Local quantification of the composition in GaAs/Al(x)Ga(1-x)As structures by thickness fringe analysis.
The increase of the complexity in semiconductor structures raises more and more the need for local evaluation techniques. For example, laser structures with graded-index waveguides are now widespread, but the characterisation of the shape of the gradient is still empirical. In this study, we use transmission electron microscopy (TEM) for the local determination of the chemical composition of GaAs/Al9x)Ga(1-x)As semiconductor laser structures, by quantifying the variation of the thickness fringe profiles with the aluminium content on wedge shaped samples. Contrary to former studies, the presented method uses experimental profiles for calibration. The quantification procedure is thus greatly simplified since no simulation program is needed. Measurements can be performed over distances of more than 1 microm with a spatial resolution of 1 nm, at any depth of the sample. The precision obtained is about +/- 0.03 for the aluminium content x, and the results show the potential of the method for the assessment of semiconductor layer structures.


Career journeys.
Capturing stories of a culture is important to its life blood. The following career stories of a sample of our colleagues describe the many and interesting journeys to advanced practice roles they have explored through their careers.


The Role Of Social Risk Factors In Dialysis Facility Ratings And Penalties Under A Medicare Quality Incentive Program.
Medicare's End-Stage Renal Disease Quality Incentive Program is a mandatory pay-for-performance program for US dialysis facilities, in which facilities are penalized up to 2 percent of their total Medicare payments based on their performance on quality metrics. While analyses of similar programs in other settings have shown performance to be related to social risk factors, it is unknown whether this program displays similar patterns. In this national study, facilities located in low-income ZIP codes and with high proportions of patients who were black or dually enrolled in Medicaid had lower performance scores and higher rates of penalization under the program. Independent (versus chain) status, large facility size, and urban location were also associated with penalties. Further study is needed to determine the degree to which these patterns reflect low-quality care delivery versus patient factors beyond providers' control. In the meantime, the impact of these penalties on providers serving vulnerable populations should be tracked closely.


On several species of Oswaldella Stechow, 1919 (Cnidaria, Hydrozoa), including the description of a new species.
Oswaldella is the most speciose genus of Antarctic hydroids, being one of the most characteristic genera of hydrozoans of the Antarctic benthic marine ecosystem. A relatively high number of taxonomic characters allow species identification, but some key ones are difficult to study properly with a light microscope. In order to improve knowledge of species of the genus, a SEM survey of five of the 27 known nominal species of Oswaldella was carried out, including type material of O. grandis and O. terranovae. The study has revealed no significant differences between O. stepanjantsae and O. terranovae and, consequently, the former is considered a junior synonym of the latter. The type material of O. terranovae included material of an unnoticed, unknown species, which is described as O. occulta sp. nov.


Antithrombotic Therapy of a Young Adult with Giant Left Main Coronary Artery Aneurysm.
Giant coronary artery aneurysm (CAA) is a rare disorder, defined as coronary artery dilatation, in which the diameter of the coronary artery exceeds more than 1.5 times of its normal size. The most common cause of CAA is coronary atherosclerosis for adults and Kawasaki disease (KD) for children and adolescents (especially for the giant CAA that occurred in adolescence). CAA complications include thrombus, acute myocardial infarction (AMI), vasospasm, rupture, ischemia, heart failure, and arrhythmia. So, antithrombotic therapy is crucial for patients with giant CAA.Although giant CAA has been reported in some cases before, few of these cases described antithrombotic therapy particularly, let alone informed direct oral anticoagulant (DOAC) use in these patients. Here, we report a case of a young patient with acute coronary artery disease caused by huge CAA. Rivaroxaban combined with clopidogrel was used for his antithrombotic therapy. Moreover, we reviewed the existing reports to provide an overview of antithrombotic treatment in patients with giant CAA.


Experiences of and responses to HIV among African and Caribbean communities in Toronto, Canada.
African and Caribbean communities in Canada and other developed countries are disproportionately affected by HIV/AIDS. This qualitative study of African and Caribbean communities in Toronto sought to understand HIV-related stigma, discrimination, denial and fear, and the effects of multiple intersecting factors that influence responses to the disease, prevention practices and access to treatment and support services. Semi-structured interviews were conducted with 30 HIV-positive men and women and focus groups were conducted with 74 men and women whose HIV status was negative or unknown. We identified a range of issues faced by African and Caribbean people that may increase the risk for HIV infection, create obstacles to testing and treatment and lead to isolation of HIV-positive people. Our findings suggest the need for greater sensitivity and knowledge on the part of healthcare providers; more culturally specific support services; community development; greater community awareness; and expanded efforts to tackle housing, poverty, racism and settlement issues.


Enhancement of intracellular signaling associated with hematopoietic progenitor cell survival in response to SDF-1/CXCL12 in synergy with other cytokines.
Stromal cell-derived factor 1 (SDF-1/CXCL12) is a multifunctional cytokine. We previously reported that myelopoiesis was enhanced in SDF-1 alpha transgenic mice, probably due in part to SDF-1 alpha enhancement of myeloid progenitor cell (MPC) survival. To understand signaling pathways involved in this activity, we studied the effects on factor-dependent cell line MO7e cells incubated with SDF-1 alpha alone or in combination with other cytokines. SDF-1 alpha induced transient activation of extracellular stress-regulated kinase (ERK1/2), ribosomal S6 kinase (p90RSK) and Akt, molecules implicated in cell survival. Moreover, ERK1/2, p90RSK, and Akt were synergistically activated by SDF-1 alpha in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), Steel factor (SLF), or thrombopoietin (TPO). Similar effects were seen after pretreatment of MO7e cells with SDF-1 alpha followed by stimulation with the other cytokines, suggesting a priming effect of SDF-1 alpha. Nuclear factor-kappa B (NF-kappa B) did not appear to be involved in SDF-1 alpha actions, alone or in combination with other cytokines. These intracellular effects were consistent with enhanced myeloid progenitor cell survival by SDF-1 alpha after delayed addition of growth factors. SDF-1 alpha alone supported survival of highly purified human cord blood CD34(+++) cells, less purified human cord blood, and MO7e cells; this effect was synergistically enhanced when SDF-1 alpha was combined with low amounts of other survival-promoting cytokines (GM-CSF, SLF, TPO, and FL). SDF-1 may contribute to maintenance of MPCs in bone marrow by enhancing cell survival alone and in combination with other cytokines.


Collateral or fistula? Coronary artery as the primary source of pulmonary blood flow in a patient with pulmonary atresia and ventricular septal defect.
In patients with pulmonary atresia and ventricular septal defect (PA/VSD), a coronary artery being the primary source of pulmonary blood flow is a rare entity. We describe two cases of PA/VSD with coronary-to-pulmonary artery fistula with emphasis on the role of Computed Tomographic Angiography (CTA) in depicting all the sources of pulmonary blood supply, to predict surgical management and need for unifocalization of Major Aortopulmonary Collateral Arteries (MAPCA's).


Successful treatment of hepatitis C virus infection with sofosbuvir and simeprevir in the early phase of an allogeneic stem cell transplant.
Currently, a lack of consensus exists on how to manage a hepatitis C virus (HCV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ribavirin alone, or in combination with interferon, has been the mainstream therapy for HCV infection after transplantation. However, very few patients have been regularly treated owing to concerns about poor tolerability, frequent side effects, and limited efficacy. The present case illustrates the striking efficacy of the combination therapy of sofosbuvir with simeprevir, early after transplantation, as it was able to completely eliminate viral replication within 1 month of initiation of treatment. Moreover, tolerance was good, with only minor interactions between the immunosuppressive drugs. This case report supports the feasibility of using this combination therapy early after allo-HSCT for patients with HCV infection.


Small bowel metastases from malignant melanoma.
Metastases of malignant melanoma to the small bowel are only rarely seen by the radiologist. In the majority of cases small bowel invasion causes only aspecific symptoms. Gastro-intestinal bleeding is frequently the first specific complaint. Enteroclysis is the most appropriate technique for demonstrating mucosal abnormalities. CT however is not only more sensitive but it also better delineates local and mesenteric involvement.


Prevention of temporal depression that follows fronto-orbital advancement for craniosynostosis.
Contour abnormalities presenting after fronto-orbital advancement for craniosynostosis are common. Often there is bilateral temporal depression, the result of leaving a coronal bony gap posterior to the advanced segments. The authors present techniques to prevent this temporal depression by utilizing full-thickness bone grafts for structural support in the inferior coronal defects, and cortico-cancellous graft in the remaining superior coronal and parietal donor defects. Prior to contouring and repositioning the frontal elements, a hand-driven Hudson brace and D'Ericco bit is used to harvest cortico-cancellous bone "mush" from the endo- and ectocortical surfaces. The bandeau and frontal elements are advanced and secured, and the resultant coronal gap is measured. Full-thickness cranial bone grafts are harvested from the parietal regions (near the vertex) and secured in the coronal defect behind the frontal elements. The temporalis muscle is rotated, advanced, and secured to the bandeau. Bone mush is used to fill the remaining superior coronal and donor site defects. Representative case examples are presented.


Immediate sonography and intervention in blunt chest trauma: A case report.
Cardiac tamponade is a leading cause of death in blunt thoracic trauma. Ultrasound improved the recognition of cardiac tamponade and therefore has a vital role in acute critical situations in the Emergency Department and in the Intensive Care Unit. Besides recognition of cardiac tamponade, treatment protocols are important. In trauma patients with hemodynamic stable cardiac tamponade, time should be taken for a proper workup for an explorative sternotomy. In hemodynamic unstable trauma patients, the pericardium should be drained, and fluid resuscitation should be performed followed by emergency sternotomy. In this case report we describe a blunt thoracic trauma victim, a 28-year-old male patient without any medical history. He suffered from the unique combination of a tear in the left atrial appendage and a papillary muscle rupture of the right ventricle because of blunt thoracic trauma. Transthoracic echocardiography revealed massive pericardial effusion with diastolic collapse of the right ventricle in our patient. Due to his hemodynamic situation, the patient was brought into the OR for immediate sternotomy and cardiac repair. The patient made a full recovery, was discharged home, and is back to work. This case report emphasizes the relevance of early recognition and treatment of cardiac tamponade in blunt thoracic trauma victims and suggests a multidisciplinary management strategy.


