Pathogenic microbiological flora recovered from ear, nose and throat specimens in a regional hospital in Kosovo.
to investigate the recovery of pathogenic bacteria, fungi and parasites isolated from ear, nose and throat specimens in large population group in a secondary health care institution. retrospective study results of all microbiologic cultures submitted from the outpatient clinic of a large, secondary health care practice, for the time period January 2001 until December 2005 were identified from a microbiologic specimen database. The results from these cultures were entered into a database, tabulating site from which the culture was taken, from whom the material was sent and the type of organism recovered. from a total of 17,362 specimens, 88% results in the normal bacterial flora. Remaining 12% were pathological bacterial, fungal and parasite flora: 1218 from ear specimens, 376 from nose and. 474 from throat specimens. In 40% of cases material was sent by primary health care provider, in 52% of cases material was taken during systematic screening and only in about 8% the material was sent from an ENT specialist. the most frequent pathogens isolated from ear specimens are Staphylococcus saprophiticus and aureus, 24.6 and 17.7%, followed by Pseudomonas auriginosa in 13.2%; from nose specimens the most often isolated pathogenic bacteria is Staphylococcus aureus in 52.4%, Streptococcus spp. in 16% and Branhamella in 13% of nose specimens. From the throat specimens Staphylococcus aureus in 48.7%, Enterococcus in 13.3%, Streptococcus beta-haemolyticus gr. A in 11.8% and Streptococcus beta-haemolyticus gr. B in 8.4% of cases. Staphylococcus spp, Pseudomonas, Escherichia and Streptococcus spp. are leading pathogens from ear, nose and throat specimens, so further investigation on appropriate antibiotics use and bacterial resistance will be welcome.


Flow cytometric measurement of STAT5 phosphorylation in cytomegalovirus-stimulated T cells.
Cytomegalovirus (CMV)-specific T cells expand with CMV reactivation and are probably prerequisite for control and protection. Given the critical role STAT5A phosphorylation (pSTAT5A) in T cell proliferation, this study presents a simple and sensitive flow cytometric-based pSTAT5A assay to quickly identify CMV-specific T cell proliferation. We determined pSTAT5A in T cells treated with CMV-specific peptide mix (pp65 + IE1 peptides) from 20 healthy adult subjects and three immunodeficient patients with CARMIL-2 mutation. After stimulation, the percentage of pSTAT5A+ T cells in CMV-seropositive (CMV+ ) subjects significantly increased from 3.0% ± 1.9% (unstimulated) to 11.4% ± 5.9% (stimulated) for 24 h. After 7 days of stimulation, the percentage of expanded T cells amounted to 26% ± 17.2%. Conversely, the percentage of pSTAT5A+ T cells and T cell proliferation from CMV-seronegative (CMV- ) subjects hardly changed (from 3.0% ± 1.3% to 3.7% ± 1.8% and from 4.3% ± 2.1% to 5.7% ± 1.7%, respectively). We analyzed the correlation between the percentage of pSTAT5A+ T cells versus (1) CMV-IgG concentrations versus (2) the percentage of expanded T cells and versus (3) the percentage of initial CMV-specific T cells. In immunodeficient patients with CARMIL-2 mutation, CMV-specific pSTAT5A and T cell proliferation were completely deficient. In conclusion, flow cytometric-based pSTAT5A assay represents an appropriate tool to quickly identify CMV-specific T cell proliferation and helps to understand dysfunctions in controlling other pathogens. Flow cytometric-based pSTAT5A assay may be a useful test in clinical practice and merits further validation in large studies.


Multiple papillary fibroelastomas and thrombus in the left heart.
Cardiac papillary fibroelastomas (CPF) are benign cardiac tumors and usually discovered incidentally during echocardiography. This report describes the case of a 68-year-old man, referred to cardiology for multiple masses of the left ventricle and left atrium. The transthoracic echocardiography revealed multiple oscillating masses in the left ventricle and aortic valve, non-mobile mass in the left atrium with severe mitral stenosis and moderate aortic regurgitation. The patient underwent surgical resection of the masses with valve replacements. Histopathologic examination confirmed the diagnosis of CPF in the left ventricle and aortic valve, thrombus in the left atrium.


Phase II study of ifosfamide, carboplatin, and etoposide in patients with a first recurrence of glioblastoma multiforme.
The prognosis of recurrent glioblastoma multiforme (GBM) remains unsatisfactory. The authors conducted a Phase II study of ifosfamide, carboplatin, and etoposide (ICE) for a first recurrence of GBM to determine whether it prolonged a patient's good-quality life. This trial was an open-label, single-center Phase II study. Forty-two patients with a first GBM relapse after surgery followed by standard radiotherapy (60 Gy) and first-line temozolomide- or nimustine-based chemotherapy were eligible to participate. The primary end point was progression-free survival at 6 months after the ICE treatment (PFS-6), and secondary end points were response rate, toxicity, and overall survival. Chemotherapy consisted of ifosfamide (1000 mg/m(2) on Days 1, 2, and 3), carboplatin (110 mg/m(2) on Day 1), etoposide (100 mg/m(2) on Days 1, 2, and 3), every 6 weeks. Progression-free survival at 6 months after ICE treatment was 35% (95% CI 22-50%). The median duration of PFS was 17 weeks (95% CI 10-24 weeks). The response rate was 25% (95% CI 9-34%). Adverse events were generally mild and consisted mainly of alopecia. This regimen was well tolerated and has some activity and could be one of the options for patients with recurrent GBM.


JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy.
Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease caused by uncontrolled polyomavirus JC (JCV) in severely immunodeficient patients. We investigated the JCV-specific cellular and humoral immunity in the Swiss HIV Cohort Study. We identified PML cases (n = 29), as well as three matched controls per case (n = 87), with prospectively cryopreserved peripheral blood mononuclear cells and plasma at diagnosis. Nested controls were matched according to age, gender, CD4(+) T-cell count, and decline. Survivors (n = 18) were defined as being alive for >1 year after diagnosis. Using gamma interferon enzyme-linked immunospot assays, we found that JCV-specific T-cell responses were lower in nonsurvivors than in their matched controls (P = 0.08), which was highly significant for laboratory- and histologically confirmed PML cases (P = 0.004). No difference was found between PML survivors and controls or for cytomegalovirus-specific T-cell responses. PML survivors showed significant increases in JCV-specific T cells (P = 0.04) and immunoglobulin G (IgG) responses (P = 0.005). IgG responses in survivors were positively correlated with CD4(+) T-cell counts (P = 0.049) and negatively with human immunodeficiency virus RNA loads (P = 0.03). We conclude that PML nonsurvivors had selectively impaired JCV-specific T-cell responses compared to CD4(+) T-cell-matched controls and failed to mount JCV-specific antibody responses. JCV-specific T-cell and IgG responses may serve as prognostic markers for patients at risk.


Air or 100% oxygen for asphyxiated babies? Time to decide.
Both experimental and clinical studies have demonstrated that room air is as efficient as 100% oxygen for newborn resuscitation and improves short-term recovery. The recent meta-analysis by Davis and colleagues in the Lancet includes five studies from the past 10 years where asphyxiated infants were randomised or pseudo-randomised to be resuscitated in room air or in 100% oxygen. A significant reduction in mortality was seen when infants were resuscitated in room air compared to 100% oxygen. It is astonishing that a brief exposure of only a few minutes to 100% oxygen may be so toxic to the newborn infant; this finding, however, is supported by increasing evidence from experimental work emphasising that resuscitation in 100% oxygen may be associated with an aggravation of cellular injury when compared with resuscitation in air. It is imperative that these findings are reflected in the new newborn resuscitation guidelines and that further research continues in this area of neonatal medicine. Key areas include defining the best resuscitation practice for the preterm infant, designing adequate multicentre, randomised and blinded studies of term newborn resuscitation with adequate outcome data, and pursuing intense experimental research into the mechanisms and prevention of injury from oxygen free radicals.


Anti‑inflammatory effect of Amomum xanthioides in a mouse atopic dermatitis model.
Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder. The present study investigated the effects of Amomum xanthioides extract (AXE) on AD‑like skin inflammation using a Dermatophagoides farinae extract (DFE) and 2,4‑dinitrochlorobenzene (DNCB)‑induced mouse AD model. Hematoxylin and eosin staining results demonstrated that repeated DFE/DNCB exposure markedly increased the thickening of the dermis and epidermis, in addition to the infiltration of eosinophils and mast cells. However, oral administration of AXE reduced these histopathological alterations in a dose‑dependent manner. Elevated serum histamine, total and DFE‑specific immunoglobulin E (IgE), and IgG2a were also decreased by treatment with AXE. In addition, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) results demonstrated that the mRNA expression of tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ, interleukin (IL)‑4, IL‑13, IL‑31 and IL‑17A was reduced in ear skin following AXE administration in AD mice. Fluorescence‑activated cell sorting demonstrated that the population of CD4+/IL‑4+, CD4+/IFN‑γ+ and CD4+/IL‑17A+ cells in draining lymph nodes was also significantly decreased in AXE‑treated mice compared with AD mice without AXE treatment. Furthermore, keratinocytes that were stimulated with TNF‑α and IFN‑γ exhibited increased gene expression of pro‑inflammatory cytokines and chemokines, including TNF‑α, IL‑1β, IL‑6, IL‑8, C‑C motif chemokine ligand (CCL)17 and CCL22, as determined by RT‑qPCR. However, upregulation of these genes was reduced by AXE pretreatment. Based on these results, we hypothesize that AXE may be useful in the treatment of allergic skin inflammation, particularly AD.


