In vitro processing of transcripts containing novel tRNA-like sequences ('t-elements') encoded by wheat mitochondrial DNA.
We have recently described the properties of a wheat mitochondrial extract that is able to process, accurately and efficiently, artificial transcripts containing wheat mitochondrial tRNA sequences, with the production of mature tRNAs (P.J. Hanic-Joyce and M.W. Gray, J. Biol. Chem., in press). Such processing involves 5'-endonucleolytic, 3'-endonucleolytic, and tRNA nucleotidyltransferase activities. Here we show that this system also acts on transcripts containing sequences corresponding to an unusual class of short repeats ('t-elements') in wheat mtDNA. These repeats are theoretically capable of assuming a tRNA-like secondary structure, although stable transcripts corresponding to them are not detectable in vivo. We find that t-element sequences are processed with the same specificity and with comparable efficiency as are authentic tRNA sequences. Because known t-elements are located close to and in the same transcriptional orientation as active genes (18S-5S, 26S, tRNA(Pro)) in wheat mtDNA, our results raise the question of whether t-elements play a role in gene expression in wheat mitochondria.


Description of a new cellulosic natural fiber extracted from Helianthus tuberosus L. as a composite reinforcement material.
Natural fiber-reinforced composites are generally known as eco-friendly, long-lasting, and recyclable materials. This study characterizes cellulosic Helianthus tuberosus L. fiber for polymer-based green composites for the first time. Helianthus tuberosus L. fiber has many advantages as a reinforcement material in polymer-based composites. For example, the high roughness of the fiber surface increases the locking into the composite body. One of the most critical advantages is its high thermal stability temperature of 247.3°C. Other advantages of the Helianthus tuberosus L. fiber are high cellulose content, high crystallinity, and high tensile strength. The hollow fiber structure allows its use in insulation materials. Finally, the high cellulose content of 62.65% supports its usage in various industries, including paper and paperboard manufacturing.


Ki-67: a prognostic factor for low-grade glioma?
Immunohistochemical techniques were used to detect the expression of Ki-67, a nuclear proliferation marker, in 180 low-grade glioma tumor specimens to determine whether Ki-67 is a prognostic predictor of survival or tumor recurrence. A clinical database of 180 low-grade glioma patients (35 children aged </=18 years and 145 adults) was compiled. Eighty patients had received postoperative radiotherapy (RT) and 100 patients had had RT deferred until the time of tumor progression/recurrence. Ki-67 indexes were evaluated retrospectively on tumor specimens from these patients using a semiautomated computer analysis technique. Ten observations were averaged per patient. The maximal Ki-67 value was recorded. The correlation between the Ki-67 index and survival was much higher for the averaged Ki-67 value than for the maximal value. Of the tumor specimens, 29% had a negative Ki-67 index (i.e., zero Ki-67 positive cells) and 7.7% had an average Ki-67 index of >/=5%. An average Ki-67 value of >/=5% was prognostically significant for reduced cause-specific survival (CSS, p = 0.05) and a Ki-67 level >/=10% was strongly significant of a poor survival outcome (p = 0.009). Ki-67 was not prognostically significant for progression-free survival. Other prognostically significant factors for CSS included age (p = 0.05), Karnofsky performance status (p = 0.0001), radiation dose (p = 0.02), extent of surgical resection (biopsy vs. others, p = 0.004), and timing of radiation (p = 0.0005). Ki-67 did not remain an independent statistically significant factor for CSS on multivariate analysis. Age and Ki-67 positivity (both maximal and average values) directly correlated (i.e., advancing age was associated with a higher Ki-67 index). When the patient group was further subdivided by age and timing of RT (postoperative vs. deferred), the prognostic significance of Ki-67 for CSS was lost. Within the deferred RT subgroup, a maximal Ki-67 >2% was associated with a worsened CSS. Within the pediatric population, Ki-67-negative patients had a 5-year CSS and progression-free survival of 100%. The 5-year CSS and progression-free survival declined significantly to 84% and 67% for patients with tumors demonstrating any degree of Ki-67 positivity (p = 0.005 and p = 0.006, respectively). Ki-67 is a useful predictor of CSS in low-grade gliomas; however, it is not independent of other prognostic factors, particularly age. Although Ki-67 was not helpful in predicting which adult patients were likely to benefit from postoperative RT, the results of the present study indicate a possible utility in the selection of pediatric patients for RT and in the selection of poorer prognosis patients for clinical trials.


Widespread microdysgenesis in therapy-resistant epilepsy--a case report on post-mortem findings.
Microdysgenesis is a subtle malformation, which is often found in specimens from epilepsy surgery. It is, however, not clear whether the changes are focal or diffuse. A recent autopsy case offered an opportunity to investigate whether microdysgenesis found after temporal lobe surgery was focal or widespread in the brain. The entire brain of a 20-year-old patient who died suddenly and unexpectedly was examined histologically. Microdysgenesis had previously been diagnosed after a left temporal lobectomy performed because of therapy-resistant seizures. A light microscopic examination was performed on specimens stained with Luxol-fast blue-cresyl violet and polyclonal antibodies to glial fibrillary acidic protein. Widespread microdysgenesis with irregular nerve cell distribution in the cortex and an increased number of nerve cells in cortical layer I and in the white matter was found in the right temporal and parietal lobes and bilaterally in the frontal and occipital lobes. The post-mortem examination confirmed the previous diagnosis of microdysgenesis and showed that the changes were widespread in a patient who was operated on because of focal epilepsy.


Polymorphisms in the angiotensin I converting enzyme (ACE) gene are associated with multiple sclerosis risk and response to Interferon-β treatment.
Multiple sclerosis (MS) as a chronic autoimmune demyelinating disorder of the central nervous system has been associated with numerous genetic and environmental factors among them are functional variants within the angiotensin I converting enzyme (ACE) gene. In the present study, we genotyped the rs4359 (C/T) and rs1799752 (Insertion (I)/Deletion (D)) of this gene in 391 MS patients and 380 age- and sex-matched controls. We found significant overrepresentation of the I allele of the rs1799752 in MS patients compared with healthy subjects (Adjusted P value = 0.03, OR (95% CI) = 1.28 (1.05-1.57). The same allele was associated with MS risk in co-dominant and dominant models (Adjusted P values of 0.007 and 0.002 respectively). The allele and genotype frequencies of the rs4359 were not significantly different between cases and controls. Moreover, the I allele of the rs1799752 was significantly overrepresented in MS patients who were irresponsive to IFN-β compared with healthy subjects (Adjusted P value = 0.04, OR (95% CI) = 1.57 (1.08-2.29)). The same allele was associated with irresponsiveness to IFN-β in dominant model (Adjusted P value = 0.02, OR (95% CI) = 2.32 (1.22-4.42)). The present study provides further evidences for the role of ACE in MS risk or response of patients to IFN-β treatment.


Overexpression of ADAMTS-2 in tumor cells and stroma is predictive of poor clinical prognosis in gastric cancer.
ADAMTS-2 is a member of the ADAMTS family and is a procollagen N-proteinase. The objective of our research is to explore the prognostic significance of ADAMTS-2 in gastric carcinoma. A total of 655 samples with full clinicopathological data were investigated in this study. Tissue microarray immunohistochemistry analysis was used to analyze the relationship between clinicopathological characteristics and ADAMTS-2 expression. Oncomine and Kaplan-Meier plotters were performed for the relationship analysis between prognosis and ADAMTS-2 expression in patients with gastric cancer. Compared with that of normal tissues, the ADAMTS-2 protein expression was remarkably higher in gastric cancer cells and fibroblast cells. The results of univariate analysis indicated that the expression of ADAMTS-2 in tumor cells and fibroblast cells, Laurén classification, TNM grade, and carcinoembryonic antigen level in gastric cancer were all correlated with overall survival. The results of multivariate analysis indicated that the high expression of ADAMTS-2 in gastric cancer cells and fibroblast cells both were independent prognostic factors. Therefore, ADAMTS-2 may be a potential biomarker for assessing the prognosis of gastric carcinoma.


Can clinical symptoms or signs accurately predict hypoxemia in children with acute lower respiratory tract infections?
To determine clinical predictors of hypoxemia in children with acute lower respiratory tract infection (ALRI). Cross-sectional study. Emergency department of All India Institute of Medical Sciences, a tertiary care hospital. 109 under five children, with ALRI. Clinical symptoms and signs were recorded. Oxygen saturation was determined by a pulse oximeter. Hypoxemia was defined as oxygen saturation less than 90%. The ability of various clinical symptoms and signs to predict the presence of hypoxemia was evaluated. Twenty-eight (25.7%) children were hypoxemic. No symptoms were statistically associated with hypoxemia. Tachypnea, suprasternal indrawing, intercostal indrawing, lower chest indrawing, cyanosis, crepitations, and rhonchi were statistically significantly associated with hypoxemia. A simple model using the presence of rapid breathing (> or =80/min in children < or =3 m, > or =70/min in >3-12 m and > or =60/min in >12 m) or lower chest indrawing had a sensitivity of 78.5% and specificity of 66.7% for detecting hypoxemia. No individual clinical symptom/sign or a combination had both sufficient sensitivity and specificity to identify hypoxemia. None of the clinical features either alone or in combination have desirable sensitivity and specificity to predict hypoxemia in children with acute lower respiratory tract infection.


Tolmesoxide, a drug that lowers blood pressure by a direct relaxant effect on vascular smooth muscle.
1 The blood pressure of conscious, deoxycorticosterone acetate (DOCA) hypertensive and 1 kidney Goldblatt hypertensive rats and renal hypertensive and normotensive cats was reduced by tolmesoxide (4,5-dimethoxy-o-tolyl methyl sulphoxide). 2 Tachycardia accompanied the hypotension. In rats the increase in heart rate was abolished by concurrent administration of propranolol. Tachycardia did not occur in pithed rats. 3 Vascoconstriction induced by sympathetic stimulation, noradrenaline, tyramine, angiotensin or vasporessin was antagonized by tolmesoxide. 4 The antagonism of vasoconstrictor responses produced by tolmesoxide was unaffected by beta-adrenoceptor, muscarinic or histamine antagonists. 5 It is concluded that the lowering of pressure produced by tolmesoxide results from a defect relaxant effect on vascular smooth muscle.