Flavobacterium ammonificans sp. nov. and Flavobacterium ammoniigenes sp. nov., ammonifying bacteria isolated from surface river water.
Three aerobic, Gram-stain-negative, non-motile, rod-shaped bacteria, designated as strains SHINM13T, GENT5T and GENT11 were isolated from surface river water (Saitama Prefecture, Japan). SHINM13T and GENT11 were positive for catalase, whereas GENT5T was negative. Phylogenetic analyses based on the 16S rRNA gene (1341 bp) or 40 marker gene (34,513 bp) sequences revealed that the strains formed distinct phylogenetic lineages within the genus Flavobacterium. The three strains shared 99.3-99.6 % 16S rRNA gene sequence similarity among each other. The average nucleotide identity by orthology (OrthoANI) and digital DNA-DNA hybridization (dDDH) values between strains SHINM13T and GENT11 were 96.56 and 82.1 %, respectively, and those between SHINM13T and GENT5T were 83.46 % and 52.9 %, respectively. The major cellular fatty acids were C15 : 1ω6c, iso-C15 : 0, iso-C15 : 1G, anteiso-C15 : 0 and iso-C15 : 0 3-OH. The major polar lipid was phosphatidylethanolamine. SHINM13T and GENT5T contained menaquinone-6 (MK-6) as the predominant respiratory quinone, and their DNA G+C contents were 34.4 and 35.1 mol%, respectively. Genome sequencing of the three isolates revealed a genome size of 2.26-2.40 Mbp. Furthermore, all three isolates converted dissolved organic nitrogen to ammonium during cell growth. On the basis of the results of phenotypic and phylogenetic analyses, strains SHINM13T and GENT11 and GENT5T represent two distinct novel species in the genus Flavobacterium, for which the names Flavobacterium ammonificans sp. nov. (type strain SHINM13T =JCM 34684T =NCIMB 15379T) and Flavobacterium ammoniigenes sp. nov. (type strain GENT5T =JCM 32249T=NCIMB 15380T) are proposed.


Self-organized semiconductor nano-network on graphene.
A network structure consisting of nanomaterials with a stable structural support and charge path on a large area is desirable for various electronic and optoelectronic devices. Generally, network structures have been fabricated via two main strategies: (1) assembly of pre-grown nanostructures onto a desired substrate and (2) direct growth of nanomaterials onto a desired substrate. In this study, we utilized the surface defects of graphene to form a nano-network of ZnO via atomic layer deposition (ALD). The surface of pure and structurally perfect graphene is chemically inert. However, various types of point and line defects, including vacancies/adatoms, grain boundaries, and ripples in graphene are generated by growth, chemical or physical treatments. The defective sites enhance the chemical reactivity with foreign atoms. ZnO nanoparticles formed by ALD were predominantly deposited at the line defects and agglomerated with increasing ALD cycles. Due to the formation of the ZnO nano-network, the photocurrent between two electrodes was clearly changed under UV irradiation as a result of the charge transport between ZnO and graphene. The line patterned ZnO/graphene (ZnO/G) nano-network devices exhibit sensitivities greater than ten times those of non-patterned structures. We also confirmed the superior operation of a fabricated flexible photodetector based on the line patterned ZnO/G nano-network.


Cardiac re-transplantation in pediatrics: a multi-institutional study.
Cardiac re-transplantation (re-Tx) among pediatric recipients remains controversial. The purpose of this study is to use the Pediatric Heart Transplant Study (PHTS) database to investigate the incidence of re-Tx and analyze the risk factors and outcomes after transplantation among children. The PHTS database was reviewed for all subjects <or=18 years of age at the time of primary transplant and re-Tx from January 1, 1993 through December 31, 2004. Multivariate analyses in the hazard-function domain were used to identify risk factors for re-Tx and for mortality after re-Tx. Risk factors for re-Tx include ventilator support, African-American ethnicity and elevated creatinine. Patient survival was inferior to that after primary transplantation (PTx) with 1-, 3- and 5-year survival probability after re-Tx of 80%, 69% and 60%, respectively (p = 0.04). Patients re-transplanted for graft coronary artery disease fared better than those re-transplanted for early graft failure. A shorter time period between PTx and re-Tx was a significant risk factor for survival according to univariate analysis. However, risk factors for death after re-Tx by multivariate analysis included only early graft failure and rejection during PTx. Survival after pediatric re-Tx is inferior to that after PTx. Re-transplantation for graft failure and rejection are associated with high relative risks for death. Given the limitations of donor availability, re-Tx for early graft failure and rejection appear contraindicated but appears acceptable for those who have survived >or=1 year after their PTx, especially those with graft coronary artery disease.


Tonal mapping of Xi'an Mandarin and Standard Chinese.
One long-neglected fact in linguistic research on Standard Chinese (SC) is that most speakers of SC also speak a local dialect, which may share phonological features with SC. Tonal information can be a determinant of the phonological similarities or differences between some Chinese dialects and SC, yet relatively little empirical research has been conducted on the tonal system of other language varieties in Chinese aside from SC. Among these dialects, Xi'an Mandarin (XM) is particularly interesting for the seemingly simple, yet intricate mapping between its lexical tones with those in SC. In this study, the tonal systems of XM and SC were compared empirically. Tones with similar contours from XM and SC were paired, and both tone production and perception experiments were carried out on bidialectal speakers of XM and SC. The two experiments together showed that there is indeed systematic mapping of tones between XM and SC. The degree of similarity of the mapped tone pair in tone perception was largely dependent on the acoustic phonetic similarity between the tones in tone production, with a phonological rule playing a role in the tone pair of low contour.


The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in Blood.
Bisphenol A (BPA), a component of some dialysis membranes, accumulates in CKD. Observational studies have linked BPA exposure to kidney and cardiovascular injury in humans, and animal studies have described a causative link. Normal kidneys rapidly excrete BPA, but insufficient excretion may sensitize patients with CKD to adverse the effects of BPA. Using a crossover design, we studied the effect of dialysis with BPA-containing polysulfone or BPA-free polynephron dialyzers on BPA levels in 69 prevalent patients on hemodialysis: 28 patients started on polysulfone dialyzers and were switched to polynephron dialyzers; 41 patients started on polynephron dialyzers and were switched to polysulfone dialyzers. Results were grouped for analysis. Mean BPA levels increased after one hemodialysis session with polysulfone dialyzers but not with polynephron dialyzers. Chronic (3-month) use of polysulfone dialyzers did not significantly increase predialysis serum BPA levels, although a trend toward increase was detected (from 48.8±6.8 to 69.1±10.1 ng/ml). Chronic use of polynephron dialyzers reduced predialysis serum BPA (from 70.6±8.4 to 47.1±7.5 ng/ml, P<0.05). Intracellular BPA in PBMCs increased after chronic hemodialysis with polysulfone dialyzers (from 0.039±0.002 to 0.043±0.001 ng/10(6) cells, P<0.01), but decreased with polynephron dialyzers (from 0.045±0.001 to 0.036±0.001 ng/10(6) cells, P<0.01). Furthermore, chronic hemodialysis with polysulfone dialyzers increased oxidative stress in PBMCs and inflammatory marker concentrations in circulation. In vitro, polysulfone membranes released significantly more BPA into the culture medium and induced more cytokine production in cultured PBMCs than did polynephron membranes. In conclusion, dialyzer BPA content may contribute to BPA burden in patients on hemodialysis.


Elucidating the impact of three metallic nanoagrichemicals and their bulk and ionic counterparts on the chemical properties of bulk and rhizosphere soils in rice paddies.
Growing applications of nanoagrichemicals have resulted in their increasing accumulation in agricultural soils, which could modify soil properties and affect soil health. A greenhouse pot trial was conducted to determine the effects of three metallic nanoagrichemicals on several fundamental chemical properties of a rice paddy soil, including zinc oxide nanoparticles (ZnO NPs) and copper oxide nanoparticles (CuO NPs) at 100 mg/kg, and silicon oxide nanoparticles (SiO2 NPs) at 500 mg/kg, as well as their bulk and ionic counterparts. The investigated soil amendments displayed significant and distinctive impact on the examined soil chemical properties relevant to agricultural production, including soil pH, redox potential, soil organic carbon (SOC), cation exchange capacity (CEC), and plant available As. For example, all amendments increased the bulk soil pH at day 47 to some extent, but the increase was substantially higher for SiO32- (37.7%) than other amendments (5.8%-13.7%). Soil Eh was elevated markedly at day 47 after the addition of soil amendments in both the bulk soil (45.9%-74.4%) and rice rhizosphere soil (20.3%-68.9%). CuO NPs and Cu2+ generally exhibited greater impact on soil chemical properties than other agrichemicals. Significantly different responses to soil amendments were observed between bulk and rhizosphere soils, suggesting the essential role of plants in affecting soil properties and their responses to environmental disturbance. Overall, our results confirmed that the tested amendments could have remarkable impacts on the fundamental chemical properties of rice paddy soils.


Secretoneurin A Directly Regulates the Proteome of Goldfish Radial Glial Cells In Vitro.
Radial glial cells (RGCs) are the main macroglia in the teleost brain and have established roles in neurogenesis and neurosteroidogenesis. They are the only brain cell type expressing aromatase B (cyp19a1b), the enzyme that synthesizes estrogens from androgen precursors. There are few studies on the regulation of RGC functions, but our previous investigations demonstrated that dopamine stimulates cyp19a1b expression in goldfish RGCs, while secretoneurin A (SNa) inhibits the expression of this enzyme. Here, we determine the range of proteins and cellular processes responsive to SNa treatments in these steroidogenic cells. The focus here is on SNa, because this peptide is derived from selective processing of secretogranin II in magnocellular cells embedded within the RGC-rich preoptic nucleus. Primary cultures of RGCs were treated (24 h) with 10, 100, or 1,000 nM SNa. By using isobaric tagging for relative and absolute quantitation and a Hybrid Quadrupole Obritrap Mass Spectrometry system, a total of 1,363 unique proteins were identified in RGCs, and 609 proteins were significantly regulated by SNa at one or more concentrations. Proteins that showed differential expression with all three concentrations of SNa included H1 histone, glutamyl-prolyl-tRNA synthetase, Rho GDP dissociation inhibitor γ, vimentin A2, and small nuclear ribonucleoprotein-associated protein. At 10, 100, and 1,000 nM SNa, there were 5, 195, and 489 proteins that were downregulated, respectively, whereas the number of upregulated proteins were 72, 44, and 51, respectively. Subnetwork enrichment analysis of differentially regulated proteins revealed that processes such as actin organization, cytoskeleton organization and biogenesis, apoptosis, mRNA processing, RNA splicing, translation, cell growth, and proliferation are regulated by SNa based on the proteomic response. Moreover, we observed that, at the low concentration of SNa, there was an increase in the abundance of proteins involved in cell growth, proliferation, and migration, whereas higher concentration of SNa appeared to downregulate proteins involved in these processes, indicating a dose-dependent proteome response. At the highest concentration of SNa, proteins linked to the etiology of diseases of the central nervous system (brain injuries, Alzheimer disease, Parkinson's disease, cerebral infraction, brain ischemia) were also differentially regulated. These data implicate SNa in the control of cell proliferation and neurogenesis.


