Multiple strategies for resilient livelihoods in communal areas of South Africa.
Livestock farming in communal areas is an activity pursued by rural households as one of a range of livelihood strategies aimed at spreading risk. The cash and non-cash benefits derived from livestock, as well as the wide range of secondary resources harvested from communal rangelands, make an important contribution to livelihood diversification, and hence, resilience. Rural development policy should therefore not focus narrowly on commercialisation of livestock production in communal areas. Rather, it should take a multi-faceted approach to building livelihood resilience while providing pathways for households to escape poverty through enhancing the multiple benefits of livestock, adding value to secondary rangeland resources, and expanding the rural non-farm economy.


Alcaligenes faecalis: an unusual cause of skin and soft tissue infection.
Skin and soft tissue infection (SSTI) due to Alcaligenes faecalis is very rare and has never been studied. The aim of the present study was to investigate the clinical and microbiological characteristics of this infection. We conducted a retrospective review of 5 cases that occurred at our institution over a period of 6 years. All patients had underlying diseases, and infection was secondary to vascular disease or recent surgery in 4 of them. The most common clinical presentations were vascular ulcer infection and surgical site infection. The clinical outcome was uniformly good after treatment, except in 1 patient. In conclusion, A. faecalis should be considered a potential pathogen of SSTI, particularly in patients with vascular diseases or after surgery. The history of contact with water or aqueous solutions should be investigated in all cases. The clinical outcome is usually good, but treatment can be difficult in some cases due to the high level of resistance to commonly used antibiotics.


Plastoglobule Lipid Droplet Isolation from Plant Leaf Tissue and Cyanobacteria.
Plastoglobule lipid droplets are a dynamic sub-compartment of plant chloroplasts and cyanobacteria. Found ubiquitously among photosynthetic species, they are believed to serve a central role in the adaptation and remodeling of the thylakoid membrane under rapidly changing environmental conditions. The capacity to isolate plastoglobules of high purity has greatly facilitated their study through proteomic, lipidomic, and other methodologies. With plastoglobules of high purity and yield, it is possible to investigate their lipid and protein composition, enzymatic activity, and protein topology, among other possible molecular characteristics. This article presents a rapid and effective protocol for the isolation of plastoglobules from chloroplasts of plant leaf tissue and presents methodological variations for the isolation of plastoglobules and related lipid droplet structures from maize leaves, the desiccated leaf tissue of the resurrection plant, Eragrostis nindensis, and the cyanobacterium, Synechocystis sp. PCC 6803. Isolation relies on the low density of these lipid-rich particles, which facilitates their purification by sucrose density flotation. This methodology will prove valuable in the study of plastoglobules from diverse species.


Evolution of the geometrical and electronic structures of Gan(n=2-26) clusters: a density-functional theory study.
Density-functional theory with generalized gradient approximation for the exchange-correlation potential has been used to calculate the lowest-energy geometries and electronic structure of neutral gallium clusters containing up to 26 atoms. Harmonic vibrational frequency analysis is undertaken to assure that the lowest-energy geometries are real local minima. With increasing cluster size, we find that the gallium clusters tend to adopt compact structures. The structures comprise triangular units that connect each other with different dihedral angles. The lowest-energy structure can be obtained by capping an atom on the structure of smaller one. The capping site occurs at a site where interactions with more atoms are available. The binding energy evolves monotonically with size, but Ga(8), Ga(14), and Ga(20) exhibit particularly higher stability. Except Ga(2) and Ga(4), all even-numbered gallium clusters we studied are closed-shell singlet states with a substantial highest occupied and lowest unoccupied molecular orbitals gap. The odd-numbered clusters are open shell with a small gap. The size dependence of cluster's ionization potentials and electron affinities is discussed and compared with available experiment.


Structural and functional brain changes in early- and mid-stage primary open-angle glaucoma using voxel-based morphometry and functional magnetic resonance imaging.
To investigate structural and functional brain changes in patients with primary open-angle glaucoma (POAG) by using voxel-based morphometry based on diffeomorphic anatomical registration through exponentiated Lie algebra (VBM-DARTEL) and blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI), respectively.Thirteen patients diagnosed with POAG and 13 age- and sex-matched healthy controls were enrolled in the study. For each participant, high-resolution structural brain imaging and blood flow imaging were acquired on a 3.0-Tesla magnetic resonance imaging (MRI) scanner. Structural and functional changes between the POAG and control groups were analyzed. An analysis was carried out to identify correlations between structural and functional changes acquired in the previous analysis and the retinal nerve fiber layer (RNFL).Patients in the POAG group showed a significant (P < 0.001) volume increase in the midbrain, left brainstem, frontal gyrus, cerebellar vermis, left inferior parietal lobule, caudate nucleus, thalamus, precuneus, and Brodmann areas 7, 18, and 46. Moreover, significant (P < 0.001) BOLD signal changes were observed in the right supramarginal gyrus, frontal gyrus, superior frontal gyrus, left inferior parietal lobule, left cuneus, and left midcingulate area; many of these regions had high correlations with the RNFL.Patients with POAG undergo widespread and complex changes in cortical brain structure and blood flow. (ClinicalTrials.gov number: NCT02570867).


Comparison between propofol and dexmedetomidine on depth of anesthesia: A prospective randomized trial.
Intravenous agents such as propofol are commonly used to maintain adequate depth of anesthesia. Dexmedetomidine which has an anesthetic sparing effect is being considered for maintaining intraoperative depth of anesthesia. We hypothesized to compare the effect of dexmedetomidine on depth of anesthesia with propofol and evaluated whether dexmedetomidine can be used as sole anesthetic agent in maintaining depth of anesthesia. Sixty patients of ASA PS I, 18-65 years of age, scheduled for laparotomy under general anesthesia were randomly divided into two groups of 30 each. Group A received propofol 1 mg/kg bolus followed by infusion (50 mcg/kg/min) and Group B received dexmedetomidine 1 mcg/kg bolus followed by infusion (0.5 mcg/kg/h). Both the groups were administered standard general anesthesia with routine monitoring along with Bispectral index (BIS) and values were recorded at intervals of 10 min. In all patients Ramsay sedation score was recorded after extubation and they were assessed for recall of intraoperative events using Modified Brice questionnaire. Heart rate and mean arterial pressure were less in Group B than Group A. Intraoperative BIS values were significantly lower in Group B (P < 0.0001). Although sedation score was more in Group B it did not prolong recovery. No recall was found in any patient. Dexmedetomidine was comparable with propofol in maintaining anesthesia and it can produce better control of hemodynamics and BIS value. Thus dexmedetomidine can be used as the sole maintenance anesthetic agent.


An integrated approach of network-based systems biology, molecular docking, and molecular dynamics approach to unravel the role of existing antiviral molecules against AIDS-associated cancer.
A serious challenge in cancer treatment is to reposition the activity of various already known drug candidates against cancer. There is a need to rewrite and systematically analyze the detailed mechanistic aspect of cellular networks to gain insight into the novel role played by various molecules. Most Human Immunodeficiency Virus infection-associated cancers are caused by oncogenic viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS-associated cancers marks the severity of AIDS, there might be possible interconnections between the targets and mechanism of both the diseases. We have explored the possibility of certain antiviral compounds to act against major AIDS-associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer with the help of systems pharmacology approach that includes screening for targets and molecules through the construction of a series of drug-target and drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B) and the target "HRAS" were finally screened with the help of molecular docking and molecular dynamics simulation. The results provide novel antiviral molecules against HRAS target to treat AIDS defining cancers and an insight for understanding the pharmacological, therapeutic aspects of similar unexplored molecules against various cancers.


Quantum Zeno effect explains magnetic-sensitive radical-ion-pair reactions.
Chemical reactions involving radical-ion pairs are ubiquitous in biology, since not only are they at the basis of the photosynthetic reaction chain, but are also assumed to underlie the biochemical magnetic compass used by avian species for navigation. Recent experiments with magnetic-sensitive radical-ion-pair reactions provided strong evidence for the radical-ion-pair magnetoreception mechanism, verifying the expected magnetic sensitivities and chemical product yield changes. It is here shown that the theoretical description of radical-ion-pair reactions used since the 70s cannot explain the observed data, because it is based on phenomenological equations masking quantum coherence effects. The fundamental density-matrix equation derived here from basic quantum measurement theory considerations naturally incorporates the quantum Zeno effect and readily explains recent experimental observations on low- and high magnetic-field radical-ion-pair reactions.


Relationship between statins and the risk of amyotrophic lateral sclerosis: A PRISMA-compliant meta-analysis.
Previous studies on overlapping surveillance databases have suggested that statin use was associated with the development of amyotrophic lateral sclerosis (ALS)-like syndrome. However, the association between statin use and ALS incidence has not been clearly elucidated. To further explore this issue, we performed a systemic review and meta-analysis of all available clinical studies on the association between statin use and ALS incidence. A comprehensive database search on PubMed, Embase, Cochrane Library, and SCOPUS was conducted. We included studies up to January 31, 2020 that fulfilled our inclusion and exclusion criteria. Statin use between the ALS and control groups was collected for the meta-analysis. Three case-control studies and 1 cohort study, that related the risk of ALS to statin use, satisfied the inclusion criteria for the meta-analysis. There was no statistically significant difference in statin use between the ALS and control groups (odds ratio, 0.75 [95% confidence interval, 0.53-1.08]). No definite association was found between statin use and the development of ALS. Further large-scale prospective randomized control studies are necessary to draw definite conclusions.


Membranoproliferative glomerulonephritis type III in a simultaneous infection of Leishmania infantum and Dirofilaria immitis in a dog.
In this report a 9-year-old female German Shepherd dog with a membranoproliferative glomerulonephritis (MPGN) type III associated with concomitant infection of Dirofilaria immitis and Leishmania infantum is presented. Light microscopic evaluation of kidney revealed a diffuse hypercellularity and thickening of glomerular basement membrane. Heavy and coarse granular complement C(3) deposition and a weaker positive reaction to immunoglobulin G were present along peripheral glomerular basement membrane and in the mesangium in the immunofluorescent study. Transmission electron microscopy revealed deposits in the mesangium, subendothelium, and subepithelium. These lesions are compatible with membranoproliferative glomerulonephritis type III in humans.


