Auditory processing of vocal sounds in birds.
The avian auditory system has become a model system to investigate how vocalizations are memorized and processed by the brain in order to mediate behavioral discrimination and recognition. Recent studies have shown that most of the avian auditory system responds preferentially and efficiently to sounds that have natural spectro-temporal statistics. In addition, neurons in secondary auditory forebrain areas have plastic response properties and are the most active when processing behaviorally relevant vocalizations. Physiological measurements show differential responses for vocalizations that were recently learned in discrimination tasks, and for the tutor song, a longer-term auditory memory that is used to guide vocal learning in male songbirds.


Recovery of dynamic muscular endurance.
Recovery of the rate of dynamic muscular endurance was measured in two groups of college-aged males. Subjects were required to perform elbow flexion (between the angles of 70 and 170 degrees) for as long as possible at the rate of 38 contractions/min while loaded with 1/6 of their maximum isometric strength (MVC). The task was terminated when the subject fell four contractions behind the required cadence or failed to complete two successive contractions. Subsequent to the task the subject was given a predetermined rest period after which a second fatigue bout to failure was performed. The rest intervals for Gp I (n = 22) were 5, 15, 45, 135, 405, and 1215 seconds, while the rest intervals for Gp II (n = 17) were 10, 30, 90, 270, 810, and 2550 s. Each subject completed six recovery intervals with the order of administration assigned at random. The percentage of recovery was calculated by dividing the exercise time of the first bout into the time of the second bout. These normalized data for the two groups were combined for analysis providing a 12 point recovery curve. The percentage of recovery ranged from 15.4% after 5 s to 91.8% after 2550 s. Analysis of the data revealed that the recovery pattern of dynamic muscular endurance progressed very rapidly initially, reached 50% at approximately 2 min and 15 s and was slightly less than 90% complete at 20 min. Exponential analysis of these data yielded a three-component curve.


Spontaneous formation of bubbles in gas-supersaturated water.
Spontaneous nucleation of bubbles may occur in water subjected to heating, tensile stress, or gas-supersaturation. Large discrepancies exist between the threshold nucleation conditions predicted theoretically and those indicated by empirical observations. The theoretical approaches have been hampered by inadequate understanding of many of the submicroscopic and molecular properties of liquids, and experimental obstacles have included the always present and difficult to control interference from pre-existing nuclei. These problems have been most pronounced for nucleation induced by dissolved gas; indeed, nucleation thresholds for any gas/liquid system are unknown due to a lack of relevant empirical data, and no quantitative theories seem to exist.


Strongyloides stercoralis infection in the immunocompromised host.
Strongyloides stercoralis is an intestinal nematode acquired in the tropics or subtropics. Most often, it causes chronic, asymptomatic infection, but a change in immune status can increase parasite numbers, leading to hyperinfection syndrome, dissemination, and death if unrecognized. Corticosteroid use is most commonly associated with hyperinfection syndrome. Diagnosis of Strongyloides infection is based on serology and serial stool examinations for larvae. The treatment of choice for chronic, asymptomatic infection is oral ivermectin. Alternative pharmacologic agents include albendazole and thiabendazole. For hyperinfection syndrome, ivermectin remains the drug of choice, though therapy duration must be individualized with the end point being complete parasite eradication. Recurrent strongyloidiasis should prompt an evaluation for human T-cell lymphotropic virus type 1 coinfection. No test of cure is currently available, although immunoglobulin G antibody levels have been shown to decline within 6 months of successful treatment.


[Studies on the determination of the part of bacterial nitrogen in relation to total nitrogen content in the duodenum of cows].
A method for estimation of content of bacterial nitrogen in duodenal intestine was described. The method of HUTTON et al. (1971) in modificated form for the own research was the best method. In two trials roughage (chopped dried forage) and ground corn were given to cows with duodenal bridge fistula in different order (90 min-intervall). Portion of bacterial nitrogen to total nitrogen was 72.5% (corn leads to roughage) and 64.7% (roughage leads to corn).


Protein profile of fiber types in human skeletal muscle: a single-fiber proteomics study.
Human skeletal muscle is composed of three major fiber types, referred to as type 1, 2A, and 2X fibers. This heterogeneous cellular composition complicates the interpretation of studies based on whole skeletal muscle lysate. A single-fiber proteomics approach is required to obtain a fiber-type resolved quantitative information on skeletal muscle pathophysiology. Single fibers were dissected from vastus lateralis muscle biopsies of young adult males and processed for mass spectrometry-based single-fiber proteomics. We provide and analyze a resource dataset based on relatively pure fibers, containing at least 80% of either MYH7 (marker of slow type 1 fibers), MYH2 (marker of fast 2A fibers), or MYH1 (marker of fast 2X fibers). In a dataset of more than 3800 proteins detected by single-fiber proteomics, we selected 404 proteins showing a statistically significant difference among fiber types. We identified numerous type 1 or 2X fiber type-specific protein markers, defined as proteins present at 3-fold or higher levels in these compared to other fiber types. In contrast, we could detect only two 2A-specific protein markers in addition to MYH2. We observed three other major patterns: proteins showing a differential distribution according to the sequence 1 > 2A > 2X or 2X > 2A > 1 and type 2-specific proteins expressed in 2A and 2X fibers at levels 3 times greater than in type 1 fibers. In addition to precisely quantifying known fiber type-specific protein patterns, our study revealed several novel features of fiber type specificity, including the selective enrichment of components of the dystrophin and integrin complexes, as well as microtubular proteins, in type 2X fibers. The fiber type-specific distribution of some selected proteins revealed by proteomics was validated by immunofluorescence analyses with specific antibodies. We here show that numerous muscle proteins, including proteins whose function is unknown, are selectively enriched in specific fiber types, pointing to potential implications in muscle pathophysiology. This reinforces the notion that single-fiber proteomics, together with recently developed approaches to single-cell proteomics, will be instrumental to explore and quantify muscle cell heterogeneity.


Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer.
To compare two commonly used schedules of fluorouracil (5FU) and leucovorin in the treatment of patients with advanced metastatic colorectal cancer. Each of these dosage administration schedules has been demonstrated to be superior to single-agent bolus 5FU in previous controlled trials. Three hundred seventy-two ambulatory patients with metastatic colorectal cancer were stratified according to performance status, and presence and location of any measurable indicator lesion(s). They were then randomized to receive chemotherapy with one of the following regimens: (1) intensive-course 5FU plus low-dose leucovorin (5FU 425 mg/m2 plus leucovorin 20 mg/m2 intravenous [IV] push daily for 5 days with courses repeated at 4- to 5-week intervals); (2) weekly 5FU plus high-dose leucovorin (5FU 600 mg/m2 IV push plus leucovorin 500 mg/m2 as a 2-hour infusion weekly for 6 weeks with courses repeated every 8 weeks). Three hundred sixty-two of 372 patients randomized (97.3%) were eligible and included in the analysis. Three hundred forty-six patients (95.6%) have died. There were no significant differences in therapeutic efficacy between the two 5FU/leucovorin regimens tested with respect to the following parameters: objective tumor response (35% v 31%), survival (median, 9.3 v 10.7 months), and palliative effects (as assessed by relief of symptoms, improved performance status, and weight gain). There were significant (P < .05) differences in toxicity, with more leukopenia and stomatitis seen with the intensive-course regimen, and more diarrhea and requirement for hospitalization to manage toxicity with the weekly regimen. Financial cost was also higher with the weekly regimen. Intensive-course 5FU plus low-dose leucovorin appears to have a superior therapeutic index compared with weekly 5FU plus high-dose leucovorin using the dosage administration schedules applied in this study based on similar therapeutic effectiveness, but lower financial cost, and less need for hospitalization to manage chemotherapy toxicity.


Effects of prenatal paraquat and mancozeb exposure on amino acid synaptic transmission in developing mouse cerebellar cortex.
The goal of this study was to analyze the effects of prenatal exposure to the pesticides paraquat (PQ) and mancozeb (MZ) on the development of synaptic transmission in mouse cerebellar cortex. Pregnant NMRI mice were treated with either saline, 10 mg/kg PQ, 30 mg/kg MZ or the combination of PQ + MZ, between gestational days 12 (E12) and E20. Variation in the levels of amino acid neurotransmitters was determined by HPLC, between postnatal day 1 (P1) and P30. Motor coordination was assessed by locomotor activity evaluation of control and experimental pups at P14, P21 and P30. Significant reductions in the levels of excitatory neurotransmitters, aspartate and glutamate, were observed in PQ-, MZ- or combined PQ + MZ-exposed pups, with respect to control, during peak periods of excitatory innervation of Purkinje cells: between P2-P5 and P11-P15. However, at P30, lower aspartate contents, in contrast with increased glutamate levels, were detected in all experimental groups. During the first two postnatal weeks, delays in GABA and glycine ontogenesis were observed in PQ- and PQ + MZ-exposed pups, whereas notable decrements in GABA and glycine levels were seen in PQ + MZ-exposed animals. Decreased taurine contents were detected at P3 and P11 in PQ- and PQ + MZ-exposed mice. Pups in different experimental groups all showed hyperactivity at P14 and then exhibited reduced locomotor activity at P30. Taken together, our results indicate that prenatal exposure to either PQ or MZ or the combination of both could alter the chronology and magnitude of synaptic transmission in developing mouse cerebellar cortex.


Growth and physiological responses of Pennisetum sp. to cadmium stress under three different soils.
Pennisetum sp. was employed as a model species to detect the growth and physiological response to cadmium (Cd) stress at different Cd concentrations (0, 20, 50, and 100 mg kg-1) in three types of soils (yellow brown soil, yellow soil, and red soil). Results showed that the growth of Pennisetum sp. was not significantly influenced by Cd in 20 mg kg-1, but significantly inhibited at higher Cd concentrations in three types of soils. Besides, the higher Cd concentrations, the lower root, stem, and leaf biomass. With Cd concentration of soil increasing, Cd content of root, stem, and leaf increased. Compared with no Cd, high Cd concentrations (50 and 100 mg kg-1) induced the physiological indices (photosynthetic rate, stomatal conductance, transpiration rate) and biochemical indices (nitrate reductase, glutamine synthetase, and glutamate synthase activities) decreasing, but the concentration of NO3- and NH4+ increasing. The activity of antioxidative enzymes (SOD, POD, and CAT) was disrupted and the content of malondialdehyde (MDA) increasing. Pennisetum sp. could protect cells from damage and maintain normal physiological metabolism via increasing the production of soluble sugar and soluble protein, but soluble proteins and soluble sugars were limited in high concentrations of Cd (50 and 100 mg kg-1). Moreover, the growth and physiological response to Cd are different in the three types of soils. The growth of Pennisetum sp. in yellow brown soil was better than that in other two soils, and the gas exchange rate, antioxidant enzyme activity, and nitrogen metabolism in yellow soil and red soil were more affected by Cd stress than that in yellow brown soil. Overall, Pennisetum sp. had certain tolerance and biosorption ability to Cd in different Cd concentrations and different types of soil. Hence, Pennisetum sp. was a suitable choice for Cd remediation, especially in yellow brown soil.


