Recent increase of genetic diversity in Plasmodium vivax population in the Republic of Korea.
The reemergence of Plasmodium vivax in South Korea since 1993 represents a serious public health concern. Despite the importance in understanding genetic diversity for control strategies, however, studies remain inconclusive with the general premise that due to low rate of malaria transmission, there is generally low genetic diversity with very few strains involved. In this study, the genetic diversity and population structure of P. vivax in South Korea were explored by analysing microsatellite polymorphism. Sequences for 13 microsatellite loci distributed across the twelve chromosomes of P. vivax were obtained from 58 South Korean isolates collected during two sampling periods, namely 1997-2000 and 2007. The sequences were used for the analysis of expected heterozygosity and multilocus genotype diversity. Population structure was evaluated using STRUCTURE version 2.3.2. Linkage disequilibrium was also analysed to investigate the extent of outbreeding in the P. vivax population. Mean expected heterozygosity significantly increased from 0.382 in 1997-2000 to 0.545 in 2007 (P < 0.05). The number of multilocus genotypes was 7 and 27; and genotype diversity was statistically significant (P < 0.01) at 0.661 and 0.995 in 1997-2000 and 2007, respectively. Analysis by STRUCTURE showed a more complex population structure in 2007 than in 1997-2000. Linkage disequilibrium between 13 microsatellites, although significant in both time points, was notably lower in 2007. The present microsatellite analysis clearly showed recent increase of genetic diversity and recent relaxation of the strong population structure observed in 1997-2000. These results suggest that multiple genotypes not present previously recently migrated into South Korea, accompanied by substantial outbreeding between different genotypes.


Effectiveness of a computer-based system to deliver a continence health promotion intervention.
The objective of this study was to test a computer-based system for continence health promotion that included self-management techniques for women with symptoms of involuntary urine loss, urinary frequency or urgency, or nocturia. A quasi-experimental trial design with repeated measures was used. Older women (n = 71) with continence problems were recruited and completed a computer session. Outcomes were measured with the Urogenital Distress Inventory-Short Form, the Incontinence Impact on Life Questionnaire-Short Form, and a bladder diary. A modified Questionnaire for User Interface Satisfaction was used to measure satisfaction with the system. Participants assigned to the intervention group (n = 36) used the computer-based system for continence health promotion, and those in the wait list control group (n = 35) used an alternate system. Data were collected at baseline and 8 weeks after the computer session. Analysis of covariance results on symptom distress and quality of life scores showed no significant treatment effect, although a trend toward improvement was observed. The intervention group improved significantly on urogenital distress (P = .01) and quality of life (P = .003) outcomes, but the control group did not. Women had little difficulty using the system and expressed satisfaction with the individualized information provided. Although the computer-based system did not result in significantly improved outcomes when comparing women in the 2 groups, the computer-based group improved significantly from baseline to follow-up. Further research on a computer-based system that women could access independently or that nurses could use to supplement traditional care is warranted.


Substance Use Among Current and Former Foster Youth: A Systematic Review.
Substance use tends to escalate across adolescence and into young adulthood, and can be intensified by experiences with trauma and maltreatment, mental illness, and exposure to parental alcohol and drug use. Despite the disproportionately high levels of these variables among youth placed in the foster care system, relatively few studies have focused on the measurement of substance use in this vulnerable population. The current review summarizes the published literature on alcohol and drug outcomes for current and former foster youth. Specifically, prevalence of use and diagnoses are presented separately, as well as a review of risk and protective factors. Discussion of results addresses limitations and suggestions for improvement in the measurement of these outcome variables.


Comparison of plasmapheresis and molecular adsorbent recirculating system efficacy in graft failure after living donor liver transplantation.
Liver transplantation may result in graft failure, requiring time and supportive treatment for regeneration of the graft. The aim of this study was to compare the laboratory parameter changes after single-session molecular adsorbent recirculating system (MARS) and plasmapheresis procedures among living donor liver transplantation patients experiencing graft failure. We analyzed retrospectively the results in 45 liver transplantation patients treated with plasmapheresis and/or MARS between June 2011 and July 2012: (plasmapheresis, n = 17; MARS, n = 15; MARS + plasmapheresis, n = 13). When cadaveric donor cases (n = 11) were excluded, the remaining 34 included patients, underwent. MARS (n = 18) or plasmapheresis (n = 16) at the first session. Both groups were similar in age, sex, and body mass index features. The MARS group displayed significantly higher levels of international normalized ratio, blood urea nitrogen, and Model for End-stage Liver Disease score. The plasmapheresis cohort, displayed significantly higher levels of initial direct bilirubin and gamma glutamyl transferase (P < .05). The plasmapheresis group showed a significant decrease in GGT after treatment (P < .05). An initial MARS session provided significantly greater decrease in renal function associated with graft failure after living donor liver transplantation.


First signature of islet beta-cell-derived naturally processed peptides selected by diabetogenic class II MHC molecules.
The diversity of Ags targeted by T cells in autoimmune diabetes is unknown. In this study, we identify and characterize a limited number of naturally processed peptides from pancreatic islet beta-cells selected by diabetogenic I-A(g7) molecules of NOD mice. We used insulinomas transfected with the CIITA transactivator, which resulted in their expression of class II histocompatibility molecules and activation of diabetogenic CD4 T cells. Peptides bound to I-A(g7) were isolated and examined by mass spectrometry: some peptides derived from proteins present in secretory granules of endocrine cells, and a number were shared with cells of neuronal lineage. All proteins to which peptides were identified were expressed in beta cells from normal islets. Peptides bound to I-A(g7) molecules contained the favorable binding motif characterized by acidic amino acids at the P9 position. The draining pancreatic lymph nodes of prediabetic NOD mice contained CD4 T cells that recognized three different natural peptides. Furthermore, four different peptides elicited CD4 T cells, substantiating the presence of such self-reactive T cells. The overall strategy of identifying natural peptides from islet beta-cells opens up new avenues to evaluate the repertoire of self-reactive T cells and its role in onset of diabetes.


Temporal dynamics in mental health symptoms and loneliness during the COVID-19 pandemic in a longitudinal probability sample: a network analysis.
Figuring out which symptoms are central for symptom escalation during the COVID-19 pandemic is important for targeting prevention and intervention. Previous studies have contributed to the understanding of the course of psychological distress during the pandemic, but less is known about key symptoms of psychological distress over time. Going beyond a pathogenetic pathway perspective, we applied the network approach to psychopathology to examine how psychological distress unfolds in a period of maximum stress (pre-pandemic to pandemic onset) and a period of repeated stress (pandemic peak to pandemic peak). We conducted secondary data analyses with the Understanding Society data (N = 17,761), a longitudinal probability study in the UK with data before (2019), at the onset of (April 2020), and during the COVID-19 pandemic (November 2020 & January 2021). Using the General Health Questionnaire and one loneliness item, we computed three temporal cross-lagged panel network models to analyze psychological distress over time. Specifically, we computed (1) a pre-COVID to first incidence peak network, (2) a first incidence peak to second incidence peak network, and (3) a second incidence peak to third incidence peak network. All networks were highly consistent over time. Loneliness and thinking of self as worthless displayed a high influence on other symptoms. Feeling depressed and not overcoming difficulties had many incoming connections, thus constituting an end-product of symptom cascades. Our findings highlight the importance of loneliness and self-worth for psychological distress during COVID-19, which may have important implications in therapy and prevention. Prevention and intervention measures are discussed, as single session interventions are available that specifically target loneliness and worthlessness to alleviate mental health problems.


Potentiation of colonic contractility to cholecystokinin and other peptides.
Changes in colonic contractility were studied in anesthetized cats following the intravenous injection of several peptides. Increases in contractile activity were observed after the octapeptide of cholecystokinin (CCK-8), pentagastrin, substance P or neurotensin. On the other hand, vasoactive intestinal peptide (VIP) caused an inhibition which, in some cases, was followed by an excitatory response. The responses produced by pentagastrin, substance P or neurotensin, but not by CCK-8, were partially inhibited by atropine. Following bethanechol pretreatment, the stimulation in contractile activity elicited by CCK-8, substance P, neurotensin or pentagastrin was markedly enhanced. Responses were also increased by pretreatment with eserine, hexamethonium or mecamylamine. This potentiation was blocked by atropine. It is concluded that, following treatments which cause an increase in the level of cholinergic input to the colon, an exaggerated motor response to some peptides can develop.


Enhancing cognitive control in amnestic mild cognitive impairment via at-home non-invasive neuromodulation in a randomized trial.
Individuals with multi-domain amnestic mild cognitive impairment (md-aMCI) have an elevated risk of dementia and need interventions that may retain or remediate cognitive function. In a feasibility pilot study, 30 older adults aged 60-80 years with md-aMCI were randomized to 8 sessions of transcranial alternating current stimulation (tACS) with simultaneous cognitive control training (CCT). The intervention took place within the participant's home without direct researcher assistance. Half of the participants received prefrontal theta tACS during CCT and the other half received control tACS. We observed high tolerability and adherence for at-home tACS + CCT. Within 1-week, only those who received theta tACS exhibited improved attentional abilities. Neuromodulation is feasible for in-home settings, which can be conducted by the patient, thereby enabling treatment in difficult to reach populations. TACS with CCT may facilitate cognitive control abilities in md-aMCI, but research in a larger population is needed to validate efficacy.


Different sources of acidity in glucose-elicited extracellular acidification in the yeast Saccharomyces cerevisiae.
Three wild-type strains of Saccharomyces cerevisiae, viz. K, Y55 and sigma 1278b, two mutants lacking one or both of the putative K+ transporters, trk1 delta and trk1 delta trk2 delta, and a mutant in the plasma membrane H(+)-ATPase, viz. pma1-105, were compared in their extracellular acidification following addition of glucose and subsequent addition of KCl; in ATPase activity in purified plasma membranes; and in respiration on glucose. The glucose-induced acidification was the greater the higher the respiratory quotient, i.e. the higher the anaerobic metabolism. A markedly lower acidification was found in the ATPase-deficient pma1-105 strain but also in the TRK-deficient double mutant. The acidification pattern after addition of KCl corresponds to expectations in the TRK mutants; however, a similarly decreased acid production was found in the ATPase-deficient mutant pma1-105. The highest rate of ATP hydrolysis in vitro was found with the trk1 delta trk2 delta mutant where glucose-, as well as KCl-induced acidification were lowest. Likewise, the pma1-105 mutant with extremely low acidification showed only a minutely lower ATP hydrolysis than did its parent Y55 strain. Apparently, several different sources of acidity are involved in the glucose-induced acidification (including extrusion of organic acids); in fact, contrary to the general belief, the H(+)-ATPase may play a minor role in this process in some strains.


