The mATPase histochemical profile of rat type IIX fibres: correlation with myosin heavy chain immunolabelling.
In the present study we report a novel histochemical method which, by sequential pre-incubations in alkaline and acidic media, selectively differentiates muscle fibres expressing myosin heavy chain IIX, on the basis of a specific profile for myofibrillar actomyosin ATPase (mATPase) activity. The enzyme reactions were tested for specificity by means of anti-myosin heavy chain monoclonal antibodies, which were characterized on Western blots of muscle homogenates. Enzyme histochemical reactions with the traditional pH buffers were compared to those of the new method and, in conjunction with the immunoreactions, used to confirm the relationship between MyHC expression and the distinct profiles for mATPase. Immunohistochemical reactions demonstrated that the new method only differentiates those fibres expressing myosin heavy chain IIX. The method revealed a continuum in which the intermediate staining intensities corresponded to hybrid fibres expressing myosin heavy chain IIX in combination with either the IIA or IIB forms. Quantitative histochemistry and immunohistochemistry (by image analysis), used to examine the relationship between staining intensities for mATPase and amounts of myosin heavy chain IIX expression, revealed that the new method discriminates well between hybrid fibres expressing variable amounts of the IIX isoform (r2 = 0.93).


Morphology enabled dipole inversion (MEDI) from a single-angle acquisition: comparison with COSMOS in human brain imaging.
Magnetic susceptibility varies among brain structures and provides insights into the chemical and molecular composition of brain tissues. However, the determination of an arbitrary susceptibility distribution from the measured MR signal phase is a challenging, ill-conditioned inverse problem. Although a previous method named calculation of susceptibility through multiple orientation sampling (COSMOS) has solved this inverse problem both theoretically and experimentally using multiple angle acquisitions, it is often impractical to carry out on human subjects. Recently, the feasibility of calculating the brain susceptibility distribution from a single-angle acquisition was demonstrated using morphology enabled dipole inversion (MEDI). In this study, we further improved the original MEDI method by sparsifying the edges in the quantitative susceptibility map that do not have a corresponding edge in the magnitude image. Quantitative susceptibility maps generated by the improved MEDI were compared qualitatively and quantitatively with those generated by calculation of susceptibility through multiple orientation sampling. The results show a high degree of agreement between MEDI and calculation of susceptibility through multiple orientation sampling, and the practicality of MEDI allows many potential clinical applications.


Site-Specific Small Molecule Labeling of an Internal Loop in JC Polyomavirus Pentamers Using the π-Clamp-Mediated Cysteine Conjugation.
The major capsid protein VP1 of JC Polyomavirus assembles into pentamers that serve as a model for studying viral entry of this potentially severe human pathogen. Previously, labeling of viral proteins utilized large fusion proteins or non-specific amine- or cysteine-functionalization with fluorescent dyes. Imaging of these sterically hindered fusion proteins or heterogeneously labeled virions limits reproducibility and could prevent the detection of subtle trafficking phenomena. Here we advance the π-clamp-mediated cysteine conjugation for site-selective fluorescent labeling of VP1-pentamers. We demonstrate a one-step synthesis of a probe consisting of a bio-orthogonal click chemistry handle bridged to a perfluoro-biphenyl π-clamp reactive electrophile by a polyethylene glycol linker. We expand the scope of the π-clamp conjugation by demonstrating selective labeling of an internal, surface exposed loop in VP1. Thus, the π-clamp conjugation offers a general method to selectively bioconjugate tags-of-interest to viral proteins without impeding their ability to bind and enter cells.


PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels.
Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism is associated with NAFLD severity and the PNPLA3 gene is expressed in the kidneys, but whether PNPLA3 rs738409 polymorphism is also associated with renal tubular injury (RTI) is uncertain. We assessed the effect of PNPLA3 genotypes on biomarkers of RTI and glomerular function in subjects with NAFLD who had either normal (nALT) or abnormal (abnALT) alanine aminotransaminase levels. Two hundred and seventeen patients with histologically proven NAFLD of which 75 had persistently nALT (below upper limit of normal for 3 months) were included. Multivariable regression analyses were undertaken to test associations between PNPLA3 genotype and biomarkers of kidney dysfunction. The nALT patient group had higher urinary neutrophil gelatinase-associated lipocalin levels (u-NGAL, a biomarker of RTI) (P < .001), higher albuminuria (P = .039) and greater prevalence of chronic kidney disease (CKD; P = .046) than the abnALT group. The association between PNPLA3 GG genotype and risk of CKD and abnormal albuminuria remained significant after adjustment for kidney risk factors and severity of NAFLD histology, mostly in the nALT group. Similarly, PNPLA3 GG genotype was associated with higher u-NGAL levels in the nALT group, even after adjustment for the aforementioned risk factors and glomerular filtration-based markers (β-coefficient: 22.29, 95% CI: 0.99-43.60, P = .041). Patients with NAFLD and persistently nALT, who carry the PNPLA3 rs738409 G allele, are at higher risk of early glomerular and tubular damage. We suggest PNPLA3 genotyping may help identify patients with NAFLD at higher risk of RTI.


The role of polycomb group proteins in cell cycle regulation during development.
Polycomb group (PcG) and trithorax group (trxG) proteins are evolutionarily conserved chromatin modifiers that have well known roles in the maintenance of silent and active expression states of homeotic genes. PcG proteins may also be involved in the control of cellular proliferation, as several PcG complexes have been shown to act either as proto-oncogenes or as tumor suppressors in vertebrates. In Drosophila, PcG factors associate with specific DNA regions termed PcG response elements (PREs), and a PRE was recently identified in the gene encoding Cyclin A. Still, it is not yet clear how PcG complexes could control cell cycle progression. Beyond acting as stable silencers of cell cycle genes during the differentiation process, PcG complexes might also be integrators and/or modulators of cell cycle checkpoints in dividing cells. Here, we discuss this dual aspect of PcG involvement in epigenetic cell cycle control.


Selective inhibition of leukotriene receptor BLT-2 reduces vascular oxidative stress and improves endothelial function in ApoE-/- mice.
Atherosclerosis is a chronic inflammatory disease and represents the main cause of death in the industrialized world. Metabolites of the arachidonic acid derived from the 5-lipoxygenase pathway are known as leukotrienes that mediate various inflammatory processes during atherogenesis. Leukotriene B4 elicits the overexpression of several proinflammatory proteins, promotes chemotaxis and foam cell formation via BLT receptors. Currently, little is known about the implications of the BLT2 receptor in atherogenesis. Here, we tested whether selective inhibition of this receptor influences the progression of atherosclerosis in mice. Apolipoprotein-E deficient mice were fed a high-fat, cholesterol-rich diet to create atherosclerotic conditions (each group n=9). Simultaneously, mice received the pharmacologic BLT2 inhibition (Ly) by intraperitoneal injection every second day 5 mg/kg bw or vehicle. After 8 weeks, mice were killed and experiments were performed. Vascular superoxide release was diminished in mice treated with Ly compared with the control group (68±15 vs 131±20 RLU, P=0.01), as measured by L012 assay. Next, endothelial function was assessed by organ chamber experiments. Endothelial-dependent relaxation was improved in mice treated with the BLT2 receptor antagonist. To determine whether selective inhibition of the BLT2 receptor affects the atherosclerotic plaque growth, immunohistochemical stainings of the aortic root were performed. Oil red O staining revealed no significant differences between both groups (36±3% vs 38±3%). Monocyte infiltration into the vessel wall was analyzed using Moma-2 staining. No significant differences were observed between both groups (31±3% vs 34±2%). Selective inhibition of the BLT2 receptor in mice reduces the release of vascular reactive oxygen species and improves endothelial function in mice. Further experiments are necessary in order to obtain tissue-specific and mechanistical insights.


Yellow fever virus: historical and current issues regarding recent epidemics and vaccination in Brazil.
Yellow fever has been recently described in nonurban areas of Brazil despite 80 years of commercial vaccine use. Although the disease does not spread fear in the general population as it did in the past, yellow fever virus continues to cause many cases of severe disease. Persistence of the virus in the host is a new mechanism to be considered in the pathology of the disease. Immunization with a fractional dose of vaccine during emergency situations needs to be evaluated for antibody duration, and new and improved vaccines should be considered.


Recent developments on gold nanostructures for surface enhanced Raman spectroscopy: Particle shape, substrates and analytical applications. A review.
Surface enhanced Raman spectroscopy (SERS) is a powerful technique for sensitive analysis which is attracting great attention in the last decades. In this review, different gold nanostructures that have been exploited for SERS analysis are described, ranging from gold nanospheres to anisotropic and complex-shaped gold nanostructures, in which the presence of high aspect ratio features leads to an increment of the electromagnetic field at the surface of the nanomaterial, resulting in enhanced SERS response. In addition to the shape of the nanostructure, the interparticle nanogaps play a prominent role in the SERS efficiency. In this sense, different approaches such as nanoaggregation and formation of assemblies and ordered structures lead to the creation of the so-called hot spots. SERS measurements may be performed in solution, while usually the nanostructures are deposited building a SERS substrate, which can be created via attachment of chemically prepared gold nanostructures, as well as via top-down physical methods. Among the classical supports for creating the SERS substrates, in the last years there is a trend towards the development of flexible supports based on polymers as well as paper. Finally, some recent applications of gold nanostructures-based SERS substrates within the analytical field are discussed to spotlight the potential of this technique in real-world analytical scenarios.


Metabolome-microbiome signatures in the fermented beverage, Kombucha.
Kombucha is a fermented tea. Here we investigate the fermentation kinetics, metabolite production, microbiome and potential health promoting properties of three different kombucha consortia. Shotgun metagenomic sequencing revealed several dominant bacterial genera such as Komagataeibacter, Gluconacetobacter and Gluconobacter. Brettanomyces and Schizosaccharomyces were the most dominant yeasts identified. Species distribution reflected different patterns of sugar consumption, with S. pombe being present in samples with the highest sugar conversion. Liquid-liquid extractions were performed with organic solvents in order to obtain dried extracts, which were later characterized. HPLC-DAD and GC-MS analysis revealed differences in the production of organic acids, sugars, alcohols and phenolic compounds, where the presence of caffeine, propanoic acid and 2,3 butanediol differ greatly across the three kombuchas. Metabolomic analysis exhibited a link between the microbiota and the production of bioactive compounds in kombucha fermentation. In vitro assays were carried out in order to evaluate potential health-promoting features of the fermented teas, with notable outcomes including antioxidant ability against DPPH radical and against the 15-lipoxygenase enzyme, indicating a potential anti-inflammatory activity. These investigations considerably enhance our understanding of the relationship between the microbiota and metabolites as well as health promoting potential of kombucha and have the potential for the development of future generations of kombucha products in which these relationships are optimized.


