Redox control in mammalian embryo development.
The development of an embryo constitutes a complex choreography of regulatory events that underlies precise temporal and spatial control. Throughout this process the embryo encounters ever changing environments, which challenge its metabolism. Oxygen is required for embryogenesis but it also poses a potential hazard via formation of reactive oxygen and reactive nitrogen species (ROS/RNS). These metabolites are capable of modifying macromolecules (lipids, proteins, nucleic acids) and altering their biological functions. On one hand, such modifications may have deleterious consequences and must be counteracted by antioxidant defense systems. On the other hand, ROS/RNS function as essential signal transducers regulating the cellular phenotype. In this context the combined maternal/embryonic redox homeostasis is of major importance and dysregulations in the equilibrium of pro- and antioxidative processes retard embryo development, leading to organ malformation and embryo lethality. Silencing the in vivo expression of pro- and antioxidative enzymes provided deeper insights into the role of the embryonic redox equilibrium. Moreover, novel mechanisms linking the cellular redox homeostasis to gene expression regulation have recently been discovered (oxygen sensing DNA demethylases and protein phosphatases, redox-sensitive microRNAs and transcription factors, moonlighting enzymes of the cellular redox homeostasis) and their contribution to embryo development is critically reviewed.


Initial contact and subsequent adhesion of human neutrophils or monocytes to human aortic endothelial cells releases an endothelial intracellular calcium store.
Increases in both leukocyte and endothelial cytosolic free [Ca2+] may be involved in intercellular adhesion by regulating the affinity of surface adhesion molecules or by facilitating transendothelial leukocyte migration. The purpose of this study was to examine the effect of initial contact and subsequent adhesion of human neutrophils or monocytes on human aortic endothelial [Ca2+]. Endothelial monolayers were loaded with the fluorescent Ca2+ indicator indo 1 and exposed to isolated human peripheral blood neutrophils or to a cultured human monocyte cell line. A rapid, fourfold to fivefold increase in endothelial cytosolic [Ca2+] occurred within seconds of leukocyte contact. No increase in endothelial [Ca2+] occurred on contact of 18.25-microns inert microspheres, isolated red blood cells, or suspensions of cultured human aortic endothelial cells. In experiments performed on monolayers grown in 1-mm2 capillary flow tubes, the increase in endothelial cytosolic [Ca2+] on initial leukocyte contact was found to be related to the subsequent resistance to leukocyte detachment during exposure to arterial levels of shear stress (13.4 dyne.cm-2). The increase in endothelial cytosolic [Ca2+] during leukocyte contact was not inhibited in Ca(2+)-free buffer but was abolished by prior depletion of an endoplasmic reticulum Ca2+ store by thapsigargin. Pretreatment of neutrophils with R15.7, a specific monoclonal antibody to the adhesion protein CD-18, inhibited the increase in endothelial cytosolic [Ca2+] on neutrophil contact. Initial contact leading to subsequent adhesion of human leukocytes to human aortic endothelial cells releases an endothelial intracellular Ca2+ store. This may, in part, be mediated by specific adhesion proteins and may in turn regulate the affinity of surface adhesion molecules or facilitate transendothelial migration of leukocytes.


Immunocytochemical analysis of the cellular infiltrate in the spinal cord lesions in HTLV-I-associated myelopathy.
Immunocytochemical staining of spinal cords from five autopsied patients with HAM/TSP was performed using a panel of monoclonal antibodies reactive with T cells. T cell subsets, B cells, macrophages, natural killer cells, IL-2 receptor-positive cells, and HLA-ABC and HLA-DR. In the spinal cords of patients with a shorter duration of illness, CD4+ cells, CD8+ cells and macrophages were evenly distributed in active-chronic inflammatory lesions. In striking contrast, we noted the predominance of CD8+ cells over CD4+ cells in the inactive-chronic inflammatory lesions of patients with longer duration of illness. Natural killer cells, IL-2 receptor-positive cells and B cells were only rarely present in both the active-chronic and inactive-chronic lesions. HLA-ABC was positive in endothelial cells and infiltrating mononuclear cells, and HLA-DR was positive in endothelial cells, microglia and infiltrating mononuclear cells. This study suggests that immune responses in the spinal cord lesions of HAM patients gradually change along with the duration of illness.


Prognostic utility of neutrophil gelatinase-associated lipocalin in predicting mortality and cardiovascular events in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.
The aim of this study was to investigate the prognostic role of neutrophil gelatinase-associated lipocalin (NGAL) in a large population of patients with ST-segment elevation myocardial infarction. NGAL is a glycoprotein released by damaged renal tubular cells and is a sensitive maker of both clinical and subclinical acute kidney injury. New data have demonstrated that NGAL is also stored in granules of mature neutrophils, and recent data suggest that NGAL may also be involved in the development of atherosclerosis. NGAL is significantly increased in patients with myocardial infarction compared with patients with stable coronary artery disease and healthy subjects. However, the prognostic value of NGAL has never been studied in patients with myocardial infarction. We included 584 consecutive ST-segment elevation myocardial infarction patients admitted to the heart center of Gentofte University Hospital, Denmark, and treated with primary percutaneous coronary intervention, from September 2006 to December 2008. Blood samples were drawn immediately before primary percutaneous coronary intervention. Plasma NGAL levels were measured using a time-resolved immunofluorometric assay. The endpoints were all-cause mortality (n = 69) and the combined endpoints (n = 116) of major adverse cardiac events (MACE) defined as cardiovascular mortality and admission due to recurrent myocardial infarction or heart failure. The median follow-up time was 23 months (interquartile range, 20 to 24 months). Patients with high NGAL (>75th percentile) had increased risk of all-cause mortality and MACE compared with patients with low NGAL (log-rank test, p < 0.001). After adjustment for confounding risk factors chosen by backward elimination by Cox regression analysis, high NGAL remained an independent predictor of all-cause mortality and MACE (hazard ratio: 2.00; 95% confidence interval: 1.16 to 3.44; p = 0.01 and hazard ratio: 1.51; 95% confidence interval: 1.00 to 2.30; p = 0.05, respectively). High plasma NGAL independently predicts all-cause mortality and MACE in ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention.


Stromal rejection following deep anterior lamellar keratoplasty: implications for postoperative care.
To better characterize stromal rejection in the context of deep anterior lamellar keratoplasty (DALK) to improve early diagnosis and proper management. The clinical records of 22 patients undergoing DALK by 2 surgeons between October 2006 and January 2008 were reviewed to identify patients who experienced stromal rejection. The diagnosis was made after the demonstration of acute stromal edema and/or stromal neovascularization in the absence of confounding preoperative conditions, such as herpetic keratitis. The incidence and clinical features of stromal rejection were compared with other descriptions found in the literature. Five of 20 eligible patients experienced stromal rejection within 12 months. Two patients were on low-dose corticosteroids when diagnosed. Four of the 5 patients were treated aggressively with q1-3 hourly prednisolone acetate 1% eye drops. The fifth was treated less aggressively with a maximum dose of only q6 hourly prednisolone acetate 1% and subsequently experienced a second rejection episode less than 5 months later. All episodes resolved completely with treatment. The incidence of stromal rejection in DALK is clinically significant, suggesting that these patients may benefit from corticosteroid regimens similar to those used in penetrating keratoplasty and implies that stromal rejection may be more common in penetrating keratoplasty than previously reported. If misdiagnosed or left untreated, stromal rejection can compromise graft clarity but prompt recognition and aggressive treatment can result in good anatomic and visual outcomes.


CT angiography and MR angiography in the evaluation of carotid cavernous sinus fistula prior to embolization: a comparison of techniques.
This study compared CT angiography (CTA), MR angiography (MRA), and digital subtraction angiography (DSA) in elucidating the size and location of carotid cavernous sinus fistulas (CCFs) before embolization treatment. This was a retrospective study of 53 patients with angiographically confirmed CCF. All patients underwent pre- and postcontrast-enhanced CTA and DSA, and 50 patients also underwent MRA. Two neuroradiologists rated detectability of the fistula tract as "good," "moderate," or "poor" in source images obtained by using each procedure. The chi(2) test was used to compare the imaging modalities with respect to their ability to detect fistulas. CTA did not differ significantly from DSA (P = .155), and both CTA (P = .001) and DSA (P = .007) performed significantly better than MRA in the population as a whole. Differences in performance among the methods, however, depended upon the segmental location of the fistula along the internal carotid artery (ICA). CTA and MRA were similar in detection of CCFs in patients with a fistula at segment 3. CTA significantly outperformed MRA in patients with a fistula at segment 4, who accounted for approximately half of the population. CTA source imaging has proved itself as useful as DSA for detecting CCFs. Of the 2 noninvasive techniques, CTA performed better than MRA in the population as a whole and in most patients whose fistula was located at segment 4 or 5 of the ICA.


Rapid response to intensive treatment for bulimia nervosa and purging disorder: A randomized controlled trial of a CBT intervention to facilitate early behavior change.
Rapid response to cognitive behavior therapy (CBT) for eating disorders (i.e., rapid and substantial change to key eating disorder behaviors in the initial weeks of treatment) robustly predicts good outcome at end-of-treatment and in follow up. The objective of this study was to determine whether rapid response to day hospital (DH) eating disorder treatment could be facilitated using a brief adjunctive CBT intervention focused on early change. 44 women (average age 27.3 [8.4]; 75% White, 6.3% Black, 6.9% Asian) were randomly assigned to 1 of 2 4-session adjunctive interventions: CBT focused on early change, or motivational interviewing (MI). DH was administered as usual. Outcomes included binge/purge frequency, Eating Disorder Examination-Questionnaire and Difficulties in Emotion Regulation Scale. Intent-to-treat analyses were used. The CBT group had a higher rate of rapid response (95.7%) compared to MI (71.4%; p = .04, V = .33). Those who received CBT also had fewer binge/purge episodes (p = .02) in the first 4 weeks of DH. By end-of-DH, CBT participants made greater improvements on overvaluation of weight and shape (p = .008), and emotion regulation (ps < .008). Across conditions, there were no significant baseline differences between rapid and nonrapid responders (ps > .05). The results of this study demonstrate that rapid response can be clinically facilitated using a CBT intervention that explicitly encourages early change. This provides the foundation for future research investigating whether enhancing rates of rapid response using such an intervention results in improved longer term outcomes. (PsycINFO Database Record


CCDC134 ameliorated experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells.
CCDC134 (coiled-coil domain containing 134), a cytokine-like molecule, was previously reported to exert antitumor effects by augmenting CD8+ T-cell mediated immunity. However, the dynamic changes in CCDC134 expression patterns in the spinal cord that may be involved in the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, remains unclear. In this study, we found that CCDC134 expression was markedly increased in the spinal cord during the progression of EAE. Furthermore, we demonstrated that CCDC134 significantly reduced the severity and slowed the progression of EAE, which correlated with reduced spinal cord inflammation and demyelination. The underlying mechanism of CCDC134-induced effects involved inhibition of T helper (Th)-1 and Th17 cell differentiation and secretion of its key effector molecules IFN-γ and IL-17A via regulation of JAK/STAT signaling. These findings indicate that CCDC134 exerts potent anti-inflammatory effects through the selective modulation of pathogenic Th1 and Th17 cells by targeting critical signaling pathways. The study provides insights into the role of CCDC134 as a unique therapeutic agent for the treatment of autoimmune diseases.


