Novel Foveal Features Associated With Vision Impairment in Multiple Sclerosis.
To characterize scattering and hyperreflective features in the foveal avascular zone of people with multiple sclerosis (MS) using adaptive optics scanning laser ophthalmoscopy (AOSLO) and to evaluate their relationship with visual function and MS disease characteristics. Twenty subjects with MS underwent confocal reflectance and non-confocal split-detection AOSLO foveal imaging. Peripapillary retinal nerve fiber layer thickness was measured using optic nerve optical coherence tomography. Blood pressure, intraocular pressure (IOP), and best-corrected high-contrast visual acuity (HCVA) and low-contrast visual acuity (LCVA) were measured. AOSLO images were graded to determine the presence and characteristics of distinct structures. Two distinct structures were seen in the avascular zone of the foveal pit. Hyperreflective puncta, present in 74% of eyes, were associated with IOP and blood pressure. Scattering features, observed in 58% of eyes, were associated with decreased HCVA and LCVA, as well as increased MS duration and disability, but were not associated with retinal nerve fiber layer thickness. Hyperreflective puncta and scattering features were simultaneously present in 53% of eyes. Hyperreflective puncta were associated with parameters affecting ophthalmic perfusion, but they were not associated with MS disease parameters. Scattering features were associated with parameters corresponding to advanced MS, suggesting that they may be related to disease progression. Scattering features were also correlated with reduced visual function independent from ganglion cell injury, suggesting the possibility of a novel ganglion cell-independent mechanism of impaired vision in people with MS.


The evolution of sexual dimorphism in New Zealand giant moa (Dinornis) and other ratites.
The extinct giant moa Dinornis is one of the most remarkable known examples of reversed sexual size dimorphism (RSD), with males weighing 34-85 kg, but females weighing up to 240 kg. However, there has been little consideration of the evolutionary mechanism that produced this level of dimorphism, and most living palaeognaths also exhibit varying levels of RSD. Using male and female body mass data for extant ratites and tinamous and four extinct moa genera, and tests of phylogenetic dependence (λ) of body size evolution among these species, we investigated whether Dinornis was truly unusual with respect to RSD relative to other palaeognaths, which sex was under greater pressure to change in size over evolutionary time, and which candidate hypotheses explaining the presence and variability of RSD in the genus are most plausible. We demonstrate that the extreme level of RSD exhibited by Dinornis represents a straightforward consequence of positive allometric scaling of body size. However, Dinornis females have undergone more evolutionary change than males, and larger females from high-productivity environments are associated with greater differentiation, possibly driven by intraspecific competition and female-biased selection for increased offspring investment.


Sequence variation in Plasmodium falciparum merozoite surface protein-2 is associated with virulence causing severe and cerebral malaria.
Parasite virulence, an important factor contributing to the severity of Plasmodium falciparum infection, varies among P. falciparum strains. Relatively little is known regarding markers of virulence capable of identifying strains responsible for severe malaria. We investigated the effects of genetic variations in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was previously postulated as a factor. We analyzed 300 msp2 sequences of single P. falciparum clone infection from patients with uncomplicated disease as well as those admitted for severe malaria with and without cerebral disease. The association of msp2 variations with disease severity was examined. We found that the N allele at codon 8 of Block 2 in the FC27-like msp2 gene was significantly associated with severe disease without cerebral complications (odds ratio = 2.73, P = 0.039), while the K allele at codon 17 of Block 4 in the 3D7-like msp2 gene was associated with cerebral malaria (odds ratio = 3.52, P = 0.024). The data suggests possible roles for the associated alleles on parasite invasion processes and immune-mediated pathogenicity. Multiplicity of infection was found to associate with severe disease without cerebral complications, but not cerebral malaria. Variations in the msp2-FC27-block 2-8N and 3D7-block 4-17K allele appear to be parasite virulence markers, and may be useful in determining the likelihood for severe and cerebral malaria. Their interactions with potential host factors for severe diseases should also be explored.


Induction of mammary cancer by 6-nitrochrysene in female CD rats.
6-Nitrochrysene (6-NC) is a pollutant generated in diesel exhaust. In order to study its propensity to induce mammary cancer, we injected 6-NC into the mammary glands of female CD rats. 4-Nitropyrene (4-NP), the most active mammary carcinogen among the mononitropyrene isomers, was used as a positive control (K. Imaida et al., Cancer Res., 51: 2902-2907, 1991). A total of 2.04 mumol of each compound in dimethyl sulfoxide was injected into each of the six mammary glands on the left side of weanling rats. The corresponding glands on the right side received injections of dimethyl sulfoxide. The thoracic glands were treated on Day 1 and those located in the inguinal area were treated on Day 2. Rats were sacrificed after 43 wk. 6-NC induced fibroadenomas, adenocarcinomas, and spindle cell sarcomas of the mammary glands in a high percentage of the rats. The numbers of animals with mammary tumors and the numbers of malignant tumors were significantly higher in the group treated with 6-NC than in those receiving 4-NP or dimethyl sulfoxide alone. The results of this study, taken together with those of previous bioassays, demonstrate the remarkable activity of 6-NC as a mammary, colon, and lung carcinogen in rodents.


Circulation of Coxiella burnetii in a Naturally Infected Flock of Dairy Sheep: Shedding Dynamics, Environmental Contamination, and Genotype Diversity.
Q fever is a worldwide zoonosis caused by Coxiella burnetii. Domestic ruminants are considered to be the main reservoir. Sheep, in particular, may frequently cause outbreaks in humans. Because within-flock circulation data are essential to implementing optimal management strategies, we performed a follow-up study of a naturally infected flock of dairy sheep. We aimed to (i) describe C. burnetii shedding dynamics by sampling vaginal mucus, feces, and milk, (ii) assess circulating strain diversity, and (iii) quantify barn environmental contamination. For 8 months, we sampled vaginal mucus and feces every 3 weeks from aborting and nonaborting ewes (n=11 and n=26, respectively); for lactating females, milk was obtained as well. We also sampled vaginal mucus from nine ewe lambs. Dust and air samples were collected every 3 and 6 weeks, respectively. All samples were screened using real-time PCR, and strongly positive samples were further analyzed using quantitative PCR. Vaginal and fecal samples with sufficient bacterial burdens were then genotyped by multiple-locus variable-number tandem-repeat analysis (MLVA) using 17 markers. C. burnetii burdens were higher in vaginal mucus and feces than in milk, and they peaked in the first 3 weeks postabortion or postpartum. Primiparous females and aborting females tended to shed C. burnetii longer and have higher bacterial burdens than nonaborting and multiparous females. Six genotype clusters were identified; they were independent of abortion status, and within-individual genotype diversity was observed. C. burnetii was also detected in air and dust samples. Further studies should determine whether the within-flock circulation dynamics observed here are generalizable.


Thermal Stability of Cellulose Nanomaterials.
Thermal stability is a crucial property of materials, especially when they have a wide range of thermally sensitive applications. Cellulose nanomaterials (CNMs) extracted from cellulosic biomass have garnered significant attention due to their abundance, biodegradability, sustainability, production scalability, and industrial versatility. To explore the correlation between the structure, chemistry, and morphology of CNMs and their thermal stability, we present a comprehensive literature review. We identify five major factors affecting CNMs' thermal stability, namely type, source, reaction conditions, post-treatment, and drying method, and analyze their impact on CNMs' thermal stability using several case studies from the literature. Using multiple linear least-squares regression (MLR), we establish a quantitative relationship between thermal stability and seven variables: crystallinity index of the source, dissociation constant of the reactant used, reactant concentration, reaction temperature, reaction time, evaporation rate, and post-treatment presence. By understanding these interdependencies, our statistical analysis enables the design of CNMs with predictable thermal properties and identification of optimal conditions for achieving high thermal stability. The results of our study provide crucial insights that can guide the development of CNMs with enhanced thermal stability for use in a variety of industrial applications.


Synthesis and pharmacological activity and some derivatives of 1-phenyl-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one.
4-N-Alkylamino derivatives and corresponding ammonium quaternary salts of tetrahydro-1,4-benzodiazepin-5-one were synthesized and evaluated for psychotropic activity in mice by ip via. This study was also extended to some nitro and amino derivatives of tetrahydro-1,4-benzodiazepin-5-one. Compounds were devoid of tranquilizing activity and in comparison with two classical benzodiazepines, chlordiazepoxide and diazepam, they showed high toxicity and little or no effect on motor coordination, motor activity, and maximal electroshock. On some "in vitro" tests the compounds exhibited pharmacological properties when they were used at high concentrations.


Short-term and Long-term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation: The FITR Heart Study Randomized Clinical Trial.
High-intensity interval training (HIIT) is recognized as a potent stimulus for improving cardiorespiratory fitness (volume of oxygen consumption [VO2] peak) in patients with coronary artery disease (CAD). However, the feasibility, safety, and long-term effects of HIIT in this population are unclear. To compare HIIT with moderate-intensity continuous training (MICT) for feasibility, safety, adherence, and efficacy of improving VO2 peak in patients with CAD. In this single-center randomized clinical trial, participants underwent 4 weeks of supervised training in a private hospital cardiac rehabilitation program, with subsequent home-based training and follow-up over 12 months. A total of 96 participants with angiographically proven CAD aged 18 to 80 years were enrolled, and 93 participants were medically cleared for participation following a cardiopulmonary exercise test. Data were collected from May 2016 to December 2018, and data were analyzed from December 2018 to August 2019. A 4 × 4-minute HIIT program or a 40-minute MICT program (usual care). Patients completed 3 sessions per week (2 supervised and 1 home-based session) for 4 weeks and 3 home-based sessions per week thereafter for 48 weeks. The primary outcome was change in VO2 peak during the cardiopulmonary exercise test from baseline to 4 weeks. Further testing occurred at 3, 6, and 12 months. Secondary outcomes were feasibility, safety, adherence, cardiovascular risk factors, and quality of life. Of 93 randomized participants, 78 (84%) were male, the mean (SD) age was 65 (8) years, and 46 were randomized to HIIT and 47 to MICT. A total of 86 participants completed testing at 4 weeks for the primary outcome, including 43 in the HIIT group and 43 in the MICT group; 69 completed testing at 12 months for VO2 peak, including 32 in the HIIT group and 37 in the MICT group. After 4 weeks, HIIT improved VO2 peak by 10% compared with 4% in the MICT group (mean [SD] oxygen uptake: HIIT, 2.9 [3.4] mL/kg/min; MICT, 1.2 [3.4] mL/kg/min; P = .02). After 12 months, there were similar improvements from baseline between groups, with a 10% improvement in the HIIT group and a 7% improvement in the MICT group (mean [SD] oxygen uptake: HIIT, 2.9 [4.5] mL/kg/min; MICT, 1.8 [4.3] mL/kg/min; P = .30). Both groups had high feasibility scores and low rates of withdrawal due to serious adverse events (3 participants in the HIIT group and 1 participant in the MICT group). One event occurred following exercise (hypotension) in the HIIT group. Over 12 months, both home-based HIIT and MICT had low rates of adherence (HIIT, 18 of 34 [53%]; MICT, 15 of 37 [41%]; P = .35) compared with the supervised stage (HIIT, 39 of 44 [91%]; MICT, 39 of 43 [91%]; P > .99). In this randomized clinical trial, a 4-week HIIT program improved VO2 peak compared with MICT in patients with CAD attending cardiac rehabilitation. However, improvements in VO2 peak at 12 months were similar for both groups. HIIT was feasible and safe, with similar adherence to MICT over 12-month follow-up. These findings support inclusion of HIIT in cardiac rehabilitation programs as an adjunct or alternative modality to moderate-intensity exercise. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001292561.