Mortality attributable to ambient fine particulate matter and nitrogen dioxide in Switzerland in 2019: Use of two-pollutant effect estimates.
Air pollution health risk assessments have traditionally used single-pollutant effect estimates for one proxy ambient air pollutant such as PM2.5. Two-pollutant effect estimates, i.e. adjusted for another correlated pollutant, theoretically enable the aggregation of pollutant-specific health effects minimizing double-counting. Our study aimed at estimating the adult mortality in Switzerland in 2019 attributable to PM2.5 from a single-pollutant effect estimate and to the sum of PM2.5 and NO2 from two-pollutant estimates; comparing the results with those from alternative global, European and Swiss effect estimates. For the single-pollutant approach, we used a PM2.5 summary estimate of European cohorts from the project ELAPSE, recommended by the European Respiratory Society and International Society for Environmental Epidemiology (ERS-ISEE). To derive the two-pollutant effect estimates, we applied ELAPSE-based conversion factors to ERS-ISEE PM2.5 and NO2 single-pollutant effect estimates. Additionally, we used World Health Organization 2021 Air Quality Guidelines as counterfactual scenario, exposure model data from 2019 and Swiss lifetables. The single-pollutant effect estimate for PM2.5 (1.118 [1.060; 1.179] per 10 μg/m3) resulted in 2240 deaths (21,593 years of life lost). Using our derived two-pollutant effect estimates (1.023 [1.012; 1.035] per 10 μg/m3 PM2.5 adjusted for NO2 and 1.040 [1.023; 1.058] per 10 μg/m3 NO2 adjusted for PM2.5), we found 1977 deaths (19,071 years of life lost) attributable to PM2.5 and NO2 together (23% from PM2.5). Deaths using alternative effect estimates ranged from 1042 to 5059. Estimated premature mortality attributable to PM2.5 alone was higher than to both PM2.5 and NO2 combined. Furthermore, the proportion of deaths from PM2.5 was lower than from NO2 in the two-pollutant approach. These seemingly paradoxical results, also found in some alternative estimates, are due to statistical imprecisions of underlying correction methods. Therefore, using two-pollutant effect estimates can lead to interpretation challenges in terms of causality.


Bioavailability and cytotoxicity of Cerium- (IV), Copper- (II), and Zinc oxide nanoparticles to human intestinal and liver cells through food.
Anthropogenic nanoparticles (NPs) are emitted to the environment and may be present in vegetables for human consumption. However, the toxicity of NPs exposure through food lack systematical investigations. In order to propose a systematical study, lettuce grown in a Cerium- (IV), Copper- (II) and Zinc oxide NP contaminated environment were digested. This digestate was used to culture human intestine cells (i.e. epithelial colorectal adenocarcinoma cells, Caco-2). The basolateral juice produced by the intestinal cells was then used to culture normal human liver (HL-7702) cells. Bioavailability and biotoxicity of the NPs in the vitro models were assessed. NPs were found to be taken up from the environment by vegetables, and may thus be transferred to humans through oral exposure. Bioavailability and the effect of their concentration in the digestate medium differed in regards to NP materials. The levels of NPs found in the digestate were detrimental to intestine cells, while the liver cells exposed to lower concentrations of NP in the bodily fluid showed no statically significant change in cell necrosis. A closer assessment of the detrimental effect of the studied NPs to Caco-2 cells revealed that the damage was mainly related to the solubility of the NPs. This may partly be due to that the more soluble NP material (ZnO > CuO > CeO2) render higher metal ion release and thus higher bioavailability. This appeared to cause more cell death, and even lead to local intestinal inflammation. Although no liver cells died, there was an increase of ROS level, causing ROS-related DNA damage prior to cell necrosis. The findings in this study enhances our understanding of the relative detrimental effect of different types of NPs, and the mechanisms causing their biotoxicity in human cells through food.


Ganglioside treatment improves recovery of alternation behavior after unilateral entorhinal cortex lesion.
Exogenous gangliosides have been reported to enhance neurite formation in vitro and in vivo after damage to peripheral nerves. We report here the effects of ganglioside treatment on the course of recovery of alternation behavior that follows a unilateral lesion of the rat entorhinal cortex. The recovery of this function is known to parallel rapid synaptic reinnervation (collateral sprouting) into the partially denervated dentate gyrus of the hippocampus which previously received afferent input from the entorhinal region. Rats trained on an alternation behavior were subjected to a unilateral entorhinal lesion and subsequently given daily injections of total ganglioside (50 mg/kg, i.m.). Testing of the behavior continued for 2 weeks to assess the extent of behavioral impairment and the rate of recovery. Rats treated with gangliosides showed reduced behavioral impairment, accelerated recovery of the learned behavior, and final performance levels greater than controls. We hypothesize that the gangliosides may be interacting with regenerating neuronal membranes, either acting as receptors for trophic growth factors or altering membrane structure itself.


Dynamic pelvic floor ultrasound for lower urinary tract symptoms in children--initial report on normative values.
Lower urinary tract symptoms (LUTS) are common in children. The aim of this study was to determine normal values for pelvic floor movement in asymptomatic controls to allow comparison with symptomatic children with dysfunctional voiding (DV) in the next phase of the study. One hundred children between the ages of 5-17 years were recruited prospectively as controls. All were asked to perform a voluntary pelvic floor contraction manoeuvre with a full bladder. All scans were performed on a Vivid I GE ultrasound machine with a 4-9 MHz curvilinear probe. M Mode was used to determine the direction of pelvic floor (levator plate-LP) movement, the distance in cms and the endurance in seconds. Each measurement was taken 3 times. Six children were unable to understand and perform the manoeuvre and were excluded. The median age was 10 years (range 4-17). The median LP movement was 0.3 cm (range 0.1-1.6) and cranial in 86/94 (91%). The median endurance time was 5.8 s (range 2.3-15.5). For the (n = 59) younger children aged 4-11, the 95% normal reference range for LP movement was 0.1 cm-1.4 cm and for endurance was 2.5-13.5 s. For the (n = 33) older children aged 12-17, the 95% normal reference range for LP movement was 0.2 cm-1.2 cm and for endurance was 2.3-15.5 s. There was a significant correlation (Pearson r = 0.39, P = 0.001) between average LP movement and endurance. This study gives the normal reference ranges for the variables measured. A further study is currently underway examining the same variables in children with dysfunctional voiding (DV) and comparing these with the reference range.


Changes in bovine mammary insulin binding during pregnancy and lactation.
1. Binding of insulin to microsomes from mammary glands of pregnant and lactating dairy cows was characterized. 2. Binding affinities of the insulin receptor did not change from pregnancy to lactation. 3. Maximal specific binding occurred in microsomes from cows in mid-pregnancy and declined in microsomes from cows in late pregnancy. 4. Insulin binding continued to decrease from early to mid-lactation and increased during late lactation. 5. Results indicate that decreased sensitivity in mammary tissue from lactating dairy cows is at least in part a result of a reduction in insulin receptor number. 6. Results demonstrate further physiological differences between the ruminant and non-ruminant mammary gland.


Insulin-like growth factor binding protein-3 (IGFBP-3) in the prostate and in prostate cancer: local production, distribution and secretion pattern indicate a role in stromal-epithelial interaction.
Insulin-like growth factor binding protein 3 (IGFBP-3) exerts inhibitory and proapoptotic effects on prostate cancer cells. Serum levels of IGFBP-3 were found to be associated with the risk of prostate cancer, but the data are still inconclusive. We present a detailed analysis of the expression and localization of IGFBP-3 in the prostate and a comparison with its expression pattern in tumors. Expression and localization of IGFBP-3 were analyzed in cellular models and tissue by real-time RT-PCR, ELISA, immunohistochemistry, and immunofluorescence. All cell types of a panel of benign epithelial, stromal and tumor prostate cells expressed IGFBP-3. Significantly higher expression levels were registered in stromal cells. TGF-beta stimulation boosted IGFBP-3 levels 60-fold in stromal cells. The pattern of expression was confirmed in microdissected tissue samples. Protein levels measured by ELISA paralleled the mRNA levels and more than 80% of IGFBP-3 was secreted. On tissue immunostaining, IGFBP-3 was found to be mainly located in the epithelium. The pattern suggested secretion of IGFBP-3, which was confirmed in prostate tissue cultured ex vivo and the ejaculate of vasectomized men. IGFBP-3 levels were increased in primary tumors but did not differ from benign epithelium in metastases and local recurrent tumors. We registered a significant local production of IGFBP-3 in the prostate, which may well override the effect of protein entering from blood. The stroma--particularly reactivated stroma--is the main source of IGFBP-3 in the prostate, suggesting that this peptide acts as a mediator of stromal-epithelial interactions.


An evaluation of a new high-sensitivity PrestoBlue assay for measuring cell viability and drug cytotoxicity using EA.hy926 endothelial cells.
Commercially-available resazurin-based reagents used for cell viability assessment contain varying amounts of resorufin; these may contribute to differences in autofluorescence, signal-to-background (S/B) ratio and the dynamic range of the assay. This in vitro study compares the sensitivity of a new, high-sensitivity PrestoBlue (hs-PB) assay with standard PrestoBlue (PB) in assessing the efficacy of valinomycin and antimycin A in human vascular endothelial EA.hy926 cells, as well as cell viability. The metabolic activity of EA.hy926 was evaluated based on resorufin fluorescence (PB assays) or formazan absorbance (MTT assay). The hs-PB assay demonstrated lower resorufin autofluorescence than the PB, resulting in a ≥ 1.4-fold increase in S/B ratio in hs-PB compared to PB. Valinomycin was more potent cytotoxic agent than antimycin A. The hs-PB, PB and MTT produced similar IC50 values for valinomycin. Antimycin A showed significantly higher potency in the MTT than in the resazurin-based assays. The EA.hy926 cells demonstrated higher metabolic activity in the presence of the antimycin A solvent - DMSO. All the examined methods may be used interchangeably to analyze drug cytotoxicity. Any differences in drug cytotoxicity observed between the assays may be due to relatively low drug potency and/or the influence of solvent on metabolism of assay reagent. The hs-PB assay appears to more effectively detect cell viability and produce a stronger signal than its conventional counterpart.