Estimation of three-dimensional cardiac velocity fields: assessment of a differential method and application to three-dimensional CT data.
We have investigated an optical flow method for the estimation of the three-dimensional endocardial wall motion from high-resolution X-ray CT data. This method was originally proposed by Song and Leahy. It is based on the optical flow, the divergence-free and the smoothness constraints. Due to the characteristics of the imaging modality, we studied the restriction of this approach to the boundary of the left ventricular (LV) cavity. The behaviour of the method is quantified through simulations approximating the overall motion of the LV cavity through an affine transform involving a dilation and a rotation. The method implies the choice of three parameters weighting the constraints. The results show a weak dependence of the velocity field on the weighting of the optical flow constraint. The accuracy of the method relies more heavily on the relative weighting of the smoothness and divergence-free constraints. In our experiments, the best results were obtained for a largely predominant divergence-free constraint. The results also show that the accuracy of the method is reasonable for low values of the rotation angle (minimum mean error of 1.1 voxel for 5 degrees). This is compatible with values reported in other studies for the overall rotation of the LV. We provide a qualitative description of the results obtained in vivo on a canine heart by visualizing the distribution of the estimated velocity vector magnitudes over the endocardial surface. These results (evolution of the field over time, maximum velocities) are in agreement with the known physiological behaviour of the heart.


Repeated central administration of selegiline attenuated morphine physical dependence in rat.
Long-term exposure to opiates induces physical dependence; however, the neurobiological mechanisms of this phenomenon are not completely clear. The purpose of this study was to evaluate the effects of systemic and intracerebroventricular (icv) administration of selegiline (a selective inhibitor of monoamine oxidase B) on the morphine withdrawal syndrome in rats. To this aim, adult male Sprague Dawley rats were selected randomly, and then growing doses of morphine were administered subcutaneously at an interval of 12 h for nine days with the intention of inducing dependency. Nine days after, only the morning dose of morphine was administered, followed by systemic or central injection of saline or selegiline. Later, naloxone was injected after 30 min and withdrawal signs recorded for a period of 60 min. Results showed failure of systemic administration of selegiline in changing the withdrawal symptoms; nevertheless, icv injection attenuated the withdrawal signs significantly. In conclusion we found that central administration of selegiline attenuated morphine withdrawal symptoms.


From aquatic to terrestrial food webs: decrease of the docosahexaenoic acid/linoleic acid ratio.
Fatty acid composition of the adipose tissue of six carnivorous mammalian species (European otter Lutra lutra, American mink Mustela vison, European Mink Mustela lutreola, European polecat Mustela putorius, stone marten Martes foina and European wild cat Felis silvestris) was studied. These species forage to differing degrees in aquatic and terrestrial food webs. Fatty acid analysis revealed significant differences in polyunsaturated fatty acid composition between species. More specifically, our results underline a gradual significant decrease in the docosahexaenoic acid (DHA)/linoleic acid (LNA) ratio of carnivore species as their dependence on aquatic food webs decreases. In conclusion, the use of the DHA/LNA ratio in long-term studies is proposed as a potential proxy of changes in foraging behaviour of semi-aquatic mammals.


Increased Incidence of Ulcerative Laryngitis During Spring 2022 Omicron-Variant Wave of COVID19.
Ulcerative laryngitis is a distinctive condition which typically follows illness with severe cough, and is characterized by dysphonia, ulcerative lesions of the vocal folds, and a prolonged clinical course. We present four patients with ulcerative laryngitis who presented in close succession amid the surge in omicron-variant COVID19 cases. Retrospective review. Patient records for patients with ulcerative laryngitis from April and May 2022 were reviewed and compared with patients who presented with the same diagnosis from January 2017 through March 2022. Incidence, patient demographics, occupation, vaccination status, disease history, and treatment were obtained and compared. Four patients presented with ulcerative laryngitis over six weeks. Compared to the previous 4 years, this represented an eight-fold increase in monthly incidence. Average time from symptom onset to presentation was 15 days. All patients presented with dysphonia, with an average VHI10 of 23 and SVHI10 of 28. Two patients were COVID positive, one negative, and one had unknown COVID status. Three patients were fully vaccinated while one patient had only received one dose. Treatments included voice rest, steroids, antibiotics, antireflux medicine, and cough suppressants. Clinical course tended to be shorter and outcomes similar to the comparison group. The incidence of ulcerative laryngitis appeared to increase markedly with the prevalence of omicron-variant COVID19. Potential explanations include the apparent upper airway focus of omicron infection in contrast with prior variants and/or change in COVID19 infection characteristics in a vaccinated population.


Lorcainide for the treatment of refractory ventricular tachycardia: clinical and electrophysiologic results.
The electrophysiologic effects and antiarrhythmic efficacy of lorcainide were evaluated using programmed electrical stimulation (PES) in 14 patients with ventricular tachycardia (VT) refractory to conventional drug therapy. Lorcainide was administered orally (200-400 mg/d, eight patients), intravenously (150 mg/d, one patient), or by both routes (250-380 mg/d, five patients) prior to PES. In 13 patients undergoing both control and lorcainide PES, lorcainide increased the QRS duration (102 +/- 28 to 125 +/- 28 ms, P less than .001) and the QTc interval (430 +/- 39 to 471 +/- 32 ms, P less than .01) but had no effect on the RR interval (786 +/- 156 to 780 +/- 172 ms, P greater than .2). The right ventricular effective refractory period increased from 258 +/- 8 to 285 +/- 22 ms (P less than .001). Lorcainide prevented VT induction or resulted in induction of only well-tolerated, nonsustained VT in six of 14 patients (43%). The cycle length of induced VT increased from 264 +/- 32 to 306 +/- 34 ms (P less than .01). Of six patients started on chronic therapy, four still receive lorcainide after 18 +/- 7 months. Adverse effects have consisted mainly of sleep disturbances. Thus, it can be stated that lorcainide is effective in certain patients with VT refractory to conventional therapy.


Posttraumatic arteriovenous fistula and subclavian vein thrombosis: treatment by percutaneous arterial embolization and vein angioplasty.
A 71-year-old woman had edema and venous dilatation of her upper right limb that caused painful functional disability following a shoulder injury. Arteriograms demonstrated an arteriovenous fistula between the subclavian artery and vein associated with thrombosis of the vein at the same level. The arteriovenous fistula was found to have multiple arteriovenous communications. Because of associated distal venous thrombosis, venous drainage was retrograde through the brachial vein. The inflow arteries of the fistula were embolized and then the subclavian vein thrombosis was recanalized, dilated, and an endoluminal stent inserted. Clinical signs completely resolved.


The cost-effectiveness of tailored, postal feedback on general practitioners' prescribing of pharmacotherapies for alcohol dependence.
The aims of this study were to conduct a randomised controlled trial to evaluate the cost-effectiveness of tailored, postal feedback on general practitioners' (GPs) prescribing of acamprosate and naltrexone for alcohol dependence relative to current practice and its impact on alcohol dependence morbidity. Rural communities in New South Wales, Australia, were randomised into experimental (N=10) and control (N=10) communities. Tailored feedback on their prescribing of alcohol pharmacotherapies was mailed to GPs from the experimental communities (N=115). Segmented regression analysis was used to examine within and between group changes in prescribing and alcohol dependence hospitalisation rates compared to the control communities. Incremental cost-effectiveness ratios (ICERs) were estimated per additional prescription of pharmacotherapies and per alcohol dependence hospitalisation(s) averted. Post-intervention changes, relative to the control communities, in GPs' prescribing rate trends in the experimental communities significantly increased for acamprosate (β=0.24, 95% CI: 0.13-0.35, p<0.001), and significantly decreased for naltrexone (β = -0.12, 95% CI: -0.17 to -0.06) per quarter. Quarterly hospitalisation trend rates for alcohol dependence, as principal diagnosis, significantly decreased (β=-0.07, 95% CI: -0.13 to -0.01, p<0.05), compared to control communities. The median ICER per quarterly hospitalisation(s) averted due to intervention was dominant (dominant--$12,750). Postal, tailored feedback to GPs on their prescribing of acamprosate and naltrexone for alcohol dependence was a cost-effective intervention, in rural communities of NSW, to increase the overall prescribing of pharmacotherapies with a plausible effect on incidence reduction of hospitalisations for alcohol dependence as principal diagnosis.


Alloantigen-specific type 1 regulatory T cells suppress through CTLA-4 and PD-1 pathways and persist long-term in patients.
Type 1 regulatory T (Tr1) cells are inducible, interleukin (IL)-10+FOXP3− regulatory T cells that can suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have optimized an in vitro protocol to generate a Tr1-enriched cell product called T-allo10, which is undergoing clinical evaluation in patients with hematological malignancies receiving a human leukocyte antigen (HLA)–mismatched allo-HSCT. Donor-derived T-allo10 cells are specific for host alloantigens, are anergic, and mediate alloantigen-specific suppression. In this study, we determined the mechanism of action of T-allo10 cells and evaluated survival of adoptively transferred Tr1 cells in patients. We showed that Tr1 cells, in contrast to the non-Tr1 population, displayed a restricted T cell receptor (TCR) repertoire, indicating alloantigen-induced clonal expansion. Tr1 cells also had a distinct transcriptome, including high expression of cytotoxic T lymphocyte–associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Blockade of CTLA-4 or PD-1/PD-L1 abrogated T-allo10–mediated suppression, confirming that these proteins, in addition to IL-10, play key roles in Tr1-suppressive function and that Tr1 cells represent the active component of the T-allo10 product. Furthermore, T-allo10–derived Tr1 cells were detectable in the peripheral blood of HSCT patients up to 1 year after T-allo10 transfer. Collectively, we revealed a distinct molecular phenotype, mechanisms of action, and in vivo persistence of alloantigen-specific Tr1 cells. These results further characterize Tr1 cell biology and provide essential knowledge for the design and tracking of Tr1-based cell therapies.


