Catching a Big Fish with a Small Net: Factors Associated with First-Choice Match from Urology Residency Applicants' Self-Reported Data.
We sought to determine the accuracy of self-reported urology applicant match data and determine which factors were most influential on successful application outcomes. A publicly accessible Google spreadsheet entitled "Urology Residency Applicant Spreadsheet" containing self-reported urology residency applicant characteristics and match outcomes was analyzed for differences across the years 2017+2018 (pre-aggregated)-2020. These data were compared to published data from the American Urological Association and the Association of American Medical Colleges. Statistical modeling of the self-reported data was performed to determine which applicant characteristics were predictive of match outcomes. Averages of self-reported data were similar to published match data with a bias towards more competitive applicants. The factors associated with increased interview offer rate were: Step 1 score, Step 2 score, number of research items, class quartile, and Alpha Omega Alpha membership. Logistic regression modeling correctly predicted an applicant matching to their first-choice program with 74.7% accuracy, with significant negative predictors being the number of programs to which the applicant applied and interviews offered from waitlist or cancellations, and positive predictors being the number of interview offers received. Many applicants "apply broadly" with the goal of improving their match outcomes, but we found that applying to more programs is associated with a decreased likelihood of the applicant matching to their first-choice program. Applicant characteristics such as United States Medical Licensing Examination® scores were not related to first-choice match, suggesting that program selection, among other factors, is vital in the match process.


The efficacy of postoperative bracing after spine surgery for lumbar degenerative diseases: a systematic review.
Postoperative bracing treatment is widely used after surgery for lumbar degenerative diseases. However, the guidelines are lacking in this regard, and its use is mainly driven by individual surgeon preferences. The objective of the current review was to evaluate the available evidence on the use of postoperative bracing after surgery for degenerative disease of the lumbar spine. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed while conducting a systematic search of the PubMed/Medline, Scopus, and Cochrane databases from January 1990 to January 2019. High-quality studies were included that evaluated disability, pain, quality of life, the rate of fusion, complications, and rate of reoperations in patients who had surgery for lumbar degenerative disease, with and without postoperative bracing. The overall strength of evidence across the studies was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework. Of the 391 citations screened, four randomized controlled trials met the inclusion criteria and were included in the review. Based on low- to moderate-quality evidence, postoperative bracing in patients with lumbar degenerative disease does not result in improved disability, pain, and quality of life compared to no bracing patients. Low-quality evidence suggests that there was no significant difference between the two groups in terms of the rate of fusion, complications, and the need for reoperation. To date, there is not a medical evidence to support the use of bracing after surgery for lumbar degenerative disease. These slides can be retrieved under Electronic Supplementary Material.


A prioritization framework for the analysis of near misses in radiation oncology.
The term near miss implies the aversion of a harm event but often there is a lack of evidence when establishing a link between a failure in process and potential harm. The focus of this study was to use reported incident data to inform a prioritization framework for the triage of near miss events in a radiation therapy program. Actual and near miss events during the study period were categorized using thematic analysis based on incident types. Near miss were characterized based upon their potential to result in harm to the patient using the concepts of failure modes and Analytic Hierarchy Process (AHP) theory. Near miss events were assessed for occurrence, detection and the potential impact and then assigned a summative normalized score reflecting prioritization recommendations, the normalized 10 point score (NTPS). 107 events were reported within the study timeframe. 65% of event type categories (n = 20) were attributed to near misses. 107 total events we analyzed using the framework with a maximum NTPS of 4 achieved across all event types. Of the 47 actual events 100% received a NTPS of 3 or greater. Of the 60 near miss invents 47% received an NTPS less than or equal to 1. Finally 15% of near miss events received a NTPS of 3 or greater. Near miss events provide a unique opportunity for learning however, can yield a great deal of data potentially limiting the resources for effective incident learning. A FMEA and AHP based prioritization framework for the triage of near miss events, including the likelihood of occurrence, probability of the event to go undetected and the potential impact if the incident did occur, allows for the optimal focus of programmatic resources in the analysis of these events.


Diagnosis and management of nonvariceal upper gastrointestinal bleeding.
Nonvariceal upper gastrointestinal bleeding (UGIB) is a major cause of morbidity and mortality worldwide. Despite the improvements in the management of this condition in western countries, mortality rates have remained at 5-10% over the past decade. This article presents the main recommendations for the management of UGIB. Pre-endoscopic management (including use of scoring scales, nasogastric tube placement and blood pressure stabilization) is crucial for triage and optimal resuscitation of patients, and should include a multidisciplinary approach at an early stage. Unless the patient has specific comorbidities, transfusion should only be considered if their hemoglobin level is ≤70 g/l. Endoscopic therapy, the cornerstone of therapeutic management of high-risk lesions, should not be delayed for more than 24 h following admission. Several endoscopic techniques, mostly using clips or thermal methods, are available and new approaches are emerging. When endoscopy fails, surgery or arterial embolization should be considered. Although the efficacy of prokinetics and high-dose intravenous PPI prior to endoscopy is controversial, the use of an intravenous PPI following endoscopy is strongly recommended. Antiplatelet therapy should be suspended and resumed in 3-5 days. Finally, all patients should be tested for Helicobacter pylori by serology in the acute setting.


Contrast trees and distribution boosting.
A method for decision tree induction is presented. Given a set of predictor variables [Formula: see text] and two outcome variables y and z associated with each x, the goal is to identify those values of x for which the respective distributions of [Formula: see text] and [Formula: see text], or selected properties of those distributions such as means or quantiles, are most different. Contrast trees provide a lack-of-fit measure for statistical models of such statistics, or for the complete conditional distribution [Formula: see text], as a function of x. They are easily interpreted and can be used as diagnostic tools to reveal and then understand the inaccuracies of models produced by any learning method. A corresponding contrast-boosting strategy is described for remedying any uncovered errors, thereby producing potentially more accurate predictions. This leads to a distribution-boosting strategy for directly estimating the full conditional distribution of y at each x under no assumptions concerning its shape, form, or parametric representation.


Deviation from homeoviscous adaptation in Escherichia coli membranes.
The process by which an organism changes the composition of its membranal fatty acids in response to growth temperature, so as to maintain optimal membrane functioning, is known as homeoviscous adaptation (HA). One expression of HA is the constancy of the fluorescence polarization (P) of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene (DPH) in membranes of cells grown at various temperatures. The P of DPH in the membranes of Escherichia coli was shown by us to be inversely proportional to bacterial growth rate on different carbon sources. This result, implying failure of HA, is now complemented by measurements of DPH lifetimes, which indicate that the dominant variables contributing to the drop in P are (a) the order parameter of the membrane, which goes down, and (b) the fluidity, which may slightly increase. These are then the changes induced by enhanced growth rate. Two additional effects, cell membrane permeability and sensitivity to thermal shock, determined by the diffusion of o-nitrophenylgalactoside (ONPG) and by exposure to 52 degrees C, respectively, are reported to increase with growth rate. We can now conclude that there is a deviation from the principle of HA in E. coli grown at various rates, brought about by controlling the growth media at constant temperatures.


Field energetics of a large carnivorous lizard, Varanus rosenbergi.
Field metabolic rates (FMRs; CO2 production) and water influx rates of Varanus rosenbergi were measured seasonally by means of doubly-labelled water (3H218O). Metabolic rates and water influexes were highest in summer (0.18 ml CO2 g-1 h-1 and 17.9 ml H2O kg-1 day-1) and lowest in winter (0.04 ml CO2 g-1 h-1 and 6.5 ml H2O kg-1 day-1). FMRs and water fluxes were intermediate in spring. It is estimated that a 1-kg V. rosenbergi would need to consume 4.7 kg of prey each year to remain in energy balance and that the energy commitment to egg production requires a 40% increase in the food acquisition of a gravid female in late spring and early summer. It is calculated that water influxes in summer are totally provided from food but in other seasons, particularly winter, pulmocutaneous water exchange and/or drinking are significant avenues of water intake.


Synthesis, reactivity, X-ray characterization and docking studies of N7/N9-(2-pyrimidyl)-adenine derivatives.
The reaction of adenine with 2-chloropyrimidine yields as a major product the unexpected N7-(2-pyrimidyl)-adenine (1) and as a minor one N9-(2-pyrimidyl)-adenine (2). Both compounds have been characterized by X-ray diffraction analysis. Moreover, we report the formation of a 1:1 co-crystal (3) composed by compound (1) and adenine that was formed serendipitously during the synthesis of (1). Unexpectedly, the treatment of (1) with Brönsted acids like HCl or HNO3 causes the opening of the imidazole ring of the N7-substituted adenine, yielding N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine (4-7) which we have X-ray characterized in its neutral, (4), monoprotonated [nitrate salt (6)] and diprotonated forms [hydrochloride salt (5) and, also, a tetrachlorozincate salt (7)]. Finally, we have used compound (5) as ligand to synthesize and X-ray characterize its complexes with Ir(III) and Ag(I) (compounds (8) and (9), respectively), where the latter is a 2D coordination polymer and the former is a discrete mononuclear complex. We have studied the supramolecular assemblies formed in the solid state by using density functional theory (DFT) calculations. Finally, DNA-docking studies of several compounds have been carried out in order to analyze their ability to interact with the DNA.


Markers for hepatitis A, B and C in methadone maintained patients: an unexpectedly high co-infection with silent hepatitis B.
To determine the prevalence of hepatitis A, B and C viruses in patients attending a methadone maintenance clinic in New York City. Cross-sectional. The Adult Services Clinic of Weill Cornell Medical College, an urban hospital-affiliated methadone program. Former heroin addicted adults (n = 103) on methadone maintenance therapy. Markers for hepatitis A virus [HAV immunoglobulin M (IgM) and imunoglobulin G (IgG)], hepatitis B [hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb)] and hepatitis C virus (HCVAb). Serum alanine aminotransferase (ALT) and quantitative HCV RNA were also obtained. Qualitative detection of HBV DNA and HCV genotype were obtained in a subset of subjects. More than 40% of subjects had markers for all three viruses. HCVAb was the most prevalent (83.5%), followed by HBcAb (65.0%), HAV IgG (46.1%) and HBsAb (41.1%). Hepatitis C RNA was detected in 70.6% of HCVAb positive subjects. While no subject had HBsAg, HBV DNA was detected in 26.4% of subjects who underwent this measure; all (n = 20) had HBcAb as their only HBV marker. The presence of HBV DNA did not influence ALT. Subjects with HCV RNA had higher ALTs than those without HCV RNA. Most methadone-maintained subjects had at least one marker for viral hepatitis, with 41.8% having markers for HAV, HBV and HCV. A quarter of subjects had silent HBV infection, defined as the presence of HBV DNA in the absence of HBsAg. These subjects should be considered infectious and pose a public health risk.


