Cell replication in the arterial wall: activation of signaling pathway following in vivo injury.
This study examined intracellular signal events of arterial cells following balloon catheter injury to rat carotid artery. Within 30 minutes, a marked increase in extracellular signal-regulated kinase-1/2 (ERK1/2) activity was observed. This activity remained elevated for 12 hours but had decreased to control levels by day 1. No increase in ERK1/2 was detected at any later times. Injection of anti-fibroblast growth factor 2 antibody (60 mg i.v.) significantly inhibited the activation of ERK1/2 at 30 minutes after the injury. PD98059 (80 micromol/L), a selective inhibitor of mitogen-activated protein kinase/ERK kinase-1 (MEK1), decreased ERK1/2 activity in injured arteries and also reduced the medial cell replication. In contrast, PD98059 did not block the intimal cell replication at day 8. Mitogen-activated protein kinase phosphatase-1 (MKP-1) was expressed within hours after injury but only weakly at later times; MKP-1 was again expressed after 7 and 14 days. The expression of MKP-1 was associated with an activation of c-Jun amino-terminal kinase. Injury to the arterial wall also stimulated the activity of p70 S6 kinase from 30 minutes to 12 hours, suggesting an alternative pathway in mitogenic signaling of early cell replication. These findings demonstrate that fibroblast growth factor 2-induced ERK1/2 activation promotes medial cell replication after balloon injury; however, signaling of intimal cell replication may not be linked to the MEK1-dependent ERK pathway.


Granger causality analysis reveals distinct spatio-temporal connectivity patterns in motor and perceptual visuo-spatial working memory.
We employed spectral Granger causality analysis on a full set of 56 electroencephalographic recordings acquired during the execution of either a 2D movement pointing or a perceptual (yes/no) change detection task with memory and non-memory conditions. On the basis of network characteristics across frequency bands, we provide evidence for the full dissociation of the corresponding cognitive processes. Movement-memory trial types exhibited higher degree nodes during the first 2 s of the delay period, mainly at central, left frontal and right-parietal areas. Change detection-memory trial types resulted in a three-peak temporal pattern of the total degree with higher degree nodes emerging mainly at central, right frontal, and occipital areas. Functional connectivity networks resulting from non-memory trial types were characterized by more sparse structures for both tasks. The movement-memory trial types encompassed an apparent coarse flow from frontal to parietal areas while the opposite flow from occipital, parietal to central and frontal areas was evident for the change detection-memory trial types. The differences among tasks and conditions were more profound in α (8-12 Hz) and β (12-30 Hz) and less in γ (30-45 Hz) band. Our results favor the hypothesis which considers spatial working memory as a by-product of specific mental processes that engages common brain areas under different network organizations.


[Robert Wartenberg: the neurologist, the teacher, and the man].
Wartenberg was born in 1887 in Grodno, old Lithuania (present-day Belarus). He received his medical degree from the University of Rostock in 1919, and worked at the University of Freiburg until 1935, when he immigrated to the United States to escape Nazi Germany. He then worked at the University of California, San Francisco, and was appointed Clinical Professor of Neurology in 1952. He died of a heart illness in 1956. Wartenberg wrote more than 150 papers on clinical neurology in German and English, especially on reflexes and signs. His books, "Examination of Reflex" and "Diagnostic Tests in Neurology" were translated into many languages, including Japanese. His contribution to the study of reflexes includes Wartenberg's reflex of the thumb, head dropping test in Parkinson's disease, necessity of differentiating abdominal muscle and abdominal skin muscle reflexes, and many others. He had knowledge, skill, art and ability enough to translate difficult problems into tangible methods of diagnosis and treatment. He tried to diagnose and treat patients quickly, with minimum laboratory tests, and avoided invasive tests and expense of time and money. His efforts to provide patients with the best treatment in terms of time, safety, and cost, is the essence of medicine and is still worth practicing in modern neurology using advanced technology.


Severity staging by early features of age-related maculopathy exhibits weak relationships with functional deficits on SWS grating acuity.
To examine the relationship between short-wavelength-sensitive (SWS) resolution acuity and epidemiologically defined stages of early age-related maculopathy (ARM). Subjects consisted of 88 adults aged 51 to 87 years. Psychophysical testing was undertaken in only one eye of each subject (the study eye). All study eyes had a LogMAR acuity of 0.30 (20/40 Snellen) or better. SWS and achromatic grating resolution acuity were measured at 6 degrees eccentricity from the fovea. Stereoscopic color fundus photographs centered on the macula were taken on both eyes of each subject and were graded using the Wisconsin Age-Related Maculopathy Grading System (WARMGS). After grading, features of ARM were combined to assign a severity stage from 0 to 5 using the methods described by the Rotterdam Eye Study. Relationships between visual function, study eye ARM stage, and fellow eye status were examined with the use of standard statistical analysis. Although SWS resolution acuity was significantly reduced in eyes classified as having any ARM compared with eyes classified as having no ARM (P = 0.002), there was no relationship between the severity of functional deficits and the morphologic severity from stage 1 to stage 4. On reassigning subject eyes to a revised severity staging (stage 0, stages 1 to 4 combined, and stage 5), SWS acuity was significantly different among these three groups (P < 0.001). No significant relationship was found between achromatic resolution acuity and ARM staging. The status of the fellow eye (advanced macular degeneration present or absent) was not significantly related to visual function in the study eye. Significant functional deficits in SWS resolution acuity were found in eyes with ARM features, but the severity of functional loss did not correlate well with the currently accepted method of assigning a morphologic severity stage. Longitudinal studies may reveal further information on the relationships between functional deficits, ARM status, disease progression, and outcome.


Efficacy and Safety of Cryoballoon Ablation in Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction - A Multicenter Study.
Second-generation cryoballoon (CB2)-based pulmonary vein isolation (PVI) has demonstrated encouraging results in the treatment of atrial fibrillation (AF). This study sought to assess data on the safety, efficacy and clinical success of CB2-based PVI in patients with heart failure (HF) and reduced ejection fraction (HFrEF).Methods and Results:CB2-based PVI was performed in 551 consecutive patients in 3 highly experienced EP centers. Patients with HF and LVEF ≤40% were included (HFrEF group, n=50/551, 9.1%). Data were compared with propensity score-matched patients without HF and preserved left ventricular EF (LVEF) (n=50, control group). The median LVEF was HFrEF: 37% (35, 40) and control: 55% (55, 55), P<0.0001. Major periprocedural complications were registered in 4/50 (8%, HFrEF group) and 3/50 (6%, control group), P=0.695. The 12-month freedom from AF recurrence was 73.1% (95% confidence interval (CI): 61-88, HFrEF group) and 72.6% (95% CI: 61-87, control group), P=0.25. NYHA class decreased from 2.4±0.8 (baseline) to 1.7±0.8 at 12-month follow-up (P<0.0001). LVEF improved from a median of 37% (35, 40) prior to ablation to a median of 55% (40, 55), P<0.0001. CB2-based PVI in patients with HFrEF appeared to be safe, was associated with comparable periprocedural complications and showed promising clinical success rates equal to those for patients with preserved LVEF. NYHA class and LVEF significantly improved at 12-month follow-up.


Activation of antioxidant defenses in response to freezing in freeze-tolerant painted turtle hatchlings.
Hatchlings of the painted turtle, Chrysemys picta marginata can endure long-term freezing of their extracellular body fluids. We hypothesized that freezing survival would include adaptive up-regulation of antioxidant defenses to deal with ischemia-reperfusion injuries associated with the freeze-thaw cycle. A number of antioxidant enzymes are under the control of the NF-E2 related factor 2 (Nrf2) transcription factor including members of the glutathione S-transferase (GST) and aldo-keto reductase (AKR) families. RT-PCR and Western immunoblotting were used to measure changes in transcript and protein levels in response to 5-h freezing exposure of hatchlings. Transcript levels of Nrf2 increased in turtle brain, liver, and muscle by 1.5- to 2-fold, and protein levels increased in the brain and muscle by 1.6- to 2.3-fold in response to freezing. GSTs responded strongly to freezing in turtle brain with amounts of GSTP1, M1, K1, and A3 elevated by 1.5- to 2.4-fold. GSTM3 and T1 rose by 1.8- to 2.3-fold in gut, whereas reduced levels of GSTP1, M1, M3, and K1 were found in livers of frozen animals. Levels of the AKR1B4 isozyme rose 2.1-fold during freezing in brain. Freezing triggered tissue-specific changes in the antioxidant defenses in C.pictamarginata organs. These data indicate that activation of an antioxidant response is an important aspect of natural freeze tolerance in turtles.


A phase I trial of immediate postoperative intraperitoneal floxuridine and leucovorin plus systemic 5-fluorouracil and levamisole after resection of high risk colon cancer.
The purpose of this study was to evaluate the toxicity of immediate postoperative intraperitoneal (IP) floxuridine (FUdR) and leucovorin (LV) after resection of high risk colon cancer, and to determine the appropriate dose of intravenous fluorouracil (FU) plus levamisole during concurrent intraperitoneal therapy. The authors conducted a tertiary referral Comprehensive Cancer Center Phase I Trial in patients with resected colon cancer at high risk for recurrence. After resection of all gross disease, intraperitoneal treatment was administered twice daily for 3 days every 2 weeks for three cycles (Days 1-3, 15-17, 29-31). Intravenous FU daily for 5 days was administered on days 29-33 concurrently with the third cycle of intraperitoneal therapy. Fluorouracil doses during the last cycle of intraperitoneal therapy were escalated; intraperitoneal FUdR and LV doses and weekly intravenous FU doses (starting on Day 58) were fixed. Twenty-six patients with resected high risk colon cancer were treated. Three had Dukes' B2, 16 Dukes' C, and 7 Dukes' D (M1) resected tumors. Intraperitoneal therapy was well tolerated with no increase in operative morbidity and no operative mortality. Two patients had > or = Grade 3+ toxicity during IP therapy alone. There were no treatment related deaths. During concurrent intraperitoneal and intravenous chemotherapy, the maximum tolerated dose of FU was 300 mg/m2/day for 5 days. The recommended dose for Phase II or III trials is 200 mg/m2/day for 5 consecutive days. Pharmacokinetic analysis indicated that using the doses used in this trial, measurable systemic concentrations of FUdR and LV were obtained during IP therapy. This may have contributed to observed toxicity with intravenous FU doses of 300-400 mg/m2. With a median duration of follow-up of 18 months, four patients had recurrence of disease. No peritoneal recurrences have been noted to date. Immediate postoperative IP FUdR and LV are well tolerated after resection of high risk colon cancer. The recommended dose of intravenous FU beginning on Day 29 (concurrent with the last dose of IP therapy) is 5FU 200 mg/m2 for 5 consecutive days. The remaining year of adjuvant fluorouracil and levamisole can be administered with standard dose attenuation. Although follow-up is short, the lack of recurrent peritoneal metastases is encouraging. Additional trials with this approach are warranted in patients with high risk colorectal cancer.


