Prevalence of high-risk human papilloma virus in liquid-based cervical samples from Turkish women with normal and abnormal cytology.
The aim of this study was to investigate the prevalence of human papilloma virus (HPV) infection from Turkish women with normal and abnormal cytology. Our study population consisted of 1252 women with normal and abnormal cytology. In our clinic, cervical cancer screening was performed by liquid-based cytology testing (ThinPrep Pap Test). Reflex high-risk (HR) HPV testing (Cervista HPV HR and HPV 16/18) was performed in cases with abnormal cytology (n = 330). HR HPV testing was performed to 922 cases with normal cytology. HR HPV was detected in 18.7% of negative for intraepithelial lesion or malignancy (NILM) samples, and in 79.7% of abnormal cytology cases. HPV types 16 and/or 18 were found in 18.6% and 35.3% of normal cytology cases and abnormal cytology cases, respectively. Of all 435 HR HPV-positive samples, HPV type 16 and/or 18 prevalence was significantly higher in cases with more severe cytological abnormalities. The HPV prevalence among Turkish women with normal and abnormal cytology identified in this study largely concurs with those in other studies throughout the world. HPV types 16 and/or 18 were detected significantly in normal cytology cases in our study. We also found that, as has been previously demonstrated, certain HPV genotypes (16/18) are associated with more severe pathologies. However, larger epidemiological studies in different regions of Turkey are needed to evaluate the accurate prevalence of HPV infection throughout the country.


Identifying Risk: Concurrent Overlap of the Antarctic Krill Fishery with Krill-Dependent Predators in the Scotia Sea.
Mitigating direct and indirect interactions between marine predators and fisheries is a motivating factor for ecosystem-based fisheries management (EBFM), especially where predators and fisheries compete for a shared resource. One difficulty in advancing EBFM is parameterizing clear functional responses of predators to indices of prey availability. Alternative characterizations of fishery-predator interactions may therefore benefit the implementation of EBFM. Telemetry data identify foraging areas used by predators and, therefore, represent critical information to mitigate potential competition between predators and fisheries. We analyzed six years (2009-2014) of telemetry data collected at Cape Shirreff, Livingston Island and Admiralty Bay, King George Island, Antarctica, on three species of Pygoscelid penguins and female Antarctic fur seals. In this region, all four species are primarily dependent on Antarctic krill. The tracking data demonstrate local movements near breeding colonies during the austral summer and dispersal from breeding colonies during the winter. We then assessed overlap between predators and the Antarctic krill fishery on a suite of spatiotemporal scales to examine how different data aggregations affect the extent and location of overlap. Concurrent overlap was observed on all spatiotemporal scales considered throughout the Antarctic Peninsula and South Orkney Islands region, including near tagging locations and in distant areas where recent fishing activity has concentrated. Overlap occurred at depths where mean krill densities were relatively high. Our results demonstrate that direct overlap of krill-dependent predators with the krill fishery on small spatiotemporal scales is relatively common throughout the Antarctic Peninsula region. As the krill fishery continues to develop and efforts to implement ecosystem-based management mature, indices of overlap may provide a useful metric for indicating where the risks of fishing are highest. A precautionary approach to allocating krill catches in space would be to avoid large increases in catch where overlap on small spatiotemporal scales is common.


Psychometric properties of the Spanish version of the once-daily Urticaria Activity Score (UAS) in patients with chronic spontaneous urticaria managed in clinical practice (the EVALUAS study).
The daily diary Urticaria Activity Score (UAS) and its weekly score (UAS7) are widely used to assess signs and symptoms in patients with chronic spontaneous urticaria (CSU). The objective of this study was to assess the psychometric properties of a Spanish version of the once-daily UAS. Observational study in patients ≥18 years old receiving usual care for CSU (daily or almost daily occurrence of generalized hives or angioedema for ≥6 weeks). Patients were included consecutively and completed the UAS, EQ-5D, and the Chronic Urticaria Quality of Life scale (CU-Q2oL) at two study visits 6 weeks apart. On each occasion, the UAS was completed once-daily for 7 consecutive days to be able to calculate the UAS7 score. Psychometric properties of reliability, construct validity, and responsiveness were assessed. The Minimal Important Difference (MID) was estimated for the UAS7 using anchor- and distribution-based approaches. Data from 166 patients was available for analysis (mean age 49 years, 65.7% female). Floor (5.4% of patients with the lowest possible score) and ceiling (1.2%) effects were low; 15% of patients had missing values. Internal consistency and test-retest reliability were good (Cronbach's alpha of 0.83 and an ICC of 0.84, respectively). Convergent validity was demonstrated through the pattern of correlations with the EQ-5D and CU-Q2oL and known groups' validity was demonstrated by the instrument's ability to discriminate between patients with different overall levels of urticaria severity, with between-group effect-sizes (ES) ranging from 0.36 to 1.19. The UAS7 proved responsive to change with effect sizes ranging from 0.3 to 1.52 in patients reporting improvement or deterioration in overall urticaria status. The MID for the UAS7 score was estimated at 7-8 points, on a scale of 0-42. The Spanish version of the UAS score has demonstrated a robust psychometric performance in patients with CSU managed in conditions of usual care. It can therefore be considered a suitable instrument to assess disease activity in clinical practice in Spanish-speaking patients. The Spanish version's reliability and validity are similar to those reported for other language versions of the once- and twice-daily variants of the UAS.


Insight into amyloid structure using chemical probes.
Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the deposition of amyloids in the brain. One prominent form of amyloid is composed of repeating units of the amyloid-β (Aβ) peptide. Over the past decade, it has become clear that these Aβ amyloids are not homogeneous; rather, they are composed of a series of structures varying in their overall size and shape and the number of Aβ peptides they contain. Recent theories suggest that these different amyloid conformations may play distinct roles in disease, although their relative contributions are still being discovered. Here, we review how chemical probes, such as Congo red, thioflavin T and their derivatives, have been powerful tools for the better understanding of amyloid structure and function. Moreover, we discuss how design and deployment of conformationally selective probes might be used to test emerging models of AD.


Wellens' Syndrome Presenting as Epigastric Pain and Syncope: An Unusual Presentation.
Wellens' syndrome, also regarded as left anterior descending coronary T-wave syndrome, is an electrocardiography (EKG) pattern that indicates critical proximal left anterior descending artery (LAD) stenosis. It is characterized by deeply inverted T-waves or biphasic T-waves in the anterior precordial chest leads in a patient with unstable angina. Patients typically present with symptoms consistent with acute coronary syndrome. We present a unique case of Wellens' syndrome with no angiographic findings of significant stenosis in the proximal LAD but with significant occlusion of the proximal circumflex artery and initial presentation with a chief complaint of epigastric pain and syncope. Physicians need to recognize these characteristic EKG changes during the pre-infarction stage, as they represent myocardial necrosis. Many of these patients eventually develop extensive anterior myocardial infarction with marked left ventricular dysfunction and death if coronary angiography and coronary revascularization are not performed within a few weeks. If Wellens' is seen, patients should undergo urgent cardiac catheterization.


MAP kinase activity increases during mitosis in early sea urchin embryos.
A MBP kinase activity increases at mitosis during the first two embryonic cell cycles of the sea urchin embryo. The activity profile of the MBP kinase is the same both in whole cell extracts and after immunoprecipitation with an anti-MAP kinase antibody (2199). An in-gel assay of MBP activity also shows the same activity profile. The activity is associated with the 44 kDa protein that cross-reacts with anti-MAP kinase antibodies. The 44 kDa protein shows cross-reactivity to anti-phosphotyrosine and MAP kinase-directed anti-phosphotyrosine/phosphothreonine antibodies at the times that MBP kinase activity is high. The 2199 antibody co-precipitates some histone H1 kinase activity, but the MBP kinase activity cannot be accounted for by histone H1 kinase-dependent phosphorylation of MBP. The MAP kinase 2199 antibody was used to purify the MBP kinase activity. Peptide sequencing after partial digestion shows the protein to be homologous to MAP kinases from other species. These data demonstrate that MAP kinase activation during nuclear division is not confined to meiosis, but also occurs during mitotic cell cycles. MAP kinase activity in immunoprecipitates also increases immediately after fertilization, which in the sea urchin egg occurs at interphase of the cell cycle. Treating unfertilized eggs with the calcium ionophore A23187 stimulates the increase in MAP kinase activity, demonstrating that a calcium signal can activate MAP kinase and suggesting that the activation of MAP kinase at fertilization is due to the fertilization-induced increase in cytoplasmic free calcium concentration. This signalling pathway must differ from the pathway responsible for calcium-induced inactivation of MAP kinase activity that is found in eggs that are fertilized in meiotic metaphase.


[Amaxa Nucleofector(TM) nuclear transfection apparatus transfers L1210 cell line].
Mouse L1210 leukemia cell line is widely used as a model in the study of tumorigenesis, as well as the efficacy of chemotherapeutic drugs; however, like other suspension cell lines, the mouse L1210 cell line has lowest transfection efficiency, that many barriers exist to study about the structure, function, as well as metabolism in leukemia cells. This study was aimed to obtain higher transfection efficiency of L1210 cell line to facilitate scientific research. The transfection efficiencies of nucleofector and liposome in L1210 leukemia cells were detected by converted fluorescence microscopy and flow cytometry using EGFP (enhance green fluorescent protein); cell viability was observed by trypan blue exclusion test. The results showed that the transfection efficiency of nucleofector primarily through reporter gene pEGFP by Amaxa Nucleofector(TM) nuclear transfer apparatus was significantly higher than lipofectamine 2000 transfection, furthermore, in the same cell density (2 × 10(6)/ml) and plasmid content (10 µg), the transfection efficiency of nuclear transfer apparatus default mode A-20 was higher than that of other modes (S-18, T-20). Its survival rate was up to 50.5% after 24 hours. Cell viability of liposome transfection reached to 88% after 24 hours, but the transfection efficiency was lower (< 1%). It is concluded that the nuclear transfer apparatus A-20 transfected L1210 can reach higher transfection efficiency up to 61.6%, which is significantly higher than that of lipofectamine transfection. The survival rate is up to 50.5% well meeting the needs of scientific research. Higher transfection efficiency is helpful for in-depth research about the morphology, functions and pathogenesis in leukemia model L1210, and provides more searching space for the treatment of leukemia diseases.