Species-independent metabolic response to an increase of [Ca(2+)](i) in quiescent cardiac muscle.
1. The aim of the present investigation was to contrast the Ca2+ dependence of cardiac energy metabolism in two species with differential reliance on extracellular Ca2+ for excitation-contraction coupling. 2. We measured energy expenditure as the rate of oxygen consumption (Vo2) of isolated, Langendorff-perfused hearts of rats and guinea-pigs during KCl arrest. In parallel experiments, we indexed intracellular Ca2+ concentration ([Ca2+]i) of isolated right-ventricular trabeculae, using the Ca2+ fluorophore fura-2 and ratiometric spectrofluorometry. By varying extracellular Na+ concentration ([Na+]o), Vo2-[Na+]o and [Ca2+]i-[Na+]o relationships were constructed for each species. 3. Reduction of [Na+]o during K+ arrest caused pronounced species-dependent elevations of both Vo2 and [Ca2+]i. Despite the species dependence of both Vo2 and [Ca2+]i on [Na+]o, a single species-independent Vo2-[Ca2+]i relationship obtained. 4. We infer that elevation of the metabolic rate of the arrested heart above its basal value is determined primarily by [Ca2+]i and is not species dependent.


Cardiovascular characterization of the novel organic mononitrate NDIBP in rats.
Organic nitrates are widely used to restore endogenous nitric oxide (NO) levels reduced by endothelial nitric oxide synthase dysfunction. However, these drugs are associated with undesirable side effects, including tolerance. This study aims to investigate the cardiovascular effects of the new organic nitrate 1,3-diisobutoxypropan-2-yl nitrate (NDIBP). Specifically, we assessed its effects on blood pressure, vascular reactivity, acute toxicity, and the ability to induce tolerance. In vitro and ex vivo techniques showed that NDIBP released NO both in a cell-free system and in isolated mesenteric arteries preparations through a process catalyzed by xanthine oxidoreductase. NDIBP also evoked endothelium-independent vasorelaxation, which was significantly attenuated by 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO, 300 μM), a nitric oxide scavenger; 1-H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 μM), a soluble guanylyl cyclase inhibitor; tetraethylammonium (TEA, 3 mM), a potassium channel blocker; febuxostat (500 nM), a xanthine oxidase inhibitor; and proadifen (10 μM), an inhibitor of cytochrome P450 enzyme. Furthermore, this organic nitrate did not induce tolerance in isolated vessels and presented low toxicity following acute oral administration. In vivo changes on cardiovascular parameters were assessed using normotensive and renovascular hypertensive rats. NDIBP evoked a reduction of blood pressure that was significantly higher in hypertensive animals. Our results suggest that NDIBP acts as a NO donor, inducing blood pressure reduction without having the undesirable effects of tolerance. Those effects seem to be mediated by activation of NO-sGC-cGMP pathway and positive modulation of K+ channels in vascular smooth muscle.


Combination of surfactants and enzyme cocktails for enhancing woody biomass saccharification and bioethanol production from lab-scale to pilot-scale.
Converting woody biomass to bioethanol might be more affordable, environmentally friendly, and efficient for making biofuel commercially feasible, but it would still need a significant optimization process and expand pilot-scale research. A combination of commercial low enzymes loading at 10 FPU/g glucan and compound additives utilizing Tween 80, PEG8000 and sophorolipid applied from lab-scale to pilot-scale have been studied in this work at economically viable dosages for enhancing bioethanol production. In lab-scale saccharification and fermentation, pretreated poplar at a high solid loading of 20% yielded the highest ethanol titers of 30.96 g/L and theoretical ethanol yield of 92.79%. Additionally, pilot-scale operation was used to investigate the bioethanol amplification, a final volume of 33 m3 which yielded the greatest ethanol amount of 599.6 kg from poplar wood while gaining on-site value-added production of hemicellulosic and cellobiose liquor 1122 kg and lignin residues 2292 kg.


Discrimination of LH, FSH, TSH and ACTH in dissociated porcine anterior pituitary cells by light and electron microscope immunocytochemistry.
Using the PAP unlabelled antibody method, LH, FSH, TSH and ACTH were localized at light microscope level in cultured cells dissociated from the porcine adenohypophysis. Antisera were shown to be specific for the beta-subunits of the porcine glycoprotein hormones by radioimmunoassay and absorption studies. Using these antisera, it was found that LH and FSH were contained within the same cell, with TSH in a separate cell. When absorbed with LH, anti-porcine ACTH stained a separate distinct population of ACTH cells. Adjacent ultra-thin sections stained with anti-pLH beta and anti-pFSH beta, and examined at electron microscope level, showed that the ovoid, 150--400nm secretory granules of the LH/FSH gonadotrophs contained both LH and FSH.


Smoking tobacco along with marijuana increases symptoms of cannabis dependence.
User practices/rituals that involve concurrent use of tobacco and marijuana - smoking blunts and "chasing" marijuana with tobacco - are hypothesized to increase cannabis dependence symptoms. Ethnographers administered group surveys to a diverse, purposive sample of marijuana users who appeared to be 17-35 years old. New York City, including non-impoverished areas of Manhattan, the transitional area of East Village/Lower East Side, low-income areas of northern Manhattan and South Bronx, and diverse areas of Brooklyn and Queens. 481 marijuana users ages 14-35, 57% male, 43% female; 27% White, 30% Black, 19% Latino, 5% Asian, 20% of other/multiple race. Among many other topics, group surveys measured cannabis dependence symptoms; frequencies of chasing, blunt smoking, joint/pipe smoking, using marijuana while alone, and general tobacco use; and demographic factors. Blunt smoking and chasing marijuana with tobacco were each uniquely associated with five of the seven cannabis dependence symptoms. Across symptoms, predicted odds were 2.4-4.1 times greater for participants who smoked blunts on all 30 of the past 30 days than for participants who did not smoke blunts in the past 30 days. Significant increases in odds over the whole range of the five-point chasing frequency measure (from never to always) ranged from 3.4 times to 5.1 times. Using tobacco with marijuana - smoking blunts and "chasing" marijuana with tobacco - contributes to cannabis dependence symptoms. Treatment for cannabis dependence may be more effective it addresses the issue of concurrent tobacco use.


Effects of supplemental dietary fatty acids on milk yield and fatty acid composition in high and medium yielding cows.
The present study tested the hypothesis that supplemental dietary fatty acids (FA) affect the energy corrected milk yield in proportion to the milk production level of dairy cows, and increase both long chain FA proportion of milk FA and milk fat globule diameter. Sixteen Danish Holstein cows were divided into four 4x4 Latin squares with two squares of medium yielding cows (32.2 kg energy corrected milk (ECM)/d; 158 days in milk (DIM)) and two squares of high yielding cows (40.0 kg ECM/d; 74 DIM). Experimental length was 12 weeks, with three weeks for each of the four periods. The four treatments were no supplementation (17 g FA/kg dry matter (DM)) and three diets with supplemented FA (29, 40, and 52 g total FA/kg DM, respectively) obtained by substituting barley with Palm Fatty Acid Distillate (PFAD) fat. Diets were offered as total mixed rations with 63% grass/clover silage (DM basis). Dry matter intake decreased with increasing FA supplementation, but net energy intake was not affected. The general linear responses to 10 g/kg DM increase in FA level were 1.1 kg ECM (P<0.0001), 0.061 kg milk fat (P<0.0001), 0.012 kg milk protein (P=0.09) and 0.052 kg lactose (P=0.0002) per day, and linear responses in milk composition were 0.39 g fat (P=0.07), -0.71 g protein (P<0.0001) and 0.05 g lactose (P=0.3) per kg milk, and 0.092 microm (P<0.0001) in milk fat average globule diameter. Fatty acid supplementation decreased short- and medium-chain FA and C16:0 and increased C18:1 proportions of total FA in milk. Supplemental dietary FA increased ECM yield but not in proportion to production level as anticipated, and increased average FA chain length and milk fat globule diameter.


The accuracy of estimated gestational age based on ultrasound measurement of biparietal diameter in preterm premature rupture of the membranes.
The management of patients with preterm premature rupture of the membranes is often influenced by the ultrasound measurement of biparietal diameter. The cephalic index has been used in pregnancies with intact membranes to predict the presence of an abnormal biparietal diameter that may be unreliable in estimating gestational age. This study analyzed 100 patients with rupture of the membranes between the beginning of gestation week 28 and the end of week 34. The cephalic index was found to be abnormal 45% of the time; all were in the brachiocephalic range. The biparietal diameter was affected by presentation and presence or absence of amniotic fluid (p less than 0.05). Use of the biparietal diameter was found to be unreliable in estimating gestational age with preterm premature rupture of the membranes. Use of the cephalic index did not enable prediction of which biparietal diameters would be abnormal; therefore use of the biparietal diameter or the cephalic index in preterm premature rupture of the membranes is not recommended. The use of the head circumference, abdominal circumference, and femur measurements may be a better way of predicting gestational age in this select population.


Visualizing minute details in light-sheet and confocal microscopy data by combining 3D rolling ball filtering and deconvolution.
We developed an open-source deconvolution software that stunningly increases the visibility of minute details, as for example, neurons or nerve fibers in light-sheet microscopy or confocal microscopy data by combining rolling ball background subtraction in three directions with deconvolution using a synthetic or measured point spread function. Via automatic block-wise processing image stacks of virtually unlimited size can be deconvolved even on small computers with 8 or 16 GB RAM. By parallelization and optional GPU-acceleration, the software works with high speed: On a PC equipped with a state-of-the-art NVidia graphic board a three dimensional (3D)-stack of about 1 billion voxels can be deconvolved within 5 to 10 minutes. The implemented variation of the Richardson-Lucy deconvolution algorithm preserves the photogrammetry of the image data by using flux-preserving regularization, an approach that to our knowledge has not been applied for deconvolving microscopy data before.


Patient education by smartphones for bowel preparation before colonoscopy.
We aim to evaluate the effect of smartphone education on the bowel preparation quality of patients undergoing colonoscopy by meta-analysis. Randomized controlled trials using smartphones to educate patients on bowel preparation for colonoscopy were screened from the PubMed, Web of Science, Cochrane Library, and Embase databases from inception to August 31, 2021. After extracting the data, Review Manager software was used for meta-analysis. A total of 12 randomized controlled trials with 4165 patients were included in the meta-analysis. There were 2060 patients in the smartphone group, including 1784 patients with adequate bowel preparation, with a rate of 86.6%, and 2105 patients in the control group, including 1614 patients with adequate bowel preparation, with a rate of 76.7%, and pooled risk ratio (RR) was 1.15 (95% confidence interval [CI]: 1.07-1.23, P < 0.01). Eight included studies reported the adenoma detection rate. The adenoma detection rate in the smartphone group was 26.2%, and the rate in the control group was 19.3%, with an RR of 1.29 (95% CI: 1.03-1.62, P < 0.05). Using smartphones to educate patients on bowel preparation for colonoscopy improved the quality of bowel preparation and increased the adenoma detection rate.