GenomeRing: alignment visualization based on SuperGenome coordinates.
The number of completely sequenced genomes is continuously rising, allowing for comparative analyses of genomic variation. Such analyses are often based on whole-genome alignments to elucidate structural differences arising from insertions, deletions or from rearrangement events. Computational tools that can visualize genome alignments in a meaningful manner are needed to help researchers gain new insights into the underlying data. Such visualizations typically are either realized in a linear fashion as in genome browsers or by using a circular approach, where relationships between genomic regions are indicated by arcs. Both methods allow for the integration of additional information such as experimental data or annotations. However, providing a visualization that still allows for a quick and comprehensive interpretation of all important genomic variations together with various supplemental data, which may be highly heterogeneous, remains a challenge. Here, we present two complementary approaches to tackle this problem. First, we propose the SuperGenome concept for the computation of a common coordinate system for all genomes in a multiple alignment. This coordinate system allows for the consistent placement of genome annotations in the presence of insertions, deletions and rearrangements. Second, we present the GenomeRing visualization that, based on the SuperGenome, creates an interactive overview visualization of the multiple genome alignment in a circular layout. We demonstrate our methods by applying them to an alignment of Campylobacter jejuni strains for the discovery of genomic islands as well as to an alignment of Helicobacter pylori, which we visualize in combination with gene expression data. GenomeRing and example data is available at http://it.inf.uni-tuebingen.de/software/genomering/.


Automated Sample Preparation Workflow for Tandem Mass Tag-Based Proteomics.
Although tandem mass tag (TMT)-based isobaric labeling has become a powerful approach for multiplexed protein quantitation, automating the workflow for this technique has not been easy to achieve for widespread adoption. This is because preparation of TMT-labeled peptide samples involves multiple steps ranging from protein extraction, denaturation, reduction, and alkylation to tryptic digestion, desalting, labeling, and cleanup, all of which require a high level of proficiency. The variability resulting from multiple processing steps is inherently problematic, especially with large-scale clinical studies that involve hundreds of samples where reproducibility is critical for quantitation. Here, we sought to compare the performance of a recently introduced platform, AccelerOme, for an automated proteomic workflow employing TMT labeling with the manual processing of samples. Cell pellets were prepared and subjected to a 16-plex experiment using an automated platform and a conventional manual protocol. Single-shot liquid chromatography with tandem mass spectrometry analysis revealed a higher number of proteins and peptides identified using the automated platform. Efficiency of tryptic digestion, alkylation, and TMT labeling were similar in both manual and automated processes. In addition, comparison of quantitation accuracy and precision showed similar performance in an automated workflow compared to manual sample preparation by an expert. Overall, we demonstrated that the automated platform performs at a level similar to a manual process performed by an expert for TMT-based proteomics. We anticipate that this automated workflow will increasingly replace manual pipelines and has the potential to be applied to large-scale TMT-based studies, providing robust results and high sample throughput.


STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production.
The proinflammatory cytokines interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are toxic to pancreatic beta-cells and are implicated in the pathogenesis of type 1 diabetes. We have previously found that GH and prolactin (PRL) stimulate both proliferation and insulin production in pancreatic beta-cells and rat insulin-producing INS-1 cells. Here we report that human (h) GH can prevent the apoptotic effects of IL-1beta, IFN-gamma and TNF-alpha in INS-1 and INS-1E cells. Using adenovirus-mediated gene transfer, we found that the anti-apoptotic effect of hGH is abrogated by expression of a dominant negative signal transducer and activator of transcription (STAT5) mutant in INS-1E cells. hGH and the cytotoxic cytokines was found to additively increase suppressor of cytokine signalling-3 mRNA expression after 4 h of exposure. In order to identify possible targets for the STAT5-mediated protection of INS-1E cells, we studied the effect of hGH on activation of the transcription factors STAT1 and nuclear factor-kappaB (NF-kappaB) by IFN-gamma and IL-1beta+TNF-alpha respectively. Gel retardation experiments showed that hGH affects neither IFN-gamma+TNF-alpha-induced STAT1 DNA binding nor IL-1beta and IFN-gamma+TNF-alpha-induced NFkappaB DNA binding. The lack of influence of hGH on cytokine-mediated activation of STAT1 and NFkappaB is in accordance with the finding that hGH had only a minor effect on cytokine-induced inducible nitric oxide synthase (iNOS) gene expression and in fact augmented the IL-1beta-stimulated nitric oxide production. As the anti-apoptotic Bcl-xL gene has been shown to harbour a STAT5-binding element we measured the expression of Bcl-xL as well as the pro-apoptotic Bax. We found that hGH increased the Bcl-xL/Bax ratio both in the absence and in the presence of cytotoxic cytokines. In conclusion, these results suggested that GH and PRL protect beta-cells against cytotoxic cytokines via STAT5-dependent mechanisms distal to iNOS activation possibly at the level of Bcl-xL.


Effect of the antineoplastic agent methotrexate on experimental heterotopic new bone formation in rats.
Heterotopic new bone formation was induced by implanting pieces of demineralized bone matrix in the abdominal wall of 22 growing Sprague-Dawley rats. The animals were divided into three groups and were given, 24 hr after initiation of the bone induction process, a single i.v. injection of methotrexate, 100 or 250 mg/kg body weight, or placebo, followed after 2 hr by leucovorin rescue. A slight and transient arrest in weight gain was noted in the methotrexate-treated animals. New bone formation during 3 weeks after implantation was analyzed by the amount of ash in implants, and as a measure of bone formation at the end of the experiment, short-time incorporation of 45Ca and [3H]proline was used. The ash content of implants was reduced by 56 and 68% in the two methotrexate groups. Uptake of both nucleotides was also greatly reduced in heterotopic bone, whereas metaphysial and diaphysial tibia and teeth were not affected. The results indicate a pronounced inhibition of methotrexate on bone induction, persisting for at least 3 weeks. Methotrexate reduces the bone-forming potential, with possible consequences for the success of limb-saving surgery and fracture healing.


Atypical mycobacteriosis in a lung transplant recipient.
Although mycobacterial infections are more frequent in lung transplant recipients than in other solid organ recipients only occasional reports of infection from atypical Mycobacteria have been reported in patients receiving lung transplantation. We present a case of pleural and cutaneous infection due to Mycobacterium fortuitum in a double-lung transplant recipient. The infection was rapidly responsive to therapy with a two drug regimen and no reduction of immunosuppression was necessary.


Purification and characterization of guinea-pig chorionic gonadotrophin.
A human chorionic gonadotrophin-like protein (GF-1, 1.0 g) from the placentae of 50 guinea-pigs killed at Day 26 of gestation was purified by pH and ammonium salt fractionation followed by column chromatography on DEAE-Sephadex and filtration on Sephadex G-100. Relative to the Second International hCG standard (MRC 61/6) GF-1 had an immunological potency of 21 000 i.u./mg as measured in a specific hCG-beta radioimmunoassay and, using the ovarian ascorbic acid depletion assay, an apparent biological potency of 24 064 i.u./mg. Isoelectric focusing yielded 6 bands between pH 4.4 and 5.7 and the material comprised two non-covalently linked subunits. The Stokes' radii were 3.40 nm for the native preparation, and 2.38 nm and 3.15 nm for GF-1-alpha and GF-1-beta subunits respectively. The guinea-pig placenta therefore produces a chorionic gonadotrophin which on purification has physicochemical, biological and immunological properties similar to those of hCG.


Isolation, Identification and Investigation of Fermentative Bacteria from Sea Bass (Dicentrarchus labrax): Evaluation of Antifungal Activity of Fermented Fish Meat and By-Products Broths.
During fish production processes, great amounts of by-products are generated, representing ≈30-70% of the initial weight. Thus, this research study is investigating 30 lactic acid bacteria (LAB) derived from the sea bass gastrointestinal tract, for anti-fungal activity. It has been previously suggested that LAB showing high proteolitic activity are the most suitable candidates for such an investigation. The isolation was made using a MRS (Man Rogosa Sharpe) broth cultivation medium at 37 ºC under anaerobiosis conditions, while the evaluation of the enzymatic activity was made using the API® ZYM kit. Taking into account the selected bacteria, a growing research was made fermenting two kinds of broths: (i) by-products (WB), and (ii) meat (MB). Both were fermented at three different times (24, 48 and 72 h). Then, the antifungal activities of both fermented by-products and meat broths were determined qualitatively and quantitatively in solid and liquid medium against two different strains of the genera Penicillium, Aspergillus and Fusarium. After the experiments, a total of 30 colonies were isolated, observing a proteolytic activity in 7 of the isolated strains, which belong to Lactobacillus genus, and the two more active strains were identified by polymerase chain reaction (PCR) as L. plantarum. Several strains evidenced antifungal activity showing an inhibition halo and Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) values between 1-32 g/L and 8-32 g/L, respectively. In conclusion, the isolated bacteria of sea bass had the ability to promote the antifungal activity after the fermentation process, thus being a useful tool to give an added value to fish industry by-products.


Does specialty board certification influence clinical outcomes?
The public seems to crave a simplistic index of 'quality', analogous to 'The Good Housekeeping Seal of Approval', for the complex endeavour of clinical medicine. The American Board of Medical Specialties (ABMS) and its member boards have purported to fill the vacuum in an effort that bears many of the earmarks of a public relations publicity campaign. The author examined the validity of the evidence touted in support of that effort. By applying Hill's causal epidemiologic criteria and logical and statistical inference, the author evaluated: (i) published data sources consisting of the most comprehensive collection of studies yet gathered that purports to provide evidence of the relevance of board certification to clinical outcomes, a collection presented by Sharp et al. apparently with the advice and consent of ABMS, that they posited as containing 'relevant findings', to what purpose they left unspecified; and (ii) the review article of Sharp et al. The data that Sharp et al. presented provided no credible link between specialty board certification and outcomes or 'quality' of clinical care. Sharp et al. ignored the evidence of absent evidence they found and proposed enthusiastic but unjustified conclusions in support of specialty board certification as an index of clinical 'expertise'. No evidence supports the touted clinical benefit of specialty board certification. Specialists in clinical medicine and surgery are unamenable to simplistic evaluation by examination, yet specialty board certification remains an ersatz standard of doctors' clinical quality in the absence of supporting evidence.