Effects of nicorandil on kinetics of oxygen uptake at the onset of exercise in patients with coronary artery disease.
The beneficial effects of coronary vasodilators on exercise capacity in patients with angina pectoris are well known. However, their effects on oxygen uptake (VO2) kinetics at the onset of exercise have not been elucidated. The present study was undertaken to determine the acute effects of nicorandil, a newer coronary vasodilator, on the kinetics of VO2 at the onset of exercise in patients with ischemic heart disease. Ten patients with significant coronary stenosis performed constant mild-intensity cycle exercise (32 +/- 3 W) for 6 minutes after oral administration of 10 mg of nicorandil or an identical placebo in a double-blind, crossover manner. Nicorandil had no effect on resting heart rate, blood pressure, or VO2. However, the time constant for the increase in VO2 during constant work rate exercise was significantly shorter (the kinetics of VO2 were faster) after administration of nicorandil than after placebo (46.5 +/- 13.3 vs 51.1 +/- 11.9 seconds; p = 0.039). The increase in VO2 at 6 minutes compared with 3 minutes of constant work, which reflects the VO2 kinetics, also was reduced with nicorandil (3.8 +/- 37.9 vs 27.5 +/- 27.1 ml/min; p = 0.022). Nicorandil was found to increase the rate of VO2, increase during the onset of constant work rate exercise, probably as a result of an improved response in cardiac output. Analysis of VO2 kinetics provides new and useful parameters for the evaluation of circulatory adjustments at the onset of exercise in patients with ischemic heart disease.


S antigen specific effector T cell activation detected by cytokine flow cytometry.
Effector T cell activation is particularly important in the initiation of autoimmune uveitis. This pilot study seeks to demonstrate activation of human peripheral effector T cells in response to the uveitis candidate autoantigen, retinal S antigen (SAg), using cytokine flow cytometry (CFC). Peripheral blood mononuclear cell (PBMC) suspensions from uveitis patients and controls were stimulated with bovine SAg. Activation responses were detected by CFC. Electronic gating enabled analysis of CD69+, IFN-gamma+ CD4+ lymphocytes. An SAg specific response was detectable in four of 13 patients and four of eight controls. SAg specific, peripheral, effector T cell activation can be detected by CFC. Similar levels of responsiveness were seen in patient and control groups. More detailed cytokine profiling may demonstrate functional differences between the groups.


MS565: A SPECT Tracer for Evaluating the Brain Penetration of BAF312 (Siponimod).
BAF312 (siponimod) is a sphingosine-1-phosphate (S1P) receptor modulator in clinical development for the treatment of multiple sclerosis, with faster organ/tissue distribution and elimination kinetics than its precursor FTY720 (fingolimod). Our aim was to develop a tracer to better quantify the penetration of BAF312 in the human brain, with the potential to be labeled for positron emission tomography (PET) or single-photon emission computed tomography (SPECT). Although the PET radioisotopes (11)C and (18)F could have been introduced in BAF312 without modifying its structure, they do not have decay kinetics compatible with the time required for observing the drug's organ distribution in patients. In contrast, the SPECT radioisotope (123) I has a longer half-life and would suit this purpose. Herein we report the identification of an iodinated derivative of BAF312, (E)-1-(4-(1-(((4-cyclohexyl-3-iodobenzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid (18, MS565), as a SPECT tracer candidate with affinity, S1P receptor selectivity, overall physicochemical properties, and blood pharmacokinetics similar to those of the original molecule. A whole-body autoradiography study performed with [(14)C]MS565 subsequently confirmed that its organ distribution is similar to that of BAF312. This validates the selection of MS565 for (123)I radiolabeling and for use in imaging studies to quantify the brain penetration of BAF312.


Sodium deficiency and salt appetite in ICR: CD1 mice.
Using an outbred strain of mouse, we examined several characteristics of sodium appetite induced by depletion. We found that an appetite for 0.15 M NaCl solution was stimulated 24 h after injection of furosemide and access to a low-sodium diet, but not by low-sodium diet alone. When the duration of exposure to low-sodium diet was increased from 1 to 7 days, there was no additional effect on either the appetite or the blood plasma changes including elevated hematocrit ratio, protein and aldosterone concentrations, and plasma renin activity (PRA). Mice also showed an appetite for hypertonic (0.5 M) NaCl in solutions or in a gel matrix; the intakes of these two were comparable but the gel measurement was gravimetric so maybe more accurate. In the same study, we showed that single injections of either 10 or 40 mg/kg furosemide followed by a 24-h low-sodium diet produced similar appetites, but that 2.5 mg/kg had a submaximal effect. Lastly, we further validated the use of the gel matrix by showing in chronically depleted mice that intake was inversely related to NaCl concentration in the range 0.5-1.5 M, and that appetite was selective for sodium but not the anion with which it was paired.


On the constancy theorem for anisotropic energies through differential inclusions.
In this paper we study stationary graphs for functionals of geometric nature defined on currents or varifolds. The point of view we adopt is the one of differential inclusions, introduced in this context in the recent papers (De Lellis et al. in Geometric measure theory and differential inclusions, 2019. arXiv:1910.00335; Tione in Minimal graphs and differential inclusions. Commun Part Differ Equ 7:1-33, 2021). In particular, given a polyconvex integrand f, we define a set of matrices C f that allows us to rewrite the stationarity condition for a graph with multiplicity as a differential inclusion. Then we prove that if f is assumed to be non-negative, then in C f there is no T N ' configuration, thus recovering the main result of De Lellis et al. (Geometric measure theory and differential inclusions, 2019. arXiv:1910.00335) as a corollary. Finally, we show that if the hypothesis of non-negativity is dropped, one can not only find T N ' configurations in C f , but it is also possible to construct via convex integration a very degenerate stationary point with multiplicity.


Experimental study of the connections of the preglomerular nuclei and corpus mamillare in the rainbow trout, Oncorhynchusmykiss.
The preglomerular complex of trout consists of the anterior (aPGN) and medial (mPGN) preglomerular nuclei and the corpus mamillare (CM). In order to improve knowledge on this complex, we applied a lipophilic neuronal tracer (DiI) to the three nuclei. These nuclei received afferents from the medial part of the dorsal telencephalic area (Dm), the ventral part of the ventral telencephalic area (Vv), the preoptic nucleus, the periventricular layer of the rostral optic tectum and the central posterior thalamic nucleus. The aPGN also received numerous toral projections and, sent efferents to the anterior tuberal nucleus. In addition, both the aPGN and the mPGN nuclei gave rise to efferents to the dorsal region of the dorsal telencephalic area (Dd), whereas the medial preglomerular nucleus and the CM sent fibers to the torus lateralis and the diffuse nucleus, as confirmed by reciprocal labeling. A small mPGN/CM subgroup projected to the optic tectum. These results suggest close functional inter-relationship between the trout preglomerular complex and two telencephalic regions (Dm and Vv). In addition, all nuclei of the complex receive preoptic, tectal and dorsal thalamic afferents, whereas the aPGN and mPGN are related with acoustic-lateral ascending pathways, and the mPGN and CM with the central region of the dorsal telencephalic area and visceral/gustatory pathways.


Prenatal exposure to di-n-butyl phthalate (DBP) differentially alters androgen cascade in undeformed versus hypospadiac male rat offspring.
This study was to compare the alterations of androgen cascades in di-n-butyl phthalate (DBP)-exposed male offspring without hypospadias (undeformed) versus those with hypospadias. To induce hypospadias in male offspring, pregnant rats received DBP via oral gavage at a dose of 750mg/kg BW/day during gestational days 14-18. The mRNA expression levels of genes downstream of the androgen signaling pathway, such as androgen receptor (AR) and Srd5a2, in testes of undeformed rat pups were similar to those in controls; in hypospadiac rat pups these levels were significantly lower than those of control pups. In contrast, both undeformed and hypospadiac rats had decreased serum testosterone levels, reduced mRNA expression of key enzymes in the androgen synthetic pathway in the testes, and ablated genes of developmental pathways, such as Shh, Bmp4, Fgf8, Fgf10 and Fgfr2, in the genital tubercle (GT) as compared to those in DBP-unexposed controls, albeit hypospadiac rats had a more severe decrement than those of undeformed rats. Although other possibilities cannot be excluded, our findings suggest that the relatively normal levels of testosterone-AR-Srd5a2 may contribute to the resistance to DBP toxicity in undeformed rats. In conclusion, our results showed a potential correlation between decreased testosterone levels, reduced mRNA expression of AR and Srd5a2 and the occurrence of hypospadias in male rat offspring prenatally exposed to DBP.


Quantifying posthospital care transitions in older patients.
Older patients frequently receive care in multiple settings. However, there has been a paucity of studies that quantify the number of care transitions or that attempt to explain utilization patterns over a given time period. Furthermore, no studies have examined transitions based on method of payment. The objective of this study was to examine the number of different posthospital interinstitutional transfers (including hospital, inpatient rehabilitation facilities [IRF], and skilled nursing facilities [SNF]) by method of payment (managed Care [MC] or fee-for-service [FFS]). Prospective cohort followed for 12 months. A total of 1055 older patients were identified on transfer from an acute hospital to either an SNF or IRF. Utilization and mortality was tracked over 12 months through analysis of administrative data, chart review, nursing assessments, and patient interviews. After 3 months, 65.3% of MC patients and 75.6% of FFS patients experienced between two and three transfers and an additional 13.8% of MC patients and 14.6% of FFS patients experienced between four and six transfers. Over the next 9 months, the frequency of patient transfers uniformly declined in both payment groups. This study demonstrates that interinstitutional transfers are common in older patients. The majority of these transfers occurred within the first 3 months after hospital discharge for both payment groups. Understanding the frequency and patterns of posthospital care transitions is an important step toward designing innovative approaches to improve the quality of care transitions and ensuring patient safety across settings.


Associations of built food environment with dietary intake among youth with diabetes.
To evaluate the associations of supermarket and fast-food outlet accessibility and availability with dietary intake among youth with diabetes. Subjects' residential location and dietary intake was obtained from the SEARCH for Diabetes in Youth study. Food outlet data obtained from the South Carolina Department of Health and Environmental Control and InfoUSA were merged based on names and addresses of the outlets. The comprehensive data were then used to construct accessibility and availability measures for each participant. State of South Carolina. Three hundred fifty-nine youths with diabetes (10 years old and older) from the SEARCH for Diabetes in Youth study. Supermarket and fast-food outlet accessibility and availability; dietary intake represented by Dietary Approaches to Stop Hypertension (DASH) score. Generalized estimating equations analyses. Increased availability and accessibility of supermarkets were significantly associated with higher DASH score, even after adjusting for individual-level correlates, urbanicity, and fast-food outlet accessibility or availability. Fast-food accessibility, however, was associated only with specific food groups (meat, sweets, and low-fat dairy intake), not with the DASH score. Efforts to promote environments conducive to healthful eating may significantly improve the overall dietary intake and reduce diet-related health complications among youth with diabetes.


