Highly conjugated multiporphyrins: synthesis, spectroscopic and electrochemical properties.
A series of meso-to-meso ethynyl-bridged multiporphyrin arrays have been synthesized using Sonogoshira palladium-catalyzed cross-coupling reactions involving the appropriate ethynylporphyrin and iodoporphyrin precursors. The absorption spectra of these multiporphyrins show splitting of the Soret bands and significant red shifts of the Q bands as compared to the combination of the corresponding components. These conjugated multiporphyrins also show red shifts in their emission spectra as the pi-conjugation is expanded. In the electrochemical measurements, the porphyrins dimer 7 shows two 1 - e- oxidations at E(1/2) = +0.63 and +0.76 V for the first electron abstraction from the two porphyrin rings, indicating electronic communication between the two porphyrin units. The porphyrin trimer 4 exhibits the first and second 1 - e- oxidations at E(1/2) = +0.68 and +0.77 V, respectively, which correspond to the two outer porphyrins. The cyclic voltammogram of pentamer 5 shows two overlapping 1 - e- couples at E(1/2) = +0.56 and +0.66 V, and one 2 - e- couple at E(1/2) = +0.86 V, for the four outer porphyrin units. These results demonstrate that in the porphyrin trimer and pentamer the individual peripheral porphyrin units are electrochemically coupled via a central porphyrin core. The UV-Vis-NIR spectra of the oxidized species of these multiporphyrins exhibit a broad intervalence charge transfer (IVCT) band in the region from 1200 to 3000 nm. The present work shows that a central porphyrin unit appended with ethynyl bridges affords strong electronic interactions between the peripheral porphyrin rings over a distance of about 15 A.


Population-Based Modeling Improves Treatment Planning Before (90)Y-Labeled Anti-CD66 Antibody Radioimmunotherapy.
For treatment planning in radioimmunotherapy (RIT), the accurate estimation of time-integrated activity coefficients (TIACs) is essential. To estimate the TIACs in RIT using (90)Y-labeled anti-CD66 antibodies, physiologically based pharmacokinetic (PBPK) models are advantageous. Further optimization in predicting therapeutic TIACs may be achieved by including population-specific parameters. Therefore, the aims of this work were (1) to estimate population parameters and (2) to show the effect of these parameters on prediction accuracy of therapeutic biodistributions. To estimate population values, a PBPK model was fitted to pretherapeutic (gamma camera and serum) and therapeutic (serum) measurements simultaneously using the standard two-stage (STS) and iterated two-stage (ITS) algorithms. Including the estimated population values as Bayesian information, the model parameters of each patient were fitted to pretherapeutic data only (simulating therapeutic TIACs). To validate the prediction accuracy of the therapeutic serum curve, the simulated and fitted TIACs were compared. Prediction accuracy expressed as relative deviation (RD) improved from RD=8%±16% to RD=0%±10% for STS and ITS, respectively. The authors demonstrated a method to estimate and apply population values for RIT using a PBPK model and population fitting. For (90)Y-labeled anti-CD66 antibodies, the prediction accuracy was substantially improved.


Aspirin Mediates Its Antitumoral Effect Through Inhibiting PTTG1 in Pituitary Adenoma.
DNA demethylation and inhibitory effects of aspirin on pituitary cell proliferation have been demonstrated. Our aim was to clarify the molecular mechanisms behind the aspirin-related effects in pituitary cells. DNA methylome and whole transcriptome profile were investigated in RC-4B/C and GH3 pituitary cell lines upon aspirin treatment. Effects of aspirin and a demethylation agent, decitabine, were further tested in vitro. PTTG1 expression in 41 human PitNET samples and whole genome gene and protein expression data of 76 PitNET and 34 control samples (available in Gene Expression Omnibus) were evaluated. Aspirin induced global DNA demethylation and consequential transcriptome changes. Overexpression of Tet enzymes and their cofactor Uhrf2 were identified behind the increase of 5-hydroxymethylcytosine (5hmC). Besides cell cycle, proliferation, and migration effects that were validated by functional experiments, aspirin increased Tp53 activity through p53 acetylation and decreased E2f1 activity. Among the p53 controlled genes, Pttg1 and its interacting partners were downregulated upon aspirin treatment by inhibiting Pttg1 promoter activity. 5hmC positively correlated with Tet1-3 and Tp53 expression, and negatively correlated with Pttg1 expression, which was reinforced by the effect of decitabine. Additionally, high overlap (20.15%) was found between aspirin-regulated genes and dysregulated genes in PitNET tissue samples. A novel regulatory network has been revealed, in which aspirin regulated global demethylation, Tp53 activity, and Pttg1 expression along with decreased cell proliferation and migration. 5hmC, a novel tissue biomarker in PitNET, indicated aspirin antitumoral effect in vitro as well. Our findings suggest the potential beneficial effect of aspirin in PitNET.


[Transient evoked otoacoustic emission measurement in infants].
Transient evoked otoacoustic emissions (TEOAEs) were measured and evaluated in 194 ears of 101 subjects under 4 years old who were suspected of hearing loss, using a ILO88 Otoacoustic Emission Analyzer, to study the basic characteristics of this measure and its utility for hearing screening. The mean time necessary to record TEOAEs in both ears was short, about 3 minutes. In 58 ears judged as normal hearing within 30 dB in ABR, TEOAE levels in infants aged less than 2 months were significantly higher than in those aged more than 1 year, especially in the high frequency bands (4-kHz and 5-kHz bands). One case which had been judged as bilateral moderate-to-profound hearing impairment in initial ABR testing showed good responses in TEOAEs, indicating normal cochlear function, and obvious wave Vs in follow-up ABRs recorded at 30 dB nHL confirmed normal auditory function. Therefore, in a case like this one, suspected of retardation in brain stem maturation, TEOAE is more useful than ABR as a hearing screening technique. Since external and middle-ear factors caused poor TEOAE responses in some cases which had been judged as normal hearing by ABR. TEOAE seems to be more sensitive in detecting external and middle ear problems than ABR. Moreover, TEOAE measurement of infants was easy and noninvasive. We conclude that TEOAE is an excellent tool for screening auditory function in infants.


Ureteral duplication with an heterotopic ureteric implantation: a less common cause of adult urinary incontinence.
A 25-year-old woman with a history of frequent urinary tract infections and dribbling urinary incontinence since early childhood was referred to our urology clinic. An accurate investigation revealed a complete right ureteral duplication, with a dysplastic upper-pole renal moiety and an ectopic right ureter draining into the vagina. The patient underwent surgical exploration which confirmed the diagnosis. It was also possible to see a communication between renal moieties which allowed for a laparoscopic ligation and excision of the heterotopic right ureter. The patient had a good recovery, with a complete resolution of her complaints and a great improvement of her quality of life.


Specific genomic alterations and prognostic analysis of perihilar cholangiocarcinoma and distal cholangiocarcinoma.
Cholangiocarcinoma (CCA), which consists of intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), is an aggressive malignancy worldwide. PCCA and dCCA are often classified as extrahepatic CCA (exCCA). However, the differences in mutational characteristics between pCCA and dCCA remain unclear. Deep sequencing targeting of 450 cancer genes was performed for genomic alteration detection. The tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was conducted using Fisher's exact test. FGFR2 and ERBB2 mutations mainly occurred in iCCA and exCCA, respectively. In exCCA, the frequencies of PIK3CA, FAT4, KDM6A, MDM2, and TCF7L2 mutations were significantly higher in pCCA compared to dCCA, while the frequencies of TP53 and KRAS mutations were markedly lower in pCCA than those in dCCA. The prognosis-related mutations were different among the CCA subtypes. NF1 mutation was associated with short disease-free survival (DFS) and overall survival (OS), and ERBB2 mutation was associated with short DFS in dCCA patients. Meanwhile, MAP2K4 mutation was associated with long DFS and OS, and TERT mutation was associated with short DFS in pCCA. A series of mutations in genes, including ARID1A, ARID2, SMAD4, TERT, TP53, and KRAS, were found to be associated with the TMB. In this study, we investigated the comprehensive genomic characterizations of CCA patients, identified the significant alterations in each subtype, and identified potential biomarkers for prognosis prediction. These results provide molecular evidence for the heterogeneity of CCA subtypes and evidence for further precision targeted therapy of CCA patients.


Drastic increase of selectivity for H2O2 formation in direct oxidation of H2 to H2O2 over supported Pd catalysts due to their bromination.
Incorporation of bromide anions (1.0 wt%) in supported Pd catalysts (viz. Pd supported on Al2O3, ZrO2, SiO2, H-beta or Ga2O3) leads to a drastic increase in their selectivity for H2O2 formation in the direct oxidation of H2 to H2O2 by O2(at room temperature) in an aqueous acidic (0.03 M H3PO4) reaction medium; the selectivity increase is accompanied by a large decrease in the H2O2 decomposition activity of the catalysts.


First crystal structure studies of CaAlH5.
A new member of the aluminum hydride family, CaAlH5, is formed during the decomposition of Ca(AlH4)2. The crystal structure of this new compound was calculated by density functional theory band-structure calculations and confirmed by X-ray powder diffraction analysis. The structure crystallizes in space group P2(1)/n (No. 14), with a = 8.3797(9) angstroms, b = 6.9293(8) angstroms, c = 9.8138(11) angstroms, beta = 93.78(1) degrees, and Z = 8.


GTP-binding protein-mediated production of superoxide anion in rabbit gastric parietal cells.
We found that guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) increased superoxide production in the suspension rich in rabbit gastric parietal cells that were permeabilized by streptolysin O. In this experiment, oxidation of non-fluorescent dihydrorhodamine 123 into the fluorescent rhodamine 123 by oxygen radicals was measured. Results support that GTP gamma S closes a housekeeping C1- channel via intracellular production of superoxide anion in the parietal cell.


Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders.
Serum autoantibodies against the water channel aquaporin-4 (AQP4) are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO). However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG) can induce an NMO-like disease in experimental animal models, we speculate that MOG might be an autoantigen in AQP4-IgG seronegative NMO. Although high-titer autoantibodies to human native MOG were mainly detected in a subgroup of pediatric acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) patients, their role in NMO and High-risk NMO (HR-NMO; recurrent optic neuritis-rON or longitudinally extensive transverse myelitis-LETM) remains unresolved. We analyzed patients with definite NMO (n = 45), HR-NMO (n = 53), ADEM (n = 33), clinically isolated syndromes presenting with myelitis or optic neuritis (CIS, n = 32), MS (n = 71) and controls (n = 101; 24 other neurological diseases-OND, 27 systemic lupus erythematosus-SLE and 50 healthy subjects) for serum IgG to MOG and AQP4. Furthermore, we investigated whether these antibodies can mediate complement dependent cytotoxicity (CDC). AQP4-IgG was found in patients with NMO (n = 43, 96%), HR-NMO (n = 32, 60%) and in one CIS patient (3%), but was absent in ADEM, MS and controls. High-titer MOG-IgG was found in patients with ADEM (n = 14, 42%), NMO (n = 3, 7%), HR-NMO (n = 7, 13%, 5 rON and 2 LETM), CIS (n = 2, 6%), MS (n = 2, 3%) and controls (n = 3, 3%, two SLE and one OND). Two of the three MOG-IgG positive NMO patients and all seven MOG-IgG positive HR-NMO patients were negative for AQP4-IgG. Thus, MOG-IgG were found in both AQP4-IgG seronegative NMO patients and seven of 21 (33%) AQP4-IgG negative HR-NMO patients. Antibodies to MOG and AQP4 were predominantly of the IgG1 subtype, and were able to mediate CDC at high-titer levels. We could show for the first time that a subset of AQP4-IgG seronegative patients with NMO and HR-NMO exhibit a MOG-IgG mediated immune response, whereas MOG is not a target antigen in cases with an AQP4-directed humoral immune response.


Stature of boys post World War II migrants.
Poland is a country with significant regional differences in socio-economic, demographic and epidemiological phenomena. This is partly due to its history; notably the division of Poland among three different countries and the change of the borders after the second World War. The latter caused massive migratory movements of population. Then from the territory which now constitutes one third of Poland, Germans were evicted and Poles settled. These, then new, Western and Northern Territories of Poland (WNTP) are still the most developed parts of Poland with better roads, better housing and easier access to medical service and schools. On the other hand, some of the statistical data concerning the health and lifestyle of the population of these parts of Poland are worse than the corresponding data concerning the rest of Poland. For example the rate of lung cancer, the rate of divorce, the rate of adolescence pregnancies, the rate of cigarette smoking and alcohol consumption are all higher in the WNTP. In 1955, a very comprehensive anthropological nationwide survey of school children was performed. Our findings based on this material exhibit a number of phenomena which might contribute to the explanation of these negative population data. We have observed that the boys born in various regions of pre-war Poland and settled with their parents in the new territories were of different height at the age of 7-18 years than those from the four other regions of Poland whose parents were not resettled. Also the average height of boys, those sons of the migrants who during post-war migration did not go to the west but settled in the central region of Poland, was greater than those who settled in the west of Poland. Our results indicate that among the migrants there was a considerable fraction of people who were physically weaker and less socially adapted in comparison to the rest of the Polish population and that these characteristics have been passed down to the subsequent generation.


Health and health care utilization among early retirement pensioners with musculoskeletal disorders.
To estimate subjective health status among early retired individuals pensioned due to disorders of the musculoskeletal system. A survey of self-reported health status and health care utilization by means of a mailed questionnaire. Early retirees (cases) and a random sample (controls) of individuals from the municipality of Kristianstad, Sweden. all individuals aged 25-59 years granted a full-time early retirement pension during the period 1986-1990 due to disorders of the musculoskeletal system (n = 450). The response rate was 83.6%. An age- and sex-matched sample (n = 450). The response rate was 82.7%. Self-reported health status and health care utilization. Early retirement entailed a deterioration in self-reported health status among men, all ages, and women aged 25-54 years. Female retirees aged 55-64 reported an improvement in health status since retirement. Early retired female immigrants were less satisfied with their health status than the Swedish ones. Early retirees reported higher health care utilization than controls, but with a reduction since retirement. Drug consumption was high. The beneficial effects of early retirement were evident among old women. Men and young and middle-aged women may need support to adjust to life as a retiree. Special attention should be given to the female immigrant retiree.


Focused goodness of fit tests for gene set analyses.
Gene set-based signal detection analyses are used to detect an association between a trait and a set of genes by accumulating signals across the genes in the gene set. Since signal detection is concerned with identifying whether any of the genes in the gene set are non-null, a goodness-of-fit (GOF) test can be used to compare whether the observed distribution of gene-level tests within the gene set agrees with the theoretical null distribution. Here, we present a flexible gene set-based signal detection framework based on tail-focused GOF statistics. We show that the power of the various statistics in this framework depends critically on two parameters: the proportion of genes within the gene set that are non-null and the degree of separation between the null and alternative distributions of the gene-level tests. We give guidance on which statistic to choose for a given situation and implement the methods in a fast and user-friendly R package, wHC (https://github.com/mqzhanglab/wHC). Finally, we apply these methods to a whole exome sequencing study of amyotrophic lateral sclerosis.


Intracranial xanthogranuloma of the dura in Hand-Schüller-Christian disease. Case report.
The authors describe a 37-year-old man with the classic clinical features of Hand-Schüller-Christian disease. He presented with symptoms of increased intracranial pressure due to obstructive hydrocephalus secondary to a huge xanthogranuloma involving falx cerebri and tentorium cerebelli. Immunohistochemical and ultrastructural studies failed to demonstrate Langerhans histiocytes, however. The implication of this finding is discussed in light of the recent relevant literature.


An Integrative Approach to Study Structural and Functional Network Connectivity in Epilepsy Using Imaging and Signal Data.
A key area of research in epilepsy neurological disorder is the characterization of epileptic networks as they form and evolve during seizure events. In this paper, we describe the development and application of an integrative workflow to analyze functional and structural connectivity measures during seizure events using stereotactic electroencephalogram (SEEG) and diffusion weighted imaging data (DWI). We computed structural connectivity measures using electrode locations involved in recording SEEG signal data as reference points to filter fiber tracts. We used a new workflow-based tool to compute functional connectivity measures based on non-linear correlation coefficient, which allows the derivation of directed graph structures to represent coupling between signal data. We applied a hierarchical clustering based network analysis method over the functional connectivity data to characterize the organization of brain network into modules using data from 27 events across 8 seizures in a patient with refractory left insula epilepsy. The visualization of hierarchical clustering values as dendrograms shows the formation of connected clusters first within each insulae followed by merging of clusters across the two insula; however, there are clear differences between the network structures and clusters formed across the 8 seizures of the patient. The analysis of structural connectivity measures showed strong connections between contacts of certain electrodes within the same brain hemisphere with higher prevalence in the perisylvian/opercular areas. The combination of imaging and signal modalities for connectivity analysis provides information about a patient-specific dynamical functional network and examines the underlying structural connections that potentially influences the properties of the epileptic network. We also performed statistical analysis of the absolute changes in correlation values across all 8 seizures during a baseline normative time period and different seizure events, which showed decreased correlation values during seizure onset; however, the changes during ictal phases were varied.


Small light-harvesting antenna does not protect from photoinhibition.
High-light-induced decrease in photosystem II (PSII) electron transfer activity was studied in high- and low-light-grown pumpkin (Cucurbita pepo L.) plants in vivo and in vitro. The PSII light-harvesting antenna of the low-light leaves was estimated to be twice as big as that of the high-light leaves. The low-light leaves were more susceptible to photoinhibition in vivo. However, thylakoids isolated from these two plant materials were equally sensitive to photoinhibition when illuminated in the absence of external electron acceptors. Only the intensity of the photoinhibitory light and the chlorophyll concentration of the sample, not the size of the light-harvesting antenna, determined the rate of PSII photoinhibition in vitro. Because excitation of the reaction center and not only the antenna chlorophylls is a prerequisite for photoinhibition of PSII activity, independence of photoinhibition on antenna size provides support for the hypothesis (Schatz EH, Brock H, Holzwarth AR [1988] Biophys J 54: 397-405) that the excitations of the antenna chlorophylls are in equilibrium with the excitations of the reaction centers. Better tolerance of the high-light leaves in vivo was due to a more active repair process and more powerful protective mechanisms, including photosynthesis. Apparently, some protective mechanism of the high-light-grown plants is at least partially active at low temperature. The protective mechanisms do not appear to function in vitro.


Police officers who responded to 9/11: Comorbidity of PTSD, depression, and anxiety 10-11 years later.
After the 9/11/2001 World Trade Center (WTC) attack, many police-responders developed PTSD and might be vulnerable to develop depression and/or anxiety. Comorbidity of PTSD, depression, and/or anxiety is examined. Police enrollees (N = 1,884) from the WTC Health Registry were categorized into four groups based on comorbidity of PTSD, depression, and anxiety. DSM-IV diagnostic criteria for PTSD were used. Depression (PHQ-8) and anxiety (GAD-7) were assessed with standardized psychometric inventories. Multinomial logistic regression was used to identify putative risk factors associated with comorbidity of PTSD. Of 243 (12.9% of total) police with probable PTSD, 21.8% had probable PTSD without comorbidity, 24.7% had depression, 5.8% had anxiety, and 47.7% had comorbid depression and anxiety. Risk factors for comorbid PTSD, depression, and anxiety include being Hispanic, decrease in income, experiencing physical injury on 9/11, experiencing stressful/traumatic events since 9/11, and being unemployed/retired. Nearly half of police with probable PTSD had comorbid depression and anxiety. Am. J. Ind. Med. 59:425-436, 2016. © 2016 Wiley Periodicals, Inc.


Foot morphology influences the change in arch index between standing and walking conditions.
Human foot morphology has been of interest to anatomists, clinicians, and paleontologists for a century due to its importance in bipedal walking. Foot shape changes as forces move through it from the body to the substrate. Although the arch of the foot has been extensively evaluated, the role of foot morphology in the change of the arch height in walking is less explored. To remedy this lacuna, the Arch Indices (AIs) of the left and right feet of 77 people were calculated in double and single stance standing and walking (dynamic) conditions. The feet were categorized into clinical foot types (cavus, normal, planus). The change in static AI between double and single stance was used to predict dynamic AI and the difference between predicted and observed dynamic AI was examined. As expected, AIs increased (i.e., arch height decreased) with increasing load on the foot for the entire sample and each foot type (p's > .001), but the ability of change in static AIs to predict dynamic AI varied among foot types, implicating the possibility of variability in foot mechanics among foot types. While planus feet change stiffness during walking, presumably due to muscular action, cavus feet are more variable in their response to load. Static and dynamic AIs are effective in reflecting the changes in foot stiffness that occur in walking and future work should examine the role of extrinsic muscle activation in this stiffness change.