Public health and environmental response to the first case of naturally acquired inhalational anthrax in the United States in 30 years: infection of a new york city resident who worked with dried animal hides.
In Pennsylvania on February 16, 2006, a New York City resident collapsed with rigors and was hospitalized. On February 21, the Centers for Disease Control and Prevention and the New York City Department of Health and Mental Hygiene were notified that Bacillus anthracis had been identified in the patient's blood. Although the patient's history of working with dried animal hides to make African drums indicated the likelihood of a natural exposure to aerosolized anthrax spores, bioterrorism had to be ruled out first. Ultimately, this case proved to be the first case of naturally occurring inhalational anthrax in 30 years. This article describes the epidemiologic and environmental investigation to identify other cases and persons at risk and to determine the source of exposure and scope of contamination. Because stricter regulation of the importation of animal hides from areas where anthrax is enzootic is difficult, public healthcare officials should consider the possibility of future naturally occurring anthrax cases caused by contaminated hides. Federal protocols are needed to assist in the local response, which should be tempered by our growing understanding of the epidemiology of naturally acquired anthrax. These protocols should include recommended methods for reliable and efficient environmental sample collection and laboratory testing, and environmental risk assessments and remediation.


Economic bismuth-film microsensor for anodic stripping analysis of trace heavy metals using differential pulse voltammetry.
Stripping analysis has been widely recognised as a powerful tool in trace metal analysis. Its remarkable sensitivity is attributed to the combination of a preconcentration step coupled with pulse measurements that generate an extremely high signal-to-background ratio. Mercury-based electrodes have traditionally been used to achieve high reproducibility and sensitivity in the stripping technique. Because of the toxicity of mercury, however, new alternative electrode materials are highly desired, particularly for on-site monitoring. Use of thin films of bismuth deposited on platinum or glassy-carbon substrates has recently been proposed as a possible alternative to mercury--bismuth is "environmentally friendly", of low toxicity, and is in widespread pharmaceutical use. In this paper the preparation of economic bismuth-film microelectrodes by electrodeposition on a copper substrate and their application to heavy metal analysis are described. Bismuth-film electrodes were prepared by potentiostatic electrodeposition. Optimum conditions for chemical and electrochemical deposition to obtain an adherent, reproducible, and robust deposit were determined. The suitability of such microelectrodes for analysis of heavy metals was evaluated by anodic stripping voltammetry of cadmium. The analytical performance of bismuth-film electrodes for anodic stripping voltammetry of heavy metals was evaluated for non-deaerated solutions containing Cd2+, Pb2+, and Zn2+ ions. Well-defined peaks with low background current were obtained by use of differential pulse voltammetry. Linear calibration plots were obtained for Cd2+ in acidified tap water at concentrations ranging from 2 x 10(-8) to 1 x 10(-7) mol L(-1) and from 1 x 10(-7) to 1 x 10(-6) mol L(-1) with relative standard deviations of 5% (n = 15) at the 1 x 10(-7) mol L(-1) level. The method was then successfully used to monitor the Cd2+ content of plant extracts and validated by polarographic and ICP-MS measurements. These results open the possibility of using bismuth-coated copper electrodes as an alternative to mercury-based electrodes for analysis of heavy metals. The main problem remaining, which prevents on-site monitoring of heavy metals, is the need to use slightly acidic media, because formation of bismuth hydroxide on the film surface above pH 4.3 leads to non-reproducible measurements. Further experiments will be performed to discover whether electrode conditioning can be used to enable reproducible measurement in on-site monitoring of cadmium in natural waters. Moreover, further study should be conducted to evaluate the potential of BiFE for analysis of several pollutants of interest that are usually determined electrochemically by using mercury-based electrodes.


Development of a model to quantify the accessibility of a Canadian trauma system.
Trauma systems have been widely implemented across Canada, but access to trauma care remains a challenge for much of the population. This study aims to develop and validate a model to quantify the accessibility of definitive care within one provincial trauma system and identify populations with poor access to trauma care. A geographic information system (GIS) was used to generate models of pre-scene and post-scene intervals, respectively. Models were validated using a population-based trauma registry containing data on prehospital time intervals and injury locations for Nova Scotia (NS). Validated models were then applied to describe the population-level accessibility of trauma care for the NS population as well as a cohort of patients injured in motor vehicle collisions (MVCs). Predicted post-scene intervals were found to be highly correlated with documented post-scene intervals (β 1.05, p<0.001). Using the model, it was found that 88.1% and 42.7% of the population had access to Level III and Level I trauma care within 60 minutes of prehospital time from their residence, respectively. Access for victims of MVCs was lower, with 84.3% and 29.7% of the cohort having access to Level III and Level I trauma care within 60 minutes of the location of injury, respectively. GIS models can be used to identify populations with poor access to care and inform service planning in Canada. Although only 43% of the provincial population has access to Level I care within 60 minutes, the majority of the population of NS has access to Level III trauma care.


New variations of the EDNRB gene and its association with sporadic Hirschsprung's disease in Korea.
The endothelin receptor B (EDNRB) signaling pathway, which is the second major susceptible gene for Hirschsprung's disease (HSCR), is crucial for the development of the enteric nervous system. The allele frequency of polymorphisms was mostly tested in the American and European population, but the data of an ethnically diverse, non-Caucasian population are unclear. To further investigate the variants and haplotypes of the EDNRB gene, this study examined sequence variations in Korean patients with sporadic HSCR. All 8 exons and intron/exon boundaries of the EDNRB gene in 18 Korean patients with sporadic HSCR and 84 healthy individuals were screened using PCR amplification and direct sequencing. A total of 8 different nucleotide substitutions were identified. Of these, 4 were new variants (promoter-116C>T; 5'UTR-121G>T; IVS4+62C>A; IVS5+121G>C) and the others were previously described variants. The distribution of variations was even different from that reported for Chinese and Japanese subjects as well as other ethnic groups. This study also analyzed the haplotypes for an association between the variants identified with HSCR. This study identified additional sequence variants of the EDNRB gene, but the estimated EDNRB haplotypes did not show any disease risk.


Spinal Wnt5a Plays a Key Role in Spinal Dendritic Spine Remodeling in Neuropathic and Inflammatory Pain Models and in the Proalgesic Effects of Peripheral Wnt3a.
Wnt signaling represents a highly versatile signaling system, which plays critical roles in developmental morphogenesis as well as synaptic physiology in adult life and is implicated in a variety of neural disorders. Recently, we demonstrated that Wnt3a is able to recruit multiple noncanonical signaling pathways to alter peripheral sensory neuron function in a nociceptive modality-specific manner. Furthermore, several studies recently reported an important role for Wnt5a acting via canonical and noncanonical signaling in spinal processing of nociception in a number of pathologic pain disorders. Here, using diverse molecular, genetic, and behavioral approaches in mouse models of pain in vivo, we report a novel role for Wnt5a signaling in nociceptive modulation at the structural level. In models of chronic pain, using male and female mice, we found that Wnt5a is released spinally from peripheral sensory neurons, where it recruits the tyrosine kinase receptors Ror2 and Ryk to modulate dendritic spine rearrangement. Blocking the Wnt5a-Ryk/Ror2 axis in spinal dorsal horn neurons prevented activity-dependent dendritic spine remodeling and significantly reduced mechanical hypersensitivity induced by peripheral injury as well as inflammation. Moreover, we observed that peripheral Wnt3a signaling triggers the release of Wnt5a in the spinal cord, and inhibition of spinal Wnt5a signaling attenuates the functional impact of peripheral Wnt3a on nociceptive sensitivity. In conclusion, this study reports a novel role for the Wnt signaling axis in coordinating peripheral and spinal sensitization and shows that targeting Wnt5a-Ryk/ROR2 signaling alleviates both structural and functional mechanisms of nociceptive hypersensitivity in models of chronic pain in vivoSIGNIFICANCE STATEMENT There is a major need to elucidate molecular mechanisms underlying chronic pain disorders to develop novel therapeutic approaches. Wnt signaling represents a highly versatile signaling system, which plays critical roles during development and adult physiology, and it was implicated in several diseases, including chronic pain conditions. Using mouse models, our study identifies a novel role for Wnt5a signaling in nociceptive modulation at the spinal cord level. We observed that Wnt5a recruits Ror2 and Ryk receptors to enhance dendritic spine density, leading to nociceptive sensitization. Blocking the Wnt5a-Ryk/Ror2 interaction in the spinal dorsal horn prevented spine remodeling and significantly reduced inflammatory and neuropathic hypersensitivity. These findings provide proof-of-concept for targeting spinal Wnt signaling for alleviating nociceptive hypersensitivity in vivo.


The Value of 320-Row Multidetector CT Bronchial Arteriography in Recurrent Hemoptysis after Failed Transcatheter Arterial Embolization.
To retrospectively assess the value of computed tomographic (CT) bronchial arteriography (BA) with 320-row multidetector CT in the management of patients with recurrent hemoptysis immediately after bronchial artery embolization (BAE). Among 135 consecutive patients treated with BAE between April 2014 and March 2016, recurrent hemoptysis developed in 15, and 10 subsequently underwent multidetector CT. Vascular abnormalities and associated anatomy were evaluated to determine the potential cause of BAE failure, and the clinical impacts of CT BA were analyzed. CT BA revealed an additional 22 abnormal vessels in the qualified 10 patients, and 8 patients were treated again within 24 hours after the first BAE based on multidetector CT findings. Of the 22 abnormal vessels, 16 were embolized, including 4 orthotopic arteries, 8 ectopic arteries, and 4 nonbronchial systemic arteries (NBSAs); the remaining 6 abnormal arteries were not embolized because of normal BA (n = 1), anatomic inaccessibility (n = 2), or cessation of hemoptysis with conservative therapy (n = 3). There were no further cases of recurrent hemoptysis after the second intervention, with a mean follow-up of 7.7 months ± 6.7. Overall, initial conventional BA missed 65% of potential bleeding arteries (22 of 34). After CT BA, 73% of the newly identified vessels (16 of 22) were embolized. Multiple unrecognized abnormal ectopic bronchial arteries and NBSAs are the major causes of failure of initial BAE. Multidetector CT BA can precisely identify a large number of feeding vessels that are missed on conventional BA, allowing for repeat embolization with a high success rate.