Concentrations of isotretinoin and the arotinoid Ro 15-0778 in plasma and tissues of hamsters and rats.
The arotinoid Ro 15-0778 is a potent inhibitor of sebum secretion in rodents but not in humans, while isotretinoin (13-cis-retinoic acid, Accutane) inhibits sebum secretion in rodents and humans. The concentrations of Ro 15-0778 and isotretinoin were determined in plasma and target tissues of castrated, testosterone-stimulated hamsters after oral and topical dosing and in castrated, testosterone-stimulated rats after oral dosing. Comparison of this concentration data to that obtained in the plasma and sebum of humans after dosing with Ro 15-0778 and with isotretinoin did not explain why Ro 15-0778 was a potent inhibitor of sebum production in rodents but not in humans.


Effects of Exercise on Extracellular Vesicles in Patients with Metabolic Dysfunction: a Systematic Review.
The aim of this study was to investigate the effect of exercise on extracellular vesicles (EVs) in patients with metabolic dysfunction. The literatures were searched until Apr 28, 2022, and 16 studies that met inclusion criteria were included in this review. The results showed that the concentrations of platelet-derived extracellular vesicles (PEVs) and endothelial cell-derived extracellular vesicles (EEVs) decreased after long-term exercise, especially for CD62E+ EEVs and CD105+ EEVs. Simultaneously, exercise improved the concentration of clinical evaluation indicators of metabolic diseases, and the changes in these indicators were positively correlated with the changes of EEVs and PEVs. The concentration of skeletal muscle-derived extracellular vesicles (SkEVs) increased after a single bout of exercise. The aforementioned results indicated that long-term exercise might improve endothelial function and hypercoagulability in patients with metabolic dysfunction. The changes in concentrations of EVs could assist in assessing effect of exercise on patients with metabolic dysfunction.


Monoclonal antibodies produced by muscle after plasmid injection and electroporation.
Antibodies are useful for the treatment of a variety of diseases. We here demonstrate that mouse muscle produced monoclonal antibodies (mAb) after a single injection of immunoglobulin genes as plasmid DNA. In vivo electroporation of muscle greatly enhanced antibody production. For chimeric antibodies, levels of 50-200 ng mAb/ml serum were obtained but levels declined after 7-14 days due to an immune response against the xenogeneic parts of the antibody. By contrast, fully mouse antibodies persisted in serum for at least 7 months. mAb produced by the muscle had correct structure, specificity, and biological effector functions. The findings were extended to a larger animal, the sheep, in which mAb serum levels of 30-50 ng/ml were obtained. Sustained levels of serum mAb, induced by single injection of Ig genes and electroporation of muscle cells, may offer significant advantages in the treatment of human diseases.


Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts.
A series of P-stereogenic chiral phosphorus acids (CPAs) were synthesized to determine the requirements for efficient asymmetric organocatalysis. In order to eliminate the need for C 2-symmetry in common CPAs, various scaffolds containing C 1-symmetrical thiophosphorus acids were chosen. These new compounds were synthesized and evaluated in the asymmetric transfer hydrogenation of 2-phenylquinoline. Although the efficacy of the thiophosphorus acids was disappointing for this reaction, the work should be useful for developing structural design elements.


Improvement in Storage Related Lower Urinary Tract Symptoms following Urethroplasty: A Prospective Cohort Study.
In patients with lower urinary tract symptoms, storage related symptoms induce the greatest degree of bother. When associated with urethral stricture, it is unclear how these specific symptoms respond to urethroplasty. This study aims to evaluate the prevalence and effect of urethroplasty on patient reported storage lower urinary tract symptoms. This prospective cohort study evaluated patients undergoing urethroplasty for urethral stricture from 2012-2019. Patients were administered the International Prostate Symptom Score preoperatively and 6 months posturethroplasty. The primary outcomes were change in urinary frequency, urgency, nocturia and composite storage symptom measure according to International Prostate Symptom Score. Symptoms were considered clinically significant if they were graded 3 or greater for the individual domains, and greater than 6 for the combined score. Wilcoxon signed-rank test was used to compare results. A total of 387 patients completed the International Prostate Symptom Score preoperatively and postoperatively. Median age was 50 years and median stricture length was 4.5 cm. Cystoscopic success at 6 months was 96.1%. Preoperatively, urinary frequency, urgency and nocturia were common symptoms (52.5%, 48.8% and 41.6%, respectively). Postoperatively, these rates decreased to 11.6%, 11.4% and 11.1%, respectively, reductions that were significant (p <0.0001) across all domains. Overall storage symptom scores improved significantly (median 8 preoperatively vs 2 postoperatively, p <0.0001). On binary logistic regression, no factor was associated with a lack of response, including stricture recurrence (p=0.44), age (p=0.45), stricture length (p=0.63), location (p=0.13), etiology (p=0.17), number of failed endoscopic treatments (p=0.53) and prior urethroplasty (p=0.06). Urethroplasty yields clinically and statistically significant improvements in storage related lower urinary tract symptoms in men with urethral stricture.


Severe inflammation may be caused by hyperferritinemia of pseudo-pseudo Meigs' syndrome in lupus patients: two cases reports and a literature review.
Pseudo-pseudo Meigs' syndrome or Tjalma syndrome is a rare manifestation of patients with systemic lupus erythematosus defined by the presence of ascites, pleural effusions, and an elevated cancer antigen 125 level. In this case, we described a patient with lupus who presented with sudden impaired renal function and subsequent development of massive ascites with marked high serum ferritin. Hyperferritinemia is one of the abnormal laboratory findings in severe inflammation with ferritin functioning as an inflammatory marker. However, its correlation with lupus activity remains unclear. Therefore, a review of the literature regarding pseudo-pseudo Meigs' syndrome associated with lupus and high ferritin level in this disease was carried out.


Plant production and alternate prey channels impact the abundance of top predators.
While numerous studies have examined the effects of increased primary production on higher trophic levels, most studies have focused primarily on the grazing food web and have not considered the importance of alternate prey channels. This has happened despite the fact that fertilization not only increases grazing herbivore abundance, but other types of consumers such as detritivores that serve as alternate prey for generalist predators. Alternate prey channels can sustain generalist predators at times when prey abundance in the grazing food web is low, thus increasing predator densities and the potential for trophic cascades. Using arthropod data from a fertilization experiment, we constructed a hierarchical Bayesian model to examine the direct and indirect effects of plant production and alternate prey channels on predators in a salt marsh. We found that increased plant production positively affected the density of top predators via effects on lower trophic level herbivores and mesopredators. Additionally, while the abundance of algivores and detritivores positively affected mesopredators and top predators, respectively, the effects of alternate prey were relatively weak. Because previous studies in the same system have found that mesopredators and top predators rely on alternate prey such as algivores and detritivores, future studies should examine whether fertilization shifts patterns of prey use by predators from alternate channels to the grazing channel. Finally, the hierarchical Bayesian model used in this study provided a useful method for exploring trophic relationships in the salt marsh food web, especially where causal relationships among trophic groups were unknown.


The science of hyaluronic acid dermal fillers.
The use of injectable materials for soft-tissue augmentation has been increasing in the United States, reflecting the introduction of new hyaluronic acid (HA)-based dermal fillers. HA dermal fillers vary widely in their physical and chemical characteristics and many variables contribute to their overall performance. This article explains the basic science of HA and describes how the physical properties of HA dermal fillers may influence clinical outcomes. The chemical composition of disaccharide HA monomers, and how they form polymer chains and are crosslinked into gels for dermal fillers are described. Key concepts and properties relevant to the production and performance of HA dermal fillers, such as the degree of crosslinking, gel hardness, gel consistency, viscosity, extrusion force, HA concentration, and extent of hydration are explained. New formulations of HA dermal fillers that have recently been approved by the US Food and Drug Administration differ from currently available HA fillers and may provide enhanced ease of extrusion and persistence over previous fillers. Knowledge of the chemical and physical blueprint of HA dermal fillers may help physicians in choosing the appropriate HA dermal filler for facial enhancements. This, together with appropriate injector training and injection experience, should lead to results that ultimately will benefit patients.


The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.
Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-Acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period. The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; years/smoking 15.7±8.9) were randomized to a double-blind course of 2400mg N-Acetylcysteine (1200mg b.i.d.) or placebo over the course of 3½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning. As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p's<.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus-key default mode network nodes, and the cerebellum [p<.025; FWE]). Taken together, these findings suggest that N-Acetylcysteine may positively affect dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt.


The role of inducible nitric oxide synthase inhibitor on the arteriolar hyporesponsiveness in hemorrhagic-shocked rats.
Hemorrhagic shock (HS) has been implicated in the induction of inducible nitric oxide synthase (iNOS) that leads to increase production of nitric oxide (NO). Recently, NO has been implicated to cause hyporesponsiveness of blood vessel in vitro towards vasoconstrictors in refractory (decompensated) HS. In our in vivo model, we examined the effects of aminoguanidine (AG), a known iNOS inhibitor, with angiotensin II (ANG II), a vasoconstrictor, following hemorrhagic shock decompensatory phase (HSDP) on percentage survival, vascular responsiveness, mean arterial blood pressure (MABP), heart rate and mean nitrate/nitrite levels in anaesthetized rats. HSDP (3 h) was achieved via constant pressure method (40-45 mmHg). MABP and heart rate was measured via the left carotid artery. Plasma collected from HSDP rats was used to measure nitrate/nitrite levels. Vascular hyporeactivity to ANG II was carried out using HSDP aortic strips, precontracted with KCl and noradrenaline. Sham-operated rats served as controls. HSDP rats decreased percentage survival, vascular contractility to ANG II and noradrenaline, MABP, heart rate while showing increased levels of nitrate/nitrite. Infusion of AG with ANG II, increased percentage survival and had reversed these cardiovascular effects of HSDP rats. This study indicates that excessive NO formation from iNOS activity induces vascular hyporeactivity and decompensation in HSDP. This might suggest that selective NOS inhibitor, AG, when coupled with ANG II, show reduction in NO's effect in HSDP.


