Psychosocial impact of visual impairment in working-age adults.
To review the evidence for the presence of lower levels of psychosocial well-being in working-age adults with visual impairment and for interventions to improve such levels of psychosocial well-being. Systematic review of quantitative studies published in English from 2001 to July 2008 that measured depression/mental health, anxiety, quality of life, social functioning or social support. Included were 29 studies that measured one or more outcomes (N = 52). Working-age adults with visual impairment were significantly more likely to report lower levels of mental health (mean difference = 14.51/100), social functioning (MD = 11.55/100) and quality of life. Studies regarding the prevalence of depressive symptoms produced inconsistent results but had methodological limitations. Future research is required into the prevalence of loneliness, anxiety and depression in adults with visual impairment, and to evaluate the effectiveness of interventions for improving psychosocial well-being such as counselling, peer support and employment programmes.


Brain morphometry and cognition in young adults born small for gestational age at term.
To examine brain volumes and cortical surface area and thickness and to relate these brain measures to cognitive function in young adults born small for gestational age (SGA) at term compared with non-SGA control patients. This population-based follow-up study at age 20 years included 58 term-born SGA (birth weight <10th percentile, mean: 2915 g) and 81 non-SGA controls (birth weight ≥ 10th percentile, mean: 3707 g). Brain volumes and cortical surface area and thickness were investigated with magnetic resonance imaging, which was successfully obtained in 47 SGA patients and 61 control patients. Cognitive function was assessed using the Wechsler Adult Intelligence Scale, 3rd edition. A subgroup analysis was performed in the SGA group among subjects diagnosed with fetal growth restriction (FGR) based on repeated fetal ultrasound measurements. The SGA group showed regional reductions in cortical surface area, particularly in the frontal, parietal, and temporal lobes. Total brain volume, cortical gray matter, cerebral white matter, and putamen volumes were reduced in the SGA group compared with control patients, but there were no differences in specific subcortical brain structure volumes when correcting for intracranial volume. Reductions were most pronounced among SGA subjects with FGR. No associations were found between brain measures and IQ measures in either group. Young adults born SGA at term show a global reduction in brain volume as well as regional reductions in cortical surface area. We speculate whether these reductions may be confined to those exposed to FGR. None of the brain measures correlated with cognition.


PECTIN ACETYLESTERASE9 Affects the Transcriptome and Metabolome and Delays Aphid Feeding.
The plant cell wall plays an important role in damage-associated molecular pattern-induced resistance to pathogens and herbivorous insects. Our current understanding of cell wall-mediated resistance is largely based on the degree of pectin methylesterification. However, little is known about the role of pectin acetylesterification in plant immunity. This study describes how one pectin-modifying enzyme, PECTIN ACETYLESTERASE 9 (PAE9), affects the Arabidopsis (Arabidopsis thaliana) transcriptome, secondary metabolome, and aphid performance. Electro-penetration graphs showed that Myzus persicae aphids established phloem feeding earlier on pae9 mutants. Whole-genome transcriptome analysis revealed a set of 56 differentially expressed genes (DEGs) between uninfested pae9-2 mutants and wild-type plants. The majority of the DEGs were enriched for biotic stress responses and down-regulated in the pae9-2 mutant, including PAD3 and IGMT2, involved in camalexin and indole glucosinolate biosynthesis, respectively. Relative quantification of more than 100 secondary metabolites revealed decreased levels of several compounds, including camalexin and oxylipins, in two independent pae9 mutants. In addition, absolute quantification of phytohormones showed that jasmonic acid (JA), jasmonoyl-Ile, salicylic acid, abscisic acid, and indole-3-acetic acid were compromised due to PAE9 loss of function. After aphid infestation, however, pae9 mutants increased their levels of camalexin, glucosinolates, and JA, and no long-term effects were observed on aphid fitness. Overall, these data show that PAE9 is required for constitutive up-regulation of defense-related compounds, but that it is not required for aphid-induced defenses. The signatures of phenolic antioxidants, phytoprostanes, and oxidative stress-related transcripts indicate that the processes underlying PAE9 activity involve oxidation-reduction reactions.


Optical distortion evaluation of an aerodynamically heated window using the interfacial fluid thickness concept.
The interfacial fluid thickness (IFT) concept was used to develop a harmonic-mean refractive index gradient magnitude threshold to retrieve the high refractive index gradient regions of an aerodynamically heated window. The retrieved high-gradient regions were used to reconstruct the refractive index field of the window. The numerical three-dimensional optical distortion evaluation was conducted for both the reconstructed and the original refractive index fields of the window using the ray-tracing program based on a recursive algorithm. Wave aberration results show that the methodology based on the IFT concept reduces the refractive index information required to capture the essential optical distortion of the window. The method can also be used for numerically evaluating the optical distortion of the window.


