey directed at North American providers caring for these patients. One hundred fifty-one of 215 responses received were eligible for analysis, with a response rate of 20.9% among physicians who treated leukemias. Overall, 47% and 45% of providers reported using pharmacologic VTE prophylaxis during induction and consolidation phases, respectively. Approximately 15% of providers did not provide any VTE prophylaxis, while 36% used mechanical methods and ambulation. Among providers who did not recommend pharmacologic prophylaxis, the most commonly cited reasons were the perceived high risk of bleeding (51%), absence of data supporting use (38%), and perceived low risk of VTE (11%). Large, prospective studies are needed to define the safest and most effective approach to VTE prevention in patients with AL.


Idiopathic retroperitonial fibrosis misinterpreted as lymphoma by computed tomography.
Two cases of idiopathic retroperitoneal fibrosis that were mistaken for lymphomas on a computed tomography scan are presented. The similar densities and anatomical appearances on cross section scans of these diseases probably account for this misinterpretation.


[Distribution characteristics of serotypes of invasive pneumococcal disease in Chinese mainland children].
To systematically estimate the regional distributions of invasive pneumococcal disease (IPD)'s serotypes in children of Chinese mainland. The literatures which described at least 20 strains of streptococcus pneumonia samples isolated from children with IPD in Chinese mainland were included in this study. Finally, 39 literatures met the inclusion criteria and were reviewed in this study. The average frequency of each serotype of streptococcus pneumonia was calculated and the uncertainty of each serotype range was described by 95% CI. This study analyzed a total of 7 391 strains of streptococcus pneumoniae samples which mainly came from north China, east China, central China, south China and southwest regions of China. The results showed that the most common streptococcus pneumonia serotype causing IPD was 19F[30.05% (28.16%-31.98%)], and the second serotype was 23F[12.16% (10.00%-14.28%)], and the others were 19A[9.19% (7.01%-11.37%)], 6B[7.30% (5.09%-9.50%)], 14[7.02% (4.82%-9.23%)], 6A[6.08% (3.87%-8.30%)]and 15B[6.53% (2.88%-7.34%)]. The most common streptococcus pneumoniae serotype is 19F, 23F, 19A, 6B, 14, 6A and 15B in Chinese Mainland.


The predictive value of cerebrospinal fluid Epstein-Barr viral load as a marker of primary central nervous system lymphoma in HIV-infected persons.
The presence of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid (CSF) is used as a marker of HIV-associated primary central nervous system lymphoma (PCNSL). In our setting, EBV DNA is frequently detected in the CSF of HIV-infected patients with miscellaneous neurological diseases and thus its presence is a poor predictor of PCNSL. To determine whether quantification of EBV DNA in CSF improves its diagnostic specificity for PCNSL. EBV viral loads were determined on CSF samples from 55 HIV-infected patients with CNS disease. Twenty of the 55 patients had detectable EBV DNA in their CSF (median viral load 6120copies/ml, range 336-1,034,000copies/ml). PCNSL was confirmed in 2 patients. Their CSF EBV loads were 1,034,000 and 15,460copies/ml, respectively. Using a cut-off of 10,000copies/ml improved the specificity and positive predictive value (PPV) compared to a qualitative result for the diagnosis of PCNSL (96% vs. 66% and 50% vs. 10%, respectively). EBV DNA is commonly detected in CSF of HIV-infected patients. Quantitative PCR improves the diagnostic specificity, however, the PPV remains too low for it to be used as an isolated marker for PCNSL.


Maternal smoking during pregnancy and infant head circumference at birth.
Using the Swedish Medical Birth Registry, information on 1,362,169 infants born during 1983-1996 was analyzed in order to investigate the relation between maternal smoking during pregnancy and infant head circumference at birth. Infants of smoking mothers were at an increased risk to have head circumference <32 cm, and the adjusted odds ratios (OR) with 95% confidence intervals (CI) for any smoking, smoking <10 cigarettes per day, and smoking >/=10 cigarettes per day were: 1.65 (1.62-1.68), 1.52 (1.48-1.56), and 1.86 (1.81-1.92), respectively. A highly significant association between small head circumference for gestational age and maternal smoking was also found (ORs (with 95% CI) were for any smoking, <10, and >/=10: 1.58 (1.55-1.61), 1.48 (1.45-1.51), and 1.74 (1.70-1.79), respectively). For both outcomes, the observed dose-response effects were highly significant (P<10(-6)). Even more alarming was the finding that given a certain level of growth retardation, infants of smoking mothers were at an increased risk of small head circumference for gestational age compared to infants of non-smoking mothers (OR (with 95% CI) for any smoking adjusted for 'percentage of expected birth weight': 1.08 (1.06-1.10)). Given the evidence that maternal smoking specifically affects head growth, until contradictory evidence has been found, it seems reasonable to assume that maternal smoking during pregnancy affects brain development negatively.


Estradiol rapidly activates male sexual behavior and affects brain monoamine levels in the quail brain.
Steroids are generally viewed as transcription factors binding to intracellular receptors and activating gene transcription. Rapid cellular effects mediated via non-genomic mechanisms have however been identified and one report showed that injections of estradiol rapidly stimulate chemoinvestigation and mounting behavior in castrated male rats. It is not known whether such effects take place in other species and what are the cellular underlying mechanisms. We show here that a single injection of estradiol (500 microg/kg) rapidly and transiently activates copulatory behavior in castrated male quail pre-treated with a dose of testosterone behaviorally ineffective by itself. The maximal behavioral effect was observed after 15 min. In a second experiment, the brain of all subjects was immediately collected after behavioral tests performed 15 min after injection. The preoptic area--hypothalamus (HPOA), hindbrain, telencephalon and cerebellum were isolated and monoamines measured by HPLC-ED. Estradiol increased levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/serotonin ratios in the telencephalon and hindbrain independently of whether animals had mated or not. Estradiol also affected these measures in HPOA and cerebellum but this effect was correlated with the level of sexual activity so that significant effects of the treatment only appeared when sexual activity was used as a covariate. Interactions between estradiol effects and sexual activity were also observed for dopamine in the HPOA and for serotonin in the hindbrain and cerebellum. Together, these data demonstrate that a single estradiol injection rapidly activates male sexual behavior in quail and that this behavioral effect is correlated with changes in monoaminergic activity.