CELL WALL VARIABILITY IN THE GREEN SEAWEED CODIUM VERMILARA (BRYOPSIDALES CHLOROPHYTA) FROM THE ARGENTINE COAST(1).
Cell wall chemistry in the coencocytic green seaweed Codium vermilara (Olivi) Delle Chiaje (Bryopsidales, Chlorophyta) is well understood. These cell walls are composed of major amounts of neutral β-(1→4)-D-mannans (Mn), sulfated polysaccharides (SPs), which include pyranosic arabinan sulfates (ArpS), pyruvylated galactan sulfates (pGaS), and mannan sulfates (MnS); also minor amounts of O-glycoproteins are present. In this study, cell wall samples of C. vermilara were investigated with regard to their monosaccharide composition and infrared spectra (using Fourier transform infrared spectroscopy coupled to principal component [FTIR-PC] analysis). Samples from three different populations of C. vermilara from the Argentine coast showed: (i) an important variation in the relative arabinan content, which increases from north to south, and (ii) a measurable degree of cell wall variability in the sulfate distribution between the different sulfated polysaccharides, independent of the amount of each polysaccharide present and of total sulfate content. When cell wall composition was analyzed over three consecutive years in a single geographic location, the quantity of Mn and overall sulfate content on SPs remained constant, whereas the pGaS:ArpS molar ratio changed over the time. Besides, similar cell wall composition was found between actively growing and resting zones of the thallus, suggesting that cell wall composition is independent of growth stage and development. Overall, these results suggest that C. vermilara has developed a mechanism to adjust the total level of cell wall sulfation by modulating the ArpS:pGaS:MnS molar ratio and also by adjusting the sulfation level in each type of polymer, whereas nonsulfated Mn, as the main structural polysaccharide, did not change over the time or growing stage.


Worldwide structure of mtDNA diversity among Cuvier's beaked whales (Ziphius cavirostris): implications for threatened populations.
We present the first description of phylogeographic structure among Cuvier's beaked whales (Ziphius cavirostris) worldwide using mitochondrial DNA (mtDNA) control region sequences obtained from strandings (n = 70), incidental fisheries takes (n = 11), biopsy (n = 1), and whale-meat markets (n = 5). Over a 290-base pair fragment, 23 variable sites defined 33 unique haplotypes among the total of 87 samples. Nucleotide diversity at the control region was relatively low (pi = 1.27%+/- 0.723%) compared to wide-ranging baleen whales, but higher than strongly matrifocal sperm, pilot and killer whales. Phylogenetic reconstruction using maximum likelihood revealed four distinct haplotype groups, each of which displayed strong frequency differences among ocean basins, but no reciprocal monophyly or fixed character differences. Consistent with this phylogeographic pattern, an analysis of molecular variance showed high levels of differentiation among ocean basins (F(ST) = 0.14, Phi ST = 0.42; P < 0.001). Estimated rates of female migration among ocean basins were low (generally < or = 2 individuals per generation). Regional sample sizes were too small to detect subdivisions within oceans except in the North Atlantic, where the Mediterranean Sea (n = 12) was highly differentiated due to the presence of two private haplotypes. One market product purchased in South Korea grouped with other haplotypes found only in the North Atlantic, suggesting a violation of current agreements banning international trade in cetacean species. Together, these results demonstrate a high degree of isolation and low maternal gene flow among oceanic, and in some cases, regional populations of Cuvier's beaked whales. This has important implications for understanding the threats of human impact, including fisheries by-catch, direct hunting, and disturbance or mortality from anthropogenic sound.


Measuring and predicting eyelid spectral transmittance.
The purpose of the present study was to objectively quantify the spectral transmittance of the eyelid. Reported here are data acquired using a technique that was developed to provide practical and accurate measurements of eyelid transmittance across the visible portion of the electromagnetic spectrum. The empirical data were analyzed in terms of the absorption and scattering characteristics of the constituents of skin to develop a method for predicting eyelid transmission. Results showed that the eyelid has a much higher optical density at short wavelengths than previously published. The mean ± standard deviation (s.d.) optical density of the eyelid from 450 to 650 nm was 2.1 ± 0.3 with an optical density range among subjects of approximately 1.0. The study results indicate that skin pigmentation is poorly correlated with eyelid transmission; eyelid transmission is most affected by wavelength-independent macromolecules in the eyelid as well as its overall thickness.


Prenatal exposure to cigarettes in infants with obstructive sleep apneas.
To investigate the effect of prenatal smoking on infant respiratory behavior during sleep. A questionnaire concerning family habits and infants' history was completed for 550 healthy infants before a 9-hour night polysomnographic study. Because the data for 41 infants were not available for analysis, 509 subjects were studied: 115 were newborns evaluated within 1 week after birth, and 394 were healthy infants admitted at 11 weeks of life (range 5 to 29 weeks) after various research protocols. According to the smoking frequency of the mothers during pregnancy, the subjects were defined as "nonsmokers" (no cigarette smoked during pregnancy; n = 400), "light smokers" (1 to 9 cigarettes per day; n = 37), or "smokers" (10 or more cigarettes per day; n = 72). Compared with nonsmokers and light smokers, "smoking" mothers had a significant increase in the number of episodes of uterine bleeding during the pregnancy. Their infants had lower birth weights and more frequent episodes of profuse sweating during sleep. Infants of smokers also had more frequent and longer obstructive sleep apneas than those of the two other groups. For infants of smokers the relative risk for obstructive apneas was 2.76 (95% confidence interval: 1.63 to 4.69; P = .001). The relation between prenatal smoking and postnatal manifestation of obstructive sleep apneas demonstrated a dose-response pattern. Paternal smoking during pregnancy increased the risk of obstructive apneas only in the infants of smoking mothers, but not in those of the two other groups. Maternal smoking after birth did not add significantly to the risk of obstructive apneas. The effect of smoking was seen in older infants, as well as in the newborn not yet exposed to ambient cigarette smoke. A stepwise logistic regression, using obstructive sleep apneas as the dependent variable identified three significant independent variables: smoking during pregnancy (P = .001), profuse sweating during sleep (P = .001), and birth weight (P = .010). No explanation was found for the effect of prenatal smoking on obstructive sleep apneas. Prenatal smoking by mothers correlated with an increase in frequency and length of obstructive apneas and a decrease in birth weight of their infants. The infants were under greater risk for obstructive apnea if both parents smoked. Explanations for our results are unknown to us, but these findings may be of interest in the study of infant breathing behavior and epidemiological characteristics of sudden infant death syndrome.


The nucleotide sequence of an equine herpesvirus 4 gene homologue of the herpes simplex virus 1 glycoprotein H gene.
The equine herpesvirus 4 (EHV-4) gene glycoprotein H (gH) gene homologue was localized by virtue of the conserved genomic position of this gene throughout members of the herpesvirus family. The gene maps immediately downstream of the thymidine kinase gene at approximately 0.49 to 0.51 map units within genomic fragment BamH1 C. The EHV-4 gH primary translation product is predicted to be a polypeptide of Mr 94,100, 855 amino acids long, which possesses features characteristic of a membrane glycoprotein, namely an N-terminal signal sequence, a large hydrophilic domain containing 11 putative N-linked glycosylation sites, a C-terminal transmembrane domain, and a charged cytoplasmic tail. Comparison to other herpesvirus glycoproteins revealed identities of 85%, 26% and 32% with the gH counterparts of the alphaherpesviruses EHV-1, herpes simplex virus 1 and varicella-zoster virus, respectively, and of 17% and 18% with those of human cytomegalovirus, herpesvirus saimiri and Epstein-Barr virus. The EHV-4 gH exhibits features previously reported to be conserved throughout the gH polypeptides of herpesviruses of all three subgroups. A region of direct repeat elements and a possible origin of DNA replication are located immediately downstream of the gH gene.


[THE VALUE OF INFORMATION AND COMMUNICATIONS TECHNOLOGY IN AGING].
Nowadays, acquiring, managing, disseminating and understanding information through new technologies is an important aspect of our daily life. We can search for and store information, but we can also spread it. The proper handling of information and communications technology (TICs) is beneficial, but does not reach all alike. The difficulties posed by the elderly when adapting to TICs are increased by the fact that they are unknown and unfamiliar to them, resulting in rejection from the elderly and thus an increased risk of inequality and social exclusion. TICs value in aging lies in the improvement of self-learning and personal development as well as in promoting participation, social integration and healthy aging.