Sexual and Reproductive Health at 2015 and Beyond: A Global Perspective.
The International Conference on Population and Development and Millennium Development Goals propelled reproductive health into priorities for international development through declarations, statements, and frameworks. However, key indicators demonstrate that progress in both service provision and clinical outcomes has not been optimal, especially for certain disadvantaged groups. With the Sustainable Development Goals, efforts over the next two decades will focus on access to and quality of health services. Advocacy for mobilizing resources will be complemented by accountability, especially monitoring and evaluation, for utilization of these resources during the life cycle. Stakeholders should emphasize national commitments, with broad partnerships, to ensure long-term sustainability.


In situ exposure to non-directional beacons for air traffic control.
In situ electromagnetic field exposure of workers and the general public due to non-directional beacons (NDB) for air traffic control is assessed and characterized. For occupational exposure, the maximal measured electric field value is 881.6 V/m and the maximal magnetic field value is 9.1 A/m. The maximum electric fields exceed the International Commission on Non-Ionizing Radiation Protection (ICNIRP) reference levels at all seven NDB sites, and the magnetic fields at two of the seven NDB sites (occupational exposure). Recommendations and compliance distances for workers and the general public are provided.


The spontaneous immortalization probability of mammalian cell culture strains, as their proliferative capacity, correlates with species body mass, not longevity.
The Peto's paradox consists in the observation that individuals from long-lived and large animal species do not experience a higher cancer incidence, despite being exposed for longer time to the possibility of accumulating mutations and having more target cells exposed to the phenomenon. The existence of this paradox has been recently confirmed (Vincze et al., 2022). Concurrently, robust evidence has been published that longevity involves a convergent evolution of cellular mechanisms that prevent the accumulation of mutations (Cagan et al., 2022). It remains unclear which cellular mechanisms are critical to allow the evolution of a large body mass while keeping cancer at bay. Adding to existing data linking cellular replicative potential and species body mass (Lorenzini et al., 2005), we have grown a total of 84 skin fibroblast cell strains from 40 donors of 17 mammalian species and analyzed their Hayflick's limit, i.e., their senescent plateau, and eventual spontaneous immortalization escape. The correlation of immortalization and replicative capacity of the species with their longevity, body mass and metabolism has been assessed through phylogenetic multiple linear regression (MLR). The immortalization probability is negatively related to species body mass. The new evaluation and additional data about replicative potential strengthen our previous observation, confirming that stable and extended proliferation is strongly correlated with the evolution of a large body mass rather than lifespan. The relation between immortalization and body mass suggests a need to evolve stringent mechanisms that control genetic stability during the evolution of a large body mass.


Pesticide exposure resulting from treatment of lice infestation in school-aged children in Georgia.
The objective of this study was to assess pesticide exposures in children being treated for head lice with either lindane or permethrin (exposed group) and children who did not have a lice infestation and thus were not being treated with chemicals for head lice or scabies (unexposed group). In 2001, we enrolled 78 children aged 6-10 years old and collected baseline urine samples and demographic information from all the children. We subsequently collected post-exposure urine samples and questionnaire information about lice treatment from the 29 (37%) children (exposed children) who had been diagnosed and were being treated for head lice. Metabolites of the pesticides lindane and permethrin were measured in the samples. The mean age of exposed and unexposed children in the study population was 9.3 years and 8.5 years, respectively. Fourteen of the 29 exposed children used prescription lice treatments (i.e., lindane or malathion); 25 of the 29 exposed children used at least one over-the-counter permethrin treatment, either alone or in addition to prescription treatments. Exposed children in both counties had higher urinary pyrethroid metabolite levels in their post-exposure samples compared with their baseline samples. However this difference was only significant in Forsyth County children. The significantly increased post-exposure pyrethroid metabolite levels in the urine of Forsyth County children suggest that the children are exposed to pyrethroid insecticides through the use of lice shampoos.


The effect of C60 fullerene on the mechanokinetics of muscle gastrocnemius contraction in chronically alcoholized rats.
The C60 fullerene effect (oral administration at a dose of 1 mg kg-1) on the selected biomechanical parameters of muscle gastrocnemius contraction, biochemical indicators of blood and muscle tissue as well as histological changes in rat muscle tissue after chronic alcoholization for 3, 6 and 9 months was studied in detail. Water-soluble C60 fullerenes were shown to reduce the pathological processes development in the muscle apparatus by an average of (35-40)%. In particular, they reduced the time occurrence of fatigue processes in muscle during the long-term development of alcoholic myopathy and inhibited oxidative processes in muscle, thereby preventing its degradation. These findings open up the possibility of using C60 fullerenes as potent antioxidants for the correction of the pathological conditions of the muscle system arising from alcohol intoxication.


Ischemic lesions in basal ganglia in children after minor head injury.
Twenty-three children under the age of 6 1/2 years developed immediate unilateral weakness after an apparently minor head injury. Computed tomography disclosed a hypodense lesion in the basal ganglia. The lesion appeared to be caused by an infarct in the basal ganglia. All but one of the children recovered completely within 4 months.


Development of an environmental radiation analysis research capability in the UAE.
The UAE has started a nuclear energy program with the aim of having its first four units on-line between 2017 and 2020 and it is important that the country has an environmental radiation analysis capability to support this program. Khalifa University is therefore implementing a research laboratory to support both experimental analysis and radionuclide transport modeling in the aquatic and terrestrial environment. This paper outlines the development of this capability as well as the work in progress and planned for the future.


The product of the pilQ gene is essential for the biogenesis of type IV pili in Neisseria gonorrhoeae.
The product of the Neisseria gonorrhoeae omc gene possesses regions homologous to those found in members of a protein superfamily that are associated with the translocation of proteins and DNA-protein complexes across the outer membrane. Amongst its protein homologues, Omc has higher overall homology to PilQ, which is required for type IV pilus expression in Pseudomonas aeruginosa, and OrfE, which is required for sequence-specific DNA uptake by Haemophilus influenzae. The function of Omc, however, is unknown and gonococcal omc mutants have not been described. We constructed gonococcal mutants expressing truncated forms of the protein, and found that these mutants are severely defective for both pilus expression and competence for natural transformation. To be consistent with pre-existing pilus gene nomenclature, we have redesignated the gene pilQ instead of omc, and its product, PilQ instead of Omc. The MS11 gene was sequenced and found to differ from the DNA sequence reported for that of another gonococcal strain; these differences were associated with a repeated DNA element, suggesting a genetic basis for structural variation in PilQ. The results also show that PilQ- mutants are distinct from previously described gonococcal pilus-assembly mutants and P. aeruginosa PilQ- mutants by virtue of their expression of rare pilus filaments. Taking these data into account, PilQ is proposed to function in the terminal steps of organelle biogenesis by acting as a pilus channel or pore.


Structural mechanisms of TRPM7 activation and inhibition.
The transient receptor potential channel TRPM7 is a master regulator of the organismal balance of divalent cations that plays an essential role in embryonic development, immune responses, cell mobility, proliferation, and differentiation. TRPM7 is implicated in neuronal and cardiovascular disorders, tumor progression and has emerged as a new drug target. Here we use cryo-EM, functional analysis, and molecular dynamics simulations to uncover two distinct structural mechanisms of TRPM7 activation by a gain-of-function mutation and by the agonist naltriben, which show different conformational dynamics and domain involvement. We identify a binding site for highly potent and selective inhibitors and show that they act by stabilizing the TRPM7 closed state. The discovered structural mechanisms provide foundations for understanding the molecular basis of TRPM7 channelopathies and drug development.


Oxidative metabolism of rabbit and rat intestine with short chain fatty acids and glucose: an evaluation of data analysis.
1. Glucose sustained VO2 of rabbit ileum, caecum, and distal colon better than SCFAs. 2. In rabbit proximal colon, while VO2 was stimulated in the presence of butyrate it was not sustained. 3. Rat caecum utilized glucose but it was not necessarily the best substrate for either the ileum or colon of this species and SCFAs appeared to stimulate VO2 of rat ileum and inhibit VO2 in rat caecum and colon. 4. It was concluded from the comparison of the two methods of data analyses that curve-fitting the data by a negative exponential equation provides for a more clear and in depth interpretation of such studies.


Quantitative susceptibility mapping (QSM) and R2* of silent cerebral infarcts in sickle cell anemia.
Silent cerebral infarction (SCI) is the most commonly reported radiological abnormality in patients with sickle cell anemia (SCA) and is associated with future clinical stroke risk. To date, there have been few histological and quantitative MRI studies of SCI and multiple radiological definitions exist. As a result, the tissue characteristics and composition of SCI remain elusive. The objective of this work was therefore to investigate the composition of segmented SCI lesions using quantitative MRI for R 2 * and quantitative magnetic susceptibility mapping (QSM). 211 SCI lesions were segmented from 32 participants with SCA and 6 controls. SCI were segmented according to two definitions (FLAIR+/-T1w-based threshold) using a semi-automated pipeline. Magnetic susceptibility (χ) and R 2 * maps were calculated from a multi-echo gradient echo sequence and mean SCI values were compared to an equivalent region of interest in normal appearing white matter (NAWM). SCI χ and R 2 * were investigated as a function of SCI definition, patient demographics, anatomical location, and cognition. Compared to NAWM, SCI were significantly less diamagnetic (χ = -0.0067 ppm vs. -0.0153 ppm, p < 0.001) and had significantly lower R 2 * (16.7 s-1 vs. 19.2 s-1, p < 0.001). SCI definition had a significant effect on the mean SCI χ and R 2 * , with lesions becoming significantly less diamagnetic and having significantly lower R 2 * after the application of a more stringent T1w-based threshold. SCI-NAWM R 2 * decrease was significantly greater in patients with SCA compared with controls (-2.84 s-1 vs. -0.64 s-1, p < 0.0001). No significant association was observed between mean SCI-NAWM χ or R2* differences and subject age, lesion anatomical location, or cognition. The increased χ and decreased R 2 * in SCI relative to NAWM observed in both patients and controls is indicative of lower myelin or increased water content within the segmented lesions. The significant SCI-NAWM R 2 * differences observed between SCI in patients with SCA and controls suggests there may be differences in tissue composition relative to NAWM in SCI in the two populations. Quantitative MRI techniques such as QSM and R 2 * mapping can be used to enhance our understanding of the pathophysiology and composition of SCI in patients with SCA as well as controls.


