Dynamics of infection and pathology induced by the aporocotylid, Cardicola laruei, in Spotted Seatrout, Cynoscion nebulosus (Sciaenidae).
The sciaenid Spotted Seatrout (Cynoscion nebulosus) are infected by blood flukes (Cardicola spp.). A 2 year survey in estuaries of South Carolina, USA, showed that adult flukes and granulomas occurred throughout the year but their prevalence was highest in summer (61% and 84%, respectively), indicating an unusually high level of infection for wild fish. Granulomas remained after adult flukes could no longer be found. PCR-Restriction Fragment Length Polymorphism (RFLP) of a subsample of specimens allowed identification of Cardicola laruei as the only species infecting these seatrout during the period of study. Mean intensity of infection by flukes was higher in female seatrout, suggesting endocrine and/or immune system involvement. The prevalence of granulomas declined sharply in winter, indicating possible mortality of infected seatrout as this species is known to be cold-sensitive. Granulomas were studied using histology, immunohistochemistry, and transmission electron microscopy. Eggs were encapsulated by an inner core of dark epithelioid cells, and an outer core of large epithelioid cells undergoing epithelialization. Fibrosis was observed around granulomas and some granulomas detached from the surrounding damaged myocardium. Numerous inflammatory cells appeared mobilised around granulomas and pathology could be severe, in some cases showing grossly visible blister-like extrusions scattered in the damaged epicardium. At the gross level, some granulomas possessing eggs with live miracidia were observed at the surface of the epicardium. These findings suggest that granulomas carrying both dead and live eggs can clear the fish heart by host-mediated transport through the myocardium, as is known to occur in related human Schistosoma infections.


The association between dilated cardiomyopathy and RTN4 3'UTR insertion/deletion polymorphisms.
The Nogo isoforms A, B and C are members of the reticulon family of proteins. Nogo-B is found in most tissues, especially highly expressed in endothelial and smooth muscle cells of the vessel wall, and Nogo-B is a regulator of cell migration in vitro and vascular remodeling in vivo. The TATC and CAA 3'UTR insertion/deletion polymorphisms of the RTN4, the gene encoding Nogo isoforms A, B and C, have been linked to schizophrenia and depression, but data were inconsistent. However, it is unclear whether these polymorphisms are associated with dilated cardiomyopathy (DCM). A total of 159 DCM patients and 215 control subjects were recruited in this study. The RTN4 TATC and CAA insertion/deletion genotypes were determined using PCR-polyacrylamide gel electrophoresis. Frequencies of (TATC)(2) allele and (TATC)(2)/(TATC)(2) genotype were significantly different from that in healthy controls (P = 0.045, OR = 1.356, 95% CI = 1.006-1.827 and P = 0.021, OR = 2.094, 95% CI = 1.113-3.940, respectively). No significant differences in CAA insertion/deletion genotype and allele frequencies were observed between the DCM and controls. These data provide evidence that RTN4 allele (TATC)(2) and (TATC)(2)/(TATC)(2) genotype are associated with DCM.


Benefits of nasal saline treatment in acute rhinosinusitis: Systematic review and meta-analysis.
Although nasal saline treatments are widely used in treating acute rhinosinusitis (ARS), the evidence in adult patients is inconclusive. Our objective was to assess the add-on benefits of saline treatment in adults with ARS. Literature searches were performed (updated May 9, 2021). Randomized, controlled trials studying the effects of nasal saline treatment in adults with ARS were included. Data were pooled for meta-analysis. Outcomes were composite symptoms score (CSS), disease-specific quality-of-life (DS-QoL) score, individual symptom score, endoscopy score, saccharin transit time, cure rate, days to resolution, and adverse events. Eleven studies (718 patients) were included in our investigation. Nasal discharge was the only symptom improved (standardized mean difference [SMD], -0.36; 95% confidence interval [CI], -0.66 to -0.05]. Saline as an add-on treatment brought no benefit to CSS and DS-QoL score at both time-points (3-10 days and at the end of the study). Other outcomes also showed no benefits with use of saline, including endoscopy score, saccharin transit time, cure rate, days to resolution, and adverse events. Subgroup analyses showed improvement in viral ARS patients for CSS (SMD, -0.60; 95% CI, -1.12 to -0.08) and DS-QoL score (mean difference, -15.90; 95% CI, -31.78 to -0.02), and also in patients using high-volume saline (SMD, -0.42; 95% CI, -0.78 to -0.06). Nasal saline as an add-on treatment improved rhinorrhea. There was no improvement in CSS and DS-QoL, except among the subgroup of viral ARS patients using high-volume saline. There were no differences in adverse events between the saline and non-saline treatments.


Wound dehiscence in bladder exstrophy: an examination of the etiologies and factors for initial failure and subsequent success.
During the last 8 years 20 patients were seen for secondary or repeat closure for exstrophy of the bladder following dehiscence after initial closure. Various factors that may have contributed to the initial problems have been investigated. Wound infection (42 per cent) and bladder prolapse (46 per cent) were the major etiologies for initial failures. In 6 patients (30 per cent) colon conduits were required for bladder augmentation or colocolostomy, which emphasized the importance of achieving a good result at initial closure. Our successful protocol (only 5 per cent reclosure rate for 60 closures) is outlined.


Large-Vessel Occlusion Stroke: Effect of Recanalization on Outcome Depends on the National Institutes of Health Stroke Scale Score.
Arterial recanalization is currently considered the main standard of successful early management of acute ischemic stroke. Intravenous (IV) thrombolysis with tissue plasminogen activator (tPa) is the only Food and Drug Administration-approved medical treatment. Large-vessel occlusion, estimated to account for up to 40% of all acute ischemic strokes, is often refractory to IV thrombolysis and is associated with a poor patient outcome. Mechanical recanalization procedures are therefore increasingly used in the treatment of large-vessel occlusion refractory to, or presenting outside the accepted time window for, IV thrombolysis. The aim of this study was to investigate the effect of early vessel recanalization on clinical outcome in patients with large-vessel occlusion stroke. This is a single-center cohort study, analyzing prospectively collected data on 152 patients with large-vessel occlusion and acute ischemic stroke. Seventy-one patients received endovascular treatment (of whom 57.7% also received IV tPA), and 81 (55.6% of whom also received IV tPa) were not treated with endovascular therapy. Clinical outcome was compared for 2 cohorts: patients who recanalized (n = 46) and patients with persisting large-vessel occlusion (n = 106). Early recanalization was an independent predictor of a good clinical outcome in only those patients who presented with a severe ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score >15; P = .017). This was not the case for less severe strokes (NIHSS score ≤ 15) where recanalization did not lead to more patients with functional independence at 90-day follow-up (P = .21). In this study of acute large-vessel occlusion stroke, we found that clinical outcome following early recanalization was dependent on the patient's pretreatment NIHSS score. A non-negligible proportion of patients with milder strokes did well despite persistent large-vessel occlusion. These results may suggest that in patients who are able to maintain adequate collateral flow despite proximal arterial occlusion, effective adaptive mechanisms are present, which for some patients are long-lasting. This may influence the process of appropriate patient selection for endovascular therapy.


Poly[dipotassium [(μ6-2,2',2'',2'''-{[pyrazine-2,3,5,6-tetra-yltetra-kis-(methyl-ene)]tetra-kis-(sulfanedi-yl)}tetra-acetato)-disilver(I)] 5.2-hydrate].
The reaction of AgNO3 with the ligand 2,2',2'',2'''-{[pyrazine-2,3,5,6-tetra-yltetra-kis-(methyl-ene)]tetra-kis-(sulfanedi-yl)}tetra-acetic acid in the presence of a potassium acetate buffer lead to the formation of a silver(I)-potassium-organic framework, poly[dipotassium [(μ6-2,2',2'',2'''-{[pyrazine-2,3,5,6-tetra-yltetra-kis(methyl-ene)]tetra-kis-(sulfanedi-yl)}tetra-acetato)-disilver(I)] 5.2-hydrate], {K2[Ag2(C16H16N2O8S4)]·5.2H2O} n , (I). The asymmetric unit is composed of half a binuclear silver complex located about a center of symmetry, a potassium cation and 2.6 disordered water mol-ecules. The whole binuclear silver complex is generated by inversion symmetry with the pyrazine ring being located about an inversion centre. The ligand coordinates in a bis-tetra-dentate manner. The binuclear silver complex anions are linked via bridging Ag⋯S⋯Ag zigzag bonds, forming a network lying parallel to the bc plane. The networks are linked by Ocarboxyl-ate⋯K +⋯Ocarboxyl-ate bridging bonds to form a framework. The disordered water mol-ecules are present near to the K+ cations.


Satellite association frequency and number of nucleoli depend on cell cycle duration and NOR-activity. Studies on first, second, and third mitoses of lymphocyte cultures.
In human lymphocyte cultures the frequencies of satellite associations in first, second, and third mitoses were investigated using the BUDR-method. A marked decrease of the association frequency with increasing numbers of cell cycles was found. The number of nucleoli seen in interphase is correlated with the satellite association frequency in the respective metaphase. Satellite association is positively correlated to Ag-staining intensity of the NORs. Individual differences in satellite association are due to differences in NOR activity and in lymphocyte activation. BUDR diminishes somewhat the Ag-staining intensity of the NORs but has no effect on satellite association frequencies. The main reason for the decrease of satellite association frequency in second and third lymphocyte mitoses is presumably a certain dislocation of the original chromosome position during mitosis and a decreased possibility of association during the short interphases. The high association frequency in first mitosis resembles the chromosome position in the long interphase of G0-lymphocytes.


Effects of verapamil on electrophysiological properties in paroxysmal atrial fibrillation.
Verapamil is used to control ventricular response during atrial fibrillation (AF). Limited data is available on the effects of verapamil on atrial vulnerability in human AF. The effects of intravenous verapamil (0.15 mg/kg) on electrophysiological properties of the atrium were investigated in 12 patients with documented paroxysmal AF by electrophysiological studies. Sinus cycle length, sinus node recovery time, and the effective refractory period of the right atrium were not significantly affected by verapamil. The intraatrial conduction delay zone was significantly increased (33 +/- 20 msec before verapamil versus 50 +/- 22 msec after verapamil, P < 0.01), and the maximal intraatrial conduction delay was also significantly prolonged by verapamil, both to the His bundle region (30 +/- 12 msec before verapamil versus 42 +/- 15 msec after verapamil, P < 0.01) and to the coronary sinus (40 +/- 15 msec before verapamil versus 53 +/- 17 msec after verapamil, P < 0.01). The fragmented atrial activity zone was significantly increased (15 +/- 14 msec before verapamil versus 25 +/- 22 msec after verapamil, P < 0.02), and the percentile fragmented atrial activity was also significantly increased by verapamil (149 +/- 18 msec before verapamil versus 174 +/- 44 msec after verapamil, P < 0.05). The repetitive atrial firing zone remained unchanged. Sustained AF spontaneously occurred in only one patient after the administration of verapamil. Thus, verapamil may modulate the abnormal atrial electrophysiology in paroxysmal AF, and would favor production of atrial reentry.