Quantitative studies of retinal ganglion cells in a turtle, Pseudemys scripta elegans: II. Size spectrum of ganglion cells and its regional variation.
Recent evidence suggests that ganglion cell size and its regional variation may be an important feature of vertebrate retinas. Accordingly, we have examined Nissl-stained, whole-mounted Pseudemys scripta retinas to determine the soma size spectrum of ganglion cells at different retinal loci. Cell size histograms reveal that at any given point on the retina, a majority of ganglion cells are small (6-10 microns), and in peripheral samples there is some evidence for a second, larger size class (12-15 microns). Comparison of samples along the dorsoventral and nasotemporal axes suggests that there are two major trends in soma size variation. Along the dorsoventral axis, ganglion cell diameter increases sharply from the visual streak (6-7 microns, cf. Peterson and Ulinski, '79) to the dorsal and ventral periphery (9-10 microns). These changes reflect a tendency toward increased size for the entire distribution as well as a relative decrease in the frequency of small ganglion cells. This soma size variation is significantly correlated with changes in ganglion cell density. Along the nasotemporal axis, temporal ganglion cells are significantly larger than those at more nasal retinal loci. This difference reflects an overall increase in the size of ganglion cells in temporal retina and a small but significant increase in the percentage of neurons larger than 15 microns.


Reproducibility of 6- and 4-category faces pain scale to the assessment of temporomandibular joint pain and muscle in school-age children.
The aim of this study was to compare the levels of reproducibility between two Faces Pain Scales (FPS) of 6 and 4 categories to the assessment of pain intensity on children with and without Temporomandibular joint and muscle pain. A total of 29 children were recruited: 13 symptomatic (9.79 ± 1.36 years old) and 16 asymptomatic (8.69 ± 0.87 years old). One previously-trained examiner applied manual palpation to evaluate orofacial structures, and FPS to assess pain intensity. All children were initial evaluated using 6-category FPS and after 3 days using 4-category FPS. The children were assessed after a seven day time interval from initial and second sessions. Weighted Kappa coefficient was used to verify reproducibility levels. Similar levels of reproducibility (moderate and fair kappa values) have been verified with the application of the 6-category FPS on symptomatic and asymptomatic children. Similar results were verified using 4-category FPS on symptomatic and asymptomatic children (poor and fair kappa values). Higher levels of reproducibility were verified with the application of the 6-category FPS in both groups and considering symptomatic and asymptomatic as single group. In this way, the 6-category FPS should be preferred over the 4-category FPS to assess pain intensity on children's orofacial structures.


Severe capillary leak syndrome after inner ear decompression sickness in a recreational scuba diver.
Post-decompression shock with plasma volume deficit is a very rare event that has been observed under extreme conditions of hypobaric and hyperbaric exposure in aviators and professional divers. We report a case of severe hypovolemic shock due to extravasation of plasma in a recreational scuba diver presenting with inner ear decompression sickness. Impaired endothelial function can lead to capillary leak with hemoconcentration and hypotension in severe cases. This report suggests that decompression-induced circulating bubbles may have triggered the endothelial damage, activating the classic inflammatory pathway of increased vascular permeability. This observation highlights the need for an accurate diagnosis of this potentially life-threatening condition at the initial presentation in the Emergency Department after a diving-related injury. An elevated hematocrit in a diver should raise the suspicion for the potential development of capillary leak syndrome requiring specific treatment using albumin infusion as primary fluid replacement.


Plasmid pUM505 encodes a Toxin-Antitoxin system conferring plasmid stability and increased Pseudomonas aeruginosa virulence.
Pseudomonas aeruginosa plasmid pUM505 possesses a pathogenicity island that contains the pumAB genes that encode products with sequence similarity to Toxin-Antitoxin (TA) modules. RT-PCR assays on the overlapping regions of the pumAB genes generated a bicistronic messenger RNA, suggesting that they form an operon. When the pumAB genes were cloned into the pJET vector, recombinant plasmid pJET-pumAB was maintained under nonselective conditions in Escherichia coli cells after six daily subcultures, whereas pJET without pumAB genes was lost. These data indicate that pumAB genes confer post-segregational plasmid stability. In addition, overexpression of the PumA protein in the E. coli BL21 strain resulted in a significant growth inhibition, while BL21 co-expressing the PumA and PumB proteins did not show growth inhibition. These results indicate that pumAB genes encode a TA system where the PumB protein counters the toxic effects of the PumA toxin. Furthermore, P. aeruginosa PAO1 transformants with the pumA gene increased Caenorhabditis elegans and mouse mortality rate and improved mouse organ invasion, effects neutralized by the PumB protein. Moreover, purified recombinant His-PumA protein decreased the viability of C. elegans, indicating that the PumA protein could acts as a toxin. These results indicate that PumA has the potential to promoter the PAO1 virulence against C. elegans and mice when is expressed in absence of PumB. This is the first description, to our knowledge, of a plasmid-encoded TA system that confers plasmid stability and encoded a toxin with the possible ability to increase the P. aeruginosa virulence.


Role of adipose tissue in regulating fetal growth in gestational diabetes mellitus.
Gestational diabetes mellitus (GDM) is a global health issue with significant short and long-term complications for both mother and baby. There is a strong need to identify an effective therapeutic that can prevent the development of GDM. A better understanding of the pathophysiology of GDM and the relationship between the adipose tissue, the placenta and fetal growth is required. The placenta regulates fetal growth by modulating nutrient transfer of glucose, amino acids and fatty acids. Various factors secreted by the adipose tissue, such as adipokines, adipocytokines and more recently identified extracellular vesicles, can influence inflammation and interact with placental nutrient transport. In this review, the role of the placental nutrient transporters and the adipose-derived factors that can influence their function will be discussed. A better understanding of these factors and their relationship may make a potential target for therapeutic interventions to prevent the development of GDM and its consequences.


Outcomes of patients with heart failure with preserved ejection fraction undergoing catheter ablation of atrial fibrillation.
Limited real-world data exist on early outcomes in patients with heart failure with preserved ejection fraction (HFpEF) undergoing atrial fibrillation (AF) ablation. The purpose of this study was to examine and compare rates of index procedural complications and 30-day readmissions after AF ablation in patients with HFpEF, with heart failure with reduced ejection fraction (HFrEF), and without heart failure. Using the Nationwide Readmissions Database (NRD), we examined 50,299 admissions of adults with heart failure undergoing AF catheter ablation between 2010 and 2014. Using ICD-9-CM codes, we identified procedural complications and causes of readmission after AF ablation. From 2010 to 2014, the prevalence of HFpEF among patients undergoing AF ablation increased from 3.05% to 7.35% (P for trend <.001). Compared to patients without heart failure, patients with HFpEF had significantly increased procedural complications and index mortality (8.4% vs 6.2% and 0.30% vs 0.08%, respectively; P = .016 and P = .010, respectively). Index complication rates between patients with HFpEF and HFrEF were similar. All-cause 30-day readmissions occurred in 18.3% of patients with HFpEF compared to 9.5% of patients without heart failure (P <.001). Compared to no heart failure, the presence of HFpEF was independently associated with all-cause readmissions (adjusted odds ratio 1.52; 95% confidence interval 1.15-1.96; P = .002), but not with procedural complications, cardiac readmissions, or early mortality. Rates of 30-day readmissions after AF ablation are high in patients with HFpEF. However, after adjustment for age and comorbidities, complications and early mortality after AF ablation between patients with HFpEF and those without heart failure are comparable.


