Changes in myocardial collagen content before and after left ventricular assist device application in dilated cardiomyopathy.
The purposes of this study were to confirm the changes in myocardial collagen level after left ventricular assist device (LVAD) support in dilated cardiomyopathy (DCM), find the relation between these changes and prognosis, and test a practical method to assess the level of myocardial collagen. Left ventricular samples were collected from DCM patients with different prognosis (transplanted group n = 8, weaning group n = 10) at the time when the LVADs were implanted and again during cardiac transplantation (n = 8). The level of neutral salt soluble collagen (NSC) and acid soluble collagen (ASC) was measured by Sircol collagen assay, and that of total collagen and insoluble collagen (ISC) by quantification of hydroxyproline (Hyp). Serum samples were collected from a portion of these patients (transplanted group, n = 6; weaning group n = 7) at the time the LVADs were implanted, 1 month after implantation and on explantation. Circulating concentration of carboxy-terminal propeptide of type I procollagen (P I CP), amino-terminal propeptide of type I procollagen (P I NP), amino-terminal propeptide of type III procollagen (P III NP) and type I collagen telopeptide (I CTP) were measured by the equilibrium type radioimmunoassay. Before LVAD implantation the level of NSC and ISC in the weaning group was higher but ASC in the transplanted group was lower than in the controls (P < 0.05). After LVAD support, the level of total collagen was higher, but ASC was also lower in the transplanted group than in the controls (P < 0.05). In comparison of the pre- and post-LVAD subgroups of the transplanted and weaning groups, all collagen fraction levels before LVAD implantation were lower in the transplanted group than in the weaning group (P < 0.05); but this difference disappeared after LVAD support. Comparison of the pre- and post-LVAD subgroups of the transplanted group showed increased level of NSC and total collagen after LVAD support. The changes of serum peptide concentration showed that P III NP increased constantly in the transplanted group, but P I CP and P I NP increased in the weaning group after LVAD implantation. The changes in myocardial collagen level as a sign of myocardial interstitial remodeling in DCM are not involved with total collagen but involved with collagen fractions, and they are related to prognosis. The changes of myocardial collagen content and serum procollagen peptide after LVAD support can be regarded as an expression of the reverse of maladaptive myocardial interstitial remodeling.


CORROBORATION OF RECENT MODELS OF THE GAMMA-G IMMUNOGLOBULIN MOLECULE.
The relationships between the polypeptide chains of gammaG immunoglobulin and fragments of the molecule produced by papain and pepsin have been investigated. Specific procedures were employed including peptide mapping of tryptic hydrolysates and analysis of molecules reconstituted from chains labeled with different iodine isotopes. By these means, the Fab fragment was shown unequivocally to consist of the light chain and a portion of the heavy chain, the Fd fragment. The Fc fragment was found to be comprised of the residual portions of the heavy chain. These findings support the gross arrangement of chains embodied in recent models of the gammaG immunoglobulin molecule. The present studies have also provided additional information on the susceptibility of gammaG immunoglobulin to proteolytic cleavage. It was found that the portion of heavy chains corresponding to the Fd fragment was extensively cleaved by papain.


Endogenous prostacyclin synthesis is decreased during activation of the renin-angiotensin system in man.
Prostacyclin has been implicated as a mediator of renin release, whereas angiotensin II evokes prostaglandin I2 (PGI2) release from both vascular and nonvascular tissues in vitro. The physiological significance of these observations was assessed by measurement of an index of endogenous prostacyclin biosynthesis in human volunteers during varied activation of the renin-angiotensin system secondary to manipulation of dietary sodium. Excretion of the major urinary metabolite of prostacyclin in man, 2,3-dinor-6-keto-PGF1 alpha (PGI-M), fell from 295 +/- 51 to 176 +/- 35 (+/- SEM) ng g creatinine-1 (P less than 0.01) in 10 normal subjects when sodium intake was decreased from 150 to 10 meq/day. In five patients with primary hyperaldosteronism, PGI-M fell from 199 +/- 34 ng g creatinine-1 preoperatively to 120 +/- 26 pg/mg creatinine-1 after removal of the adenoma. In such patients, the reduction in PGI-M was associated with a significant increase in PRA. Thus, in both normal subjects and patients with hyperaldosteronism, PGI-M excretion fell rather than increased with activation of the renin-angiotensin system. This suggests that systemic biosynthesis of PGI2 is unrelated to renin release and that angiotensin II is unlikely to stimulate endogenous prostacyclin biosynthesis under these conditions in man.


Insight into binding of phosphodiesterase-9A selective inhibitors by crystal structures and mutagenesis.
PDE9 inhibitors have been studied as therapeutics for treatment of cardiovascular diseases, diabetes, and neurodegenerative disorders. To illustrate the inhibitor selectivity, the crystal structures of the PDE9A catalytic domain in complex with the enantiomers of PDE9 inhibitor 1-(2-chlorophenyl)-6-(3,3,3-trifluoro-2-methylpropyl)-1H-pyrazolo[3,4-d]pyrimidine-4(5H)-one ((R)-BAY73-6691 or (S)-BAY73-6691, 1r or 1s) were determined and mutagenesis was performed. The structures showed that the fluoromethyl groups of 1r and 1s had different orientations while the other parts of the inhibitors commonly interacted with PDE9A. These differences may explain the slightly different affinity of 1r (IC(50) = 22 nM) and 1s (IC(50) = 88 nM). The mutagenesis experiments revealed that contribution of the binding residues to the inhibitor sensitivity varies dramatically, from few-fold to 3 orders of magnitude. On the basis of the crystal structures, a hypothesized compound that simulates the recently published PDE9 inhibitors was modeled to provide insight into the inhibitor selectivity.


Streamlined Protein-Protein Interface Loop Mimicry.
Cyclic peptides comprising endocyclic organic fragments, "cyclo-organopeptides", can be probes for perturbing protein-protein interactions (PPIs). Finding loop mimics is difficult because of high conformational variability amongst targets. Backbone Matching (BM), introduced here, helps solve this problem in the illustrative cases by facilitating efficient evaluation of virtual cyclo-organopeptide core-structure libraries. Thus, 86 rigid organic fragments were selected to build a library of 602 cyclo-organopeptides comprising Ala and organic parts: "cyclo-{-(Ala)n -organo-}". The central hypothesis is "hit" library members have accessible low energy conformers corresponding to backbone structures of target protein loops, while library members which cannot attain this conformation are probably unworthy of further evaluation. BM thereby prioritizes candidate loop mimics, so that less than 10 cyclo-organopeptides are needed to be prepared to find leads for two illustrative PPIs: iNOS ⋅ SPSB2, and uPA ⋅ uPAR.


Comparative studies on the chemical composition and pharmacological effects of vinegar-processed antler glue modified from Lei Gong Pao Zhi Lun and traditional water-processed antler glue.
Antler glue is a classic medicinal to enhance sexual function in traditional Chinese medicine (TCM), which was first recorded in Shen Nong Ben Cao Jing (Shennong's Classic of the Materia Medica). Vinegar-processing is a classic method of processing traditional Chinese medicine. The method of preparing antler glue by boiling antlers in vinegar and then concentrating them is recorded in Lei Gong Pao Zhi Lun (Master Lei's Discourse on Medicinal Processing). In modern times, the typical processing method of antler glue is water extraction and concentration. However, it is not clear whether there is a difference in the effect of these two processing methods on the chemical composition and pharmacological activity of antler glue. The Chinese Pharmacopoeia (2020) records that the processing method of antler glue is water extraction and concentration. But Lei Gong Pao Zhi Lun differs in Chinese Pharmacopoeia (2020), which records the processing method of vinegar extraction and concentration. The effect of the two processing methods on antler glue's chemical composition and pharmacological activity is unknown. So this study aimed to elucidate the difference between different processing methods on the chemical composition and the treatment effect on oligoasthenospermia of antler glue. So the automatic amino acid analyzer is used to determine the amino acid content of two different processing methods of antler glue. Proteomics was performed to detect the protein components of two different processing methods of antler glue and analyze them. Cyclophosphamide-induced mice models of oligoasthenospermia were used to study the different pharmacological effects of antler glue in two different processing methods. An automatic sperm analyzer observed the quantity and quality of sperm in mice epididymis. Serum sex hormone testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in mice were tested using the enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin-eosin (H&E) staining was used to analyze pathological alterations in mouse testicular tissue. The transcriptome has been used to reveal the potential mechanism of antler glue in treating oligoasthenospermia. Mitochondrial complex activity assay kits were used to assay the activity of mitochondrial respiratory chain complex I-V in mouse testicular tissue. Western blot was used to determine the expression of related proteins in mouse testicular tissue. Vinegar-processing can increase the alanine, proline, and glycine content in antler glue, reduce the length of protein peptides in antler glue, and produce a variety of unique proteins. Vinegar-processed antler glue (VAG) increased sperm density, sperm survival, sperm viability, and serum sex hormone levels in oligozoospermic mice. It reversed testicular damage caused by cyclophosphamide, and the effects were differently superior to those of water-processed antler glue (WAG). In addition, transcriptomics and related experiments have shown that VAG can increase the expression of Ndufa2, Uqcr11, Cox6b1, and Atp5i genes and proteins in mouse testis, thus promoting adenosine diphosphate (ATP) synthesis by increasing the activity of mitochondrial respiratory chain complexes I, III, IV and V. By promoting the oxidative phosphorylation process to produce more ATP, VAG can achieve the therapeutic effect of oligoasthenospermia. Vinegar-processing method can increase the content of active ingredients in antler glue. VAG increases ATP levels in the testes by promoting the process of oxidative phosphorylation to treat oligozoospermia.


Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries.
We have accumulated information of the coding sequences of uncharacterized human genes, which are known as KIAA genes, and the number of these genes exceeds 2000 at present. As an extension of this sequencing project, we recently have begun to accumulate mouse KIAA-homologous cDNAs, because it would be useful to prepare a set of human and mouse homologous cDNA pairs for further functional analysis of the KIAA genes. We herein present the entire sequences of 400 mouse KIAA cDNA clones and 4 novel cDNA clones which were incidentally identified during this project. Most of clones entirely sequenced in this study were selected by computer-assisted analysis of terminal sequences of the cDNAs. The average size of the 404 cDNA sequences reached 5.3 kb and that of the deduced amino acid sequences from these cDNAs was 868 amino acid residues. The results of sequence analyses of these clones showed that single mouse KIAA cDNAs bridged two different human KIAA cDNAs in some cases, which indicated that these two human KIAA cDNAs were derived from single genes although they had been supposed to originate from different genes. Furthermore, we successfully mapped all the mouse KIAA cDNAs along the genome using a recently published mouse genome draft sequence.