Cell fusion generates an inhomogeneous distribution of elasticity and rigidity in plasma membranes.
The post-electrofusion oscillation cycle of human erythrocytes (doublets) was evaluated for the first four pump events in order to quantify the spectrin-network rearrangement in the fusion zone. Experiments were carried out on control cells and on cells that received a 40 degree C and a 45 degree C 20-min heat treatment. The amplitude of the geometrical changes depended on the heat-treatment procedure, whereas the roundness on entering the pump event was always identical. The rigid influence of the fusion zone prevented the doublets from adopting a spherical shape. The fusion zone was characterized by a linear elongation modulus that could be calculated from geometrical measurements and earlier findings on erythrocyte membrane mechanics, and that ranged between 1.44E6 Nm(-2) for control doublets and 0.99E6 Nm(-2) after 45 degrees C heat treatment. The membrane composition of the fusion zone differs greatly from that of the other membrane parts not involved in fusion processes and evidence is given that this inhomogeneity stems from a rearrangement of the triangulated spectrin network and other membrane skeletal proteins in the fusion zone.


Perillaldehyde is a new ferroptosis inducer with a relevant clinical potential for acute myeloid leukemia therapy.
Ferroptosis induction is an emerging strategy to treat cancer and contrast the tricky issue of chemoresistance, which can arise towards apoptosis. This work elucidates the anticancer mechanisms evoked by perillaldehyde, a monoterpenoid isolated from Ammodaucus leucotrichus Coss. & Dur. We investigated and characterized its antileukemic potential in vitro, disclosing its ability to trigger ferroptosis. Specifically, perillaldehyde induced lipid peroxidation, decreased glutathione peroxidase 4 protein expression, and depleted intracellular glutathione on HL-60 promyelocytic leukemia cells. Besides, it stimulated the active secretion of ATP, one of the most crucial events in the induction of efficient anticancer response, prompting further studies to disclose its possible nature as an immunogenic cell death inducer. To preliminarily assess the clinical relevance of perillaldehyde, we tested its ability to induce cell death on patient-derived acute myeloid leukemia biopsies, recording a similar mechanism of action and potency compared to HL-60 cells. To round the study off, we tested its selectivity towards tumor cells and disclosed lower toxicity on normal cells compared to both HL-60 and acute myeloid leukemia biopsies. Altogether, these data depict a favorable risk-benefit profile for perillaldehyde and reveal its peculiar antileukemic potential, which qualifies this natural product to proceed further through the drug development pipeline.


Validity of the memorial symptom assessment scale-short form psychological subscales in advanced cancer patients.
The Memorial Symptom Assessment Scale-Short Form (MSAS-SF) is designed to evaluate physical and psychological symptom burden in advanced cancer patients. There are no current data assessing the validity of the MSAS-SF psychological symptom scores when compared with anxiety and depression. This observational cross-sectional study was designed to determine the relationship between the MSAS-SF subscales and the presence of anxiety and depression. Advanced cancer patients attending a U.K. oncology center completed the MSAS-SF and the Hospital Anxiety and Depression Scale. One hundred twenty patients participated in the study. There was an association between the presence of anxiety and depression and the MSAS-SF global distress index. There was no association between the presence of anxiety and depression and the MSAS-SF physical symptom subscale. The MSAS-SF psychological symptom subscale was more closely correlated with anxiety than depression. These results support the validity of the MSAS-SF global distress index and psychological subscales in the assessment of patients with anxiety and depressive disorders.


Production of non-alcoholic beer using free and immobilized cells of Saccharomyces cerevisiae deficient in the tricarboxylic acid cycle.
Production of non-alcoholic beer using Saccharomyces cerevisiae has been studied. Non-recombinant mutant strains with a defect in the synthesis of tricarboxylic-acid-cycle enzymes were used and applied in both free and pectate-immobilized form, using both batch and packed-bed continuous systems. After fermentation, basic parameters of the beer produced by five mutant strains were compared with a standard strain of brewing yeast. Results showed that the beer prepared by mutant yeast cells was characterized by lower levels of total alcohols, with ethanol concentrations between 0.07 and 0.31% (w/w). The organic acids produced, especially lactic acid, in concentrations up to 1.38 g x l(-1) had a strong protective effect on the microbial stability of the final product and thus the usual addition of lactic acid could be omitted. Application of the yeast mutants appears to be a good alternative to the classical methods for the production of non-alcoholic beer.


NanoUPLC/MS(E) proteomic analysis reveals modulation on left ventricle proteome from hypertensive rats after exercise training.
NanoUPLC/MS(E) was used to verify the effects of 8weeks of low (SHR-LIT=4) and high (SHR-HIT=4) intensity training over the left ventricle proteome of hypertensive rats (SHR-C=4). Training enhanced the aerobic capacity and reduced the systolic blood pressure in all exercised rats. NanoUPLC/MS(E) identified 250 proteins, with 233 in common to all groups and 16 exclusive to SHR-C, 2 to SHR-LIT, and 2 to the SHR-HIT. Cardiac hypertrophy related proteins appeared only in SHR-C. The SHR-LIT enhanced the abundance of 30 proteins and diminished 6, while SHR-HIT enhanced the abundance of 39 proteins and reduced other 7. The levels of metabolic (β and γ-enolase, adenine phosphoribosultransferase, and cytochrome b-c1), myofibril (myosin light chain 4, tropomyosin α and β-chain), and transporter proteins (hemoglobin, serum albumin, and hemopexin) were increased by both intensities. Transcription regulator and histone variants were enhanced by SHR-LIT and SHR-HIT respectively. SHR-LIT reduced the concentration of myosin binding protein C, while desmin and membrane voltage dependent anion selective channel protein-3 were reduced only by SHR-HIT. In addition, polyubiquitin B and C, and transcription regulators decreased in both intensities. Exercise also increased the concentration of anti-oxidant proteins, peroxiredozin-6 and glutathione peroxidase-1. Pathologic left ventricle hypertrophy if one of the major outcomes of hypertension being a strong predictor of heart failure. Among the various risk factors for cardiovascular disorders, arterial hypertension is responsible for the highest rates of mortality worldwide. In this way, this present study contribute to the understanding of the molecular mechanisms involved in the attenuation of hypertension and the regression of pathological cardiac hypertrophy induced by exercise training.


Validity of covering-up sun-protection habits: Association of observations and self-report.
Few studies have reported the accuracy of measures used to assess sun-protection practices. Valid measures are critical to the internal validity and use of skin cancer control research. We sought to validate self-reported covering-up practices of pool-goers. A total of 162 lifeguards and 201 parent/child pairs from 16 pools in 4 metropolitan regions in the United States completed a survey and a 4-day sun-habits diary. Observations of sun-protective behaviors were conducted on two occasions. Agreement between observations and diaries ranged from slight to substantial, with most values in the fair to moderate range. Highest agreement was observed for parent hat use (kappa = 0.58-0.70). There was no systematic pattern of over- or under-reporting among the 3 study groups. Potential reactivity and a relatively affluent sample are limitations. There was little over-reporting and no systematic bias, which increases confidence in reliance on verbal reports of these behaviors in surveys and intervention research.


Parental Impressions and Perspectives of Efficacy in Prenatal Counseling for Single Ventricle Congenital Heart Disease.
Although commonly performed, optimal techniques, strategies, and content to achieve the most effective prenatal counseling have not been explored. We investigate the efficacy of prenatal counseling via survey feedback of parents of children with prenatally diagnosed single ventricle. Grades of counseling using a Likert scale (1-5) were solicited to assess: (1) overall impression of quantity of counseling, (2) explanation of the heart defect, (3) preparation for heart surgery, (4) preparation for hospital course and care, (5) preparation for complications and outcomes of a Fontan circulation, and (6) preparation for neurological, school-related, or behavioral problems. Impressions were solicited concerning specific providers. A comprehensive fetal counseling score was calculated for each participant. Burden of care including length of hospitalization was explored as impacting prenatal counseling grades. There were 59 survey respondents. Average age of the children at the time of survey was 4.6 ± 3.3 years (range 1-10 years). Highest grades were for explanation of the heart condition, with lowest grades for preparation for neurological, school-related, or behavioral problems. Cardiac surgeon received the highest with social worker lowest grade for provider. Negative correlation was found between the composite fetal counseling score and parental recollection of length of hospitalization (Pearson r = - 0.357, p < 0.01). Prenatal counseling for neurological, school-related, and behavioral problems in single ventricle is deficient. Further studies analyzing prenatal counseling techniques and content can help improve upon the delivery of this important aspect of prenatal care.


Delirium, a 'confusing' condition in general hospitals: The experience of a Consultation-Liaison Psychiatry Unit in Greece.
A plethora of studies showed that delirium is common in hospitalized populations. We aimed to examine the characteristics of delirium patients referred to our Consultation-Liaison Psychiatry Unit (CLPU). Our CLPU database was used to obtain data of all referred patients admitted to our hospital and diagnosed with delirium. All referred nondelirious patients served as controls. During one year, 483 patients were referred to the CLPU. Ninety-three (19.3%) were diagnosed with delirium. Delirious patients were older than nondelirious patients (P < 0.001), with 76.3% aged over 70 years. The majority of the referrals came from surgical specialties. Common etiological factors were fluid and electrolyte imbalance (29%), fractures (28%) and infections (24%), but laboratory tests for the investigation of the etiology prior to the consultation had been performed in only 12 patients (12.9%). The syndrome resulted in prolonged hospitalization and greater use of CLPU services. Referrals for delirium are frequent in CLPUs in Greece. Although delirium is common, it remains a 'confusing' condition for health practitioners. The under-diagnosis of delirium, the prolonged hospitalization and the time that the CLPU dedicated to these patients underlines the role of the CLPU psychiatrists in the management of the syndrome.