Circadian clocks go in vitro: purely post-translational oscillators in cyanobacteria.
Recent findings about the core of the circadian oscillator in cyanobacteria are challenging the dogma that such clocks are driven through transcriptional-translational feedback regulation. Instead, the master pacemaker is independent of both transcription and translation, and consists of self-sustained oscillations in the phosphorylation status of the KaiC protein in vivo. Using a minimal cocktail of three recombinant proteins with adenosine triphosphate, the core clock was even reproduced in vitro. The so-born chemical oscillator could reproduce accurately temperature compensation and altered period phenotypes in mutants. This system now provides an ideal playground for rebuilding the circadian clock by adding successive components while understanding every single step with chemical resolution.


Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation.
One action of cyclosporin A thought to be central to many of its immunosuppressive effects is its ability to inhibit the early events of T lymphocyte activation such as lymphokine gene transcription in response to signals initiated at the antigen receptor. Cyclosporin A was found to specifically inhibit the appearance of DNA binding activity of NF-AT, AP-3, and to a lesser extent NF-kappa B, nuclear proteins that appear to be important in the transcriptional activation of the genes for interleukin-2 and its receptor, as well as several other lymphokines. In addition, cyclosporin A abolished the ability of the NF-AT binding site to activate a linked promoter in transfected mitogen-stimulated T lymphocytes and in lymphocytes from transgenic mice. These results indicate that cyclosporin A either directly inhibits the function of nuclear proteins critical to T lymphocyte activation or inhibits the action of a more proximal member of the signal transmission cascade leading from the antigen receptor to the nucleus.


Stillbirths in an urban community in Pakistan.
The purpose of this study was to determine stillbirth risk factors and gestational age at delivery in a prospective developing country birth cohort. At 20-26 weeks of gestation, 1369 Pakistani women were prospectively enrolled in the study; the gestational age was determined by ultrasound evaluation, and risk factors and pregnancy outcomes were assessed. The stillbirth rate was 33.6 of 1000 births, despite the fact that 96% of the women received prenatal care, 83% of the women were attended by skilled providers in the hospital, and a 20% of the women underwent cesarean delivery. Fifty-one percent of stillbirths occurred at > or = 37 weeks of gestation and 19% occurred from 34-36 weeks of gestation. Only 4% of the births had congenital anomalies. Hemoglobin of < 8 g/dL, vaginal bleeding, and preeclampsia were associated with increased stillbirth risk. In this developing country with reasonable technical resources defined by hospital delivery and a high cesarean delivery rate, stillbirth rates were much higher than rates in the United States. That most of the stillbirths were term and did not have congenital anomalies and that the death appeared to be recent suggests that many Pakistani stillbirths may be preventable with higher quality obstetric care.


Examining the effect of household wealth and migration status on safe delivery care in urban India, 1992-2006.
Although the urban health issue has been of long-standing interest to public health researchers, majority of the studies have looked upon the urban poor and migrants as distinct subgroups. Another concern is, whether being poor and at the same time migrant leads to a double disadvantage in the utilization of maternal health services? This study aims to examine the trends and factors that affect safe delivery care utilization among the migrants and the poor in urban India. Using data from the National Family Health Survey, 1992-93 and 2005-06, this study grouped the household wealth and migration status into four distinct categories poor-migrant, poor-non migrant, non poor-migrant, non poor-non migrant. Both chi-square test and binary logistic regression were performed to examine the influence of household wealth and migration status on safe delivery care utilization among women who had experienced a birth in the four years preceding the survey. Results suggest a decline in safe delivery care among poor-migrant women during 1992-2006. The present study identifies two distinct groups in terms of safe delivery care utilization in urban India--one for poor-migrant and one for non poor-non migrants. While poor-migrant women were most vulnerable, non poor-non migrant women were the highest users of safe delivery care. This study reiterates the inequality that underlies the utilization of maternal healthcare services not only by the urban poor but also by poor-migrant women, who deserve special attention. The ongoing programmatic efforts under the National Urban Health Mission should start focusing on the poorest of the poor groups such as poor-migrant women. Importantly, there should be continuous evaluation to examine the progress among target groups within urban areas.


Small RNA sequencing evaluation of renal microRNA biomarkers in dogs with X-linked hereditary nephropathy.
Dogs with X-linked hereditary nephropathy (XLHN) are an animal model for Alport syndrome in humans and progressive chronic kidney disease (CKD). Using mRNA sequencing (mRNA-seq), we have characterized the gene expression profile affecting the progression of XLHN; however, the microRNA (miRNA, miR) expression remains unknown. With small RNA-seq and quantitative RT-PCR (qRT-PCR), we used 3 small RNA-seq analysis tools (QIAGEN OmicSoft Studio, miRDeep2, and CPSS 2.0) to profile differentially expressed renal miRNAs, top-ranked miRNA target genes, and enriched biological processes and pathways in CKD progression. Twenty-three kidney biopsies were collected from 5 dogs with XLHN and 4 age-matched, unaffected littermates at 3 clinical time points (T1: onset of proteinuria, T2: onset of azotemia, and T3: advanced azotemia). We identified up to 23 differentially expressed miRNAs at each clinical time point. Five miRNAs (miR-21, miR-146b, miR-802, miR-142, miR-147) were consistently upregulated in affected dogs. We identified miR-186 and miR-26b as effective reference miRNAs for qRT-PCR. This study applied small RNA-seq to identify differentially expressed miRNAs that might regulate critical pathways contributing to CKD progression in dogs with XLHN.