Treatment of acne scarring with a novel fractionated, dual-wavelength, picosecond-domain laser incorporating a novel holographic beam-splitter.
Fractional treatment with a dual wavelength 1,064 and 532 nm picosecond-domain laser, delivering a 10 × 10 array of highly focused beamlets via a holographic optic, was investigated for the treatment of acne scars. Twenty-seven of 31 subjects completed the study, 19 were treated using 1,064 nm and 8 were treated at 532 nm, all having four-monthly treatments. Blinded evaluation of digital images by three physician evaluators comparing pre- and 3-month post-treatment images measured efficacy using a 10-point scale. Subject self-assessment of treatment effects were also recorded. Safety was measured by recording subject discomfort scores and adverse effects. Blinded reviewers correctly identified the baseline image in 61 of the 81 image sets (75%), and baseline acne scar scores were 1.8 ± 0.7 and 1.8 ± 0.5 for the 1,064 and 532 nm cohorts, and decreased to 1.1 ± 0.5 (P < 0.001) and 1.1 ± 0.0 (P < 0.005), respectively. Post-treatment erythema, mild edema, and petechiae were the only side effects noted. The 1,064 and 532 nm picosecond-domain laser incorporating a 10 × 10 holographic beam-splitting handpiece was found to be safe and effective for the treatment of facial acne scars. The treatments were well tolerated and the subjects experienced little to no downtime. Lasers Surg. Med. 49:796-802, 2017. © 2017 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.


[Update on the diagnosis and treatment of delirium].
Delirium is an acute confusional state with typically fluctuating disturbances of attention, cognition, and qualitative awareness. Its incidence depends on the patient group. In the development of delirium, predisposing factors such as age, frailty, multimorbidity, surgical interventions, and pre-existing dementia are of high clinical relevance. The diagnosis of delirium should be based on symptoms and validated screening methods (e.g., Confusion Assessment Method). As delirium is a direct physiological consequence of a medical condition, the potential underlying cause(s) should be diagnosed. Prevention and therapy are primarily multimodal, non-pharmacological treatments such as reorientation, early mobilization, and sleep improvement. If symptomatic pharmacological treatment is necessary (e.g., due to delirium-related agitation), careful drug selection should be made depending on the patient population and symptoms.


Versatility of reconfigured-colon-segment technique for urinary reconstruction requiring use of tubular structures.
When a colon segment is used for urinary reconstruction and a tubular structure is necessary, the option for the tubular structures is limited. We prepared a short colon segment in advance for creating a reconfigured tube. Short colon segments are separated beforehand from the edges of the main colon segment for a continent urinary reservoir or augmentation cystoplasty. The short segments are either reconfigured, if necessary, into tubular structures to produce a continent valve or to replace a ureteral defect or discarded if they prove not to be needed. The number of short segments can be predicted on the basis of the clinical situation before and during the operation. Preparation of short colon segments is useful for urinary reconstruction using a colon segment that might require a number of tubular structures. The technique provides versatility and flexibility in difficult clinical conditions.


Simple and rapid methods for bacterial identifications.
Simple, inexpensive procedures for rapid identification of the common bacterial pathogens are outlined in detail. When the tests are judiciously applied, most isolates can be identified within minutes or hours, and strains that require more extensive testing for accurate identification will be recognized.


The potential application of organoids in breast cancer research and treatment.
Tumor heterogeneity is a major challenge for breast cancer researchers who have struggled to find effective treatments despite recent advances in oncology. Although the use of 2D cell culture methods in breast cancer research has been effective, it cannot model the heterogeneity of breast cancer as found within the body. The development of 3D culture of tumor cells and breast cancer organoids has provided a new approach in breast cancer research, allowing the identification of biomarkers, study of the interaction of tumor cells with the microenvironment, and for drug screening and discovery. In addition, the possibility of gene editing in organoids, especially using the CRISPR/Cas9 system, is convenient, and has allowed a more detailed study of tumor behavior in models closer to the physiological condition. The present review covers the application of organoids in breast cancer research. The recent use of gene-editing systems to provide insights into therapeutic approaches for breast cancer, is highlighted. The study of organoids and the possibility of gene manipulation may be a step towards the personalized treatment of breast cancer, which has so far remained unattainable due to the high heterogeneity of breast cancer.


Metagenomics and metatranscriptomics suggest pathways of 3-chloroaniline degradation in wastewater reactors.
Biological wastewater treatment systems are often affected by shifts in influent quality, including the input of toxic chemicals. Yet the mechanisms underlying the adaptation of activated sludge process performance are rarely studied in a controlled and replicated experimental setting, particularly when challenged with a sustained toxin input. Three replicate bench-scale bioreactors were subjected to a chemical disturbance in the form of 3-chloroaniline (3-CA) over 132 days, after an acclimation period of 58 days, while three control reactors received no 3-CA input. Ammonia oxidation was initially affected by 3-CA. Within three weeks of the experiment, microbial communities in all three treatment reactors adapted to biologically degrade 3-CA resulting in partial ammonia oxidation recovery. Combining process and microbial community data from amplicon sequencing with potential functions gleaned from assembled metagenomics and metatranscriptomics data, two putative degradation pathways for 3-CA were identified. The first pathway, determined from metagenomics data, involves a benzoate dioxygenase and subsequent meta-cleavage of the aromatic ring. The second, determined from intensive short-term sampling for gene expression data in tandem with 3-CA degradation, involves a phenol monooxygenase followed by ortho-cleavage of the aromatic ring. The relative abundances of amplicon sequence variants associated with the genera Gemmatimonas, OLB8, and Taibaiella correlated significantly with 3-CA degradation. Metagenome-assembled genome data also showed the genus OLB8 to be differentially enriched in treatment reactors, making it a strong candidate as 3-CA degrader. Using replicated reactors, this study has demonstrated the impact of a sustained stress on the activated sludge process. The unique and novel features of this study include the identification of putative pathways and potential degraders of 3-CA using long-term and short-term sampling in tandem with multiple methods in a controlled and replicated experiment.


Isolated changes in femoral version do not alter intra-articular contact mechanics in cadaveric hips.
Abnormal femoral version is a deformity in the angle between the femoral neck and the transcondylar axis of the knee. Both femoral anteversion and retroversion alter passive and active rotation of the hip and are associated with intra-articular or extra-articular impingement. However, little is known about the effect of abnormal femoral version on intra-articular hip contact stresses. To quantify the effect of femoral version on hip contact stress, five cadaveric pelvis specimens were mechanically tested with a hip-specific Tekscan sensor inserted in the joint space. Specimens were oriented in a heel-strike position and loaded with 1000 N of compressive force. Pressure measurements were recorded by the Tekscan sensor with the femur oriented in 0°, 15°, and 30° of version. At the completion of testing, specimens were locked into place at 0° and post-test CT scans were obtained to register the pressure sensor measurements to the joint anatomy. There were minor changes in contact area (<7%) and translation of the peak contact stress location (8.8 ± 7.6 mm). There was no significant change in peak contact stress (p = 0.901) in either the retroverted (0°) or anteverted (30°) conditions relative to normal version (15°) under identical gait-related loading conditions. While abnormalities in patient gait and resultant joint loading caused by femoral version abnormalities may contribute to hip pain, the present findings would suggest that future joint degeneration in hips with version abnormalities are not simply the result of abnormal contact stress induced by joint incongruity due to femoral version abnormalities.


[Alteration of enzyme activities in serum of Eimeria stiedai infected rabbits (author's transl)].
In experimental investigations on Eimeria stiedai infected rabbits, serum enzymatic studies have been carried out in correlation with the examination of parasitological and pathological parameters. The rabbits were orally infected with a single dose of either 100,000 or 250,000 sporulated oocysts. Increase of the activity of the sorbit dehydrogenase (SDH), glutamate oxalate transaminase (GOT), glutamate pyruvate transaminase (GPT) and glutamate dehydrogenase (GlDH) could be found first between 3 and 10 days after infection indicating the beginning of the acute phase of liver coccidiosis. The increase of the conjugated bilirubin and of the gamma-glutamyl-transferase (gamma-GT) could be found not earlier than 10 days after infection and is to be explained as sign of disturbed efficiency of excretion. The various investigated parameters reached their peak of alteration about the end of the prepatent period and at the beginning of patency between 14 and 21 days after infection. The results emphasize the value and usefulness of serum enzymes, particularly the glutamate dehydrogenase (GlDH) and the gamma-glutamyl-transferase (gamma-GT) with about 30fold activity, as indicators in the course of Eimeria stiedai infection of rabbits. The enzymes returned to physiological values at the end of the experiment, 42 days after infection. Significant differences could not be detected within the infected groups. The activities of the alkaline phosphatase (AP), leucine aminopeptidase (LAP), choline esterase (ChE), lactate dehydrogenase (LDH) and isoenzym 1 (alpha-HBDH) showed only slight alterations and proved to be no significant parameters for the pathophysiological evaluation of the liver coccidiosis.


The normal distribution and projections of constitutive NADPH-d/NOS neurons in the brainstem vestibular complex of the rat.
The vestibular system is a highly conserved sensory system in vertebrates that is largely responsible for maintenance of one's orientation in space, posture, and balance and for visual fixation of objects during motion. In light of the considerable literature indicating an involvement of nitric oxide (NO) in sensory systems, it is important to determine whether NO is associated with vestibular pathways. To study the relationship of NO to vestibular pathways, we first examined the normal distribution of constitutive NADPH-diaphorase (NADPH-d), a marker for nitric oxide synthase (NOS), in the vestibular complex (VC) and then examined its association with selected vestibular projection neurons. Survey of the four major vestibular nuclei revealed that only the medial vestibular nucleus contained significant numbers of perikarya stained for NADPH-d/NOS. By contrast, all the vestibular nuclei contained a network of fine processes that stained positive for NADPH-d, although the density of this network varied among the individual nuclei. To determine whether NADPH-d/NOS neurons project to vestibular efferent targets, injections of the retrograde tracer Fluoro-Gold were made into known targets of second-order vestibular neurons. Vestibular neurons containing constitutive NADPH-d/NOS were found to project predominantly to the oculomotor nucleus. A small number of neurons also participate in vestibulothalamic and intrinsic vestibular connections. These results indicate that NADPH-d/NOS neurons are prevalent in the MVN and that a subpopulation of these neurons project to the oculomotor complex. Nitric oxide is probably released locally from axons located throughout the vestibular complex but may play a particularly important role in vestibulo-ocular pathways.