Novel indolocarbazole protein kinase C inhibitors prevent reactivation of HIV-1 in latently infected cells.
Suppression of human immunodeficiency virus-1 (HIV-1) reactivation in latently infected cells by protein kinase C (PKC) inhibitors has been described. Based on an initial finding with the indolocarbazole inhibitor Gö 6976 we have examined several members of this new class of potent and specific PKC inhibitors with respect to their ability to prevent the PKC-mediated induction of HIV-1 replication in the latently infected U1 cell line. Two of these compounds strongly inhibited not only PMA-induced release of p24-antigen and infectious virus particles into the supernatant (50% inhibition at 0.04-0.35 microM) but also TNF-alpha-mediated HIV-1 reactivation in the same concentration range. Significant lower toxicities compared to Gö 6976 were observed for the new compounds, with 50% cytotoxic concentrations at 5.2 microM for Gö 7775 and 3.4 microM for Gö 7716. This resulted in selectivity indices which were 10-20-times higher compared to the reference compound Gö 6976 and were comparable to those of registered anti-AIDS drugs. No anti-HIV-1 activity was observed for a closely related indolocarbazole analogue with no inhibitory activity in the PKC in vitro enzyme assay. This study demonstrates the important role of PKC in reactivation of HIV-1 in latently infected cells and points to the potential of indolocarbazoles to preserve the latent state of HIV-1 infection.


Barrett's epithelium with complete stricture of the esophagus: hypothesis of its etiology.
A 4-year-old very debilitated boy, who suffered from recurrent vomiting (regurgitation) since birth, is described. At the age of 18 months, partial obstruction of the esophagus was apparent, and only semisolid food could be swallowed. The signs of obstruction progressed, and the child was admitted urgently, at the age of 4 years, to the authors' department because of severe dehydration. After resuscitation, a barium swallow and esophagoscopy showed a complete obstruction of the esophagus between its middle and lower third. Through a left thoracotomy incision, 4 cm of the diseased esophagus were resected and continually established by end-to-end esophagoesophageal anastomosis. Pathological examination showed complete obstruction of the esophagus with Barrett's epithelium above and below the stricture. Severe periesophagitis was also present because of sealed perforation of the esophagus. One week after the operation the child was on a normal diet. On follow-up, 6 months later, he has no signs of obstruction and is gaining weight. It is postulated that the presence of Barrett's epithelium in the esophagus in congenital, but the complications, such as stricture formation, are usually caused by chronic irritation, such as gastroesophageal reflux. Barrett's epithelium alone infrequently will cause


Capillary zone electrophoresis investigation of the interaction between heparin and granulocyte-colony stimulating factor.
The interaction between standard heparin, low-molecular-weight heparin (LMWH), and granulocyte-colony stimulating factor (G-CSF) was studied by capillary zone electrophoresis. Both qualitative and quantitative characterizations of the heparin-protein binding were determined. The binding constants of the two different groups of heparins with G-CSF, calculated from the Scatchard plot by regression, were 4.805 x 10(5) M(-1) and 4.579 x 10(5) M(-1), respectively. The two binding constants measured are of the same order of magnitude at 10(5) M(-1), indicating that LMWH contains most of the functional groups bound to G-CSF by standard heparin.


Polymer chain flexibility-induced differences in fetuin A adsorption and its implications on cell attachment and proliferation.
Tissue cells are known to respond to the stiffness of the polymer substrate on which they are grown. It has been suggested that material stiffness influences the composition of the protein layer that adsorbs to the material surface, which affects subsequent cell behavior. Previously, the stiffness of a biomaterial elastomer formed from an acrylated star-poly(d,l lactide-co-ε-caprolactone) was found to influence both fibroblast proliferation as well as the adsorption of certain proteins. However, it remained unresolved as to whether material stiffness influenced protein adsorption from serum supplemented environments and which protein(s) may have been responsible for the difference in fibroblast proliferation. Using quantitative proteomics, we show that polymer stiffness influenced the composition of the protein layers that adsorb from serum supplemented media. Fetuin A was identified as a protein that influenced fibroblast proliferation and, when combined with basic fibroblast growth factor as a medium supplement, improved fibroblast proliferation over 14days. This study is the first to correlate cell proliferation to surface adsorbed fetuin A and presents the potential new application for fetuin A as biomaterial coating or surface modifier. This work also demonstrates a novel application of quantitative proteomics for the investigation of competitive protein adsorption to biomaterial surfaces. Cells are able to respond to the stiffness of their material substrate, but the method by which they sense material stiffness is still under investigation. Previously, material stiffness was found to impact the individual adsorption of fibronectin, a protein associated with cell attachment; however, it was unclear if stiffness was able to affect protein adsorption in environments with multiple proteins. This study shows that material stiffness affects the compositions of protein layers adsorbed from supplemented media, and suggests that cells may sense material stiffness via the adsorbed protein layer. Interestingly, fetuin A was found to be affecting cell proliferation and not fibronectin. Finally, this research demonstrates the use of relative quantitation proteomics as a potentially powerful method to improve biomaterial compatibility.


Assessment of spinal cord injury by counting corticospinal and rubrospinal neurons.
This paper describes an objective, quantifiable technique for assaying the degree of severity of spinal cord injury. Twenty-one rats underwent a C7-T1 laminectomy: 12 received a C8 spinal cord clip compression injury with forces of either 2.3, 16.9 or 53.0 g; 4 had cord transection at C8, and 5 had no cord lesion. Postoperative clinical neurological assessment was performed by the inclined plane method. At 4 weeks, the spinal cord-injured rats underwent a T10 transection and insertion of a Gelfoam pledget impregnated with horseradish peroxidase (HRP). HRP was similarly administered to 9 normal rats. Longitudinal sections of the spinal cord encompassing the injury site were stained with Luxol fast blue, and coronal sections from the cerebrum and midbrain were processed for HRP reactivity with tetramethylbenzidine. Labelled corticospinal and rubrospinal neurons were counted in every 6th section to derive a cortical score (CS) and a red nucleus score (RNS) for each animal. The CS reflected the extent of the pathological changes at the site of cord injury and the ln CS decreased linearly with increasing injury severity (P less than 0.0001). In contrast, the RNS was only reduced in animals with severe (53.0 g) cord injuries (P less than 0.0006). The degree of preservation of the dorsal columns including the corticospinal tracts at the injury site correlated with the CS, whereas the RNS was related to the degree of preservation of the lateral columns. Counts of rubrospinal neurons, but not corticospinal neurons, correlated closely (r = 0.96, P less than 0.001) with the inclined plane results, suggesting the importance of non-pyramidal tracts in controlling gross motor function. Thus, counting corticospinal and rubrospinal neurons is an objective, reliable test of the severity of experimental spinal cord injury.


The Development of Sociobiology in Relation to Animal Behavior Studies, 1946-1975.
This paper aims at bridging a gap between the history of American animal behavior studies and the history of sociobiology. In the post-war period, ecology, comparative psychology and ethology were all investigating animal societies, using different approaches ranging from fieldwork to laboratory studies. We argue that this disunity in "practices of place" (Kohler, Robert E. Landscapes & Labscapes: Exploring the Lab-Field Border in Biology. Chicago: University of Chicago Press, 2002) explains the attempts of dialogue between those three fields and early calls for unity through "sociobiology" by J. Paul Scott. In turn, tensions between the naturalist tradition and the rising reductionist approach in biology provide an original background for a history of Edward Wilson's own version of sociobiology, much beyond the William Hamilton's papers (Journal of Theoretical Biology 7: 1-16, 17-52, 1964) usually considered as its key antecedent. Naturalists were in a defensive position in the geography of the fields studying animal behavior, and in reaction were a driving force behind the various projects of synthesis called "sociobiology".


[Lambdamycin, an antibiotic from strain IMET 31118 of Streptomyces glaucoachromogenes Prauser. II. Physiochemical properties and comparison with chartreusin].
The isolation and purification of the antibiotic lambdamycin are described. The physicochemical properties of the chromoglysoide lambdamycin resemble those of chartreusin. In this paper we compare the physicochemical properties of chartreusin and antibiotic X 465 with lambdamycin (alpha D, UV, IR). Lambdamycin is identified with chartreusin.


A developmental study of hemisphere specialization for recognition of faces in normal subjects.
In a developmental study of hemisphere lateralization for recognition of faces in normal subjects three groups of subjects (mean ages: 7 years 9 months; 13 years 10 months; and 19 years 6 months) were tested. The procedure was a go-no go reaction time task in which the subject responded to faces tachistoscopically presented to the right or left visual field. A left visual field superiority was found for the two older age groups, which is interpreted as a right hemisphere dominance for recognition of faces. However, the 7 and 8 year old group did not demonstrate a significant visual field difference. These results indicate that the hemisphere specialization (lateralization) for recognition of faces involves processes which develop with increasing age through childhood and is not well-established until some time after the age of 8 and before age 13.


[Workload in emergency departments : A Problem for personnel and patients?]
Apart from operating theaters, intensive care units and diagnostic services, the central emergency department is one of the areas of any hospital with a high workload, which is very susceptible to risk. The following aspects of routine daily work can lead to a great strain on the personnel working in the central emergency department: the need for quick, targeted decisions, especially for patients with life-threatening disorders, a high number of patients with insufficient available resources, dissatisfaction of patients with low treatment priority and longer waiting times and delayed inpatient admissions with long stays. Interruptions in the individual work process during activities are not uncommon but represent additional disruptive factors for employees and can lead to treatment errors. Furthermore, a workload that is permanently perceived as too high leads to psychological and physical disturbances for the team members. Suitable structural, organizational and personnel prerequisites as well as solution strategies for the central emergency department are necessary to avoid corresponding treatment errors and also as a duty of care for employees.


Changes in the clinico-functional characteristics of stroke patients in the acute phase during the COVID-19 pandemic.
To compare the sociodemographic and clinico-functional characteristics of patients admitted to a stroke unit immediately before and during two different COVID-19 pandemic phases. This exploratory study was conducted in the stroke unit of a public hospital in Brazil. Patients consecutively admitted to a stroke unit for 18 months with primary stroke aged ≥20 years were included and divided into three groups: G1: Pre-pandemic; G2: Early pandemic; and G3: Late pandemic. The sociodemographic and clinico-functional characteristics of the groups were compared (α=0.05). The study included 383 individuals (G1=124; G2=151; G3=108). The number of risk factors (higher in G2; p≤0.001), smoking (more common in G2; p≤0.01), type of stroke (ischemic more common in G3; p=0.002), stroke severity (more severe in G2; p=0.02), and level of disability (more severe in G2: p≤0.01) were significantly different among the groups. A greater number of serious events and risk factors including smoking and higher level of disability was observed in patients in the beginning of the pandemic than in the late phases. Only the occurrence of ischemic stroke increased in the late phase. Therefore, these individuals may have an increased need for rehabilitation services monitoring and care during their lifespan. Additionally, these results indicate that health promotion and prevention services should be strengthened for future health emergencies.