Super-resolution imaging using a camera array.
The angular resolution of many commercial imaging systems is limited, not by diffraction or optical aberrations, but by pixilation effects. Multiaperture imaging has previously demonstrated the potential for super-resolution (SR) imaging using a lenslet array and single detector array. We describe the practical demonstration of SR imaging using an array of 25 independent commercial-off-the-shelf cameras. This technique demonstrates the potential for increasing the angular resolution toward the diffraction limit, but without the limit on angular resolution imposed by the use of a single detector array.


The long-term outcomes of radiosurgery for arteriovenous malformations in pediatric and adolescent populations.
OBJECT Although stereotactic radiosurgery (SRS) has been accepted as a therapeutic option for arteriovenous malformations (AVMs) in children and adolescents, substantial data are still lacking regarding the outcomes of SRS for AVMs in this age group, especially long-term complications. This study aimed to clarify the long-term outcomes of SRS for the treatment of AVM in pediatric patients aged ≤ 18 years. METHODS Outcomes of 116 patients who were aged 4-18 years when they underwent SRS between 1990 and 2009 at the study institute were analyzed retrospectively. RESULTS The median follow-up period after SRS was 100 months, with 6 patients followed up for more than 20 years. Actuarial obliteration rates at 3 and 5 years after SRS were 68% and 88%, respectively. Five hemorrhages occurred in 851 patient-years of follow-up. The annual bleeding rate after SRS before obliteration was calculated as 1.3%, which decreased to 0.2% after obliteration. Shorter maximum nidus diameter (p = 0.02) and higher margin dose (p = 0.03) were associated with a higher obliteration rate. Ten patients experienced adverse events after SRS. Of them, 4 patients presented with delayed complications years after SRS (range 9-20 years after SRS). CONCLUSIONS SRS can reduce the risk of hemorrhage in pediatric and adolescent AVMs, with an acceptable risk of complications in the long term. However, adverse events such as expanding hematoma and radiation necrosis that can occur after substantial follow-up should be taken into account at the time that treatment decisions are made and informed consent is obtained.


Prediction of beauty and liking ratings for abstract and representational paintings using subjective and objective measures.
Recent research on aesthetics has challenged the adage that "beauty is in the eye of the beholder" by identifying several factors that predict ratings of beauty. However, this research has emerged in a piecemeal fashion. Most studies have examined only a few predictors of beauty, and measured either subjective or objective predictors, but not both. Whether the predictors of ratings of beauty versus liking differ has not been tested, nor has whether predictors differ for major distinctions in art, such as abstract vs. representational paintings. Finally, past studies have either relied on experimenter-generated stimuli-which likely yield pallid aesthetic experiences-or on a curation of high-quality art-thereby restricting the range of predictor scores. We report a study (N = 598) that measured 4 subjective and 11 objective predictors of both beauty ratings and liking ratings, for 240 abstract and 240 representational paintings that varied widely in beauty. A crossover pattern occurred in the ratings, such that for abstract paintings liking ratings were higher than beauty ratings, whereas for representational paintings beauty ratings were higher than liking ratings. Prediction was much better for our subjective than objective predictors, and much better for our representational than abstract paintings. For abstract paintings, liking ratings were much more predictable than beauty ratings. Implications and directions for future research are discussed.


Nightshift work and risk of ovarian cancer.
Animal evidence suggests that circadian disruption may be associated with ovarian cancer, though very little epidemiological work has been done to assess this potential association. We evaluated the association between self-reported nightshift work, a known circadian disruptor, and ovarian cancer in a population-based case-control study. The study included 1101 women with invasive epithelial ovarian cancer, 389 women with borderline epithelial ovarian tumours and 1832 controls and was conducted in western Washington state. Shift work data were collected as part of inperson interviews. Working the nightshift was associated with an increased risk of invasive (OR=1.24, 95% CI 1.04 to 1.49) and borderline (OR=1.48, 95% CI 1.15 to 1.90) tumours; however, we observed little evidence that risks increased with increasing cumulative duration of nightshift work, and risks were not elevated in the highest duration category (>7 nightshift work-years). Increased risks were restricted to women who were 50 years of age and older and to serous and mucinous histologies of invasive and borderline tumours. There was suggestive evidence of a decreased risk of ovarian cancer among women reporting a preference for activity during evenings rather than mornings. We found evidence suggesting an association between shift work and ovarian cancer. This observation should be followed up in future studies incorporating detailed assessments of diurnal preference (ie, chronotype) in addition to detailed data on shift schedules.