History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials by Miscarriage or Stillbirth History and Disease Subtype.
Despite the putative intrauterine origins of childhood (0-14 years) leukaemia, it is complex to assess the impact of perinatal factors on disease onset. Results on the association of maternal history of fetal loss (miscarriage/stillbirth) with specific disease subtypes in the subsequent offspring are in conflict. We sought to investigate whether miscarriage and stillbirth may have different impacts on the risk of acute lymphoblastic leukaemia (ALL) and of its main immunophenotypes (B-cell and T-cell ALL), as contrasted to acute myeloid leukaemia (AML). One thousand ninety-nine ALL incidents (957 B-ALL) and 131 AML cases along with 1:1 age and gender-matched controls derived from the Nationwide Registry for Childhood Hematological Malignancies and Brain Tumors (1996-2013) were studied. Multivariable regression models were used to assess the roles of previous miscarriage(s) and stillbirth(s) on ALL (overall, B-, T-ALL) and AML, controlling for potential confounders. Statistically significant exposure and disease subtype-specific associations of previous miscarriage(s) exclusively with AML [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.00, 2.81] and stillbirth(s) with ALL [OR 4.82, 95% CI 1.63, 14.24] and B-ALL particularly, emerged. Differential pathophysiological pathways pertaining to genetic polymorphisms or cytogenetic aberrations are likely to create hostile environments leading either to fetal loss or the development of specific leukaemia subtypes in subsequent offspring, notably distinct associations of maternal miscarriage history confined to AML and stillbirth history confined to ALL (specifically B-ALL). If confirmed and further supported by studies revealing underlying mechanisms, these results may shed light on the divergent leukemogenesis processes.


Ubiquitylation of FACT by the cullin-E3 ligase Rtt101 connects FACT to DNA replication.
FACT plays important roles in both gene transcription and DNA replication. However, how this protein complex is targeted to these two distinct cellular processes remains largely unknown. Here we show that ubiquitylation of the Spt16 subunit of FACT by Rtt101, the cullin subunit of an E3 ubiquitin ligase in Saccharomyces cerevisiae, links FACT to DNA replication. We find Rtt101 interacts with and ubiquitylates Spt16 in vitro and in vivo. Deletion of RTT101 leads to reduced association of both FACT and the replicative helicase MCM with replication origins. Loss of Rtt101 also reduces binding of FACT to MCM, but not the association of FACT with Leo1 and Spt5, two proteins involved in transcription. Origin function is compromised in cells lacking Rtt101 or with an Spt16 mutation. These findings identify Spt16 as an Rtt101 substrate, and suggest that Spt16 ubiquitylation is important for FACT to function during DNA replication.


When structure-affinity relationships meet structure-kinetics relationships: 3-((Inden-1-yl)amino)-1-isopropyl-cyclopentane-1-carboxamides as CCR2 antagonists.
Chemokine ligand 2 (CCL2) mediates chemotaxis of monocytes to inflammatory sites via interaction with its G protein-coupled receptor CCR2. Preclinical animal models suggest that the CCL2-CCR2 axis has a critical role in the development and maintenance of inflammatory disease states (e.g., multiple sclerosis, atherosclerosis, insulin resistance, restenosis, and neuropathic pain), which can be treated through inhibition of the CCR2 receptor. However, in clinical trials high-affinity inhibitors of CCR2 have often demonstrated a lack of efficacy. We have previously described a new approach for the design of high-affinity CCR2 antagonists, by taking their residence time (RT) on the receptor into account. Here, we report our findings on both structure-affinity relationship (SAR) and structure-kinetic relationship (SKR) studies for a series of 3-((inden-1-yl)amino)-1-isopropyl-cyclopentane-1-carboxamides as CCR2 antagonists. SAR studies showed that this class of compounds tolerates a vast diversity of substituents on the indenyl ring with only small changes in affinity. However, the SKR is affected greatly by minor modifications of the structure. The combination of SAR and SKR in the hit-to-lead process resulted in the discovery of a new high-affinity and long-residence-time CCR2 antagonist (compound 15a, Ki = 2.4 nM; RT = 714 min).


Current Perspectives for the use of Gonane Progesteronergic Drugs in the Treatment of Central Hypoventilation Syndromes.
Central alveolar hypoventilation syndromes (CHS) encompass neurorespiratory diseases resulting from congenital or acquired neurological disorders. Hypercapnia, acidosis, and hypoxemia resulting from CHS negatively affect physiological functions and can be lifethreatening. To date, the absence of pharmacological treatment implies that the patients must receive assisted ventilation throughout their lives. To highlight the relevance of determining conditions in which using gonane synthetic progestins could be of potential clinical interest for the treatment of CHS. The mechanisms by which gonanes modulate the respiratory drive were put into the context of those established for natural progesterone and other synthetic progestins. The clinical benefits of synthetic progestins to treat respiratory diseases are mixed with either positive outcomes or no improvement. A benefit for CHS patients has only recently been proposed. We incidentally observed restoration of CO2 chemosensitivity, the functional deficit of this disease, in two adult CHS women by desogestrel, a gonane progestin, used for contraception. This effect was not observed by another group, studying a single patient. These contradictory findings are probably due to the complex nature of the action of desogestrel on breathing and led us to carry out mechanistic studies in rodents. Our results show that desogestrel influences the respiratory command by modulating the GABAA and NMDA signaling in the respiratory network, medullary serotoninergic systems, and supramedullary areas. Gonanes show promise for improving ventilation of CHS patients, although the conditions of their use need to be better understood.


Research on the Influence of Paradoxical Leadership on Compulsory Organizational Citizenship Behavior.
According to attribution theory, the purpose of this paper is to examine the relationship between paradoxical leadership and employees' compulsory organizational citizenship behavior, research the mediating and moderating effects of work pressure perception and leadership member exchange differentiation. The data collection work was carried out with 329 employees as the research object, and empirical tests were carried out using confirmatory factor analysis and hierarchical regression analysis methods. The results of the empirical test show that: paradoxical leadership has a significant positive effect on employees' compulsory organizational citizenship behavior; work pressure perception plays a mediating role between paradoxical leadership and employee's compulsory organizational citizenship behavior; leadership member exchange differentiation plays a moderating role between paradoxical leadership and work pressure perception. Paradoxical leadership will lead employees to adopt compulsory organizational citizenship behavior. Moreover, organizations should reduce employees' perception of work pressure and leadership member exchange differentiation. The results of the study provide positive suggestions for reducing the compulsory organizational citizenship behavior of employees by focusing on the behavior of paradoxical leadership, thereby promoting the improvement of corporate performance. 1) The research on the influence of paradoxical leadership on compulsory organizational citizenship behavior reveals the "dark side" of the influence of paradoxical leadership on employee behavior. 2) By introducing work pressure perception, this paper reveals the mechanism of action between paradoxical leadership and compulsory organizational citizenship behavior, which provides a new research perspective for understanding the formation mechanism of employees adopting compulsory organizational citizenship behavior. 3) This paper confirms that leadership member exchange differentiation can positively moderate the relationship between paradoxical leadership and work pressure perception.


Transplantation of primary bovine adrenocortical cells into scid mice.
Bovine adrenocortical cells were transplanted into scid mice, using a small cylinder inserted beneath the kidney capsule. The tissue formed from primary bovine adrenocortical cells replaced the essential functions of the animals' own adrenal glands, which were removed during the cell transplantation procedure. Most adrenalectomized animals bearing transplanted cells survived indefinitely, whereas adrenalectomized control animals died following surgery. Formation of well-vascularized tissue at the site of transplantation was associated with stable levels of cortisol in the blood, replacing the mouse glucocorticoid (corticosterone). Ultrastructurally, the cultured cells before transplantation had characteristics of rapidly growing cells, but tissue formed in vivo showed features associated with active steroidogenesis. We investigated two potentially critical aspects of the procedure: the provision of support for angiogenesis in the transplant by the inclusion of FGF-secreting 3T3 cells with the adrenocortical cells; and the administration of synthetic steroids as a temporary replacement for steroids lost by adrenalectomy. We found that FGF was required for the rapid formation of well-vascularized tissue, whereas steroid administration avoided some early mortality but was not absolutely required. In contrast to transplants formed from clonal cells, which did not usually secrete aldosterone, transplants formed from primary bovine adrenocortical cells, even though derived from the zona fasciculata, secreted aldosterone as well as cortisol.


[Effect of high and superhigh doses of 60Co gamma-quanta and fission neutrons on rats].
A transient form of acute radiation sickness could be distinguished in Wistar rats after total-body exposure to 60Co-gamma-rays in high doses (150-200 Gy). With local exposure of head, in addition to direct damaging effect on the nervous system, the organismic factors play an important role in the development of the CNS syndrome. Effects of fractionation of superhigh doses of gamma-quanta and fission neutrons were not observed. The RBE of neutrons should constitute 1.8 for the transient form of radiation sickness to develop. This value is much lesser than that needed for the development of haemopoietic and intestinal lesions. PAPP, "gammaphos" and the combination of these agents do not influence the affection of rats by high doses of gamma-quanta.


Granulocyte transfusions for treating infections in patients with neutropenia or neutrophil dysfunction.
Transfusions of granulocytes have a long history of usage in clinical practice to support and treat severe infection in high risk groups of patients with neutropenia or neutrophil dysfunction. However, there is considerable current variability in therapeutic granulocyte transfusion practice, and uncertainty about the beneficial effect of transfusions given as an adjunct to antibiotics on mortality. To determine the effectiveness of granulocyte transfusions compared to no granulocyte transfusions for treating infections in patients with neutropenia or disorders of neutrophil function in reducing mortality. Randomised controlled trials (RCTs) were searched for in the Cochrane Central Register of Controlled Trials (CENTRAL) in 2003. Searching was also undertaken on the OVID versions of Medline and Embase using an RCT search filter strategy. RCTs involving transfusions of granulocytes, given therapeutically, to patients with neutropenia or disorders of neutrophil dysfunction. Two reviewers completed data extraction independently. Relative risk (RR) with 95% confidence intervals (CI) using the random effects model were reported for dichotomous outcomes. Pre-specified subgroup analyses were done and reported eg granulocyte dose. Eight parallel RCTs were included with 310 total analysed patient episodes. Different policies were applied for the schedule of transfusion, method of granulocyte procurement and process of donor selection including leucocyte compatibility. Each study used different criteria for neutropenia (range < 0.1 to < 1.0 x 10(9)/L) and definition of infection requiring treatment. For mortality, which was extracted from six trials, the summary RR = 0.64 in favour of transfusion (95% CI 0.33, 1.26), but with evidence of significant statistical heterogeneity (Chi-square 11.3 and I(2) = 56%). The data for the combined RR for mortality for the four studies transfusing higher granulocyte doses greater than 1x10(10) indicated a significant summary RR= 0.37 (95% CI 0.17, 0.82); Chi-square 3.9, I(2) 23%. Data on rates of reversal of infection could be extracted from four studies, and the combined RR was 0.94 (95% CI 0.71, 1.26), again with evidence of heterogeneity. In addition to the observed clinical diversity between all studies, uncertainty about the quantitative and qualitative analyses for these studies is compounded by methodological deficiencies. Currently, there is inconclusive evidence from RCTs to support or refute the generalised use of granulocyte transfusion therapy in the most common neutropenic patient populations, that is caused by myeloablative chemotherapy with or without haematopoietic stem cell support. Contemporary well designed prospective trials are required to evaluate the efficacy of this intervention in these patient populations and to establish definitively whether it has clinical benefit. In such studies, average numbers of collected granulocytes for adults should be (at least) greater than 1x10(10).