Hospital mortality and long-term survival after pulmonary resection in the elderly.
We have studied the hospital mortality and long-term survival in two groups of patients: those between 50 and 69 years of age (group 1, n = 136) and those older than 70 years of age (group 2, n = 43). The two groups were similar in terms of the distribution of histological type and postsurgical staging. The patients were treated by either lobectomy or pneumonectomy; the lobectomy rate was similar in both groups: 61% and 51% (not significant). Hospital mortality for group 1 was 4.4% and for group 2, 6.9%. Mortality was higher in both groups after pneumonectomy compared with lobectomy, but this was not significant (group 1, 6.2% versus 1.9%; group 2, 9.1% versus 4.7%). Hospital mortality after pulmonary resection was greater in the elderly, but this was not significant (lobectomy: 1.9% [group 1] versus 4.7% [group 2]; pneumonectomy: 6.2% [group 1] versus 9.1% [group 2]. The overall long-term survival at 2 and 4 years was 62.3% and 50.0% for group 1 and 72.5% and 66.6% for group 2. We suggest that the operative risk in the elderly is not prohibitive and the long-term results are acceptable. Patients should not be denied operation on the basis of age alone.


In vitro anti-leukemic assessment and sustained release behaviour of cytarabine loaded biodegradable polymer based nanoparticles.
The study aimed to develop, characterize, and evaluate poly (ɛ-caprolactone) (PCL) based nanoparticles for the sustained release behaviour of cytarabine and to investigate the in vitro anti-cancer influence on KG-1 leukemic cell line. Nanoprecipitation method was used for the preparation of cytarabine loaded PCL nanoparticles. The developed nanoparticles were characterized for physicochemical properties and the anti-leukemic effect on the KG-1 cell line was evaluated. A total number of five formulations were prepared with size range from 120.5 ± 1.18 to 341.5 ± 3.02, entrapment efficiency (41.31 ± 0.49 to 62.28 ± 0.39%), spherical morphology, negative zeta potentials, considerable particle size distribution, compatibility between the drug and excipients and thermal stability. X-ray diffraction analysis confirmed the successful incorporation of cytarabine in PCL polymer. In vitro drug release in phosphate buffer saline (pH 7.4) showed initial burst release followed by sustained release up to 48 h. The sustained release behaviour efficiently increased the toxicity of cytarabine-loaded PCL nanoparticles to KG-1 (leukemic) and MCF-7 (breast cancer) cell lines in time dependent manner with lower IC50 values than that of drug solution. The flow cytometry study revealed the better apoptotic activity of cytarabine loaded PCL nanoparticle against treated KG-1 cell line. The western blot analysis confirmed the upregulation of cleaved caspase-3 and downregulation of Bcl-2 protein. The experimental results suggest that cytarabine loaded PCL nanoparticles is an efficient carrier to prevent the dose associated toxicity while providing sustained release pattern to ensure maximum anti-cancer influence.


Bis(trimethylsilyl)chromate catalyzed oxidations of alcohols to aldehydes and ketones with periodic acid.
A facile, selective and high yielding bis(trimethylsilyl) chromate (BTSC) catalyzed selective oxidation of alcohols to aldehydes and ketones with periodic acid is reported.


The impact of glycogen synthase kinase 3β gene on psychotic mania in bipolar disorder patients.
The aim of this study was to examine the relationships between glycogen synthase 3β gene polymorphisms and bipolar I disorder, manic in a Korean sample. Patients with bipolar disorder (n=118) and a control group (n=158) were assessed by genotyping for GSK3β single nucleotide polymorphisms (SNPs) -1727A/T and -50C/T. The patients were divided into two groups according to the presence of psychotic symptoms (psychotic mania, n=92; non-psychotic mania, n=26) and also divided based on gender and age of onset. The severity of symptoms was measured using the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). There were no significant differences in the genotype distributions or allelic frequencies of GSK3β polymorphisms and gender between patients with bipolar disorder and a normal control group. According to haplotype analysis, there was no association between these two groups. However, analysis of the age of onset of bipolar disorder revealed significant differences in genotype and allele distributions among the patients. Patients who were homozygous for the wild-type variant (TT) had an older age of onset than carriers of the mutant allele (A/A: 27.4±9.1; A/T: 30.1±11.8; T/T: 42.3±19.9; p=0.034). We detected differences in allele frequencies of the GSK3β -1727A/T polymorphism between the psychotic mania group and the non-psychotic mania group. This study suggests that GSK3β polymorphisms are not associated with bipolar disorder. However, the GSK3β SNP -1727A/T is associated with age of onset and presence of psychotic symptoms in bipolar disorder.


Perfluorinated compounds in surface waters from Northern China: comparison to level of industrialization.
Inclusion of Perfluorooctane Sulfonate (PFOS) in the Stockholm Convention because of its exemptions, has resulted in increased annual production of PFOS-containing chemicals in China to accommodate domestic and overseas demands. Accordingly, concern about environmental contamination with perfluorinated compounds (PFCs), such as PFOS, has arisen. However, little information is available on the status and trends in the distribution, sources or risk of PFCs in aquatic environments of China. In the present study, forty two surface water samples collected from five regions with different levels of industrialization were monitored for concentrations of PFCs by use of solid phase extraction and LC/MS/MS. Mean concentrations (maximum concentration) of PFOA and PFOS, which were the dominant PFCs, were 1.2 (2.3) and 0.16 (0.52)ng/l for Guanting, 1.2 (1.8) and 0.32 (1.1)ng/l for Hohhot, 2.7 (15) and 0.93 (5.7)ng/l for Shanxi, 6.8 (12) and 2.6 (11)ng/l for Tianjin, 27 (82) and 4.7 (31)ng/l for Liaoning, respectively. The greatest concentrations of PFCs (121 ng/l), PFOA (82 ng/l) and PFOS (31 ng/l) were observed in Liaoning, which might originate from tributaries of the Liaohe River, the most polluted watershed in Northeast China. While, concentrations of PFCs in the Guanting and Hohhot regions were 3 to 20 fold less than those from Tianjin and Liaoning. This result is consistent with little contribution of PFCs being released from agricultural and non-industrial activities. The magnitudes of mass flow for PFOA and PFOS in decreasing order were: Guanting<Hohhot<Tianjin<Liaoning<Shanxi and Guanting<Hohhot<Shanxi<Tianjin<Liaoning. The larger mass flows of PFOS were accompanied by relatively larger magnitudes of PFOA. Concentrations of both PFOA and PFOS in waters from all regions were less than suggested allowable concentrations. However, the relatively greater concentrations of PFCs in Tianjin and Liaoning suggest that further studies characterizing their sources and potential risk to both humans and wildlife are needed.


Assimilation by the third generation? Marital choices of white ethnics at the dawn of the twentieth century.
It is well known that marital ethnic endogamy declines by immigrant generation, but there is little information on how many generations are required for full marital assimilation. This study for 1880-1910 includes information on the birthplace of men's grandparents, so we can compare the first, second, third, and later generations. We estimate the odds of marrying a native white woman with native-born parents (NWNP) for Irish, Germans, British, and men of other ethnicities. Most groups even in their third generation still show a significantly lower rate of marital assimilation than native stock men. But mixed ancestry (having at least one NWNP parent or grandparent) can result in nearly complete marital assimilation by the third generation.


Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Imaging for Diagnosis, Tumor Response to Treatment and Liver Response to Radiation.
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) comprise the majority of primary liver cancers. Both HCC and ICC have characteristic imaging appearances on multiphase computed tomography (CT) and magnetic resonance imaging (MRI). Several locoregional therapies, including radiation therapy, are used to treat unresectable disease and residual or recurrent tumor. The tumor response following locoregional therapies has variable imaging manifestations. Focal liver reaction, the imaging changes of the liver following radiation treatment, should be recognized and not mistaken for tumor. We review the diagnostic imaging of HCC and ICC, imaging of tumor response to treatment, and imaging of the liver response to radiation.


Surgical correction of virilised female external genitalia.
Recent investigations and reports on late results indicate that vaginal orgasm is more the exception than the rule, so that, for a woman, preservation of clitoral sensitivity is essential to a satisfying sexual life. All techniques involving total clitoridectomy, plastic imitations, or displacement of the clitoris under the symphysis must therefore be discarded. Even if plication or trapping of an enlarged clitoral shaft under the mons veneris can be regarded as sensitivity-maintaining procedures, they nevertheless do not yield satisfactory results, since painful sensations or a feeling of pressure may occur during erection. Hence, reduction-planess should use techniques which shorten the erectile parts of the clitoris and reduce its size, while still maintaining sensitivity. Good cosmetic and tactile results may be achieved by means of selective excision of the corpora cavernosa and lateral clitoral excisions. Reconstruction of the labia minora out of clitoral shaft skin is combined with separate creation of a neo-preputium clitoridis. Vaginal enlargement plasties have always been problematic, since shrinking particularly of the vaginal introitus, occurs in up to 25% of patients who undergo this operation. However, a sufficiently large pediculated perineal skin flap inserted into the "defect" of the posterior vaginal wall provides sufficient width of the vaginal introitus and canal. Partial vaginal aplasia, with the vagina opening into a urogenital sinus near the bladder, calls for additional abdominal mobilisation. For psychological reasons, vaginal dilatations are not to be recommended. If necessary, a second vaginal enlargement plasty should instead be performed later; this may be carried out without problems before puberty. To avoid the disadvantage of a dry skin flap which does not assimilate to normal vaginal mucosa even after many years and with oestrogen treatment, mobilisation of the posterior vaginal wall with displacement of real vaginal mucosa towards the perineum can be carried out. However, one-stage reconstruction of clitoris, vulva and vagina during early childhood is preferable in every case, in order to avoid the psychological damage which can undoubtedly otherwise be caused. An exception is the late onset form of congenital adrenal hyperplasia.


[Extramedullary tumor formation by acute myeloid leukoses in children (author's transl)].
In rare cases, leukoses can produce tumors before general symptoms and changes in the blood picture appear. Two boys were reported in whom tumors of the eye socket were removed, the tumors were histologically classified as myelosarcoma. During the course of several months, the clinical picture of an acute leukemia developed. The difficulties involved in the exact histologic recognition of myelosarcoma, its localization, the differential diagnosis of tumors of the eye socket in children as well as the therapy and prognosis for children with myelosarcoma were discussed.