Stable sinusoidal driver circuit for tuning fork choppers.
A circuit is presented which can drive tuning fork choppers, such as the Bulova L40 and L2 series. The advantages of this circuit over the factory-supplied 5A-type driver are better drive-amplitude stability, freedom from drift due to line-voltage variations, and a cleaner, transient-free sinusoidal reference signal. Test results indicate an improvement in long-term stability by as much as a factor of 4.


Biomimetic approach to perophoramidine and communesin via an intramolecular cyclopropanation reaction.
[reaction: see text] Starting from tryptamine 4 and isatin 5, a biomimetic approach to the pentacyclic substructure 1 of perophoramidine and communesin was developed. The key steps were to create a stable three/six bicyclic system 2 on the 2,3-double bond of an indole derivative 3 by an intramolecular cyclopropanation, followed by ring opening of the resulting cyclopropane ring with the in situ generated amine group of an aniline.


Resident perspectives on a dermatology Quality Improvement curriculum: the University of Colorado experience.
The Centers for Medicare and Medicaid Services (CMS) have prioritized the objective of optimizing quality healthcare though quality improvement initiatives, yet research on dermatology-specific QI programs and their perceptions among dermatology residents remains limited. We explore residents' opinions of a dermatology-specific QI scholarly project curriculum implemented at University of Colorado Denver (UCD) in 2010 and also evaluate residents' attitudes regarding the value of this curriculum in aiding them to meet ACGME core competencies.


In vitro antiviral diterpenes from the Brazilian brown alga Dictyota pfaffii.
Specimens of Dictyota pfaffii from Atol das Rocas, Northeast Brazil, afforded the rare dolabellane diterpene 10,18-diacetoxy-8-hydroxy-2, 6-dolabelladiene (1) and the new 10-acetoxy-8,18-di-hydroxy-2,6-dolabelladiene (2). Reduction of 1 yielded 8,10,18-trihydroxy-2,6-dolabelladiene (3), also present in the crude ex-tract of D. pfaffii. All three structures were assigned by 1D and 2D NMR spectral data. These substances showed strong anti-HSV-1 activity in vitro but only 3 inhibited the reverse transcriptase enzyme of HIV-1.


Comparison of the efficiency of large-scale ceramic and membrane aeration systems with the dynamic off-gas method.
The aeration systems of two full-scale activated sludge basins were compared over 2.5 years under the same operating conditions using dynamic off-gas testing. Only the material of the diffuser was different, membrane vs. ceramic tube diffusers. The experimental design took the complexity and dynamics of the system into consideration. The investigation has shown that, although the membrane diffusers have higher initial standard oxygen transfer efficiency (SOTE) and standard aeration efficiency (SAE), these decreased over time, while the SAE of the ceramic diffusers started lower, but increased slightly over the whole period. Measurement of air distribution in the basins along with dissolved oxygen concentration profiles have provided important information on improving process control and reducing energy costs. The results show that dynamic off-gas testing can effectively be used for monitoring the aeration system and to check design assumptions under operating conditions. The information can be used to improve the design of new aeration systems or in retro-fitting existing basins.


Efficiency of the Guide Extension Catheter-Facilitated Tip-in Technique in the Recanalization of Coronary Chronic Total Occlusion.
The tip-in technique, which involves advancing an antegrade microcatheter cross the lesion over a retrograde guidewire, is an elaborated maneuver in the recanalization of coronary chronic total occlusion (CTO). We seek to assess the efficiency of a guide extension catheter-facilitated tip-in technique in comparison to the traditional retrograde approach, which is accomplished by an externalization wire. Thirty-three CTO patients successfully revascularized using guide extension catheter-facilitated "tip-in" were included and matched with another 33 patients by J-CTO score and operators, whose CTO was recanalized using an externalized wire. The manipulation time from the first retrograde wire entering the antegrade guide to the first antegrade balloon inflation in the occlusion was calculated. Compared with the wire-externalization group, the manipulation time in the tip-in group was significantly shortened [389s; interquartile range (IQR), 272-478 vs 706s; IQR, 560-914; p < 0.001]. There was a trend in decreasing total operation time and radiation dose, but it did not reach statistical significance. Guide extension catheter-facilitated tip-in is an efficient method to achieve the recanalization of CTO in a retrograde way, which would be pivotal when the retrograde microcatheter could not be advanced into the antegrade guide catheter.


Psychosocial stress and its relation to obstetrical complications.
A Greek adaptation of the Schedule of Recent Experience of Holmes and Rahe was employed to study the relationship of psychosocial stress to symptoms during pregnancy, obstetric complications, family planning and breast feeding. An initial experiment with 130 pregnant women in the third trimester indicated that psychosocial stress was not related to education, whether they were from Athens or the provinces, nor age. The second experiment with 103 mothers 3 or 4 days after delivery indicated that high psychosocial stress is related to increased symptom scores during pregnancy and to obstetric complications. Symptoms were not related to obstetric complications, nor were family planning nor breast feeding. Psychosocial stress was also related to family planning and also to whether or not the mother breast fed.


[Predictive value of molecular response after treatment with tyrosine kinase inhibitor for 3 months in patients with chronic myeloid leukemia].
To understand the predictive value of early monitoring BCR-ABL transcripts in patients with chronic myeloid leukemia (CML) after treatment with tyrosine kinase inhibitor (TKI), and to provides the information for early assessment of prognosis and treatment options. BCR-ABL transcripts of 53 CML patients before and after TKI treatment were detected by using real-time quantitative RT-PCR. The relationship between BCR-ABL transcripts level after TKI treatment for 3 months and the later molecular response, progression and mutation was analyzed. The median values of BCR-ABL transcripts in peripheral blood samples from 30 newly diagnosed patients were 43.99%, which was used as a baseline of BCR-ABL transcripts for molecular response evaluation. Of 53 patients, 31 (58.49%) had a BCR-ABL mRNA ≤ 4.40% (reduced more than 1 log) and 22 (41.51%) greater than 4.40% (reduced to less than 1 log) after 3 months of TKI treatment. The former 31 patients had a significantly higher 18-months cumulative incidence of major molecular response (MMR) (90.32% vs 18.18%, P=0.000) and 3-year cumulative incidence of complete molecular response (CMR) (48.39% vs 0, P=0.000) compared with the latter 22 patients. The lower BCR-ABL level was, the earlier MMR reached. The proportion of patients with a mutation in group of BCR-ABL mRNA>4.40% was significantly higher than that of BCR-ABL mRNA ≤ 4.40% (22.73% vs 0, P=0.021). The incidence of progression increased in group of BCR-ABL mRNA>4.40%, but the difference was not statistically significant (P=0.052). It is important for the prognosis evaluation of the patients to monitor the level of BCR-ABL transcripts at 3 months after TKI treatment, which might help to early optimization of treatment and to improve curative effect of CML patients.


The feeling of action tendencies: on the emotional regulation of goal-directed behavior.
In this article, we review the nature of the functional and causal relationship between neurophysiologically/psychologically generated states of emotional feeling and action tendencies and extrapolate a novel perspective. Emotion theory, over the past century and beyond, has tended to regard feeling and action tendency as independent phenomena: attempts to outline the functional and causal relationship that exists between them have been framed therein. Classically, such relationships have been viewed as unidirectional, but an argument for bidirectionality rooted in a dynamic systems perspective has gained strength in recent years whereby the feeling-action tendency relationship is viewed as a composite whole. On the basis of our review of somatic-visceral theories of feelings, we argue that feelings are grounded upon neural-dynamic representations (elevated and stable activation patterns) of action tendency. Such representations amount to predictions updated by cognitive and bodily feedback. Specifically, we view emotional feelings as minimalist predictions of the action tendency (what the agent is physiologically and cognitively primed to do) in a given situation. The essence of this point is captured by our exposition of action tendency prediction-feedback loops which we consider, above all, in the context of emotion regulation, and in particular, of emotional regulation of goal-directed behavior. The perspective outlined may be of use to emotion theorists, computational modelers, and roboticists.


Contrast-enhanced micro-computed tomography using ExiTron nano6000 for assessment of liver injury.
To explore the potential of contrast-enhanced computed tomography (CECT) using ExiTron nano6000 for assessment of liver lesions in mouse models. Three mouse models of liver lesions were used: bile duct ligation (BDL), lipopolysaccharide (LPS)/D-galactosamine (D-GalN), and alcohol. After injection with the contrast agent ExiTron nano6000, the mice were scanned with micro-CT. Liver lesions were evaluated using CECT images, hematoxylin and eosin staining, and serum aminotransferase levels. Macrophage distribution in the injury models was shown by immunohistochemical staining of CD68. The in vitro studies measured the densities of RAW264.7 under different conditions by CECT. In the in vitro studies, CECT provided specific and strong contrast enhancement of liver in mice. CECT could present heterogeneous images and densities of injured livers induced by BDL, LPS/D-GalN, and alcohol. The liver histology and immunochemistry of CD68 demonstrated that both dilated biliary tracts and necrosis in the injured livers could lead to the heterogeneous distribution of macrophages. The in vitro study showed that the RAW264.7 cell masses had higher densities after LPS activation. Micro-CT with the contrast agent ExiTron nano6000 is feasible for detecting various liver lesions by emphasizing the heterogeneous textures and densities of CECT images.


[Is it necessary to use an isotopic diuretic renogram in grade II pyelocaliceal dilatations diagnosed with ultrasonography?].
The increasing number of ultrasonographically detected asymptomatic, renal dilations have caused a lot of explorations to be performed in these patients. The Society of Fetal Urology proposed a four grades classification of echographic renal dilations and renographic studies are recommended in grades II to IV. However we have observed that grade II dilations don't evolve to obstruction. The aim of this work is to evaluate the obstruction rate in this group of patients, and the necessity or not of practising diuretic renography. We studied 42 children diagnosed of grade II renal dilation during a 1.5 year period. Left side was more frequently affected, 23 cases, 7 cases were bilateral what means 49 affected renal units. There was a male predominance (69%). Mean age at diagnosis was 2 months (0 to 36 months). Seventy nine per cent were prenatally diagnosed. The MAG-3 renal scan showed 48 unobstructed renal units and 1 obstructed. The F-15 variant was made in 15 cases by a doubtful curve or retarded elimination. The patient with obstructive curve presented an 15 mm renal pelvic diameter echographically measured and the intravenous urography showed a higher dilation being operating on. The mean time follow up was 23.5 months (13 to 53 months) without any change. Grade II pielocalicial dilations with renal pelvis lesser than 15 mm can be echographically controlled without renal scan. It should be performed only if renal dilation increases.