[Resampling combined with stacking learning for prediction of blood-brain barrier permeability of compounds].
It is a significant challenge to improve the blood-brain barrier (BBB) permeability of central nervous system (CNS) drugs in their development. Compared with traditional pharmacokinetic property tests, machine learning techniques have been proven to effectively and cost-effectively predict the BBB permeability of CNS drugs. In this study, we introduce a high-performance BBB permeability prediction model named balanced-stacking-learning based BBB permeability predictor(BSL-B3PP). Firstly, we screen out the feature set that has a strong influence on BBB permeability from the perspective of medicinal chemistry background and machine learning respectively, and summarize the BBB positive(BBB+) quantification intervals. Then, a combination of resampling algorithms and stacking learning(SL) algorithm is used for predicting the BBB permeability of CNS drugs. The BSL-B3PP model is constructed based on a large-scale BBB database (B3DB). Experimental validation shows an area under curve (AUC) of 97.8% and a Matthews correlation coefficient (MCC) of 85.5%. This model demonstrates promising BBB permeability prediction capability, particularly for drugs that cannot penetrate the BBB, which helps reduce CNS drug development costs and accelerate the CNS drug development process.


Study of Candida ingens grown on the supernatant derived from the anaerobic fermentation of monogastric animal wastes.
A pellicle-forming yeast, identified as Candida ingens, was found to grow on substrates derived from the anerobic fermentation of monogastric animal wastes. The organism used volatile fatty acids C2 to C6 and ammonia nitrogen. It had a preferential uptake of the acids in increasing order of molecular weight, removing 90% of the total titratable volatile acid. The nonwrinkled pellicle had a doubling time of 3.2 h, and the doubling time of the wrinkled pellicle was 4.2 h. Proximate amino acid and nucleic acid analyses suggested that the organism might be acceptable as a source of single cell protein. Its vitamin B group content compared favorably with that of other yeasts. It contained 6% calcium and 7% phosphorus. It could be useful in removing these minerals from effluents as well as in providing them as nutrients in livestock rations.


Identification and Validation of a Ferroptosis-Related Long Non-Coding RNA (FRlncRNA) Signature to Predict Survival Outcomes and the Immune Microenvironment in Patients With Clear Cell Renal Cell Carcinoma.
Background: The incidence of clear cell renal cell carcinoma (ccRCC) is increasing worldwide, contributing to 70-85% of kidney cancer cases. Ferroptosis is a novel type of programmed cell death and could predict prognoses in cancers. Here, we developed a ferroptosis-related long non-coding RNA (FRlncRNA) signature to improve the prognostic prediction of ccRCC. Methods: The transcriptome profiles of FRlncRNAs and clinical data of ccRCC were obtained from The Cancer Genome Atlas and ICGC databases. Patients were randomly assigned to training cohorts, testing cohorts, and overall cohorts. The FRlncRNA signature was constructed by Lasso regression and Cox regression analysis, and Kaplan-Meier (K-M) analysis was used to access the prognosis of each group. The accuracy of this signature was evaluated by the receiver operating characteristic (ROC) curve. The visualization of functional enrichment was carried out by the gene set enrichment analysis (GSEA). Internal and external datasets were performed to verify the FRlncRNA signature. Results: A FRlncRNA signature comprising eight lncRNAs (AL590094.1, LINC00460, LINC00944, AC024060.1, HOXB-AS4, LINC01615, EPB41L4A-DT, and LINC01550) was identified. Patients were divided into low- and high-risk groups according to the median risk score, in which the high-risk group owned a dramatical shorter survival time than that of the low-risk group. Through ROC analysis, it was found that this signature had a greater predictive capability than traditional evaluation methods. The risk score was an independent risk factor for overall survival suggested by multivariate Cox analysis (HR = 1.065, 95%CI = 1.036-1.095, and p < 0.001). We constructed a clinically predictive nomogram based on this signature and its clinical features, which is of accurate prediction about the survival rate of patients. The GSEA showed that primary pathways were the P53 signaling pathway and tumor necrosis factor-mediated signaling pathway. The major FRlncRNAs (LINC00460, LINC00944, LINC01550, and EPB41L4A-DT) were verified with the prognosis of ccRCC in the GEPIA and K-M Plotter databases. Their major target genes (BNIP3, RRM2, and GOT1) were closely related to the stage, grade, and survival outcomes of ccRCC by the validation of multiple databases. Additionally, we found two groups had a significant distinct pattern of immune function, immune checkpoint, and immune infiltration, which may lead to different survival benefits. Conclusions: The FRlncRNA signature was accurate and act as reliable tools for predicting clinical outcomes and the immune microenvironment of patients with ccRCC, which may be molecular biomarkers and therapeutic targets.


Influence of Saccharomyces boulardii on the intestinal permeability of patients with Crohn's disease in remission.
Crohn's disease (CD) is characterized by a reduction in mucosal integrity that permits antigen penetration into the intestinal tissue. The administration of probiotics has been suggested to improve the barrier function of the mucosa. The objective of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability in CD. Thirty-four patients were randomized according to the Vienna classification for treatment with either placebo or Saccharomyces boulardii. Baseline medications (mesalamine, azathioprine, prednisone, metronidazole and/or thalidomide) were maintained. Intestinal permeability (lactulose/mannitol ratio) was evaluated immediately before the beginning of treatment and at the end of the first and third treatment month. Fifteen healthy volunteers were also submitted for the intestinal permeability test. In volunteers, the lactulose/mannitol ratio was 0.005+/-0.0037, whereas this value was 0.021+/-0.01 in patients with CD (p=0.001). In the placebo group, there was an increase in lactulose/mannitol ratio by 0.004+/-0.010 (p=0.12) at the end of the third month. In the S. boulardii group, there was an improvement in intestinal permeability, with a decrease in the lactulose/mannitol ratio by 0.008+/-0.006 (p=0.0005) in the same period. Patients with CD in remission present alterations in the integrity of the intestinal mucosal barrier according to lactulose/mannitol ratio. S. boulardii added to baseline therapy improved intestinal permeability in these patients, even though complete normalization was not achieved.


Evaluation of Pyloriset Screen, a rapid whole-blood diagnostic test for Helicobacter pylori infection.
Helicobacter pylori infection can be detected by several invasive tests based on gastroscopy and by noninvasive methods such as serologic assays. Noninvasive tests can be used not only in addition to invasive tests but also by themselves to screen for H. pylori infection in patients who are not in urgent need of endoscopy. Lately, rapid qualitative serologic tests have been developed. In the present study, the accuracy of a novel rapid whole-blood test, Pyloriset Screen, detecting immunoglobulin G (IgG) and IgA antibodies against H. pylori was evaluated. A total of 207 consecutive adult outpatients referred for upper endoscopy were enrolled. Gastric biopsy specimens were taken from the antrum and corpus for histologic examination and rapid urease testing. Cultures were available for 113 patients. Serum samples collected from all patients were tested for H. pylori antibodies by two enzyme immunoassays (EIAs) (Pyloriset EIA and an in-house EIA), a rapid latex agglutination test (Pyloriset Dry), and Pyloriset Screen. Patients were considered H. pylori positive if helicobacters were seen on histologic examination (77 patients) or, if in combination with histologically verified (although helicobacter-negative) gastritis, their IgG antibody titers were elevated in the two EIAs (five patients). The Pyloriset Screen test had a sensitivity of 95%, a specificity of 94%, a positive predictive value of 91%, and a negative predictive value of 97%. Among 63 patients under the age of 45 years, the Pyloriset Screen test did not miss a single H. pylori diagnosis, and only 1 patient had a false-positive result. Pyloriset Screen could be used reliably to screen for H. pylori infection.


P66Shc-rac1 pathway-mediated ROS production and cell migration is downregulated by ascorbic acid.
The oxidative role(s) of p66Shc protein has been increasingly expanded over the last decade. However, its relation with the most potent antioxidant molecule, i.e. ascorbic acid has never been studied. We have previously shown that p66Shc mediates rac1 activation, reactive oxygen species (ROS) production and cell death. Here we studied the effect of ascorbic acid on the pathway involving p66Shc and rac1. Our results indicate a decrease in the expression of p66Shc in a dose- and time-dependent manner. We studied the effect of ascorbic acid on rac1 expression and its activity. Ascorbic acid has no effect on total rac1 expression; however, rac1 activation was inhibited in a dose-dependent manner. Results suggest that the decrease in rac1 activity is mediated through ascorbic acid-modulated p66Shc expression. The decrease in rac1 activity was evident in cells transfected with the p66shc mutant (proline motif mutant, at residues P47 to P50). Our studies indicate that p66Shc-mediated ROS upregulation is significantly decreased in the presence of ascorbic acid. Cell migration experiments point towards the inhibition of p66Shc-rac1-mediated migration in the presence of ascorbic acid. Finally, results are suggestive that ascorbic acid-mediated decrease in Shc expression occurs through an increased Shc ubiquitination. Overall, the study brings out the novel role of ascorbic acid in antioxidant signal transduction.