[The pathogenetic characteristics of the anemic syndrome in liver cirrhosis].
Overall sixty-two patients, in different age brackets, with cirrhosis of the liver were examined. Of these, 42 presented with anemia, while 20 with no anemia. All patients were evaluated for activity of lipid peroxidation and state of the antioxidant systems. Cirrhotic patients with anemia displayed more profound dysfunction of antioxidant systems. This led to disorganization of the erythrocytic membranes' lipid and protein components, worsening of their rheologic properties, causing morbid shifts in the receptors' function. The above pathologies combined affect the degree of anemia in cirrhotic patients. Anemic syndrome in this patient population was managed with anaprilin, a beta-adrenoblocker.


Determination of the complete nucleotide sequence and haplotypes in the D-loop region of the mitochondrial genome in the oriental white stork, Ciconia boyciana.
The complete nucleotide sequence of the mitochondrial genome of the Oriental white stork, Ciconia boyciana, has been determined from captive storks by a novel method incorporating Long PCR and shotgun sequencing. 13 protein-coding genes, two ribosomal RNA genes and 22 transfer RNA genes were identified as in other vertebrate mitochondrial genomes. The position and direction of the NADH6 and tRNA-Glu genes were the same as previously reported for avian mitochondrial genomes. A 71 bp direct repeat and long CAAA repeat sequences were found at the 3' end of the D-loop region, together with SCB-1, SCB-2, SCB-3, and three TAS sequences. Direct sequencing of the PCR fragments in the D-loop region in 26 captive Oriental white storks originating from Japan, China, and Russia revealed nucleotide differences at 18 sites along 1,248 bp, and a total of nine haplotypes have been identified. It was found that one pair of individuals in the Japanese captive breeding program were of the same haplotype, suggesting that they were caught from the same nest. The pair has since been dissolved in consideration of the possibility of inbreeding depression.


Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death.
We have proposed the "glucolipotoxicity" hypothesis in which elevated free fatty acids (FFAs) together with hyperglycemia are synergistic in causing islet beta-cell damage because high glucose inhibits fat oxidation and consequently lipid detoxification. The effects of 1-2 d culture of both rat INS 832/13 cells and human islet beta-cells were investigated in medium containing glucose (5, 11, 20 mM) in the presence or absence of various FFAs. A marked synergistic effect of elevated concentrations of glucose and saturated FFA (palmitate and stearate) on inducing beta-cell death by apoptosis was found in both INS 832/13 and human islet beta-cells. In comparison, linoleate (polyunsaturated) synergized only modestly with high glucose, whereas oleate (monounsaturated) was not toxic. Treating cells with the acyl-coenzyme A synthase inhibitor triacsin C, or the AMP kinase activators metformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside that redirect lipid partitioning to oxidation, curtailed glucolipotoxicity. In contrast, the fat oxidation inhibitor etomoxir, like glucose, markedly enhanced palmitate-induced cell death. The data indicate that FFAs must be metabolized to long chain fatty acyl-CoA to exert toxicity, the effect of which can be reduced by activating fatty acid oxidation. The results support the glucolipotoxicity hypothesis of beta-cell failure proposing that elevated FFAs are particularly toxic in the context of hyperglycemia.


Shape of a slowly rotating star measured by asteroseismology.
Stars are not perfectly spherically symmetric. They are deformed by rotation and magnetic fields. Until now, the study of stellar shapes has only been possible with optical interferometry for a few of the fastest-rotating nearby stars. We report an asteroseismic measurement, with much better precision than interferometry, of the asphericity of an A-type star with a rotation period of 100 days. Using the fact that different modes of oscillation probe different stellar latitudes, we infer a tiny but significant flattening of the star's shape of ΔR/R = (1.8 ± 0.6) × 10-6. For a stellar radius R that is 2.24 times the solar radius, the difference in radius between the equator and the poles is ΔR = 3 ± 1 km. Because the observed ΔR/R is only one-third of the expected rotational oblateness, we conjecture the presence of a weak magnetic field on a star that does not have an extended convective envelope. This calls to question the origin of the magnetic field.


Cone dystrophy with supernormal rod response is strictly associated with mutations in KCNV2.
Cone dystrophy with supernormal rod response (CDSRR) is a retinal disorder characterized by reduced visual acuity, color vision defects, and specific alterations of ERG responses that feature elevated scotopic b-wave amplitudes at high luminance intensities. Mutations in PDE6H and in KCNV2 have been described in CDSRR. A combined clinical and genetic study was conducted in a cohort of patients with CDSRR, to substantiate these prior Seventeen patients from 13 families underwent a detailed ophthalmic examination including color vision testing, Goldmann visual fields, fundus photography, Ganzfeld and multifocal ERGs, and optical coherence tomography. The coding sequences and flanking intron/UTR sequences of PDE6C and KCNV2 were screened for mutations by means of DHPLC and direct DNA sequencing of PCR-amplified genomic DNA. results. Whereas no mutations were detected in the PDE6H gene, mutations in KCNV2 were identified in all patients, in either the homozygous or compound heterozygous state. Ten of the 11 identified mutations were novel, including three missense and six truncating mutations and one gross deletion. The mutations concordantly segregate in all available families according a recessive mode of inheritance. The CDSRR phenotype was associated with reduced visual acuity of variable degree and color vision defects. Macular defects ranging from mild pigmentary changes to distinct foveal atrophy were present in nine patients. Progression of the disease was observed in only three of seven patients with follow-up data. The phenotype of cone dystrophy with supernormal rod response is tightly linked with mutations in KCNV2.


Mutations in eukaryotic release factors 1 and 3 act as general nonsense suppressors in Drosophila.
In a screen for suppressors of the Drosophila wingless(PE4) nonsense allele, we isolated mutations in the two components that form eukaryotic release factor. eRF1 and eRF3 comprise the translation termination complex that recognizes stop codons and catalyzes the release of nascent polypeptide chains from ribosomes. Mutations disrupting the Drosophila eRF1 and eRF3 show a strong maternal-effect nonsense suppression due to readthrough of stop codons and are zygotically lethal during larval stages. We tested nonsense mutations in wg and in other embryonically acting genes and found that different stop codons can be suppressed but only a subset of nonsense alleles are subject to suppression. We suspect that the context of the stop codon is significant: nonsense alleles sensitive to suppression by eRF1 and eRF3 encode stop codons that are immediately followed by a cytidine. Such suppressible alleles appear to be intrinsically weak, with a low level of readthrough that is enhanced when translation termination is disrupted. Thus the eRF1 and eRF3 mutations provide a tool for identifying nonsense alleles that are leaky. Our findings have important implications for assigning null mutant phenotypes and for selecting appropriate alleles to use in suppressor screens.


Treatment of metastatic spinal epidural disease: a review of the literature.
Spinal cord compression is one of the most dreaded complications of metastatic cancer. It can lead to a number of sequelae, including pain, spinal instability, neurological deficits, and a reduction in the patient's quality of life. Except in selected circumstances, treatment is palliative. Treatment options include surgery, radiation, and chemotherapy. The goal of this study was to summarize the existing data on the outcomes of various treatment methods for metastatic spinal epidural disease and to make appropriate recommendations for their use. The authors used a search strategy that included an electronic database search, a manual search of journals, analysis of bibliographies in relevant review papers, and consultation with the senior author. There is good evidence, including Class I data, that steroid drugs constitute a beneficial adjunctive therapy in patients with myelopathy from epidural compression. Historically, conventional radiation therapy has been viewed as the first-line treatment because it has been shown to be as effective as a decompressive laminectomy, with a lower incidence of complications (Class II data). Nevertheless, in the last 20 years there has been remarkable progress in surgical techniques and technology. Currently, the goals of surgery are to achieve a circumferential decompression of the spinal cord, and to reconstruct and immediately stabilize the spinal column. Results in a large body of literature support the belief that surgery is better at retaining or regaining neurological function than radiation and that surgery is highly effective in relieving pain. Most of the data on the treatment of metastatic spinal disease are Class II or III, but the preliminary results of a well-designed, randomized controlled trial in which surgery is compared with standard radiation therapy represents the first Class I data. As the number of treatment options for metastatic spinal disease has grown, it has become clear that effective implementation of these treatments can only be achieved by a multidisciplinary approach.


The use of cost-effectiveness by the National Institute for Health and Clinical Excellence (NICE): no(t yet an) exemplar of a deliberative process.
Democratic societies find it difficult to reach consensus concerning principles for healthcare distribution in the face of resource constraints. At the same time the need for legitimacy of allocation decisions has been recognised. Against this background, the National Institute for Health and Clinical Excellence (NICE) aspires to meet the principles of procedural justice, specifically the conditions of accountability for reasonableness as espoused by Daniels and Sabin, that is, publicity, relevance, revisions and appeal, and enforcement. Although NICE has adopted a highly standardised approach and continuously publishes key documents on its website, its technology appraisal programme does not fulfil the publicity condition of accountability for reasonableness. Economic models are not made sufficiently transparent to enable public scrutiny, and decision criteria other than cost-effectiveness remain enigmatic. NICE's reliance on cost-utility analysis and "plausible" cost-per-quality-adjusted life year (QALY) benchmarks further raises serious issues with regard to the relevance condition of accountability for reasonableness. This is illustrated by counterintuitive cost-per-QALY rankings that are difficult to justify using reflective equilibrium methods, and by the current debate surrounding expensive therapies for rare diseases ("orphan" treatments). In addition, an excessive focus on QALYs may stand in the way of exploiting the best available effectiveness evidence. The NICE mechanism for revision and appeals is also more restrictive than provided in accountability for reasonableness. As to the enforcement condition, no effective quality assurance processes are in place for technology assessments, and implementation of guidance remains imperfect. NICE, despite impressive efforts, appears to have a long way to go before meeting the conditions of accountability for reasonableness.