Lipid storage disease: Part III. Ultrastructural evaluation of cultured fibroblasts in sphingolipidoses.
For the purpose of evaluating electron microscopy of tissue culture in making the diagnosis of sphingolipidoses, an ultrastructural study was made on the cultured fibroblasts from 23 patients with the disorders. The characteristic cytoplasmic inclusions were observed in the cultured cells of Fabry disease, Tay-Sachs disease, Sandhoff disease, generalized gangliosidosis, Niemann-Pick disease, metachromatic leukodystrophy, and multiple sulfatase deficiency, and differ in fine structure with these diseases. All these cytoplasmic inclusions were surrounded by a single limiting membrane and enzyme cytochemically showed acid phosphatase activity, indicating their lysosomal origin. Ultrastructurally, the cytoplasmic inclusions showed pleomorphic osmiophilic inclusions in Fabry disease, membranous cytoplasmic bodies (MCB) in Tay-Sachs disease and Sandhoff disease, MCB and vacuolar inclusions containing finely reticulogranular materials in generalized gangliosidosis, myelin-like inclusions in Niemann-Pick disease, concentric lamellar inclusions in metachromatic leukodystrophy, and polymorphic cytoplasmic inclusions in multiple sulfatase deficiency. In the heterozygous carriers of Fabry disease, pleomorphic osmiophilic inclusions were also detected. However, any specific inclusions were not detectable in the cultured fibroblasts of Gaucher disease and Krabbe disease. Availability of electron microscopy in the cultured fibroblasts of sphingolipidoses is discussed.


Brain structural correlates of depressive comorbidity in obsessive-compulsive disorder.
The high comorbidity of obsessive-compulsive disorder (OCD) with major depressive disorder (MDD) suggests common neurobiological substrates. We assessed the contribution of lifetime MDD to brain structural alterations in OCD using magnetic resonance imaging. OCD patients with (n=33) or without (n=39) lifetime MDD, and 72 control subjects were assessed. Comparative region of interest (ROI) analyses assessed the contribution of lifetime MDD to gray matter volume alterations in OCD patients. Interregional correlations of gray matter volume were also examined and voxelwise analyses were performed to identify alterations in other brain regions. OCD patients with lifetime MDD showed a larger reduction of medial orbitofrontal cortex (mOFC) gray matter volume. Both OCD groups showed distinct correlations of mOFC gray matter volume with other relevant brain regions. For patients with MDD, this involved the medial frontal gyrus, and right insula and amygdala regions, whereas for those OCD patients without MDD, the rostral anterior cingulate cortex was involved. Our findings support existing evidence suggesting a non-specific involvement of mOFC alterations in a range of neuropsychiatric disorders. Nevertheless, volume reduction in this region, together with an abnormal pattern of interregional correlations with other emotion-relevant brain areas, may contribute to explain the diathesis for MDD comorbidity in OCD.


Characterization of immunogenic properties of haptenated liposomal model membranes in mice. II. Induction of delayed-type hypersensitivity.
This paper describes the induction of delayed-type hypersensitivity (DH) in the mouse and guinea-pig to haptenated liposomes. The tripeptide-enlarged hapten 3-(p-azobenzenearsonate)-N-acetyl-L-tyrosylglycylglycine (A) was coupled to phosphatidylethanolamine (PE) and incorporated into liposomal membranes (A-PE-liposomes). In mice DH was measured as footpad swelling and in guinea pigs by skin testing. To induce hapten A-specific DH in mice with A-PE-liposomes the application of the cationic, surface-active lipid, dimethyl dioctadecyl ammonium bromide (DDA) was necessary. The use of Freund's complete adjuvant (FCA) did not result in the induction of DH to hapten A. In guinea-pigs, however, FCA and DDA had equally good adjuvant properties in the induction of DH. The time course of the DH and the optimal time interval between immunization and elicitation were determined for the mouse system. Also, the effect of dose and epitope density was studied in that system. Cyclophosphamide treatment, before immunizing mice with A-PE-liposomes and DDA, resulted in greatly impaired DH, probably caused by the short lifetime of the integrity of liposomes after intracutaneous administration to mice. The results make it very likely that presentation of hapten A in a liposomal or micellar structure is required to induce a cellular immune response to this hapten in mice.


Cellular protein GLTSCR2: A valuable target for the development of broad-spectrum antivirals.
Viral infection induces translocation of the nucleolar protein GLTSCR2 from the nucleus to the cytoplasm, resulting in attenuation of the type I interferon IFN-β. Addressing the role of GLTSCR2 in viral replication, we detect that knocking down GLTSCR2 by shRNAs results in significant suppression of viral replication in mammalian and chicken cells. Injection of chicken embryo with the GLTSCR2-specific shRNA-1370 simultaneously or 24 h prior to infection with Newcastle disease virus (NDV) substantially reduces viral replication in chicken embryo fibroblasts. Injection of shRNA-1370 into chicken embryo also reduces the replication of avian influenza virus (AIV). In contrast, GLTSCR2-derived protein G4-T, forming α-helical dimers, increases replication of seven various DNA and RNA viruses in cells. Our studies reveal that alteration of the function of cellular GLTSCR2 plays a role in supporting viral replication. GLTSCR2 should be seriously considered as a therapeutic target for developing broad spectrum antiviral agents to effectively control viral infection.


Sensitizing effect of early adversity on depressive reactions to later proximal stress: Moderation by polymorphisms in serotonin transporter and corticotropin releasing hormone receptor genes in a 20-year longitudinal study.
Previous research supports gene-environment interactions for polymorphisms in the corticotropin hormone receptor 1 gene (CRHR1) and the serotonin transporter gene linked polymorphic region (5-HTTLPR) in predicting depression, but it has rarely considered genetic influences on stress sensitization processes, whereby early adversities (EA) increase depressive reactivity to proximal stressors later in life. The current study tested a gene-environment-environment interaction (G × E × E; specifically, gene-EA-proximal stress interaction) model of depression in a 20-year longitudinal study. Participants were assessed prospectively for EA up to age 5 and recent chronic stress and depressive symptoms at age 20 and genotyped for CRHR1 single nucleotide polymorphism rs110402 and 5-HTTLPR. EA predicted stronger associations between recent chronic stress and depression, and the effect was moderated by genes. CRHR1 A alleles and 5-HTTLPR short alleles were associated with greater stress sensitization (i.e., greater depressive reactivity to chronic stress for those also exposed to high levels of EA). The results are consistent with the notion that EA exposure results in neurobiological and cognitive-emotional consequences (e.g., altered hypothalamic-pituitary-adrenal axis functioning), leading to emotional distress in the face of recent stressors among those with certain genetic characteristics, although further research is needed to explore explanatory mechanisms.


Noninvasive thermometry using hyperfine-shifted MR signals from paramagnetic lanthanide complexes.
MR thermometry techniques based on the strong water 1H signal provide high spatial and temporal resolution and have shown promise for applications such as laser surgery and RF ablation. However, these techniques have low temperature sensitivity for hyperthermia applications and are greatly influenced by local motion and susceptibility variations. 1H NMR signals from paramagnetic lanthanide complexes of Pr3+, Yb3+ and Tm3+ show up to 300-fold stronger temperature dependence compared to the water 1H signal. In addition, 1H chemical shifts of many of these complexes are insensitive to other factors such as the concentration of the paramagnetic complex, pH, [Ca2+], and the presence of plasma macro-molecules and ions. Applications of lanthanide complexes for temperature measurement in intact animals and the feasibility of mapping temperatures in phantoms have been demonstrated. Among all the lanthanide complexes examined so far, thulium 1, 4, 7, 10-tetramethyl-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetate (TmDOTMA-) appears to be the most attractive for in vivo MR thermometry. The 1H signal from the methyl groups on this complex is relatively intense because of 12 equivalent protons and provides high temperature sensitivity because of the large paramagnetic shifts induced by thulium. The possibility of imaging TmDOTMA2--in intact animals at physiologically safe concentrations has recently been demonstrated. Overall, MR thermometry methods based on hyperfine-shifted MR signals from paramagnetic lanthanide complexes appear promising for animal applications, but further studies relating to acceptable dose and signal-to-noise ratio are necessary before clinical use.


Chromosomal mapping of five highly conserved murine homologues of the Drosophila RING finger gene seven-in-absentia.
Seven-in-absentia (sina) is epistatic to all other known genes in the sevenless-ras signaling pathway, which mediates R7 photoreceptor formation in the Drosophila eye. The murine genome contains several closely related sina homologues (Siah1A-D, Siah2) that are also likely to participate in ras signaling. As part of a genetic and biochemical analysis of the mammalian Siah genes, we have used gene-specific probes to map the chromosomal positions of each family member. Here we report their chromosomal positions in relation to a number of known mouse mutations and also describe an analysis of the human Siah genes. By comparing the complexity of the Siah genes in these two mammalian species we have gained further insight into which members of this murine multigene family are likely to be functional.


Isobutanol tolerance and production of Saccharomyces cerevisiae can be improved by engineering its TATA-binding protein Spt15.
Low isobutanol tolerance of Saccharomyces cerevisiae limits its application in isobutanol fermentation. Here, we used global transcription machinery engineering to screen mutants with higher isobutanol tolerance and elevated isobutanol titres. TATA-binding protein Spt15 was used as the target of global transcription machinery engineering for improvement of such complex phenotypes. A random mutagenesis library of S. cerevisiae TATA-binding protein Spt15 was constructed and subjected to screening under isobutanol stress. A mutant strain (denoted as spt15-3) with improved isobutanol tolerance was identified. There were three mutations of Spt15 in strain spt15-3, including deletion of A at position -132 nt upstream of initiation codon, insertion of G at position -65 nt upstream of initiation codon and a synonymous mutation at position 315 nt (T → C) downstream of initiation codon. We then metabolically engineered isobutanol synthesis in strains harbouring plasmids YCplac22 containing these Spt15 mutations. Delta integration was used to overexpress ILV3 gene, and 2μ plasmids carrying PGK1p-ILV2 and PGK1p-ARO10 were used to overexpress ILV2 and ARO10 genes. After 24-h micro-aerobic fermentation, Engi-3 produced 0·556 g l-1 isobutanol, which was 404% and 25·3% greater than isobutanol produced by control Engi-1 and engineered Engi-2, respectively. After 28 h, Engi-4 produced 0·459 g l-1 isobutanol, which was 315% and 3·2% greater than isobutanol produced Engi-1 and Engi-2, respectively. RNA-Seq-based transcriptome analysis shows that mutations of Spt15 in strain spt15-3 increased the expression of SPT15. Meanwhile, compared with strain Engi-3, the spt15-3 mutation downregulated the expression of genes involved in the TCA cycle and glyoxylic acid cycle, but increased the expression of genes related to cell stability. This work demonstrates that isobutanol tolerance and production of S. cerevisiae can be improved by engineering its TATA-binding protein Spt15. This study clarified the molecular mechanisms regulating isobutanol production and tolerance in S. cerevisiae.