Performance assessment of coupled green-grey-blue systems for Sponge City construction.
In recent years, Sponge City has gained significant interests as a way of urban water management. The kernel of Sponge City is to develop a coupled green-grey-blue system which consists of green infrastructure at the source, grey infrastructure (i.e. drainage system) at the midway and receiving water bodies as the blue part at the terminal. However, the current approaches for assessing the performance of Sponge City construction are confined to green-grey systems and do not adequately reflect the effectiveness in runoff reduction and the impacts on receiving water bodies. This paper proposes an integrated assessment framework of coupled green-grey-blue systems on compliance of water quantity and quality control targets in Sponge City construction. Rainfall runoff and river system models are coupled to provide quantitative simulation evaluations of a number of indicators of land-based and river quality. A multi-criteria decision-making method, i.e., Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) is adopted to rank design alternatives and identify the optimal alternative for Sponge City construction. The effectiveness of this framework is demonstrated in a typical plain river network area of Suzhou, China. The results demonstrate that the performance of Sponge City strategies increases with large scale deployment under smaller rainfall events. In addition, though surface runoff has a dilution effect on the river water quality, the control of surface pollutants can play a significant role in the river water quality improvement. This framework can be applied to Sponge City projects to achieve the enhancement of urban water management.


MicroRNA-processing enzyme Dicer is required in epicardium for coronary vasculature development.
The epicardium is a sheet of epithelial cells covering the heart during early cardiac development. In recent years, the epicardium has been identified as an important contributor to cardiovascular development, and epicardium-derived cells have the potential to differentiate into multiple cardiac cell lineages. Some epicardium-derived cells that undergo epithelial-to-mesenchymal transition and delaminate from the surface of the developing heart subsequently invade the myocardium and differentiate into vascular smooth muscle of the developing coronary vasculature. MicroRNAs (miRNAs) have been implicated broadly in tissue patterning and development, including in the heart, but a role in epicardium is unknown. To examine the role of miRNAs during epicardial development, we conditionally deleted the miRNA-processing enzyme Dicer in the proepicardium using Gata5-Cre mice. Epicardial Dicer mutant mice are born in expected Mendelian ratios but die immediately after birth with profound cardiac defects, including impaired coronary vessel development. We found that loss of Dicer leads to impaired epicardial epithelial-to-mesenchymal transition and a reduction in epicardial cell proliferation and differentiation into coronary smooth muscle cells. These results demonstrate a critical role for Dicer, and by implication miRNAs, in murine epicardial development.


Is all cancer therapy immunotherapy?
Researchers must renew efforts to decipher how standard chemotherapies enhance the effects of targeted immunotherapeutic agents (Müller et al., this issue).


Prenatal fluoxetine exposure induces life-long serotonin 5-HT₃ receptor-dependent cortical abnormalities and anxiety-like behaviour.
Selective serotonin reuptake inhibitors (SSRIs) are the first choice of drugs to treat depression and anxiety during pregnancy. However, there is evidence that in utero exposure to SSRIs leads to adverse effects in offspring. Here we show that in mice, the adverse effects of the widely used antidepressant and SSRI fluoxetine are critically dependent on the 5-HT(3) receptor, the only ligand-gated ion channel in the family of serotonin receptors. In utero exposure to fluoxetine induces anxiety-like behavior in wildtype, but not in mice lacking the 5-HT(3) receptor. In addition to this behavioral phenotype, these mice show life-long abnormalities of cortical cytoarchitecture, which can be reversed in vitro by pharmacological block of 5-HT(3) receptors. Moreover, the effect of fluoxetine on the development of cortical neurons is absent in 5-HT(3) receptor knockout mice. These findings pinpoint the pivotal role of serotonergic signaling during development and provide a novel basis to investigate the adverse effects of the use of fluoxetine during pregnancy. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.


Prospective evaluation of a small caliber upper endoscope for colonoscopy after unsuccessful standard examination.
Colonoscopy is unsuccessful in some patients because of a fixed sigmoid loop or anatomical stenoses. We prospectively evaluated 1600 patients undergoing colonoscopy at Virginia Mason Medical Center from December 1, 1986 to November 31, 1987. Thirty-one procedures (1.9%) failed to reach the splenic flexure because of functional or anatomic stenoses. Attempt at pancolonoscopy with a 9.8-mm diameter, 102-cm length endoscope (Olympus XQ) was successful to the right colon in 73% and cecum in 60% of these patients. Two thirds of the successfully intubated patients had clarification of radiographic abnormalities or delineation of additional colon pathology. There were no complications or instrument damages, but limitations included short scope length and small suction channel. We conclude that small diameter upper endoscopes can be used safely and effectively for colonoscopy in a subset of patients in whom conventional colonoscopy is unsuccessful.


Benchmark data for sulcal pits extraction algorithms.
This article contains data related to the research article Auzias et al. (2015) [1]. This data can be used as a benchmark for quantitative evaluation of sulcal pits extraction algorithm. In particular, it allows a quantitative comparison with our method, and the assessment of the consistency of the sulcal pits extraction across two well-matched populations.


Paclitaxel effect on a leukemia cell line: importance of paclitaxel concentration.
The efficacy of a drug may be a complex function of the length of drug exposure and the drug concentration. One traditional way to model these variables together has been to look at the area under the curve (AUC) when drug concentration is plotted against time. Experiments in an HL60 leukemia cell model suggest that, for the antineoplastic drug paclitaxel, AUC is not a good predictor of efficacy.


Nanopattern formation on polymer substrate using star-hyperbranched nanospheres.
Hyperbranched polystyrenes (PS) were prepared by living radical photopolymerization of 4-vinylbenzyl N,N-diethyldithiocarbamate as an inimer under UV irradiation. These hyperbranched PS exhibited large amounts of photofunctional dithiocarbamate groups on their outside surfaces. Subsequently, we derived the star-hyperbranched copolymers by grafting from hyperbranched macroinitiator with t-butyl methacrylate. We obtained poly(methacrylic acid) star-hyperbranched PS nanospheres by hydrolysis of poly(t-butyl methacrylate) grafted chains. We studied in detail two-dimensional nanopattern formation on poly(4-vinylpyridine) (P4VP) or partially quaternized P4VP substrate using such nanospheres by electrostatic interaction.


On the type specimens of Pareas macularius Theobald, 1868 and Pareas berdmorei Theobald, 1868 with the designation of a lectotype for Pareas macularius (Squamata: Serpentes: Pareidae).
In two different publications, William Theobald described, during the same year (1868), two taxa at species level in the snake genus Pareas, namely Pareas macularius and Pareas berdmorei, both based on the same syntypes. However, these two taxa are distinct at species level. We here discuss these descriptions, especially that of P. berdmorei which might have raised a nomenclatural problem. We examined their respective type specimens and we here designate a lectotype for Pareas macularius.


Pharmaceutical payments to Japanese board-certified dermatologists: a 4-year retrospective analysis of personal payments from pharmaceutical companies between 2016 and 2019.
There are prevalent financial relationships between dermatologists and pharmaceutical companies in Japan. However, little was known about the extent of whole picture of the personal payments made to dermatologists by pharmaceutical companies. This study aimed to examine the personal payments to the board-certified dermatologists by the Japanese Dermatological Association from the pharmaceutical companies between 2016 and 2019. Using the publicly disclosed payments data by the pharmaceutical companies between 2016 and 2019, we evaluated the magnitude, prevalence, and trends in the personal payments made to all board-certified dermatologists for the lecturing, writing, and consulting compensations. The payments were descriptively analyzed overall and by dermatologist demographics. Additionally, the payment trends were assessed by generalized estimating equation models. Of 6883 active board-certified dermatologists, 3121 (45.3%) received a total of $33,223,806 personal payments between 2016 and 2019. The median per-physician payments and number of payments (interquartile range) were $1737 ($613-$5287) and 4.0 (2.0-10.0) over the 4 years, respectively. Only top 1%, 5%, 10% of dermatologists received 41.7% (95% confidence interval [CI] 38.2-45.1%), 76.9% (95% CI 74.7-79.1%), and 87.6% (95% CI 86.2-88.9%) of overall payments. The number of dermatologists receiving payments and per-dermatologist payments increased by 4.3% (95% CI 3.1‒5.5%, p < 0.001) and 16.4% (95% CI 13.5‒19.4%, p < 0.001) each year. The board-certification in dermatology-oncology, in cosmetic dermatology, and male sex were significantly associated with higher personal payments with relative monetary values of 2.29 (95% CI 1.65-3.19, p < 0.001), 3.16 (95% CI 1.89-5.26, p < 0.001), and 5.38 (95% CI 4.12-7.04, p < 0.001). Less than half of Japanese board-certified dermatologists received lower personal payments from the pharmaceutical companies than those to other specialists. However, these personal payments were increasingly more prevalent and greater over the 4 years.


Difficulty accessing supervised consumption services during the COVID-19 pandemic among people who use drugs in Vancouver, Canada.
The overdose crisis in Canada has worsened since the emergence of the COVID-19 pandemic. Although this trend is thought to be driven in part by closures or reduced capacity of supervised consumption services (SCS), little is known about the factors that may impede access to such services during the COVID-19 pandemic among people who use drugs. This study sought to characterize the prevalence and correlates of having difficulty accessing SCS during the COVID-19 pandemic among people who use drugs in Vancouver, Canada. Cross-sectional data from two open prospective cohorts of people who use drugs were collected via phone or videoconferencing interviews conducted between July 2020 and November 2020. Multivariable logistic regression analyses were used to examine factors associated with experiencing difficulty accessing SCS. Among the 428 people who use drugs who participated in the study, 223 (54.7%) self-identified as men and the median age was 51 years (1st to 3rd quartile: 42-58). A total of 58 (13.6%) participants reported experiencing difficulty accessing SCS. In a multivariable analysis, factors positively associated with difficulty accessing SCS included daily crystal methamphetamine use (Adjusted odds ratio [AOR] = 2.60; 95% confidence interval [CI] 1.28-5.30), active injection drug use (AOR = 4.06; 95% CI 1.38-11.90), recent non-fatal overdose (AOR = 2.45; 95% CI 1.24-4.85), and unstable housing (AOR = 2.14; 95% CI 1.08-4.23). Age was inversely associated with the outcome (AOR = 0.96; 95% CI 0.93-0.99) in multivariable analyses. The most commonly reported reasons for experiencing difficulty accessing SCS were: COVID-19-related site closure or shortened hours (42.9%) and having to wait too long to use a site (39.3%). We found that people who use drugs with markers of structural vulnerability and drug-related risk were more likely to experience difficulty accessing SCS during the COVID-19 pandemic. These findings point to the need for strategies to support access to such services as part of pandemic response efforts.