The Need for Beneficence and Prudence in Clinical Innovation with Autologous Stem Cells.
The term innovation is frequently used as a justification for allowing clinicians to offer unproven autologous stem cell-based interventions (SCBIs) to their patients. Proponents of this kind of innovation (which we refer to as "clinical innovation") argue that physicians should be free to administer whatever interventions they choose, and informed consumers should be free to receive them. This article refutes the notion that clinician autonomy and consumer demand are a sufficient justification for offering patients unproven autologous SCBIs. We argue that, while clinician and consumer preferences need to be taken seriously, access to unproven SCBIs can only be fully justified when it is based on a commitment to beneficence and prudence. We also argue that there is a need for a clearer distinction between the definition of clinical innovation with autologous stem cells, which is morally neutral, and its justification, which entails a commitment to beneficence and prudence. Finally, we argue that regulation of clinical innovation with autologous stem cells needs to be based on a bioethics of innovation that attends to beneficence and prudence alongside other ethical principles.


Subsequent shock deliveries are associated with increased favorable neurological outcomes in cardiac arrest patients who had initially non-shockable rhythms.
Previous studies evaluating whether subsequent conversion to shockable rhythms in patients who had initially non-shockable rhythms was associated with altered clinical outcome reported inconsistent results. Therefore, we hypothesized that subsequent shock delivery by emergency medical service (EMS) providers altered clinical outcomes in patients with initially non-shockable rhythms. We tested for an association between subsequent shock delivery in EMS resuscitation and clinical outcomes in patients with initially non-shockable rhythms (n = 11,481) through a survey of patients after out-of-hospital cardiac arrest in the Kanto region (SOS-KANTO) 2012 study cohort, Japan. The primary investigated outcome was 1-month survival with favorable neurological functions. The secondary outcome variable was the presence of subsequent shock delivery. We further evaluated the association of interval from initiation of cardiopulmonary resuscitation to shock with clinical outcomes. In the univariate analysis of initially non-shockable rhythms, patients who received subsequent shock delivery had significantly increased frequency of return of spontaneous circulation, 24-hour survival, 1-month survival, and favorable neurological outcomes compared to the subsequent not shocked group (P < 0.0001). In the multivariate logistic regression analysis, subsequent shock was significantly associated with favorable neurological outcomes (vs. not shocked; adjusted P = 0.0020, odds ratio, 2.78; 95% confidence interval, 1.45-5.30). Younger age, witnessed arrest, initial pulseless electrical activity rhythms, and cardiac etiology were significantly associated with the presence of subsequent shock in patients with initially non-shockable rhythms. In this study of cardiac arrest patients with initially non-shockable rhythms, patients who received early defibrillation by EMS providers had increased 1-month favorable neurological outcomes.


Flavoring exposure in food manufacturing.
Flavorings are substances that alter or enhance the taste of food. Workers in the food-manufacturing industry, where flavorings are added to many products, may be exposed to any number of flavoring compounds. Although thousands of flavoring substances are in use, little is known about most of these in terms of worker health effects, and few have occupational exposure guidelines. Exposure assessment surveys were conducted at nine food production facilities and one flavor manufacturer where a total of 105 area and 74 personal samples were collected for 13 flavoring compounds including five ketones, five aldehydes, and three acids. The majority of the samples were below the limit of detection (LOD) for most compounds. Diacetyl had eight area and four personal samples above the LOD, whereas 2,3-pentanedione had three area samples above the LOD. The detectable values ranged from 25-3124 ppb and 15-172 ppb for diacetyl and 2,3-pentanedione respectively. These values exceed the proposed National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit for these compounds. The aldehydes had the most detectable samples, with each of them having >50% of the samples above the LOD. Acetaldehyde had all but two samples above the LOD, however, these samples were below the OSHA PEL. It appears that in the food-manufacturing facilities surveyed here, exposure to the ketones occurs infrequently, however levels above the proposed NIOSH REL were found. Conversely, aldehyde exposure appears to be ubiquitous.