DIAGNOcam--a Near Infrared Digital Imaging Transillumination (NIDIT) technology.
In developed countries, clinical manifestation of carious lesions is changing: instead of dentists being confronted with wide-open cavities, more and more hidden caries are seen. For a long time, the focus of the research community was on finding a method for the detection of carious lesions without the need for radiographs. The research on Digital Imaging Fiber-Optic Transillumination (DIFOTI) has been an active domain. The scope of the present article is to describe a novel technology for caries diagnostics based on Near Infrared Digital Imaging Transillumination (NIDIT), and to give first examples of its clinical indications. In addition, the coupling of NIDIT with a head-mounted retinal image display (RID) to improve clinical workflow is presented. The novel NIDIT technology was shown to be useful as a diagnostic tool in several indications, including mainly the detection of proximal caries and, less importantly, for occlusal caries, fissures, and secondary decay around amalgam and composite restorations. The coupling of this technology with a head-mounted retinal image system allows for its very efficient implementation into daily practice.


Back to School: An Updated Evaluation of the Effectiveness of a Long-Term Trap-Neuter-Return Program on a University's Free-Roaming Cat Population.
A growing body of evidence indicates that trap-neuter-return (TNR) is not only effective at reducing community cat numbers, but that such reductions are sustainable over extended periods. Recently, a series of peer-reviewed articles documenting long-term declines in community cat populations associated with TNR have been published. The present study adds to this pool of evidence by updating and reexamining results reported from the campus of the University of Central Florida (UCF) in 2003 by Levy et al. From 1991 to 2019, a total of 204 cats were enrolled in a volunteer-run TNR program on the university grounds; 10 cats (5%) remained on site at the conclusion of the present study. The campus community cat population declined by 85% between 1996, the year an initial census (indicating the presence of 68 cats) was completed, and 2019. In addition, 11 of 16 total colonies were eliminated over a 28-year period. These results occurred despite significant growth in enrollment at UCF over the same time frame, which suggests that with sufficient ongoing management of colony sites, declines in community cat populations associated with TNR are sustainable over long periods and under varying conditions.


Association of kidney function and uncarboxylated matrix Gla protein: data from the Heart and Soul Study.
Vascular calcification is highly prevalent in persons with chronic kidney disease (CKD) and predicts cardiovascular disease (CVD) events. Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification, and lower levels of its precursor-uncarboxylated MGP (ucMGP)--are associated with vascular calcification and atherosclerosis. Whether mild to moderate decrements in kidney function are associated with lower serum ucMGP is unknown. In a cross-sectional study among 842 outpatients with stable CVD, estimated glomerular filtration rate (eGFR), serum cystatin-C and urine albumin-to-creatinine ratio (ACR) were measured and serum ucMGP levels were determined by ELISA. Multivariate linear regression evaluated the association of each kidney function measure with serum ucMGP levels. The mean eGFR was 76 +/- 23 mL/min/1.73 m(2), and 186 subjects (22%) had moderate CKD (eGFR <60 mL/min/1.73 m(2)). The mean +/- SD ucMGP level was 3289 +/- 1177 nM. In unadjusted analysis, each 10 mL/ min/1.73 m(2) lower eGFR was associated with 101 nM lower ucMGP level. This association was only minimally attenuated in final multivariate models wherein each 10 mL/ min/1.73 m(2) lower eGFR was associated with 79 nM lower ucMGP (95% confidence interval [CI]; 44 to 115; P < 0.001) after adjustment for age, sex, race, body mass index, blood pressure, smoking, hypertension, diabetes; and serum albumin, calcium, phosphorus, and fetuin-A levels. Similarly, in models adjusted for identical covariates, each 0.1 mg/L higher cystatin-C was associated with 39 nM lower ucMGP (95% CI 23 to 55; P < 0.001). In contrast, no significant association was observed between ACR and ucMGP in either unadjusted or adjusted analyses (adjusted P = 0.17). All associations were similar among subjects with or without diabetes (P-values for interaction > 0.50). Among outpatients with stable CVD, a reduced glomerular filtration rate is associated with a decreased serum ucMGP level. In contrast, ACR is not associated with ucMGP levels. Whether ucMGP is a useful marker of vascular calcification and CVD event risk in persons with CKD deserves future study.


Construction and analysis of a suppression subtractive hybridization library of regeneration-related genes in soybean.
The development of a genetic transformation system is needed to address the problem of the low efficiency associated with soybean regeneration. To contribute to the enhancement of the soybean regenerative capacity, we explored the developmental mechanisms of soybean regeneration at the molecular level using a suppression subtractive hybridization cDNA library constructed from cotyledonary nodes of soybean cultivar DN50. A total of 918 positive clones were identified and screened, with most inserted fragments ranging from 100 to 750 bp. Of these, 411 differentially expressed functional expressed sequence tags were identified and annotated based on their similarity to orthologs and paralogs detected in GenBank using the nucleotide and translated nucleotide Basic Local Alignment Search Tools. Functional analysis revealed that the associated genes were involved in signal transduction, synthesis, and metabolism of macromolecules, glucose and protein synthesis and metabolism, light and leaf morphogenesis, regulation of apoptosis, cell defense, cell wall differentiation, and a variety of hormone and cytokinin-mediated signaling pathways. The information uncovered in our study should serve as a foundation for the establishment of an efficient and stable genetic transformation system for soybean regeneration.


Impairment of Retinoic Acid Signaling in Cornelia de Lange Syndrome Fibroblasts.
Cornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting the neurodevelopment, gastrointestinal, musculoskeletal systems. CdLS is caused by mutations within NIPBL, SMC1A, SMC3, RAD21, and HDAC8 genes. These genes codify for the "cohesin complex" playing a role in chromatid adhesion, DNA repair and gene expression regulation. The aim of this study was to investigate retinoic acid (RA) signaling pathway, a master developmental regulator, in CdLS cells. Skin biopsies from CdLS patients and healthy controls were cultured and derived primary fibroblast cells were treated with RA or dimethyl sulfoxide (vehicle). After RA treatment, cells were harvested and RNA was isolated for quantitative real-time polymerase chain reaction experiments. We analyzed several components of RA metabolism in a human cell line of kidney fibroblasts (293T), in addition to fibroblasts collected from both NIPBL-mutated patients and healthy donors, with or without RA treatment. In all cases, ADH and RALDH1 gene expression was not affected by RA treatment, while CRABP1 was induced. CRABP2 was dramatically upregulated upon RA treatment in healthy donors but not in CdLS patients cells. We investigated if CdLS alterations are associated to perturbation of RA signaling. Cells derived from CdLS patients do not respond to RA signaling as efficiently as healthy controls. RA pathway alterations suggest a possible underlying mechanism for several cellular and developmental abnormalities associated with cohesin function. Birth Defects Research 109:1268-1276, 2017. © 2017 Wiley Periodicals, Inc.


Evaluating the systemic right ventricle by CMR: the importance of consistent and reproducible delineation of the cavity.
The method used to delineate the boundary of the right ventricle (RV), relative to the trabeculations and papillary muscles in cardiovascular magnetic resonance (CMR) ventricular volume analysis, may matter more when these structures are hypertrophied than in individuals with normal cardiovascular anatomy. This study aimed to compare two methods of cavity delineation in patients with systemic RV. Twenty-nine patients (mean age 34.7 +/- 12.4 years) with a systemic RV (12 with congenitally corrected transposition of the great arteries (ccTGA) and 17 with atrially switched (TGA) underwent CMR. We compared measurements of systemic RV volumes and function using two analysis protocols. The RV trabeculations and papillary muscles were either included in the calculated blood volume, the boundary drawn immediately within the apparently compacted myocardial layer, or they were manually outlined and excluded. RV stroke volume (SV) calculated using each method was compared with corresponding left ventricular (LV) SV. Additionally, we compared the differences in analysis time, and in intra- and inter-observer variability between the two methods. Paired samples t-test was used to test for differences in volumes, function and analysis time between the two methods. Differences in intra- and inter-observer reproducibility were tested using an extension of the Bland-Altman method. The inclusion of trabeculations and papillary muscles in the ventricular volume resulted in higher values for systemic RV end diastolic volume (mean difference 28.7 +/- 10.6 ml, p < 0.001) and for end systolic volume (mean difference 31.0 +/- 11.5 ml, p < 0.001). Values for ejection fraction were significantly lower (mean difference -7.4 +/- 3.9%, p < 0.001) if structures were included. LV SV did not differ significantly from RV SV for both analysis methods (p = NS). Including structures resulted in shorter analysis time (p < 0.001), and showed better inter-observer reproducibility for ejection fraction (p < 0.01). The choice of method for systemic RV cavity delineation significantly affected volume measurements, given the CMR acquisition and analysis systems used. We recommend delineation outside the trabeculations for routine clinical measurements of systemic RV volumes as this approach took less time and gave more reproducible measurements.


Genetic organization of the broad-host-range IncP-1 plasmid R751.
We have identified regions encoding conjugal transfer, plasmid maintenance, and trimethoprim resistance on the IncP-1 plasmid R751 by complementation tests with cloned deoxyribonucleic acid fragments and self-replicating derivatives constructed in vitro. The genes for replication and transfer show a scattered organization similar to that previously determined for RK2, another IncP-1 plasmid. Derivatives of RK2 are able to complement R751 derivatives defective in these functions. Restriction enzyme cleavage sites in R751 deoxyribonucleic acid are clustered in regions of the plasmid physical map. Neither region is required for plasmid maintenance or transfer, although one determines resistance to trimethoprim. A similar clustering of cleavage sites is seen with RK2, which nevertheless has a very different restriction map.