37/67-laminin receptor facilitates neural crest cell migration during enteric nervous system development.
Enteric nervous system (ENS) development is governed by interactions between neural crest cells (NCC) and the extracellular matrix (ECM). Hirschsprung disease (HSCR) results from incomplete NCC migration and failure to form an appropriate ENS. Prior studies implicate abnormal ECM in NCC migration failure. We performed a comparative microarray of the embryonic distal hindgut of wild-type and EdnrBNCC-/- mice that model HSCR and identified laminin-β1 as upregulated in EdnrBNCC-/- colon. We identified decreased expression of 37/67 kDa laminin receptor (LAMR), which binds laminin-β1, in human HSCR myenteric plexus and EdnrBNCC-/- NCC. Using a combination of in vitro gut slice cultures and ex vivo organ cultures, we determined the mechanistic role of LAMR in NCC migration. We found that enteric NCC express LAMR, which is downregulated in human and murine HSCR. Binding of LAMR by the laminin-β1 analog YIGSR promotes NCC migration. Silencing of LAMR abrogated these effects. Finally, applying YIGSR to E13.5 EdnrBNCC-/- colon explants resulted in 80%-100% colonization of the hindgut. This study adds LAMR to the large list of receptors through which NCC interact with their environment during ENS development. These results should be used to inform ongoing integrative, regenerative medicine approaches to HSCR.


Introducing the Reflexion pressure-redistributing cushion.
Preventing pressure ulcer incidence and ensuring patient comfort are essential components of providing quality clinical care (Hampton, 2001), and therefore comfortable pressure-redistributing seating should be a prerequisite to care provision. However, even though education in tissue viability has increased, it is only within the last 2 years that chair cushions have been noted for their importance in reducing pressure ulceration. It is not unknown for patients to have excellent pressure-reducing equipment on the bed but have chair cushions that are of an inferior standard (Hampton, 1999). This article, therefore, examines the Reflexion cushion, manufactured by Vitafoam, and the role it may have in preventing pressure ulceration.


The transmission and control of XDR TB in South Africa: an operations research and mathematical modelling approach.
Extensively drug-resistant tuberculosis (XDR TB) has emerged as a threat to TB control efforts in several high-burden areas, generating international concern. XDR TB is now found in every region of the world, but appears most worrisome in the context of HIV and in resource-limited settings with congregate hospital wards. Here, we examine the emergence and transmission dynamics of the disease, incorporating the mathematical modelling literature related to airborne infection and epidemiological studies related to the operations of TB control programmes in resource-limited settings. We find that while XDR TB may present many challenges in the setting of resource constraints, the central problems highlighted by the emergence of XDR TB are those that have plagued TB programmes for years. These include a slow rate of case detection that permits prolonged infectiousness, the threat of airborne infection in enclosed spaces, the problem of inadequate treatment delivery and treatment completion, and the need to develop health systems that can address the combination of TB and poverty. Mathematical models of TB transmission shed light on the idea that community-based therapy and rapid detection systems may be beneficial in resource-limited settings, while congregate hospital wards are sites for major structural reform.


Enhanced biodegradation of iopromide and trimethoprim in nitrifying activated sludge.
Iopromide (an X-ray contrast agent) and trimethoprim (an antibacterial drug) are frequently detected pharmaceuticals in effluents of wastewater treatment plants (WWTPs) and in surface waters due to their persistence and high usage. Laboratory-scale experiments showed that a significantly higher removal rate in nitrifying activated sludge as compared to conventional activated sludge was observed for both iopromide and trimethoprim. When the activity of the nitrifying bacteria was inhibited, the percent removal of iopromide decreased from 97 to 86% while trimethoprim removal decreased from 70 to 25%. The metabolite of iopromide identified when nitrification was not inhibited was a dehydroxylated iopromide at the two side chains. However, when the nitrifying bacteria were inhibited the metabolite identified was a carboxylate, formed during the oxidation of the primary alcohol on the side chain of iopromide. These results suggest that the nitrifying bacteria are important in the observed biodegradation of iopromide in the activated sludge with higher solid retention time (SRT). Results from the laboratory-scale study were corroborated by the observed removal efficiencies in a full-scale municipal WWTP, which showed that iopromide (ranging from 0.10 to 0.27 microg/L) and trimethoprim (ranging from 0.0.08 to 0.53 microg/L) were removed more effectively in the nitrifying activate sludge which has a higher SRT (49 days) than in the conventional activated sludge (SRT of 6 days). In nitrifying activated sludge, the percent removal of iopromide in the WWTP reached 61%, while in conventional activated sludge, average removal was negligible. For trimethoprim, removal was limited to about 1% in the conventional activated sludge, while in the nitrifying activated sludge, the removal was increased to 50%.


Assessment of Sperm Viability and Computer-Assisted Motility Analysis in Budgerigars (Melopsittacus undulatus): Effect of Several In Vitro Processing Conditions.
In order to preserve endangered psittacine species, more basic and applied research in reproductive biology is required. Assisted reproductive technologies such as artificial insemination play an important role in parrots species conservation programs to overcome the problem of infertile eggs and male infertility. The aim of this study was to define an effective in vitro protocol in order to standardize the sperm quality evaluation in psittacines, studying Melopsittacus undulatus as model species. Semen was collected from twenty adult males by massage technique from May to June. Sperm concentration was measured by the spectrophotometric method. Sperm quality (sperm membrane integrity (SMI), motility, and kinetic parameters) was assessed on fresh semen. Three different experimental protocols were performed to compare the effects of various processing conditions on SMI, motility, and kinetic parameters. In protocol 1, test was performed by Lake extender with three different pH, 7.4 versus 8.2 versus 8.4, and two different equilibration temperatures after dilution of fresh semen (4°C versus 25°C). In protocol 2, two dilution rates of semen after collection were valuated, 1 : 3 versus 1 : 4, as well as three different semen storage temperatures (4°C versus 25°C versus 38°C) before sperm motility analysis with the computer-assisted sperm analysis (CASA). In protocol 3, two different Makler chamber temperatures (38 versus 41°C) during motility analysis were tested. A significant progressive improvement in spermatozoa motility and kinetic parameters was registered with pH 8.4. Progressive motility and all kinetic parameters were higher at 4°C equilibration temperature. Straightness (STR) kinetic parameter was better with 1 : 4 dilution rate. Total motile sperm was higher in 41°C Makler chamber. In this study, for the first time, the effects of different processing protocols on psittacines seminal quality analysis were investigated. Significant differences conditioning the effectiveness of analysis protocols have been described.


Molecular diagnostics and mitochondrial dysfunction: a future perspective.
This review deals with the state of the art in knowledge about molecular diagnostics in mitochondrial diseases. A considerable development over the last years of several lines of biological, biochemical and biophysical investigation techniques has enormously enlarged the chance to obtain significant information by their application in the study of mitochondrial diseases in both in vivo and in vitro clinical applied research. The nosography of mitochondrial diseases is, therefore, day by day enriched by reports of new acquisitions that merge with the innovative contribution that novel laboratory and clinical investigative technologies add to the knowledge of the physiopathology and management of these complex diseases. Apart from the molecular genetic characterization of mitochondrial diseases, different experimental laboratory approaches have contributed, from a molecular point of view, to add new insights in this field of medicine. The strategies of these investigations can be targeted to detect and evaluate the significance of molecules that can play a relevant role in the determination of clinical phenotypes, making it possible to better understand several still unexplained mechanisms of cell damage.


[High carboxylic acid level in the gingival crevicular fluid (GCF) of the patients with advanced periodontal disease].
The carboxylic acids are known to be produced by the bacteria in the dental plaque. The purpose of the present study is to investigate the concentrations of carboxylic acids in the whole saliva and the gingival crevicular fluid (GCF) of periodontal patients. The effects of these acids on human gingival fibroblasts were also examined. Nine males and 9 females patients were divided into two groups (Group A and Group B), according to the differences in probing depth (PD) and alveolar bone loss. Patients of Group A had gingivitis or slight adult periodontitis (PD less than or equal to 4 mm, alveolar bone loss less than or equal to 33%), whereas patients of Group B had moderate to advanced adult periodontitis (PD greater than 4 mm, alveolar bone loss greater than 33%). Carboxylic acids in the whole saliva and the GCF which were collected from the patients of Group A and Group B were examined using high performance liquid chromatography. The effects of two carboxylic acid salts (butyrate and formate) on the proliferation of human gingival fibroblasts from normal human gingiva were also examined by cell culture. Results obtained were as follows. 1. The concentrations of four carboxylic acids (acetic, propionic, succinic and butyric acids) in the GCF collected from patients of Group B were significantly higher than that of Group A. On the contrary, all carboxylic acid contents in the whole saliva were not significantly different between the patients of Group A and Group B. 2. Formate (1 or 3 mM) showed only a small degree of inhibition against the proliferation of human gingival fibroblasts, but butyrate (3 mM) almost completely (95.2%) inhibited the proliferation of human gingival fibroblasts. 3. The results of the present study may indicate that the carboxylic acids are involved in the initiation and development of the periodontal disease and that they can be one of the indicators in the diagnosis of the periodontal disease.


RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems.
Reactivation of p53 and induction of tumor cell apoptosis (RITA) is a small molecule that blocks p53-MDM2 interaction, thereby reactivating p53 in tumors. RITA can induce exclusive apoptosis in cancer cells independently of the p53 pathway; however, the resistance of cancer cells remains a major drawback. Here, we found a novel resistance mechanism of RITA treatment and an effective combined treatment to overcome RITA resistance in head and neck cancer (HNC) cells. The effects of RITA and 3-methyladenine (3-MA) were tested in different HNC cell lines, including cisplatin-resistant and acquired RITA-resistant HNC cells. The effects of each drug alone and in combination were assessed by measuring cell viability, apoptosis, cell cycle, glutathione, reactive oxygen species, protein expression, genetic inhibition of p62 and Nrf2, and a mouse xenograft model of cisplatin-resistant HNC. RITA induced apoptosis of HNC cells at different levels without significantly inhibiting normal cell viability. Following RITA treatment, RITA-resistant HNC cells exhibited a sustained expression of other autophagy-related proteins, overexpressed p62, and displayed activation of the Keap1-Nrf2 antioxidant pathway. The autophagy inhibitor 3-MA sensitized resistant HNC cells to RITA treatment via the dual inhibition of molecules related to the autophagy and antioxidant systems. Silencing of the p62 gene augmented the combined effects. The effective antitumor activity of RITA plus 3-MA was also confirmed in vivo in mouse xenograft models transplanted with resistant HNC cells, showing increased oxidative stress and DNA damage. The results indicate that RITA plus 3-MA can help overcome RITA resistance in HNC cells. This study revealed a novel RITA resistant mechanism associated with the sustained induction of autophagy, p62 overexpression, and Keap1-Nrf2 antioxidant system activation. The combined treatment of RITA with the autophagy inhibitor 3-methyladenine overcomes RITA resistance via dual inhibition of autophagy and antioxidant systems in vitro and in vivo.


