Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells.
Tumor necrosis factor (TNF) functions both as a soluble molecule and as a cell surface 26 kDa transmembrane protein, from which the soluble form is proteolytically derived. The 26 kDa TNF molecules isolated from 32P labeled HeLa cells that had been transfected with the cDNA of a partially cleavable TNF mutant were found labeled. Phosphorylated 26 kDa TNF molecules could also be isolated from human LPS stimulated monocytic Mono Mac 6. Phosphoaminoacid analysis revealed that the labeled phosphate is bound to serine residues. No label was found incorporated in soluble 17 kDa TNF, indicating that the phosphorylated residue(s) of membrane-associated TNF occur in the cytoplasmic portion of the molecule. Phosphorylation of the intracellular domain of the 26 kDa TNF molecules may play a role in the regulation of expression or proteolytic processing of TNF, modulate TNF bioactivity, or take part in intracellular signaling by cell-surface TNF.


The changing motivation of massage therapy students.
The study was conducted in order to determine whether the level of motivation related to intrinsic (people-oriented) and extrinsic (external reward) value complexes in a class of massage therapy students changed during their professional education. The research was a quasi-experimental within-subject design, in which survey data was collected from students on their first day in the massage therapy program and again towards the end of their final term. The data were collated and summarized, and the differences in motivation scores were assessed using Fisher's Least Significant Difference procedure. The results support the hypothesis that massage therapy students are motivated more strongly by intrinsic than extrinsic rewards both at the commencement of their studies and as they approach entry to practice. Also evident from the data is the fact that the students' motivation changed during their professional studies. This change involved a significant decrease in the level of intrinsic motivation and significant increase in the level of extrinsic motivation. Thus, although intrinsic motivation reduced while extrinsic motivation increased, the former remained the more powerful influence. Professional programs should consider the balance between intrinsic and extrinsic student motivation and attempt to control influences that might shift this such that the humanistic / altruistic mission of health care is undermined.


Functional investigation of a QTL affecting resistance to Haemonchus contortus in sheep.
This study reports a functional characterization of a limited segment (QTL) of sheep chromosome 12 associated with resistance to the abomasal nematode Haemonchus contortus. The first objective was to validate the identified QTL through the comparison of genetically susceptible (N) and resistant (R) sheep produced from Martinik × Romane back-cross sheep. The R and N genotype groups were then experimentally infected with 10 000 H. contortus larvae and measured for FEC (every three days from 18 to 30 days post-challenge), haematocrit, worm burden and fertility. Significant differences in FEC and haematocrit drop were found between R and N sheep. In addition, the female worms recovered from R sheep were less fecund. The second step of the characterization was to investigate functional mechanisms associated with the QTL, thanks to a gene expression analysis performed on the abomasal mucosa and the abomasal lymph node. The gene expression level of a candidate gene lying within the QTL region (PAPP-A2) was measured. In addition, putative interactions between the chromosome segment under study and the top ten differentially expressed genes between resistant MBB and susceptible RMN sheep highlighted in a previous microarray experiment were investigated. We found an induction of Th-2 related cytokine genes expression in the abomasal mucosa of R sheep. Down-regulation of the PAPP-A2 gene expression was observed between naïve and challenged sheep although no differential expression was recorded between challenged R and N sheep. The genotyping of this limited region should contribute to the ability to predict the intrinsic resistance level of sheep.


A solution method for the determination of cardiac potential distributions with an alternating current source.
A recently presented solution method for the bidomain model (Johnston et al. 2006), which involves the application of direct current for studying electrical potential in a slab of cardiac tissue, is extended here to allow the use of an applied alternating current. The advantage of using AC current, in a four-electrode method for determining cardiac conductivities, is that instead of using 'close' and 'wide' electrode spacings to make potential measurements, increasing the frequency of the AC current redirects a fraction of the current from the extracellular space into the intracellular space. The model is based on the work of Le Guyader et al. (2001), but is able to include the effects of the fibre rotation between the epicardium and the endocardium on the potentials. Also, rather than using a full numerical technique, the solution method uses Fourier series and a simple one dimensional finite difference scheme, which has the advantage of allowing the potentials to be calculated only at points, such as the measuring electrodes, where they are required. The new alternating current model, which includes intracellular capacitance, is used with a particular four-electrode configuration, to show that the potential measured is affected by changes in fibre rotation. This is significant because it indicates that it is necessary to include fibre rotation in models, which are to be used in conjunction with measuring arrays that are more complex than those involving simply surface probes or a single vertical probe.


One-shot domain adaptation in multiple sclerosis lesion segmentation using convolutional neural networks.
In recent years, several convolutional neural network (CNN) methods have been proposed for the automated white matter lesion segmentation of multiple sclerosis (MS) patient images, due to their superior performance compared with those of other state-of-the-art methods. However, the accuracies of CNN methods tend to decrease significantly when evaluated on different image domains compared with those used for training, which demonstrates the lack of adaptability of CNNs to unseen imaging data. In this study, we analyzed the effect of intensity domain adaptation on our recently proposed CNN-based MS lesion segmentation method. Given a source model trained on two public MS datasets, we investigated the transferability of the CNN model when applied to other MRI scanners and protocols, evaluating the minimum number of annotated images needed from the new domain and the minimum number of layers needed to re-train to obtain comparable accuracy. Our analysis comprised MS patient data from both a clinical center and the public ISBI2015 challenge database, which permitted us to compare the domain adaptation capability of our model to that of other state-of-the-art methods. In both datasets, our results showed the effectiveness of the proposed model in adapting previously acquired knowledge to new image domains, even when a reduced number of training samples was available in the target dataset. For the ISBI2015 challenge, our one-shot domain adaptation model trained using only a single case showed a performance similar to that of other CNN methods that were fully trained using the entire available training set, yielding a comparable human expert rater performance. We believe that our experiments will encourage the MS community to incorporate its use in different clinical settings with reduced amounts of annotated data. This approach could be meaningful not only in terms of the accuracy in delineating MS lesions but also in the related reductions in time and economic costs derived from manual lesion labeling.


Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered, indicating initiation of early luteal phase transformation in the absence of secretory changes.
Ovarian stimulation for IVF profoundly alters the early luteal phase endometrial development. It has been hypothesized that this process has already started in the late follicular phase, as the endometrium has already been exposed to high steroid concentrations since that phase. The aim of the present study was to prospectively investigate the effect of multi-follicular ovarian stimulation for IVF on the late follicular phase endometrium histology and the expression of estrogen receptor (ER) and progesterone receptor (PR). In a cross-over study, 11 infertile women with normal ovulatory function, participating in an IVF programme and treated with GnRH antagonist/recombinant FSH ovarian stimulation, were enrolled in the study. Endometrial biopsies were taken in a natural cycle on the day of the onset of the surge of the LH, and in a subsequent stimulation cycle on the day of hCG administration for final oocyte maturation. Endometrial histological dating was carried out according to Noyes' criteria. Immunohistochemistry was performed, using commercially available antibodies for ER and PR endometrial expression. The immunohistochemical signal was recorded in 1000 epithelial cells in each compartment (glands and stroma). Endometrial expression for each of the two receptors was graded on a scale of 0-3, based on the intensity of nuclear staining. Then a score range between 0 and 3000 was recorded, and expressed as a mean score per 1000 stroma or glandular cells per sample (range: 0-3). Histological examination of biopsies both in natural and stimulated cycles showed no secretory changes. However, in stimulated cycles, PR expression was significantly up-regulated compared to natural cycles in both glands (1.67 versus 1.34, P < 0.05) and stroma (1.98 versus 1.62, P < 0.05), whereas ER was down-regulated in glands (1.15 versus 1.43, P < 0.05). In IVF cycles, the progesterone measurements, although within normal values (range 0.8-1.4 microg/l), were significantly higher than in natural cycles (0.99 vs 0.63 microg/l, respectively, P = 0.008). An ongoing pregnancy rate of 37.5% was achieved in the stimulated cycles. Although the current study found no early secretory transformation in stimulated endometria before hCG administration, the ER and PR expression in these endometria is similar to the one described during the first days of the luteal phase in natural cycles. Supraphysiological concentrations of estradiol and subtle progesterone rises in the late follicular phase might be responsible for this modulated steroid receptor profile. This phenomenon indicates accentuated maturation of the endometrium in IVF cycles from the pre-ovulatory phase onwards.


UHRF1 depletion suppresses growth of gallbladder cancer cells through induction of apoptosis and cell cycle arrest.
Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1), overexpressed in various human malignancies, functions as an important regulator in cell proliferation and epigenetic regulation. Depletion of UHRF1 has shown potential antitumor activities in several types of cancer. However, the role of UHRF1 in gallbladder cancer (GBC) has not been investigated. RT-PCR, western blotting and immunohistochemistry were performed to examine UHRF1 expression at mRNA and protein levels in GBC tissues and cell lines. UHRF1 siRNA and UHRF1 shRNA were used to deplete the expression of UHRF1. The results showed that UHRF1 was overexpressed in GBC and its expression correlated with advanced TNM stage and presence of lymph node metastasis. UHRF1 depletion in GBC-SD and NOZ cells markedly inhibited proliferation, migration in vitro and the ability of these cells to form tumors in vivo. UHRF1 depletion upregulated the expression of PML and triggered extrinsic and intrinsic apoptotic pathways by promoting the expression of FasL/FADD, bax, cytosolic cytochrome c, cleaved caspase-8, -9 and -3 and cleaved PRAP and by suppressing bcl-2 expression in GBC-SD and NOZ cells. In addition, UHRF1 depletion induced cell cycle arrest at G1/S transition by inducing p21 in a p53-independent manner in GBC-SD and NOZ cells. Our findings suggest that UHRF1 is involved in the proliferation and migration of GBC cells and may serve as a biomarker or even a therapeutic target for GBC.