The Biomechanical Stability of Bone Staples in Cortical Fixation of Tendon Grafts for Medial Collateral Ligament Reconstruction Depends on the Implant Design.
The promising biomechanical stability of bone staples (BSs) in cortical fixation of tendon grafts for medial collateral ligament (MCL) reconstruction has been revealed by a previous investigation. However, it is currently unknown if the biomechanical stability of cortical fixation of tendon grafts depends on the BS design. To assess the biomechanical stability of cortical fixation of tendon grafts in knee surgery using 4 different BS designs. Controlled laboratory study. Cortical fixation of tendon grafts was performed in a porcine knee model at the tibial insertion area of the MCL using 4 different BS designs (n = 40): 8-mm width without spikes (n = 10), 8-mm width with spikes (n = 10), 14-mm width with spikes (n = 10), and 13 mm-wide 4-prong staples with spikes (n = 10). Specimens were mounted in a materials testing machine, and cyclic loading was applied to the tendon graft (500 cycles at 50 and 100 N, respectively), followed by load-to-failure testing. The Kruskal-Wallis test was performed for statistical analysis (P < .05), and the post hoc Dunn test was performed for multiple comparisons. In 4 of 10 specimens with graft fixation using BSs without spikes, slippage of the tendon underneath the BS led to failure of the construct during cyclic loading to 100 N. In the other groups, no fixation failure was observed during cyclic loading. Furthermore, graft fixation using BSs without spikes was found to have significantly more elongation during cyclic loading (8.2 ± 1.9 mm) and a lower ultimate failure load (170 ± 120 N) compared with graft fixation using narrow BSs with spikes (3.4 ± 1.2 mm [P < .0001] and 364 ± 85 N [P < .05], respectively) and graft fixation using broad BSs with spikes (4.5 ± 1.4 mm [P < .05] and 429 ± 67 N [P < .001], respectively). No statistical differences in elongation during cyclic loading or ultimate failure load were found between 4-prong staples with spikes (5.0 ± 1.3 mm and 304 ± 85 N) and narrow or broad staples with spikes. The biomechanical stability of cortical fixation of an MCL graft was comparable between each BS design with spikes (narrow, broad, and 4-prong) in a porcine knee model, whereas BSs without spikes led to failure of the fixation construct during cyclic loading in 4 of 10 specimens and increased elongation and lower ultimate failure loads in the remainder of the group. BSs without spikes may therefore not be recommended for graft fixation. The use of BSs can help to avoid the conflict of converging tunnels in multiligament reconstruction surgery. An implant design with spikes yields significantly higher biomechanical stability than BSs without spikes.


[Loss of smell and taste within the scope of vitamin B 12 deficiency].
The article deals with the case of a patient who had a partial gastrectomy and developed a vitamin B12 deficiency syndrome with anemia, myelopathy and complete loss of the senses of taste and smell. Regression of the symptoms followed liberal dosing with vitamin B12.


A new automated fourth-generation HIV screening assay with sensitive antigen detection module and high specificity.
New screening enzyme immunoassays, which permit the simultaneous detection of HIV antigens reduce the diagnostic window period between the time of immunodeficiency virus (HIV) infection and seroconversion. The VIDAS HIV DUO Ultra is an enzyme-linked fluorescent assay (ELFA) for the screening of HIV infection. It is performed with the fully automated VIDAS or mini-VIDAS instruments, which are so-called walk away systems. The detection limit is 3 pg of HIV-1 p24 Ag/mL serum. HIV antibody is detected with the same sensitivity as stand-alone third-generation antibody tests. The total incubation time is about 2 h. Results are calculated, interpreted, and printed by the VIDAS instrument. Usually, fourth-generation assays demand a special algorithm for the analysis of reactive samples. For the anti-HIV part of the assay, confirmation of reactivity should be done with an assay that lacks the p24-antigen detection module and when reactivity persists subsequently by immunoblot. For the p24-antigen part, confirmation of reactivity should be analyzed in an assay that lacks the anti-HIV detection part.


Therapy of chronic myeloid leukaemia can benefit from the activation of stem cells: simulation studies of different treatment combinations.
Newly diagnosed patients with chronic myeloid leukaemia (CML) are currently treated with tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib or dasatinib. However, incomplete eradication of residual disease is a general problem of long-term TKI therapy. Activation of mouse haematopoietic stem cells by interferon-α (IFNα) stimulated the discussion of whether a combination treatment leads to accelerated eradication of the CML clone. We base our simulation approach on a mathematical model describing human CML as a competition phenomenon between normal and malignant cells. We amend this model to incorporate the description of IFNα activity and simulate different scenarios for potential treatment combinations. We demonstrate that the overall sensitivity of CML stem cells to IFNα activation is a crucial determinant for the benefit of a potential combination therapy. We furthermore show that pulsed IFNα together with continuous TKI administration is the most promising strategy for a combination treatment in which the therapeutic benefit prevails adverse side effects. Our modelling approach is a highly beneficial tool to quantitatively address the competition between normal and leukaemic haematopoiesis in treated CML patients. We derive testable predictions for different experimental settings that are suggested before the clinical implementation of the combination treatment.


Bifurcation analysis on ion sound and Langmuir solitary waves solutions to the stochastic models with multiplicative noises.
This article explores on a stochastic couple models of ion sound as well as Langmuir surges propagation involving multiplicative noises. We concentrate on the analytical stochastic solutions including the travelling and solitary waves by using the planner dynamical systematic approach. To apply the method, First effort is to convert the system of equations into the ordinary differential form and present it in form of a dynamic structure. Next analyze the nature of the critical points of the system and obtain the phase portraits on various conditions of the corresponding parameters. The analytic solutions of the system in an account of distinct energy states for each phase orbit are performed. We also show how the results are highly effective and interesting to realize their exciting physical as well as the geometrical phenomena based on the demonstration of the stochastic system involving ion sound as well as Langmuir surges. Descriptions of effectiveness of the multiplicative noise on the obtained solutions of the model, and its corresponding figures are demonstrated numerically.


Prospects for electron beam aberration correction using sculpted phase masks.
Technological advances in fabrication methods allowed the microscopy community to take incremental steps towards perfecting the electron microscope, and magnetic lens design in particular. Still, state of the art aberration-corrected microscopes are yet 20-30 times shy of the theoretical electron diffraction limit. Moreover, these microscopes consume significant physical space and are very expensive. Here, we show how a thin, sculpted membrane is used as a phase-mask to induce specific aberrations into an electron beam probe in a standard high resolution TEM. In particular, we experimentally demonstrate beam splitting, two-fold astigmatism, three-fold astigmatism, and spherical aberration.


Modification of transport function of plasma albumin during atherosclerosis and diabetes mellitus.
Parameters characterizing the processes of association, transport, and dissociation of fatty acid molecules on the corresponding binding sites of plasma albumin in patients with atherosclerosis and diabetes mellitus were studied by electron paramagnetic resonance method. In these patients transport function of albumin differed from normal. It should be emphasized that these differences were specific for atherosclerosis and diabetes mellitus, which is of considerable diagnostic value.


N-heterocyclic carbene catalyzed regioselective oxo-acyloxylation of alkenes with aromatic aldehydes: a high yield synthesis of α-acyloxy ketones and esters.
An N-heterocyclic carbene (NHC)-catalyzed reaction of alkenes with aromatic aldehydes providing for a high yield synthesis of α-acyloxy ketones and esters has been described. This unprecedented regioselective oxidative process employs NBS and Et3N in stoichiometric amounts and O2 (1 atm) as an oxidant under ambient conditions in DMSO as a solvent.


Mitomycin C plus vindesine or cisplatin plus epirubicin in previously treated patients with symptomatic advanced non-small-cell lung cancer.
A total of 40 previously treated patients with symptomatic advanced non-small-cell lung cancer (NSCLC) were subjected to second-line chemotherapy with mitomycin C plus vindesine (MV) or cisplatin plus epirubicin (PE). The 12 patients treated with the MV regimen showed no objective response (OR) or symptom palliation. In the 28 patients who received the PE regimen, we obtained a 25% partial response rate, with amelioration of tumor-related symptoms occurring in 35.7% of cases and improvement in the performance status being noted in 25% of subjects. Both regimens were well tolerated. These data show that the administration of cisplatin-based second-line chemotherapy to patients with symptomatic advanced NSCLC may be useful.


Antiepithelial autoantibodies associated with the feline eosinophilic granuloma complex.
A retrospective study of banked sera from 19 cats with the eosinophilic granuloma complex revealed that 68% of affected cats had circulating antibodies to components of normal cat epithelium. Seemingly, the eosinophilic granuloma complex of cats may be an autoimmune disease; however, epidermal damage caused by the eosinophilic granuloma complex may release altered self-antigens to which the cat's immune system responds.


Bacterial lipopolysaccharide protects the retina from light-induced damage.
Light-induced damage is a widely used model to study retinal degeneration. We examined whether bacterial lipopolysaccharide (LPS) protects the retina against light-induced injury. One day before intense light exposure for 24 h, rats were intravitreally injected with LPS in one eye and vehicle in the contralateral eye. At several time points after light exposure, rats were subjected to electroretinography and histological analysis. Bax, Bcl-xL, p-Akt, and p-Stat3 levels were assessed by Western blotting, and retinal thiobarbituric acid reactive substances levels were measured as an index of lipid peroxidation. One group of animals received injections of dexamethasone, aminoguanidine (an inducible NOS inhibitor), 5-hydroxydecanoic acid (a mitochondrial K(+) /ATP channel blocker), or wortmannin [a phosphoinositide-3-kinase (PI3K) inhibitor] in order to analyze their effect on the protection induced by LPS. LPS afforded significant morphologic and functional protection in eyes exposed to intense light. Light damage induced an increase in mitochondrial Bax/cytoplasmic Bax ratio, and lipid peroxidation which were prevented by LPS. Dexamethasone and wortmannin (but not aminoguanidine or 5-hydroxydecanoic acid) prevented the effect of LPS. Moreover, wortmannin prevented the effect of LPS on p-Akt levels. These results indicate that LPS provides retinal protection against light-induced stress, probably through a PI3K/Akt-dependent mechanism.