Insulin and glucagon secretion in BB wistar rats with impaired glucose tolerance.
Glucose tolerance and insulin secretion were studied in non-diabetic littermates (n = 154) of BB diabetic rats, aged 4-6 months. Initial screening involved two intraperitoneal glucose tolerance tests (0.2 g/100 g body weight) performed one week apart. Nineteen rats (12%) were found to have impaired tolerance which persisted in 14 (74%) (group 1) and was transient in five animals (group 2). Seven rats progressed to overt diabetes in group 1, but none in group 2. Group 1 was characterized by (a) sustained abnormalities in glucose response to oral and intraperitoneal glucose, as well as intraperitoneal tolbutamide and arginine; (b) fasting hypoinsulinaemia; (c) decreased insulin response to glucose and tolbutamide; (d) suppression of the early and late phases of immunoreactive insulin response to intravenous glucose; (e) no systematic abnormalities in glucagon secretion; and (f) the presence of significant insulitis. The group 2 rats had (a) normal glycaemic response to oral and intraperitoneal glucose, tolbutamide and arginine on further testing; (b) normal fasting insulin but excessive insulin response to glucose and tolbutamide, but not to arginine, and (c) mainly normal islet morphology. Thus, impaired glucose tolerance may occur in BB rats with either hypoinsulinaemia or hyperinsulinaemia.


Interferon production and response to exogenous interferon in two cell lines of mouse brain origin persistently infected with Sendai virus.
Two persistently infected cell lines established from C3H mouse brain cells infected in vivo with Sendai virus were shown to differ with respect to interferon (IF) production and response to exogenous IF. MB/Sen carrier cells contained 1-5 per cent antigen positive cells when examined by immunofluorescence, and virus was occasionally recovered from the culture medium. MB/SenAS carrier cells were maintained with 0.16 per cent Sendai antiserum in the supernatant medium. All MB/SenAS cells contained viral antigen and infectious virus was present in the culture medium. MB/Sen released IF spontaneously into the culture medium. Further IF production could be stimulated in MB/Sen by superinfection with Newcastle disease virus (NDV) or vesicular stomatitis virus (VSV). Exogenous IF provided good protection against VSV challenge. In contrast, MB/SenAS produced no IF spontaneously but could be stimulated by NDV and VSV to produce IF. Exogenous IF failed to reduce the amount of VSV released into the supernatant fluid. Replication of VSV was restricted in MB/SenAS as shown by a 2.3 log10 lower virus yield compared to MB/Sen.


Structure-Tailored Non-Noble Metal-based Ternary Chalcogenide Nanocrystals for Pt-like Electrocatalytic Hydrogen Production.
A facile microwave-assisted strategy was employed to synthesize Ni3 Bi2 S2 nanocrystals. Variation in the synthesis conditions tuned the composition of monoclinic and orthorhombic phases of Ni3 Bi2 S2 . The electrochemical hydrogen evolution activity of the catalyst with highest percentage of monoclinic phase demonstrated a negligible onset potential of only 24 mV close to that of state-of-the-art Pt/C with an overpotential as low as 88 mV. Density functional theory calculations predicted the monoclinic phase exhibit the lowest adsorption free energy corresponding to hydrogen adsorption ( Δ G ads H * ) and, therefore, the highest hydrogen evolution activity amongst the considered phases. The quasi-2D structure of monoclinic phase facilitated an increased charge-transfer between Ni and Bi, favoring the downward shift of the d-band center to enhance the catalytic activity.


Allopregnanolone in mood disorders: Mechanism and therapeutic development.
The neuroactive steroid allopregnanolone (ALLO) is an endogenous positive allosteric modulator of GABA type A receptor (GABAAR), and the down-regulation of its biosynthesis have been attributed to the development of mood disorders, such as depression, anxiety and post-traumatic stress disorder (PTSD). ALLO mediated depression/anxiety involves GABAergic mechanisms and appears to be related to brain-derived neurotrophic factor (BDNF), dopamine receptor, glutamate neurotransmission, and Ca2+ channel. In the clinical, brexanolone, as a newly developed intravenous ALLO preparation, has been approved for the treatment of postpartum depression (PPD). In addition, traditional antidepressants such as selective serotonin reuptake inhibitor (SSRI) could reverse ALLO decline. Recently, the translocation protein (TSPO, 18 kDa), which involves in the speed-limiting step of ALLO synthesis, and ALLO derivatization have been identified as new directions for antidepressant therapy. This review provides an overview of ALLO researches in animal model and patients, discusses its role in the development and treatment of depression/anxiety, and directs its therapeutic potential in future.


Influence of shading technique on mechanical fatigue performance and optical properties of a 4Y-TZP ceramic for monolithic restorations.
This study aimed to evaluate the effect of shading procedures on the fatigue performance and optical properties of an yttria-stabilized tetragonal zirconia polycrystal ceramic (4Y-TZP - stabilized by 4 mol% Y2O3). Disc-shaped specimens were produced at pre-sintered stage and randomly allocated into 5 groups (n=15) considering the shading technique: Ctrl (no pigmentation); Brush 1× and Brush 3× (brushing on 1 or 3 applications, respectively); Immer 2min and Immer 4min (immersion for 2 or 4 min, respectively). Following each pigment application, the specimens were dried in accordance with the manufacturers' guidelines (15 min in a stove at 70 °C) and sintered in a specific furnace. Biaxial flexural fatigue test followed a step-stress approach (initial strength: 200 MPa; step-size: 25 MPa; 10.000 cycles/step; frequency: 20 Hz). Optical measurements were conducted in a spectrophotometer following the CIEDE2000 parameters. Roughness, topography, crystalline grain size, crystalline phase content and fractography analysis were also performed. The flexural fatigue strength (FFS) and the number of cycles to fracture (CFF) were statistically affected by pigmentation techniques (mean FFS in MPa/mean CFF): Ctrl (446.7/105,619) > Brush 1 × (436.7/102,854) ≥ Brush 3 × (405.0/89,962) ≥ Immer 2 min (395.0/85,103) ≥ Immer 4 min (383.3/81,382), although the exposure intensity (increase in number of applications or in application time) to the pigment had no effect (Brush 1 × = Brush 3 × ; Immer 2 min = Immer 4 min). Regarding optical properties, shading techniques similarly affected translucency and opalescence parameters, regardless of the exposure intensity to the pigment (Brush 1 × = Brush 3 × = Immer 2 min = Immer 4 min > Ctrl), whereas the exposure intensity to the pigment only promoted relevant alterations in the color change parameter (ΔE00) for the brushing technique (Brush 3 × > Brush 1 × ). No difference was observed in crystalline phase content, topographic pattern or roughness, although an increase in the zirconia grain size could be detected. Thus, the shading technique might affect the fatigue behavior and promote optical changes in a 4Y-TZP ceramic.


Folate and folic acid in the periconceptional period: recommendations from official health organizations in thirty-six countries worldwide and WHO.
To summarize the recommendations on folate intake and folic acid supplementation and fortification in the periconceptional period, aimed at prevention of neural tube defects (NTD), provided by official health organizations in different countries worldwide and WHO. Information on recommendations for folate and folic acid intake in the periconceptional period was gathered from the websites of official national health organizations of several countries worldwide and from the WHO website. WHO, selected developed countries and emerging economies, totalling thirty-six countries worldwide (some European, BRICS, G8, Asian Tiger/Asian Dragon and Australia). Recommendations differ between countries, although the majority (69·4 %) recommend a healthy diet plus a folic acid supplement of 400 µg/d from preconception (4-12 weeks) until the end of the first trimester of pregnancy (8-12 weeks). The same recommendation is issued by the WHO. Dosages for women at high risk of NTD are up to 4-5 mg/d (for 41·7 % of studied countries). The recommended intake for folate is in the range of 300-400 µg/d for women of childbearing age and 500-600 µg/d for pregnant women in different countries and WHO. Five countries emphasize the importance of a healthy diet rendering supplementation needless. By contrast, five others advise a healthy diet and supplementation plus mandatory fortification. Only one mentions the importance of ensuring an adequate folate status and refers to checking with a health-care provider on the need for supplements. Different recommendations regarding folate and folic acid, seeking NTD prevention, are available worldwide; however, most countries and WHO focus on a healthy diet and folic acid supplementation of 400 µg/d periconceptionally.


Circulating CD8+ lymphocytes, white blood cells, and survival in patients with mycosis fungoides.
There is a need for reliable, easily measurable laboratory markers that may help dermatologists to predict the course of mycosis fungoides (MF) when they first evaluate their patients. Our objective was to identify clinical, haematological or immunological parameters as predictors of mortality in patients with MF. We conducted a retrospective study on a prevalent cohort of 124 patients with MF hospitalized at IDI-IRCCS, Rome, Italy, from 1983 to 2001. We calculated the proportion of patients surviving (Kaplan-Meier product-limit estimates) 5 and 10 years after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model. Patients' survival was linked to age and staging (lower survival in older patients and in patients with staging IIB-IV). Higher numbers of white blood cells (WBC) and neutrophils, lower numbers of CD8+ lymphocytes, low haematocrit and lower levels of albumin were significantly associated with a lower survival probability. When simultaneously accounting for age and staging, CD8+ [HR = 3.02, 95% confidence interval (CI) 1.01-9.07 for CD8+ < 250 vs. > or = 600 cells microL(-1)] and WBC (HR = 2.59, 95% CI 0.96-6.96 for WBC > or = 9000 vs. < 6000 cells microL(-1)) were associated with survival. In addition, we observed an exceedingly high risk of death (HR = 12.40, 95% CI 3.11-49.43) for patients with a combination of WBC > or = 9000 and CD8+ < 600 cells microL(-1) vs. WBC < 9000 and CD8+ > or = 600 cells microL(-1)). The measurement of CD8+ cells and WBC in MF seems to be a promising criterion to predict survival, and possibly to support treatment decisions and inclusion of patients in randomized controlled trials.


Evidence-based protocol for diagnosis and treatment of hepatorenal syndrome is independently associated with lower mortality.
Hepatorenal syndrome (HRS) is the deadliest complication of cirrhosis. The purpose of this study is to analyze if the use of a protocol for HRS is associated with higher survival in these patients. An evidence-based protocol for the diagnosis and treatment of HRS was instituted in 2013. Data from medical records from 2010 to 2016 were obtained by searching the hospital database for patients who received terlipressin, in the three years before and after the institution of the protocol. Data were reviewed to confirm the diagnosis of HRS and multiple variables were collected. Liver-specific scores were calculated and a stepwise Cox regression approach was used for univariate and multivariate analysis. The study included 46 patients, 20 from the pre-protocol period and 26 from the post-protocol period. Respectively, mortality at 30 days, 90 days and 365 days was 75%, 75% and 90% for the pre-protocol period, and 61%, 69% and 80% for the post-protocol period. In the multivariate analysis, an aspartate aminotransferase (AST) of <40U/L, the pre-protocol period and higher Child-Turcotte-Pugh scores were associated with higher 30-day and 90-day mortality. The total mean dose of terlipressin and human albumin used per patient was reduced from 27mg to 22mg and from 236g to 144g, respectively, after the institution of the protocol. This was not associated with higher mortality. The use of an evidence-based protocol for the treatment of HRS translated into a higher survival. The authors suggest that the use of evidence-based protocols for the diagnosis and treatment of HRS could reduce cost and mortality in tertiary hospitals.