Nicotine enhances context learning but not context-shock associative learning.
Nicotine has been found to enhance learning in a variety of tasks, including contextual fear conditioning. During contextual fear conditioning animals have to learn the context and associate the context with an unconditioned stimulus (footshock). As both of these types of learning co-occur during fear conditioning, it is not clear whether nicotine enhances one or both of these types of learning. To tease these two forms of learning apart, the authors made use of the context preexposure facilitation effect (CPFE). Acquisition of the CPFE requires that contextual and context-shock learning occurs on separate days, allowing for their individual manipulation. Nicotine (0.09 mg/kg) administered prior to contextual learning and retrieval enhanced the CPFE whereas administration prior to context-shock learning and retrieval had no effect. Thus, nicotine enhances contextual learning but not context-shock associative learning. Finally, the results are discussed in terms of a theory of how nicotine could alter hippocampal-cortical-amygdala interactions to facilitate contextual learning.


Video-oculography in mice.
Eye movements are very important in order to track an object or to stabilize an image on the retina during movement. Animals without a fovea, such as the mouse, have a limited capacity to lock their eyes onto a target. In contrast to these target directed eye movements, compensatory ocular eye movements are easily elicited in afoveate animals. Compensatory ocular movements are generated by processing vestibular and optokinetic information into a command signal that will drive the eye muscles. The processing of the vestibular and optokinetic information can be investigated separately and together, allowing the specification of a deficit in the oculomotor system. The oculomotor system can be tested by evoking an optokinetic reflex (OKR), vestibulo-ocular reflex (VOR) or a visually-enhanced vestibulo-ocular reflex (VVOR). The OKR is a reflex movement that compensates for "full-field" image movements on the retina, whereas the VOR is a reflex eye movement that compensates head movements. The VVOR is a reflex eye movement that uses both vestibular as well as optokinetic information to make the appropriate compensation. The cerebellum monitors and is able to adjust these compensatory eye movements. Therefore, oculography is a very powerful tool to investigate brain-behavior relationship under normal as well as under pathological conditions (f.e. of vestibular, ocular and/or cerebellar origin). Testing the oculomotor system, as a behavioral paradigm, is interesting for several reasons. First, the oculomotor system is a well understood neural system. Second, the oculomotor system is relative simple; the amount of possible eye movement is limited by its ball-in-socket architecture ("single joint") and the three pairs of extra-ocular muscles. Third, the behavioral output and sensory input can easily be measured, which makes this a highly accessible system for quantitative analysis. Many behavioral tests lack this high level of quantitative power. And finally, both performance as well as plasticity of the oculomotor system can be tested, allowing research on learning and memory processes. Genetically modified mice are nowadays widely available and they form an important source for the exploration of brain functions at various levels. In addition, they can be used as models to mimic human diseases. Applying oculography on normal, pharmacologically-treated or genetically modified mice is a powerful research tool to explore the underlying physiology of motor behaviors under normal and pathological conditions. Here, we describe how to measure video-oculography in mice.


Self-Testing as a Hope to Reduce HIV in Transgender Women-Literature Review.
So far, the rate of HIV-positive people who do not know their sero-status is about 14% and the percentage is higher among transgender women (TGW). They represent one of the most vulnerable groups to infection. HIV self-testing (HIVST) may be a way to reduce transmission of the virus. The aim of this analysis and in-depth review was to collect available data on factors that may influence the use and dissemination of HIVST among TGW. This review was conducted in accordance with PRISMA guidelines for systematic reviews and meta-analyses. All data from 48 papers were used. From the available literature, HIVST is a convenient and preferred method of testing due to its high confidentiality and possibility of being performed at home. However, there are barriers that limit its use, including marginalization of transgender people, stigma by medical personnel, lack of acceptance of sexual partners, and even cultural standards. Therefore, there is a need for activities that promote and inform on the possibility of using HIVST as well as enable easier access to it.


Reliability of history and physical examination findings for assessing control of glycemia in dogs with diabetes mellitus: 53 cases (1995-1998).
To evaluate the reliability of history and physical examination findings for assessing control of glycemia in insulin-treated diabetic dogs. Retrospective study. 53 insulin-treated dogs with diabetes mellitus. Medical records of insulin-treated diabetic dogs from June 1995 to June 1998 were reviewed, and information on owner perception of their dog's response to insulin treatment, physical examination findings, body weight, insulin dosage, and concentrations of food-withheld (i.e., fasting) blood glucose (FBG), mean blood glucose (MBG) during an 8-hour period, blood glycosylated hemoglobin (GHb), and serum fructosamine was obtained. Owner's perception of their dog's response to insulin treatment, physical examination findings, and changes in body weight were used to classify control of glycemia as good or poor for each dog. The FBG, MBG/8 h, blood GHb, and serum fructosamine concentrations were compared between well-controlled and poorly controlled insulin-treated diabetic dogs. Presence or absence of polyuria, polydipsia, polyphagia, lethargy, and weakness were most helpful in classifying control of glycemia. Mean FBG and MBG/8 h concentrations, blood GHb concentrations, and serum fructosamine concentrations were significantly decreased in 25 well-controlled diabetic dogs, compared with 28 poorly controlled diabetic dogs. Most well-controlled diabetic dogs had concentrations of FBG between 100 and 300 mg/dl, MBG/8 h < or = 250 mg/dl, blood GHb < or = 7.5%, and serum fructosamine < or = 525 mumol/L, whereas most poorly controlled diabetic dogs had results that were greater than these values. Reliance on history, physical examination findings, and changes in body weight are effective for initially assessing control of glycemia in insulin-treated diabetic dogs.


Instructional behaviors of more and less effective beginning regular and special educators.
To enhance understanding of effective teaching, we studied 117 elementary and intermediate secondary general and special educators who were more and less effective in maintaining class participation. We performed MANOVAs on 22 variables associated with positive student outcomes in the process-product literature and found that teachers who maintained higher levels of participation provided effective transitions, made assignments, and approved of students' verbal responses more often than less effective educators. In addition, they demonstrated negative regard less often than less effective teachers. They also acknowledged learner-initiated interactions and employed strategies for managing student inattention and disruption less frequently than teachers who were less effective in maintaining active student involvement. We also found differences in the frequencies with which elementary and secondary teachers and general and special educators exhibited specific behaviors.


MariClus: Your One-Stop Platform for Information on Marine Natural Products, Their Gene Clusters and Producing Organisms.
The marine environment hosts the vast majority of living species and marine microbes that produce natural products with great potential in providing lead compounds for drug development. With over 70% of Earth's surface covered in water and the high interaction rate associated with liquid environments, this has resulted in many marine natural product discoveries. Our improved understanding of the biosynthesis of these molecules, encoded by gene clusters, along with increased genomic information will aid us in uncovering even more novel compounds. We introduce MariClus (https://www.mariclus.com), an online user-friendly platform for mining and visualizing marine gene clusters. The first version contains information on clusters and the predicted molecules for over 500 marine-related prokaryotes. The user-friendly interface allows scientists to easily search by species, cluster type or molecule and visualize the information in table format or graphical representation. This new online portal simplifies the exploration and comparison of gene clusters in marine species for scientists and assists in characterizing the bioactive molecules they produce. MariClus integrates data from public sources, like GenBank, MIBiG and PubChem, with genome mining results from antiSMASH. This allows users to access and analyze various aspects of marine natural product biosynthesis and diversity.


Slime moulds use heuristics based on within-patch experience to decide when to leave.
Animals foraging in patchy, non-renewing or slowly renewing environments must make decisions about how long to remain within a patch. Organisms can use heuristics ('rules of thumb') based on available information to decide when to leave the patch. Here, we investigated proximate patch-departure heuristics in two species of giant, brainless amoeba: the slime moulds Didymium bahiense and Physarum polycephalum. We explicitly tested the importance of information obtained through experience by eliminating chemosensory cues of patch quality. In P. polycephalum, patch departure was influenced by the consumption of high, and to a much lesser extent low, quality food items such that engulfing a food item increased patch-residency time. Physarum polycephalum also tended to forage for longer in darkened, 'safe' patches. In D. bahiense, engulfment of any food item increased patch residency irrespective of that food item's quality. Exposure to light had no effect on the patch-residency time of D. bahiense. Given that these organisms lack a brain, our results illustrate how the use of simple heuristics can give the impression that individuals make sophisticated foraging decisions.


Interferon-γ-induced protein 10 in Lyme disease.
Lyme disease is an infectious disease caused by bacteria of the Borrelia type, that affects about 300,000 people a year in the USA and 65,000 people a year in Europe. Borrelia infection, and Lyme disease, following occupational exposure has been frequently reported in USA, Europe and Asia. The manifestations of Lyme disease include erythema migrans (EM), arthritis, neuroborrelliosis (NB), and others. Cytokines and chemokines primarily orchestrate leukocyte recruitment to the areas of Borrelia infection, and they are critical mediators of immune and inflammatory responses, in particular of the induction of interferon (IFN)-γ and IFN-γ dependent chemokines. In EM high levels of T helper (Th) 1 cells chemoattranctants [monokine induced by IFN-γ (MIG), IFN-γ-induced protein 10 (IP- 10), and IFN-inducible T cell alpha chemoattractant (I-TAC)] have been shown. Synovial tissues and fluids of patients with Lyme Arthritis (LA) (overall with antibiotic-refractory LA) contained exceptionally high levels of Th1 chemoattractants and cytokines, particularly MIG and IFN-γ. In NB concentrations of IP-10 and I-TAC in the cerebrospinal fluid (CSF) were significantly higher, suggesting that IP-10 and I-TAC create a chemokine gradient between the CSF and serum and recruite C-X-C chemokine receptor 3-expressing memory CD4+ T-cells into the CSF of these patients. A positive association between the disseminating capacity of B. burgdorferi and early type I IFN induction has also been shown. These results suggest that IFN-γ dependent chemokines are important biomarkers to monitor the progression and diffusion of the disease in patients with Borrelia infection; further larger studies are needed.