[Sonography in malignant tonsillar tumors].
In this retrospective study the value of sonography in the preoperative staging of malignant tumours of the tonsils was evaluated in 36 patients. According to our results sonography is indicated in small tumours. In greater tumours, especially if bone destruction could be expected, MR or CT should be performed additionally to sonography. Good results were achieved in assessing the infiltration of the tongue with or without crossing the midline (accuracy 92 to 97%) and the detection of cervical lymph node metastasis (accuracy 94%).


Incidence of malignant melanoma of the skin in England and Wales and its relationship to sunshine.
In most of England and Wales the incidence of malignant melanoma of the skin has risen rapidly in recent years, especially in women. Mean incidences in the 14 English health regions and Wales correlated negatively with latitude and positively with hours of sunshine, suggesting that exposure to sunshine was an important causal factor. Male and female incidences within a region tended to show similar yearly fluctuations, implying a common factor affecting the incidence in both men and women with a short latent period of action. This factor may be exposure to sunshine, which may cause melanoma after an induction period of about two years; for women the incidence of melanoma in the regions of England and Wales correlated positively with hours of sunshine two years earlier.


Iatrogenic corneal perforation in Terrien Marginal Degeneration.
This case report is about a rare disease with unusual presentation. Failure to recognise atypical presentation may lead to error in managing the patient and cause disastrous complications. Here we highlight a case of Terrien Marginal Degeneration in both eyes with atypical presentation; namely pseudopterygium. A 22 year old man was referred to our centre for iatrogenic right eye corneal perforation after having an atypical pterygium removed at another hospital. On arrival, his vision was 1/60 in both eyes with bilateral cornea Terrien Marginal Degeneration. His right eye anterior chamber was deep with a conjunctival flap covering the perforation site which was located from the 2.30 - 3.30 clock position nasally with no aqueous leak. However after a day his right eye anterior chamber became flat and there was fast aqueous leak from the perforation site. An emergency C shaped peripheral corneal lamellar keratoplasty was performed to seal the perforation. Post operatively his right eye improved to 6/24.


Benchmarking of cognitive-behavioral therapy for depression in efficacy and effectiveness studies--how do exclusion criteria affect treatment outcome?
Little is known about how exclusion criteria applied in randomized controlled trials (RCTs) affect the transfer of psychotherapy outcome research to naturalistic settings. This study evaluated the effects of naturalistic depression therapies and benchmarked them with published RCTs. Commonly used exclusion criteria were applied to n=338 depressive patients receiving cognitive-behavioral therapy. Outcomes of the resulting subsample eligible for RCTs were compared to those reported in RCTs. Treatment outcomes of the total sample (d=1.16) and the subsample eligible for RCTs (d=1.15) were highly similar. Therapy outcome was worse than in high-quality RCTs (d=1.39). No systematic bias was demonstrated due to patient selection criteria that are typically applied in RCTs. The comparability of psychotherapies conducted in RCTs and in real-world settings might be underestimated. Conclusions concerning the improvement of therapies in naturalistic settings are discussed.


Estimate of CRP and TNF-alpha level before and after periodontal therapy in cardiovascular disease patients.
Epidemiological studies show that individuals with periodontitis have a radically amplified threat to develop cardiovascular disease. CRP& TNF-α, are acute phase proteins monitored as a marker of inflammatory status, which have been identified as a major risk factor for atherosclerotic complications. Elevated CRP & TNF-α level in periodontitis patients have been reported by several groups. The present study was performed to determine whether presence of periodontitis and periodontal therapy could influence the serum levels of CRP & TNF-α in cardiovascular disease patients. Forty cardiovascular disease subjects participated in the study. They were classified into two groups. Group A (Control) where no periodontal treatment was given, Group B (Test) where periodontal treatment (scaling & root planing) was performed. Periodontal clinical parameters like OHI-S, probing pocket depth, were evaluated together with serum CRP, TNF-α, at baseline and reassessed after 8 weeks for all the subjects in both the groups. The CRP & TNF-α levels in both the groups decreased but the decrease in the Group A was minimal and was not statistically significant (P > 0.05); whereas in Group B where periodontal therapy was performed, there was statistically significant decrease. It can be concluded from the study that there can be a possible causal relationship between pathogenesis of periodontal disease and CVD as inferred from the statistical significant outcome in the form of decreased inflammatory biomarkers after the periodontal treatment.


Graphiumins, new thiodiketopiperazines from the marine-derived fungus Graphium sp. OPMF00224.
Eight new thiodiketopiperazines, designated as graphiumins A to H (1-8), were isolated along with bisdethiobis(methylthio)-deacetylaranotin (9) and bisdethiobis(methylthio)-deacetylapoaranotin (10) from the culture broth of the marine-derived fungus Graphium sp. OPMF00224. The structures of the graphiumins were elucidated based on spectroscopic analyses (1D and 2D NMR data, ROESY correlations and CD data) and chemical methods. The absolute configuration of the common (3S)-3-hydroxy-octanoyl acid residue in 1, 3 and 4 was determined by hydrolysis, benzoyl derivatization and HPLC analysis using a chiral column. Five graphiumins moderately inhibited yellow pigment production by methicillin-resistant Staphylococcus aureus.


The Brief Young Adult Alcohol Consequences Questionnaire: A cross-country examination among university students in Australia, New Zealand, Canada, Argentina, and the United States.
The Brief Young Adult Alcohol Consequences Questionnaire (B-YAACQ) was designed to measure alcohol consequences and identify at-risk students. It was developed and originally validated among university students in the United States (U.S.), yet it is widely used in both the U.S. and abroad. Using the alignment method, we tested whether the B-YAACQ measures alcohol consequences similarly across university students in several countries where heavy alcohol use and related outcomes are prevalent. The sample consisted of 1473 university students (ages 18-30) from five university sites: Australia (n = 315), New Zealand (n = 270), Canada (n = 276), Argentina (n = 232), and the U.S. (n = 380). Participants completed a confidential, online alcohol use survey which included the B-YAACQ. Overall, 12 of the 24 B-YAACQ items had invariant factor loading and threshold parameters, suggesting that these items exhibited similar reliability and difficulty among university students across the five countries. Of the 24 B-YAACQ items, 21 exhibited comparable reliability across the five countries; the remaining 3 items were slightly less reliable indicators of alcohol consequences among U.S. students. Thus, several items on the B-YAACQ may be particularly informative for identifying students who are experiencing high levels of drinking harm across multiple countries. The present study is an important step toward (a) validating the B-YAACQ among university students in New Zealand and Canada, and (b) furthering our understanding of the psychometric properties of the B-YAACQ among university students in Australia, Argentina, and the U.S.


The effects of population heterogeneity on disease invasion.
The incorporation of population heterogeneity is a central issue in theoretical biology, and it has received considerable attention in epidemiology recently. This paper presents general conclusions and interpretations about the effects of heterogeneity, with and without positive assortative mating, on the ability of a disease to establish itself. We show that the invasion of a disease into a population with random mixing is determined by an average of reproductive numbers for each subgroup, weighted by the total amount of mixing activity of the subgroup. In particular, if the mixing rate is constant across the population, invasion occurs if and only if the average reproductive number for the population exceeds 1. In the case of "preferred mixing," one can find a critical number for each subgroup such that invasion occurs if and only if a suitably defined average over subgroups exceeds 1.


Activation of Self-Incompatibility Signaling in Transgenic Arabidopsis thaliana Is Independent of AP2-Based Clathrin-Mediated Endocytosis.
Internalization of plasma membrane (PM)-localized ligand-activated receptor kinases and their trafficking to sorting endosomes have traditionally been viewed as functioning primarily in the down-regulation of receptor signaling, but are now considered to be also essential for signaling by some receptors. A major mechanism for internalization of PM proteins is clathrin-mediated endocytosis (CME). CME is mediated by the Adaptor Protein Complex 2 (AP2), which is involved in interaction of the AP2 μ-adaptin subunit with a tyrosine-based Yxxϕ motif located in the cytoplasmic domain of the cargo protein. In this study, we investigated the role of AP2-mediated CME for signaling by the S-locus receptor kinase (SRK), a protein localized in the PM of stigma epidermal cells, which, together with its pollen coat-localized S-locus cysteine-rich (SCR) ligand, functions in the self-incompatibility (SI) response of the Brassicaceae. Using Arabidopsis thaliana plants that were made self-incompatible by transformation with an A. lyrata-derived SRK/SCR gene pair, we tested the effect on SI of site-directed mutations in each of the two Yxxϕ motifs in SRK and of a CRISPR/Cas9-induced null mutation in the AP2 μ-adaptin gene AP2M Both in vitro SRK kinase activity and the in planta SI response were abolished by substitution of tyrosine in one of the two Yxxϕ motifs, but were unaffected by elimination of either the second Yxxϕ motif or AP2M function. Thus, AP2-mediated CME is considered to be unnecessary for SRK signaling in the SI response.


Effects of peanut oil load on energy expenditure, body composition, lipid profile, and appetite in lean and overweight adults.
We evaluated the effects of peanut oil intake on appetite, energy expenditure, body composition, and lipid profile in lean and overweight adults. In a parallel-arm, long-term feeding trial, lean and overweight participants received a daily peanut oil load in a milk shake equivalent to 30% of their resting energy expenditure for 8 wk. Forty-eight adults (24 lean and 24 overweight, 12 male and 12 female in each group) completed the protocol. Anthropometric indices, appetite, dietary intake, energy expenditure, and plasma lipids were monitored. Energy intake increased significantly in the overweight but not in the lean participants. A statistically significant body weight gain (median 2.35 kg) was also observed among the overweight subjects, although this corresponded to only 43% of the theoretical weight gain. Among overweight subjects, high-density lipoprotein cholesterol increased significantly and low-density lipoprotein cholesterol decreased at week 4, but neither concentration was significantly different from baseline at week 8. Similar, but less marked, changes were observed in lean subjects. Resting energy expenditure was 5% greater (P < 0.01) in the overweight group, but no significant difference was observed in the lean subjects. No marked differences of appetite were observed over time in either group or between overweight and lean participants. These data indicate that ingestion of peanut oil elicits a weaker compensatory dietary response among overweight compared with lean individuals. Body weight increased, albeit less than theoretically predicted. The weaker effect of whole nuts on body weight reported in previous studies suggests components other than oil may be responsible.