Radon measurement and age-independent effective dose attributed to ingestion of bottled water in Iran: sensitivity analysis.
A comprehensive study was made to measure the radon concentration in bottled water available in Iran market. The 222Rn concentration in 70 bottled water samples were measured by the sniffing mode technique and RTM 1688-2 (SARAD, Germany) in immediate sampling time and 3 months later for determination of radon decay. The measured radon concentration ranged from 0.003 to 0.618 Bq L-1 in bottled water samples, which were much lower than the recommended value for radon in drinking water by WHO (100 Bq L-1) and United states environmental protection agency (USEPA) (11.1 Bq L-1). The annual effective dose of 222Rn due to ingestion bottled water was also evaluated in this research. The mean annual effective dose due to ingestion of radon in bottled water for adults, children, and infants were estimated to vary from 5.30 × 10-4 mSv-1, 4.90 × 10-4 mSv-1, and 2.15 × 10-4 mSv-1, respectively. Overall, this study indicated that the Iranian people receive no significant radiological risk due to exposure to radon concentration in bottled water brands common consumed in Iranian market.


Estrogen treatment increases phospholipid transfer activities in chicken liver.
The effect of subcutaneous beta-estradiol injection on liver phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol transfer activity of immature chicken has been determined. The estrogen administration significantly enhanced the transfer activity of both phosphatidylcholine (100%), phosphatidylethanolamine (160%), and phosphatidylinositol (150%). In vivo experiments revealed that the hormone-induced changes in liver lipid transfer activity were sensitive to a protein synthesis inhibitor, cycloheximide. A partial characterization of liver protein transfer on Sephacryl S-200 showed that multiple transfer proteins are involved in the beta-estradiol effect. This is the first time that hormonal modulation of phospholipid transfer activities is described, and the results suggest that the hepatic phospholipid transfer activities might be involved in the biosynthesis of plasma lipoproteins in vivo.


The energy consumption-environmental quality nexus in BRICS countries: the role of outward foreign direct investment.
This paper examines the role of outward foreign direct investment on energy consumption and environmental quality in BRICS from 1990 to 2019. Most of the previous research considered foreign direct investment mainly focused on the environmental impact on the host country effect and ignored the home country effect. Therefore, the current study examines the home country effect of environmental pollution. We use various methodologies like cross-sectional dependence and the Pesaran-Yamagata slope homogeneity for the diagnostic test. After confirming the diagnosis test, we employ second-generation panel unit root tests, which confirms that all elements are stationary at first difference. The pooled mean group (PMG), Westerlund cointegration, two-step generalised method of moments (GMM), panel fully modified ordinary least square (FMOLS), and dynamic ordinary least square (DOLS) model have been used to determine the short-term and long-term association among the variables. The cointegration and PMG results confirm that the short-run and long-run association exists among the considered variables. The results reveal that developing countries produced environmental pollution at the early stage of development and checked in the long run. The study used the STIRPAT model to build an extended carbon dioxide emissions model by incorporating outward FDI, GDP per capita, and technology to achieve our objectives. The empirical results hold up the environmental Kuznets curve hypothesis, implying that outward FDI and energy consumption help expand greener technology to host countries' environmental improvement in the long run and confirm that an inverted U-shaped linkage exists. Hence, the study suggests that developing countries should pay more attention to sustainable development and technological development that encourages more eco-friendly and environment-friendly technology.


What does magnetic resonance imaging add to the prenatal sonographic diagnosis of ventriculomegaly?
The purpose of this study was to determine the contribution of magnetic resonance imaging (MRI) in evaluating fetuses with the sonographic diagnosis of ventriculomegaly (VM). Over 4 years, consecutive fetuses with the sonographic diagnosis of VM at 1 facility who underwent prenatal MRI at a second facility were included. The roles of MRI and follow-up sonography were tabulated. The patients were analyzed in 2 groups based on the presence or absence of other central nervous system (CNS) abnormalities. Twenty-six fetuses with a gestational age range of 17 to 37 weeks had sonographically detected VM (atria > or =10-29 mm), including 19 with mild VM (atria 10-12 mm). In group 1, 14 had isolated VM, 6 of which reverted to normal by the third trimester. Magnetic resonance imaging showed cerebellar hypoplasia not shown by sonography in 1 fetus and an additional finding of a mega cisterna magna in a second fetus. In group 2, 12 fetuses had VM and other CNS anomalies on sonography. Additional findings were seen with MRI in 10 of these fetuses, including migrational abnormalities (n = 4), porencephaly (n = 4), and 1 diagnosis each of abnormal myelination, hypoplasia of the corpus callosum, microcephaly, a kinked brain stem, cerebellar hypoplasia, and congenital infarction. There were significantly more fetuses with additional CNS anomalies found by MRI among those in group 2 compared with those in group 1 (Fisher exact test, P = .001). Although sonography is an accurate diagnostic modality for the evaluation of fetuses with VM, MRI adds important additional information, particularly in fetuses in whom additional findings other than an enlarged ventricle are seen sonographically.


The prostaglandin E₂ type 4 receptor participates in the response to acute oxidant stress in airway epithelial cells.
Oxidative stress is implicated in the pathogenesis of many inflammatory pulmonary diseases, including cystic fibrosis (CF). Delineating how oxidative stress stimulates CF transmembrane conductance regulator (CFTR) in airway epithelial cells is useful, both to increase the understanding of airways host defense and suggest therapeutic approaches to reduce the oxidant stress burden in the CF lung. Using the airway epithelial cell line Calu-3, we investigated the hypothesis that hydrogen peroxide (H₂O₂), which stimulates anion efflux through CFTR, does so via the production of prostaglandin E₂ (PGE₂). Using iodide efflux as a biochemical marker of CFTR activity and short circuit current (I(sc)) recordings, we found that the H₂O₂-stimulated efflux was abolished by cyclooxygenase-1 inhibition and potentially also involves microsomal prostaglandin E synthase-1 activity, implicating a role for PGE₂ production. Furthermore, H₂O₂ application resulted in a rapid release of PGE₂ from Calu-3 cells. We additionally hypothesized that the PGE₂ subtype 4 (EP(4)) receptor was involved in mediating this response. In the presence of (4Z)-7-[(rel-1S,2S,5R)-5-((1,1'-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid (AH23848) (which blocks the EP₄ receptor), the H₂O₂-stimulated response was abolished. To investigate this finding in a polarized system, we measured the increase in I(sc) induced by H₂O₂ addition in the presence and absence of AH23848. H₂O₂ induced a robust increase in I(sc), which was significantly attenuated in the presence of AH23848, suggesting some role for the EP₄ receptor. In conclusion, with H₂O₂ as a model oxidant stress, stimulation of CFTR seems to involve PGE₂ production and likely EP₄ receptor activation in Calu-3 airway epithelial cells. This mechanism would be compromised in the CF airways.


Should adjustment disorder be conceptualized as transitional disorder? In pursuit of adjustment disorders definition.
The DSM classification of an adjustment disorder is frequently criticized for not being well differentiated from other disorders. A possible reason for this is the vague definition of the term adjustment in social science literature. Hence, the current paper discusses the definition of adjustment and its implications for understanding maladjustment. Differential definitions of the terms adjustment, adaptation, socialization and coping are outlined, leading to the proposition that each one of them represents a different type of demand that is imposed on an individual who encounters a transitional event. Moreover, the four types of demands might be the possible sources of maladjustment. Helping people in transition requires an identification of the source, or combination of sources, that have led to the adjustment problem first, followed by the implementation of an adequate helping approach.


Trade-driven relocation of air pollution and health impacts in China.
Recent studies show that international trade affects global distributions of air pollution and public health. Domestic interprovincial trade has similar effects within countries, but has not been comprehensively investigated previously. Here we link four models to evaluate the effects of both international exports and interprovincial trade on PM2.5 pollution and public health across China. We show that 50-60% of China's air pollutant emissions in 2007 were associated with goods and services consumed outside of the provinces where they were produced. Of an estimated 1.10 million premature deaths caused by PM2.5 pollution throughout China, nearly 19% (208,500 deaths) are attributable to international exports. In contrast, interprovincial trade leads to improved air quality in developed coastal provinces with a net effect of 78,500 avoided deaths nationwide. However, both international export and interprovincial trade exacerbate the health burdens of air pollution in China's less developed interior provinces. Our results reveal trade to be a critical but largely overlooked consideration in effective regional air quality planning for China.International and domestic interprovincial trade of China are entangled, but their health impacts have been treated separately in earlier studies. Here Wang. quantify the complex impacts of trade on public health across China within an integrative framework.


Impact of carob (Ceratonia siliqua L.) pulp inclusion and warm season on gastrointestinal morphological parameters, immune-redox defences and coccidiosis in concentrate-fed light lambs.
This study aimed to evaluate the effects of dietary carob (Ceratonia siliqua L.) pulp and warm season on gastrointestinal morphological parameters, immune-redox defences and coccidiosis in concentrate-fed light lambs. Weaned lambs were assigned to one of three concentrate-based diets: C0 (without carob pulp), C15 (150 g/kg of carob pulp) and C30 (300 g/kg of carob pulp) from 40 to 80 days of age in two consecutive cold and warm batches. Blood samples were collected at Day 80 to determine the metabolic status. Rectal faeces were sampled at Days 50, 65 and 80 to determine consistency and oocyst count per gram. Inclusion of carob pulp in lamb diets did not affect lamb growth but reduced coccidia oocyst excretion, improved faecal consistency and gastrointestinal morphological parameters, enhancing the ruminal thickness of the papilla living strata and reducing the darkness of the epithelium colour. Moreover, carob condensed tannins in the lambs' diet enhanced the expression of antioxidant SOD2 in rumen, while down-regulated NRF2, SOD1, CAT and PPARG in ileum. There was no interaction between the treatments and season in the evaluated variables. Lambs from the warm season exhibited reduced growth performance, altered ruminal epithelium, lower circulating iron levels, increased protein concentrations and higher coccidiosis susceptibility. In addition, regulatory immune and antioxidant mechanisms to counterbalance reactive oxygen species production in gastrointestinal tissues were evident. Dietary inclusion of carob pulp (150 and 300 g/kg) in lamb diets improved gastrointestinal health and homeostasis but did not ameliorate the deleterious effects of warm season.