No detectable cytomegalovirus and Epstein-Barr virus genomes in the pancreas of recent-onset IDDM patients.
Viral infection is assumed to trigger or exacerbate autoimmune responses against pancreatic beta cells leading to the development of insulin-dependent diabetes mellitus (IDDM). We therefore examined by polymerase chain reaction the presence of two candidate viruses, cytomegalovirus and Epstein-Barr virus, in IDDM pancreases. Pancreas tissues were obtained by biopsy under laparoscopy from 16 recent-onset IDDM patients: age 17-53 years; disease duration 0-7 months; six had flu-like symptoms before onset. Frozen sections were made and subjected to DNA amplification. DNA samples were prepared from the frozen sections and polymerase chain reaction was performed using primers specific to cytomegalovirus, Epstein-Barr virus and control gene for HLA-DP. Cytomegalovirus- and Epstein-Barr virus-infected cells were used for positive control. Southern blot analysis could detect cytomegalovirus DNA from as few as 2 x 10(-1) cytomegalovirus-infected cells and Epstein-Barr virus DNA from two Epstein-Barr virus-infected cells. This highly sensitive analysis, however, could not detect cytomegalovirus or Epstein-Barr virus genomes in pancreases of recent-onset IDDM. A single copy human gene (HLA-DP) was amplified from all IDDM pancreases indicating that DNA amplification was performed without inhibition. We conclude that cytomegalovirus or Epstein-Barr virus genomes are unlikely to exist in pancreas biopsy specimens of recent-onset IDDM patients.


Remission of giant lymph node hyperplasia with anemia after radiotherapy.
We have described a 51-year-old patient with unresectable mesenteric giant lymph node hyperplasia of the plasma cell type, severe systemic manifestations, and profound anemia. Supression of erythropoiesis may have been related to the presence of a circulating erythropoietic inhibitor produced by the lymphoid tumor. Markedly elevated titers to Epstein-Barr virus capsid antigen suggest that this virus may be important in the etiology of the abnormal lymphoid proliferation. The marked clinical response and decrease in the size of the tumor following irradiation suggests that radiation therapy may be an alternative form of treatment for similar patients with unresectable lesions.


Homodigital Pedicled Digital Artery Perforator flaps for fingertip reconstruction - a review of flap options.
Digital artery perforator flaps provide a useful option for reconstruction of soft tissue defects of the digits, and many variations of these flaps have been described for fingertip defects. This review aims to summarize various pedicled digital artery perforator flap anatomical configurations described in literature for fingertip reconstruction and their results. A literature review of PubMed, Medline and Embase databases was conducted. Studies reporting homodigital digital artery perforator flaps for fingertip reconstruction without sacrificing the proper digital artery were included in the review. Data collected included flap design, perforator location, pathology, defect location, flap dimensions, flap survival, sensory recovery, range of movement, outcome measures, and complications. The flaps were analysed and categorized based on flap location, flap design, transfer method, and flap innervation. Pedicled digital artery perforators have been described in various configurations by different authors including propeller, bilobed, V-Y advancement, rotation and turnover flaps. Variations to make these flaps sensate have also been described. According to the available reports, these flaps have low complications and high patient satisfaction rates. Pedicled digital artery perforator flaps provide a versatile option for the reconstruction of fingertip and thumb tip defects. Various flap options are available for use depending on the reconstructive need. They are quicker and easier to perform than free flaps and can provide excellent outcomes in suitable cases.


Radial scanning technique for volume selective 31P spectroscopy.
An interlaced radial scanning method that is ideally suited for 31P spectroscopy with short T2 components and a wide spectral range is presented. The proposed method, which uses an additional radial gradient and radial scans in the k-space, minimizes T2 decay during the selection time and also optimizes the volume selectivity in a given gradient field strength. Simulation and experimental results with a short selection time of 2 ms demonstrate that the proposed method is suitable for volume selective 31P spectroscopy.


Layer-by-layer self-assembly xylenol orange functionalized CdSe/CdS quantum dots as a turn-on fluorescence lead ion sensor.
A new turn-on fluorescence sensor based on xylenol orange (XO) functionalized CdSe/CdS quantum dots (QDs) is developed for the determination of lead ion. CdSe/CdS QDs were first modified by mercaptoacetic acid (MAA). The MAA-modified QDs were then capped with the natural biopolymer chitosan and the negatively charged XO. The XO-functionalized QDs were formed via the layer-by-layer self-assembly reaction. The fluorescence of the QDs was quenched by electron transfer mechanism after XO was bound to the QDs. Upon the addition of Pb(2+), a dramatic enhancement of the fluorescence intensity was observed, which resulted from the coordination between Pb(2+) and XO on QDs surface and the disruption of the electron transfer mechanism. Hence the fluorescence of the QDs was recovered. The recovery of the fluorescence intensity showed a good linear relationship with the concentration of Pb(2+) added from 0.05 to 6 μmol L(-1). A detection limit of 0.02 μmol L(-1) was achieved. This method was successfully applied to the determination of lead in real samples with satisfactory results.


Form function of sulcus acusticus of the sagittal otolith in seven Sciaenidae (Acanthuriformes) species using geometric morphometrics (southwestern Atlantic).
The morphology of otoliths determines the function they perform, and it is influenced by genetic and environmental factors. Knowing those relationships is necessary to understand the role of hearing in fish. The objectives of this work were: exploring the shape of the sulcus of the sagittal otolith in seven species of Sciaenidae, in relation to sound production, and analyzing whether the shape and size of the sulcus can be used as a phylogenetic character. For this purpose, geometric morphometry analysis was carried out using landmarks data. It was found that there is an influence of size on the shape of the sulcus, and significant differences were found between the shapes of the sulcus (permutational multivariate analysis of variance). Three general shapes of the sulcus were identified (using principal component analysis, canonical variate analysis, and clustering): (1) in species that produce sounds at dominant frequencies <350 Hz, the deformation of the sulcus showed a tendency towards circularity of the ostium; (2) in those species that produce sounds at frequencies >350 Hz, the ostium showed a flattened ovoid shape, and the cauda increased its length; (3) the species that do not produce sounds, did not show any modifications, relative to the form of consensus. Despite finding sister species that presented similar sulcus shapes in the phylogeny, the results did not confirm that this can be used as a phylogenetic character. This work discusses whether the combined effects of phylogenetic legacy and natural functional selection have led to convergent evolution for the sulcus form. The differences presented by the sulcus of species that occupy the same clade, could indicate that there is a displacement of characters. The sagittal otolith and the sensory macula associated with the sulcus acusticus are highly plastic structures that are subject to strong evolutionary pressure in relation to environmental and behavioral factors, resulting in great variability in shapes that can be associated with a specific character. The variation in the shape of the sulcus would allow the analysed species to coexist in the same coastal soundscapes, without losing their particular hearing needs, even in case of overlapping their spatial and temporal distribution areas.


Lay facilitators as effective smoking cessation counselors.
The present study assessed the relative effectiveness of doctoral counseling students and lay facilitators in conducting smoking cessation programs. Subjects (55 women and 61 men) were randomly assigned to doctoral or to lay facilitators. Consistent with prediction, lay facilitators were at least as effective as doctoral students. Overall results were comparable to those obtained in previous work in this laboratory. Allowing a choice of preparation technique may in itself enhance treatment outcome. The ability of lay facilitators to achieve clinically effective results provides further support for the generalizability of treatment to community settings.


p53 gene mutations in non-small cell lung cancer detected by polymerase chain reaction single-strand conformation polymorphism analysis.
Mutations of the p53 tumor suppressor gene are the most frequent genetic alterations detected in human lung cancer. To assess the pathogenic significance of p53 gene alterations in Chinese non-small cell lung cancer (NSCLC), 74 paired samples of primary lung cancer and normal lung tissue far away from the cancer were analyzed for mutations of the p53 gene (exons 5-8) using exon-specific PCR, single-strand conformation polymorphism (PCR-SSCP). p53 mutations were observed in 55.4% (41/74) of the samples. No linkages were detected between the incidence of p53 mutations and histological type, lymph node metastasis, age or sex. Significant association between p53 mutations and degree of differentiation in adenocarcinomas, not in squamous cell carcinomas, was observed. The frequency of p53 mutations in smokers (65.3%) was higher than in nonsmokers (33.3%) and reached statistical significance. We also found p53 mutations in 6/7 samples which had tissue invasion and distant metastasis. These results suggest that smoking could be an important factor in lung carcinogenesis, p53 mutation is a worse prognosis indicator in adenocarcinomas and related to high aggressive behavior of human lung cancer.


Pd-catalyzed [3 + 2] cycloaddition of vinylcyclopropanes with 1-azadienes: synthesis of 4-cyclopentylbenzo[e][1,2,3]oxathiazine 2,2-dioxides.
The palladium-catalyzed [3 + 2] cycloaddition of vinylcyclopropanes and 1-azadienes has been developed under mild reaction conditions, giving the multisubstituted cyclopentane derivatives in good to excellent yields with moderate to good diastereoselectivities. The relative configuration of both diastereomers of the products have been determined through X-ray crystallographic diffraction.


Pain management during radiotherapy and radiochemotherapy in oropharyngeal cancer patients: single-institution experience.
Radiotherapy (RT) is a radical therapeutic option for patients with oropharyngeal cancer (OPC). It induces an acute postradiation reaction that may cause significant pain. The aim of this study was to analyse pain occurrence and intensity, as well as type and effectiveness of analgesic treatment, in OPC patients undergoing RT or radiochemotherapy (RT-CT). Retrospective data were obtained for 42 OPC patients at clinical stages I-IVA, treated with adjuvant RT or RT-CT or definite RT or RT-CcT at the Comprehensive Cancer Center in Bialystok, Poland. Pain intensity and type of analgesic treatment during the therapy were analysed and compared with the intensity of the radiation-induced acute reaction, assessed weekly according to the Dische score. Thirty-nine (92.9%) patients received analgesic treatment. Analgesic therapy was started in 27 (64.3%) patients with administration of non-steroidal anti-inflammatory drugs (NSAIDs) and/or paracetamol, in seven (16.7%) with mild opioids and in five (11.9%) with strong opioids. Strong opioids were used during therapy in 21 (50%) patients. Co-analgesics were administered to six patients. Breakthrough pain was observed in 10 (23.8%) patients. High incidence of pain during RT and RT-CT calls for increased awareness of the importance of pain monitoring and treatment during RT of OPC patients. The analgesic treatment had to be adjusted individually.