Morphology of cerebral plaque-like lesions in hereditary cerebral hemorrhage with amyloidosis (Dutch).
We studied the presence and morphology of plaque-like lesions in the frontal cortex of six patients, aged 40 to 76 years, with hereditary cerebral hemorrhage with amyloidosis--Dutch type (HCHWA-D), using beta/A4 immuno-, silver, Congo red and thioflavin S staining. Two types of beta/A4 immunoreactive and Congo red-negative plaques were detected. The first type was composed of argyrophilic fibrous material in periodic acid-methenamine silver (PAM) and modified Bielschowsky staining and lacked silver-stained degenerating neurites. Therefore, this type of plaque has the same staining properties as the diffuse plaque described in Alzheimer's disease, Down's syndrome and nondemented elderly. The second type of plaque, occurring only in the three oldest patients and numerically increasing with age, consisted of a spherical non-argyrophilic area of granular texture with a rim of PAM-positive material. The PAM-positive fibrous material of both types of plaques was mingled with coarser and compact, irregular-shaped argyrophilic structures in the oldest patient. The described plaques did not show bright fluorescence with thioflavin S staining. These results indicate, that the morphology of plaques, encountered in HCHWA-D, is diverse and changes with age.


Feature extraction and selection for the automatic detection of hard exudates in retinal images.
Diabetic Retinopathy (DR) is a common cause of visual impairment among people of working age in industrialized countries. Automatic recognition of DR lesions, like hard exudates (HEs), in fundus images can contribute to the diagnosis and screening of this disease. In this study, we extracted a set of features from image regions and selected the subset which best discriminates between HEs and the retinal background. The selected features were then used as inputs to a multilayer perceptron (MLP) classifier to obtain a final segmentation of HEs in the image. Our database was composed of 100 images with variable color, brightness, and quality. 50 of them were used to train the MLP classifier and the remaining 50 to assess the performance of the method. Using a lesion-based criterion, we achieved a mean sensitivity of 84.4% and a mean positive predictive value of 62.7%. With an image-based criterion, our approach reached a 100% mean sensitivity, 84.0% mean specificity and 92.0% mean accuracy.


Increased risk of urinary tract infection associated with the use of calcium supplements.
Since ions are known to influence the interaction between cells, we undertook an examination of the effect of various ions on bacterial adherence to uroepithelial cells. While most of the ions examined had no effect or decreased bacterial adherence, calcium ions significantly increased bacterial adherence. It was demonstrated, in vitro that as the concentration of calcium was increased to levels higher than normally found in the urine, there was a significant increase in bacterial adherence. It was also found that if the diet was supplemented with calcium there was an increase in the excretion of calcium in the urine and a corresponding increase in bacterial adherence when bacteria and uroepithelial cells were incubated in this urine. It is suggested that an excretion of excess calcium in the urine may lead to an increased bacterial adherence in vivo and an increased potential for urinary tract infections.


Brain Stimulation in Eating Disorders: State of the Art and Future Perspectives.
The management of eating disorders (EDs) is still difficult and few treatments are effective. Recently, several studies have described the important contribution of non-invasive brain stimulation (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and electroconvulsive therapy) and invasive brain stimulation (deep brain stimulation and vagal nerve stimulation) for ED management. This review summarizes the available evidence supporting the use of brain stimulation in ED. All published studies on brain stimulation in ED as well as ongoing trials registered at clinicaltrials.gov were examined. Articles on neuromodulation research and perspective articles were also included. This analysis indicates that brain stimulation in EDs is still in its infancy. Literature data consist mainly of case reports, cases series, open studies, and only a few randomized controlled trials. Consequently, the evidence supporting the use of brain stimulation in EDs remains weak. Finally, this review discusses future directions in this research domain (e.g., sites of modulation, how to enhance neuromodulation efficacy, personalized protocols).


A Low-Cost Programmable Reversing Flow Column Apparatus for Investigating Mixing Zones.
This note describes the development and testing of a novel, programmable reversing flow 1D (R1D) experimental column apparatus designed to investigate reaction, sorption, and transport of solutes in aquifers within dynamic reversing flow zones where waters with different chemistries mix. The motivation for constructing this apparatus was to understand the roles of mixing and reaction on arsenic discharging through a tidally fluctuating riverbank. The apparatus can simulate complex transient flux schedules similar to natural flow regimes The apparatus uses an Arduino microcontroller to control flux magnitude through two peristaltic pumps. Solenoid valves control flow direction from two separate reservoirs. In-line probes continually measure effluent electrical conductance, pH, oxidation-reduction potential, and temperature. To understand how sensitive physical solute transport is to deviations from the real hydrograph of the tidally fluctuating river, two experiments were performed using: (1) a simpler constant magnitude, reversing flux direction schedule (RCF); and (2) a more environmentally relevant variable magnitude, reversing flux direction schedule (RVF). Wherein, flux magnitude was ramped up and down according to a sine wave. Modeled breakthrough curves of chloride yielded nearly identical dispersivities under both flow regimes. For the RVF experiment, Peclet numbers captured the transition between diffusion and dispersion dominated transport in the intertidal interval. Therefore, the apparatus accurately simulated conservative, environmentally relevant mixing under transient, variable flux flow regimes. Accurately generating variable flux reversing flow regimes is important to simulate the interaction between flow velocity and chemical reactions where Brownian diffusion of solutes to solid-phase reaction sites is kinetically limited.


New Vein Compression Entities in Patients with Unexplained Leg Swelling.
This retrospective study identifies often overlooked anatomical sites for nonthrombotic venous outflow obstruction (NTVO) in patients with unexplained lower extremity edema and pain. We reviewed the charts of 75 consecutive patients experiencing symptoms of unexplained lower extremity edema with pain that were unexplained by ultrasound, computed tomography angiography (CTA), and magnetic resonance imaging (MRI), who subsequently underwent venography in an outpatient medical office from 2010 to 2014. We categorized venograms based on the presence or absence of NTVO lesions and calculated prevalence of each at specific sites. The patients with NTVO lesions showing >50% stenosis on venography were then treated with angioplasty and/or stenting. After intervention, we documented subjective levels of pain and edema. Of the 75 venograms reviewed, physicians classified 52 as normal and 23 as showing evidence of compression, including 9 with May-Thurner syndrome and 14 with anatomical compressions at previously underreported sites. These 14 compression sites occurred at the following: iliofemoral vein at the inguinal ligament region (n = 7, 50%), external iliac vein at the iliac artery bifurcation (n = 1, 7.1%), both inguinal ligament region and iliac artery bifurcation (n = 4, 28.6%), and popliteal vein at the popliteal fossa (n = 2, 14.3%). Nine of the 14 patients (64.3%) reported total or near total resolution of lower extremity pain and edema at follow-up between 1 and 7 months (mean = 5.3 ± 2 months, median = 6 months) after balloon angioplasty and/or stent. Five with failed primary interventions underwent subsequent stenting and/or angioplasty and reported total or near total resolution of pain and clinical resolution of edema. This study provides evidence to broaden the disease profile of venous compression syndromes to other sites such as the hypogastric artery, inguinal ligament, and popliteal fossa. The results support previous research that suggests increased incidence of NTVO exists among patients with unexplained lower extremity edema and pain. In an effort to encourage further exploration, we developed a diagnostic algorithm to support a critical and systematic review of patients with lower extremity edema and pain that may go unexplained using traditional diagnostic measures, including ultrasound, CTA, and MRI alone.


Epidemic modeling in complex realities.
In our global world, the increasing complexity of social relations and transport infrastructures are key factors in the spread of epidemics. In recent years, the increasing availability of computer power has enabled both to obtain reliable data allowing one to quantify the complexity of the networks on which epidemics may propagate and to envision computational tools able to tackle the analysis of such propagation phenomena. These advances have put in evidence the limits of homogeneous assumptions and simple spatial diffusion approaches, and stimulated the inclusion of complex features and heterogeneities relevant in the description of epidemic diffusion. In this paper, we review recent progresses that integrate complex systems and networks analysis with epidemic modelling and focus on the impact of the various complex features of real systems on the dynamics of epidemic spreading.


Nuclear pores and DNA ploidy in human bladder carcinomas.
The number of nuclear pores per sq micron was determined on the freeze-fractured nuclei of 20 human bladder tumors and five control samples of normal bladder epithelium. Measurements of the nuclear surface and volume were also performed, and the mean number of pores per nucleus and the ratio of pore to volume were calculated. The DNA distribution pattern on the same samples was determined by flow cytometry. All control samples and 12 tumors were diploid, and eight tumors were aneuploid. The mean number of pores per sq micron and mean total number of pores per nucleus in the control samples and in diploid tumors were similar. In the aneuploid tumors, both values were significantly higher. However, the ratio of pore to volume was shown to be constant regardless of the DNA content. It was further observed that, in aneuploid tumors, there are two populations of nuclei, one with density of pores similar to the diploid tumor and one with a higher pore density. Because aneuploid bladder tumors have been shown to have more aggressive behavior than diploid tumors, increased density of nuclear pores or their total number per nucleus may be related to tumor behavior. This view is supported by the observation that five of eight tumors with increased density and total pore number were invasive, while all tumors with low pore number were noninvasive.


Sitosterol and glucosylceramide cooperative transversal and lateral uneven distribution in plant membranes.
The properties of biomembranes depend on the presence, local structure and relative distribution assumed by the thousands of components it is made of. As for animal cells, plant membranes have been demonstrated to be organized in subdomains with different persistence lengths and times. In plant cells, sitosterol has been demonstrated to confer to phospholipid membranes a more ordered structure while among lipids, glycosphingolipids are claimed to form rafts where they tightly pack with sterols. Glucosylceramides are glycosphingolipids involved in plant signalling and are essential for viability of cells and whole plant. The glucosylceramide-sitosterol structural coupling within PLPC membranes is here investigated by Langmuir films, in silico simulations and neutron reflectometry, unveiling that a strong direct interaction between the two molecules exists and governs their lateral and transversal distribution within membrane leaflets. The understanding of the driving forces governing specific molecules clustering and segregation in subdomains, such as glucosylceramide and sitosterol, have an impact on the mechanical properties of biomembranes and could reflect in the other membrane molecules partitioning and activity.