Constructing recombinant herpesvirus BAC vectors with mating-assisted genetically integrated clone method.
The large capacity of pseudorabies virus (PRV) for foreign DNA and broad host range make it a prospective tool for the preparation of vaccines and agents of gene and tumour therapy. Here we introduced a cloning strategy that facilitates construction of recombinant PRV-BAC vectors based on mating-assisted genetically integrated clone (MAGIC). The target gene was cloned into a small conditionally replicating donor plasmid, followed by shuffling to a recipient PRV-BAC plasmid in vivo of Escherichia coli through MAGIC. The average efficiency of successful clones was 89%. Moreover, permanent integration of unwanted sequences was avoided.


Blinatumomab compared with standard of care for the treatment of adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia.
A single-arm, phase 2 trial demonstrated the efficacy and safety of blinatumomab, a bispecific T-cell-engaging antibody construct, in patients with relapsed/refractory (r/r) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), a rare hematologic malignancy with limited treatment options. This study compared outcomes with blinatumomab with those of a historical control treated with the standard of care (SOC). The blinatumomab trial enrolled adult patients with Ph+ ALL who were r/r to at least 1 second-generation tyrosine kinase inhibitor (n = 45). Propensity score analysis (PSA) was used to compare outcomes with blinatumomab with those of an external cohort of similar patients receiving SOC chemotherapy (n = 55). The PSA mitigated confounding variables between studies by adjusting for imbalances in the age at diagnosis and start of treatment, sex, duration from diagnosis to most recent treatment, prior allogeneic hematopoietic stem cell transplantation, prior salvage therapy, and number of salvage therapies. Bayesian data augmentation was applied to improve power to 80% with data from a phase 3 blinatumomab study in r/r Philadelphia chromosome-negative ALL. In the PSA, the rate of complete remission or complete remission with partial hematologic recovery was 36% for blinatumomab and 25% for SOC, and this resulted in an odds ratio of 1.54 (95% confidence interval [CI], 0.61-3.89) or 1.70 (95% credible interval [CrI], 0.94-2.94) with Bayesian data augmentation. Overall survival favored blinatumomab over SOC, with a hazard ratio of 0.81 (95% CI, 0.57-1.14) or 0.77 (95% CrI, 0.61-0.96) with Bayesian data augmentation. These results further support blinatumomab as a treatment option for patients with r/r Ph+ ALL.


Cumulative positive fluid balance is a risk factor for acute kidney injury and requirement for renal replacement therapy after liver transplantation.
To analyze whether fluid overload is an independent risk factor of adverse outcomes after liver transplantation (LT). One hundred and twenty-one patients submitted to LT were retrospectively evaluated. Data regarding perioperative and postoperative variables previously associated with adverse outcomes after LT were reviewed. Cumulative fluid balance (FB) in the first 12 h and 4 d after surgery were compared with major adverse outcomes after LT. Most of the patients were submitted to a liberal approach of fluid administration with a mean cumulative FB over 5 L and 10 L, respectively, in the first 12 h and 4 d after LT. Cumulative FB in 4 d was independently associated with occurrence of both AKI and requirement for renal replacement therapy (RRT) (OR = 2.3; 95%CI: 1.37-3.86, P = 0.02 and OR = 2.89; 95%CI: 1.52-5.49, P = 0.001 respectively). Other variables on multivariate analysis associated with AKI and RRT were, respectively, male sex and Acute Physiology and Chronic Health Disease Classification System (APACHE II) levels and sepsis or septic shock. Mortality was shown to be independently related to AST and APACHE II levels (OR = 2.35; 95%CI: 1.1-5.05, P = 0.02 and 2.63; 95%CI: 1.0-6.87, P = 0.04 respectively), probably reflecting the degree of graft dysfunction and severity of early postoperative course of LT. No effect of FB on mortality after LT was disclosed. Cumulative positive FB over 4 d after LT is independently associated with the development of AKI and the requirement of RRT. Survival was not independently related to FB, but to surrogate markers of graft dysfunction and severity of postoperative course of LT.


Two new black fly species of the Simulium (Gomphostilbia) asakoae species-group (Diptera: Simuliidae) from Taiwan.
Two new black fly species, Simulium (Gomphostilbia) kaohsiungense and S. (G.) shoufengense, are described from females, males and pupae in Taiwan. These new species are placed in the S. asakoae species-group. Simulium (G.) kaohsiungense sp. nov. is characterized by a combination of the elongate female sensory vesicle, male upper-eye (large) facets in 15 vertical columns and 15 or 16 horizontal rows, male hind basitarsus 1.02-1.15 times the width of the hind femur, and widened pupal terminal hooks. These characteristics distinguish this new species from most species of the S. asakoae species-group. Simulium (G.) shoufengense sp. nov. is similar in the female and male to S. (G.) asakoae Takaoka & Davies originally described from Peninsular Malaysia but is distinguished from the latter species in the pupa by the combined length of the primary and secondary stalks of the dorsal triplet of gill filaments as long as or longer than the common basal stalk of the gill, and dorsum of abdominal segments 1 and 2 not darkened. The species previously regarded in Taiwan as S. (G.) metatarsale Brunetti, originally described from India, is morphologically and molecularly identified as S. (G.) asakoae.


Perceiver and target partisanship shift facial trustworthiness effects on likability.
The affective polarization characteristic of the United States' political climate contributes to pervasive intergroup tension. This tension polarizes basic aspects of person perception, such as face impressions. For instance, face impressions are polarized by partisanship disclosure such that people form positive and negative impressions of, respectively, shared and opposing partisan faces. How partisanship interacts with other facial cues affecting impressions remains unclear. Building on work showing that facial trustworthiness, a core dimension of face perception, is especially salient for ingroup members, we reasoned that shared and opposing partisanship may also affect the relation between facial trustworthiness characteristics and subsequent likability impressions. A stronger positive relation emerged for shared versus opposing partisan faces across more conservative and liberal perceivers (Experiments 1 and 2). Exploratory analyses showed that this difference links to perceived partisan threat (Experiment 1) and that experimentally manipulating inter-party threat strengthened opposing partisan derogation and shared partisan enhancement patterns (Experiment 2). These findings suggest that partisanship extends from affecting overall face impressions of partisans to affecting the relation between a core dimension of face perception and subsequent impressions. These findings highlight the prevalence of partisanship effects in basic aspects of person perception and have implications for intergroup behavior.


Quantitative evaluation of the microstructure of rapid eye movement sleep in refractory epilepsy: a preliminary study using electroencephalography and heart rate variability analysis.
Patients with epilepsy have a disturbed sleep architecture. Polysomnographic studies have shown that patients with refractory epilepsy have decreased rapid eye movement (REM) sleep and longer REM latency than those with medically controlled epilepsy. However, little is known about the differences in the REM sleep microstructure between these patient groups. We conducted a retrospective case-control study of 20 patients with refractory epilepsy (refractory group) and 28 patients with medically controlled epilepsy (medically controlled group). All patients completed sleep questionnaires and underwent overnight in-lab polysomnography. Five-minute electroencephalogram recordings at the C3 and C4 electrodes from each REM sleep were selected for spectral analysis, and 5-min electrocardiogram segments recorded during REM sleep were used for heart rate variability analysis. The groups' scores on the sleep questionnaires, polysomnographic sleep parameters, indices of sleep-related breathing disorders, and REM sleep electroencephalogram spectra were compared. The refractory group had decreased REM sleep (p < 0.001) and longer REM latency (p = 0.0357) than those of the medically controlled group. Moreover, electroencephalogram spectral analysis revealed that the refractory group had decreased absolute beta power (p = 0.0039) and relative beta power (p = 0.0035) as well as increased relative delta power (p = 0.0015) compared with the medically controlled group. Differences in the polysomnographic macrostructure and REM sleep microstructure between the study groups suggest REM sleep dysregulation in patients with refractory epilepsy.


The Association Between Functional Movement Screen Scores and Knee Valgus Moments During Unplanned Sidestep Cutting in Netball.
Regular employment of three-dimensional (3D) motion analyses to assess and monitor knee valgus moments; a contributor to non-contact anterior cruciate ligament (ACL) injury; during unplanned sidestep cutting (USC) is costly and time-consuming. An alternative quick-to-administer assessment tool to infer an athlete's risk for this injury could allow prompt and targeted interventions to mitigate this risk. This study investigated whether peak knee valgus moments (KVM) during weight-acceptance phase of an unplanned sidestep cut were correlated with composite and component scores of the Functional Movement Screen (FMS™). Cross-sectional, Correlation. Thirteen female national-level netballers performed six movements of the FMS™ protocol and three trials of USC. A 3D motion analysis system captured lower limb kinetics and kinematics of each participant's non-dominant leg during USC. Averages of peak KVM across USC trials were calculated and examined for correlations with composite and component scores of the FMS™. No correlations were found between FMS™ composite or any of its component scores with peak KVM during USC. The current FMS™ did not show any correlations with peak KVM during USC on the non-dominant leg. This suggests that the FMS™ has limited utility in screening for non-contact ACL injury risks during USC. 3.


Comparison between oxaliplatin therapy and capecitabine monotherapy for high-risk stage II - III elderly patients with colon cancer.
45% of colon cancer patients are elderly, yet they are often deviated from standard cancer management. The MOSAIC trial favored FOLFOX over FL with superior oncologic outcomes; however, which regimen is most beneficial in elderly population remains unclear. This study aimed to compare the efficacy of oxaliplatin-added chemotherapy and capecitabine monotherapy in high-risk stage II/stage III elderly colon cancer patients. Colon cancer patients ≥70 years of age who received adjuvant chemotherapy at Inje University Busan Paik Hospital between February 2009 to April 2016 were included. Patients were separated into the oxaliplatin-added group and capecitabine monotherapy group. The primary outcomes were CSS and OS. Of 74 patients, 45 received oxaliplatin-added chemotherapy and 29 received capecitabine monotherapy. There was no difference between the two groups in CSS or OS (p = 0.9670 and p = 0.6801, respectively). The N stage was significantly associated with CSS in both uni/multivariate analysis (p = 0.0565 and p = 0.0347, respectively). The oxaliplatin-added group had more stage III patients, so we performed a subgroup analysis of CSS and OS based on stage, which also showed no significant difference. Capecitabine monotherapy is an oncologically safe regimen compared to oxaliplatin-added regimens in elderly patients with high-risk stage II/stage III colon cancer.