Health Related Quality of Life and Its Socio-Demographic Determinants among Iranian Elderly People: a Population Based Cross-Sectional Study.
Introduction: In the stage of demographic transition, the rate of elderly is increasing and their health condition is a matter of concern. Thus, the objective of this study was to investigate the health related quality of life (QoL) and the associated socio-demographic determinants among Iranian elderly people. Methods: We conducted a cross-sectional study with a representative samples of 750 elderly people whom community dwelling in urban area of Babol, in the north of Iran. In a household survey, the demographic data were collected and the health related QoL was assessed with a validated standard short form questionnaire (SF-36). The multiple linear regression analysis was performed to determine the demographic characteristics in predicting QoL using SPSS ver 13. Results: The overall mean (SD) scores of QoL was 62.4(17.2) for men and 51.2 (17.9) for women. The mean scores of QoL in all dimensions in men had significantly higher than women. The adjusted regression coefficient of gender, age, educational level, being couple were significant on overall scores of QoL. Aging is inversely associated while male gender and education at high school or higher and being couple are positively associated in prediction of overall scores of QoL. Conclusion: The findings indicate that the health related QoL is rather poor in old people particular in women, elderly with low education level and being single. Therefore, healthcare policy makers should consider an urgent health interventional program among elderly people at present stage of demographic transition with emphasis on high risk demographic profiles.


Games people play-toward an enactive view of cooperation in social neuroscience.
The field of social neuroscience has made considerable progress in unraveling the neural correlates of human cooperation by making use of brain imaging methods. Within this field, neuroeconomic research has drawn on paradigms from experimental economics, such as the Prisoner's Dilemma (PD) and the Trust Game. These paradigms capture the topic of conflict in cooperation, while focusing strongly on outcome-related decision processes. Cooperation, however, does not equate with that perspective, but relies on additional psychological processes and events, including shared intentions and mutually coordinated joint action. These additional facets of cooperation have been successfully addressed by research in developmental psychology, cognitive science, and social philosophy. Corresponding neuroimaging data, however, is still sparse. Therefore, in this paper, we present a juxtaposition of these mutually related but mostly independent trends in cooperation research. We propose that the neuroscientific study of cooperation could benefit from paradigms and concepts employed in developmental psychology and social philosophy. Bringing both to a neuroimaging environment might allow studying the neural correlates of cooperation by using formal models of decision-making as well as capturing the neural responses that underlie joint action scenarios, thus, promising to advance our understanding of the nature of human cooperation.


Photodynamic therapy for stage I and II non-small cell lung cancer: A SEER-Medicare analysis 2000-2016.
We analyzed mortality (all-cause and lung cancer-specific) and time to follow-up treatment in stage I and II non-small cell lung cancer (NSCLC) patients treated with photodynamic therapy (PDT) compared with ablation therapy and radiation therapy.From Surveillance, Epidemiology, and End Results-Medicare linked data, patients diagnosed with stage I and II NSCLC between 2000 and 2015 were identified. Outcomes were mortality (overall and lung cancer-specific) and time to follow-up treatment. We analyzed mortality using Cox proportional hazard models. We used generalized linear model to assess time to follow-up treatment (PDT and ablation groups). Models were adjusted for inverse probability weighted propensity score.Of 495,441 NSCLC patients, 56 with stage I and II disease received PDT (mono or multi-modal), 477 received ablation (mono or multi-modal), and 14,178 received radiation therapy alone. None from PDT group had metastatic disease (M0) and 70% had no nodal involvement (N0). Compared with radiation therapy alone, PDT therapy was associated with lower hazard of overall (hazard ratio = 0.56, 95% CI = 0.39-0.80), and lung cancer-specific mortality (hazard ratio = 0.64, 95% CI = 0.43-0.97). Unadjusted mean time to follow-up treatment was 70days (standard deviation = 146) for PDT group and 67 days (standard deviation = 174) for ablation group. Compared with ablation, PDT was associated with an average increase of 125days to follow-up treatment (P = .11).Among stage I and II NSCLC patients, PDT was associated with improved survival, compared with radiation alone; and longer time to follow-up treatment compared with ablation. Currently, PDT is offered in various combinations with surgery and radiation. Larger studies can investigate the efficacy and effectiveness of these combinations.


Cold-active lipolytic activity of psychrotrophic Acinetobacter sp. strain no. 6.
A lipolytic bacterium, strain no. 6, was isolated from Siberian tundra soil. It was a gram-negative coccoid rod capable of growing at 4 degrees C but not at 37 degrees C and was identified as a psychrotrophic strain of the genus Acinetobacter. Strain no. 6 extracellularly produced a lipolytic enzyme that efficiently hydrolyzed triglycerides such as soybean oil during bacterial growth even at 4 degrees C; it degraded 60% of added soybean oil (initial concentration, 1% w/v) after cultivation in LB medium at 4 degrees C for 7 d. Thus, the bacterium is potentially applicable to in-situ bioremediation or bioaugumentation of fat-contaminated cold environments. We partially purified the lipolytic enzyme from the culture filtrate by acetone fractionation and characterized it. The enzyme preparation contained a single species of cold-active lipase with significant activity at 4 degrees C, which was 57% of the activity at the optimum temperature (20 degrees C). The enzyme showed a broad specificity toward the acyl group (C8-C16) of substrate ethyl esters.


Dopamine and opioids inhibit synaptic outputs of the main island of the intercalated neurons of the amygdala.
Neural circuits in the amygdala are important for associating the positive experience of drug taking with the coincident environmental cues. During abstinence, cue re-exposure activates the amygdala, increases dopamine release in the amygdala and stimulates relapse to drug use in an opioid dependent manner. Neural circuits in the amygdala and the learning that underlies these behaviours are inhibited by GABAergic synaptic inhibition. A specialised subtype of GABAergic neurons in the amygdala are the clusters of intercalated cells. We focussed on the main-island of intercalated cells because these neurons, located ventromedial to the basolateral amygdala, express very high levels of dopamine D1-receptor and μ-opioid receptor, release enkephalin and are densely innervated by the ventral tegmental area. However, where these neurons project to was not fully described and their regulation by opioids and dopamine was incomplete. To address this issue we electrically stimulated in the main-island of the intercalated cells in rat brain slices and made patch-clamp recordings of GABAergic synaptics from amygdala neurons. We found that main-island neurons had a strong GABAergic inhibitory output to pyramidal neurons of the basolateral nucleus and the medial central nucleus, the major output zones of the amygdala. Opioids inhibited both these synaptic outputs of the intercalated neurons and thus would disinhibit these target zones. Additionally, dopamine acting at D1-receptors inhibited main-island neuron synapses onto other main-island neurons. This data indicates that the inhibitory projections from the main-island neurons could influence multiple aspects of addiction and emotional processing in an opioid and dopamine dependent manner.


Up-regulation of tau, a brain microtubule-associated protein, in lens cortical fractions of aged alphaA-, alphaB-, and alphaA/B-crystallin knockout mice.
Alpha-crystallin is expressed at high levels in the lens in a complex of alphaA- and alphaB-crystallin subunits in 3:1 molar ratios, and is known to maintain the solubility of unpolymerized tubulin and enhance the resistance of microtubules to depolymerization, but its effect on proteins classically associated with microtubule stability (microtubule associated proteins) in the lens is unknown. In the present study we examined the expression of the brain microtubule associated protein tau in lenses of alpha-crystallin gene knockout mice. Quantitative RT-PCR, immunoblotting, cryo-immunoelectron microscopic and immunohistochemical methods were used to characterize the expression of tau in the lenses of alphaA(-/-)-, alphaB(-/-)-, and alphaA/B(-/-)-crystallin mice. Immunoreactivity to tau, a 45-66 kDa brain microtubule associated protein that has been best characterized in neurons and neuronal pathologies, was uniquely upregulated in lens cortical fiber cells with aging and was associated with the microtubule fraction of alphaA(-/-)-, alphaB(-/-)-, and alphaA/B(-/-)-crystallin mouse lenses, but was undetectable in wild type lenses. Quantitative RT-PCR analysis further showed an upregulation of tau transcripts in alphaA(-/-)- and alphaA/B(-/-)-crystallin lenses. Brain microtubule fractions served as a positive control for tau in these experiments. An increase in phosphorylation of tau was detected in alphaA(-/-)- and alphaB(-/-)-crystallin brain proteins. Although tau aggregation and alphaB-crystallin expression have been shown to increase in neurodegenerative diseases, surprisingly tau expression increases in the alpha-crystallin knockout lenses, suggesting that alphaA- and alphaB-crystallins are potentially important regulators of tau expression in lens.


YOLOv5s-gnConv: detecting personal protective equipment for workers at height.
Falls from height (FFH) accidents can devastate families and individuals. Currently, the best way to prevent falls from heights is to wear personal protective equipment (PPE). However, traditional manual checking methods for safety hazards are inefficient and difficult to detect and eliminate potential risks. To better detect whether a person working at height is wearing PPE or not, this paper first applies field research and Python crawling techniques to create a dataset of people working at height, extends the dataset to 10,000 images through data enhancement (brightness, rotation, blurring, and Moica), and categorizes the dataset into a training set, a validation set, and a test set according to the ratio of 7:2:1. In this study, three improved YOLOv5s models are proposed for detecting PPE in construction sites with many open-air operations, complex construction scenarios, and frequent personnel changes. Among them, YOLOv5s-gnconv is wholly based on the convolutional structure, which achieves effective modeling of higher-order spatial interactions through gated convolution (gnConv) and cyclic design, improves the performance of the algorithm, and increases the expressiveness of the model while reducing the network parameters. Experimental results show that YOLOv5s-gnconv outperforms the official model YOLOv5s by 5.01%, 4.72%, and 4.26% in precision, recall, and mAP_0.5, respectively. It better ensures the safety of workers working at height. To deploy the YOLOv5s-gnConv model in a construction site environment and to effectively monitor and manage the safety of workers at height, we also discuss the impacts and potential limitations of lighting conditions, camera angles, and worker movement patterns.