Community nurses' practices in managing perianal abscesses.
A survey of community nurses identified that a wide range of dressings, and in some cases unethical practices, are being used for this simple postoperative condition. Communication between hospital, community staff and patients was poor.


Sagittal geometry of the middle and lower cervical endplates.
Construct subsidence is a relatively common complication following anterior cervical fusion. Its occurrence has been revealed to be closely related to endplate-implant contact interface. But current literature focusing on the anatomy of cervical endplate is very scarce. The purpose of this morphometric study was to analyse the sagittal geometry, especially the concavity and slope, of vertebral endplates from C3 to C7 by employing data from CT scans. Reformatted CT scans of 97 individuals were analyzed and endplate concavity depth, endplate concavity apex location, as well as endplate slope were measured in midsagittal plane. Those specific parameters were compared among different age and gender groups. Meanwhile, comparison between superior and inferior endplate of each vertebra was also performed. Age and gender did not influence endplate concavity depth, endplate concavity apex location, or endplate slope significantly (P > 0.05). Endplate concavity depths of superior endplates (range 0.9-1.2 mm) were significantly smaller than those of inferior endplates (range 2.1-2.7 mm). Endplate concavity apex was always located in the posterior half of the endplate, with the superior one ranged from 56 to 67% and the inferior one 52 to 57%. Average endplate slopes of superior endplates were between 4.5° and 9.0°, and average inferior endplate slopes ranged from 4.5° to 7.5°. Among all measured segments, C5 had the largest endplate slope values, while C7 the least. Superior endplate is more flat than its inferior counterpart in middle and lower cervical spine, and the concavity apex is always located in the posterior half of the endplate. Endplate slope is correlated with cervical curvature, greater slope implying more significant lordosis. These sagittal endplate geometrical parameters should be taken into consideration when investigating implant subsidence following anterior cervical fusion.


Time saving protein binding assay for the simultaneous determination of guanosine 3':5'-monophosphate (cGMP) and adenosine 3':5'-monophosphate (cAMP) in human urine.
A time-saving protein binding assay for the simultaneous determination of cGMP and cAMP has been adapted for human urine, using [3H]cGMP, [14C]cAMP, protein fractions from calf skeletal and lobster tail muscles and the phosphodiesterase inhibitor SQ 20.009. Recovery, accuracy, and precision are approximately at the 10% limit. Good specificity and no interference were observed with diluted urine samples (10 to 20 times).


Fatty acylation enhances the cellular internalization and cytosolic distribution of a cystine-knot peptide.
Delivering peptides into cells could open up possibilities for targeting intracellular proteins. Although fatty acylation of peptide therapeutics improves their systemic half-life, it remains unclear how it influences their cellular uptake. Here, we demonstrate that a fatty acylated peptide exhibits enhanced cellular internalization and cytosolic distribution compared to the un-acylated version. By using a cystine-knot peptide as a model system, we report an efficient strategy for site-specific conjugation of fatty acids. Peptides modified with fatty acids of different chain lengths entered cells through clathrin-mediated and macropinocytosis pathways. The cellular uptake was mediated by the length of the hydrocarbon chain, with myristic acid conjugates displaying the highest distribution across the cytoplasm including the cytosol, and endomembranes of the ER, Golgi and mitochondria. Our studies demonstrate how fatty acylation improves the cellular uptake of peptides, and lay the groundwork for future development of bioactive peptides with enhanced intracellular distribution.


Unusual ultrasound appearance of small bowel intussusception and secondary bowel obstruction in a child with Peutz-Jeghers syndrome.
Small bowel intussusception (SBI) in pediatric patients resolves spontaneously in the majority of cases. Pathologic small bowel intussusception with a lead point is rare in children. Ultrasound (US) is the preferred initial imaging study for the diagnosis of intussusception. We report a case of long-segment SBI and secondary bowel obstruction caused by a large hamartomatous polyp. This case emphasizes unique, atypical ultrasound findings that may be encountered in small bowel intussusception, with correlative radiographic, CT (computed tomography) and intra-operative findings. Increased awareness of these atypical imaging features can lead to early diagnosis and decrease the risk of potential complications including mesenteric venous thrombosis, bowel ischemia and necrosis.


KRAS and HRAS mutations confer resistance to MET targeting in preclinical models of MET-expressing tumor cells.
The MET receptor tyrosine kinase is often deregulated in human cancers and several MET inhibitors are evaluated in clinical trials. Similarly to EGFR, MET signals through the RAS-RAF-ERK/MAPK pathway which plays key roles in cell proliferation and survival. Mutations of genes encoding for RAS proteins, particularly in KRAS, are commonly found in various tumors and are associated with constitutive activation of the MAPK pathway. It was shown for EGFR, that KRAS mutations render upstream EGFR inhibition ineffective in EGFR-positive colorectal cancers. Currently, there are no clinical studies evaluating MET inhibition impairment due to RAS mutations. To test the impact of RAS mutations on MET targeting, we generated tumor cells responsive to the MET inhibitor EMD1214063 that express KRAS G12V, G12D, G13D and HRAS G12V variants. We demonstrate that these MAPK-activating RAS mutations differentially interfere with MET-mediated biological effects of MET inhibition. We report increased residual ERK1/2 phosphorylation indicating that the downstream pathway remains active in presence of MET inhibition. Consequently, RAS variants counteracted MET inhibition-induced morphological changes as well as anti-proliferative and anchorage-independent growth effects. The effect of RAS mutants was reversed when MET inhibition was combined with MEK inhibitors AZD6244 and UO126. In an in vivo mouse xenograft model, MET-driven tumors harboring mutated RAS displayed resistance to MET inhibition. Taken together, our results demonstrate for the first time in details the role of KRAS and HRAS mutations in resistance to MET inhibition and suggest targeting both MET and MEK as an effective strategy when both oncogenic drivers are expressed.


Thiazolo[3,2-a]benzimidazol-3(2H)-one derivatives: Structure-activity relationships of selective nucleotide pyrophosphatase/phosphodiesterase1 (NPP1) inhibitors.
Ecto-nucleotide pyrophosphatase/phosphodiesterase1 (NPP1) is the most important member of the NPP family, which consists of seven closely related proteins (NPP1-NPP7). This glycoprotein is a membrane-associated or secreted enzyme, which catalyzes the hydrolysis of a wide range of phosphodiester bonds, e.g., in nucleoside triphosphates, dinucleotides and nucleotide sugars. NPP1 plays a crucial role in various physiological functions including bone mineralization, soft-tissue calcification, and insulin receptor signaling. Recently, an upregulated expression of NPP1 has been observed in astrocytic brain cancers. Therefore, NPP1 has been proposed as a novel drug target for the treatment of glioblastoma. Despite their therapeutic potential, only few NPP1 inhibitors have been reported to date, which are in most cases non- or only moderately selective. The best investigated NPP1 inhibitors so far are nucleotide derivatives and analogs, however they are not orally bioavailable due to their high polarity. We identified thiazolo[3,2-a]benzimidazol-3(2H)-one derivatives as a new class of NPP1 inhibitors with drug-like properties. Among the 25 derivatives investigated in the present study, 2-[(5-iodo-2-furanyl)methylene]thiazolo[3,2-a]benzimidazol-3(2H)-one (17) was found to be the most potent NPP1 inhibitor with a Ki value of 467nM versus ATP as a substrate and an un-competitive mechanism of inhibition. Compound 17 did not inhibit other human ecto-nucleotidases, including NTPDase1 (CD39), NTPDases2-3, NPP2, NPP3, tissue-nonspecific alkaline phosphatase (TNAP), and ecto-5'-nucleotidase (eN, CD73), and is thus highly selective for NPP1.


Prevalence of Ivermectin use to prevent COVID-19 during the pandemic in Mato Grosso: cross-sectional home-based study.
To analyze the use of ivermectin as COVID-19 prevention method by the population of Mato Grosso in 2020. This is a home-based survey, carried out between September and October 2020, in 10 pole cities of the socioeconomic regions of State. The use of ivermectin was evaluated through the question: "Did you take ivermectin to prevent COVID-19?". Sociodemographic variables (sex, age group, education, family income), current work situation, being benefitted by government financial programs, as well as symptoms, seroprevalence of antibodies against SARS-CoV-2, and previous diagnosis of COVID-19 were evaluated. Prevalence and their associations were estimated using the chi-square test. 4.206 individuals were evaluated for prevalence of ivermectin use; 58.3% of the individuals responded positively, this rate being higher in the municipalities of the western region of the state (66.6%). There was no significant difference between sexes, but the prevalence was higher among people aged 50-59 years (69.7%), who were white (66.5%), with complete higher education or more (68.8%) and higher family income (≥3 minimum wages-64.2%). The use of this drug was even higher among participants who considered their knowledge of the disease good or very good (65.0%), who reported having symptoms of COVID-19 (75.3%), and who had been previously diagnosed with the disease (91.2%). There was a high prevalence of use of ivermectin as a method to prevent covid-19 by the population of Mato Grosso, indicating the need for strategies to inform the population about the risks of off-label use of drugs and to combat the advertising of drugs that are ineffective against COVID-19.


[The blood lead level and pregnant outcome in pregnant women with non-occupational lead exposure].
The aim of this study is to find out the relations between maternal blood lead and pregnancy complications, neonatal physical and neurobehavioral development respectively. 1,151 samples of maternal venous blood and 434 samples of umbilical cord blood were collected. Graphite stove atomic absorption spectrophotometer was used to detect the lead concentration. Neonatal physical indexes were measured within 24 hours of age, including weight, length, head circumference, chest circumference and abdomen circumference. The neurobehavioral developments were scored at 42 days of age. Meanwhile, the pregnancy complications were obtained from the medical records. (1) the mean lead concentration of maternal blood is 43.4 microg/L while 44.5 microg/L of first trimester, 37.4 microg/L of second trimester and 45.1 microg/L of third trimester. The mean lead concentration of cord blood is 26.4 microg/L. (2) In this study, the blood lead level is not correlated with pregnancy complications and neonatal physical and neurobehavioral development, but it is positively correlated with maternal haemoglobin concentration. In this study, the situation of maternal blood lead level is acceptable. At such level, the lead concentration of pregnant women blood can't influence the incidence of pregnancy complications, neonatal physical and neurobehavioral development.