Expression of human adenosine deaminase after fusion of adenosine deaminase-deficient cells with mouse fibroblasts.
Two human choriocarcinoma cell lines were shown to be deficient in adenosine deaminase (ADA; adenosine aminohydrolase, EC 126.96.36.199) such that they did not produce bands on starch gels after electrophoresis and histochemical staining. Radiometric assay indicated that their ADA specific activity was approximately 2% that of HeLa (human) cell controls. Subclone analysis of one of the lines indicated that this deficiency was representative of individual cells of the line. After fusion of these cells with mouse fibroblasts having high ADA activity, most independently isolated hybrid clones expressed one of two, or both, additional (to the mouse) bands of ADA activity after electrophoresis. The expression of these extra bands in hybrids was dependent upon actual fusion. The phenomenon was observed in 30 of 45 independently derived hybrid clones from four different fusion experiments involving two different parental lines from each species. The pattern of appearance of the extra bands in independent hybrid clones and the tendency of a hybrid clone to lose one of the extra bands through subsequent passages suggests that the bands were the products of human genetic material. The extra bands electrophoretically comigrated with human ADA 1 and 2 from human ADA-1-2 heterozygotes and the faster-migrating of the two extra bands comigrated with human ADA 1 from HeLa cells. Therefore, we suggest that the bands appearing in hybrids are the products of the 1 and 2 alleles of the human ADA locus. The human cells used for fusion were deficient in ADA activity but contained the genetic information for ADA 1 and 2. Fusion with mouse cells having ADA activity resulted in the activation of both human gene products coded for on separate homologous chromosomes. We conclude that the human ADA locus is under manipulatable genetic regulation.


Bile acid aspiration associated with lung chemical profile linked to other biomarkers of injury after lung transplantation.
Aspiration of gastrointestinal contents has been linked to worse outcomes following lung transplantation but uncertainty exists about underlying mechanisms. We applied high-resolution metabolomics of bronchoalveolar lavage fluid (BALF) in patients with episodic aspiration (defined by bile acids in the BALF) to identify potential metabolic changes associated with aspiration. Paired samples, one with bile acids and another without, from 29 stable lung transplant patients were studied. Liquid chromatography coupled to high-resolution mass spectroscopy was used to interrogate metabolomic contents of these samples. Data were obtained for 7068 ions representing intermediary metabolites, environmental agents and chemicals associated with microbial colonization. A substantial number (2302) differed between bile acid positive and negative samples when analyzed by false discovery rate at q = 0.01. These included pathways associated with microbial metabolism. Hierarchical cluster analysis defined clusters of chemicals associated with bile acid aspiration that were correlated to previously reported biomarkers of lung injury including T cell granzyme B level and the chemoattractants CXCL9 and CXCL10. These data specifically link bile acids presence in lung allografts to inflammatory pathways known to segregate with worsening allograft outcome, and provide additional mechanistic insight into the association between reflux and lung allograft injury.


The human GPI1 gene is required for efficient glycosylphosphatidylinositol biosynthesis.
The first step in glycosylphosphatidylinositol (GPI) membrane anchor biosynthesis that is defective in paroxysmal nocturnal haemoglobinuria is mediated by an N-acetylglucosaminyl transferase expressed in the endoplasmic reticulum. Six human genes encode subunits of this enzyme, namely PIG-A, PIG-C, PIG-H, PIG-P, GPI1, and DPM2. Here, the human GPI1 gene is characterised. This gene is organised into eleven exons. The locus was mapped to chromosome 16p13.3 near the haemoglobin alpha chain locus. GPI1 is expressed ubiquitously in human cells and tissues. Expression levels are markedly elevated in haematopoietic tissues (bone marrow, foetal liver). To determine whether human GPI1 is essential for human GPI biosynthesis, antisense RNA was expressed in HEK293 cells. Transfectants exhibited a marked but incomplete decrease in the expression of a GPI-linked reporter protein, confirming that GPI1 is required for efficient GPI biosynthesis. In contrast, expression of GPI-linked proteins is normal in lymphatic cell lines from individuals with the alpha thalassaemia/mental retardation syndrome, which is characterised by large deletions from chromosome 16p removing one of the two GPI1 alleles along with the haemoglobin alpha locus. In conclusion, GPI1 plays an important role in the biosynthesis of GPI intermediates. Due to its autosomal localisation, the heterozygous deletion of GPI1 does not lead to an overt defect in the expression of GPI-linked proteins.


Effects of Dipeptidyl Peptidase-4 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.
To investigate the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal outcomes in patients with type 2 diabetes. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched to identify randomized controlled trials (RCTs) of DPP-4 inhibitors from inception to September 2017. We selected eligible RCTs comparing DPP-4 inhibitors with placebo or other antidiabetic agents and reporting at least one renal outcome. A meta-analysis was conducted to calculate standardized mean differences, weighted mean differences (WMDs), relative risks (RRs), and 95% confidence intervals (CIs) for each renal outcome. We included 23 RCTs with 19 publications involving 41,359 patients. Overall changes in urine albumin-to-creatinine ratio were comparable between DPP-4 inhibitors and controls (P=0.150). However, DPP-4 inhibitors were associated with significantly lower risk of incident microalbuminuria (RR, 0.89; 95% CI, 0.80 to 0.98; P=0.022) and macroalbuminuria (RR, 0.77; 95% CI, 0.61 to 0.97; P=0.027), as well as higher rates of regression of albuminuria (RR, 1.22; 95% CI, 1.10 to 1.35; P<0.001) compared with controls. Although DPP-4 inhibitors were associated with small but significantly lower estimated glomerular filtration rate (WMD, -1.11 mL/min/1.73 m²; 95% CI, -1.78 to -0.44; P=0.001), there was no difference in the risk of end-stage renal disease between two groups (RR, 0.93; 95% CI, 0.76 to 1.14; P=0.475). DPP-4 inhibitors had beneficial renal effects mainly by reducing the risk of development or progression of albuminuria compared with placebo or other antidiabetic agents.