Autonomous detection and sorting of litter using deep learning and soft robotic grippers.
Road infrastructure is one of the most vital assets of any country. Keeping the road infrastructure clean and unpolluted is important for ensuring road safety and reducing environmental risk. However, roadside litter picking is an extremely laborious, expensive, monotonous and hazardous task. Automating the process would save taxpayers money and reduce the risk for road users and the maintenance crew. This work presents LitterBot, an autonomous robotic system capable of detecting, localizing and classifying common roadside litter. We use a learning-based object detection and segmentation algorithm trained on the TACO dataset for identifying and classifying garbage. We develop a robust modular manipulation framework by using soft robotic grippers and a real-time visual-servoing strategy. This enables the manipulator to pick up objects of variable sizes and shapes even in dynamic environments. The robot achieves greater than 80% classified picking and binning success rates for all experiments; which was validated on a wide variety of test litter objects in static single and cluttered configurations and with dynamically moving test objects. Our results showcase how a deep model trained on an online dataset can be deployed in real-world applications with high accuracy by the appropriate design of a control framework around it.


Unsharp Mask Guided Filtering.
The goal of this paper is guided image filtering, which emphasizes the importance of structure transfer during filtering by means of an additional guidance image. Where classical guided filters transfer structures using hand-designed functions, recent guided filters have been considerably advanced through parametric learning of deep networks. The state-of-the-art leverages deep networks to estimate the two core coefficients of the guided filter. In this work, we posit that simultaneously estimating both coefficients is suboptimal, resulting in halo artifacts and structure inconsistencies. Inspired by unsharp masking, a classical technique for edge enhancement that requires only a single coefficient, we propose a new and simplified formulation of the guided filter. Our formulation enjoys a filtering prior from a low-pass filter and enables explicit structure transfer by estimating a single coefficient. Based on our proposed formulation, we introduce a successive guided filtering network, which provides multiple filtering results from a single network, allowing for a trade-off between accuracy and efficiency. Extensive ablations, comparisons and analysis show the effectiveness and efficiency of our formulation and network, resulting in state-of-the-art results across filtering tasks like upsampling, denoising, and cross-modality filtering. Code is available at https://github.com/shizenglin/Unsharp-Mask-Guided-Filtering.


Food anticipatory behaviour as an indicator of stress response and recovery in Atlantic salmon post-smolt after exposure to acute temperature fluctuation.
In this study we evaluated Pavlovian conditioned food anticipatory behaviour as a potential indicator for stress in groups of Atlantic salmon, and compared this with the physiological stress responses of cortisol excretion into water and hyper-consumption of oxygen. We hypothesised that environmental stress would result in reduced feeding motivation. To assess this, we measured the strength of anticipatory behaviour during a period of flashing light that signalled arrival of food. Further, we expected that fish given a reduced food ration would be less sensitive to environmental stress than fish fed full ration. The fish responded to an acute temperature fluctuation with hyper-consumption of oxygen that decreased in line with the temperature, and elevated cortisol excretion up to 1h after the stressor. These physiological responses did not differ significantly between the food ration groups. The anticipatory behaviour was significantly reduced after the stressor and returned to control levels after 1 to 2 h in the reduced ration group, but not until after 3 to 4 h in the full ration group. Our results show that acute stress can be measured in terms of changes to feeding motivation, and that it is a more sensitive indicator of stress that influences the fish over a longer time period than measures of change in cortisol excretion.


Oncogenic transformation in C3H10T1/2 cells by low-energy neutrons.
Occupational exposure to neutrons typically includes significant doses of low-energy neutrons, with energies below 100 keV. In addition, the normal-tissue dose from boron neutron capture therapy will largely be from low-energy neutrons. Microdosimetric theory predicts decreasing biological effectiveness for neutrons with energies below about 350 keV compared with that for higher-energy neutrons; based on such considerations, and limited biological data, the current radiation weighting factor (quality factor) for neutrons with energies from 10 keV to 100 keV is less than that for higher-energy neutrons. By contrast, some reports have suggested that the biological effectiveness of low-energy neutrons is similar to that of fast neutrons. The purpose of the current work is to assess the relative biological effectiveness of low-energy neutrons for an endpoint of relevance to carcinogenesis: in vitro oncogenic transformation. Oncogenic transformation induction frequencies were determined for C3H10T1/2 cells exposed to two low-energy neutron beams, respectively, with dose-averaged energies of 40 and 70 keV, and the results were compared with those for higher-energy neutrons and X-rays. These results for oncogenic transformation provide evidence for a significant decrease in biological effectiveness for 40 keV neutrons compared with 350 keV neutrons. The 70 keV neutrons were intermediate in effectiveness between the 70 and 350 keV beams. A decrease in biological effectiveness for low-energy neutrons is in agreement with most (but not all) earlier biological studies, as well as microdosimetric considerations. The results for oncogenic transformation were consistent with the currently recommended decreased values for low-energy neutron radiation weighting factors compared with fast neutrons.


Lin28B is an oncofetal circulating cancer stem cell-like marker associated with recurrence of hepatocellular carcinoma.
By using an expressed sequence tag bioinformatic algorithm, we identified that Lin28 homolog B (Lin28B) may have an oncofetal expression pattern which may facilitate detecting cancer cells in adults. It is also reported to be a potential marker for cancer stem cells. Therefore, we sought to verify oncofetal-stemness characters of Lin28B and test its potential as a circulating cancer stem cell-like marker in adult HCC patients. Lin28B mRNA was examined in a panel of fetal tissue, adult tissue and tumors. Lin28B was over-expressed or knocked down in HepG2 cells to evaluate its potential as a stem cell-like marker. RT-qPCR for Lin28B was performed in the peripheral blood mononuclear cells from patients with HCC receiving surgery (n=96) and non-HCC controls (n=60) and analyzed its clinical significance. Lin28B showed an oncofetal expression pattern. Its overexpression could upregulate stemness markers (OCT4, Nanog and SOX2) and enhance tumorsphere formation in vitro. Lin28B knockdown had opposite effects. Circulating Lin28B was detected in peripheral blood mononuclear cells in 3 cases (5%) of non-HCC controls and 32 cases (33.3%) of HCC patients. In HCC patients, circulating Lin28B was associated with high tumor grade (P=0.046), large size (P=0.005), high AJCC stage (P=0.044) and BCLC stage (P=0.017). Circulating Lin28B was significantly associated with decreased recurrence-free survival (P<0.001). Circulating Lin28B separated early stage HCC into 2 recurrence-free survival curves (P=0.003). In multivariate analysis, circulating Lin28B was an independent variable associated with early recurrence (P=0.045) and recurrence in early stage HCC (P=0.006). In conclusion, the oncofetal gene Lin28B is a potential oncofetal cancer-stem-cell-like circulating tumor cell marker that correlates with HCC recurrence after hepatectomy. Circulating Lin28B could refine early AJCC stages. Our finding supports the possible use of a TNMC (C for circulating tumor cells) staging system in HCC.


Monitoring Female Fertility Through 'Femtech': The Need for a Whole-System Approach to Regulation.
Concurrent with the rise of digital health and personal health tracking technologies, a market has also emerged of products targeted specifically at women: 'femtech'. This article is motivated by the concern that insufficient regulatory attention has been devoted to this growing market, and that extant ambiguity in the regulation of femtech leaves its users at risk of relying on technologies of as-yet unproven worth. It is posited that femtech profoundly disrupts well-established regulatory mechanisms of protection in ways that mean that these silos of protection will not be adequate. This is because regulation, as it is currently constructed, is insufficiently sensitive to feminist perspectives regarding what these technologies mean for women. As a result, the regulatory sphere in which femtech operates fundamentally fails to ensure that the health and safety of femtech users are protected as this market continues to expand. To counteract this, the argument is made that an appropriate regulatory response to femtech must respond to the distinctive unmet need in the regulation of this technological realm and the acute risk that femtech poses. This must include a multidimensional whole-system approach grounded in feminist perspectives on health, fertility, and technology.


Internet-delivered CBT for children with specific phobia: a pilot study.
Cognitive behavior therapy (CBT) has been shown to be an effective treatment for specific phobia in youth, but not all affected seek or receive treatment. Internet-delivered CBT could be a way to increase the availability of empirically supported treatments. An open trial was conducted to evaluate Internet-delivered CBT for children with specific phobia. Children (N = 30) aged 8-12, and their parents, with a principal diagnosis of specific phobia were recruited through media advertisement. Participants received six weeks of Internet-delivered CBT with therapist support. The treatment was aimed for the parents and the children, with the first part being only for the parents. The primary outcome measure was the Clinician Severity Rating (CSR), and secondary measures included clinician-rated global functioning and child- and parent-reported anxiety and quality of life. All assessments were made at pretreatment, posttreatment, and three-month follow-up. At posttreatment, there were significant reductions on the CSR, with a large within-group effect size (Cohen's d = 1.0) and 35% of children no longer meeting criteria for specific phobia. Self-report measures from parents and children showed significant effects on anxiety, with small to moderate effect sizes. Effects were maintained at three-month follow-up. Results show that Internet-delivered CBT with therapist support for children with specific phobia has the potential to reduce symptom severity. Randomized controlled trials are needed to further evaluate this treatment format.


No association between coffee, tea or caffeine consumption and breast cancer risk in a prospective cohort study.
Numerous mechanisms for the effects of coffee, tea and caffeine on the risk of breast cancer have been suggested. Caffeine intake has already been associated with high plasma levels of female hormones, but associations have not been clearly demonstrated in epidemiological studies. We examined prospectively the association of coffee, tea and caffeine consumption with breast cancer risk in a French cohort study. Dietary information was obtained from a 208-item diet history questionnaire self-administered in 1993-1995. Multivariable Cox proportional hazards regression models were used to estimate hazards ratios and 95 % confidence intervals. The study was conducted on 67 703 women with available dietary information. During a median follow-up of 11 years, 2868 breast cancer cases were diagnosed. Median intake was 280 ml/d (2·2 cups/d) for coffee and 214 ml/d (1·7 cups/d) for tea. Median caffeine intake was 164 mg/d. No association was found between consumption of coffee, tea or caffeine and breast cancer risk. Sub-analyses by tumour receptor status, menopausal status, type of coffee (regular or decaffeinated) and meals at which beverages were drunk led to the same conclusion. Results from this prospective study showed no relationship between coffee, tea or caffeine intake and breast cancer risk overall or by hormone receptor status.