A new chromene from the fruiting bodies of Chroogomphus rutilus.
A new chromene, acetic acid 2R-(4,8-dimethylnona-3,7-dienyl)-8-hydroxy-2-methyl-2H-chromen-6-yl ester (1), was isolated from the fruiting bodies of Chroogomphus rutilus, together with six known compounds (2-7). The structures of these compounds were identified based on 1D and 2D NMR, including (1)H-(1)H COSY, HMQC and HMBC spectroscopic methods. Of these seven compounds, 2 and 3 showed cytotoxicity against HSC-T6, SK-Hep1 and A549 cell lines.


Neglected Achilles Tendon Rupture Treated with Flexor Hallucis Longus transfer with two turndown gastrocnemius fascia flap and reinforced with plantaris tendon.
Neglected Achilles Tendon Ruptures are commonly seen by orthopaedic surgeons. In cases resistant to conservative treatment, a variety of surgical procedures have been utilized in the past. The senior -surgeon at our institution has utilized a technique -employing two turndown fascia flaps fashioned from the proximal Achilles tendon augmented by a tenomyodesis of the flexor hallucis longus and plantaris tendon. The purpose of this study was to assess the clinical outcome of all patients who underwent this procedure. The medical records of 10 cases that underwent this procedure were retrospectively reviewed. We completed data collection sets using the American Orthopaedic Foot and Ankle Society ankle-hind foot scores, isokinetic evaluation, and postoperative magnetic resonance imaging (MRI) at 1 year of follow-up. The mean American Orthopaedic Foot and Ankle Society ankle-hind foot scores improved from 64.4±3.54. Isokinetic testing at 30º/sec and 120º/sec revealed an mean deficits of 24.5%, respectively, in the plantar flexion peak torque of the involved ankle than non-involved ankle. The flexor hallucis longus tendon, gastrocnemius fascia flap and plantaris were well -integrated into the Achilles tendon forming a homogenous tendon, which was confirmed in MRI. Our subjective and objective data indicate that the reconstructive technique using flexor hallucis longus transfer with two turndown gastrocnemius fascia flaps and plantaris tendon is a good option for repairing large gap defect of Achilles tendon.


Legal regulation of the production and trade of medical devices and medical equipment in the EU and US: experience for Ukraine.
The need for effective legal regulation of production and sale of medical products in Ukraine due to its social effect is obvious and requires a high level of clarity. The experience of more advanced countries in this area, given the way chosen by Ukraine to harmonize our laws with EU legislation, is certainly could be a useful source of information. The urgency of issues need further intensification of national legal reforms. Some key points on concept of legal regulation of abovementioned sphere is a base of this study. Legislation of Ukraine, European Union, United States of America, Guidelines, developed by European Commission & Food and Drug Administration's (FDA), recommendations represented by international voluntary group and scientific works. This article is based on dialectical, comparative, analytic, synthetic and comprehensive research methods. This study provide a possibility to state that main difference of regulatory systems in EU and US is that the legal framework of the EU is more flexible. This flexibility is grounded on main principle that only basic quality requirements for medical devices is defined by legislative acts however more detailed requirements are defined in standards, technical regulations, specifications, which are discretionary in nature. Contractors are free to choose any technical solution that provides compliance with the essential requirements, they can choose among different conformity assessment procedures and between accredited conformity assessment bodies to which they want to apply. The contractors themselves is interested to pass the conformity assessment procedure and have the right to put a conformity mark on their medical device because it will give them a real competitive advantage. In contrast, US State regulatory system provides strict control over business entities and law act establishes the quality requirements of medical products. The only body that can authorize the introduction of medical products and perform post-market monitoring is Food and Drug Administration (FDA), which has almost unlimited competence in this sphere. Taking into account further deepening of the European integration process of Ukraine, establishing of the regulatory system as much similar to that of the EU as possible is a main goal of legal reforms in abovementioned sphere. On the one hand, such system allows to implement effective control of contractors in the sphere of production and sale of medical products and provide safety of medical devices that are introduced, on the other hand, it does not afflict contractors with excessive and total control, allowing them to choose behavior that is most acceptable, understandable and user-specific. However, US's experience also has some positive characteristics, which could be taken into account. Therefore, such complex symbiosis of approaches from our point of view will balance controversial interest of manufacturers, sellers and consumers of medical devices.


Solid and papillary epithelial neoplasm of the pancreas--a case report.
Solid and papillary epithelial neoplasm (SPENP) of the pancreas is a rare pancreatic tumour of low malignant potential, that is seen mostly in young females. The aetiology and pathogenesis is unclear but it is considered to be arising from primordial pancreatic cells. We report two cases of SPENP who had palpable abdominal lumps and were diagnosed on histopathology. In the first case, the tumour was unresectable and patient died within one year. In the second case, at laprotomy the patient had perineurial as well as capsular infiltration but after wide resection of the growth, patient has been doing well for the past 6 months. Since SPENP is a low grade malignant neoplasm, it should be treated aggressively with complete resection and metastatectomy. Prognosis after adequate surgery is good. A clinicopathological study and brief review of literature is presented.


Becoming the Monsoon Forest - Emergence in the Breakdown of Categories.
How do we understand more-than-human vegetal emergence in/with/under monsoonal transformation. I often like to introduce the monsoon to people by telling them that it is the change in the direction of the wind that carries the ocean to the sky, blanketing the geological spatio-temporality of the Indian subcontinent, transforming its air and everything in its temporal wake with the possibility of life. This paper thinks through the invasive vilayati kikar which has overwhelmed native monsoon forests and arid ecologies. Drawing from fieldwork in the Delhi region conducted during monsoon 2018, 2019 and the winter of 2018, and by thinking with literature and reports from ecology, biology, politics, anthropology and natural science-I attempt a brief situated narrative that explores the vegetal emergence of the plant, its natureculture spirits and embodiment in/with the monsoon-finally, closing this work with an argument and discussion on the monsoon and its ontological stickiness.


Evaluation of an indigenously manufactured rapid immunochromatographic test for detection of HBsAg.
A 'rapid' one step immunochromatographic, visually read, antigen capture assay--the "HEPACARD" (J Mitra & Co. Ltd., New Delhi, India) used for rapid screening of HBsAg was evaluated. Thousand consecutive sera sent to our laboratory for the purpose of HBsAg screening were tested by this device and by a third generation enzyme immunoassay (EIA) (Auszyme Monoclonal, Abbott Laboratories, Chicago, Illinois) or an automated Axsym microparticle enzyme immunoassay (MEIA) (Axsym HBsAg V2, Abbott Laboratories, Abbott Park, Chicago, Illinois, ISA). Hepacard showed a sensitivity of 79% (CU: 57.3-92%) and specificity of 98.9% (CI: 97.9-99.4%) when compared to the findings by the third generation EIA assays. This study suggested that this particular rapid HBsAg test results have to be confirmed by either an EIA or MEIA where the facility exists. The test may be used only in a small hospital setting where the facilities for enzyme immuno assays do not exist.


A multi-step transmission electron microscopy sample preparation technique for cracked, heavily damaged, brittle materials.
A new technique for the preparation of heavily cracked, heavily damaged, brittle materials for examination in a transmission electron microscope (TEM) is described in detail. In this study, cross-sectional TEM samples were prepared from indented silicon carbide (SiC) bulk ceramics, although this technique could also be applied to other brittle and/or multiphase materials. During TEM sample preparation, milling-induced damage must be minimized, since in studying deformation mechanisms, it would be difficult to distinguish deformation-induced cracking from cracking occurring due to the sample preparation. The samples were prepared using a site-specific, two-step ion milling sequence accompanied by epoxy vacuum infiltration into the cracks. This technique allows the heavily cracked, brittle ceramic material to stay intact during sample preparation and also helps preserve the true microstructure of the cracked area underneath the indent. Some preliminary TEM results are given and discussed in regards to deformation studies in ceramic materials. This sample preparation technique could be applied to other cracked and/or heavily damaged materials, including geological materials, archaeological materials, fatigued materials, and corrosion samples.


An introduction to provisional stenting.
Provisional or conditional stenting should be defined as the use of stents limited to those conditions and cases in which the operator, despite an aggressive balloon angioplasty technique with large balloons and high pressure, has been unable to obtain a result that ensures optimal chances of early and late patency. The paramount issue is how to discriminate the patients with optimal results after balloon angioplasty for whom additional stent implantation is unlikely to improve or may even worsen long-term outcome. The better results of elective stent implantation in the OPUS study suggest that visual assessment of the PTCA result is not sufficient to detect lesions with suboptimal lumen gain after PTCA. The addition of physiologic parameters (Doppler flow velocity measurements, fractional flow reserve) has improved the results of the provisional stent group, with the best outcome observed when complex lesions and multivessel treatment were included in these studies (FROST, DESTINI). Intravascular ultrasound, although more expensive and time-consuming, has the additional advantage to guide the dilatation strategy.


Periodontal infections and cardiovascular disease: is it a mere association?
The oral cavity is a major site of chronic infection and inflammation, particularly periodontal or chronic gum diseases. In recent years there has been increasing interest in the "periodontal systemic connection" between periodontal health parameters and risks of cardiovascular disease. Given that poor oral health and cardiovascular disease are major worldwide health problems, their association are potentially important. The article summarizes the evidences from epidemiologic studies and studies that focused on potential contributing mechanisms to provide an insight of this association.