Reactions of myeloperoxidase-derived oxidants with biological substrates: gaining chemical insight into human inflammatory diseases.
The heme enzyme myeloperoxidase (MPO) is released at sites of inflammation by activated leukocytes. A key function of MPO is the production of hypohalous acids (HOX, X = Cl, Br) which are strong oxidants with potent antibacterial properties. However, HOX can also damage host tissue when produced at the wrong place, time or concentration; this has been implicated in several human diseases. Thus, elevated blood and leukocyte levels of MPO are significant independent risk factors for atherosclerosis, and specific markers of HOX-mediated protein oxidation are often present at elevated levels in patients with inflammatory diseases (e.g. asthma). HOX react readily with amino acids, proteins, carbohydrates, lipids, nucleobases and antioxidants. Sulfur-containing amino acids (Cys, Met, cystine) and amines on amino acids, nucleobases, sugars and lipids are the major targets for HOX. Reaction with amines generates chloramines (RNHCl) and bromamines (RNHBr), which are more selective oxidants than HOX and are key intermediates in HOX biochemistry. As these and other products of MPO-derived oxidants are unstable, understanding the role of HOX-induced damage in disease cannot be obtained solely by stable product analysis, and knowledge of the reaction kinetics is essential. This review collates kinetic and product data for HOX, chloramine and bromamine reactions with biological substrates. It highlights how kinetic data may be used to predict the effect of HOX-mediated oxidation on complex biological targets, such as lipoproteins and extracellular matrix in atherosclerosis, or protein-DNA complexes in cancer, thereby providing a basis for unraveling the mechanisms by which these oxidants generate biological damage.


The influence of wheel/rail contact conditions on the microstructure and hardness of railway wheels.
The susceptibility of railway wheels to wear and rolling contact fatigue damage is influenced by the properties of the wheel material. These are influenced by the steel composition, wheel manufacturing process, and thermal and mechanical loading during operation. The in-service properties therefore vary with depth below the surface and with position across the wheel tread. This paper discusses the stress history at the wheel/rail contact (derived from dynamic simulations) and observed variations in hardness and microstructure. It is shown that the hardness of an "in-service" wheel rim varies significantly, with three distinct effects. The underlying hardness trend with depth can be related to microstructural changes during manufacturing (proeutectoid ferrite fraction and pearlite lamellae spacing). The near-surface layer exhibits plastic flow and microstructural shear, especially in regions which experience high tangential forces when curving, with consequentially higher hardness values. Between 1 mm and 7 mm depth, the wheel/rail contacts cause stresses exceeding the material yield stress, leading to work hardening, without a macroscopic change in microstructure. These changes in material properties through the depth of the wheel rim would tend to increase the likelihood of crack initiation on wheels toward the end of their life. This correlates with observations from several train fleets.


Tissue necrosis following extravasation of acyclovir in an adolescent: A case report.
Extravasation of intravenously infused vesicant solutions is a common problem in medical practice, which can lead to severe and progressive tissue dysfunction, ranging from persistent tissue oedema and fibrosis to delayed tissue necrosis. Acyclovir is a known vesicant medication administrated in paediatric patients, which appears to irritate venous and soft tissue if extravasated. We present the first case involving the extravasation of intravenously infused acyclovir in a female adolescent patient, which caused tissue necrosis and left behind a residual scar lesion. Nursing and medical staff should be aware of the potential dermatological side effects of intravenously infused acyclovir and other medications, even a long time after infusion, and the possible lack of initial local symptoms and signs. Early recognition of extravasation and prompt management are critical in preventing further morbidity, and optimizing outcomes.