Use of substance P fragments to differentiate substance P receptors of different tissues.
The C- and N-terminal fragments of substance P were compared to the parent molecule with respect to their ability to: (a) contract the isolated guinea pig ileum, (b) induce salivation in the rat, (c) excite single cat dorsal horn neurones, and (d) induce scratching by intracranial injections in mice. C-terminal fragments as small as the heptapeptide were potent SP agonists on all assay systems. C-terminal fragments containing five amino acids or less were, at most, only weakly active. The C-terminal hexapeptide was a potent SP receptor stimulant on the isolated guinea pig ileum and, when directly applied by microiontophoresis, on cat dorsal horn neurons. However, the same compound was only 2-5% as potent as substance P in eliciting salivation and scratching in vivo, an indication that this fragment may be especially labile to enzymatic degradation. N-terminal fragments were totally inactive on the isolated guinea pig ileum. On the rat salivation and central nervous system assays, however, N-terminal fragments were capable of weak SP-like activity. It is concluded that SP receptors exist in multiple forms which we have labelled SP1 and SP2 receptors for those insensitive or sensitive to N-terminal fragments, respectively.


Factor Structure of the Cultural Competence Items in the National Home and Hospice Care Survey.
There is a need for validated measures of cultural competency practices in home health and hospice care (HHHC). To establish the factor structure of the cultural competency items included in the agency-component of the 2007 public-use National Home and Hospice Care Survey file. We used weighted survey data from 1036 HHHC agencies. We used exploratory factor analyses to identify a preliminary factor structure, and then performed confirmatory factor analysis to provide further support for identified factor structure. We examined 9 cultural competency items. Exploratory factor analyses suggested an interpretable 2-factor solution: (1) the provision of mandatory cultural competency training; and (2) the provision of cultural competency communication practices. Each factor consisted of 3 items. The remaining 3 items did not load well on these factors. A similar, but more restrictive, confirmatory factor analysis model without cross-loadings supported the 2-factor model: (Equation is included in full-text article.)=9.50, P=0.30, root mean square error of approximation (RMSEA)=0.01, comparative fit index (CFI)=0.99, Tucker-Lewis Index (TLI)=0.99. Two constructs with 3 items each appeared to be internally valid measures of cultural competency in this nationally representative survey of HHHC agencies: cultural competency training and cultural competency communication practices. These measures could be used by HHHC managers in quality improvement efforts and by policy makers in monitoring cultural competency practices.


Native mass spectrometry of human carbonic anhydrase I and its inhibitor complexes.
Native mass spectrometry is a potent technique to study and characterize biomacromolecules in their native state. Here, we have applied this method to explore the solution chemistry of human carbonic anhydrase I (hCA I) and its interactions with four different inhibitors, namely three sulfonamide inhibitors (AAZ, MZA, SLC-0111) and the dithiocarbamate derivative of morpholine (DTC). Through high-resolution ESI-Q-TOF measurements, the native state of hCA I and the binding of the above inhibitors were characterized in the molecular detail. Native mass spectrometry was also exploited to assess the direct competition in solution among the various inhibitors in relation to their affinity constants. Additional studies were conducted on the interaction of hCA I with the metallodrug auranofin, under various solution and instrumental conditions. Auranofin is a selective reagent for solvent-accessible free cysteine residues, and its reactivity was analyzed also in the presence of CA inhibitors. Overall, our investigation reveals that native mass spectrometry represents an excellent tool to characterize the solution behavior of carbonic anhydrase.


Cuckoo search algorithm based on cloud model and its application.
Cuckoo search algorithm is an efficient random search method for numerical optimization. However, it is very sensitive to the setting of the step size factor. To address this issue, a new cuckoo search algorithm based on cloud model is developed to dynamically configure the step size factor. More specifically, the idea of giving consideration to both fuzziness and randomness of cloud model is innovatively introduced into cuckoo search algorithm, and the appropriate step size factor can be determined according to the membership degree and an exponential function, so as to realize the adaptive adjustment of the control parameter. After that, simulation experiments are conducted on 25 benchmark functions with different dimensions and two chaotic time series prediction problems to comprehensively evaluate the superiority of the proposed algorithm. Numerical results demonstrate that the developed method is more competitive than the other five CS and several non-CS algorithms.


Control of spontaneous glucose intolerance, hyperinsulinemia, and islet hyperplasia in nonobese C3H.SW male mice by Y-linked locus and adrenal gland.
An inbred strain predisposition to maturity-onset impairment of glucose tolerance was discovered in C3H.SW/SnJ inbred male mice. Males were group-caged from weaning and subjected to repetitive handling stress; deterioration of glucose tolerance developed between 5 and 8 months of age in association with extreme hyperinsulinemia. Some males developed transient chemical diabetes in which plasma glucose concentrations were inappropriately high in relation to the high levels of plasma insulin. By 12 months of age, males previously glucose intolerant had regained a normal glucose tolerance. At death, a massive hypertrophy and hyperplasia of the islet beta-cells was documented in these mice. The impaired glucose tolerance could be circumvented by adrenalectomy at weaning. Although these finding suggested the presence of an obesity gene, the C3H.SW group-caged males were not obese when compared with C3HeB/FeJ males which, although moderately hyperinsulinemic, did not develop the glucose intolerance syndrome. Transfer of the Y chromosome from the C3HeB/FeChp background into the C3H.SW inbred background led to a reduction in the hyperinsulinemic and hyperglycemic stress on the pancreatic islets. Thus the extrinsic environment (caging and handling stress), mediated in part via the adrenal gland, could interact with sex-linked genetic susceptibility modifiers to stimulate hyperplasia of the pancreatic islets and produce a transient insulin resistant state of impaired glucose tolerance in the absence of obesity.


Low perforin and elevated SHIP-1 expression is associated with functional anergy of natural killer cells in chronic HIV-1 infection.
Natural killer (NK) cells are critical for the first-line defense in infection. Treated viremic HIV-1 infection is associated with the expansion of an anergic subset of CD3-CD56-CD16+ NK cells unable to respond to stimulation with MHC-devoid target cells or with mitogens. These CD3-CD56-CD16+ NK cells expressed SHIP-1 and had significantly reduced perforin levels. This observation suggests a mechanism for the reduced functional activity of CD3-CD56-CD16+ NK cells in chronic HIV-1 infection.