Diet and exercise are equally effective in reducing risk for cardiovascular disease. Results of a randomized controlled study in men with slightly to moderately raised cardiovascular risk factors.
To study the impact of diet and exercise and the combination thereof on cardiovascular risk factors, 157 healthy men aged 35-60 years (mean +/- S.D.; 46.2 +/- 5.0) with slightly to moderately raised cardiovascular risk factors, were randomized to 4 groups, diet (D, n = 40), exercise (E, n = 39), diet plus exercise (DE, n = 39), and no active intervention (controls (C, n = 39)), and investigated at baseline and after 6 months. BMI was significantly reduced in Groups E and DE (mean difference and 95% confidence intervals (CI), -0.3 (-0.5, -0.01) and -0.6 (-0.9, -0.3) kg/m2, respectively). Waist circumference was reduced in all 3 intervention groups (D, E, and DE), -1.3 (-2.5, -0.1), -2.2 (-3.2, -1.3) and -3.0 (-3.9, -2.0) cm, but not in the control group. Blood pressure (BP) was reduced in all 3 intervention groups, systolic BP 4-7 mmHg and diastolic BP 2-6 mmHg. Serum cholesterol was reduced in Group DE, -0.45 (-0.77, -0.13) mmol/l. VLDL-cholesterol was reduced in Groups E and DE, -0.14 (-0.26, -0.03) and -0.09 (-0.18, -0.01) mmol/l, whereas LDL-cholesterol was reduced in Groups D and DE -0.30 (-0.54, -0.06) and -0.35 (-0.64, -0.05) mmol/l. In contrast, neither HDL-cholesterol nor serum triglycerides were influenced by the interventions. According to the coronary risk profile derived from the Framingham study, all 3 intervention groups (D, E, and DE) significantly reduced their estimated 10-year risk (-13, -12, and -14%, respectively). We conclude that even with rather moderate changes in diet and exercise, several important cardiovascular risk factors can be affected and that diet and exercise were about equally effective in reducing cardiovascular risk.


Testicular hormones during the first few hours after birth augment the tendency of adult male rats to mount receptive females.
In the male rat, a dramatic increase in serum testosterone of testicular origin occurs during the first two hours of postnatal life. This experiment was designed to determine whether this increase contributes to the development of the propensity for adult male rats to mount sexually receptive females. Male rats were castrated at either 0-hours (virtually at the moment of birth), or at 6 hours, or at 24 hours after birth. Some males castrated at 0-hours were injected with 1 microgram of testosterone after surgery. Control males were sham-operated at birth, and castrated in adulthood. At about 90 days of age, each male was given testosterone replacement therapy and tested over a period of 6 weeks for mounting. Castration of newborn males retards the development of mounting in the sense that males castrated at 0-hours require a longer period of hormone stimulation before beginning to mount, a greater percentage of males castrated at 0-hours fail to mount altogether, and even those who do mount do so at a frequency significantly lower than that for males castrated later in life. These effects are not seen when males are given an injection of testosterone immediately after castration at 0-hours, or when castration occurs at 6 hours after birth or later. We conclude that gonadal hormonal stimulation during the first several hours after birth contributes to, although is perhaps not essential for, the development of mounting.


[Delayed incision time of the first case : Analysis of incidences and causes and the effect of list planning instability].
Delays in beginning operations in the morning lead to a loss of valuable operating time and can cause frustration among the medical personnel involved. So far there are no prospective, multicentric investigations of the incidence and reasons for delayed first incision times in the morning. The effect of planning list instability of first cases on late operating room starts has not yet been evaluated. In this multicenter prospective study delays in surgical incision time in all first cases of the day were investigated in 36 German and Swiss hospitals (14 surgical specialties) over a period of 2 weeks. A total of 3628 first of the day cases were included in the study. Looking at all subspecialties combined 50.8% of the first cases of the day were delayed by more than 5 min and in 30.2% of cases longer than 15 min. Incidences of delayed surgical incision time >5 min ranged from 40.0% (gynecology) to 66.8% (neurosurgery). The main reasons for delays in ascending order were prolonged induction of anesthesia compared to the planned time, the delayed appearance of the surgeon and prolonged preparation for surgery. The incidence of delays in incision times for planning list instability was increased by 10% and the average delay increased by 7 min. Delays in surgical incision times of the first operation of the day have a high incidence in most surgical specialties; however, the reasons for delays are manifold. Plan instability of operating room lists with respect to the first cases has a negative effect on the punctuality of the incision time and should therefore be avoided.


Contributions of increased osteopontin and hypophosphatemia to dentoalveolar defects in osteomalacic Hyp mice.
X-linked hypophosphatemia (XLH) is an inherited disorder caused by inactivating mutations in the PHEX gene leading to renal phosphate wasting, rickets and osteomalacia. XLH is also associated with dentoalveolar mineralization defects in tooth enamel, dentin and cementum, and in alveolar bone, which lead to an increased prevalence of dental abscesses, periodontal disease and tooth loss. Genetic mouse experiments, and deficiencies in XLH patient therapies where treatments do not fully ameliorate mineralization defects, suggest that other pathogenic mechanisms may exist in XLH. The mineralization-inhibiting, secreted extracellular matrix phosphoprotein osteopontin (OPN, gene Spp1) is a substrate for the PHEX enzyme whereby extensive and inactivating degradation of inhibitory OPN by PHEX facilitates mineralization. Conversely, excess OPN accumulation in skeletal and dental tissues - for example in XLH where inactivating mutations in the PHEX gene limit degradation of inhibitory OPN, or as occurs in Fgf23-null mice - contributes to mineralization defects. We hypothesized that Spp1/OPN ablation in Hyp mice (a mouse model for XLH) would reduce dentoalveolar mineralization defects. Immunostaining revealed increased OPN in Hyp vs. wild-type (WT) alveolar bone, particularly in osteocyte lacunocanalicular networks where Hyp mice have characteristic hypomineralized peri-osteocytic lesions (POLs). Micro-computed tomography and histology showed that ablation of Spp1 in Hyp mice (Hyp;Spp1-/-) on a normal diet did not ameliorate bulk defects in enamel, dentin, or alveolar bone. On a high-phosphate diet, both Hyp and Hyp;Spp1-/- mice showed improved mineralization of enamel, dentin, and alveolar bone. Silver staining indicated Spp1 ablation did not improve alveolar or mandibular bone osteocyte POLs in Hyp mice; however, they were normalized by a high-phosphate diet in both Hyp and Hyp;Spp1-/- mice, although inducing increased OPN. Collectively, these data indicate that despite changes in OPN content in the dentoalveolar mineralized tissues, there exist other compensatory mineralization mechanisms that arise from knockout of Spp1/OPN in the Hyp background.


Predictors of atrial fibrillation detection and features of recurrent strokes in patients after cryptogenic stroke.
Use of implantable cardiac monitors (ICMs) has increased diagnosis of atrial fibrillation (AF) in cryptogenic stroke (CS) patients. Identifying AF predictors may enhance the yield of AF detection. Recurrent strokes after CS are not well described. We aimed to assess the predictors for AF detection and the characteristics of recurrent strokes in patients after CS. We reviewed electronic medical records of CS patients who were admitted between February 2014 and September 2017 and underwent ICM placement with minimum one-year follow-up. Patient demographics, stroke characteristics, pre-defined risk factors as well as recurrent strokes were compared between patients with and without AF detection. 389 patients with median follow-up of 548 days were studied. AF was detected in 102 patients (26.2%). Age (per decade increase, OR 2.10, CI 1.64-2.68, with vs. without AF) and left atrium diameter (per 5 mm increase, OR 1.91, CI 1.33-2.74) were identified as AF predictors. Intracranial large vessel stenosis >50% irrelevant to the index strokes was associated with AF detection within 30 days (OR 0.24, CI 0.09-0.69, >30 vs. <30 days). Recurrent strokes occurred in 14% patients with median follow-up about 2.5 years. Topography of these strokes resembled embolic pattern and was comparable between patients with and without AF. Among recurrent strokes in patients with AF, the median time to AF detection was much shorter (90 vs. 251 days), and the median time to first stroke recurrence was much longer (422 vs. 76 days) in patients whose strokes recurred after AF detection than those before AF detection. Older age and enlarged left atrium are predictors for AF detection in CS patients. Intracranial atherosclerosis is more prevalent in patients with early AF detection within 30 days. Recurrent strokes follow the embolic pattern, and early AF detection could delay the stroke recurrence.


The effects of oxytocin on the activity of cells in the anterior hypothalamus in experimental stress.
Acute experiments on white laboratory rats were performed to study spike activity in neurons of the anterior hypothalamus in response to i.v. injections of different doses of oxytocin. The results showed that oxytocin evoked different types of rearrangement of neuron activity both in intact and in stressed animals. The dose-related effects of oxytocin affected the latent periods of neuron responses and the nature of rearrangements in spike activity. The greater the frequency of the baseline activity of the cells, the less marked was the response of the neurons to administration of oxytocin.


The tempo of Ediacaran evolution.
The rise of complex macroscopic life occurred during the Ediacaran Period, an interval that witnessed large-scale disturbances to biogeochemical systems. The current Ediacaran chronostratigraphic framework is of insufficient resolution to provide robust global correlation schemes or test hypotheses for the role of biogeochemical cycling in the evolution of complex life. Here, we present new radio-isotopic dates from Ediacaran strata that directly constrain key fossil assemblages and large-magnitude carbon cycle perturbations. These new dates and integrated global correlations demonstrate that late Ediacaran strata of South China are time transgressive and that the 575- to 550-Ma interval is marked by two large negative carbon isotope excursions: the Shuram and a younger one that ended ca. 550 Ma ago. These data calibrate the tempo of Ediacaran evolution characterized by intervals of tens of millions of years of increasing ecosystem complexity, interrupted by biological turnovers that coincide with large perturbations to the carbon cycle.


Laparoscopic management for spontaneous rupture of left gastroepiploic vessel after forceful retching.
Spontaneous rupture of the left gastroepiploic vessel causing abdominal apoplexy or spontaneous hemoperitoneum is extremely rare. Such ambiguous condition can delay diagnosis, resulting in hypovolemic shock. Reporting such rare cases is valuable to clinicians. Here, we report a 19-year-old man who initially presented left upper quadrant pain and diaphoresis followed by vomiting after ingesting alcohol. He was diagnosed with diffuse hemoperitoneum and large amount of hematoma in left side of lesser sac due to spontaneous rupture of left gastroepiploic vessel. The patient underwent emergency exploratory laparoscopy. Bleeding was controlled by clipping the teared vessel.


Amplification of bacterial plasmids without blocking protein biosynthesis.
The effect of amino acids (presence or absence from the growth media) and metal ions on the replication of Escherichia coli plasmids in rel A+ strains was studied. It was found that: (i) The absence of one amino acid from the growth media had no effect on the plasmid copy number in prototrophic E. coli strains: (ii) The presence of only one amino acid in artificial media free of amino acids had a negligible effect on the plasmid copy number for the amino acids Ala, Arg, Glu, His, Leu, Phe, Thr, Trp, and Tyr: (iii) The combination of Met and Thr caused a rise in pBR322 plasmid copy number up to 90-100 plasmid copies per cell: (iv) The Fe3+ concentration had an amplification effect on E. coli plasmids. The pBR322 plasmid copy number for media free of amino acids and supplemented with 0.2-0.4 mM FeCl3 was 60-80 plasmid copies per cell: (v) The combination of Fe3+ with certain amino acids (Ala, Arg, Glu, Leu, Thr, and Trp) leads to a dramatic increase in the plasmid copy number reaching 180-270 plasmid copies per cell for the plasmid pBR322 and 20-24 for the plasmid pR100.