Stability studies of the effect of crosslinking on hydrochlorothiazide release.
The aim of this study was to determine the changes in the in vitro drug release from cross-linked hard gelatin capsules containing a water-insoluble drug. An immediate release hydrochlorothiazide (HCTZ) capsule formulations containing drug, lactose, starch 1500 were prepared and exposed to accelerated stability study (40°C/ambient RH, 40°C/60% RH, 40°C/75% RH, and 40°C/90% RH) in a closed dark bottles for 4 weeks. Notable decrease in drug dissolution was observed after the 4 weeks in all humidity conditions as compared with freshly prepared capsules. In an attempt to overcome capsule cross-linking, glycine alone, citric acid alone and both glycine and citric acid were added to the prepared formulations. In all humidity conditions, addition of glycine alone or citric acid alone did not affect the decrease in dissolution profile. On the other hand, addition of both glycine and citric acid together was found to prevent capsule cross-linking completely. Fourier transfer infra-red (FTIR) spectroscopy and differential scanning calorimetry (DSC) were performed on blank capsules and after storage for 4 weeks to identify the physicochemical changes in drug and other capsule components hence its effect on dissolution.


The association of longitudinal and interpersonal continuity of care with emergency department use, hospitalization, and mortality among Medicare beneficiaries.
Continuity of medical care is widely believed to lead to better health outcomes and service utilization patterns for patients. Most continuity studies, however, have only used administrative claims to assess longitudinal continuity with a provider. As a result, little is known about how interpersonal continuity (the patient's experience at the visit) relates to improved health outcomes and service use. We linked claims-based longitudinal continuity and survey-based self-reported interpersonal continuity indicators for 1,219 Medicare beneficiaries who completed the National Health and Health Services Use Questionnaire. With these linked data, we prospectively evaluated the effect of both types of continuity of care indicators on emergency department use, hospitalization, and mortality over a five-year period. Patient-reported continuity was associated with reduced emergency department use, preventable hospitalization, and mortality. Most of the claims-based measures, including those most frequently used to assess continuity, were not associated with reduced utilization or mortality. Our results indicate that the patient- and claims-based indicators of continuity have very different effects on these important health outcomes, suggesting that reform efforts must include the patient-provider experience when evaluating health care quality.


Use of the Branemark implant in the cleft palate patient.
This paper describes the clinical and surgical management of a patient presenting with a unilateral alveolar cleft and associated oronasal fistula. After orthodontic expansion of the maxilla, a secondary osseous graft was placed. A single Branemark implant was subsequently utilized to allow for prosthetic restoration of the dental arch. Through case presentation, a detailed course of treatment is outlined that effectively restores the anatomy, integrity, and function of both the alveolar and dental arches.


Haem oxygenase-1: a target for dietary antioxidants.
HO-1 (haem oxygenase-1) is a stress-response enzyme involved in the catabolism of haem. In animal models, it plays a key protective role in vascular disease. HO-1 has anti-inflammatory effects in macrophages and is induced by a range of stimuli, including antioxidants, in various cell types. As dietary antioxidants are considered to be beneficial in vascular disease, their protective effects may occur through induction of HO-1. Emerging evidence suggests that a range of dietary and other naturally occurring antioxidants stimulate HO-1 expression in various cell types, although regulation by these compounds has not been investigated in detail. These studies suggest that HO-1 may be a target for dietary therapy in vascular disease.


Hemangioblastoma diagnosis and surveillance in von Hippel-Lindau disease: a consensus statement.
Hemangioblastomas are a frequent underlying cause of neurological morbidity and death in patients with von Hippel-Lindau disease (VHL). Although these benign tumors can cause significant neurological debility when undetected and untreated, unified evidence-based surveillance recommendations for VHL patients have not been established. To develop consensus recommendations, the VHL Alliance established an expert committee, named the International VHL Surveillance Guidelines Consortium, to define surveillance recommendations. The Central Nervous System (CNS) Hemangioblastoma Subcommittee of the Guidelines Consortium was formed as a multidisciplinary team of experts in the diagnosis and management of hemangioblastomas. Recommendations were formulated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) and National Comprehensive Cancer Network Categories of Evidence and Consensus categorization after a comprehensive literature review. Published studies (n = 49) that discussed age at onset, MRI frequency, natural history of VHL, and the risks and benefits of surveillance were analyzed. Based on this analysis, the authors recommend that clinical evaluation (yearly) be used as the primary screening tool for hemangioblastomas in VHL. The subcommittee suggests that screening be performed between the ages of 11 and 65 years, or with the onset of symptoms, for synchronicity with other testing regimens in VHL. The subcommittee also recommends that baseline MRI be first performed at the age of 11 years (suggested 2B, level of evidence D) or after identification of neurological symptoms or signs (if earlier) and continue every 2 years (recommended 2A, level of evidence A). The CNS Hemangioblastoma Subcommittee of the International VHL Surveillance Guidelines Consortium here proposes guidelines that aim to increase the early detection of VHL-associated hemangioblastomas to reduce their morbidity and mortality.


Mini-scale bioprocessing systems for highly parallel animal cell cultures.
Animal cells have been used extensively in therapeutic protein production. The growth of animal cells and the expression of therapeutic proteins are highly dependent on the culturing environments. A large number of experimental permutations need to be explored to identify the optimal culturing conditions. Miniaturized bioreactors are well suited for such tasks as they offer high-throughput parallel operation and reduce cost of reagents. They can also be automated and be coupled to downstream analytical units for online measurements of culture products. This review summarizes the current status of miniaturized bioreactors for animal cell cultivation based on the design categories: microtiter plates, flasks, stirred tank reactors, novel designs with active mixing, and microfluidic cell culture devices. We compare cell density and product titer, for batch or fed-batch modes for each system. Monitoring/controlling devices for engineering parameters such as pH, dissolved oxygen, and dissolved carbon dioxide, which could be applied to such systems, are summarized. Finally, mini-scale tools for process performance evaluation for animal cell cultures are discussed: total cell density, cell viability, product titer and quality, substrates, and metabolites profiles.


Reduction of Outdoor and Indoor PM2.5 Source Contributions via Portable Air Filtration Systems in a Senior Residential Facility in Detroit, Michigan.
Background: The Reducing Air Pollution in Detroit Intervention Study (RAPIDS) was designed to evaluate cardiovascular health benefits and personal fine particulate matter (particulate matter < 2.5 μm in diameter, PM2.5) exposure reductions via portable air filtration units (PAFs) among older adults in Detroit, Michigan. This double-blind randomized crossover intervention study has shown that, compared to sham, air filtration for 3 days decreased 3-day average brachial systolic blood pressure by 3.2 mmHg. The results also showed that commercially available HEPA-type and true HEPA PAFs mitigated median indoor PM2.5 concentrations by 58% and 65%, respectively. However, to our knowledge, no health intervention study in which a significant positive health effect was observed has also evaluated how outdoor and indoor PM2.5 sources impacted the subjects. With that in mind, detailed characterization of outdoor and indoor PM2.5 samples collected during this study and a source apportionment analysis of those samples using a positive matrix factorization model were completed. The aims of this most recent work were to characterize the indoor and outdoor sources of the PM2.5 this community was exposed to and to assess how effectively commercially available HEPA-type and true HEPA PAFs were able to reduce indoor and outdoor PM2.5 source contributions. Methods: Approximately 24 h daily indoor and outdoor PM2.5 samples were collected on Teflon and Quartz filters from the apartments of 40 study subjects during each 3-day intervention period. These filters were analyzed for mass, carbon, and trace elements. Environmental Protection Agency Positive Matrix Factorization (PMF) 5.0 was utilized to determine major emission sources that contributed to the outdoor and indoor PM2.5 levels during this study. Results: The major sources of outdoor PM2.5 were secondary aerosols (28%), traffic/urban dust (24%), iron/steel industries (15%), sewage/municipal incineration (10%), and oil combustion/refinery (6%). The major sources of indoor PM2.5 were organic compounds (45%), traffic + sewage/municipal incineration (14%), secondary aerosols (13%), smoking (7%), and urban dust (2%). Infiltration of outdoor PM2.5 for sham, HEPA-type, and true HEPA air filtration was 79 ± 24%, 61 ± 32%, and 51 ± 34%, respectively. Conclusions: The results from our study showed that intervention with PAFs was able to significantly decrease indoor PM2.5 derived from outdoor and indoor PM2.5 sources. The PAFs were also able to significantly reduce the infiltration of outdoor PM2.5. The results of this study provide insights into what types of major PM2.5 sources this community is exposed to and what degree of air quality and systolic blood pressure improvements are possible through the use of commercially available PAFs in a real-world setting.


The effect of homogenising tissues either before or after storage on the isolation of Chlamydia trachomatis.
To determine whether freezing before homogenisation or the reverse procedure was the best way of achieving maximal recovery of chlamydiae from solid tissues, specimens from mice infected experimentally with Chlamydia trachomatis were used. For 10 of 12 mice, three-fold to over fifty-fold more chlamydiae were isolated from portions of spleens which were homogenised before freezing in liquid nitrogen than from those which were homogenised after being stored frozen. The value of homogenising small strips of infected genital tissue before freezing was less apparent. Nevertheless, if this was undertaken, the number of chlamydiae recovered from the tissues of four of 10 mice was three-fold to seven-fold more than if the tissues were homogenised after freezing.


Adverse effects in homeopathy. A systematic review and meta-analysis of observational studies.
Almost all health care interventions have the potential to be associated with risk to patient safety. Different terminologies are used to define treatment induced risk to patient safety and a common definition is the term adverse effect. Beyond the concept of adverse effect and specific to homeopathy is the concept of homeopathic aggravation. Homeopathic aggravation describes a transient worsening of the patients' symptoms, which is not understood as an adverse effect. In order to ensure patient safety within a homeopathic treatment setting, it is important to identify adverse effects, as well as homeopathic aggravations, even though it may be challenging to distinguish between these two concepts. To date there is an obvious lack of systematic information on how adverse effects and homeopathic aggravations are reported in studies. This systematic review and meta-analysis focuses on observational studies, as a substantial amount of the research base for homeopathy are observational. Eight electronic databases, central webpages and journals were searched for eligible studies. The searches were limited from the year 1995 to January 2020. The filters used were observational studies, human, English and German language. Adverse effects and homeopathic aggravations were identified and graded according to The Common Terminology Criteria for Adverse Effects (CTCAE). Meta-analysis was performed separately for adverse effects and homeopathic aggravations. A total of 1,169 studies were identified, 41 were included in this review. Eighteen studies were included in a meta-analysis that made an overall comparison between homeopathy and control (conventional medicine and herbs). Eighty-seven percent (n = 35) of the studies reported adverse effects. They were graded as CTCAE 1, 2 or 3 and equally distributed between the intervention and control groups. Homeopathic aggravations were reported in 22,5% (n = 9) of the studies and graded as CTCAE 1 or 2. The frequency of adverse effects for control versus homeopathy was statistically significant (P < 0.0001). Analysis of sub-groups indicated that, compared to homeopathy, the number of adverse effects was significantly higher for conventional medicine (P = 0.0001), as well as other complementary therapies (P = 0.05). Adverse effects of homeopathic remedies are consistently reported in observational studies, while homeopathic aggravations are less documented. This meta-analysis revealed that the proportion of patients experiencing adverse effects was significantly higher when receiving conventional medicine and herbs, compared to patients receiving homeopathy. Nonetheless, the development and implementation of a standardized reporting system of adverse effects in homeopathic studies is warranted in order to facilitate future risk assessments.


