Phenotypic differences in virulence and immune response in closely related clinical isolates of influenza A 2009 H1N1 pandemic viruses in mice.
To capture the possible genotypic and phenotypic differences of the 2009 influenza A virus H1N1 pandemic (H1N1pdm) strains circulating in adult hospitalized patients, we isolated and sequenced nine H1N1pdm viruses from patients hospitalized during 2009-2010 with severe influenza pneumonia in Kentucky. Each viral isolate was characterized in mice along with two additional H1N1 pandemic strains and one seasonal strain to assess replication and virulence. All isolates showed similar levels of replication in nasal turbinates and lung, but varied in their ability to cause morbidity. Further differences were identified in cytokine and chemokine responses. IL-6 and KC were expressed early in mice infected with strains associated with higher virulence. Strains that showed lower pathogenicity in mice had greater IFNγ, MIG, and IL-10 responses. A principal component analysis (PCA) of the cytokine and chemokine profiles revealed 4 immune response phenotypes that correlated with the severity of disease. A/KY/180/10, which showed the greatest virulence with a rapid onset of disease progression, was compared in additional studies with A/KY/136/09, which showed low virulence in mice. Analyses comparing a low (KY/136) versus a high (KY/180) virulent isolate showed a significant difference in the kinetics of infection within the lower respiratory tract and immune responses. Notably by 4 DPI, virus titers within the lung, bronchoalveolar lavage fluid (BALf), and cells within the BAL (BALc) revealed that the KY/136 replicated in BALc, while KY/180 replication persisted in lungs and BALc. In summary, our studies suggest four phenotypic groups based on immune responses that result in different virulence outcomes in H1N1pdm isolates with a high degree of genetic similarity. In vitro studies with two of these isolates suggested that the more virulent isolate, KY/180, replicates productively in macrophages and this may be a key determinant in tipping the response toward a more severe disease progression.


Stoichiometric and Oxygen-Deficient VO2 as Versatile Hole Injection Electrode for Organic Semiconductors.
Using photoemission spectroscopy, we show that the surface electronic structure of VO2 is determined by the temperature-dependent metal-insulator phase transition and the density of oxygen vacancies, which depends on the temperature and ultrahigh vacuum (UHV) conditions. The atomically clean and stoichiometric VO2 surface is insulating at room temperature and features an ultrahigh work function of up to 6.7 eV. Heating in UHV just above the phase transition temperature induces the expected metallic phase, which goes in hand with the formation of oxygen defects (up to 6% in this study), but a high work function >6 eV is maintained. To demonstrate the suitability of VO2 as hole injection contact for organic semiconductors, we investigated the energy-level alignment with the prototypical organic hole transport material N, N'-di(1-naphthyl)- N, N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine (NPB). Evidence for strong Fermi-level pinning and the associated energy-level bending in NPB is found, rendering an Ohmic contact for holes.


Emphysematous phenotype is an independent predictor for frequent exacerbation of COPD.
Frequent exacerbation is an important phenotype in chronic obstructive pulmonary disease (COPD), while emphysema is associated with many comorbidities and lung function decline. To investigate unique features of frequent exacerbators and test the hypothesis that emphysematous phenotype is associated with frequent exacerbations of COPD. A total of 380 COPD patients were recruited from 16 hospitals in Korea from June 2005 to April 2012 for analysis. We searched for independent predictors of frequent exacerbators in comparison with non-exacerbators. As the severity of emphysema increased, forced expiratory volume in 1 s (FEV₁), and FEV₁/FVC (forced volume capacity) worsened; hyperinflationary features characterised by higher total lung capacity (TLC) were observed (P < 0.05). Frequent exacerbators had lower body mass index (BMI), higher St George's Respiratory Questionnaire (SGRQ) scores, higher residual volume (RV)/TLC, more severe airflow limitation (lower FEV₁ and FEV₁/FVC), lower carbon monoxide diffusion capacity, lower serum protein levels and a higher emphysema index than non-exacerbators (P < 0.05). In multivariate analysis, frequent exacerbators were independently associated with a higher emphysema index, lower serum protein levels and higher RV/TLC (P < 0.05). Our data show that the severity of emphysema, severe static hyperinflation and serum lower protein levels are independent predictors of frequent exacerbations in COPD patients.


Bis[2-meth-oxy-6-(phenyl-iminiomethyl)phenolate-κO,O']bis-(thio-cyanato-κN)manganese(II).
The Mn(II) atom in the title complex, [Mn(NCS)(2)(C(14)H(13)NO(2))(2)], lies on a center of inversion in a MnO(4)N(2) octa-hedral geometry. The Schiff base is present in its zwitterionic form and is O,O'-chelated to the metal atom. The imino N atom is protonated and is involved in an intra-molecular hydrogen bond with the phenolate O atom.


Role of TOP2A and CDC6 in liver cancer.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality worldwide, which is characterized by aggressive growth and metastasis. However, the relationship between TOP2A and CDC6 and HCC remains unclear. GSE121248 and GSE101728 profiles for liver cancer were downloaded from the gene expression omnibus database generated using GPL21047and GPL570. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis was performed. The construction and analysis of protein-protein interaction network, functional enrichment analysis, gene set enrichment analysis. Gene expression heat map was drawn and survival analysis was performed. Comparative toxicogenomics database analysis were performed to find the disease most related to the core gene. TargetScan was used to screen miRNAs regulating central DEGs. 885 DEGs were identified. According to gene ontology analysis, they were mainly enriched in organic acid metabolism process, metabolic pathway, p53 signal pathway and PPAR signal pathway. The enrichment items are similar to the GOKEGG enrichment items of differentially expressed genes, mainly in the process of organic acid metabolism, p53 signal pathway and PPAR signal pathway. In the enrichment project of metascape, gene ontology has PIDPLK1 pathway, mitotic cell cycle, tumor retinoblastoma gene. The construction and analysis of protein-protein interaction network obtained 10 core genes (TOP2A, CDK1, ASPM, RACGAP1, ZWINT, CDC6, AURKA, NCAPG, BUB1B, CCNB1), and found that these core genes were highly expressed in tumor tissues and low in normal tissues. Comparative toxicogenomics database analysis showed that 10 genes (TOP2A, CDK1, ASPM, RACGAP1, ZWINT, CDC6, AURKA, NCAPG, BUB1B, CCNB1) were related to necrosis, inflammation, HCC, liver cirrhosis, and adenoid cystic carcinoma. TOP2A and CDC6 are highly expressed in liver cancer, which may become molecular targets for early diagnosis and precise treatment.


A role for stefin B (cystatin B) in inflammation and endotoxemia.
Stefin B (cystatin B) is an endogenous cysteine cathepsin inhibitor, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht-Lundborg disease (EPM1). In this study we demonstrated that stefin B-deficient (StB KO) mice were significantly more sensitive to the lethal LPS-induced sepsis and secreted higher amounts of pro-inflammatory cytokines IL-1β and IL-18 in the serum. We further showed that increased caspase-11 gene expression and better pro-inflammatory caspase-1 and -11 activation determined in StB KO bone marrow-derived macrophages resulted in enhanced IL-1β processing. Pretreatment of macrophages with the cathepsin inhibitor E-64d did not affect secretion of IL-1β, suggesting that the increased cathepsin activity determined in StB KO bone marrow-derived macrophages is not essential for inflammasome activation. Upon LPS stimulation, stefin B was targeted into the mitochondria, and the lack of stefin B resulted in the increased destabilization of mitochondrial membrane potential and mitochondrial superoxide generation. Collectively, our study demonstrates that the LPS-induced sepsis in StB KO mice is dependent on caspase-11 and mitochondrial reactive oxygen species but is not associated with the lysosomal destabilization and increased cathepsin activity in the cytosol.


Nitric oxide synthase inhibitors modulate lipopolysaccharide-induced hepatocyte injury: dissociation between in vivo and in vitro effects.
Effects of endotoxemia-induced NO production on rat liver and hepatocytes in culture were investigated. Rats were treated intraperitoneally with saline, lipopolysaccharide (LPS, 10 mg/kg), L-nitroarginine methyl ester (L-NAME)+LPS, aminoguanidine (AG)+LPS, FK 506+LPS, S-nitroso-N-acetyl penicillamine (SNAP)+L-NAME+LPS and SNAP+FK 506+LPS. Mortality, hepatocyte viability and liver function test were estimated. Liver morphology was observed by light and electron microscopy. Hepatocyte cultures were treated with LPS, cytokine mixture (CM) with or without FK 506, L-NAME or AG. Hepatocyte function and inducible form of NOS (iNOS) expression were evaluated. Twenty-four hours after treatments with saline, LPS, L-NAME+LPS, AG+LPS, FK 506+LPS, SNAP+L-NAME+LPS and SNAP+FK 506+LPS, rat mortalities were 0%, 10%, 48%, 8%, 20%, 38% and 0%, and hepatocyte viabilities were 93+/-3%, 80+/-3%, 52+/-8%, 88+/-1%, 70+/-3%, 80+/-4% and 82+/-3%, respectively. AG+LPS or L-NAME+LPS administration was followed by excessive vacuolization of hepatocytes with lesions in the intermediary lobule zone characterized by features of secondary necrosis as a continuation of apoptotic processes. SNAP+L-NAME+LPS resulted in a well-preserved structure of central vein lobules with sparse signs of apoptosis. Treatment with LPS or CM increased iNOS expression in hepatocyte culture, which was inhibited by L-NAME, FK 506 or AG. AG reduced LPS-induced rise in alanine aminotransferase leakage. LPS-induced NO exerts cytoprotective effects in vivo, while LPS-induced NO in vitro appears to be toxic. Based on the data of this report, one cannot use in vitro results to predict in vivo responses to LPS-induced NO production. The pharmacological modulation of iNOS expression or NO production in vivo or in vitro, therefore, by the development of specific NO donors or inhibitors is promising for improvement of hepatocyte functions under the two experimental conditions, respectively.