Cyberbullying and post-traumatic stress symptoms in UK adolescents.
Cyberbullying involvement carries mental health risks for adolescents, although post-traumatic stress (PTS) symptoms have not received strong attention in the UK. This study aimed to assess the overlap between cyber and traditional (ie, face-to-face) bullying, and the relationship to PTS symptoms in UK adolescents. A cross-sectional survey. Four secondary schools in London,UK. 2218 secondary school students (11-19 years). The Olweus Bully/Victim Questionnaire and the Children Revised Impact of Events Scale. There was a significant overlap between traditional bullying and cyberbullying. However, cyberperpetrators were less frequently involved in concurrent traditional bullying. Of 2218 pupils, 46% reported a history of any kind of bullying (34% were involved in traditional bullying and 25% in cyberbullying), 17% as victims, 12% as perpetrators, and 4% as both victims and perpetrators. A significant proportion of those who were cybervictims (n=280; 35%), cyberbullies (n=178; 29.2%) or cyberbully-victims (n=77; 28.6%) presented clinically significant PTS symptoms. Cybervictims (both cyber-only and cyberbully-victims) suffered more intrusion (p=0.003; p<0.001) and avoidance (p=0.005; p<0.001) than cyberbullies. However, cyberbullies still suffered more PTS symptoms than the non-involved (intrusion: z=-3.67, p=0.001; avoidance: z=-3.57, p=0.002). Post-traumatic stress symptoms were significantly predicted (R2=13.6) by cyber and traditional victimisation. Cyberbullying, as victim only or as a victim-perpetrator, seems to be associated with multiple types of PTS symptoms. Cyber and traditional victimisation significantly predicted intrusion and avoidance. Paediatricians, general practitioners and mental health professionals need to be aware of possible PTS symptoms in young people involved in cyberbullying. Screening and early cost-effective treatments could be implemented.


The synergism between atrial fibrillation and heart failure.
Atrial fibrillation (AF) is a common comorbidity in heart failure (HF) patients and is classically associated with acceleration in the rate of HF progression. The precise mechanism for this interaction is unclear, but comprises "bidirectional" aspects in which AF promotes HF and HF also increases the likelihood of AF. We therefore studied the relationship between AF in an ovine model of pacing-induced congestive HF, in an attempt to identify the mechanisms that underpin the apparent synergistic relationship between AF and HF. Sixteen adult sheep were paced at 190 beats/min for 21 days (HF). AF was induced in 8 of these animals at 14 days' pacing using programmed extrastimuli (HF + AF). Left ventricular hemodynamics and the pattern of cardiac neurohormonal activation, via coronary sinus (CS) sampling, were determined at rest and during submaximal exercise testing in both groups at 21 days and after AF reversion (by atrial defibrillation) at 21 days. CS norepinephrine (NE), endothelin (ET-1), and brain natriuretic peptide (BNP) levels were significantly increased in HF + AF animals, whereas LV end-diastolic pressure (EDP) and LV dP/dt max were significantly reduced compared with moderate HF alone. Cardioversion significantly reduced CS NE and BNP levels and improved contractility in AF + HF animals. In a further 6 animals, we explored the mechanism by which HF increases susceptibility to AF, with specific emphasis on the influence of functional mitral regurgitation. The elimination of MR in HF animals using a percutaneous mitral annular reduction device significantly decreased the inducibility of AF. AF induction significantly depresses left ventricular function and causes activation of myocardial neurohormones. In conjunction, the presence of functional MR increases susceptibility to AF and this may be attenuated by MR reduction by percutaneous mitral annular reduction.


LncRNA XIST Depletion Prevents Cancer Progression in Invasive Pituitary Neuroendocrine Tumor by Inhibiting bFGF via Upregulation of microRNA-424-5p [Retraction].
[This retracts the article DOI: 10.2147/OTT.S208329.].


Modified Dual-Zone Therapeutic Concept of Single Immediate Implants with Bone and Soft Tissue Augmentation: Technical Report with Three Cases.
Although connective tissue grafts (CTGs) have been found to increase gingival thickness and reduce facial gingival recession in immediate implant placement and provisionalization (IIPP), they are associated with significant loss of buccal bone thickness. This loss is thought to be related to the preparation of the facial CTG recipient site. This technical report presents a modified dual-zone therapeutic concept in which the bone zone is grafted with bone graft and the tissue zone is grafted with tuberosity CTG without elevation of a facial partial- or full-thickness envelope.


Joint European Society of Paediatric Radiology (ESPR) and International Society for Forensic Radiology and Imaging (ISFRI) guidelines: paediatric postmortem computed tomography imaging protocol.
Postmortem CT for investigating childhood deaths is increasingly utilised as a noninvasive adjunct or alternative to standard autopsy; however there are no standardised published imaging protocols. This article describes a standardised imaging protocol that has been developed based on current practices of international postmortem imaging practitioners and experts. This recommendation is expected to be useful for postmortem imaging centres wishing to update their existing practices and for those starting paediatric postmortem CT as a new service.


Heritability of the Fibromyalgia Phenotype Varies by Age.
Many studies suggest a strong familial component to fibromyalgia (FM). However, those studies have nearly all been confined to individuals with primary FM, i.e., FM without any other accompanying disorder. The current 2011 and 2016 criteria for diagnosing FM construct a score using a combination of the number of painful body sites and the severity of somatic symptoms (FM score). This study was undertaken to estimate the genetic heritability of the FM score across sex and age groups to identify subgroups of individuals with greater heritability, which may help in the design of future genetic studies. We collected data on 26,749 individuals of European ancestry undergoing elective surgery at the University of Michigan (Michigan Genomics Initiative study). We estimated the single-nucleotide polymorphism-based heritability of FM score by age and sex categories using genome-wide association study data and a linear mixed-effects model. Overall, the FM score had an estimated heritability of 13.9% (SE 2.9%) (P = 1.6 × 10-7 ). Estimated FM score heritability was highest in individuals ≤50 years of age (23.5%; SE 7.9%) (P = 3.0 ×10-4 ) and lowest in individuals >60 years of age (7.5%; SE 8.1%) (P = 0.41). These patterns remained the same when we analyzed FM as a case-control phenotype. Even though women had an ~30% higher average FM score than men across age categories, FM score heritability did not differ significantly by sex. Younger individuals appear to have a much stronger genetic component to the FM score than older individuals. Older individuals may be more likely to have what was previously called "secondary FM." Regardless of the cause, these results have implications for future genetic studies of FM and associated conditions.


A protocol for the use of cloud-based quantum computers for logical network analysis of biological systems.
Boolean networks are commonly used in systems biology to dynamically model gene regulatory interactions. Here, we present a protocol for implementing Boolean network dynamics as quantum circuits. We describe steps for accessing cloud-based quantum processing units offered by IBM and IonQ and downloading and parsing logic for gene regulatory networks. We then detail procedures for performing simulations of quantum circuits on local devices and visualizing measurement results. For complete details on the use and execution of this protocol, please refer to Weidner et al.1.