Three-dimensional hierarchically ordered porous carbons with partially graphitic nanostructures for electrochemical capacitive energy storage.
Three-dimensional, hierarchically ordered, porous carbon (HOPC) with designed porous textures, serving as an ion-buffering reservoir, an ion-transport channel, and a charge-storage material, is expected to be advanced an energy material for high-rate supercapacitors. Herein, HOPC without/with partially graphitic nanostructures have been directly synthesized by means of a simple one-pot synthesis procedure. The designed porous textures of the 3D HOPC materials are composed of highly ordered, fcc macroporous (300 nm), interconnected porous structures, including macroporous windows (170 nm), hexagonally ordered mesopores (5.0 nm), and useful micropores (1.2 nm). 3D HOPC-g-1000 (g=graphitic, 1000=pyrolysis temperature of 1000 °C) with partially graphitic nanostructures has a low specific surface area (296 m(2) g(-1)) and a low gravimetric specific capacitance (73.4 F g(-1) at 3 mV s(-1)), but improved electrical conductivity, better rate performance, higher electrolyte accessibility (24.8 μF cm(-2) at 3 mV s(-1)), faster frequency response (≈1 Hz), and excellent cycling performance (>5400 cycles). The specific capacitance per surface area is higher than that of conventional porous carbons, carbon nanotubes, and modified graphene (10-19 μF cm(-2)).


Automated unrestricted multigene recombineering for multiprotein complex production.
Structural and functional studies of many multiprotein complexes depend on recombinant-protein overexpression. Rapid revision of expression experiments and diversification of the complexes are often crucial for success of these projects; therefore, automation is increasingly indispensable. We introduce Acembl, a versatile and automatable system for protein-complex expression in Escherichia coli that uses recombineering to facilitate multigene assembly and diversification. We demonstrated protein-complex expression using Acembl, including production of the complete prokaryotic holotranslocon.


Comparison of active and passive forces of the pelvic floor muscles in women with and without stress urinary incontinence.
The reduction of the pelvic floor muscles (PFM) strength is a major cause of stress urinary incontinence (SUI). To compare active and passive forces, and vaginal cavity aperture in continent and stress urinary incontinent women. The study included a total of thirty-two women, sixteen continent women (group 1--G1) and sixteen women with SUI (group 2--G2). To evaluate PFM passive and active forces in anteroposterior (sagittal plane) and left-right directions (frontal plane) a stainless steel specular dynamometer was used. The anteroposterior active strength for the continent women (mean±standard deviation) (0.3±0.2 N) was greater compared to the values found in the evaluation of incontinent women (0.1±0.1 N). The left-right active strength (G1=0.43±0.1 N; G2=0.40±0.1 N), the passive force (G1=1.1±0.2 N; G2=1.1±0.3 N) and the vaginal cavity aperture (G1=21±3 mm; G2=24±4 mm) did not differ between groups 1 and 2. The function evaluation of PFM showed that women with SUI had a lower anteroposterior active strength compared to continent women.


Gene expression patterns underlying changes in xylem structure and function in response to increased nitrogen availability in hybrid poplar.
Nitrogen availability has a strong influence on plant growth and development. In this study, we examined the effect of nitrogen availability on xylogenesis in hybrid poplar (Populus trichocarpa x deltoides H11-11). Saplings of hybrid poplar were fertilized for 33 d with either high or adequate levels of ammonium nitrate. We observed enhanced radial growth, wider vessels and fibres and thinner fibre walls in the secondary xylem of high N relative to adequate N plants. These anatomical differences translated into altered hydraulic properties with xylem being more transport efficient but also more vulnerable to drought-induced cavitation in high N plants. The changes in xylem structure and function were associated with differences in gene expression as revealed by the transcriptome analysis of the developing xylem region. We found 388 genes differentially expressed (fold change ±1.5, P-value ≤ 0.05), including a number of genes putatively involved in nitrogen and carbohydrate metabolism and various aspects of xylem cell differentiation. Several genes encoding known transcriptional regulators of secondary cell wall deposition were down-regulated in high N plants, corresponding with thinner secondary cell walls in these plants. The results of this study provide us with gene candidates potentially affecting xylem hydraulic and structural traits.


A method for multitask fMRI data fusion applied to schizophrenia.
It is becoming common to collect data from multiple functional magnetic resonance imaging (fMRI) paradigms on a single individual. The data from these experiments are typically analyzed separately and sometimes directly subtracted from one another on a voxel-by-voxel basis. These comparative approaches, although useful, do not directly attempt to examine potential commonalities between tasks and between voxels. To remedy this we propose a method to extract maximally spatially independent maps for each task that are "coupled" together by a shared loading parameter. We first compute an activation map for each task and each individual as "features," which are then used to perform joint independent component analysis (jICA) on the group data. We demonstrate our approach on a data set derived from healthy controls and schizophrenia patients, each of which carried out an auditory oddball task and a Sternberg working memory task. Our analysis approach revealed two interesting findings in the data that were missed with traditional analyses. First, consistent with our hypotheses, schizophrenia patients demonstrate "decreased" connectivity in a joint network including portions of regions implicated in two prevalent models of schizophrenia. A second finding is that for the voxels identified by the jICA analysis, the correlation between the two tasks was significantly higher in patients than in controls. This finding suggests that schizophrenia patients activate "more similarly" for both tasks than do controls. A possible synthesis of both findings is that patients are activating less, but also activating with a less-unique set of regions for these very different tasks. Both of the findings described support the claim that examination of joint activation across multiple tasks can enable new questions to be posed about fMRI data. Our approach can also be applied to data using more than two tasks. It thus provides a way to integrate and probe brain networks using a variety of tasks and may increase our understanding of coordinated brain networks and the impact of pathology upon them.


A combination vaccine consisting of three live attenuated enterotoxigenic Escherichia coli strains expressing a range of colonization factors and heat-labile toxin subunit B is well tolerated and immunogenic in a placebo-controlled double-blind phase I trial in healthy adults.
Immune responses against colonization factors (CFs) and the nontoxic B component of the enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LTB) are considered to be important for immunity against diarrhea caused by ETEC. Individual live attenuated ETEC derivatives that have had their toxin genes removed and whose aroC, ompC, and ompF genes are deleted have shown promise as vaccines against ETEC. The development of such strains has culminated in the testing of a three-strain-combination live attenuated vaccine known as ACE527, comprised of strains ACAM2025 expressing colonization factor antigen I (CFA/I) and LTB; ACAM2022, expressing CS5, CS6, and LTB; and ACAM2027, expressing CS1, CS2, CS3, and LTB. The recombinant CF and LTB genes expressed in the three strains were inserted into the bacterial chromosome to ensure their stable inheritance and expression without the requirement for any selection. ACE527 has been tested in a randomized placebo-controlled, double-blind, phase I safety and immunogenicity study in healthy adult volunteers and proved to be well tolerated and immunogenic at dose levels of 10(10) and 10(11) total CFU. There was no indication of strain interference on the basis of fecal shedding patterns, with all three being detected in the feces of 50% and 83% of low- and high-dose vaccine recipients, respectively. Similarly, strong immune responses to LTB and to CFs expressed on all three constituent strains were induced, with at least 50% of subjects in the high-dose group responding to LTB, CFA/I, CS3, and CS6.


Targeting the human thioredoxin system by diverse strategies to treat cancer and other pathologies.
Redox control is an important determinant of cellular function and viability. The thioredoxin system is a major antioxidant system that influences cellular redox state, stimulates cell growth, inhibits apoptosis, activates numerous transcription factors and regulates immune function. Both over and under expression of the thioredoxin system can result in a disease phenotype and therefore it has been the target of many therapeutic strategies. High levels of thioredoxin expression have been associated with aggressive cancers, poor patient prognosis and resistance to some chemotherapy treatments. In contrast, low levels of thioredoxin can cause diseases that develop because of an imbalance between antioxidant systems and oxidative stress, stimulants. A number of recent patents and patent applications have been published that describe inventions that either inhibit or enhance thioredoxin functionality. Thioredoxin expression levels have been decreased through antisense approaches and thioredoxin functionality has been inhibited by synthetic compounds or by stimulating the production of VDUP1, a natural thioredoxin inhibitor. Strategies designed to enhance thioredoxin functionality include the addition of recombinant thioredoxin or using gene delivery to treat hepatic disease, inflammatory bowel disease, cardiovascular disease, skin damage or cystic fibrosis. Mutant thioredoxin molecules that target specific pathways or that exhibit increased stability are also utilised.


Human Papillomavirus Vaccination Awareness and Acceptability Among U.S.-Born and U.S. Foreign-Born Women Living in California.
We examined human papillomavirus vaccine awareness and acceptance between U.S.-born and U.S. foreign-born women by utilizing California Health Interview Survey data from 1,672 women (ages 18-27) and 2,994 mothers (ages 28-65). Foreign-born women and mothers had lower vaccine awareness. Foreign-born young adult Latinas had greater vaccine acceptance than U.S.-born Latinas. Other factors associated with young adult women's vaccine acceptability were being younger, unmarried, and sexually active in the past year; having poorer self-reported health; and having heard of the vaccine. Variables associated with mothers' vaccine acceptability were being White, insured, and unmarried; having had a Pap test in past 3 years; being less educated; and being impoverished.


A murine monoclonal antibody directed against the carboxyl-terminal domain of GRP78 suppresses melanoma growth in mice.
The HSP70 family member GRP78 is a selective tumor marker upregulated on the surface of many tumor cell types, including melanoma, where it acts as a growth factor receptor-like protein. Receptor-recognized forms of the proteinase inhibitor α2-macroglobulin (α2M*) are the best-characterized ligands for GRP78, but in melanoma and other cancer patients, autoantibodies arise against the NH2-terminal domain of GRP78 that react with tumor cell-surface GRP78. This causes the activation of signaling cascades that are proproliferative and antiapoptotic. Antibodies directed against the COOH-terminal domain of GRP78, however, upregulate p53-mediated proapoptotic signaling, leading to cell death. Here, we describe the binding characteristics, cell signaling properties, and downstream cellular effects of three novel murine monoclonal antibodies. The NH2-terminal domain-reactive antibody, N88, mimics α2M* as a ligand and drives PI 3-kinase-dependent activation of Akt and the subsequent stimulation of cellular proliferation in vitro. The COOH-terminal domain-reactive antibody, C38, acts as an antagonist of both α2M* and N88, whereas another, C107, directly induces apoptosis in vitro. In a murine B16F1 melanoma flank tumor model, we demonstrate the acceleration of tumor growth by treatment with N88, whereas C107 significantly slowed tumor growth whether administered before (P<0.005) or after (P<0.05) tumor implantation.