Atrophy pattern in SCA2 determined by voxel-based morphometry.
We applied voxel-based morphometry, an indirect volumetric technique, to MRI volumes of patients carrying the spinocerebellar ataxia type 2 mutation to determine patterns of brain atrophy. Nine patients were compared to 27 controls matched for age, sex and handedness. An optimised voxel-based morphometry protocol was used for pre-processing to minimize systematic bias. We observed significant volume loss in the cerebellar hemispheres, vermis, pons, mesencephalon and thalamus. Also affected were several supratentorial areas such as the right orbito-frontal cortex, right temporo-mesial cortex and the primary sensorimotor cortex bilaterally. The volumetric changes of cerebellar hemispheres were inversely correlated to cerebellar symptoms rated by a cerebellar ataxia scale. Two mechanisms could contribute to the observed cortical atrophy. It could be either the result of primary supratentorial degeneration as part of the disease process and/or secondary atrophy due to cerebellar deafferentation.


Decreasing the duration of untreated illness for individuals with anorexia nervosa: study protocol of the evaluation of a systemic public health intervention at community level.
Anorexia nervosa (AN) is a mental disorder with grave burdens for affected individuals as well as for the healthcare system. One of the strongest predictors of a poor outcome is a long Duration of Untreated Illness (DUI), which is defined as the time between the onset of the disease and treatment initiation. Reducing the DUI is an important step to optimize care of individuals with AN. In order to achieve this aim, systemic public health interventions are necessary. Objective of this study is to evaluate a systemic public health intervention at Community level aiming to reduce the DUI in individuals with AN. The intervention includes the establishment of a network of health care professionals within the area of eating disorders (EDs), the development of an internet-based treatment guide, the presentation of informative short-films about EDs in cinemas and a corresponding poster campaign as well as a special outpatient clinic. For the evaluating study a pre-post between-subject design is chosen. The DUI, and the duration until first contact (DUC) with a health care professional, ED pathology as well as comorbidity are assessed before and after the systemic intervention is carried out. The study attempts to provide evidence of the effectiveness of an ED-related systematic public health intervention. Additionally, the study will lead to a better understanding of the DUI, which is essential in order to improve care of individuals with AN. Current Controlled Trials ISRCTN44979231 ; Registered 11 November 2011.


Exercise-induced saphenous vein graft spasm prevented by stenting.
Recurrence of anginal symptoms following coronary artery bypass surgery is usually secondary to graft closure or progression of native vessel disease. The present case demonstrates severe exercise-induced saphenous vein graft (SVG) spasm associated with transmural ischemia refractory to maximal vasodilator therapy. Symptoms resolved and exercise electrocardiography normalized following stenting of SVG regions demonstrating spasm. © 2017 Wiley Periodicals, Inc.


A simple rat model of in situ reversible obstructive jaundice in situ reversible obstructive jaundice model.
To develop a simple and reliable rat model of in situ reversible obstructive jaundice with low morbidity and mortality rates. Rats were divided into 4 groups with 8 rats each: the sham-operated (SH) group only underwent laparotomy, the control internal drainage (ID-C) group underwent choledochoduodenostomy, the new internal drainage (ID-N) group and the long-term internal drainage (ID-L) group underwent choledochocholedochostomy. Common bile duct ligation was performed in all the drainage groups 7 days before reversal procedures. All rats were sacrificed for samples 7 days after the last operation except rats of the ID-L group that survived 28 days before sacrifice. Body weight, liver function, histopathological changes, morbidity and mortality were assessed. One rat died and 2 rats had complications with tube blockage in the ID-C group. No death or complications occurred in the ID-N and ID-L groups. The drainage tube remained patent in the long-term observation ID-L group. Body weight showed no significant difference between the ID-C and ID-N groups after 7 days drainage. Liver function was not fully recovered in the ID-C and ID-N groups after 7 days drainage, but statistical differences were only observed in the ID-C group compared with the SH and ID-L groups. Periportal inflammation and bile duct proliferation showed severer in the ID-C group than in the ID-N group. The present study provided an efficient, simple, and reliable rat model that is especially suitable for long-term or consecutive studies of reversible obstructive jaundice.


Successful Treatment of Transplantation-associated Atypical Hemolytic Uremic Syndrome With Eculizumab.
We herein reported a 4-month-old boy with transplantation-associated atypical hemolytic uremic syndrome (TA-aHUS) who was successfully treated with eculizumab. The patient diagnosed with type 3 of familial hemophagocytic lymphohistiocytosis underwent cord blood transplantation. After transplantation, he developed TA-aHUS, but plasma exchanges were unsuccessful. We identified deletions in CFH-related gene 1 (del-CFHR1) by the multiplex ligation-dependent probe amplification testing procedure and CFH autoantibodies. Eculizumab has been administered to the patient, with a marked improvement being achieved in thrombocytopenia. He has been well except for the persistent microhematuria for a year after transplantation. Uncontrolled complement activation might be involved in the pathophysiology of TA-aHUS.


Analysis of the impact of traditional ethnic villages in Hani area on sustainable development.
Rapid economic development and accelerated urbanization have seriously affected the development of traditional ethnic villages in China. We used the minimum cumulative resistance (MCR) model based on land use, landscape pattern, and ecosystem service value (ESV) to evaluate the spatio-temporal dynamics of sustainable development in Hani traditional ethnic villages from 1995 to 2020. By analyzing changes in sustainability indicators in the Hani area and different buffer zones, this paper aims to assess the impact of ethnic villages in the Hani Area on sustainable development and provide recommendations for the sustainable development of traditional ethnic Hani villages. The results indicated that: (1) The area of construction land and landscape fragmentation in the Hani area significantly increased and the value of ecosystem services and levels of sustainable development decreased each year during the study period; (2) The area of cropland in the 2 km buffer zone of the traditional ethnic villages increased, the degree of landscape fragmentation, the value of ecosystem services, and the level of sustainable development were lower than in the 4 km buffer zone during the study period. This is due to population increases in traditional ethnic Hani villages, as well as the intensive reclamation of cropland, increased construction land, and landscape fragmentation. We suggest that the Hani should implement scientific land planning and management policies to protect the local ecosystem and realize the sustainable development of traditional ethnic Hani villages.


The molecular ecology of Microcystis sp. blooms in the San Francisco Estuary.
Harmful blooms of the cyanobacterium Microcystis sp. have become increasingly pervasive in the San Francisco Estuary Delta (USA) since the early 2000s and their rise has coincided with substantial decreases in several important fish species. Direct and indirect effects Microcystis blooms may have on the Delta food web were investigated. The Microcystis population was tracked for 2 years at six sites throughout the Delta using quantitative PCR. High-throughput amplicon sequencing and colony PCR sequencing revealed the presence of 10 different strains of Microcystis, including 6 different microcystin-producing strains. Shotgun metagenomic analysis identified a variety of Microcystis secondary metabolite pathways, including those for the biosynthesis of: aeruginosin, cyanopeptolin, microginin, microviridin and piricyclamide. A sizable reduction was observed in microbial community diversity during a large Microcystis bloom (H' = 0.61) relative to periods preceding (H' = 2.32) or following (H' = 3.71) the bloom. Physicochemical conditions of the water column were stable throughout the bloom period. The elevated abundance of a cyanomyophage with high similarity to previously sequenced isolates known to infect Microcystis sp. was implicated in the bloom's collapse. Network analysis was employed to elucidate synergistic and antagonistic relationships between Microcystis and other bacteria and indicated that only very few taxa were positively correlated with Microcystis.


[TUB9 polymorphism in the CFTR gene of cystic fibrosis patients, carriers, and healthy donors from the Moscow region. SSCP and restriction analyses].
Data on the screening of 266 non-delta F508 chromosomes (42 cystic fibrosis patients, 43 carriers, and 48 healthy donors from the Moscow region) for the presence of structural abnormalities within the tenth exon of the CFTR gene conducted by means of the single-stranded conformation polymorphism (SSCP) technique in nonisotope modification are presented. The method used made it possible to detect three SSCP variants, one of which was present in cystic fibrosis patients (23.8%) and carriers (9.3%), but not in healthy donors. Sequencing of the 5 amplified DNA fragments carrying this SSCP variant revealed an A-->G substitution in the 1525-61 position, which indicated the presence of TUB9 polymorphism with allele 1 in the homozygous state in all cases tested. The three SSCP variants described corresponded to the three allelic variants of TUB9 polymorphism as judged by MnlI restriction analysis of the amplified tenth exon sequence. The modified SSCP technique is also suitable for routine screening for the G542X, G55ID, and W1282X point mutations within the CFTR gene. The frequency distribution of polymorphic TUB9 marker alleles across the non-delta F508 chromosomes in the three studied groups were estimated. Homozygotes for the TUB9 allele 1 were shown to have identical GATT-TUB9-M470V haplotypes.


Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part II: A Scoping Review of Continuous Methods.
A scoping review of the literature was performed systematically on commonly described continuous autoregulation measurement techniques in adult traumatic brain injury (TBI) to provide an overview of methodology and comprehensive reference library of the available literature for each technique. Five separate small systematic reviews were conducted for each of the continuous techniques: pressure reactivity index (PRx), laser Doppler flowmetry (LDF), near infrared spectroscopy (NIRS) techniques, brain tissue oxygen tension (PbtO2), and thermal diffusion (TD) techniques. Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to December 2016), and reference lists of relevant articles were searched. A two-tier filter of references was conducted. The literature base identified from the individual searches was limited, except for PRx. The total number of articles using each of the five searched techniques for continuous autoregulation in adult TBI were: PRx (28), LDF (4), NIRS (9), PbtO2 (10), and TD (8). All continuous techniques described in adult TBI are based on moving correlation coefficients. The premise behind the calculation of these moving correlation coefficients focuses on the impact of slow fluctuations in either mean arterial pressure (MAP) or cerebral perfusion pressure (CPP) on some indirect measure of cerebral blood flow (CBF), such as: intracranial pressure (ICP), LDF, NIRS signals, PbtO2, or TD CBF. The thought is the correlation between a hemodynamic driving factor, such as MAP or CPP, and a surrogate for CBF or cerebral perfusion sheds insight on the state of cerebral autoregulation. Both PRx and NIRS indices were validated experimentally against the "gold standard" static autoregulatory curve (Lassen curve) at least around the lower threshold of autoregulation. The PRx has the largest literature base supporting the association with patient outcome. Various methods of continuous autoregulation assessment are described within the adult TBI literature. Many studies exist on these various indices, suggesting an association between their values and patient morbidity/death.