Participants' Lived Experience with the Illness Management and Recovery (IMR) Program in Relation to their Recovery-Process.
The Illness Management and Recovery program (IMR) is developed to support people with severe mental illnesses in their recovery-process. The theory behind the program highlight the importance of helping people develop tailored illness management skills which will help achieve personal and clinical recovery. However, little is known about participants' experience with IMR in relation to their recoveryprocess. The aim of the present study is to describe the participants' lived experience with IMR, explore whether they experienced changes, and examine how these changes related to their recovery during or after their participation in IMR. A Qualitative study. The participants' experience with the IMR program in relation to their recovery unveiled three main themes; "Social connection with other IMR-group members', 'In IMR, we talked about our everyday lives with mental illness' and 'In IMR we learned about recovery as a personal experience'.


Effects of active and passive warming of the foot sole on vibration perception thresholds.
Skin temperatures are known to increase cutaneous sensitivity. However, it is unclear whether the amount of improved sensitivity differs depending on the protocol of heat application. Therefore, this study aimed to investigate the effects of active (treadmill walking) and passive (infrared radiator) warming of the foot sole on vibration perception thresholds. Sixty healthy and injury-free subjects voluntarily participated in this study. Vibration perception thresholds (200 Hz) and plantar temperatures were measured at the hallux and 1st metatarsal head. In experiment 1, warming and mechanically stimulating the skin was achieved by walking on a treadmill for 30 min. In a follow-up study (experiment 2), external plantar heat was administered via an infrared radiator (30 min). In both experiments, increasing temperatures led to increased plantar sensitivity. However, the amount of improved sensitivity was greater in experiment 1, although plantar temperature increases were lower compared to experiment 2. Warming in conjunction with mechanical stimulation seems to have a greater potential to enhance plantar sensitivity compared to external heat supply only. The possible influence of mechanical stimulation and warming towards superior plantar afferent feedback highlights its importance regarding human posture and fall prevention.


[Clinical Research of EGFR and KRAS Mutation in Fine Needle Aspiration Cytology Specimens of Non-small Cell Lung Carcinoma].
Epidermal growth factor receptor (EGFR) and KRAS must be detected mutation status before patients of lung cancer use targeted drugs. The aim of this study is to elucidate the significance of EGFR and KRAS mutation in fine needle aspiration (FNA) cytology suspension specimens of non-small cell lung carcinoma. EGFR gene exons 18-21 and KRAS codons 12, 13 of exons 2 were performed by Real-time PCR methods in fine needle aspiration cytology suspension specimens of lymph nodes. 85 metastasis lymph nodes were detected in fine needle aspiration cytology samples of lung cancer. EGFR mutation rate was 37.3%. KRAS mutation rate was 7.2%. 19 formalin fixed paraffin-embedded tissue specimens were available and match cytology specimens. Analysis of EGFR mutation status in those samples revealed agreement with the results obtained in cytological samples (kappa=1.0). Clinical follow-up was available for 13 who presented with stage IV disease. Based on the identification of such mutations, these patients received subsequent therapy with a TKI in clinic. We observed two cases complete remission (16.7%) and 8 cases partial remission (66.7%) and three had ongoing stable disease. Fine-needle aspiration cytology samples were detected EGFR and KRAS mutation. The method which collects samples was easier, simple and convenient. This method has higher application value in clinical treatment. .


Cluster analysis to explore additive-genetic patterns for the identification of sheep resistant, resilient and susceptible to gastrointestinal nematodes.
Infection caused by gastrointestinal nematodes is an important issue for animal health and production. Controlling worm infections improves the sustainability of the sheep industry. Genetic selection of animals that are resistant to gastrointestinal nematodes is another strategy to render sheep production more sustainable by decreasing the use of anthelmintics. The aims of this study were (1) to explore the additive-genetic pattern of EBVs for Famacha© (FAM), packed-cell volume (PVC), and fecal egg counts (FEC) of Santa Ines sheep, (2) to propose a classification of animals that are resistant, resilient and susceptible to gastrointestinal nematodes based on their additive-genetic patterns, and (3) to identify the most suitable animals for selection based on their genetic pattern. A dataset of 2,241 records from 747 animals was used to predict the breeding values for indicator traits of resistance to gastrointestinal nematodes with THRGIBBS1F90 and to carry out cluster analyses was used R software. Three clusters of animals were found in the population using hierarchical cluster analysis of the breeding values for FAM, PCV and FEC. Each cluster was characterized by different additive-genetic patterns identified by k-means non-hierarchical cluster analysis. Among a total of 747 animals, 196 were classified as resistant, 288 as resilient, and 263 as susceptible. Cluster analysis is a valuable tool for data screening that permits to evaluate only selection candidates based on their additive-genetic pattern for gastrointestinal nematode resistance. EBVs for FEC were decisive to divide the population into resilient, resistant and susceptible animals. It is also important to include the EBVs for PCV and FAM to adequately distinguish resistant from resilient animals. Finally, the resistant cluster consisted of the most desirable animals to be used as selection candidates in order to genetically improve resistance to infection with gastrointestinal nematodes. This cluster contained animals with the most appropriate additive-genetic pattern to achieve the breeding goal, with positive breeding values for PCV and negative breeding values for FAM and FEC.


[68Ga]Ga-FAPI PET for the evaluation of digestive system tumors: systematic review and meta-analysis.
Digestive system tumors are a group of tumors with high incidence in the world nowadays. The assessment of digestive system tumor metastasis by conventional imaging seems to be unsatisfactory. [68Ga]Ga-FAPI, which has emerged in recent years, seems to be able to evaluate digestive system tumor metastasis. We aimed to summarize the current evidence of [68Ga]Ga-FAPI PET/CT or PET/MR for the assessment of primary tumors, lymph node metastases, and distant metastases in digestive system tumors. Besides, we also aimed to perform a meta-analysis of the sensitivity of [68Ga]Ga-FAPI PET diagnosis to discriminate between digestive system tumors, primary lesions, and non-primary lesions (lymph node metastases and distant metastases). PubMed, MEDLINE and Cochrane Library databases were searched from the beginning of the database build to August 12, 2022. All studies undergoing [68Ga]Ga-FAPI PET for the evaluation of digestive tumors were included in the screening and review. Screening and full text review was performed by 3 investigators and data extraction was performed by 2 investigators. Risk of bias was examined with the QUADAS-2 criteria. Diagnostic test meta-analysis was performed with a random-effects model. A total of 541 studies were retrieved. Finally, 22 studies were selected for the systematic review and 18 studies were included in the meta-analysis. In the 18 publications, a total of 524 patients with digestive system tumors, 459 primary tumor lesions of digestive system tumors, and 1921 metastatic lesions of digestive system tumors were included in the meta-analysis. Based on patients, the sensitivity of [68Ga]Ga-FAPI PET for the diagnosis of digestive system tumors was 0.98 (95% CI: 0.94-0.99). Based on lesions, the sensitivity of [68Ga]Ga-FAPI PET for the diagnostic evaluation of primary tumor lesions of the digestive system was 0.97 (95% CI: 0.93-0.99); the sensitivity of [68Ga]Ga-FAPI PET for the diagnostic evaluation of non-primary lesions (lymph node metastases and distant metastases) of the digestive system tumors was 0.94 (95% CI: 0.79-0.99). [68Ga]Ga-FAPI PET has high accuracy and its sensitivity is at a high level for the diagnostic evaluation of digestive system tumors. Clinicians, nuclear medicine physicians, and radiologists may consider using [68Ga]Ga-FAPI PET/CT or PET/MR in the evaluation of primary tumors, lymph node metastases, and distant metastases in digestive system tumors.


Mutagenicity of azo dyes in the Salmonella/microsome assay using in vitro and in vivo activation.
The mutagenicity of 6 azo dyes, including direct black 38 (DB38), direct black 19 (DB19), direct brown 95 (DB95), solvent yellow 3 (SY3), trypan blue (TPB), and food black 2 (FB2), was examined in the Salmonella/microsome assay. The effect of chemical azo reduction (dithionite) and in vivo metabolism on the mutagenicity of the dyes was also studied. In vivo azo-dye metabolites were isolated from the urine of rats intubated with dyes by XAD-2 column chromatography. Urinary metabolites from all the treated animals, except animals treated with FB2, induced frame-shift mutations in strains TA1538 and TA98 in the presence of liver S9 activation. The control urine did not increase the incidence of revertants in strains TA1538 and TA98. Thus, XAD-2 chromatography can be used to isolate genotoxic metabolites from the urine of animals intubated with azo dyes.


Nail surgery.
An update of recent surgical techniques as applied to the nail unit is presented. The procedures discussed touch on areas of internal medicine, oncology, biomechanics, trauma, podiatry, infectious disease, and genodermatoses. It is evident in reviewing the literature that a mushrooming of interest in the nail unit is taking place and that this structure has inherent importance in that it may involve all facets of health care. I hope that the reader will emerge from this chapter with a greater respect for the nail and will be stimulated to learn more about it.


Synergy between Th1 and Th2 responses during endometriosis: A review of current understanding.
Endometriosis is widely perceived as an estrogen-dependent chronic disorder with infertility and pelvic pain. Although the etiology of endometriosis has remained elusive, many studies have proclaimed the relevance of immune system disorders with endometriosis. With the discovery that the dysregulation of multiple biological functions in endometriosis is caused by the aberrant differentiation of T helper cells, a shift towards Th2 immune response may account for the disease progression. This review attempts to present mechanisms of cytokines, chemokines, signal pathways, transcription factors and some other factors related with the derivation of Th1/Th2 immune response involved in the development of endometriosis. The current understanding of treatment approaches and potential therapeutic targets will also be outlined with brief discussion.