Psychosocial and physical work environment, and risk of pelvic pain in pregnancy. A study within the Danish national birth cohort.
The sparse knowledge of the aetiology of pelvic pain in pregnancy makes evidence based prevention a limited option. The aim of this study was to examine the relation between pelvic pain in pregnancy and physical and psychosocial working conditions. This study used self reported data on working conditions for 1219 cases and 1539 controls, sampled as a nested case-control study within the Danish national birth cohort. Cases and controls were selected on the basis of self reported pelvic pain intensity, pain localisation, and pain impact on daily living activities. Exposure data were collected prospectively; early in pregnancy and before the onset of pelvic pain. Main outcome measures were odds ratios for pelvic pain in pregnancy as a function of physical and psychosocial working conditions. Pregnant women with fixed evening work and with rotating shifts (without night shift) had odds ratios for pelvic pain in pregnancy of 1.76 (95% confidence intervals 1.04 to 2.96) and 1.65 (1.22 to 2.24), respectively, compared with women with day work. Physically strenuous work was associated with an almost 50% increased risk of pelvic pain in pregnancy (1.47; 1.17 to 1.84). In women who were under high psychosocial strain at work odds ratio was 1.39 (1.12 to 1.74) compared with women with low job strain. Both physically and psychosocially demanding working conditions, measured by physically strenuous work, rotating shifts, and high job strain, are associated with an increased reporting of pelvic pain in pregnancy.


[The evolution of use of anti-Parkinson drugs in Spain].
In recent years new anti Parkinson drugs have been marketed and there has been controversy over the safety of some drugs. To analyze the evolution of the consumption of anti Parkinson drugs and the effect of the newer drugs. A study of the consumption of anti Parkinson drugs (1989 1998). Data were obtained from the ECOM database of the Ministry of Health and TEMPUS of the National Statistics Institute. The drugs were classified using the Anatomo Therapeutic Clinical Classification (ATC). Consumption was expressed in defined daily dosage (DDD) and the costs in euros. The drugs marketed since 1990 were classified as new drugs and the others as classical drugs. The total consumption of drugs increased from 1.92 DDD/1,000 inhabitants/day in 1989 to 3.64 DDD/1,000 inhabitants/day in 1998. The drugs showing the greatest increase were selegiline, pergolide and levodopa. The total pharmaceutical expenses tripled. There was a smaller increase in the consumption of new drugs (1.2% of the total in 1991 and 6.6% in 1998) than in their costs (6.7% of the total in 1991 and 38.8% in 1998). The cost per DDD of the new drugs increased five times (1989: 2.55 euros and 1998: 13.59 euros) and that of the classical drugs was similar (1989: 0.54 euros and 1998: 0.62 euros). The total consumption of anti Parkinson drugs has progressively increased. The consumption of selegiline has also increased in spite of controversy over its safety. The new drugs have a major economic effect.


Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells.
Epidemiological studies suggest that consumption of vegetables rich in the xanthophylls lutein (LUT) and zeaxanthin (ZEA) reduces the risk for developing age-related cataract, a leading cause of vision loss. Although LUT and ZEA are the only dietary carotenoids present in the lens, direct evidence for their photoprotective effect in this organ is not available. The present study examined the effects of xanthophylls and alpha-tocopherol (alpha-TC) on lipid peroxidation and the mitogen-activated stress signaling pathways in human lens epithelial (HLE) cells following ultraviolet B light (UVB) irradiation. When presented with LUT, ZEA, astaxanthin (AST), and alpha-TC as methyl-beta-cyclodextrin complexes, HLE cells accumulated the lipophiles in a concentration- and time-dependent manner with uptake of LUT exceeding that of ZEA and AST. Pretreatment of cultures with either 2 micromol/L xanthophyll or 10 micromol/L alpha-TC for 4 h before exposure to 300 J/m(2) UVB radiation decreased lipid peroxidation by 47-57% compared with UVB-treated control HLE cells. Pretreatment with the xanthophylls and alpha-TC also inhibited UVB-induced activation of c-JUN NH(2)-terminal kinase (JNK) and p38 by 50-60 and 25-32%, respectively. There was substantial inhibition of UVB-induced JNK and p38 activation for cells containing <0.20 and approximately 0.30 nmol xanthophylls/mg, respectively, whereas >2.3 nmol alpha-TC/mg protein was required to significantly decrease UVB-induced stress signaling. These data suggest that xanthophylls are more potent than alpha-TC for protecting human lens epithelial cells against UVB insult.


Effects of Narrowband Light on Choroidal Thickness and the Pupil.
To determine the effects of narrowband light exposure on choroidal thickness and the pupil response in humans. Twenty subjects, ages 21 to 43 years, underwent 1 hour of exposure to broadband, short wavelength "blue," or long wavelength "red" light, or darkness. Choroidal thickness, imaged with spectral domain optical coherence tomography, axial length, determined from biometry, and rod/cone- and intrinsically photosensitive retinal ganglion cell-driven pupil responses were measured before and after exposure. Pupil stimuli were six 1 second alternating red (651 nm) and blue (456 nm) stimuli, 60 seconds apart. Pupil metrics included maximum constriction and the 6 second post-illumination pupil response (PIPR). Compared with before exposure, the choroid significantly thinned after broadband light, red light, and dark exposure (all P < 0.05), but not after blue light exposure (P = 0.39). The maximum constriction to 1 second red stimuli significantly decreased after all light exposures (all P < 0.001), but increased after dark exposure (P = 0.02), compared with before exposure. Maximum constriction and 6-second PIPR to 1 second blue stimuli significantly decreased after all light exposures compared with before exposure (all P < 0.005), with no change after dark exposure (P > 0.05). There were no differences in axial length change or 6-second PIPR to red stimuli between exposures. Narrowband blue and red light exposure induced differential changes in choroidal thickness. Maximum constriction, a function of rod/cone activity, and the intrinsically photosensitive retinal ganglion cell-mediated PIPR were attenuated after all light exposures. Findings demonstrate differing effects of short-term narrowband light and dark exposure on the choroid, rod/cone activity, and intrinsically photosensitive retinal ganglion cells.


Supermarket sales data: feasibility and applicability in population food and nutrition monitoring.
Population food and nutrition monitoring plays a critical role in understanding suboptimal nutrition at the population level, yet current monitoring methods such as national surveys are not practical to undertake on a continuous basis. Supermarket sales data potentially address this gap by providing detailed, timely, and inexpensive monitoring data for informing policies and anticipating trends. This paper reviews 22 studies that used supermarket sales data to examine food purchasing patterns. Despite some methodological limitations, feasibility studies showed promising results. The potential and limitations of using supermarket sales data to supplement food and nutrition monitoring methods are discussed.


Acute mitral regurgitation from ruptured chordae tendineae in systemic lupus erythematosus.
A patient with systemic lupus erythematosus developed acute mitral regurgitation due to ruptured chordae tendineae, requiring mitral valve replacement. Typical changes of Libman-Sacks endocarditis were observed in the excised mitral valve. Immunofluorescent studies revealed antinuclear antibody and deposits of immunoglobulins and complement within small vessels.


[Length of stay and length of work incapacity in patients with Type I diabetes. Effects of a diabetes treatment and education program].
Objective data on duration of hospital stay and of incapacity to work were collected for 137 type I diabetics who had taken part in a structured diabetes treatment and training scheme. Before the training period the average hospital stay had been 0.76 per patient per year, duration per stay 21 days, number of episodes of work incapacity 1.6 per patient per year, duration of incapacity 23.6 days. For a subgroup of patients (62) the influence of the training programme could be demonstrated: hospital stay fell to 0.49 per patient per year, duration per stay to 12.0 days, number of incapacity episodes to 1.4 per patient per year, and the days lost from work to 12.1 per patient per year.


LIGHT is dispensable for CD4+ and CD8+ T cell and antibody responses to influenza A virus in mice.
The tumor necrosis factor family ligands, LIGHT (lymphotoxin like, exhibits inducible expression and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes), 4-1BBL and CD70, are found in the same gene cluster on mouse chromosome 17. Although the roles of 4-1BB-4-1BBL and CD27-CD70 interactions in anti-viral T cell responses have been well established, the role of LIGHT in T cell activation/expansion in vivo is less clear. Under conditions that were previously employed to demonstrate a role for 4-1BBL in CD8+ T cell memory, wild-type and LIGHT-/- mice were infected with influenza A virus and primary and memory/recall responses were measured at various time points thereafter. Neither primary expansion nor memory/recall CD8+ T cell responses were affected by the absence of LIGHT, as measured up to 2 months post-infection. CD4+ T cell responses were also unaffected by LIGHT deficiency. Furthermore, we found that LIGHT played no role in the induction of influenza-specific IgG1 and IgG2a serum antibodies. Taken together, these data suggest that LIGHT is dispensable for the acquired immune response to influenza virus in mice with no effect on the induction, maintenance or reactivation of CD8+ T cell memory.


Structure of the AlaX-M trans-editing enzyme from Pyrococcus horikoshii.
The editing domain of alanyl-tRNA synthetase (AlaRS) contributes to high-fidelity aminoacylation by hydrolyzing (editing) the incorrect products Ser-tRNA(Ala) and Gly-tRNA(Ala) (cis-editing). The AlaX protein shares sequence homology to the editing domain of AlaRS. There are three types of AlaX proteins, with different numbers of amino-acid residues (AlaX-S, AlaX-M and AlaX-L). In this report, AlaX-M from Pyrococcus horikoshii is shown to deacylate Ser-tRNA(Ala) and Gly-tRNA(Ala) (trans-editing). The crystal structure of P. horikoshii AlaX-M has been determined at 2.7 A resolution. AlaX-M consists of an N-terminal domain (N-domain) and a C-terminal domain (C-domain). A zinc ion is coordinated by the conserved zinc-binding cluster in the C-domain, which is expected to be the enzymatic active site. The glycine-rich motif, consisting of successive conserved glycine residues in the N-domain, forms a loop (the 'glycine-rich loop'). The glycine-rich loop is located near the active site and may be involved in substrate recognition and/or catalysis.


The development of the atrioventricular bundle and its branches in the avian heart.
A light microscopic study of serial sections of the hearts of 64 avian embryos (chicken, turkey, duck and goose) was undertaken in order to elucidate the development of the atrioventricular bundle and its branches. The developing atrioventricular bundle and its branches were shown to appear simultaneously (at about a third of the way through incubation) as relatively large, discrete fasciculi, which were dark-staining when compared with developing cardiac muscle. Prior to the appearance of the bundle and branches, the developing conducting tissue was found to be present as a widespread precursor tissue, which was distributed as a complete, dark-staining subendocardial sleeve, lining the whole of the ventricular canal, ventriculobulbar loop, and extending into the common atrial cavity. From these observations, it is concluded that, with septation and chamber formation, the tissue of the sleeve is partly incorporated within the chamber walls to give origin to diffuse Purkinje tissue, and is partly retained as the bundle and branches. The manner of derivation of the bundle and branches is discussed, and it is stressed that the definitive positions of the bundle and branches denote the junctional zones of the components of septation.