Exposure of pregnant mice to triclosan impairs placental development and nutrient transport.
Triclosan (TCS) is associated with spontaneous abortions and fetal growth restriction. Here, we showed that when pregnant mice were treated with 8 mg/kg TCS (8-TCS mice) on gestational days (GD) 6-18 fetal body weights were lower than controls. Placental weights and volumes were reduced in 8-TCS mice. The placental proliferative cells and expression of PCNA and Cyclin D3 on GD13 were remarkably decreased in 8-TCS mice. The decreases in activities and expression of placental System A amino acid or glucose transporters on GD14 and GD17 were observed in 8-TCS mice. Levels of serum thyroxine (T4) and triiodothyronine (T3) were lower in 8-TCS mice than those in controls. Declines of placental Akt, mTOR and P70S6K phosphorylation in 8-TCS mice were corrected by L-thyroxinein (T4). Treating 8-TCS mice with T4 rescued the placental cell proliferation and recovered the activity and expression of amino acid and glucose transporters, which were sensitive to mTOR inhibition by rapamycin. Furthermore, the replacement of T4 could rescue the decrease in fetal body weight, which was blocked by rapamycin. These findings indicate that TCS-induced hypothyroxinemia in gestation mice through reducing Akt-mTOR signaling may impair placental development and nutrient transfer leading to decreases in fetal body weight.


[The significance of the degree of malignancy and proliferation activity of laryngeal carcinoma for regional lymph node metastasis].
On the basis of histoautoradiography of 79 laryngeal tumours, the importance of the degree of malignancy and of 3H-TdR labelling index was analysed. The "dynamic histology" (degree of structural differentiation and proliferation activity) seems to be correlated with the frequency of neck lymph node metastases. This relation provides possibilities for an early diagnosis of node involvement and an early adequate treatment.


Electron-transfer oxidation of coenzyme B12 model compounds and facile cleavage of the cobalt(IV)-carbon bond via charge-transfer complexes with bases. A negative temperature dependence of the rates.
The electron-transfer oxidation and subsequent cobalt-carbon bond cleavage of vitamin B12 model complexes were investigated using cobaloximes, (DH)2Co(III)(R)(L), where DH- = the anion of dimethylglyoxime, R = Me, Et, Ph, PhCH2, and PhCH(CH3), and L = a substituted pyridine, as coenzyme B12 model complexes and [Fe(bpy)3](PF6)3 or [Ru(bpy)3](PF6)3 (bpy = 2,2'-bipyridine) as a one-electron oxidant. The rapid one-electron oxidation of (DH)2Co(III)(Me)(py) (py = pyridine) with the oxidant gives the corresponding Co(IV) complexes, [(DH)2Co(IV)(Me)(py)]+, which were well identified by the ESR spectra. The reorganization energy (lambda) for the electron-transfer oxidation of (DH)2Co(Me)(py) was determined from the ESR line broadening of [(DH)2Co(Me)(py)]+ caused by the electron exchange with (DH)2Co(Me)(py). The lambda value is applied to evaluate the rate constants of photoinduced electron transfer from (DH)2Co(Me)(py) to photosensitizers in light of the Marcus theory of electron transfer. The Co(IV)-C bond cleavage of [(DH)2Co(Me)(py)]+ is accelerated significantly by the reaction with a base. The overall activation energy for the second-order rate constants of Co(IV)-C bond cleavage of [(DH)2Co(IV)(Me)(py)]+ in the presence of a base is decreased by charge-transfer complex formation with a base, which leads to a negative activation energy for the Co(IV)-C cleavage when either 2-methoxypyridine or 2,6-dimethoxypyridine is used as the base.


Exposure of mice to a predator odor increases acoustic startle but does not disrupt the rewarding properties of VTA intracranial self-stimulation.
The present investigation assessed the propensity of an acute psychogenic stressor exposure to induce behavioral change in paradigms assessing fear/anxiety (acoustic startle) and motivation/anhedonia (intracranial self-stimulation) in CD-1 mice. In the acoustic startle paradigm, a 10-min exposure of 2-4 month old mice (young adult mice) to fox odor (2,5-dihydro-2,4,5-trimethylthiazoline; TMT) was associated with decreased acoustic startle relative to mice exposed to the control odor, butyric acid (BA), immediately and relative to both saline and BA exposure 24 h following odor exposure in the home cage. In contrast, a 2-min exposure of young adult mice to TMT was associated with an increase in startle relative to saline and BA during the immediate post-odor test session only. In young adult mice a 2-min and a 10-min exposure to BA resulted in a startle profile of mice reminiscent of saline-treated mice. In comparison to young adult mice, a 2-min exposure of mature adult mice (5-7 months old) to TMT enhanced startle for up to 48 h relative to both saline and BA, while a 10-min exposure of mature adult mice to TMT enhanced startle for 168 h post-odor exposure relative to saline-exposed mice only. However, the greatest increase in startle amplitude (i.e. 48 h) was acquired following the 2-min exposure of mature mice to TMT. Among mature adult mice, a 10-min exposure to BA in the home cage eventuated in enhanced startle relative to saline-exposed animals 168 h following odor exposure. In comparison, exposure of mice to 10 min of TMT depressed responding for VTA brain stimulation at the initial 80 Hz frequency, but was ineffective in elevating reward thresholds relative to mice merely exposed to saline. Mice assessed in the ICSS paradigm were approximately 2-4 months old at the time of surgery and 5-7 months old at the completion of testing. These data suggest that acute odor exposure may induce a fear gradient dependent upon the perceived stressor severity and that the resultant anxiety-like effects are dependent on the duration of odor exposure, age of the animals and the temporal interval between odor presentation and behavioral testing. Moreover, the anxiogenic properties of psychogenic stressors can be separated from their anhedonic effects. The implications of these data for clinical psychopathology are discussed.


Cell-type specific responses in prostaglandin secretion by glandular and stromal cells from pig endometrium treated with catecholestrogens, methoxyestrogens and progesterone.
The pig conceptus and endometrium possess the ability to convert estrogens into catecholestrogens and catecholestrogens into methoxyestrogens. Experiments were carried out to evaluate the effect of catecholestrogens, methoxyestrogens and progesterone on the secretion of prostaglandin (PG) E and F2 alpha by porcine endometrial glandular and stromal cells in vitro. Both 2-hydroxyestradiol (2-OH-E2, 0-20 microM) and 4-hydroxyestradiol (4-OH-E2, 0-20 microM) increased (P less than .05) PGE and PGF2 alpha secretion by stromal cells in a dose response manner. Two-hydroxyestradiol tended (P less than .1) to decrease PGF2 alpha production by glandular cells. Two-methoxyestradiol (20 microM) suppressed (P less than .05) PGF2 alpha secretion by glandular and stromal cells. Four-methoxyestradiol (20 microM) stimulated (P less than .05) PGE production and PGE:PGF2 alpha ratio. Progesterone (.1 microM) suppressed (P less than .05) PG secretion in both cell types. We conclude that catecholestrogens, methoxyestrogens, and progesterone may participate in the establishment of pregnancy by modulating PG production in the endometrium.


Doxorubicin-transferrin conjugate triggers pro-oxidative disorders in solid tumor cells.
The formation of reactive oxygen species (ROS) is a widely accepted mechanism of doxorubicin (DOX) toxicity toward cancer cells. However, little is known about the potential of new systems, designed for more efficient and targeted doxorubicin delivery (i.e. protein conjugates, polymeric micelles, liposomes, monoclonal antibodies), to induce oxidative stress (OS) in tumors and hematological malignancies. Therefore, the objective of our study was to determine the relation between the toxicity of doxorubicin-transferring (DOX-TRF) conjugate and its capability to generate oxidative/nitrosative stress in solid tumor cells. Our research proves that DOX-TRF conjugate displays higher cytotoxicity towards lung adenocarcinoma epithelial (A549) and hepatocellular carcinoma (HepG2) cell lines than the reference free drug (DOX) and induces more extensive OS, characterized by a significant decrease in the total cellular antioxidant capacity, glutathione level and amount of -SH groups and an increase in hydroperoxide content. The intracellular redox imbalance was accompanied by changes in the transcription of genes encoding key antioxidant enzymes engaged in the sustaining of cellular redox homeostasis: superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST) and glutathione peroxidase (GP).


Production of adeno-associated viral vector serotype 6 by triple transfection of suspension HEK293 cells at higher cell densities.
In recent years, the use of adeno-associated viruses (AAVs) as vectors for gene and cell therapy has increased, leading to a rise in the amount of AAV vectors required during pre-clinical and clinical trials. AAV serotype 6 (AAV6) has been found to be efficient in transducing different cell types and has been successfully used in gene and cell therapy protocols. However, the number of vectors required to effectively deliver the transgene to one single cell has been estimated at 106 viral genomes (VG), making large-scale production of AAV6 necessary. Suspension cell-based platforms are currently limited to low cell density productions due to the widely reported cell density effect (CDE), which results in diminished production at high cell densities and decreased cell-specific productivity. This limitation hinders the potential of the suspension cell-based production process to increase yields. In this study, we investigated the improvement of the production of AAV6 at higher cell densities by transiently transfecting HEK293SF cells. The results showed that when the plasmid DNA was provided on a cell basis, the production could be carried out at medium cell density (MCD, 4 × 106 cells mL-1 ) resulting in titers above 1010 VG mL-1 . No detrimental effects on cell-specific virus yield or cell-specific functional titer were observed at MCD production. Furthermore, while medium supplementation alleviated the CDE in terms of VG/cell at high cell density (HCD, 10 × 106 cells mL-1 ) productions, the cell-specific functional titer was not maintained, and further studies are necessary to understand the observed limitations for AAV production in HCD processes. The MCD production method reported here lays the foundation for large-scale process operations, potentially solving the current vector shortage in AAV manufacturing.