Understanding the Links Between Lung Cancer, COPD, and Emphysema: A Key to More Effective Treatment and Screening.
Lung cancer has been linked to the changes in lung function characteristic of chronic obstructive pulmonary disease (COPD) and to the changes in lung morphology seen in emphysema. It seems that a common thread of smoking-induced lung injury can be traced to all three diseases. However, the association is not as straightforward as it may seem; for example, even never-smokers with emphysema have an increased risk of lung cancer. Whether lung cancer, COPD, and emphysema are linked by common genes, mechanisms, causes, or a combination thereof, understanding the associations between them has become a priority for research regarding tobacco-related illnesses. A better delineation of the relationships between these three entities may lead to significant improvements in the effectiveness of lung cancer screening programs, and to reductions in the morbidity and mortality associated with these deadly diseases.


Use of hexapole magnet and spin flipper combined with time-of-flight analysis to characterize state-selected paramagnetic atomic/molecular beams.
In the past, the Stern-Gerlach experiment has been used as a standard method for analyzing the population of magnetic substates contained in spin-polarized and/or state-selected atomic/molecular beams. However, this experiment is quite demanding due to its low signal intensity and difficulty in beam alignment. The present study shows that the use of a hexapole magnet and a spin flipper, together with the time-of-flight analysis, allows us to conduct an almost equivalent analysis while greatly improving the signal intensity. Applications to the analysis of spin-polarized triplet excited helium and state-selected O2( 3 Σg -) beams are presented.


Self-Assembly and Water-like Anomalies in Janus Nanoparticles.
We explore the pressure versus temperature phase diagram of a system of dimeric Janus nanoparticles using molecular dynamics simulations. Each nanoparticle is modeled as a dumbbell which has one monomer that interacts by a standard Lennard-Jones potential while the other monomer interacts by a core-softened potential. The systems composed by particles interacting only by core-softened potential exhibit the density and the diffusion anomalous behavior observed in water while if the particles interact only by the Lennard-Jones potential no anomaly is present. Here we explore if the anomalous behavior is present when half of the particles are modeled by a core-softened potential and half with Lennard-Jones potential. We show that the diffusion anomaly is preserve, while the density anomaly can disappear depending on the nonanomalous monomer characteristics. We also show that the self-assembly structures characteristics of the dumbbell systems are affected by the balance between core-softened and non-core-softened monomers.


Glucagon-like peptide-1 receptor agonists suppress water intake independent of effects on food intake.
Glucagon-like peptide-1 (GLP-1) is produced by and released from the small intestine following ingestion of nutrients. GLP-1 receptor (GLP-1R) agonists applied peripherally or centrally decrease food intake and increase glucose-stimulated insulin secretion. These effects make the GLP-1 system an attractive target for the treatment of type 2 diabetes mellitus and obesity. In addition to these more frequently studied effects of GLP-1R stimulation, previous reports indicate that GLP-1R agonists suppress water intake. The present experiments were designed to provide greater temporal resolution and site specificity for the effect of GLP-1 and the long-acting GLP-1R agonists, exendin-4 and liraglutide, on unstimulated water intake when food was and was not available. All three GLP-1R ligands suppressed water intake after peripheral intraperitoneal administration, both in the presence of and the absence of food; however, the magnitude and time frame of water intake suppression varied by drug. GLP-1 had an immediate, but transient, hypodipsic effect when administered peripherally, whereas the water intake suppression by IP exendin-4 and liraglutide was much more persistent. Additionally, intracerebroventricular administration of GLP-1R agonists suppressed water intake when food was absent, but the suppression of intake showed modest differences depending on whether the drug was administered to the lateral or fourth ventricle. To the best of our knowledge, this is the first demonstration of GLP-1 receptor agonists affecting unstimulated, overnight intake in the absence of food, the first test for antidipsogenic effects of hindbrain application of GLP-1 receptor agonists, and the first test of a central effect (forebrain or hindbrain) of liraglutide on water intake. Overall, these results show that GLP-1R agonists have a hypodipsic effect that is independent of GLP-1R-mediated effects on food intake, and this occurs, in part, through central nervous system GLP-1R activation.


Dietary squid ink polysaccharide could enhance SIgA secretion in chemotherapeutic mice.
Secretory immunoglobulin A (SIgA) is a non-inflammatory antibody that shields internal body surfaces, such as in the intestine to neutralize pathogens in the lumen of the intestine. As chemotherapy seriously damages the mucosal immune system, we herein demonstrated that polysaccharide from the squid ink of Ommastrephes bartrami (OBP) activated intestinal SIgA secretion to prevent chemotherapeutic injury. Using a mouse model of chemotherapy induced intestinal injury by intraperitoneal injection of 50 mg kg(-1) cyclophosphamide, our results showed an enhanced SIgA concentration in intestinal mucosa by OBP administration and the higher production of SIgA relied on the greater expression of IgA, J chain and pIgR. Furthermore, the higher expressions of IL-6, IL-10 and TNF-α increased by OBP treatment contributed to enhanced IgA and J chain synthesis in IgA(+) plasma cells, and pIgR expression in epithelial cells. It also triggered a prompt immunoglobulin secretory pathway confirmed by enhanced UPR (unfolded protein response) effectors XBP-1s and Bip expression. Our results have important implications for the mucosal immunity enhancement effects of OBP as a functional food component for chemotherapeutic patients.


The Role of Voltage-Gated Sodium Channel 1.8 in the Effect of Atropine on Heart Rate: Evidence From a Retrospective Clinical Study and Mouse Model.
Atropine is commonly used to counter the effects of the parasympathetic neurotransmitter acetylcholine on heart rate in clinical practice, such as in the perioperative period; however, individual differences in the response to atropine are huge. The association between SCN10A/voltage-gated sodium channel 1.8 (NaV1.8) and cardiac conduction has been demonstrated; however, the exact role of SCN10A/NaV1.8 in the heart rate response to atropine remains unclear. To identify the role of SCN10A variants that influence the heart rate responses to atropine, we carried out a retrospective study in 1,005 Han Chinese subjects. Our results showed that rs6795970 was associated with the heart rate response to atropine. The heart rate responses to atropine and methoctramine in NaV1.8 knockout mice were lower, whereas the heart rate response to isoproterenol was like those in wild type mice. Furthermore, we observed that the NaV1.8 blocker A-803467 alleviated the heart rate response to atropine in wild type mice. The retrospective study revealed a previously unknown role of NaV1.8 in controlling the heart rate response to atropine, as shown by the animal study, a speculative mechanism that may involve the cardiac muscarinic acetylcholine receptor M2.


Complement sensitivity of erythrocytes in a patient with inherited complete deficiency of CD59 or with the Inab phenotype.
We investigated the complement sensitivity of erythrocytes from three patients, one with inherited complete deficiency of CD59, one with the Inab phenotype, and one with paroxysmal nocturnal haemoglobinuria (PNH). The complement lysis sensitivity units on the erythrocytes were 11.7, 4.6, and 47.6 for inherited CD59 deficiency, Inab phenotype, and PNH, respectively. Two-colour flow cytometric analysis showed that the erythrocytes from the three patients consisted of a single population negative for CD59, negative for decay accelerating factor (DAF), and negative for both proteins, respectively. In addition, only the Inab phenotype patient had no haemolysis in vivo. These facts suggest that CD59 deficiency plays a more important role than DAF deficiency in complement-mediated haemolysis in vitro and in vivo, and that deficiency of both proteins, but not CD59 or DAF alone, causes complement sensitivity corresponding to that of PNH III erythrocytes in vitro.


The Challenge of Achieving Greater Generalization in Phonological Treatment of Aphasia.
Stimulus selection is important to anomia treatment because similarity between trained and untrained words in the mental lexicon may influence treatment generalization. We focused on phonological similarity between trained and untrained words from a clinical trial of Phonomotor Treatment (PMT) that showed gains in confrontation naming accuracy of untrained words post-treatment. One way to capture the amount of similarity between the trained and untrained words is to consider the phonological network path distance between words. We posited that the distance between trained and untrained words in a phonological network could account for the improvement in confrontation naming accuracy post-treatment. To define the phonological network distance between trained and untrained words that influences change in confrontation naming accuracy post-treatment. We retrospectively analyzed data from 28 people with aphasia who received PMT as part of a clinical trial. Participants completed confrontation naming (baseline, post-treatment, and 3-months post-treatment) of words varying in phonological distance to the treatment stimuli. We used a phonological network to calculate the average shortest path length (ASPL), defined by number of phoneme differences, between an untrained word and all trained words. We used mixed effects regression models to predict change in confrontation naming accuracy of untrained words post-treatment from ASPL. Several post-hoc analyses were also conducted. We found no effect of ASPL on change in confrontation naming accuracy of untrained words immediately post- and 3-months post-treatment. However, post-hoc analyses indicated significant subject heterogeneity and limitations in observable path distance between trained and untrained words. Despite the clinical trial report that confrontation naming of untrained words improved after PMT, we found no overall effect of ASPL on the amount of improvement. We discuss further investigation of the entire domain of phonological sequence knowledge (the phonological sequence knowledge landscape) and its influence on treatment generalization, and the potential importance of identifying predictors of treatment response to enhance the effects of treatment generalization.