Characteristics of the series resonant-frequency shift of a quartz crystal microbalance in electrolyte solutions.
We report the novel characteristics of the series resonant-frequency shift, DeltaF, of a one-face sealed quartz crystal microbalance (QCM) in solutions of monovalent electrolytes and divalent electrolytes. In the present study, we used NaCl, KCl, LiCl, NaNO3 and CH3COONa as monovalent electrolytes, and MgCl2, CaCl2, MgSO4 and Na2SO4 as divalent electrolytes. These experiments reveal that, in all the solutions, the DeltaF values vary linearly with an increase in the square root of the density-viscosity product of the solutions, and the immersion angle dependence of DeltaF appears. Moreover, we have found that the intercept values of DeltaF are dependent only on the cation species, and that the slope values of DeltaF with the viscosity and density of the solutions are related only to the valence of ions. We also suggest that the DeltaF values are independent of anion species, conductivity and permittivity of the solutions.


Oncogenic Fusions in Gliomas: An Institutional Experience.
Gliomas are primary malignancies of the central nervous system (CNS). High-grade gliomas are associated with poor prognosis and modest survival rates despite intensive multimodal treatment strategies. Targeting gene fusions is an emerging therapeutic approach for gliomas that allows application of personalized medicine principles. The aim of this study was to identify detectable fusion oncogenes that could serve as predictors of currently available or newly developed targeted therapeutics in cross-sectional samples from glioma patients using next-generation sequencing (NGS). A total of 637 patients with glial and glioneuronal tumours of the CNS who underwent tumour resection between 2017 and 2020 were enrolled. Detection of fusion transcripts in FFPE tumour tissue was performed by a TruSight Tumour 170 assay and two FusionPlex kits, Solid Tumour and Comprehensive Thyroid and Lung. Oncogene fusions were identified in 33 patients. The most common fusion was the KIAA1549-BRAF fusion, detected in 13 patients, followed by FGFR fusions (FGFR1-TACC1, FGFR2-CTNNA3, FGFR3-TACC3, FGFR3-CKAP5, FGFR3-AMBRA1), identified in 10 patients. Other oncogene fusions were also infrequently diagnosed, including MET fusions (SRPK2-MET and PTPRZ1-MET) in 2 patients, C11orf95-RELA fusions in 2 patients, EGFR-SEPT14 fusion in 2 patients, and individual cases of SRGAP3-BRAF, RAF1-TRIM2, EWSR1-PALGL1 and TERT-ALK fusions. The introduction of NGS techniques provides additional information about tumour molecular alterations that can aid the multimodal management of glioma patients. Patients with gliomas positive for particular targetable gene fusions may benefit from experimental therapeutics, enhancing their quality of life and prolonging survival rates.


Cross-sectional growth and decline of human stature and brain weight in 19th-century Germany.
A new six-parameter two-phase nonlinear growth and decline model is fitted to cross-sectional data on human stature and brain weight obtained from autopsies in Germany at the end of the 19th century. Brain growth may have ended at a total age of approximately seven years, much younger than estimated in previous studies. Earlier statistical approaches may not have pinpointed the beginning of the plateau. The decline of stature was slight and is weakly significant. The decline of brain weight was stronger but occurred mostly after sixty years of age. Secular increase may have been unimportant from 1820 to 1900.


Mucoadhesive bilayer tablets of propranolol hydrochloride.
The purpose of this research was to study mucoadhesive bilayer buccal tablets of propranolol hydrochloride using the bioadhesive polymers sodium alginate (Na-alginate) and Carbopol 934P (CP) along with ethyl cellulose as an impermeable backing layer. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, mucoadhesive strength, swelling index, in vitro drug release, ex vivo drug permeation, ex vivo mucoadhesion, and in vivo pharmacodynamics in rabbits. Tablets containing Na-alginate and CP in the ratio of 5:1 (F2) had the maximum percentage of in vitro drug release without disintegration in 12 hours. The swelling index was proportional to Na-alginate content and inversely proportional to CP content. The surface pH of all tablets was found to be satisfactory (7.0 +/- 1.5), close to neutral pH; hence, buccal cavity irritation should not occur with these tablets. The mechanism of drug release was found to be non-Fickian diffusion and followed zero-order kinetics. The formulation F4 was optimized based on good bioadhesive strength (28.9 +/- 0.99 g) and sustained in vitro drug permeation (68.65% +/- 3.69% for 12 hours). The behavior of formulation F4 was examined in human saliva, and both the drug and the buccal tablet were found to be stable. The formulation F4 was applied to rabbit oral mucosa for in vivo studies. The formulation inhibited isoprenaline-induced tachycardia. The studies conducted in rabbits confirmed the sustained release as compared with intravenous administration.


Isolation of coated vesicles, plain synaptic vesicles, and flocculent material from a crude synaptosome fraction of guinea pig whole brain.
Two vesicular fractions and one nonvesicular fraction were prepared from crude synaptosomes by differential centrifugation and salting out with ammonium sulfate. Fraction 1 contained a mixture of coated vesicles, material thought to be derived from breakdown of the coats (shell fragments), and plain synaptic vesicles. Fraction 2 contained a mixture of plain synaptic vesicles and flocculent material. Fraction 3 contained flocculent material only. Fractions 1 and 3 were partially purified by passage through a Sephadex column. Fraction 3 contained no shell fragments but contained finer flocculent material which, it is suggested, is composed of unit particles either occurring singly or linked together into chainlike or amorphous aggregates. Each unit particle appears to have four subunits and is here referred to as a tetrasome. Tetrasomes sometimes appear to be attached to the surfaces of the plain synaptic vesicles. Also, it is possible that aggregates of tetrasomes form part of the structure of the presynaptic dense projections.


Exercise tolerance and selected motor skills in young females with idiopathic scoliosis treated with different physiotherapeutic methods.
Scoliosis is a disorder that leads to dysfunction of a number of systems in the body, especially in young females. Physical capacity is one of the most important elements of good health as well as ofbiological development. Adolescence is a time when physical capacity develops intensively, and the condition of the respiratory system is one of many factors that have an impact on the level of physical capacity. This paper aims to evaluate a short-term application of two methods of physiotherapy and their influence on the level of exercise tolerance in young females suffering from idiopathic scoliosis. The study involved a group of 49 young females aged 14-15 years diagnosed with (2040°) thoracic and lumbar scoliosis who were in-patients at the rehabilitation ward of the Regional Paediatric Rehabilitation Hospital in Jastrzębie Zdrój. The group was divided into two subgroups depending on the method of rehabilitation employed: the first subgroup received asymmetric breathing exercise therapy by Dobosiewicz and the second subgroup practised symmetric remedial exercises. Cobb's angle, the degree of skeletal maturity, i.e. the Risser sign and the degree trunk rotation of the apex of the curvature by means of Raimondi's coefficient were determined once in an x-ray image. Basic somatic features, maximal voluntary ventilation (MVV parameter), selected motor skills and exercise tolerance were assessed on two occasions (before beginning and after completion of the rehabilitation treatment). 1. Young females suffering from (20-40°) thoracic and lumbar scoliosis demonstrate respiratory dysfunction, as shown by decreased maximal voluntary ventilation (MVV) in the two subgroups in the present study. Exercises according to Dobosiewicz's method brought about a significantly higher degree of improvement in this parameter. 2. The physiotherapeutic regimen administered to the young girls with scoliosis significantly improved their strength motor skills and exercise tolerance. A significantly higher improvement was observed in the subgroup treated using Dobosiewicz's method, in particular, in the strength of abdominal muscles, which play an important role in both respiratory function and body posture maintenance.


Urbanization and economic development policy in Korea.
"This paper has firstly discussed the development strategy and urbanization in [the Republic of] Korea for the period 1960-1980. [This is] followed with an intensive review of the past and recent population redistribution policy of Korea. Finally the authors make some general suggestions which are characterized as an expansion of opportunities and services in the underprivileged areas." (summary in CHI)


Perspectives of Youth in Foster Care on Essential Ingredients for Promoting Self-determination and Successful Transition to Adult Life: My Life Model.
Research clearly documents the serious challenges and poor outcomes experienced by many young people exiting foster care, as well as compounded disparities for the high percentage of youth in care who are identified with disabilities and/or mental health challenges. However, very little research has been conducted to specify or validate effective models for improving the transition trajectories of youth exiting care. Evidence suggests the My Life self-determination enhancement model offers a promising approach for supporting youths' self-determined and positive transition to adulthood. The model includes youth-directed, experientially oriented coaching in the application of self-determination skills to achieve youth-identified transition goals, coupled with peer mentoring workshops that provide opportunities for learning, networking and fun. This in depth qualitative study of 10 youth who completed the My Life intervention focused on investigating coaching and mentoring elements and processes that youth participants identify as most important to their success, with the intention of informing the further development of youth-directed approaches to supporting young people who are transitioning to adulthood. Themes emerged around the centrality of youth self-direction, important processes in the coaching relationship, the essential value of experiential activities and self-determination skill development, and peer mentoring experiences that youth identified as fostering their success. Implications are discussed for research and practice in supporting youth exiting foster care.


Recruiting and Retaining Individuals with Serious Mental Illness and Diabetes in Clinical Research: Lessons Learned from a Randomized, Controlled Trial.
Recruitment and retention of individuals with serious mental illness (SMI) and comorbid diabetes mellitus (DM) in research studies can be challenging with major impediments being difficulties reaching participants via telephone contact, logistic difficulties due to lack of transportation, ongoing psychiatric symptoms, and significant medical complications. Research staff directly involved in recruitment and retention processes of this study reviewed their experiences. The largest barriers at the macro, mediator, and micro levels identified in this study were inclement weather, transportation difficulties, and intermittent and inaccessible telephone contact. Barrier work-around practices included using the health system's EHR to obtain current phone numbers, providing transportation assistance (bus passes or parking reimbursement), and flexible scheduling of appointments. Suggestions are intended to assist in planning for recruitment and retention strategies.