Bradyrhizobium sp. nodulating the Mediterranean shrub Spanish broom (Spartium junceum L.).
The molecular diversity of 25 strains of rhizobia, isolated in Sicily from root nodules of the Mediterranean shrubby legume Spanish broom (Spartium junceum L.), is presented in relation to the known rhizobial reference strains. Our approach to the study of the S. junceum rhizobial diversity combined the information given by the 16S and the intergenic spacer (IGS) 16S-23S rDNA polymorphic region by obtaining them in a single polymerase chain reaction (PCR) step. The PCR fragment size of the S. junceum isolates was 2400-2500 bp and that of the reference strains varied from 2400 in Bradyrhizobium strains to 2800 in Sinorhizobium strains. Inter- and intrageneric length variability was found among the reference strains. Restriction fragment length polymorphisms (RFLP) analysis allowed us to identify eight genotypes among the S. junceum rhizobia that were clustered into two groups, both related to the Bradyrhizobium lineage. Sequencing of representative strains of the two clusters confirmed these data. The 16S-IGS PCR-RFLP approach, when applied to rhizobial reference strains, allowed very close species (i.e. Rhizobium leguminosarum/R. tropici) to be separated with any of the three enzymes used; however, cluster analysis revealed inconsistencies with the 16S-based phylogenesis of rhizobia. Rhizobia nodulating S. junceum in the Mediterranean region belong to the Bradyrhizobium lineage. Our results confirm the resolution power of the 16S-23S rDNA in distinguishing among rhizobia genera and species, as well as the usefulness of the PCR-RFLP method applied to the entire 16S-IGS region for a rapid tracking of the known relatives of new isolates. The present paper is, to our knowledge, the first report on rhizobia nodulating a Mediterranean wild woody legume.


New species, hyper-diversity and potential importance of Calonectria spp. from Eucalyptus in South China.
Plantation forestry is expanding rapidly in China to meet an increasing demand for wood and pulp products globally. Fungal pathogens including species of Calonectria represent a serious threat to the growth and sustainability of this industry. Surveys were conducted in the Guangdong, Guangxi and Hainan Provinces of South China, where Eucalyptus trees in plantations or cuttings in nurseries displayed symptoms of leaf blight. Isolations from symptomatic leaves and soils collected close to infected trees resulted in a large collection of Calonectria isolates. These isolates were identified using the Consolidated Species Concept, employing morphological characters and DNA sequence comparisons for the β-tubulin, calmodulin, histone H3 and translation elongation factor 1-alpha gene regions. Twenty-one Calonectria species were identified of which 18 represented novel taxa. Of these, 12 novel taxa belonged to Sphaero-Naviculate Group and the remaining six to the Prolate Group. Southeast Asia appears to represent a centre of biodiversity for the Sphaero-Naviculate Group and this fact could be one of the important constraints to Eucalyptus forestry in China. The remarkable diversity of Calonectria species in a relatively small area of China and associated with a single tree species is surprising.


Moniliformin production in the genusFusarium.
More than 600Fusarium strains were screened for their ability to produce moniliformin in vitro. They represented 90 species and 15 sections (without sectionPseudomicrocera). A simple TLC-method (agar plug method) was tested for its applicability to detect moniliformin in fungal cultures. It revealed moniliformin production in 146 strains representing 32 species, all belonging to sections of which the teleomorph is known to beGibberella. The results by and large agree with earlier published data. However, some species did not show any moniliformin production in contrast to other reports. Furthermore, moniliformin production is reported for the first time in two known and in two not yet described species. 58 species were unable to generate the toxin. The results support the importance to include mycotoxin production of fungi as a criterion in a polyphasic taxonomy.


Examining nutrition among a sample of 3- to 5-year-old children living in rural Jamaica.
The period of early childhood, defined as three to five years of age, is an important and distinct stage in childhood development. Changes in dietary patterns and composition of diets are exposing children in developing countries to over-nutrition as well as under-nutrition. To describe the nutritional status, dietary patterns, and socio-economic conditions of three to five-year-old children living in rural Jamaica. A convenience sample of 142 children was recruited over a three-year period. Height and weight measurements were collected. Household dietary patterns and socio-economic indicators were available from a small group (n = 6) of parents. Children experiencing both under-nutrition and over-nutrition were identified. Nine percent (n = 13) could be classified as moderately to severely under-nourished, and 6.9% (n = 10) classified as overweight. Frying was a common cooking method, and fruits and vegetables were eaten often. Economic and political changes may place children in developing countries at risk for over-nutrition as well as under-nutrition. The school setting may be an important place to address nutritional issues. This analysis describes the nutritional status of a sample of three to five-year-old children living in rural Jamaica and provides suggestions for future research.


A promising tool for clinical diagnostics: Dual-emissive carbonized polymer dots based cross-linking enhanced emission for sensitive detection of alkaline phosphatase and butyrylcholinesterase.
Compared with single signal readout, dual-signal readout commendably corrects the impact of systematic or background error, achieving more accurate results for the diagnosis of many diseases. This work aimed to design and prepare dual-emissive fluorescent probes for the construction of ratiometric fluorescence biosensors to detect liver disease biomarkers. Sodium alginate (SA) with numerous potential sub-fluorophores and active sites and 4,4',4'',4'''-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid) (TCPP) with macrocyclic conjugated structures were introduced to prepare the carbonized polymer dots (CPDs) with red/blue dual emission based on the cross-linking enhanced emission (CEE) effect and the luminescence of macrocyclic conjugated structures. The ratiometric fluorescence sensing systems were constructed by integrating the specific response of CPDs to Cu2+ and the affinity difference of Cu2+ to substrates or products of enzymes. The sensing systems, CPDs/Cu2+/PPi and CPDs/Cu2+/BTCh, were designed to detect liver disease biomarkers, alkaline phosphatase (ALP) and butyrylcholinesterase (BChE), respectively. The limit of detection for ALP and BChE was 0.35 U/L and 0.19 U/L, respectively. The proposed sensors were successfully applied to human serum samples from different health stages with satisfactory recoveries. These results demonstrate the successful design of a novel dual-emissive fluorescent probe and provide a feasible strategy for clinical detection.


Survival and development of health conditions after iron depletion therapy in C282Y-linked hemochromatosis patients.
We report long-term survival and development of selected health conditions in Ontario-based referred and screened C282Y homozygotes for hemochromatosis treated by phlebotomy compared with an untreated control group known to be without HFE mutations. Patient characteristics and outcomes (all-cause mortality, liver cancer, diabetes, cirrhosis, hip or knee joint replacement, and osteoarthritis) were ascertained using a linked health administrative database held at ICES. Outcomes were assessed between groups without the outcome at baseline using Cox proportional hazards regression adjusted for age and sex. All C282Y homozygotes with elevated serum ferritin were treated by phlebotomy to reach serum ferritin of 50 µg/L. Our cohort included 527 C282Y homozygotes (311 men, 216 women, mean age 48 years) and 12,879 control participants (5,667 men and 7,212 women). C282Y homozygotes had an increased risk of all-cause mortality (aHR 1.44 [1.19-1.75], p <0.001); hepatocellular carcinoma (aHR 8.30 [3.97-17.34], p <0.001); hip or knee joint replacement (aHR 3.06 [2.46-3.81], p <0.001); osteoarthritis (aHR 1.72 [1.47-2.01], p <0.001); and cirrhosis (aHR 3.87 [3.05-4.92], p <0.001). C282Y homozygotes did not have an increased risk for diagnosis of diabetes) (aHR 0.84 [0.67-1.07], p = 0.16) during follow-up (median 17.7 y). C282Y homozygotes experience higher death and complication rates than individuals without HFE mutations, despite treatment by phlebotomy. Diabetes did not increase after phlebotomy therapy.


Psychological distress influences lung cancer: Advances and perspectives on the immune system and immunotherapy.
Lung cancer has the highest incidence rate and mortality worldwide. Moreover, multiple factors may cause heterogeneity in the efficacy of immunotherapy for lung cancer, and preclinical studies have gradually uncovered the promotive effects of psychological distress (PD) on tumor hallmarks. Therefore, treatment targeted at PD may be a vital factor in adjusting and improving immunotherapy for lung cancer. Here, by focusing on the central nervous system, as well as stress-related crucial neurotransmitters and hormones, we highlight the effects of PD on the lung immune system, the lung tumor microenvironment (TME) and immunotherapy, which brings a practicable means and psychosocial perspective to lung cancer treatment.


The pharmacokinetics of intravenous estradiol--a preliminary study.
Estradiol USP was extemporaneously compounded for intravenous administration. Eight postmenopausal women were randomized to receive one of four estradiol dosages. Serum estradiol concentrations were determined at frequent intervals after single bolus dosing. The concentration-time profile was stripped and fit, and pharmacokinetic values were generated. Approximate dosage proportionality was seen with area under the curve, the terminal half-life was 27.45+/-5.65 minutes, and volume of distribution was very low (0.082+/-0.015 L/kg). Estradiol was well tolerated by all study participants.


Developmental arachnoid cysts of the posterior fossa-an analysis of 13 cases.
Thirteen cases of posterior fossa arachnoid cyst are described. Presenting features were usually headache, vomiting, lethargy, and delayed development in infants. Association with congenital defects is sometimes noted. The cysts are considered to result from abnormalities occurring in foetal life.


Evidence for the efficacy of statins in animal stroke models: a meta-analysis.
Protective effects of statins have been well documented for stroke therapy. Here, we used a systematic review and meta-analysis to assess these evidences. We identified 190 studies using statin treatment in stroke animal models by electronic searching. From those, only studies describing ischemic occlusive stroke and reporting data on infarct volume and/or neurological outcome were included in the analysis (41 publications, 1882 animals). The global estimate effect was assessed by Weighted Mean Difference meta-analysis. Statins reduced infarct volume by 25.12% (20.66%-29.58%, P < 0.001) and consistently, induced an improvement on neurological outcome (20.36% (14.17%-26.56%), P < 0.001). Stratified analysis showed that simvastatin had the greatest effect on infarct volume reduction (38.18%) and neurological improvement (22.94%), whereas bigger infarct reduction was observed giving the statin as a pre-treatment (33.5%) compared with post-treatment (16.02%). The use of pentobarbital sodium, the timing of statin administration, the statement of conflict of interest and the type of statin studied were found to be independent factors in the meta-regression, indicating their influence on the results of studies examining statin treatment. In conclusion, this meta-analysis provides further evidences of the efficacy of statins, supporting their potential use for human stroke therapy.