Acupuncture or cupping plus standard care versus standard care in moderate to severe COVID-19 patients: An assessor-blinded, randomized, controlled trial.
Non-pharmacological strategies that have been proposed by complementary medical systems, can be effective in management of COVID-19. This study was designed as a three-arm, assessor-blinded, randomized controlled trial. A total of 139 hospitalized COVID-19 patients were randomly assigned into three groups: (1) acupuncture (ACUG), (2) cupping (CUPG), and (3) control (CTRG). All participants received conventional treatment. The primary study endpoint included changes in respiratory signs including oxygen saturation (SpO2) and respiratory rate (RR). The secondary endpoints were COVID-19-related hospitalization duration and serious adverse events such as intensive care unit (ICU) admission, intubation or death, all up to day 30. Also, improvements in cough, dyspnea, chest tightness, oxygen demand, anorexia, headache, weakness, sore throat, and myalgia were evaluated. Forty-two patients in ACUG, 44 patients in CUPG, and 42 patients in CTRG completed the trial. After 3 days, SpO2 and RR improved significantly in CUPG and ACUG compared with CTRG (effect size: 8.49 (6.4 to 10.57) and 8.51 (6.67 to 10.34), respectively: p<0.001). Compared with CTRG, patients in CUPG and ACUG recovered faster (mean difference: 6.58 (4.8 to 8.35) and 9.16 (7.16 to 11.15), respectively) and except for two patients in ACUG who were admitted to ICU, none of patients in ACUG or CUPG needed ICU or intubation (p<0.001 in comparison to CTRG). Amelioration of clinical COVID-19 related symptoms reached a high level of statistical significance in CUPG and ACUG in comparison with CTRG (p<0.01). Cupping and acupuncture are promising safe and effective therapies in management of COVID-19. Trial registration: This study was registered at Iranian Registry of Clinical Trials: IRCT20201127049504N1 (https://en.irct.ir/trial/52621).


Bromocriptine-induced rotation: characterization using a striatal efferent lesion in the mouse.
Two lesion techniques were used to elucidate the mode of action of bromocriptine (BRC)-induced behavior in mice. With the first lesion, a unilateral 6-hydroxydopamine (6-OHDA) preparation, BRC administration resulted in contralateral rotation which was blocked by alpha-methyl-para-tyrosine (AMPT), comparable to previous reports using rats. After striatonigral/entopeduncular lesion, mice did not rotate in response to doses of BRC up to 30 mg/kg but did show general activation which was also inhibited by AMPT pretreatment. It is concluded that BRC does not elicit rotation when there is no dopaminergic asymmetry such as that caused by a unilateral 6-OHDA lesion or no asymmetry in the striatonigral or striatoentopeduncular efferents. Since BRC-induced behaviors are dependent on intact presynaptic dopamine and BRC is predominantly a D-2 agonist, behaviors elicited in response to BRC must be the result of coactivation of D-1 receptors by endogenous dopamine. Thus, the behavioral effects of BRC, and perhaps D-2 agonists in general, must be mediated by efferents other than the striatonigral and striatoentopeduncular pathways.


Boosting the growth of the probiotic strain Lactobacillus paracasei ssp. paracasei F19.
Single so-called booster substances were added to the fermentation medium of the probiotic strain Lactobacillus (L.) paracasei ssp. paracasei F19 to enhance its growth. A wide screening was carried out in microtiter plates and a statistical analysis of the growth parameters was performed. CFU counts were used to correlate the increase in OD590nm with the increase in viable cell number. Sodium ascorbate, sodium pyruvate, manganese sulfate and cysteine had a remarkable boosting effect on the growth of L. paracasei F19. Three of the boosters increased the growth rate of the strain and led to a higher cell density and biomass yield in laboratory conditions. Cysteine significantly shortened the lag phase, therefore reducing the fermentation times. The boosters were tested on four additional Lactobacillus species and their growth boosting activity was retained. To investigate whether the growth boosters could improve the tolerance of L. paracasei F19 to the adverse condition in the GI tract, additional tests were performed. Sodium ascorbate and sodium pyruvate exerted a certain antioxidant effect, as they improved the tolerance of L. paracasei F19 to H2O2. Sodium ascorbate enhanced the growth of the strain in low pH.


Allergic bronchopulmonary aspergillosis with coexistant aspergilloma: a case report.
The coexistence of allergic bronchopulmonary aspergillosis and aspergilloma is rare. We present the case of a 56-year-old Caucasian man who worked as a farmer, with infiltrates in the right lower and middle lung lobes, partial consolidation of the middle lobe and with previous diagnosis of chronic obstructive bronchitis. Evaluation of our patient led to the diagnosis of allergic bronchopulmonary aspergillosis with coexistent aspergilloma in the right lower lobe. He was treated with oral methylprednisolone and itraconazole. At the five-year follow-up he is without any sign of recurrence. Aspergillus infection after the inhalation of spores in the form of a hypersensitivity reaction and saprophytic colonization can be coexistent.


Epigallocatechin Gallate-Mediated Alteration of the MicroRNA Expression Profile in 5α-Dihydrotestosterone-Treated Human Dermal Papilla Cells.
Dihydrotestosterone (DHT) induces androgenic alopecia by shortening the hair follicle growth phase, resulting in hair loss. We previously demonstrated how changes in the microRNA (miRNA) expression profile influenced DHT-mediated cell death, cell cycle arrest, cell viability, the generation of reactive oxygen species (ROS), and senescence. Protective effects against DHT have not, however, been elucidated at the genome level. We showed that epigallocatechin gallate (EGCG), a major component of green tea, protects DHT-induced cell death by regulating the cellular miRNA expression profile. We used a miRNA microarray to identify miRNA expression levels in human dermal papilla cells (DPCs). We investigated whether the miRNA expression influenced the protective effects of EGCG against DHT-induced cell death, growth arrest, intracellular ROS levels, and senescence. EGCG protected against the effects of DHT by altering the miRNA expression profile in human DPCs. In addition, EGCG attenuated DHT-mediated cell death and growth arrest and decreased intracellular ROS levels and senescence. A bioinformatics analysis elucidated the relationship between the altered miRNA expression and EGCG-mediated protective effects against DHT. Overall, our results suggest that EGCG ameliorates the negative effects of DHT by altering the miRNA expression profile in human DPCs.


Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial.
Giant cell arteritis is an immune-mediated disease of medium and large-sized arteries that affects mostly people older than 50 years of age. Treatment with glucocorticoids is the gold-standard and prevents severe vascular complications but is associated with substantial morbidity and mortality. Tocilizumab, a humanised monoclonal antibody against the interleukin-6 receptor, has been associated with rapid induction and maintenance of remission in patients with giant cell arteritis. We therefore aimed to study the efficacy and safety of tocilizumab in the first randomised clinical trial in patients with newly diagnosed or recurrent giant cell arteritis. In this single centre, phase 2, randomised, double-blind, placebo-controlled trial, we recruited patients aged 50 years and older from University Hospital Bern, Switzerland, who met the 1990 American College of Rheumatology criteria for giant cell arteritis. Patients with new-onset or relapsing disease were randomly assigned (2:1) to receive either tocilizumab (8 mg/kg) or placebo intravenously. 13 infusions were given in 4 week intervals until week 52. Both groups received oral prednisolone, starting at 1 mg/kg per day and tapered down to 0 mg according to a standard reduction scheme defined in the study protocol. Allocation to treatment groups was done using a central computerised randomisation procedure with a permuted block design and a block size of three, and concealed using central randomisation generated by the clinical trials unit. Patients, investigators, and study personnel were masked to treatment assignment. The primary outcome was the proportion of patients who achieved complete remission of disease at a prednisolone dose of 0·1 mg/kg per day at week 12. All analyses were intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01450137. Between March 3, 2012, and Sept 9, 2014, 20 patients were randomly assigned to receive tocilizumab and prednisolone, and ten patients to receive placebo and glucocorticoid; 16 (80%) and seven (70%) patients, respectively, had new-onset giant cell arteritis. 17 (85%) of 20 patients given tocilizumab and four (40%) of ten patients given placebo reached complete remission by week 12 (risk difference 45%, 95% CI 11-79; p=0·0301). Relapse-free survival was achieved in 17 (85%) patients in the tocilizumab group and two (20%) in the placebo group by week 52 (risk difference 65%, 95% CI 36-94; p=0·0010). The mean survival-time difference to stop glucocorticoids was 12 weeks in favour of tocilizumab (95% CI 7-17; p<0·0001), leading to a cumulative prednisolone dose of 43 mg/kg in the tocilizumab group versus 110 mg/kg in the placebo group (p=0·0005) after 52 weeks. Seven (35%) patients in the tocilizumab group and five (50%) in the placebo group had serious adverse events. Our findings show, for the first time in a trial setting, the efficacy of tocilizumab in the induction and maintenance of remission in patients with giant cell arteritis. Roche and the University of Bern.


Midfoot and ankle movement coordination during heel rise is disrupted in people with diabetes and peripheral neuropathy.
A heel rise task can be used to evaluate midfoot and ankle movement dysfunction in people with diabetes mellitus and peripheral neuropathy. Quantifying movement coordination during heel rise is important to better understand potentially detrimental movement strategies in people with foot pathologies; however, coordination and the impact of limited excursion on coordination is not well-understood in people with diabetes. Sixty patients with diabetes mellitus and peripheral neuropathy, and 22 older and 25 younger controls performed single-limb heel rise task. Midfoot (forefoot relative to hindfoot) sagittal and ankle (hindfoot relative to shank) sagittal and frontal kinematics were measured and normalized to time (0 to 100%). Cross-correlation coefficients were calculated across individuals in each group. A graphical illustration was used to interpret the relationship of midfoot and ankle excursion and cross-correlation coefficient during heel rise. People with diabetes mellitus and peripheral neuropathy showed significantly lower midfoot and ankle cross-correlation coefficients during heel rise compared to older controls (p = 0.003-0.007). There was no difference in the midfoot and ankle cross-correlation coefficients during heel rise for the older and younger controls (p = 0.059-0.425). The graphic data illustrated a trend of greater excursion of two joints and a higher cross-correlation coefficient. Some individuals with lower excursion showed a high cross-correlation coefficient. Foot pathologies, but not aging, impairs midfoot and ankle movement coordination during heel rise task. Investigating both movement coordination as well as joint excursion would better inform and characterize the dynamic movements of midfoot and ankle during heel rise task.


Acute cytotoxicity of mineral fibres observed by time-lapse video microscopy.
Inhalation of mineral fibres is associated with the onset of an inflammatory activity in the lungs and the pleura responsible for the development of fatal malignancies. It is known that cell damage is a necessary step for triggering the inflammatory response. However, the mechanisms by which mineral fibres exert cytotoxic activity are not fully understood. In this work, the kinetics of the early cytotoxicity mechanisms of three mineral fibres (i.e., chrysotile, crocidolite and fibrous erionite) classified as carcinogenic by the International Agency for Research on Cancer, was determined for the first time in a comparative manner using time-lapse video microscopy coupled with in vitro assays. All tests were performed using the THP-1 cell line, differentiated into M0 macrophages (M0-THP-1) and exposed for short times (8 h) to 25 μg/mL aliquots of chrysotile, crocidolite and fibrous erionite. The toxic action of fibrous erionite on M0-THP-1 cells is manifested since the early steps (2 h) of the experiment while the cytotoxicity of crocidolite and chrysotile gradually increases during the time span of the experiment. Chrysotile and crocidolite prompt cell death mainly via apoptosis, while erionite exposure is also probably associated to a necrotic-like effect. The potential mechanisms underlying these different toxicity behaviours are discussed in the light of the different morphological, and chemical-physical properties of the three fibres.


Renal Outcomes in Neonates and Infants with Transposition Physiology Undergoing Arterial Switch Procedure.
Acute kidney injury (AKI) in children with Transposition of Great arteries (TGA) undergoing Arterial Switch operation (ASO) is an important complication in the post-operative period associated with worse outcomes. AKI in children post open cardiac surgery has been well studied, with lesser data in literature pertaining to TGA and its sub-types specifically. This was a prospective, observational study enrolling infants with TGA undergoing ASO at a single center over a span of a decade from January 2010 to December 2020. The infants were followed during the duration of ICU and hospital stay, with documentation of baseline and intraoperative parameters as well as post-operative course. Out of 145 infants enrolled in the study, 83.1% developed AKI with majority (83.9%) having stage 1 AKI. Higher odds of AKI were seen in infants requiring Norepinephrine [odds ratio - 16.76 (95% CI 2.19-128.2), p < 0.001] and those who developed gram-negative infections [2.81 (1.04-7.56), p - 0.036]. Infants with AKI had significantly higher vasoactive-inotropic support at day 1 than those without AKI [16 (12.5-21.50 vs 13 (10.25-15.75), p - 0.014]. Seventeen infants in the AKI group (14%) died as opposed to none in the non-AKI group (p = 0.076). Median hours of ventilator support required were significantly higher in those with AKI than those who did not develop AKI (48 vs 45.5 p = 0.015). The infants with ASO + ASD + PDA (53% of neonates who died) were younger, had less weight at admission, more gram-negative sepsis and need for dopamine, as compared to ASO + VSD + ASD (23.5% of mortality) and ASO + ASD + VSD + aortic arch repair (23.5% of mortality). AKI in infants with TGA undergoing ASO is common and associated with poorer outcomes. In this subpopulation, AKI development is associated most commonly with hemodynamic instability and infections. This is the first study, looking at outcomes of TGA depending on the sub-types of ASO surgeries done in the infants [ASO with ASD + PDA or ASD + VSD or ASD + VSD + Arch Repair].