Bacterial chemotaxis to naphthalene desorbing from a nonaqueous liquid.
Bacterial chemotaxis has the potential to increase the rate of degradation of chemoattractants, but its influence on degradation of hydrophobic attractants initially dissolved in a non-aqueous-phase liquid (NAPL) has not been examined. We studied the effect of chemotaxis by Pseudomonas putida G7 on naphthalene mass transfer and degradation in a system in which the naphthalene was dissolved in a model NAPL. Chemotaxis by wild-type P. putida G7 increased the rates of naphthalene desorption and degradation relative to rates observed with nonchemotactic and nonmotile mutant strains. While biodegradation alone influenced the rate of substrate desorption by increasing the concentration gradient against which desorption occurred, chemotaxis created an even steeper gradient as the cells accumulated near the NAPL source. The extent to which chemotaxis affected naphthalene desorption and degradation depended on the initial bacterial and naphthalene concentrations, reflecting the influences of these variables on concentration gradients and on the relative rates of mass transfer and biodegradation. The results of this study suggest that chemotaxis can substantially increase the rates of mass transfer and degradation of NAPL-associated hydrophobic pollutants.


[Case of late onset and isolated lattice corneal dystrophy with Asn544Ser (N544S) mutation of transforming growth factor beta-induced (TGFBI, BIGH3) gene].
To report a case of lattice corneal dystrophy (LCD) with Asn544Ser (N544S) mutation of the transforming growth factor beta-induced (TGFBI) gene. A 68-year-old male patient with late-onset, sporadic LCD without corneal erosion. Amyloid deposits showing dot and lattice lines were seen in the mid to deep stroma. After obtaining appropriate informed consent, genomic DNA was amplified by polymerase chain reaction (PCR) and directly sequenced. A heterozygous single base pair transition (AAT --> AGT), resulting in substitution of serine for asparagine at codon 544 of the TGFBI gene, was detected. The case was classified as atypical type IV because of the late onset, lack of corneal erosion, and amyloid deposits in the mid to deep stroma.


Design, Synthesis and Biological Evaluation of Novel Osimertinib-Based HDAC and EGFR Dual Inhibitors.
Herein a novel series of histone deacetylases (HDACs) and epidermal growth factor receptor (EGFR) dual inhibitors were designed and synthesized based on the structure of the approved EGFR inhibitor osimertinib (AZD9291). Among them, four compounds 5D, 5E, 9D and 9E exhibited more potent total HDAC inhibition than the approved HDAC inhibitor SAHA. However, these compounds only showed moderate to low inhibitory potency towards EGFR with compounds 5E and 9E possessing IC50 values against EGFRWT and EGFRT790M in the micromolar range. 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay revealed the potent antiproliferative activities of compounds 5D, 5E, 9D and 9E, among which 9E was even more potent against HeLa, MDA-MB-231, MDA-MB-468, HT-29 and KG-1 cell lines than SAHA and AZD9291. Further selectivity profile of 9E showed that this compound was not active against other 13 cancer-related kinases and two epigenetic targets lysine specific demethylase 1 (LSD1) and bromodomain-containing protein 4 (BRD4). These results support further structural modification of 9E to improve its EGFR inhibitory activity, which will lead to more potent and balanced HDAC and EGFR dual inhibitors as anticancer agents.


Phase I trial of cisplatin and topotecan in children with recurrent solid tumors: Children's Cancer Group Study 0942.
To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cisplatin after a 72-hour continuous infusion of topotecan. Thirty-six children younger than age 22 years (range 3-21) with recurrent solid tumors were treated with cisplatin 45 to 75 mg/m2 infused over the course of 6 hours, followed by a 72-hour continuous infusion of topotecan 0.75 or 1 mg/m2 per day, followed by granulocyte colony stimulating factor (G-CSF), either immediately after treatment or when neutropenia developed. Patients were stratified by the presence of bone marrow tumor involvement and previous radiation to the bone marrow. The DLT was neutropenia (absolute neutrophil count <500/microL for >7 days). The MTD was cisplatin 60 mg/m2 and topotecan 1 mg/m2 per day followed by G-CSF starting 24 hours after chemotherapy for patients without marrow involvement or previous radiation to the bone marrow. An acceptable MTD was not found for patients with previous radiation to the bone marrow or bone marrow involvement or without the use of G-CSF starting 24 hours after chemotherapy was completed. Topotecan clearance and steady-state levels were determined. Limited evidence for antitumor activity with this combination was found in rhabdomyosarcoma. The recommended dose for phase II trials is cisplatin 60 mg/m2 followed by a 72-hour infusion of topotecan 1 mg/m2 per day with G-CSF starting 24 hours after the completion of topotecan.


Inside edge - prevalence and factors associated with symptoms of anxiety/depression in professional cricketers.
The purpose of this study was to i) determine the prevalence of anxiety/depression symptoms in professional cricketers and ii) identify factors associated with symptoms of anxiety/depression. One-hundred and seventy-seven (n = 177, response rate of 76%) professional cricketers completed the General Health Questionnaire 12 (GHQ-12). Odd ratios (OR) for anxiety/depression symptoms were related to players' career, family and education. Prevalence of symptoms of anxiety/depression was 59% (n = 104/177). Anxiety/depression symptoms increased when players were contracted for more than 2 years (OR: 5.0; 95% CI: 1.2-21.3; p = 0.028) and if they played their last offseason overseas (OR: 3.5; 95% CI: 1.3-9.6; p = 0.013). Anxiety/depression symptoms decreased by 70% when players made "productive use" of their time in the offseason (OR: 0.3; 95% CI: 0.1-0.9; p = 0.036) and contracted for 2 years (OR: 0.3; 95% CI: 0.1-1.0; p = 0.049). These findings can be incorporated into cricket mental health literacy programmes to improve awareness and understanding, and to encourage early help-seeking.


Generalized principle of designing neutral superstrong Brønsted acids.
A generalized principle of designing superstrong Brønsted acids is suggested according to the following scheme: M=O --> M=Z(X)(n). It consists of the formal replacement of =O fragment in carbonyl, sulfonyl, etc. groups in various acidic systems (e.g., CH(3)CHO, FSO(3)H, where M is the CH(3)CH= or FSO(2)H=fragment, respectively) by =NSO(2)F, =NCN, =C(CN)(2), =P(SO(2)F)(3), =S(CN)(4), or any other formally bivalent group =Z(X)(n) (where the formal valency of the central atom Z is n + 2), leading to highly acidic systems (e.g., HC(=P(CN)(3))NH(2), FS(=C(CN)(2))(2)OH, etc.). It is demonstrated that in several cases the introduction of the double-bonded substituent at the central atom (e.g., N, C, P, S, Cl) that carries the potentially acidic proton or the acidity site (e.g., OH, NH(2), CH(3), etc. groups) will lead to the enormous (up to ca. 120 kcal/mol or 88 pK(a) units!) increase of the intrinsic acidity of the respective parent acid. The acidity of the resulting acids and the scope and limitations of the principle are explored using density functional theory calculations at B3LYP 6-311+G level. Some of the resulting acids (or their anions) were found to undergo fragmentation in the course of the geometry optimization. The general trend that follows from the results of the calculations is that the stability of the resulting compounds is influenced by both the M and the Z. If M is a first row element (carbon or nitrogen), then stable species are produced with almost any Z. If M is a second row element (sulfur or phosphorus), then the species with first row Z are mostly predicted to be stable, but most of the species with second row Z are expected to undergo fragmentation during the geometry optimization. The Z = N and Z = C derivatives (e.g., =NSO(2)CF(3), =C(CN)(2), =C(SO(2)CF(3))(2), etc.) are predicted to be the most stable. However, they have relatively modest electron-accepting power as compared to their penta-, hexa-, and heptavalent counterparts. The acidifying effects of the =Z(X)(n)() groups with the same X increase with increasing n: =NCN < =C(CN)(2) < =P(CN)(3) < =S(CN)(4) and =NSO(2)F < =C(SO(2)F)(2) < =P(SO(2)F)(3). Also, the acidifying effect of a fluorosulfonyl-substituted substituent is higher than that of the corresponding cyano-substituted substituent.


Classical spin and quantum-mechanical descriptions of geometric spin frustration.
Geometric spin frustration (GSF) in isolated plaquettes with local spin s, i.e., an equilateral-triangle spin trimer and a regular-tetrahedron spin tetramer, was examined on the basis of classical spin and quantum-mechanical descriptions to clarify their differences and similarities. An analytical proof was given for how the state degeneracy and the total spin S of their ground states depend on the local spin s. The quantum-mechanical conditions for the occurrence of GSF in isolated plaquettes were clarified, and their implications were explored. Corner sharing between plaquettes and how it affects GSF in the resulting spin systems was examined.


The dual CCR2/CCR5 chemokine receptor antagonist Cenicriviroc reduces macrophage infiltration and disease severity in Duchenne muscular dystrophy (Dmdmdx-4Cv) mice.
Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness which is ultimately fatal, most often due to involvement of the diaphragm. Macrophage infiltration of dystrophic muscles has been strongly linked to muscle damage and fibrosis in DMD. We hypothesized that cenicriviroc (CVC), a dual chemokine receptor (CCR2/CCR5) antagonist currently under clinical evaluation for other diseases, could prevent macrophage accumulation and blunt disease progression in the diaphragms of mdx mice (genetic homologue of DMD). Treatment with CVC (20 mg/kg/day intraperitoneally) or vehicle was initiated in mdx mice at 2 weeks of age (prior to the onset of muscle necrosis) and continued for 4 weeks. Flow cytometry to assess inflammatory cell subsets as well as histological and force generation parameters were determined in mdx diaphragms at the conclusion of the treatment. CVC therapy induced a major (3.9-fold) reduction in total infiltrating macrophages, whereas total numbers of neutrophils and T lymphocytes (CD4+ and CD8+) were unaffected. No changes in macrophage polarization status (inflammatory versus anti-inflammatory skewing based on iNOS and CD206 expression) were observed. Muscle fiber size and fibrosis were not altered by CVC, whereas a significant reduction in centrally nucleated fibers was found suggesting a decrease in prior necrosis-regeneration cycles. In addition, maximal isometric force production by the diaphragm was increased by CVC therapy. These results suggest that CVC or other chemokine receptor antagonists which reduce pathological macrophage infiltration may have the potential to slow disease progression in DMD.