Improving Discourse following Traumatic Brain Injury: A Tale of Two Treatments.
Persons with traumatic brain injury (TBI) often present with discourse-level deficits that affect functional communication. These deficits are not thought to be primarily linguistic in nature but instead are thought to arise from the interaction of linguistic and cognitive processes. Discourse processing treatment (DPT) is a discourse-based treatment protocol which targets discourse deficits frequently seen in TBI. Attention Process Training-2 (APT-2) is a published treatment protocol which targets four levels of attention. The purpose of this article is to investigate the effectiveness of DPT and APT-2 in improving discourse production and cognition in adults with TBI. Our results suggest that DPT results in greater improvement in discourse informativeness and coherence, but the combination of DPT and APT-2 resulted in greater generalization to untrained stimuli. Both DPT and APT-2 appear to have some potential to improve cognition, but there was intersubject variability with regard to which treatment is more effective.


The polo-like kinase 1 inhibitor volasertib synergistically increases radiation efficacy in glioma stem cells.
Despite the availability of hundreds of cancer drugs, there is insufficient data on the efficacy of these drugs on the extremely heterogeneous tumor cell populations of glioblastoma (GBM). The PKIS of 357 compounds was initially evaluated in 15 different GSC lines which then led to a more focused screening of the 21 most highly active compounds in 11 unique GSC lines using HTS screening for cell viability. We further validated the HTS result with the second-generation PLK1 inhibitor volasertib as a single agent and in combination with ionizing radiation (IR). In vitro studies showed that volasertib inhibited cell viability, and high levels of the anti-apoptotic protein Bcl-xL expression were highly correlated with volasertib resistance. Volasertib sensitized GSCs to radiation therapy by enhancing G2/M arrest and by inducing apoptosis. Colony-formation assay demonstrated that volasertib plus IR synergistically inhibited colony formation. In intracranial xenograft mouse models, the combination of volasertib and radiation significantly inhibited GSC tumor growth and prolonged median survival compared with radiation treatment alone due to inhibition of cell proliferation, enhancement of DNA damage, and induction of apoptosis. Our results reinforce the potential therapeutic efficacy of volasertib in combination with radiation for the treatment of GBM. We used high-throughput screening (HTS) to identify drugs, out of 357 compounds in the published Protein Kinase Inhibitor Set, with the greatest efficacy against a panel of glioma stem cells (GSCs), which are representative of the classic cancer genome atlas (TCGA) molecular subtypes.


Recognition of highly branched N-glycans of the porcine whipworm by the immune system.
Glycans are key to host-pathogen interactions, whereby recognition by the host and immunomodulation by the pathogen can be mediated by carbohydrate binding proteins, such as lectins of the innate immune system, and their glycoconjugate ligands. Previous studies have shown that excretory-secretory products of the porcine nematode parasite Trichuris suis exert immunomodulatory effects in a glycan-dependent manner. To better understand the mechanisms of these interactions, we prepared N-glycans from T. suis and both analyzed their structures and used them to generate a natural glycan microarray. With this array we explored the interactions of glycans with C-type lectins, C-reactive protein and sera from T. suis infected pigs. Glycans containing LacdiNAc and phosphorylcholine-modified glycans were associated with the highest binding by most of these proteins. In-depth analysis revealed not only fucosylated LacdiNAc motifs with and without phosphorylcholine moieties, but phosphorylcholine-modified mannose and N-acetylhexosamine-substituted fucose residues, in the context of maximally tetraantennary N-glycan scaffolds. Furthermore, O-glycans also contained fucosylated motifs. In summary, the glycans of T. suis are recognized by both the innate and adaptive immune systems, and also exhibit species-specific features distinguishing its glycome from those of other nematodes.


[Evolutionary plasticity of highly specialized organisms with eriophyoid mites (Acariformes: Eriophyoidea) as an example].
Eriophyoids is a group of highly specialized plant-feeding acariform mites. As a result of adaptation to phytoparasitism, they lacked III and IV pairs of legs and acquired elongated vermiform body and unique structure of gnathosoma. Despite the high degree of specialization, eriophyoid mites demonstrate remarkable evolutionary plasticity which manifests itself in numerous morphological reversions, parallelisms, and modifications associated with occupying variety of niches, processes of gall formation, transitions to new groups of hosts, and various adaptations to climate change.


Homozygous lecithin:cholesterol acyltransferase (LCAT) deficiency due to a new loss of function mutation and review of the literature.
A case of homozygous familial lecithin:cholesterol acyltransferase (LCAT) deficiency with a novel homozygous LCAT missense mutation (replacement of methionine by arginine at position 293 in the amino acid sequence of the LCAT protein) is reported. The probable diagnosis was suggested by findings of marked high density lipoprotein (HDL) deficiency, corneal opacification, anemia, and renal insufficiency. The diagnosis was confirmed by two dimensional gel electrophoresis of HDL, the measurement of free and esterified cholesterol, and sequencing of the LCAT gene. In our view the most important aspects of therapy to prevent the kidney disease that these patients develop is careful control of blood pressure and lifestyle measures to optimize non HDL lipoproteins. In the future replacement therapy by gene transfer or other methods may become available.


[Zinc levels in prostatic fluid of patients with prostate pathologies].
The prostate is a gland that surrounds the posterior urethra in man and, along with seminal vesicles, produces prostatic and seminal fluids. Prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer are the most frequent pathologies of this gland. Zinc is an important element in the makeup of prostatic fluid and plays an important role in the immunology of the infectious and neoplastic pathologies of the prostate. The aim of this study was to determine zinc concentrations in prostatic fluid of patients with prostate pathologies and to use this measurement as a diagnostic parameter. Thirty patients with prostatic pathologies and ten healthy controls were studied. Prostatic fluid samples were collected using prostatic massage. Zinc concentration was determined using electrothermal atomizeratomic absorption spectrometry (ETA-AAS). The mean zinc concentrations obtained in the studied population were as follows: 11 patients with BPH: 15.087,78 micromol/dL, 10 patients with prostatis: 863,33 micromol/dL, 9 patients with prostate cancer: 1.027,60 micromol/dL and 10 healthy subjects: 7.467,52 micromol/dL. The low zinc concentrations obtained in patients with prostatitis and prostate cancer, in contrast to the control group, led us to consider the possibility of recommending zinc supplements as a coadjuvant therapy in patients with prostatitis and also, to use zinc measurements as another diagnostic tool, for cases in which it is necessary to differentiate benign prostatic hyperplasia from prostate cancer.


Variations in cesarean and repeated cesarean section rates in Brazil according to gestational age at birth and type of hospital.
This study aimed to describe cesarean and repeated cesarean section rates in Brazil according to gestational age (GA) at birth and type of hospital. This is an ecologic study using data from the Brazilian Information System on Live Births and the 2017 National Registry of Health Facilities. Overall and repeated cesarean section rates were calculated and analyzed according to GA, region of residence, and type of hospital. Spearman correlations were performed between cesarean and repeated cesarean section rates by GA subgroups at birth (≤ 33, 34-36, 37-38, 39-41, and ≥ 42 weeks) and analyzed according to the type of hospital. Overall and repeated cesarean section rates were 55.1% and 85.3%, respectively. More than 60% of newborns between 37-38 weeks were delivered via cesarean section. Private hospitals in all regions showed the highest cesarean section rates, especially those in the Central-West Region, with more than 80% at all GAs. The overall cesarean section rate was highly correlated with all cesarean section rates of GA subgroups (r > 0.7, p < 0.01). Regarding repeated cesarean sections, the overall rate was strongly correlated with the rates of 37-38 and 39-41 weeks in public/mixed hospitals, differing from private hospitals, which showed moderate correlations. This finding indicates the decision for cesarean section is not based on clinical factors, which can cause unnecessary damage to the health of both the mother and the baby. Then, changes in the delivery care model, strengthening public policies, and encouragement of vaginal delivery after a cesarean section in subsequent pregnancies are important strategies to reduce cesarean section rates in Brazil.


The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell response to respiratory virus infections.
Innate recognition of invading pathogens in peripheral tissues results in the recruitment of circulating memory CD8(+) T cells to sites of localized inflammation during the early phase of a recall response. However, the mechanisms that control the rapid recruitment of these cells to peripheral sites are poorly understood, particularly in relation to influenza and parainfluenza infections of the respiratory tract. In this study, we demonstrate a crucial role for C-C chemokine receptor 5 (CCR5) in the accelerated recruitment of memory CD8(+) T cells to the lung airways during virus challenge. Most importantly, CCR5 deficiency resulted in decreased recruitment of memory T cells expressing key effector molecules and impaired control of virus replication during the initial stages of a secondary response. These data highlight the critical importance of early memory T cell recruitment for the efficacy of cellular immunity in the lung.