Empyema and lung abscess as complication of a perforated appendicitis in a pregnant woman.
The development of empyema as a result of an intra-abdominal pathology is a rare condition. We present a 31-year-old woman at 28 weeks' gestation who was referred to our hospital with diagnosis of pneumonia with pleural effusion. She presented with signs of septicemia and fetal distress. A thoracic-abdominal-pelvic CT-scan showed a right pleural effusion with a retroperitoneal collection in contact with the pleural space. Due to her critical condition, immediate surgical exploration and pregnancy interruption was decided. The fetus was delivered by cesarean with satisfactory vitality. After abdominal exploration, a retrocecal appendicular abscess was evidenced and appendectomy was performed. Subsequently, the right chest was accessed through a posterolateral thoracotomy. An empyema with lung abscess and purulent fluid accessing from the retroperitoneum at the posterior pleural space was found. Due to parenchymal compromise, a right inferior lobectomy was performed. The patient had an uneventful recovery and was discharged at postoperative day 10. A septic condition in a pregnant patient with significant thoraco-abdominal infection requires an aggressive approach, with interruption of pregnancy and urgent exploration of the chest and abdomen. When an empyema is developed in absence of lung disease or other intrathoracic cause, intra-abdominal origin should be considered.


Oral administration of diphenylarsinic acid, a degradation product of chemical warfare agents, induces oxidative and nitrosative stress in cerebellar Purkinje cells.
A new clinical syndrome with prominent cerebellar symptoms in patients living in Kamisu City, Ibaraki Prefecture, Japan, is described. Since the patients ingested drinking water containing diphenylarsinic acid (DPA), a stable degradation product of both diphenylcyanoarsine and diphenylchloroarsine, which were developed for use as chemical weapons and cause severe vomiting and sneezing, DPA was suspected of being responsible for the clinical syndrome. The purpose of the present study was to elucidate prominent cerebellar symptoms due to DPA. The aim of the study was to determine if single (15 mg/kg) or continuous (5 mg/kg/day for 5 weeks) oral administration of DPA to ICR-strain mice induced oxidative and/or nitrosative stress in their brain. Significantly positive staining with malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) was observed in the cerebellar Purkinje cells by repeated administration (5 mg/kg/day) with DPA for 5 weeks that led to the cerebellar symptoms from a behavioral pharmacology standpoint and by single administration of DPA (15 mg/kg). Furthermore, it is possible that the production of 3-NT was not caused by peroxynitrite formation. The present results suggest the possibility that arsenic-associated novel active species may be a factor underlying the oxidative and nitrosative stress in Purkinje cells due to exposure to DPA, and that the damage may lead to the cerebellar symptoms.


A comparative study of the psychiatric practice of a tantrik healer and a hospital out-patient clinic in the Kathmandu Valley.
This paper summarizes the information gathered from healer and hospital patients consulting for mental illness in the Kathmandu Valley. While the tantrik healer appeared to be emulating the hospital in the speed and impersonality with which patients were processed, healer patients appeared to enjoy a greater degree of family support than did hospital patients.


lncRNA Signature for Predicting Cerebral Vasospasm in Patients with SAH: Implications for Precision Neurosurgery.
Subarachnoid hemorrhage (SAH) patients' surgery is performed to prevent extravasation of blood into the subarachnoid space. Cerebral vasospasm (CVS; narrowing of cerebral arteries) occurs following SAH and represents a major cause of associated mortality and morbidity. To improve postsurgery care of SAH patients and their prognosis, the ability to predict CVS onset is critical. We report a long noncoding RNA (lncRNA) signature to distinguish SAH patients with CVS from SAH patients without CVS. Cerebrospinal fluid (CSF) was obtained from SAH patients without CVS (n = 10) and SAH patients with CVS (n = 10). lncRNAs ZFAS1 and MALAT1 were significantly upregulated (p < 0.05), whereas lncRNAs LINC00261 and LINC01619 were significantly downregulated in SAH patients with CVS (p < 0.05) compared to SAH patients without CVS. We applied this lncRNA signature to retrospectively predict CVS in SAH patients (n = 38 for SAH patients without CVS, and n = 27 for SAH patients with CVS). The 4-lncRNA signature was found to be predictive in >40% of samples and the 2-lncRNA comprising MALAT1 and LINC01619 accurately predicted CVS in ∼90% cases. These results are initial steps toward personalized management of SAH patients in clinics and provide novel CSF biomarkers that can substantially improve the clinical management of SAH patients.


Reinterpreting the work of Charles Breder: Sensory neuromasts and orbital skeleton variation in eyeless Astyanax cavefish.
Charles Breder, a pioneering researcher of blind Mexican cavefish was the first to note extreme variation in the facial skeleton of this intriguing subterranean-dwelling organism. Using a system of polar coordinate plots, he identified substantial dysmorphic changes affecting bones of the orbital skeleton. A complication of his landmark publication from 1944 was an error in the number of orbital bones depicted for this species. Intriguingly, however, he proposed an unknown "organizing force" likely influences final bone position and associated dysmorphia. At the time this was merely hypothetical. Roughly eight decades since its publication, however, insights into sensory influences on facial bone development may explain dysmorphia and variation in bone numbers for Astyanax cavefish. A morphological association between mechano-sensory neuromasts of the lateral line and dermal bones of the facial skeleton had been appreciated in the classical literature, but the polarity of this interaction has long remained unclear. Here, we propose that sensory-skeletal integration between sensory neuromasts and bones explain the incomplete numbers of bones, and dysmorphic features such as fusion between neighboring elements. We propose that in closely-related surface fish (and most teleost fish) this developmental coupling enables the sensory and skeletal systems to become integrated into a functional unit over the course of life history. In this opinion article, we discuss the relevance of this (poorly understood) phenomenon as a potential evolutionary source of variation in the facial bone structures of taxa across deep geologic time. We provide three potential explanations for the error in Breder's drawings, that may be explained by natural developmental variation documented in other related species. Moreover, we argue that the natural variation in this "evolutionary" model system is useful for explaining diverse cranial features by uniting aberrations occurring during embryogenesis with long-term adult dysmorphia.