Survey on the use of intraocular lenses.
A birth of interest in lens implantation occurred especially in the United states in 1974. This coincides with the beginning of four major American lens manufacturers. This interest expoded in 1975 and 1976 and seems to be continuing to grow. Only a few surgeons have stopped implants, most of them after having done ten or less. Half of the surgeons now doing implants have done 25 or less, while 40% have performed a series of 25 to 200. Intracapsular lens styles were the most often used, and the Worst Medallion lens was by far the most popular. Medical Workshop was the leading supplier of lens implants. Accounting for 25%, and European lenses were more often used (61%). The majority of surgeons beginning lens implants after 1974 used either American lenses exclusively or both sources. The majority of lenses used were designed by Binkhorst and Worst. Only 4% of lenses implanted were done secondarily, but one third of the surgeons have performed this procedure; more do them as their experience grows. An overall visual acuity of 20/40 or better postoperatively was found in 83.8% of cases. Significant lens power errors were rare but increased with increasing experience. One third of the surgeons have reported removing a lens implant at a rate of 0.8%, but only 3% of the surgeons have reported removing an eye with a lens implant at a rate of 0.05%.


Functional improvement in heart failure patients treated with beta-blockers is associated with a decline of cytokine levels.
In patients with severe heart failure (CHF), chronically elevated cytokine levels document a systemic inflammation. Experimental data suggest that activation of the beta-adrenergic system may participate in this inflammatory response. Herein, we studied as to whether beta-adrenergic blockade on top of standard CHF therapy affects plasma cytokine levels (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNFalpha]). Moreover, we studied if beta-blocker related changes of these cytokines correspond to changes in left ventricular (LV) function and exercise capacity. In a prospective study, 21 patients with stable CHF (NYHA functional class II-III, ejection fraction <40%, mean age 57.6+/-12.4 years) were treated with captopril (100-150 mg/day), furosemide (40-120 mg/day), and/or digoxin (0.1-0.2 mg/day) for at least 1 month before they entered a 4 week run-in period in which dosages were kept unchanged. Metoprololsuccinate was administered in increasing dosages (up to 190 mg/day) for the following 3 months. Clinical, echocardiographic, spiroergometric, and biochemical changes were assessed at the start and the end of the run-in period as well as after 3 month of beta-blockade. As compared to 210 healthy volunteers, CHF patients, prior to beta-blockade, presented with markedly elevated IL-6 (8.9+/-9.9 vs. 2.1+/-0.5 pg/ml; p<0.05) and TNFalpha levels (1.51+/-0.49 vs. 0.64+/-0.15 pg/ml; p<0.05) levels. In CHF patients, 3 month of beta-blockade lowered heart rate (84+/-14 vs. 68+/-12 bpm; p<0.01), systolic (131+/-7 vs. 118+/-6 mm Hg; p<0.01), and diastolic blood pressure (78+/-5 vs. 71+/-6 mm Hg; p<0.01). Spiroergometric determined VO2 max (17.8+/-4.5 vs. 19.8+/-4.3 ml/min kg; p=0.013) increased significantly during 3 month of beta-blockade. Moreover, LV functional parameters tended to improve but the interindividual response varied and changes were non-significant. Interestingly, IL-6 levels decreased markedly during beta-blockade (8.9+/-9.9 vs. 4.5+/-3.1 pg/ml; p=0.036), whereas TNFalpha levels remained unchanged. Moreover, significant positive correlations were found between decrease of IL-6 levels and left ventricular end diastolic diameters (r2=0.59; p=0.012), whereas an inverse correlation was found between the decrease of IL-6 and the increase of VO2 max (r2=0.54; p=0.037), respectively. In heart failure patients, beta-blockade may lower IL-6 but not TNFalpha levels. Changes of IL-6 during beta-blockade may be related to changes of LV function and geometry.


Differential protein expression analysis of degenerative aortic stenosis by iTRAQ labeling.
Degenerative aortic stenosis is the most common worldwide cause of valve replacement. While it shares certain risk factors with coronary artery disease, it is not delayed or reversed by reducing exposure to risk factors (e.g., therapies that lower lipids). Therefore, it is necessary to better understand its pathophysiology for preventive measures to be taken. In order to identify proteins that are involved in AS, we designed a simple method for protein extraction, digestion, labeling, identification, and differential protein expression analysis of both normal and stenotic aortic valve to identify biomarkers of this pathology, which may facilitate early diagnosis and treatment.


Multiple comparisons, interaction effects, and statistical inference: lessons from chronic kidney disease progression among blacks.
A post hoc analysis of a randomized trial comparing progression of chronic kidney disease among blacks and non-blacks provides an opportunity to explore statistical inference. Multiple comparisons without penalizing the P-value can lead to false positive results; this is illustrated using simulation. Tests of statistical interaction are then applied and interpreted to understand effect modification (or lack thereof) in the context of this trial.


Thinking about your future: nursing in the 21st century.
Successful preparation for the future requires strategic exploration--"what you do before you plan." Scouting the future involves quickness, sampling rather than exhaustive examination, and qualitative information that will enhance leaders' decision making. Strategic exploration requires skills in monitoring trends, innovations, and paradigm shifts (TIPS); examining the long-term implications of those elements; examining the impact of specific changes; and creating visions based on what we have learned.


Correction: Alternative mRNA splicing can attenuate the pathogenicity of presumed loss-of-function variants in BRCA2.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Teratoma Growth Retardation by HDACi Treatment of the Tumor Embryonal Source.
Among testicular germ cell tumors, teratomas may often be very aggressive and therapy-resistant. Our aim was to investigate the impact of histone deacetylase inhibitors (HDACi) on the in vitro growth of experimental mouse teratoma by treating their embryonic source, the embryo-proper, composed only of the three germ layers. The growth of teratomas was measured for seven days, and histopathological analysis, IHC/morphometry quantification, gene enrichment analysis, and qPCR analysis on a selected panel of pluripotency and early differentiation genes followed. For the first time, within teratomas, we histopathologically assessed the undifferentiated component containing cancer stem cell-like cells (CSCLCs) and differentiated components containing numerous lymphocytes. Mitotic indices were higher than apoptotic indices in both components. Both HDACi treatments of the embryos-proper significantly reduced teratoma growth, although this could be related neither to apoptosis nor proliferation. Trichostatin A increased the amount of CSCLCs, and upregulated the mRNA expression of pluripotency/stemness genes as well as differentiation genes, e.g., T and Eomes. Valproate decreased the amount of CSCLCs, and downregulated the expressions of pluripotency/stemness and differentiation genes. In conclusion, both HDACi treatments diminished the inherent tumorigenic growth potential of the tumor embryonal source, although Trichostatin A did not diminish the potentially dangerous expression of cancer-related genes and the amount of CSCLC.


Novel radiological technique to recognize acute liver failure caused by yellow phosphorous containing rodenticides.
Yellow phosphorous rodenticide (YPR) poisoning is the commonest cause for acute liver failure (ALF) in southern and western India. Due to medicolegal issues, history of YPR ingestion may not be available. As early recognition of YPR poisoning is important and there are no specific biochemical assays, other early predictors to identify this entity is necessary. We evaluated the diagnostic role of plain computed tomography (CT) in identifying YPR-induced ALF. All patients admitted to the liver unit with a diagnosis of ALF underwent a plain CT scan abdomen. Demographic details, clinical history, laboratory parameters, liver attenuation index (LAI) calculated on CT scan, treatment details, need for liver transplantation and clinical outcome were analyzed. Parameters for YPR-induced ALF (ALF-YPR) and other causes (ALF-OTH) were compared. Ability of LAI to distinguish ALF-YPR and ALF-OTH was analyzed using receiver operating characteristic (ROC) curve analysis. Twenty-four patients (15 female [62.5%]) were included in the study. Thirteen patients (54%) had YPR poisoning, while the rest formed the ALF-OTH group (11,46%). ALF-YPR patients had higher transaminase levels, lower peak serum bilirubin levels. ALF-YPR livers had significantly lower LAI as compared to ALF-OTH (- 30 vs. - 8, p = 0.001). On ROC curve analysis, an LAI greater than - 18 ruled out YPR as the cause for ALF with 91% sensitivity and 85% specificity. On regression analysis, LAI was the only independent factor predicting ALF-YPR (odds ratio - 0.86, [0.76, 0.96] p = 0.008). Our data shows that LAI on plain abdominal CT scan can be used to quickly recognize ALF-YPR in unclear cases so that necessary treatment protocol can be activated, or patient transfer arranged. Our analysis shows that an LAI greater than - 18 can reliably rule out YPR ingestion as the cause for ALF.


Development and applications of diffusive gradients in thin films for monitoring pharmaceuticals in surface waters.
Pharmaceutical contaminants in surface water have raised significant concerns because of their potential ecological risks. In particular, coronavirus disease 2019 (COVID-19)-related pharmaceuticals can be released to surface water and reduce environmental water quality. Therefore, reliable and robust sampling tools are required for monitoring pharmaceuticals. In this study, passive sampling devices of diffusive gradients in thin films (DGTs) were developed for sampling 35 pharmaceuticals in surface waters. The results demonstrated that hydrophilic-lipophilic balance (HLB) was more suitable for DGT-based devices compared with XAD18 and XDA1 resins. For most pharmaceuticals, the performance of the HLB-DGT devices were independent of pH (5.0-9.0), ionic strength (0.001-0.5 M), and flow velocity (0-400 rpm). The HLB-DGT devices exhibited linear pharmaceutical accumulation for 7 days, and time-weighted average concentrations provided by the HLB-DGT were comparable to those measured by conventional grab sampling. Compared to previous studies, we extended DGT monitoring to include three antiviral drugs used for COVID-19 treatment, which may inspire further exploration on identifying the effects of COVID-19 on ecological and human health.


DMD transcript imbalance determines dystrophin levels.
Duchenne and Becker muscular dystrophies are caused by out-of-frame and in-frame mutations, respectively, in the dystrophin encoding DMD gene. Molecular therapies targeting the precursor-mRNA are in clinical trials and show promising results. These approaches will depend on the stability and expression levels of dystrophin mRNA in skeletal muscles and heart. We report that the DMD gene is more highly expressed in heart than in skeletal muscles, in mice and humans. The transcript mutated in the mdx mouse model shows a 5' to 3' imbalance compared with that of its wild-type counterpart and reading frame restoration via antisense-mediated exon skipping does not correct this event. We also report significant transcript instability in 22 patients with Becker dystrophy, clarifying the fact that transcript imbalance is not caused by premature nonsense mutations. Finally, we demonstrate that transcript stability, rather than transcriptional rate, is an important determinant of dystrophin protein levels in patients with Becker dystrophy. We suggest that the availability of the complete transcript is a key factor to determine protein abundance and thus will influence the outcome of mRNA-targeting therapies.