Enalapril reduces collagen type IV synthesis and expansion of the interstitium in the obstructed rat kidney.
Chronic unilateral ureteral obstruction (UUO) results in interstitial fibrosis of the affected kidney. In this study we determined that enalapril ameliorates the increased production of extracellular matrix (ECM) protein in the tubulointerstitium during UUO. The relative volume (Vv) of the tubulointerstitium measured by a point-counting method increased significantly at three or five days of UUO as compared to the contralateral kidney. Enalapril significantly blunted this increase at either three or five days. Immunofluorescence studies revealed that collagen type IV increased remarkably in both the tubular basement membrane (TBM) and the interstitial space at three or five days of UUO. Glomeruli did not show any change. Collagen types I and III were faintly stained in the control kidneys while they were obviously increased in the interstitial space of the obstructed kidney. We examined the expression of collagen type IV (COL IV) because this basement membrane matrix protein appeared to be a major ECM protein deposited in the tubulointerstitium of the obstructed kidney. Semiquantitative analysis of COL IV by immunofluorescence microscopy revealed that enalapril reduced slightly (21%) but significantly (P < 0.01) the deposition of COL IV in the obstructed kidney. Measurement of cyanogen bromide peptides from the obstructed kidney by Western blotting showed an increase of COL IV. This increase was reduced slightly (20%) by enalapril. The level of COL IV mRNA measured by reverse transcription-PCR was very low or undetectable in the control and contralateral kidneys, while it was significantly increased in the obstructed kidney at three or five days of UUO. COL IV mRNA was abundant in glomeruli while it was almost undetectable in renal tubules in the control and contralateral kidneys. However, COL IV mRNA was increased in renal tubules but not in the glomeruli of the obstructed kidney. Enalapril treatment resulted in a 42% decrease (P < 0.01) in COL IV mRNA in the cortex and a remarkable decrease in the renal tubules of the obstructed kidney at five days. Enalapril treatment resulted in an 89% decrease in the number of infiltrating ED-1 positive monocytes/macrophages. These results indicate that enalapril treatment ameliorates the tubulointerstitial fibrosis of the affected kidney in UUO. This effect of enalapril on fibrosis may be due to the severe reduction in monocytes/macrophages capable of secreting the profibrotic factor TGF-beta 1.


A randomized controlled trial comparing the effectiveness of individual versus household treatment for Scabies in Lambaréné, Gabon.
It is unclear whether individual treatment of scabies is similarly effective compared to household treatment. This study compared these two treatment strategies with topical benzyl benzoate for treating scabies in Lambaréné, Gabon. Participants presenting with uncomplicated scabies were randomized into either the Individual Treatment group, where only the affected participants received treatment, or the Household Treatment group, where all family members were treated in parallel to the affected participants regardless of signs and symptoms. The primary endpoint was clinical cure after 28 days; the secondary endpoint was the proportion of affected household members per household after 28 days. After 28 days, from a total of 79 participants assessed, 67% (n = 53) were clinically cured; 59% (20/34) in the Individual Treatment group and 73% (33/45) in the Household Treatment group. Participants in the Household Treatment group had about twice the odds of being cured (odds ratio 1.9, 95% confidence interval: 0.8-4.9; p = 0.17). For the secondary outcome, an effect of similar size was observed. Our findings show that treating close contacts of persons affected by scabies may be beneficial to patients and contacts, however, the benefit was less pronounced than anticipated and further research is needed to definitively answer this question.


Familial and social support as protective factors against the development of dissociative identity disorder.
The incidence of dissociative identity disorder (DID) is strongly correlated with exposure to serious physical and sexual abuse. Although studies of more than 1,000 DID sufferers indicate that severe child abuse is a predisposing factor in 95% to 98% of cases (B. Braun, 1988), abuse alone is not, in fact, predictive of DID (B. Rind & P. Tromovitch, 1997). Disorganized/disoriented attachment style and the absence of social and familial support, in combination with abuse history, best predict DID (D. Howe, 2006; R. Kluft, 1984; K. Lyons-Ruth, L. Dutra, M. Schuder, & I. Bianchi, 2006). Individuals who are securely attached are less likely to develop serious psychopathology in the event of abuse and are more likely to build a strong extrafamilial system of support--also a protective factor against psychopathology (S. Asher & J. Parker, 1989; D. Howe, M. Brandon, D. Hinings, & G. Schofield, 1999; G. Ladd & B. Golter, 1988). Recognition of the significance of secure attachment and familial and social support as protective factors against the development of DID suggests social intervention as an important area of research to mitigate the psychological consequences of insecure attachment, social disconnection, and abuse.


[Transpalpebral Tetrapolar Reoophtalmography in the Assessment of Parameters of the Eye Blood Circulatory System].
Quantitative assessment of hemodynamic parameters is an important element of ophthalmic diagnostics especially in early detection of myopia, glaucoma, diabetic retinopathy. The assessment of hemodynamic changes is essential in evaluating of the efficiency of treatment. Objective: Our aim was to determine the adequate of eye hemodynamics assessment using reoophtalmography in patients with various clinical refractions. A controlled study was carried out. All tests were performed using transpalpebral tetrapolar method. Signal registration lasted for 20 seconds in the supine position, and then the diagnostic parameters were calculated. We present the results of examination of 76 patients aged 5 to 22 years (average age 13.0 ± 1.1). 32 patients had low myopia (62 reoophtalmography records), 23 patients had moderate myopia (42 records) and 5 patients had high myopia (12 records). The control group was composed of 16 patients. The main differences were found in the rheographic index, which is equal to 58.1 ± 4.1 mOhm in the control group. It is significantly reducing with refraction increase, from 47.8 ± 3.2 mOhm in low myopia to 34.0 ± 2.5 mOhm in high myopia (p = 0.050). This is an evidence of blood supply deficiency in the myopic eyes. Rheographic index was shown to differ in different breathing phases, which agrees with the known physiological regularities. The proposed method is highly informative and sufficiently accurate what allows assessing the eye blood supply state objectively. It is easy to apply and requires no contact with the eye surface, which is especially important in pediatric practice.


Biochanin A enhances RORγ activity through STAT3-mediated recruitment of NCOA1.
Interleukin (IL)-17-producing T cells play important roles in autoimmunity, chronic inflammation and host protection against extracellular bacteria and fungi. The retinoic acid receptor-related orphan receptors (ROR) α and γ are key regulators of the IL-17-producing phenotype. We previously showed that the isoflavone biochanin A enhanced ROR-mediated transcriptional activity. Here, we investigated the possible mechanisms underlying this ROR activation. Biochanin A-treated murine thymoma EL4 and primary splenocytes demonstrated enhanced induction of IL-17. Biochanin A also induced tyrosine-phosphorylation of signal transducer and activator of transcription 3 (STAT3) in these cells. Stable knockdown of either RORγ or STAT3 in EL4 cells canceled biochanin A-induced upregulation of IL-17 expression. Importantly, biochanin A enhanced complex formation between RORγ and STAT3 or nuclear-receptor coactivator 1 (NCOA1). Furthermore, the biochanin A-induced RORγ-NCOA1 complex was disrupted by a dominant negative mutant of STAT3 or by the STAT3 specific inhibitor Stattic. These results suggest that biochanin A activates RORγ-dependent IL-17 transcription through the enhancement of STAT3 phosphorylation and STAT3-mediated recruitment of NCOA1 to RORγ.


Adenosine inhibits ENaC via cytochrome P-450 epoxygenase-dependent metabolites of arachidonic acid.
We used the patch-clamp technique to examine the effect of adenosine on epithelial sodium channel (ENaC) activity in rat cortical collecting duct (CCD). Application of adenosine inhibits ENaC activity, and the effect of adenosine was mimicked by cyclohexyladenosine (CHA), an A(1) adenosine-receptor agonist that reduced channel activity from 1.32 to 0.64. The inhibitory effect of CHA on ENaC was mimicked by cyclopentyladenosine (CPA), which reduced channel activity from 1.1 to 0.55. In contrast, application of CGS-21680, an A(2a) adenosine-receptor agonist, had no effect on ENaC and increased channel activity from 0.96 to 1.22. This suggests that the inhibitory effect of adenosine analogs resulted from stimulation of the A(1) adenosine receptor. Inhibition of PLC with U-73122 failed to abolish the effect of CHA on ENaC. In contrast, the inhibitory effect of CHA on ENaC was absent in the presence of the PLA(2) inhibitor arachidonyl trifluoromethyl ketone (AACOCF(3)). This suggests a role of arachidonic acid (AA) in mediating the effect of adenosine on ENaC. To determine the metabolic pathway of AA responsible for the effect of adenosine, we examined the effect of CHA in the presence of indomethacin or N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH). Inhibition of cytochrome P-450 (CYP) epoxygenase with MS-PPOH blocked the effect of CHA on ENaC. In contrast, CHA reduced ENaC activity in the presence of indomethacin. This suggests that CYP epoxygenase-dependent metabolites of AA mediate the effect of adenosine. Because 11,12-epoxyeicosatrienoic acid (11,12-EET) inhibits ENaC activity in the CCD (Wei Y, Lin DH, Kemp R, Yaddanapudi GSS, Nasjletti A, Falck JR, and Wang WH. J Gen Physiol 124: 719-727, 2004), we examined the role of 11,12-EET in mediating the effect of adenosine on ENaC. Addition of 11,12-EET inhibited ENaC channels in the CCD in which adenosine-induced inhibition was blocked by AACOCF3. We conclude that adenosine inhibits ENaC activity by stimulation of the A(1) adenosine receptor in the CCD and that the effect of adenosine is mediated by 11,12-EET.


Indirect monitoring of TORC1 signalling pathway reveals molecular diversity among different yeast strains.
Saccharomyces cerevisiae is the main species responsible for the alcoholic fermentation in wine production. One of the main problems in this process is the deficiency of nitrogen sources in the grape must, which can lead to stuck or sluggish fermentations. Currently, yeast nitrogen consumption and metabolism are under active inquiry, with emphasis on the study of the TORC1 signalling pathway, given its central role responding to nitrogen availability and influencing growth and cell metabolism. However, the mechanism by which different nitrogen sources activates TORC1 is not completely understood. Existing methods to evaluate TORC1 activation by nitrogen sources are time-consuming, making difficult the analyses of large numbers of strains. In this work, a new indirect method for monitoring TORC1 pathway was developed on the basis of the luciferase reporter gene controlled by the promoter region of RPL26A gene, a gene known to be expressed upon TORC1 activation. The method was tested in strains representative of the clean lineages described so far in S. cerevisiae. The activation of the TORC1 pathway by a proline-to-glutamine upshift was indirectly evaluated using our system and the traditional direct methods based on immunoblot (Sch9 and Rps6 phosphorylation). Regardless of the different molecular readouts obtained with both methodologies, the general results showed a wide phenotypic variation between the representative strains analysed. Altogether, this easy-to-use assay opens the possibility to study the molecular basis for the differential TORC1 pathway activation, allowing to interrogate a larger number of strains in the context of nitrogen metabolism phenotypic differences.