Low-density lipoprotein apheresis in the treatment of two patients with coronary heart disease and extremely elevated lipoprotein (a) levels.
Hyperlipidemia and elevated lipoprotein (a) (Lp[a]) levels have been linked to the development and progression of premature atherosclerosis. Our study concerned 2 white male patients (aged 36 and 42 years) with heterozygous familial hypercholesterolemia and extremely elevated Lp(a) concentrations that were resistant to diet regimens and lipid-lowering drugs. The patients were treated with low-density lipoprotein (LDL) apheresis for 59 months (Liposorber system, Kaneka, Japan) and 19 months (immunoadsorption system, special Lp(a) columns; Lipopak; Pocard, Russia), respectively. The concentration of Lp(a) decreased on average by 50%, total cholesterol by 27%, LDL cholesterol by 41%, triglycerides by 43%, and fibrinogen by 16%. High-density lipoprotein (HDL) cholesterol increased by approximately 4%. Before treatment with LDL apheresis, each patient had suffered 3 myocardial infarctions, and had had 4 and 6 coronary angiographies with 2 and 4 percutaneous transluminal angioplasties (PTCAs), respectively. Since treatment with LDL apheresis, no myocardial infarctions or cardiac complaints were observed. In the course of treatment, both patients reported an increased performance. Available data suggest that LDL apheresis may be effective in the treatment of patients, the only risk factor for premature atherosclerosis being extremely elevated Lp(a) concentrations.


Ensuring reliability in UK written tests of general practice: the MRCGP examination 1998-2003.
Reliability in written examinations is taken very seriously by examination boards and candidates alike. Within general education many factors influence reliability including variations between markers, within markers, within candidates and within teachers. Mechanisms designed to overcome, or at least minimize, the impact of such variables are detailed. Methods of establishing reliability are also explored in the context of a range of assessment situations. In written tests of general practice within the Membership of the Royal College of General Practitioner (MRCGP) examination considerable effort has put been put into achieving acceptable levels of reliability. Current mechanisms designed to ensure high reliability are described and related to the evolution of the written component of the examination. In addition to description of marker selection and training, question development including construct a detailed example of specific and generic marking schedules is provided. Examination results for the Written Paper of the MRCGP from 1998 to 2003 are reported including Cronbach's alpha coefficients and standard error of measurements, mean scores (and SD) and pass rates. In addition individual discrimination scores for each question in the October 2002 paper are shown. Consistent high reliability of the written component of the MRCGP examination provides valuable lessons in terms of selection, training and monitoring of markers as well as practical methods of moderating factors affecting candidate variability. The challenge for examination developers is to carry these important lessons forward into a modernized assessment structure of UK general practice.


The role of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in cryptogenic organizing pneumonia.
The processes observed in interstitial lung disease are associated with the production, deposition, and proteolysis of the extracellular matrix (ECM), which may lead to irreversible pulmonary structural remodeling or to appropriate repair without fibrosis. Matrix metalloproteinases (MMPs) and a tissue inhibitor of metalloproteinases (TIMPs) are known to regulate remodeling of the ECM and thus to be important in the process of lung fibrosis. Pulmonary structures are extensively remodeled in usual interstitial pneumonia (UIP), whereas severe architectural remodeling is minimally present in cryptogenic organizing pneumonia (COP). However, not much is known about the roles of MMP-9 and/or TIMP-1 in COP. Levels of MMP-9, TIMP-1 and the molar ratio of MMP-9/TIMP-1 in BAL fluids were investigated in 11 patients with UIP, in 8 patients with COP, and in 10 control subjects. We checked the levels of MMP-9 and TIMP-1 by means of enzyme immunoassay, and the hydrolytic activity of MMP-9 in BAL fluids was measured by gelatin zymography. Further, we evaluated the expression of MMP-9 and TIMP-1 in lung tissue by immunohistochemistry. The concentrations of MMP-9 and TIMP-1 were significantly increased in patients with UIP and were even higher in patients with COP compared with control subjects. The levels of MMP-9 and TIMP-1 were significantly higher in patients with COP than in patients with UIP. The molar ratio of MMP-9/TIMP-1 was significantly higher in patients with COP than in control subjects. In patients with COP, the concentration of MMP-9 significantly correlated with the number of neutrophils and lymphocytes. Zymographic analysis revealed that the activity of the 92-kd pro-MMP-9 was increased in patients with UIP and was even higher in patients with COP, compared with control subjects. These data suggest that overproduction of MMP-9 and TIMP-1, and an imbalance between MMP-9 and TIMP-1, may have a role as diagnostic references in COP.


TL -DNA transformation decreases ABA level.
The endogenous levels of ABA were measured in Agrobacterium rhizogenes A4 Tl -DNA transformed oilseed rape (Brassica napus L. var. oleifera cv. Brutor and cv. Drakkar), cabbage (Brassica oleracea). A4 transformed tobacco (Nicotiana tabacum cv. Xanthi) and their normal counterparts, using high performance liquid chromatography and enzyme-liked immunosorbent assay. Measurements were made on different plant tissues (i. e. floral stem, terminal bud, young leaf, mature leaf, root and root tips) and ABA levels were compared in unstressed and osmotically stressed oilseed rape plants (cv. Brutor). In unstressed Plants. in each of the 5 independent transformation events studied, a significant reduction (about 65% of control) in ABA concentration was observed in all transformed plants. When subjected to an osmotic stress, TL transformed Brutor plants showed a higher ABA accumulation than untransformed plants. The change in ABA content as a consequence of TL -DNA transformation is discussed with regard to phenotype, drought resistance and adaptability.


Distribution of vasopressin in the brain of the eusocial naked mole-rat.
Naked mole-rats are eusocial rodents that live in large subterranean colonies in which one queen breeds with one to three males. All other animals are nonbreeding subordinates. The external features of male and female subordinates, including their genitalia, are remarkably monomorphic, as is their behavior. Because vasopressin (VP) is associated with social behaviors and sex differences in other species, its distribution in naked mole-rats was of interest. We used immunohistochemistry to examine VP in the brains of subordinate and breeding naked mole-rats of both sexes. As in other mammals, VP-immunoreactive (-ir) somata were found in the paraventricular (PVN) and supraoptic nuclei (SON) and VP-ir projections from these nuclei ran through the internal and external zone of the median eminence. However, naked mole-rats had very few VP-ir cells in the bed nucleus of the stria terminalis (BST) and none in the suprachiasmatic nucleus (SCN); the extensive network of fine-caliber VP-ir fibers usually seen in projection sites of the BST and SCN were also absent. Equally unexpected was the abundance of large-caliber VP-ir fibers in the dorsomedial septum. VP immunoreactivity was generally similar in all groups, with the exception of VP-ir cell number in the dorsomedial hypothalamus (DMH). Breeders had a population of labeled cells in the DMH that was absent, or nearly absent, in subordinates. Future studies on the function of VP in these areas are needed to determine how the atypical distribution of VP immunoreactivity relates to eusociality and the unusual physiology of naked mole-rats.


Rational design, synthesis and binding mechanisms of novel benzyl geranate derivatives as potential eco-friendly aphid repellents.
The push-pull strategy is considered as a promising eco-friendly method for pest management. Plant volatile organic compounds (PVOCs) act as semiochemicals constitute the key factor in implementing this strategy. Benzyl alcohol and geraniol, as functional PVOCs, were reported to regulate insect behavior, showing the potential application in pest control. Using geraniol as lead, a geraniol derivative 5i with fine repellent activity was discovered in our previous work. In order to explore novel, eco-friendly aphid control agents, a series of benzyl geranate derivatives was designed and synthesized using 5i as the lead and benzyl alcohol as the active fragment. Benzyl alcohol was firstly evaluated to have repellent activity to Acyrthosiphon pisum. Based on this repellent fragment, a series of novel benzyl geranate derivatives was rationally designed and synthesized using a scaffold-hopping strategy. Among them, compound T9, with a binding affinity (Kd = 0.43 μm) and a substantial repellency of 64.7% against A. pisum, is the most promising compound. Molecule docking showed that hydrophobic and hydrogen-bonding interactions substantially influenced the binding affinity of compounds with ApisOBP9. Additionally, T9 exhibited low-toxicity to honeybees and ladybugs. Using a simple scaffold-hopping strategy combined with active fragment benzyl alcohol, a new derivative T9, with high aphid-repellency and low-toxicity to nontarget organisms, can be considered as a novel potential eco-friendly aphid control agent for sustainable agriculture. © 2023 Society of Chemical Industry.


The Chemistry of Europium(III) Encountering DNA: Sprouting Unique Sequence-Dependent Performances for Multifunctional Time-Resolved Luminescent Assays.
Screening functional DNA that can fruitfully interact with metal ions is a long-standing hot topic in the fields of biotechnology, medicine, and DNA-based sensors. In this paper, we focus on the chemistry of europium(III) (Eu) coupled with single-stranded DNA (ssDNA), and we innovatively unveil that cytosine- and thymine-rich ssDNA oligomers (e.g., C16 and T16) can be effective antenna ligands to sensitize the luminescence of Eu. Luminescence lifetime spectroscopy, circular dichroic (CD) spectroscopy, and isothermal titration calorimetry (ITC) have been used to systematically characterize the interaction involved between Eu and ssDNA. In light of the resultant sequence-dependent performances, the long luminescence lifetime Eu/ssDNA-based label-free and versatile probes are further devised as a pattern distinction system for time-resolved luminescent (TRL) sensing applications. The interactions of metal ions and ssDNA can distinctively shift the antenna effect of ssDNA toward Eu as accessible pattern signals. As a result, as few as two Eu/ssDNA label-free TRL probes can discriminate 17 metal ions via principal component analysis (PCA). In addition, thiols can readily capture metal ions to switch the luminescence of Eu/ssDNA probes initially altered by metal ions. Hence, four Eu/ssDNA-metal ion ensembles are demonstrated to be a powerful label-free TRL sensor array for pattern differentiation of eight thiols and even chiral recognition of cysteine enantiomers with different concentrations. Moreover, the sensitive TRL detection of thiols in biofluids can be successfully realized by using our method, promising its potential practical usage. This is the first report of a ssDNA-sensitized Eu-based TRL platform for label-free yet multifunctional background-free sensing and would open a door for sprouting of more novel lanthanide ion/DNA-relevant strategies toward widespread applications.