Multiple Antitumor Molecular Mechanisms Are Activated by a Fully Synthetic and Stabilized Pharmaceutical Product Delivering the Active Compound Sulforaphane (SFX-01) in Preclinical Model of Human Glioblastoma.
Frequent relapses and therapeutic resistance make the management of glioblastoma (GBM, grade IV glioma), extremely difficult. Therefore, it is necessary to develop new pharmacological compounds to be used as a single treatment or in combination with current therapies in order to improve their effectiveness and reduce cytotoxicity for non-tumor cells. SFX-01 is a fully synthetic and stabilized pharmaceutical product containing the α-cyclodextrin that delivers the active compound 1-isothiocyanato-4-methyl-sulfinylbutane (SFN) and maintains biological activities of SFN. In this study, we verified whether SFX-01 was active in GBM preclinical models. Our data demonstrate that SFX-01 reduced cell proliferation and increased cell death in GBM cell lines and patient-derived glioma initiating cells (GICs) with a stem cell phenotype. The antiproliferative effects of SFX-01 were associated with a reduction in the stemness of GICs and reversion of neural-to-mesenchymal trans-differentiation (PMT) closely related to epithelial-to-mesenchymal trans-differentiation (EMT) of epithelial tumors. Commonly, PMT reversion decreases the invasive capacity of tumor cells and increases the sensitivity to pharmacological and instrumental therapies. SFX-01 induced caspase-dependent apoptosis, through both mitochondrion-mediated intrinsic and death-receptor-associated extrinsic pathways. Here, we demonstrate the involvement of reactive oxygen species (ROS) through mediating the reduction in the activity of essential molecular pathways, such as PI3K/Akt/mTOR, ERK, and STAT-3. SFX-01 also reduced the in vivo tumor growth of subcutaneous xenografts and increased the disease-free survival (DFS) and overall survival (OS), when tested in orthotopic intracranial GBM models. These effects were associated with reduced expression of HIF1α which, in turn, down-regulates neo-angiogenesis. So, SFX-01 may have potent anti-glioma effects, regulating important aspects of the biology of this neoplasia, such as hypoxia, stemness, and EMT reversion, which are commonly activated in this neoplasia and are responsible for therapeutic resistance and glioma recurrence. SFX-01 deserves to be considered as an emerging anticancer agent for the treatment of GBM. The possible radio- and chemo sensitization potential of SFX-01 should also be evaluated in further preclinical and clinical studies.


Serum antibody response to the superficial and released components of Helicobacter pylori.
Superficial and released components were extracted from six selected Helicobacter pylori strains. The protein and antigenic profiles of these extracts were representative of the profiles found most frequently among the clinical strains and included major peptidic fractions at 19, 23.5, 57, 68, 76, 118, and 132 kDa and major antigens at 68, 57, and 23.5 kDa. Immuno-cross-reactions were seen with a hyperimmune rabbit serum to Campylobacter fetus but not with sera to Campylobacter jejuni or Salmonella spp. An antigenic preparation was obtained by pooling equivalent quantities of each extract, and the antigenic preparation was used to study the antibody responses of sera from 65 French patients and 127 Tunisian patients. By enzyme-linked immunosorbent assay, we observed that the sera from French and Tunisian patients clustered into two populations, defined as antibody positive (72 patients) and antibody negative (120 patients). The antibody-positive patients were more frequently infected with H. pylori (P < 0.01) and were more frequently affected with gastritis (P = 0.05). However, no correlation between antibody levels and clinical signs of dyspepsia was noticed. The proportions of antibody-positive patients were similar in France and Tunisia. Antibody-positive and antibody-negative sera were studied by western blot (immunoblot) analysis. The antibody-positive sera revealed an average of 7.7 antigenic bands, whereas the antibody-negative sera revealed an average of 2.4 antigenic bands (P < 0.01). The antigens between 15 and 40 kDa and greater than 66 kDa were specifically recognized by the antibody-positive sera, although in this molecular size range the antibody profiles of these sera exhibited a fairly high degree of diversity. We conclude that the superficial and released components from H. pylori contain a variety of bacterial immunogens and may be useful in antigenic preparations for the serodiagnosis of H. pylori infections. Moreover, a group of antigens in combination appears to be useful for discriminating antibody-positive and antibody-negative patients.


Toxicity testing of crude oil and related compounds using early life stages of the crimson-spotted rainbowfish (Melanotaenia fluviatilis).
The toxicity of petroleum hydrocarbons to marine aquatic organisms has been widely investigated; however, the effects on freshwater environments have largely been ignored. In the Australian freshwater environment, the potential impacts of petroleum hydrocarbons are virtually unknown. The toxicity of crude oil and related compounds were measured in the sensitive early life stages of the crimson-spotted rainbowfish (Melanotaenia fluviatilis). Waterborne petroleum hydrocarbons crossed the chorion of embryonic rainbowfish, reducing survival and hatchability. Acute exposures resulted in developmental abnormalities at and above 0.5 mg/L total petroleum hydrocarbons (TPH). Deformities included pericardial edema, disturbed axis formation, and abnormal jaw development. When assessing the acute toxicities of the water-accommodated fraction (WAF) of crude oil, dispersants, dispersant-oil mixtures, and naphthalene to larval rainbowfish, the lowest to highest 96-h median lethal concentrations for day of hatch larvae were naphthalene (0.51 mg/L), dispersed crude oil WAF (DCWAF)-9527 (0.74 mg/L TPH), WAF (1.28 mg/L TPH), DCWAF-9500 (1.37 mg/L TPH), Corexit 9500 (14.5 mg/L TPH), and Corexit 9527 (20.1 mg/L). Using naphthalene as a reference toxicant, no differences were found between the sensitivities of larval rainbowfish collected from adults exposed to petroleum hydrocarbons during embryonic development and those collected from unexposed adults.


Micropulse Transscleral Cyclophotocoagulation as Primary Surgical Treatment for Primary Open Angle Glaucoma in Taiwan during the COVID-19 Pandemic.
Glaucoma is the leading cause of irreversible blindness worldwide, with primary open angle glaucoma (POAG) accounting for the greatest number of total glaucoma cases. This study aimed to evaluate the efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-TSCPC) as a primary procedure in POAG during the COVID-19 pandemic. We retrospectively analyzed 60 eyes of 52 patients, who were diagnosed with mild-to-end-stage POAG without previous glaucoma surgery and received MP-TSCPC between 1 January 2020 and 31 August 2020. The mean preoperative intraocular pressure (IOP) significantly decreased from 27.8 mm Hg to 19.8, 20.1, 20.3, 20.4, and 20.2 mm Hg at 1, 3, 6, 9, and 12 months, respectively (all p < 0.05). The mean number of IOP-lowering medications used significantly decreased from 3.3 at the baseline to 1.6, 1.8, 1.8, 1.9, and 1.9 at 1, 3, 6, 9, and 12 months, respectively (all p < 0.001). Total withdrawal of antiglaucoma medications was fulfilled in five patients. The main outcome was achieved in 81.7% at postoperative month 12. The most common adverse effect was transient mydriasis (28.3%). No major complications were encountered. MP-TSCPC seems to be an effective and safe treatment to reduce IOP and the medication burden with minimal vision-threatening complications in mild-to-end-stage POAG patients without previous glaucoma surgery.


Hepato-splenic candidiasis confirmed following splenectomy: a case report.
We report a case of severe refractory hepato-splenic candidiasis confirmed following splenectomy in an immunocompromised 54-year-old woman treated for acute lymphoblastic leukemia. Liver biopsies did not contribute to identifying the etiology of the multiple hepato-splenic lesions. In view of the lack of improvement after several lines of antifungal treatments, a splenectomy was performed and confirmed splenic candidiasis. PET/CT scan was used to monitor the evolution of hepato-splenic hypermetabolism. Splenectomy can be envisaged to establish fungal infection in immuno-compromised patients, to exclude relapse, and to guide the choice of antifungal agents.


[Neuroendocrine tumors of the pancreas].
Neuroendocrine tumours are rare and often include insulinoma, gastrinoma and other low frequency tumours that secrete gastrointestinal hormones. Their preoperative localization, despite continuous medical advances, is extremely difficult but helpful in guiding the surgeon towards a proper form of treatment. After presenting their cases, the authors conclude that the treatment of choice for these tumours is surgery due to their anatomopathological features (benign, scarcely malign or invasive, slow growth). On the other hand, medical therapy plays an important role in either preparing the surgical intervention or alleviating symptoms when the patient is inoperable.


Facile Preparation and Characteristic Analysis of Sulfated Cellulose Nanofibril via the Pretreatment of Sulfamic Acid-Glycerol Based Deep Eutectic Solvents.
A deep eutectic solvent (DES) composed of sulfamic acid and glycerol allowed for the sustainable preparation of cellulose nanofibrils (CNF) with simultaneous sulfation. The reaction time and the levels of sulfamic acid demonstrated that fibers could be swelled and sulfated simultaneously by a sulfamic acid-glycerol-based DES and swelling also promoted sulfation with a high degree of substitution (0.12). The DES-pretreated fibers were further nanofibrillated by a grinder producing CNF with diameters from 10 nm to 25 nm. The crystallinity ranged from 53-62%, and CNF maintained the original crystal structure. DES pretreatment facilitated cellulose nano-fibrillation and reduced the energy consumption with a maximum reduction of 35%. The films prepared from polyvinyl alcohol (PVA) and CNF showed good UV resistance ability and mechanical properties. This facile and efficient method provided a more sustainable strategy for the swelling, functionalization and nano-fibrillation of cellulose, expanding its application to UV-blocking materials and related fields.


[Use of muscular and cutaneous fascial flaps in treatment of open tibial fracture with soft tissue defects].
Owen experience in treatment of 14 patients with tibial fracture complicated by wasted soft tissue defect is presented. External fixation has been combined with transposition of medial head of gastrocnemius, soleus muscle or transposition of cutaneous fascial flap has healed the infection ceased and the fracture united in all cases. Encouraging results prove efficacy and usefulness of this method.


Current challenges in the treatment of complicated urinary tract infections and prostatitis.
Serious urinary tract infections (UTIs) and acute bacterial prostatitis in adults cause significant morbidity and economic burden. Chronic bacterial prostatitis is a rather rare condition seen in urological practice, however, in certain occasions difficult to treat. In this paper, we review the bacterial etiologies and the resistance patterns found in adults with serious UTIs and bacterial prostatitis, and discuss considerations for selecting optimal antimicrobial therapy. The role of fluoroquinolones as targeted therapy for serious UTIs is highlighted. The use of effective antimicrobial therapy is the foundation of management of serious UTIs and bacterial prostatitis. Selection of the optimal antimicrobial agent must take into account patient-specific factors; infection characteristics (e.g., severity, community- vs. institutional- or hospital-acquired, need for IV agent, UTI, prostatitis); local resistance pattern; pharmacokinetic and pharmacodynamic principles; and cost. Fluoroquinolones are among the alternatives for empirical antibiotic treatment of serious UTIs and acute bacterial prostatitis. In serious UTIs activity of the antimicrobial agent against Pseudomonas aeruginosa needs to be taken into account. In chronic bacterial prostatitis fluoroquinolones are the first choice because of their favourable pharmacokinetic properties at the site of infection. Targeted antimicrobial therapy--emphasising the correct antibacterial spectrum and correct dosage--is likely to provide important benefits, such as reduced morbidity and associated costs, reduced emergence of resistance and maintenance of class efficacy.