The Oral Microbiome in the Elderly With Dental Caries and Health.
With the aging of the population, dental caries in the elderly has received increasing attention. A comprehensive study of the oral microbiome is required to understand its polymicrobial etiology. The results of previous studies are limited and remain controversial. In this study, subjects 60 years and older with and without caries were recruited. Unstimulated saliva and dental plaque were collected from each subject and the bacterial 16S rDNA was amplified using PCR and sequenced by Illumina MiSeq high-throughput sequencing. A total of 92 samples were collected from 24 caries patients and 22 healthy controls. Sequences clustered into 147,531 OTUs, representing 16 phyla, 29 classes, 49 orders, 79 families, 149 genera, and 305 species. All predominant phyla, including Proteobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Actinobacteria, and Saccharibacteria, were largely consistent in different groups, but different relative abundances could be observed. The core microbiome was defined with 246 shared species among groups, which occupied 80.7% of all the species detected. Alpha diversity showed no significant differences in bacterial richness or diversity between caries patients and healthy controls, but distinction existed between samples collected from dental plaque and saliva. Beta diversity analysis was performed by PCoA and hierarchical clustering analysis, showing similar results that microorganisms vary between the two niches. The biomarkers of different groups were defined by LEfSe analysis to identify potential caries-related and health-related bacteria. The co-occurrence analysis of the predominant genera revealed significant interactions among oral microbiota and exhibited more complex and aggregated bacterial correlations in caries-free groups. Finally, the functional prediction of the microbiota present in oral samples was performed by PICRUSt, indicating vigorous microbial metabolism in the oral bacterial community. Our study provides thorough knowledge of the microbiological etiology of elderly individuals with caries and is expected to provide novel methods for its prevention and treatment.


Perirhinal cortex lesions impair tests of object recognition memory but spare novelty detection.
The present study examined why perirhinal cortex lesions in rats impair the spontaneous ability to select novel objects in preference to familiar objects, when both classes of object are presented simultaneously. The study began by repeating this standard finding, using a test of delayed object recognition memory. As expected, the perirhinal cortex lesions reduced the difference in exploration times for novel vs. familiar stimuli. In contrast, the same rats with perirhinal cortex lesions appeared to perform normally when the preferential exploration of novel vs. familiar objects was tested sequentially, i.e. when each trial consisted of only novel or only familiar objects. In addition, there was no indication that the perirhinal cortex lesions reduced total levels of object exploration for novel objects, as would be predicted if the lesions caused novel stimuli to appear familiar. Together, the results show that, in the absence of perirhinal cortex tissue, rats still receive signals of object novelty, although they may fail to link that information to the appropriate object. Consequently, these rats are impaired in discriminating the source of object novelty signals, leading to deficits on simultaneous choice tests of recognition.


PHYLOGENY OF THE TRIBE CERATAPHIDINI (HOMOPTERA) AND THE EVOLUTION OF THE HORNED SOLDIER APHIDS.
The horned soldier aphids of the Cerataphidini, unlike most social insects that reside in nests, live on the open surface of plants. The lack of a nest and other obvious ecological correlates makes it unclear why secondary-host soldiers might have evolved. Here I present a molecular phylogenetic analysis of 32 species of the Cerataphidini, including 10 species from the genera Ceratovacuna and Pseudoregma that produce horned soldiers. The phylogeny suggests that horned soldiers evolved once and were lost once or twice. Most horned soldiers are a morphologically specialized caste and two species that have unspecialized soldiers are independently derived from species with specialized castes. The genus Ceratovacuna appears to have undergone a relatively rapid radiation. Mapping secondary-host plants and geographic ranges onto the phylogeny suggests that bamboos were the ancestral secondary-host plants and that the Asian tropics and subtropics were the ancestral geographic regions for the genera Astegopteryx, Ceratoglyphina, Ceratovacuna Chaitoregma, and Pseudoregma and possibly for the entire tribe. There is evidence for vicariant events that separate the tropical and subtropical lineages in all of the major lineages of the tribe and for dispersal of some lineages. Based on these results, I present hypotheses for the causes and consequences of horned-soldier evolution.


Antigen-induced bronchial anaphylaxis in actively sensitized guinea pigs. The effect of booster injection and cyclophosphamide treatment.
This investigation examines the effect of a booster dose and cyclophosphamide treatment in guinea pigs sensitized according to different sensitization regimens. The results show that guinea pigs sensitized with a high dose of ovalbumin (10 microgram) develop a transient bronchial reactivity. The administration of a booster dose to guinea pigs sensitized according to this regimen does not result in any secondary response. Cyclophosphamide 30 mg/kg given 2 days before the booster injection or the primary sensitization results in a marked increase in bronchial reactivity when challenged with ovalbumin. This increased bronchial reactivity is reflected in the IgE-like antibody titre examined by PCA. Guinea pigs primarily sensitized with a low dose of ovalbumin (0.5 microgram) show no bronchial reactivity when challenged with antigen. However, guinea pigs sensitized according to this regimen and given a booster dose show a marked secondary response when challenged 7 days after the booster injection. An examination of the antibody classes by PCA show that the booster injection causes an increase in the IgG1--and also in the IgE-like antibody production.


[FREE CONSUMPTION OF GLUCOSE SOLUTION BY RATS AS A CRITERION FOR EVALUATION ITS ABSORPTION IN THE SMALL INTESTINE (Experimental study and mathematical modeling)].
The aim of the work is to analyze the relationship between consumption of glucose solution by rats and its absorption, and to use this fact for assessment of the absorptive capacity of the small intestine in non anesthetized animals in vivo. Consumption of glucose solution (200 g/l) by fasted rats was recorded in the control, and after administration of phloridzin--inhibitor of glucose active transport- or 3 hours after the restriction stress. On the mathematical model we studied the relative role of factors that can influence the temporal dynamics of glucose consumption by rats. The rate of glucose consumption was observed being decreased in the presence of phloridzin (1 mM), and be increased after the stress. The results of modeling are consistent with the experimental data and show that the rate of consumption of glucose solutions considerably more depends on the transport activity of the small intestine than on glucose concentration in the solution, or on the substrate regulation of the stomach emptying. Analysis of dynamics of consumption of glucose solution by intact rats may be considered as one of promising approaches to assessing the absorptive capacity of the small intestine under natural conditions.


Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine.
Choline kinase, responsible for the phosphorylation of choline to phosphocholine as the first step of the CDP-choline pathway for the biosynthesis of phosphatidylcholine, has been recognized as a new target for anticancer therapy. Crystal structures of human choline kinase in its apo, ADP and phosphocholine-bound complexes, respectively, reveal the molecular details of the substrate binding sites. ATP binds in a cavity where residues from both the N and C-terminal lobes contribute to form a cleft, while the choline-binding site constitutes a deep hydrophobic groove in the C-terminal domain with a rim composed of negatively charged residues. Upon binding of choline, the enzyme undergoes conformational changes independently affecting the N-terminal domain and the ATP-binding loop. From this structural analysis and comparison with other kinases, and from mutagenesis data on the homologous Caenorhabditis elegans choline kinase, a model of the ternary ADP.phosphocholine complex was built that reveals the molecular basis for the phosphoryl transfer activity of this enzyme.


Epidemiology of CN IV Palsies.
To examine the etiologies of CN IV palsies based on age and aid the clinician in more effective work-up and treatment. Retrospective chart review of 124 patients presenting to Houston Eye Associates between 1968 and January 1999 with superior oblique palsies. Patients were divided into the following age groups: birth to 10 years, 11-20 years, 21-40 years, 41-60 years and over 60 years. Etiologies and treatment were then examined within each age group. Etiologies were categorized as congenital, traumatic, vascular, neoplastic, and idiopathic. Treatment was classified as observation, prisms alone, surgical repair, and surgical repair combined with prisms. Bilateral, unilateral, and masked bilateral palsies were included. Nine of 13 bilateral palsies were due to trauma. The masked bilateral palsy was congenital. Between the ages of birth and 10 years 26 of 37 (70.1%) palsies were congenital. Between the ages of 21 and 40 years 17/35 (48.6%) were due to trauma. Within the remaining age groups 11-20 years, 41-60 years, and over 60 years, the most common etiology was idiopathic 7/13 (53.8%), 11/24 (45.8%), and 7/15 (46.7%) respectively. Surgery was the most common treatment option within all age groups with the exception of the over 60 group. In this age group, prisms alone was most common.


Sensitization of midbrain dopamine neuron reactivity promotes the pursuit of amphetamine.
Stimulant drugs such as amphetamine are readily self-administered by humans and laboratory animals by virtue of their actions on dopamine (DA) neurons of the midbrain. Repeated exposure to this drug systemically or exclusively in the cell body region of these neurons in the ventral tegmental area (VTA) leads to long-lasting changes in dopaminergic function that can be assessed by increased locomotor activity and enhanced DA overflow in the nucleus accumbens (NAcc) after re-exposure to the drug. Three experiments were conducted to evaluate the possibility that this enduring sensitized reactivity underlies compulsive drug self-administration. In all experiments, rats were pre-exposed to amphetamine and, starting 10 d later, their intravenous self-administration of the drug was assessed. In the first experiment, rats previously exposed to amphetamine systemically or exclusively in the VTA subsequently worked harder than untreated animals to obtain the drug when the work required to obtain successive infusions was increased progressively. In the second experiment, this progressively increasing workload was found to decrease the magnitude of amphetamine-induced DA overflow observed with successive infusions until responding ceased. Rats previously exposed to amphetamine were more resistant to this decline and more apt to maintain responding. Finally, in experiment three, a noncontingent priming injection of the drug produced a greater NAcc DA response and a greater parallel increase in lever pressing in drug compared with saline pre-exposed rats. Together, these results demonstrate a direct relation between drug-induced sensitization of midbrain dopamine neuron reactivity and the excessive pursuit and self-administration of an abused substance.