Can the job content questionnaire be used to assess structural and organizational properties of the work environment?
The theory behind the Job Content Questionnaire (JCQ) presumes that the "objective" social environment is measurable via self-report inventories such as the JCQ. Hence, it is expected that workers in identical work will respond highly similar. However, since no studies have evaluated this basic assumption, we decided to investigate whether workers performing highly similar work also responded similarly to the JCQ. JCQ data from a rubber-manufacturing (RM: n = 95) and a mechanical assembly company (MA: n = 119) were examined. On each worksite, men and women performed identical machine-paced job tasks. A population sample (n = 8,542) served as a reference group. In both the RM and MA groups, the job support questions were rated most similar. Yet, there was a substantial variation as regards choosing to agree or disagree with single JCQ items. The variation was also reflected in the scale scores. In the RM and MA groups, the variance of job demand and job control scores was 64-87% of that of the population sample. For job support scores, the corresponding variation was 42-87%. Conducting highly similar work does not lead to highly similar reports in the JCQ. In view of the large response variation, it seems that the attempt to avoid personal influence by minimizing the self-reflexive component in the questions asked, and using response alternative that indicates degree of agreement, does not seem to work as intended.


Functional complementation of anthocyanin sequestration in the vacuole by widely divergent glutathione S-transferases.
Glutathione S-transferases (GSTs) traditionally have been studied in plants and other organisms for their ability to detoxify chemically diverse herbicides and other toxic organic compounds. Anthocyanins are among the few endogenous substrates of plant GSTs that have been identified. The Bronze2 (Bz2) gene encodes a type III GST and performs the last genetically defined step of the maize anthocyanin pigment pathway. This step is the conjugation of glutathione to cyanidin 3-glucoside (C3G). Glutathionated C3G is transported to the vacuole via a tonoplast Mg-ATP-requiring glutathione pump (GS-X pump). Genetically, the comparable step in the petunia anthocyanin pathway is controlled by the Anthocyanin9 (An9) gene. An9 was cloned by transposon tagging and found to encode a type I plant GST. Bz2 and An9 have evolved independently from distinct types of GSTs, but each is regulated by the conserved transcriptional activators of the anthocyanin pathway. Here, a phylogenetic analysis is presented, with special consideration given to the origin of these genes and their relaxed substrate requirements. In particle bombardment tests, An9 and Bz2 functionally complement both mutants. Among several other GSTs tested, only soybean GmGST26A (previously called GmHsp26A and GH2/4) and maize GSTIII were found to confer vacuolar sequestration of anthocyanin. Previously, these genes had not been associated with the anthocyanin pathway. Requirements for An9 and Bz2 gene function were investigated by sequencing functional and nonfunctional germinal revertants of an9-T3529, bz2::Ds, and bz2::Mu1.


Correlation of topographic surface and volume data from three-dimensional electron microscopy.
Three-dimensional(3D) reconstructions from tilt series in an electron microscope show in general an anisotropic resolution due to an instrumentally limited tilt angle. As a consequence, the information in the z direction is blurred, thus making it difficult to detect the boundary of the reconstructed structures. In contrast, high-resolution topography data from microscopic surface techniques provide exactly complementary information. The combination of topographic surface and volume data leads to a better understanding of the 3D structure. The new correlation procedure presented determines both the height scaling of the topographic surface and the relative position of surface and volume data, thus allowing information to be combined. Experimental data for crystalline T4 bacteriophage polyheads were used to test the new method. Three-dimensional volume data were reconstructed from a negatively stained tilt series. Topographic data for both surfaces were obtained by surface relief reconstruction of electron micrographs of freeze-dried and unidirectionally metal-shadowed polyheads. The combined visualization of volume data with the scaled and aligned surface data shows that the correlation technique yields meaningful results. The reported correlation method may be applied to surface data obtained by any microscopic technique yielding topographic data.


Incidence and Prognostic Impact of Incomplete Revascularization Documented by Coronary Angiography 1 Year After Coronary Artery Bypass Grafting.
Complete revascularization (CR) at the time of coronary artery bypass graft (CABG) surgery improves long-term cardiac outcomes. No studies have previously reported angiographically confirmed CR rates post-CABG. This study's aim was to assess the impact upon long-term outcomes of CR versus incomplete revascularization (IR), confirmed by coronary angiography 1 year after CABG. Randomized On/Off Bypass Study patients who returned for protocol-specified 1-year post-CABG coronary angiograms were included. Patients with a widely patent graft supplying the major diseased artery within each diseased coronary territory were considered to have CR. Outcomes were all-cause mortality and major adverse cardiovascular events (MACE; all-cause mortality, nonfatal myocardial infarction, repeat revascularization) over the 4 years after angiography. Of the 1,276 patients, 756 (59%) had CR and 520 (41%) had IR. MACE was 13% CR versus 26% IR, p <0.001. This difference was driven by fewer repeat revascularizations (5% CR vs 18% IR; p <0.001). There were no differences in mortality (7.1% CR vs 8.1% IR, p = 0.13) or myocardial infarction (4% in both). Adjusted multivariable models confirmed CR was associated with reduced MACE (odds ratio 0.44, 95% confidence interval 0.33 to 0.58, p <0.01), but had no impact on mortality. In conclusion, CR confirmed by post-CABG angiography was associated with improved MACE but not mortality. Repeat revascularization of patients with IR, driven by knowledge of the research angiography results, may have ameliorated potential mortality differences.


Living with breathlessness in chronic heart failure: a qualitative study.
To explore how patients with Chronic Heart Failure describe their experiences of breathlessness, the pattern of their breathlessness, how daily life is affected and how they adjust to and manage these symptoms. Chronic Heart Failure is a highly prevalent syndrome often with poor outcomes and in a patient group who are predominately elderly. Breathlessness is the main symptom experienced by patients and often relates to decompensation and hospitalisation, yet subtle changes described by patients are often not discussed with health care professionals. A descriptive qualitative design. Twenty-five participants with heart failure with reduced ejection fraction (HF-rEF) from a tertiary referral centre in England were recruited. Each participant took part in a semi-structured interview exploring the effect of breathlessness had on their lives. Data was analysed through Braun and Clarke's framework for thematic analysis. All participants reported experiencing breathlessness daily. Four sub-themes were identified in their accounts: nature of breathlessness, emotional impact of breathlessness, impact of breathlessness on daily life and managing breathlessness. Participants were able to give vivid descriptions of breathlessness and the way it affected their lives. Health care professionals need to take account of each patient's personal assessment of their own breathlessness and how this is having an effect on their life and ability to undertake activities of daily living. Self-care management strategies need to be developed so that subtle changes can be assessed by the patient and reviewed by the healthcare professional to avoid hospitalisation and increased mortality risks.


Knockdown of CCNO decreases the tumorigenicity of gastric cancer by inducing apoptosis.
Recently, Cyclin O (CCNO) has been reported to be a novel protein of the cyclin family. However, the clinical significance and functional roles of CCNO in human cancer, including gastric cancer (GC), remain largely unexplored. In this study, we investigated the clinical and functional roles of CCNO in GC. We analyzed CCNO expression patterns in GC patients. To investigate the role of CCNO in malignancy of GC, we used lentivirus-delivered short hairpin RNA to knockdown CCNO expression in GC cell lines. Then multiparametric high-content screening and MTT incorporation assay were used to assess the cell proliferation capability. Cell apoptosis was detected by flow cytometry and Caspase 3/7 assays. Furthermore, the effect of CCNO on tumorigenicity of GC was also determined in vivo. Finally, microarray analysis was performed to elucidate the molecular mechanisms by which shCCNO inhibited the malignancy of GC cells. The analysis from The Cancer Genome Atlas database revealed elevated CCNO mRNA expression in GC tissue than in the adjacent normal tissue. Immunohistochemical studies also showed that stronger cytoplasmic staining of CCNO was detected in GC tissues. Downregulation of CCNO in GC cells efficiently, through infection with the lentivirus-mediated specific short hairpin RNA, could significantly induce cell apoptosis and inhibit the proliferative properties both in vitro and in vivo. Microarray analysis further revealed 652 upregulated genes and 527 downregulated genes in the shCCNO group compared with control, and indicated that CCNO knockdown could inhibit the malignancy of GC cells through inducing genome-wide gene expression changes. Our work is the first to reveal that elevated CCNO expression is closely associated with human GC development and that CCNO knockdown could efficiently inhibit the malignant properties of GC cells by inducing cell apoptosis. Therefore, CCNO could be used as a potential biomarker for prognosis or even as a therapeutic target in human GC.


Nerve-associated transient receptor potential ion channels can contribute to intrinsic resistance to bacterial adhesion in vivo.
The cornea of the eye differs from other mucosal surfaces in that it lacks a viable bacterial microbiome and by its unusually high density of sensory nerve endings. Here, we explored the role of corneal nerves in preventing bacterial adhesion. Pharmacological and genetic methods were used to inhibit the function of corneal sensory nerves or their associated transient receptor potential cation channels TRPA1 and TRPV1. Impacts on bacterial adhesion, resident immune cells, and epithelial integrity were examined using fluorescent labeling and quantitative confocal imaging. TRPA1/TRPV1 double gene-knockout mice were more susceptible to adhesion of environmental bacteria and to that of deliberately-inoculated Pseudomonas aeruginosa. Supporting the involvement of TRPA1/TRPV1-expressing corneal nerves, P. aeruginosa adhesion was also promoted by treatment with bupivacaine, or ablation of TRPA1/TRPV1-expressing nerves using RTX. Moreover, TRPA1/TRPV1-dependent defense was abolished by enucleation which severs corneal nerves. High-resolution imaging showed normal corneal ultrastructure and surface-labeling by wheat-germ agglutinin for TRPA1/TRPV1 knockout murine corneas, and intact barrier function by absence of fluorescein staining. P. aeruginosa adhering to corneas after perturbation of nerve or TRPA1/TRPV1 function failed to penetrate the surface. Single gene-knockout mice showed roles for both TRPA1 and TRPV1, with TRPA1-/- more susceptible to P. aeruginosa adhesion while TRPV1-/- corneas instead accumulated environmental bacteria. Corneal CD45+/CD11c+ cell responses to P. aeruginosa challenge, previously shown to counter bacterial adhesion, also depended on TRPA1/TRPV1 and sensory nerves. Together, these results demonstrate roles for corneal nerves and TRPA1/TRPV1 in corneal resistance to bacterial adhesion in vivo and suggest that the mechanisms involve resident immune cell populations.