Hepatitis C viral infection and the risk of dementia.
Hepatitis C virus (HCV) infection may cause cognitive impairment, but no studies have focused specifically on cognitive impairment stemming from HCV. The purpose of this study was to investigate the potential increased risk for dementia in HCV-infected patients. A population-based cohort study based on the Taiwan National Health Insurance Research Database was conducted. From all potential participants aged 50 years or more, a total of 58,570 matched (1:1) pairs of HCV-infected patients and non-HCV-infected patients were included. Each subject was individually tracked from 1997 to 2009 to identify incident cases of dementia (onset in 1999 or later). Cox proportional hazards regressions were employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HCV infection and dementia. There were 2989 dementia cases from the HCV-infected cohort during the follow-up period of 533,861.1 person-years; the overall incidence rates of dementia differed from the non-HCV cohort (56.0 vs. 47.7 cases per 10,000 person-years, P < 0.05). The adjusted HR for dementia was 1.36 (95% CI 1.27-1.42) for HCV-infected patients after adjusting for alcohol-related disease, liver cirrhosis, hepatic encephalopathy and hepatocellular carcinoma. HCV infection may increase the risk for dementia. Further mechanistic research is needed.


[PAI-1, the primary plasmatic inhibitor of fibrinolysis. Physiopathologic role and molecular mechanisms].
Plasminogen activator inhibitor 1 (PAI-1) is the primary physiological inhibitor of plasminogen activation in blood. PAI-1 is known to contribute to thrombus formation and to the development and the clinical course of acute and chronic cardiovascular diseases. Plasma levels of PAI-1 are regulated on a genetic basis but, more important, is the dependence on a series of other atherosclerotic risk factors like hypertriglyceridemia, diabetes and insulin resistance. The insulin resistance syndrome, which is characterized partly by obesity with visceral fat accumulation, is considered as a major regulator of PAI-1 expression. At least in vitro, insulin is a potent inducer of PAI-1 synthesis by human hepatic cells, and, we have recently disentangled the molecular mechanisms responsible for enhanced PAI-1 gene expression by insulin. However, clinical data fail to support a direct acute contribution of insulin in regulating circulating PAI-1 levels. Recently, it has been proposed that adipose tissue could be responsible for the elevated plasma PAI-1 level observed in insulin resistance. It now seems reasonable to view PAI-1 as one of the factors contributing to the complex gene-environment interactions involved in the formation and dissolution of thrombi.


Continued Adaptation of C4 Photosynthesis After an Initial Burst of Changes in the Andropogoneae Grasses.
C$_{4}$ photosynthesis is a complex trait that sustains fast growth and high productivity in tropical and subtropical conditions and evolved repeatedly in flowering plants. One of the major C$_{4}$ lineages is Andropogoneae, a group of $\sim $1200 grass species that includes some of the world's most important crops and species dominating tropical and some temperate grasslands. Previous efforts to understand C$_{4}$ evolution in the group have compared a few model C$_{4}$ plants to distantly related C$_{3}$ species so that changes directly responsible for the transition to C$_{4}$ could not be distinguished from those that preceded or followed it. In this study, we analyze the genomes of 66 grass species, capturing the earliest diversification within Andropogoneae as well as their C$_{3}$ relatives. Phylogenomics combined with molecular dating and analyses of protein evolution show that many changes linked to the evolution of C$_{4}$ photosynthesis in Andropogoneae happened in the Early Miocene, between 21 and 18 Ma, after the split from its C$_{3}$ sister lineage, and before the diversification of the group. This initial burst of changes was followed by an extended period of modifications to leaf anatomy and biochemistry during the diversification of Andropogoneae, so that a single C$_{4}$ origin gave birth to a diversity of C$_{4}$ phenotypes during 18 million years of speciation events and migration across geographic and ecological spaces. Our comprehensive approach and broad sampling of the diversity in the group reveals that one key transition can lead to a plethora of phenotypes following sustained adaptation of the ancestral state. [Adaptive evolution; complex traits; herbarium genomics; Jansenelleae; leaf anatomy; Poaceae; phylogenomics.].


Archetypes as action patterns.
The discovery of mirror neurons by researchers at the University of Parma promises to radically alter our understanding of fundamental cognitive and affective states. This paper explores the relationship of mirror neurons to Jung's theory of archetypes and proposes that archetypes may be viewed as elementary action patterns. The paper begins with a review of a proposed interpretation of the fainting spells of S. Freud in his relationship with Jung as an example of an action pattern that also defines an archetypal image. The challenge that mirror neurons present to traditional views in analytical psychology and psychoanalysis, however, is that they operate without recourse to a cognitive processing element. This is a position that is gaining increasing acceptance in other fields as well. The paper therefore reviews the most recent claims made by the Boston Process of Change Study Group as well as conclusions drawn from dynamic systems views of development and theoretical robotics to underline the conclusion that unconscious agency is not a requirement for coherent action. It concludes with the suggestion that this entire body of research may lead to the conclusion that the dynamic unconscious is an unnecessary hypothesis in psychoanalysis and analytical psychology.


An epidemic of dengue fever in Wewak.
143 clinical cases of dengue fever were reported in Wewak between April and August 1976. 15 patients demonstrated a diagnostic rise in antibody titre for Group B arbovirus. Tests for complement-fixing antibody to dengue viruses did not indicate what type of dengue virus was responsible for the epidemic. Vector species Aedes aegypti and Aedes scutellaris were found before control measures were adopted but were not found four months later. The epidemiology of dengue fever is discussed and measures for prevention and control of epidemics are recommended.


Dissolution without disappearing: multicomponent gas exchange for CO2 bubbles in a microfluidic channel.
We studied the dissolution dynamics of CO2 gas bubbles in a microfluidic channel, both experimentally and theoretically. In the experiments, spherical CO2 bubbles in a flow of a solution of sodium dodecyl sulfate (SDS) first shrink rapidly before attaining an equilibrium size. In the rapid dissolution regime, the time to obtain a new equilibrium is 30 ms regardless of SDS concentration, and the equilibrium radius achieved varies with the SDS concentration. To explain the lack of complete dissolution, we interpret the results by considering the effects of other gases (O2, N2) that are already dissolved in the aqueous phase, and we develop a multicomponent dissolution model that includes the effect of surface tension and the liquid pressure drop along the channel. Solutions of the model for a stationary gas bubble show good agreement with the experimental results, which lead to our conclusion that the equilibrium regime is obtained by gas exchange between the bubbles and liquid phase. Also, our observations from experiments and model calculations suggest that SDS molecules on the gas-liquid interface form a diffusion barrier, which controls the dissolution behaviour and the eventual equilibrium radius of the bubble.


Administrative data used to identify patients with irritable bowel syndrome.
To assess the usefulness of health plan administrative data for identifying patients with irritable bowel syndrome (IBS). In this retrospective study of 442 medical records of patients in nine U.S. health plans, five sets of criteria that used administrative data were used to identify potential IBS patients. Physician reviewers provided an assessment of the likelihood of the diagnosis of IBS being present. IBS was considered to be present if the physician reviewer categorized the case as definite, probable, or possible based on medical record review. Analyses were also performed with cases categorized as possible placed in an "IBS not present" category. The positive predictive value (PPV) for the five sets of criteria ranged from 63% to 83% with the highest PPV found with one of the most restrictive criteria. When cases characterized as possible were included in the "IBS not present" category, the PPV for each of the five sets of criteria decreased substantially, ranging from 33% to 63%. The PPV of different criteria used to identify patients with IBS from administrative data varies substantially based on the criteria that are used. Use of criteria with a higher PPV may come at the expense of generalizability.


A Transit Time-Resolved Microflow Cytometry-Based Agglutination Immunoassay for On-Site C-Reactive Protein Detection.
An accurate and rapid microflow cytometry-based agglutination immunoassay (MCIA) suitable for on-site antibody or antigen detection was proposed. In this study, quantitative C-reactive protein (CRP) detection was chosen as a model assay in order to demonstrate the detection principle. The average transit time was employed to estimate the extent of the agglutination reaction and improve the detection accuracy as compared to the intensity-dependent methods. The detection time was less than 8 min. and only a 20 µL serum sample was needed for each test. The results showed a linear relationship between the average transit time of aggregates and CRP concentrations ranging from 0 to 1 µg/mL. The R2 of this relationship was 0.99. The detection limit of this technology was 0.12 µg/mL CRP. The system used for CRP detection can be extended to also monitor other clinically relevant molecules.


Connection between gene dosage and protein stability revealed by a high-yield production of recombinant proteins in an E. coli LexA1(Ind-) background.
Bacterial production of a plasmid-encoded bacteriophage P22 tailspike protein shows different yield and impact on cell viability in RecA+ LexA+, RecA- LexA+ and RecA+ LexA1(Ind-) backgrounds. In a LexA1(Ind-) context, we have observed lesser toxicity and higher productivity than in the wild-type strain, in which the bacterial growth was inhibited after induction of recombinant gene expression. Also, a negative effect of the incubation temperature on the growth of producing cells was also detected. By exploring the molecular basis of these inhibitory events, we found a connection between the dosage of the recombinant gene and the proteolytic stability of the encoded protein. Under both genetic and environmental conditions favoring higher plasmid copy number and consequently increasing the synthesis rate of the recombinant protein, enhanced protein degradation was observed in parallel with an important growth inhibition. Altogether, the obtained data suggest the existence of a critical concentration of recombinant protein over which cell proteolysis is stimulated at rates not compatible with optimal physiological conditions for bacterial growth.


A Peer-Support and Mindfulness Program to Improve the Mental Health of Medical Students.
There is evidence that peer-support programs can improve mental health indices and help-seeking behavior among students in some secondary school and university settings and that mindfulness can improve mental health in medical students. Peer-led programs have not been formally assessed in a medical student population, where psychological issues exist and where it has been shown that students approach peers for help in preference to staff members or professional services. Medical students elected peer leaders who underwent training and then provided the intervention. The peer leaders provided support to students in the intervention group, as well as offering teaching in mindfulness meditation. An exploratory study was conducted with 2nd- and 3rd-year medical students at 1 medical school in New Zealand randomized into 2 groups. In addition to existing mental health resources, intervention participants received a program including peer support and peer-taught mindfulness practice. Study participants not offered the intervention participants could use existing mental health resources. Primary measures included depression (PHQ-9) and anxiety (GAD-7) scores. Secondary measures were quality of life, resilience (15-item resilience scale), academic self-concept, and motivation to learn, assessed at baseline and 6 months. Of the 402 students eligible, 275 (68%) participated and 232 (58%) completed the study. At baseline, 53% were female and mean age was 21 years (SD = 3)-PHQ-9 score (M = 5.2, SD = 3.7) and GAD-7 score (M = 4.5, SD = 3.4). Twelve peer leaders were elected. There was good participation in the intervention. One fourth of intervention students used the face-to-face peer support and more than 50% attended a peer social event and/or participated in the mindfulness program. Although improvements in mental health were seen in the intervention group, the difference between the intervention and nonintervention groups did not reach statistical significance. Although evidence exists for effectiveness of peer support and mindfulness in other contexts, this exploratory study was not able to show a statistically significant effect. Future studies could consider using a longer training period for the peer leaders, as well as targeting the study population to those most likely to benefit such as those with poorer mental health, or using a more intensive intervention or larger sample size. A cluster randomized study design would also reduce the risk of contamination.