Plant species dispersed by Galapagos tortoises surf the wave of habitat suitability under anthropogenic climate change.
Native biodiversity on the Galapagos Archipelago is severely threatened by invasive alien species. On Santa Cruz Island, the abundance of introduced plant species is low in the arid lowlands of the Galapagos National Park, but increases with elevation into unprotected humid highlands. Two common alien plant species, guava (Psidium guajava) and passion fruit (Passiflora edulis) occur at higher elevations yet their seeds are dispersed into the lowlands by migrating Galapagos tortoises (Chelonoidis spp.). Tortoises transport large quantities of seeds over long distances into environments in which they have little or no chance of germination and survival under current climate conditions. However, climate change is projected to modify environmental conditions on Galapagos with unknown consequences for the distribution of native and introduced biodiversity. We quantified seed dispersal of guava and passion fruit in tortoise dung piles and the distribution of adult plants along two elevation gradients on Santa Cruz to assess current levels of 'wasted' seed dispersal. We computed species distribution models for both taxa under current and predicted future climate conditions. Assuming that tortoise migratory behaviour continues, current levels of "wasted" seed dispersal in lowlands were projected to decline dramatically in the future for guava but not for passion fruit. Tortoises will facilitate rapid range expansion for guava into lowland areas within the Galapagos National Park where this species is currently absent. Coupled with putative reduction in arid habitat for native species caused by climate change, tortoise driven guava invasion will pose a serious threat to local plant communities.


Expression of kit ligand and insulin-like growth factor binding protein 3 during in vivo or in vitro development of ovarian follicles in sheep.
Expression of Kit ligand (KL) and insulin-like growth factor binding protein (IGFBP3) genes was studied at different in vivo and corresponding in vitro stages of development of the ovarian follicles in sheep. The expression of both KL and IGFBP3 was significantly higher in the primordial follicles relative to any other stage of development. Compared to the other stages, the KL expression in the cumulus cells from in vivo grown large antral follicles and that of IGFBP3 in COCs' isolated from large antral follicles matured in vitro for 24 hr were significantly higher. In the oocytes from in vivo grown ovarian follicles, the expression of KL was the same at all the stages of development. Insulin-like growth factor binding protein 3 expression was also the same in the oocytes at all the stages of the development except for a significantly lower expression in those from antral follicles. The expression of KL in the cumulus cells decreased significantly in the in vitro grown early antral follicles but did not change further as the development progressed. The expression of IGFBP3 in the cumulus cells from in vitro grown ovarian follicles appeared to increase as the development progressed although the increase was not significant between any two consecutive stages of development. In the oocytes in in vitro grown ovarian follicles, the expression levels of KL and IGFBP3 genes did not change with development. It is concluded that (i) KL and IGFBP3 genes follow specific patterns of expression during ovarian folliculogenesis and (ii) in vitro culture of preantral follicles compromises the development potential through alterations in the stage-specific patterns of expression of these and other developmentally important genes.


Accurate extraction of Lagrangian coherent structures over finite domains with application to flight data analysis over Hong Kong International Airport.
Locating Lagrangian coherent structures (LCS) for dynamical systems defined on a spatially limited domain present a challenge because trajectory integration must be stopped at the boundary for lack of further velocity data. This effectively turns the domain boundary into an attractor, introduces edge effects resulting in spurious ridges in the associated finite-time Lyapunov exponent (FTLE) field, and causes some of the real ridges of the FTLE field to be suppressed by strong spurious ridges. To address these issues, we develop a finite-domain FTLE method that renders LCS with an accuracy and fidelity that is suitable for automated feature detection. We show the application of this technique to the analysis of velocity data from aircraft landing at the Hong Kong International Airport.


The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol.
The six commonly used trade herbal products, St. John's wort, common valerian, common sage, Ginkgo biloba, Echinacea purpurea and horse chestnut, and ethanol, were investigated for their in vitro inhibitory potential of cytochrome P450 2D6 (CYP2D6)-mediated metabolism. Herbal components were extracted from commercially available products in a way that ensured the same composition of constituents in the extract as in the original trade products. c-DNA baculovirus expressed CYP2D6 was used with dextromethorphan as substrate. Quinidine was included as a positive control inhibitor. A validated high performance liquid chromatography methodology was used to quantify the formation of dextrorphan (product of dextromethorphan O-demethylation). Ethanol showed a biphasic effect on CYP2D6 metabolism, increasing initially the CYP2D6 activity with 175% of control up to a concentration of 1.1%, where after ethanol linearly inhibited the CYP2D6 activity. All the investigated herbs inhibited CYP2D6 activity to some extent, but only St. John's wort, common sage and common valerian were considered possible candidates for in vivo clinically significant effects. They showed IC50 values of 0.07 +/- 7 x 10(-3) mg/ml, 0.8 +/- 0.05 mg/ml and 1.6 +/- 0.2 mg/ml, respectively. St. John's wort inhibited CYP2D6-mediated metabolism in an uncompetitive manner, while common valerian and common sage in a non-competitive manner demonstrated interherb differences in inhibition patterns and differences when compared to the more homogenous competitive inhibitor quinidine. Common valerian was the only herb that showed a mechanistic inhibition of CYP2D6 activity and attention should be paid to a possible toxicity of this herb.


Impact Over 3 Years of a Family Medicine-led Addiction Medicine Curriculum for Medical Students.
Innovations in medical school training are essential for family physicians to enter practice confident in addressing the opioid epidemic and substance use disorders. The objective of this study was to evaluate the effectiveness of a distance-learning addiction medicine curriculum led by family medicine physicians for third-year medical students. Our prospective cohort study of third-year medical students compared our educational model to a traditional curriculum. Our distance-learning collaboration employed videoconferencing and community experts to engage students across Minnesota in an addiction medicine curriculum. Students in a family medicine-focused 9-month longitudinal integrated curriculum (LIC) participated in this 16-session curriculum while embedded in a rural or urban underserved community for their core third-year clerkships. We evaluated program effectiveness through a knowledge and attitude self-assessment survey of student participants before and after the program compared to students in a traditional curriculum. The pre- and postsurvey response rates, respectively, were 22.8% for the control group and 98.4% for the ECHO (Extension for Community Healthcare Outcomes) group. Compared to classmates in a traditional curriculum, program participants reported significantly higher self-perceived ability managing addiction concerns upon completing this curriculum (mean score of 3.2 vs 2.2 on a 5-point Likert scale, P<.001). Data from our LIC showed promise that the model can be effective in building confidence in students' abilities to practice addiction medicine. Because of its broad reach and low cost, this form of medical education may be a key model for medical schools to respond to the opioid epidemic and better serve our patients.


The influence of birth weight and length on bone mineral density and content in adolescence: The Tromsø Study, Fit Futures.
The influence of birth weight and length on bone mineral parameters in adolescence is unclear. We found a positive association between birth size and bone mineral content, attenuated by lifestyle factors. This highlights the impact of environmental stimuli and lifestyle during growth. The influence of birth weight and length on bone mineral density and content later in life is unclear, especially in adolescence. This study evaluated the impact of birth weight and length on bone mineral density and content among adolescents. We included 961 participants from the population-based Fit Futures study (2010-2011). Dual-energy X-ray absorptiometry (DXA) was used to measure bone mineral density (BMD) and bone mineral content (BMC) at femoral neck (FN), total hip (TH) and total body (TB). BMD and BMC measures were linked with birth weight and length ascertained from the Medical Birth Registry of Norway. Linear regression models were used to investigate the influence of birth parameters on BMD and BMC. Birth weight was positively associated with BMD-TB and BMC at all sites among girls; standardized β coefficients [95% CI] were 0.11 [0.01, 0.20] for BMD-TB and 0.15 [0.06, 0.24], 0.18 [0.09, 0.28] and 0.29 [0.20, 0.38] for BMC-FN, TH and TB, respectively. In boys, birth weight was positively associated with BMC at all sites with estimates of 0.10 [0.01, 0.19], 0.12 [0.03, 0.21] and 0.15 [0.07, 0.24] for FN, TH and TB, respectively. Corresponding analyses using birth length as exposure gave significantly positive associations with BMC at all sites in both sexes. The significant positive association between birth weight and BMC-TB in girls, and birth length and BMC-TB in boys remained after multivariable adjustment. We found a positive association between birth size and BMC in adolescence. However, this association was attenuated after adjustment for weight, height and physical activity during adolescence.


Establishment of a CD45-positive immature plasma cell line from an aggressive multiple myeloma with high serum lactate dehydrogenase.
A myeloma cell line (KHM-11) was established from the pleural effusion of a patient with IgA-kappa type aggressive myeloma with high serum lactate dehydrogenase who was extremely resistant to vincristin, adriamycin and dexamethasone combination therapy (VAD). The morphology of fresh tumor cells and KHM-11 was plasmablast according to Greipp's criteria. In addition to the expression of regular plasma cell antigens, CD38 and PCA-1, CD45 was found on both fresh cells and KHM-11. Other T- or B-cells antigens, such as CD2, 4, 8, 19, and 20 were negative. Cytoplasmic immunoglobulin kappa light chain in KHM-11 was found by flowcytometry. Southern blot analysis revealed that fresh sample and KHM-11 shared the same immunoglobulin gene rearrangement. IL-6 was found in the culture supernatant of KHM-11, and this supernatant stimulated the growth of this cell line, indicating an IL-6 autocrine mechanism. These findings indicate that KHM-11 is a CD45-positive immature plasma cell line. As far as we know, there is no report of CD45-positive myeloma cell line. KHM-11 should be a useful tool for understanding not only the pathogenesis of aggressive multiple myeloma with high LDH but also for understanding the mechanism which underlies the terminal differentiation of B-cells.


The Effects of Postdischarge Telephone Counseling and Short Message Service on the Knee Function, Activities of Daily Living, and Life Satisfaction of Patients Undergoing Total Knee Replacement.
No study comparing short message service (SMS) texts and telephone counseling for patients undergoing total knee replacement (TKR) has been reported. The purpose of the study was to provide postdischarge telephone counseling and SMS texts to TKR patients and to analyze the effects of these services on their knee function (KF), activities of daily living (ADL), and life satisfaction (LS). This study used a randomized clinical trial design. This study was conducted with 40 patients (counseling group: 21; SMS group: 19). In the telephone counseling group and the SMS group, KF, ADL, and LS were assessed before surgery and 1 and 3 months after TKR. Telephone counseling and SMS texts have the same effects on KF, ADL, and LS of TKR patients. Future research is needed to determine optimal frequency and duration of post-TKR SMS to support patients who have undergone TKR.