Enhanced hydrolysis of lignocellulose in corn cob by using food waste pretreatment to improve anaerobic digestion performance.
This study aims to enhance hydrolysis and anaerobic digestion of corn cob (CC) by using food waste (FW) pretreatment. FW, which tends to be acidification in fermentation, was applied in this process as an acid-like agent to accelerate lignocellulose hydrolysis, aiming to promote methane yield in further digestion process. The effect of FW pretreatment on pH, soluble chemical oxygen demand (SCOD), volatile fatty acids (VFAs), cellulose/hemicellulose contents and cellulose crystallinity are specially focused. FW:CC = 1:3 based on volatile solid (VS) was found to be the optimal mixing ratio in pretreatment and its hydrolysis efficiency was 28% higher than the control group. An increase of 13.2% in cellulose reduction and a decrease of 6.7% in cellulose crystallinity was achieved at this ratio. Supplementation of FW increased VFA concentrations in slurry mixture that directly change the activities of enzymes and microorganisms. In the stage of methane production, the digester A3 (FW:CC = 1:6 based on VS) with higher hydrolysis efficiency presented the best performance in methane production with a specific methane yield of 401.6 mL/g·VS, due to the recovery of the pH in this digester to the optimal pH range for methanogens' metabolism (pH 6.3-7.2). Kinetics studies of cellulose/hemicellulose degradation indicated that the pretreatment of FW could improve the degradation of cellulose. Three-dimensional excitation emission matrix (3DEEM) results further confirmed that FW play an important role in lignocellulose hydrolysis. In addition, variations of lignocellulosic textures during the pretreatment were also cleared by using field emission-scanning electron microscopy (FE-SEM) analysis.


Predicting esthetics in implant dentistry using multiplanar angulation: a technical note.
Although the permucosal site of implants can be made to coincide with tooth position, the problem of aligning multiple abutments remains. To use the maximum amount of available bone, an implant must often be placed at an angle to the long axis of the prosthetic replacement tooth, and it also can deviate mesiodistally. This paper discusses a technique using trial abutments to create parallelism while ensuring that each abutment is ideally positioned with respect to the final restoration. The procedure also encourages patient acceptance by transferring the appearance created by a preliminary diagnostic waxup through to the finished prosthesis.


Tuberculosis Knowledge and Delayed Health Care Seeking Among New Diagnosed Tuberculosis Patients in Primary Health Facilities in an Urban District, South Africa.
Patients' delay in seeking health care is a major problem in the control of tuberculosis (TB) and increases the risk of TB transmission. This study determined health-seeking practices and delays that occurred from the onset of TB symptoms until diagnosis and assessed the patients' TB-related knowledge. This was a cross-sectional study involving 391 new TB patients recruited from health facilities at an urban sub-district in South Africa from December 2016 to March 2017. Descriptive statistics and logistic regression analyses were performed using Stata 14. Over half (56.3%) of the patients delayed seeking health care for more than 30 days after the onset of their symptoms, 32% sought treatment from informal providers, and 13.3% self-medicated. Lack of suspicion of a TB diagnosis, which was prevalent in 45% of respondents, was statistically associated with delay in seeking healthcare (AOR = 0.53, CI: 0.32-1.87). Overall TB knowledge was high, correct knowledge about TB transmission was 92.6%. TB knowledge was significantly associated with educational status (AOR = 3.96, CI: 1.69-9.28) and seeking treatment from informal sectors (AOR = 0.17, CI: 0.03-0.95). High overall TB knowledge was not statistically associated with seeking health care for TB diagnosis and treatment. We found a substantial delay between the onset of TB symptoms and seeking healthcare from a public health facility providing TB screening services. Promoting early screening and diagnosis through increasing awareness of TB is key in the elimination of TB in communities with a high TB burden.


Single-night stay for open radical prostatectomy.
The aim of this study was to assess the effect of an enhanced care pathway on length of stay (LOS) for open radical prostatectomy (RP) given that robotic-assisted laparoscopic prostatectomy (RALP) is not available to all patients in Canada. A retrospective review was conducted of all RPs performed. An enhanced care pathway was established for RPs in 2011. Patients were compared in the period before (2005-2010) and after (2011-2019) the introduction of the pathway. During the study period, 581 RPs were performed by a single surgeon with a median followup of 66.9 months (range 3-176). A total of 211 (36.3%) RPs were performed from 2005-2010, while 370 (63.9%) were performed from 2011-2019. The median age at RP was 65 years (range 44-81). Following the introduction of an enhanced care pathway, there were significant decreases in intraoperative blood loss (350 ml vs. 200 ml; p=0.0001) and the use of surgical drains (90% vs. 9.5%; p=0.0001). The median LOS over the whole study period was one day (range 1-7), which significantly decreased with the enhanced care pathway (3 vs. 1 day; p=0.0001). Since introducing the enhanced care pathway in 2011, 344 (93%) patients were discharged day 1 following surgery. There were no differences in post-discharge presentations to the emergency department (5.7% vs. 9%; p=0.15) or 30-day readmission rates (3.8% vs. 3.8%; p=1.00). A single-night stay for open RP is safe and achievable for most patients. A dedicated, multifaceted pathway is required to attain targets for a safe and timely discharge.


Expression of noncoding mRNA in human blood cells activated with synthetic peptide of HIV.
T cells activation includes several steps such as translational events, activation of transcription for different genes, expression of surface molecules, secretion of cytokines, effectors functions. Knowledge has been accumulated on various nontranslatable RNA transcripts that are synthesized. In this context, a member of T cell noncoding transcripts (NTT) has been identified. It has been known that this gene is selectively expressed in activated T cells, as a 17-kb transcript. In this study, we investigate cell activation using RT-PCR to detect NTT. We investigated the expression of IFNgamma mRNA, a cytokine produced by activated blood mononuclear cells treated with HLA-A2 restricted synthetic peptide of HIV (p9) by RT-PCR detecting a fragment of 300 bp. This finding demonstrated that human HLA-A2 blood mononuclear cells have been activated in the presence of synthetic peptide of HIV (p9) and can induce expression of mRNA of NTT and IFNgamma which was confirmed by direct sequencing. For the first time, we have demonstrated an endogenous noncoding human RNA molecule, NTT mRNA, suggesting its implication in the cellular immune response.


Evolutionary protein stabilization in comparison with computational design.
Two major strategies are currently used for stabilizing proteins: in vitro evolution and computational design. Here, we used gene libraries of the beta1 domain of the streptococcal protein G (Gbeta1) and Proside, an in vitro selection method, to identify stabilized variants of this protein. In the Gbeta1 libraries, the codons for the four boundary positions 16, 18, 25, and 29 were randomized. Many Gbeta1 variants with strongly increased thermal stabilities were found in 11 selections performed with five independent libraries. Previously, Mayo and co-workers used computational design to stabilize Gbeta1 by sequence optimization at the same positions. Their best variant ranked third within the panel of the selected variants. None of the ten computed sequences was found in the Proside selections, because several computed residues for positions 18 and 29 were not optimal for stability.


A simple test for erythropoietin.
In Gelfiltration on Sephadex G-100 crude protein prepared from the urine of anemic patients incubated with 59Fe+++ -ions was separated and a distinct fraction isolated having high erythropoietic activity and a high 59Fe+++ -absorption. Increased amount of erythropoietin resulted in a higher incorporation of 59Fe+++ -ions in this fraction. From this we propose to replace the time consuming and very expensive bioassay for erythropoietin in poly-cythemic mice by gelfiltration of the material under investigation preincubated with 59Fe+++ -ions to test the Fe+++ uptake in the forementioned fraction.


Induction of pulmonary HLA-G expression by SARS-CoV-2 infection.
The non-classical human leukocyte antigen (HLA)-G exerts immune-suppressive properties modulating both NK and T cell responses. While it is physiologically expressed at the maternal-fetal interface and in immune-privileged organs, HLA-G expression is found in tumors and in virus-infected cells. So far, there exists little information about the role of HLA-G and its interplay with immune cells in biopsies, surgical specimen or autopsy tissues of lung, kidney and/or heart muscle from SARS-CoV-2-infected patients compared to control tissues. Heterogeneous, but higher HLA-G protein expression levels were detected in lung alveolar epithelial cells of SARS-CoV-2-infected patients compared to lung epithelial cells from influenza-infected patients, but not in other organs or lung epithelia from non-viral-infected patients, which was not accompanied by high levels of SARS-CoV-2 nucleocapsid antigen and spike protein, but inversely correlated to the HLA-G-specific miRNA expression. High HLA-G expression levels not only in SARS-CoV-2-, but also in influenza-infected lung tissues were associated with a high frequency of tissue-infiltrating immune cells, but low numbers of CD8+ cells and an altered expression of hyperactivation and exhaustion markers in the lung epithelia combined with changes in the spatial distribution of macrophages and T cells. Thus, our data provide evidence for an involvement of HLA-G and HLA-G-specific miRNAs in immune escape and as suitable therapeutic targets for the treatment of SARS-CoV-2 infections.


Users with spinal cord injury experience of robotic Locomotor exoskeletons: a qualitative study of the benefits, limitations, and recommendations.
Persons with spinal cord injury (SCI) may experience both psychological and physiological benefits from robotic locomotor exoskeleton use, and knowledgeable users may have valuable perspectives to inform future development. The objective of this study is to gain insight into the experiences, perspectives, concerns, and suggestions on the use of robotic locomotor exoskeletons by civilians and veterans living with SCI. Participants reported their demographic characteristics and the extent of robotic exoskeleton use in an online survey. Then, 28 experienced robotic locomotor exoskeleton users participated in focus groups held at three regional hospitals that specialize in rehabilitation for persons with SCI. We used a qualitative description approach analysis to analyze the data, and included thematic analysis. Participants expressed that robotic exoskeletons were useful in therapy settings but, in their current form, were not practical for activities of daily living due to device limitations. Participants detailed the psychological benefits of being eye-level with their non-disabled peers and family members, and some reported physiologic improvements in areas such as bowel and bladder function. Participants detailed barriers of increased fatigue, spasticity, and spasms and expressed dissatisfaction with the devices due to an inability to use them independently and safely. Participants provided suggestions to manufacturers for technology improvements. The varied opinions and insights of robotic locomotor exoskeletons users with SCI add to our knowledge of device benefits and limitations.