Cellular and subcellular localization of syntaxin-like immunoreactivity in the rat striatum and cortex.
Syntaxin is a synapse-specific protein previously localized to the plasma membrane of axon terminals. Biochemical and molecular biological studies indicate a prominent role for syntaxin 1A and 1B in synaptic vesicle docking and/or fusion, suggesting that these proteins are localized to active zone regions of most terminal varicosities in the central nervous system. We sought to test this hypothesis by examining the cellular and subcellular immunocytochemical localization of syntaxin 1 proteins in the striatum and frontal cortex of rats. Using either a polyclonal anti-syntaxin antibody, or a monoclonal antibody directed against the identical protein, HPC-1, immunoperoxidase reaction product was localized to preterminal axons and terminal varicosities that made almost exclusively Type I (asymmetric) synapses on dendritic spines or distal shafts. Immunoreactive terminals forming Type II (symmetric) synapses were observed rarely and only in tissue that was pretreated by rapid freeze-thaw to enhance antibody penetration. From a semi-quantitative analysis, it was estimated that at least 48-62% of all vesicle-filled varicosities and 67-69% of all terminals forming Type I synapses were immunoreactive for syntaxin or HPC-1, respectively. Using a pre-embedding immunogold-silver technique to provide a non-diffusible marker for subcellular localization, gold-silver particles for syntaxin or HPC-1 were localized to the cytoplasmic surface of non-synaptic portions of the plasma membrane of preterminal axons and terminal varicosities. Enrichment of presynaptic active zone regions was not observed with immunogold-silver staining. These findings suggest that syntaxin is primarily contained in a subpopulation of terminals that are associated with excitatory amino acid transmitters, but appears not to be ubiquitously expressed in all terminal classes. The results further indicate that syntaxin is localized to non-synaptic regions of axon and terminal membranes, but may not be enriched in presynaptic active zones. The apparent inconsistency between the subcellular localization of syntaxin and its proposed role in vesicle exocytosis is discussed in terms of possible technical limitations and alternative functions for syntaxin.


Mechanical concepts for disc regeneration.
Different strategies exist to treat intervertebral disc degeneration. Biological attempts to regenerate the disc are promising. However, degeneration of the disc is always accompanied by alterations of disc height, intradiscal pressure, load distribution, and motion patterns, respectively. Since those preconditions are independent factors for disc degeneration, it is unlikely that regeneration may occur without firstly restoring the physiological status of the affected spinal segment. In vitro and in vivo animal studies demonstrate that disc distraction normalizes intradiscal height and pressure. Furthermore, histological and radiological examinations provided some evidence for regenerative processes in the disc. Only dynamic stabilization systems currently offer the potential of a mechanical approach to intervertebral disc regeneration. Dynamic stabilization systems either using pedicle screws or with an interspinous device, demonstrate restabilization of spinal segments and reduction of intradiscal pressure. Clinical reports of patients with degenerative disc disease who underwent dynamic stabilization are promising. However, there is no evidence that those implants will lead to disc regeneration. Future treatment concepts should combine intradiscal cell based therapy together with dynamic restoration of the affected spinal segment.


Magnetically Functionalized Moss Biomass as Biosorbent for Efficient Co2+ Ions and Thioflavin T Removal.
Microwave synthesized iron oxide nanoparticles and microparticles were used to prepare a magnetically responsive biosorbent from Rhytidiadelphus squarrosus moss for the rapid and efficient removal of Co2+ ions and thioflavin T (TT). The biocomposite was extensively characterized using Fourier transformed infrared (FTIR), XRD, SEM, and EDX techniques. The magnetic biocomposite showed very good adsorption properties toward Co2+ ions and TT e.g., rapid kinetics, high adsorption capacity (218 μmol g-1 for Co and 483 μmol g-1 for TT), fast magnetic separation, and good reusability in four successive adsorption-desorption cycles. Besides the electrostatic attraction between the oxygen functional moieties of the biomass surface and both Co2+ and TT ions, synergistic interaction with the -FeOH groups of iron oxides also participates in adsorption. The obtained results indicate that the magnetically responsive biocomposite can be a suitable, easily separable, and recyclable biosorbent for water purification.


Induction of efficient apoptosis and cell-cycle arrest in tumor cells by adenovirus-mediated p53 A4 mutant.
p53 is an effective tumor suppressor and is inactivated in numerous cancer cells. In the present study, p53 mutant A4, which carries mutations in C-terminus of the protein and is resistant to murine double minute 2-mediated degradation, was exploited to introduce p53 function in tumor cells. The effect of p53 A4 mutant with recombinant adenovirus vector (Ad-p53 A4) was examined. Ad-p53 A4 infection at a low multiplicity of infection showed significant accumulation of p53 protein and strongly induced a killing effect on osteosarcoma cell line MG-63 that is less sensitive to transduction of wild-type p53. DNA fragmentation assay and caspase assay showed that the cell death induced by Ad-p53 A4 was more rapid and higher than that by Ad-p53 wild-type infection. It is also showed Ad-p53 A4 induces cell-cycle arrest in G1 phase. Moreover, a similar effect was observed in some human cancer cell lines (HeLa, HepG2, KATO III and Saos-2) in various status of endogenous p53 expression. These results suggest that Ad-p53 A4 has the ability to strongly suppress tumor cells and is a promising, novel tool for cancer gene therapy.


Membrane potential dependence of intracellular pH regulation by identified glial cells in the leech central nervous system.
1. We have measured the intracellular pH (pHi) and membrane potential of identified glial cells in the central nervous system of the leech, Hirudo medicinalis, using double-barrelled pH-sensitive microelectrodes. 2. When extracellular K+ concentration was increased, the glial membrane potential decreased and pHi increased; lowering the extracellular K+ concentration hyperpolarized the glial membrane and decreased pHi. These pHi changes were largely dependent upon the presence of CO2-HCO3-; in nominally CO2-HCO3(-)-free saline solution, they were 50-80% smaller. 3. The steady-state pHi of the glial cells in CO2-HCO3(-)-buffered saline solution strongly correlated with the membrane potential between -40 and -90 mV. The slope of this relationship was 60 mV/pH unit. 4. The neurotransmitter 5-hydroxytryptamine (50 microM), which hyperpolarizes the glial membrane, also produced a large, CO2-HCO3(-)-dependent decrease in pHi. The size of the pHi change depended upon the amplitude of the membrane hyperpolarization. 5. The increase in pHi produced by the membrane depolarization in 20 mM-K+ was abolished in Na(+)-free saline. Removal of external Na+ in the presence of 20 mM-K+ reversed the pHi increase. 6. The pHi increase in 20 mM-K+ was also inhibited by the stilbene 4,4-diisothiocyanostilbene-2'-disulphonic acid (DIDS, 0.5 mM). In a DIDS-poisoned preparation a small decrease of pHi was observed in 20 mM-K+ both in the presence and nominal absence of CO2-HCO3-. 7. In neurones, neither CO2-HCO3- nor 20 mM-K+ produced an intracellular alkanization. The steady-state pHi of several identified neurones was not correlated with the membrane potential. 8. We conclude that in glial cells, but not in neurones, the pHi is dependent upon the membrane potential. This membrane potential dependence is due to the activity of the electrogenic Na(+)-HCO3- co-transporter in the glial cell membrane.


Differential disclosure of suicidal intent to clinicians versus researchers: Associations with concurrent suicide crisis syndrome and prospective suicidal ideation and attempts.
Several patient and setting characteristics have been found to predict disclosure of suicidality to clinicians versus researchers. Less understood, however, is whether differential disclosure of suicidality predicts concurrent indirect indicators of suicide risk and future suicide-related outcomes. The present study examined differential disclosure of suicidal intent in clinical versus research settings as a predictor of (1) concurrent symptoms of the Suicide Crisis Syndrome (SCS); and (2) suicidal ideation and attempts within one month in patients (n = 1039) and their clinicians (n = 144), who completed a battery of self-report and interview measures at baseline. Patients who reported suicidal intent to anyone had higher concurrent SCS symptoms than those who denied suicidal intent, with no differences between those who reported intent to clinicians versus researchers only. Severity of suicidal ideation and rates of suicide attempts at one-month follow-up were higher among those who disclosed suicidal intent to a research assistant than among those who did not-regardless of whether suicidal intent was disclosed to their clinician. Overall, an improved understanding of the factors contributing to differential disclosure will improve both scientific inquiry and patient safety.


Comparison of two rapid cortisol radioimmunoassays for use in the fetal sheep.
Cortisol radioimmunoassays (RIA's) utilizing highly specific antisera combined with a simple ethanol protein precipitation procedure (ETOH-PPT) are widely utilized to measure cortisol in human plasma. This same type of RIA has been assumed specific for measurement of cortisol in the plasma of several different species of experimental animals. In order to test this assumption as applied to fetal ovine plasma, we compared an ETOH-PPT cortisol RIA with another rapid cortisol assay which utilizes a dichloromethane extraction (DM-E) step. The DM-E assay in turn was compared with a chromatographic assay previously shown to be highly specific for measurement of fetal plasma cortisol in this species. Fetal ovine plasma cortisol concentrations determined by the DM-E method were nearly identical to the concentrations obtained by the specific chromatographic RIA procedure. On the other hand, the ETOH-PPT RIA grossly overestimated cortisol concentrations when compared with the DM-E RIA. While the rapid DM-E RIA appears to be suitable for use in fetal ovine plasma, the widely used ETOH-PPT RIA yields spuriously high and unpredictable values and must be considered unreliable. These comparisons demonstrate the need for careful reassessment of steroid assays prior to their application in experimental animals even though they have been previously documented as specific in human plasma.


Prostaglandin stimulation of adenosine 3',5'-monophosphate accumulation in cultured chondrocytes in the presence or absence of parathyroid hormone.
The effect of prostaglandin analogues on the cyclic AMP level in cultured chondrocytes were examined. Prostaglandin E1 at 0.4 to 30 microM, increased the intracellular concentration of cyclic AMP in chondrocytes. Its effect was rapid, being evident within 1 min and reaching a maximum in 10 to 20 min. The maximum level was sustained until 30 min after its addition and then decreased gradually. Prostaglandin D2 and E2 also increased the cyclic AMP level in chondrocytes, but they had less effect than prostaglandin E1. Prostaglandin A1 had no effect on the nucleotide level in chondrocytes, although they markedly increased the level in fibroblasts. The time course of stimulation of cyclic AMP accumulation in chondrocytes by prostaglandin E1, D2 or E2 was quite different from that by parathyroid hormone (PTH): the effect of prostaglandin was slower and more sustained than that of PTH. PTH potentiated the effect of prostaglandin E1, E2, or D2 on the cyclic AMP level in chondrocytes and that the combined effects of prostaglandin and PTH were more than additive. Addition of an inhibitor of cyclic nucleotide phosphodiesterase with prostaglandin, PTH or both produced a synergistic effect on the accumulation of cyclic AMP in the chondrocytes. These findings suggest that prostaglandin E1, E2, and D2 increase the synthesis of cyclic AMP and that the combined effect of the prostaglandins and PTH on the cyclic AMP level in chondrocytes is partly attributed to the synergistic synthesis of cyclic AMP in the cells.