Modeling Impulsivity in Forensic Patients: A Three-Dimensional Model of Impulsivity.
The current study investigated whether a multidimensional model could underlie impulsivity and its associations with various disorders in a forensic sample. Data were available from self-report and behavioral impulsivity instruments of 87 forensic patients. Principal component analysis (PCA) was used to derive a dimensional impulsivity model, and the relationship between and possible predictive validity of impulsivity dimensions for psychopathology was investigated using product moment correlations and regression analysis. A 3-dimensional model of impulsivity was derived, with factors labeled impulsive decision making, sensation seeking, and response inhibition. Impulsive decision making was a predictor for a history of drug dependence, the impulsive lifestyle facet of psychopathy, and antisocial personality disorder. Sensation seeking was not related to any psychopathology. Inadequate response inhibition was a predictor for drug dependence, psychopathy, and antisocial personality disorder. Given the importance of the concept of impulsivity with regard to forensic risk assessment, the current results replicated earlier impulsivity models and imply that impulsivity is a crucial target for diagnosis and interventions and underlines the importance to consider impulsivity as a multidimensional construct.


The Collateral Impacts of Pandemic.
A pandemic that covers the whole world occurs relatively in every 100 years. Thus, it can be said that no expert has ever experienced directly dealing with a global pandemic. In the absence of people who are truly experts who know the problems and impacts of a global pandemic, various studies need to be carried out extensively between fields and across regions in the world. Likewise, the results of the study need to be recorded permanently so that it can still be useful over a long period of time, preferably for more than a hundred years.Studies of the short-term and long-term impacts of the pandemic on things other than mortality are calling us to be worked upon. It is the time for us to be concerned with the risk assessment of benefits before a decision is taken and its openly scientific reporting. It is necessary to develop strategies to mitigate or avoid dire consequences of a policy. Until now, studies of health policy on the vulnerable group seem to be minimally done. It would be wise to encourage more studies to groups that are vulnerable to the impact of a policy.The collateral impacts of the pandemic do not only affect the health services on diseases other than Covid-19, but also includes the collateral impact of humanitarian threats in other fields. Management of a global pandemic needs to be carried out comprehensively, both in handling the disease, support for and access to other diseases, as well as collaboration and socioeconomic policies that maintain the pillars of humanity. Lessons must be taken by humans in order to defend their race in the future, including pandemics that occur repeatedly over a span that is longer than the age of three generations.


Stabilizing ryanodine receptor type 2: a novel strategy for the treatment of atrial fibrillation.
We propose that stabilizing ryanodine receptor type 2 (RyR2) may be a novel strategy for the treatment of atrial fibrillation (AF). Sarcoplasmic reticulum (SR) dysfunction caused by hyperphosphorylation of RyR2 and/or partial depletion of the stabilizing subunit calstabin2 has been indicated in AF. RyR2 stabilization may prevent SR dysfunction and thereby protect the heart from damage. Hypertrophy, hyperthyroidism and heart failure, three common pathological conditions associated with AF, result in increased SR Ca(2+) leak via RyR2. RyR2 stabilization may prevent SR Ca(2+) leak and thereby prevent AF. Triggered activity appears to underlie atrial ectopic foci, which cause AF. Diastolic Ca(2+) leak from SR via RyR2 may initiate triggered activity. Therefore, modulating RyR2 opening probability would be predicted to protect against triggered activity. Atrial oxidative stress plays a contributing role in the pathogenesis of AF. RyR2 is a target of reactive oxygen species, and chronic RyR2 oxidation increases RyR2 opening probability in a more sustained, less reversible manner. Strategies that attenuate oxidative stress and protect against AF may also contribute to RyR2 stabilization. Finally, KN-3 and JTV519, two compounds that stabilize RyR2 in the closed state, prevent the induction of triggered activity and suppress the inducibility of sustained AF. Thus, it is reasonable to speculate that experimental approaches designed to improve RyR2 stabilization will drive a novel conceptual revolution in AF drug development and lead to new clinical investigations.


Molar incisor hypomineralization in Hong Kong Chinese children.
Most prevalence studies on molar incisor hypomineralization (MIH) were carried out in European countries, and data from the East-Asian populations were lacking. This study aimed to investigate the prevalence of MIH in Hong Kong Chinese children. Since 2006, charting of teeth with MIH was included into the routine dental examination in a school dental clinic. The dental records of grade 6 primary school children who attended annual check-up in this clinic in 2006 were subsequently reviewed retrospectively. The records were selected for this study if the charting indicated that the children were affected by MIH. A total of 2635 records were reviewed and 73 cases of MIH were identified. The prevalence of MIH in this group of children was 2.8%. Their mean age was 12, and the male-to-female ratio was 1 : 1.2. The mean decayed, missing, or filled permanent teeth value of those affected was 1.5, which was higher than that of the general Hong Kong Chinese children aged 12 years old (0.8). A total of 192 teeth were affected. The most commonly affected teeth were permanent maxillary first molars, followed by mandibular first molars and maxillary central incisors. Dental fillings and fissure sealants were found in 52 (38%) and 65 (47%) permanent first molars with hypomineralization, respectively. Medical histories were unremarkable in 60 children, whereas early childhood diseases were reported in 13 cases. The prevalence of MIH in the permanent dentition of Hong Kong Chinese children was 2.8%. Children with MIH showed higher caries experience in the permanent dentition than the general population of similar age.


[Mathematical approach of the SIR epidemiological model for the comprehension of the containment measures against the Covid-19.]
In December 2019, an acute respiratory disease outbreak from zoonotic origin was detected in the city of Wuhan, China. The outbreak's infectious agent was a type of coronavirus never seen. Thenceforth, the Covid-19 disease has rapidly spread to more than 200 countries around the world. To minimize the devastating effects of the virus, the States have adopted epidemiological measures of various kinds that involved enormous economic expenses and the massive use of the media to explain the measures to the entire population. For the prediction and mitigation of infectious events, various epidemiological models, such as SIR, SEIR, MSIR and MSEIR, are used. Among them, the most widely used is the SIR model, which is based on the analysis of the transition of individuals susceptible to infection (S) to the state of infected individuals that infect (I) and, finally, to that of recovered (cured or deceased) (R), by using differential equations. The objective of this article was the mathematical development of the SIR model and its application to predict the course of the Covid-19 pandemic in the city of Santa Marta (Colombia), in order to understand the reason behind several of the measures of containment adopted by the States of the world in the fight against the pandemic.


Characterization of CB2 Receptor Expression in Peripheral Blood Monocytes of Acute Ischemic Stroke Patients.
Both preclinical and clinical evidence supports the involvement of the endocannabinoid system in the pathobiology of cerebral ischemia. Selective cannabinoid-2 (CB2) receptor agonists exert significant neuroprotection in animal models of focal brain ischemia through a robust anti-inflammatory effect, involving both resident and peripheral immune cells. Nevertheless, no definitive studies demonstrating the relevance of CB2 receptors in human stroke exist.Using rtPCR and flow cytometry assays, we investigated CB2 receptor expression in circulating monocytes from 26 acute ischemic stroke patients and 16 age-matched healthy controls (CT). We also evaluated miR-665 expression, as potential CB2 receptor regulator. The median mRNA levels of CB2 were significantly (p < 0.0001) increased in total monocytes 24 h and 48 h after stroke as compared with CT. This was paralleled by elevation of miR-665 levels in monocytes collected from patients 24 h (p < 0.05 vs CT) and 48 h (p < 0.05 vs CT and p < 0.0001 vs 24 h) after ischemic stroke. Furthermore, an increased percentage of CB2+/CD16+ events, but not CB2+/CD14+ events, was found 24 h [20.17% (IQR, 17.22-23.58)] and 48 h [18.61% (IQR, 15.44-22.06)] after ischemic stroke when compared with CT [10.96% (IQR, 9.185-13.32)]. The percentage of CB2+/CD16+ events in monocytes was positively correlated with NIHSS score at entrance (r = 0.4327, p = 0.027). The potential beneficial functions of CD16+ intermediate and nonclassical monocytes in stroke and the elevated expression of CB2 receptor in these subsets strongly suggest that CB2 receptor agonists can be exploited for the treatment of ischemic stroke patients.


Transcriptional regulation of the human manganese superoxide dismutase gene: the role of specificity protein 1 (Sp1) and activating protein-2 (AP-2).
Manganese superoxide dismutase (MnSOD) plays an important role in regulating cellular redox conditions. Expression of MnSOD has been shown to protect against damage by oxidative stress and to suppress the malignant phenotype of human cancer cells. We have previously cloned the human MnSOD (SOD2) gene and analysed its 5' proximal promoter, which has been characterized by a lack of a TATA or CAAT box and the presence of multiple GC boxes. To define further the molecular mechanisms for the regulation of MnSOD expression, multiple transcription factor-binding motifs containing overlapping specificity protein 1 (Sp1)- and activator protein (AP)-2-binding sites were identified by DNase I footprinting analysis. Functional studies in three cell lines with different levels of Sp1 and AP-2 proteins suggested that the cellular levels of these proteins may differentially regulate transcription via GC-binding motifs in the human SOD2 promoter. Co-transfection of an Sp1 expression vector resulted in an increase in the transcription of the promoter-driven reporter gene. In contrast, co-transfection of the AP-2 expression vector caused a decrease in transcription. Direct mutagenesis analysis of Sp1- and AP-2-binding sites showed that Sp1 is essential for transcription of the human SOD2 gene, whereas AP-2 plays a negative role in the transcription. Immunoprecipitation of Sp1 and AP-2 proteins demonstrated that Sp1 interacts with AP-2 in vivo. Two-hybrid analysis revealed that interaction between Sp1 and AP-2 plays both a positive and negative role in the transcription of the reporter gene in vivo. Taken together, our data indicate that AP-2 down-regulates transcription of the human SOD2 gene via its interaction with Sp1 within the promoter region. These findings, coupled with our previous observation that several cancer cell lines have mutations in the promoter region of the human MnSOD gene, which lead to an increase in an AP-2-binding site and a decrease in the promoter activity, signal the importance of understanding the promoter structure and the regulation of the human SOD2 gene by Sp1 and AP-2.