[Traumatic retroperitoneal haematoma].
The management of traumatic retroperitoneal haematomas is still a much debated question. Although the diagnosis has become easier using CT with contrast medium, the therapeutic decisions are still difficult because of the great variability of the lesions, which may be simple but very often complicated. Our study is based on 1086 treated patients, 29.5% of the 3682 critical abdominal polytrauma seen in 35 years. Mortality has been 12.9% with a medium ISS (Injury Severity Score) of 23.4. 71.4% of the cases were closed traumas, 28,6% were open traumas. The most common single lesions have been pelvic (43%), followed by the renal traumas (39%). Regarding the associated lesions, the thoracic traumas cause an increment of the ISS score up to 26.2% and of mortality up to 14.6%. The maxillofacial traumas associated with traumatic retroperitoneal haematomas represent 11%, mainly associated with motorcycle accidents, which have increased in the last years from 2,4% in the 70s to 32% these days. Our approach to these patients has been basically conservative. Following the indications obtained by the CT, we widely used interventional angiography, especially for renal lesions and, after pelvic stabilization, for pelvic haematomas. We have chosen surgery considering the kind of traumas (open or closed), the location of the haematoma and especially, the clinical course of the patient's hemodynamic condition.


Attitudes and trends in the use of radiolucent spinal implants: A survey of the North American Spine Society section of spinal oncology.
In spinal oncology, titanium implants pose several challenges including artifact on advanced imaging and therapeutic radiation perturbation. To mitigate these effects, there has been increased interest in radiolucent carbon fiber (CF) and CF-reinforced polyetheretherketone (CFR-PEEK) implants as an alternative for spinal reconstruction. This study surveyed the members of the North American Spine Society (NASS) section of Spinal Oncology to query their perspectives regarding the clinical utility, current practice patterns, and recommended future directions of radiolucent spinal implants. In February 2021, an anonymous survey was administered to the physicians of the NASS section of Spinal Oncology. Participation in the survey was optional. The survey contained 38 items including demographic questions as well as multiple-choice, yes/no questions, Likert rating scales, and short free-text responses pertaining to the "clinical concept", "efficacy", "problems/complications", "practice pattern", and "future directions" of radiolucent spinal implants. Fifteen responses were received (71.4% response rate). Six of the participants (40%) were neurosurgeons, eight (53.3%) were orthopedic surgeons, and one was a spinal radiation oncologist. Overall, there were mixed opinions among the specialists. While several believed that radiolucent spinal implants provide substantial benefits for the detection of disease recurrence and radiation therapy options, others remained less convinced. Ongoing concerns included high costs, low availability, limited cervical and percutaneous options, and suboptimal screw and rod designs. As such, participants estimated that they currently utilize these implants for 27.3% of anterior and 14.7% of all posterior reconstructions after tumor resection. A survey of the NASS section of Spinal Oncology found a lack of consensus with regards to the imaging and radiation benefits, and several ongoing concerns about currently available options. Therefore, routine utilization of these implants for anterior and posterior spinal reconstructions remains low. Future investigations are warranted to practically validate these devices' theoretical risks and benefits.


Cardiac nitric oxide synthases are elevated in dietary copper deficiency.
Dietary copper (Cu) deficiency leads to cardiac morphological and functional defects suggestive of heart failure. However, simultaneous cytoprotective events also appear to occur. The molecular mechanisms responsible for this complex alteration of cardiac function by Cu deficiency have not been elucidated. Because prior work has implicated altered nitric oxide (NO) metabolism in this altered function, we have examined this pathway in further detail. Male Sprague-Dawley rats were fed diets that were either Cu adequate (6 mg Cu/kg diet) or Cu deficient (<0.5 mg Cu/kg diet) for 5 weeks. Endothelial NO synthase (NOS) and inducible NOS (iNOS) protein expressions, as measured by Western blot analysis, were 58% and 40% higher, respectively, in Cu-deficient than in Cu-adequate rat hearts. Cardiac NOS activity, as measured by conversion of (3)H-arginine to (3)H-citrulline, was 130% higher in Cu-deficient than in Cu-adequate rats. NFkappaB is a known transcription factor for iNOS. Activation of NFkappaB, determined by an ELISA for the p65 subunit, was found to be 33% higher in Cu-deficient than in Cu-adequate rats. Coupled with prior evidence of elevated cardiac nitrate/nitrite production in Cu-deficient rats, these data suggest multiple pathways for enhanced NO production that may contribute to altered cardiac function under dietary Cu deficiency.


HO-1 induction lowers blood pressure and superoxide production in the renal medulla of angiotensin II hypertensive mice.
Heme oxygenase-1 (HO-1) induction can attenuate the development of angiotensin II (ANG II)-dependent hypertension. However, the mechanism by which HO-1 lowers blood pressure in this model is not clear. The goal of this study was to test the hypothesis that induction of HO-1 in the kidney can attenuate the increase in reactive oxygen species (ROS) generation in the kidney that occurs during ANG II-dependent hypertension. Mice were divided into four groups, control (Con), cobalt protoporphyrin (CoPP), ANG II, and ANG II + CoPP. CoPP treatment (50 mg/kg) was administered in a single subcutaneous injection 2 days prior to implantation of an osmotic minipump that infused ANG II at a rate of 1 microg x kg(-1) x min(-1). At the end of this period, mean arterial blood pressure (MAP) averaged 93 +/- 5, 90 +/- 5, 146 +/- 8, and 105 +/- 6 mmHg in Con, CoPP-, ANG II-, and ANG II + CoPP-treated mice. To determine whether HO-1 induction resulted in a decrease in ANG II-stimulated ROS generation in the renal medulla, superoxide production was measured. Medullary superoxide production was increased by ANG II infusion and normalized in mice pretreated with CoPP. The reduction in ANG II-mediated superoxide production in the medulla with CoPP was associated with a decrease in extracellular superoxide dismutase protein but an increase in catalase protein and activity. These results suggest that reduction in superoxide and possibly hydrogen peroxide production in the renal medulla may be a potential mechanism by which induction of HO-1 with CoPP lowers blood pressure in ANG-II dependent hypertension.


Molecular alterations during development of esophageal adenocarcinoma.
The incidence of esophageal adenocarcinoma has risen significantly over the last decades. During esophageal carcinogenesis many molecular alterations occur that disrupt essential cellular processes, directing the cell to a rapidly proliferating, immortal state. The chronic inflammation that is present in Barrett's esophagus creates an environment in which such molecular alterations are both induced and tolerated. Here, the novel insights in the molecular mechanisms that underlie the development of esophageal adenocarcinoma are reviewed, focusing on the role of inflammation, angiogenesis, apoptosis inhibition, loss of cell cycle control, and loss of cell-cell adhesion. These novel developments will open new perspectives for diagnosis, treatment, and prevention of esophageal adenocarcinoma.


A psychoacoustic method to find the perceptual cues of stop consonants in natural speech.
Synthetic speech has been widely used in the study of speech cues. A serious disadvantage of this method is that it requires prior knowledge about the cues to be identified in order to synthesize the speech. Incomplete or inaccurate hypotheses about the cues often lead to speech sounds of low quality. In this research a psychoacoustic method, named three-dimensional deep search (3DDS), is developed to explore the perceptual cues of stop consonants from naturally produced speech. For a given sound, it measures the contribution of each subcomponent to perception by time truncating, highpass/lowpass filtering, or masking the speech with white noise. The AI-gram, a visualization tool that simulates the auditory peripheral processing, is used to predict the audible components of the speech sound. The results are generally in agreement with the classical studies that stops are characterized by a short duration burst followed by a F2 transition, suggesting the effectiveness of the 3DDS method. However, it is also shown that /ba/ and /pa/ may have a wide band click as the dominant cue. F2 transition is not necessary for the perception of /ta/ and /ka/. Moreover, many stop consonants contain conflicting cues that are characteristic of competing sounds. The robustness of a consonant sound to noise is determined by the intensity of the dominant cue.


The brain-in-motion study: effect of a 6-month aerobic exercise intervention on cerebrovascular regulation and cognitive function in older adults.
Aging and physical inactivity are associated with declines in some cognitive domains and cerebrovascular function, as well as an elevated risk of cerebrovascular disease and other morbidities. With the increase in the number of sedentary older Canadians, promoting healthy brain aging is becoming an increasingly important population health issue. Emerging research suggests that higher levels of physical fitness at any age are associated with better cognitive functioning and this may be mediated, at least in part, by improvements in cerebrovascular reserve. We are currently conducting a study to determine: if a structured 6-month aerobic exercise program is associated with improvements or maintenance of both cerebrovascular function and cognitive abilities in older individuals; and, the extent to which any changes seen persist 6 months after the completion of the structured exercise program. Two hundred and fifty men and women aged 55-80 years are being enrolled into an 18-month combined quasi-experimental and prospective cohort study. Participants are eligible for enrollment into the study if they are inactive (i.e., not participating in regular physical activity), non-smokers, have a body mass index <35.0 kg/m(2), are free of significant cognitive impairment (defined as a Montreal Cognitive Assessment score of 24 or more), and do not have clinically significant cardiovascular, cerebrovascular disease, or chronic obstructive pulmonary airway disease. Repeated measurements are done during three sequential six-month phases: 1) pre-intervention; 2) aerobic exercise intervention; and 3) post-intervention. These outcomes include: cardiorespiratory fitness, resting cerebral blood flow, cerebrovascular reserve, and cognitive function. This is the first study to our knowledge that will examine contemporaneously the effect of an exercise intervention on both cerebrovascular reserve and cognition in an older population. This study will further our understanding of whether cerebrovascular mechanisms might explain how exercise promotes healthy brain aging. In addition our study will address the potential of increasing physical activity to prevent age-associated cognitive decline.


Utilization of dental care in Finnish industrial population.
Ninety-three percent of the 300 employees of a paper mill in central-eastern Finland answered a questionnaire in the context of a clinical dental survey. One third had visited the dentist annually, 22% once in 2 years and the rest irregularly. Dental visit frequency of females was somewhat higher than that of males. People in younger age groups and higher income groups used more dental services, whereas those who had dentures used clearly less dental services than others. Subjective assessment of treatment need was the main reason for dental visits, more than half of the subjects had attended the dentist the last time because of self-assessed need. Thirty-eight percent went to the dentist because of toothache and only 9% for regular check-up. Although more than one third had gone to the dentist because of toothache only one third of those who had toothache during the preceding year had visited the dentist during that period. People without toothache, in fact, used more dental services than those who had had it.