Geochronology: age of Mexican ash with alleged 'footprints'.
A report of human footprints preserved in 40,000-year-old volcanic ash near Puebla, Mexico (http://www.royalsoc.ac.uk/exhibit.asp?id=3616&tip=1), was the subject of a press conference that stirred international media attention. If the claims (http://www.mexicanfootprints.co.uk) of Gonzalez et al. are valid, prevailing theories about the timing of human migration into the Americas would need significant revision. Here we show by 40Ar/39Ar dating and corroborating palaeomagnetic data that the basaltic tuff on which the purported footprints are found is 1.30+/-0.03 million years old. We conclude that either hominid migration into the Americas occurred very much earlier than previously believed, or that the features in question were not made by humans on recently erupted ash.


Magnetic resonance imaging of the prostate.
Magnetic resonance imaging offers new possibilities in the investigation of the prostate. The current results of imaging and tissue discrimination in the evaluation of prostatic disease are reviewed. Magnetic resonance imaging may be of value in the staging of carcinoma of the prostate.


Introducing the Mangrove Microbiome Initiative: Identifying Microbial Research Priorities and Approaches To Better Understand, Protect, and Rehabilitate Mangrove Ecosystems.
Mangrove ecosystems provide important ecological benefits and ecosystem services, including carbon storage and coastline stabilization, but they also suffer great anthropogenic pressures. Microorganisms associated with mangrove sediments and the rhizosphere play key roles in this ecosystem and make essential contributions to its productivity and carbon budget. Understanding this nexus and moving from descriptive studies of microbial taxonomy to hypothesis-driven field and lab studies will facilitate a mechanistic understanding of mangrove ecosystem interaction webs and open opportunities for microorganism-mediated approaches to mangrove protection and rehabilitation. Such an effort calls for a multidisciplinary and collaborative approach, involving chemists, ecologists, evolutionary biologists, microbiologists, oceanographers, plant scientists, conservation biologists, and stakeholders, and it requires standardized methods to support reproducible experiments. Here, we outline the Mangrove Microbiome Initiative, which is focused around three urgent priorities and three approaches for advancing mangrove microbiome research.


Gene expression analysis of the microdissected trophoblast layer of human placenta after the spontaneous onset of labor.
Despite increasing evidence that human parturition is associated with alteration in gene expression in the uteroplacental unit, the precise mechanisms that elicit spontaneous term labor in humans remain unknown. Our goal in this study was to compare the mRNA expression pattern of the trophoblast layer of normal term placenta between women who had given natural birth (labor group) and those who had undergone an elective cesarean section without labor (non-labor group). We collected placental tissue samples from six pregnant women after term vaginal deliveries (labor group) and from six pregnant women after scheduled Cesarean sections (non-labor group). Frozen sections were made immediately after placental delivery. Because the placenta is a heterogeneous tissue composed of several cell types, we used laser capture microdissection to separate the trophoblast layer from the rest of the placental tissues. A number of genes were differentially expressed in the trophoblast layer when the labor and non-labor groups were compared. The expression of SIRT1, KAP1, and CRH was significantly lower in the trophoblast layer of the labor group than of the non-labor group. The expression of IL-1b, NF-kB1 and TLR 8 in the labor group was significantly higher than that in the non-labor group. Human term labor may be closely associated with inflammatory response. We suggest that downregulation of SIRT1, KAP1, and CRH gene expression in the trophoblast may play a key role in parturition and initiation of labor in pregnant human females.


Discrete breakpoint mapping and shortest region of overlap of chromosome arm 1q gain and 1p loss in human hepatocellular carcinoma detected by semiquantitative microsatellite analysis.
Recurrent chromosomal gain at 1q is one of the most common features of human hepatocellular carcinoma (HCC), but how the gain at 1q contributes to hepatocarcinogenesis is still unclear. To identify the target genes, precise determination of the shortest region of overlap (SRO) and of breakpoints is necessary. Similarly, the role of loss at 1p, which is also a major cytogenetic aberration in HCC, needs to be determined. Fifty HCCs were examined with the aid of 59 microsatellite markers distributed throughout both arms of chromosome 1. To detect allelic gain effectively, the cutoff value of the allelic imbalance index was set at 0.70. Alleles showing imbalance were subjected to multiplex PCR, using a retained allele as an internal control, to determine whether the imbalance was the result of chromosomal gain or loss. The SRO of the gains was defined as D1S2878-D1S2619 (1q23.-q25.3, 16.9 Mb), which involved 36 cases (72%). Gains in the number of copies of certain oncogenes within this region seemed to be critical for the pathogenesis of HCC. In contrast, the centromeric breakpoints of these gains varied, but they tended to occur mainly in the pericentromeric region (26 of 50 cases, 52%). Rearrangement of specific genes associated with the gains is unlikely. On the other hand, the SRO of deletion was defined as D1S2893-D1S450 (1p36.32-p36.22, 5.1 Mb). Four known putative tumor-suppressor genes (TP73, RIZ1, NBL1/DAN, and CDKN2C) were outside the SRO, suggesting the presence of other candidate genes with critical roles in hepatocarcinogenesis.


Adolescents and asthma: why bother with our meds?
Adherence to inhaled steroid regimens for asthma is poor in adults and children. Although it is assumed that nonadherence contributes to morbidity in older adolescents, investigation is limited. We sought to describe adherence to preventive asthma medications and explore relevant beliefs and attitudes in older urban adolescents, including their ideas for improving adherence. Quantitative and qualitative methods were used to collect data from a convenience sample of adolescents with asthma previously prescribed fluticasone/salmeterol (F/S). Two semistructured face-to-face interviews were conducted 1 month apart and analyzed for themes. F/S use was electronically monitored between visits and calculated as the number of actuations divided by the number of inhalations prescribed. Forty participants, (15-18 years of age, 19 female subjects, 30 black/African American subjects, 11 Medicaid-insured subjects, and 24 previously hospitalized for asthma) with a median FEV1 of 98% of predicted value (range, 67% to 127%) had median adherence of 43% (range, 4% to 89%). Adherence was not associated with FEV1 or emergency department visits. Themes emerged from interviews as follows. Teens (1) take F/S inconsistently; (2) believe F/S is "supposed to help me breathe"; (3) dislike its taste; (4) are "too busy" and "forget"; and (5) recommend "reminder" solutions to poor adherence. Twenty percent believed that taking F/S was unnecessary, and another 18% expressed ambivalence about its benefits. Adherence was poor. Examining and acknowledging health beliefs of older teens in the context of their complicated lives might facilitate discussions about self-management.


Physiology in daily hemodialysis in terms of the time average concentration/time average deviation concept.
Quotidian or "daily" hemodialysis (DHD) is practiced in widely differing schedules. Yet all those schedules are reported to significantly ameliorate clinical outcome of patients. It is, however, not clear what is the actual cause of this amelioration. Rational possibilities include increased overall dialysis dose and increased weekly time. Conventional mathematical approaches (Kt/V(urea) concept, equivalent renal clearance) cannot be used to study those issues because they do not consider number of dialysis per week and thus ignore the issue of treatment schedule "unphysiology." The time average concentration/time average deviation (TAC/TAD) concept may well be used to visualize impact of treatment schedule on both plasma urea profile statics (TAC) and dynamics (TAD). The concept may further help to stratify studies for elucidation of the key factors of clinical outcome improvement seen on DHD. Actual physiologic mechanisms responsible for this improvement are to be sought among those with having derivative component (i.e., reacting to the rate of a change rather than to the magnitude of the change). It should, however, be kept in mind that the TAC/TAD concept is able to assess unphysiology of a treatment schedule, not unphysiology of a single treatment session.


Malignant Solitary Fibrous Tumor of the Pancreas.
Solitary fibrous tumor (SFT) arising in the pancreas is exceedingly rare, with only 11 cases reported in the English literature. All cases described thus far have exhibited benign histology. We report the first case of malignant SFT of the pancreas. The patient was a 52-year-old woman who presented with obstructive jaundice and a 15-cm pancreatic head mass. The mass showed areas with typical histologic features for SFT including small fibroblastlike cells arranged in the well-characterized "patternless pattern" of architecture, hemangiopericytomalike vessels, areas with dense collagen and infrequent mitoses (0-2 per 10 high-power fields [HPFs]). In addition, multiple areas with an overtly sarcomatous morphology were present, containing large spindle and epithelioid cells with nuclear pleomorphism, marked cellularity, up to17 mitoses per 10 HPFs, and necrosis. Immunohistochemical stains were positive for CD34 and B-cell CLL/lymphoma 2 (Bcl-2) in both benign and malignant components and showed strong, diffuse p53 and p16 staining in the malignant component. At last follow-up (40 months), the patient was alive and well without evidence of disease. However, given that the presence of a malignant component in extrapancreatic SFT has been associated with recurrence/metastasis and death, complete surgical resection and close long-term follow-up is required.


Clinical outcome of bioceramic sealer iRoot SP extrusion in root canal treatment: a retrospective analysis.
During the obturation procedure, sealer extrusion occurs in some cases. iRoot SP is a kind of bioceramic sealer with superior physicochemical and biological properties. This article reports the outcome of iRoot SP extrusion in root canal treatment and the potential factors associated with the outcome. Ninety-nine patients and one hundred and eighty-five teeth treated between 2014 and 2020 were included in this retrospective study. All of the cases were filled with a single-cone technique and the iRoot SP sealer. The minimum follow-up visit period was 1 year. The outcome was evaluated by clinical examination and radiographic examination at recall and was classified as healed, healing (success), or not healed (failure). The overall success rate of all teeth was 96.8%. The success rate of adequately filled teeth was 97.3%, while that of iRoot SP extrusion was 95.8%; the difference was not statistically significant. Factors such as gender, age, tooth position, follow-up visit period, size of periapical lesion, treatment type and extruding sealer amount had no influence on the outcome of iRoot SP extruded teeth. The results suggested that iRoot SP extrusion has no adverse effect on the outcome of root canal treatment, which may contribute to the endodontic treatment.