Spontaneous rupture of bladder in puerperium.
Spontaneous rupture of bladder and extravasation of urine in the peritoneum without evidence of trauma is rare. This condition is an emergency. It presents in a unique way therefore, the diagnosis and treatment is usually delayed. This patient presented with an acute abdominal pain and oliguria. She had delivered normally eight days before re-admission. Investigations were done and an exploratory laparotomy was performed. There was a tear in the fundus of the bladder and the peritoneal cavity contained urine. Peritoneal lavage was done and the bladder was repaired in layers. She was put on continuous bladder drainage for three weeks followed by bladder training. The bladder resumed its normal function. Early diagnosis and appropriate management decreases the morbidity and mortality associated with this condition.


An ab initio study of nuclear volume effects for isotope fractionations using two-component relativistic methods.
We investigate the accuracy of two-component Douglas-Kroll-Hess (DKH) methods in calculations of the nuclear volume term (≡ lnK(nv)) in the isotope fractionation coefficient. lnK(nv) is a main term in the chemical equilibrium constant for isotope exchange reactions in heavy element. Previous work based on the four-component method reasonably reproduced experimental lnK(nv) values of uranium isotope exchange. In this work, we compared uranium reaction lnK(nv) values obtained from the two-component and four-component methods. We find that both higher-order relativistic interactions and spin-orbit interactions are essential for quantitative description of lnK(nv). The best alternative is the infinite-order Douglas-Kroll-Hess method with infinite-order spin-orbit interactions for the one-electron term and atomic-mean-field spin-same-orbit interaction for the two-electron term (IODKH-IOSO-MFSO). This approach provides almost equivalent results for the four-component method, while being 30 times faster. The IODKH-IOSO-MFSO methodology should pave the way toward computing larger and more general molecules beyond the four-component method limits.


Effect of antiepileptic drugs on bodyweight: overview and clinical implications for the treatment of epilepsy.
The potential of specific antiepileptic drugs (AEDs) to cause clinically significant changes in bodyweight is a key consideration in the management of epilepsy; changes in weight can pose health hazards, impair body image and self-esteem, and lead to noncompliance with therapy. This article reviews the data regarding the effects of conventional and newer AEDs on weight and discusses the clinical implications of these effects for the management of patients with epilepsy. The data demonstrate that AEDs can differ substantially in their effects on weight. Some, such as valproate and carbamazepine, increase weight; others, such as topiramate and felbamate, decrease it. Still others, such as lamotrigine, levetiracetam and phenytoin, are weight neutral. Because most data regarding the effects of AEDs on weight are circumstantial, the incidence, magnitude and determinants of weight changes with AEDs remain poorly elucidated. Furthermore, little is known about the mechanisms of AED-induced changes in weight. The importance of effects on weight in selecting an AED depends largely upon the individual patient's needs and the risks and benefits of therapy for that patient. The most appropriate therapeutic choice is a weight-neutral medication unless circumstances dictate otherwise.


Intracellular and extracellular pH and Ca are bound to control mitosis in the early sea urchin embryo via ERK and MPF activities.
Studies aiming to predict the impact on marine life of ocean acidification and of altered salinity have shown altered development in various species including sea urchins. We have analyzed how external Na, Ca, pH and bicarbonate control the first mitotic divisions of sea urchin embryos. Intracellular free Ca (Cai) and pH (pHi) and the activities of the MAP kinase ERK and of MPF regulate mitosis in various types of cells including oocytes and early embryos. We found that intracellular acidification of fertilized eggs by Na-acetate induces a huge activation of ERK at time of mitosis. This also stops the cell cycle and leads to cell death, which can be bypassed by treatment with the MEK inhibitor U0126. Similar intracellular acidification induced in external medium containing low sodium or 5-(N-Methyl-N-isobutyl) amiloride, an inhibitor of the Na(+)/H(+) exchanger, also stops the cell cycle and leads to cell death. In that case, an increase in Cai and in the phosphorylation of tyr-cdc2 occurs during mitosis, modifications that depend on external Ca. Our results indicate that the levels of pHi and Cai determine accurate levels of Ptyr-Cdc2 and P-ERK capable of ensuring progression through the first mitotic cycles. These intracellular parameters rely on external Ca, Na and bicarbonate, alterations of which during climate changes could act synergistically to perturb the early marine life.


Effects of Dietary Methionine Restriction on Cognition in Mice.
Dietary restriction of the essential amino acid, methionine, has been shown to induce unique metabolic protection. The peripheral benefits of methionine restriction (MR) are well established and include improvements in metabolic, energy, inflammatory, and lifespan parameters in preclinical models. These benefits all occur despite MR increasing energy intake, making MR an attractive dietary intervention for the prevention or reversal of many metabolic and chronic conditions. New and emerging evidence suggests that MR also benefits the brain and promotes cognitive health. Despite widespread interest in MR over the past few decades, many findings are limited in scope, and gaps remain in our understanding of its comprehensive effects on the brain and cognition. This review details the current literature investigating the impact of MR on cognition in various mouse models, highlights some of the key mechanisms responsible for its cognitive benefits, and identifies gaps that should be addressed in MR research moving forward. Overall findings indicate that in animal models, MR is associated with protection against obesity-, age-, and Alzheimer's disease-induced impairments in learning and memory that depend on different brain regions, including the prefrontal cortex, amygdala, and hippocampus. These benefits are likely mediated by increases in fibroblast growth factor 21, alterations in methionine metabolism pathways, reductions in neuroinflammation and central oxidative stress, and potentially alterations in the gut microbiome, mitochondrial function, and synaptic plasticity.


Inhibition of lipopolysaccharide-induced TNF-alpha production by semisynthetic polymyxin-B conjugated dextran.
During episode of severe endotoxemia, concentrations of both lipopolysaccharide and its lipid A-core subfraction are liberated from gram-negative bacteria and become elevated within the systemic circulation. Lipid-A core is the most homogeneous and physiologically toxic segment of the lipopolysaccharide molecule. Polymyxin-B has profound binding avidity for the lipid A-core subfraction of lipopolysaccharide. The mechanism of this binding avidity involves the development of attractive forces between the cationic groups of polymyxin-B and the anionic groups of the lipid A-core moiety of lipopolysaccharide. Complementary attractive forces include hydrophobic interactions which additionally become established between the octylheptanoyl group of polymyxin-B and the saturated carbon chains of the lipid A-core moiety. This paper describes a method for the semisynthetic production of polymyxin-B conjugated dextran in the form of polymyxin-B.ABH.dextran applying the photoreactive crosslinking reagent azidobenzoyl hydrazide (ABH). Molecular design and development of a semisynthetic technique for the conjugation of polymyxin-B to purified dextran fractions was motivated by the pronounced nephrotoxicity associated with this cationic polypeptide antibiotic. Conjugation of polymyxin-B to a relatively large molecular weight carrier compound would increase the overall size of the complex to a degree sufficient to theoretically reduce clearance through glomerular filtration mechanisms. Attributes of such a large molecular weight polymyxin-B conjugated biopharmaceutical would include diminished levels of nephrotoxicity due to a reduction of renal tubular concentrations and a simultaneous prolongation of its intravascular half-life (t (1/2)) and pharmacokinetic profile. Lipopolysaccharide (LPS) binding avidity of polymyxin-B.ABH.dextran was verified by Dot-Blot analysis in conjunction with the application of fluorescein isothiocyanate conjugated E. coli (0.55:B5) LPS (FITC-LPS). Capacity of polymyxin-B.ABH.dextran conjugates to inhibit in vitro LIP-induced synthesis of tumor necrosis factor-alpha (TNF-alpha) was assessed by the application of a tissue culture based biological assay system capable of detecting cytotoxicity mediated by this potent monokine. Semisynthetic conjugates of polymyxin-B.ABH.dextran conjugates (0.6 microns/mL), thereby providing cytoprotectivity (95%; p < or - 0.001. to WEHI 164 clone 13 cell populations relative to untreated reference controls. Since TNF-alpha is currently believed to be the principal endogenous mediator involved in the host's inflammatory response during episodes of endotoxemia, results from these investigations provide a scientific foundation for warranting the elevation of the in vivo efficacy of large molecular weight semisynthetic polymyxin-B conjugates. Results from these investigations may ultimately lead to the application of semisynthetic polymyxin-B.ABH.dextran as a model for the molecular design of semisynthetic production of alternative biopharmaceutical or pharmaceutical agents possessing prophylactic and/or therapeutic efficacy for the management of severe endotoxemia conditions.


Is a biopsychosocial-spiritual approach relevant to cancer treatment? A study of patients and oncology staff members on issues of complementary medicine and spirituality.
Complementary and alternative medicine (CAM) is increasingly being used by patients with cancer. Our aim is to compare the attitudes of cancer patients who use CAM to those of nonusers, on issues of CAM, biopsychosocial considerations, and spiritual needs. Questionnaires were administered to patients and medical care providers in a tertiary teaching hospital with a comprehensive cancer center. Forty-nine percent of the study patients reported integrating CAM into their conventional care. Health care providers considered psychological and spiritual needs as major reasons for CAM use, while patients considered the familial-social aspect to be more important. Cancer patients do not correlate CAM use with spiritual concerns but expect their physicians to attend to spiritual themes. Health care providers involved in oncology cancer care should emphasize spiritual as well as CAM themes. The integration of these themes into a biopsychosocial-spiritual approach may enrich the dialogue between patients and health providers.