Ceramic Biocomposites as Biodegradable Antibiotic Carriers in the Treatment of Bone Infections.
Local release of antibiotic has advantages in the treatment of chronic osteomyelitis and infected fractures. The adequacy of surgical debridement is still key to successful clearance of infection but local antibiotic carriers seem to afford greater success rates by targeting the residual organisms present after debridement and delivering much higher local antibiotic concentrations compared with systemic antibiotics alone. Biodegradable ceramic carriers can be used to fill osseous defects, which reduces the dead space and provides the potential for subsequent repair of the osseous defect as they dissolve away. A dissolving ceramic antibiotic carrier also raises the possibility of single stage surgery with definitive closure and avoids the need for subsequent surgery for spacer removal. In this article we provide an overview of the properties of various biodegradable ceramics, including calcium sulphate, the calcium orthophosphate ceramics, calcium phosphate cement and polyphasic carriers. We summarise the antibiotic elution properties as investigated in previous animal studies as well as the clinical outcomes from clinical research investigating their use in the surgical management of chronic osteomyelitis. Calcium sulphate pellets have been shown to be effective in treating local infection, although newer polyphasic carriers may support greater osseous repair and reduce the risk of further fracture or the need for secondary reconstructive surgery. The use of ceramic biocomposites to deliver antibiotics together with BMPs, bisphosphonates, growth factors or living cells is under investigation and merits further study. We propose a treatment protocol, based on the Cierny-Mader classification, to help guide the appropriate selection of a suitable ceramic antibiotic carrier in the surgical treatment of chronic osteomyelitis.


Functional near-infrared spectroscopy in the evaluation of urban rail transit drivers' mental workload under simulated driving conditions.
The objective of this study is to investigate the potential of functional near-infrared spectroscopy (fNIRS) combined with heart rate variability indices, for the evaluation of the mental workload of urban rail transit drivers under simulated driving conditions, particularly during task engagement and disengagement. Experienced metro drivers wearing fNIRS monitoring systems were asked to drive for 90 min in a professional metro driving simulator. Workload stimulus tasks were added and an n-back task (n = 3) was implemented to induce workload in the simulated driving experiment. Experimental results indicate that fNIRS are sensitive to mental workload and reliable for discriminating the degree of mental workload. Research findings demonstrate the feasibility and reliability of fNIRS as a tool for real-time evaluating and monitoring driver mental workload along with task factors from a perspective of brain activations during simulated or actual driving. Practitioner Summary: This study provides evidence for the potential of functional near-infrared spectroscopy (fNIRS) for the evaluation of the mental workload of urban rail transit drivers under simulated driving conditions. The first fNIRS application to mental workload evaluation in the field of urban rail transportation helps companies develop reasonable shiftwork schedule and ensure operation safety. Abbreviations: fNIRS: functional near-infrared spectroscopy; oxy-Hb: Oxy-hemoglobin; NASA-TLX: National Aeronautics and Space Administration Task Load Index; EEG: electroencephalogram; ECG: electrocardiogram; HRV: variability; LF: low-frequency power; HF: high-frequency power; PFC: prefrontal cortex; NIRS: near-infrared spectroscopy; DWT: discrete wavelet transform; EMG: electromyography; DT: determination test; TP: total power; LFnorm: standardized LF; HFnorm: standardized HF; VLF: very low frequency; deoxy-Hb: deoxy-hemoglobin.


Chromosome mapping of 18S rDNA and 5S rDNA by dual-color fluorescence in situ hybridization in the half-smooth tongue sole (Cynoglossus semilaevis).
Half-smooth tongue sole (Cynoglossus semilaevis) is an important aquaculture flatfish in China. Cytogenetic analysis has revealed that its sex determination system is female heterogametic (ZZ/ZW). The W chromosome is morphologically larger and has been considered evolutionarily younger than any other chromosome in the set. However, the genetic origin and evolution process of this neo-chromosome remains unclear. In this study, 2 tandem arrays of rRNA genes were chosen to address this question. Both the major rDNA (18S rDNA) and the minor rDNA (5S rDNA) were located on the C. semilaevis chromosomes by fluorescence in situ hybridization (FISH). Six 18S rDNA signals were observed on the centromeric regions of 3 pairs of autosomes in both males and females. In females, there was an additional 18S rDNA signal mapping to the telomeric region of the W chromosome long arm. With respect to the 5S rDNA, 12 signals were mapped to the centromeric regions of six pairs of autosomes. Two-color FISH further confirmed that the two pairs of the 5S rDNA signals were correspondingly located at the same positions of the same autosomes as those of the 18S rDNA signals. These results allowed us to speculate about the evolution process of the W chromosome. Chromosome fusions and repetitive sequence accumulations might have occurred in C. semilaevis. The synteny and non-synteny of C. semilaevis 18S rDNA and 5S rDNA might imply the original and evolutionary characteristics of this species. These findings will facilitate studies on karyotype evolution of the order Pleuronectiformes.


Extraction and translation of collagen mRNA from fetal calf skin.
RNA was extracted from fetal calf skin by two different procedures, using phenol or guanidine hydrochloride. Poly(A)-rich RNA was separated by oligo(dT)-cellulose affinity chromatography and was further fractionated by sucrose density gradient centrifugation. When translated in an optimized wheat germ extract cell-free system, unfractionated guanidine-hydrochloride-extracted poly(A)-rich RNA directed the synthesis of two collagenase-sensitive protein bands, while phenol-extracted poly(A)-rich RNA with a sedimentation coefficient higher than 25 S was the only fraction to direct the same synthesis. On the basis of their electrophoretic mobility on a sodium dodecylsulfate/urea/polyacrylamide gel, these proteins were identified with procollagen alpha 1(I) and procollagen alpha 2. Inhibition of translation by phenol-extracted poly(A)-rich RNA with a sedimentation coefficient lower than 25 S was also observed. Guanidine-hydrochloride-extracted poly(A)-rich RNA from fetal skin directed the synthesis of three distinct collagenase-sensitive proteins in the micrococcal-nuclease-digested rabbit reticulocyte cell-free system; these seemed to correspond to procollagen alpha 1(I), procollagen alpha 2 and procollagen alpha 1 (III).


Cytotoxicity, Uptake Behaviors, and Oral Absorption of Food Grade Calcium Carbonate Nanomaterials.
Calcium is the most abundant mineral in human body and essential for the formation and maintenance of bones and teeth as well as diverse cellular functions. Calcium carbonate (CaCO₃) is widely used as a dietary supplement; however, oral absorption efficiency of CaCO₃ is extremely low, which may be overcome by applying nano-sized materials. In this study, we evaluated the efficacy of food grade nano CaCO₃ in comparison with that of bulk- or reagent grade nano CaCO₃ in terms of cytotoxicity, cellular uptake, intestinal transport, and oral absorption. Cytotoxicity results demonstrated that nano-sized CaCO₃ particles were slightly more toxic than bulk materials in terms of oxidative stress and membrane damage. Cellular uptake behaviors of CaCO₃ nanoparticles were different from bulk CaCO₃ or Ca2+ ions in human intestinal epithelial cells, showing efficient cellular internalization and elevated intracellular Ca2+ levels. Meanwhile, CaCO₃ nanoparticles were efficiently transported by microfold (M) cells in vitro model of human intestinal follicle-associated epithelium, in a similar manner as Ca2+ ions did. Biokinetic study revealed that the biological fate of CaCO₃ particles was different from Ca2+ ions; however, in vivo, its oral absorption was not significantly affected by particle size. These findings provide crucial information to understand and predict potential toxicity and oral absorption efficiency of food grade nanoparticles.


[Management and quality: in search of nursing].
Quality management involves everyone in the hospital to a different degree. The head-nurses are key elements for the realization of these programs. Throughout this discussion regarding management, this article explores the links between quality management and nursing. The interviews conducted show that management has over-invested in quality. Therefore it will respond to problems concerning work organization and will also allow a professional acknowledgement. The analysis confirms that the quality values come before that of a pragmatic conception of health care based on a disjunctive viewpoint, both linear and timeless. Furthermore, because nursing is not considered as a discipline, quality healthcare remains undefined. The recommendations focus on the manager's role and particularity on the definition of the principal problems of different services.


Microwave Detection of Electron-Phonon Interactions in a Cavity-Coupled Double Quantum Dot.
Quantum confinement leads to the formation of discrete electronic states in quantum dots. Here we probe electron-phonon interactions in a suspended InAs nanowire double quantum dot (DQD) that is electric-dipole coupled to a microwave cavity. We apply a finite bias across the wire to drive a steady state population in the DQD excited state, enabling a direct measurement of the electron-phonon coupling strength at the DQD transition energy. The amplitude and phase response of the cavity field exhibit oscillations that are periodic in the DQD energy level detuning due to the phonon modes of the nanowire. The observed cavity phase shift is consistent with theory that predicts a renormalization of the cavity center frequency by coupling to phonons.


Willing and able: a closer look at pain Willingness and Activity Engagement on the Chronic Pain Acceptance Questionnaire (CPAQ-8).
An 8-item version of the Chronic Pain Acceptance Questionnaire (CPAQ-8) has recently been proposed and validated. The aims of this study were to further investigate the reliability and validity of the CPAQ-8 in a new sample. Questionnaires were completed by 550 people with chronic pain (478 online survey, 72 paper survey). A demographic and pain history questionnaire was administered along with the CPAQ-8 and measures of pain self-efficacy, pain catastrophizing, psychological flexibility in pain, anxiety, and mood. In addition, 105 respondents completed the CPAQ-8 within 6 weeks to provide test-retest reliability data. The 2-factor structure of the CPAQ-8 (Activity Engagement [AE] and Pain Willingness [PW]) was confirmed and had reasonable-to-good scale score reliability and test-retest reliability. Pain acceptance as measured by the CPAQ-8 was associated with less depression, anxiety, pain interference, fear of reinjury, pain catastrophizing, and psychological inflexibility in pain, and higher levels of satisfaction with life, pain self-efficacy, and general acceptance. Furthermore, pain acceptance fully mediated the relationship between reported pain severity and emotional distress (anxiety and depression) and partially mediated the relationship between pain severity and pain interference in a structural equation model. The test-retest reliability after 4 to 6 weeks ranged from .68 for PW to .86 for AE; the overall score correlation was .81. We conclude that the CPAQ-8 is a reliable and valid measure of pain acceptance and that the 2 subscales of the measure each make an individual contribution to the prediction of adjustment in people with chronic pain. The present study provides further evidence for the reliability and validity of the CPAQ-8. Support was found for the 2 related subscales, PW and AE, which appear to work in synergy to influence levels of pain interference and emotional distress in people living with chronic pain.