Health literacy: an overlooked factor in understanding HIV health disparities.
Limited health literacy may be a contributing factor to racial disparities in health care. This study examined the mediating effect of limited health literacy on the relationship between race and HIV-medication adherence. A total of 204 patients infected with HIV were recruited from two clinics in 2001. Structured in-person interviews were conducted to obtain information on patient demographics, medication adherence, and health literacy. Multivariate regression models were run in 2006 to examine the associations among race, literacy, and HIV-medication adherence after adjusting for relevant covariates. In an adjusted analysis that excluded literacy, African Americans were 2.40 times more likely to be nonadherent to their HIV-medication regimen than whites (95% confidence interval [CI]=1.14-5.08). When literacy was included in the final model, the effect estimates of race diminished 25% to nonsignificance. Literacy remained a significant independent predictor of nonadherence (adjusted odds ratio [AOR]=2.12, 95% CI=1.93-2.32). In this study, limited health literacy mediated the relationship between race and HIV-medication adherence. Investigators need to consider the potential utility of responding to literacy and communication barriers in health care as part of interventions to reduce racial disparities.


Lowering of liver acetaldehyde but not ethanol concentrations by pretreatment with taurine in ethanol-loaded rats.
A rise in blood and liver acetaldehyde concentrations following ethanol loading (1.5 g/kg b.wt) was significantly reduced when rats were pretreated orally with taurine (0.5 g/kg), a potent in vitro activator of yeast aldehyde dehydrogenase. This taurine pretreatment produced a 4-fold increase in liver taurine content.


Effect of lesion length on fractional flow reserve in intermediate coronary lesions.
Fractional flow reserve (FFR) has become a gold standard in physiological assessment of coronary artery stenosis. An FFR < 0.75 is considered as a reliable physiological parameter indicating functionally significant lesion. Lesion length (LL) may affect the translesional hemodynamics. However, the effect of LL on FFR has not been adequately assessed. We sought to evaluate the effect of LL on FFR in patients with angiographically intermediate coronary artery disease. We performed FFR measurements by pressure guidewire in 63 intermediate-grade lesions (63 patients) by visual assessment. Lesion length and percent diameter stenosis (%DS) at the lesion site were determined by performing off-line quantitative coronary angiography analysis. Overall, there was a moderate inverse correlation between FFR and %DS (r = -0.55, P < .001). In addition, there was a weak inverse correlation between LL and FFR (r = -0.31, P < .001). Using a receiver operating characteristic curve analysis, an LL > or = 10 mm was identified as the best cutoff value for predicting an FFR < 0.75 (sensitivity 95%, specificity 66%, positive predictive power 48%, and negative predictive power 97%). The correlation between FFR and %DS was significantly improved for LL > or = 10 mm, as compared with LL < 10 mm (r = -0.78, P < .001; r = 0.16, P = NS; respectively). Similar improvement with LL was also observed for intermediate lesions by quantitative coronary angiography (%DS 50%-70%; r = 0.19, P = NS for LL < 10 mm; r = -0.74, P < .001 for LL > or = 10 mm). This study demonstrates that LL differentially affects the correlation between the functional assessment (FFR) and the "anatomic" severity (%DS) of coronary lesions and suggests that LL has a significant impact on the physiological significance of intermediate-grade coronary lesions.


Using RNAi screening technologies to interrogate the extrinsic apoptosis pathway.
Despite the knowledge accumulated during the last two decades about programmed cell death, further investigations of the complex regulatory network of apoptosis, including the extrinsic pathways, are still needed to gain an exhaustive and comprehensive understanding of this critical biological process. In addition, the identification of novel modulators of apoptosis may represent a good opportunity for making new paths into an otherwise heavily investigated area, therefore providing a molecular basis for new therapeutic strategies. In the last decade, RNA interference has become the technology of choice for discovering genes that encode molecules with previously unknown functions in biological pathways of interest. Various RNAi reagents and library formats have been developed and harnessed for high-throughput screening technologies to enable almost limitless investigation to uncover gene functions and networks in the context of basic biology and biomedical research including cancer biology. Although RNAi screening has been demonstrated to be a very powerful tool, various caveats and pitfalls have been progressively uncovered, including, but not limited to the enduring off-target effects. As the novelty of its bells and whistles have begun to diminish, functional genomic screens have morphed into a specialized field within the high-throughput screening community, where expert investigators progressively establish rigorous strategies to mitigate most of its possible flaws. Using various examples of RNAi screens conducted to further understand the extrinsic apoptosis pathway, this chapter describes the different RNAi tools and screening formats available and reviews the parameters one has to critically consider in order to be successful in implementing this technology.


High-speed AFM and nano-visualization of biomolecular processes.
Conventional atomic force microscopes (AFMs) take at least 30-60 s to capture an image, while dynamic biomolecular processes occur on a millisecond timescale or less. To narrow this large difference in timescale, various studies have been carried out in the past decade. These efforts have led to a maximum imaging rate of 30-60 ms/frame for a scan range of approximately 250 nm, with a weak tip-sample interaction force being maintained. Recent imaging studies using high-speed AFM with this capacity have shown that this new microscope can provide straightforward and prompt answers to how and what structural changes progress while individual biomolecules are at work. This article first compares high-speed AFM with its competitor (single-molecule fluorescence microscopy) on various aspects and then describes high-speed AFM instrumentation and imaging studies on biomolecular processes. The article concludes by discussing the future prospects of this cutting-edge microscopy.


Laparo-assisted vaginal radical hysterectomy as a safe option for minimal invasive surgery in early stage cervical cancer: A systematic review and meta-analysis.
Radical hysterectomy and pelvic lymphadenectomy are considered the standard treatment for early-stage cervical cancer (ECC). Minimal Invasive approach to this surgery has been debated after the publication of a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC trial). It demonstrated poorer oncological outcomes for Minimal Invasive Surgery in ECC. However, the reasons are still an open debate. Laparo-Assisted Vaginal Hysterectomy (LAVRH) seems to be a logical option to Abdominal Radical Hysterectomy (ARH). This meta-analysis has the aim to prove it. Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the Pubmed database and Scopus database were systematically searched in January 2022 since early first publications. No limitation of the country was made. Only English article were considered. The studies containing data about Disease-free Survival (DFS) and/or Overall Survival (OS) and/or Recurrence Rate (RcR) were included. 18 studies fulfilled inclusion criteria. 8 comparative studies were enrolled in meta-analysis. Patients were analyzed concerning surgical approach (Laparo-Assisted Vaginal Radical Hysterectomy) and compared with ARH Oncological outcomes such as DFS and OS were considered. 3033 patiets were included. Meta-analysis highlighted a non-statistic significant difference between LARVH and ARH (RR 0.82 [95% CI 0.55-1.23] p = 0.34; I2 = 0%; p = 0.96). OS was feasible only for 3 studies (RR 1.14 [95% CI 0.28-4.67] p = 0.43; I2 = 0 p = 0.86). Data about the type of recurrences (loco-regional vs distant) were collected. LARVH does not appear to affect DFS and OS in ECC patients. The proposed results seem to be comparable with the open approach group of the LACC trial, which today represents the reference standard for the treatment of this pathology. More studies will be needed to test the safety and efficacy of LARVH in the ECC.


Comparative Synthesis and Characterization of Bio-Cellulose from Local Waste and Cheap Resources.
Bacterial cellulose (BC) has been extensively utilized in a wide range of applications specifically in the biomedical field thanks to its excellent physico-chemical and biological features. The major limitation restricting its application in certain areas is its high production cost. Its widespread applications demand exploration of alternative production media compared to the existing expensive ones. Herein, an effort has been made to utilize waste and cheaply available local resources including; waste (expired) orange juice (WOJ), sugarcane juice (SC) and coconut water (CW) as alternative media for BC production in comparison to the synthetic media (control). Waste and cheap resources were collected from the local market, screened filtered and optimized for the development of BC culture media. BC production from all media was observed under static cultivation for 10 days. The results indicated 2.75, 2.56, 3.32 and 1.68 g/L BC production that corresponded to 27.5%, 21.7 %, 20.1 % and 31.6 % sugar to BC conversion from control, WOJ, SC and CW media, respectively. Morphology and crystalline features of produced BC samples were observed through FE-SEM and XRD analysis. It was noteworthy that BC produced from all alternative sources indicated high water holding capabilities (WHC) and water retention time (WRT) that augment their applicability in drug delivery and wound healing applications. The BC production from cheap resources and its high physical, mechanical and biological properties can be of high interest for scaling up and commercialization of BC production processes. Furthermore, its liquidabsorbing capabilities and retention time can help in drug carrying and medical application.


Ro-vibrational energies of cesium dimer and lithium dimer with molecular attractive potential.
An approximate solution of the Schrӧdinger equation for a molecular attractive potential was obtained using the parametric Nikiforov-Uvarov method. The energy equation and the corresponding radial wave functions were calculated. The effects of the potential parameters on the energy eigenvalues were examined. The thermal properties under the molecular attractive potential were calculated and the behaviour of the thermal properties with the maximum quantum state (λ) and the temperature parameter (β) respectively, were studied. Using the molecular spectroscopic parameters, the Rydberg-Klein-Rees (RKR) of cesium dimer and lithium dimer were both obtained and compared with the experimental values. The RKR values of both cesium dimer and lithium dimer calculated aligned with the observed values. The deviation and average deviation of the RKR for each molecule were also calculated.