Demographic costs of Chaoborus-induced phenotypic plasticity in Daphnia pulex.
It has been proposed that morphological defenses against predation have demographic costs. We measured the cost of a predator-induced morphological defense, using predaceous phantom midge larvae Chaoborus americanus (Insecta, Diptera) and the prey species Daphnia pulex (Crustacea, Cladocera). The induced defense is a neck tooth (and other pleiotropic structures) developed in juvenile D. pulex in the presence of C. americanus. Laboratory life table experiments, in the absence of predation, indicated the population growth rate of typical D. pulex was 11% to 39% greater than that of D. pulex exposed to C. americanus extract, or C. americanus-conditioned water. The reduction in population growth rate was most frequently associated with an increase in the time between birth and first reproduction. Induced individuals required twenty more hours at 23°C, and twenty five more hours at 20°C, to develop to the age of first reproduction. Under limiting food conditions age-specific survivorship and the number of offspring produced per female by the induced form were reduced relative to the typical form. As a result, the difference in population growth rates among forms was greater at the low food level as indicated by a highly significant food by form interaction effect. In addition to neck teeth and lowered reproductive rates, the offspring of induced form individuals had significantly longer tail-spines (7.2-7.5%), and primiparous adults from the induction treatment were significantly shorter than controls (3-8%).


Theory's role in shaping behavioral health research for population health.
The careful application of theory often is used in the behavioral health field to enhance our understanding of how the world currently works. But theory also can help us visualize what the world can become, particularly through its potential impacts on population-wide health. Applying a multi-level ecological perspective can help in expanding the field's focus upward toward the population at large. While ecological frameworks have become increasingly popular, arguably such perspectives have fallen short of their potential to actively bridge conceptual constructs and, by extension, intervention approaches, across different levels of population impact. Theoretical and conceptual perspectives that explicitly span levels of impact offer arguably the greatest potential for achieving scientific insights that may in turn produce the largest population health effects. Examples of such "bridging" approaches include theories and models that span behavioral + micro-environment, behavioral + social/cultural, and social + physical environment constructs. Several recommendations are presented related to opportunities for leveraging theories to attain the greatest impact in the population health science field. These include applying the evidence obtained from person-level theories to inform methods for positively impacting the behaviors of community gatekeepers and decision-makers for greater population change and reach; leveraging the potential of residents as "citizen scientists"--a resource for enacting behavioral health changes at the individual, environmental, and policy levels; using empirical observations and theory in equal parts to build more robust, relevant, and solution-oriented behavior change programs; exploring moderators and mediators of change at levels of impact that go beyond the individual; and considering the circumstances in which applying conceptual methods that embrace a "complexity" as opposed to "causality" perspective may lead to more flexible and agile scientific approaches that could accelerate both population-relevant discoveries and applications in the field. The commentary closes with suggestions concerning additional areas to be considered to facilitate continued advances in the health behavior field more generally to attain the greatest impacts on population health.


GPSM2 Serves as an Independent Prognostic Biomarker for Liver Cancer Survival.
Liver cancer is a malignancy with a poor prognosis. G protein signaling modulator 2 is mainly related to cell division and cell cycle regulation. In this review, the relationship between G protein signaling modulator 2 and clinical characteristics of patients with liver cancer has been explored, especially with respect to its prognostic value. G protein signaling modulator 2 messenger RNA expression and clinicopathological characteristics of patients with liver cancer were obtained from The Cancer Genome Atlas. The expression level of G protein signaling modulator 2 RNA-Seq was validated by using Gene Expression Omnibus. Chi-square test was performed to evaluate the relationship between G protein signaling modulator 2 expression and clinical characteristics. The threshold value of G protein signaling modulator 2 in the diagnosis of liver cancer was evaluated by a receiver-operating characteristic curve. Cox regression analysis and Kaplan-Meier curves were performed to evaluate the relationship between G protein signaling modulator 2 and liver cancer prognosis, which included overall and residual-free survival, and explored the prognostic value of G protein signaling modulator 2. Liver cancer survival analyses were validated by using the data of G protein signaling modulator 2 RNA-Seq from the International Cancer Genome Consortium. The expression level of G protein signaling modulator 2 messenger RNA was remarkably higher in liver cancer than that in healthy tissues (P < 2.2 × e-16), which was also validated by data from the GSE14520 database. In addition, high G protein signaling modulator 2 expression significantly correlated with histological grade (P = .020), vital status (P < .001), clinical (P = .001), and T stage (P = .001). The receiver-operating characteristic curves showed G protein signaling modulator 2 to be an advantageous diagnostic molecule for liver cancer (area under curve = 0.893). Furthermore, the results of Cox analysis and Kaplan-Meier curves suggested that the upregulation of G protein signaling modulator 2 expression is linked to poor prognosis and G protein signaling modulator 2 messenger RNA could be an independent predictor for liver cancer, which was validated by data from the International Cancer Genome Consortium database. G protein signaling modulator 2 messenger RNA was overexpressed in liver cancer, and G protein signaling modulator 2 is an independent prognostic factor. G protein signaling modulator 2 is expected to be a treatment target for cancer.


High-performance liquid chromatographic method for the determination of pindolol in human plasma.
A sensitive, simple and highly reliable high-performance liquid chromatographic method using fluorescence detection is reported for the determination of pindolol in plasma. This method involves a single extraction of pindolol from alkalinized plasma into methyl tert.-butyl ether followed by a back-extraction into dilute hydrochloric acid. Injection of the dilute acid phase directly onto an octyl (LC-8) bonded-phase column provides the final separation, and detection of pindolol is achieved by monitoring the intrinsic fluorescence of pindolol at 315 nm following excitation at 255 nm. The method is sensitive enough to measure with confidence pindolol plasma concentrations of 2 ng/ml using a 2-ml sample. No internal standard is required. This method has been applied to the analysis of 1500 human plasma samples by two different laboratories.


Recombinant activated factor VII: a solution to refractory haemorrhage in vascular surgery?
Post-operative haemorrhage is a recognised complication and independent predictor of outcome in complex vascular surgery. The off-license administration of activated Recombinant Factor VII (rFVIIa) to treat haemorrhage in other surgical settings has been investigated, but concerns over potential adverse events have limited its use in vascular surgery. This article reports rFVIIa's method of action and systematically reviews rFVIIa's role in complex vascular surgery. A systematic literature search identified articles reporting on rFVIIa administration within vascular surgery patients. Patient-specific data regarding transfusion requirements was extracted and pooled statistical analysis performed. 15 articles reporting 43 patients were identified. RFVIIa has been administered in open and endovascular procedures and in both elective and emergency settings. Major aortic surgery accounted for 75% of cases. The range of rFVIIa administered as a cumulative dose was large, as was the variation in initial dose. Transfusion data from 9 patients was pooled and analysed. Significant differences were found between pre- and post- rFVIIa for packed red cell transfusions (mean 29.2 vs. 8.2, p=0.015). Intra-arterial thrombosis was reported in 3 cases. RFVIIa may reduce haemorrhage in selected vascular surgical patients. Randomized controlled trials are justified to definitively investigate its role within this setting.


Lipid remodeling in Rhodopseudomonas palustris TIE-1 upon loss of hopanoids and hopanoid methylation.
The sedimentary record of molecular fossils (biomarkers) can potentially provide important insights into the composition of ancient organisms; however, it only captures a small portion of their original lipid content. To interpret what remains, it is important to consider the potential for functional overlap between different lipids in living cells, and how the presence of one type might impact the abundance of another. Hopanoids are a diverse class of steroid analogs made by bacteria and found in soils, sediments, and sedimentary rocks. Here, we examine the trade-off between hopanoid production and that of other membrane lipids. We compare lipidomes of the metabolically versatile α-proteobacterium Rhodopseudomonas palustris TIE-1 and two hopanoid mutants, detecting native hopanoids simultaneously with other types of polar lipids by electrospray ionization mass spectrometry. In all strains, the phospholipids contain high levels of unsaturated fatty acids (often >80%). The degree to which unsaturated fatty acids are modified to cyclopropyl fatty acids varies by phospholipid class. Deletion of the capacity for hopanoid production is accompanied by substantive changes to the lipidome, including a several-fold rise of cardiolipins. Deletion of the ability to make methylated hopanoids has a more subtle effect; however, under photoautotrophic growth conditions, tetrahymanols are upregulated twofold. Together, these results illustrate that the 'lipid fingerprint' produced by a micro-organism can vary depending on the growth condition or loss of single genes, reminding us that the absence of a biomarker does not necessarily imply the absence of a particular source organism.


Near-infrared spectroscopic characterization of human advanced atherosclerotic plaques.
OBJECTIVES; Living human carotid atherosclerotic plaques were examined in vitro by near-infrared (NIR) spectroscopy to determine the spectral features of plaque vulnerability. Plaque disruption, a major cause of heart attacks and strokes, cannot generally be predicted, but is thought to depend mainly on plaque composition. Near-infrared spectroscopy has been used to detect components in tissues noninvasively. Using an NIR spectrometer fitted with a fiberoptic probe, living human carotid atherosclerotic plaques (from 25 patients) were examined ex vivo for plaque vulnerability. The plaques were cut into smaller sections according to their gross pathologic features, and NIR measurements were done at 20 degrees C, usually within 10 min. According to the American Heart Association's recommended classification scheme, the lesions were classified into three groups: the first group comprised of vulnerable type V/VI lesions; the second group, stable type I/II lesions; and the third (intermediate) group, mainly type III/IV lesions. Cluster analysis of the specimens' NIR spectra identified three major composition groups in each of the three NIR spectral regions: 2,200 to 2,330 nm, 1,620 to 1,820 nm and 1,130 to 1,260 nm. Calculation of the lipid/protein ratios in each group at two NIR regions (2,200 to 2,330 nm) revealed ratios of 1.49 +/- 1.20, 2.12 +/- 1.00 and 3.37 +/- 0.88 for type I/II, type III/IV and advanced type V/VI lesions, respectively (p < 0.03). At 1,620 to 1,820 nm, the respective ratios for these histologic groups were 0.57 +/- 0.21, 1.54 +/- 0.46 and 2.40 +/- 0.44 (p < 0.00003). The good ex vivo discrimination of histologically vulnerable and stable plaques in this study suggests that NIR spectroscopy has the potential to identify vulnerable atherosclerotic plaques in vivo.