Impact of Vitamin C on Gene Expression Profile of Inflammatory and Anti-Inflammatory Cytokines in the Male Partners of Couples with Recurrent Pregnancy Loss.
Immune system disorders and increased inflammation in the male reproductive system can lead to fetal risk in the early stages of development and implantation. Antioxidants such as vitamin C can play a protective role against sperm inflammatory reactions. This study aimed to evaluate the effect of vitamin C on the expression of inflammatory and anti-inflammatory cytokine genes in the male partners of couples with recurrent pregnancy loss. In this randomized clinical trial, twenty male partners of couples with RPL were examined for sperm parameters and expression profile of some inflammatory and anti-inflammatory cytokine genes before and after treatment with vitamin C. There was a statistically significant higher rate of normal morphology and sperm concentration in each patient before and after treatment with vitamin C (p ≤ 0.05). The mRNA levels of interleukin 6 and tumor necrosis factor-alpha were significantly decreased in the sperm of patients after treatment with vitamin C compared to before treatment. In contrast, the gene expression levels of interleukin 4 and transforming growth factor-beta showed a significant increase in the sperm of patients after treatment with vitamin C. Oral daily administration of vitamin C may be effective in the fertility potential of male partners of couples with RPL not only through the improvement of the sperm parameters but also by modulating the expression profile of inflammatory and anti-inflammatory genes. Further studies on protein levels are needed to clarify the role of TNF-⍺ and IFN-γ as a prognostic value in evaluating the recurrent abortion risk in infertile male partners. This trial is registered with IRCT20180312039059N1.


Impact of eLearning course on nurses' professional competence in seclusion and restraint practices: 9-month follow-up results of a randomized controlled study (ISRCTN32869544).
eLearning may facilitate continuing vocational education, but data on the long-term effects of an eLearning course are lacking. The aim of this study was to explore the long-term impact of an eLearning course entitled ePsychNurse.Net on psychiatric nurses' professional competence in practicing seclusion and restraint and on their job satisfaction and general self-efficacy at 9-month follow-up. In a randomized controlled study, 12 wards were randomly assigned to the ePsychNurse.Net (intervention) or training as usual (control). Baseline and 9-month follow-up data on nurses' knowledge of coercion-related legislation, physical restraint and seclusion, their attitudes towards physical restraint and seclusion, job satisfaction and general self-efficacy were analysed for 137 completers (those who participated in the 9-month follow-up assessment). No between-group differences were found on any variable, with the exception of a change in attitude to seclusion in favour of the control group. The findings of the long-term effects did not differ from the immediate outcomes (3-month follow-up) and the improved level of knowledge acquired and further consolidation of that knowledge did not take place in the 6-month period after the 3-month ePsychNurse.Net course. The ePsychNurse.Net should be further developed and its future modifications will require additional studies, probably with some new outcome measures.


Lessons learned from 2001-2021 - from the bioterrorism to the pandemic era.
The aim of the study was to analyze available literature on the development of biological warfare and combating the SARS CoV-2 pandemic. Against the background of contemporary threats from biological factors, the strengths and weaknesses of response in the event of a bioterrorist attack during the ongoing COVID-19 pandemic have been identified. The scope and importance of international cooperation in the fight against the pandemic is assessed. The more important literature on bioterrorism, biological weapons and the COVID-19 pandemic, both from earlier work and recent publications, was analyzed, emphasizing new threats and adequate defence against them. The bio-warfare threat and the current COVID 19 pandemic that has hit mankind on a global scale has clearly shown how dangerous biological agents are and what effects they can cause, negatively affecting every sphere of human activity with catastrophic consequences. Data on examples of bioterrorist attacks carried out and research on the development of biological weapons and methods of combating pandemic COVID-19, were reviewed. New threats related to technological development,including those resulting from genetic manipulation, biosynthesis, and modern means of delivery, are pointed out. Attention has been paid to the implications of controlling the proliferation of biological weapons and the issues of international cooperation in the fight against bioterrorism and the COVD-19 pandemic. The lesson learned clearly demonstrates the weakness of states in responding to such threats. The risks of uncontrolled scientific advances are still underestimated. Appropriate international control measures must be taken urgently to prepare for new pandemics, bioterrorist attacks, and the possibility of using modern biological weapons.


Computed tomographic features of mandibular osteochondroma.
Osteochondroma of the mandibular condyle is fairly rare. We describe a case of this lesion in a 52-year-old woman who presented with symptoms of temporomandibular joint dysfunction. Although a panoramic radiograph demonstrated the bony exostosis, a pre-operative CT examination showed the relationship of the tumour to the condyle and also depicted soft-tissue changes secondary to the growth.


Antifungal susceptibility of oral isolates of Candida species from chronic kidney disease patients on chronic dialysis.
Chronic renal disease patients under chronic dialysis (CRDD) have a multifactorial immunological deterioration with an increased risk of Candida infections. Incidence of Candida infections is increasing. Choice of suitable antifungal agents is limited due to the resistance of some species to several antifungals. Aim of the present study was to identify the distribution and antifungal susceptibility patterns of oral isolated Candida species from infected and colonized patients, as well as to investigate the risk factors for oral infection in patients on dialysis. Cross-sectional study, approved by the institutional bioethics committees was performed in CRDD patients. Demographic, clinic data, and oral mucosa samples were obtained. Infection diagnosis was established clinically and confirmed with exfoliative cytology, each sample was plated on CHROMagar Candida and incubated at 36°C for 2 days. Yeast species were identified by carbohydrate assimilation ID 32C AUX system and the apiweb database. For the antifungal susceptibility test, the M44 A-3 method (CLSI) using fluconazole (FCZ), miconazole (MCZ), nystatin (NYS), and voriconazole (VCZ). Study included 119 participants, the main cause of CRD was nephropathy due to DM2 (58%), and three-fourths of the patients were under hemodialysis. Candida prevalence was 56.3% of 67 colonized or infected patients, 88 isolates were obtained. Principal identified species were C. albicans (51.1%), C. glabrata (25%), and C. tropicalis (14.8%). C. glabrata showed a reduced response to FCZ in 50% of isolates and C. albicans had a reduced response in 16% of the isolates. Antifungal agent with the least efficacious response or with the lowest susceptibility in the isolates of these patients was MCZ, followed by VCZ and FCZ, whereas NYS induced the best antifungal response.


Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue.
Perivascular adipose tissue (PVAT) reduces vasoconstriction to norepinephrine (NE). A mechanism by which PVAT could function to reduce vascular contraction is by decreasing the amount of NE to which the vessel is exposed. PVATs from male Sprague-Dawley rats were used to test the hypothesis that PVAT has a NE uptake mechanism. NE was detected by HPLC in mesenteric PVAT and isolated adipocytes. Uptake of NE (10 μM) in mesenteric PVAT was reduced by the NE transporter (NET) inhibitor nisoxetine (1 μM, 73.68 ± 7.62%, all values reported as percentages of vehicle), the 5-hydroxytryptamine transporter (SERT) inhibitor citalopram (100 nM) with the organic cation transporter 3 (OCT3) inhibitor corticosterone (100 μM, 56.18 ± 5.21%), and the NET inhibitor desipramine (10 μM) with corticosterone (100 μM, 61.18 ± 6.82%). Aortic PVAT NE uptake was reduced by corticosterone (100 μM, 53.01 ± 10.96%). Confocal imaging of mesenteric PVAT stained with 4-[4-(dimethylamino)-styrl]-N-methylpyridinium iodide (ASP(+)), a fluorescent substrate of cationic transporters, detected ASP(+) uptake into adipocytes. ASP(+) (2 μM) uptake was reduced by citalopram (100 nM, 66.68 ± 6.43%), corticosterone (100 μM, 43.49 ± 10.17%), nisoxetine (100 nM, 84.12 ± 4.24%), citalopram with corticosterone (100 nM and 100 μM, respectively, 35.75 ± 4.21%), and desipramine with corticosterone (10 and 100 μM, respectively, 50.47 ± 5.78%). NET protein was not detected in mesenteric PVAT adipocytes. Expression of Slc22a3 (OCT3 gene) mRNA and protein in PVAT adipocytes was detected by RT-PCR and immunocytochemistry, respectively. These end points support the presence of a transporter-mediated NE uptake system within PVAT with a potential mediator being OCT3.


Pharmacokinetic interaction between fluvastatin and diltiazem in rats.
The present study aimed to investigate the effect of fluvastatin on the pharmacokinetics of diltiazem in rats. Pharmacokinetic parameters of diltiazem were determined in rats following an oral administration of diltiazem (15 mg/kg) in the presence and absence of fluvastatin (0.6 and 2.0 mg/kg). Compared with the control given diltiazem alone, the C(max) and AUC of diltiazem increased by 30-70% in rats with the concurrent use of fluvastatin, while there was no significant change in T(max) and the plasma half-life (T(1/2)) of diltiazem. Consequently, absolute and relative bioavailability values of diltiazem in the presence of fluvastatin were significantly higher (p<0.05) than those from the control group, implying that fluvastatin could reduce the presystemic extraction of diltiazem. In conclusion, the concurrent use of fluvastatin significantly enhanced the oral exposure of diltiazem in rats.


Comparison of radial versus femoral approach for percutaneous coronary interventions in octogenarians.
The safety and efficacy of a radial approach for percutaneous coronary intervention (PCI) in octogenarians is not well established. To evaluate the benefits of a radial approach for preventing vascular complications after PCI, clinical, procedural, and outcome data were prospectively collected and compared for 228 octogenarians undergoing elective PCI either through a radial or a femoral approach. Radial approach was associated with longer cannulation (3.1 +/- 2.9 vs. 2.0 +/- 2.0 min, P < 0.001) and fluoroscopy times (19.3 +/- 16.1 vs. 16.1 +/- 11.8 min, P = 0.04), greater utilization of contrast media (224 +/- 46 vs. 182 +/- 20 ml, P < 0.001) and higher crossover rate (11 vs 4%, P = 0.03) to alternate access site compared with the femoral approach. However, ambulation time (5.2 +/- 3.1 vs. 11.6 +/- 6.3 hr, P < 0.001), access site bleeding (4 vs. 14%, P = 0.007), hematoma (1 vs. 11%, P = 0.001) or any vascular complication (5 vs 26%, P = 0.001) were significantly reduced with a radial approach. Procedural success rates were equivalent with both approaches. Multivariate regression analysis identified radial approach (OR = 0.23; CI = 0.08, 0.65) as an independent negative predictor of postprocedural vascular complications. Radial approach for PCI in octogenarians is technically challenging for the operator and exposes patients to greater volume of nephrotoxic contrast media. However, it results in early ambulation and significantly reduces vascular complications in this high risk population. These findings support a strategy of preprocedural risk assessment and use of radial approach for PCI in a select group of octogenarians to maximize benefits offered by this technique.