Gadolinium-enhanced versus time-of-flight magnetic resonance angiography: what is the benefit of contrast enhancement in evaluating carotid stenosis?
Accurate patient selection based on preoperative imaging is imperative to good risk reduction in patients undergoing carotid endarterectomy (CEA). The goal of this study was to assess the accuracy of gadolinium-enhanced magnetic resonance angiography (GE MRA) versus time-of-flight (TOF) MRA in the work-up of patients undergoing CEA. Patients undergoing CEA between 1999 and 2001 were identified from a prospectively maintained institutional database. GE or TOF MRA was obtained on extracranial carotid arteries (n = 319) in patients undergoing CEA. Stenosis on MRA images was graded as moderate (n = 76) or severe (n = 243) by an attending radiologist who was blind to duplex results. Duplex imaging was performed in an Intersocietal Commission for the Accreditation of Vascular Labs (ICAVL) accredited lab, and stenosis was stratified as moderate (50-79%, n = 76) or high (80-99%, n = 243) grade using University of Washington criteria. For each patient, the degree of stenosis as determined by MRA (GE versus TOF) was compared to percent stenosis on duplex. For moderate-grade lesions, GE MRA concurred with duplex in 11.1% (4/36), underestimated in 2.8% (1/36), and overestimated in 86.1% (31/36) of carotid arteries imaged. TOF MRA concurred with duplex in 35% (14/40), underestimated in 0% (0/40), and overestimated in 65% (26/40) of carotid arteries. High-grade lesions demonstrated improved concordance between MRA and duplex. For these lesions, GE MRA concurred with duplex in 95.6% (130/136) of carotid arteries imaged, never overestimated stenosis (0/136), and underestimated in 4.4% (6/136). TOF MRA concurred with duplex 96.3% (103/107), overestimated stenosis as an occlusion in 0.9% (1/107), and underestimated in 2.8% (3/107). In addition to neck visualization, the GE technique allowed simultaneous aortic arch imaging. This was accomplished in 79.1% (136/172) of all GE MRAs. Simultaneous aortic arch imaging was not technically feasible with TOF MRA. For moderate-grade lesions, both MR techniques are inaccurate predictors of degree of carotid stenosis and result in a significant overestimation of stenosis. Each technique demonstrates improved concordance with duplex ultrasound in the setting of severe carotid artery stenoses. The ability of GE MRA to simultaneously image the aortic arch and the neck may allow for detection of occult tandem lesions and other anatomic variations, which may be particularly important in preoperative planning for carotid artery stenting.


Periodontal condition of the mandibular anterior dentition in patients with conventional and self-ligating brackets.
To explore whether the use of self-ligating brackets is associated with better values for periodontal indices because of the lack of elastomeric modules and concomitantly, reduced availability of retentive sites for microbial colonization and plaque accumulation. Private practice of the first author. Patients were selected using the following inclusion criteria: age range 12-17 years, fixed appliances on both arches, aligned mandibular arch, and absence of oral habits and anterior crossbites. Prospective cohort investigation. Participants were grouped for bracket type, thus 50 patients formed the conventional bracket cohort and 50 patients the self-ligating bracket cohort. Both cohorts were followed with the purpose to examine periodontal status. Average length of follow-up was 18 months. This time period was considered adequate for a proportion of study participants to experience the outcome of interest. Outcome variables were plaque index, gingival index, calculus index, and probing depth for the two bracket cohorts. No difference was found in the indices recorded between the two bracket cohorts studied. Under the conditions as applied in this study, the self-ligating brackets do not have an advantage over conventional brackets with respect to the periodontal status of the mandibular anterior teeth.


Palliative portal vein stent placement in malignant and symptomatic extrinsic portal vein stenosis or occlusion.
This article evaluates the results of portal vein (PV) stent placement in patients with malignant extrinsic lesions stenosing or obstructing the PV and causing symptomatic PV hypertension (PVHT). Fourteen patients with bile duct cancer (n = 7), pancreatic adenocarcinoma (n = 4), or another cancer (n = 3) underwent percutaneous transhepatic portal venous stent placement because of gastroesophageal or jejunal varices (n = 9), ascites (n = 7), and/or thrombocytopenia (n = 2). Concurrent tumoral obstruction of the main bile duct was treated via the transhepatic route in the same session in four patients. Changes in portal venous pressure, complications, stent patency, and survival were evaluated. Mean +/- standard deviation (SD) gradient of portal venous pressure decreased significantly immediately after stent placement from 11.2 mmHg +/- 4.6 to 1.1 mmHg +/- 1.0 (P < 0.00001). Three patients had minor complications, and one developed a liver abscess. During a mean +/- SD follow-up of 134.4 +/- 123.3 days, portal stents remained patent in 11 patients (78.6%); stent occlusion occurred in 3 patients, 2 of whom had undergone previous major hepatectomy. After stent placement, PVHT symptoms were relieved in four (57.1%) of seven patients who died (mean survival, 97 +/- 71.2 days), and relieved in six (85.7%) of seven patients still alive at the end of follow-up (mean follow-up, 171.7 +/- 153.5 days). Stent placement in the PV is feasible and relatively safe. It helped to relieve PVHT symptoms in a single session.


Clinical evaluation of the effects of signal integrity and saturation on data availability and accuracy of Masimo SE and Nellcor N-395 oximeters in children.
Pulse oximetry manufacturers have introduced technologies that claim improved detection of hypoxemic events. Because improvements in signal processing and data rejection algorithms may differentially affect data reporting, we compared the data reporting and signal heuristic performance and agreement among the Nellcor N-395, Masimo SET, and GE Solar 8000 oximeters under a spectrum of conditions of signal integrity and arterial oxygen saturations. A blinded side-by-side comparison of technologies was performed in 27 patients, and data were analyzed for time of data availability, measures of agreement and signal heuristics, and warnings stratified by signal integrity and SpO(2). The Solar 8000 had less total data dropout than either of the new technologies. Masimo's LoSIQ (signal quality) heuristic rejected less data than Nellcor's MOT/PS (motion/pulse search) flag. When no signal heuristic was displayed, there was little difference in precision and bias between the two newer technologies; however, agreement between devices deteriorated in the presence of SIQ, MOT, or hypoxemia. Both newer devices flagged questionable data, but their use of different rejection algorithms resulted in different probabilities of presenting data. Therefore, with poor SIQ or during hypoxemia, the Nellcor N-395 and Masimo oximeters are not clinically equivalent to each other or to the older Solar 8000 oximeter. We compared new pulse oximeters from Nellcor and Masimo and found that, with good signal conditions, both new devices performed similarly to older technology. Overall, Masimo reported less data as questionable than Nellcor. With poor signal conditions or during hypoxemia, the new devices are not clinically equivalent to each other or to the older technology.