Glucose-stimulated PGC-1α couples with CBP and Runx2 to mediate intervertebral disc degeneration through transactivation of ADAMTS4/5 in diet-induced obesity mice.
Emerging evidence suggests that type 2 diabetes mellitus (T2DM) is associated with the pathogenesis of intervertebral disc degeneration (IDD). However, it is still unclear how T2DM contributes to IDD. Herein, we observed the accumulation of blood glucose and degenerative lumbar discs in mice fed a high-fat diet. Detection of differentially expressed genes in degenerative lumbar discs revealed that ADAMTS4 (A Disintegrin and Metalloproteinase with Thrombospondin motifs) and ADAMTS5 genes were significantly increased. In vitro analyses demonstrated that Runt-Related Transcription Factor 2 (Runx2) recruited both PPARgamma Coactivator 1alpha (PGC-1α) and CREB-Binding Protein (CBP) to transactivate the expression of ADAMTS4/5. Glucose stimulation could dose-dependently induce the accumulation of PGC-1α and promoted the binding of the CBP-PGC-1α-Runx2 complex to the promoters of ADAMTS4/5. Depletion of CBP-PGC-1α-Runx2 complex members and treatment with either PGC-1α inhibitor SR-18292 or CBP inhibitor EML425 in vitro could dramatically inhibit the glucose-induced expression of ADAMTS4/5. Administration of SR-18292 and EML425 in diabetic mice could prevent the degeneration of lumbar discs. Collectively, our results revealed a molecular mechanism by which the hyperglycemia-dependent CBP-PGC-1α-Runx2 complex was required for the transactivation of ADAMTS4/5. The blockage of this complex in diabetic mice may help prevent IDD.


Toxicity and carcinogenicity of nitrofurazone in F344/N rats and B6C3F1 mice.
Toxicology and carcinogenesis studies were conducted by feeding diets containing nitrofurazone (99% pure) to groups of F344/N rats and B6C3F1 mice for 14 days, 13 wk or 2 yr. In the 14-day studies, in which doses ranged from 630 to 10,000 ppm, nitrofurazone was more toxic to mice than to rats. Accordingly, in the 13-wk studies, doses for rats ranged from 150 to 2500 ppm and for mice from 70 to 1250 ppm. At the higher doses, convulsive seizures and gonadal hypoplasia were observed in both species. Evidence of toxicity in rats also included degenerative arthropathy. For the 2-yr studies, rats were exposed to 0, 310 or 620 ppm nitrofurazone and the survival of male rats given 620 ppm was lower than that of controls (33/50, 30/50 and 20/50 in the control, 310- and 620-ppm groups, respectively). Nitrofurazone administration increased the incidences of mammary gland fibroadenomas in female rats (8/49, 36/50 and 36/50 in the control, 310- and 620-ppm groups, respectively). In male rats it was associated with a marginal increase in sebaceous gland adenomas and trichoepitheliomas of the skin, mesotheliomas of the tunica vaginalis, and tumours of the perputial gland. Nitrofurazone caused testicular degeneration (atrophy of germinal epithelium and aspermatogenesis) in rats, and degeneration of vertebral and knee articular cartilage in rats of both sexes. In mice, dietary concentrations of nitrofurazone for the 2-yr studies were 0, 150 or 310 ppm. In mice of each sex, nitrofurazone administration induced stimulus-sensitive convulsive seizures, primarily during the first year of study. In male mice, there was no evidence of any chemically-related carcinogenic effects, but there was a treatment-related decrease in survival (39/50, 31/50 and 27/50 in the control, 150- and 310-ppm groups, respectively). In female mice nitrofurazone induced ovarian lesions with increased incidences of benign mixed tumours (0/47, 17/50 and 20/50 in control, low- and high-dose groups, respectively) and granulosa cell tumours (1/47, 4/50 and 9/50 in control, low- and high-dose groups, respectively).


'They leave at least believing they had a part in the discussion': understanding decision aid use and patient-clinician decision-making through qualitative research.
This study explores how patient decision aids (DAs) for antihyperglycemic agents and statins, designed for use during clinical consultations, are embedded into practice, examining how patients and clinicians understand and experience DAs in primary care visits. We conducted semistructured in-depth interviews with patients (n=22) and primary care clinicians (n=19), and videorecorded consultations (n=44). Two researchers coded all transcripts. Inductive analyses guided by grounded theory led to the identification of themes. Video and interview data were compared and organized by themes. DAs used during consultations became flexible artifacts, incorporated into existing decision making roles for clinicians (experts, authority figures, persuaders, advisors) and patients (drivers of healthcare, learners, partners). DAs were applied to different decision making steps (deliberation, bargaining, convincing, case assessment), and introduced into an existing knowledge context (participants' literacy regarding shared decision-making (SDM) and DAs). DAs' flexible use during consultations effectively provided space for discussion, even when SDM was not achieved. DAs can be used within any decision-making model. Clinician training in DA use and SDM practice may be needed to facilitate DA implementation and promote more ideal-type forms of sharing in decision making.


Covalently immobilized chemically modified lysozyme as a sorbent for bacterial endotoxins (lipopolysaccharides).
Chemical modification of lysozyme was carried out using benzaldehyde and anisaldehyde. It was shown that chemical modification affects only 1-2 amino groups of the protein molecule which does not prevent further covalent immobilization of lysozyme using the remaining free amino groups. The bacteriolytic activity of lysozyme is preserved after chemical modification and after subsequent covalent immobilization. As a result of chemical modification immobilized lysozyme more effectively adsorbs bacterial lipopolysaccharides (endotoxins). Adsorption of immunoglobulin G does not increase after modification. The sorbents obtained in this work can be used for the future development of new medical material for the extracorporeal treatment of sepsis. The proposed scheme for the modification and immobilization of lysozyme can be used with various aldehydes for the preparation of sorbents with different properties.


THE AMERICAN SOCIETY OF CLINICAL PSYCHOPHARMACOLOGY SURVEY OF PSYCHOPHARMACOLOGISTS' PRACTICE PATTERNS FOR THE TREATMENT OF MOOD DISORDERS.
Optimal successive treatment decisions are not well established after an initial medication nonresponse in major depressive disorder or bipolar disorder. While practice guidelines offer consensus-based expert treatment recommendations, little is known about "real world" pharmacology decision making by practicing psychopharmacologists. We surveyed via Internet the national membership of the American Society of Clinical Psychopharmacology (ASCP) to study preferred pharmacotherapy strategies and factors that influence medication choices for patients with mood disorders. Surveys were returned by 154/752 ASCP members (21%). After nonresponse to a serotonin reuptake inhibitor in major depressive disorder, participants equally favored switching within or across antidepressant classes. After a partial response, adjunctive bupropion was the preferred intervention, followed by changing antidepressant classes. Atypical antipsychotic augmentation was only a fourth-line consideration, even though moderate or marked efficacy was perceived in most instances with olanzapine, aripiprazole, and quetiapine. Respondents favored avoiding antidepressants in bipolar I patients with mixed/cycling features or prior antidepressant-associated mania/hypomania. In rapid cyclers, they advocated antidepressant cessation and preferred the use of atypical antipsychotics and lamotrigine. Participating psychopharmacologists treating adults with mood disorders report prescribing medications that largely mirror the evidence base with only a few notable exceptions, in consideration of the characteristics of definable clinical subpopulations.


The value of genetic polymorphisms to predict toxicity in metastatic colorectal patients with irinotecan-based regimens.
We are trying to identify predictive factors of high risk of toxicity by analyzing candidate genes in the irinotecan pathways in order to identify useful tools to improve mCRC patient management under real practice conditions. Genomic DNA was genotyped for UGT1A1 (*28, *60 and *93) from all 101 patients, and irinotecan dose was 180 mg/m(2) every second week. Clinical data were obtained by retrospective chart review. The primary endpoint is to find out whether the pharmacogenetic test in the clinical practice may predict toxicity. Grade 3/4 diarrhea occurred in twelve patients and required dose reduction in six patients, and neutropenia reached grade 3/4 in 19 patients (only one patient with *28/*28 genotype). The UGT1A1*93 seemed to relate with grade 3/4 neutropenia but only in the heterozygote state (G/A), p = 0.071, and UGT1A*60 showed no association with neutropenia. Twenty-eight percentage of patients required the use of G-CSF; 64.3% of them harbored *1/*28 or *28/*28 genotypes, p = 0.003. Thirty-seven (36.6%) patients required dose reduction of irinotecan and/or 5-FU owing to toxicity, mainly neutropenia and diarrhea. No significant association was detected between *28, *60 and *93 UGT1A variants and severe irinotecan-associated hematologic or GI toxicity. The impact of increased risk of toxicity attributed to the UGT1A variants may be offset by irinotecan in clinical practice by dose reduction or the use of colony-stimulating factor.


The relationship of growth hormone to 1,25-dihydroxyvitamin D3 in intestinal calcium transport.
The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and bovine growth hormone (bGH) on intestinal calcium transport have been assessed in vitamin D deficient rats. Calcium transport did not increase after 7 days bGH treatment. A single dose of 1,25(OH)2D3 significantly increased calcium transport in the hypophysectomized (Hx) rats treated with bGH but not in the Hx rats who did not receive bGH, unless the dosage of 2,25(OH)2D3 was increased to 500 p moles. Even though calcium transport in the Hx rats was stimulated by the high dose of 1,25(OH)2D3, this response was less in the Hx than in bGh treated group. These results suggest that growth hormone status may be important in the expression of 1,25-(OH)2D3 action on intestinal calcium transport.