Effects of visual and audiovisual distraction on pain and anxiety among patients undergoing colonoscopy.
The aim of this study was to test the effects of visual and audiovisual distraction on pain, anxiety, and procedure tolerance among patients undergoing colonoscopy. A prospective, randomized, controlled design was used with 180 consecutive patients who underwent colonoscopy. Subjects were randomly allocated into 3 groups: Group A received visual distraction, Group B received audiovisual distraction, Group C with routine care. Outcome variables included pain, anxiety, and willingness to undergo colonoscopy again if the procedure was to be repeated. No significant difference was found on the pain scores of the 3 groups. However, when groups A and B were further divided into groups A1, A2, A3 (low-, middle-, high-involvement groups), and B1, B2, B3 (low-, middle-, high-involvement groups) according to the level of distraction involvement, significant differences in pain scores were found between 7 groups (A1 and A3, A2 and A3, A1 and B3, A2 and B3, A3 and C, B1 and B3, B3 and C). The pain score of Group A3 was significantly lower than those of groups A1, A2, and C, and the pain score of Group B3 was significantly lower than those of groups B1 and C. The reduction of anxiety levels after procedure was insignificant between the 2 intervention groups and control group. The rates of willingness to undergo colonoscopy again if the procedure was to be repeated of the 2 intervention groups were significantly higher than that of the control group. Visual and audiovisual distraction is effective in promoting pain control for patients undergoing colonoscopy and improving their tolerance of the procedure.


The climacteric-like behaviour of young, mature and wounded citrus leaves.
Although leaves and other vegetative tissues are generally considered as non-climacteric, citrus leaves show a climacteric system II behaviour after detachment. Upon harvest, young, fully expanded 'Valencia' orange (Citrus sinensis) leaves ( approximately 60-d-old) exhibited two phases of ethylene production. The first phase, up to 6 d after detachment, was characterized by a low and constant ethylene production (system I pathway), associated with a constitutive expression of ACC synthase 2 (CsACS2), CsERS1, and CsETR1. ACC synthase 1 (CsACS1) was not expressed during this phase and autoinhibition of ethylene production was apparent following treatment with exogenous ethylene or propylene. The second phase, 7-12 d after detachment, was characterized by a climacteric rise in ethylene production, preceded by the induction of CsACS1 and ACC oxidase 1 (CsACO1) gene expression in the system II pathway. This induction was accelerated and augmented by exogenous ethylene or propylene, indicating an autocatalytic system II ethylene biosynthesis. Mature leaves (6-8-months-old) behaved similarly, except that the climacteric peak in ethylene production occurred earlier (day 5). Young and mature leaves varied in the timing of the climacteric ethylene rise and CsACS1 and CsACO1 induction. The two phases of ethylene production, system I and system II, were also detected in wounded leaf discs of both young and mature leaves. The first phase peaked 15 min after excision and the second phase peaked after 6 h.


A device that operates within a self-assembled 3D DNA crystal.
Structural DNA nanotechnology finds applications in numerous areas, but the construction of objects, 2D and 3D crystalline lattices and devices is prominent among them. Each of these components has been developed individually, and most of them have been combined in pairs. However, to date there are no reports of independent devices contained within 3D crystals. Here we report a three-state 3D device whereby we change the colour of the crystals by diffusing strands that contain dyes in or out of the crystals through the mother-liquor component of the system. Each colouring strand is designed to pair with an extended triangle strand by Watson-Crick base pairing. The arm that contains the dyes is quite flexible, but it is possible to establish the presence of the duplex proximal to the triangle by X-ray crystallography. We modelled the transition between the red and blue states through a simple kinetic model.


Jeddah Retinopathy of Prematurity (JED-ROP) Screening Algorithm.
Background. The Jeddah retinopathy of prematurity (JED-ROP) algorithm, which is more specific to the population in Saudi Arabia, was established to decrease the number of infants screened without missing type 1 ROP cases. Methods. The data reviewed were birth weight (BW), gestational age (GA), weekly postnatal weight gain (PWG), and relevant perinatal risk factors. The sensitivities and specificities for detecting type 1 ROP were calculated. Results. Of the 502 infants included in the study, 148 developed ROP. The JED-ROP algorithm demonstrated 100% sensitivity and 38.9% specificity for recommending the screening of infants with GA ≤30 weeks and BW <1501 g and blood transfused <6 weeks and/or 3-week PWG <100 g in the type 1 ROP group. Conclusion. The JED-ROP algorithm can reduce the number of infants requiring ROP screening by 35.7% without missing type 1 ROP. The algorithm can be an adjunct to current national screening guidelines.


No support for white matter connectivity differences in the combined and inattentive ADHD presentations.
Evidence from functional neuroimaging studies support neural differences between the Attention Deficit Hyperactivity Disorder (ADHD) presentation types. It remains unclear if these neural deficits also manifest at the structural level. We have previously shown that the ADHD combined, and ADHD inattentive types demonstrate differences in graph properties of structural covariance suggesting an underlying difference in neuroanatomical organization. The goal of this study was to examine and validate white matter brain organization between the two subtypes using both scalar and connectivity measures of brain white matter. We used both tract-based spatial statistical (TBSS) and tractography analyses with network-based Statistics (NBS) and graph-theoretical analyses in a cohort of 35 ADHD participants (aged 8-17 years) defined using DSM-IV criteria as combined (ADHD-C) type (n = 19) or as predominantly inattentive (ADHD-I) type (n = 16), and 28 matched neurotypical controls. We performed TBSS analyses on scalar measures of fractional anisotropy (FA), mean (MD), radial (RD), and axial (AD) diffusivity to assess differences in WM between ADHD types and controls. NBS and graph theoretical analysis of whole brain inter-regional tractography examined connectomic differences and brain network organization, respectively. None of the scalar measures significantly differed between ADHD types or relative to controls. Similarly, there were no tractography connectivity differences between the two subtypes and relative to controls using NBS. Global and regional graph measures were also similar between the groups. A single significant finding was observed for nodal degree between the ADHD-C and controls, in the right insula (corrected p = .029). Our result of no white matter differences between the subtypes is consistent with most previous findings. These findings together might suggest that the white matter structural architecture is largely similar between the DSM-based ADHD presentations is similar to the extent of being undetectable with the current cohort size.


Hoarding symptoms and workplace impairment.
A prior study found that over 50% of treatment-seeking individuals who hoard incur at least one psychiatric work impairment day (i.e., they are unable to work or are less effective at work due to poor mental health) each month. The aim of the current study was to assess work-related variables associated with workplace impairment in a non-treatment-seeking sample. Cross-sectional. Self-report questionnaires were administered via Amazon's Mechanical Turk. One hundred and eighty-five employed individuals who reported elevated hoarding symptoms completed questionnaires regarding hoarding symptoms, work engagement, psychiatric work impairment, work control, attention and concentration difficulties at work, and quality of workplace relationships. Greater workplace control and higher quality workplace relationships were associated with greater work engagement. Greater hoarding symptoms and attention difficulties at work were associated with more psychiatric work impairment days. Work engagement statistically mediated the association between the quality of workplace relationships and work impairment, though mediation was also significant when reversing the mediating and outcome variables. Among a community sample of employed individuals, greater hoarding symptoms were associated with greater psychiatric work impairment. Work-related variables, such as co-worker relationships and attention difficulties, contributed additional variance above that accounted for by hoarding symptoms. There were significant associations between co-worker relationships, work engagement, and workplace impairment, though the direction of the mediation model is unclear. Future research should examine factors associated with unemployment in hoarding disorder. Clinicians should be aware that greater hoarding severity directly contributes to greater workplace impairment. Clinicians should consider prioritizing the reduction in clutter in living areas that impact one's daily activities and subsequent ability to attend work. Clinicians should assess and treat workplace impairment by helping individuals achieve greater control at work, developing higher quality interpersonal relationships, and improving their attentional abilities.


Screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell-gene level.
Identifying a novel method to monitor metastatic bladder cancer status at the cell-gene level could lead to earlier appropriate therapeutic intervention and better outcomes. In this study, we evaluated a practical method to monitor the cancer status at the circulating cell-gene level before and after treatment in fourteen patients with metastatic bladder cancer who were indicated for systemic drug therapy. Patients were assessed via imaging before and after drug treatment, and cell-free DNA (cfDNA) analysis was performed to detect three parameters: cfDNA level, ERRB2 gene copy numbers, and telomerase reverse transcriptase (TERT) gene mutations. We hypothesized that decreased cfDNA levels, a normal copy number of ERB-B2 receptor tyrosine kinase 2 (ERBB2), and the absence of the TERT C228T mutation indicate cancer suppression. We found that a > 1.8-fold increase in cfDNA levels, increased copy number of ERBB2, or the existence of the TERT C228T mutation indicated disease progression. Stable cfDNA levels, normal ERBB2 copy number, and the absence of TERT C228T mutations indicate a stable cancer status. Collectively, our results show that the combination of cfDNA concentration, TERT mutation, and ERBB2 copy number may be useful for determining the efficacy of drug therapy in patients with metastatic bladder cancer.