Combined neoadjuvant chemotherapy with bevacizumab improves pathologic complete response in patients with hormone receptor negative operable or locally advanced breast cancer.
To evaluate the pathologic complete response (pCR) and safety of bevacizumab (B) with chemotherapy in the neoadjuvant setting of breast cancer (BC). A prospective single-arm, single-institution phase II trial for women with stage IIA-B/IIIA-B-C BC. Patients received neoadjuvant docetaxel, cyclophosphamide, B every 3 weeks for 4 cycles followed by doxorubicin every 3 weeks for 4 cycles followed by surgery. After healing, B was given every 3 weeks for 9 cycles. Radiation therapy, trastuzumab and endocrine therapy were given as indicated. Thirty-nine of 40 patients were evaluable. Median age of participants was 45 years (range, 26 to 72 y). The most serious grade ≥3 adverse events were infection (4), congestive heart failure (2), and pulmonary embolism (1). Thirty-eight of 39 patients underwent surgery. The pCR rate was 41% (16/39), significantly higher than the null-hypothesis rate of 25% (P=0.0204). Rates of pCR were 52% (15/29) in ductal carcinoma compared with 10% (1/10) in nonductal disease (P=0.021), and 59% (10/17) in estrogen receptor-/progesteron receptor- patients compared with 27% (6/22) among patient with at least one positive hormone receptor (P=0.047). African Americans (AA) had 75% pCR (9/12), whereas Whites had only 28% pCR (7/25; P=0.0069), possibly in part because 100% of AA (12/12) had ductal carcinoma compared with only 64% (16/25) of Whites (P=0.017). Chemotherapy with B improved pCR in BC patients, but was associated with significant toxicity and rare but very serious complications. The improvement was more pronounced in AA patients, those with ductal carcinoma, and those with estrogen receptor-/progesteron receptor - BC.ClinicalTrials.gov Identifier: NCT00203502.


Who can recognize unfamiliar faces? Individual differences and observer consistency in person identification.
It can be remarkably difficult to determine whether two photographs of unfamiliar faces depict the same person or two different people. This fallibility is well established in the face perception and eyewitness domain, but most of this research has focused on the "average" observer by measuring mean performance across groups of participants. This study deviated from this convention to provide a detailed description of individual differences and observer consistency in unfamiliar face identification by assessing performance repeatedly, across a 3-day (Experiment 1) and a 5-day period (Experiment 2). Both experiments reveal considerable variation between but also within observers. This variation is such that the same observers frequently made different identification decisions to the same faces on different days (Experiment 1). And when new faces were shown on each day, observers that produced perfect accuracy on one day made many misidentifications on another (Experiment 2). However, a few individuals also performed with consistent high accuracy in these tests. These findings suggest that accuracy and consistency are separable indices of face-matching ability, and both measures are necessary to provide a precise index of a person's face processing skill. We discuss whether these measures could provide the basis for a selection tool for occupations that depend on accurate person identification.


Role of intestinal Hsp70 in barrier maintenance: contribution of milk to the induction of Hsp70.2.
Necrotizing enterocolitis (NEC) is a gastrointestinal disease of complex etiology resulting in devastating systemic inflammation and often death in premature newborns. We previously demonstrated that formula feeding inhibits ileal expression of heat shock protein-70 (Hsp70), a critical stress protein within the intestine. Barrier function for the premature intestine is critical. We sought to determine whether reduced Hsp70 protein expression increases neonatal intestinal permeability. Young adult mouse colon cells (YAMC) were utilized to evaluate barrier function as well as intestine from Hsp70-/- pups (KO). Sections of intestine were analyzed by Western blot, immunohistochemistry, and real time PCR. YAMC cells were sub-lethally heated or treated with expressed milk (EM) to induce Hsp70. Immunostaining demonstrates co-localized Hsp70 and tight junction protein zona occludens-1 (ZO-1), suggesting physical interaction to protect tight junction function. The permeability of YAMC monolayers increases following oxidant injury and is partially blocked by Hsp70 induction either by prior heat stress or EM. RT-PCR analysis demonstrated that the Hsp70 isoforms, 70.1 and 70.3, predominate in WT pup; however, Hsp70.2 predominates in the KO pups. While Hsp70 is present in WT milk, it is not present in KO EM. Hsp70 associates with ZO-1 to maintain epithelial barrier function. Both induction of Hsp70 and exposure to EM prevent stress-induced increased permeability. Hsp70.2 is present in both WT and KO neonatal intestine, suggesting a crucial role in epithelial integrity. Induction of the Hsp70.2 isoform appears to be mediated by mother's milk. These results suggest that mother's milk feeding modulates Hsp70.2 expression and could attenuate injury leading to NEC. Level III.


End of life in nursing homes: connections between structure, process, and outcomes.
This study was a prospective, in-depth exploration of the experience of dying in two nursing homes from the perspective of residents, staff, and family members. A qualitative, case study design was used. Formal and informal interviews, participant observation, and document review were the primary data collection methods. A total of 56 declining residents were followed until death or for 6 months, whichever occurred first. The intimate linkages between structure, process, and outcome were evident in both nursing homes. The two homes had contrasting institutional philosophies, reflected in staffing and environment (structure) and processes of care. Processes included different patterns of planning, communication, and decision making. Most importantly, outcomes (residents' satisfaction with care and quality of life while approaching death) were substantively different. Institutional philosophy and leadership permeate all aspects of care. A compliance- centered, deficiency-free approach to assessing quality of care is not sufficient to address the needs of declining residents. A client-centered philosophy that embraces "caring for dying people," combined with integrated care planning, contributes to improved resident outcomes.


Avian orientation at steep angles of inclination: experiments with migratory white-crowned sparrows at the magnetic North Pole.
The Earth's magnetic field and celestial cues provide animals with compass information during migration. Inherited magnetic compass courses are selected based on the angle of inclination, making it difficult to orient in the near vertical fields found at high geomagnetic latitudes. Orientation cage experiments were performed at different sites in high Arctic Canada with adult and young white-crowned sparrows (Zonotrichia leucophrys gambelii) in order to investigate birds' ability to use the Earth's magnetic field and celestial cues for orientation in naturally very steep magnetic fields at and close to the magnetic North Pole. Experiments were performed during the natural period of migration at night in the local geomagnetic field under natural clear skies and under simulated total overcast conditions. The experimental birds failed to select a meaningful magnetic compass course under overcast conditions at the magnetic North Pole, but could do so in geomagnetic fields deviating less than 3 degrees from the vertical. Migratory orientation was successful at all sites when celestial cues were available.


[Primary paraganglioma of the urinary bladder: a report of two cases].
We report two cases of primary paraganglioma of the urinary bladder. Case 1. A 61-year-old man was hospitalized with the chief complaints of gross hematuria, dysuria and headache. The patient had a history of hypertension. Cystoscopy disclosed a nonpapillary, sessile tumor in the retrotrigonum of the bladder. An attack of paroxysmal hypertension was induced by bimanual palpation of the tumor, and paraganglioma was suspected. Partial cystectomy with staging pelvic lymphadenectomy was performed. Case 2. A 65-year-old man was hospitalized with the chief complaints of gross hematuria and urinary retention. The patient had no history of hypertension. Cystoscopy disclosed a nonpapillary tumor in the right lateral wall of the bladder. Transurethral resection was performed with no cardiovascular complication. Prostatic needle biopsy showed the histological evidence of prostatic adenocarcinoma. Radical retropubic prostatectomy with limited lymphadenectomy was performed. There was no histological evidence of lymph node involvement of paraganglioma or adenocarcinoma. The histological and biochemical examinations revealed a chromaffin positive, functioning and non-malignant tumor in Case 1, and a chromaffin negative, non-functioning and non-malignant tumor in Case 2. In total, 29 cases of primary paraganglioma of the urinary bladder have been so far reported in Japan. The tumor recurrence, multiple or metastases were recorded in 8 of 29 cases (27.6%), mainly in regional lymph node metastases. We recommend lymphadenectomy at the initial operation, irrespective of pathological finding of the primary paraganglioma of the urinary bladder.


Effects of predation risk on the grouping patterns of white-bellied spider monkeys (Ateles belzebuth belzebuth) in Western Amazonia.
Predation is proposed to be one of the most important factors influencing the evolution of mammalian societies. Although predation risk is thought to influence both the behavior and grouping patterns of most diurnal primates, evidence supporting this hypothesis is still limited. The spatial and temporal patterns of mineral lick use by one group of white-bellied spider monkeys (Ateles belzebuth) were evaluated, based on the growing evidence that mineral licks are perceived as areas of relative high predation risk by Neotropical primates. The area immediately surrounding the mineral lick was the most intensively used area within the home range of the study group, particularly by large subgroups of monkeys, and there were differences in mean subgroup size on days of mineral lick visitation versus days without lick visits. Additionally, on days of mineral lick visitation, subgroup size reached its maximum specifically during the period of lick visitation. Finally, on visit days subgroups showed a greater increase in size and higher fusion rates in the 2 hr before arriving at the lick in comparison with matched time windows on non-visit days. Together, these results provide an example of how primates employ behavioral strategies that might reduce the effects of predation. This study also demonstrates how taxa characterized by a high degree of fission-fusion dynamics can allow us to test hypotheses regarding the effects of socioecological variables on primate grouping patterns.


The response of an arboreal mammal to livestock grazing is habitat dependant.
Inappropriate livestock grazing is implicated in the decline of vertebrate fauna species globally. Faunal responses to grazing can interact with the vegetation community in which they occur. We measured the response of an arboreal marsupial, the common brushtail possum (Trichosurus vulpecula vulpecula) to different cattle grazing strategies and vegetation types, and examined whether micro-habitat selection is driving this response. We hypothesised that where arboreal habitat is intact, brushtail possums would be resistant to the impacts of heavy grazing. We conducted a mark-recapture survey among four grazing treatments and in two vegetation types (Box and Ironbark), at a 20-year grazing trial in northern Australia. We found that brushtail possums were resistant to the impact of heavy grazing in both vegetation types, but preferred the heavy grazing treatment in the Box vegetation type. Complex arboreal habitat and low ground cover was preferred, and high grass cover and low tree species richness avoided. Most individuals exclusively used one vegetation type, with few using both, suggesting a 'matrix' vegetation between the Box and Ironbark may be creating a movement barrier. Vegetation type should provide a context for determining the benefits to arboreal wildlife of adopting a particular grazing management strategy.