Translational neuroprotection research in glaucoma: a review of definitions and principles.
The maintenance of vision, through prevention and attenuation of neuronal injury in glaucoma, forms the basis of current clinical practice. Currently, the reduction of intraocular pressure is the only proven method to achieve these goals. Although this strategy enjoys considerable success, some patients progress to blindness; hence, additional management options are highly desirable. Several terms describing treatment modalities of neuronal diseases with potential applicability to glaucoma are used in the literature, including neuroprotection, neurorecovery, neurorescue and neuroregeneration. These phenomena have not been defined within a coherent framework. Here, we suggest a set of definitions, postulates and principles to form a foundation for the successful translation of novel glaucoma therapies from the laboratory to the clinic.


Enhanced crude oil biodegradative potential of natural phytoplankton-associated hydrocarbonoclastic bacteria.
Phytoplankton have been shown to harbour a diversity of hydrocarbonoclastic bacteria (HCB), yet it is not understood how these phytoplankton-associated HCB would respond in the event of an oil spill at sea. Here, we assess the diversity and dynamics of the bacterial community associated with a natural population of marine phytoplankton under oil spill-simulated conditions, and compare it to that of the free-living (non phytoplankton-associated) bacterial community. While the crude oil severely impacted the phytoplankton population and was likely conducive to marine oil snow formation, analysis of the MiSeq-derived 16S rRNA data revealed dramatic and differential shifts in the oil-amended communities that included blooms of recognized HCB (e.g., Thalassospira, Cycloclasticus), including putative novel phyla, as well as other groups with previously unqualified oil-degrading potential (Olleya, Winogradskyella, and members of the inconspicuous BD7-3 phylum). Notably, the oil biodegradation potential of the phytoplankton-associated community exceeded that of the free-living community, and it showed a preference to degrade substituted and non-substituted polycyclic aromatic hydrocarbons. Our study provides evidence of compartmentalization of hydrocarbon-degrading capacity in the marine water column, wherein HCB associated with phytoplankton are better tuned to degrading crude oil hydrocarbons than that by the community of planktonic free-living bacteria.


Prdx5 in the Regulation of Tuberous Sclerosis Complex Mutation-Induced Signaling Mechanisms.
(1) Background: Tuberous sclerosis complex (TSC) mutations directly affect mTORC activity and, as a result, protein synthesis. In several cancer types, TSC mutation is part of the driver mutation panel. TSC mutations have been associated with mitochondrial dysfunction, tolerance to reactive oxygen species due to increased thioredoxin reductase (TrxR) enzyme activity, tolerance to endoplasmic reticulum (ER) stress, and apoptosis. The FDA-approved drug rapamycin is frequently used in clinical applications to inhibit protein synthesis in cancers. Recently, TrxR inhibitor auranofin has also been involved in clinical trials to investigate the anticancer efficacy of the combination treatment with rapamycin. We aimed to investigate the molecular background of the efficacy of such drug combinations in treating neoplasia modulated by TSC mutations. (2) Methods: TSC2 mutant and TSC2 wild-type (WT) cell lines were exposed to rapamycin and auranofin in either mono- or combination treatment. Mitochondrial membrane potential, TrxR enzyme activity, stress protein array, mRNA and protein levels were investigated via cell proliferation assay, electron microscopy, etc. (3) Results: Auranofin and rapamycin normalized mitochondrial membrane potential and reduced proliferation capacity of TSC2 mutant cells. Database analysis identified peroxiredoxin 5 (Prdx5) as the joint target of auranofin and rapamycin. The auranofin and the combination of the two drugs reduced Prdx5 levels. The combination treatment increased the expression of heat shock protein 70, a cellular ER stress marker. (4) Conclusions: After extensive analyses, Prdx5 was identified as a shared target of the two drugs. The decreased Prdx5 protein level and the inhibition of both TrxR and mTOR by rapamycin and auranofin in the combination treatment made ER stress-induced cell death possible in TSC2 mutant cells.


Statistical and pathological analysis of oral tumors in the Hong Kong Chinese.
A total of 805 intra-oral neoplasms was diagnosed in Chinese subjects from 1964-1982 in the University Department of Pathology, Hong Kong. Squamous cell carcinoma (SCC) totalled 502 and constituted 86% of 582 malignant tumors. Although the majority (82%) of SCC were of the well-differentiated type, the relatively poor differentiation exhibited by palatal SCC in the females, was noteworthy. There was a marked male predominance in all SCC subgrouped by anatomic site, but the sex difference declined after the 6th decade and disappeared by the 9th decade. A significant rise in the incidence rate was observed in the decade after 1973 compared to that for 1964-72 in both male (p less than 0.0001) and female (p less than 0.001). It is speculated that, in the absence of improved oral hygiene and dental care, changes in the smoking and drinking habits in the local Chinese are of causal importance.


Clomiphene citrate-induced visual hallucinations: a case report.
Polycystic ovary syndrome is a common cause of chronic anovulation and infertility in otherwise healthy fertile couples. Clomiphene citrate is used as a first-line ovulation induction therapy in patients with polycystic ovary syndrome. Clomiphene citrate can cause both systemic and ocular side effects. We report a rare side effect of illusory palinopsias in a patient with polycystic ovary syndrome treated with ovulation induction therapy with clomiphene citrate, and emphasize the need for gynecologists and their patients to be aware of this rare ocular side effect. A 30-year-old Asian woman complained of persistent visual afterimages following treatment with 100 mg clomiphene citrate for anovulation. Her symptoms started on the fourth day after commencing the treatment and would last for 5 to 10 minutes. Similar visual symptoms were noted during her second cycle of treatment with clomiphene citrate. The severity of her symptoms reduced following the stoppage of the medication; however, the symptoms have persisted for more than 1 year since she stopped taking the drug. Clomiphene citrate can cause disturbing illusory palinopsias. These afterimages persist even after stopping the infertility medication. It is a side effect not frequently seen by gynecologists or ophthalmologists. Gynecologists should make their patients aware of this rare ocular side effect when their patients start treatment with clomiphene citrate for infertility.


Oral antidiabetic agents as cardiovascular drugs.
The increased risk of cardiovascular disease associated with type 2 diabetes is well documented. Lesser degrees of abnormal glucose metabolism including impaired fasting glycaemia and impaired glucose tolerance are also associated with increased cardiovascular risk. Studies showing improved cardiovascular outcomes with oral antidiabetic agents are limited, with the UKPDS demonstrating improved macrovascular outcomes only in a subgroup of obese patients with type 2 diabetes treated with metformin, and the heavily criticized STOP NIDDM trial showing a reduction in the number of cardiovascular events with the alpha glucosidase inhibitor acarbose. In recent years there has been an increase in the number of oral antidiabetic drugs available to treat the hyperglycaemia of diabetes. Some of these drugs have complex metabolic properties, additional to their antihyperglycaemic effect, improving endothelial function and markers of atherogenesis, with the potential to reduce cardiovascular morbidity and mortality, as supported by the recently published results of the PROACTIVE study. The results of further long-term cardiovascular outcome studies with these newer agents are awaited.


Production and secretion of fatty acids in genetically engineered cyanobacteria.
Our purpose is to apply a fatty acid secretion strategy in photosynthetic microbial biofuel production, which will avoid the costly biomass recovery processes currently applied in algal biofuel systems. Starting with introducing acyl-acyl carrier protein thioesterases, we made five successive generations of genetic modifications into cyanobacterium Synechocystis sp. PCC 6803. The mutant strains were able to overproduce fatty acids (C10-C18) and secrete them into the medium at an efficiency of up to 133 +/- 12 mg/L of culture per day at a cell density of 1.5 x 10(8) cells/mL (0.23 g of dry weight/liter). Fatty acid secretion yields were increased by weakening the S layer and peptidoglycan layers. Although the fatty acid secreting strains had a long lag phase with many cells having damaged cell membranes when grown at low cell densities, these strains grew more rapidly in stationary phase and exhibited less cell damage than wild-type in a stationary culture. Our results suggest that fatty acid secreting cyanobacteria are a promising technology for renewable biofuel production.


Differential effects of pharmacologically generated reactive oxygen species upon functional activity of epididymal mouse spermatozoa.
Several studies indicate that reactive oxygen species (ROS) are involved in defective sperm function pathophysiology. In this study we attempted to determine differentially the effects of xanthine (0.12 mM) plus xanthine oxidase (0.035 U/mL) (X+XO, a ROS promoter system), ROS scavengers (Tiron (TIR, 15 mM); catalase (CAT, 10 micrograms/mL); dimethylsulfoxide (DMSO, 140 mM)), and X+XO plus scavengers on several epididymal mouse spermatozoa functional parameters, incubated in NTPC medium, for 29 min. In the presence of X+XO, progressive gametes significantly diminished. TIR or CAT attenuated this effect, but DMSO did not. Inversely, X+XO increased the bending-forms population; only TIR reversed this phenomenon. The ROS promoter system diminished the viable cell population; all scavengers assayed maintained sperm viability at levels similar to control ones. When exposed to hypoosmotic shock after 29 min incubation with X+XO, the percentage of swollen cells decreased; TIR, CAT, or DMSO did not prevent this effect. Our experiments demonstrate that it is possible to differentiate the deleterious ROS effects upon sperm functional activity. O-2. and H2O2 preferentially seem to modify sperm motility, O-2. exhibiting the greatest ability for generating bending-form gametes, OH-being the most lethal ROS. In addition, sperm membrane clearly appears as the most damaged structure.


Effects of a weight loss plus exercise program on physical function in overweight, older women: a randomized controlled trial.
Obesity and a sedentary lifestyle are associated with physical impairments and biologic changes in older adults. Weight loss combined with exercise may reduce inflammation and improve physical functioning in overweight, sedentary, older adults. This study tested whether a weight loss program combined with moderate exercise could improve physical function in obese, older adult women. Participants (N = 34) were generally healthy, obese, older adult women (age range 55-79 years) with mild to moderate physical impairments (ie, functional limitations). Participants were randomly assigned to one of two groups for 24 weeks: (i) weight loss plus exercise (WL+E; n = 17; mean age = 63.7 years [4.5]) or (ii) educational control (n = 17; mean age = 63.7 [6.7]). In the WL+E group, participants attended a group-based weight management session plus three supervised exercise sessions within their community each week. During exercise sessions, participants engaged in brisk walking and lower-body resistance training of moderate intensity. Participants in the educational control group attended monthly health education lectures on topics relevant to older adults. Outcomes were: (i) body weight, (ii) walking speed (assessed by 400-meter walk test), (iii) the Short Physical Performance Battery (SPPB), and (iv) knee extension isokinetic strength. Participants randomized to the WL+E group lost significantly more weight than participants in the educational control group (5.95 [0.992] vs 0.23 [0.99] kg; P < 0.01). Additionally, the walking speed of participants in the WL+E group significantly increased compared with that of the control group (reduction in time on the 400-meter walk test = 44 seconds; P < 0.05). Scores on the SPPB improved in both the intervention and educational control groups from pre- to post-test (P < 0.05), with significant differences between groups (P = 0.02). Knee extension strength was maintained in both groups. Our findings suggest that a lifestyle-based weight loss program consisting of moderate caloric restriction plus moderate exercise can produce significant weight loss and improve physical function while maintaining muscle strength in obese, older adult women with mild to moderate physical impairments.