Mapping aquifer salinity gradients and effects of oil field produced water disposal using geophysical logs: Elk Hills, Buena Vista and Coles Levee Oil Fields, San Joaquin Valley, California.
The effects of oil and gas production on adjacent groundwater quality are becoming a concern in many areas of the United States. As a result, it has become increasingly important to identify which aquifers require monitoring and protection. In this study, we map the extent of groundwater with less than 10,000 mg/L TDS both laterally and vertically near the Elk Hills, Buena Vista and Coles Levee Oil Fields in the San Joaquin Valley, California and note evidence of effects of produced water disposal on salinity within the Tulare aquifer. Subsurface maps showing the depth at which groundwater salinity is less than 10,000 mg/L (or Base 10K) in the Tulare aquifer are generated using geophysical logs and verified by comparison to water sample analyses. The depth to Base 10K ranges from 240 m (800 ft) in Elk Hills to 800 m (2650 ft) in the adjacent Buena Vista syncline and is 670 m (2,200 ft) deep in the Coles Levee area to the east. Log-calculated salinities show a relatively smooth increase with depth prior to disposal activities whereas salinities calculated from logs collected near and after disposal activities show a more variable salinity profile with depth. The effect of produced water injection is represented by log resistivity profiles that change from low resistivity at the base of the sand to higher resistivity near the top due to density differences between the saline produced water and the brackish groundwater within each sand. Continued post-disposal logging in new wells in the 18G disposal area on the south flank of Elk Hills shows that injected water has migrated approximately 1,200 m (4,000 ft) downdip (south) over a period of 20 years since the inception of disposal activity.


Four-port SNAP microresonator device.
It is well known from quantum mechanics that the transmission amplitude of a symmetric double-barrier structure can approach unity at the resonance condition. A similar phenomenon is observed in optics for light which propagates between two waveguides weakly coupled through a microresonator. Examples of microresonators used for this purpose include ring, photonic crystal, toroidal, and bottle microresonators. However, ring and photonic crystal photonic circuits, once fabricated, cannot be finely tuned to arrive at the mentioned resonant condition. In turn, it is challenging to predictably adjust coupling to toroidal and bottle microresonators by translating the input-output microfibers, since the modes of these resonators are difficult to separate spatially. Here we experimentally demonstrate a four-port micro-device based on a SNAP microresonator introduced at the surface of an optical fiber. The eigenmodes and corresponding eigenwavelengths of this resonator are clearly identified for both polarization states by the spectrograms measured along the length of the fiber. This allows us to choose the resonant wavelength and simultaneously determine the positions of the input-output microfiber tapers to arrive at the required resonance condition.


Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial.
Rimegepant, a small molecule calcitonin gene-related peptide receptor antagonist, has shown efficacy in the acute treatment of migraine using a standard tablet formulation. The objective of this trial was to compare the efficacy, safety, and tolerability of a novel orally disintegrating tablet formulation of rimegepant at 75 mg with placebo in the acute treatment of migraine. In this double-blind, randomised, placebo-controlled, multicentre phase 3 trial, adults aged 18 years or older with history of migraine of at least 1 year were recruited to 69 study centres in the USA. Participants were randomly assigned to receive rimegepant (75 mg orally disintegrating tablet) or placebo and instructed to treat a single migraine attack of moderate or severe pain intensity. The randomisation was stratified by the use of prophylactic medication (yes or no), and was carried out using an interactive web response system that was accessed by each clinical site. All participants, investigators, and the sponsor were masked to treatment group assignment. The coprimary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 h postdose. The efficacy analyses used the modified intention-to-treat population, which included all patients who were randomly assigned, had a migraine attack with pain of moderate or severe intensity, took a dose of rimegepant or placebo, and had at least one efficacy assessment after administration of the dose. The safety analyses included all randomly assigned participants who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, number NCT03461757, and is closed to accrual. Between Feb 27 and Aug 28, 2018, 1811 participants were recruited and assessed for eligibility. 1466 participants were randomly assigned to the rimegepant (n=732) or placebo (n=734) groups, of whom 1375 received treatment with rimegepant (n=682) or placebo (n=693), and 1351 were evaluated for efficacy (rimegepant n=669, placebo n=682). At 2 h postdose, rimegepant orally disintegrating tablet was superior to placebo for freedom from pain (21% vs 11%, p<0·0001; risk difference 10, 95% CI 6-14) and freedom from the most bothersome symptom (35% vs 27%, p=0·0009; risk difference 8, 95% CI 3-13). The most common adverse events were nausea (rimegepant n=11 [2%]; placebo n=3 [<1%]) and urinary tract infection (rimegepant n=10 [1%]; placebo n=4 [1%]). One participant in each treatment group had a transaminase concentration of more than 3 × the upper limit of normal; neither was related to study medication, and no elevations in bilirubin greater than 2 × the upper limit of normal were reported. Treated participants reported no serious adverse events. In the acute treatment of migraine, a single 75 mg dose of rimegepant in an orally disintegrating tablet formulation was more effective than placebo. Tolerability was similar to placebo, with no safety concerns. Biohaven Pharmaceuticals.


Polyelectrolyte and Antipolyelectrolyte Effects for Dual Salt-Responsive Interpenetrating Network Hydrogels.
This work presents a salt-responsive interpenetrating network (IPN) hydrogel with effective antimicrobial properties and surface regeneration. The hydrogels were engineered using the double network strategy to form loosely cross-linked zwitterionic poly(sulfobetaine vinylimidazole) (pSBVI) networks into the highly cross-linked cationic poly((trimethylamino)ethyl methacrylate chloride) (pTMAEMA) framework via photopolymerization. The pTMAEMA/pSBVI hydrogel has strong mechanical properties, with a fracture stress 120× higher than single network pTMAEMA hydrogel. In addition, there is inverse correlation between elastic modulus and elastic strain of pTMAEMA/pSBVI hydrogels as a function of ionic strength. The cationic pTMAEMA and zwitterionic pSBVI show opposite swelling behaviors in salt solutions due to the polyelectrolyte effect and antipolyelectrolyte effect. Therefore, the pTMAEMA/pSBVI hydrogel elicits a significant interfacial transition in solutions with different ionic strengths. The IPN hydrogels have switchable lubrication and optical transmittance between deionized water and 1.0 M NaCl solution. The protein adsorption tests further confirmed the switchable interface of salt-responsive IPN hydrogels. In addition, bacterial attachment test on pTMAEMA/pSBVI hydrogels with Staphylococcus epidermidis (S. epidermidis) and Escherichia coli (E. coli) show bacterial killing rates of the IPN hydrogel over 80% for S. epidermidis and 90% for E. coli after incubating the hydrogels in the bacterial solutions for 24 h. The bacterial release rate from the IPN hydrogel reached 96% after washing with 1.0 M NaCl solution. Furthermore, the excellent reusability of the pTMAEMA/pSBVI hydrogels was demonstrated by the high bacterial killing and bacterial release rates after five kill/release cycles. The work presents a new stimuli-responsive IPN hydrogel with structural modulation, tunable antimicrobial properties, and surface regeneration by ionic strength. Integrating two salt-responsive polymers with mutually independent actions into a single material provides a new direction for smart materials with potential medical and industrial applications.


Efficacy of a single-dose ondansetron for preventing post-operative nausea and vomiting after laparoscopic cholecystectomy with sevoflurane and remifentanil infusion anaesthesia.
In this randomized study we compared the efficacy of ondansetron 4 mg with ondansetron 8 mg for the prevention of postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy with sevoflurane and remifentanil infusion anaesthesia. Sixty patients were randomized to receive ondansetron 8 mg (30 pts) or ondansetron 4 mg (30 pts) before the induction of anaesthesia with thiopental and remifentanil. Anaesthesia was maintained with sevoflurane (0.5 MAC), oxygen and remifentanil infusion (0.25, 0.35, 0.5 microg/kg/min). Postoperative analgesia was provided by intravenous ketorolac 60 mg. The incidence of PONV, the pain score, and the analgesic requirement were recorded for 24 hours. There was no difference among groups in patient characteristics, risk factors for PONV, or side effects. During the first 6 h postoperatively, the incidence of PONV after ondansetron 4 mg and 8 mg were similar (p < 0.001). After 6 h the incidence of PONV increased significantly in patients who had received ondansetron 4 mg (p = 0.01) and was greater than that in patients who had received ondansetron 8 mg (p = 0.001). We conclude that single-dose ondansetron 8 mg is more effective than ondansetron 4 mg in the prevention of PONV after laparoscopic cholecystectomy. This surgery is associated with a high incidence of postoperative nausea and vomiting. A single dose of IV ondansetron 8 mg is well tolerated and decrease the number of nausea and vomiting episodes after surgery.


Resistance training to counteract the catabolism of a low-protein diet in patients with chronic renal insufficiency. A randomized, controlled trial.
Chronic renal insufficiency leads to muscle wasting, which may be exacerbated by low-protein diets prescribed to delay disease progression. Resistance training increases protein utilization and muscle mass. To determine the efficacy of resistance training in improving protein utilization and muscle mass in patients with chronic renal insufficiency treated with a low-protein diet. Randomized, controlled trial. Tufts University, Boston, Massachusetts. 26 older patients with moderate renal insufficiency (17 men, 9 women) who had achieved stabilization on a low-protein diet. During a run-in period of 2 to 8 weeks, patients were instructed and their adherence to the low-protein diet (0.6 g/kg of body weight per day) was evaluated. They were randomly assigned to a low-protein diet plus resistance training (n = 14) or a low-protein diet alone (n = 12) for 12 weeks. Total body potassium, mid-thigh muscle area, type I and II muscle-fiber cross-sectional area, and protein turnover. Mean protein intake was 0.64 +/- 0.07 g/kg per day after stabilization. Total body potassium and type I and II muscle-fiber cross-sectional areas increased in patients who performed resistance training by a mean (+/-SD) of 4% +/- 8%, 24% +/- 31%, and 22% +/- 29%, respectively, compared with those who did not. Leucine oxidation and serum prealbumin levels also improved significantly. Patients assigned to resistance training maintained body weight compared with those who were not. Improvement in muscle strength was significantly greater with resistance training (32% +/- 14%) than without (-13% +/- 20%) (P < 0.001). By improving muscle mass, nutritional status, and function, resistance training seems to be effective against the catabolism of a low-protein diet and uremia in patients with renal failure.