Professionalism and Communication Education in Pediatric Critical Care Medicine: The Learner Perspective.
Communication and professionalism are often challenging to teach, and the impact of the use of a given approach is not known. We undertook this investigation to establish pediatric critical care medicine (PCCM) trainee perception of education in professionalism and communication and to compare their responses from those obtained from PCCM fellowship program directors. The Education in Pediatric Intensive Care (E.P.I.C.) Investigators used the modified Delphi technique to develop a survey examining teaching of professionalism and communication. After piloting, the survey was sent to all 283 PCCM fellows in training in the United States. Survey response rate was 47% (133 of 283). Despite high rates of teaching overall, deficiencies were noted in all areas of communication and professionalism assessed. The largest areas of deficiency included not being specifically taught how to communicate: as a member of a nonclinical group (reported in 24%), across a broad range of socioeconomic and cultural backgrounds (19%) or how to provide consultation outside of the intensive care unit (17%). Only 50% of fellows rated education in communication as "very good/excellent." However, most felt confident in their communication abilities. For professionalism, fellows reported not being taught accountability (12%), how to conduct a peer review (12%), and how to handle potential conflict between personal beliefs, circumstances, and professional values (10%). Fifty-seven percent of fellows felt that their professionalism education was "very good/excellent," but nearly all expressed confidence in these skills. Compared with program directors, fellows reported more deficiencies in both communication and professionalism. There are numerous components of communication and professionalism that PCCM fellows perceive as not being specifically taught. Despite these deficiencies, fellow confidence remains high. Substantial opportunities exist to improve teaching in these areas.


Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on serum inhibin concentrations and inhibin immunostaining during follicular development in female Sprague-Dawley rats.
Intact and hypophysectomized immature rats were pretreated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0 or 32 microg/kg p.o.) and sacrificed throughout synchronized follicular development (0, 12, 24, 48, and 72 h after equine chorionic gonadotropin, eCG). TCDD administration to intact rats resulted in a premature elevation of serum FSH and LH by 12 h post-eCG. In intact rats pretreated with TCDD, the intensity of ovarian immunoreactivity for inhibin and the number of ovarian follicles staining for inhibin in midsaggital ovarian sections were decreased at the time of eCG administration (24 h post-TCDD) in comparison to controls. However, this decreased ovarian staining for inhibin was not associated with alterations in serum inhibin concentrations. Serum inhibin was suppressed in TCDD-treated rats when compared to intact controls only at 24 h post-eCG. Hypophysectomized animals exhibited no effect of TCDD on serum inhibin at any timepoint but did have decreased estradiol concentrations during follicular development. In summary, TCDD reduced serum concentrations of inhibin after the premature increases in FSH and LH suggesting that inhibin is not important in the initial elevation of FSH following exposure to TCDD.


Screening of key flavonoids and monoterpenoids for xanthine oxidase inhibitory activity-oriented quality control of Chrysanthemum morifolium Ramat. 'Boju' based on spectrum-effect relationship coupled with UPLC-TOF-MS and HS-SPME-GC/MS.
This study aimed at obtaining precise quality control standards to efficiently screen Chrysanthemum morifolium Ramat. 'Boju' with strong xanthine oxidase (XO) inhibitory activity for developing C. morifolium 'Boju' extract based-hypouricemic functional food. The results indicated significant differences in volatile and phenolic profiles and XO inhibitory (XOI) activities of 31 batches of C. morifolium 'Boju' collected in herb/tea market. The minority of C. morifolium 'Boju' having abundant characteristic monoterpenoids and flavonoid aglycones showed strong XOI activities, while the majority of C. morifolium 'Boju' possessing few corresponding monoterpenoids and flavonoid aglycones exhibited moderate XOI activities. Seven XOI activity-directly related phenolics and ten XOI activity-indirectly related volatiles were identified by UPLC-ESI-QTOF/MS-based and HS-SPME-GC/MS-based spectrum-effect relationships, respectively. Three flavonoids (luteolin, apigenin and acacetin) identified as key XO inhibitors and four monoterpenoids (filifolone, α-terpineol, thymol and piperitenone) closely related to key XO inhibitors were screened for XOI activity-oriented quality control of C. morifolium 'Boju'.


Quality-of-life outcomes following pelvic exenteration for primary rectal cancer.
For patients with locally advanced tumours and contiguous organ involvement, pelvic exenteration (PE) can offer cure with relatively low mortality. The literature surrounding quality of life (QoL) in patients undergoing PE is limited. Furthermore, there are no matched comparisons of QoL between abdominoperineal resection (APR) and PE. The aim of this study was to compare differences in long-term QoL for patients with primary rectal cancer undergoing APR versus PE. All patients who underwent either APR or PE between January 2011 and December 2012 were identified. Patients were asked to complete the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire before surgery and 2 weeks afterwards. Subsequent questionnaires were requested at 3, 6, 12 and 24 months after operation. A total of 110 patients were included in the study (54 APR, 56 PE). Median length of stay following operation was 11 (range 3-70) days for APR and 15 (7-84) days for PE. Patients undergoing PE experienced lower physical (mean score 42 versus 56; P = 0.010), role (20 versus 33; P = 0.047), emotional (57 versus 73; P = 0.010) and social (34 versus 52; P = 0.005) functional levels 2 weeks after surgery. Long-term dyspnoea and financial worries were experienced only after PE. Patients undergoing PE had a lower overall global health status at 2 weeks after operation (40 versus 53; P = 0.012). Levels were comparable between groups from 3 months after surgery. QoL recovery following PE was equivalent to that after APR alone. Patients should not be denied exenterative surgery based on perceived poor QoL.


Perceptions of student nurses regarding the use of a popular autobiography as a teaching tool.
Recent studies encourage educators in nursing to use innovative and non-traditional teaching methods, such as using popular movies, posters, portfolios and surfing the internet, to stimulate students' interest, participation and interaction to enhance academic performance as well as knowledge retention. In this, descriptive cross-sectional study, we used self-administered questionnaires with statements graded on 5-points Likert scale (quantitative measures) and open-ended questions (qualitative measures), to assess the feasibility and students' perceptions regarding the use of Lance Armstrong's autobiography of surviving against cancer as a teaching tool. At the beginning of the lecture copies of selected chapters from: "It's Not About the Bike; My Journey Back to Life" [Armstrong, L., Jenkins, S. 2001. It's Not About The Bike: My Journey Back To Life. Yellow Jersey Press, Random House (Pty) Limited, Great Britain], were given to students. Willing students were requested to read for the whole class while the lecturer interjected periodically to explain and expound on certain pharmacological concepts. Eighty percent (80%) of participants felt that the use of an autobiography stimulated their interesting in cancer drugs and 84% agreed/strongly agreed that it contributed to their knowledge of pharmacology. Using Lance Armstrong's autobiography of survival to teach cytotoxic drugs is a worthwhile and rewarding exercise from the student nurses' perspective.


Impact of Myopia on Corneal Biomechanics in Glaucoma and Nonglaucoma Patients.
We evaluated the impact of myopia on corneal biomechanical properties in primary open-angle glaucoma (POAG) and nonglaucoma patients, and the effect of modification of glaucoma on myopic eyes. This cross-sectional study included 66 POAG eyes (33 myopia, 33 nonmyopia) and 66 normal eyes (33 myopia, 33 nonmyopia). Seven corneal biomechanical parameters were measured by ultra-high-speed Scheimpflug imaging, including corneal deformation amplitude (CDA), inward/outward corneal applanation length (ICA, OCA), inward/outward corneal velocity (ICV, OCV), radius, and peak distance (PD). Mean age (SD) of the 65 male (49%) and 67 female (51%) patients was 59 (9.82) years. Myopia was associated with significantly higher CDA (adjusted effect = 0.104, P = 0.001) and lower OCV (adjusted effect = -0.105, P < 0.001) in the POAG group. Within the nonglaucoma group, myopic eyes had a significantly lower OCV (adjusted effect = -0.086, P < 0.001) and higher CDA (adjusted effect = 0.079, P = 0.001). All parameters except PD suggested that glaucoma modified the effect of myopia on corneal biomechanics. Percentage differences in the adjusted myopic effect between POAG and nonglaucoma patients was 31.65, 27.27, 31.65, 50.00, 22.09, and 60.49 for CDA, ICA, OCA, ICV, OCV, and radius, respectively. Myopia had a significant impact on corneal biomechanical properties in the POAG and nonglaucoma groups. The differences in corneal biomechanical parameters suggest that myopia is correlated with significantly lower ocular rigidity. POAG may enhance the effects of myopia on most of these parameters.


Epidermal growth factor and thrombin induced proliferation of immortalized human keratinocytes is coupled to the synthesis of Egr-1, a zinc finger transcriptional regulator.
The epidermal growth factor (EGF) receptor is highly expressed in HaCaT keratinocytes as shown by Western blotting. Stimulation of HaCaT cells with EGF, and also with the serine protease thrombin, induced DNA synthesis, measured by incorporation of 5-bromo-2'-deoxyuridine into the DNA of proliferating cells. Using antibodies directed against the active form of the EGF receptor, we show that in HaCaT cells EGF and thrombin triggered a rapid activation of the EGF receptor, followed by the phosphorylation and activation of the extracellular signal-regulated protein kinase (ERK). Moreover, EGF and thrombin induced a transient synthesis of the zinc finger transcriptional regulator Egr-1. Proliferation, activation of ERK, and biosynthesis of Egr-1 was completely inhibited in EGF or thrombin-treated HaCaT cells by the MAP kinase kinase inhibitor PD98059 and by AG1487, an EGF receptor-specific tyrosine kinase inhibitor. These data indicate that phosphorylation and activation of both the EGF receptor and ERK are essential for mitogenic signaling via EGF and thrombin. The synthesis of Egr-1 in HaCaT cells as a result of EGF or thrombin stimulation suggests that Egr-1 may be an important "late" part of the EGF and thrombin-initiated signaling cascades. We postulate that Egr-1 may function as a "third messenger" in keratinocytes connecting mitogenic stimulation with changes in gene transcription.


Special Issue "Volatile Compounds and Smell Chemicals (Odor and Aroma) of Food".
Among the constituents of food, volatile compounds are a particularly intriguing group of molecules, because they give rise to odour and aroma [...].