Synthesis, DNA Binding, and Anticancer Properties of Bis-Naphthalimide Derivatives with Lysine-Modified Polyamine Linkers.
A series of bis-naphthalimide derivatives with different diamine linkers were designed and synthesized. All of the synthesized bis-naphthalimide derivatives were characterized by NMR and HRMS spectra. The binding ability between the compounds and CT DNA was evaluated by using UV-Vis titration experiments. The bis-naphthalimide compound with an ethylenediamine linker showed the largest binding constant with CT DNA. Hence, it was used as the model compound to study the DNA binding selectivity by UV-Vis titration aiming at different DNA duplexes. As a result, this compound showed binding preference to AT-rich duplexes. The DNA binding modes of the compounds were also measured by viscosity titration. The cytotoxicity of the compounds was evaluated by MTT assay. Compounds with 1,6-diaminohexane or 1,4-phenylenedimethanamine linkers showed higher cytotoxicity compared with other bis-naphthalimide derivatives.


A comparison between direct and indirect measurements of blood flow in the follicular ovary of the rabbit.
A comparison was carried out between direct and indirect measurements of blood flow in follicular ovaries of anaesthetized laparotomized rabbits: Direct measurements by timed quantitative sampling of ovarian venous blood yielded blood flow values 3 times higher than those found with the use of 15 mugm radioactive microspheres. However, when simulating the surgical trauma associated with direct measurements, the microsphere technique gave the same high ovarian flow values, indicating that this type of trauma caused ovarian hyperemia. It is concluded that direct measurements of blood flow, as performed in the present study, are unsuitable for investigations of circulatory events in the ovary. Mechanically induced ovarian vasodilatation is probably a factor which helps to explain the diverging data on blood flow obtained with direct and indirect methods. The radioactive microsphere technique appears to provide a means for reasonably reliable ovarian blood flow measurements in laboratory animals.


Why BLUF photoreceptors with roseoflavin cofactors lose their biological functionality.
The photophysics of roseoflavin in three different environments is investigated by using ab initio and quantum mechanics/molecular mechanics methods. Intramolecular charge transfer is shown to be responsible for the quenching of the fluorescence in the gas phase, and in the water environment. However, for the roseoflavin incorporated into the blue light using flavin (BLUF) protein environment (substituting the native flavin) no such deactivation is found. The conical intersection between the locally excited state of the chromophore and the charge transfer state involving the tyrosine residue, which in the native BLUF domain is responsible for initiating the photocycle, is missing for the roseoflavin substituted protein. This explains the experimental observations of the lack of any photocycle, and the loss of the biological function of the BLUF photoreceptor reported earlier.


Improved respirable fraction of budesonide powder for dry powder inhaler formulations produced by advanced supercritical CO2 processing and use of a novel additive.
A budesonide (BDS) suspension was obtained via advanced supercritical carbon dioxide (scCO2) processing. Thereafter, the suspension was freeze-dried (FD) to produce BDS particles for dry powder inhaler formulations (scCO2/FD processing). The scCO2/FD processed BDS powder showed low crystallinity by powder X-ray diffraction and a rough surface by scanning electron microscopy. The respirable fraction of BDS was assessed using a twin impinger and revealed that the amount of the scCO2/FD processed sample that reached stage 2 was 4-fold higher than that of the supplied powder. To extend the utility of scCO2 processing, BDS particles for dry powder inhalers were fabricated by combining the scCO2 system with various additives. When BDS was processed via scCO2/FD in the presence of the novel additive, namely, monoglyceride stearate (MGS), the residual BDS/MGS particles remaining in the capsule and devices decreased, followed by an increase in the respirable fraction of BDS 6-fold higher than with the supplied powder. The scCO2/FD processed BDS/MGS particles had a smooth surface, in contrast to the scCO2/FD processed BDS particles. A combination of BDS and an appropriate additive in scCO2 treatment may induce changes in particle surface morphology, leading to an improvement in the inhalation properties of BDS.


Molecular assembled self-doped polyaniline interlayer for application in polymer light-emitting diode.
Self-doped polyaniline (SPANI) ultrathin films were prepared by using a self-assembly process consisting of a self-doping monomer (o-aminobenzenesulfonic acid, SAN) and aniline (AN). SAN-AN copolymerization and film formation were simultaneously performed in aqueous solution. An immersing self-assembly method was developed to build up a SPANI nanofilm on an ITO glass, providing a hole injection layer in a double-layer electroluminescence (EL) device ITO/SPANI nanofilm//MEH-PV//Ca/Al. This device produces an orange EL as compared with a single-layer EL device of ITO//MEH-PV//Ca/Al. A double-layer device demonstrates that a SPANI film is capable of transporting holes in a polymer light-emitting diode (PLED).


Transcriptome changes during intestinal cell differentiation.
The expression of 18149 genes have been analysed during the differentiation of the human intestinal cell line Caco-2. cDNA probes from undifferentiated and differentiated Caco-2 cells were separately hybridised to EST DNAs spotted in an array on a nylon membrane. A remarkable change in the transcriptome was observed during the differentiation of the Caco-2 cells. 8762 of the 18149 genes analysed were expressed above background level in the undifferentiated Caco-2 cells, whereas only 5767 genes were expressed above background in differentiated Caco-2 cells. This pattern of expression was caused by a general down-regulation of genes in the low abundance class. Similar results were found using mouse small intestinal crypt and villus cells, suggesting that the phenomenon also occurs in the intestine in vivo. The expression data were subsequently used in a search for markers for subsets of epithelial cells by performing reverse transcriptase-polymerase chain reaction on RNA extracted from laser dissected intestinal crypt and villi. In a screen of eight transcripts one - SART3 - was identified as a marker for human colonic crypts.


A "pillar-free", highly porous metalloporphyrinic framework exhibiting eclipsed porphyrin arrays.
A "pillar-free", highly porous metalloporphyrinic framework (UNLPF-1) exhibiting eclipsed porphyrin arrays has been constructed from an octacarboxylate ligand connected with paddlewheel secondary building units. UNLPF-1 possesses two types of open metal sites and exhibits an efficient selectivity toward capture of CO2 over N2.


Immediate Surgical Skills Feedback in the Operating Room Using "SurF" Cards.
Ensuring residents develop operative skills requires application of the principles of guided learning, deliberate practice, and directed feedback. We sought to create and implement a tool to promote procedural "key" step review and immediate feedback on surgical skills, and examined faculty and resident satisfaction with surgical skills feedback. We created surgical skills feedback (SurF) cards for 8 gynecologic procedures. Faculty/fellows and residents completed prestudy surveys querying frequency of preoperative key step review and satisfaction with surgical skill feedback, a SurF card each time 1 of 8 procedures was performed, and poststudy surveys to evaluate for changes. Prestudy surveys were completed by 31 faculty/fellows and 20 residents, with 55% (17 of 31) of the faculty/fellows and 5% (1 of 20) of the residents reporting key step review before surgery. All reported low satisfaction rates with feedback frequency, quality, and timeliness. After implementation of SurF cards, preoperative key step review occurred in 78% (82 of 105) of the procedures. Twenty-one faculty/fellows (68%) and 16 residents (80%) completed our poststudy survey. Faculty/fellows reported statistically similar key step review (n = 15 [71%], P = .23), while residents reported that key step review had significantly improved (n = 6 [38%], P = .01). Resident satisfaction with feedback frequency (5% to 50%, P = .002) and quality (15% to 50%, P = .02) increased significantly. The SurF cards we developed facilitated procedural key step review, were associated with significantly improved resident satisfaction with surgical feedback, and could prove helpful with outcomes assessments, such as Accreditation Council for Graduate Medical Education-required documentation of Milestone attainment.


The application of ultrasound to the study of thyroid enlargement: management of 450 cases.
Four hundred fifty cases of thyroid enlargement were studied by B-mode ultrasonography. Specific ultrasonographic patterns could be established for cyst, solid tumors, multinodular goiter, cystadenoma, and thyroiditis. Benign and malignant tissue could not be differentiated. In 155 cases, tissue diagnosis was established usually by operation but also by aspiration cytology. One hundred forty-two were hypofunctioning solitary nodules. The reliability of ultrasonographic diagnosis was 94 percent. It permitted safe aspiration of cysts, early operation of solid lesions, and avoidance of radiation hazard in the management of pregnant and pediatric patients. Our operative series showed the following incidences: cancer 16 percent, cyst 20 percent, and neoplasm 62 percent.


Psychogenic speech disorder--a case report.
Conversion (dissociative) disorder is a psychiatric disorder in which somatic symptoms or deficits are present in the absence of a definable organic cause. The etiology of this disorder is not yet fully understood. The most characteristic presentations are: pseudosensory syndromes, pseudoseizures, psychogenic movement disorders and pseudoparalysis. Psychogenic speech disorder is a rare form of conversion (dissociative) disorder. The aim of present case study is to complete the knowledge on this subject. The article presents a case of a fifty year old woman who developed psychogenic disorder of speech after being degraded to a lower position at work. After excluding organic background of observed symptoms, the diagnosis of conversion (dissociative) disorder was stated and adequate therapy was implemented, within the capabilities of the Ward. Partial remission of presented symptoms was achieved as a result of psychopharmacotherapy and psychotherapy. Before stating the diagnosis of conversion (dissociative) disorder, possible somatic causes of the observed symptoms should be excluded. Special attention should be drawn to the importance of studying the psychological and family context of this case and the patient's difficulty to understand and accept that produced symptoms might be triggered by a psychogenic factor.