Cytogenetic Single-Institution Analysis: 101 Consecutive Cases of Soft-Tissue Tumors of the Extremities.
We summarize the results and clinical usefulness of cytogenetic analysis that is routinely performed for musculoskeletal tumors. We performed cytogenetic analysis and traditional histologic evaluation on 101 (51 malignant/ 50 benign) consecutive tumors that were surgically excised. The successful culture rate for cytogenetic analysis was 86% (87/101). Fifty-four percent (25/46) of clearly malignant tumors that were successfully cultured demonstrated significant clonal abnormalities. Fifty-one percent (21/41) of benign tumors that were cultured had significant cytogenetic clonal aberrations. Increased cellular ploidy (> 50 chromosomes/cell) was demonstrated in 14/46 malignant and 1/41 benign tumors that were successfully cultured. Hyperploidy was highly correlated with malignancy (p < 0.001); the only "benign" tumor was a multiply recurrent and giant cell, demonstrating histologic changes consistent with early sarcomatous transformation. As expected, cytogenetic abnormalities frequently occurred in malignant tumors. Surprisingly, almost half of the benign tumors had significant clonal cytogenetic aberrations. Consistent findings of extra chromosomes 5 and 7 in samples of pigmented villonodular synovitis strongly favored a neoplastic origin for this condition. Although the presence or absence of cytogenetic aberrations cannot be used to determine malignant potential, increased cellular ploidy is highly indicative of malignancy. Modern molecular genetics have become more popular, but cytogenetic analysis can be useful for classifying the malignant potential of recurrent and difficult to diagnose tumors of the musculoskeletal system.


Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from alpha beta TCR transgenic mice: IL-12 substitution for macrophages to stimulate IFN-gamma production is IFN-gamma-dependent.
We have examined the antigen presenting cell (APC) requirements for primary T cell activation and T helper (Th) cell phenotype differentiation using naive CD4+ T cells from alpha beta TCR transgenic mice. Purified dendritic cells were the principal cell required for induction of primary ovalbumin peptide specific T cell activation and clonal expansion. However, dendritic cells did not induce differentiation of T cells toward Th1 or Th2 phenotype. Addition of IL-4 during primary dendritic cell stimulations of T cells resulted in the development of a Th2 phenotype which produced high levels of IL-4 during secondary and tertiary stimulation. In contrast, development of Th1 cells producing high levels of IFN-gamma could not be induced with dendritic cells alone but required the addition of appropriately activated macrophages. Addition of splenic or peritoneal B cells did not induce Th1 development. Activated splenic macrophages induced Th1 development via a non-MHC restricted mechanism. Thus, requirements for induction of proliferation of naive CD4+ T cells are distinct from those directing Th1 phenotype development. IL-12 could replace the requirement for macrophages to induce Th1 development when T cells were activated with dendritic cells. Furthermore, this IL-12 mediated development of Th1 cells producing high levels of IFN-gamma was dependent on IFN-gamma.


Oleaginous yeasts for biochemicals, biofuels and food from lignocellulose-hydrolysate and crude glycerol.
Microbial lipids produced from lignocellulose and crude glycerol (CG) can serve as sustainable alternatives to vegetable oils, whose production is, in many cases, accompanied by monocultures, land use changes or rain forest clearings. Our projects aim to understand the physiology of microbial lipid production by oleaginous yeasts, optimise the production and establish novel applications of microbial lipid compounds. We have established methods for fermentation and intracellular lipid quantification. Following the kinetics of lipid accumulation in different strains, we found high variability in lipid formation even between very closely related oleaginous yeast strains on both, wheat straw hydrolysate and CG. For example, on complete wheat straw hydrolysate, we saw that one Rhodotorula glutinis strain, when starting assimilating D-xylosealso assimilated the accumulated lipids, while a Rhodotorula babjevae strain could accumulate lipids on D-xylose. Two strains (Rhodotorula toruloides CBS 14 and R. glutinis CBS 3044) were found to be the best out of 27 tested to accumulate lipids on CG. Interestingly, the presence of hemicellulose hydrolysate stimulated glycerol assimilation in both strains. Apart from microbial oil, R. toruloides also produces carotenoids. The first attempts of extraction using the classical acetone-based method showed that β-carotene is the major carotenoid. However, there are indications that there are also substantial amounts of torulene and torularhodin, which have a very high potential as antioxidants.


Renal Cell Carcinoma Presenting as an Ampullary Mass: A Case Report and Review of Literature.
We present a case of a 60-year-old female patient who has significant medical history of renal cell carcinoma diagnosed 2 years back and had undergone right nephrectomy and chemotherapy. She presented to the hospital with complaints of abdominal pain and jaundice of 2 weeks duration and was found to have periampullary mass lesion causing compression of distal common bile duct on imaging with computed tomography of abdomen. Endoscopic retrograde cholangiography and endoscopic ultrasound showed ampullary mass lesion causing biliary obstruction along with abdominal lymphadenopathy. A temporary plastic stent was placed to relieve obstruction. Fine needle aspiration cytology of the periampullary mass along with immunohistochemical staining confirmed the diagnosis of metastatic renal cell carcinoma.


Assessment of long-acting synthetic corticotrophin in hypersensitive asthmatics and normal subjects.
The synthetic polypeptide depot-tetracosactrin (Synacthen-Depot) was given to nine steroid-treated asthmatic patients hypersensitive to animal corticotrophin. Eight had a satisfactory increase in plasma and urinary 17-hydroxycorticosteroids (17-OHCS). The remaining patient had been shown previously to have adrenal suppression. None of the patients developed allergic reactions to depot-tetracosactrin, and seven have been receiving regular injections of the polypeptide twice weekly for the past eight months.In 13 normal subjects intramuscular injections of 1 mg. and 0.5 mg. of depot-tetracosactrin and 40 units of corticotrophin-gel were equally potent in raising the plasma 17-OHCS, but depot-tetracosactrin had a significantly longer action than corticotrophin-gel.


The enhancer of polycomb gene of Drosophila encodes a chromatin protein conserved in yeast and mammals.
The Polycomb group of genes in Drosophila are homeotic switch gene regulators that maintain homeotic gene repression through a possible chromatin regulatory mechanism. The Enhancer of Polycomb (E(Pc)) gene of Drosophila is an unusual member of the Polycomb group. Most PcG genes have homeotic phenotypes and are required for repression of homeotic loci, but mutations in E(Pc) exhibit no homeotic transformations and have only a very weak effect on expression of Abd-B. However, mutations in E(Pc) are strong enhancers of mutations in many Polycomb group genes and are also strong suppressors of position-effect variegation, suggesting that E(Pc) may have a wider role in chromatin formation or gene regulation than other Polycomb group genes. E(Pc) was cloned by transposon tagging, and encodes a novel 2023 amino acid protein with regions enriched in glutamine, alanine and asparagine. E(Pc) is expressed ubiquitously in Drosophila embryogenesis. E(Pc) is a chromatin protein, binding to polytene chromosomes at about 100 sites, including the Antennapedia but not the Bithorax complex, 29% of which are shared with Polycomb-binding sites. Surprisingly, E(Pc) was not detected in the heterochromatic chromocenter. This result suggests that E(Pc) has a functional rather than structural role in heterochromatin formation and argues against the heterochromatin model for PcG function. Using homology cloning techniques, we identified a mouse homologue of E(Pc), termed Epc1, a yeast protein that we name EPL1, and as well as additional ESTs from Caenorhabditis elegans, mice and humans. Epc1 shares a long, highly conserved domain in its amino terminus with E(Pc) that is also conserved in yeast, C. elegans and humans. The occurrence of E(Pc) across such divergent species is unusual for both PcG proteins and for suppressors of position-effect variegation, and suggests that E(Pc) has an important role in the regulation of chromatin structure in eukaryotes.


Growth-induced water potentials originate from wall yielding during growth.
Multicellular plants display growth-induced water potentials that generate tensions on water in the apoplast and move water into the growing cells. The potentials are sometimes assumed to arise from wall yielding, keeping the turgor pressure below what otherwise would occur. There has been no direct test of this theory, and therefore whole plants or growing regions of stems (hypocotyls) of dark-grown soybean (Glycine max L. Merr.) seedlings were sealed in a pressure chamber, and wall yielding was decreased by applying external pressure. In whole plants, external pressure had little effect because the plants and water supply were uniformly exposed to the pressure. If pressure was applied to the stem while the roots were outside in water, stem elongation was markedly inhibited because the pressure raised the water potential of the growing region and decreased water entry, reducing wall yielding. Further increasing the pressure prevented water entry completely and measured the tensions in the apoplast in the same growing regions. Tensions were about 0.19 MPa at low external pressure, but diminished as wall yielding was inhibited. At external pressures of about 0.63 MPa, wall yielding was abolished and tensions approached zero. There was a linear relation between wall yielding and tension, supporting the theory that wall yielding lowers the turgor thus causing most of the growth-induced water potential.


Provision of contraceptive counseling by internal medicine residents.
Internists care for women of reproductive age, but little is known about internists' training in contraceptive counseling or provision of contraceptive methods. We surveyed 152 residents in nine internal medicine programs in Los Angeles County during the 2004-2005 academic year. The self-administered, 29-item survey included demographic, contraceptive practice pattern, and training variables. Descriptive statistics and multivariable logistic regression were used to illustrate counseling and prescribing practices and to identify predictors of counseling and provision of contraceptives. Most (95%) future internists surveyed reported clinical responsibility for women of reproductive age. However, few (17%) routinely provided contraceptive counseling, and 39% rarely or never provided contraceptive counseling. Residents had prescribed contraception on a median of 2 (range 0-30) occasions in the past year. Some formal education in contraceptive methods was reported by 51% of respondents; however, 75% of residents reported a desire for more training about contraception. Internal medicine residents commonly care for women of reproductive age but infrequently assess or address contraceptive needs. Further training on how to provide contraception is desired by many internal medicine residents.


Role of NMDA receptors in lesion-induced plasticity.
The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on the acquisition and maintenance of a compensated state following unilateral labyrinthectomy was investigated in two species, grass frog and goldfish. MK-801: 1) inhibits the acquisition of a compensated state, and 2) causes a loss of compensation in early phases of the compensation process, but 3) has no such effect to the long-term maintenance of compensation. It is concluded that NMDA receptors perform a transient function by inducing a sensory or functional substitution process in the deafferented vestibular system. A hypothesis is presented explaining the lesion-induced adaptive process as a result of a self-organizing process in a neural net using Hebb-like algorithms to organize the strength of connections.