Physical and social trauma: Towards an integrative transdiagnostic perspective on psychological trauma that involves threats to status and belonging.
Current theories of psychological trauma assume that posttraumatic symptoms originate from stress reactions caused by extremely adverse life experiences. Since the diagnosis of PTSD is restricted to events that involve threats to the physical or sexual integrity of a person, such as accidents and physical and sexual violence, these theories are not well suited to explain the psychopathological consequences of severe violations of one's social integrity, such as emotional abuse and bullying. However, it is evident that social threats contribute to a broad range of mental disorders and increase symptom severity in patients with posttraumatic stress disorder. The aim of the Physical and Social Trauma (PAST) framework is to extend current memory theories of psychological trauma to incorporate threats to a person's social integrity. Within this perspective, the harmful effects of events that involve social threats result from violations of core social motives such as the need for status and belonging that bring about intense affective reactions, including despair and defeat. Within associative threat structures, these emotions are tied to the stimulus characteristics of the experiences and can be re-activated in social situations. The resulting psychopathology transcends PTSD criteria and other current classifications and suggests a transdiagnostic perspective of psychological trauma. Implications for treatment and further directions for research are discussed.


Factors associated with mortality in early stages of parkinsonism.
Prognosis of patients with parkinsonism varies greatly between the various parkinsonian syndromes. However, it is often difficult to distinguish the different forms, particularly in early stages. We examined predictors of mortality and functional outcome in patients with recent-onset parkinsonism with an initially uncertain diagnosis (n = 156). Patients were recruited between 2003 and 2006, comprehensively investigated, and followed prospectively (up to 15 years, mean 7 years). A final clinical diagnosis was established after follow-up. Independent predictors of mortality were investigated with multivariable Cox regression and combined into a simple prediction model. Model performance to predict 5- and 10-year mortality and functional outcome after 3 years was evaluated and externally validated in a second cohort of 62 patients with parkinsonism with an initially uncertain diagnosis. Ninety-one patients died (58%). Orthostatic hypotension, impaired cognition, abnormal tandem gait, and elevated neurofilament light chain concentration in serum or CSF were associated with mortality. A simple model that combined these factors showed excellent performance for prediction of functional outcome after 3 years and mortality after 5 and 10 years (c-statistic ~0.90 for all models). Model performance was confirmed after external validation: prediction of functional outcome after 3 years (c-statistic 0.89, 95% CI 0.80-0.98) and mortality after 5 years (c-statistic 0.91, 95% CI 0.84-0.99) were comparable to the results in the discovery cohort. These findings help clinicians to estimate a patient's prognosis, irrespective of the specific diagnosis.


Cytostatic drugs are without significant effect on digitoxin plasma level and renal excretion.
In three patients with malignant lymphoma who received 0.5 mg digitoxin before and 24 hr after combination therapy with cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP) or cyclophosphamide, Oncovin, and prednisone (COP), plasma glycoside concentrations and renal excretion were measured 0 to 168 hr after digitoxin and the areas under plasma concentration-time curves *(AUCs) were calculated. In 10 patients receiving 0.1 mg digitoxin, daily plasma glycoside concentration and daily renal excretion were measured before and after COPP, COP, or cyclophosphamide, Oncovin, cytosine-arabinoside, and prednisone (COAP) treatment schemes. In contrast to previous reports on digoxin, cytostatic drug therapy does not lead to a reduction in steady-state digitoxin plasma levels and daily renal excretion. During cytostatic therapy attainment of peak digitoxin level was delayed after a single dose, showing that the rate of digitoxin absorption was reduced, but that the AUCs and renal excretion of digitoxin (parameters of the extent of digitoxin absorption) were not diminished. Since the absorption rate is not clinically relevant in patients on long-term glycoside therapy, our results indicate that digitoxin is preferable to digoxin in such patients.


Development of an Innovative Surgical Navigation System for Sacrospinous Fixation in Pelvic Surgery.
To validate the use of an innovative navigation method for sacrospinous fixation in surgery-like conditions as a new teaching tool and surgical method. Two-month experimental prospective pilot study between July and August 2021. Biomechanics laboratory academic research. A total of 29 participants took part in the study: 9 gynecological surgeons and 20 participants with no medical background. All participants used the 2 mocks-up. The experiment was composed of 2 training phases dedicated to improving the hand-eye coordination and suture skills on a training mock-up and of a suturing phase on a pelvic mock-up designed to recreate the surgery-like conditions of a sacrospinous fixation. The surgeons provided qualitative feedback on the bio-accuracy of the mock-ups and evaluated the ease of use of the navigation software. Nonsurgeons were included to assess the progression of the suture performance between 2 experiments performed 1 week apart (session 1 and 2). The main objective for participants was to reach a virtual target and to stitch sacrospinous ligaments. For session 1, an overall comfort score of 7.2 of 10 was attributed to the tool; 14 (42%) surgeon suture attempts and 63 (65%) nonsurgeon suture attempts were accurate (i.e., below the 5-mm threshold). Twenty-two (67%) surgeon suture attempts and 28 (34%) nonsurgeon suture attempts were fast (i.e., in the first 2 quantiles of the duration dataset). An improvement in the nonsurgeon performance was observed between the 2 sessions in terms of duration (session 1: 46 ± 20 s; session 2: 37 ± 18 s; p = .047) and distance (session 1: 3.8 ± 1.3 mm; session 2: 3.2 ± 1.4 mm; p = 10-5) for the last suturing exercise. This new motion capture-based navigation method for sacrospinous fixation tested under surgery-like conditions seemed to be accurate and effective. The next step will be to design a pelvis model more adapted to the constraints of a sacrospinous fixation and to validate the benefits of this method compared with current techniques.


Elucidation of potentially virulent factors of Candida albicans during serum adaptation by using quantitative time-course proteomics.
Candida albicans is an opportunistic pathogen that causes fatal disease if the host immunity is compromised. The mortality rate of systemic candidiasis is very high; hence, there is a ceaseless demand for novel pharmaceuticals. In this study, quantitative time-course proteomics of C. albicans during adaptation to fetal bovine serum (FBS) is described. Survival in blood is essential for virulence of C. albicans, and a detailed analysis is required. We cultivated C. albicans in FBS for 0-180min, and determined quantitative time-course variations of 1024 proteins in the cultured cells by using a LC-MS/MS system with a long monolithic silica capillary column. Clustering analysis identified FBS-induced proteins associated with detoxification of oxidative species, high-affinity glucose transport, citrate cycle, oxidative phosphorylation, and iron acquisition. Furthermore, we identified possible virulence factors such as orf19.4914.1 (named Blood-induced peptide 1, Blp1). Heterologous expression of BLP1 in Saccharomyces cerevisiae shortened the lag phase and resulted in a pleiotropic stress-tolerance phenotype, indicating a possible role for quick adaptation to a stressful environment. While further experiments are necessary to prove virulence of the identified factors, systematic identification of candidate virulence proteins in this study will lead to profound understanding of virulence of C. albicans. This paper describes time-course proteomics of C. albicans during adaptation to serum, which is an essential process for fatal systemic candidiasis. Using a LC-MS/MS system with a monolithic silica capillary column, we have successfully characterized time-course variations of 1024 proteins. Among them, orf19.4914.1 (Blp1) was identified as a novel pleiotropic stress-tolerance peptide, which could have an important role for virulence of C. albicans.


What's happening? The quality of methylene blue treated FFP and cryo.
It is currently unclear to what degree methylene blue in combination with removal, of cells from plasma, by filter, can directly influence the loss of active components of plasma and whether the co-precipitation of FVIII/vWf with fibrinogen/fibronectin is affected by combined methylene blue and light treatment (MBLT). These questions are investigated using the Fenwal system. Our results indicate that up to 15% of the FVIII and IX are lost due to exposure of plasma to filters and methylene blue (MB). The illumination leads to a further 10-15% loss of all other major clotting factors. Factor XI appears to be highly sensitive to the MBLT-process, while inhibitors of the coagulation system are less affected. MBLT did not grossly influence the distribution of fVIII/vWf:Ag between cryoprecipitate and cryosupernatant using a paired control/test protocol, although the fVIII/vWf recovery is reduced in MBLT samples. The three commercially available MBLT processes differ in terms of operational aspects. These may have some impact on overall quality/safety and bioequivalency.


Evoked potentials during recovery from blindness recorded serially from an infant and his normally sighted twin.
Visual evoked potentials (VEPs) elicited by diffuse field flashes wee recorded from a behaviourally blind infant with his twin as control. The patient was tested at ages 4, 5, 6, 8, 10 and 15 months. In spite of his behavioural blindness, clear VEPs were recorded from the patient at age 4 months, although the wave form was monophasic as contrasted with the multiphasic wave form recorded from his twin at the same age. Latency to first deflection and to first peak were considerably longer for the patient. The patient's VEP wave forM grew progressively more complex with age, paralleling recovery of useful vision. However, the VEP development anticipated behavioural recovery.


Inhibition of idiotype-anti-idiotype reaction in particle counting immunoassay as a tentative assay of IgE.
Rabbit antibodies were raised against a purified mouse monoclonal IgG1 antibody having specificity for the D epsilon 2 determinant of human IgE. After appropriate absorption this antiserum was anti-idiotype specific and was used to set up a particle counting immunoassay for human IgE. Latex particles coated with F(ab')2 fragments of the anti-idiotypic antibodies were agglutinated by the monoclonal anti-IgE antibody (20 ng/ml). This reaction was inhibited up to 100% by human IgE and the assay took 30 min to perform with a sensitivity of 40 IU/ml. The coefficient of correlation with a routine IgE assay was r = 0.96, and the mean analytical recovery tested on 10 sera was 95.8%.


Efficacy, safety, and pharmacokinetics of oral valganciclovir in patients with congenital cytomegalovirus infection.
Valganciclovir (VGCV) has been shown to improve sensorineural hearing loss (SNHL) and neurological outcomes in patients with neonatal symptomatic congenital cytomegalovirus (cCMV) infection. However, reports on the pharmacokinetics, efficacy and safety of oral VGCV are limited. The aim of this study is to evaluate the pharmacokinetics of VGCV for use in the treatment of cCMV. This was a single-center, retrospective observational study conducted at Saitama Children's Medical Center in Japan between 2012 and 2017. CMV DNA copy number, maximum plasma VGCV concentration (Cmax), and adverse events (ADEs) during treatment were evaluated. A total of 26 patients with cCMV who received VGCV were included in this study. The median age at VGCV initiation was 9.5 months (range 0-46). Twenty-one patients (81%) had SNHL at baseline. Of these, five patients (19%) presented with improved SNHL, and none experienced worsened SNHL during treatment. The mean VGCV Cmax was 3.5 μg/mL (range 2-5.3), with no significant variation among individual values, and the values were maintained during treatment. Furthermore, there were no correlations between the Cmax values and age, sex, SNHL improvement or ADEs. Neutropenia (<1000/mm3) was observed in six patients (23%); however, no serious ADEs occurred. VGCV prevented the progression of SNHL without serious ADEs due to its stable pharmacokinetics. This study provides safety and tolerability of VGCV for the treatment of cCMV patients.