The safety of rosuvastatin: effects on renal and hepatic function.
Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have been shown to reduce elevated serum cholesterol resulting in a reduced risk of coronary artery disease and its complications. Rosuvastatin is the latest of the class of HMG-CoA reductase inhibitors and has the most potent reduction of low-density lipoprotein and elevation of high-density lipoprotein in the class. Questions have been raised about its safety. In a careful examination of the data, rosuvastatin has the same rate of elevations of hepatic enzymes as the other statins. Whether any of the statins actually cause significant liver injury is doubtful, and this raises questions about the usefulness of routine monitoring of liver enzymes in statin patients. Rosuvastatin has been noted to produce low levels of transient proteinuria. However, transient proteinuria is seen with other comparable statins. Long-term administration of rosuvastatin and other statins have been shown not to be associated with any decline in renal function, but instead have been shown to produce modest but clear improvement in glomerular filtration rate. Therefore, it is clear that rosuvastatin, and other statins, are very safe and useful agents and do not appear to present significant risks to hepatic or renal safety.


Semantic Ambiguity Resolution in Patients With Bipolar Disorder-An Event-Related Potential Study.
Deficits in inhibitory function are assumed to underlie psychopathology in bipolar disorder (BD), especially in states of mania. A subdomain of inhibition, semantic inhibition (SI), referring to the suppression of irrelevant word meanings, may underlie formal thought disorder, such as flights of ideas. In the present study, we investigated SI in patients with BD during semantic ambiguity resolution using behavioral and event-related potential (ERP) measures. We presented 14 patients with BD with current manic, hypomanic, or mixed clinical states and 28 healthy controls sequentially with word triplets containing either a homonym (e.g., "organ") or a comparable unambiguous word (e.g., "piano"). Participants were instructed to make a decision whether or not the target word was related to the meaning field of the first two words. The inappropriate homonym meaning had to be inhibited to correctly perform the target decision. In addition to reaction times (RT) and error rates (ER), the N400 ERP component to the target, an electrophysiological index of semantic processing, was analyzed as measure of the amount of SI that had taken place. Analyses of the behavioral data revealed that BD patients exhibited an overall worse performance in terms of RT and ER. In the ERP data, we found differences in N400 amplitude to ambiguous and unambiguous conditions over the right hemisphere in patients with BD depending on target congruence: In incongruent trials, N400 amplitude was smaller in ambiguous than in unambiguous words. In congruent trials, in contrast, N400 amplitude was larger in ambiguous than in unambiguous words. Such ERP differences between ambiguous and unambiguous words were absent in controls. We conclude that N400 amplitude differences in the ambiguous and unambiguous conditions of the BD group may reflect insufficient suppression of irrelevant homonym meanings in the right hemisphere. Disturbed SI processes might contribute to formal thought disorder in BD.


Endoscopic management of a major bile duct stricture from surgical clips following laparoscopic hemicolectomy.
Benign postoperative bile duct strictures are usually complications of cholecystectomies. However, development of obstructive jaundice and biliary stricture as a result of surgical clips after laparoscopic right hemicolectomy is rare and has not been reported in the literature. We present a case of a 64-year-old woman who presented with sudden onset jaundice and abdominal pain, 1 week following right hemicolectomy. Laboratory reports suggested obstructive jaundice. Subsequent imaging studies showed biliary dilation of both intrahepatic and extrahepatic ducts with no evidence of bile duct stones. The endoscopic retrograde cholangiopancreatography (ERCP) showed an abrupt, complete obstruction of the common bile duct at the level of the surgical clips. The bile duct stricture formed at the site of surgical clips improved significantly after serial incremental biliary dilations with successive placement of increasing number of endoprostheses side-by-side at repeat ERCP sessions.


Deaths due to delayed presentation to the hospital from fear of contracting COVID-19 during lockdown period: a tertiary care center experience.
Background: Sudden rise in COVID-19 cases in March 2020 due to spread of pandemic led to immediate lockdown order in many states and cities across the USA. Everyone had to stay home to stop the spread of the virus. We investigated all deaths in our hospital during lockdown period and assessed how many presented and died from non-COVID-19-related illness. Among those deaths, we assessed how many presented late due to excessive fear of catching coronavirus in the hospital and succumbed to the same illness due to very late presentation. Methods: We retrospectively reviewed charts of every patient who expired in the hospital in a 45-day period, March-April 2020. Results: Three of 107 (2.8%) deaths during lockdown period in this hospital were clearly attributable to delayed presentation arising specifically from fear of coming to the hospital. All three died from non-COVID-19-related illnesses. Conclusions: Authors hereby propose enhanced efforts in the direction to alleviate unnecessary fear among public even during lockdown. People should be encouraged to continue to access health care for serious/fatal medical conditions regardless of the pandemic.


Comparison of the cardiovascular responses to intracerebroventricular administration of tryptamine, 5-hydroxytryptamine, tryptophan and 5-hydroxytryptophan in rats.
General characteristics of the cardiovascular responses to intracerebroventricular (i.c.v.) injection of tryptamine, 5-hydroxytryptamine (5-HT), tryptophan and 5-hydroxytryptophan (5-HTP) were compared. Relatively small doses of tryptamine and 5-HT (0.005-0.1 microM) produced considerable, long-lasting and dose-dependent pressor effects, which sometimes were followed by prolonged depressor effects. Tryptophan (0.02-0.5 microM) and 5-HTP (0.02-0.2 microM) caused variable and usually slight, but long-lasting, vascular responses or no vascular response A large dose of tryptamine (0.5 microM) evoked variable vascular effects, while the same dose of 5-HT and 5-HTP evoked marked and prolonged depressor effects. The vascular responses to the drugs were accompanied by variable changes in heart rate. Tryptamine, 5-HT and 5-HTP, in the majority of rats, produced a bradycardia. The present study provides evidence that the cardiovascular response to i.c.v. administration of tryptamine is similar to that of 5-HT, supporting the idea that tryptamine, in addition to 5-HT, participates in the central physiological regulation of the rat cardiovascular system. The role of tryptophan and 5-HTP by themselves in this regulation, if any is of secondary importance.


Gamma glutamyl transpeptidase expression in foetal skin, inflammatory dermatoses and cutaneous neoplasia.
Gamma glutamyl transpeptidase (GGT) is an enzyme expressed by some epithelial neoplasms but not normal interfollicular epidermis. In order to examine the relationship between malignant change and de-differentiation we studied histochemically the expression of GGT in human foetal skin, various inflammatory dermatoses and epidermal neoplasms. In foetal skin GGT was detectable after 7 weeks' gestation, reached a maximum at 11 weeks and was undetectable by 24 weeks. It was expressed strongly by squamous cell carcinoma and focally in Bowen's disease and actinic keratoses. There was no GGT expression in basal cell carcinoma or most benign skin tumours, but keratoacanthomas were weakly positive. Keratinocytes in the vicinity of malignant melanocytes also expressed GGT. This study suggests that GGT expression, while not a simple marker of malignancy, may represent reversion to a less differentiated or 'foetal' phenotype.


Prevention of post-operative nausea and vomiting following laparoscopic surgery--ephedrine vs propofol.
Postoperative nausea and vomiting (PONV) are relatively common troublesome distressing symptoms. The incidence is reported to be as high as 20-51%. Ninety adult ASA I and II patients scheduled for laparoscopic gynecological or surgical interventions, were randomly and equally assigned to one of the three groups in the immediate postoperative period: Group 1 received 0.1 ml.kg(-1) normal saline intravenously, while Group 2 received 0.5 mg.kg(-1) ephedrine intramuscularly and Group 3 received 0.25 mg.kg(-1) propofol intravenously as preventive antiemetic therapy. Sixty-six, 33 and 50 percent of patients experienced nausea and vomiting syndrome in Group 1, 2 and 3 respectively. Both ephedrine and propofol proved to have antiemetic properties. Ephedrine treated group of patient had significant less emetic score than propofol. No significant hemodynamic changes were recorded in both groups.


The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines.
Staphylococcus aureus infections can lead to diseases that range from localized skin abscess to life-threatening toxic shock syndrome. The SrrAB two-component system (TCS) is a global regulator of S. aureus virulence and critical for survival under environmental conditions such as hypoxic, oxidative, and nitrosative stress found at sites of infection. Despite the critical role of SrrAB in S. aureus pathogenicity, the mechanism by which the SrrAB TCS senses and responds to these environmental signals remains unknown. Bioinformatics analysis showed that the SrrB histidine kinase contains several domains, including an extracellular Cache domain and a cytoplasmic HAMP-PAS-DHp-CA region. Here, we show that the PAS domain regulates both kinase and phosphatase enzyme activity of SrrB and present the structure of the DHp-CA catalytic core. Importantly, this structure shows a unique intramolecular cysteine disulfide bond in the ATP-binding domain that significantly affects autophosphorylation kinetics. In vitro data show that the redox state of the disulfide bond affects S. aureus biofilm formation and toxic shock syndrome toxin-1 production. Moreover, with the use of the rabbit infective endocarditis model, we demonstrate that the disulfide bond is a critical regulatory element of SrrB function during S. aureus infection. Our data support a model whereby the disulfide bond and PAS domain of SrrB sense and respond to the cellular redox environment to regulate S. aureus survival and pathogenesis.


Imaging of tumors of the trachea and central bronchi.
Tumors of the trachea and central bronchi can be benign or malignant. Clinical presentation may be confusing, particularly in benign tumors that can be misdiagnosed as asthma or chronic bronchitis. Chest radiography has many limitations and is often considered unremarkable in patients with tumors of the central airways; therefore, multidetector CT (MDCT) has become the most useful noninvasive method for diagnosing and assessing the central airways. The purpose of this article is to provide a review of imaging of the tumors of the trachea and central bronchi. We emphasize the crucial role of MDCT and postprocessing techniques in assessing neoplasms of the central airways.


Efficacy of oral acyclovir treatment of acute herpes zoster.
Oral acyclovir, 800 mg five times per day for seven days, was compared with placebo in a randomized, double-blind trial conducted at three centers in the United Kingdom. The study group consisted of 364 elderly immunocompetent patients with herpes zoster who were entered within 72 hours of the onset of rash. Acyclovir significantly reduced the times to last new lesion formation (p less than 0.01), loss of vesicles (p less than 0.01), and full crusting (p = 0.03). No significant hastening of rash healing was seen in those who started therapy later than 48 hours after the onset of rash. There was also a significant reduction pain during treatment with acyclovir (p = 0.02). Acyclovir produced no effects on the frequency or severity of post-herpetic neuralgia. No clinically important adverse effects of acyclovir were reported.