Analysis of reverse total shoulder joint forces and glenoid fixation.
Reverse total shoulder arthroplasty (rTSA) implants are intended to restore stability and function to shoulders with rotator cuff deficiency. The implant consists of a glenosphere projecting from a glenoid baseplate and articulating in a socket at the proximal end of a humeral component. Despite the demonstrated clinical efficacy, little information is available regarding the joint forces about this construct and the stability of the glenoid component against these forces. Our hypotheses were that the joint forces about the rTSA were comparable to that about a normal shoulder joint, and that the micromotion between the baseplate and the scapula against these loads would be sufficiently low to induce bone ingrowth. To investigate this, a custom testing rig was constructed to simulate active shoulder elevation in fresh-frozen shoulder specimens. The forces about the rTSA were calculated and found to include compressive and shear forces up to 0.7 and 0.4 BW, respectively. In contrast to a normal shoulder, where the joint forces peak at 90° of abduction, forces about the rTSA were highest at about 60° of abduction. These forces were then applied in cyclic loading conditions to the glenoid baseplate, and the micromotion of the implant relative to the bone was measured in the four quadrants of the component. For two different rTSA designs (DePuy Delta III® and Encore RSP®) and in the entire range of the fixation testing, the cyclical micromotions were always less than 62 µm. Thus, under loading conditions similar to physiological shoulder elevation, micromotion of the glenoid component was sufficiently low and within previously published limits to induce bone ingrowth.


Folliculotropic mycosis fungoides.
Folliculotropic mycosis fungoides (MF) is a distinct subset of cutaneous T cell lymphoma (CTCL). The disease is typically marked by an aggressive course and is often recalcitrant to skin-direct therapy. We report a case of an 83-year-old woman with folliculotropic MF characterized by erythematous, scaly plaques on the forehead along with poliosis and alopecia of the right medial eyebrow.


Aggregation is a critical cause of poor transfer into the brain tissue of intravenously administered cationic PAMAM dendrimer nanoparticles.
Dendrimers have been expected as excellent nanodevices for brain medication. An amine-terminated polyamidoamine dendrimer (PD), an unmodified plain type of PD, has the obvious disadvantage of cytotoxicity, but still serves as an attractive molecule because it easily adheres to the cell surface, facilitating easy cellular uptake. Single-photon emission computed tomographic imaging of a mouse following intravenous injection of a radiolabeled PD failed to reveal any signal in the intracranial region. Furthermore, examination of the permeability of PD particles across the blood-brain barrier (BBB) in vitro using a commercially available kit revealed poor permeability of the nanoparticles, which was suppressed by an inhibitor of caveolae-mediated endocytosis, but not by an inhibitor of macropinocytosis. Physicochemical analysis of the PD revealed that cationic PDs are likely to aggregate promptly upon mixing with body fluids and that this prompt aggregation is probably driven by non-Derjaguin-Landau- Verwey-Overbeek attractive forces originating from the surrounding divalent ions. Atomic force microscopy observation of a freshly cleaved mica plate soaked in dendrimer suspension (culture media) confirmed prompt aggregation. Our study revealed poor transfer of intravenously administered cationic PDs into the intracranial nervous tissue, and the results of our analysis suggested that this was largely attributable to the reduced BBB permeability arising from the propensity of the particles to promptly aggregate upon mixing with body fluids.


Cluster-state quantum computing enhanced by high-fidelity generalized measurements.
We introduce and implement a technique to extend the quantum computational power of cluster states by replacing some projective measurements with generalized quantum measurements (POVMs). As an experimental demonstration we fully realize an arbitrary three-qubit cluster computation by implementing a tunable linear-optical POVM, as well as fast active feedforward, on a two-qubit photonic cluster state. Over 206 different computations, the average output fidelity is 0.9832+/-0.0002; furthermore the error contribution from our POVM device and feedforward is only of O(10(-3)), less than some recent thresholds for fault-tolerant cluster computing.


Threat of establishment of non-indigenous potato blackleg and tuber soft rot pathogens in Great Britain under climate change.
Potato blackleg and soft rot caused by Pectobacterium and Dickeya species are among the most significant bacterial diseases affecting potato production globally. In this study we estimate the impact of future temperatures on establishment of non-indigenous but confirmed Pectobacterium and Dickeya species in Great Britain (GB). The calculations are based on probabilistic climate change data and a model fitted to disease severity data from a controlled environment tuber assay with the dominant potato blackleg and soft rot-causing species in GB (P. atrosepticum), and three of the main causative agents in Europe (P. carotovorum subsp. brasiliense, P. parmentieri, Dickeya solani). Our aim was to investigate if the European strains could become stronger competitors in the GB potato ecosystem as the climate warms, on the basis of their aggressiveness in tubers at different temperatures. Principally, we found that the tissue macerating capacity of all four pathogens will increase in GB under all emissions scenarios. The predominant Pectobacterium and Dickeya species in Europe are able to cause disease in tubers under field conditions currently seen in GB but are not expected to become widely established in the future, at least on the basis of their aggressiveness in tubers relative to P. atrosepticum under GB conditions. Our key take-home messages are that the GB potato industry is well positioned to continue to thrive via current best management practices and continued reinforcement of existing legislation.


Off-axis behavior of an infrared meander-line waveplate.
An infrared meander-line waveplate has been modeled and measured over the 8 to 12 microm spectral band in terms of its differential phase delay, axial ratio of the output polarization ellipse, and power throughput for angles of incidence between 0 degrees and 60 degrees. The study has been performed for planes of incidence parallel and perpendicular to the meander-line axis. The main significance is that the phase delay remains almost unaffected by the angle of incidence. Infrared meander-line retarders can thus be used well beyond the paraxial range as in low-f/# optical systems and in non-normal-incidence applications.


Downregulation of CEACAM6 gene expression in laryngeal squamous cell carcinoma is an effect of DNA hypermethylation and correlates with disease progression.
We have turned our attention to CEACAM6 gene, already described as deregulated in various types of cancer. By using the expression microarrays performed on the set of 16 laryngeal squamous cell carcinoma (LSCC) samples: 11 cell lines and 5 primary tumors we have shown downregulation of CEACAM6 gene as compared to non cancer controls from head and neck region. CEACAM6 gene downregulation, further confirmed by quantitative PCR on 25 LSCC cell lines, was observed in cell lines derived from recurrent tumors in comparison to controls. A significant gene downregulation was observed in cell lines derived from advanced, high grade tumors in comparison to controls. Intrigued by the recurrent transcriptional loss of CEACAM6 we searched for the mechanism potentially responsible for its downregulation and hence we analyzed DNA copy number changes (a-CGH), promoter DNA methylation status and occurrence of gene mutations (in silico). Neither the analysis of gene copy number, nor the mutation screen has shown recurrent deletions or mutations, that could contribute to the observed downregulation of the gene. However, by using bisulfite pyrosequencing, we have shown DNA hypermethylation (mean DNA methylation > 78%) of CEACAM6 promoter region in 9/25 (36%) LSCC cell lines. Importantly, the 5-aza-2-deoxycytidine-induced inhibition of DNA methylation resulted in restoration of CEACAM6 expression in the two LSCC cell lines on mRNA level. In summary, we have shown that recurrent downregulation of CEACAM6 in LSCC is dependent on the gene's promoter DNA methylation and is observed predominantly in large, poorly differentiated tumors and recurrences.


[High frequency sonography in the detection of finger injuries in sport climbing].
Sport climbing shows an increasing popularity, including even school sport activity on high climbing levels. Climbing related injuries are predominantly located in fingers/ hands ("climber's finger"), and can present as annular pulley rupture or more common as overuse injury. Beside clinical examination imaging modalities such as MRI and high frequency sonography have shown to allow for detection of climbing related injuries. High frequency sonography enables for exact differential diagnosis of climbing related finger/hand injuries and therefore plays a central role in adequate therapeutic management.


[Use of essentiale and cholagogum in prevention of cholelithiasis in fat hepatosis with concomitant cholecystitis].
To assess efficacy of essentiale in combination with cholagogum in prevention of cholelithogenesis in patients with fat hepatosis (FH) and concomitant cholecystitis (CC). 100 patients aged 31-60 years with FH and CC were examined using clinical, device and biochemical tests. The diagnosis was verified by the results of ultrasonography, computed and MR tomography. Fractionated duodenal tubing followed by biochemical examination of bile was conducted in all the patients. Changes in physico-chemical properties of hepatic and vesical bile corresponding to stage I of cholelithiasis occurred in most of the examinees. Treatment with essentiale +cholagogum is clinically effective, improves functional condition of bile ducts and the liver, diminishes bile lithogenicity. In fat hepatosis and concomitant cholecystitis, essentiale and cholagogum improve biochemical composition of bile, resulting finally in decreased risk of cholelithogenesis.


Periodic Patchy Spheres Self-Assembled by AmBCAn' Multiblock Terpolymers.
We have designed AmBCAn' multiblock terpolymers and studied their self-assembly using self-consistent field theory, aiming to generate the periodically arranged patchy spheres and thus to clarify the regulation mechanism of the number of patches. A number of two-dimensional phase diagrams are constructed for three typical architectures A2BCA2', A2BCA3', and A3BCA2'. Four kinds of stable patchy spheres with the number of patches as 2 (S2), 4 (S4), 5 (S5), and 6 (S6) are obtained. These phases follow a common transition sequence of S2 → S4 → S5 → S6 along with the increasing of the volume fraction of C-block (fC), which forms the core sphere patched with B-domains. Moreover, the S6 phase exhibits the widest stability window, while S5 has the narrowest one. The increased arms of A'-blocks in A2BCA3' architecture deflect the phase boundaries toward large fC and accordingly expand the regions of these patchy spheres due to the amplified effect of spontaneous curvature. In contrast, the increased arms of A-blocks in A3BCA2' remarkably expands the window of S6 but narrows those of the other patchy spheres, which is mainly caused by increased packing frustration resulting from the reduced extension of the more divided A-blocks. The widest window of the S6 phase reaches ΔfC ∼ 0.13, which is readily accessed by experiment. Our work not only demonstrates a self-assembly strategy to engineer the patchy spheres, but also sheds light on the regulation mechanism of the patchy number.