The influence of synovial inflammation and hyperplasia on symptomatic outcomes up to 2 years post-operatively in patients undergoing partial meniscectomy.
Synovitis is associated with pain and other symptoms in patients with knee osteoarthritis (OA), and in patients with meniscal tears even in the absence of radiographic OA. Patients undergoing arthroscopic partial meniscectomy were followed for 2 years to determine whether synovitis predicts post-operative symptoms. Thirty-three patients scheduled for arthroscopy were recruited for this pilot study. Symptoms were assessed using a knee pain scale, the Lysholm score, and the short form-12 (SF-12(®)) pre-operatively and at 16 weeks, 1 year and 2 years post-operatively. Synovial inflammation and hyperplasia were graded on surgical biopsies. Linear mixed effects models were tested to determine whether inflammation or hyperplasia is associated with outcome scores over time. Lysholm scores and SF-12(®) physical component sub-scores were worse pre-operatively in patients with inflammation (Lysholm: 52.42 [95% confidence interval (CI) 42.37, 62.47] vs 72.38 [66.03, 78.72], P < 0.001; SF-12: 36.81 [28.26, 45.37] vs 46.23 [40.14, 52.32], P < 0.05). Up to 2-years post-operatively, patients with inflammation achieved mean scores similar to those without inflammation. As a result, the mean improvement in Lysholm scores was 13.01 [1.48-24.53] points higher than patients without inflammation, P = 0.03. 33% (4/12) of patients with inflammation still had fair to poor Lysholm scores 2 years after surgery compared to 7% (1/15, P=0.14) without inflammation. No association between hyperplasia and symptoms was noted. In this pilot study of patients undergoing partial meniscectomy, synovial inflammation was associated with worse pre-operative symptoms, but not with poorer outcomes in the first 2 years post-arthroscopy. Larger cohorts and longer follow-up should be pursued to confirm this relationship, and determine if the initial response is sustained.


Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype.
Impulsivity and hyperactivity share common ground with numerous mental disorders, including schizophrenia. Recently, a population-specific serotonin 2B (5-HT2B) receptor stop codon (ie, HTR2B Q20*) was reported to segregate with severely impulsive individuals, whereas 5-HT2B mutant (Htr2B(-/-)) mice also showed high impulsivity. Interestingly, in the same cohort, early-onset schizophrenia was more prevalent in HTR2B Q*20 carriers. However, the putative role of 5-HT2B receptor in the neurobiology of schizophrenia has never been investigated. We assessed the effects of the genetic and the pharmacological ablation of 5-HT2B receptors in mice subjected to a comprehensive series of behavioral test screenings for schizophrenic-like symptoms and investigated relevant dopaminergic and glutamatergic neurochemical alterations in the cortex and the striatum. Domains related to the positive, negative, and cognitive symptom clusters of schizophrenia were affected in Htr2B(-/-) mice, as shown by deficits in sensorimotor gating, in selective attention, in social interactions, and in learning and memory processes. In addition, Htr2B(-/-) mice presented with enhanced locomotor response to the psychostimulants dizocilpine and amphetamine, and with robust alterations in sleep architecture. Moreover, ablation of 5-HT2B receptors induced a region-selective decrease of dopamine and glutamate concentrations in the dorsal striatum. Importantly, selected schizophrenic-like phenotypes and endophenotypes were rescued by chronic haloperidol treatment. We report herein that 5-HT2B receptor deficiency confers a wide spectrum of antipsychotic-sensitive schizophrenic-like behavioral and psychopharmacological phenotypes in mice and provide first evidence for a role of 5-HT2B receptors in the neurobiology of psychotic disorders.


Dominant subtype switch in avian influenza viruses during 2016-2019 in China.
We have surveyed avian influenza virus (AIV) genomes from live poultry markets within China since 2014. Here we present a total of 16,091 samples that were collected from May 2016 to February 2019 in 23 provinces and municipalities in China. We identify 2048 AIV-positive samples and perform next generation sequencing. AIV-positive rates (12.73%) from samples had decreased substantially since 2016, compared to that during 2014-2016 (26.90%). Additionally, H9N2 has replaced H5N6 and H7N9 as the dominant AIV subtype in both chickens and ducks. Notably, novel reassortants and variants continually emerged and disseminated in avian populations, including H7N3, H9N9, H9N6 and H5N6 variants. Importantly, almost all of the H9 AIVs and many H7N9 and H6N2 strains prefer human-type receptors, posing an increased risk for human infections. In summary, our nation-wide surveillance highlights substantial changes in the circulation of AIVs since 2016, which greatly impacts the prevention and control of AIVs in China and worldwide.


Ethyl pyruvate improves systemic and hepatosplanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia.
To investigate the systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of delayed treatment with ethyl pyruvate in a long-term porcine model of hyperdynamic endotoxemia. Prospective, randomized, controlled experimental study with repeated measures. Investigational animal laboratory. Anesthetized, mechanically ventilated, and instrumented pigs. After 12 hrs of continuous infusion of lipopolysaccharide and hydroxyethyl starch to keep mean arterial pressure >60 mm Hg, swine randomly received placebo (Ringer's solution; control group, n = 11) or ethyl pyruvate in lactated Ringer's solution (n = 8; 0.03 g.kg(-1) loading dose over 10 mins, thereafter 0.03 g.kg(-1)hr(-1) for 12 hrs). Whereas mean arterial pressure significantly decreased in control animals, mean arterial pressure was maintained at the baseline level in pigs treated with ethyl pyruvate. Global oxygen uptake was comparable, so that the trend toward a higher oxygen transport and the significantly higher mixed venous hemoglobin oxygen saturation resulted in a significantly lower oxygen extraction in the ethyl pyruvate group. Ethyl pyruvate reduced intrapulmonary venous admixture and resulted in significantly greater Pa(O2)/F(IO2) ratios. Despite comparable urine production in the two groups during the first 18 hrs of endotoxemia, ethyl pyruvate significantly increased diuresis during the last 6 hrs of the study. Lipopolysaccharide-induced systemic and regional venous metabolic acidosis was significantly ameliorated by ethyl pyruvate. Endotoxemia increased both blood nitrate + nitrite and isoprostane concentrations, and ethyl pyruvate attenuated the response of these markers of nitric oxide production and lipid peroxidation. Ethyl pyruvate infusion resulted in improved hemodynamic stability and ameliorated acid-base derangements induced by chronic endotoxemia in pigs. Reduced oxidative stress and an decreased nitric oxide release probably contributed to these effects.


Correction: Using stochastic language models (SLM) to map lexical, syntactic, and phonological information processing in the brain.
[This corrects the article DOI: 10.1371/journal.pone.0177794.].


A two-locus model of spatially varying stabilizing or directional selection on a quantitative trait.
The consequences of spatially varying, stabilizing or directional selection on a quantitative trait in a subdivided population are studied. A deterministic two-locus two-deme model is employed to explore the effects of migration, the degree of divergent selection, and the genetic architecture, i.e., the recombination rate and ratio of locus effects, on the maintenance of genetic variation. The possible equilibrium configurations are determined as functions of the migration rate. They depend crucially on the strength of divergent selection and the genetic architecture. The maximum migration rates are investigated below which a stable fully polymorphic equilibrium or a stable single-locus polymorphism can exist. Under stabilizing selection, but with different optima in the demes, strong recombination may facilitate the maintenance of polymorphism. However usually, and in particular with directional selection in opposite direction, the critical migration rates are maximized by a concentrated genetic architecture, i.e., by a major locus and a tightly linked minor one. Thus, complementing previous work on the evolution of genetic architectures in subdivided populations subject to diversifying selection, it is shown that concentrated architectures may aid the maintenance of polymorphism. Conditions are obtained when this is the case. Finally, the dependence of the phenotypic variance, linkage disequilibrium, and various measures of local adaptation and differentiation on the parameters is elaborated.


The effect of visual transformation on bimanual circling movement.
In order to examine the effect of visual transformation on bimanual movements of various difficulty, fourteen participants performed bimanual circling tasks in three asymmetric movement modes--90 degrees (the left hand precedes the right hand by 1/4 cycle), 180 degrees (the delay between two hands is 1/2 cycle), and 270 degrees (the left hand precedes the right hand by 3/4 cycle)--under the normal vision condition and the visual transformation condition. In the visual transformation condition, movement of the right hand was transformed so that the required bimanual movement was always presented visually as a symmetric pattern. Additionally, the participants also performed a 0 degrees mode (in-phase symmetric) movement. Results revealed that the visual transformation increased the movement accuracy, with the variability of the right-left difference unchanged. Thus, proper visual transformation can improve the accuracy of a movement task. The 0 degrees mode was performed with higher stability and accuracy than any other movement modes of the visual transformation condition and normal vision conditions. In addition, the constant error associated with the 90 degrees and 270 degrees modes indicated that, in the normal vision condition, the executed movement was shifted to the 180 degrees mode, whereas in the visual transformation condition it stayed around the required mode and was slightly shifted to the 0 degrees mode. This result suggests that visual transformation can change the relationship between the intention to realize the required mode and the intrinsic neuromuscular dynamics. The effect size of visual transformation was larger in the 90 degrees and 270 degrees modes than in the 180 degrees mode. It is thus concluded that the effect of visual transformation depends upon the difficulty of the movement task.


(±)-Japonones A and B, two pairs of new enantiomers with anti-KSHV activities from Hypericum japonicum.
Two pairs of new enantiomers with unusual 5,5-spiroketal cores, termed (±)-japonones A and B [(±)-1 and (±)-2], were obtained from Hypericum japonicum Thunb. The absolute configurations of (±)-1 and (±)-2 were characterized by extensive analyses of spectroscopic data and calculated electronic circular dichroism (ECD) spectra, the application of modified Mosher's methods, and the assistance of quantum chemical predictions (QCP) of (13)C NMR chemical shifts. Among these metabolites, (+)-1 exhibited some inhibitory activity on Kaposi's sarcoma associated herpesvirus (KSHV). Virtual screening of (±)-1 and (±)-2 were conducted using the Surflex-Dock module in the Sybyl software, and (+)-1 exhibited ability to bind with ERK to form key interactions with residues Lys52, Pro56, Ile101, Asp165, Gly167 and Val99.