A health clinic for people with learning disabilities.
The needs of people with a learning disability are not always met due to inequalities in healthcare provision. This study set out to explore the effectiveness of a 'pop in' clinic for these clients. It was found that the clinic was used by about one third of the population under study and a wide range of health problems were dealt with as a result. The author concludes that such a clinic is an effective method of reducing inequality and that specialist health visitors are in an ideal position to provide this type of service.


Management of aromatase inhibitor induced musculoskeletal symptoms in postmenopausal early Breast cancer: A systematic review and meta-analysis.
Aromatase Inhibitors (AI) are widely used for the adjuvant treatment of hormone receptor positive breast cancers in the post-menopausal population. AI are often associated with significant joint and muscular symptoms; symptoms that are commonly referred to as aromatase inhibitor-associated musculoskeletal syndrome (AIMSS). AIMSS adversely impacts health-related quality of life of many patients, and reduces AI compliance. Although there are informal practice recommendations, the limited current level of evidence for management of AIMSS for breast cancer patients on aromatase inhibitors has made development of formal guidelines challenging, and remains an unmet need. This is the first systematic review to consider the evidence for all pharmacological and non-pharmacological interventions in the treatment of AIMSS, including physical therapy, acupuncture and complementary therapies.


Persistent constipation and abdominal adverse events with newer treatments for constipation.
Clinical trials of several new treatments for opioid-induced constipation (OIC), chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) have focused on differences between subjects relieved of constipation with placebo and active treatment. Patients and clinicians however, are more interested in the probability these treatments provide actual relief of constipation and its associated symptoms. We searched the medical literature using MEDLINE and Cochrane central register of controlled trials. Randomised, placebo-controlled trials that examined the use of methylnaltrexone, naloxegol, lubiprostone, prucalopride or linaclotide in adults with OIC, CIC and IBS-C were eligible for inclusion. The primary efficacy measure was relief of constipation. Adverse event data for abdominal symptoms were also analysed. 25 publications were included in our analyses. The proportion of constipated individuals with active treatment was significantly lower than the proportion with placebo; however, in 15 of these 20 trials analysed, a majority of patients remained constipated with active treatment. Analyses of adverse event data revealed that the percentage of participants who experienced abdominal pain, diarrhoea and flatulence with active treatment was higher than that with placebo in the majority of trials analysed. Newer pharmacological treatments for constipation are superior to placebo in relieving constipation, but many patients receiving active treatment may remain constipated. In addition, all 5 of the treatments studied are accompanied by no change or a possible increase in the prevalence of abdominal symptoms, such as abdominal pain, diarrhoea and flatulence.


Unionization, strikes, threatened strikes, and hospitals--the view from hospital management.
The history of union organizing efforts in the hospital field is discussed in this article, along with the factors judged necessary for successful union organizing. The role played by labor legislation in the unionization of hospital workers is shown, and the influences of the National Labor Relations Act, the Taft-Hartley amendments, and labor legislation at the local level are described. Management has largely resisted unionization because of the social nature of hospitals. Competitive market forces do not confront the not-for-profit hospitals, which are dependent upon third-party reimbursement. While strikes are an integral and essential part of collective bargaining in industry, they are, in fact, detrimental to hospitals because of these institutions' concern with human life. Despite laws and assurances from labor leaders that strikes will not occur, strikes have been used as a method for resolving disputes, through they are basically inconsistent with the economic characteristics and objectives of the hospital. The authors conclude that arbitration awards should be made by arbitrators appointed from outside of the local region of the hospital involved, ant that, because of the catastrophic effect of strikes upon patients as well as employees, arbitration awards should be required, should be binding upon both parties, and should be federally enforced.


[Quantification of metallothionein induced with selenium by using competitive ELISA].
Metallothionein induced by selenium was assayed with competitive ELISA. It was found that in control mice, the liver contained (2.47+/-0.90) microgram MT/g wet weight tissue, while the mice administered with ZnSO(4) contained (8.15+/-2.20) microgram MT/g wet weight liver tissue and the mice given with selenium malt contained (12.80+/-1.44) microgram MT/g wet weight liver. A significant difference was found between the control and the latter two groups (P<0.05, P<0.05). The MT content of selenium group was significantly higher than the zinc group. It is suggested that the selenium was more potent in induction of MT and was a stronger inducer than ZnSO(4) in its effective dose range, therefore selenium may be developed into a novel and safe MT inducer.


Qing-Qi Rickshaw : A Boon Or Bane For Public Transportation? A Study Of Road Traffic Injury Patterns Involving Qing-Qi Rickshaws In Karachi Pakistan.
The three-wheeler Qing-qi and Compressed Natural Gas (CNG) auto-rickshaws were introduced in Karachi to meet the transportation demand of the growing population. These vehicles have directly or indirectly been implicated in a number of road traffic violations as well as road accidents. This study aims to describe the crash characteristics and injury patterns for Qing-qi rickshaw occupants and other road users hit by Qing-qi rickshaw in Karachi, Pakistan. An Observational/ Descriptive study was conducted at Accident & Emergency and Orthopaedic Surgery Department, Jinnah Post Graduate Medical Centre, Karachi Pakistan from July 2014 to June 2015.All patients who came with Qing-qi rickshaw accident in Accident & Emergency (A&E) of JPMC were included. Crash characteristics, details of injuries, injury severity parameters and outcome were documented in detailed interviews. Four hundred and eighty-six rickshaw related injuries were noted in road traffic accidents by Qing-gi rickshaw. Age range was 2-85 (43.5±58.68). 350 injured victims were males and 136 were females. By occupation most victims were laborers and daily wage workers (45%) and students (21%). Overloading of vehicle with more than two passengers was found in (28.5%). The most common cause of injury was collision with a moving vehicle (56%), followed by fall from rickshaw. The most common contributing factor was the overloading of rickshaw and roll over on turning (61%). Injury severity on arrival were mild (49%), moderate were (32%), and severe were (19%). Injuries related to head and neck (26%), face (14%), thorax and abdomen (5%), lower extremity and pelvic girdle (31%) and upper extremity (23%) were observed. Qing-qi rickshaw injuries are common and these vehicles are vulnerable to road traffic accidents. Occupants and road users are both at risk of injuries.


[Diffuse normolipemic xanthoma planum].
We comment on the case of a 75-year-old woman whose dermatologic process had started 15 years before with the onset of xanthelasma on the lower eyelids which were surgically removed, recurring on the scar areas two months later. At the same time new lesions involved the forehead as well as the periorbital and malar regions. Some months later new yellow papular lesions appeared involving the neck, thorax, pelvis and extremities which grew eccentrically covering large areas. Five years later the lesions localized on the face and showed a progressive tendency to atrophy in their centers while those localized on the trunk showed an evolution to sclerosis of their central area. There was no mucosal involvement or ulceration in any of the xanthomatous lesions. The microscopic study revealed the existence of a dermal infiltrate formed by histiocyte foamy frothy cells and Touton cells, among which there were some lymphocytes, which occasionally adopted a perianexial, perineural and perivascular pattern but there were no signs of thrombosis or degenerative changes in the perilesional connective tissue. The study by chromatography of the lipid composition of the pathologic skin revealed an increase in cholesterol esters. The laboratory exams as well as the general physical examination performed every six months for a period of 15 years' time were always normal except for a moderate elevation of ESR which persisted throughout the process.(ABSTRACT TRUNCATED AT 250 WORDS)


Alfalfa (Medicago sativa L.).
A protocol for rapid, highly efficient transformation of alfalfa is described. Leaf explants from growth chamber-grown plants of a highly regenerable genotype are surface-sterilized, the margins are removed, and explants are inoculated with Agrobacterium tumefaciens strain LBA4404 carrying the T-DNA vector of interest. The explants and bacteria are cocultured for 7 to 8 d. Bacteria are removed by rinsing explants in sterile distilled water and by culture on regeneration medium containing the antibiotics carbenicillin or ticarcillin. Transformed callus is selected using kanamycin. Somatic embryos are induced by culture of callus on medium lacking plant growth regulators. As mature cotyledonary stage embryos arise, they are transferred to a fresh medium for shoot development and finally to a medium lacking kanamycin for continued shoot and root development. Transgenic plants can be produced in 9 wk with this protocol. Typically 60 to 80% of inoculated explants produce transgenic plants, and escapes are rare.


Direct Conversion of Fibroblast into Neurons for Alzheimer's Disease Research: A Systematic Review.
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder without a cure. Innovative disease models, such as induced neurons (iNs), could enhance our understanding of AD mechanisms and accelerate treatment development. However, a review of AD human iN studies is necessary to consolidate knowledge. The objective of this review is to examine the current body of literature on AD human iN cells and provide an overview of the findings to date. We searched two databases for relevant studies published between 2010 and 2023, identifying nine studies meeting our criteria. Reviewed studies indicate the feasibility of generating iNs directly from AD patients' fibroblasts using chemical induction or viral vectors. These cells express mature neuronal markers, including MAP-2, NeuN, synapsin, and tau. However, most studies were limited in sample size and primarily focused on autosomal dominant familial AD (FAD) rather than the more common sporadic forms of AD. Several studies indicated that iNs derived from FAD fibroblasts exhibited abnormal amyloid-β metabolism, a characteristic feature of AD in humans. Additionally, elevated levels of hyperphosphorylated tau, another hallmark of AD, were reported in some studies. Although only a limited number of small-scale studies are currently available, AD patient-derived iNs hold promise as a valuable model for investigating AD pathogenesis. Future research should aim to conduct larger studies, particularly focusing on sporadic AD cases, to enhance the clinical relevance of the findings for the broader AD patient population. Moreover, these cells can be utilized in screening potential novel treatments for AD.