The endocannabinoid system and Huntington's disease.
The research in Huntington's disease (HD) has been growing exponentially during the last decade, since the discovery of the genetic basis that leads to neurodegeneration. HD is one of several progressive neurodegenerative disorders, in which the underlying mutation is a CAG expansion encoding a polyglutamine tract in a specific protein, which in the case of HD, is called huntingtin. The first clinical symptoms of HD are generally psychiatric abnormalities, most commonly depression and mood disturbances. Involuntary choreiform movements and dementia develop over the next 15-20 years, and death generally results from complications derived from immobility. There is currently no cure, or even an effective therapy to offset the decline in mental and motor capabilities suffered by those affected by HD, but recent studies have started to examine the usefulness of different classes of new compounds. Among these, plant-derived, synthetic or endogenous cannabinoids have been proposed to have therapeutic value for the treatment of HD, since they act on cannabinoid CB(1) receptors located in the basal ganglia circuitry, that is affected by the striatal atrophy typical of HD. Recent studies have characterized the changes in these receptors, as well as their endogenous ligands, in the basal ganglia in a variety of animal models of HD. The results are indicative that the endocannabinoid system becomes hypofunctional in this disease, which could be related to the hyperkinesia typical of the earliest phases of this disease. In addition, it has been proposed that the loss of these receptors might be involved in the process of pathogenesis itself. This, together with the well-known protective properties of cannabinoid-related compounds, suggest that, in addition to a symptomatic usefulness, cannabinoids might also serve to delay or to arrest the development of this disease. The present article will review all recent data dealing with the biochemical, pharmacological and therapeutic bases that support a potential role of cannabinoids in the pathogenesis and/or therapeutic treatment of this motor disorder.


A selective aldose reductase inhibitor of a new structural class prevents or reverses early retinal abnormalities in experimental diabetic retinopathy.
Previously studied inhibitors of aldose reductase were largely from two chemical classes, spirosuccinamide/hydantoins and carboxylic acids. Each class has its own drawbacks regarding selectivity, in vivo potency, and human safety; as a result, the pathogenic role of aldose reductase in diabetic retinopathy remains controversial. ARI-809 is a recently discovered aldose reductase inhibitor (ARI) of a new structural class, pyridazinones, and has high selectivity for aldose versus aldehyde reductase. To further test the possible pathogenic role of aldose reductase in the development of diabetic retinopathy, we examined the retinal effects of this structurally novel and highly selective ARI in insulinized streptozotocin-induced diabetic rats. ARI-809 treatment was initiated 1 month after diabetes induction and continued for 3 months at a dose that inhibited the polyol pathway in the retina of diabetic rats to a similar extent as sorbinil, a poorly selective hydantoin ARI previously shown to prevent retinopathy in this model. ARI-809 improved survival, inhibited cataract development, normalized retinal sorbitol and fructose, and protected the retina from abnormalities that also occur in human diabetes: neuronal apoptosis, glial reactivity, and complement deposition. Because ARI-809 is a novel chemotype highly selective for aldose reductase, these results support the notion that aldose reductase is the key relay that converts hyperglycemia into glucose toxicity in neural and glial cell types in the retina.


[The efficacy of temporary retention chemotherapy of the treatment of polyps in the remnant rectum of familial polyposis after total colectomy and ileorectostomy--a case report].
A case of familial polyposis is reported. The patient was a 24-year-old woman on whom total colectomy followed by ileorectostomy had been performed. However, there were multiple polyps remaining in the remnant rectum. For the treatment of these residual polyps, a new chemotherapeutic method known as Temporary Retention Chemotherapy (TRC), originally devised by us for the treatment of advanced gastric cancer, was applied. A balloon catheter was inserted and fixed into the rectum via the anus for the treatment of the rectal tumors. Through the catheter, high-dose 5-fluorouracil (5-FU) solution was injected into the rectum and retained there for one hour before being discarded. During the therapy, the patient was asked to change her position of recumbency at certain intervals, so that the 5-FU solution could act evenly on the lesions in question. This therapy was repeated twice a week, and followed by routine endoscopic studies. A total dose of 5,700 mg of 5-FU was necessary for obtaining a complete response of the remnant lesions. 6 months later, 4 polyps were found, and TRC was again applied, resulting in disappearance of the polyps again after the therapy. So far, no side-effect have been noted as a result of this therapy. She is currently still alive without any residual polyps, carcinoma or metastasis 6 years after the operation.


Carbapenemase-producing bacteria in companion animals: a public health concern on the horizon.
Clinical infections attributed to carbapenemase-producing bacteria are a pressing public health concern owing to limited therapeutic options and linked antimicrobial resistance. In recent years, studies have reported the emergence and spread of carbapenemase-producing Enterobacteriaceae and their public health impact. This has been closely followed by the global dissemination of highly resistant and virulent zooanthroponotic extraintestinal pathogenic Escherichia coli (ExPEC) ST131 clones. It has also been hypothesized that companion animals may act as a reservoir for Gram-negative multidrug-resistant pathogens in the community. Two recent reports have documented the emergence of carbapenemase-producing bacteria in companion animals. This phenomenon is of great concern because of the close contact between humans and their pets, and the potential for cross-species transmission. This scenario suggests a role for multifaceted control of Gram-negative multidrug-resistant infections in companion animals. This short article addresses this issue and identifies steps that could facilitate this process.


Restriction of P-element insertions at the Notch locus of Drosophila melanogaster.
P elements move about the Drosophila melanogaster genome in a nonrandom fashion, preferring some chromosomal targets for insertion over others (J. C. J. Eeken, F. H. Sobels, V. Hyland, and A. P. Schalet, Mutat. Res. 150:261-275, 1985; W. R. Engels, Annu. Rev. Genet. 17:315-344, 1983; M. D. Golubovsky, Y. N. Ivanov, and M. M. Green, Proc. Natl. Acad. Sci. USA 74:2973-2975, 1977; M. J. Simmons and J. K. Lim, Proc. Natl. Acad. Sci. USA 77:6042-6046, 1980). Some of this specificity may be due to recognition of a particular DNA sequence in the target DNA; derivatives of an 8-base-pair consensus sequence are occupied by these transposable elements at many different chromosomal locations (K. O'Hare and G. M. Rubin, Cell 34:25-36, 1983). An additional level of specificity of P-element insertions is described in this paper. Of 14 mutations induced in the complex locus Notch by hybrid dysgenesis, 13 involved P-element insertions at or near the transcription start site of the gene. This clustering was not seen in other transposable element-induced mutations of Notch. DNA sequences homologous to the previously described consensus target for P-element insertion are not preferentially located in this region of the locus. The choice of a chromosomal site for integration appears to be based on more subtle variations in chromosome structure that are probably associated with activation or expression of the target gene.


Observation of Arginine Side-Chain Motions Coupled to the Global Conformational Exchange Process in Deubiquitinase A.
Coupled motions have been demonstrated to be functionally important in a number of enzymes. Noncovalent side-chain interactions play essential roles in coordinating the motions across different structural elements in a protein. However, most of the dynamic studies of proteins are focused on backbone amides or methyl groups in the side chains and little is known about the polar and charged side chains. We have previously characterized the conformational dynamics of deubiquitinase A (DUBA), an isopeptidase, on the microsecond-to-millisecond (μs-ms) time scales with the amide 1H Carr-Purcell-Meiboom-Gill (CPMG) experiment. We detected a global conformational exchange process on a time scale of approximately 200 μs, which involves most of the structural elements in DUBA, including the active site and the substrate binding interface. Here, we extend our previous study on backbone amides to the arginine side-chain Nε-Hε groups using a modified 1H CPMG pulse sequence that can efficiently detect both backbone amide and arginine side-chain Nε-Hε signals in a single experiment. We found that the side chains of three arginines display motions on the same time scale as the backbone amides. Mutations of two of the three arginines to alanines result in a decrease in enzyme activity. One of these two arginines is located in a loop involved in substrate binding. This loop is not visible in the backbone amide-detected experiments due to excess line broadening induced by motions on the μs-ms time scales. These results clearly demonstrate that the motions of some arginine side chains are coupled to the global conformational exchange process and provide an additional probe for motions in a functionally important loop that did not yield visible backbone amide signals, suggesting the value of side-chain experiments on DUBA. The modified 1H CPMG pulse sequence allows the simultaneous characterization of backbone and arginine side-chain dynamics without any increase in data acquisition time and can be applied to the dynamic studies of any protein that displays measurable amide 1H relaxation dispersion.


Institutional logic in self-management support: coexistence and diversity.
The prevalence of chronic conditions in Europe has been the subject of health-political reforms that have increasingly targeted collaboration between public, private and voluntary organisations for the purpose of supporting self-management of long-term diseases. The international literature describes collaboration across sectors as challenging, which implies that their respective logics are conflicting or incompatible. In line with the European context, recent Norwegian health policy advocates inter-sectorial partnerships. The aim of this policy is to create networks supporting better self-management for people with chronic conditions. The purpose of our qualitative study was to map different understandings of self-management support in private for-profit, volunteer and public organisations. These organisations are seen as potential self-management support networks for individuals with chronic conditions in Norway. From December 2012 to April 2013, we conducted 50 semi-structured interviews with representatives from relevant health and well-being organisations in different parts of Norway. According to the theoretical framework of institutional logic, representatives' statements are embedded with organisational understandings. In the analysis, we systematically assessed the representatives' different understandings of self-management support. The institutional logic we identified revealed traits of organisational historical backgrounds, and transitions in understanding. We found that the merging of individualism and fellowship in contemporary health policy generates different types of logic in different organisational contexts. The private for-profit organisations were concerned with the logic of a healthy appearance and mindset, whereas the private non-profit organisations emphasised fellowship and moral responsibility. Finally, the public, illness-oriented organisations tended to highlight individual conditions for illness management. Different types of logic may attract different users, and simultaneously, a diversity of logic types may challenge collaboration at the user's expense. Moral implications embed institutional logic implying a change towards individual responsibility for disease. Policy makers ought to consider complexities of logic in order to tailor the different needs of users.


Adherence of Helicobacter pylori to the gastric mucosa.
Bacterial adhesion to the intestinal epithelium is a critical initial step in the pathogenesis of many enteric diseases. Helicobacter pylori is a duodenal pathogen that adheres to the gastric epithelium and causes gastritis and peptic ulceration. The mechanism by which H pylori causes disease has not been elucidated but adherence to the gastric mucosa is thought to be an important virulence determinant of the organism. What is known about adherence of H pylori to the gastric mucosa is summarized. Topics discussed are the mechanism of H pylori adherence; in vitro and in vivo models of H pylori infection; and adherence and potential adhesins and receptors for H pylori.