Diacylglycerol kinases are essential for hepatocyte growth factor-dependent proliferation and motility of Kaposi's sarcoma cells.
Hepatocyte growth factor (HGF) is involved in the pathogenesis of Kaposi's sarcoma (KS), the most frequent neoplasia in patients with AIDS, characterized by proliferating spindle cells, infiltrating inflammatory cells, angiogenesis, edema, and invasiveness. In vitro, this factor sustains the biological behavior of KS derived cells, after activation of its receptor and the downstream MAPK and AKT signals. In other cell types, namely endothelial and epithelial cells, movement, proliferation, and survival stimulated by HGF and other growth factors and cytokines depend on diacylglycerol kinases (DGK). In an effort to identify new intracellular transducers operative in KS cells, which could represent therapeutic targets, we investigated the role of DGK in KS cell movement and proliferation by treating cells with the DGK pharmacological inhibitor R59949. We report that R59949 strongly inhibits HGF-induced KS motility, proliferation, and anchorage-independent growth with only a partial effect on cell adhesion and spreading. R59949 does not affect cell survival, HGF receptor activation, or the classical MAPK and AKT signalling pathways. Furthermore, we carried out an siRNA screen to characterize the DGK isoforms involved in KS motility and anchorage independent growth. Our data indicate a strong involvement of DGK-δ in KS motility and of DGK-ι in anchorage-independent growth. These results indicate that DGK inhibition is sufficient to impair in vitro KS cell proliferation and movement and suggest that selected DGK represent new pharmacological targets to interfere with the malignant properties of KS, independently from the well-known RAS/MAPK and PI3K/AKT pathways.


[Liquid perfluorocarbon in treatment of giant tears].
In 20 cases of giant tears with considerable proliferative changes, vitreoretinal silicone-oil-surgery was performed. With liquid perfluorocarbon, the involuted retina could easily be fixed during the operation in its former position without difficulties, before silicone oil as a permanent tamponade was used. The good results prove that more invasive manipulations, which were formerly necessary, become superfluous using this method.


Cell Adhesion Molecule CD166 Drives Malignant Progression and Osteolytic Disease in Multiple Myeloma.
Multiple myeloma is incurable once osteolytic lesions have seeded at skeletal sites, but factors mediating this deadly pathogenic advance remain poorly understood. Here, we report evidence of a major role for the cell adhesion molecule CD166, which we discovered to be highly expressed in multiple myeloma cell lines and primary bone marrow cells from patients. CD166+ multiple myeloma cells homed more efficiently than CD166- cells to the bone marrow of engrafted immunodeficient NSG mice. CD166 silencing in multiple myeloma cells enabled longer survival, a smaller tumor burden, and less osteolytic lesions, as compared with mice bearing control cells. CD166 deficiency in multiple myeloma cell lines or CD138+ bone marrow cells from multiple myeloma patients compromised their ability to induce bone resorption in an ex vivo organ culture system. Furthermore, CD166 deficiency in multiple myeloma cells also reduced the formation of osteolytic disease in vivo after intratibial engraftment. Mechanistic investigation revealed that CD166 expression in multiple myeloma cells inhibited osteoblastogenesis of bone marrow-derived osteoblast progenitors by suppressing Runx2 gene expression. Conversely, CD166 expression in multiple myeloma cells promoted osteoclastogenesis by activating TRAF6-dependent signaling pathways in osteoclast progenitors. Overall, our results define CD166 as a pivotal director in multiple myeloma cell homing to the bone marrow and multiple myeloma progression, rationalizing its further study as a candidate therapeutic target for multiple myeloma treatment. Cancer Res; 76(23); 6901-10. ©2016 AACR.


Feasibility of a Weight Management Program Tailored for Overweight Men with Localized Prostate Cancer - A Pilot Study.
Overweight men with prostate cancer are more likely to suffer from recurrence and death following prostatectomy compared with healthy weight men. This study tested the feasibility of delivering a comprehensive program to foster weight loss before and weight maintenance after surgery in overweight men with localized prostate cancer. Twenty overweight men scheduled for prostatectomy elected either the intervention (n = 15) or the nonintervention (n = 5). Anthropometrics, biomarkers, diet quality, nutrition literacy, quality of life, and long-term follow-up were assessed in both groups. The intervention led to 5.55 kg of weight loss including 3.88 kg of fat loss from baseline to surgery (mean = 8.3 weeks). The intervention significantly increased fiber, protein, fruit, nut, and vegetable intake; and decreased trans fats intake during weight loss. The intervention significantly reduced insulin, C-peptide, systolic blood pressure, leptin:adiponectin ratio, and visceral adiposity compared to the nonintervention. Post-surgically, weight loss was maintained. Changes in lipid profiles, nutrition literacy, and follow-up were not statistically significant in either group. Significant weight loss (≥5%) is feasible with a coaching intervention in overweight men preparing for prostatectomy and is associated with favorable cardiometabolic effects. This study is registered under NCT02252484 (www.clinicaltrials.gov).


The choice of anaesthetic--sevoflurane or propofol--and outcome from cancer surgery: a retrospective analysis.
Commonly used inhalational hypnotics, such as sevoflurane, are pro-inflammatory, whereas the intravenously administered hypnotic agent propofol is anti-inflammatory and anti-oxidative. A few clinical studies have indicated similar effects in patients. We examined the possible association between patient survival after radical cancer surgery and the use of sevoflurane or propofol anaesthesia. Demographic, anaesthetic, and surgical data from 2,838 patients registered for surgery for breast, colon, or rectal cancers were included in a database. This was record-linked to regional clinical quality registers. Cumulative 1- and 5-year overall survival rates were assessed using the Kaplan-Meier method, and estimates were compared between patients given propofol (n = 903) or sevoflurane (n = 1,935). In a second step, Cox proportional hazard models were calculated to assess the risk of death adjusted for potential effect modifiers and confounders. Differences in overall 1- and 5-year survival rates for all three sites combined were 4.7% (p = 0.004) and 5.6% (p < 0.001), respectively, in favour of propofol. The 1-year survival for patients operated for colon cancer was almost 10% higher after propofol anaesthesia. However, after adjustment for several confounders, the observed differences were not statistically significant. Propofol anaesthesia might be better in surgery for some cancer types, but the retrospective design of this study, with uneven distributions of several confounders, distorted the picture. These uncertainties emphasize the need for a randomized controlled trial.


The extent of genome flux and its role in the differentiation of bacterial lineages.
Horizontal gene transfer (HGT) and gene loss are key processes in bacterial evolution. However, the role of gene gain and loss in the emergence and maintenance of ecologically differentiated bacterial populations remains an open question. Here, we use whole-genome sequence data to quantify gene gain and loss for 27 lineages of the plant-associated bacterium Pseudomonas syringae. We apply an extensive error-control procedure that accounts for errors in draft genome data and greatly improves the accuracy of patterns of gene occurrence among these genomes. We demonstrate a history of extensive genome fluctuation for this species and show that individual lineages could have acquired thousands of genes in the same period in which a 1% amino acid divergence accrues in the core genome. Elucidating the dynamics of genome fluctuation reveals the rapid turnover of gained genes, such that the majority of recently gained genes are quickly lost. Despite high observed rates of fluctuation, a phylogeny inferred from patterns of gene occurrence is similar to a phylogeny based on amino acid replacements within the core genome. Furthermore, the core genome phylogeny suggests that P. syringae should be considered a number of distinct species, with levels of divergence at least equivalent to those between recognized bacterial species. Gained genes are transferred from a variety of sources, reflecting the depth and diversity of the potential gene pool available via HGT. Overall, our results provide further insights into the evolutionary dynamics of genome fluctuation and implicate HGT as a major factor contributing to the diversification of P. syringae lineages.


Influence of multiple organ dysfunction syndrome on duration of critical illness and hospitalization.
Multiple organ dysfunction syndrome (MODS) is the leading cause of death in the general surgery intensive care unit (SICU). The development of MODS is a powerful predictor of prolonged SICU stay in survivors and nonsurvivors of critical illness, but its relation to less severe illness and briefer duration of care is unknown. To determine the relation between modest degrees of MODS and length of stay in the SICU and hospital and whether daily MOD score calculations can distinguish survivors from nonsurvivors before the SICU stay becomes prolonged. An SICU of a university tertiary care medical center. Prospective inception-cohort study. Illness severity data were collected in retrospect only for the calendar year 1991. Of 2646 consecutive patients studied, 115 stayed in the SICU more than 21 days. Acute Physiology and Chronic Health Evaluation (APACHE) II and III scores were calculated after 24 hours, with daily and cumulative MOD scores (0-4 points for 6 organs, 24 points maximum). Patients were followed up until hospital discharge or death. Data analysis was performed by unpaired 2-tailed t test, exact contingency analysis for multiple groups, univariate 1- or 2-way analysis of variance with repeated measures, or linear or polynomial regression tests as appropriate, alpha = .05. The mean (+/-SEM) age of the patients was 65 +/- 1 years; mean (+/-SEM) APACHE II score, 13.8 +/- 0.2; APACHE III score, 44.2 +/- 0.7; incidence of MODS, 1173 of 2646 patients, 44.3%; and hospital mortality rate, 9.2%. Cumulative MOD scores correlated closely with SICU length of stay in survivors, especially for SICU stays of less than 10 days (R2 = 0.99, P < .001). Similar correlations existed between the prevalence of MODS related to the increasing length of the SICU stay (R2 = 0.98, P < .001) and between the length of hospital stay and the cumulative MOD score (R2 = 0.79, P < .05). Daily MOD scores in patients whose SICU stay was more than 21 days distinguished survivors from nonsurvivors by day 2 of the SICU stay (P < .05) and thereafter. Modest degrees of MODS correlate closely with the duration of care in less severely ill patients. Early identification and daily quantitation of MODS may help identify patients at risk for prolonged illness and death. Prevention of outcomes that contribute to organ dysfunction is critical for reduction of length of stay and cost of care.