[Praxis approach in educational interventions at the Institute of Nursing Education].
The current development of health awareness in France will not be felt in hospitals and other healthcare organizations in regards to health and health education. Curative and preventive do not seem to be in complete interaction. None-the-less, in the face of a conceptual and political evolution, it is urgent to enlighten, through initial nursing training, future health-care workers towards new functions in the area of education. Therefore in this study we suggest a reflective study on the creation of practical educational competencies. We will be able to demonstrate through this praxiological approach how we will succeed in elaborating two work models: the elaboration of a competency reference pertinent to public health-care the conception of a didactic learning strategy based on a progressiveness concept.


Effects of Concomitant Administration of PXR Ligand Drugs on the Anticoagulant Effects of Warfarin.
We encountered cases in which the anticoagulant effects of warfarin (CYP2C9 substrate) were reversibly attenuated by the concomitant administration of rifampicin or bosentan, which are potent pregnane X receptor (PXR) ligands. The purpose of the present study is to report the previous case with rifampicin, and to evaluate the changes in the warfarin anticoagulant effects when withdrawing or switching bosentan treatment. The former is a case study of a 4-year-old girl undergoing warfarin treatment. The latter is a longitudinal study of 20 pediatric patients receiving stable warfarin treatment. The prothrombin time and international normalized ratio (PT-INR) values were extracted from the medical records and normalized by the daily-dose per body size as an index for the warfarin anticoagulant effects. Rifampicin treatment resulted in a 52.0% decrease in the anticoagulant index. On the other hand, 10 of 20 patients started bosentan and their anticoagulant index was reduced by a median of 2.00. Bosentan was withdrawn in 4 of 20 patients and their anticoagulant index increased by a median of 3.67. Six of 20 patients switched from bosentan to macitentan, which is considered not to activate PXR in clinical settings. However, switching from bosentan to macitentan resulted in a median of 2.25 reduction of the anticoagulant index rather than recovery of the response to warfarin. This study suggests not only the possibility of heterogeneity in the response to PXR activation and deactivation, but also the importance of long-term monitoring of drug-drug interactions when switching from bosentan to macitentan.


Potential avenues for exercise to activate episodic memory-related pathways: a narrative review.
Memory function plays an important role in activities of daily living, and consequently, quality and quantity of life. In this narrative review, we discuss the anatomical components of episodic memory, including the structure of the hippocampus and the routes of communication to and from this structure. We also highlight cellular traces of memory, such as the engram cell and pathway. To provide etiological insight, the biological mechanisms of episodic memory are discussed, including factors subserving memory encoding (e.g., cognitive attention, neuroelectrical indices), consolidation (i.e., synaptic and brain systems level), and retrieval (e.g., availability of cues, context-dependent, state-dependent, and cognitive processing). Central to this manuscript, we highlight how exercise may influence each of these aforementioned parameters (e.g., exercise-induced hippocampal growth, synaptic plasticity, and cue retrieval) and then discuss the implications of these findings to enhance and preserve memory function. Collectively, this narrative review briefly summarizes potential mechanisms of episodic memory, and how exercise may activate these mechanistic pathways.


Nitrate Reduction in Bacillus licheniformis in the Presence of Ammonium Salt by Shaking Culture.
A nitrate-reducing bacterium was isolated from a hot spring and identified as Bacillus licheniformis. This strain was found to accumulate NO2(-) in the medium even in the presence of NH4(+) by shaking culture when FeSO4 was added to the medium. The NO2(-) accumulation was due to nitrate reductase activity, and the same accumulation was also recognized in some other bacteria. Since the nitrate reduction had no marked effect on the cell growth, it is possible that this nitrate reduction may not be involved in either an assimilatory or a dissimilatory one like those hitherto reported.


Surgical treatment of Graves' disease in children.
Thyroidectomy may be indicated in children with Graves' disease who have adverse reactions to antithyroid drugs or who relapse after antithyroid drug therapy. We investigated the characteristics of childhood Graves' disease from the standpoint of surgical outcome. Between 1989 and 1998, 1897 patients with Graves' disease underwent thyroidectomy and their thyroid function could be evaluated 2 to 3 years after thyroidectomy. The patients were divided into three groups according to age at thyroidectomy: 74 patients were 15 years old or less (children), 345 patients 16 to 20 years of age (adolescents), and 1478 patients 21 years of age or more (adults). The children included higher proportions of patients who had a large goiter (> 100 g), high thyrotropin-binding inhibitory immunoglobulin (TBII) level (> 50%), and small remnant thyroid (< 4 g). At 2 to 3 years after thyroidectomy, the overt recurrence rate of the children, adolescents, and adults was 9.5%, 4.9%, and 5%, respectively. The cumulative recurrence-free rate of the children, adolescents, and adults at 5 years after thyroidectomy was 82%, 90%, and 92%, respectively. Surgical complications were more frequently observed in children. Considering the aggressiveness of childhood Graves' disease, subtotal thyroidectomy with thyroid remnant less than 3 g is the procedure of choice for preventing recurrent hyperthyroidism.


Reference ranges for serum dehydroepiandrosterone sulfate and testosterone in adult men.
Dehydroepiandrosterone (DHEA) is the main adrenal androgen, which mostly exists in a sulfated version (DHEAS). Both DHEA and DHEAS are metabolic intermediates in the biosynthesis of the male sex hormone testosterone. In men, testosterone is involved in the regulation of fertility, libido, and muscle mass and is valuable for the assessment of gonadal, adrenal, and pituitary function and for the diagnosis of hypogonadism. The objective of the present study was to calculate age-specific reference ranges for serum DHEAS and serum testosterone using 1) linear regression and the mean +/- 1.96 standard deviation concept and 2) quantile regression. From the cross-sectional Study of Health in Pomerania a total of 1078 men aged 20-79 years were included in the analyses. Serum DHEAS and testosterone levels were quantified using IMMULITE 2500 immunoassays. Linear and quantile regression were performed to calculate age-specific reference ranges. Both statistical methods generated different results: The reference ranges based on linear regression identified 17 men (1.6%) with DHEAS levels and 45 men (4.2%) with serum testosterone levels outside the reference range. Using quantile regression, 54 men (5.0%) and 50 men (4.6%) with serum DHEAS and testosterone levels outside the range were detected, respectively. The present study established age-specific reference ranges for serum DHEAS and testosterone levels for men. Quantile regression should be preferred to calculate reference ranges; a better concordance with original data is possible because no distribution assumption is required and the robustness against outliers is given.


A Leg to Stand On: Working With Marginal Decision-making Capacity in a Patient With a Severe Leg Infection and Schizophrenia.
Assessment of a patient's capacity to make treatment decisions and working with the wishes of a patient with mental illness against the best medically indicated plan is a complex and dynamic task. It is particularly challenging when the course of deterioration of the illness is meandering and slow, and the time horizon for recovery is uncertain, providing no clear point of entry for definitive crisis intervention. High-impact decisions concerning body integrity, such as the amputation of a leg, further complicate the task. To highlight these challenges and complexities, we present the case of a man who suffered from schizophrenia, with a worsening diabetic foot ulcer and suboptimal acceptance of proper wound care. The patient died as a result of his refusal of a proposed amputation to address his life-threatening infection. Medical system and cultural issues are also considered.


Low-Temperature Atomic Layer Deposition of MoS2 Films.
Wet chemical screening reveals the very high reactivity of Mo(NMe2 )4 with H2 S for the low-temperature synthesis of MoS2 . This observation motivated an investigation of Mo(NMe2 )4 as a volatile precursor for the atomic layer deposition (ALD) of MoS2 thin films. Herein we report that Mo(NMe2 )4 enables MoS2 film growth at record low temperatures-as low as 60 °C. The as-deposited films are amorphous but can be readily crystallized by annealing. Importantly, the low ALD growth temperature is compatible with photolithographic and lift-off patterning for the straightforward fabrication of diverse device structures.


SURF1 gene mutations in Polish patients with COX-deficient Leigh syndrome.
One of the most frequent forms of Leigh syndrome (LS), a severe neurodegenerative, genetically heterogenous disease, is associated with cytochrome c oxidase (COX) deficiency. No mutations in any of the 13 polypeptide subunits of human COX have been detected in LS patients. Recently, SURF1, a positional candidate gene for LS has been identified on chromosome 9q34. We present the identification of SURF1 mutations in a randomly chosen group of Polish patients with a classical form of LS. Sequence analysis revealed the presence of a novel 704T-->C transition (Met235Thr), and two recurrent dinucleotide deletions (758delCA, 845delCT), as well as one novel polymorphic 573C-->G transversion (Thr191Thr). 845delCT was identified in 66% of all our patients in homozygous or heterozygous form. Our study confirms the recent observations that SURF1 is consistently involved in disorders of the mitochondrial respiratory chain in patients with typical Leigh syndrome.


A quantitative study of the susceptibility of cockroach species to Moniliformis moniliformis (Acanthocephala).
We exposed 19 species of cockroaches to Moniliformis moniliformis by administering shelled acanthors orally and by injecting hatched acanthors directly into the body cavity. The exposure method had little influence on susceptibility: with one exception, species that were susceptible to oral exposure were also susceptible to injected acanthors and, in no case, did acanthors develop in injected animals when they did not develop in orally exposed conspecifics. We found no support for the hypothesis that the intestine may be a barrier to M. moniliformis establishment in cockroaches. There is, however, clear interspecific variation in susceptibility to M. moniliformis infection.


The tonga healthy weight loss program 1995-97.
A health and weight awareness program was initiated in 1995 by the Tonga National Food and Nutrition Committee to combat a high prevalence of obesity and its associated non-communicable diseases. The strategy of the program was to provide a fun activity in which people wanted to join, and at the same time gain health benefits. Three successive weight loss competitions were organized, of 4 to 6 months in length, in which radio, television, and newspaper media were major elements. A Tongan version of the 1993 South Pacific Commission weight for height chart was produced, allowing identification of overweight/obesity using body mass index. Participants were registered and given individual encouragement on diet/exercise. Prizes donated by local businesses added to the campaign, as well as the involvement of His Majesty King Taufa'ahau Tupou IV. Aerobic exercise, public walks, weigh station manager training, and weight watcher group meetings were special activities. An unexpected element was the interest by the international press, which proclaimed the Tonga national weight loss competitions to be the first in the world. A total of 3429 participants registered in the three competitions, with 1617 competing to the end. First place winners lost from 25.5 to 28.4 kg in the competitions. Difficulties encountered included problems of coordination, funds, scales, newness of the healthy weight concept, and weight gain at the close of the competition. The activity was received positively by the community, with requests for the competitions and exercise activities to continue, and much awareness on health issues relating to overweight was achieved.