Cardiac allograft vasculopathy: diagnosis, therapy, and prognosis.
Development of cardiac allograft vasculopathy represents the major determinant of long-term survival in patients after heart transplantation. Due to graft denervation, these patients seldom present with classic symptoms of angina pectoris, and the first clinical presentations are progressive heart failure or sudden cardiac death. Although coronary angiography remains the routine technique for coronary artery disease detection, it is not sensitive enough for screening purposes. This is especially the case in the first year after transplantation when diffuse and concentric vascular changes can be easily detected only by intravascular ultrasound. The treatment of the established vasculopathy is disappointing, so the primary effort should be directed toward early prevention and diagnosis. Due to diffuse vascular changes, revascularization procedures are restricted only to a relatively small proportion of patients with favorable coronary anatomy. Percutaneous coronary intervention is preferred over surgical revascularization since it leads to better acute results and patient survival. Although there is no proven long-term advantage of drug-eluting stents for the treatment of in-stent restenosis, they are preferred over bare-metal stents. Severe vasculopathy has a poor prognosis and the only definitive treatment is retransplantation. This article reviews the present knowledge on the pathogenesis, diagnosis, treatment, and prognosis of cardiac allograft vasculopathy.


[Prevalence of positive gonococcal and chlamydial findings in women applying for termination of pregnancy. A screening evaluation].
All 335 pregnant women referred for termination of pregnancy in the first trimester were examined preoperatively for infection with Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) and were questioned about symptoms of gynaecological infection. Only 0.6% had positive cultures for gonorrhoeae while CT infection was demonstrated in 7.8%. Half of the women with infection had one of the following symptoms: discharge, pain or dysuria. These same symptoms were, however, also found in half of the women without infection. All gynaecological special departments in Denmark and a few of the surgical departments which carry out termination of pregnancy replied to a questionnaire about routine examinations for NG and CT in cases of termination of pregnancy. Only 29.2% of the departments made routine preoperative examinations for CT, NG or both. It is concluded that there are no indications for routine examination for gonococcal infection whereas screening for CT infection appears to be indicated.


Cibinetide Protects Isolated Human Islets in a Stressful Environment and Improves Engraftment in the Perspective of Intra Portal Islet Transplantation.
During intra-portal pancreatic islet transplantation (PITx), innate immune reactions such as the instant blood mediated inflammatory reaction (IBMIR) cause an immediate loss of islets. The non-hematopoietic erythropoietin analogue cibinetide has previously shown islet-protective effects in mouse PITx. Herein, we aimed to confirm cibinetide's efficacy on human islets, and to characterize its effect on IBMIR. We cultured human islets with pro-inflammatory cytokines for 18 hours with or without cibinetide. ATP content and caspase 3/7 activity were measured. Dynamic glucose perfusion assay was used to evaluate islet function. To evaluate cibinetides effect on IBMIR, human islets were incubated in heparinized polyvinyl chloride tubing system with ABO compatible blood and rotated for 60 minutes to mimic the portal vein system. Moreover, human islets were transplanted into athymic mice livers via the portal vein with or without perioperative cibinetide treatment. The mice were sacrificed six days following transplantation and the livers were analyzed for human insulin and serum for human C-peptide levels. Histological examination of recipient livers to evaluate islet graft infiltration by CD11b+ cells was performed. Our results show that cibinetide maintained human islet ATP levels and reduced the caspase 3/7 activity during culture with pro-inflammatory cytokines and improved their insulin secreting capacity. In the PVC loop system, administration of cibinetide reduced the IBMIR-induced platelet consumption. In human islet to athymic mice PITx, cibinetide treatment showed an increased amount of human insulin in the livers and higher serum human C-peptide, while histological examination of the livers showed reduced infiltration of pro-inflammatory CD11b+ cells around islets grafts compared to the controls. In summary, Cibinetide protected isolated human islets in a pro-inflammatory milieu and reduced IBMIR related platelet consumption. It improved engraftment of human islets in athymic mice. The study confirms that cibinetide is a promising agent to be used in clinical PITx.


Erythema-inducing effects of solvents following epicutaneous administration to man--studied by laser Doppler flowmetry.
Skin exposure to solvents can cause erythema, edema, scaling, and, eventually, irritant contact dermatitis. The irritant potential of chemicals is usually assessed by visual scoring, but in recent years a more objective measuring technique, laser Doppler flowmetry (LDF), has been introduced for the assessment of erythema. The method is noninvasive and allows continuous recording. In the present study 11 solvents were applied for 5 min or less to the volar forearms of a man and the kinetics of the response is shown. For seven solvents (dimethyl sulfoxide, trichloroethylene, n-hexane, carbon tetrachloride, toluene, 1,1,1-trichloroethane, 1,1,2-trichloroethane) an increase was found over the pretreatment values, whereas four solvents (methyl ethyl ketone, ethanol, propylene glycol, distilled water) did not influence blood flow. The findings are discussed in relation to the macroscopic picture (whitening and erythema) and in relation to previous studies of the edema-inducing effects of the same solvents on man and experimental animals. It is concluded that LDF is well worth trying in cases of marginal irritancy and for predictive testing, since it seems to be more sensitive and reliable than the naked eye.


Totally percutaneous endovascular repair for ruptured abdominal aortic aneurysms.
The PEVAR Trial demonstrated that compared to open femoral exposure, elective percutaneous endovascular AAA repair (ePEVAR) is associated with decreased perioperative morbidity and access site complications. We hypothesized that PEVAR for ruptured AAA (rPEVAR) may also improve perioperative morbidity compared to open femoral exposure (rEVAR). There are currently no reports that evaluate the utility and outcomes of rPEVAR. From 2015 to 2021, all patients who underwent an endovascular repair of a ruptured AAA at a single institution were included in the study and grouped into rPEVAR and rEVAR. Demographics, procedural details (successful preclose technique, conversion to femoral cutdown), postoperative variables (blood transfusion, ICU and hospital length of stay) and short-term outcomes (30-day major adverse events (30-day MAE) and 30-day femoral access-site complications (30-day FAAC)) were collected and compared with 50 historical ePEVAR patients from the PEVAR Trial. Statistical significance was determined using χ 2 or Fisher's exact test for categorical variables, and Mann-Whitney U-test for continuous variables. 35 patients were identified (21 rPEVAR; 14 rEVAR), 86% were male with a mean age of 72 ± 9 years. All patients underwent emergent endovascular aortic repair with 100% technical success. Seventeen patients (49%) presented with evidence of hemorrhagic shock and 22 patients (63%) had blood transfusion. 30-day MAE occurred in 12 patients (34%) (7 rPEVAR; 5 rEVAR). There was no difference in demographic, perioperative outcomes and 30-day MAE rate between rPEVAR and rEVAR patients. Compared to ePEVAR patient (from PEVAR trial), rPEVAR patients had higher rate of 30-day MAE (34% vs. 6%; p < 0.006) but no difference in 30-day FAAC (19% vs. 12%; p = 0.54). The success rate of the preclose technique was higher in ePEVAR compared to rPEVAR (96% vs. 76%; p = 0.02), but the rate of conversion to femoral cutdown was similar between the two groups (10% vs. 4%; p = 0.57). Emergent rPEVAR appears to have similar outcomes when compared to rEVAR. Although patients undergoing rPEVAR have higher 30-day major adverse events rate compared to ePEVAR, the method of percutaneous femoral cannulation does not appear to increase the overall procedural or 30-day femoral artery access-site complications.


The plant MBF1 protein family: a bridge between stress and transcription.
The Multiprotein Bridging Factor 1 (MBF1) proteins are transcription co-factors whose molecular function is to form a bridge between transcription factors and the basal machinery of transcription. MBF1s are present in most archaea and all eukaryotes, and numerous reports show that they are involved in developmental processes and in stress responses. In this review we summarize almost three decades of research on the plant MBF1 family, which has mainly focused on their role in abiotic stress responses, in particular the heat stress response. However, despite the amount of information available, there are still many questions that remain about how plant MBF1 genes, transcripts, and proteins respond to stress, and how they in turn modulate stress response transcriptional pathways.


Dominance of international 'high-risk clones' among metallo-β-lactamase-producing Pseudomonas aeruginosa in the UK.
Carbapenem-resistant isolates of Pseudomonas aeruginosa producing metallo-β-lactamases (MBLs) are increasingly reported worldwide and often belong to particular 'high-risk clones'. This study aimed to characterize a comprehensive collection of MBL-producing P. aeruginosa isolates referred to the UK national reference laboratory from multiple UK laboratories over a 10 year period. Isolates were referred to the UK national reference laboratory between 2003 and 2012 for investigation of resistance mechanisms and/or outbreaks. MBL genes were detected by PCR. Typing was carried out by nine-locus variable-number tandem repeat (VNTR) analysis and MLST. MBL-producing P. aeruginosa isolates were referred from 267 source patients and 89 UK laboratories. The most common isolation sites were urine (24%), respiratory (18%), wounds (17%) and blood (13%). VIM-type MBLs predominated (91% of all MBLs found), but a few IMP- and NDM-type enzymes were also identified. Diverse VNTR types were seen, but 86% of isolates belonged to six major complexes. MLST of representative isolates from each complex showed that they corresponded to STs 111, 233, 235, 357, 654 and 773, respectively. Isolates belonging to these complexes were received from between 9 and 25 UK referring laboratories each. The incidence of MBL-producing P. aeruginosa is increasing in the UK. The majority of these isolates belong to several 'high-risk clones', which have been previously reported internationally as host clones of MBLs.


A prospective clinical trial on the influence of a triamcinolone/demeclocycline and a calcium hydroxide based temporary cement on pain perception.
The aim of this clinical trial was to compare the degree of short term post-operative irritation after application of a triamcinolone/demeclocycyline based or a calcium hydroxide based provisional cement. A total of 109 patients (55 female and 54 male; mean age: 51 ± 14 years) with primary or secondary dentinal caries were randomly assigned to the two treatment groups of this biomedical clinical trial (phase III). Selection criteria were good systemic health and treated teeth, which were vital and showed no symptoms of pulpitis. Up to three teeth were prepared for indirect metallic restorations, and the provisional restorations were cemented with a triamcinolone/demeclocycyline (Ledermix) or a calcium hydroxide (Provicol) based material. The intensity of post-operative pain experienced was documented according to the VAS (4, 12, 20, 24, and 82 h) and compared to VAS baseline. A total of 159 teeth were treated (Ledermix: 83 teeth, Provicol: 76 teeth). The minor irritation of the teeth, experienced prior to treatment, was similar in both groups; however, 4 h after treatment this value was significantly higher in the Provicol group than in the Ledermix group (p < 0.005, t-test). After 12 h, the difference was no longer significant. The number of patients taking analgesics for post-treatment pain was higher in the Provicol group (n = 11/53) than in the Ledermix group (n = 3/56). The patients had no long term post-operative pain experience in both groups. However, within the first hours after cementation the sensation of pain was considerably higher in the Provicol group than in the Ledermix group.