Effects of parathyroid hormone on plasma and urinary adenosine 3',5'-monophosphate in man.
The effects of parathyroid hormone (PTH) on plasma and urinary adenosine 3',5'-monophosphate (cyclic AMP) levels were studied in normal subjects. Under basal conditions normal adults have plasma concentrations of cyclic AMP ranging from 10 to 25 nmoles/liter and excrete from 1.5 to 5 mumoles of cyclic AMP per g of urinary creatinine. About one-half to two-thirds of the cyclic AMP excreted in the urine is derived from the plasma by glomerular filtration, and the remainder is produced by the kidney. Renal production of cyclic AMP is partly under the control of PTH. It can be suppressed by infusions of calcium and stimulated by infusions of the calcium chelating agent, EDTA. Infusions of PTH in doses up to 10 mU/kg per min were associated with dose-related increases both in urinary cyclic AMP and phosphate. Infusions of PTH in doses ranging from 20 to 80 mU/kg per min did not lead to any further increase in phosphaturia but did lead to further marked increases in urinary cyclic AMP. A modest increase in plasma cyclic AMP was noted when PTH was infused at 40 mU/kg per min. Anephric patients failed to show appreciable increases in plasma cyclic AMP in response to large doses of PTH but did show expected increases in response to glucagon. Surgical removal of parathyroid adenomas from nine patients with primary hyperparathyroidism was invariably followed by a decrease in urinary cyclic AMP, PTH, in large doses, and calcium infusion produced up to 2-fold increases in the other known naturally occurring cyclic nucleotide, guanosine 3',5'-monophosphate (cyclic GMP).


Trauma-informed care training with HIV and related community service workers: Short and long term effects on attitudes.
Although the experience of trauma is a widespread, global phenomenon, individuals living with HIV, who are two-spirit, lesbian, gay, bisexual, transgender, queer+ (2SLGBTQ+), who use injection drugs, and/or who have marginalized status, are disproportionately affected (Harris & Fallot, 2006; Hopper, Bassuk, & Olivet, 2009; Seedat, 2012). The need for trauma competent service provision, meaning integrating psychoeducation about trauma, and knowledge of its prevalence, impact, and outcomes, is clear. Numerous HIV service and affiliated agencies in Ontario requested a Trauma-Informed Care workshop for their staff and volunteers, and the current project reports on the outcomes of this workshop. There were 150 community, health, and social service providers in the HIV, hepatitis C, LGBTQ, harm reduction, and related sectors who participated in a full- or half-day Trauma-Informed Care workshop. Participants completed the Attitudes Related to Trauma-Informed Care scale (ARTIC-10) at preworkshop, postworkshop, and at 6-month follow-up, as well as a brief phone interview. There was a significant increase in ARTIC scores, indicating more favorable attitudes toward trauma-informed care, from preworkshop (M = 58.01, SE = 0.64) to postworkshop (M = 61.73, SE = 0.67), M = -3.72, BCa 95% confidence interval [-4.65, -2.82], t(149) = -7.79, p < .001, resulting in a medium-sized effect, d = 0.48. These gains were maintained at follow-up. Results were complemented by participant interviews. These results demonstrate that a brief workshop on Trauma-Informed Care can improve attitudes relatively quickly, that are generally maintained over time, creating a trauma-informed environment for clients. Future directions include assessing client outcomes as they may relate to changes in provider attitudes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Devic's neuromyelitis optica in an infant case.
Devic's neuromyelitis optica was orginally described as an acute severe monophasic syndrome characterised by myelitis and optic neuritis. The mean age at onset was reported to be around 40 years, with a wide range. However, Devic's neuromyelitis optica has also been seen in children. Prognosis of the syndrome was poor, and no satisfactory treatment was known. This article reports a 23-month-old boy with acute myelitis and optic neuritis who was diagnosed with Devic's neuromyelitis optica. The response of the patient to therapy was poor, and he developed severe sequelae.


Polycyclic Polyprenylated Acylphloroglucinol Congeners from Hypericum scabrum.
Twenty polycyclic polyprenylated acylphloroglucinols (PPAPs), including the new compounds hyperscabrones A-I (1-9), were isolated from the air-dried aerial parts of Hypericum scabrum. These compounds comprise seven different structural types. All structures were determined by NMR spectroscopic methods and both experimental and calculated electronic circular dichroism (ECD) spectra. The evaluation of their neuroprotective effects on glutamate-induced toxicity in SK-N-SH cells showed that compounds 4-7 exhibited significant neuroprotection at 10 μM. Additionally, compounds 3, 4, 7, and 9 showed moderate hepatoprotective activities against paracetamol-induced HepG2 cell damage at 10 μM.


Intermediate phenotypes and genetic mechanisms of psychiatric disorders.
Genes are major contributors to many psychiatric diseases, but their mechanisms of action have long seemed elusive. The intermediate phenotype concept represents a strategy for characterizing the neural systems affected by risk gene variants to elucidate quantitative, mechanistic aspects of brain function implicated in psychiatric disease. Using imaging genetics as an example, we illustrate recent advances, challenges and implications of linking genes to structural and functional variation in brain systems related to cognition and emotion.


Structural and functional genomics of the CPT1B gene for muscle-type carnitine palmitoyltransferase I in mammals.
Muscle-type carnitine palmitoyltransferase I (M-CPT I) is a key enzyme in the control of beta-oxidation of long-chain fatty acids in the heart and skeletal muscle. Because knowledge of the mammalian genes encoding M-CPT I may aid in studies of disturbed energy metabolism, we obtained new genomic and cDNA data for M-CPT I for the human, mouse, rat, and sheep. The introns of these compact genes are 80% (mouse versus rat) and 60% (mouse versus human) identical. Sheep and goat, but not cow, pig, rodent, or human promoter sequences contain a short interspersed repeated sequence (SINE) upstream of highly conserved regulatory elements. These elements constitute two promoters in humans, sheep, and mice, and, contrary to previous reports, there is a second promoter in rats as well. Thus, the transcriptional organization of these genes is more uniform than previously supposed, with interspecies differences in the 5'-ends of the mRNAs reflecting differences in splicing; only in humans extensive splicing and splice variation is found in the 5'- and 3'-untranslated regions. In the mouse, intron retention was detected in heart, muscle, and testes and may indicate an additional mechanism of regulation of M-CPT I expression. Splice variation in the coding region was previously proposed to lead to expression of CPT I enzymes with altered malonyl-CoA sensitivity (Yu, G. S., Lu, Y. C., and Gulick, T. (1998) Biochem. J. 334, 225-231). However, when expressed in the yeast Pichia pastoris, none of three earlier described splice variants had CPT I activity. Therefore, the involvement of splice variation of M-CPT I in the modulation of malonyl-CoA inhibition of fatty acid oxidation may be less relevant than hitherto assumed.


Inhibition of p90 ribosomal S6 kinases disrupts melanoma cell growth and immune evasion.
The mitogen-activated protein kinase (MAPK) signaling pathway is frequently hyperactivated in malignant melanoma and its inhibition has proved to be an efficient treatment option for cases harboring BRAFV600 mutations (BRAFMut). However, there is still a significant need for effective targeted therapies for patients with other melanoma subgroups characterized by constitutive MAPK activation, such as tumors with NRAS or NF-1 alterations (NRASMut, NF-1LOF), as well as for patients with MAPK pathway inhibitor-resistant BRAFMut melanomas, which commonly exhibit a reactivation of this pathway. p90 ribosomal S6 kinases (RSKs) represent central effectors of MAPK signaling, regulating cell cycle progression and survival. RSK activity and the functional effects of its inhibition by specific small molecule inhibitors were investigated in established melanoma cell lines and patient-derived short-term cultures from different MAPK pathway-hyperactivated genomic subgroups (NRASMut, BRAFMut, NF-1LOF). Real-time qPCR, immunoblots and flow cytometric cell surface staining were used to explore the molecular changes following RSK inhibition. The effect on melanoma cell growth was evaluated by various two- and three-dimensional in vitro assays as well as with melanoma xenograft mouse models. Co-cultures with gp100- or Melan-A-specific cytotoxic T cells were used to assess immunogenicity of melanoma cells and associated T-cell responses. In line with elevated activity of the MAPK/RSK signaling axis, growth and survival of not only BRAFMut but also NRASMut and NF-1LOF melanoma cells were significantly impaired by RSK inhibitors. Intriguingly, RSK inhibition was particularly effective in three-dimensional growth settings with long-term chronic drug exposure and suppressed tumor cell growth of in vivo melanoma models. Additionally, our study revealed that RSK inhibition simultaneously promoted differentiation and immunogenicity of the tumor cells leading to enhanced T-cell activation and melanoma cell killing. Collectively, RSK inhibitors exhibited both multi-layered anti-tumor efficacy and broad applicability across different genomic melanoma subgroups. RSK inhibition may therefore represent a promising novel therapeutic strategy for malignant melanoma with hyperactivated MAPK signaling.


Effect of fusion/activation protocol on in vitro development of porcine nuclear transfer embryos constructed with foreign gene-transfected fetal fibroblasts.
The effect of fusion/activation protocol on in vitro development of porcine nuclear transfer (NT) embryos constructed with foreign gene-transfected somatic cells were investigated. NT embryos were produced by using enucleated M II oocytes and enhanced green fluorescence protein (EGFP) gene-transfected or non-transfected porcine fetal fibroblasts. One group of NT embryos received a single electrical pulse to induce fusion and activation simultaneously (FAS). The other group was fused 2 hr before activation (FBA) using two kinds of electrical pulses. Electrically activated NT embryos in both groups were treated with cycloheximide (CHX) before culture to assess the development to the blastocyst stage. After 6 days of culture, all morulae and blastocysts derived from EGFP-transfected fibroblasts emitted green fluorescence without mosaicism, and EGFP-gene product was also detected in all morulae and blastocysts examined. NT embryos undergoing FAS showed higher developmental capacity to blastocysts than those undergoing FBA, regardless of the EGFP transfection into the nuclear donor cells. The results also indicated that EGFP-gene transfection into nuclear donor cells has no obvious deleterious effect on the development of NT embryos to blastocysts.