Synthesis and investigation of anti-COVID19 ability of ferrocene Schiff base derivatives by quantum chemical and molecular docking.
The recent outbreak of coronavirus disease (COVID-19) has rampaged the world with more than 236 million confirmed cases and over 4.8 million deaths across the world reported by the world health organization (WHO) till Oct 5, 2021. Due to the advent of different variants of coronavirus, there is an urgent need to identify effective drugs and vaccines to combat rapidly spreading virus varieties across the globe. Ferrocene derivatives have attained immense interest as anticancer, antifungal, antibacterial, and antiparasitic drug candidates. However, the ability of ferrocene as anti-COVID-19 is not yet explored. Therefore, in the present work, we have synthesized four new ferrocene Schiff bases (L1-L4) to understand the active sites and biological activity of ferrocene derivatives by employing various molecular descriptors, frontier molecular orbitals (FMO), electron affinity, ionization potential, and molecular electrostatic potential (MEP). A theoretical insight on synthesized ferrocene Schiff bases was accomplished by molecular docking, frontier molecular orbitals energies, active sites, and molecular descriptors which were further compared with drugs being currently used against COVID-19, i.e., dexamethasone, hydroxychloroquine, favipiravir (FPV), and remdesivir (RDV). Moreover, through the molecular docking approach, we recorded the inhibitions of ferrocene derivatives on core protease (6LU7) protein of SARS-CoV-2 and the effect of substituents on the anti-COVID activity of these synthesized compounds. The computational outcome indicated that L1 has a powerful 6LU7 inhibition of SARS-CoV-2 compared to the currently used drugs. These results could be helpful to design new ferrocene compounds and explore their potential application in the prevention and treatment of SARS-CoV-2.


Site tenacity and nomadism in Tengmalm's owl (Aegolius funereus (L.)) in relation to cyclic food production.
In northern Sweden breeding males of Tengmalm's owls (Aegolius funereus (L.)) were site tenacious during and between the peaks of the vole (staple food) cycles, but females only during the peaks. Most of these adults shifted nest boxes between successive years. They selected nest boxes randomly in a radius of 3 km. Juveniles, in contrast to site tenacious adults, dispersed outside their natal area. The females moved longer than the males prior to their first breeding. Five adult females were found to be nomadic. One of these nomadic females previously bred site tenaciously as long as food was abundant. Juveniles and adult males were not found to be nomadic. Emigration of adult females and juveniles occurred most frequently when vole populations declined. The breeding population increased sharply and received immigrants suggesting that nomadism may be essential in the population dynamics. Site tenacity and nomadism are discussed in terms of costbenefit to males and females, respectively. Emphasis is on the main functional roles of males (feeding femle and young) and females (incubation).


Simple instructions for partial sleep deprivation prior to pediatric EEG reduces the need for sedation.
To study the effects of providing simple instructions for partial sleep deprivation on the necessity for sedation in children and adolescents undergoing electroencephalography (EEG). Children and adolescents below 18 years undergoing non-urgent routine EEG were studied for the need for sedation during the EEG test. Two consecutive 3-year periods were reviewed. During the first 3 years no instructions for sleep deprivation were given, and during the second 3-year period, simple instructions were given to the patient or parents of young children to have less sleep prior to the EEG test. This was achieved by using the same sleep deprivation schedule irrespective of the age of the patient. In the first 3-year period between January 1996 and December 1998, 785 non-urgent routine EEG recordings were performed in which only 146 (19%) pediatric patients managed to fall asleep without the need for any sedation within 30 min of being ready for the sleep recording. When partial sleep deprivation was implemented in the 3-year period between January 2000 and December 2002, 449 (55%) out of 821 patients undergoing the test fell asleep in the laboratory without sedation, an overall increase of 36%. Analyzing the different age-specific groups, the maximal increase in the success for natural sleep following partial sleep deprivation was 44% for pediatric patients aged above 10 years. Simple instructions for partial sleep deprivation prior to the EEG reduced the need for sedation in children and adolescents undergoing the test.


Bilateral vascularized rib grafts to promote spinopelvic fixation in patients with sacral agenesis and spinopelvic dissociation: a new surgical technique.
Sacral agenesis is a rare congenital disorder that may have spinopelvic instability due to sacroiliac joint malformation. Surgical indication in patients with sacral agenesis is to improve their sitting balance and protect the visceral organs. Achieving solid arthrodesis across this congenital malformation is challenging and prone to non-union. The purpose of this study was to describe a novel surgical technique with vascularized ribs for management of sacral agenesis and complex spinopelvic dissociation. Retrospective study. Six patients with sacral agenesis were reviewed and followed for a mean of 8.5 years after spinopelvic fusion augmented with vascularized rib graft spanning the lumbo-pelvic junction. The primary outcome measure was the presence or absence of a stable spinopelvic junction and fusion across the spine-vascular rib grafts-pelvis interface. The secondary outcome measures were maintenance of pelvic obliquity, lumbosacral kyphosis, and overall sagittal balance. The surgical procedure consisted of two-stage surgeries performed 6-12 weeks apart. The first stage consisted of spinal instrumentation and correction of the deformity via a posterior approach and impaction of one of the vascularized ribs from the spine to the iliac crest. The second stage consisted of an anterior thoraco-lumbar approach for spinal fusion and the second vascularized rib spanning the spine to the iliac crest. All six patients eventually achieved a solid spinal and spinopelvic fusion. All vascularized ribs increased in diameter over time. A high complication rate consisted mainly of spinal infections and prominent hardware requiring revision surgeries (a total of seven procedures in four patients). Two patients had decreased mobility secondary to spinopelvic surgery at last follow-up. Spinopelvic fusion can be successfully achieved with this novel surgical technique using vascularized rib grafts. This technique allows for biological long-term maintenance of the sagittal deformity correction. Fusion across the lumbosacral junction in patients with sacral agenesis may place them at risk of losing the ability to mobilize independently. Recent lower profile implants have prevented implant-related complications.


Previous SARS-CoV-2 Infection Is Not Associated With Increased Celiac Disease Autoimmunity in Children and Adolescents.
Recent reports suggest severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections may increase the risk of celiac disease autoimmunity. This study aims to evaluate potential associations between coronavirus disease 2019 infection and tissue transglutaminase autoantibodies (TGA) immunoglobulin A. From 2020 to 2021, cross-sectional screening for SARS-CoV-2 antibodies and TGA was offered to 4,717 children in Colorado through the Autoimmunity Screening for Kids study. Multivariable logistic regression assessed association between previous SARS-CoV-2 infection and TGA positivity. Previous SARS-CoV-2 infection was not associated with TGA positivity (odds ratio 1.02, 95% confidence interval 0.63-1.59; P = 0.95). In this large-scale analysis, previous SARS-CoV-2 infection was not associated with celiac disease autoimmunity in Colorado children.


The sporulation capable (sca) mutation of Saccharomyces cerevisiae is an allele of the SIR2 gene.
We have used the special properties of the spo13-1 mutation in order to study the regulation of yeast meiosis by the mating type loci. We have found that both the rme1-1 mutation and the sca mutation allow haploid meiosis in spo13-1 strains. Therefore, haploid meiosis is regulated in the same manner as diploid meiosis. Unlike rme1-1, the sca mutation allows meiosis through derepression of the silent mating type cassettes; sca strains can sporulate only because they express both MATa and MAT alpha information. We have found further that sca is an allele of SIR2, one of the genes involved in repression of the silent cassettes. Therefore, the RME1 gene is the only known candidate for a master negative regulator through which the MAT locus controls meiosis.


Molecular mechanisms for plasmacytoid dendritic cell function and development.
Dendritic cells (DCs) are activated by immune adjuvants in a DC subset-specific manner. Plasmacytoid DC (pDC) is a unique subset that senses nucleic acid immune adjuvants only through two Toll-like receptors (TLRs), TLR7 and TLR9 and produces large amounts of type I interferons. Here I review recent trend in pDC function and development.


Plzf as a candidate gene predisposing the spontaneously hypertensive rat to hypertension, left ventricular hypertrophy, and interstitial fibrosis.
The spontaneously hypertensive rat (SHR) is the most widely used model of essential hypertension and is susceptible to left ventricular hypertrophy (LVH) and myocardial fibrosis. Recently, a quantitative trait locus (QTL) that influences heart interstitial fibrosis was mapped to chromosome 8. Our aim was to dissect the genetic basis of this QTL(s) predisposing SHR to hypertension, LVH, and interstitial fibrosis. Hemodynamic and histomorphometric analyses were performed in genetically defined SHR.PD-chr.8 minimal congenic strain (PD5 subline) rats. The differential segment, genetically isolated within the PD5 subline, spans 788kb and contains 7 genes, including the promyelocytic leukemia zinc finger (Plzf) gene that has been implicated in hypertrophy and cardiac fibrosis. Mutant Plzf allele contains a 2,964-bp deletion in intron 2. The PD5 congenic strain, when compared with the SHR, showed significantly reduced systolic blood pressure by approximately 15mm Hg (P = 0.002), amelioration of LVH (0.23±0.02 vs. 0.39±0.02g/100g body weight; P < 0.00001), and reduced interstitial fibrosis (17,478±1,035 vs. 41,530±3,499 μm(2); P < 0.0001). The extent of amelioration of LVH and interstitial fibrosis was disproportionate to blood pressure decrease in congenic rats, suggesting an important role for genetic factors. Cardiac expression of Plzf was significantly reduced in prehypertensive (8 and 21 days) congenic animals compared with controls. These results provide compelling evidence of a significant role for genetic factors in regulating blood pressure, LVH, and cardiac fibrosis and identify mutant Plzf as a prominent candidate gene.


Lysine-specific demethylase 1 (LSD1/KDM1A/AOF2/BHC110) is expressed and is an epigenetic drug target in chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma.
Lysine-specific demethylase 1 (GeneID 23028), a flavin-dependent monoamine oxidoreductase and a histone demethylase, serves as an epigenetic coregulator of transcription. Lysine-specific demethylase 1 is up-regulated in neuroblastoma and in bladder, breast, colorectal, gastric, lung, and neuroendocrine cancers, and its overexpression drives the cell cycle of otherwise nontransformed human cells, suggesting oncogenic properties. Lysine-specific demethylase 1 was recently reported to be also overexpressed in several different mesenchymal tumors. We investigated lysine-specific demethylase 1 expression in over 500 sarcomas by gene expression profiling and tissue microarray-coupled immunohistochemical analyses and confirmed lysine-specific demethylase 1 overexpression in rhabdomyosarcoma and synovial sarcoma. We also show for the first time that lysine-specific demethylase 1 is also overexpressed in chondrosarcoma, Ewing's sarcoma, and osteosarcoma wherein it localizes in cell nuclei. We further show that a US Food and Drug Administration-approved drug that inhibits lysine-specific demethylase 1 also inhibits chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma cell growth in vitro. These data suggest that lysine-specific demethylase 1 plays a role in sarcoma pathology and that lysine-specific demethylase 1 inhibition strategies might represent a novel means to inhibiting growth of lysine-specific demethylase 1-overexpressing sarcomas.