Elevated serum uric acid is associated with a greater inflammatory response and with short- and long-term mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.
Despite elevated serum uric acid (eSUA) has been identified as independent risk factor for cardiovascular diseases, its prognostic value in the setting of ST-segment elevation myocardial infarction (STEMI) is still controversial. Although the mechanisms of this possible relationship are unsettled it has been suggested that eSUA could trigger the inflammatory response. This study sought to investigate the association between eSUA with short- and long-term mortality and with inflammatory response in patients with STEMI treated with primary percutaneous coronary intervention (pPCI). Blood samples were collected on admission and at 24 and 48 h after pPCI: the inflammatory biomarkers C-reactive protein (CRP), neutrophil count and neutrophil to lymphocytes ratio (NLR) were considered. Baseline eSUA was defined as ≥6.8 mg/dl. Cumulative 30-days and 1-year mortalities were estimated using the Kaplan-Meyer analysis. Multivariable analyses were performed by Cox proportional hazard models. In the 2369 patients with STEMI considered, 30-day mortality was 5.8% among patients with eSUA and 2% among patient with normal SUA level (p < 0.001); 1-year mortality was 8.5% vs 4%, respectively (p < 0.001). At multivariable analyses eSUA was an independent predictor of 30-day mortality (HR 1.196, 95%CI 1.006-1.321, p = 0.042) and 1-year mortality (HR 1.178, 95%CI 1.052-1.320, p = 0.005). eSUA patients presented higher values in on admission CRP (p < 0.001) and in neutrophil count and NLR at 24 h (respectively, p = 0.020 and p < 0.001) and at 48 h (p = 0.018 and p < 0.001) compared to patients with normal SUA levels. Elevated serum uric acid is associated with higher short- and long-term mortality and with a greater inflammatory response after reperfusion in patients with STEMI treated with primary PCI.


Efficient terpene hydroxylation catalysts based upon P450 enzymes derived from actinomycetes.
The hydroxylation of alpha-ionone 1 and beta-ionone 2 to their corresponding mono-hydroxylated derivatives has been examined using a recombinant E. coli whole cell system, in which cytochromes P450 SU1 and SU2, and P450 SOY were over-expressed with their cognate ferrodoxins. Both substrates are hydroxylated with a high degree of regioselectivity and for alpha-ionone 1 the reaction is highly diastereoselective yielding the anti-isomer.


"Artificial grammar learning" in pigeons: a preliminary analysis.
An avian analogue to human artificial or synthetic grammar learning (Reber, 1967) was developed. Pigeons viewed horizontal strings of three to eight colored letters. These strings either conformed to Reber's artificial grammar or violated it in one or two locations. Pigeons categorized the letter strings as grammatical (left keypeck) or nongrammatical (right keypeck). Overall accuracy of categorization was above chance to both familiar training strings and to novel transfer strings, thereby satisfying a conventional criterion for learning an abstract concept. The results support a multiple mechanisms point of view according to which pigeons, like humans, learn both abstract concepts and specific strings, or specific parts of strings, in artificial grammar learning tasks.


Signaling between SR and plasmalemma in smooth muscle: sparks and the activation of Ca2+-sensitive ion channels.
Intracellular calcium ions are involved in the regulation of nearly every aspect of cell function. In smooth muscle, Ca2+ can be delivered to Ca2+-sensitive effector molecules either by influx through plasma membrane ion channels or by intracellular Ca2+ release events. Ca2+ sparks are transient local increases in intracellular Ca2+ that arise from the opening of ryanodine-sensitive Ca2+ release channels (ryanodine receptors) located in the sarcoplasmic reticulum. In arterial myocytes, Ca2+ sparks occur near the plasma membrane and act to deliver high (microM) local Ca2+ to plasmalemmal Ca2+-sensitive ion channels, without directly altering global cytosolic Ca2+ concentrations. The two major ion channel targets of Ca2+ sparks are Ca2+-activated chloride (Cl(Ca)) channels and large-conductance Ca2+-activated potassium (BK) channels. The activation of BK channels by Ca2+ sparks play an important role in the regulation of arterial diameter and appear to be involved in the action of a variety of vasodilators. The coupling of Ca2+ sparks to BK channels can be influenced by a number of factors including membrane potential and modulatory beta subunits of BK channels. Cl(Ca) channels, while not present in all smooth muscle, can also be activated by Ca2+ sparks in some types of smooth muscle. Ca2+ sparks can also influence the activity of Ca2+-dependent transcription factors and expression of immediate early response genes such as c-fos. In summary, Ca2+ sparks are local Ca2+ signaling events that in smooth muscle can act on plasma membrane ion channels to influence excitation-contraction coupling as well as gene expression.


["From the origin and development of the French disease" to "Major wound treatment". The work and contributions of Theophrastus Bombastus von Hohenheim, called Paracelsus, on the occasion of the 500th anniversary of his birth year].
On the occasion of Paracelsus's 500th anniversary his life and works are critically portrayed and appreciated. The present state of Paracelsian research in different fields of academic science is shown in the congress report 'Neue Wege der Paracelsus-Forschung'.


A kinematic model for calculating cup alignment error during total hip arthroplasty.
Reduced range of motion, prosthetic impingement, and joint dislocation can all result from misalignment of the acetabular component (i.e. cup alignment) in patients undergoing total hip arthroplasty. Most methods for acetabular component alignment are designed to provide 45-50 degrees abduction and 15-25 degrees of operative anteversion (also known as flexion) with respect to the anterior pelvic plane coordinate system. Yet in most cases, this coordinate system is not assigned properly, due to differences in patient anatomy and improper positioning in the operating room. This misalignment can result in an error in the cup alignment, which can cause the above-mentioned consequences. This work presents a complete mathematical formulation for the analysis of the inaccuracies related to the anterior pelvic plane axes (APPA) definition and their effect on final cup orientation. We do this by introducing a method taken from Kinematics of Mechanisms, and by representing the errors in the APPA as three concurrent axes of rotation, followed by the version and abduction rotations which are defined relative to the previous rotations. We also present a sensitivity analysis of the results by introducing differential changes between sequential coordinate frames, which simulates the errors in the APPA and their effect on cup orientation. Finally, we demonstrate a computational method which provides corrected version and abduction angles to achieve the desired cup orientation, given that the actual measurement errors are known.


Visible-light-driven 3D Bi5O7I/BiOCl microsphere with enhanced photocatalytic capability: Performance, degradation pathway, antibacterium and mechanism.
It is well known that both of the separation efficiency of photogenerated carriers and the response capability to visible light remarkably affect the photocatalytic performance. In the present work, a 3D microsphere of Bi5O7I/BiOCl heterojunction catalyst was synthetised. The synergy of Bi5O7I and BiOCl not only significantly enhances the transfer rate and separation efficiency of carriers, but also heightens light absorption capacity. As-prepared Bi5O7I/BiOCl (40 wt% BiOCl) has a higher degradation efficiency on doxycycline hydrochloride (DC) (90 min, 83.0%) and super high inhibition rate (90 min, 99.92%) on Escherichia coli under visible light, compared to the two monomers. Pollutants DC is finally decomposed into CO2, H2O and small molecule intermediates by generated h+, •OH and •O2-. The effects of reactive radicals follow the order of •OH radicals > h+ radicals ≫ •O2- and e- radicals. The possible structures of intermediates and four possible degradation pathways involved were also discussed. In addition, As-synthetised Bi5O7I/BiOCl has preferable reusability and excellent chemical stability. Biological toxicity experiments also verify that Bi5O7I/BiOCl is a green and environmentally friendly composite material. This strategy provides a green, low-toxic way for the application of traditional type II heterojunction in the fields of environmental remediation and photocatalysis.


Long-term vasodilator treatment with flosequinan does not lead to hemodynamic tolerance or neurohormonal activation in severe heart failure.
Flosequinan is a balanced-type vasodilator with a prolonged mode of action due to an approximate 38-hour half-life of its active first metabolite, BTS 53554. As this may lead to tolerance and neurohormonal activation, the acute and long-term pharmacokinetic, hemodynamic, and neurohormonal profile of flosequinan was evaluated. On three consecutive days, 23 patients with heart failure (New York Heart Association classes II-IV), despite digitalis and diuretics, underwent invasive hemodynamic studies after receiving 100 mg oral flosequinan (day 1), placebo (day 2), and 100 mg flosequinan (day 3), followed by repeat invasive evaluation after long-term flosequinan (100 mg daily) for 17 +/- 2 weeks. On each study day, plasma flosequinan levels increased to 1.9 +/- 0.2 mg/L after 1 hour, but returned to baseline levels at 24 hours. In contrast, BTS 53554 increased progressively, reaching relatively high plateau levels (6 mg/L) during chronic therapy. First-dose flosequinan decreased the pulmonary wedge, right atrial pressure, and systemic resistance by 50, 60, and 22%, respectively, whereas the cardiac index was increased by 40%; these effects lasted for 48 hours. During long-term treatment, baseline values of the pulmonary wedge and right atrial pressure were comparable to prestudy values, whereas systemic resistance had decreased by 22%, and the cardiac index and heart rate had increased by 22 and 14%, respectively. Readministration of flosequinan did not further affect hemodynamics, apart from a moderate reduction in the pulmonary wedge and right atrial pressure. Neurohumoral activation did not occur during acute or long-term therapy. Thus, although changes in left and right heart filling pressures are attenuated during long-term treatment, flosequinan induces sustained arterial dilatation and improves cardiac pump function without activation of circulating neurohormones.


Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome.
Changes in microbiome composition are associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet, clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here, we infuse gut organ cultures with longitudinal microbiota samples collected from therapy-naive patients with irritable bowel syndrome (IBS) under a low-fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) diet. We show that post-diet microbiota regulates intestinal expression of inflammatory and neuro-muscular gene sets. Specifically, we identify Bifidobacterium adolescentis as a diet-sensitive pathobiont that alters tight junction integrity and disrupts gut barrier functions. Collectively, we present a pathway discovery platform for mechanistic dissection and identification of functional diet-host-microbiota modules. Our data support the hypothesis that the gut microbiota mediates the beneficial effects of a low-FODMAP diet and reinforce the potential feasibility of microbiome-based therapies in IBS.