Perceived orientation of complex shape reflects graded part decomposition.
Although the orientation of line segments and simple shapes is a well-studied area of vision, little is known about geometric factors that influence perceived orientation of complex multipart shapes. The study of these factors is of interest because it allows for an insight into the basic problem of how local geometric attributes are integrated perceptually into a global shape representation. We examined the perceived orientation of two-part shapes using an adjustment method and a 2AFC task. In particular, we investigated the influence of the perceptual salience, or distinctiveness, of a part--as defined by the turning angles at its boundaries--and its area relative to the main "base" part. In contrast to previous results on simple shapes, our results exhibited large and systematic deviations of perceived orientation from the principal axis of the shape. For shapes with sharp part boundaries, perceived global orientation deviated maximally from the principal axis and was approximated by the axis of the main base part of the shape. With weakening part boundaries, the perceived orientation gradually approached the principal axis of the entire shape, reflecting that both parts were taken into account in estimating orientation. The results are consistent with a differentially weighted principal-axis computation in which the attached part is given systematically lower weighting with increasing turning angles at the part boundaries. They thus allow a quantitative characterization of part salience in terms of part independence: Turning angles at a part's boundaries determine the extent to which its influence is perceptually separable from the rest of the shape. We suggest that Robust Statistics may provide a useful framework for quantifying the influence of part segmentation on visual estimation.


Preparation of paeoniflorin-glycyrrhizic acid complex transethosome gel and its preventive and therapeutic effects on melasma.
Paeoniflorin (PF) and glycyrrhizic acid (GL) have skin beautifying effects of anti-inflammation, anti-oxidation, inhibition of melanin formation, and reduction of skin pigmentation. To improve the transdermal permeability of PF and GL in transdermal drug delivery system (TDDS) and enhance their anti-melasma efficacy, PF-GL transethosome (PF-GL-TE) was prepared by ethanol injection method, and finally gelled with carbomer-940 to form PF-GL-TE gel. Consequently, the obtained PF-GL-TE is small and uniform, with an average particle size and a PDI value of about 167.9 nm and 0.102. PF-GL-TE gel showed sustained release behavior and high transdermal permeability in vitro release and transdermal tests. Meanwhile, PF-GL-TE gel played significant preventive effects on melasma induced by progesterone injection and ultraviolet radiation B (UVB) irradiation. According to the results of H&E staining and Masson staining of rat skin, PF-GL-TE gel can alleviate the skin inflammation of and reduce the loss of collagen fibers of back skin in the melasma model rats. Compared with the PF-GL mixture gel, PF-GL-TE gel significantly attenuated the oxidative damage of liver and skin by increasing the activity of SOD and reducing the content of MDA. The results of Western blot showed that PF-GL-TE gel might down-regulate melanin-related proteins expressions of MITF/TYR/TRP1 and TRP2 to prevent and treat melasma. These findings indicate that PF-GL-TE gel is an effective TDDS for delivering PF and GL into the skin, providing a promising preparation for effective prevention and treatment of melasma.


Maximum parsimony on subsets of taxa.
In this paper we investigate mathematical questions concerning the reliability (reconstruction accuracy) of Fitch's maximum parsimony algorithm for reconstructing the ancestral state given a phylogenetic tree and a character. In particular, we consider the question whether the maximum parsimony method applied to a subset of taxa can reconstruct the ancestral state of the root more accurately than when applied to all taxa, and we give an example showing that this indeed is possible. A surprising feature of our example is that ignoring a taxon closer to the root improves the reliability of the method. On the other hand, in the case of the two-state symmetric substitution model, we answer affirmatively a conjecture of Li, Steel and Zhang which states that under a molecular clock the probability that the state at a single taxon is a correct guess of the ancestral state is a lower bound on the reconstruction accuracy of Fitch's method applied to all taxa.


A Quasi-experimental Evaluation of Performance Improvement Teams in the Safety-Net: A Labor-Management Partnership Model for Engaging Frontline Staff.
Unit-based teams (UBTs), initially developed by Kaiser Permanente and affiliated unions, are natural work groups of clinicians, managers, and frontline staff who work collaboratively to identify areas for improvement and implement solutions. We evaluated the UBT model implemented by the Los Angeles County Department of Health Services in partnership with its union to engage frontline staff in improving patient care. We conducted a quasi-experimental study, comparing surveys at baseline and 6 months, among personnel in 10 clinics who received UBT training to personnel in 5 control clinics. We also interviewed staff from 5 clinics that received UBT training and 3 control clinics. We conducted 330 surveys and 38 individual, semi-structured interviews with staff at an outpatient facility in South Los Angeles. Each UBT leader received an 8-hour training in basic performance improvement methods, and each UBT was assigned a team "coach." Our outcome measure was 6-month change in the "adaptive reserve" score, the units' self-reported ability to make and sustain change. We analyzed transcripts of the interviews to find common themes regarding the UBT intervention. The survey response rate was 63% (158/252) at baseline and 75% (172/231) at 6 months. There was a significant difference-in-change in adaptive reserve between UBTs and non-UBTs at 6 months (+0.11 vs -0.13; P = .02). Nine of the 10 UBTs reported increases in adaptive reserve and 8 UBTs reported decreased no-show rates or patient length of stay in clinic. Staff overwhelmingly felt the UBTs were a positive intervention because it allowed all levels of staff to have a voice in improvement. Our results indicate that partnership between management and unions to engage frontline staff in teams may be a useful tool to improve delivery of health care in a safety-net setting.


Protective effect of chloral hydrate against lipopolysaccharide/D-galactosamine-induced acute lethal liver injury and zymosan-induced peritonitis in mice.
In recent years, certain anesthetics have been shown to have protective effects against acute inflammation in experimental animals, an observation that may yield new options for adjunctive treatment of acute inflammation. In this study, we investigated the effects of chloral hydrate (CH) on the acute inflammatory response in BALB/c mice using lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced acute lethal liver injury and zymosan A-induced peritonitis models. The survival of mice following LPS/D-GalN treatment was significantly improved by a single injection with chloral hydrate, which could be administered simultaneously or as late as 3h after challenge with LPS/D-GalN; liver injury was also attenuated. A sharp rise in serum levels of MCP-1, IL-6 and TNF-alpha was attenuated or delayed after chloral hydrate treatment. Furthermore, the mechanism by which chlorate hydrate inhibits inflammation was associated with an attenuated increase in nuclear factor kappaappaB (NF-kappaB) activity in NF-kappaB-RE-luc mice upon LPS/D-GalN treatment. In mice with acute peritonitis, leukocyte number and protein concentration in peritoneal exudates peaked with a 16h lag, and serum levels of MCP-1, IL-6 and TNF-alpha were significantly lower at certain time points in the chloral hydrate-treated group compared to those in the normal saline (NS)-treated control group. In addition, chloral hydrate treatment in vitro attenuated the upregulation of TNF-alpha and IL-6 by peritoneal macrophages and NF-kappaB activity in RAW264.7 cells stimulated with LPS, suggesting that monocytes/macrophages may be a target of chloral hydrate. These results indicate that chloral hydrate has a protective effect against LPS/D-GalN-induced acute lethal liver injury in mice, which may be associated with an inhibition of NF-kappaB activity and delays in proinflammatory cytokine production. However, this phenomenon was not associated with levels of serum corticosterone. Chloral hydrate also attenuated the inflammatory response in zymosan A-induced acute peritonitis, a model of mild inflammation. In conclusion, treatment with only a single injection of chloral hydrate could significantly attenuate acute inflammation in mice treated with LPS/D-GalN and zymosan A. These effects are also likely associated with the inhibition of NF-kappaB activity.


Pontocerebellar hypoplasia type 6: A British case with PEHO-like features.
Six subtypes of autosomal recessive pontocerebellar hypoplasia (PCH) have been identified and the genetic basis of four of these (PCH1, PCH2, PCH4, and PCH6) is known. PCH6 is associated with cerebral atrophy and multiple but variable respiratory chain defects in muscle and has been reported in one consanguineous Sephardic Jewish family. It is caused by mutations in the RARS2 gene which encodes mitochondrial arginine-transfer RNA synthetase. Here we describe a female patient born to nonconsanguineous British parents. She presented in the neonatal period with increased respiratory rate, poor feeding and transiently elevated blood and CSF lactate levels. She went on to manifest profound developmental delay and severe microcephaly. Edema of the hands, feet, and face were suggestive of a PEHO-like condition (progressive encephalopathy, edema, hypsarrhythmia and optic atrophy), although optic atrophy and hypsarrhythmia were absent. Cranial MRI at age 14 months showed generalized cerebral atrophy, thinning of the pons and gross atrophy and flattening of the cerebellar hemispheres. Muscle biopsies on two occasions were normal with normal respiratory chain studies. Despite the absence of respiratory chain defects, the phenotype was felt to be consistent with PCH6 and indeed two novel pathogenic RARS2 mutations were identified. Ours is the second report of PCH6 due to RARS2 mutations and demonstrates that respiratory chain abnormalities are not obligatory, whereas some features of PEHO might be present.


Pedestrian self-reports of factors influencing the use of pedestrian bridges.
The study was designed to find out factors that influence use/non-use of pedestrian bridges. The use rate of five pedestrian bridges was observed in the central business district (CBD) of Ankara. After the observations, a survey was conducted among pedestrians using those bridges and crossing contrary to safe practice under them at street level (n=408). In the present data, the use rate of pedestrian bridges varied from 6 to 63%. The frequent use of the bridge when crossing the road concerned, and seeing bridge use as time saving and safe in general were positively related to respondents' bridge use. Frequent visits to CBD decreased the likelihood of using the bridge. Other factors accounted only for a small proportion of variance in bridge use. The study suggests that bridge use or non-use is a habit and not coincidental behaviour. For increasing the pedestrians' bridge use, escalators seem to be a good solution, but traffic signals under a bridge may deteriorate the use rate. In addition, increasing the number of legs leading to the bridge may not increase the use rate. The use rate is likely to improve, if the safety benefits and convenience of using the bridge without considerable time loss are clearly visible to pedestrians.