Where does the electron go? Electron distribution and reactivity of peptide cation radicals formed by electron transfer in the gas phase.
We report the first detailed analysis at correlated levels of ab initio theory of experimentally studied peptide cations undergoing charge reduction by collisional electron transfer and competitive dissociations by loss of H atoms, ammonia, and N-C alpha bond cleavage in the gas phase. Doubly protonated Gly-Lys, (GK + 2H) (2+), and Lys-Lys, (KK + 2H) (2+), are each calculated to exist as two major conformers in the gas phase. Electron transfer to conformers with an extended lysine chain triggers highly exothermic dissociation by loss of ammonia from the Gly residue, which occurs from the ground ( X ) electronic state of the cation radical. Loss of Lys ammonium H atoms is predicted to occur from the first excited ( A ) state of the charge-reduced ions. The X and A states are nearly degenerate and show extensive delocalization of unpaired electron density over spatially remote groups. This delocalization indicates that the captured electron cannot be assigned to reduce a particular charged group in the peptide cation and that superposition of remote local Rydberg-like orbitals plays a critical role in affecting the cation-radical reactivity. Electron attachment to ion conformers with carboxyl-solvated Lys ammonium groups results in spontaneous isomerization by proton-coupled electron transfer to the carboxyl group forming dihydroxymethyl radical intermediates. This directs the peptide dissociation toward NC alpha bond cleavage that can proceed by multiple mechanisms involving reversible proton migrations in the reactants or ion-molecule complexes. The experimentally observed formations of Lys z (+*) fragments from (GK + 2H) (2+) and Lys c (+) fragments from (KK + 2H) (2+) correlate with the product thermochemistry but are independent of charge distribution in the transition states for NC alpha bond cleavage. This emphasizes the role of ion-molecule complexes in affecting the charge distribution between backbone fragments produced upon electron transfer or capture.


A comprehensive review of lysine-specific demethylase 1 and its roles in cancer.
Histone methylation plays a key role in the regulation of chromatin structure, and its dynamics regulates important cellular processes. The investigation of the role of alterations in histone methylation in cancer has led to the identification of histone methyltransferases and demethylases as promising novel targets for therapy. Lysine-specific demethylase 1(LSD1, also known as KDM1A) is the first discovered histone lysine demethylase, with the ability to demethylase H3K4me1/2 and H3K9me1/2 at target loci in a context-dependent manner. LSD1 regulates the balance between self-renewal and differentiation of stem cells, and is highly expressed in various cancers, playing an important role in differentiation and self-renewal of tumor cells. In this review, we summarize recent studies about the LSD1, its role in normal and tumor cells, and the potential use of small molecule LSD1 inhibitors in therapy.


Functions of early (AP-2) and late (AIP1/ALIX) endocytic proteins in equine infectious anemia virus budding.
The proline-rich L domains of human immunodeficiency virus 1 (HIV-1) and other retroviruses interact with late endocytic proteins during virion assembly and budding. In contrast, the YPDL L domain of equine infectious anemia virus (EIAV) is apparently unique in its reported ability to interact both with the mu2 subunit of the AP-2 adaptor protein complex and with ALG-2-interacting protein 1 (AIP1/Alix) protein factors involved in early and late endosome formation, respectively. To define further the mechanisms by which EIAV adapts vesicle trafficking machinery to facilitate virion production, we have examined the specificity of EIAV p9 binding to endocytic factors and the effects on virion production of alterations in early and late endocytic protein expression. The results of these studies demonstrated that (i) an approximately 300-residue region of AIP1/Alix-(409-715) was sufficient for binding to the EIAV YPDL motif; (ii) overexpression of AIP1/Alix or AP-2 mu2 subunit specifically inhibited YPDL-mediated EIAV budding; (iii) virion budding from a replication-competent EIAV variant with its L domain replaced by the HIV PTAP sequence was inhibited by wild type or mutant mu2 to a level similar to that observed when a dominant-negative mutant of Tsg101 was expressed; and (iv) overexpression or siRNA silencing of AIP1/Alix and AP-2 revealed additive suppression of YPDL-mediated EIAV budding. Taken together, these results indicated that both early and late endocytic proteins facilitate EIAV production mediated by either YPDL or PTAP L domains, suggesting a comprehensive involvement of endocytic factors in retroviral assembly and budding that can be accessed by distinct L domain specificities.


Effects of diets high in saturated fatty acids, canola oil, or safflower oil on platelet function, thromboxane B2 formation, and fatty acid composition of platelet phospholipids.
Platelet function and fatty acid composition were investigated in 30 healthy male subjects who ate a controlled-saturated-fatty-acid (baseline) diet for 3 wk and then consumed either safflower oil or canola oil as a major fat source for 8 wk. Fatty acid composition of platelet phospholipids reflected changes in dietary fatty acid composition. Compared with baseline a 35% decrease (P less than 0.05) in arachidonic acid was observed in platelet phospholipids of the canola-oil diet group while long chain n-3 fatty acids rose 7-26% (P greater than 0.05). Compared with baseline both unsaturated-fatty-acid diets reduced platelet aggregation at 3 wk of oil-based diet feeding (P less than 0.01) whereas only canola oil influenced platelet function (lowered ATP secretion) at 8 wk (P less than 0.01). No significant difference was observed in thromboxane B2 concentrations between oil-treatment groups at 8 wk. Both oil-based diets had short-term beneficial effects on platelet function but the effect of canola oil persisted longer.


Transbronchial lung biopsy: can specimen quality be predicted at the time of biopsy?
To determine the bronchoscopist's ability to predict specimen quality at the time of transbronchial biopsy and to determine the influence of biopsy specimen size and alveolar content on diagnostic value. Prospective, blinded, observational analysis. Tertiary care academic hospital-based pulmonary practice. Forty-three adult patients who underwent transbronchial lung biopsy. Each of 170 biopsy specimens was rated as to likelihood of containing diagnostic tissue, size and ability to float, tissue types present, number of alveoli, and pathologic diagnosis. Fifteen percent of biopsy specimens were small and 40% were large. Seventy-six percent of specimens floated; 61.8% of the 170 biopsy specimens contained abnormal lung tissue; and 14.7% of individual specimens were diagnostic. Fifty-two percent of specimens contained >20 alveoli. Larger biopsy specimens were more likely to contain diagnostic tissue (r=0.29, p=0.001). Cup forceps retrieved smaller pieces of tissue (p=0.007) and were less likely to obtain diagnostic tissue (p=0.06). Physician ratings of specimen quality (mean+/-SD) did not differ between specimens containing normal and abnormal tissue (5.98+/-2.3 vs 5.46+/-5.5; p=0.24) or between specimens containing diagnostic vs nondiagnostic tissue (5.56+/-2.5 vs 6.25+/-2.1; p=0.14). Specimens that floated were no more likely to be diagnostic or abnormal than specimens that sank (p<0.05). Diagnosis when established was made by the first biopsy specimen in 53.3% and the second in 33.3% Physician estimate of biopsy specimen quality and the float sign are not helpful in predicting that the biopsy specimen contains abnormal or diagnostic tissue. Diagnostic biopsy specimen will likely be obtained if the size of the specimen fills the forceps, 2 to 4 biopsies are performed, and toothed forceps are used.


A nutritional analysis of food provided to Royal Naval personnel at sea.
The aim of this study was to determine the nutritional content of the foods provided to, and the confectionary purchased by, personnel serving at sea in British warships. Data were collected from the stores accounts of six ships over a period of 32,354 man-victualling-days. Analysis was carried out at the Nuffield Laboratories of Comparative Medicine. The food from the ships' gallies provided mean daily intakes of 3750 kcal, of which 42 per cent were derived from fats (17 per cent from saturated fats) and 9 per cent from added sugars. In taking account of confectionary purchased from NAAFI sources the total energy intake was raised to 4200 kcal of which 40 per cent were derived from fats (15 per cent saturated fats) and 12 per cent from added sugars. The results do not compare favourably with the recommendations of the reports of expert committees.


Predictive value of the frontal QRS-T angle for a permanent pacemaker requirement in patients undergoing transcatheter aortic valve implantation.
Despite recent advances, the requirement for permanent pacemaker (PPM) implantation after transcatheter aortic valve implantation (TAVI) remains high. The frontal QRS-T angle (fQRS-Ta) indicates ventricular electrical instability as well as ventricular depolarization and repolarization heterogeneity. The predictive value of fQRS-Ta for the PPM requirement after TAVI is lacking. Therefore, we aimed to investigate the predictive value of baseline fQRS-Ta for the requirement of PPM after TAVI. This is a retrospective study conducted at a single tertiary care center. The patients were divided into two groups: those who required a pacemaker (PPM group) and those who did not (No-PPM group). The optimal fQRS-Ta cut-off value for predicting a PPM requirement was determined by using receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were used to determine the independent predictors of post-TAVI PPM placement. Final study population consisted of 184 patients. The mean age of the patients was 79.41 ± 7.88 years, and 61% (n = 113) were women. Twenty-seven patients who required PPM after TAVI were considered as the 'PPM group'. The baseline frontal QRS and T axes did not differ between the groups, but the fQRS-Ta was significantly higher in the PPM group. ROC analysis performed for the prediction of post-TAVI PPM need, the fQRS-Ta cut-off value was found to be 100.5 with a sensitivity of 74.1% and a specificity of 60.5% [AUC (95% CI): 0.637 (0.520 - 0.755), p: 0.023]. In multivariate analysis, age [HR (95% CI): 1.071 (1.005 - 1.142), p: 0.034] and fQRS-Ta [HR (95% CI): 2.509 (1.084 - 6.399), p: 0.044] were identified as independent risk factors for PPM requirement after TAVI. This study demonstrated that age and baseline fQRS-Ta were independent predictors of PPM requirements after TAVI in patients with aortic stenosis.


Composition, nutritional aspects and effect on serum parameters of marine algae Ulva rigida.
Algae are commonly consumed in Asia and have also gained popularity in Europe. However, data on the bioavailability of their components are limited. The present study was designed to determine the composition of Ulva rigida and the effects of inclusion of 10% of the algae in a standard diet for 4 weeks on nutritive value and serum parameters in order to consider the usefulness of Ulva as a dietary supplement. Ulva rigida is rich in protein, carbohydrates, fibre, vitamins and minerals and has a low lipid content. Analysis of the amino acid composition revealed good-quality protein. The algae were well accepted by experimental animals and did not significantly change nutritional parameters but reduced LDL cholesterol. Ulva rigida is an excellent source of nutrients and could improve a balanced diet. Further studies are required to research the potential of the seaweed as a natural source of bioactive compounds.