Magnetic entrapment for fast, simple and reversible electrode modification with carbon nanotubes: application to dopamine detection.
Carbon nanotubes (CNT) have been exploited for an important number of electroanalytical and sensing purposes. Specifically, CNT incorporation to an electrode surface coating increases its roughness and area, provides electrocatalytic activity towards a variety of molecules, and improves electron transfer. This modification is generally based on the irreversible deposition of CNT on surface. Nevertheless, CNT are highly porous materials that might promote molecule non-specific adsorption and/or electrodeposition, which could induce sample-to-sample cross-contamination and affect measurement specificity and reproducibility. This drawback has been often circumvented by combining CNT with charged polymers able to repel molecules of opposed charge. We demonstrate that single-walled CNT (SWCNT) have a strong tendency to non-specifically adsorb onto the surface of protein-coated magnetic particles (MP). Magnetic capture of those MP generates CNT coentrapment and allows extremely fast, simple and reversible production of SWCNT electrodes. We have exploited this phenomenon for the production of modified screen-printed electrodes (MP/CNT-SPE), which have been characterized by Scanning Electron Microscopy. The surface has been additionally optimized by evaluating the electrochemical performance of SPE modified with different amounts and proportions of MP and CNT. The modified devices have then been used for dopamine detection. MP/CNT-SPE generated improved assay sensitivity, lower limit of detection, and up to 500% higher current signals than bare electrodes. Magnetic entrapment is proposed as a promising strategy for the fast, simple and reversible generation of nanostructured electrodes of enhanced performance within a few minutes and electrode re-utilisation by simple magnet removal and surface washing.


Assessing Short-Term Voltage Stability of Electric Power Systems by a Hierarchical Intelligent System.
In the smart grid paradigm, growing integration of large-scale intermittent renewable energies has introduced significant uncertainties to the operations of an electric power system. This makes real-time dynamic security assessment (DSA) a necessity to enable enhanced situational-awareness against the risk of blackouts. Conventional DSA methods are mainly based on the time-domain simulation, which are insufficiently fast and knowledge-poor. In recent years, the intelligent system (IS) strategy has been identified as a promising approach to facilitate real-time DSA. While previous works mainly concentrate on the rotor angle stability, this paper focuses on another yet increasingly important dynamic insecurity phenomenon-the short-term voltage instability, which involves fast and complex load dynamics. The problem is modeled as a classification subproblem for transient voltage collapse and a prediction subproblem for unacceptable dynamic voltage deviation. A hierarchical IS is developed to address the two subproblems sequentially. The IS is based on ensemble learning of random-weights neural networks and is implemented in an offline training, a real-time application, and an online updating pattern. The simulation results on the New England 39-bus system verify its superiority in both learning speed and accuracy over some state-of-the-art learning algorithms.


Tuning the chemical selectivity of SWNT-FETs for detection of heavy-metal ions.
A method to functionalize single-walled carbon nanotubes (SWNTs) in a field-effect transistor (FET) device for the selective detection of heavy-metal ions is presented. In this method, peptide-modified polymers were electrochemically deposited onto SWNTs and the selective detection of metal ions was demonstrated by choosing appropriate peptide sequences. The signal transduction mechanism of the peptide-modified SWNT-FETs has also been studied.


Chest wall motion in sleep apnea.
Patterns of rib cage (RC) and abdomen (ABD) motion obtained from a respiratory inductive plethysmograph were studied during disordered breathing events - obstructive apnea, obstructive hypopnea, mixed apnea, and central apnea - in 54 patients with sleep apnea. The type of disordered breathing event was verified by esophageal pressure and bias-flow mask recordings. Obstructive apnea occurred to a variable extent in all patients and was characterized by stereotyped paradoxical motion of the RC or ABD or both in 49 patients (91%). There was no paradox in 2 patients with "feeble" inspiratory effort during obstructions and in 3 patients with normal inspiratory effort during obstructed breaths. The more obese patients displayed paradox of the ABD rather than of the RC. Paradox did not occur in central apnea or in the central component of mixed apnea. Obstructive hypopnea was characterized by paradox during part of the breath. We conclude that RC and ABD motion can adequately characterize apnea in most patients and thus avoid invasive monitoring techniques that can adversely affect sleep. However, if chest wall motion suggests that all apneas are central, a direct measurement of respiratory effort is necessary to exclude obstruction.


A long-range fronto-parietal 5- to 10-Hz network predicts "top-down" controlled guidance in a task-switch paradigm.
The capacity to rapidly adjust behavioral strategies according to changing task demands is closely associated with coordinated activity in lateral and medial prefrontal cortices. Subdivisions within prefrontal cortex are implicated to encode attentional task sets and to update changing task rules, particularly when changing task demands require top-down control. Here, we tested whether these top-down processes precede stimulus processing and constitute a preparatory attentional state that functionally couples with parietal cortex. We examined this functional coupling by recording from intracranial EEG electrodes in macaques during performance of a task-switching paradigm that separates task performance that is based on controlled top-down guidance from automatic, stimulus-triggered processing modes. We identify a prefrontal-parietal network that phase synchronizes at 5-10 Hz, particularly during preparatory states that indicate top-down controlled task-processing modes. Phase relations in the network suggest that medial and lateral prefrontal cortices synchronize bidirectionally, with medial prefrontal cortex showing a phase-lead relative to left parietal recorded 5- to 10-Hz preparatory signals. These findings reveal a 5- to 10-Hz coordinated, long-range fronto-parietal network prior to actual task-relevant stimulus processing, particularly when subjects engage in controlled task processing modes.


Degradation kinetics of pentachlorophenol by Phanerochaete chrysosporium.
The extracellular enzymes and cell mass from the pregrown Phanerochaete chrysosporium cultures were used for the degradation of PCP. The use of both extracellular enzymes and cell mass resulted in extensive mineralization of PCP, while the action of only the crude extracellular enzymes led to the formation of a degradation intermediate (TCHD). A kinetic model, which describes the relationship among PCP degradation, initial PCP concentration, dosage of extracellular enzymes, and cell mass concentration, was developed. Based on this model, various effects of initial PCP concentration, dosage of extracellular enzymes, and cell mass concentration were evaluated experimentally. It was found that when initial PCP concentration is lower than 12 mumol/L, the model of a parallel-series first-order reaction is sufficient to describe the degradation process. PCP disappearance and mineralization were enhanced by increasing either the extracellular enzyme concentration or the cell mass concentration. As high as 70% of PCP mineralization could be obtained by using a higher dosage of extracellular enzymes and cell mass. Various parameters of the kinetic model were determined and the model was verified experimentally. Simulation using this model provided the criteria needed to choose rational dosages of extracellular enzymes and cell mass for the degradation of PCP. Data reported allow some insight into the function of the extracellular enzymes and cell mass of P. chrysosporium in degradation processes of toxic pollutants and assist in the design and evaluation of practical bioremediation methods.


Genome Sequence of a Rabies Virus Isolated from a Dog in Chiapas, Mexico, 2013.
Rabies virus (RABV), a member of the genus Lyssavirus, causes encephalitis that is almost always fatal following the onset of clinical signs. Here, we report the complete codifying sequence of an RABV isolated from a dog in Mexico. Molecular data showed that this strain belongs to the Chiapas lineage.


[Intraductal neoplasms of the pancreas].
The latest WHO classification of tumors of the digestive system (2019) has introduced new concepts for the stratification of intraductal neoplasms of the pancreas, mostly based on molecular genetics and malignant potential. Among them, pancreatic intraepithelial neoplasias (PanINs) and intraductal papillary mucinous neoplasms (IPMN) are both precursors of pancreatic ductal adenocarcinoma, whereas intraductal oncocytic papillary neoplasms (IOPN) and intraductal tubulopapillary neoplasms (ITPN) are usually associated with less aggressive subtypes of pancreatic cancer and therefore have a much better prognosis. Hence, it is of utmost importance to correctly classify these lesions and to distinguish them from each other as well as from other nonductal types of neoplasms, which can rarely display an intraductal growth, such as neuroendocrine tumors and acinar cell carcinomas. PanIN are microscopic lesions with limited clinical significance. In contrast, all other intraductal neoplasms can be identified as cystic processes and/or solid tumors by means of imaging, thereby setting an indication for a potential surgical resection. This review presents diagnostically relevant aspects of intraductal neoplasms of the pancreas, which are instrumental for the discussion within interdisciplinary tumor boards (resection vs. watch-and-wait strategies) as well as to determine the extent of resection intraoperatively.


Evaluating the Potential of Boswellia rivae to Provide Sustainable Livelihood Benefits in Eastern Ethiopia.
Frankincense is an oleo-gum-resin collected from wild Boswellia spp. trees, and widely used in perfumery, cosmetics, aromatherapy, incense, and other industries. Boswellia rivae, growing in Ethiopia, Somalia, and Kenya, is one source of frankincense, but is little-commercialized compared to species such as B. sacra, B. frereana, and B. papyrifera. In this study, we examine the resin essential oil chemistry and harvesting systems of B. rivae in order to evaluate its potential for increased trade and potential positive livelihood benefits. Boswellia rivae produces an essential oil rich in α-thujene (0.1-12.4%), α-pinene (5.5-56.4%), β-pinene (0.3-13.0%), δ-3-carene (0.1-31.5%), p-cymene (1.4-31.2%), limonene (1.8-37.3%), β-phellandrene (tr-5.6%), trans-pinocarveol (0.1-5.0%), trans-verbenol (0.1-11.2%), and trans-β-elemene (0-5.7%), similar to major commercial species, although it is difficult to detect mixing of B. rivae and Commiphora africana resins from chemistry alone. The B. rivae trees are not actively tapped, so resin collection has a neutral impact on the health of the trees, and resin production is unaffected by drought. Consequently, collecting resins acts as a key income supplementing livestock herding, as well as a safety net protecting pastoral communities from the severe negative effects of climate change-exacerbated drought on livestock. Therefore, Boswellia rivae is well positioned chemically, ecologically, and socially to support expanded trade.


Complete chloroplast genome sequence of Magnolia grandiflora and comparative analysis with related species.
Magnolia grandiflora is an important medicinal, ornamental and horticultural plant species. The chloroplast (cp) genome of M. grandiflora was sequenced using a 454 sequencing platform and the genome structure was compared with other related species. The complete cp genome of M. grandiflora was 159623 bp in length and contained a pair of inverted repeats (IR) of 26563 bp separated by large and small single copy (LSC, SSC) regions of 87757 and 18740 bp, respectively. A total of 129 genes were successfully annotated, 18 of which included introns. The identity, number and GC content of M. grandiflora cp genes were similar to those of other Magnoliaceae species genomes. Analysis revealed 218 simple sequence repeat (SSR) loci, most composed of A or T, contributing to a bias in base composition. The types and abundances of repeat units in Magnoliaceae species were relatively conserved and these loci will be useful for developing M. grandiflora cp genome vectors. In addition, results indicated that the cp genome size in Magnoliaceae species and the position of the IR border were closely related to the length of the ycf1 gene. Phylogenetic analyses based on 66 shared genes from 30 species using maximum parsimony (MP) and maximum likelihood (ML) methods provided strong support for the phylogenetic position of Magnolia. The availability of the complete cp genome sequence of M. grandiflora provides valuable information for breeding of desirable varieties, cp genetic engineering, developing useful molecular markers and phylogenetic analyses in Magnoliaceae.