Phenotypic Profiles Among 72 Caucasian and Afro-Caribbean Patients with Antisynthetase Syndrome Involving Anti-PL7 or Anti-PL12 Autoantibodies.
Antisynthetase syndrome (ASyS) is a rare autoimmune disease. We aimed to determine clinical, biological, radiological, and evolutive profiles of ASyS patients with anti-PL7 or anti-PL12 autoantibodies. We performed a retrospective study that included adults with overt positivity for anti-PL7/anti-PL12 autoantibodies and at least one Connors' criterion. Among 72 patients, 69% were women, 29 had anti-PL7 and 43 anti-PL12 autoantibodies, median age was 60.3 years, and median follow-up period was 52.2 months. At diagnosis, 76% of patients had interstitial lung disease, 61% had arthritis, 39% myositis, 25% Raynaud's phenomenon, 18% mechanic's hands, and 17% had fever. The most frequent pattern on initial chest computed tomography was non-specific interstitial pneumonia and 67% had fibrosis at last follow-up. During follow-up, 12 patients had pericardial effusion (18%), 19 had pulmonary hypertension (29%), 9 (12.5%) had neoplasms, and 14 (19%) died. Sixty-seven patients (93%) received at least one steroid or immunosuppressive drug. Patients with anti-PL12 autoantibodies were younger (p=0.01) and more frequently exhibited anti-SSA autoantibodies (p=0.01); patients with anti-PL7 autoantibodies had more severe weakness and higher maximum creatine kinase levels (p=0.03 and 0.04, respectively). Initial severe dyspnoea was more common in patients from the West Indies (p=0.009), with lower predicted values of forced vital capacity, forced expiratory volume in 1s, and total lung capacity (p=0.01, p=0.02, p=0.01, respectively) contributing to a more severe 'respiratory' initial presentation. The high mortality and significant numbers of cardiovascular events, neoplasms and lung fibrosis in anti-PL7/12 patients justify close monitoring and question addition of antifibrotic drugs.


Police agencies on Facebook overreport on Black suspects.
A large and growing share of the American public turns to Facebook for news. On this platform, reports about crime increasingly come directly from law enforcement agencies, raising questions about content curation. We gathered all posts from almost 14,000 Facebook pages maintained by US law enforcement agencies, focusing on reporting about crime and race. We found that Facebook users are exposed to posts that overrepresent Black suspects by 25 percentage points relative to local arrest rates. This overexposure occurs across crime types and geographic regions and increases with the proportion of both Republican voters and non-Black residents. Widespread exposure to overreporting risks reinforcing racial stereotypes about crime and exacerbating punitive preferences among the polity more generally.


Diphosphacarbollide analogues of the C5H5- anion: isolation of the nido-di- and triphosphacarboranes 7,8,9-P2CB8H10, [7,8,9-P2CB8H9]-, [7,8,10-P2CB8H9]-, and 7,8,9,10-P3CB7H8.
Treatment of a solution of excess PCl(3) and PS (PS = "proton sponge" = 1,8-dimethylamino naphthalene) with arachno-4-CB(8)H(14) (1) in CH(2)Cl(2), followed by hydrolysis of the reaction mixture, resulted in the isolation of the eleven-vertex diphosphacarbaborane nido-7,8,9-P(2)CB(8)H(10) (2) (yield 34%) as the main product. Other products isolated from this reaction were the phosphacarboranes nido-7,8,9,10-P(3)CB(7)H(8) (3) (yield 5%) and closo-2,1-PCB(8)H(9) (4) (yield 15%). Compound 2 can be deprotonated by PS in CH(2)Cl(2) or NaH in diethyl ether to give the [nido-7,8,9-P(2)CB(8)H(9)](-) (2(-)()) anion, which gives back the original compound, 2, upon re-protonation. Thermal rearrangement of anion 2(-) (Na(+) salt) at 350 degrees C for 2 h produced the isomeric [nido-7,8,10-P(2)CB(8)H(9)](-) (5(-)()) anion, which was isolated as a PPh(4)(+) salt (yield 86%). Multinuclear ((1)H, (11)B, (31)P, and (13)C), two-dimensional [(11)B-(11)B] COSY, (1)H{(11)B(selective)}, (1)H{(31)P(selective)}, and gradient-enhanced ([(1)H-(13)C] HSQC) magnetic resonance measurements led to complete assignments of all resonances which are in excellent agreement with the structures proposed. Coupling constants, (1)J((31)P,(13)C), (2)J((31)P,C,(1)H), and (1)J((31)P,(31)P), were calculated using the DFT method B3LYP/6-311+G(d,p). The molecular geometries of all compounds were optimized ab initio at a correlated level of theory (RMP2(fc)) using the 6-31G basis set, and their correctness was assessed by comparison of the experimental (11)B and (13)C chemical shifts with those calculated by the GIAO-SCF/II//RMP2(fc)/6-31G method. The computations also include the structures and chemical shieldings of the still unknown isomers [nido-7,10,8-P(2)CB(8)H(9)](-) (6(-)) and [nido-7,9,8-P(2)CB(8)H(9)](-) (7(-)).


A Role for The P2Y1 Receptor in Nonsynaptic Cross-depolarization in the Rat Dorsal Root Ganglia.
Non-synaptic transmission is pervasive throughout the nervous system. It appears especially prevalent in peripheral ganglia, where non-synaptic interactions between neighboring cell bodies have been described in both physiological and pathological conditions, a phenomenon referred to as cross-depolarization (CD) and thought to play a role in sensory processing and chronic pain. CD has been proposed to be mediated by a chemical agent, but its identity has remained elusive. Here, we report that in the rat dorsal root ganglion (DRG), the P2Y1 purinergic receptor (P2RY1) plays an important role in regulating CD. The effect of P2RY1 is cell-type specific: pharmacological blockade of P2RY1 inhibited CD in A-type neurons while enhancing it in C-type neurons. In the nodose ganglion of the vagus, CD requires extracellular calcium in a large percentage of cells. In contrast, we show that in the DRG extracellular calcium appears to play no major role, pointing to a mechanistic difference between the two peripheral ganglia. Furthermore, we show that DRG glial cells also play a cell-type specific role in CD regulation. Fluorocitrate-induced glial inactivation had no effect on A-cells but enhanced CD in C-cells. These findings shed light on the mechanism of CD in the DRG and pave the way for further analysis of non-synaptic neuronal communication in sensory ganglia.


The 14th of April, Past and Present.
In May 2019, the World Health Organization established the "World Chagas Disease Day", to be celebrated on the 14th of April [...].


A comparison of a CB17 scid mouse model and the tetrazolium-dye assay using human haematological tumour cell lines.
Haematological tumours in the CB17 scid mouse produce a disseminated blood-borne disease analogous to that seen in humans. The CB17 scid mouse model has been applied to study the efficacy of chemotherapeutic agents on tumours. Using three human tumour-cell lines of haemopoietic origin (CCRF-CEM, Raji, HS-Sultan), we established disseminated tumours in scid mice and studied the in vivo response of these tumours to four chemotherapeutic agents (daunorubicin, idarubicin, ifosfamide, etoposide). The in vitro drug-resistance profiles of the same cell lines to these drugs were also determined by the tetrazolium-dye (MTT) assay. Differences were found in the patterns of resistance and sensitivity of the cell lines in the in vivo and in vitro systems tested. Since the scid mouse model determines the in vivo response of both host and tumour to cytotoxic agents, it may be more valid than the other models in determining drug resistance of haematological malignancies.


Post-discharge changes in NT-proBNP and quality of life after acute dyspnea hospitalization as predictors of one-year outcomes.
The association of serial NT-proBNP changes and poor quality of life (QOL) with progressive heart failure (HF) and clinical outcomes in emergency department dyspnea patients is poorly understood. The predictive value of changes in NT-proBNP and QOL (Minnesota Living with Heart Failure scale) from baseline to 30-day follow-up was examined for all-cause 1-year mortality and HF hospitalization. Patients with an initially elevated NT-proBNP (≥300 ng/L) which persisted at 30-days (no ≥25% decrease) were at high risk of death or HF hospitalization (HR=6.36, 95%CI=3.04-13.28). Combined with sustained poor QOL, these subjects with persistently elevated NT-proBNP were at highest mortality risk or HF hospitalization (HR=8.75, 95%CI=3.62-21.16). Dyspnea patients with elevated NT-proBNP concentrations and no improvement in either NT-proBNP or QOL at 30-days are at high risk of mortality and HF hospitalization. These data highlight the value of serial biomarker measurements combined with serial evaluations for QOL.


A two-enzyme constituted mixture to improve the degradation of Arthrospira platensis microalga cell wall for monogastric diets.
The main goal of this study was to test a rational combination of pre-selected carbohydrate-active enzymes (CAZymes) and sulphatases, individually or in combination, in order to evaluate its capacity to disrupt Arthrospira platensis cell wall, allowing the release of its valuable nutritional bioactive compounds. By the end, a two-enzyme constituted mixture (Mix), composed by a lysozyme and a α-amylase, was incubated with A. platensis suspension. The microalga cell wall disruption was evaluated through the amount of reducing sugars released from the cell wall complemented with the oligosaccharide profile by HPLC. An increase of the amount of reducing sugars up to 2.42 g/L in microalgae treated with the Mix relative to no treatment (p < .05), as well as a 7-fold increase of oligosaccharides amount (p < .001), were obtained. With resort of fluorescence microscopy, a 36% reduction of fluorescence intensity (p < .001) was observed using Calcofluor White staining. In the supernatant, the Mix caused a 1.34-fold increase in protein content (p = .018) relative to the control. Similarly, n-6 polyunsaturated fatty acids (PUFA) (p = .007), in particular 18:2n-6 (p = .016), monounsaturated fatty acids (MUFA) (p = .049) and chlorophyll a (p = .025) contents were higher in the supernatant of microalgae treated with the enzyme mixture in relation to the control. Taken together, these results point towards the disclosure of a novel two-enzyme mixture able to partial degrade A. platensis cell wall, improving its nutrients bioavailability for monogastric diets with the cost-effective advantage use of microalgae in animal feed industry.


Beta-galactosidase histochemistry and telomere loss in senescent retinal pigment epithelial cells.
To investigate the relation of senescence-related beta-galactosidase activity and telomere shortening to replicative senescence in cultured human retinal pigment epithelial (RPE) cells. A human RPE cell line was serially passaged until 80% of cells were nondividing in a 72-hour 5-bromo-2'-deoxyuridine (BrdU) labeling study. Early- and late-passage cells were double-stained for BrdU and senescence-related beta-galactosidase activity (pH 6). The average chromosomal telomere length at several population doublings was estimated by Southern blot analysis after double digestion of DNA with RsaI and HinfI and using a telomere-specific probe. BrdU-beta-galactosidase double-staining revealed an inverse correlation between the number of BrdU-labeled nuclei and beta-galactosidase-labeled cells as a function of population doubling level (PDL). At PDL 58, only 20% of all cells labeled for BrdU, whereas 57% stained for beta-galactosidase. The mean terminal restriction fragment length (TRF) was reduced from 10 kb in early (PDL 12) cultures to 4 kb in late (PDL 57) cultures. Senescence-related beta-galactosidase activity and mean TRF length may prove useful in studying the senescence of RPE cells in vitro. These techniques may be valuable in determining senescence of the retinal pigment epithelium in vivo, where senescent RPE cells could be involved in the development of age-related maculopathy and age-related macular degeneration.