Effect of amrinone during group B Streptococcus-induced pulmonary hypertension in piglets.
Intravenous infusion of group B Streptococcus (GBS) into neonatal animals produces pulmonary hypertension, ventilation/perfusion (VA/Q) mismatch, and an increase in serum levels of thromboxane B2 (TxB2) and tumor necrosis factor (TNF) alpha. The vasodilator amrinone (amr) is a cGMP-inhibited phosphodiesterase inhibitor and is reported to inhibit thromboxane A2 and TNF production. We hypothesized that infusion of amr would cause pulmonary vasodilation and reduce serum TxB2 and TNF levels in piglets with late phase GBS-induced pulmonary hypertension. The effect of amr on gas exchange was also determined. A continuous infusion of GBS was administered for 5 hr to 4 groups of anesthetized, mechanically ventilated neonatal piglets. An amr bolus of 8 mg/kg was given at 4 hr followed by a 1 hr continuous infusion of either 10 or 20 micrograms/kg/min of amr (amr 10 and amr 20, respectively). Control piglets received a bolus and 1 hr infusion of amr carrier. The infusion of amr, but not of carrier reversed late phase GBS-induced pulmonary hypertension. Piglets infused with amr 20 showed transient selective pulmonary vasodilation, based on a reduced ratio of pulmonary to systemic vascular resistance (PVR/SVR ratio) value at 30 min but not at 1 hr, compared to pre-amr treatment values. The PVR/SVR ratio values for amr 10 and control group did not change after treatment with either amr or carrier. Treatment with amr 10 or 20 did not decrease serum TxB2 or TNF levels or increase VA/Q mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)


Facial palsy as an unusual presenting symptom associated with acute myeloid leukemia.
Extramedullary infiltration is common in acute myeloid leukemia (AML) patients. Although AML can cause neurological symptoms, especially when associated with extramedullary infiltration, a presenting manifestation of facial palsy is rare. We report on a 1-year-old boy who developed right facial palsy. Detailed examination led to a diagnosis of AML (French-American-British classification M1). Magnetic resonance imaging enhanced with gadolinium-diethylenetriamine penta-acetic acid showed abnormal enhancement of the right facial nerve, which disappeared after chemotherapy. AML should be considered as a differential diagnosis of facial palsy. Enhanced magnetic resonance imaging may be useful for diagnosing facial palsy associated with AML and for evaluating treatment outcome.


Evaluating OzHarvest's primary-school Food Education and Sustainability Training (FEAST) program in 10-12-year-old children in Australia: protocol for a pragmatic cluster non-randomized controlled trial.
The promotion of healthy eating is a public health priority. Poor dietary behaviours, including low fruit and vegetable (F&V) consumption are of particular concern among children. Novel nutrition promotion strategies are needed to improve F&V consumption. Sustainability education could be used to support nutrition education within the school context. The purpose of this paper is to report the protocol for impact and process evaluation of the school-based Food Education and Sustainability Training (FEAST) program, designed to educate children about sustainability, food waste and nutrition, using hands-on cooking activities. A pragmatic, parallel, cluster non-randomized controlled trial with pre- and post-measures, will be implemented among 20 primary schools (10 intervention vs 10 wait-list-control) within NSW, Australia, involving children in Grades 5-6. FEAST is a curriculum-aligned program, delivered as a 1.5-h lesson/week, for a 10-week unit of inquiry, incorporating theory and cooking. FEAST was developed using theoretical frameworks which included Social Cognitive Theory and the Precede-Proceed Planning model. Primary outcomes include children's self-reported F&V intakes (serves/day). Food literacy constructs such as: nutrition knowledge, food preparation and cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours and food production knowledge, will be assessed as secondary outcomes. Process evaluation will assess program reach, adoption, implementation, maintenance, satisfaction and perceived benefits by teachers and students. An online survey (including quantitative and qualitative questions) was developed for administration at baseline (impact evaluation) and immediately post-intervention (impact and process evaluation). Intervention effects on quantitative study outcomes will be estimated with generalised linear mixed models, including random effects and will follow the intention-to-treat principles. Open-ended questions embedded within the surveys will be analysed qualitatively using content and thematic analyses. Results from this trial will provide valuable information on the value of adding environmental sustainability strategies to nutrition education in schools. Results will inform the design of future research and programs focused on primary-school children's nutrition, sustainability-related behaviours and experiential school-based interventions. Trial registered 14th December 2020 with the Australian and New Zealand Clinical Trials Registry ( ACTRN12620001347954 ).


Learning deficit in cognitively normal APOE ε4 carriers with LOW β-amyloid.
In cognitively normal (CN) adults, increased rates of amyloid beta (Aβ) accumulation can be detected in low Aβ (Aβ-) apolipoprotein E (APOE) ε4 carriers. We aimed to determine the effect of ε4 on the ability to benefit from experience (ie, learn) in Aβ- CNs. Aβ- CNs (n = 333) underwent episodic memory assessments every 18 months for 108 months. A subset (n = 48) completed the Online Repeatable Cognitive Assessment-Language Learning Test (ORCA-LLT) over 6 days. Aβ- ε4 carriers showed significantly lower rates of improvement on episodic memory over 108 months compared to non-carriers (d = 0.3). Rates of learning on the ORCA-LLT were significantly slower in Aβ- ε4 carriers compared to non-carriers (d = 1.2). In Aβ- CNs, ε4 is associated with a reduced ability to benefit from experience. This manifested as reduced practice effects (small to moderate in magnitude) over 108 months on the episodic memory composite, and a learning deficit (large in magnitude) over 6 days on the ORCA-LLT. Alzheimer's disease (AD)-related cognitive abnormalities can manifest before preclinical AD thresholds.


Regulation mechanism of hydrazine and hydroxylamine in nitrogen removal processes: A Comprehensive review.
As the new fashioned nitrogen removal process, short-cut nitrification and denitrification (SHARON) process, anaerobic ammonium oxidation (anammox) process, completely autotrophic nitrogen removal over nitrite (CANON) process, partial nitrification and anammox (PN/A) process and partial denitrification and anammox (PD/A) process entered into the public eye due to its advantages of high nitrogen removal efficiency (NRE) and low energy consumption. However, the above process also be limited by long-term start-up time, unstable operation, complicated process regulation and so on. As intermediates or by-metabolites of functional microorganisms in above processes, hydroxylamine (NH2OH) and hydrazine (N2H4) improved NRE of the above processes by promoting functional enzyme activity, accelerating electron transport efficiency and regulating distribution of microbial communities. Therefore, this review discussed effects of NH2OH and N2H4 on stability and NRE of above processes, analyzed regulatory mechanism from functional enzyme activity, electron transport efficiency and microbial community distribution. Finally, the challenges and limitations for nitric oxide (NO) and nitrous oxide (N2O) produced from regulation of NH2OH and N2H4 are discussed. In additional, perspectives on future trends in technology development are proposed.


A low-complexity and robust minimum variance beamformer for ultrasound imaging systems using beamspace dominant mode rejection.
Minimum variance beamformer (MVB) has a high computational complexity that is mainly due to the inversion of an L×L covariance matrix involved during weight vector estimation, where L is the length of the subarray. In this work an attempt is made to reduce the computational complexity as well as increase the robustness against signal mismatch. The computational complexity is reduced by projecting the element-space data on to beamspace domain and then using dominant mode rejection on the beamspace covariance matrix (BCM). This reduces the dimension of covariance matrix and also eliminates the matrix inversion thereby reducing the computational complexity. Further, a closeness factor is introduced to determine the interference components that have to be suppressed, leading to increased robustness against signal mismatch. Performance of the proposed method has been evaluated on both simulated and experimental datasets. Results indicate that the proposed beamformer has a lateral resolution of 0.07 mm and a contrast resolution of 0.80, which are comparable to that of MVB which has a lateral and contrast resolution of 0.10 mm and 0.78, that too with a 12-fold reduction in computational complexity. The robustness of the peak magnitude estimate and spatial resolution of the beamformer with respect to error in estimation of sound velocity in the medium have also been evaluated. The variation in lateral resolution of proposed beamformer and MVB is approximately 1.21 mm and 1 mm. Further, the proposed beamformer has a maximum deviation in peak magnitude estimate of 0.7 dB whereas that of MVB is 2.5 dB, thus indicating the increased robustness of proposed method in peak magnitude estimate. Overall, the proposed beamformer has a 12-fold lower computational complexity compared to MVB with additional flexibility to increase the robustness against error in sound velocity.


Genes involved in phosphatidylcholine biosynthesis correlate with nuclear factor-κB in biliary tract cancer patients: Evidence from 1H NMR and computational analyses.
Gallbladder cancer (GBC) is an aggressive malignancy of gastrointestinal tract. Due to uncontrolled growth, GBC cells rapidly synthesize biomolecules including lipids. The lipids are integral component of cell membrane with a wide range of cellular functions. In this study, we measured the clinicopathological features in 40 cases of histologically confirmed GBC and 16 cases of chronic cholecystitis (CC). The female to male ratio in the GBC and CC groups were 3.44:1 and 2.2:1, respectively. The GBC patients exhibited well to poorly differentiated tumor. In the CC group, all patients showed cholecystitis with no evidence of dysplasia or malignancy. The majority of GBC and CC patients reported pain. Using 1H NMR spectroscopy, we observed 4-folds increase in the level of choline containing phospholipids (CCPLs) in the gallbladder of GBC patients as compared to CC patients. Other lipid metabolites such as cholesterol ester, C18-cholesterol and saturated fatty acids were insignificantly changed between GBC and CC patients. Moreover, the level of CCPLs in the GBC patients with BMI <25 kg/m2 was significantly higher as compared to CC patients. Further, a significant increase in the CCPLs level was observed in GBC female patients in comparison to CC patients. From the computational analyses, we observed that the genes involved in the biosynthesis of phosphatidylcholine (PtdCho) indirectly interact with the RELA, which encodes the NF-κB p65 subunit. The genes involved in the PtdCho biosynthesis were also correlated with the overall and disease-free survival of cholangiocarcinoma patients. The study opens new window for exploring the diagnostic and therapeutic potential of CCPLs in GBC patients.


Inhibition of the intestinal transport of uracil by hexoses and amino acids.
Various hexoses and amino acids were tested as potential inhibitors of the active mucosal to serosal transport of uracil across the everted rat jejunum. Uracil transport displayed Michaelis-Menten type kinetics with a Vmax of 10.4 +/- 0.2 mumol X g-1 X h-1 and an apparent Km of 0.047 +/- 0.002 mM (means +/- S.D.). Scilliroside, an inhibitor of the basolateral (Na+ + K+)-ATPase, dose-dependently inhibited the transport of uracil consistent with the Na+ dependency of uracil transport. Thymine was a full competitive inhibitor (Ki = 0.021 +/- 0.002 mM) of uracil transport. All actively transported substances tested including L-phenylalanine, L-leucine, D-galactose, D-glucose, and 3-O-methylglucose inhibited the transport of uracil. In contrast, L-glucose and fructose, substances which are not actively transported, were without effect on uracil transport. Further studies with D-galactose indicated that it acts as a partial noncompetitive inhibitor (Ki = 6.0 +/- 1.4 mM) of uracil transport. This Ki is in good agreement with the apparent Kt (5.8 +/- 1.1 mM) for D-galactose transport. Phlorizin (0.1 mM), an inhibitor of galactose transport, blocked the inhibitory effect of galactose on uracil transport. In the ileum D-galactose had no effect on uracil transport but thymine caused the same degree of inhibition as in the jejunum. The results demonstrate that heterologous inhibition is a more general phenomenon than had previously been realized.