Does the presence of an emergency physician improve access based quality indicators in a rural emergency department?
To assess the effect that the presence of an emergency physician in the ED has on the access indicators of the Australian Council on Healthcare Standards. A retrospective study was carried out in a 265 bed regional referral hospital in Victoria. The performance of the ED over a 6 month period, during which time there was incomplete emergency physician coverage, was monitored using The Australian Council on Healthcare Standards (ACHS) access indicators as the benchmark. These indicators are waiting time by triage category, and access block. A total of 11 999 patient presentations were eligible for inclusion in the study. Emergency physicians were present for 76.5% of these presentations. All the indicators show a trend towards improvement when an emergency physician was present. However, the only indicator that shows a significant improvement is waiting time by triage category, and this is due mainly to an improvement within triage category 4. There is some evidence that the presence of an emergency physician improves performance within this group of access based indicators within a rural ED, however, the effect seen here is small. More studies are needed on this topic and also on the development of quality indicators for rural ED.


'Candyflipping': synergistic discriminative effect of LSD and MDMA.
The co-administration of D-lysergic acid diethylamide (LSD; 'Acid') and 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy'; 'XTC'), has reached a prevalence that has allowed for the street terminology 'candyflipping' to describe the combination. Internet sites indicate a significant enhancement of central effects with their simultaneous use. In this preliminary observation, male Fawn-Hooded rats were trained to discriminate 1.5 mg/kg MDMA and were, subsequently, tested with doses of MDMA (0.15 mg/kg) or LSD (0.04 mg/kg) that each produced a saline-like response. Co-administration of these doses of MDMA and LSD synergized to produce a maximal MDMA-like response. The possible mechanism for synergistic action upon central serotonergic neurons is discussed to explain the observed effect.


Time-Dependent Factors Influencing Cardiocerebral Vascular Events in Chronic Hemodialysis Patients: Insights from a Longitudinal Study.
BACKGROUND Cardiocerebral vascular events (CVCs) are significant complications in patients undergoing hemodialysis (HD). Given the increased morbidity and mortality associated with CVCs in this population, understanding the factors influencing CVC occurrence over time is crucial. This study aimed to investigate these time-dependent factors in HD patients. MATERIAL AND METHODS A total of 228 HD patients from 2 dialysis centers, with at least 3 months of treatment between 2017 and 2021, were included. Annual clinical data were collected, and patients were monitored until CVC development. Kaplan-Meier analysis and a time-dependent Cox regression model were used for data analysis. RESULTS The mean age of 228 patients was 55.0±15.0 years, and 64.76% were male. For 5 years of monitoring, the mean follow-up interval was 3.1±1.0 years for patients to develop CVCs. The 1-year, 3-year, and 5-year CVC-free rates were 97.47%, 81.31%, and 70.71%, respectively. Time-dependent Cox regression revealed that C-reactive protein was an independent time-dependent risk factor in HD patients and blood flow rate was an independent time-dependent protective factor. The male subgroup and non-diabetic subgroup had these same results. The following were was the independent time-dependent risk factors: white blood cell count for the female subgroup; blood flow rate for the non-elderly subgroup; and C-reactive protein for the diabetic subgroup. None were risk factors for the elderly subgroup. CONCLUSIONS It took an average of 3.1±1.0 years for patients with HD to develop CVCs. C-reactive protein and blood flow rate emerged as key time-dependent influencing factors for CVCs in this population.


Expression of two zebrafish homologues of the murine Six3 gene demarcates the initial eye primordia.
The murine homeobox gene Six3 and its Drosophila homologue sine oculis both have regulatory functions in eye development. We report the isolation and characterization of two zebrafish genes, six3 and six6, that are closely related to the murine Six3 gene. Zebrafish six3 may be the structural orthologue, while the six6 gene is more similar with respect to embryonic expression. Transcripts of both zebrafish six genes are first detected in involuting axial mesendoderm and, subsequently, in the overlying anterior neural plate from which the optic vesicles and the forebrain will develop. Direct correspondence between six3/six6 expression boundaries and the optic vesicles indicate essential roles in defining the eye primordia. During later stages only the six6 gene displays similar features of expression in the eyes and rostral brain as reported previously for murine Six3.


Relationship of embryonic development to egg weight, hatch weight, and growth in Japanese quail.
Relationships between egg, embryo, hatch, two-week and four-week body weights of three quail lines differing in growth rate were investigated. Two of the quail lines had previously undergone 29 generations of selection for increased four-week body weight, and the third line was a nonselected control. Selected lines produced heavier eggs, larger 10 to 11 day embryos, and larger chicks. Percent embryo weights were similar for all three lines indicating that correction for egg size eliminated differences in embryo weight. Percentages of hatch weights of selected lines were significantly (P less than .01) larger than comparable percentages in the control line. Correlations between egg and embryo weights were of low magnitude but correlations between egg and hatch weights were large (.7 to .8). Mean regression coefficients for four-week body weight on egg weight were 5.11 and 2.67 g. in trials 1 and 2, respectively. Relationships between egg, embryo, hatch, and body weights of Japanese quail appeared to be of the same general magnitude as those observed in the domestic fowl.


Systematic identification of core transcription factors mediating dysregulated links bridging inflammatory bowel diseases and colorectal cancer.
Accumulating evidence shows a tight link between inflammation and cancer. However, comprehensive identification of pivotal transcription factors (i.e., core TFs) mediating the dysregulated links remains challenging, mainly due to a lack of samples that can effectively reflect the connections between inflammation and tumorigenesis. Here, we constructed a series of TF-mediated regulatory networks from a large compendium of expression profiling of normal colonic tissues, inflammatory bowel diseases (IBDs) and colorectal cancer (CRC), which contains 1201 samples in total, and then proposed a network-based approach to characterize potential links bridging inflammation and cancer. For this purpose, we computed significantly dysregulated relationships between inflammation and their linked cancer networks, and then 24 core TFs with their dysregulated genes were identified. Collectively, our approach provides us with quite important insight into inflammation-associated tumorigenesis in colorectal cancer, which could also be applied to identify functionally dysregulated relationships mediating the links between other different disease phenotypes.


Cis-regulatory elements in the Accord retrotransposon result in tissue-specific expression of the Drosophila melanogaster insecticide resistance gene Cyp6g1.
Transposable elements are a major mutation source and powerful agents of adaptive change. Some transposable element insertions in genomes increase to a high frequency because of the selective advantage the mutant phenotype provides. Cyp6g1-mediated insecticide resistance in Drosophila melanogaster is due to the upregulation of the cytochrome P450 gene Cyp6g1, leading to the resistance to a variety of insecticide classes. The upregulation of Cyp6g1 is correlated with the presence of the long terminal repeat (LTR) of an Accord retrotransposon inserted 291bp upstream of the Cyp6g1 transcription start site. This resistant allele (DDT-R) is currently at a high frequency in D. melanogaster populations around the world. Here, we characterize the spatial expression of Cyp6g1 in insecticide-resistant and -susceptible strains. We show that the Accord LTR insertion is indeed the resistance-associated mutation and demonstrate that the Accord LTR carries regulatory sequences that increase the expression of Cyp6g1 in tissues important for detoxification, the midgut, Malpighian tubules, and the fat body. This study provides a significant example of how changes in tissue-specific gene expression caused by transposable-element insertions can contribute to adaptation.


A model for extradenticle function as a switch that changes HOX proteins from repressors to activators.
The Drosophila EXD protein and its mammalian counterparts, the PBX proteins, have been proposed to function in HOX target selectivity. Here we show that exd function is required for the autoactivation phase of Dfd expression in the posterior head. Mutations that change the affinity of a small autoactivation element for EXD protein result in corresponding changes in the element's embryonic activity. Our data suggest that the EXD and DFD proteins directly activate this element in maxillary cells without cooperatively binding to a specialized heterodimer binding site. Based on the types of homeotic transformations and changes in gene expression observed in exd mutant embryos, we propose a new model for EXD/PBX action in which these proteins are required for HOX protein transcriptional activation functions, but dispensable for HOX transcriptional repression functions. Although the selection of a specific target gene by a HOX protein versus another may be explained in some cases by the selective modulation of HOX binding specificity by EXD, we favor the idea that EXD interacts in a more general sense with most HOX proteins to switch them into a state where they are capable of transcriptional activation.


Giant thoracic discs: treatment, outcome, and follow-up of 33 patients in a single centre.
To help guide treatment strategies and create insight into functional outcomes in patients with Giant herniated thoracic discs (GHTD), which are defined as occupying more than 40% of spinal canal. Authors did a retrospective analysis of prospective cohort of 33 cases of GHTD, using clinical letters, notes, and telephonic questionnaires to determine their pre and postoperative functional status, surgical details, and complication rates. 16 males and 17 females operated between 2006 and 2014 were included in the study. A total of 23 patients underwent thoracotomy, 9 costotransversectomy, and 2 transpedicular approaches for excision of thoracic discs. Neuromonitoring was used in seven patients. Frankel grade improved by 1 in 13 patients and by 2 in 1 patient. One patient of T11/12 GHTD with neurogenic claudication recovered completely, taking the overall improvement rate to 45.5%. It remained static in 15 patients (45.5%) and deteriorated by 1 in 3 patients (9%). By mJOA scoring too, the outcome was favorable in majority (84.4%) of patients. There were three intraoperative complications (9%), which included two incidental durotomies and one massive blood loss. Late postoperative complications were seen in 12(39%) patients. They included intercostal neuralgia, mechanical pain around costotransversectomy, progressive thoracic paraplegia due to spinal cord herniation and residual disc fragments, reactive pleural effusion, CSF fistula induced pleural effusion, and infective discitis. Surgery for giant herniated thoracic disc has favorable outcome in majority (91%) of patients. However, significant approach-related complications are to be anticipated in patients undergoing thoracotomies, most of them being manageable. Author recommends costotransversectomy, only in paracentral discs with smaller percentage canal stenosis.


Gossypiboma as a cause of intestinal obstruction.
Gossypiboma / textiloma / retained surgical sponge is an avoidable surgical complication which can lead to patient morbidity, mortality and profound medicolegal implications. Retained surgical sponge can present early as abscess formation and septic complications or follow a silent course for many years to present later as intestinal obstruction, fistula formation or simply be extruded through rectum. A lady presented 8 months after laparotomy with symptoms of bowel obstruction due to a retained surgical sponge that had eroded into the rectosigmoid junction. The introduction of WHO Safety Checklist in operation theatres where advance tagging systems are not available, would lead to development of standard protocols and help in avoiding the occurrence of such retained surgical foreign bodies.