Lethal challenge of gnotobiotic weanling rats with bacterial isolates from cases of sudden infant death syndrome (SIDS).
An attempt was made to produce an animal model of sudden infant death syndrome (SIDS). The experimental animals (germ free weanling rats) were exposed to nasopharyngeal isolates from cases of SIDS to test the hypothesis that common bacteria may have an aetiological role in the disease. Negative results were obtained when the strains were tested in isolation, but certain combinations of organisms (specifically some Staphylococcus aureus and Escherichia coli) killed the animals rapidly (less than 18 hours) without prolonged terminal illness. Post mortem histological findings were consistent with those of SIDS. The lethal toxigenic potential of nasopharyngeal bacteria, which are regarded as harmless in adults, should be reconsidered in respect of the aetiology of SIDS.


On regional convergence in a transitional economy: the roles of migration and wages.
The role of migration in influencing convergence between regions at different levels of economic development is analyzed using the example of Germany following reunification, with particular reference to the impact of migration on wages. "Several ways of regional wage formation are investigated, among them a full employment wage mechanism as well as a fast regional convergence of wages which is independent of productivity movements. The conclusion is that the impact of wage mechanisms on the convergence of per capita output is ambiguous. However social costs in terms of unemployment are high in case of a wage adjustment which is regardless of productivity growth." (SUMMARY IN GER)


Antioxidants in oral cancer prevention.
I present evidence in support of a chemopreventive role for the so-called antioxidant nutrients, beta-carotene and vitamin E, against oral cavity cancer. This evidence is from laboratory studies, animal model systems, epidemiologic surveys, intervention trials involving reversal of premalignant changes, and prevention of malignancies in particularly high-risk subjects. Because agents proposed for disease prevention are meant to be used widely without close medical supervision, almost any toxicity is unacceptable. beta-Carotene and vitamin E fulfill this criterion for a suitable chemopreventive agent. In several epidemiologic studies, low intakes of vitamin E, carotenoids, or both have been associated with a higher cancer risk. Smoking, a major risk factor, results in lower beta-carotene concentrations in plasma and oral mucosal cells. In several laboratory and animal model systems, beta-carotene and other antioxidant nutrients are inhibitors of oral cavity carcinogenesis. beta-Carotene and vitamin E can produce clinical regression of oral leukoplakia, a premalignant lesion for oral cancer. The design and limitations of such studies in oral leukoplakia are discussed. Cancer incidence reduction trials in high-risk groups have targeted prevention of second malignancies in patients cured of a primary oral cancer. These trials are in progress. The data thus far are supportive of a significant preventive role for these nutrients in oral cancer.


Methods for summarizing the risk associations of quantitative variables in epidemiologic studies in a consistent form.
A major problem in reviewing the published results of different epidemiologic studies of the relation between a quantitative variable and the risk of disease is that the results are presented in many different ways. The purpose of this paper is to exemplify methods by which results expressed either as risks (or rates) according to quantlle groups of the quantitative variable or as results derived from a logistic regression analysis can be reexpressed in a uniform manner, as a mean difference in the quantitative variable between the cases of disease and the other subjects in the study. An important assumption of the methods is that the quantitative variable has an approximately normal distribution, and a way of investigating the appropriateness of this assumption is given. The methods can be applied to both prospective and case-control studies and are exemplified by a number of studies of serum albumin concentrations and mortality. In some applications, these methods can be used as a precursor to formal meta-analysis, for example, when differential control of potential confounding factors is not a problem. At the least, the methods can be useful either in quantitatively reviewing published studies before undertaking new research or in putting the results of a new study into the context of previously published ones.


Extreme value statistics and traveling fronts: application to computer science.
We study the statistics of height and balanced height in the binary search tree problem in computer science. The search tree problem is first mapped to a fragmentation problem that is then further mapped to a modified directed polymer problem on a Cayley tree. We employ the techniques of traveling fronts to solve the polymer problem and translate back to derive exact asymptotic properties in the original search tree problem. The second mapping allows us not only to again derive the already known results for random binary trees but to obtain exact results for search trees where the entries arrive according to an arbitrary distribution, not necessarily randomly. Besides it allows us to derive the asymptotic shape of the full probability distribution of height and not just its moments. Our results are then generalized to m-ary search trees with arbitrary distribution.


Assessing the credibility of young children's allegations of sexual abuse: clinical issues.
In assessing the credibility of young children's (ages 2-7) allegations of sexual abuse clinicians need to know how dynamics of sexual abuse affect disclosure, what situations are most commonly associated with fictitious allegations and how the child's developmental stage affects disclosures. Understanding these issues allows for clear decision making. A clear decision making process flows naturally from an understanding of these issues.


Diaphragmatic hernia with strangulated loop of bowel presenting after colonoscopy: case report.
The incidence of diaphragmatic hernias caused or exacerbated by diagnostic colonoscopy is not well elucidated at this time, and is believed to be very rare. We present the case of a 57 year old man with remote history of traumatic injury who first presented with vague left shoulder pain for two weeks, mild anemia, and tested positive for fecal occult blood. Four days post colonoscopy the patient was found to have a strangulated loop of bowel herniated through the diaphragm into the left hemithorax. In patients with previous history of serious traumatic injury and particularly those with previous splenectomy, a thorough history and physical examination before routine colonoscopy is important. A high level of suspicion for post-operative complications should also be maintained when assessing such patients.


Differences in energy and nutrient-intake among Greek children between 1992/93 and 2006/07.
There is lack of data in Greece on the trends in energy and nutrient intake. The present study aimed to examine differences in these parameters among first-grade children of Crete, Greece, between 1992/93 and 2006/07. Children (aged 5.7-7.6 years) from two-representative cross-sectional samples participated during 1992/93 (n = 245) and 2006/07 (n = 257). Nutrient and food intakes were assessed using estimated 3-day-food records. Nutrient intakes were estimated as amounts per 4185 kJ (1000 kcal) of energy intake (EI), whereas macronutrients were estimated as percentage of total EI. Between 1992/93 and 2006/07, respectively, significant increases (P < 0.05) were observed in the intake of energy (boys: 7996 versus 8646 kJ; girls: 7265 versus 7963 kJ), calcium (boys: 488 versus 587 mg; girls: 464 versus 594 mg), iron (boys: 5.8 versus 7.3 mg; girls: 5.7 versus 7.4 mg) and vitamins B2 (boys: 1.01 versus 1.17 mg; girls: 1.0 versus 1.16 mg) and B6 (boys: 0.80 versus 0.87 mg; girls: 0.75 versus 0.95 mg), for boys and girls, respectively. Among boys, the intake of protein (13.6 versus 14.6% of EI) and total trans fatty acids (TTFA) (0.84 versus 0.99 g) was also significantly lower in 1992/93 (P < 0.016). Between 1992/93 and 2006/07, total fat (boys: 42.9% versus 42.8%, girls: 42% versus 43.1%) and saturated fat (boys: 15.5% versus 15.4%, girls: 15% versus 15.3%) exceeded the 30-35% and <10% dietary recommendations, respectively, A significantly higher proportion of children in 2006/07, compared to 1992/93, had a higher intake of total energy (>120% of the recommended energy allowance). The intake of several macronutrients (protein, TTFA, total and saturated fat) in this sample of children did not meet the recommended intakes in either time period.


Hypophosphataemia due to FGF-23 producing B cell non-Hodgkin's lymphoma.
Oncogenic osteomalacia (or tumour-induced osteomalacia) is a rare paraneoplastic syndrome caused by overproduction of fibroblastic growth factor 23 (FGF-23) by tumours. Excessive production of FGF-23 can lead to severe, symptomatic hypophosphataemia. The majority of cases have been associated with benign tumours of bone or soft tissue, such as haemangiopericytomas or other neoplasms of mesenchymal origin. We present a case of a 68-year-old woman with an FGF-23 producing B cell non-Hodgkin's lymphoma. Treatment with immunochemotherapy resulted in normalisation of serum FGF-23 and phosphate levels.


Magnetic metal phenolic networks: expanding the application of a promising nanoprobe to phosphoproteomics research.
A Ti-tannic acid modified magnetic nanoprobe was synthesized via one step, and applied to phosphopeptide extraction. 3456 phosphopeptides and 1285 phosphoproteins were finally identified from 100 μg HeLa cell extracts. This opens up a new avenue for metal phenolic networks in phosphoproteomics research.


Sexuality and psychoanalytic aggrandisement: Freud's 1908 theory of cultural history.
In 1908, in his article "'Civilized" sexual morality and modern nervous illness', Freud presented neuroses as the consequence of a restrictive state of cultural development and its 'civilized morality'. He found the inspiration for this idea by expanding upon previous formulations in this area by his predecessors (notably Christian von Ehrenfels) that focused on a cultural process earlier introduced by Kant, while also integrating in his analysis the principles of Haeckel's evolutionism (history of development, recapitulation) which eventually re-defined the psychoanalytic theory of neuroses. These new theoretical elements became the basis of psychoanalytic theory and thereby influenced subsequent thinking in the cultural process itself and in human sciences. This transformation of underlying theory provided a unique historical and analytical framework for psychoanalysis which allowed Freud to claim for it a pre-eminent position among the human sciences.


Implication of Gastric Cancer Molecular Genetic Markers in Surgical Practice.
We have investigated aberrant methylation of genes CDH1, RASSF1A, MLH1, N33, DAPK, expression of genes hTERT, MMP7, MMP9, BIRC5 (survivin), PTGS2, and activity of telomerase of 106 gastric tumor samples obtained intra-operatively and 53 gastric tumor samples from the same group of patients obtained endoscopically before surgery. Biopsy specimens obtained from 50 patients with chronic calculous cholecystitis were used as a control group. Together with tissue samples obtained from different sites remote to tumors, a total of 727 samples have been studied. The selected parameters comprise a system of molecular markers that can be used in both diagnostics of gastric cancer and in dynamic monitoring of patients after surgery. Special attention was paid to the use of molecular markers for the diagnostics of malignant process in the material obtained endoscopically since the efficacy of morphological diagnostics in biopsies is compromised by intratumoral heterogeneity, which may prevent reliable identification of tumor cells in the sampling. Our data indicated that certain molecular genetic events provided more sensitive yet specific markers of the tumor. We demonstrated that molecular profiles detected in preoperative biopsies were confirmed by the material obtained intra-operatively. The use of endoscopic material facilitates gastric tumors pre-operative diagnostics, improving early detection of gastric cancer and potential effective treatment strategies.