Redundant proteolytic activation of a viral superantigen.
Proteolytic activation of viral superantigens (vSAgs)4 expressed in Chinese hamster ovary (CHO) cells is required for T cell stimulation, and is mediated primarily by the protein convertase (PC) furin. Three PC recognition sites are highly conserved in vSAgs, but it was not known which sites are required for PC dependent vSAg activation. Moreover, because the PC recognition sites are not conserved in all functional vSAgs it was possible that activation could occur by processing at any of several sites. To identify the location(s) where processing of vSAg7 generates an active superantigen, each of two PC recognition sites, and a third related site were altered by in vitro mutagenesis, and the mutant proteins were tested for their abilities to activate T cells. Mutation of the PC recognition site at position 68-71 in vSAg7 had no effect on its ability to activate T cells. Mutation of the processing site at position 169-172 completely abolished T cell activation, and indicated that cleavage at this position was obligatory for proteolytic activation of vSAg7. However, introduction of a PC recognition site at position 192-195, a position that in many other vSAgs encodes a PC recognition site, restored activity to a vSAg7 protein that lacked a recognition site at position 169-172. The data revealed that processing of vSAgs at either position 169-172 or 192-195 was sufficient for vSAg7 activation, and explain how vSAgs that lack some PC recognition sites can be activated by proteolytic processing.


mTORC and PKCε in Regulation of Alcohol Use Disorder.
Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.


[Fosfomycin: an underrated antibiotic for urinary tract infections due to Escherichia coli].
To evaluate the sensitivity patterns of Escherichia coli isolates obtained from urine specimens from patients with community-acquired urinary tract infections, with a special emphasis on fosfomycin trometamol for the treatment of UTI. Retrospective analysis of the sensitivity pattern of 16,227 E. coli isolates recovered from urine cultures performed at the Microbiology Laboratory of Madrid Area 11 from 1997 to 2000. The antimicrobial agents tested included ampicillin, amoxycillin-clavulanate, cephalotin, cefuroxime, trimethoprim-sulphamethoxazol, fosfomycin trometamol, nitrofurantoin, and ciprofloxacin. Antibiotic sensitivity testing was performed with the Vitek automatic microdilution system (bioMèrieux, France). E. coli represented 80.1% of all uropathogens recovered. The percentages of sensitive strains to ampicillin, amoxycillin-clavulanate, cephalotin, cefuroxime, trimethoprim-sulphamethoxazol, nitrofurantoin, and ciprofloxacin were 42.25%, 81.5%, 58.75%, 87.5%, 70%, 94.75%, and 84.75%, respectively. Fosfomycin trometamol was the antibiotic with the highest activity against E. coli, with 95.5% of sensitive isolates. Fosfomycin trometamol (single dose) is a good alternative that should be considered for the treatment of non-complicated lower urinary tract infections.


Basic fibroblast growth factor accelerates matrix degradation via a neuro-endocrine pathway in human adult articular chondrocytes.
Pain-related neuropeptides released from synovial fibroblasts, such as substance P, have been implicated in joint destruction. Substance P-induced inflammatory processes are mediated via signaling through a G-protein-coupled receptor, that is, neurokinin-1 tachykinin receptor (NK(1)-R). We determined the pathophysiological link between substance P and its receptor in human adult articular cartilage homeostasis. We further examined if catabolic growth factors such as basic fibroblast growth factor (bFGF or FGF-2) or IL-1beta accelerate matrix degradation via a neural pathway upregulation of substance P and NK(1)-R. We show here that substance P stimulates the production of cartilage-degrading enzymes, such as matrix metalloproteinase-13 (MMP-13), and suppresses proteoglycan deposition in human adult articular chondrocytes via NK(1)-R. Furthermore, we have demonstrated that substance P negates proteoglycan stimulation promoted by bone morphogenetic protein-7, suggesting the dual role of substance P as both a pro-catabolic and anti-anabolic mediator of cartilage homeostasis. We report that bFGF-mediated stimulation of substance P and its receptor NK(1)-R is, in part, through an IL-1beta-dependent pathway.


Transcranial Doppler and cerebral augmentation in acute ischemic stroke.
Collateral flow augmentation using partial aortic occlusion may improve cerebral perfusion in acute stroke. We assessed the effect of partial aortic occlusion on arterial flow velocities of acute stroke patients. Patients with neurological deficits following thrombolysis were treated with partial aortic occlusion. Transcranial Doppler ultrasound (TCD) was used to measure arterial flow velocities at baseline, before and during balloon inflation. The augmented mean flow velocity (MFV), peak systolic velocity (PSV), and end diastolic velocity flow percentages (aMFV%, aPSV%, aEDV%) were calculated and compared based on outcome. Of 11 patients, 3 did not have a temporal window and thus were excluded from our analysis. Six of the remaining 8 patients had middle cerebral artery (MCA) occlusions; the final 2 had terminal internal carotid artery (TICA) occlusions. Three of these 8 patients had good outcome at 90 days (mRS < 3). Before intra-aortic balloon inflation (IABI), the mean affected artery MFV was 23 ± 11 cm/s; during the procedure it was 26 ± 12 cm/s (P = .2). Mean affected artery PSV at baseline and during balloon inflation were 37 ± 16 and 46 ± 23, respectively (P = .1). Mean augmented affected artery MFV% in patients with good long-term outcome was 65.4 ± 46, while the result in those with poor outcome was -3.7 ± 21 (P = .03). Three patients developed anterior cross-filling, and of these 2 had good long-term outcome. TCD monitoring of patients treated with IABI may help in predicting outcome in this novel device.


Ileal Pouch-anal Anastomosis Complications and Pouch Failure: A systematic review and meta-analysis.
This systematic review aims to assess the incidence of pouch failure and the correlation between ileal pouch-anal anastomosis (IPAA)-related complications and pouch failure. Previous studies demonstrated wide variation in postoperative complication rates following IPAA. A systematic review was performed by searching the MEDLINE, EMBASE, and Cochrane Library databases for studies reporting on pouch failure published from January 1, 2010, to May 6, 2020. A meta-analysis was performed using a random-effects model, and the relationship between pouch-related complications and pouch failure was assessed using Spearman's correlations. Thirty studies comprising 22,978 patients were included. Included studies contained heterogenic patient populations, different procedural stages, varying definitions for IPAA-related complications, and different follow-up periods. The pooled pouch failure rate was 7.7% (95% confidence intervals: 5.56-10.59) and 10.3% (95% confidence intervals: 7.24-14.30) for studies with a median follow-up of ≥5 and ≥10 years, respectively. Observed IPAA-related complications were anastomotic leakage (1-17%), pelvic sepsis (2-18%), fistula (1-30%), stricture (1-34%), pouchitis (11-61%), and Crohn's disease of the pouch (0-18%). Pelvic sepsis (r = 0.51, P < 0.05) and fistula (r = 0.63, P < 0.01) were correlated with pouch failure. A sensitivity analysis including studies with a median follow-up of ≥5 years indicated that only fistula was significantly correlated with pouch failure (r = 0.77, P < 0.01). The single long-term determinant of pouch failure was pouch fistula, which is a manifestation of a chronic leak. Therefore, all effort should be taken to prevent an acute leak from becoming a chronic leak by early diagnosis and proactive management of the leak. This systematic review aims to assess the incidence of pouch failure and the correlation between IPAA-related complications and pouch failure. Long-term pouch failure was correlated with fistula, suggesting that early septic complications may result in fistula formation during long-term follow-up, leading to an increased risk of pouch failure.


Human amnion epithelial cells reduce ventilation-induced preterm lung injury in fetal sheep.
The objective of the study was to explore whether human amnion epithelial cells (hAECs) can mitigate ventilation-induced lung injury. An established in utero ovine model of ventilation-induced lung injury was used. At day 110 of gestation, singleton fetal lambs either had sham in utero ventilation (IUV) (n = 4), 12 hours of IUV alone (n = 4), or 12 hours of IUV and hAEC administration (n = 5). The primary outcome, structural lung injury, was assessed 1 week later. Compared with sham controls, IUV alone was associated with significant lung injury: increased collagen (P = .03), elastin (P = .02), fibrosis (P = .02), and reduced secondary-septal crests (P = .009). This effect of IUV was significantly mitigated by the administration of hAECs: less collagen (P = .03), elastin (P = .04), fibrosis (P = .02), normalized secondary-septal crests (P = .02). The hAECs were immunolocalized within the fetal lung and had differentiated into type I and II alveolar cells. The hAECs mitigate ventilation-induced lung injury and differentiated into alveolar cells in vivo.


[Lidocaine pharmacokinetics and substantiation of the new method of its administration in myocardial infarct].
Lidocain pharmacokinetics was studied in 12 patients with acute myocardial infarction (males and females from 40 to 90 years of age with obvious disorders of hepatic and kidney function or severe hemodynamic disorders). In ten of them the main pharmacokinetic parameters were determined; the average value of lidocain clearance was 0.45 1/min. The optimum rate of continuous drip infusion was calculated (1.35 mg/min). It is shown that the existing method of lidocain administration by the "initial dose + infusion" schedule is unsatisfactory from the pharmacokinetic standpoint. Recommendations are given for the choice of the optimum concentrations of lidocain solution used in different rates of continuous infusion.


Prognostic significance of periodic acid-Schiff-positive patterns in primary breast cancer and its lymph node metastases.
Invasive ductal carcinoma is by far the largest histological subtype of breast cancer, but clinical behavior can differ greatly. Reliable morphological markers are, therefore, of invaluable help to distinguish between patients with good and poor prognosis. Histological patterns stained with periodic acid-Schiff (PAS) were previously shown to be of prognostic significance in cutaneous and uveal melanoma. In this study, we examined the presence of different PAS-positive (PAS+) structures in 54 women with infiltrating ductal adenocarcinoma of the breast and at least one axillary lymph node metastasis but no distant metastases who were followed for at least 11 years. We found that the complexity of the thin PAS+ patterns in lymph node metastases is associated with a shorter period of disease free survival (DFS) as well as of total survival (Kaplan-Meier curves). Furthermore, the presence of PAS+ networks - the most complex thin PAS+ pattern - in lymph node metastases is one of the two independent factors associated with the occurrence of a distant metastasis (multivariate Cox model). Moreover, the presence of PAS+ networks in positive lymph nodes is the feature most strongly associated with DFS. In conclusion, the presence of PAS+ networks in lymph node metastases is a new, reliable and convenient indicator for prognosis of breast cancer patients.


Is breast cancer in young Latinas a different disease?
Breast cancer appears to be more aggressive in young women (< or =35 years). Race/ethnicity may further influence prognosis. The purpose of this review is to determine whether breast cancer in young Latinas differs from that in other women. Our institutional (1977-2000) and state (1988-2000) tumor registries were reviewed and breast cancer cases analyzed. Data are expressed as mean +/- SEM. At our institution, 56 (7%) of 748 breast cancer patients were < or =35 years old; 32 (57%) were Latina. Compared with non-Latinas, Latinas presented at a younger age (P <0.05) and had more stage III/IV disease (38% versus 29%; P >0.05) and bilaterality (22% versus 8%; P >0.05), and worse 5-year survival (63% versus 83%; P >0.05). Statewide data were consistent with our institutional data. Latinas comprise a disproportionate share of our young breast cancer population, and may suffer more aggressive disease than other young women. Young Latinas may benefit from more vigilant screening and should be considered for novel therapeutic protocols.