Penetrating heart wounds.
In 3 years, 26 patients were operated for penetrating heart wounds at our institution, the majority between 30 to 60 minutes after injury. Twenty-two patients with a possible heart wound were immediately taken to the operating room for thoracotomy. One patient initially underwent laparotomy while 2 were observed before operating-room thoracotomy. One patient underwent emergency-room thoracotomy. Three patients with no vital signs on admission died, 82.6% of the remainder survived. Stab wounds determined the best survival rate: 94%, whereas for gunshot wounds it was only 50%. Our experience at this Brazilian Trauma Center reveals that delay in reaching the hospital selected the patients, that clinical condition on arrival, method of injury (knife or gunshot), emergency room staffed with trauma surgeons and aggressive operating room treatment for penetrating heart wounds results in a remarkable survival rate. Emergency-room thoracotomy should be reserved for patients "in extremis" or when there is no operating room available.


Prisoner health and valuation of life, loneliness, and depressed mood.
To examine valuation of life, loneliness, and depressed mood as mediating the association between age and race/ethnicity and health outcomes among older adult male prisoners. Survey of 261 male prisoners ages 45-80 from 8 Oklahoma correctional facilities. African American prisoners report fewer health conditions than White prisoners - a finding mediated by significantly greater valuation of life, less loneliness, and lower depressed mood among African American prisoners. Older prisoners reported more health conditions than younger prisoners independent of other study variables. Results suggest improving inmates' internal states will reduce incidence of illness and disease among older male offenders and associated healthcare costs.


Toxicity of thiols and disulphides: involvement of free-radical species.
Sulphur is essential to life, and thiols and disulphides play essential roles in cellular biochemistry. Such compounds are also widely distributed in the food of man and his domestic animals, and they are extensively used in industry. However, many thiols and disulphides have been shown to be toxic. Aliphatic, aromatic, and heterocyclic compounds of this type are haemolytic agents in animals while aminothiols have been shown to induce many cytotoxic effects in vitro and the epidithiodioxopiperazine mycotoxin, sporidesmin, is a potent hepatotoxic agent. Structure-activity relationships among these compounds and factors which modulate their harmful effects are consistent with a toxic mechanism involving redox cycling between the thiol and the corresponding disulphide. Thiyl radicals and "active oxygen" species are formed in this process, and it is suggested that these substances are responsible for initiating the tissue damage provoked by thiols and disulphides.


Spindle cell carcinoma of the head and neck region: treatment and outcomes of 15 patients.
Spindle cell carcinoma of the head and neck is a rare entity and the evidence of optimal management is lacking. The objective of our study was to report the treatment and outcomes of 15 patients treated in a single institution over a seven year period. A total of 15 patients (12 males and 3 females) with spindle cell carcinoma of the head and neck were treated between July 2007 to June 2014. In six patients the disease developed after previous radiotherapy. Of the 15 patients, five patients had their primary in the tongue, four in the paranasal sinuses, two in the hypopharynx, two in the vocal cords, and one each in the soft palate and the floor of mouth. Eleven patients were treated with radical intent (seven patients required surgery only and four were treated with combined modality). The remaining four patients were treated with palliative intent. Among 11 patients treated with radical intent eight are alive or died of non-oncological causes. The disease recurred locally in three patients and they died of the disease (two patients with locally advanced disease in the tongue and one patient with T1N0 tumour in the hypopharynx). Median overall survival (OS) was 18 months. Surgery or surgery combined with radiotherapy has a real impact on the natural cause of spindle cell carcinoma of the head and neck region. Even locally advanced tumours can be controlled with aggressive treatment. The worst outcome is seen with the tongue as the primary site because of a high local recurrence rate.


Phenolic compounds from the branches of Eucalyptus maideni.
Three new phenolic compounds, eucalmaidin F (1), (3S)-5-guaiacyl-3-hydroxypentanoic acid (2), and 8-β-C-glucopyranosyl-5,7-dihydroxy-2-isobutylchromone (3), were isolated from the branches of E. maideni, together with 30 known compounds, including four phenylpropanoids, three lignans, four phloroglucinol glucosides, five dihydroflavonoids, seven simple phenolic compounds, six terpenoids, and glycerol. The new structures were established by spectroscopic studies (MS, and 1D- and 2D-NMR), chemical degradation, and modified Mosher's method. Compounds 3, guaiacylglycerol, 3-hydroxy-1-(4-hydroxyphenyl)propan-1-one, caffeic acid, (2E)-3-(4-hydroxyphenyl)prop-2-enoic acid, (7'S,8R,8'R)-lyoniresinol, (+)-lyoresinol 3α-O-α-L-rhamnopyranoside, garcimangosone, phlorocetophenone 2'-glucopyranoside, (+)-taxifolin 3α-O-α-L-rhamnopyranoside, (+)-aromadendrin, (+)-taxifolin, resveratrol, piceatannol, 3,4,5-trihydroxyphenol. Tachiaside, gallic acid, macrocapals A und G, and oleuropeic acid were evaluated for their cytotoxicities against five human cancer cell lines. Resveratrol, piceatannol, gallic acid, and macrocapal G exhibited moderate inhibitory effects on human myeloid heukemia HL-60 cell, with IC(50) values of 22.05, 22.05, 7.75, and 31.93 μM, respectively; and only macrocapal G showed inhibitory effect on hepatocellular carcinoma SMMC-7721 cell, with an IC(50) value of 26.75 μM.


Cytotoxic activity of methanolic fractions of different Marrubium spp. against melanoma cells is independent of antioxidant activity and total phenolic content.
The Marrubium genus (horehound) has proved to be an abundant source of biologically active compounds, but there is little knowledge about its potential anticancer activity. Moreover, some Marrubium species have not been the subject of study in this regard. In this study, we performed comparative analysis of phenolic acid (PhA) content and total phenolic content in fractions obtained from methanolic extracts of Marrubium vulgare L. (common horehound), Marrubium cylleneum Boiss. & Heldr. and Marrubium friwaldskyanum Boiss herbs. We examined the cytotoxicity of these fractions against a human melanoma cancer cell line (A375) and normal human skin fibroblasts (BJ) using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide test, cell cycle analysis and real-time monitoring of cell viability. We detected caffeic, p-coumaric, ferulic and gentisic acids among the PhAs. Although the extracts obtained demonstrated low total phenolic content and did not show significant antioxidative properties, the nonhydrolyzed PhA fraction exhibited cytotoxic activity against a human melanoma cancer cell line, without affecting normal fibroblasts. Both acidic and alkaline hydrolysis abolished this activity, indicating that the esterified forms of phenolic compounds caused the observed cytotoxic effects. Further investigation of these compounds may facilitate the development of novel drugs for cancer treatment.


Automated framework for accurate segmentation of pressure ulcer images.
Ulcer tissue segmentation is of immense importance in helping medical personnel to assess wounds. This paper introduces a new computational framework employing state-of-the-art image processing techniques to segment pressure ulcer tissue structures from color images. The framework integrates a visual appearance model of an observed input image with prior color information from an available database of previously stored color RGB images. The following four processing steps are performed. First, to minimize the execution time and enhance the segmentation accuracy, a region-of-interest (ROI) of the whole ulcer area is automatically identified based on contrast changes. This step exploits synthetic frequencies of pixelwise intensities, which are calculated by using an electric field energy model to describe relations between the pixelwise intensities. Secondly, visual appearance of the observed image is modeled by a linear combination of discrete Gaussians (LCDG) model in order to estimate marginal probability distributions of three main tissue classes for the grayscale ROI image. Next, the pixel-wise probabilities of these classes for the color ROI image are calculated using the available prior information about the RGB colors on manually segmented database images. Initial labeling is obtained based on both the observed and prior probabilities of pixelwise colors. Finally, to preserve continuity, the labels are refined and normalized using the generalized Gauss-Markov random field (GGMRF) model. Experimental validation on 24 clinical images of pressure ulcers, provided by the Centre IGURCO, showed the high segmentation accuracy of 90.4%.


[Evaluation of occupational chromium exposure through the determination of urinary chromium].
Determinations of urinary chromium on 26 workers from 6 chromium electroplating workshops are presented and discussed in relation with results of airborne chromium. Rapid apparition of chromium in urine after the beginning of exposure tends to show that urinary analysis are a convenient test for the biological monitoring of chromium exposure.


A critical review on brain and heart axis response in COVID-19 patients: Molecular mechanisms, mediators, biomarkers, and therapeutics.
Since the outbreak of highly virulent coronaviruses, significant interest was assessed to the brain and heart axis (BHA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected patients. The majority of clinical reports accounted for unusual symptoms associated with SARS-CoV-2 infections which are of the neurological type, such as headache, nausea, dysgeusia, anosmia, and cerebral infarction. The SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE-2) receptor. Patients with prior cardiovascular disease (CVD) have a higher risk of COVID-19 infection and it has related to various cardiovascular (CV) complications. Infected patients with pre-existing CVDs are also particularly exposed to critical health outcomes. Overall, COVID-19 affected patients admitted to intensive care units (ICU) and exposed to stressful environmental constraints, featured with a cluster of neurological and CV complications. In this review, we summarized the main contributions in the literature on how SARS-CoV-2 could interfere with the BHA and its role in affecting multiorgan disorders. Specifically, the central nervous system involvement, mainly in relation to CV alterations in COVID-19-affected patients, is considered. This review also emphasizes the biomarkers and therapy options for COVID-19 patients presenting with CV problems.