Clinical and laboratory differences between Epstein-Barr and cytomegalovirus infectious mononucleosis in children.
Infective mononucleosis is most commonly caused by Epstein-Barr virus (EBV), and in smaller percentage by cytomegalovirus (CMV). The aim of this paper was to determine the clinical and laboratory differences between EBV and CMV infectious mononucleosis in children. Cohort retrospective analytical research was conducted. We used data from medical history in six years period and monitored anamnestic data, frequency of inspection and palpation obtained data during physical examination, several laboratory tests, abdomen ultrasonography examination finding and emergence of disease complications. Statistical processing of data has been performed using SPSS 20. Total number of examined children was 137, out of which 85.4% were with EBV and 14.6% with CMV infection. Affected children were most commonly younger than eight years. Boys were affected more often. There was no difference in frequency of high temperature, sore throat, bad breath, and respiratory symptomatology between examined children. Differences were discovered in frequency of stomachaches, eyelid swelling, skin rash and fatigue. Differences were not proven in the frequency of angina, lymphadenopathy and splenohepatomegaly between the groups. Values of transaminases and lactic dehydrogenases significantly decreased after seven days of hospitalization in both groups. In children with EBV, values of transaminases declined faster than in children with CMV. Anemia and bacterial superinfection of pharynx were most common disease complications. Thrombocytopenia was more common in children with CMV infection. Average duration of hospitalization was 6.7 days. In children with CMV abdominal pain, eyelid swelling, skin rash, fatigue and thrombocytopenia were more common. In children with EBV values of transaminases declined significantly faster.


Combination sensitivity and processing of communication calls in the inferior colliculus of the Moustached Bat Pteronotus parnellii.
Many animals use complex communication calls in social behaviors. In some species we know the features in the calls that elicit particular behaviors, but we do not understand how the auditory system encodes the calls. Nor do we understand the mechanisms underlying neural selectivity to calls. Our studies of the auditory midbrain of the Moustached Bat Pteronotus parnellii have revealed a neural mechanism important for generating selective responses to calls. Neurons that integrate information across different frequencies show selectivity to communication calls. "Combination sensitivity" may be a common mechanism for encoding complex sounds because it is also important for encoding echolocation signals.


LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival.
Epithelial dysfunction and crypt destruction are defining features of inflammatory bowel disease (IBD). However, current IBD therapies targeting epithelial dysfunction are lacking. The nuclear receptor LRH-1 (NR5A2) is expressed in intestinal epithelium and thought to contribute to epithelial renewal. Here we show that LRH-1 maintains intestinal epithelial health and protects against inflammatory damage. Knocking out LRH-1 in murine intestinal organoids reduces Notch signaling, increases crypt cell death, distorts the cellular composition of the epithelium, and weakens the epithelial barrier. Human LRH-1 (hLRH-1) rescues epithelial integrity and when overexpressed, mitigates inflammatory damage in murine and human intestinal organoids, including those derived from IBD patients. Finally, hLRH-1 greatly reduces disease severity in T-cell-mediated murine colitis. Together with the failure of a ligand-incompetent hLRH-1 mutant to protect against TNFα-damage, these findings provide compelling evidence that hLRH-1 mediates epithelial homeostasis and is an attractive target for intestinal disease.


Histological study of two cases of Coxsackie B virus pneumonia in children.
Two cases of interstitial pneumonia are described. They were characterized by mononuclear cell infiltration of the alveolar walls and protein-rich exudate into the alveolar cavities, with localized hyaline membrane formation. Coxsackie B5 virus was isolated from the lungs of both patients at necropsy.


Superior efficacy of MMCP regimen compared with VMCP and MMPP regimens in the treatment of multiple myeloma.
A newly designed combination chemotherapy for multiple myeloma, MMCP [ranimustine (MCNU), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL)], was analyzed and compared with the results of our previous randomized trial of VMCP [vincristine, MPH, CPM and PSL] and MMPP [MCNU, MPH, procarbazine and PSL]. MCNU (33.3 mg/m2, div) on day 1 and MPH (4 mg/m2, po), CPM (66.7 mg/m2, po) and PSL (30 mg/m2, po) from day 1 to 4, were administered. Each cycle was repeated every 3 weeks. From January 1991 until August 1995, 104 patients with multiple myeloma diagnosed at 10 hospitals of Nagoya Cooperative Study Group were enrolled. Of the 87 evaluable patients, partial response rate for MMCP was 65.5% and was significantly higher than that of VMCP (13/47=27.7%, p<0.0001) and that of MMPP (21/47=44.7%, p=0.0196). A plateau attainment was observed in 49.4%. The percentage of the patients who attained plateau was significantly increased in the MMCP arm than in the VMCP arm (19.1 %, p=0.0017) but was not in comparison with that of MMPP arm (42.6%, p=0.6790). Patients treated with MMCP survived significantly longer than those treated with VMCP or MMPP (p=0.0009 by generalized Wilcoxon test, p=0.0023 by log-rank test) with median survival for MMCP being 31.6 months, for VMCP 22.5 months, and for MMPP 22.9 months. No significant differences were observed with respect to adverse effects among the three regimens. The newly designed MMCP is a candidate as an induction chemotherapy for multiple myeloma.


Transient overexpression of DNA adenine methylase enables efficient and mobile genome engineering with reduced off-target effects.
Homologous recombination of single-stranded oligonucleotides is a highly efficient process for introducing precise mutations into the genome of E. coli and other organisms when mismatch repair (MMR) is disabled. This can result in the rapid accumulation of off-target mutations that can mask desired phenotypes, especially when selections need to be employed following the generation of combinatorial libraries. While the use of inducible mutator phenotypes or other MMR evasion tactics have proven useful, reported methods either require non-mobile genetic modifications or costly oligonucleotides that also result in reduced efficiencies of replacement. Therefore a new system was developed, Transient Mutator Multiplex Automated Genome Engineering (TM-MAGE), that solves problems encountered in other methods for oligonucleotide-mediated recombination. TM-MAGE enables nearly equivalent efficiencies of allelic replacement to the use of strains with fully disabled MMR and with an approximately 12- to 33-fold lower off-target mutation rate. Furthermore, growth temperatures are not restricted and a version of the plasmid can be readily removed by sucrose counterselection. TM-MAGE was used to combinatorially reconstruct mutations found in evolved salt-tolerant strains, enabling the identification of causative mutations and isolation of strains with up to 75% increases in growth rate and greatly reduced lag times in 0.6 M NaCl.


Direct resin composite restorations in vital versus root-filled posterior teeth: a controlled comparative long-term follow-up.
This study compared direct composite restorations on vital versus endodontically-treated posterior teeth, six to eight years after placement. All clinical procedures were performed using standardized materials and protocols. The patients were identified with the aid of a computerized billing system followed by a chart search. With each patient, the prime investigator matched a randomly chosen endodontically-treated tooth (test tooth) with a vital counterpart (control tooth) with a direct composite restoration. Of the 84 patients who fulfilled the inclusion criteria, 44 were available for recall. Two calibrated observers, blinded to the tooth vitality status, evaluated the fillings by applying the modified USPHS criteria. The outcome was dichotomized to revision indicated/recommended vs revision not indicated. Odds Ratios (OR) and corresponding 95% Confidence Intervals (95% CI) were calculated. Residual confounding was corrected using a multivariable regression analysis with the remaining known confounders filling size, tooth type and age of the fillings in months as independent variables. The crude association between the presence/absence of root canal treatment and the need for revision (OR, 95% CI) was 2.12 (1.02-4.38; p = 0.04). Correcting for all potential confounders in the multivariable analysis changed this association marginally to an OR of 1.98 (0.90-4.38; p = 0.09).


Lipoprotein lipase deficiency and CETP in streptozotocin-treated apoB-expressing mice.
Both hyperglycemia and hyperlipidemia have been postulated to increase atherosclerosis in patients with diabetes mellitus. To study the effects of diabetes on lipoprotein profiles and atherosclerosis in a rodent model, we crossed mice that express human apolipoprotein B (HuB), mice that have a heterozygous deletion of lipoprotein lipase (LPL1), and transgenic mice expressing human cholesteryl ester transfer protein (CETP). Lipoprotein profiles due to each genetic modification were assessed while mice were consuming a Western type diet. Fast-protein liquid chromatography analysis of plasma samples showed that HuB/LPL1 mice had increased VLDL triglyceride, and HuB/LPL1/CETP mice had decreased HDL and increased VLDL and IDL/LDL. All strains of mice were made diabetic using streptozotocin (STZ); diabetes did not alter lipid profiles or atherosclerosis in HuB or HuB/LPL1/CETP mice. In contrast, STZ-treated HuB/LPL1 mice were more diabetic, severely hyperlipidemic due to increased cholesterol and triglyceride in VLDL and IDL/LDL, and had more atherosclerosis.


A patient post hoc perspective on advantages and disadvantages of blended cognitive behaviour therapy for depression: A qualitative content analysis.
Background: Blended cognitive behavioural therapy (bCBT), which combines face-to-face (FtF), and internet-based cognitive behavioural therapy (iCBT), may be a particularly promising approach, but little is known about the effectiveness and patients' subjective evaluations of the bCBT format. The aim of this qualitative study is to explore perceived advantages and disadvantages of bCBT from the patients' perspective in specialized mental health care. Methods: Semi-structured interviews were conducted with 15 patients suffering from major depression who underwent treatment in a bCBT format. The interview data were processed by means of a qualitative content analysis. Results: The content analysis generated 18 advantages and 15 disadvantages which were grouped into 6 main topics. In general, bCBT was perceived as purposive and effective for treating depression. The patients perceived the combined treatment as complementary and emphasized the advantage of the constant availability of the online programme. Furthermore, a segment analysis revealed that patients reported different advantages and disadvantages of bCBT as a function of the severity of their depressive episode. Conclusion: The findings of the present study reveal advantages and disadvantages of bCBT, which should be taken into account in the further implementation of this new treatment format. Clinical or methodological significance of this article: Blended treatment seems to balance missing aspects of stand-alone internet-based and face-to-face treatment for depression. Patients suffering from major depression perceived the blended format as purposive and effective after 18 weeks. Patients with different levels of depression severity may perceive different advantages and disadvantages of blended treatment for depression.