Introduction to the special issue on the scientific assessment of biomeasures in the Panel Study of Income Dynamics.
This special issue of Biodemography and Social Demography assesses the value to social science and health research of incorporating biomeasures in a social survey. The focus is on the Panel Study of Income Dynamics (PSID), an ongoing, nationally representative panel study of U.S. households. A brief description of the PSID and the features that make it a promising survey for biomeasures is provided along with an overview of each individual article. Seven of the nine articles cover a major health domain: fatness and obesity, metabolic syndrome and cardiovascular disease, infectious disease, inflammation and immune function and cardiovascular disease, daily stress exposure and reactivity, respiratory health, and genetics. These articles describe the scientific rationale for collecting data in each domain as well as the specific biological samples or measurements needed to assess the domain, potential respondent burden, ethical- and legal issues, fieldwork logistics, and costs. The final two articles address a pair of overarching issues: one provides international comparisons and perspectives and the other discusses ethical and legal concerns.


First Streptococcus agalactiae isolates highly resistant to quinolones, with point mutations in gyrA and parC.
Three isolates of Streptococcus agalactiae highly resistant to multiple fluoroquinolones were isolated in Japan. Compared with susceptible strains of S. agalactiae, these quinolone-resistant strains had double point mutations within the quinolone resistance-determining regions of gyrA and parC; Ser-81 was changed to Leu (TCA --> TTA) in the amino acid sequence deduced from gyrA, and Ser-79 was changed to Phe (TCC --> TTC) in the amino acid sequence deduced from parC. Comparative sequence analysis revealed the possibility of gene transfer between S. agalactiae and another beta-hemolytic streptococcus, Streptococcus difficile.


Small-sized, flat-type invasive branch duct intraductal papillary mucinous neoplasm: a case report.
Recent improvements in diagnostic modalities are increasing the frequency of detection of small-sized branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). International consensus guidelines for IPMN recommend surveillance without immediate resection for small-sized (<3 cm) BD-IPMNs without malignant features on imaging. Our patient is the first to have undergone resection of a small-sized BD-IPMN containing invasive cancer, but without malignant features on imaging. We herein report a case involving a 70-year-old man with a small cystic lesion in the pancreas head detected by health screening ultrasonography. Detailed examination revealed that the cystic lesion was a BD-IPMN measuring about 2 cm, with no malignant features. However, cytological examination of the pancreatic juice showed atypical cells with high-grade dysplasia storing intracytoplasmic mucin, indicating malignant BD-IPMN. Pathological examination of the resected specimen showed a BD-IPMN measuring 16 mm with an associated invasive carcinoma that invaded the pancreatic parenchyma over a distance of 11 mm. In this patient, invasive cancer was present within a small BD-IPMN with no high-risk stigmata on imaging. Cytological examination of the pancreatic juice allowed for the detection of pancreatic cancer in such a small-sized IPMN. Although routine endoscopic retrograde cholangiopancreatography (ERCP) with cytology is not recommended in all patients with BD-IPMNs, ERCP may contribute to the detection of small pancreatic cancers in select cases. Accumulation of cases of pancreatic cancer within small BD-IPMNs may help establish the indications for ERCP with cytological examination for the purpose of early detection of small pancreatic cancer.


Evaluation of laboratory coagulation and lytic parameters resulting from autologous whole blood transfusion during primary aortocoronary artery bypass grafting.
To determine if autologous blood reinfusion influences overall hemostatic function following aortocoronary artery bypass graft (CABG) surgery, and if so, where the predominant area of this influence lies. Prospective, with control values on each patient. Cardiac operating room of a major university-affiliated county hospital. 20 patients undergoing elective CABG surgery. Following heparinization, and prior to cardiopulmonary bypass (CPB), venous blood (average 4.9 ml/kg) was removed via an indwelling internal jugular catheter into a preservative-free plastic transfer pack unit and stored without agitation at room temperature. This autologous whole blood was reinfused after systemic protamine reversal of heparin. Blood samples for analysis were drawn immediately before and 5 minutes after completion of the reinfusion. Autologous blood reinfusion appears to be significantly related to increased hemoglobin, hematocrit, platelet count, fibrinogen, plasminogen, and antiplasmin levels. The prothrombin time and activated partial thromboplastin times decreased significantly, whereas activated clotting times and D-dimer levels were unchanged. Significant increases occurred in the following thromboelastography parameters: maximum amplitude, amplitude 60 minutes after the maximum amplitude, and whole blood clot lysis index. Reaction time and coagulation time were not statistically different from control values. Significant improvements in coagulation and lytic parameters occur following CPB after the infusion of autologous blood. These improvements in coagulation indices may be the result of the infused blood or hemoconcentration, which is also known to occur during this period. Additional control studies are needed to differentiate these effects.


Percutaneous ethanol sclerotherapy of venous malformations of the tongue.
Percutaneous ethanol sclerotherapy has been reported to be efficacious for head and neck venous malformations. We sought to evaluate the safety and efficacy of percutaneous sclerotherapy by using ethanol for treatment of symptomatic venous malformations of the tongue. Eleven sclerotherapy procedures were performed in seven patients from January 1995 to February 2001. Patient age ranged from 19 months to 57 years (mean age, 32 years). Four patients were male and three were female. Mean follow-up was 36 months. The volume of ethanol used per treatment session ranged from 2 to 32 cc (mean, 16 cc). Sclerotherapy provided significant improvement or resolution of symptoms for all patients. There were no major complications. One patient had a small (3 x 2 cm) area of skin blistering at the injection site. All patients experienced pain and swelling to a variable degree. Sclerotherapy resulted in resolution of symptoms in six of seven patients. Three patients had resolution of symptoms after one procedure. Four patients each underwent two sclerotherapy procedures. One patient who remained symptomatic but improved after undergoing two procedures underwent an anterior glossectomy and is now asymptomatic. Percutaneous ethanol sclerotherapy is a safe and effective method of treating symptomatic venous malformations of the tongue.


Prediction of grief and HIV/AIDS-related burnout in volunteers.
Burnout in volunteer workers in the HIV/AIDS area results in the loss of dedicated personnel, consequently straining the HIV/AIDS care delivery system. By assessing the predictors of burnout and grief this study describes the role of grief in HIV/AIDS volunteer burnout. Voluntary and anonymous questionnaires were sent to members of the Foundation for Interfaith Research and Ministry (FIRM), a multi-religious organization formed to provide volunteer work in HIV/AIDS care facilities around Houston, Texas. In 174 valid responses, grief was measured against work characteristics, burnout, rewards, stressors, and the general health questionnaire (GHQ). No significant relationship was found between grief and burnout; however, burnout in volunteers may be different from that in health care professionals for the following reasons: (1) volunteers choose to work in the HIV/AIDS area; (2) they have control over the time they spend volunteering; (3) volunteers are internally motivated to work in the HIV/AIDS area; and (4) if the volunteers do not enjoy the work, they can terminate their involvement with minimal cost. The best univariate predictors of grief are time spent as a volunteer and volunteer hours per week, where those who spend the most hours volunteering experience less grief The Reward/Stress measures most significantly associated with grief include empathy/self-knowing reward, emotional support reward, and emotional overload stress. The strongest predictors of grief in the regression analysis, which account for 21% of the variance, were time as a volunteer, emotional support, emotional overload, GHQ-somatic symptoms, and GHQ social dysfunction. The data suggest that in order to reduce grief special attention should be paid te allowing volunteers freely to express problems with emotional overload and workload adjustments, and providing clear emotional support as a reward.


Correlates of health-related social media use among adults.
Sixty percent of Internet users report using the Internet to look for health information. Social media sites are emerging as a potential source for online health information. However, little is known about how people use social media for such purposes. The purpose of this study was two-fold: (1) to establish the frequency of various types of online health-seeking behaviors, and (2) to identify correlates of 2 health-related online activities, social networking sites (SNS) for health-related activities and consulting online user-generated content for answers about health care providers, health facilities, or medical treatment. The study consisted of a telephone survey of 1745 adults who reported going online to look for health-related information. Four subscales were created to measure use of online resources for (1) using SNS for health-related activities; (2) consulting online rankings and reviews of doctors, hospitals or medical facilities, and drugs or medical treatments; (3) posting a review online of doctors, hospitals or medical facilities, and drugs or medical treatments, and (4) posting a comment or question about health or medical issues on various social media. Univariate and multivariate logistic regression analyses were performed. Respondents consulted online rankings or reviews (41.15%), used SNS for health (31.58%), posted reviews (9.9%1), and posted a comment, question, or information (15.19%). Respondents with a chronic disease were nearly twice as likely to consult online rankings (odds ratio [OR] 2.09, 95% CI 1.66-2.63, P<.001). Lower odds of consulting online reviews were associated with less formal education (OR 0.49, 95% CI 0.37-0.65, P<.001) and being male (OR 0.71, 95% CI 0.57-0.87, P<.001). Respondents with higher incomes were 1.5 times as likely to consult online rankings or reviews (OR 1.49, 95% CI 0.10-2.24, P=.05), than respondents with a regular provider (OR 2.05, 95% CI 1.52-2.78, P<.001), or living in an urban/suburban location (OR 1.61, 95% CI 1.17-2.22, P<.001). Older respondents were less likely to use SNS for health-related activities (OR 0.96, 95% CI 0.95-0.97, P<.001), as were males (OR 0.70, 95% CI 0.56-0.87, P<.001), whereas respondents with a regular provider had nearly twice the likelihood of using SNS for health-related activities (OR 1.89, 95% CI 1.43-2.52, P<.001). People are using social media for seeking health information. However, individuals are more likely to consume information than they are to contribute to the dialog. The inherent value of "social" in social media is not being captured with online health information seeking. People with a regular health care provider, chronic disease, and those in younger age groups are more likely to consult online rankings and reviews and use SNS for health-related activities.