Therapy of malignant brain tumors: comparison of the in vitro activities of vidarabin-monophosphate, BCNU and 5-fluorouracil.
BCNU (carmustine), 5-Fluorouracil (5-FU) and Vidarabin-monophosphate (ARA-A5'P) were compared in their activities against 30 cell lines of primary (n = 21) and metastatic (n = 9) brain tumors, which were characterized in tissue culture by cytochemical, immunological and cytogenetic criteria. In vivo achievable concentration-time products were correlated with in vitro pharmacokinetic data. A micro assay was employed to screen for drug toxicity in individual tumor cell lines; cells were exposed to the drugs at exposure doses relevant to in vivo pharmacokinetics. After 5-8 population doubling times of untreated controls, RNA-synthesis, as a parameter of cell metabolism and proliferation, was determined by incorporation of (5, 6-3H)-uridine into cellular RNA (liquid scintillation counting protocol). A tumor stem cell assay was performed under similar conditions. The cytotoxic effect of each drug on individual cell lines was expressed in terms of a sensitivity index SI (SI = 1 indicating complete resistance) to compare effects of different drugs on the individual tumor cell lines. Mean sensitivity indices for ARA-A5'P, BCNU and 5-FU in brain tumor cell lines (in brackets: primary CNS-tumors) were 0.64 (0.59), 0.89 (0.82) and 0.35 (0.33) respectively. 5-FU was significantly more active than BCNU and ARA-A5'P (P less than 0.001), whereas BCNU was significantly less active than ARA-A5'P (P less than 0.001). ARA-A5'P had a suppressive effect on formation of brain tumor stem cell colonies. There was no cross-resistance of ARA-A5'P to either BCNU or 5-FU. We conclude that ARA-A5'P and 5-FU are potent agents in experimental therapy of human brain tumors, compared with BCNU.


Non-group A beta-hemolytic streptococcal cellulitis. Association with venous and lymphatic compromise.
Cellulitis occurring in the limbs of patients who have previously undergone saphenous venectomy and coronary bypass surgery has been the subject of several recent reports. Although isolation of pathogenic microorganisms from these lesions has been uncommon, this report describes three patients who had undergone venectomy previously and in whom non-group A beta-hemolytic streptococci were recovered either during acute episodes of cellulitis or during quiescent intervals. There are to date only four other reported cases of post-venectomy cellulitis from which beta-hemolytic streptococci were isolated: one was non-group A and the others were not serologically characterized. Moreover, studies in patients without bypass who have experienced cellulitis in extremities with compromised venous and/or lymphatic circulation have also yielded a substantial number of non-group A streptococci. The data thus far implicate non-group A beta-hemolytic streptococci as a major cause of cellulitis, especially in the setting of circulatory compromise.


T-DNA transfer to maize plants.
Agrobacterium-mediated transformation is the method of choice to engineer desirable genes into plants. Here we describe a protocol for demonstrating T-DNA transfer from Agrobacterium into the economically important graminaceous plant maize. Expression of the T-DNA-located GUS gene was observed with high efficiency on shoots of young maize seedlings after cocultivation with Agrobacterium.


"No-effect-level" of malathion (o,o'-dimethyl dithiophosphate of diethyl mervaptosuccinate) in Bubalus bubalis.
An oral dose of 0.5 mg/kg/day malathion continuously administered for one year has been investigated to produce no change in biochemical (RChE, PChE, aspartate- and alanine aminotransferases, blood glucose, serum urea and plasma total proteins) or haematological (Hb, PCV, tRBC and tWBC) parameters and, therefore, considered to be "no-effect-level" in Bubalus bubalis. However, the administration of higher doses (1.0 and 1.5 mg/kg/day) produced significant (P less than 0.05) changes in all biochemical parameters studied. With these doses leucocytosis was evident among haematological parameters measured.


Protection of pigs against genital Chlamydia trachomatis challenge by parenteral or mucosal DNA immunization.
The current study evaluates combined aerosol-vaginal delivery of a MOMP-based Chlamydia trachomatis (serovar E) DNA vaccine in a pig genital challenge model. Most non-replicating antigens are rather poor mucosal immunogens in comparison to replicating antigens. Therefore, a mucosal administered DNA vaccine, which actually mimics a live vaccine, could be promising. Protection was promoted by plasmids encoding the porcine granulocyte macrophage-colony stimulating factor (pcDNA3.1zeo::GM-CSF), the Escherichia coli thermo-labile enterotoxin (LT) subunit A (plasmid PJV2004::LTa) and subunit B (plasmid PJV2005::LTb). Mucosal C. trachomatis DNA vaccination induced significant protection against genital C. trachomatis challenge although the infection could not be eradicated. Intradermal immunization was significantly less efficient in protecting experimentally infected pigs. Protection was correlated with efficient T cell priming and significantly higher serum IgA titers following primo vaccination.


Eosinophils and mastocytes in healing laser excision wounds.
Eosinophils can influence fibroblasts and the extracellular matrix in vitro and can participate in tissue remodelling in vivo. Therefore; we analysed the expression of eosinophils and mastocytes in healing laser excisions and control excisions made by scalpel. Carbon dioxide (CO(2)) laser (continuous wave, 5 W) or scalpel excision wounds were created in the dorsal tongue mucosa of 96 rats. Sixteen additional rats were kept as untreated controls. Specimens from the tongues were cut at 16 different healing time points and fixed in 10% formalin. Histological staining with slow Giemsa was done to determine microscopically the eosinophils and mastocytes. Mastocytes were always present, especially in large numbers around blood vessels, in scalpel and in laser wounds. The maximum number of eosinophils was almost two times higher in scalpel excisions than in laser excisions. The peak value was reached after 6 days in laser wounds and after 3 days in scalpel wounds. The increase reverted to normal levels after 10 days in laser wounds and after 6 days in scalpel wounds. The appearance and disappearance of eosinophils was slower in laser wounds. Mastocytes were always present in both groups. This identification as a potential source of transforming growth factor (TGF) alpha and TGF beta clearly permits a role for the eosinophils and influences epithelial cell proliferation, angiogenesis and organization of the wound.


Cryptosporidium equi n. sp. (Apicomplexa: Cryptosporidiidae): Biological and genetic characterisations.
The horse genotype is one of three common Cryptosporidium spp. in equine animals and has been identified in some human cases. The species status of Cryptosporidium horse genotype remains unclear due to the lack of extensive morphological, biological, and genetic data. In the present study, we have conducted biological and whole genome sequence analyses of an isolate of the genotype from hedgehogs and proposed to name it Cryptosporidium equi n. sp. to reflect its common occurrence in equine animals. Oocysts of C. equi measured 5.12 ± 0.36 μm × 4.46 ± 0.21 μm with a shape index of 1.15 ± 0.08 (n = 50). Cryptosporidium equi was infectious to 3-week-old four-toed hedgehogs (Atelerix albiventris) and mice, with a prepatent period of 2-9 days and a patent period of 30-40 days in hedgehogs. It was not infectious to rats and rabbits. Phylogenetic analyses of small subunit rRNA, 70 kDa heat shock protein, actin, 60 kDa glycoprotein and 100 other orthologous genes revealed that C. equi is genetically distinct from other known Cryptosporidium species and genotypes. The sequence identity between C. equi and Cryptosporidium parvum genomes is 97.9%. Compared with C. parvum, C. equi has lost two MEDLE genes and one insulinase-like protease gene and gained one SKSR gene. In addition, 60 genes have highly divergent sequences (sequence differences ≥ 5.0%), including those encoding mucin-like glycoproteins, insulinase-like peptidases, and MEDLE and SKSR proteins. The genetic uniqueness of C. equi supports its increasing host range and the naming of it as a valid Cryptosporidium species. This is the first known use of whole genome sequence data in delineating new Cryptosporidium species.


Genetic polymorphism of the major parotid salivary glycoprotein (Gl) with linkage to the genes for Pr, Db, and Pa.
Genetic polymorphism of the major glycoprotein (Gl) found in parotid saliva is determined by autosomal inheritance of one unexpressed and four expressed alleles. This hypothesis is supported by studies in 41 white families including 146 children. For 143 randomly collected salivas from whites and 82 randomly collected salivas from blacks, maximum likelihood estimates of the gene frequencies are as follows: for whites, Gl1 = 0.742, Gl2 = 0.040, Gl3 = 0.155, Gl4 = 0.017, Gl0 = 0.46; for blacks, Gl1 = 0.459, Gl2 = 0.050, Gl3 = 0.337, Gl4 = 0.044, Gl0 = 0.110. There is strong evidence for linkage of Gl/Pr (seven families, lod score at theta = 0 is 5.24) and G1/Db (eight families, lod score at theta = 0 is 4.45). The allelic products of Gl show evidence for linkage disequilibrium with the products of the Pr, Db, and Pa loci (P less than 0.0005). On the basis of varying degrees of linkage disequilibrium, Gl may be closer to Db than to Pr or Pa and on the "outside" of Db with respect to Pr or Pa. Amino acid analyses of Gl 1 and Gl 4 proteins show strong resemblances in composition to the major basic glycoprotein and the acidic proline-rich proteins of parotid saliva described by other workers. The polymorphic forms of the Gl proteins show microheterogeneity due to variability in charge and molecular weight. The electrophoretic polymorphism appears to be determined by apparent differences in molecular weights between the Gl proteins.


High pressure matrix-assisted laser desorption/ionization Fourier transform mass spectrometry for minimization of ganglioside fragmentation.
Transiently elevating pressure in a matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS) source into the 1-10 mbar range during ionization decreases the metastable fragmentation of gangliosides. This allows detection of the molecular ion species without loss of the highly labile sialic acid residues. In these experiments, gangliosides with up to five sialic acids were ionized by MALDI and detected with the FTMS. In each case, when the high pressure collisional cooling was used, the singly charged molecular ion was the base peak in the spectra, both in the positive and negative ion modes, and minimal metastable fragmentation was observed. This result is promising, as the previously developed TLC separation methods can be coupled to MALDI-FTMS.


Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders.
The sigma-1 receptor is a 223 amino acid-long protein with a recently identified structure. The sigma-2 receptor is a genetically unrelated protein with a similarly shaped binding pocket and acts to influence cellular activities similar to the sigma-1 receptor. Both proteins are highly expressed in neuronal tissues. As such, they have become targets for treating neurological diseases, including Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), multiple sclerosis (MS), Rett syndrome (RS), developmental and epileptic encephalopathies (DEE), and motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). In recent years, there have been many pre-clinical and clinical studies of sigma receptor (1 and 2) ligands for treating neurological disease. Drugs such as blarcamesine, dextromethorphan and pridopidine, which have sigma-1 receptor activity as part of their pharmacological profile, are effective in treating multiple aspects of several neurological diseases. Furthermore, several sigma-2 receptor ligands are under investigation, including CT1812, rivastigmine and SAS0132. This review aims to provide a current and up-to-date analysis of the current clinical and pre-clinical data of drugs with sigma receptor activities for treating neurological disease.


Survey of libraries in veterinary practice.
Responses were received to a survey of practice libraries, from 537 practices. The average practice library contained between 11 and 30 books and one or two journals. Between 50 pounds and 100 pounds was spent on books each year. Practitioners wished they had more time to read and that the literature was orientated towards practice.