Use of a pharmacokinetic-driven computational fluid dynamics model to predict nasal extraction of hydrogen sulfide in rats and humans.
Hydrogen sulfide (H2S) is a naturally occurring and industrially generated gas. Human exposure to H2S results in dose-related neurological, respiratory, and cardiovascular effects. Subchronic exposure of rats to 30 or 80 ppm H2S results in olfactory neuron loss and basal cell hyperplasia. Olfactory lesions commonly border main airflow streams in the rat, indicating an influence of airflow on H2S-induced lesion locations. In this study, anatomically accurate computational fluid dynamics (CFD) models were used to quantitatively predict H2S tissue dose in rat and human nasal passages. Air-tissue flux was defined in terms of H2S solubility, diffusivity, and reaction kinetics in nasal tissue. Kinetic parameters for the rat were estimated from an air-tissue pharmacokinetic (PK) model that was fit to experimental nasal extraction (NE) data. Using this PK-driven CFD model, predicted flux at the mid-dorsomedial meatus and the middle portion of the ethmoid recess showed a good correlation with olfactory lesion incidence. Scaled kinetic parameters were incorporated into a human CFD model to predict H2S flux in human nasal passages. Assuming that equivalent H2S flux values will induce similar responses in the olfactory regions of rats and humans, a no-observed-adverse-effect-level human-equivalent concentration was estimated to be 5 ppm. This estimate was based on quantitative tissue dose estimates extrapolated from both lesion and NE data in rats and represents a risk estimate that is science based and does not rely on simplified dosimetric assumptions for interspecies extrapolation.


A randomized, placebo-controlled study of the NS5B inhibitor beclabuvir with peginterferon/ribavirin for HCV genotype 1.
Beclabuvir is a potent, non-nucleoside inhibitor of the HCV NS5B RNA polymerase, with nanomolar activity against HCV genotypes 1, 3, 4, 5 and 6 in vitro. This study evaluated the efficacy and safety of beclabuvir, in combination with peginterferon alfa-2a (pegIFN) and ribavirin (RBV), in HCV genotype 1. In this randomized (1:1:1), double-blinded, placebo-controlled, dose-ranging phase 2a study, 39 treatment-naive patients chronically infected with HCV genotype 1 were treated for 48 weeks with beclabuvir (75 mg or 150 mg) plus pegIFN (180 μg) and RBV (1000 mg/day [<75 kg] or 1200 mg/day [≥ 75 kg]) vs pegIFN/RBV alone. The primary efficacy endpoint of extended rapid virologic response (undetectable HCV RNA at treatment weeks 4 and 12) was achieved by 76.9% (10/13) of patients receiving beclabuvir 75 mg and 38.5% (5/13) receiving beclabuvir 150 mg vs 0% receiving pegIFN/RBV alone. Higher response rates were observed among patients receiving beclabuvir 75 mg for all secondary efficacy endpoints, including sustained virologic response at follow-up weeks 12 or 24. Three patients experienced virologic breakthrough on treatment, all in the beclabuvir 150-mg treatment group. Beclabuvir was well tolerated at both doses, with the most commonly observed adverse events (headache, fatigue, nausea, decreased appetite, irritability, depression and insomnia) consistent with those observed with pegIFN/RBV. In conclusion, beclabuvir was both effective and well tolerated when administered in combination with pegIFN/RBV for the treatment of chronic HCV GT 1, supporting the study of beclabuvir as part of an all-oral regimen for HCV GT1.


Usefulness of a quantitative real-time PCR assay using serum samples to discriminate between inactive, serologically positive and active human brucellosis.
Diagnosis of brucellosis can be difficult in certain scenarios where conventional microbiological techniques have important limitations. The aim of this study was to develop a LightCycler Quantitative PCR assay in serum samples to discriminate between active and past brucellosis. In total, 110 serum samples from 46 brucellosis patients and 64 controls, including persons who had recently been treated for brucellosis, asymptomatic persons exposed to brucellosis, and patients with febrile syndromes involving a differential diagnosis with brucellosis, were studied. Brucella spp.-specific sequences of the PCR primers and probe were selected from the gene encoding an immunogenic membrane protein of 31 kDa (BCSP31). The analytical sensitivity was 1 x 10(1) fg of Brucella DNA. The mean threshold cycles for brucellosis patients and controls were 31.8 +/- 1.7 and 35.4 +/- 1.1, respectively (p <0.001). The best cut-off for bacterial DNA load was 5 x 10(3) copies/mL. At this cut-off, the area under the receiver operating characteristic curves was 0.963 (95% CI 0.920-1.005), with a sensitivity of 93.5% and a specificity of 98.4%. Under the assay conditions, the LightCycler Quantitative PCR in serum samples seems to be highly reproducible, rapid, sensitive and specific. It is therefore a useful method for both the initial diagnosis and the differentiation between past and active brucellosis.


Discriminatory Ability of Visceral Adiposity Index (VAI) in Diagnosis of Metabolic Syndrome: A Population Based Study.
Background Visceral adiposity index (VAI) has been suggested as an index of visceral adiposity. This study was conducted to determine the discriminatory ability of VAI in diagnosis of metabolic syndrome (MetS). Methods and materials We used the data of 5 312 subjects aged 18-74 years of a cohort study conducted among 6 140 individuals aged 10-90 years in Amol, northern Iran. The city population was divided into 16 strata based on gender and age groups in 10-year intervals. The subjects were randomly selected from each stratum. MetS was defined based on National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII), American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) update of Adult Treatment Panel III (ATPIII), International Diabetes Federation (IDF) and joint interim statement (JIS) definitions. The discriminatory ability of VAI and other obesity measures were evaluated using receiver operating characteristic (ROC) curves. Results While waist circumference (WC) showed the highest discriminatory ability for MetS in IDF definition in men (AUC=0.899 [CI=0.888-0.910]), VAI had the greatest discriminatory ability according to other definitions in men and women. The related AUCs of VAI were 0.866 (95%CI: 0.850-0.881), 0.829 (95%CI: 0.813-0.846), 0.859 (95%CI: 0.844-0.873) and 0.876 (95%CI: 0.863-0.889) based on NCEP/ATPIII, AHA/NHLBI update of ATPIII, IDF and JIS definition in men, and also 0.888 (95%CI: 0.875-0.902), 0.894 (95%CI: 0.881-0.907), 0.883 (95%CI: 0.869-0.897) and 0.879 (95%CI: 0.864-0.894) in women, respectively. Conclusion VAI showed an excellent discriminatory ability in diagnosis of MetS. Considering its relatively simple calculation, this index could be suggested as a reliable tool in medical practice.


One-Step Synthesis of Amphiphilic Nonylphenol Polyethyleneimine for Demulsification of Water in Heavy Crude Oil Emulsions.
The demulsification of water-in-heavy crude oil emulsion with water droplet size in the microscale has drawn great attention because of their high stability and difficulty of separation. In the present work, a series of ethylene amine-based demulsifiers were prepared in one step through the interaction of pentaethylene hexamine, tetraethylene pentamine, and triethylene tetramene with glycidyl 4-nonylphenyl ether. The amphiphilic polyethyleneimine (APEI) abbreviated as DNPA-6, DNPA-5, and DNPA-4 were prepared to adjust their hydrophile-lipophile balances (HLB) to meet the requirement of the demulsification. 1HNMR, 13CNMR, and FTIR spectra were utilized to verify their chemical structures. The surface properties and zeta potential were also investigated. Demulsifier dose, separation time, and HLB values were taken into account to evaluate the demulsification efficiency of the synthesized APEI. The results suggested that the prepared demulsifiers had high ability to reduce the surface and interfacial tensions and also broke successfully water-in-Arabian heavy crude oil emulsions. The demulsification efficiency of DNPA-5 reached 100% for crude oil/water emulsion (90/10 vol %).


Human immunodeficiency virus-associated diffuse non-Hodgkin's lymphoma in Venezuelan patients: treatment with full-dose cyclophosphamide-doxorubicin-vincristine-prednisone without routine use of granulocyte-colony stimulating factor.
The routine use of granulocyte-colony stimulating factor (G-CSF) for 10 days during full-dose cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy in HIV-associated diffuse non-Hodgkin's lymphoma (NHL) patients is very expensive in developing countries. We treated 22 HIV-associated diffuse NHL patients with standard-dose CHOP and used G-CSF after an episode of febrile neutropenia until neutrophil count reached 1000/mm3. The clinical response was: complete response (36%), partial response (32%), stable disease (14%) and progression (18%). There were no toxicity-related deaths. Grade 3 or 4 neutropenia was observed in 16% of cycles, but only 8% were complicated with febrile neutropenia. Seventeen patients died (median survival 15 months; range 2-70). There are five patients alive (median survival 24+ months; range 17-36+). Our experience showed that we can treat HIV-related NHL patients with full-dose CHOP, achieve good responses and have an acceptable toxicity profile, with the use of G-CSF as needed.


In vitro and in silico assessment of flow modulation after deploying the Contour Neurovascular System in intracranial aneurysm models.
The novel Contour Neurovascular System (Contour) has been reported to be efficient and safe for the treatment of intracranial, wide-necked bifurcation aneurysms. Flow in the aneurysm and posterior cerebral arteries (PCAs) after Contour deployment has not been analyzed in detail yet. However, this information is crucial for predicting aneurysm treatment outcomes. Time-resolved three-dimensional velocity maps in 14 combinations of patient-based basilar tip aneurysm models with and without Contour devices (sizes between 5 and 14 mm) were analyzed using four-dimensionsal (4D) flow MRI and numerical/image-based flow simulations. A complex virtual processing pipeline was developed to mimic the experimental shape and position of the Contour together with the simulations. On average, the Contour significantly reduced intra-aneurysmal flow velocity by 67% (mean w/ = 0.03m/s; mean w/o = 0.12m/s; p-value=0.002), and the time-averaged wall shear stress by more than 87% (mean w/ = 0.17Pa; mean w/o = 1.35Pa; p-value=0.002), as observed by numerical simulations. Furthermore, a significant reduction in flow (P<0.01) was confirmed by the neck inflow rate, kinetic energy, and inflow concentration index after Contour deployment. Notably, device size has a stronger effect on reducing flow than device positioning. However, positioning affected flow in the PCAs, while being robust in effectively reducing flow. This study showed the high efficacy of the Contour device in reducing flow within aneurysms regardless of the exact position. However, we observed an effect on the flow in PCAs, which needs to be investigated further.