Experimental bacterial meningitis in rats: demonstration of hydrocephalus and meningeal enhancement by magnetic resonance imaging.
We investigated whether magnetic resonance imaging (MRI) is able to detect intracranial manifestations of advanced bacterial meningitis in rats. Meningitis was induced in nine animals by injecting 150 microl 10(7) colony forming units per ml of Streptococcus pneumoniae into the cisterna magna. MRI was performed 24 h (n = 5) and 48 h (n = 4) after infection. Controls included (I) animals that were injected intracisternally with 150 microl phosphate-buffered saline or (II) animals without puncture of the cisterna magna. T2-weighted and T1-weighted MR images before and after administration of 0.3 mmol kg(-1) of gadolinium-DTPA were obtained. Hydrocephalus was found in 7 of 9 infected animals, but not in the control group. Abnormal leptomeningeal enhancement was found in all infected animals, but in none of the controls. The animals imaged after 48 h showed a more pronounced hydrocephalus and a more intense leptomeningeal enhancement than animals imaged after 24 h. Even in small animals such as rats, MRI can be used to detect the presence of bacterial meningitis and its associated complications. MRI may be a useful noninvasive method for monitoring the possible effect of adjunctive therapeutic strategies in experimental studies of meningitis.


Tocopheryl polyethylene glycol 1000 succinate therapy for vitamin E deficiency during chronic childhood cholestasis: neurologic outcome.
Treatment of the vitamin E deficiency neurologic syndrome in children with chronic cholestasis is hampered by the very poor intestinal absorption of available forms of vitamin E, thus requiring prolonged treatment with intramuscular injections of vitamin E in many patients. D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble investigational form of vitamin E that is well absorbed during cholestasis. We studied the effect of TPGS therapy on the neurologic function in 12 children with vitamin E deficiency (aged 9 months to 6 years) with prolonged forms of neonatal cholestasis. Each child had failed to respond to up to 100 to 200 IU/kg/d of standard oral preparations of vitamin E. Treatment with 15 to 25 IU/kg/d TPGS for a mean of 19.3 months normalized the biochemical indices of vitamin E status and was well tolerated by all patients. Neurologic function, assessed by serial neurologic examinations, remained normal during therapy in the two children with no neurologic symptoms younger than age 3 years at onset of therapy. Neurologic function, which had deteriorated before this study, improved in six of seven patients with symptoms who were younger than 3 years and in all three with symptoms older than 3 years. TPGS appears to be a safe and effective form of orally administered vitamin E for use in children with chronic cholestasis who are unresponsive to available oral preparations of vitamin E.


Crimean-Congo hemorrhagic fever in Southeast of Iran.
In June 1999, a cluster of patients with viral hemorrhagic fever were reported in central provinces of Iran. Similar cases were subsequently verified in other parts of Iran. During June 1999 to February 2004, a total of 255 patients were recorded in Southeast of Iran. The epidemiological features, clinical manifestations, treatment and outcome will be discussed.


The use of δ15N and δ18O tracers with an understanding of groundwater flow dynamics for evaluating the origins and attenuation mechanisms of nitrate pollution.
During early 2000, a new analytical procedure for nitrate isotopic measurement, termed the "denitrifier method", was established. With the development of the nitrate isotope tracer method, much research has been reported detailing sources of groundwater nitrate and denitrification mechanisms. However, a shortcoming of these tracer studies has been indicated owing to some overlapping of isotope compositions among different source materials and denitrification trends. In order to reduce these uncertainties, we examined nitrate isotope ratios within a frame of "regional groundwater flow dynamics" to eliminate unnecessary uncertainties in elucidating nitrate sources and behaviors. A total of 361 samples were collected from the Kumamoto area: the circulated groundwater system with a scale of 10(3) km(2) in southern Japan. Subsequently, the nitrate pollution was examined within the above-mentioned framework. As a result, a reasonable identification of the sources and attenuation behaviors (both denitrification and dilution) of groundwater nitrate pollution was obtained over the study area. This study demonstrates that the use of nitrate isotope tracers efficiently improves with a comprehensive understanding of groundwater flow dynamics. The approach emphasized in this study is important and should be applicable in other areas.


Early enteral feeding after pediatric abdominal surgery: A systematic review of the literature.
Traditionally enteral nutrition has been delayed following abdominal surgery in children, to prevent complications. However, recent evidence in the adult literature refutes the supposed benefits of fasting and suggests decreased complications with early enteral nutrition (EEN). This review aimed to compile the evidence for EEN in children in this setting. Databases Pubmed, EmBase, Medline and reference lists were searched for articles containing relevant search terms according to PRISMA guidelines. First and second authors reviewed abstracts. Studies containing patients less than 18 years undergoing abdominal surgery, with feeding initiated earlier than standard practice, were included. Studies including pyloromyotomy were excluded. Primary outcome was length of stay (LOS). Secondary outcomes included time to full enteral nutrition, time to stool and postoperative complications. Fourteen articles met inclusion criteria - five on neonatal abdominal surgery, three on gastrostomy formation and six on intestinal anastomoses. There were three randomized control trials (RCTs), five cohort studies, four historical control trials, one nonrandomized trial and one case series. Nine studies showed a decreased LOS with EEN. Most studies which reported time to full enteral nutrition showed improvement with EEN; however, time to stool was similar in most studies. Postoperative complications were either decreased or not statistically different in EEN groups in all studies. Studies to date in a limited number of procedures suggest EEN appears safe and effective in children undergoing abdominal surgery. Although robust evidence is lacking, there are clear benefits in LOS and time to full feeds, and no increase in complications. IV.


Amylase-producing lung cancer.
A bronchioloalveolar carcinoma of lung associated with hyperamylasemia occurring in a 40-year-old woman is described. Another 13 cases of such a tumor from the English literature are reviewed. A majority of the lung tumors associated with hyperamylasemia were adenocarcinomas. When the amylase isoenzymes were determined, the amylase appeared to be salivary-gland type (S-type). Electron microscopic studies had revealed membrane-bound electron-dense granules within the tumor cells.


Scapulothoracic dissociation (closed avulsion of the scapula, subclavian artery, and brachial plexus): a newly recognized variant, a new classification, and a review of the literature and treatment options.
Scapulothoracic (ST) dissociation is a closed complete traumatic forequarter amputation manifested by a flail pulseless arm and well-defined roentgenographic findings. These roentgenographic findings were previously reported to be lateral displacement of the scapula and either acromioclavicular separation (17) or displaced clavicular fracture (20). In this paper we present four patients with ST dissociation who had a previously unreported combination of roentgenographic findings: lateral displacement of the scapula and sternoclavicular separation. Polytrauma was present in all previously reported cases of patients with ST dissociation. We present one patient, however, in whom ST dissociation is an isolated finding. A review of the literature, and a review of treatment options that includes some combination of amputation, shoulder arthrodesis, prosthetic fitting, and reconstructive tendon transfers, are presented.


Ventricular assist devices in patients with chemotherapy-induced cardiomyopathy: new modalities.
Cardiotoxicity is a fatal complication of chemotherapeutic agents in which the implantation of a mechanical circulatory support system (MCS) can be a life-saving modality. The aim of this article is to analyse this available therapeutic option for patients with cardiotoxicity induced by treatment of malignancy in the light of current literature. We analysed our recent experience with MCS implantations in patients who have advanced heart failure associated with chemotherapy-induced cardiotoxicity. Methods In the hospital registries of 386 adult cardiomyopathy patients who were supported with a long-term impantable MCS in our institution between January 2008 and June 2012, were retrospectively evaluated. In 11 of these patients (mean age ?SD years; overall %; female/male (n); 42 +/- 14, 2.8%, 4/7) MCS was implemented due to chemotherapeutic drug-induced cardiomyopathy (CDIC). Pre-operative and post-operative data of CDIC patients were analysed. In this cohort of CDIC patients, mean duration of circulatory support was 413 ?445 days. One of the patients was successfully bridged to heart transplantation (HTx) after exclusion of possible contraindications. In one patient, left ventricular assist device (LVAD) was successfully explanted after myocardial recovery. In the late post-operative period, five patients expired due to multi-organ failure and gastrointestinal haemorrhage. The remaining 4 patients are still under follow-up on LVAD-support. One of these patients was listed for high-urgency HTx because of device-related infection. Cardiotoxicity leading to advanced heart failure is a serious complication of chemotherapeutic agents with a high risk of mortality. In our series LVAD therapy seems to be a beneficial and safe option. LVAD therapy is an acceptable option in chemotherapy-induced, advanced cardiomyopathy.


Evaluation of transanal minimally invasive surgery for submucosal rectal resection in cadaveric canine specimens.
To evaluate the feasibility of transanal minimally invasive surgery (TAMIS) for submucosal rectal resection in large breed dogs. Cadaveric study. Canine cadavers (n = 6) weighing between 37.5 and 60 kg. Dogs were positioned in sternal recumbency. After rectal cleansing, a transanal access platform was placed in the rectum, and a pneumorectum was established. An area of ventral rectal wall approximately 2 × 2 cm was resected in a submucosal plane by using laparoscopic instruments and submitted for histopathological evaluation. The rectal wall defect was closed with a single-layer continuous suture pattern with barbed suture. Postoperatively, the rectum was removed en bloc and evaluated for suture or surgical penetration of the serosal surface. Submucosal rectal resection was successfully completed by using TAMIS in all dogs. The median length of resected specimens after fixation was 24.5 mm (range 9.8-26.5). In two of six dogs, suture was macroscopically visible on the serosal surface, but no dogs had evidence of iatrogenic full-thickness surgical penetration of the rectum. The median distance from the aborad extent of the suture closure line to the anocutaneous junction was 35 mm (range, 35-105). Submucosal resection of the canine rectal wall was feasible in large breed dogs by using TAMIS. No evidence of full-thickness penetration of the rectal wall was seen in these cadaveric specimens. Transanal minimally invasive surgery may provide an alternative minimally invasive approach for resection for benign adenomatous rectal polyps in large breed dogs that might otherwise require a rectal pull-through.