Physiological and pathophysiological roles of excitatory amino acids during central nervous system development.
Recent studies suggest that excitatory amino acids (EAAs) have a wide variety of physiological and pathophysiological roles during central nervous system (CNS) development. In addition to participating in neuronal signal transduction, EAAs also exert trophic influences affecting neuronal survival, growth and differentiation during restricted developmental periods. EAAs also participate in the development and maintenance of neuronal circuitry and regulate several forms of activity-dependent synaptic plasticity such as LTP and segregation of converging retinal inputs to tectum and visual cortex. Pre- and post-synaptic markers of EAA pathways in brain undergo marked ontogenic changes. These markers are commonly overexpressed during development; periods of overproduction often coincide with times when synaptic plasticity is great and when appropriate neuronal connections are consolidated. The electrophysiological and biochemical properties of EAA receptors also undergo marked ontogenic changes. In addition to these physiological roles of EAAs, overactivation of EAA receptors may initiate a cascade of cellular events which produce neuronal injury and death. There is a unique developmental profile of susceptibility of the brain to excitotoxic injury mediated by activation of each of the EAA receptor subtypes. Overactivation of EAA receptors is implicated in the pathophysiology of brain injury in several clinical disorders to which the developing brain is susceptible, including hypoxia-ischemia, epilepsy, physical trauma and some rare genetic abnormalities of amino acid metabolism. Potential therapeutic approaches may be rationally devised based on recent information about the developmental regulation of EAA receptors and their involvement in the pathogenesis of these disorders.


Transplantation elicits a clonally diverse CD8+ T cell response that is comprised of potent CD43+ effectors.
CD8+ T cells mediate acute rejection of allografts, which threatens the long-term survival of transplanted organs. Using MHC class I tetramers, we find that allogeneic CD8+ T cells are present at an elevated naive precursor frequency relative to other epitopes, only modestly increase in number after grafting, and maintain high T cell receptor diversity throughout the immune response. While antigen-specific effector CD8+ T cells poorly express the canonical effector marker KLRG-1, expression of the activated glycoform of CD43 defines potent effectors after transplantation. Activated CD43+ effector T cells maintain high expression of the coreceptor induced T cell costimulator (ICOS) in the presence of CTLA-4 immunoglobulin (Ig), and dual CTLA-4 Ig/anti-ICOS treatment prolongs graft survival. These data demonstrate that graft-specific CD8+ T cells have a distinct response profile relative to anti-pathogen CD8+ T cells and that CD43 and ICOS are critical surface receptors that define potent effector CD8+ T cell populations that form after transplantation.


Multidrug resistance protein 4 (MRP4) expression in prostate cancer is associated with androgen signaling and decreases with tumor progression.
Multidrug resistance protein 4 (MRP4) is a transmembrane transport protein found in many cell types and is involved in substrate-specific transport of endogenous and exogenous substrates. Recently, it has shown to be expressed in prostate cancer cell lines and to be among the most commonly upregulated transcripts in prostate cancer, although a comprehensive expression analysis is lacking so far. We aimed to investigate its expression by immunohistochemistry in a larger cohort of neoplastic and nonneoplastic prostate tissues (n = 441) and to correlate its expression with clinicopathological parameters including PSA-free survival times and molecular correlates of androgen signaling (androgen receptor (AR), prostate-specific antigen (PSA), and forkhead box A (FoxA)). MRP4 is widely expressed in benign and neoplastic prostate epithelia, but its expression gradually decreases during tumor progression towards castrate-resistant disease. Concordantly, it correlated with conventional prognosticators of disease progression and-within the group of androgen-dependent tumors-with AR and FoxA expression. Moreover, lower levels of MRP4 expression were associated with shorter PSA relapse-free survival times in the androgen-dependent group. In benign tissues, we found zone-dependent differences of MRP4 expression, with the highest levels in the peripheral and central zones. Although MRP4 is known to be regulated in prostate cancer, this study is the first to demonstrate a gradual downregulation of MRP4 protein during malignant tumor progression and a prognostic value of this loss of expression.


Alpharma Beef Cattle Nutrition Symposium: predictability of feedlot cattle growth performance.
Predicting performance is vital to management and marketing decisions in commercial feedlots. Agreement between performance predicted from NE equations or empirical regression relationships and actual performance is generally very good, suggesting that factors affecting performance by finishing cattle are fairly well documented. The challenge for feedlot managers is to predict performance with limited information at the start of the feeding period. Data on sex and initial shrunk BW (ISBW) are typically available when cattle start on feed. Relationships between ISBW, sex, and performance were evaluated using 3,363 pen records collected over 4 yr from 3 commercial feedlots in the Texas Panhandle. Mixed-model regression was used to account for random effects of feedlot × season × year and fixed effects of ISBW (range = 227 to 451 kg), sex (steer or heifer), and ISBW × sex (P < 0.10 for all variables evaluated). Previously developed equations indicated that with intercept and slope adjustments for sex, ISBW accounted for 76 and 84% of the variation in DMI and final shrunk BW (FSBW), respectively. Similarly, newly developed regression equations that included ISBW, sex, and ISBW × sex accounted for 46 and 81% of the variation in ADG and HCW, respectively. Initial BW was negatively related to G:F (R(2) = 0.22). Including early DMI data (DMI from d 8 to 28) increased R(2) and decreased prediction error for DMI, indicating that updating predictions with interim intake data might prove beneficial. An independent data set (781 lots of steers and heifers) collected during 1 yr from 2 Texas Panhandle feedlots was used to validate equations developed with the larger database. Dry matter intake predicted from ISBW and sex accounted for 69% of the variation in observed DMI (SE of prediction = 0.47; mean bias = 0.42 kg). Predicting DMI with ISBW, sex, and DMI from d 8 to 28 of the feeding period increased r(2) to 0.76 and slightly decreased the SE of prediction (0.42 kg), but the equation had a strong linear bias (-0.174; P < 0.001). The r(2) values for regression of observed on predicted ADG, G:F, FSBW, and HCW were 0.37, 0.08, 0.74, and 0.73, respectively, with positive mean bias (underprediction for all equations). Average daily gain calculated with NE equations from predicted DMI (ISBW and sex equation) and predicted FSBW had a similar r(2) (0.38) but less mean bias (-0.08 kg) than ADG predicted directly from ISBW and sex. Adjustments to equations for animal type, health, and management effects would likely improve predictions. Nonetheless, results suggest that predicting performance from initial BW with adjustments for steers vs. heifers should have considerable utility in practical settings.


Employee Sleep and Workplace Health Promotion: A Systematic Review.
Workplace-based employee health promotion programs often target weight loss or physical activity, yet there is growing attention to sleep as it affects employee health and performance. The goal of this review is to systematically examine workplace-based employee health interventions that measure sleep duration as an outcome. We conducted systematic searches in PubMed, Web of Knowledge, EMBASE, Scopus, and PsycINFO (n = 6177 records). To be included in this systematic review, studies must include (1) individuals aged >18 years, (2) a worker health-related intervention, (3) an employee population, and (4) sleep duration as a primary or secondary outcome. Twenty studies met criteria. Mean health promotion program duration was 2.0 months (standard deviation [SD] = 1.3), and mean follow-up was 5.6 months (SD = 6.5). The mean sample size of 395 employees (SD = 700.8) had a mean age of 41.5 years (SD = 5.2). Measures of sleep duration included self-report from a general questionnaire (n = 12, 66.6%), self-report based on Pittsburgh Sleep Quality Index (n = 4, 22.2%), and self-report and actigraphy combined (n = 5, 27.7%). Studies most commonly included sleep hygiene (35.0%), yoga (25.0%), physical activity (10.0%), and cognitive-behavioral therapy for insomnia (10.0%) interventions. Across the interventions, 9 different behavior change techniques (BCTs) were utilized; the majority of interventions used 3 or fewer BCTs, while 1 intervention utilized 4 BCTs. Study quality, on average, was 68.9% (SD = 11.1). Half of the studies found workplace-based health promotion program exposure was associated with a desired increase in mean nightly sleep duration (n = 10, 50.0%). Our study findings suggest health promotion programs may be helpful for increasing employee sleep duration and subsequent daytime performance.


Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity.
To review doxorubicin-induced cardiotoxicity and to evaluate the use of dexrazoxane in its prevention. All animal and human reports involving doxorubicin-induced cardiac adverse effects were searched using MEDLINE combined with a fan search of relevant papers. Animal, in vitro cellular, and human data are thoroughly reviewed with particular emphasis on doxorubicin-induced cardiotoxicity, including clinical manifestations, risk factors, and mechanisms of toxicity. The role of dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity is reviewed, including mechanism of effect, animal data, and human trials. Anthracyclines are associated with a cumulative, dose-dependent, irreversible cardiomyopathy that can lead to congestive heart failure and death. The incidence of cardiotoxicity rises sharply at a total lifetime dose of more than 550 mg/m2. Through its semiquinone metabolite, doxorubicin appears to generate superoxide anion and superhydroxide free radicals with iron as a cofactor. Because of poor myocardial concentrations of superoxide dismutase, catalase, and glutathione peroxidase, these free radicals cause extensive lipid peroxidation and mitochondrial destruction. Dexrazoxane is hydrolyzed to its active form intracellularly and binds iron to prevent the formation of superhydroxide radicals, thus preventing mitochondrial destruction. The effect of dexrazoxane on the prevention of doxorubicin-induced cardiotoxicity is impressive in both animal and human studies. Further research is needed to clearly demonstrate the effect dexrazoxane has on the antitumor effects of combination chemotherapy while defining optimal dosing strategies to minimize myelosuppression and maximize cardioprotection.


Food Insecurity and Body Mass Index: A Longitudinal Mixed Methods Study, Chelsea, Massachusetts, 2009-2013.
Cross-sectional studies show an association between food insecurity and higher body mass index (BMI), but this finding has not been evaluated longitudinally. Patient perspectives on food choice in resource-constrained environments are not well understood. The objective of this study was to evaluate the longitudinal association between food insecurity and BMI. This mixed methods study used both a retrospective matched cohort and focus groups. For the quantitative analysis, all patients in a community health center who reported food insecurity from October 2009 through March 2010 (n = 457) were followed through August 2013 and compared with controls matched by age, sex, and race/ethnicity (n = 1,974). We evaluated the association between food insecurity and change in BMI by using linear, mixed effects longitudinal models. The qualitative analysis included patients with food insecurity, stratified by BMI. Qualitative data were analyzed by using open coding and grounded theory. The mean age of participants was 51 years; 61% were women, and 73% were Hispanic. Baseline BMI was similar in food insecure participants and matched controls. After adjustment in longitudinal analyses, food insecurity was associated with greater increase in BMI (0.15 kg/m(2) per year more than controls, P < .001). Themes identified in 4 focus groups included attitudes and knowledge about food, food access, and food practices. Participants with BMI of 30 kg/m(2) or less highlighted skills such as budgeting and portion control. Food insecurity is associated with increase in BMI. The skills of food insecure participants who were not obese, such as portion control and budgeting, may be useful in weight management interventions for vulnerable patients.