Structure-guided design of a high-affinity platelet integrin αIIbβ3 receptor antagonist that disrupts Mg²⁺ binding to the MIDAS.
An integrin found on platelets, α(IIb)β(3) mediates platelet aggregation, and α(IIb)β(3) antagonists are effective antithrombotic agents in the clinic. Ligands bind to integrins in part by coordinating a magnesium ion (Mg(2+)) located in the β subunit metal ion-dependent adhesion site (MIDAS). Drugs patterned on the integrin ligand sequence Arg-Gly-Asp have a basic moiety that binds the α(IIb) subunit and a carboxyl group that coordinates the MIDAS Mg(2+) in the β(3) subunits. They induce conformational changes in the β(3) subunit that may have negative consequences such as exposing previously hidden epitopes and inducing the active conformation of the receptor. We recently reported an inhibitor of α(IIb)β(3) (RUC-1) that binds exclusively to the α(IIb) subunit; here, we report the structure-based design and synthesis of RUC-2, a RUC-1 derivative with a ~100-fold higher affinity. RUC-2 does not induce major conformational changes in β(3) as judged by monoclonal antibody binding, light scattering, gel chromatography, electron microscopy, and a receptor priming assay. X-ray crystallography of the RUC-2-α(IIb)β(3) headpiece complex in 1 mM calcium ion (Ca(2+))/5 mM Mg(2+) at 2.6 Å revealed that RUC-2 binds to α(IIb) the way RUC-1 does, but in addition, it binds to the β(3) MIDAS residue glutamic acid 220, thus displacing Mg(2+) from the MIDAS. When the Mg(2+) concentration was increased to 20 mM, however, Mg(2+) was identified in the MIDAS and RUC-2 was absent. RUC-2's ability to inhibit ligand binding and platelet aggregation was diminished by increasing the Mg(2+) concentration. Thus, RUC-2 inhibits ligand binding by a mechanism different from that of all other α(IIb)β(3) antagonists and may offer advantages as a therapeutic agent.


A Systematic Review Comparing the Play Profiles of Children with Special Health Care Needs with Typically Developing Children.
Although play has been used as a means to meet therapeutic goals by health care practitioners for a long time, there is a need to continuously review its conceptualisation and use in everyday practice to promote evidence-based practice. This systematic review aimed to evaluate the evidence on how the play of children with Special Health Care Needs (SHCN) is similar or different to that of typically developing children. Guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, we conducted a comprehensive review across five electronic databases for all studies that compared how the play of children with SHCN was similar or different to that of typically developing children. Data were extracted from the included studies, and methodological quality was assessed. Eighteen studies met eligibility criteria. All the studies in this review were at risk of bias due to the study design. There was great variation in sample sizes, ranging between five and 112 participants in the diagnostic groups and five and 546 participants in control groups (typically developing children). The included studies investigated different aspects of play, which made it difficult to synthesise. However, of the 18 studies reviewed, thirteen reported that children with SHCN engage in less play, compared with typically developing children. Evidence supports the assumption that children with SHCN are less playful and spend less time engaging in play compared with typically developing children. This systematic review reveals paucity of research on play for children with several common chronic conditions such as HIV/AIDS, cancer, and cardiovascular diseases. Future studies need to reduce risks of bias, including the use of appropriate sample sizes, and must provide detailed results after investigating play in children with SHCN.


Community assembly in the presence of disturbance: a microcosm experiment.
Ecologists know relatively little about the manner in which disturbance affects the likelihood of alternative community stable states and how the history of community assembly affects the relationship between disturbance and species diversity. Using microbial communities comprising bacterivorous ciliated protists assembled in laboratory microcosms, we experimentally investigated these questions by independently manipulating the intensity of disturbance (in the form of density-independent mortality) and community assembly history (including a control treatment with simultaneous species introduction and five sequential assembly treatments). Species diversity patterns consistent with the intermediate disturbance hypothesis emerged in the controls, as several species showed responses indicative of a tradeoff between competitive ability and ability to recover from disturbance. Species diversity in communities with sequential assembly, however, generally declined with disturbance, owing to the increased extinction risk of later colonizers at the intermediate level of disturbance. Similarities among communities subjected to different assembly histories increased with disturbance, a result due possibly to increasing disturbance reducing the importance of competition and hence priority effects. This finding is most consistent with the idea that increasing disturbance tends to reduce the likelihood of alternative stable states. Collectively, these results indicate the strong interactive effects of disturbance and assembly history on the structure of ecological communities.


Velocity and doubling time of prostate-specific antigen: mathematics can matter.
Changes in prostate-specific antigen (PSA) values are often reported as velocity or doubling time. We compared the association of these two calculations-at the time of PSA failure after primary treatment for prostate cancer-with prostate cancer mortality. From a source population of 1313 US Veterans with prostate cancer, including 623 treated with curative intent, the study population included 242 men experiencing biochemical failure, 81 after surgery and 161 after radiation therapy. Clinically relevant calculations of PSA velocity (linear slope) and PSA doubling time (logarithmic slope) were assessed for their association with 11-16 years of mortality from prostate cancer. Death due to prostate cancer occurred in 52/242 (21.5%) men. Among men receiving surgery, PSA velocity ≥1.0 ng/mL/year was associated with increased prostate cancer mortality (HR=4.2, p value=0.037), whereas doubling time ≤12 months did not confer risk (HR=1.0, p value=0.95). Conversely, among patients receiving radiation therapy, doubling time ≤12 months was associated with increased prostate cancer mortality (HR=2.4, p value=0.049), but velocity did not confer a statistically significant risk (HR=3.8, p value=0.19). When assessing risk of prostate cancer mortality, PSA velocity can be more predictive after surgery and PSA doubling time can be more predictive after radiation therapy.