New species of springtails in the Proisotoma genus complex from Vermont and New York, USA with descriptive notes on Ballistura alpa Christiansen & Bellinger 1980 (Hexapoda, Collembola, Isotomidae).
Three new species of Isotomidae springtails are described from the Lake Champlain Basin (Vermont and New York, USA), Lake Willoughby and Greater Averril Pond in Vermont. Subisotoma joyceisp. n. and Scutisotoma champisp. n. were collected in sandy beaches whereas Ballistura rossisp. n. was found only in a constructed wetland built and managed by the University of Vermont. Scutisotoma champisp. n. was found in Lakes Champlain and Willoughby, and Greater Averril Pond and is probably present in most lakes and large ponds in the area. Subisotoma joyceisp. n. was found only along the southern and eastern coast of South Hero, and the mainland coast facing eastern South Hero. Ballistura alpa is redescribed and transferred to the genus Pachyotoma based on the absence of tibiotarsal seta B4/B5, the presence of secondary cuticular granules, 4 prelabral setae, a full complement of guard setae on labial papilla E and in having a bifurcate outer maxillary lobe with 4 sublobal setae.


The cross-resistance of mouse blasticidin S-resistant cell lines to puromycin and sparsomycin, inhibitors of ribosome function.
The antibiotic blasticidin S inhibits peptide-chain elongation in extracts of bacteria and mammalian cells. After spontaneous or nitrosoguanidine mutagenesis, we have isolated 46 blasticidin S-resistant (Blar) cell lines independently from mouse mammary carcinoma cells (FM3a). Among those Blar clones, we studied two clones, a spontaneously induced one (S501) and a nitrosoguanidine mutagenized one (N742) in more detail. The resistant phenotype of these Blar cells is retained without change for at least four months in the absence of the antibiotic. These Blar cells are 10- to 20-fold more resistant to the cytotoxic action of the antibiotic than their parental cells in vivo. Polyuridylate dependent polyphenylalanine synthesis in vitro with S-30 extracts either from N742 or S501 is 10- to 50-fold more resistant to the inhibitory action of blasticidin S compared to the parental FM3a cells. Ribosomes from FM3a and N742 are fractionated into 40-S and 60-S subunits, and polyphenylalanine synthesis by mixing them in various combinations with S-100 fraction from mouse leukemia L5178Y cells indicating that the resistant phenotype of Blar cells is due to the alteration of 60 S ribosomal subunit. We also found that these two Blar cell lines (N742 and S501) show cross-resistance to gougerotin, puromycin and sparsomycin, but not to emetine or cycloheximide. The polyribosomal pattern of FM3a (Blas) and N742 was compared when the cells were incubated with 3 microgram/ml puromycin for 6 h. Puromycin treatment of Blas cells induced accumulation of monosomes and ribosomal subunits, while little if any transition of polyribosomes into monosome and ribosomal subunits appeared in its counterpart N742 treated with the same dose of puromycin.


Daily cigarette consumption in early adulthood: age of smoking initiation and duration of smoking.
This study considers the extent to which daily consumption of cigarettes in young adults varies by age at first cigarette and duration of smoking. Data come from a random sample of 21- to 30-year-old members of a large HMO in the Detroit area. Daily cigarette consumption by current smokers varied by duration of daily smoking: the longer the duration, the higher the number of cigarettes smoked. Duration from first cigarette to daily smoking bore no relationship to cigarette consumption. When duration of daily smoking was statistically controlled, the association between cigarette consumption and age at first cigarette was not statistically significant. The findings suggest that public health efforts to delay daily smoking among adolescents might reduce cigarette consumption in early adulthood.


Assessing patterns in cancer screening use by race and ethnicity during the coronavirus pandemic using electronic health record data.
Efforts to prevent the spread of the coronavirus led to dramatic reductions in nonemergency medical care services during the first several months of the COVID-19 pandemic. Delayed or missed screenings can lead to more advanced stage cancer diagnoses with potentially worse health outcomes and exacerbate preexisting racial and ethnic disparities. The objective of this analysis was to examine how the pandemic affected rates of breast and colorectal cancer screenings by race and ethnicity. We analyzed panels of providers that placed orders in 2019-2020 for mammogram and colonoscopy cancer screenings using electronic health record (EHR) data. We used a difference-in-differences design to examine the extent to which changes in provider-level mammogram and colonoscopy orders declined over the first year of the pandemic and whether these changes differed across race and ethnicity groups. We found considerable declines in both types of screenings from March through May 2020, relative to the same months in 2019, for all racial and ethnic groups. Some rebound in screenings occurred in June through December 2020, particularly among White and Black patients; however, use among other groups was still lower than expected. This research suggests that many patients experienced missed or delayed screenings during the first few months of the pandemic, which could lead to detrimental health outcomes. Our findings also underscore the importance of having high-quality data on race and ethnicity to document and understand racial and ethnic disparities in access to care.


Longitudinal trends in prostate cancer incidence, mortality, and survival of patients from two Shanghai city districts: a retrospective population-based cohort study, 2000-2009.
Prostate cancer is the fifth most common cancer affecting men of all ages in China, but robust surveillance data on its occurrence and outcome is lacking. The specific objective of this retrospective study was to analyze the longitudinal trends of prostate cancer incidence, mortality, and survival in Shanghai from 2000 to 2009. A retrospective population-based cohort study was performed using data from a central district (Putuo) and a suburban district (Jiading) of Shanghai. Records of all prostate cancer cases reported to the Shanghai Cancer Registry from 2000 to 2009 for the two districts were reviewed. Prostate cancer outcomes were ascertained by matching cases with individual mortality data (up to 2010) from the National Death Register. The Cox proportional hazards model was used to analyze factors associated with prostate cancer survival. A total of 1022 prostate cancer cases were diagnosed from 2000 to 2009. The average age of patients was 75 years. A rapid increase in incidence occurred during the study period. Compared with the year 2000, 2009 incidence was 3.28 times higher in Putuo and 5.33 times higher in Jiading. Prostate cancer mortality declined from 4.45 per 105 individuals per year in 2000 to 1.94 per 105 in 2009 in Putuo and from 5.45 per 105 to 3.5 per 105 in Jiading during the same period. One-year and 5-year prostate cancer survival rates were 95% and 56% in Putuo, and 88% and 51% in Jiading, respectively. Staging of disease, Karnofsky Performance Scale Index, and selection of chemotherapy were three independent factors influencing the survival of prostate cancer patients. The prostate cancer incidence increased rapidly from 2000 to 2009, and prostate cancer survival rates decreased in urban and suburban Chinese populations. Early detection and prompt prostate cancer treatment is important for improving health and for increasing survival rates of the Shanghai male population.


The H3K27 demethylase controls the lateral line embryogenesis of zebrafish.
Kdm6b, a specific histone 3 lysine 27 (H3K27) demethylase, has been reported to be implicated in a variety of developmental processes including cell differentiation and cell fate determination and multiple organogenesis. Here, we regulated the transcript level of kdm6bb to study the potential role in controlling the hearing organ development of zebrafish. A morpholino antisense oligonucleotide (MO) strategy was used to induce Kdm6b deficiency; immunohistochemical staining and in situ hybridization analysis were conducted to figure out the morphologic alterations and embryonic mechanisms. Kdm6bb is expressed in the primordium and neuromasts at the early stage of zebrafish embryogenesis, suggesting a potential function of Kdm6b in the development of mechanosensory organs. Knockdown of kdm6bb severely influences the cell migration and proliferation in posterior lateral line primordium, abates the number of neuromasts along the trunk, and mRNA-mediated rescue test can partially renew the neuromasts. Loss of kdm6bb might be related to aberrant expressions of chemokine genes encompassing cxcl12a and cxcr4b/cxcr7b in the migrating primordium. Moreover, inhibition of kdm6bb reduces the expression of genes in Fgf signaling pathway, while it increases the axin2 and lef1 expression level of Wnt/β-catenin signaling during the migrating stage. Collectively, our results revealed that Kdm6b plays an essential role in guiding the migration of primordium and in regulating the deposition of zebrafish neuromasts by mediating the gene expression of chemokines and Wnt and Fgf signaling pathway. Since histone methylation and demethylation are reversible, targeting Kdm6b may present as a novel therapeutic regimen for hearing disorders.


Design, synthesis and validation of anti-microbial coumarin derivatives: An efficient green approach.
An ecofriendly itinerary for the synthesis of newly substituted chromene-3-carboxamide derivatives was undertaken to avoid impurities, usage of toxic solvents, toxic catalyst, and having improved quantitative yields. The green synthesis involves the condensation of substituted salicylaldehyde with N-(substituted)phenyl malonic acid in the presence of a base catalyst, piperidine. All reported compounds were assessed for their antimicrobial activities which clearly suggested their therapeutic implications to address antimicrobial pathogenesis. The synthesized coumarin compounds were examined for their antimicrobial activity against 7 fungal strains and 2 bacterial strains at concentration 125-1000 μg/mL. In particular, the compounds 4 and 5 showed lower minimum inhibitory concentration value (125 μg/mL) against maximum microbial strains. Further, docking of all the synthesized compounds was performed with the enzymes lanosterol 14α-demethylase and glucosamine-6-phosphate synthase and a significant binding affinity was observed which supports in vivo antimicrobial study. In addition, the thermal analysis revealed good thermal stability of compounds up to 250 °C. The compounds showed abroad absorption spectrum between 280-550 nm establishing them to be good UV absorbers.


The increased risk of proximal colonic cancer after cholecystectomy.
In a retrospective case control review we determined the cholecystectomy frequency of 479 index cases of colonic carcinoma and 479 age, sex, and admission date matched controls. The frequency distribution patterns of cholecystectomy with reference to subsite specific cancer of the large bowel were determined. The cholecystectomy frequency in patients with proximal colonic cancer was higher than those in whom cancer was present in areas other than the proximal colon (12.3 per cent vs. 6.6 per cent, P less than 0.02). There was a gradient of previous cholecystectomy history from the proximal colon to the rectum. The overall frequency of previous cholecystectomy in the index cases was 8.1 per cent while that in the matched control was 5.4 per cent. The difference was not statistically significant. However, the cholecystectomy frequency of the proximal colonic cancer subgroup was significantly higher than its matched control group (12.3 per cent vs. 4.6 per cent, P less than 0.02). The difference was greater in females with proximal colonic cancer compared with their matched controls (14.3 per cent vs. 3.6 per cent, P less than 0.02). Our data supported the hypothesis that either (1) altered bile salt metabolism after cholecystectomy may increase colonic cancer formation, or (2) gallbladder disease and colonic cancer may share common etiologic factors.