Brain parenchyma penetration by intrathecal ionic and nonionic contrast media.
Metrizamide, a nonionic water-soluble contrast medium, has been shown to penetrate normal brain when injected intrathecally. Recently it was suggested that the complications following intrathecal metrizamide are directly related to the cerebral concentration reached. Metrizamide, both in experimental animals and clinically, is regarded as less neurotoxic than equivalent iodine concentrations of ionic contrast media. In this study the degree and depth of brain penetration of intrathecal metrizamide and methylglucamine iothalamate (Conray 280), using a similar iodine concentration (280 mg l/ml), was compared at 1 hr in adult greyhound dogs. The depth of penetration and concentration reached in the cortical gray matter was determined by coronal computed tomographic scanning of the brain after removal. No significant difference was found between the two contrast media, suggesting that the rate of diffusion across the cerebrospinal fluid-brain interface is similar and that the difference in neurotoxicity is not explained by a reduced concentration of contrast medium in the case of nonionic metrizamide, when compared with ionic methylglucamine iothalamate. Using Evans blue as a qualitative marker, no evidence of gross blood-brain disruption was demonstrated in the area of maximum penetration with either contrast medium.


Role of intravascular ultrasound in patients with acute myocardial infarction undergoing percutaneous coronary intervention.
Stent thrombosis and restenosis remain drawbacks of drug-eluting stents in patients with acute myocardial infarction (AMI). Intravascular ultrasound (IVUS) guidance for stent deployment helps optimize its results in stable patients. The aim of this study was to examine the utility of routine IVUS guidance in patients with AMI undergoing percutaneous coronary intervention (PCI). Employing data from Korea Acute Myocardial Infarction Registry (KAMIR), we analyzed 14,329 patients with AMI from April 2006 through September 2010. Patients with cardiogenic shock and rescue PCI after thrombolysis were excluded. Clinical outcomes of 2,127 patients who underwent IVUS-guided PCI were compared to those of 8,235 patients who did not. Mean age was 63.6 ± 13.5 years and 72.3% were men. Patients undergoing IVUS-guided PCI were younger, more often men, more hyperlipemic, and had increased body mass index and left ventricular ejection fraction. Number of treated vessels and stents used, stent length, and stent diameter were increased in the IVUS-guided group. Multivessel involvement was less frequent and American College of Cardiology/American Heart Association type C lesion was more frequent in the IVUS-guided group. Drug-eluting stents were more frequently used compared to bare-metal stents in the IVUS group. There was no significant relation of stent thrombosis between the 2 groups. Twelve-month all-cause death was lower in the IVUS group. After multivariate analysis and propensity score adjustment, IVUS guidance was not an independent predictor for 12-month all-cause death (hazard ratio 0.212, 0.026 to 1.73, p = 0.148). In conclusion, this study does not support routine use of IVUS guidance for stent deployment in patients who present with AMI and undergo PCI.


Protection of LPS-induced murine acute lung injury by sphingosine-1-phosphate lyase suppression.
A defining feature of acute lung injury (ALI) is the increased lung vascular permeability and alveolar flooding, which leads to associated morbidity and mortality. Specific therapies to alleviate the unremitting vascular leak in ALI are not currently clinically available; however, our prior studies indicate a protective role for sphingosine-1-phosphate (S1P) in animal models of ALI with reductions in lung edema. As S1P levels are tightly regulated by synthesis and degradation, we tested the hypothesis that inhibition of S1P lyase (S1PL), the enzyme that irreversibly degrades S1P via cleavage, could ameliorate ALI. Intratracheal instillation of LPS to mice enhanced S1PL expression, decreased S1P levels in lung tissue, and induced lung inflammation and injury. LPS challenge of wild-type mice receiving 2-acetyl-4(5)-[1(R),2(S),3(R),4-tetrahydroxybutyl]-imidazole to inhibit S1PL or S1PL(+/-) mice resulted in increased S1P levels in lung tissue and bronchoalveolar lavage fluids and reduced lung injury and inflammation. Moreover, down-regulation of S1PL expression by short interfering RNA (siRNA) in primary human lung microvascular endothelial cells increased S1P levels, and attenuated LPS-mediated phosphorylation of p38 mitogen-activated protein kinase and I-κB, IL-6 secretion, and endothelial barrier disruption via Rac1 activation. These results identify a novel role for intracellularly generated S1P in protection against ALI and suggest S1PL as a potential therapeutic target.


Introduction of 3D-classification and its derived surgical sequence of Schatzker type IV tibial plateau fractures.
Schatzker IV tibial plateau fractures usually have a worse prognosis due to their high variability and the accompanied bony and soft tissue injuries. This study aimed to introduce an injury mechanism-based new classification of Schatzker IV tibial plateau fractures and evaluate its reliability. Additionally, this study aimed to evaluate the outcomes of operative Schatzker IV tibial plateau fractures treated according to the surgical sequences determined by the new classification. A total of 63 cases of operative Schatzker IV tibial plateau fractures that were treated following the new surgical sequences were enrolled in our study. The CT images of these patients were reviewed and classified twice according to the new 3D classification by 4 independent observers. The reliability of the classification was calculated through kappa analysis. The classification-determined surgical sequence was evaluated by observing the postoperative efficacy during the follow-up. Both the intra-observer (the mean k = 0.897, CI 0.806-0.971) and inter-observer (the mean k = 0.883, CI 0.786-0.961) reliability of 3D-classification showed excellent agreement according to Landis and Koch. All the patients were followed up for 6-28 months (average 12.8 months). As for the evaluation of the postoperative efficacy, according to KSS, 53 cases were rated as excellent, 8 cases as good, and 2 cases as fair results. The new proposed classification showed high intra-observer and inter-observer reliability in our study. The surgical sequence determined by the classification can help surgeons to acquire good reduction and rigid internal fixation. Therefore the new classification of Schatzker IV tibial plateau fractures and the derived surgical sequences are worthy of further popularization and application in clinical trials.


A reference map of the human binary protein interactome.
Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype-phenotype relationships1,2. Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies. The integration of HuRI with genome3, transcriptome4 and proteome5 data enables cellular function to be studied within most physiological or pathological cellular contexts. We demonstrate the utility of HuRI in identifying the specific subcellular roles of protein-protein interactions. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms that might underlie tissue-specific phenotypes of Mendelian diseases. HuRI is a systematic proteome-wide reference that links genomic variation to phenotypic outcomes.


Live and let live: Residents' perspectives on alcohol and tobacco (mis)use in residential care facilities.
Alcohol and tobacco use could cause health problems in older adults. Older adults who become in need of 24/7 care due to physical and/or neurological disabilities may need to move to a Residential Care Facility (RCF). RCFs aim to provide person-centred care (PCC) to enhance quality of life (QoL) of residents. This study aims to explore perspectives of residents on alcohol and tobacco use, which is essential to provide PCC. A qualitative research design was chosen, and semi-structured interviews were conducted. Residents who use alcohol and/or tobacco and those who do not use these substances were purposively selected in two organisations on two types of units: psychogeriatric units and units providing care for residents with mainly physical disabilities. The results were analysed using thematic analysis. Thematic analysis resulted in five themes: Current use and self-reflection, knowledge and attitudes, addiction or habit, policies and availability, dependency versus autonomy. Residents in this study value their autonomy regarding alcohol and tobacco use. They experience dependency on their (in)formal caregivers to use these substances and acknowledge that their use could cause a nuisance to others, challenging the ability of caregivers to implement PCC. Future research could assess how to integrate providing PCC to residents by offering choices and autonomy, while considering the addictive component of these substances, health and safety risks for all. This study could help care professionals to become aware of the habits and wishes of residents regarding alcohol and tobacco use and to discuss the possibilities and limitations within RCFs.


Acquired immunity in experimental murine aspergillosis is mediated by macrophages.
A number of studies have substantiated the pivotal role of innate defense mechanisms in protection against invasive aspergillosis. However, experiments demonstrating increased resistance to lethal intravenous (i.v.) infection with Aspergillus fumigatus conidia in cortisone-treated or untreated mice preinfected with a sublethal dose of conidia and protection of turkeys inoculated subcutaneously with a killed A. fumigatus germling vaccine against subsequent aerosol challenge led us to speculate that acquired immunity may also contribute to host defense against Aspergillus infection. Five-week-old male BALB/c mice were inoculated i.v. with 1.0 x 10(4) viable conidia or saline and challenged i.v. with 1.0 x 10(6) conidia after 7, 15, or 21 days. No protection against challenge was found after 7 days. However, significant and reproducible protection was observed after 15 and 21 days. Mortality was reduced from 90% in control mice to 53% in preinfected mice 40 days after challenge (P = 0.0002). Increased survival was correlated with decreased content of chitin in lungs, liver, and kidneys 4 and 7 days after challenge (P < 0.05). Mice were again inoculated with 1.0 x 10(4) conidia or saline, and after 21 days, 1.0 x 10(8) or 2.0 x 10(8) splenocytes were transferred to naive syngeneic recipients; 2.0 x 10(8) immune splenocytes conferred significant protection (P = 0.0001) against i.v. challenge with 1.0 x 10(6) conidia, and mortality decreased from 83 to 48% 40 days after challenge. Transfer of immune serum offered no protection despite the presence of antibody against a hyphal homogenate of A. fumigatus, which was absent in the sera of control mice. Protection by immune splenocytes was maintained after selective depletion of T cells but was abolished after removal of plastic-adherent splenocytes. Adherent cells were characterized as macrophages by using morphological criteria, nonspecific esterase, and MAC-1 monoclonal antibody. Production of hydrogen peroxide by peritoneal and splenic macrophages from preinfected mice was the same as and lower than, respectively, that from uninfected controls. However, phagocytosis of conidia by peritoneal or splenic macrophages from mice preinfected i.v. or intratracheally was significantly increased after 2 and 3 h of coculture compared with that from uninfected animals, whereas in vitro killing of conidia by splenic macrophages was unaltered. Peritoneal or splenic macrophages from control or preinfected mice failed to kill hyphae in vitro. Killing of hyphae by polymorphonuclear leukocytes was not significantly different between mice preinfected i.v. and uninfected controls. Taken together, the results indicate that acquired immunity mediated by activated macrophages can be demonstrated in experimental murine aspergillosis.(ABSTRACT TRUNCATED AT 400 WORDS)


The value of platelet-rich plasma-derived extracellular vesicles in modern medicine.
Platelet-rich plasma (PRP) has been widely used in clinical practice. The mechanism by which PRP promotes tissue repair lies in the release of multiple growth factors upon platelet activation, which accelerates the proliferation and differentiation of repair cells and the synthesis of extracellular matrix. In recent years, as extracellular vesicles (EVs) research has increased and intensified, it has been found that EVs also play an important role in tissue repair. This article provides a comprehensive review of the role of PRP and PRP-derived extracellular vesicles (PRP-EVs) in tissue repair. It discusses the biological characteristics, extraction, identification, activation, and preservation of PRP-EVs. It also reviews their applications in orthopedics and wound repair. The article highlights the importance of PRP-EVs in modern medicine and suggests that they could be a promising natural nanocarrier.