Elastic property of vertically aligned nanowires.
An atomic force microscopy (AFM) based technique is demonstrated for measuring the elastic modulus of individual nanowires/nanotubes aligned on a solid substrate without destructing or manipulating the sample. By simultaneously acquiring the topography and lateral force image of the aligned nanowires in the AFM contacting mode, the elastic modulus of the individual nanowires in the image has been derived. The measurement is based on quantifying the lateral force required to induce the maximal deflection of the nanowire where the AFM tip was scanning over the surface in contact mode. For the [0001] ZnO nanowires/nanorods grown on a sapphire surface with an average diameter of 45 nm, the elastic modulus is measured to be 29 +/- 8 GPa.


Long-distance calls in Neotropical primates.
Long-distance calls are widespread among primates. Several studies concentrate on such calls in just one or in few species, while few studies have treated more general trends within the order. The common features that usually characterize these vocalizations are related to long-distance propagation of sounds. The proposed functions of primate long-distance calls can be divided into extragroup and intragroup ones. Extragroup functions relate to mate defense, mate attraction or resource defense, while intragroup functions involve group coordination or alarm. Among Neotropical primates, several species perform long-distance calls that seem more related to intragroup coordination, markedly in atelines. Callitrichids present long-distance calls that are employed both in intragroup coordination and intergroup contests or spacing. Examples of extragroup directed long-distance calls are the duets of titi monkeys and the roars and barks of howler monkeys. Considerable complexity and gradation exist in the long-distance call repertoires of some Neotropical primates, and female long-distance calls are probably more important in non-duetting species than usually thought. Future research must focus on larger trends in the evolution of primate long-distance calls, including the phylogeny of calling repertoires and the relationships between form and function in these signals.


Diffusion-controlled formation and collapse of a d-dimensional A-particle island in the B-particle sea.
We consider diffusion-controlled evolution of a d-dimensional A-particle island in the B-particle sea at propagation of the sharp reaction front A+B→0 at equal species diffusivities. The A-particle island is formed by a localized (point) A-source with a strength λ that acts for a finite time T. We reveal the conditions under which the island collapse time t_{c} becomes much longer than the injection period T (long-living island) and demonstrate that regardless of d the evolution of the long-living island radius r_{f}(t) is described by the universal law ζ_{f}=r_{f}/r_{f}^{M}=sqrt[eτ|lnτ|], where τ=t/t_{c} and r_{f}^{M} is the maximal island expansion radius at the front turning point t_{M}=t_{c}/e. We find that in the long-living island regime the ratio t_{c}/T changes with the increase of the injection period T by the law ∝(λ^{2}T^{2-d})^{1/d}, i.e., increases with the increase of T in the one-dimensional (1D) case, does not change with the increase of T in the 2D case and decreases with the increase of T in the 3D case. We derive the scaling laws for particles death in the long-living island and determine the limits of their applicability. We demonstrate also that these laws describe asymptotically the evolution of the d-dimensional spherical island with a uniform initial particle distribution generalizing the results obtained earlier for the quasi-one-dimensional geometry. As striking results, we present a systematic analysis of the front relative width evolution for fluctuation, logarithmically modified, and mean-field regimes, and we demonstrate that in a wide range of parameters the front remains sharp up to a narrow vicinity of the collapse point.


Do Brelfies Help to Normalize Breastfeeding in Public: Lewd or Food?
Often, lack of support results in early termination of breastfeeding compromising infant health. Lactivists argue one way to normalize public breastfeeding is by posting brelfies on social network sites. An online experiment tested a 2 × 2 between-subjects factorial design. Participants (N = 296) were randomly assigned to one of the four experimental conditions varying the valence of comments or the control where no user comments were present. Most participants posted supportive comments. Compared to participants who only viewed brelfies, those who read any type of comment posted by other users showed negative attributions and emotions to brelfies. A number of other variables were also measured. Identification with other social media users was associated with approval for posting brelfies and supporting mothers. Emotional arousal and cognitive appraisal may be two sources of stigma about comments for brelfies even though people recognize that breastfeeding is an important health issue.


Photocatalytic Water Splitting Reaction Catalyzed by Ion-Exchanged Salts of Potassium Poly(heptazine imide) 2D Materials.
Potassium poly (heptazine imide) (K-PHI), a crystalline two-dimensional carbon-nitride material, is an active photocatalyst for water splitting. The potassium ions in K-PHI can be exchanged with other ions to change the properties of the material and eventually to design the catalysts. We report here the electronic structures of several ion-exchanged salts of K-PHI (K, H, Au, Ru, and Mg) and their feasibility as water splitting photocatalysts, which were determined by density functional theory (DFT) calculations. The DFT results are complemented by experiments where the performances in the photocatalytic hydrogen evolution reaction (HER) were recorded. We show that due to its narrow band gap, Ru-PHI is not a suitable photocatalyst. The water oxidation potentials are straddled between the band edge potentials of H-PHI, Au-PHI, and Mg-PHI; thus, these are active photocatalysts for both the oxygen and hydrogen evolution reactions, whereas K-PHI is active only for the HER. The experimental data show that these are active HER photocatalysts, in agreement with the DFT results. Furthermore, Mg-PHI has shown remarkable performance in the HER, with a rate of 539 μmol/(h·g) and a quantum efficiency of 7.14% at 410 nm light irradiation, which could be due to activation of the water molecule upon adsorption, as predicted by our DFT calculations.


Ileal gallstone obstruction: Single-balloon enteroscopic removal.
Gallstone-induced ileus is a rare complication of cholelithiasis. Since localization of gallstones impacted in the small bowel, especially in the ileum, prevents access by conventional endoscopy in most cases, the mainstay of treatment remains surgical. Recent invention of double- and single-balloon enteroscopy has added much to the ability of imaging the small bowel and enables endoscopically directed therapy. Herein, for the first time, we report a successful endoscopic calculus removal via peroral single-balloon enteroscopy in an 81-year-old woman suffering from gallstone ileus of the ileum.


Meridional heat transport variability induced by mesoscale processes in the subpolar North Atlantic.
The ocean's role in global climate change largely depends on its heat transport. Therefore, understanding the oceanic meridional heat transport (MHT) variability is a fundamental issue. Prevailing observational and modeling evidence suggests that MHT variability is primarily determined by the large-scale ocean circulation. Here, using new in situ observations in the eastern subpolar North Atlantic Ocean and an eddy-resolving numerical model, we show that energetic mesoscale eddies with horizontal scales of about 10-100 km profoundly modulate MHT variability on time scales from intra-seasonal to interannual. Our results reveal that the velocity changes due to mesoscale processes produce substantial variability for the MHT regionally (within sub-basins) and the subpolar North Atlantic as a whole. The findings have important implications for understanding the mechanisms for poleward heat transport variability in the subpolar North Atlantic Ocean, a key region for heat and carbon sequestration, ice-ocean interaction, and biological productivity.


Endothelial-to-Mesenchymal Transition in Bone Marrow and Spleen of Primary Myelofibrosis.
Primary myelofibrosis is characterized by the development of fibrosis in the bone marrow that contributes to ineffective hematopoiesis. Bone marrow fibrosis is the result of a complex and not yet fully understood interaction among megakaryocytes, myeloid cells, fibroblasts, and endothelial cells. Here, we report that >30% of the endothelial cells in the small vessels of the bone marrow and spleen of patients with primary myelofibrosis have a mesenchymal phenotype, which is suggestive of the process known as endothelial-to-mesenchymal transition (EndMT). EndMT can be reproduced in vitro by incubation of cultured endothelial progenitor cells or spleen-derived endothelial cells with inflammatory cytokines. Megakaryocytes appear to be implicated in this process, because EndMT mainly occurs in the microvessels close to these cells, and because megakaryocyte-derived supernatant fluid can reproduce the EndMT switch in vitro. Furthermore, EndMT is an early event in a JAK2-V617F knock-in mouse model of primary myelofibrosis. Overall, these data show for the first time that microvascular endothelial cells in the bone marrow and spleen of patients with primary myelofibrosis show functional and morphologic changes that are associated to the mesenchymal phenotype.


[Prokaryotic expression and antigenic activity analysis on the matrix protein genes of two strains of human metapneumovirus recently identified in Beijing].
Human metapneumovirus (hMPV) is a recently identified respiratory virus more like human respiratory syncytial virus in clinical symptoms. Matrix protein (M) is one of the most important structural proteins. For further studying of hMPV, the full length of M genes from the recombinant plasmid pUCm-M1816 and pUCmM1817 were cloned by PCR and sub-cloned into the pET30a(+) vector, which is a prokaryotic expression vector, after dual-enzyme digestion with Bam HI and Xho I. The positive recombinated plasmids were transformed into E. coli BL21 (DE3) and expressed under the inducing of IPTG. Target proteins were characterized by SDS-PAGE and Western blotting. In this article, we' ve successfully constructed the recombinated plasmids pET30a-M1816 and pET30a-M1817 which have correct open reading frames confirmed by dual-enzyme digestion analysis and sequencing. The fusion proteins with 6 x His-N were highly produced after inducing by 1mmol/ L IPTG at 37 degrees C. A unique protein band with approximate 27.6 kD was characterized by SDS-PAGE. Most of the target protein existed in inclusion body. Western blot analysis showed that the target protein has specific binding reaction to rabbit antiserum against polypeptides of the matrix protein of hMPV. So the M genes were highly expressed in the prokaryotic system and the expressed M proteins have specific antigenic activities. It can be used for further studying of hMPV infections in Beijing.


Closed chromatin loops at the ends of chromosomes.
The termini of eukaryotic chromosomes contain specialized protective structures, the telomeres, composed of TTAGGG repeats and associated proteins which, together with telomerase, control telomere length. Telomere shortening is associated with senescence and inappropriate telomerase activity may lead to cancer. Little is known about the chromatin context of telomeres, because, in most cells, telomere chromatin is tightly anchored within the nucleus. We now report the successful release of telomere chromatin from chicken erythrocyte and mouse lymphocyte nuclei, both of which have a reduced karyoskeleton. Electron microscopy reveals telomere chromatin fibers in the form of closed terminal loops, which correspond to the "t-loop" structures adopted by telomere DNA. The ability to recognize isolated telomeres in their native chromatin conformation opens the way for detailed structural and compositional studies.