Regulation of glycolysis in rat aorta.
Certain factors that might contribute to the regulation of the rate of glycolysis by rat aorta were investigated. Rat aortic rings were incubated with [14C]glucose, and the release of [14C]lactate was determined. There was good agreement between the lactate production estimated by enzymatic assay and by [14C]lactate release, suggesting that almost all the lactate produced under our experimental conditions was derived from exogenous glucose. When the glucose concentration in the medium was 10 mM or higher, the rate of glucose transport did not limit the rate of lactate production. In most cases studies were done both aerobically and anaerobically. In Hanks' Balanced Salt Solution the aerobic rate of lactate production was 18% of the anaerobic rate. We tested the effects on glycolysis of agents that alter ATP generation by mitochondria or ATP splitting by Na+-K+-ATPase or the mitochondrial ATPase. Under aerobic conditions, ouabain (5 mM) caused a 54% decrease in lactate production, and gramicidin (5 micrograms/ml) caused a 45% increase. Under anaerobic conditions, neither ouabain nor gramicidin affected lactate production. Aerobically dinitrophenol (25 microM) and carboxyatractyloside (0.5 mM) caused substantial increases in lactate production, 72 and 98% respectively. Under anaerobic conditions the effects of dinitrophenol and carboxyatractyloside were much smaller, with dinitrophenol causing a 15% increase and carboxyatractyloside a 12% decrease in lactate production. Increasing the concentration of phosphate in the incubation medium caused marked increases in lactate production. Both aerobically and anaerobically, shifting from 1.3 to 50 mM phosphate in the incubation medium caused a 3.5-fold increase in lactate production.(ABSTRACT TRUNCATED AT 250 WORDS)


Myocardial disease, anemia, and erythrocyte-stimulating proteins in chronic kidney disease.
The combination of heart failure and chronic kidney disease (CKD) has received comparatively little attention in terms of clinical research versus investigations of each state individually. It has been known for over a decade that anemia, a cardinal feature of CKD, is associated with higher cardiovascular event rates in late-stage and end-stage renal disease. Although the biological mechanisms linking anemia, renal failure, and heart failure are incompletely understood, more prevalent anemia is consistent in patients with more severe heart failure and is associated with higher mortality rates. Impaired erythropoietin production and resistance to erythropoietin are major contributors to anemia in patients with heart failure. By targeting hemoglobin levels in anemic patients with CKD, through the use of recombinant erythropoietin (epoetin) therapy, it has been hoped that anemia, CKD, and heart failure outcomes can be improved. Darbepoetin alfa was engineered to contain more N-linked carbohydrate chains than erythropoietin, and has an approximately 3 times longer serum half-life. Several clinical trials have addressed the hypothesis that darbepoetin alfa can effectively treat renal anemia at dose frequencies of once per week, or less often, with positive outcomes.


Rational Design of Porous Conjugated Polymers and Roles of Residual Palladium for Photocatalytic Hydrogen Production.
Developing highly efficient photocatalyts for water splitting is one of the grand challenges in solar energy conversion. Here, we report the rational design and synthesis of porous conjugated polymer (PCP) that photocatalytically generates hydrogen from water splitting. The design mimics natural photosynthetics systems with conjugated polymer component to harvest photons and the transition metal part to facilitate catalytic activities. A series of PCPs have been synthesized with different light harvesting chromophores and transition metal binding bipyridyl (bpy) sites. The photocatalytic activity of these bpy-containing PCPs can be greatly enhanced due to the improved light absorption, better wettability, local ordering structure, and the improved charge separation process. The PCP made of strong and fully conjugated donor chromophore DBD (M4) shows the highest hydrogen production rate at ∼33 μmol/h. The results indicate that copolymerization between a strong electron donor and weak electron acceptor into the same polymer chain is a useful strategy for developing efficient photocatalysts. This study also reveals that the residual palladium in the PCP networks plays a key role for the catalytic performance. The hydrogen generation activity of PCP photocatalyst can be further enhanced to 164 μmol/h with an apparent quantum yield of 1.8% at 350 nm by loading 2 wt % of extra platinum cocatalyst.


The groES and groEL heat shock gene products of Escherichia coli are essential for bacterial growth at all temperatures.
The products of the groES and groEL genes of Escherichia coli, constituting the groE operon, are known to be required for growth at high temperature (42 degrees C) and are members of the heat shock regulon. Using a genetic approach, we examined the requirement for these gene products for bacterial growth at low temperature (17 to 30 degrees C). To do this, we constructed various groES groEL heterodiploid derivative strains. By inactivating one of the groE operons by a polar insertion, it was shown by bacteriophage P1 transduction that at least one of the groE genes was essential for growth at low temperature. Further P1 transduction experiments with strains that were heterodiploid for only one of the groE genes demonstrated that both groE gene products were required for growth at low temperature, which suggested a fundamental role for the groE proteins in E. coli growth and physiology.


Contribution of the Juxtatransmembrane Intracellular Regions to the Time Course and Permeation of ATP-gated P2X7 Receptor Ion Channels.
P2X7 receptors are ATP-gated ion channels that contribute to inflammation and cell death. They have the novel property of showing marked facilitation to repeated applications of agonist, and the intrinsic channel pore dilates to allow the passage of fluorescent dyes. A 60-s application of ATP to hP2X7 receptors expressed in Xenopus oocytes gave rise to a current that had a biphasic time course with initial and secondary slowly developing components. A second application of ATP evoked a response with a more rapid time to peak. This facilitation was reversed to initial levels following a 10-min agonist-free interval. A chimeric approach showed that replacement of the pre-TM1 amino-terminal region with the corresponding P2X2 receptor section (P2X7-2Nβ) gave responses that quickly reached a steady state and did not show facilitation. Subsequent point mutations of variant residues identified Asn-16 and Ser-23 as important contributors to the time course/facilitation. The P2X7 receptor is unique in having an intracellular carboxyl-terminal cysteine-rich region (Ccys). Deletion of this region removed the secondary slowly developing current, and, when expressed in HEK293 cells, ethidium bromide uptake was only ∼5% that of WT levels, indicating reduced large pore formation. Dye uptake was also reduced for the P2X7-2Nβ chimera. Surprisingly, combination of the chimera and the Ccys deletion (P2X7-2NβdelCcys) restored the current rise time and ethidium uptake to WT levels. These findings suggest that there is a coevolved interaction between the juxtatransmembrane amino and carboxyl termini in the regulation of P2X7 receptor gating.


Explaining the social gradient in sickness absence: a study of a general working population in Sweden.
Some previous studies have proposed potential explanatory factors for the social gradient in sickness absence. Yet, this research area is still in its infancy and in order to comprise the full range of socioeconomic positions there is a need for studies conducted on random population samples. The main aim of the present study was to investigate if somatic and mental symptoms, mental wellbeing, job strain, and physical work environment could explain the association between low socioeconomic position and belonging to a sample of new cases of sick-listed employees. This study was conducted on one random working population sample (n = 2763) and one sample of newly sick-listed cases of employees (n = 3044), drawn from the same random general population in western Sweden. Explanatory factors were self-rated 'Somatic and mental symptoms', 'Mental well-being', 'job strain', and 'physical work conditions' (i.e. heavy lifting and awkward work postures). Multiple logistic regression analyses were used. Somatic and mental symptoms, mental well-being, and job strain, could not explain the association between socioeconomic position and sickness absence in both women and men. However, physical work conditions explained the total association in women and much of this association in men. In men the gradient between Non-skilled manual OR 1.76 (1.24;2.48) and Skilled manual OR 1.59 (1.10;2.20), both in relation to Higher non-manual, remained unexplained. The present study strengthens the scientific evidence that social differences in physical work conditions seem to comprise a key element of the social gradient in sickness absence, particularly in women. Future studies should try to identify further predictors for this gradient in men.


Impact of co-occurring substance use on 6 month outcomes for young people seeking mental health treatment.
Co-occurring substance use and mental health disorders are highly prevalent among young people attending services, yet few studies have examined the effect of such comorbidity among those referred for treatment. The aim of the current study was to examine the impact of co-occurring substance use disorders (SUDs) on 6 month outcomes for young people seeking mental health treatment. One hundred and six young people (aged 15-24 years) with a non-psychotic DSM-IV Axis I disorder were assessed following referral to a specialist youth public mental health service. Participants were given a structured interview, as well as questionnaires assessing drug use, psychopathology, psychosocial functioning and self-esteem at baseline and 6 month follow up. At baseline, 23 participants met criteria for a co-occurring SUD and 83 had a non-psychotic Axis I disorder. Both the non-SUD and the co-occurring SUD groups had high levels of psychopathology, serious impairments in functioning and moderate levels of suicidal ideation, although those with co-occurring SUD had significantly poorer levels of functioning. At 6 month follow up the co-occurring SUD group continued to experience substantial problems with symptoms and functioning whereas the non-SUD group had significant improvement in both of these domains. The present findings are consistent with studies examining the impact of co-occurring substance use and mental health issues across different treatment settings, and reinforce recommendations that young people with co-occurring disorders require more intensive and integrated interventions. The present findings also highlight the need for routine assessment and management of substance use issues within youth mental health settings.


Immunohistochemical demonstration of sensory nerve fibers and endings in lumbar intervertebral discs of the rat.
Although it is accepted that the intervertebral disc has a sensory component, it has not been previously shown by any specific method. Immunoreactivity of the physiologically active neuropeptide, calcitonin gene-related peptide (CGRP), was used as a specific marker of sensory nerve fibers and their endings in the intervertebral disc of the rat. In this study, positive fiber immunoreactivity was taken as an indication that those fibers were of sensory, and not sympathetic, origin. Immunoreactivity was found in the outer annulus fibrosus of all intervertebral discs studied. The CGRP-like immunoreactivity was also found in structures that resembled nerve endings. To the authors' knowledge, this is the first report presenting detailed positive evidence of sensory fibers and their endings in the lumbar intervertebral disc of any mammalian species.