A common, non-optimal phenotypic endpoint in experimental adaptations of bacteriophage lysis time.
Optimality models of evolution, which ignore genetic details and focus on natural selection, are widely used but sometimes criticized as oversimplifications. Their utility for quantitatively predicting phenotypic evolution can be tested experimentally. One such model predicts optimal bacteriophage lysis interval, how long a virus should produce progeny before lysing its host bacterium to release them. The genetic basis of this life history trait is well studied in many easily propagated phages, making it possible to test the model across a variety of environments and taxa. We adapted two related small single-stranded DNA phages, ΦX174 and ST-1, to various conditions. The model predicted the evolution of the lysis interval in response to host density and other environmental factors. In all cases the initial phages lysed later than predicted. The ΦX174 lysis interval did not evolve detectably when the phage was adapted to normal hosts, indicating complete failure of optimality predictions. ΦX174 grown on slyD-defective hosts which initially entirely prevented lysis readily recovered to a lysis interval similar to that attained on normal hosts. Finally, the lysis interval still evolved to the same endpoint when the environment was altered to delay optimal lysis interval. ST-1 lysis interval evolved to be ~2 min shorter, qualitatively in accord with predictions. However, there were no changes in the single known lysis gene. Part of ST-1's total lysis time evolution consisted of an earlier start to progeny production, an unpredicted phenotypic response outside the boundaries of the optimality model. The consistent failure of the optimality model suggests that constraint and genetic details affect quantitative and even qualitative success of optimality predictions. Several features of ST-1 adaptation show that lysis time is best understood as an output of multiple traits, rather than in isolation.


Epigenetic Changes as a Target in Aging Haematopoietic Stem Cells and Age-Related Malignancies.
Aging is associated with multiple molecular and functional changes in haematopoietic cells. Most notably, the self-renewal and differentiation potential of hematopoietic stem cells (HSCs) are compromised, resulting in myeloid skewing, reduced output of red blood cells and decreased generation of immune cells. These changes result in anaemia, increased susceptibility for infections and higher prevalence of haematopoietic malignancies. In HSCs, age-associated global epigenetic changes have been identified. These epigenetic alterations in aged HSCs can occur randomly (epigenetic drift) or are the result of somatic mutations in genes encoding for epigenetic proteins. Mutations in loci that encode epigenetic modifiers occur frequently in patients with haematological malignancies, but also in healthy elderly individuals at risk to develop these. It may be possible to pharmacologically intervene in the aberrant epigenetic program of derailed HSCs to enforce normal haematopoiesis or treat age-related haematopoietic diseases. Over the past decade our molecular understanding of epigenetic regulation has rapidly increased and drugs targeting epigenetic modifications are increasingly part of treatment protocols. The reversibility of epigenetic modifications renders these targets for novel therapeutics. In this review we provide an overview of epigenetic changes that occur in aging HSCs and age-related malignancies and discuss related epigenetic drugs.


Protein conformation from electron spin relaxation data.
Electron spin relaxation data from five ferric proteins are analyzed in terms of the fractal model of protein structures. Details of this model are presented. The results lead to a characterization of protein structures by a single parameter, the fractal dimension, d. This structural parameter is shown to determine the temperature dependence of the Raman electron spin relaxation rate, which varies as T3 + 2d. Computations of d are made using x-ray data for 17 proteins. The results range from d = 1.76 for lysozyme to d = 1.34 for ferredoxin. These values are compared with values of d obtained from the present electron spin relaxation data on five ferric proteins. Typical results are d = 1.34 +/- 0.06 from relaxation data and 1.34 +/- 0.05 from x-ray data for ferredoxin; d = 1.67 +/- 0.03 from relaxation data and 1.66 +/- 0.05 from x-ray data for ferricytochrome c. The data thus support the theoretical model. Applications of this spin resonance technique to the study of changes in protein conformation are discussed.


Stanford Seven-Day Physical Activity Recall questionnaire in COPD.
Quantification of daily physical activity is of clinical interest in chronic obstructive pulmonary disease (COPD). Objective measures using activity monitors may take several days to obtain reliable results. The aim of our study was to evaluate the Stanford Seven-Day Physical Activity Recall questionnaire (PAR) against the SenseWear armband (SWA) and compare its validity with three other physical activity questionnaires. 43 COPD patients wore the SWA for 7 days. Patients completed the PAR, Baecke, Physical Activity Scale for the Elderly (PASE) and Zutphen questionnaires. Spearman rank correlation, intraclass correlation coefficients (ICC) and receiver-operating characteristics (ROC) curves were used to assess the relationship between the questionnaires and SWA. Assessed by PAR, time spent at ≥3.0 metabolic equivalents (METs) correlated significantly (r=0.54, p<0.001) with equivalent measures from SWA, with an ICC of 0.40. No relationship was seen between the other questionnaires and the SWA. The PAR predicted active patients (≥30 min at ≥3.0 METs or a physical activity level (PAL) ≥1.55) and very inactive patients (PAL <1.40) with an area under ROC curve of 0.83, 0.77 and 0.70, respectively. While the PAR did not measure physical activity sufficiently accurately to make individual recommendations, it was able to identify COPD patients at extremes of the physical activity spectrum, potentially reducing the number of patients requiring direct measurement.


Dissociation of chronic vascular cell proliferation and vascular contractility after chronic cigarette smoke exposure.
In guinea pigs, chronic cigarette smoke exposure produces physiological and structural alterations in the pulmonary vasculature via unknown mechanisms. This study aimed to determine whether chronic cigarette smoke exposure can induce altered pulmonary vascular reactivity, and whether chronic smoke exposure would be associated with a continued increase in vascular cell deoxyribonucleic acid (DNA) synthesis, indicative of cell proliferation. Guinea-pigs were therefore exposed to two regimens of smoke. In the first experiment, animals were exposed once to the smoke of seven cigarettes, and sacrificed 24 h post-smoke, while in the second experiment, the guinea-pigs were exposed for 5 days each week for 4 months. Control animals were exposed to air. Lung explant preparations and computer linked image photography were utilized to determine vascular reactivity, and DNA synthesis was assessed using the 5-bromo-2'-deoxyuridine technique. Neither acute nor chronic smoke exposure affected vascular reactivity, although the older animals had lesser reactivity. In the chronically smoked animals, evidence was found of ongoing vascular DNA synthesis, and evidence of structural alterations with increased muscularization of the arterioles (34.7+/-7.6% of arterioles in control versus 62.7+/-5.5% after smoke exposure). Despite evidence of continued deoxyribonucleic acid synthesis in the peribronchiolar vessels, the alterations of vascular physiology previously found in this model cannot be ascribed to increased reactivity at this site. Instead, the chronic deoxyribonucleic acid synthesis in the arterioles adjacent to the alveolar ducts, culminating in an increased number of fully muscularized vessels, would suggest this compartment as the most probable source.


Special Supplemental Nutrition Program for Women, Infants and Children (WIC): non-discretionary funding provisions of the William F. Goodling Child Nutrition Reauthorization Act of 1998. Food and Nutrition Service, USDA. Final rule.
This final rule incorporates into the WIC program regulations numerous non-discretionary funding provisions mandated in the William F. Goodling Child Nutrition Reauthorization Act of 1998. This rule revises and expands backspend and spendforward authority, conversion of funds, multipurpose/infrastructure grants and the use of food funds for the purchase of breast pumps. The rule also revises nutrition services and administration expenditure standards and expands the timing for the use of vendor and participant collections. The provisions in this rule provide greater flexibility for State agencies in the operation of WIC program relating to funds management.


Human microparticles generated during sepsis in patients with critical illness are neutrophil-derived and modulate the immune response.
Microparticles (MPs) are 0.3 μm to 1.0 μm vesicles generated after cell activation or apoptosis that may play a role in the pathophysiology of sepsis. We sought to elucidate the role of MPs in patients with critical illness and hypothesized that MPs are generated at the site of inflammation and can modulate the immune response. Surgical patients with critical illness with ongoing sepsis were enrolled from the intensive care unit of an urban, Level I trauma center from March to June 2011. Abdominal washings and bronchoalveolar lavage fluid were collected from sites of inflammation. MPs were isolated using differential centrifugation, then characterized by flow cytometry. Immunologic assays were conducted by incubating neutrophil-derived MPs (NDMPs) with a human monocytic cell line (THP-1). A p value ≤0.05 was considered significant. MPs were absent in noninflamed foci in patients, whereas NDMPs were present in locations of inflammation. NDMPs were added to cultured THP-1 cells to quantify immunomodulatory effects. THP-1 cells were able to phagocytose NDMPs. Cells that ingested NDMPs demonstrated increased activation. In contrast, bystander THP-1 cells without ingested NDMPs demonstrated decreased activation. NDMPs are generated at the site of inflammation in patients with critical illness during sepsis. They have a divergent effect on the immune response by activating phagocytic cells and deactivating bystander cells. NDMPs may play an important role in regulating the inflammatory response to sepsis in patients with critical illness.


High-dimensional assessment of B-cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine.
Neisseria meningitidis is a globally important cause of meningitis and septicaemia. Twelve capsular groups of meningococci are known, and quadrivalent vaccines against four of these (A, C, W and Y) are available as plain-polysaccharide and protein-polysaccharide conjugate vaccines. Here we apply contemporary methods to describe B-cell responses to meningococcal polysaccharide and conjugate vaccines. Twenty adults were randomly assigned to receive either a meningococcal plain-polysaccharide or conjugate vaccine; one month later all received the conjugate vaccine. Blood samples were taken pre-vaccination and 7, 21 and 28 days after vaccination; B-cell responses were assessed by ELISpot, serum bactericidal assay, flow cytometry and gene expression microarray. Seven days after an initial dose of either vaccine, a gene expression signature characteristic of plasmablasts was detectable. The frequency of newly generated plasma cells (CXCR3+HLA-DR+) and the expression of transcripts derived from IGKC and IGHG2 correlated with immunogenicity. Notably, using an independent dataset, the expression of glucosamine (N-acetyl)-6-sulfatase was found to reproducibly correlate with the magnitude of immune response. Transcriptomic and flow cytometric data revealed depletion of switched memory B cells following plain-polysaccharide vaccine. These data describe distinct gene signatures associated with the production of high-avidity antibody and a plain-polysaccharide-specific signature, possibly linked to polysaccharide-induced hyporesponsiveness.