The Inflammatory Cytokine Imbalance for Miscarriage, Pregnancy Loss and COVID-19 Pneumonia.
Pregnancy can be defined a vascular event upon endocrine control. In the human hemo-chorial placentation the chorionic villi penetrate the wall of the uterine spiral arteries, to provide increasing amounts of nutrients and oxygen for optimal fetal growth. In any physiological pregnancy the natural maternal response is of a Th1 inflammatory type, aimed at avoiding blood loss through the arteriolar wall openings. The control of the vascular function, during gestation as in any other condition, is achieved through the action of two main types of prostanoids: prostaglandin E2 and thromboxane on the one hand (for vasoconstriction and coagulation), prostacyclin on the other (for vasodilation and blood fluidification). The control of the maternal immune response is upon the responsibility of the fetus itself. Indeed, the chorionic villi are able to counteract the natural maternal response, thus changing the inflammatory Th1 type into the anti-inflammatory Th2. Clinical and experimental research in the past half century address to inflammation as the leading cause of abortion, pregnancy loss, premature delivery and related pulmonary, cerebral, intestinal fetal syndromes. Increased level of Interleukin 6, Interleukin 1-beta, Tumor Necrosis Factor-alfa, Interferon-gamma, are some among the well-known markers of gestational inflammation. On the other side, COVID-19 pneumonia is a result of extensive inflammation induced by viral replication within the cells of the respiratory tract. As it may happen in the uterine arteries in the absence of an effective fetal control, viral pneumonia triggers pulmonary vascular coagulation. The cytokines involved in the process are the same as those in gestational inflammation. As the fetus breathes throughout the placenta, fetal death from placental thrombosis is similar to adult death from pulmonary thrombosis. Preventing and counteracting inflammation is mandatory in both conditions. The most relevant literature dealing with the above-mentioned concepts is reviewed in the present article.


Evolution of characterized phosphorylation sites in budding yeast.
Phosphorylation is one of the most studied and important regulatory mechanisms that modulate protein function in eukaryotic cells. Recently, several studies have investigated the evolution of phosphorylation sites identified by high-throughput methods. These studies have revealed varying degrees of evidence for constraint and plasticity, and therefore, there is currently no consensus as to the evolutionary properties of this important regulatory mechanism. Here, we present a study of high-confidence annotated sites from budding yeast and show that these sites are significantly constrained compared with their flanking region in closely related species. We show that this property does not change in structured or unstructured regions. We investigate the birth, death and compensation rates of the phosphorylation sites and test if sites are more likely to be gained or lost in proteins with greater numbers of sites. Finally, we also show that this evolutionary conservation can yield significant improvement for kinase target predictions when the kinase recognition motif is known, and can be used to infer the recognition motif when a set of targets is known. Our analysis indicates that phosphorylation sites are under selective constraint, consistent with their functional importance. We also find that a small fraction of phosphorylation sites turnover during evolution, which may be an important process underlying the evolution of regulatory networks.


How spatial and feature-based attention affect the gain and tuning of population responses.
How does attention optimize our visual system for the task at hand? Two mechanisms have been proposed for how attention improves signal processing: gain and tuning. To distinguish between these two mechanisms we use the equivalent-noise paradigm, which measures performance as a function of external noise. In the present study we explored how spatial and feature-based attention affect performance by assessing their threshold-vs-noise (TvN) curves with regard to the signature behavioral effects of gain and tuning. Furthermore, we link our psychophysical results to neurophysiology by implementing a simple, biologically-plausible model to show that attention affects the gain and tuning of population responses differentially, depending on the type of attention being deployed: Whereas spatial attention operates by boosting the gain of the population response, feature-based attention operates by both boosting the gain and sharpening the tuning of the population response.


Transfusion-Related Acute Lung Injury (TRALI) in Postoperative Anesthesia Care Unit (PACU) After One Unit of Platelets: A Case Report.
Transfusion-related acute lung injury (TRALI) following transfusion of all plasma-containing blood products is a rare but serious syndrome characterized by the acute onset of non-cardiogenic pulmonary edema with severe hypoxemia with or without symptoms of hypotension, pinkish frothy secretions, fever, and cyanosis. In this report, we present a case of a 66-year-old female with a medical history significant for hypertension, hyperlipidemia, hepatitis C, liver cirrhosis, tobacco use disorder, metastatic spindle cell carcinoma of the lung status post chemotherapy who developed TRALI after administration of one unit of platelets. Although a rare occurrence, there can be a considerable risk of TRALI following transfusion of all plasma-containing blood products and there is great importance in considering each patient's risk factors for TRALI development prior to blood product administration.


Antibodies to deamidated gliadin peptide in diagnosis of celiac disease in children.
Determination of antibodies to synthetic deamidated gliadin peptides (anti-DGPs) may work as an alternative or complement the commonly used test for tissue transglutaminase antibodies (TGA) in the diagnosis of celiac disease (CD). We analyzed the performance of a time-resolved immunofluorometric anti-DGP assay (TR-IFMA) in the diagnosis of CD in children and also retrospectively analyzed the appearance of anti-DGP antibodies before TGA seroconversion. The study included 92 children with biopsy-confirmed CD. Serum samples were taken at the time or just before the clinical diagnosis. The control group comprised 82 TGA-negative children who were positive for human leucocyte antigen-DQ2 or -DQ8. Based on receiver operating characteristic curves, the optimal cutoff value for immunoglobulin (Ig) A anti-DGP positivity was 153 arbitrary units (AUs) with a sensitivity of 92.4% and specificity of 97.6% and that for IgG anti-DGP 119 AU, with a sensitivity of 97.8% and specificity of 97.6%. All 92 children with CD were either IgA or IgG anti-DGP positive at the time of diagnosis. Sera from 48 children with CD were also analyzed retrospectively before the diagnosis. Anti-DGP antibodies preceded TGA positivity in 35 of the 48 children with CD and appeared a median of 1 year earlier. The TR-IFMA assay for detecting anti-DGP antibodies shows high sensitivity and specificity for the diagnosis of CD in children. In a majority of our study population, anti-DGP seropositivity preceded TGA positivity, indicating that earlier detection of CD may be possible by monitoring anti-DGP antibodies frequently in genetically susceptible children.


Ruptured bicornuate uterus mimicking ectopic pregnancy: A case report.
Ruptured uterus presenting in first trimester of pregnancy is extremely uncommon and should raise the suspicion of uterine malformations. We report a case of a 24-year-old primigravida with 10 weeks of gestation presenting with acute abdomen and hemoperitoneum. Laparotomy revealed bicornuate uterus with ruptured rudimentary horn. The incidence, diagnosis and management of such cases is discussed.


Clinical use of octreotide in unresectable meningiomas. A report of three cases.
Unresectable meningioma is the cause of a serious clinical problem, for whom no satisfactory mode of treatment is currently available. Meningiomas are known to have receptors for diverse hormones. In this sense, somatostatin receptors were found in every meningioma specimen studied in a recent report. In addition, somatostatin has been able to inhibit meningioma cell proliferation in vitro. A brief report of clinical use of somatostatin long-life analogue octreoctide upon three patients diagnosed of unresectable meningioma is here presented. Doses used were gradually increased up to 1000, 900 and 1500 micrograms/24 h during 16, 6 and 7 weeks, respectively. There was an almost perfect tolerance to the drug (in one case a mild and transient abdominal discomfort and diarrhea could be observed). An important alleviation of headaches in 2 cases, and a transient but objective improvement in ocular movements and signs in 1 case were noticed. No change (neither growth nor shrinkage) was observed by CT scan at the end of treatment course in the three cases studied. In 1 case a partial resection was performed and tissue specimen was found to contain somatostatin receptors. Although in our very limited experience no brilliant results are presented, duration of treatment or doses used could have been insufficient. Data herein presented seem to support recently reported findings in which no growth inhibition of meningioma cells cultured in vitro by adding octreoctide to the medium was observed. So, in our opinion, clinical use of octreoctide on unresectable meningioma deserves further experience, that must be carried out with great caution.


[Preoperative halo-traction in severe paralytic scoliosis].
During the past decades the treatment of severe paralytic scoliosis has developed towards surgical treatment. However there is controversial discussion about the need of pre-operative Halo-traction. The aim of this study was to built two groups of patients -- one group with and another one without pre-operative Halo-traction -- and to compare the results after surgical correction of scoliotic deformity with data from literature. Between 2000-2003 twenty-five patients with severe neuromuscular spine deformity were treated surgically. Eight patients had preoperative Halo-traction, seventeen patients underwent directly operative correction and instrumentation. The evaluation included the pre- and postoperative X-rays as well those after Halo-traction before surgery. In the group without Halo-traction the scoliotic angle according to Cobb was reduced from 77 degrees to 33 degrees on average (mean correction of 44 degrees [57 %]). In the group with Halo-traction scoliosis was reduced from 85 degrees to 33 degrees on average (mean correction of 52 degrees [61 %]). The preoperative Halo-traction in patients with severe neuromuscular scoliosis indeed leads to radiologically higher correction, but this is not significant (p = 0.19) and only in single cases clinically relevant. In our point of view except from specific indications Halo-traction should not be applied in general as a standard procedure.


Tacrolimus as a steroid-sparing agent for adults with steroid-dependent minimal change nephrotic syndrome.
Treatment of adults with steroid-dependent minimal change nephrotic syndrome (SD-MCNS) can be a significant challenge. Cyclophosphamide (CYC) and cyclosporin (CYA) are often effective steroid-sparing agents. Tacrolimus (TAC) may be another treatment option. This open, prospective cohort study enrolled Chinese adults with SD-MCNS. At the start of the study, we administered TAC or intravenous CYC together with prednisone (0.5 mg/kg/day), the dose of which was tapered off throughout the study. The TAC cohort received oral TAC (target trough blood level of 4-8 ng/ml) for 24 weeks and the CYC cohort received intravenous CYC (750 mg/m(2) body surface) once every 4 weeks for 24 weeks. Twenty-six patients met the criteria for enrollment (14 patients in the CYC group and 12 patients in the TAC group). One patient from each group discontinued treatment because of a drug-related side effect. Complete remission (CR) after the 24-week therapeutic period was 76.9% (10/13) in the CYC group and 90.9% (10/11) in the TAC group. The mean time required for CR in the TAC group was significantly less than in the CYC group (P = 0.031). Eight of 13 (61.5%) patients in the CYC group and 8 of 11 (72.7%) patients in the TAC group successfully stopped steroids and changed their status from steroid dependence. Sixty percent (6/10) of the CYC patients and 50% (5/10) of the TAC patients who achieved CR maintained remission during the follow-up period of 23.0 +/- 10.1 months. Four (40%) CYC patients and five (50%) TAC patients experienced relapses, and two CYC patients experienced frequent relapses. A 24-week course of TAC is a favorable steroid-sparing agent for treatment of Chinese adults with SD-MCNS. Therapy with TAC accompanied by a tapering dose of prednisolone appears to yield quicker remission than treatment with CYC together with prednisone.