Experiment and computation: a combined approach to study the reactivity of palladium complexes in oxidation states 0 to IV.
As the accuracy of computational chemistry increases, and the advent of more powerful computers decreases the amount of time required to perform complex calculations, the use of this to investigate chemical systems becomes increasingly attractive. Particularly in combination with practical lab-based experimental and spectroscopic studies the application of in silico studies is a powerful tool for mechanistic investigations. In this review we demonstrate how a combined experimental and computational approach can yield mechanistic insight that could frequently not have been accessible to this high degree of certainty by utilising one of these two approaches alone. After an introduction describing the challenges of studying palladium-based chemistry, and how this combined approach can help to tackle these challenges (Section 1), we provide examples in which experiments have been used in tandem with computational chemistry. This discussion is categorised by palladium oxidation state for convenience: Pd(0) chemistry comprises discussion on oxidative addition in traditional Pd(0)/Pd(II) cross-coupling (Section 2); a section on odd oxidation state chemistry includes oxidation of Pd(0) to Pd(I) dimers, oxidative addition to Pd(I) dimers, oxidation of Pd(II) to Pd(III) dimers and subsequently reductive elimination from these Pd(III) dimers (Section 3); Pd(II) chemistry includes transmetallation, reductive elimination and the field of C-H activation relating to palladium catalysis (Section 4); and finally, a section on Pd(IV) chemistry focusses on reductive elimination from these complexes (Section 5).


An adenovirus vector for efficient RNA interference-mediated suppression of target genes in insulinoma cells and pancreatic islets of langerhans.
Silencing gene expression by RNA interference (RNAi) can provide insight into gene function but requires efficient delivery of small interfering RNAs (siRNAs) into cells. Introduction of exogenous nucleic acids can be especially difficult in cultured pancreatic islets. This article describes a method for making recombinant adenoviruses that efficiently drive expression of siRNAs in islet beta-cells and a beta-cell-derived cell line. Transduction with a virus expressing an siRNA specific for GLUT2 reduced GLUT2 mRNA and protein levels by 80% in the INS-1-derived beta-cell line, 832/13, and GLUT2 protein levels by >90% in primary rat islets. Another virus expressing an siRNA specific for glucokinase (GK) caused 80% suppression of GK mRNA and 50% suppression of GK protein levels in 832/13 cells. These experiments validate recombinant adenoviral RNAi vectors as a useful tool for suppression of the expression of specific genes in pancreatic islets and beta-cell lines. Advantages of this approach include 1) the high efficiency of adenovirus-mediated gene transfer in insulinoma cell lines and rat islets and 2) the rapidity with which RNAi constructs can be prepared and tested relative to stable-transfection strategies.


[Theory of generator mechanisms in several neuropathologic syndrome].
This report formulates a general concept of the role played by determinant structures in CNS functioning and a related theory of generator mechanism which underlines neuropathological syndromes characterized by hyperactivity of cerebral centers. The theory postulates that due to deficiency of inhibitory mechanisms some populations of neurones become generators of abnormally enhanced excitation. Such generators operate as hyperactive determinant structures (or hyperactive determinant dispatch stations, DDS) inducing pathological changes in various functional systems and determining their behaviour. Formation of hyperactive DDS generating excitation in certain parts of the CNS leads to the appearance of corresponding neuropathological syndromes. This theory was used as a basis for experiments which reproduced pain syndromes of a central origin (including the trigeminal syndrome, the thalamic syndrome and phantom pains) vestibulopathy, photogenous epilepsy, catalepsy, manifestations of parkinsonism, etc. The report describes the characteristics of the generators of abnormally enhanced excitation. Some features of their operation are correlated with the course of the syndromes. Certain problems of pathogenetically oriented therapy are also discussed.


[Time-dependent hemodynamic effects of monosan (Isosorbide-5-mononitrate) in anginal patients].
Chronosensitivity to monosan was studied in acute clinicopharmacological tests at 7.00, 11.00, 15.00, 19.00 and 23.00 in 20 patients with ischemic heart disease, angina pectoris (class II-III). Arterial pressure, heart rate, hemodynamic parameters were measured before monosan intake, 1.5, 2, 3 and 21 hours after the intake of 20 mg. The findings indicate the existence of chronosensitivity of hemodynamics to monosan, circadian rhythm of sensitivity of the heart rate, systolic pressure, peripheral resistance. Acrophase of the sensitivity rhythm of the heart rate occurred at 13.42, systolic pressure at 21.54, mean arterial pressure at 00.41, total and peripheral resistance at 14.13, 15.18, respectively.


A Prospective Study of Causes of Illness and Death in Preterm Infants in Ethiopia: The SIP Study Protocol.
With nearly 15 million annual preterm births globally, preterm birth is the most common cause of neonatal death. Forty to 60 % of neonatal deaths are directly or indirectly associated with preterm mortality. As countries aim to meet the Sustainable Development Goals to reduce neonatal mortality, significant reductions in preterm mortality are needed. This study aims to identify the common causes of preterm illness and their contribution to preterm mortality in low-resource settings. This article will describe the methods used to undertake the study. This is a prospective, multi-centre, descriptive clinical study. Socio-demographic, obstetric, and maternal factors, and clinical and laboratory findings will be documented. The major causes of preterm mortality will be identified using clinical, laboratory, imaging, and autopsy methods and use the national Ethiopian guidelines on management of preterm infants including required investigations to reach final diagnoses. The study will document the clinical and management protocols followed in these settings. The approach consists of clinical examinations and monitoring, laboratory investigations, and determination of primary and contributory causes of mortality through both clinical means and by post-mortem examinations. An independent panel of experts will validate the primary and contributory causes of mortality. To obtain the estimated sample size of 5000 preterm births, the study will be undertaken in five hospitals in three regions of Ethiopia, which are geographically distributed across the country. All preterm infants who are either born or transferred to these hospitals will be eligible for the study. Three methods (last menstrual period, physical examination using the New Ballard Score, and ultrasound) will be used to determine gestational age. All clinical procedures will be conducted per hospital protocol and informed consent will be taken from parents or caretakers prior to their participation in the study as well as for autopsy if the infant dies. This study will determine the major causes of death and illness among hospitalized preterm infants in a low-resource setting. The result will inform policy makers and implementers of areas that can be prioritized in order to contribute to a significant reduction in neonatal mortality.


Estimating the health-care usage associated with osteoarthritis and rheumatoid arthritis in an older adult population in Ireland.
An ageing population leads to increasing prevalence of age-related chronic conditions that present challenges to the health-care services. Despite this, in countries including Ireland, little is known about the health-care impact of conditions such as osteoarthritis or rheumatoid arthritis amongst older adults. A series of count models are developed to investigate the incremental health-care usage of individuals with either osteoarthritis or rheumatoid arthritis on the use of general practitioners (GP) services, outpatients' services, accident and emergency visits and inpatient nights. Both types of arthritic conditions lead to increased usage of GP and outpatients' services but not other hospital services. Differences in entitlements to care, as captured by the presence of a medical card in Ireland, lead to different health-care usage among arthritis sufferers. Translating the additional utilization into cost suggests a combined incremental annual cost of both types of arthritis of €13.6 million. Osteoarthritis and rheumatoid arthritis present challenges to health-care services in the context of an ageing population. In the case of Ireland the burden falls predominantly on primary health-care and outpatient services. Within the context of changing health-care service provision in Ireland, the results of this study have implications for future planning of service delivery.


Effects of a stay-green mutation on plant nitrogen relations in Lolium perenne during N starvation and after defoliation.
The stay-green mutation of the nuclear gene sid results in inhibition of chlorophyll degradation during leaf senescence in grasses, reducing N remobilization from senescing leaves. Effects on growth of Lolium perenne L. were investigated during N starvation (over 18 d) and after severe defoliation, when leaf growth depends on the remobilization of internal N. Rates of dry mater production, partitioning between shoots and roots, and re-partitioning of N from shoots to roots were very similar in stay-green and normal plants under N starvation. Km and Vmax for net uptake of NH4+ were also similar for both genotypes, and Vmax increased with the duration of N deprivation. The mutation had little effect on recovery of leaf growth following severe defoliation, but stay-green plants recommenced NO3- and K+ uptake 1 d later than normal plants. Import of remobilized N into new leaves was generally similar in both lines. However, stay-green plants remobilized less N from stubble compared with normal plants. It was concluded that the sid locus stay-green mutation has no significant adverse effect on the growth of L perenne during N starvation, or recovery from severe defoliation when plants are grown under an optimal regime of NO3- supply both before and after defoliation. The absence of any effect on leaf dry matter production implies that the difference in foliar N availability attributable to this mutation has little bearing on productivity, at least in the short to medium term.


Targeted Ptpn11 deletion in mice reveals the essential role of SHP2 in osteoblast differentiation and skeletal homeostasis.
The maturation and function of osteoblasts (OBs) rely heavily on the reversible phosphorylation of signaling proteins. To date, most of the work in OBs has focused on phosphorylation by tyrosyl kinases, but little has been revealed about dephosphorylation by protein tyrosine phosphatases (PTPases). SHP2 (encoded by PTPN11) is a ubiquitously expressed PTPase. PTPN11 mutations are associated with both bone and cartilage manifestations in patients with Noonan syndrome (NS) and metachondromatosis (MC), although the underlying mechanisms remain elusive. Here, we report that SHP2 deletion in bone gamma-carboxyglutamate protein-expressing (Bglap+) bone cells leads to massive osteopenia in both trabecular and cortical bones due to the failure of bone cell maturation and enhanced osteoclast activity, and its deletion in Bglap+ chondrocytes results in the onset of enchondroma and osteochondroma in aged mice with increased tubular bone length. Mechanistically, SHP2 was found to be required for osteoblastic differentiation by promoting RUNX2/OSTERIX signaling and for the suppression of osteoclastogenesis by inhibiting STAT3-mediated RANKL production by osteoblasts and osteocytes. These findings are likely to explain the compromised skeletal system in NS and MC patients and to inform the development of novel therapeutics to combat skeletal disorders.


Neurophysiologic follow-up of long-term dietary treatment in adult-onset adrenoleukodystrophy.
To monitor the effects of dietary treatment in adult-onset adrenoleukodystrophy (ALD) by means of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs). SEPs and MEPs have proved useful in revealing signs of progressively severe, central dying-back axonopathy in early stages of adult-onset ALD. Eight patients with adult-onset ALD underwent clinical examination, brain and spine MRI, and SEP and MEP studies before and after 3 years of Lorenzo's oil dietary therapy. Before treatment, brain MRI was normal in five patients. Three of these patients had pure spinal SEP abnormalities and in the remaining two patients SEPs showed signs of involvement of both the spinal and cerebral somatosensory tracts. After treatment, the three patients with pure spinal abnormalities showed clinical and neurophysiologic worsening, whereas the two patients with a more advanced stage of disease (exhibited by SEPs) showed substantially unchanged clinical and neurophysiologic features. The patients with abnormal brain MRI at the onset of treatment showed clinical and neurophysiologic worsening. Lorenzo's oil therapy had no effect on patients with evidence of inflammatory brain lesions. Moreover, in patients without clear signs of inflammatory damage, this treatment does not modify significantly the natural course of the disease. However, because effective treatments should begin before the onset of severe neurologic symptoms, SEPs and MEPs should be considered to evaluate the effectiveness of other experimental treatments in the patient with a negative brain MRI.