[Timely screening routines for prostatic cancer by Norwegian physicians].
It has been claimed, though not scientifically proven, that early diagnosis and treatment of prostate cancer reduce cancer-related mortality. The aim of the present study is to assess the frequency of PSA-based screening in Norwegian primary health care. In 1998 Norwegian general practitioners and occupational physicians reported their use of diagnostic PSA (prostatic specific antigen) testing in men without urinary symptoms (opportunistic PSA screening). There were considerable variations between counties and an increasing tendency to screen 60% of physicians performed opportunistic PSA screening; however, 55% only "sometimes". Men over 75 were frequently tested. The results reflect the scientific uncertainty regarding opportunistic PSA screening. PSA screening as an element of health care policy can only be recommended if cancer-related mortality is reduced by early diagnosis and treatment of prostate cancer.


Whole transcriptome analysis of the ERα synthetic fragment P295-T311 (ERα17p) identifies specific ERα-isoform (ERα, ERα36)-dependent and -independent actions in breast cancer cells.
ERα17p is a peptide corresponding to the sequence P295LMIKRSKKNSLALSLT311 of the estrogen receptor alpha (ERα) and initially found to interfere with ERα-related calmodulin binding. ERα17p was subsequently found to elicit estrogenic responses in E2-deprived ERα-positive breast cancer cells, increasing proliferation and ERE-dependent gene transcription. Surprisingly, in E2-supplemented media, ERα17p-induced apoptosis and modified the actin network, influencing cell motility. Here, we report that ERα17p internalizes in breast cancer cells (T47D, MDA-MB-231, SKBR3) and induces a massive early (3 h) transcriptional activity. Remarkably, about 75% of significantly modified transcripts were also modified by E2, confirming the pro-estrogenic profile of ERα17p. The different ER spectra of the used cell lines allowed us to identify a specific ERα17p signature related to ERα as well as its variant ERα36. With respect to ERα, the peptide activates nuclear (cell cycle, cell proliferation, nucleic acid and protein synthesis) and extranuclear signaling pathways. In contrast, through ERα36, it mainly triggers inhibitory actions on inflammation. This is the first work reporting a detailed ERα36-specific transcriptional signature. In addition, we report that ERα17p-induced transcripts related to apoptosis and actin modifying effects of the peptide are independent from its estrogen receptor(s)-related actions. We discuss our findings in view of the potential use of ERα17p as a selective peptidomimetic estrogen receptor modulator (PERM).


Comprehensive cost-effectiveness of diabetes management for the underserved in the United States: A systematic review.
Diabetes mellitus affects almost 10% of U.S. adults, leading to human and financial burden. Underserved populations experience a higher risk of diabetes and related complications resulting from a combination of limited disposable income, inadequate diet, and lack of insurance coverage. Without the requisite resources, underserved populations lack the ability to access healthcare and afford prescription drugs to manage their condition. The aim of this systematic review is to synthesize the findings from cost-effectiveness studies of diabetes management in underserved populations. Original, English, peer-reviewed cost-effectiveness studies of diabetes management in U.S. underserved populations were obtained from 8 databases, and PRISMA 2009 reporting guidelines were followed. Evidence was categorized as strong or weak based on a combination of GRADE and American Diabetes Association guidelines. Internal validity was assessed by the Cochrane methodology. Studies were classified by incremental cost-effectiveness ratio as very cost-effective (ICER≤US$25,000), cost-effective (US$25,000<ICER≤US$50,000), marginally cost-effective (US$50,000<ICER≤US$100,000) or cost-ineffective (ICER>US$100,000). Reporting and quality of economic evaluations was assessed using the CHEERS guidelines and Recommendations of Second Panel for Cost-Effectiveness in Health and Medicine, respectively. Fourteen studies were included. All interventions were found to be cost-effective or very cost-effective. None of the studies reported all 24 points of the CHEERS guidelines. Given the considered cost categories vary significantly between studies, assessing cost-effectiveness across studies has many limitations. Program costs were consistently analyzed, and a third of the included studies (n = 5) only examined these costs, without considering other costs of diabetes care. Cost-effectiveness studies are not based on a standardized methodology and present incomplete or limited analyses. More accurate assessment of all direct and indirect costs could widen the gap between intervention and usual care. This demonstrates the urgent need for a more standardized and comprehensive cost-effectiveness framework for future studies.


EyeArt artificial intelligence analysis of diabetic retinopathy in retinal screening events.
Early detection and treatment of diabetic retinopathy (DR) are critical for decreasing the risk of vision loss and preventing blindness. Community vision screenings may play an important role, especially in communities at higher risk for diabetes. To address the need for increased DR detection and referrals, we evaluated the use of artificial intelligence (AI) for screening DR. Patient images of 124 eyes were obtained using a 45° Canon Non-Mydriatic CR-2 Plus AF retinal camera in the Department of Endocrinology Clinic (Newark, NJ) and in a community screening event (Newark, NJ). Images were initially classified by an onsite grader and uploaded for analysis by EyeArt, a cloud-based AI software developed by Eyenuk (California, USA). The images were also graded by an off-site retina specialist. Using Fleiss kappa analysis, a correlation was investigated between the three grading systems, the AI, onsite grader, and a US board-certified retina specialist, for a diagnosis of DR and referral pattern. The EyeArt results, onsite grader, and the retina specialist had a 79% overall agreement on the diagnosis of DR: 86 eyes with full agreement, 37 eyes with agreement between two graders, 1 eye with full disagreement. The kappa value for concordance on a diagnosis was 0.69 (95% CI 0.61-0.77), indicating substantial agreement. Referral patterns by EyeArt, the onsite grader, and the ophthalmologist had an 85% overall agreement: 96 eyes with full agreement, 28 eyes with disagreement. The kappa value for concordance on "whether to refer" was 0.70 (95% CI 0.60-0.80), indicating substantial agreement. Using the board-certified retina specialist as the gold standard, EyeArt had an 81% accuracy (101/124 eyes) for diagnosis and 83% accuracy (103/124 eyes) in referrals. For referrals, the sensitivity of EyeArt was 74%, specificity was 87%, positive predictive value was 72%, and negative predictive value was 88%. This retrospective cross-sectional analysis offers insights into use of AI in diabetic screenings and the significant role it will play in automated detection of DR. The EyeArt readings were beneficial with some limitations in a community screening environment. These limitations included a decreased accuracy in the presence of cataracts and the functional cost of EyeArt uploads in a community setting.


Rehabilitation of Guillain-Barré syndrome patients: an observational study.
Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculopathy resulting in severe impairments of many body structures and functions with consequent limitations of activities and participation. The aim of our study was to evaluate rehabilitation outcome in these patients. Forty-five (20 women, 25 men) with GBS patients who had completed primary comprehensive rehabilitation were included in the study. Medical Research Council Scale for Muscle Strength was used for assessment of lower-limb function. Patients' activities were assessed using the Functional Independence Measure and two walking tests (6 min and 10 m). The patients were also described using an adapted International Classification of Functioning, Disability and Health checklist. Assessment was performed at admission and at discharge. Clinically important and statistically significant improvements were found in all outcome measures. Strong and significant correlations were found between the outcome measures. International Classification of Functioning, Disability and Health coding also clearly reflected the progress. Improvement in patients' activities increased statistically significantly with time for up to 3 months of rehabilitation. The outcome was not related to the time interval from establishing the diagnosis to the start of rehabilitation. Hence, multidisciplinary care for GBS patients is effective, because clinically important and statistically significant improvements regarding body functions and activities are achieved during relatively short inpatient rehabilitation.


Objective detection of subtle freezing of gait episodes in Parkinson's disease.
Freezing of gait (FOG) is a clinically defined phenomenon of Parkinson's disease (PD). Recent evidence suggests that subtle FOG episodes can be elicited in a gait laboratory using suddenly appearing obstacles during treadmill walking. We evaluated which quantitative gait parameters identify such subtle FOG episodes. We included 10 PD patients with FOG, 10 PD patients without FOG, and 10 controls. Subjects walked on a motorized treadmill while avoiding unexpectedly appearing obstacles. Treadmill walking was videotaped, and FOG episodes were identified by two independent experts. Gait was also analyzed using detailed kinematics. Knee joint signals were processed using time-frequency analysis with combinations of sliding fast Fourier transform and wavelets transform. Twenty FOG episodes occurred during treadmill walking in 5 patients (all with clinically certified FOG), predominantly in relation to obstacle avoidance. FOG was brief when it occurred just before or after obstacle crossing and was characterized by short, rapid steps. Frequency analysis showed a typical qualitative pattern: before the FOG episode an increase in dominant frequency in the 0 to 3 Hz band (festination), followed by decreased power in 0 to 3 Hz band and an increased power in the 3 to 8 Hz band during the FOG episode. This pattern led to an increased FOG index as a qualitative measure. These approaches detected even very brief FOG with acceptable sensitivity (75-83%) and specificity (>95%). We conclude that time-frequency analysis is an appropriate approach to detect brief and subtle FOG episodes. Future work will need to decide whether this approach can support or even replace expert clinical opinion.


Detection of tumor DNA at the margins of colorectal cancer liver metastasis.
Defining an adequate resection margin of colorectal cancer liver metastases is essential for optimizing surgical technique. We have attempted to evaluate the resection margin through a combination of histopathologic and genetic analyses. We evaluated 88 samples of tumor margins from 12 patients with metastatic colon cancer who each underwent partial hepatectomy of one to six liver metastases. Punch biopsies of surrounding liver tissue were obtained at 4, 8, 12, and 16 mm from the tumor border. DNA from these biopsies was analyzed by a sensitive PCR-based technique, called BEAMing, for mutations of KRAS, PIK3CA, APC, or TP53 identified in the corresponding tumor. Mutations were identified in each patient's resected tumor and used to analyze the 88 samples circumscribing the tumor-normal border. Tumor-specific mutant DNA was detectable in surrounding liver tissue in 5 of these 88 samples, all within 4 mm of the tumor border. Biopsies that were 8, 12, and 16 mm from the macroscopic visible margin were devoid of detectable mutant tumor DNA and of microscopically visible cancer cells. Tumors with a significant radiologic response to chemotherapy were not associated with any increase in mutant tumor DNA in beyond 4 mm of the main tumor. Mutant tumor-specific DNA can be detected beyond the visible tumor margin, but never beyond 4 mm, even in patients whose tumors were larger prior to chemotherapy. These data provide a rational basis for determining the extent of surgical excision required in patients undergoing resection of liver metastases.