Efficacy and Safety of Combined Embolization and Radiofrequency Ablation in Stage 1 Renal Cell Carcinomas.
To retrospectively evaluate outcomes of a combined interventional approach to stage 1 (cT1cN0cM0) renal cell carcinomas (RCCs) by transarterial embolization (TAE) followed by percutaneous CT-guided radiofrequency ablation (RFA) in patients ineligible for surgery. 13 patients (9 male, 4 female, 69.6 ± 16.6 y/o) with 14 RCCs (largest diameter: 40.4 ± 6.7 mm, cT1a: 4, cT1b: 10) were treated by RFA a median of one day after TAE in a single center. Indications for minimally invasive interventional therapy were bilateral RCCs (n = 4), RCCs in a single kidney after nephrectomy (n = 3), increased surgical risk due to comorbidities (n = 4), and rejection of surgical therapy (n = 2). Technical success, effectiveness, safety, ablative margin, cancer-specific survival, overall survival, and tumor characteristics were analyzed. All RCCs were successfully ablated after embolization with a minimum ablative margin of 1.2 mm. The median follow-up was 27 (1-83) months. There was no residual or recurrent tumor in the ablation zone. No patient developed metastasis. Two minor and two major complications occurred. Four patients with severe comorbidities died during follow-up due to causes unrelated to therapy. The 1-year and 5-year overall survival was 74.1 % each. Cancer-specific survival was 100 % after 1 and 5 years. There was no significant decline in mean eGFR directly after therapy (p = 0.226). However, the mean eGFR declined from 62.2 ± 22.0 to 50.0 ± 27.8 ml/min during follow-up (p < 0.05). The combination of TAE and RFA provides an effective minimally invasive therapy to stage 1 RCCs in patients ineligible for surgery. The outcomes compare favorably with data from surgery. · Interventional treatment by TAE and ablation is a safe and effective alternative to surgery in stage 1 RCCs.. · Focal therapy of RCCs preserves renal function.. · A small ablative margin appears to be sufficient in the ablation of RCCs.. · Wessendorf J, König AM, Heers H et al. Efficacy and Safety of Combined Embolization and Radiofrequency Ablation in Stage 1 Renal Cell Carcinomas. Fortschr Röntgenstr 2022; 194: 1020 - 1025.


The adaptor protein Nck links receptor tyrosine kinases with the serine-threonine kinase Pak1.
Nck is an adaptor protein composed of a single SH2 domain and three SH3 domains. Upon growth factor stimulation, Nck is recruited to receptor tyrosine kinases via its SH2 domain, probably initiating one or more signaling cascades. In this report, we show that Nck is bound in living cells to the serine-threonine kinase Pak1. The association between Nck and Pak1 is mediated by the second SH3 domain of Nck and a proline-rich sequence in the amino terminus of Pak1. We also show that Pak1 is recruited by activated epidermal growth factor (EGF) and platelet-derived growth factor receptors. Moreover, Pak1 kinase activity is increased in response to EGF in HeLa cells transfected with human Pak1, and the kinase activity was enhanced when Nck was co-transfected. It is concluded that Nck links receptor tyrosine kinases with Pak1 and is probably involved in targeting and regulation of Pak1 activity.


Oxford unicompartmental knee arthroplasty: medial pain and functional outcome in the medium term.
In our experience results of the Oxford unicompartmental knee replacement have not been as good as had been expected. A common post operative complaint is of persistent medial knee discomfort, it is not clear why this phenomenon occurs and we have attempted to address this in our study. 48 patients were retrospectively identified at a mean of 4.5 years (range = 3 to 6 years) following consecutive Oxford medial Unicompartmental Knee arthroplasties for varus anteromedial osteoarthritis. The mean age at implantation was 67 years (range 57-86). Of these 48 patients, 4 had died, 4 had undergone revision of their unicompartmental knee replacements and 2 had been lost to follow up leaving 38 patients with 40 replaced knees available for analysis using the 'new Oxford Knee Score' questionnaire. During assessment patients were asked specifically whether or not they still experienced medial knee discomfort or pain. The mean 'Oxford score' was only 32.7 (range = 16 to 48) and 22 of the 40 knees were uncomfortable or painful medially.The accuracy of component positioning was recorded, using standard post operative xrays, by summing the angulation or displacement of each component in two planes from the ideal position (according to the 'Oxford knee system radiographic criteria'). No correlation was demonstrated between the radiographic scores and the 'Oxford scores', or with the presence or absence of medial knee discomfort or pain. In our hands the functional outcome following Oxford Unicompartmental knee replacement was variable, with a high incidence of medial knee discomfort which did not correlate with the postoperative radiographic scores, pre-op arthritis and positioning of the prosthesis.


Socioeconomic Status, Race/Ethnicity, and Unexpected Variation in Dementia Classification in Longitudinal Survey Data.
As dementia affects a growing number of older adults, it is important to understand its detection and progression. We identified patterns in dementia classification over time using a longitudinal, nationally representative sample of older adults. We examined the relationship between socioeconomic status and race/ethnicity, and patterns in dementia classification. Data for 7,218 Medicare beneficiaries from the 2011-2017 National Health and Aging Trends Study (NHATS) were classified into five categories: consistently no dementia, consistently cognitive impairment, "typical" dementia progression, "expected" variation, and "unexpected" variation. Multivariable multinomial logistic regression assessed relative risk of dementia classification by sociodemographic and health factors. Among NHATS respondents, 59.5% consistently were recorded as having no dementia, 7% consistently cognitively impaired, 13% as having typical progression, 15% as having expected variation, and 5.5% as having unexpected variation. In multivariable models, compared with consistent dementia classification, less education, Medicare-Medicaid-dual enrollment, and identifying as non-Hispanic Black were associated with increased likelihood of unexpected variation (e.g., non-Hispanic Black adjusted risk ratio: 2.12, 95% CI: 1.61-2.78, p < .0001). A significant minority of individuals have unexpected patterns of dementia classification over time, particularly individuals with low socioeconomic status and identifying as non-Hispanic Black. Dementia classification uncertainty may make it challenging to activate resources (e.g., health care, caregiving) for effective disease management, underscoring the need to support persons from at-risk groups and to carefully evaluate cognitive assessment tools to ensure they are equally reliable across groups to avoid magnifying disparities.


Update: respiratory syncytial virus activity--United States, 1998-1999 season.
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in infants and young children worldwide. In temperate climates, RSV infections occur primarily during annual outbreaks, which peak during winter months . In the United States, RSV activity is monitored by the National Respiratory and Enteric Virus Surveillance System (NREVSS), a voluntary, laboratory-based system. This report summarizes trends in RSV activity reported to NREVSS during July 1998 June 1999 and presents preliminary surveillance data during July 1-November 12, 1999, which show that RSV community outbreaks are becoming widespread.


Effect of transcutaneous electrical nerve stimulation characteristics on clinical pain.
We compared the effects of four treatment variables on the pain reduction produced by transcutaneous electrical nerve stimulation and attempted to establish indications for TENS based on patient history and pain evaluation items. Treatment variables were the therapist and the three TENS stimulus characteristics--pulse width, frequency, and amplitude. We randomly assigned 192 consecutive adult patients suffering from painful conditions to one of four physical therapists and one of 12 stimulus characteristic combinations. We used a standard evaluation form that included a visual analog scale (VAS) to evaluate pain. Patients were given a 30-minute trial using TENS, followed by reevaluation. The VAS line length change after treatment was the criterion score for comparison of stimulus characteristic effectiveness. Although pain was reduced greatly with TENS (p = .01), a four-way analysis of variance (pulse width, frequency, amplitude, and therapist) attributed little of the treatment effect to the treatment variables or their interactions (r2 = .101). The amplitude effect, however, was borderline (p = .056), and subthreshold stimulation proved more effective than stimulation to tolerance (p = .05). Extensive multiple linear regression analyses failed to provide indications for TENS based on patient information and pain evaluation items. Therefore, pain remains the only indication for TENS, and we recommend subthreshold rather than higher amplitude stimulation on the initial TENS trial.


Current results of elective aortic reconstruction for aneurysmal and occlusive disease.
Decisions to resect small aortic aneurysms or employ non-operative treatment for aorto-iliac occlusive disease must depend on current rather than historical surgical results. To assess current morbidity and mortality, we reviewed 200 consecutive aortic resections in two groups of patients treated from 1981 to 1989: those undergoing elective aortofemoral bypass for occlusive disease (AFB, no. 100) or resection of infrarenal abdominal aortic aneurysms (AAA, no. 100). Indications for AFB included claudication (54%), rest pain (32%), and gangrene (13%). AAA size ranged from 3 to 14 cm (mean 6.5 +/- 2.4 cm); 45% presented with abdominal or back pain. Patients undergoing AFB were younger (AFB 61.5 +/- 10 years vs AAA 68.7 +/- 8.9 years) with a higher incidence of some atherosclerotic risk factors, diabetes mellitus 30% vs 10%, tobacco use 77% vs 49%, hyperlipidemia 21% vs 7%; p less than 0.001). Coronary artery disease (CAD) was more prevalent in AAA patients (49% vs 34%; p less than 0.001). Postoperative mortality was not different in occlusive or aneurysmal disease (3% AFB vs 2% AAA), nor was the occurrence of serious complications such as myocardial infarction (2% vs 1%) or pulmonary embolism (2% vs 3%). Improvements in patient selection, perioperative care and surgical technique have lowered the mortality of elective aortic surgery. Given the current standard of care, an aggressive approach to AAA even in high risk patients is appropriate. The low morbidity of AFB for occlusive disease mandates a critical appraisal of less effective nonoperative therapies.


The G4 genome.
Recent experiments provide fascinating examples of how G4 DNA and G4 RNA structures--aka quadruplexes--may contribute to normal biology and to genomic pathologies. Quadruplexes are transient and therefore difficult to identify directly in living cells, which initially caused skepticism regarding not only their biological relevance but even their existence. There is now compelling evidence for functions of some G4 motifs and the corresponding quadruplexes in essential processes, including initiation of DNA replication, telomere maintenance, regulated recombination in immune evasion and the immune response, control of gene expression, and genetic and epigenetic instability. Recognition and resolution of quadruplex structures is therefore an essential component of genome biology. We propose that G4 motifs and structures that participate in key processes compose the G4 genome, analogous to the transcriptome, proteome, or metabolome. This is a new view of the genome, which sees DNA as not only a simple alphabet but also a more complex geography. The challenge for the future is to systematically identify the G4 motifs that form quadruplexes in living cells and the features that confer on specific G4 motifs the ability to function as structural elements.