A Draconian Law: Examining the Navigation of Coalition Politics and Policy Reform by Health Provider Associations in Karnataka, India.
A comprehensive picture of provider coalitions in health policy making remains incomplete because of the lack of empirically driven insights from low- and middle-income countries. The authors examined the politics of provider coalitions in the health sector in Karnataka, India, by investigating policy processes between 2016 and 2018 for developing amendments to the Karnataka Private Medical Establishments Act. Through this case, they explore how provider associations function, coalesce, and compete and the implications of their actions on policy outcomes. They conducted in-depth interviews, document analysis, and nonparticipant observations of two conferences organized by associations. They found that provider associations played a major role in drafting the amendments and negotiating competing interests within and between doctors and hospital associations. Despite the fragmentation, the associations came together to reinterpret the intentions of the amendments as being against the interests of the profession, culminating in a statewide protest and strike. Despite this show of strength, provider associations only secured modest modifications. This case demonstrates the complex and unpredictable influence of provider associations in health policy processes in India. The authors' analysis highlights the importance of further empirical study on the influence of professional and trade associations across a range of health policy cases in low- and middle-income countries.


Accurate protein structure modeling using sparse NMR data and homologous structure information.
While information from homologous structures plays a central role in X-ray structure determination by molecular replacement, such information is rarely used in NMR structure determination because it can be incorrect, both locally and globally, when evolutionary relationships are inferred incorrectly or there has been considerable evolutionary structural divergence. Here we describe a method that allows robust modeling of protein structures of up to 225 residues by combining (1)H(N), (13)C, and (15)N backbone and (13)Cβ chemical shift data, distance restraints derived from homologous structures, and a physically realistic all-atom energy function. Accurate models are distinguished from inaccurate models generated using incorrect sequence alignments by requiring that (i) the all-atom energies of models generated using the restraints are lower than models generated in unrestrained calculations and (ii) the low-energy structures converge to within 2.0 Å backbone rmsd over 75% of the protein. Benchmark calculations on known structures and blind targets show that the method can accurately model protein structures, even with very remote homology information, to a backbone rmsd of 1.2-1.9 Å relative to the conventional determined NMR ensembles and of 0.9-1.6 Å relative to X-ray structures for well-defined regions of the protein structures. This approach facilitates the accurate modeling of protein structures using backbone chemical shift data without need for side-chain resonance assignments and extensive analysis of NOESY cross-peak assignments.


Diverging associations of an intended early invasive strategy compared with actual revascularization, and outcome in patients with non-ST-segment elevation acute coronary syndrome: the problem of treatment selection bias.
In several observational studies, revascularization is associated with substantial reduction in mortality in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS). This has strengthened the belief that routine early angiography would lead to a reduction in mortality. We investigated the association between actual in-hospital revascularization and long-term outcome in patients with nSTE-ACS included in the ICTUS trial. The study population of the present analysis consists of ICTUS participants who were discharged alive after initial hospitalization. The ICTUS trial was a randomized, controlled trial in which 1200 patients were randomized to an early invasive or selective invasive strategy. The endpoints were death from hospital discharge until 4 year follow-up and death or spontaneous myocardial infarction (MI) until 3 years. Among 1189 patients discharged alive, 691 (58%) underwent revascularization during initial hospitalization. In multivariable Cox regression analyses, in-hospital revascularization was independently associated with a reduction in 4 year mortality and 3 year event rate of death or spontaneous MI: hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.37-0.96] and 0.46 (95% CI 0.31-0.68). However, when intention-to-treat analysis was performed, no differences in cumulative event rates were observed between the early invasive and selective invasive strategies: HR 1.10 (95% CI 0.70-1.74) for death and 1.27 (95% CI 0.88-1.85) for death or spontaneous MI. The ICTUS trial did not show that an early invasive strategy resulted in a better outcome than a selective invasive strategy in patients with nSTE-ACS. However, similar to retrospective analyses from observational studies, actual revascularization was associated with lower mortality and fewer MI. Whether an early invasive strategy leads to a better outcome than a selective invasive strategy cannot be inferred from the observation that revascularized patients have a better prognosis in non-randomized studies.


[Asymptomatic coronaro-cardiac fistula. Apropos of a case].
The case of a 20 year old woman with a right coronary-right atrial fistula is reported. The diagnosis was made during investigation of a continuous murmur and the tolerance was excellent. Aortic root angiography demonstrated a fistula between the initial part of the right coronary artery and a right heart cavity. Selective coronary angiography visualised pseudo-aneurysmal dilatation of the first segment of the right coronary artery, the calibre and trajectory of which was then normal. The medical literature suggests surgical correction even in asymptomatic cases because of the risk of spontaneous complications (cardiac failure 15 p. 100, endocarditis 7 p. 100, infection 4 p. 100). Since 1968, there has been no operative mortality in 145 subjects with isolated coronaro-cardiac fistulae without cardiac failure. In the case presented, the fistula was successfully closed under cardiopulmonary bypass and endoaneurysmorrhaphy was performed to remodel the lumen of the right coronary artery.


The adherens junction protein afadin is an AKT substrate that regulates breast cancer cell migration.
The PI3K-AKT signaling pathway regulates all phenotypes that contribute to progression of human cancers, including breast cancer. AKT mediates signal relay by phosphorylating numerous substrates, which are causally implicated in biologic responses such as cell growth, survival, metabolic reprogramming, migration, and invasion. Here a new AKT substrate is identified, the adherens junction protein Afadin, which is phosphorylated by AKT at Ser1718. Importantly, under conditions of physiologic IGF-1 signaling and oncogenic PI3K and AKT, Afadin is phosphorylated by all AKT isoforms, and this phosphorylation elicits a relocalization of Afadin from adherens junctions to the nucleus. Also, phosphorylation of Afadin increased breast cancer cell migration that was dependent on Ser1718 phosphorylation. Finally, nuclear localization of Afadin was observed in clinical breast cancer specimens, indicating that regulation of Afadin by the PI3K-AKT pathway has pathophysiologic significance. Phosphorylation of the adhesion protein Afadin by AKT downstream of the PI3K pathway, leads to redistribution of Afadin and controls cancer cell migration.


Antibiotic Resistance of Airborne Viable Bacteria and Size Distribution in Neonatal Intensive Care Units.
Despite their significant impact on public health, antibiotic resistance and size distributions of airborne viable bacteria in indoor environments in neonatal intensive care units (NICU) remain understudied. Therefore, the objective of this study was to assess the antibiotic resistance of airborne viable bacteria for different sizes (0.65-7 µm) in private-style and public-style neonatal intensive care units (NICU). Airborne bacteria concentrations were assessed by a six-stage Andersen impactor, operating at 28.3 L/min. Public-style NICU revealed higher concentrations of airborne viable bacteria (53.00 to 214.37 CFU/m3) than private-style NICU (151.94-466.43), indicating a possible threat to health. In the public-style NICU, Staphylococcus was the highest bacterial genera identified in the present study, were Staphylococcus saprophyticus and Staphylococcus epidermidis predominated, especially in the second bronchi and alveoli size ranges. Alloiococcus otitidis, Bacillus subtiles, Bacillus thuringiensis, Kocuria rosea, and Pseudomonas pseudoalcaligene, were identified in the alveoli size range. In NICU#2, eight species were identified in the alveoli size range: Bacillus cereus, Bacillus subtilis, Bacillus thuringiensis, Eikenella corrodens, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus gordoni. Multi-drug-resistant organisms (MDROs) were found in both of the NICUs. Bacillus cereus strains were resistant to Ampicillin, Cefoxitin, Ceftaroline, and Penicillin G. Staphylococcus cohnii ssp. cohnii was resistant in parallel to ampicillin and G penicillin. Staphylococcus saprophyticus strains were resistant to Ampicillin, Penicillin G, Oxaxilin, and Erythromycin. Results may indicate a potential threat to human health due to the airborne bacteria concentration and their antibiotic resistance ability. The results may provide evidence for the need of interventions to reduce indoor airborne particle concentrations and their transfer to premature infants with underdeveloped immune systems, even though protocols for visitors and cleaning are well-established.


UCH/RNID single channel cochlear implant: surgical technique.
In a series of thirty patients who received single-channel cochlear implants a simple standard operative procedure has been developed. No life-threatening complication and no wound breakdown occurred. The only problems encountered during surgery were related to the position or obliteration of the round window niche. The commonest reason for removing the implant was device failure; this was caused by a single defective electronic component. No further failures have occurred since this was modified. The second commonest reason for failure was related to the position of the implant, both cases occurred early in the series and the operative technique was altered to prevent further episodes. The infection rate has been low, partly because a simple postaural incision does not put the local blood supply to the skin at risk. Synkinetic facial nerve stimulation seems difficult to predict and may be hard to avoid until more is known about its aetiology.


Research and instruction services for online advanced practice nursing programs: a survey of North American academic librarians.
The increasing popularity of distance education has led many advanced practice nursing (APN) programs to shift to either online or hybrid models. To meet the needs of these students, some nursing librarians are using technology for virtual research and instruction. This study was designed to assess the extent to which librarians in North America are providing virtual research and instruction services for APN students. An institutional review board-approved, ten-question survey was developed to determine how librarians are providing services for APN students. It was announced in October 2017 through several health sciences librarian email discussion lists. The survey ran for four weeks. Data were analyzed using Qualtrics and Excel. Eighty complete responses were received. The majority of respondents (66%) indicated that their universities' APN programs were conducted in a hybrid format. Sixty-seven percent also indicated that they provide library instruction in person. Most librarians indicated that they have provided research assistance through some virtual method (phone or email, at 90% and 97%, respectively), and some have used online chat (42%) and video chat (35%). A strong majority of librarians (96%) indicated that they felt comfortable using technology to provide research assistance and instruction. Opportunities exist to leverage technology to provide virtual research assistance and instruction. Greater promotion of these alternative methods can supplement traditional in-person services to provide greater flexibility for graduate nursing students' busy schedules. Some outreach may be necessary to highlight the advantages of virtual services, and further research is needed to identify other barriers and potential solutions.