Multilevel modeling versus cross-sectional analysis for assessing the longitudinal tracking of cardiovascular risk factors over time.
Correlated data are obtained in longitudinal epidemiological studies, where repeated measurements are taken on individuals or groups over time. Such longitudinal data are ideally analyzed using multilevel modeling approaches, which appropriately account for the correlations in repeated responses in the same individual. Commonly used regression models are inappropriate as they assume that measurements are independent. In this tutorial, we use multilevel modeling to demonstrate its use for analysis of correlated data obtained from serial examinations on individuals. We focus on cardiovascular epidemiological research where investigators are often interested in quantifying the relations between clinical risk factors and outcome measures (X and Y, respectively), where X and Y are measured repeatedly over time, for example, using serial observations on participants attending multiple examinations in a longitudinal cohort study. For instance, it may be of interest to evaluate the relations between serial measures of left ventricular mass (outcome) and of its potential determinants (i.e., body mass index and blood pressure), both of which are measured over time. In this tutorial, we describe the application of multilevel modeling to cardiovascular risk factors and outcome data (using serial echocardiographic data as an example of an outcome). We suggest an analytical approach that can be implemented to evaluate relations between any potential outcome of interest and risk factors, including assessment of random effects and nonlinear relations. We illustrate these steps using echocardiographic data from the Framingham Heart Study with SAS PROC MIXED.


Cognitive behavioural therapy significantly reduces anxiety in patients with implanted cardioverter defibrillator compared with usual care: Findings from the Screen-ICD randomised controlled trial.
The aim of this study was to investigate the effect of a cognitive behavioural therapy intervention provided by trained cardiac nurses plus usual care compared with usual care alone in patients with an implanted cardioverter defibrillator who, prior to randomization, had presented with symptoms of anxiety measured by the Hospital Anxiety and Depression Scale. Around 20-25% of all patients with an implanted cardioverter defibrillator experience anxiety. Among these patients anxiety is associated with mortality, presumably explained by risk behaviour and activation of the autonomic nervous system. We hypothesised that cognitive behavioural therapy provided by cardiac nurses in an out-patient setting would be an effective treatment of anxiety. This was an investigator-initiated randomised clinical superiority trial with blinded outcome assessment, with 1:1 randomisation to cognitive behavioural therapy plus usual care or to usual care. The primary outcome was Hospital Anxiety and Depression Scale-Anxiety mean score at 16 weeks. Secondary outcomes included Hospital Anxiety and Depression Scale-Depression, Becks Anxiety Inventory, HeartQoL and Hamilton Anxiety Scale. Primary outcome analysis was based on the intention-to-treat principle. A total of 88 participants were included, 66% men, mean age 64.3 years and 61% had primary indication implantable cardioverter defibrillator. A significant difference after 16 weeks was found between groups: intervention group (Hospital Anxiety and Depression Scale-A mean (standard deviation) 4.95 points (3.30) versus usual care group 8.98 points (4.03) (p < 0.0001)). Cohen's d was -0.86, indicating a strong clinical effect. The effect was supported by secondary outcomes. Cognitive behavioural therapy provided by cardiac nurses to patients with a positive screening for anxiety had a statistically and clinically significant effect on anxiety compared with patients not receiving cognitive behavioural therapy.


Segment-Based Predominant Learning Swarm Optimizer for Large-Scale Optimization.
Large-scale optimization has become a significant yet challenging area in evolutionary computation. To solve this problem, this paper proposes a novel segment-based predominant learning swarm optimizer (SPLSO) swarm optimizer through letting several predominant particles guide the learning of a particle. First, a segment-based learning strategy is proposed to randomly divide the whole dimensions into segments. During update, variables in different segments are evolved by learning from different exemplars while the ones in the same segment are evolved by the same exemplar. Second, to accelerate search speed and enhance search diversity, a predominant learning strategy is also proposed, which lets several predominant particles guide the update of a particle with each predominant particle responsible for one segment of dimensions. By combining these two learning strategies together, SPLSO evolves all dimensions simultaneously and possesses competitive exploration and exploitation abilities. Extensive experiments are conducted on two large-scale benchmark function sets to investigate the influence of each algorithmic component and comparisons with several state-of-the-art meta-heuristic algorithms dealing with large-scale problems demonstrate the competitive efficiency and effectiveness of the proposed optimizer. Further the scalability of the optimizer to solve problems with dimensionality up to 2000 is also verified.


Insulin receptor expression during development and a reproductive cycle in the ovary of the mosquito Aedes aegypti.
A key tyrosine kinase receptor regulates steroidogenesis during egg maturation in the mosquito Aedes aegypti. This study examined expression patterns and phosphorylation states of the mosquito insulin receptor (MIR) in ovaries during the previtellogenic stage and a reproductive cycle. Little or no MIR protein was present until 24 h after adult eclosion, when the mature MIR appeared as a approximately 400-kDa tetrameric protein composed of two 116-kDa alpha-subunits and two 95-kDa beta-subunits. Immunocytochemistry showed that MIR was localized in the cell membranes of follicle cells surrounding the oocyte and nurse cells. Protein and mRNA transcript levels gradually increased in ovaries during the first few days after eclosion, and remained constant during previtellogenic arrest for up to 21 days. During a reproductive cycle, MIR protein levels remained constant up to 12 h post-bloodmeal (pbm). However, from 24 to 48 h pbm, during chorion deposition, the MIR protein was not detected. By 72 h pbm, after oviposition, the level of MIR protein returned to pre-bloodmeal levels. Two peaks of MIR transcript occurred in ovaries after a bloodmeal, immediately following a bloodmeal and after oviposition. MIR protein was constitutively phosphorylated on tyrosine residues at low levels during the previtellogenic arrest stage. Tyrosine phosphorylation increased three- to fourfold when ovaries were incubated with bovine insulin in vitro, and twofold when incubated with sodium orthovanadate, thus demonstrating a role for MIR in activating steroidogenesis. Notably, MIR protein and transcript were not detected in eggs, larvae, pupae, or pharate adults.


Modification of blood pressure in postmenopausal women: role of hormone replacement therapy.
The rate of hypertension increases after menopause. Whether estrogen and progesterone deficiency associated with menopause play a role in determining a worst blood pressure (BP) control is still controversial. Also, studies dealing with the administration of estrogens or hormone therapy (HT) have reported conflicting evidence. In general it seems that, despite some negative data on subgroups of later postmenopausal women obtained with oral estrogens, in particular conjugated equine estrogens (CEE), most of the data indicate neutral or beneficial effects of estrogen or HT administration on BP control of both normotensive and hypertensive women. Data obtained with ambulatory BP monitoring and with transdermal estrogens are more convincing and concordant in defining positive effect on BP control of both normotensive and hypertensive postmenopausal women. Overall progestin adjunct does not hamper the effect of estrogens. Among progestins, drospirenone, a spironolactone-derived molecule, appears to be the molecule with the best antihypertensive properties.


Effects of date palm pollen on fertility: research proposal for a systematic review.
Over 10-15% of couples in different countries are infertile. Male infertility is a contributing factor and the only cause of infertility in respectively 50% and 20-30% of all cases of infertility. According to previous research, micro-elements isolated from date palm pollen (DPP), e.g. estrogen and sterols, may enhance male and female fertility. DPP has also been reported to improve sperm parameters including sperm motility and viability, acrosome reaction, and lipid peroxidation. This article may justify the need for a future systematic review and meta-analysis about the effects of DPP on the reproductive system and DPP's ability to enhance fertility. It will then describe the methodology of such a study. A comprehensive search of relevant randomized and quasi-randomized controlled trials will be performed in MEDLINE, EMBASE, Web of Science, Cochrane Central, ProQuest, and Google Scholar databases. Two authors will independently assess the eligibility of the studies and consult the third author in cases of disagreement. The risk of bias of the randomized controlled trials and animal studies will be evaluated using the Cochrane risk of bias tool and the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, respectively. This study will raise no ethical issues as it will review the findings of previous research. The results are intended to be published in a peer-reviewed medical journal.


[Reinfusion of blood in combined trauma of hollow abdominal organs].
The authors performed 122 blood reinfusions in patients with trauma to the chest and abdomen, in 25 of them with associated injury to the hollow abdominal organs. The mean volume of blood loss was 2225 ml, that of reinfusion--1092 ml. Nine patients died, 6 developed complications. The authors substantiate the tactics of transfusion therapy in massive hemoperitoneum in patients with associated trauma to the hollow abdominal organs.


Implementation of an advance directives program in an HMO.
In 1992, Group Health Association (GHA), an HMO in the Washington, DC, metropolitan area, under the auspices of its Ethics Forum, undertook a major and ongoing project to educate its medical staff and patient members about the advantages and uses of advance directives. The following article describes how this project was implemented.


Fatal encephalopathy due to Lagochilascaris minor infection.
A 14-year-old boy with a tetralogy of Fallot showed a subacute, progressive encephalopathy characterized by headache, stupor and coma. Death occurred three months after the beginning of the illness. Neuropathologic examination revealed diffuse foci of necrosis of the cerebral hemispheres and cerebellum, and the presence of the nematode Lagochilascaris minor in the parenchyma and in the cisterns at the base of the brain. In almost all 28 cases of human lagochilascaris previously reported, the worms were located in the soft tissues of the neck and throat, tonsils, mastoids and paranasal sinuses. This is the first reported case in which Lagochilascaris infected the brain. Since the life cycle of the worm is unknown the pathogenesis of the central nervous system lesions is obscure.


Genetic control of oral susceptibility to infection of Culicoides variipennis with bluetongue virus.
A family selection scheme, based on the progeny from individual females, was used to select several families of the insect vector Culicoides variipennis that were resistant or susceptible to oral infection with bluetongue virus. Genetic crosses between families showed results consistent with control by a single genetic locus (blu). Reciprocal crosses suggested a maternal effect in which the genotype of the mother determined the phenotype of the offspring. The dominant and recessive natures of the resistant (blu(r)) and susceptible (blu(s)) alleles were determined by the sex of the parent. The results provide the first evidence to suggest a genetic locus controlling insect vector competence for infection with an arbovirus.