New aspects of the treatment of tubal infertility.
Three aspects of the treatment of tubal infertility are discussed: current surgical procedures, including the use of microsurgery; an attempt at tubal transplantation; and the use of in vitro fertilization.


Menopause knowledge and attitude among Iranian women.
Objective: The present study was done to assess the effects of training on knowledge and attitude level promotion of post menopause women about menopause. Methods & Material: The research communication included 100 menopausal women aged 45-60 years, who were selected in a stratified manner (according to the economic status: poor, average, and good). The tool used was an examiners-made questionnaire, which contained 3 parts: demographic characteristics, knowledge and attitude measurement. Results: Eleven percent of the studied women had a low knowledge regarding menopause and 1% was good. After training, 27% got a good knowledge and no one remained at the low level. The attitude of 59% of the studied women regarding menopause was positive and 80% got a positive attitude after training. A significant relation was found between knowledge and attitude, before and after training. Conclusion: Despite the fact that the majority of women judge menopause as a positive incident, it seems that paying attention to their training caused the bringing to their knowledge of the natural menopause and having a healthy and jolly life.


Impact of an interdisciplinary approach in children and adolescents with lower urinary tract dysfunction (LUTD).
The lower urinary tract dysfunction (LUTD) corresponds to changes in the filling or emptying of urine caused by neurogenic, anatomical and functional alterations. To evaluate the impact of treatment in children and adolescents with LUTD. Historical cohort of 15 year follow-up with the participation of 192 patients (123F, 69M), aged 0.1 to 16.8 years, analyzed at admission (T0) and at final follow-up (T1). Most patients belong to a neurologic bladder dysfunction group (60.4%). The treatment was uroterapy with behavioral and cognitive intervention, timed voiding, oral hydration, laxative diet, biofeedback, sacral nerve stimulation, clean intermittent catheterization (CIC), anticholinergic therapy, rectal enema, treatment of urinary tract infection (UTI) and, in refractory cases, surgical procedures such as continent and incontinent urinary diversion (vesicostomy), bladder augmentation and conduit for performing antegrade colonic enema. The main symptoms were daytime urinary incontinence (82.3%), the non-monosymptomatic nocturnal enuresis (78.6%), fecal incontinence (54.2%) and constipation (47.9%). There was a significant reduction of urinary tract infection (p = 0.0027), daytime urinary incontinence (p < 0.001), nocturnal enuresis (p < 0.001), fecal incontinence (p = 0.010) and of vesicoureteral reflux (p = 0.01). There was significant increase in the use of CIC (p = 0.021), of anticholinergic therapy (p < 0.001) and decrease of chemoprophylaxis (p < 0.001). This study showed that treatment of LUTD in children must be individualized, and requires constant monitoring of clinical, laboratory and imaging to minimize the risk of kidney damage.


Do anti-smoking media campaigns help smokers quit?
As part of an evaluation of the 1990-91 anti-tobacco media campaign carried out by the California Department of Health Services, a study was conducted among 417 regular smokers who had quit during the period of the media campaign. In brief telephone interviews, all respondents identified up to three events or experiences that had influenced them to quit. In response to uncued questions, 6.7 percent of those interviewed indicated that they had been influenced to quit by an advertisement they had seen or heard on radio, television, or billboards. In response to direct questions about the media campaign, 34.3 percent of the respondents indicated that the media campaign's advertisement had played a part in their decision to quit. Applying the 6.7 percentage to the number of Californians who quit smoking in 1990-91, it can be estimated that for 33,000 former smokers, the anti-tobacco media advertisements were an important stimulus in their quit decision. Multiplying the 34.3 percent by the number of former California smokers who quit in 1990-91, the estimate of former smokers for whom the media campaign's advertisements played at least some part in their decision to quit rises to 173,000 persons. While causal attributions from such investigations should be made with caution, the evidence suggests that the 1990-91 campaign did influence substantial number of smokers in California to quit.


Intolerance of Uncertainty and Coping Mechanisms in Nonclinical Young Subjects.
We aimed to explore the relationship between intolerance of uncertainty (IU) and coping mechanisms in a nonclinical sample with the same age and educational level. The Coping Orientations to Problems Experienced (COPE) scale was used to evaluate the coping mechanisms. The IU scale was used to evaluate IU situations. We found that the negative impact of uncertainty on the action in female students was greater than males. While female students used more planning, instrumental support, reinterpretation, religion, emotional support, venting, and mental disengagement coping styles, male students used more humor, denial, and alcohol/drug abuse coping styles. Subjects with psychological problems had higher IU scores and used some more coping mechanisms (restraint, acceptance, behavioral disengagement, and alcohol/drug abuse) than the others. Our results suggest that healthy subjects use different coping styles and respond differently to uncertainty in both genders.


The relationship between sleep and glucagon-like peptide 1 in patients with abnormal glucose tolerance.
Glucagon-like peptide 1 plays a role in glucose regulation. Sleep disturbances (obstructive sleep apnea, insufficient or poor sleep quality) have been shown to adversely affect glucose metabolism. This study aimed to explore the relationship between sleep and glucagon-like peptide 1 regulation in patients with abnormal glucose tolerance. Seventy-one adults with haemoglobin A1c levels between 5.7% and < 6.5% and no history of diabetes participated. Habitual sleep duration and efficiency were obtained from 7-day actigraphy recordings. Obstructive sleep apnea was assessed using an overnight home monitor. Glucagon-like peptide 1 levels were measured during a 75-g glucose tolerance. The area under the curve of glucagon-like peptide 1 was calculated. The mean age (SD) was 55.1 (8.3) years and median (interquartile range) haemoglobin A1c was 5.97% (5.86, 6.23). There was no relationship between sleep duration or efficiency and fasting or area under the curve glucagon-like peptide 1. Glucagon-like peptide 1 levels did not differ among those sleeping ≤ 5.75, > 5.75-< 6.5 or ≥ 6.5 h per night. Increasing apnea-hypopnea index, an indicator of obstructive sleep apnea severity, correlated with lower area under the curve glucagon-like peptide 1 (B -0.242, P = 0.045), but not with fasting glucagon-like peptide 1 (B -0.213, P = 0.079). After adjusting for sex, haemoglobin A1c and body mass index, increasing apnea-hypopnea index was negatively associated with having area under the curve glucagon-like peptide 1 in the highest quartile (odds ratio 0.581, P = 0.028, 95% CI 0.359, 0.942). This study demonstrated that increasing obstructive sleep apnea severity was associated with lower glucagon-like peptide 1 response to glucose challenge. This could possibly be an additional mechanism by which obstructive sleep apnea affects glucose metabolism. Whether raising glucagon-like peptide 1 levels in patients with abnormal glucose tolerance with more severe obstructive sleep apnea will be beneficial should be explored.


Effect of perfusion of bile salts solutions into the oesophagus of hiatal hernia patients and controls.
Tests of the response to perfusion of the oesophagus were made in 54 patients divided into three groups. Group I consisted of patients with symptomatic hiatal hernia, group II hiatal hernia patients with peptic stricture, and group III normal individuals. Each individual oesophagus was perfused at a rate of 45-65 drops per minute over 25 minutes with six solutions: normal saline, N/10 HCl, taurine conjugates of bile salts in normal saline, taurine conjugates of bile salts in N/10 HCl, glycine conjugates of bile salts in normal saline, and taurine and glycine conjugates in a ratio of 1 to 2 in normal saline. It was found that acidified taurine solutions were more irritating than acid alone. With a 2mM/l solution of taurine in acid, symptoms are produced even in controls. With a 1 mM/l solution of the same conjugates, the majority of normal people feel slight heartburn or nothing, and therefore perfusion into the oesophagus of such a solution could be used as a test for oesophagitis.


Protective effect of aerobic fitness on the detrimental influence of exhaustive exercise on information processing capacity.
Although aerobic fitness has been thought to protect against the detrimental cognitive effects following exhaustive exercise, available evidence from studies using traditional mean behavioral measures remain somewhat equivocal. This study aimed to reconcile this discrepancy by using a novel theory-driven diagnostic tool, the Systems Factorial Technology (SFT). Sixty-six healthy young adults aged from 18 to 30 years old with different levels of aerobic fitness (n = 33 for the higher-fit and lower-fit groups) completed a go/nogo version of redundant-target task before and after a graded exercise test (GXT) until exhaustion. SFT was used to calculate the resilience capacity, which reflects the information processing capacity underlying inhibitory control. Following the GXT, both higher-fit and lower-fit groups showed faster responses while leaving accuracy unchanged as compared to the performance at the pretest. On the other hand, the resilience capacity decreased for the lower-fit group but was maintained for the higher-fit group. The present findings suggest that aerobic fitness may modulate the individual difference in decisional mechanism following exhaustive exercise. In sum, this study offers an alternative mechanistic explanation regarding cognitive individual differences in response to exhaustive exercise and provides novel insights into the significance of maintaining a state of high physical fitness for those who need to perform cognitively challenging tasks under physically stressful conditions (e.g., elite athletes).


The In Ovo Chick Chorioallantoic Membrane (CAM) Assay as an Efficient Xenograft Model of Hepatocellular Carcinoma.
The chick chorioallantoic membrane (CAM) begins to develop by day 7 after fertilization and matures by day 12. The CAM is naturally immunodeficient and highly vascularized, making it an ideal system for tumor implantation. Furthermore, the CAM contains extracellular matrix proteins such as fibronectin, laminin, collagen, integrin alpha(v)beta3, and MMP-2, making it an attractive model to study tumor invasion and metastasis. Scientists have long taken advantage of the physiology of the CAM by using it as a model of angiogenesis. More recently, the CAM assay has been modified to work as an in vivo xenograft model system for various cancers that bridges the gap between basic in vitro work and more complex animal cancer models. The CAM assay allows for the study of tumor growth, anti-tumor therapies, and pro-tumor molecular pathways in a biologically relevant system that is both cost- and time-effective. Here, we describe the development of CAM xenograft model of hepatocellular carcinoma (HCC) with embryonic survival rates of up to 93% and reliable tumor take leading to growth of three-dimensional, vascularized tumors.


N,N'-Dibenzyl-N,N'-dimethyl-N''-(methyl-sulfon-yl)phospho-ric triamide.
In the title compound, C(17)H(24)N(3)O(3)PS, the P and the S atoms are each in a distorted tetra-hedral environment and the N atoms display sp(2) character. The phosphoryl group and the NH unit are anti with respect to one another. The dihedral angle between the mean planes of the benzene rings is 31.08 (8)°. The crystal packing is stabilized by N-H⋯O hydrogen bonds, forming an extended chain parallel to the b axis.