The effects of light lanthanoid elements (La, Ce, Nd) on (Ar)CF-Ln coordination and C-F activation in N,N-dialkyl-N'-2,3,5,6-tetrafluorophenylethane-1,2-diaminate complexes.
A new class of homoleptic organoamido rare earth complexes [Ln(L(Me) or L(Et))(3)] (Ln = La, Ce, Nd; L(Me/Et) = p-HC(6)F(4)N(CH(2))(2)NMe(2)/Et(2)) exhibiting (Ar)CF-Ln interactions has been isolated from redox-transmetallation/protolysis (RTP) reactions between the free metals, Hg(C(6)F(5))(2) and L(Me/Et)H in tetrahydrofuran, together with low yields of [Ln(L(Me))(2)F](3) (Ln = La, Ce) or [Nd(L(Et))(2)F](2) species, resulting from C-F activation reactions. The structures of the homoleptic complexes have eight-coordinate Ln metals with two tridentate (N,N',F) amide ligands including (Ar)CF-Ln bonds and either a bidentate (N,F) ligand (Ln = La, Ce, Nd; L(Et)) or a bidentate (N,N') ligand (Ln = Nd; L(Me)), in an unusual case of linkage variation. All (Ar)CF-Ln bond lengths are shorter than or similar to the corresponding Ln-NMe(2)/Et(2) bond lengths. In [Ln(L(Me))(2)F](3) (Ln = La, Ce) complexes, there is a six-membered ring framework with alternating F and Ln atoms and the metal atoms are eight-coordinate with two tridentate (N,N',F) L(Me) ligands, whilst [Nd(L(Et))(2)F](2) is a fluoride-bridged dimer.


A Flexible and Highly Sensitive Pressure Sensor Based on AgNWs/NRLF for Hand Motion Monitoring.
Flexible, highly sensitive, easy fabricating process, low-cost pressure sensors are the trend for flexible electronic devices. Inspired by the softness, comfortable, environmental friendliness and harmless of natural latex mattress, herein, we report an agile approach of constructing a flexible 3D-architectured conductive network by dip-coating silver nanowires (AgNWs) on the natural rubber latex foam (NRLF) substrate that provide the 3D micro-network structure as the skeleton. The variation of the contact transformed into the electrical signal among the conductive three-dimensional random networks during compressive deformation is the piezoresistive effect of AgNWs/NRLF pressure sensors. The resulting AgNWs/NRLF pressure sensors exhibit desirable electrical conductivity (0.45-0.50 S/m), excellent flexibility (58.57 kPa at 80% strain), good hydrophobicity (~128° at 5th dip-coated times) and outstanding repeatability. The AgNWs/NRLF sensors can be assembled on a glove to detect hand motion sensitively such as bending, touching and holding, show potential application such as artificial skin, human prostheses and health monitoring in multifunctional pressure sensors.


Comparison of Intravitreal Ranibizumab, Aflibercept, and Dexamethasone Implant after Bevacizumab Failure in Macular Edema Secondary to Retinal Vascular Occlusions.
To compare the visual and anatomic outcomes of macular edema secondary to retinal vein occlusion after switching from bevacizumab to ranibizumab, aflibercept, or dexamethasone implant. Fifteen eyes were switched to ranibizumab, 12 to aflibercept, and 10 to dexamethasone. At 3, 6, 9, and 12 months, the outcome measures were visual acuity (VA) and central macular thickness (CMT). One year after the switch, CMT decreased from 430.11 ± 91.21 to 291.86 ± 43.87 μm (p < 0.001). VA increased in 59.5% of the eyes. No difference between the groups was found in those outcomes at 1 year, but the number of injections varied: 3.30 ± 0.95 for dexamethasone, 6.50 ± 2.11 for aflibercept, and 8.27 ± 2.37 for ranibizumab (p < 0.001). Most of the eyes that failed initial bevacizumab therapy benefit from switching to another modality. The number of required injections during the first year after the switch varies.


Enhancing appropriate and variable responding in young children with autism spectrum disorder.
The present study utilized lag schedules of reinforcement, in conjunction with training multiple exemplars and provision of prompts, to promote appropriate variability of social skills. Participants included in three children between the ages of 5 and 7 with ASD. Participants attended a social skills training program twice per week for eight weeks. A multiple probe design across target social skills was used to assess the effects of intervention. Findings indicate that training multiple exemplars alone did not appreciably increase appropriate and variable responding, whereas the addition of lag schedules of reinforcement and prompting to training multiple exemplars resulted in appropriate and variable responding that exceeded baseline levels. Use of lag schedule of reinforcement in conjunction with prompts was more effective than multiple exemplar training in isolation for increasing appropriate variability of social skills.


Fine-needle aspiration biopsy of cold thyroid nodules.
This study analyzes the results of fine-needle aspiration biopsy (FNAB) of hypofunctioning thyroid nodules performed by one physician. There were 68 patients (age range, 20 to 73 years) with 83 aspirations; 30 were interpreted as positive for neoplasm (adenoma or carcinoma), 43 were negative, and ten (12%) were technically unsatisfactory. Thyroidectomy was performed on 25 patients who had positive aspirates. Subsequent morphologic study showed that 13 patients had carcinomas, ten had adenomas, and two had adenomatoid nodules (false-positive rate of FNAB for neoplasms was 8%). One of three thyroidectomy patients with negative preoperative aspirates had a carcinoma and two had adenomas (estimated minimal false-negative rate of FNAB was 9%). Nineteen patients who underwent thyroidectomies had dynamic radioisotopic thyroid angiography. There was no correlation between the pattern of vascularity and the type of neoplasm. Ultrasound (US) study was performed on 17 patients. Both adenoma and carcinoma can be solid or partially cystic. Although approximately 33% of the nodules initially diagnosed by FNAB as follicular or papillary neoplasms had different interpretations on subsequent examination of thyroidectomy specimens, 93% of the patients selected to be operated on had either adenoma or carcinoma. Thus, in this series, FNAB of cold thyroid nodules gave more useful diagnostic information than nodule size, dynamic radioisotopic scan, or US studies.


Antimicrobial peptides: Application informed by evolution.
Antimicrobial peptides (AMPs) are essential components of immune defenses of multicellular organisms and are currently in development as anti-infective drugs. AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. However, if AMPs are to be used clinically, it is crucial to understand their natural biology in order to lessen the risk of collateral harm and avoid the crisis of resistance now facing conventional antibiotics.


A specific alkaline phosphatase from Saccharomyces cerevisiae with protein phosphatase activity.
In this paper, specific PHO13 alkaline phosphatase from Saccharomyces cerevisiae was demonstrated to possess phosphoprotein phosphatase activity on the phosphoseryl proteins histone II-A and casein. The enzyme is a monomeric protein with molecular mass of 60 kDa and hydrolyzes p-nitrophenyl phosphate with maximal activity at pH 8.2 with strong dependence on Mg2+ ions and an apparent Km of 3.6 x 10(-5) M. No other substrates tested except phosphorylated histone II-A and casein were hydrolyzed at any significant rate. These data suggest that the physiological role of the p-nitrophenyl phosphate-specific phosphatase may involve participation in reversible protein phosphorylation. 1988 Federation of European Microbiological Societies.


On the cyclotron resonance model of ion transport.
The cyclotron-resonance model, which has been suggested as an explanation of a purported enhancement of transport of ions through the membranes of cells exposed to weak, low-frequency-modulated RF fields, is shown to be inconsistent with basic physical principles. Under the conditions of the model, in which the ions are presumed to circulate under the constraint of the earth's magnetic field, the radii of gyration of the ions would approximate 50 m and, thus, are much larger than the cells. Moreover, from general considerations, the collision-damping time of such ions is expected to be less than 10(-10) s, much smaller than the times of the order of 10(-2) s, shown to be necessary if the conditions for low-frequency resonance are to be satisfied.


Lower Background Infusion of Oxycodone for Patient-Controlled Intravenous Analgesia, Combined with Ropivacaine Intercostal Nerve Block, in Patients Undergoing Thoracoscopic Lobectomy for Lung Cancer: A Randomized, Double-Blind, Controlled Clinical Trial.
To compare the efficacy of a lower dose background infusion of oxycodone for patient-controlled intravenous analgesia (PCIA) with the conventional dose, following intercostal nerve block, for the management of postoperative pain in patients undergoing thoracoscopic lobectomy for lung cancer. This was a prospective, single-center, randomized, parallel-group, double-blind, controlled clinical trial. In total, 155 patients scheduled for elective radical lobectomy via video-assisted thoracoscopy were recruited from December 2018 to July 2019, of whom 140 were ultimately included in the study population. Patients were randomized to receive either oxycodone 0.25 mg/h (low-dose group, n=70) or oxycodone 0.5 mg/h (control group, n=70) as a background infusion for PCIA, following ropivacaine intercostal nerve block, for postoperative pain management. The primary endpoints were rest and dynamic visual analogue scale (VAS) scores within 72 h of the operation. The secondary endpoints were patient satisfaction scores, consumption of postoperative analgesics, times of patient-controlled analgesia (PCA), and adverse events. All 140 enrolled patients completed the study requirements and were included in the final analysis. The rest and dynamic VAS scores at 4 h, 24 h, 48 h, and 72 h postoperative were comparable between the low-dose group and the control group (P>0.05). However, the low-dose group had statistically significantly higher patient satisfaction scores (P<0.001) and lower postoperative analgesic consumption (P<0.001) as well as lower incidence of nausea and vomiting (P<0.05). The times of PCA was not statistically significantly different between the two groups, and no serious adverse events occurred in either group (P>0.05). A low-dose background infusion of oxycodone for postoperative PCIA can achieve a comparable analgesic effect to the conventional dose after thoracoscopic lobectomy for lung cancer. Furthermore, the low-dose regimen was associated with reduced consumption of oxycodone and increased patient satisfaction.


[Incidence of influenza virus infection in black-headed gulls].
Two strains of influenza A viruses were isolated in 1978 from tracheal washings of 18 nestlings of black-headed gulls examined for influenza. Three strains of influenza A viruses were isolated in 1979 from 55 gull embryos collected in the same colony, the isolates being similar in their antigenic characteristics with the influenza virus isolated from a gull nestling in 1978. This confirms the possibility of simultaneous circulation of antigenically different variants of influenza A virus among birds in the same colony and transoviral transmission of virus to the offsprings.


Cervical ranulas.
Cervical ranulas, known also as plunging or burrowing ranulas, are an outcome of extravasated sublingual gland mucin that has gained access to the soft tissues of the neck. These pseudocystic lesions may be localized or extensive, and they require surgical excision of the sublingual gland for effective management.