Statistical context shapes stimulus-specific adaptation in human auditory cortex.
Stimulus-specific adaptation is the phenomenon whereby neural response magnitude decreases with repeated stimulation. Inconsistencies between recent nonhuman animal recordings and computational modeling suggest dynamic influences on stimulus-specific adaptation. The present human electroencephalography (EEG) study investigates the potential role of statistical context in dynamically modulating stimulus-specific adaptation by examining the auditory cortex-generated N1 and P2 components. As in previous studies of stimulus-specific adaptation, listeners were presented with oddball sequences in which the presentation of a repeated tone was infrequently interrupted by rare spectral changes taking on three different magnitudes. Critically, the statistical context varied with respect to the probability of small versus large spectral changes within oddball sequences (half of the time a small change was most probable; in the other half a large change was most probable). We observed larger N1 and P2 amplitudes (i.e., release from adaptation) for all spectral changes in the small-change compared with the large-change statistical context. The increase in response magnitude also held for responses to tones presented with high probability, indicating that statistical adaptation can overrule stimulus probability per se in its influence on neural responses. Computational modeling showed that the degree of coadaptation in auditory cortex changed depending on the statistical context, which in turn affected stimulus-specific adaptation. Thus the present data demonstrate that stimulus-specific adaptation in human auditory cortex critically depends on statistical context. Finally, the present results challenge the implicit assumption of stationarity of neural response magnitudes that governs the practice of isolating established deviant-detection responses such as the mismatch negativity.


Intracellular Ca2+ release-dependent inactivation of Ca2+ currents in thalamocortical relay neurons.
Neuronal Ca(2+) channels are rapidly inactivated by a mechanism that is termed Ca(2+)-dependent inactivation (CDI). In this study we investigated the influence of intracellular Ca(2+) release on CDI of high-voltage-activated Ca(2+) channels in rat thalamocortical relay neurons by combining voltage-clamp, Ca(2+) imaging and immunological techniques. Double-pulse protocols revealed CDI, which depended on the length of the conditioning pulses. Caffeine caused a concentration-dependent increase in CDI that was accompanied by an increase in the duration of Ca(2+) transients. Inhibition of ryanodine receptors and endoplasmic Ca(2+) pumps (by thapsigargin or cyclopiazonic acid) resulted in a reduction of CDI. In contrast, inhibition of inositol 1,4,5-tris-phosphate receptors by intracellular application of 2-aminoethoxy diphenyl borate or heparin did not influence CDI. The block of transient receptor potential channels by extracellular application of 2-aminoethoxy diphenyl borate, however, resulted in a significant reduction of CDI. The central role of L-type Ca(2+) channels was emphasized by the near-complete block of CDI by nifedipine, an effect only surpassed when Ca(2+) was replaced by Ba(2+) and chelated by 1,2-bis(o-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid (BAPTA). Trains of action potential-like stimuli induced a strong reduction in high-voltage-activated Ca(2+) current amplitude, which was significantly reduced when intracellular Ca(2+) stores were made inoperative by thapsigargin or Ba(2+)/BAPTA. Western blotting revealed expression of L-type Ca(2+) channels in thalamic and hippocampal tissue but not liver tissue. In summary, these results suggest a cross-signalling between L-type Ca(2+) channels and ryanodine receptors that controls the amount of Ca(2+) influx during neuronal activity.


Oxygen adsorption properties of small cobalt oxide clusters: application feasibility as oxygen gas sensors.
In this paper, a theoretical mechanism for oxygen adsorption on small-size cobalt oxide clusters is investigated. For this purpose, we employed dispersion-corrected density functional theory (DFT-D2). In this scheme, van der Waals interactions and the spin polarization mode are activated. Our calculations show the most stable oxygen adsorption configurations on the small-size thermodynamically stable cobalt oxide clusters, which are considered as (CoO)n (n = 2, 3, 4) and (Co3O4)n (n = 1, 2). The equilibrium geometries, adsorption energies, and electronic structures in terms of ionization potential, electron affinity, energy gap, spatial distribution of orbitals, partial density of states of the oxygen molecule, and charge transfer are calculated. Spin-distinct charge transfer is comprehensively studied employing schematic representations of energy levels along with the Lowdin charge analysis and visualization of charge density redistribution near the adsorption sites. Studies indicate that charge is totally transferred from cobalt oxide clusters to oxygen, which consists of spin-up charge transfer from oxygen to the clusters and spin-down charge transfer from the clusters to oxygen. It was seen that upon oxygen adsorption, the energy gap of the clusters increases and therefore conductivity decreases. Also, oxygen chemically adsorbs on the cobalt oxide clusters in an exothermic process. Therefore, oxygen molecules could be detected by pristine cobalt oxide clusters via conductometric and thermoelectric type sensors.


Hemostatic abnormalities and liver diseases.
Professor Eberhard F. Mammen greatly contributed to the understanding of the relationship between hemostatic abnormalities and liver diseases. The physiology of the hemostatic system is closely linked to liver function because the liver parenchymal cells produce most of the factors of the clotting and fibrinolytic systems. Acute or chronic hepatocellular diseases and hepatic failure including liver cirrhosis, vitamin K deficiency, liver surgery including liver transplantation, and sclerotherapy of bleeding esophageal varices, which were classified by Prof. Mammen, show various hemostatic abnormalities in the coagulation system, fibrinolytic system, platelets, and the reticuloendothelial system. Hemostatic abnormalities in patients with hepatic failure or in those that have undergone liver surgery are similar to those in disseminated intravascular coagulation. Prof. Mammen also contributed to the study of vitamin K-dependent clotting factors, antithrombin, and hemostatic molecular markers. Partly based on this work, the prothrombin time-international normalized ratio, several hemostatic molecular markers, and antithrombin therapy have been recently developed for the diagnosis and treatment of thrombosis.


TRIM4 modulates type I interferon induction and cellular antiviral response by targeting RIG-I for K63-linked ubiquitination.
RIG-I is a pivotal cytoplasmic sensor that recognizes different species of viral RNAs. This recognition leads to activation of the transcription factors NF-κB and IRF3, which collaborate to induce type I interferons (IFNs) and innate antiviral response. In this study, we identified the TRIM family protein TRIM4 as a positive regulator of RIG-I-mediated IFN induction. Overexpression of TRIM4 potentiated virus-triggered activation of IRF3 and NF-κB, as well as IFN-β induction, whereas knockdown of TRIM4 had opposite effects. Mechanistically, TRIM4 associates with RIG-I and targets it for K63-linked polyubiquitination. Our findings demonstrate that TRIM4 is an important regulator of the virus-induced IFN induction pathways by mediating RIG-I for K63-linked ubiquitination.


Medical Complications of Anorexia Nervosa and Bulimia.
Anorexia nervosa and bulimia nervosa are serious psychiatric illnesses related to disordered eating and distorted body images. They both have significant medical complications associated with the weight loss and malnutrition of anorexia nervosa, as well as from the purging behaviors that characterize bulimia nervosa. No body system is spared from the adverse sequelae of these illnesses, especially as anorexia nervosa and bulimia nervosa become more severe and chronic. We review the medical complications that are associated with anorexia nervosa and bulimia nervosa, as well as the treatment for the complications. We also discuss the epidemiology and psychiatric comorbidities of these eating disorders.


Deep Heterogeneous Hashing for Face Video Retrieval.
Retrieving videos of a particular person with face image as query via hashing technique has many important applications. While face images are typically represented as vectors in Euclidean space, characterizing face videos with some robust set modeling techniques (e.g. covariance matrices as exploited in this study, which reside on Riemannian manifold), has recently shown appealing advantages. This hence results in a thorny heterogeneous spaces matching problem. Moreover, hashing with handcrafted features as done in many existing works is clearly inadequate to achieve desirable performance for this task. To address such problems, we present an end-toend Deep Heterogeneous Hashing (DHH) method that integrates three stages including image feature learning, video modeling, and heterogeneous hashing in a single framework, to learn unified binary codes for both face images and videos. To tackle the key challenge of hashing on manifold, a well-studied Riemannian kernel mapping is employed to project data (i.e. covariance matrices) into Euclidean space and thus enables to embed the two heterogeneous representations into a common Hamming space, where both intra-space discriminability and inter-space compatibility are considered. To perform network optimization, the gradient of the kernel mapping is innovatively derived via structured matrix backpropagation in a theoretically principled way. Experiments on three challenging datasets show that our method achieves quite competitive performance compared with existing hashing methods.


Long non-coding RNA H19 regulates the development of gliomas through the Wnt/β-catenin signaling pathway.
We investigated the effects of long non-coding RNA (lncRNA) H19 on glioma cell proliferation, invasion, migration, and apoptosis and the underlying mechanisms. H19 expression in glioma tissues, para-carcinoma tissues, and glioma cell lines was analyzed by Real-time polymerase chain reaction (RT-PCR). After transfecting U251 and U87MG cells with siRNA-H19, cell proliferation was detected by the cell counting kit-8 (CCK8) assay. Invasion and migration were detected by a transwell assay; cell cycle distribution and apoptosis were measured by flow cytometry analysis; Dvl2, GSK-3β, cyclin D1, and β-catenin expressions were detected by RT-PCR and Western blotting. H19 expression in glioma tissues was higher than that in para-carcinoma tissues and associated with poor prognosis in glioma patients. Cell proliferation, invasion, and migration significantly decreased, the percentage of glioma cells in G0/G1 significantly increased, the percentage of glioma cells in the S phase significantly decreased, and apoptosis significantly increased in U251 and U87MG cells transfected with siRNA-H19 compared to those in the siRNA-NC group. Downregulation of H19 decreased DVL2, cyclin D1, and β-catenin expression and increased GSK-3β expression. The inhibitory effects of downregulation of H19 on glioma cell proliferation, invasion, and migration were reversed by SKL2001 via the activation of the Wnt/β-catenin signal pathway, which was further enhanced by inhibition of the Wnt/β-catenin signal pathway by XAV939. H19 was overexpressed in glioma tissues and glioma cell lines. Downregulation of H19 inhibited cell proliferation, invasion, and migration, arrested cell cycle progression in the G0/G1 phase, and induced cell apoptosis by restraining activation of the Wnt/β-catenin signaling pathway in glioma cells. Therefore, H19 is a potential therapeutic target for glioma therapy.