Metabolic adjustments to dynamic hypoxic hypoxemia in feline brain tissue.
Three different metabolic models were incorporated in a compartmental simulation of brain tissue pO2 response to rapid changes in arterial pO2. The first was the frequently utilized constant metabolism assumption. The second model was a 4-step kinetic simplification of glucose conversion to CO2 with an intermediate reversible reaction of pyrovate to lactate. The most sophisticated model was a new 11-step reaction scheme with the same start and end points accounting for glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation. A unique representation was derived for the oxygen consumption depending on reduced cytochrome a3+(3) consistent with diverse observations in the literature. The theoretical predictions were compared to previously published cortical tissue pO2 recordings from detailed experiments with pentobarbital anesthetized cats. The 11-step metabolic model invariably provided the best match between the theoretical calculations and the observed responses. These results indicate that cellular metabolism rapidly adjusts to changes in O2 in a manner which reduces the tissue pO2 fluctuation. In concert with the large compensatory arterial blood flow response there was extensive damping of intracellular pO2 compared to arterial O2 changes.


Neuronal markers in the rodent pineal gland--an immunohistochemical investigation.
Although some embryological and morphological features speak in favour of a neuronal character of rodent pinealocytes, histochemistry and ultrastructure let this issue appear controversial. Using antibodies to different neurofilaments, the neural adhesion molecule L1, synaptophysin and tubulin as neuronal markers, the pineal glands of rat and guinea-pig were studied by means of immunofluorescence. Neurofilament-immunoreactivity was present in some rat pineal nerve fibers and in the majority of guinea-pig pinealocytes, L1 decorated rat intrapineal nerve fibers, synaptophysin was almost ubiquitously distributed in the pineal of both species, while tubulin-immunofluorescence was seen in nerve fibers of rat and guinea-pig pineal and in some pinealocytes of the latter. These findings speak in favour of the neuronal character of guinea-pig pinealocytes. The lack of neurofilament- and tubulin-immunoreactivity in rat pinealocytes might be attributable to very low concentrations of these proteins or species differences as to their expression. Further studies including in situ-hybridisation of relevant mRNAs will be necessary to answer these questions definitely.


Inhibition of Inducible Nitric Oxide Synthase Attenuates Monosodium Urate-induced Inflammation in Mice.
The present study elucidated the effect of the selective inducible nitric oxide synthase (iNOS) inhibitor N(6)-(1-iminoethyl)-L-lysine (L-NIL) on monosodium urate (MSU) crystal-induced inflammation and edema in mice feet. L-NIL (5 or 10 mg/kg/day) was administered intraperitoneally 4 h before injection of MSU (4 mg) into the soles of mice hindlimb feet. Twenty-four hours after MSU injection, foot thickness was increased by 160% and L-NIL pretreatment reduced food pad swelling in a dose dependent manner. Pretreatment of 10 mg/kg/day L-NIL significantly suppressed the foot pad swelling by MSU. Plasma level of nitric oxide (NO) metabolites and gene expression and protein level of iNOS in feet were increased by MSU, which was suppressed by L-NIL pretreatment. Similar pattern of change was observed in nitrotyrosine level. MSU increased the gene expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and L-NIL pretreatment suppressed MSU-induced cytokines expression. The mRNA levels of superoxide dismutase and glutathione peroxidase1 were increased by MSU and L-NIL pretreatment normalized the gene expression. Phosphorylation of extracellular signal-regulated kinase 1/2 and p38 was increased by MSU, which was suppressed by L-NIL pretreatment. The mRNA levels of iNOS, TNF-α, and IL-1β were increased by MSU in human dermal fibroblasts, C2C12 myoblasts, and human fetal osteoblasts in vitro, which was attenuated by L-NIL in a dose dependent manner. This study shows that L-NIL inhibits MSU-induced inflammation and edema in mice feet suggesting that iNOS might be involved in MSU-induced inflammation.


Can the official soccer game be considered the most important contribution to player's physical fitness level?
During competitive soccer match play, elite players are subdued to vigorous physical and psychological strains. Thus, some changes in overall physical fitness can be expected. The objective of this paper was to determine whether official games influence physical fitness in soccer players. The participants were divided according to the number of minutes spent in the game as well as according to some additional criteria into starters (STA; N.=33, >1000 minutes spent in the official game) and non-starters (NON; N.=31, <1000 minutes spent in the official game). Both groups participated in the initial (end of pre-season) and in the final testing procedures (one week after the end of the competition period). The total of 24 variables covered players' power performance, kicking the ball, aerobic capacity, agility and flexibility. The STA group showed positive significant differences (P<0.05) from the NON group in 21 out of 24 variables. The most significant findings of this study point to the fact that official games help in maintaining and improving agility parameters (6 out of 7 tests) as well as in maintaining and improving overall power performance of soccer players which includes sprinting, jumping and kicking the ball. Due to specific physiological and psychological factors, official matches make it possible for the starters to develop the mentioned aspects to a higher level when compared to the non-starting team colleagues.


Pulmonary emphysema not combined with lung fibrosis in systemic sclerosis.
Interstitial Lung Disease (ILD) is a common finding of Systemic Sclerosis (SSc) mainly presenting in the form of Nonspecific Interstitial Pneumonia (NSIP) and deeply affecting patients' prognosis. Beside NSIP, other types of ILD have been reported. The most recently described pattern is the so-called Combined-pulmonary emphysema and lung fibrosis, characterized by the coexistence of both upper lobes centrilobular and paraseptal emphysema and lower lobes ILD. We presented three cases of patients with SSc, in which High Resolution Computed Tomography examinations showed emphysema with atypical distribution and radiological presentation, without or with mild signs of fibrosing lung disease, that stabilized after immunosuppressive treatment.


Margin re-excision and local recurrence in invasive breast cancer: A cost analysis using a decision tree model.
SSO-ASTRO recently published guidelines defining adequate margins in breast conservation therapy (BCT) as no tumor on ink based on studies demonstrating little difference in local recurrence (LR) with wider margins. We hypothesize that not routinely re-excising close margins results in decreased costs without compromising care. A decision tree model was developed for the management of margins after BCT for invasive cancer. Patients were compared among three margin status groups: positive, close (≤2 mm) and negative (>2 mm). Ten publications provided re-excision rates (RER) and LR rates. The model assumed 140,000 BCT/year. Sensitivity analyses determined the most cost-effective strategy. Surgical costs were estimated using 2013 Medicare reimbursement rates. Re-excising close margins was significantly more costly than the alternative, $233.1 million versus $214.3 million, per year in the United States. Total surgical cost was most sensitive to re-excision of close margins-increasing the RER from 0% to 100% resulted in an $18.8 million cost difference. The strategy of re-excising close margins resulted in a predicted cost of $18.8 million per year. This does not include hospital costs, the cost of surgical complications after re-excision, and underestimates the potential savings by using Medicare reimbursement rates.


Effects of thyroid state on serotonin, 5-hydroxyindoleacetic acid and substance P contents in discrete brain nuclei of adult rats.
The effects of chemical thyroidectomy produced by propylthiouracil treatment or hyperthyroidism produced by daily injections of thyroxine on the content of serotonin, its metabolite 5-hydroxyindoleacetic acid and of substance P in discrete brain nuclei of adult rats have been studied. Brain nuclei were removed by punches of frozen brain slices. The serotonin and 5-hydroxyindoleacetic acid contents were measured by high performance liquid chromatography with electrochemical detection while substance P was assayed by radioimmunoassay. The serotonin level was significantly increased in 11 nuclei of the hypothyroid and in 12 nuclei of the hyperthyroid rats. The 5-hydroxyindoleacetic acid levels were higher in 16 nuclei of the hypothyroid and 7 nuclei of the hyperthyroid animals. The state of the thyroid gland in adult rats also affected the substance P system but less consistently than the serotonin pathway. Thus, the substance P content in the brain of propylthiouracil-treated animals increased significantly in 4 nuclei while it decreased in the septum lateralis and the striae terminalis. Following the chronic thyroxine injections, the substance P level was increased in the nucleus caudatus putamen and the tractus diagonalis and was decreased in the area ventralis tegmenti. We previously reported that neonatal thyroidectomy caused a general increase of the substance P and serotonin contents in many brain nuclei of young rats. It appears that the effects of chemical thyroidectomy on mature and immature rat brain are different for the substance P system, suggesting that thyroxine plays an important role in the maturation of substance P-containing neurons.


Enhanced electro-generated ferrate using Fe(0)-plated carbon sheet as an anode and its online utilization for removal of cyanide.
Efficient electrochemical generation of ferrate (Fe(VI)) is still challenged by the passivation of iron materials. Herein, we employed Fe(0)-plated carbon sheet as an anode to enable an efficient production of Fe(VI) with its concentration reached up to 55 mM, which was 8 times higher than that with iron sheet of the same size as an anode. The SEM results showed that the close and uniform dispersion of tapered Fe(0) particles on the surface of carbon sheet helped prevent the formation of passivated layer. The preparative process of electro-deposited Fe(0) affected the generation of Fe(VI). The increase of electroplating time to 40 min and electroplating temperature to 30 °C promoted the production of Fe(VI), and the change in the concentration of Fe2+ in electroplated solution showed little impact on Fe(VI) generation. However, the addition of additives inhibited Fe(VI) generation. As well, an effective removal of cyanide was achieved using on-line production of Fe(VI), comparable to that by NaClO and higher than that by other traditional oxidants containing H2O2, O3, and KMnO4. This study would provide an simple and promising iron anode for efficient production of Fe(VI) by electrochemical method.


Social withdrawal and academic achievement, intertwined over years? Bidirectional effects from primary to upper secondary school.
Socially withdrawn children tend to perform poorer academically than their peers. What remains unknown, is the temporal ordering of the two phenomena. Also, substantial gender differences exist in both social withdrawal and academic achievement; thus, it is conceivable that the strength of the relation between them is gendered as well. To investigate cross-sectional correlates and test directional effects of social withdrawal and academic achievement from primary to upper secondary school, and to examine potential gendered effects. Prospective associations were analysed from age 6 to age 14 using biannual teacher ratings of children's social withdrawal and academic achievement in a representative community sample (n = 845), by means of random intercept cross-lagged panel modelling. In boys, increased academic achievement at ages 8 and 12 forecasted decreased social withdrawal 2 years later, whereas increased social withdrawal at age 10 predicted reduced academic achievement at age 12. No such effects were seen in girls. Social withdrawal and academic achievement are bidirectionally related among boys, but not girls. Results are discussed in light of need-to-belong theory, and practical implications for schools and teachers are illuminated.