Flexible sigmoidoscopy: an important screening option for average-risk individuals.
Colorectal cancer screening techniques should be effective, acceptable to patients, affordable, widely available, and safe. For average-risk adults aged more than 50 years who do not have significant colorectal symptoms, significant family history, or significant predisposing conditions, flexible sigmoidoscopy is an important option for reducing the risk for colorectal cancer, meeting all criteria for an effective and feasible screening modality. This article discusses evidence supporting flexible sigmoidoscopy, practical issues in implementation, and current controversies.


Functional Organ Replacement, The New Technology of Tissue Engineering.
Functional failure of one vital organ results in death. The surgical implantation of tissue with the capacity to replace lost organ function, from one individual into another, is termed transplantation. In Boston, in 1954, Joseph E Murray performed the first successful human organ transplant, that of a kidney from an identical twin into his brother.


Eustachian valve myxoma: a rare cause of Budd-Chiari syndrome.
Budd-Chiari syndrome caused by right atrial myxomas are extremely rare. We report the case of a patient who presented with chronic liver disease who upon consequent investigation was found to have a mass occupying the right atrium and ventricle consistent with cardiac tumour. Intraoperatively, a giant mass was removed from the right atrium with the tumour stalk originating from the Eustachian valve. Histologic findings were consistent with myxoma.


Effect of patient completed agenda forms and doctors' education about the agenda on the outcome of consultations: randomised controlled trial.
To assess the effect of patient completed agenda forms for the consultation and doctors' education on identifying patients' agendas on the outcome of consultations. Randomised controlled trial. General practices in Leicestershire and Nottinghamshire, United Kingdom. 46 general practitioners and 976 patients. Education for general practitioners, with an embedded clustered randomised controlled trial of a patient agenda form. Number of problems identified, time required to manage each problem, duration of consultations, number of problems raised after the doctor considered the consultation finished ("by the way" questions), and patient satisfaction. Data were available from 45 doctors (98%) and 857 patients (88%). The number of problems identified in each consultation increased by 0.2 (95% confidence interval 0.1 to 0.4) with the agenda form, by 0.3 (0.1 to 0.6) with education, and by 0.5 (0.3 to 0.7) with both interventions. The time required to manage each problem was not affected. The duration of consultations with the agenda form was increased by 0.9 minutes (0.3 to 1.5 minutes) and with the combined intervention by 1.9 minutes (1.0 to 2.8 minutes). Patient satisfaction with the depth of the doctor-patient relationship was increased with the agenda form. The occurrence of "by the way" presentations did not change. A patient completed agenda form before the consultation or general practitioner education about the agenda form, or both, enabled the identification of more problems in consultations even though consultations were longer.


Prospective Multicenter Assessment of a New Intraprocedural Automated System for Localizing Idiopathic Ventricular Arrhythmia Origins.
The objective of this study was to present a new system, the Automatic Arrhythmia Origin Localization (AAOL) system, which used incomplete electroanatomic mapping (EAM) for localization of idiopathic ventricular arrhythmia (IVA) origin on the patient-specific geometry of left ventricular, right ventricular, and neighboring vessels. The study assessed the accuracy of the system in localizing IVA source sites on cardiac structures where pace mapping is challenging. An intraprocedural automated site of origin localization system was previously developed to identify the origin of early left ventricular activation by using 12-lead electrocardiograms (ECGs). However, it has limitations, as it could not identify the site of origin in the right ventricle and relied on acquiring a complete EAM. Twenty patients undergoing IVA catheter ablation had a 12-lead ECG recorded during clinical arrhythmia and during pacing at various locations identified on EAM geometries. The new system combined 3-lead (III, V2, and V6) 120-ms QRS integrals and patient-specific EAM geometry with pace mapping to predict the site of earliest ventricular activation. The predicted site was projected onto EAM geometry. Twenty-three IVA origin sites were clinically identified by activation mapping and/or pace mapping (8, right ventricle; 15, left ventricle, including 8 from the posteromedial papillary muscle, 2 from the aortic root, and 1 from the distal coronary sinus). The new system achieved a mean localization accuracy of 3.6 mm for the 23 mapped IVAs. The new intraprocedural AAOL system achieved accurate localization of IVA origin in ventricles and neighboring vessels, which could facilitate ablation procedures for patients with IVAs.


Interphase cytogenetics in pathology: principles, methods, and applications of fluorescence in situ hybridization (FISH).
Characteristic chromosome aberrations have been identified in various tumors. Fluorescence in situ hybridization (FISH) using specific probes that are generated by vector cloning or in vitro amplification and labeled with fluorescent dyes allow for the detection of these genetic changes in interphase cells. This technique, that is also referred to as "interphase cytogenetics", can be performed in cytological preparations as well as in sections of routinely formaldehyde-fixed and paraffin-embedded tissue. In cancer research and diagnostics, interphase cytogenetics by FISH is used to detect numerical chromosome changes and structural aberrations, e.g., translocations, deletions, or amplifications. In this technical overview, we explain the principles of the FISH method and provide protocols for FISH in cytological preparations and paraffin sections. Moreover, possible applications of FISH are discussed.


Maternal Apical Periodontitis Increases Insulin Resistance and Modulates the Antioxidant Defense System in the Gastrocnemius Muscle of Adult Offspring.
Maternal apical periodontitis (AP) is associated with insulin resistance (IR) in adult offspring. Oxidative stress has been linked to IR. This study investigated insulin sensitivity (IS) and oxidative stress in the gastrocnemius muscle (GM) of adult offspring of rats with AP. Fifteen female Wistar rats were distributed into a control group, a group with 1 tooth with AP, and a group with 4 teeth with AP. Thirty days after AP induction, female rats were mated with healthy male rats. When male offspring reached 75 days of age, glycemia, insulinemia, and IS were determined. In the GM, the oxidative damage products (thiobarbituric acid reactive substances and carbonyl protein) and activities of enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) and nonenzymatic (glutathione and total antioxidant capacity) antioxidants were quantified. Analysis of variance was performed followed by the Tukey post hoc test (P < .05). Maternal AP was associated with decreased IS and changes in antioxidant activities (reduced superoxide dismutase and increased catalase, glutathione peroxidase, and glutathione) and decreased thiobarbituric acid reactive substance concentration in the GM of their adult offspring. However, maternal AP does not appear to affect glycemia, carbonyl protein concentration, and the nonenzymatic total antioxidant capacity in the GM of this offspring. Maternal AP modulates the antioxidant defense system in the GM of their adult offspring, attenuating lipid peroxidation in this tissue. This reflects part of an adaptive response of the offspring to the stimulation of the maternal chronic oral inflammatory process in which the organism acts by decreasing oxidative tissue damage in the postnatal stage. The present study improves knowledge about the impact of maternal oral inflammation on healthy offspring.


Apatinib combined with Keytruda treatment induces apoptosis of gastric carcinoma cells through CES4/miR-616-5p/DUSP2 axis.
Gastric carcinoma (GC) is a highly malignant and heterogeneous tumour. Long non-coding RNA CES4 is down-regulated in GC. However, whether CES4 can participate in GC remains unclear; we have carried out research on this topic. GC cells (HGC-27 and MKN-7) were treated with anti-tumour drugs: apatinib combined with Keytruda. Cell viability and apoptosis were detected by CCK-8 assay and flow cytometry. Gene and protein expression were examined by quantitative real-time PCR and western blot. Luciferase reporter assay was performed to verify the relationship among CES4, miR-616-5p and dual-specificity phosphatase-2 (DUSP2). CES4 was highly expressed in the apatinib combined with Keytruda-treated HGC-27 and MKN-7 cells. Apatinib combined with Keytruda treatment repressed cell viability and promoted apoptosis of HGC-27 and MKN-7 cells, which was abrogated by CES4 knockdown. Furthermore, CES4 promoted DUSP2 expression by sponging miR-616-5p in HGC-27 and MKN-7 cells. CES4 knockdown promoted cell viability and inhibited apoptosis of drug-treated HGC-27 and MKN-7 cells by regulating miR-616-5p/DUSP2 axis. In conclusion, these data demonstrate that apatinib combined with Keytruda treatment induces apoptosis of GC cells through CES4/miR-616-5p/DUSP2 axis. Thus, this work provides the experimental basis for the combination of apatinib and Keytruda as a treatment for GC.


Scripts of Sexual Desire and Danger in US and Dutch Teen Girl Magazines: A Cross-National Content Analysis.
The aim of this comparative quantitative content analysis was to investigate how US and Dutch teen girl magazines cover sexual desire (i.e., sexual wanting, and pleasure) and sexual danger (i.e., sexual risk, and negative physical/health consequences of sex). Relying on the sexual scripts framework and Hofstede's cultural dimension of masculinity/femininity, we examined (a) how the coverage varied for boys and girls, (b) how it differed between the United States and the Netherlands, and (c) how gender differences varied by country. The sample comprised 627 sex-related feature stories from all 2006-2008 issues of three US (i.e., Seventeen, CosmoGirl! United States edition, and Teen) and three Dutch teen girl magazines (i.e., Fancy, CosmoGirl! Netherlands edition, and Girlz!). Overall, sexual wanting occurred more frequently in the US magazines than in the Dutch magazines. In the US coverage, boys' sexual wanting received more attention than girls' sexual wanting, whereas in the Dutch coverage sexual wanting was depicted equally often for boys and girls. The depiction of sexual pleasure did not vary by gender in either country, but was generally more visible in the Dutch magazines than in the US magazines. Sexual risks and the negative consequences of sex were associated with girls more than with boys, and were primarily depicted in the US magazines rather than in the Dutch magazines.


Perioperative management of the thyrotoxic patients: A systematic review.
Thyrotoxicosis is a clinical syndrome produced by a multitude of disorders. Thyrotoxicosis is a serious medical condition that, if left untreated, can lead to a fatal illness. This review of recent evidences give additional input for perioperative management of thyrotoxic patients. The literatures were found with Boolean operators in the form of thyrotoxicosis AND anesthesia, antithyroid medications AND perioperative optimization AND beta blockers OR calcium channel blockers in electronic data base sources such as the Cochrane library, PubMed, and Google scholar. This review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. and recommendations: Before surgery and anesthesia, manifestation of thyrotoxicosis including palpitation, irritability etc should be ruled out.