Cellular mediators of inflammation: tregs and TH17 cells in gastrointestinal diseases.
Human lymphocyte subpopulations were originally classified as T- and B-cells in the 70s. Later, with the development of monoclonal antibodies, it became possible to recognize, within the T-cells, functional populations: CD4(+) and CD8(+). These populations were usually referred to as "helper" and "suppressor" cells, respectively. However several investigations within the CD8 cells failed to detect a true suppressor activity. Therefore the term suppressor was neglected because it generated confusion. Much later, true suppressor activity was recognized in a subpopulation of CD4 cells characterized by high levels of CD25. The novel population is usually referred to as T regulatory cells (Tregs) and it is characterized by the expression of FoxP3. The heterogeneity of CD4 cells was further expanded by the recent description of a novel subpopulation characterized by production of IL-17. These cells are generally referred to as T(H)17. They contribute to regulate the overall immune response together with other cytokine-producing populations. Treg and T(H)17 cells are related because they could derive from a common progenitor, depending on the presence of certain cytokines. The purpose of this review is to summarize recent findings of the role of these novel populations in the field of human gastroenterological disease.


ABCB1 and GST polymorphisms associated with TP53 status in breast cancer.
Many environmental and genetic factors influence the development of chemoresistance. The goal of this study was to characterize the genetic variation in the ABCB1, GSTM1, GSTT1 and GSTP1 genes, as well as the haplotype structure in the ABCB1 gene. Variants in these genes were studied in 109 healthy controls and 93 breast cancer cases, both of Caucasian origin. The cases were analyzed in relation to TP53 mutation status and response to doxorubicin. Both single and multiple single nucleotide polymorphism analyses were performed. Chi-square analyses revealed a significant association between TP53 mutation status and both the GA genotype of ABCB1 exon 11 (Ser400Asn) and the GG genotype of GSTP1 (Ile105Val; P<0.01 and P<0.05, respectively). Multifactor dimensionality reduction showed that carriers of the combined GG genotype for GSTP1 and the GG for ABCB1 exon 11 had the highest chance of acquiring a mutation in the TP53 gene (P<0.02). Haplotype analysis of ABCB1 revealed a significantly different distribution of haplotypes between the breast cancer cases and the controls (P<0.01). A specific haplotype association to TP53 mutation (P<0.01) distant metastases (P<0.05) and estrogen receptor status (P<0.05) was also observed in the case group. An association between polymorphisms in GSTP1 and ABCB1 and risk of acquiring intratumoral TP53 mutations suggests the existence of putative predisposing genotype backgrounds. The degree of linkage disequilibrium in the ABCB1 gene was higher in healthy individuals, whereas haplotypes in the cases seemed degenerated by a number of low frequency variants. This observation may either point to the existence of a protective haplotype in the controls or may underline the importance of the accumulation of low frequency variants as susceptibility factors.


Anti-aggressive activity of a standardized extract of Marsilea minuta Linn. in rodent models of aggression.
The present study was undertaken to evaluate in vivo anti-aggressive potential of a standardized extract of Marsilea minuta Linn. (Marsileaceae). The standardized extract of Marsilea minuta was evaluated for its potential effects against defensive and offensive aggressive behavior models of rodents. Marsilea minuta extract was orally administered at three dose levels (100, 200, and 400 mg/kg BW) once daily for 14 consecutive days as a suspension in polyethylene glycol (PEG), diazepam (2.5 mg/kg, p.o.) was used as a standard anti-aggressive agent. Control group animals were given an equal volume of vehicle (10%, v/v, PEG suspension). Anti-aggressive activity was evaluated using the following validated models of aggression, viz.: foot shock-induced aggression, isolation-induced aggression and resident-intruder aggression, in rodents. As a result, Marsilea minuta extract showed dose dependant anti-aggressive activity in the aforementioned, validated models of aggression. This suggests that the extract from Marsilea minuta has a promising anti-aggressive activity qualitatively comparable to that of diazepam.


Studies on the endogenous metabolism and senescence of starved Sarcina lutea.
1. When washed suspensions of Sarcina lutea are starved aerobically in phosphate buffer at the growth temperature of 37 degrees , the rate of endogenous oxygen consumption decreases to very low values after 10hr., although many of the cells survive for 40hr. If starvation is prolonged further, the bacteria die at a rate of approximately 1.5% of the initial viable population per hour. 2. Oxidation of intracellular free amino acids accounts for most of the observed endogenous oxygen uptake but RNA is also utilized and a portion of the component bases and pentose is degraded and presumably oxidized. Ammonia appears in the supernatant and some pentose and ultraviolet-absorbing nucleotide are released from the cells. DNA, protein and polysaccharide are not measurably degraded. 3. Survival can be correlated with the ability of aerobically starved bacteria to oxidize exogenous l-glutamate and glucose. When starved under nitrogen for 40hr. cells continue to oxidize their endogenous reserves at undiminished rates when transferred to aerobic conditions; on prolonging anaerobic starvation the rate of oxidation declines during the period of most rapid loss of viability. 4. In the presence of Mg(2+), RNA degradation during aerobic starvation is almost completely suppressed without affecting the period for which the bacteria survive. 5. Cells grown in peptone supplemented with glucose accumulate reserves of polysaccharide which are metabolized in aerobic starvation, together with free amino acids. Ammonia is evolved and RNA is degraded to a greater extent than in peptone-grown suspensions. Bacteria rich in polysaccharide survive less well than those which are deficient in the polymer; the reason for this phenomenon has yet to be established. 6. In peptone medium, endogenous oxygen uptake and the concentration of intracellular free amino acids decline as growth progresses and they continue to decrease when the organism is held in stationary phase. Under the conditions used, the endogenous Q(o2) and free amino acid pool of cells grown in peptone with 2% (w/v) glucose did not decline so markedly and the bacteria contained large amounts of polysaccharide at all stages of growth.


Barriers and enablers for adopting lifestyle behavior changes in adolescents with obesity: A multi-centre, qualitative study.
Many adolescents with obesity do not meet recommendations for nutrition, physical and sedentary activities, and sleep habits, all of which can influence weight management. To explore barriers and enablers that influenced the adoption of lifestyle behavior changes among adolescents receiving multidisciplinary clinical care for pediatric weight management. In this multi-centre, qualitative description study, we used purposeful sampling to recruit 13-17 year olds (body mass index ≥85th percentile) enrolled in one of two pediatric weight management clinics in Edmonton and Ottawa, Canada. Adolescents participated in one-on-one, in-person, semi-structured interviews in English or French. Interviews lasted 30-60 minutes, were audio-recorded, transcribed verbatim, and managed using NVivo 11. Data were triangulated using transcripts, field notes, and memos and analyzed by two independent researchers using inductive, semantic thematic analysis. In total, 19 adolescents (12 Anglophone and 7 Francophone; 15.1±1.7 years old; 3.5±0.6 BMI z-score; n = 11 female; n = 13 Caucasian) participated. Adolescents reported diverse barriers to and enablers of healthy nutrition, physical and sedentary activities, and sleep habits, which we organized into the following themes: physiological mechanisms and physical health status, self-regulation for behavior change, controllability and competence beliefs, social relationships and interactions, and accessibility to and availability of opportunities for lifestyle enhancement. Across these themes and lifestyle areas, we identified three shared barriers and/or enablers, including the degree of controllability, the impact of mental health, and social pressures related to weight management. This research provides evidence that can be used to tailor interventions and health services delivery, including a focus on psychosocial well-being, to support adolescents with obesity in making and maintaining healthy lifestyle behavior changes.


Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis.
Consumption of sugar-sweetened beverages (SSBs), which include soft drinks, fruit drinks, iced tea, and energy and vitamin water drinks has risen across the globe. Regular consumption of SSBs has been associated with weight gain and risk of overweight and obesity, but the role of SSBs in the development of related chronic metabolic diseases, such as metabolic syndrome and type 2 diabetes, has not been quantitatively reviewed. We searched the MEDLINE database up to May 2010 for prospective cohort studies of SSB intake and risk of metabolic syndrome and type 2 diabetes. We identified 11 studies (three for metabolic syndrome and eight for type 2 diabetes) for inclusion in a random-effects meta-analysis comparing SSB intake in the highest to lowest quantiles in relation to risk of metabolic syndrome and type 2 diabetes. Based on data from these studies, including 310,819 participants and 15,043 cases of type 2 diabetes, individuals in the highest quantile of SSB intake (most often 1-2 servings/day) had a 26% greater risk of developing type 2 diabetes than those in the lowest quantile (none or <1 serving/month) (relative risk [RR] 1.26 [95% CI 1.12-1.41]). Among studies evaluating metabolic syndrome, including 19,431 participants and 5,803 cases, the pooled RR was 1.20 [1.02-1.42]. In addition to weight gain, higher consumption of SSBs is associated with development of metabolic syndrome and type 2 diabetes. These data provide empirical evidence that intake of SSBs should be limited to reduce obesity-related risk of chronic metabolic diseases.


Supporting working carers: do policies in England and The Netherlands reflect 'doulia rights'?
Governments of advanced European welfare states with ageing populations are struggling to reconcile what seem to be conflicting policies. On the one hand, they are trying to increase the labour market participation of women and older workers. On the other hand, they are making more demands on people to care for disabled, chronically ill and frail older relatives and friends. Those caregivers are more likely to be women and older people. In this paper, we present the policies and experiences of carers from two countries that differ in type of welfare state, health and social care system and labour market context: England and The Netherlands. The aim was to compare English and Dutch policy measures for carers and examine their impact with evidence from two studies of people who combine work and care. The analysis is informed by the theoretical concepts of 'doulia' (whereby the state, employers and other sections of society reciprocate carers and other dependency workers for their unpaid caregiving) and 'doulia rights' (a carer's right to provide care without the risk of impoverishment). The evidence suggests that English and Dutch carers' policies have different strengths and weaknesses, but in neither country do they show strong commitment to the right to doulia.