Overview of Home Parenteral Nutrition: An Update.
The trend in modern medicine is to transition care from the hospital to home or other nonacute settings as soon as possible. Increasingly, nutrition support professionals are being asked to help facilitate discharge and/or manage patients who require prolonged intravenous fluid and/or nutrition after having been stabilized during a hospitalization. This updated tutorial reviews many of the concepts and challenges that must be considered for successful care that helps to focus on the patients and their quality of life.


Complexing receptor pharmacology: modulation of family B G protein-coupled receptor function by RAMPs.
The most well-characterized subgroup of family B G protein-coupledreceptors (GPCRs) comprises receptors for peptide hormones, such as secretin, calcitonin (CT), glucagon, and vasoactive intestinal peptide (VIP). Recent data suggest that many of these receptors can interact with a novel family of GPCR accessory proteins termed receptor activity modifying proteins (RAMPs). RAMP interaction with receptors can lead to a variety of actions that include chaperoning of the receptor protein to the cell surface as is the case for the calcitonin receptor-like receptor (CLR) and the generation of novel receptor phenotypes. RAMP heterodimerization with the CLR and related CT receptor is required for the formation of specific CT gene-related peptide, adrenomedullin (AM) or amylin receptors. More recent work has revealed that the specific RAMP present in a heterodimer may modulate other functions such as receptor internalization and recycling and also the strength of activation of downstream signaling pathways. In this article we review our current state of knowledge of the consequence of RAMP interaction with family B GPCRs.


Genetic control of immune response to pseudorabies and atrophic rhinitis vaccines: II. Comparison of additive direct and maternal genetic effects.
Data from 52 litters farrowed in two seasons of a cross-fostering experiment were analyzed to estimate variances and covariances for additive direct and maternal genetic effects on immune response to pseudorabies virus and B. bronchiseptica vaccine. Twenty purebred boars and 44 sows of the Duroc, Landrace and Yorkshire breeds were used. Immune response was measured after vaccine challenge. A modified-live pseudorabies (PR) vaccine was administered to piglets at 28 d of age; response was measured by log2 serum neutralization titers at 56 d. An inactivated B. bronchiseptica bacterin was administered at 28, 42 and 112 d. Antibody levels were measured relative to positive and negative controls at 28, 56 and 119 d by using an enzyme-linked immunosorbent assay (ELISA). Results from this study for heritability were .18 +/- .09 for PR titer and .15 +/- .07 and .52 +/- .15 for 56- and 119-d ELISA values, respectively. The variability due to nurse environment (maternal genetic variance and common environmental variance) as a percentage of phenotypic variance was 11.1% for PR titers and 29.6 and 8.8% for 56- and 119-d ELISA values, respectively. The heritabilities estimated in this study indicate that, if improved immune response to vaccines is desired, selection may be useful. However, the importance of maternal environment would make early selections less accurate than selections based on immune response measured later in life.


Acculturation as a Determinant of Obesity and Related Lifestyle Behaviors in a Multi-Ethnic Asian Population.
Limited attention has been given to the role of cultural orientation towards different ethnic groups in multi-ethnic settings without a dominant host culture. We evaluated whether acculturation levels, reflecting cultural orientation towards other ethnic groups, were associated with obesity and related lifestyle behaviors in a cosmopolitan Asian population. We conducted the current study based on data from the Singapore Multi-Ethnic Cohort (N = 10,622) consisting of ethnic Chinese, Malays, and Indians aged 21 to 75 years. Multivariable linear and logistic regression analyses were used to examine associations between the acculturation level (z-score), obesity, and related lifestyle behaviors, including dietary habits and physical activity. A higher acculturation level was directly associated with a higher prevalence of obesity among Chinese, whereas an inverse association was found for ethnic Indians, and no significant association in Malays. In ethnic Malays, greater acculturation was significantly associated with higher dietary quality and less sedentary time. Furthermore, a high acculturation level was significantly associated with higher sugar-sweetened beverage consumption and more leisure-time PA in all ethnic groups. Our findings suggest that greater cultural orientation towards other ethnic groups was associated with convergence in obesity levels. More research is required to understand how acculturation affects obesity-related lifestyle factors in multi-ethnic settings.


Actinomycin D and Hydrocortisone: intracellular binding in rat liver.
DNA was found to be the major intracellular binding site for labeled actinomycin D administered in vivo. In analogous studies, hydrocortisone did not bind to nuclear structures. Furthermore, following the administration of actinomycin D, a highly positive correlation was found between the RNA content of the nucleus and the ability of the nucleus to synthesize RNA.


Prognostic value of neutrophil-lymphocyte ratio and lactate dehydrogenase in melanoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.
Immune checkpoint inhibitors (ICIs) showed promising therapeutic efficacy on melanoma. Neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (LDH) showed predictive values on prognosis of various tumors, but not on melanoma yet. This meta-analysis was conducted to investigate the prognostic role of NLR and LDH levels in melanoma treated with ICIs. A search was conducted for all reports published till March 2020 in PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). Studies were included if they investigated the association between pretreatment NLR/LDH and prognosis in melanoma patients treated with ICIs. Subgroup analysis, publication bias, and meta-regression were conducted to investigate heterogeneity. A total of 6817 melanoma patients were included. Overall, high pretreatment NLR and LDH were associated with poor overall survival (OS) (P < .001) and PFS (P < .001). Subgroup analyses revealed that elevated NLR and LDH levels were associated with poor OS and PFS in patients treated with anti-CTLA-4 or anti-PD-1/PD-L1 alone. NLR level was superior in predicting OS if compared with LDH level in patients treated with anti-PD-1/PD-L1 + anti-CTLA-4. In subgroup analysis stratified by cutoff value, high NLR level was associated with poor OS and PFS regardless of cutoff value, but LDH works when cutoff value = upper normal limit (UNL). The predictive value of NLR and LDH levels on OS and PFS was partially compromised in the Asian populations, compared with the Western countries. Blood NLR and LDH levels showed great potential to be used as early prognostic biomarkers in melanoma patients treated with ICIs.


Hepatobiliary abnormalities and disease in cystic fibrosis: epidemiology and outcomes through adulthood.
There is limited data regarding the prevalence of hepatobiliary disease in North American patients with cystic fibrosis (CF) through adulthood. Our aim was to determine the prevalence of, and risk factors for, CF-related hepatobiliary abnormalities and determine factors that predict the development of CF-related hepatobiliary disease. We performed a retrospective cohort study of all CF patients who presented to a UnitedStates tertiary care referral academic center over a 32-year period. "CF-related hepatobiliary abnormality" was defined as the presence of abnormal liver chemistries on one or more occasion and "CF-related hepatobiliary disease" was defined as biochemical, physical examination, or ultrasonographic abnormalities on at least 2 consecutive examinations spanning a 1-year period. Two-hundred eighty-three CF patients who presented between the years 1970 and 2002 were identified, with an age range of 2 months to 63 years. Sixty-five percent had CF-related hepatobiliary abnormalities with a higher prevalence seen in CF patients <18 years of age (84% vs. 16%, P<0.01). Fifteen percent of our cohort had CF-related hepatobiliary disease with 93% of cases occurring in individuals before age 18. One quarter of individuals with CF-related hepatobiliary abnormalities developed hepatobiliary disease. Abnormal liver chemistries in CF are common though most of CF patients lack clinical evidence of liver disease and the severe complications of fibrosis/cirrhosis are rare. The risk of liver involvement decreases significantly with age, falling by 10% per annum for those described as having CF-related hepatobiliary disease. CF-related hepatobiliary disease is a rare occurrence after age 18.


Grass genomes.
For the most part, studies of grass genome structure have been limited to the generation of whole-genome genetic maps or the fine structure and sequence analysis of single genes or gene clusters. We have investigated large contiguous segments of the genomes of maize, sorghum, and rice, primarily focusing on intergenic spaces. Our data indicate that much (>50%) of the maize genome is composed of interspersed repetitive DNAs, primarily nested retrotransposons that insert between genes. These retroelements are less abundant in smaller genome plants, including rice and sorghum. Although 5- to 200-kb blocks of methylated, presumably heterochromatic, retrotransposons flank most maize genes, rice and sorghum genes are often adjacent. Similar genes are commonly found in the same relative chromosomal locations and orientations in each of these three species, although there are numerous exceptions to this collinearity (i.e., rearrangements) that can be detected at the levels of both the recombinational map and cloned DNA. Evolutionarily conserved sequences are largely confined to genes and their regulatory elements. Our results indicate that a knowledge of grass genome structure will be a useful tool for gene discovery and isolation, but the general rules and biological significance of grass genome organization remain to be determined. Moreover, the nature and frequency of exceptions to the general patterns of grass genome structure and collinearity are still largely unknown and will require extensive further investigation.


55Mn-ENDOR of the S2-state multiline signal of Photosystem II from Thermosynechococcus elongatus.
Pulse EPR and 55Mn-ENDOR (electron nuclear double resonance) experiments at 34 GHz (Q-band) were performed on the S2 state of the OEC (oxygen-evolving complex) in PSII (Photosystem II) from Thermosynechococcus elongatus. The ENDOR spectra are discussed with respect to earlier data obtained from X- (9 GHz) and Q-band experiments on PSII preparations from spinach with and without the addition of methanol.