Reversed saphenous bypass for hepatic artery pseudoaneurysm after liver transplantation.
Hepatic artery pseudoaneurysm (HAP) is found in 1-2% of liver transplantation (LT) patients. The mortality associated with pseudoaneurysm formation after orthotopic LT is reported to be as high as 75%. Because of the rarity of complications, particularly when considered individually, much of the direction for the management of complications is anecdotal. This article discusses the presentation, etiology, types, treatment indications, and vascular procedures used to manage complications with LT. Between January 2004 and December 2011, 464 LTs were performed at our institution. Of these, 9 (1.9%) consecutive patients underwent surgical treatment of HAP (8 men and 1 woman; median age, 58.4 years [range, 46-67 years]). Four patients underwent transarterial chemoembolization before LT for hepatocellular carcinoma. In all cases, revascularization with a reversed autologous saphenous vein bypass was performed. Four patients had ruptured pseudoaneurysms, and the others were diagnosed as having asymptomatic pseudoaneurysms during the follow-up period. The median delay between LT and the diagnosis of HAP was 39.6 days (range, 22-92 days). All were anatomically extrahepatic. The median diameter was 15.3 mm (range, 9-30 mm). Four patients had a T-tube. In 6 cases, biliary leakage was associated with the LT and, in the remaining 3, mycosis was recorded. After surgery, 1 patient underwent retransplantation because of ischemic cholangitis. Five years later, 5 patients had normal arterial anatomy, and the other 3 patients had stenosis that was successfully treated by stents. All of the patients had normal liver function at follow-up. One patient died 16 months later because of a heart attack. HAP with massive intraperitoneal bleeding is a rare but serious life-threatening complication when it occurs after LT. The majority of HAP cases are associated with bile leakage and mycosis; therefore, surgery must be the treatment of choice. Our conclusions support surgical revascularization with reversed saphenous grafts as a feasible and efficient treatment in cases of HAP.


A rare case of jejunal atresia.
Intestinal atresia more common in the small bowel, apart from large intestine. Jejunal atresia characterized by complete occlusion of the intestinal lumen, is a rare congenital anomaly occurring in 1 in 12,000 live births. The jejunal atresia can be single or multiple occurring anywhere from the ligament of Treitz to the jejuno-ileal junction, requiring immediate surgical attention to prevent mortality and morbidity among these neonates. A rare case of jejunal atresia in neonate and its management has been discussed here. Surgical excision of the involved bowel and end to end anastomosis of the normal bowel is definitive treatment. The morbidity associated with post-operative hypo persistaltic bowel can be minimised by adding oral prokinetics in controlled manner.


Cylindroxanthones A-C, three new xanthones and their cytotoxicity from the stem bark of Garcinia cylindrocarpa.
Three new xanthones, cylindroxanthones A-C (1-3), were isolated from the stem bark of Garcinia cylindrocarpa. The structures were established on the basis of spectroscopic analysis. The molecular structure of 1 was unequivocally confirmed by single-crystal X-ray diffraction analysis. These three xanthones were evaluated regarding their cytotoxicity against KB, HeLa S-3, HT-29, MCF-7, and Hep G2 cancer cell lines. Compound 1 exhibited good cytotoxicity against KB cell with IC50 value of 2.36 μM.


Liver transplantation for unresectable colorectal liver metastasis.
To summarize the current state of liver transplantation (LT) for unresectable colorectal liver metastases (uCRLM), and to address future directions. The Norwegian secondary cancer (SECA) I and SECA II studies demonstrated that after LT the 5-year survival of a highly selected group of patients with uCRLM could be as high as 60% and 83%, respectively. After long-term follow-up, the 5- and 10-year survival was shown to be 43% and 26%, respectively. Furthermore, data has accumulated in other countries and a North American study reported a 1.5-year survival of 100%. In addition, steady growth has been demonstrated in the US, with 46 patients transplanted to date and 19 centers enrolling patients for this indication. Lastly, although recurrence is almost universal in patients with a high tumor burden, it has not been an accurate surrogate for survival, reflecting the relatively indolent nature of recurrence after LT. Growing evidence has shown that excellent survival and even cure can be achieved in highly selected patients with uCRLM, with survival rates far superior than in patients treated with chemotherapy. The next step is to create national registries to standardize selection criteria and establish the optimal approach and best practices for incorporating LT for uCRLM into the treatment armamentarium.


Resonance energy transfer study of lysozyme-lipid interactions.
Resonance energy transfer (RET) between the tryptophan residues of lysozyme as donors and anthrylvinyl-labeled phosphatidylcholine (AV-PC) or phosphatidylglycerol (AV-PG) as acceptors has been examined to gain insight into molecular level details of the interactions of lysozyme with the lipid bilayers composed of PC with 10, 20, or 40 mol% PG. Energy transfer efficiency determined from the enhanced acceptor fluorescence was found to increase with content of the acidic lipid and surface coverage. The results of RET experiments performed with lipid vesicles containing 40 mol% PG were quantitatively analyzed in terms of the model of energy transfer in two-dimensional systems taking into account the distance dependence of orientation factor. Evidence for an interfacial location of the two predominant lysozyme fluorophores, Trp62 and Trp108, was obtained. The RET enhancement observed while employing AV-PG instead of AV-PC as an energy acceptor was interpreted as arising from the ability of lysozyme to bring about local demixing of the neutral and charged lipids in PC/PG model membranes.


Listeria monocytogenes sensitivity to antimicrobial treatments depends on cell origin.
In this study we investigated how cell origin could affect the efficacy of an antimicrobial treatment (mild heating combined with terpenoids) in Listeria monocytogenes Scott A, considering cells from: 1. single colony, 2. glycerol stock, 3. cold adapted culture, and 4. fresh culture in stationary phase. After treatment, culturability on BHI medium and viability assessed by flow cytometry were evaluated. Our results showed that the cell origin significantly impacted viability and culturability of L. monocytogenes towards antimicrobial treatment. The mild heat treatment combined or not with terpenoids mainly affected culturability rather than viability, although the culturability of cells from single colony was less impacted. Therefore, to mimic the worst scenario, these latter were selected to contaminate Gorgonzola rind and roast beef slices and we evaluated the ability of L. monocytogenes cells to recover their culturability (on ALOA agar medium) and to growth on the food matrix stored at 4 °C for 7 days. Our results suggest that only Gorgonzola rind allowed a partial recovery of the culturability of cells previously heated in presence or not of terpens. In conclusion, we found a connection between the cell history and sensitivity toward an antimicrobial treatment, underlying the importance to standardize the experimental procedures (starting from the cells to be used in the assay) in the assessment of cell sensitivity to a specific treatment. Finally, our study clearly indicated that VBNC cells can resuscitate under favorable conditions on a food matrix, becoming a threat for consumer's health.


Nodulation number tempers the relative importance of stochastic processes in the assembly of soybean root-associated communities.
Identifying the ecological forces that structure root-associated microbial communities is an essential step toward more sustainable agriculture. Legumes are widely utilized as model plants to study selective forces and their functioning in plant-microbial interactions owing to their ability to establish mutualism with rhizobia. Root nodules act as symbiotic organs to optimize the cost-benefit balance in this mutualistic relationship by modulating the number of nodules. However, it is not known whether the number of nodules is related to the structure of root-associated bacterial communities. Here, the root-associated bacterial communities of soybean grown in native soil by means of soybean cultivars with super- or normal nodulation were investigated across four developmental stages. We compared ecological processes between communities and found decreased relative importance of neutral processes for super-nodulating soybean, although the overall structures resembled those of normal-nodulating soybean. We identified the generalist core bacterial populations in each root-associated compartment, that are shared across root-associated niches, and persist through developmental stages. Within core bacterial species, the relative abundances of bacterial species in the rhizosphere microbiome were linked to host-plant functional traits and can be used to predict these traits from microbes using machine learning algorithms. These findings broaden the comprehensive understanding of the ecological forces and associations of microbiotas in various root-associated compartments and provide novel insights to integrate beneficial plant microbiomes into agricultural production to enhance plant performance.


Paget Disease of the Breast in Pregnancy and Lactation.
Paget's disease of the breast (PDB) is a rare breast carcinoma believed to arise from an underlying in situ or invasive ductal cancer that migrates through the epidermis causing characteristic skin changes including scaling, redness, and itching of the nipple, areola, and sometimes the surrounding skin. Although Paget's may mimic benign conditions such as contact or allergic eczema and mastitis, it should remain a strong consideration in the differential diagnosis , especially in peripartum women for whom benign conditions such as bacterial mastitis from breastfeeding are common. The workup of Paget's should focus on both making the diagnosis with nipple/skin scrape cytology or punch biopsy as well as evaluating any underlying mass with mammogram, breast ultrasound , and also a core needle biopsy , if required. Treatment focuses on management of the underlying breast cancer as usual. The purpose of this chapter is to describe the presentation of PDB as well as outline an approach to its diagnosis and management, especially in the setting of pregnancy and lactation.


Which incision is better for Lewis to Brown Norway rat liver transplantation, transverse or midline?
Orthotopic rat liver transplantation (OLT) is a complex microsurgical procedure extensively applied to basic science, myriad complications can occur, but incision-related self-biting has not been reported after OLT. For the project of tolerance induction through stem cells, we performed OLT from Lewis to Brown Norway (BN) rats as an acute rejection model and divided the study was into the transverse incision group (n = 15) and midline incision group (n = 22), while cyclosporine A was subcutaneously injected for 10-day immunosuppression use, lidocaine cream was used for pain-relieving. The recipient survival and wound status were the primary endpoint of this study. For the transverse incision group, 30-day survival rate was 40% (6/15), self-biting occurred in 13 cases in 7-39 days, the degree 1 of biting occurred in 1 cases, the degree 2 in 2 cases. The degree 3 in 10 cases, which caused death or euthanasia, the self-biting rate was 86.7% (13/15), For the midline incision group, 30-day survival rate was 100% (22/22), the degree 1 of self-biting occurred in 3 cases, no severe self-biting occurred. There were significant differences for survival (p = 0.0003) and for self-biting rate (p < 0.01) between two groups. In conclusion, incision-related self-biting behavior occurs due to incisional injury, the transverse incision is severely pain-causing; the midline one is effective to avert occurrences.