The Effect of the 5-HT4 Agonist, Prucalopride, on a Functional Magnetic Resonance Imaging Faces Task in the Healthy Human Brain.
Depression is a common and often recurrent illness with significant negative impact on a global scale. Current antidepressants are ineffective for up to one third of people with depression, many of whom experience persistent symptomatology. 5-HT4 receptor agonists show promise in both animal models of depression and cognitive deficit. We therefore studied the effect of the 5-HT4 partial agonist prucalopride (1 mg daily for 6 days) on the neural processing of emotional faces in 43 healthy participants using a randomised placebo-controlled design. Participants receiving prucalopride were more accurate at identifying the gender of emotional faces. In whole brain analyses, prucalopride was also associated with reduced activation in a network of regions corresponding to the default mode network. However, there was no evidence that prucalopride treatment produced a positive bias in the neural processing of emotional faces. Our study provides further support for a pro-cognitive effect of 5-HT4 receptor agonism in humans. While our current behavioural and neural investigations do not suggest an antidepressant-like profile of prucalopride in humans, it will be important to study a wider dose range in future studies.


Endothelin in human congestive heart failure.
Although recent investigations report the elevation of plasma endothelin (ET) in congestive heart failure (CHF), it remains unclear if this elevation is that of the biologically active peptide ET-1 or of its precursor big-ET. Furthermore, it is unclear if such elevation is associated with increased myocardial ET and if the molecular form from cardiac tissue is altered ET. Last, it remains to be established whether circulating ET is increased at the earliest stage of CHF in patients with asymptomatic left ventricular dysfunction and correlates with the magnitude of ventricular dysfunction. The present study was designed to investigate concentrations and molecular forms of ET in plasma and cardiac tissue in healthy subjects and CHF patients with New York Heart Association (NYHA) class I through IV using cardiac radionuclide angiogram, cardiac myocardial biopsy, radioimmunoassay, gel permeation chromatography (GPC), and immunohistochemical staining (IHCS). Plasma ET was increased only in patients with moderate (NYHA class III) or severe (NYHA class IV) CHF compared with healthy subjects and individuals with asymptomatic (NYHA class I) or mild (NYHA class II) CHF. The elevation of circulating ET in CHF showed a negative correlation with left ventricular ejection fraction and cardiac index and a positive correlation with functional class and left ventricular end-diastolic volume index. GPC demonstrated that immunoreactive plasma ET was ET-1 in healthy subjects and both mature ET-1 and its precursor big-ET in severe CHF patients, with big-ET the predominant molecular form. Cardiac tissue concentrations and IHCS revealed ET presence in healthy atrial and ventricular tissue, which were not different in severe CHF. GPC revealed that the molecular form of cardiac ET was ET-1 in both healthy and CHF hearts. The present study establishes for the first time that the elevation of plasma ET in severe human CHF represents principally elevation of big-ET. Second, ET is present in healthy and failing myocardia, and its activity by both immunohistochemistry and radioimmunoassay is not changed in CHF. Furthermore, the elevated plasma ET is characteristic of severe CHF and not asymptomatic or mild CHF. In addition, the degree of plasma elevation of ET correlates with the magnitude of alterations in cardiac hemodynamics and functional class. The present study confirms and extends previous investigations of ET in human CHF and establishes the evolution of circulating and local cardiac ET in the spectrum of human CHF.


Time course gene expression profiling of yeast spore germination reveals a network of transcription factors orchestrating the global response.
Spore germination of the yeast Saccharomyces cerevisiae is a multi-step developmental path on which dormant spores re-enter the mitotic cell cycle and resume vegetative growth. Upon addition of a fermentable carbon source and nutrients, the outer layers of the protective spore wall are locally degraded, the tightly packed spore gains volume and an elongated shape, and eventually the germinating spore re-enters the cell cycle. The regulatory pathways driving this process are still largely unknown. Here we characterize the global gene expression profiles of germinating spores and identify potential transcriptional regulators of this process with the aim to increase our understanding of the mechanisms that control the transition from cellular dormancy to proliferation. Employing detailed gene expression time course data we have analysed the reprogramming of dormant spores during the transition to proliferation stimulated by a rich growth medium or pure glucose. Exit from dormancy results in rapid and global changes consisting of different sequential gene expression subprograms. The regulated genes reflect the transition towards glucose metabolism, the resumption of growth and the release of stress, similar to cells exiting a stationary growth phase. High resolution time course analysis during the onset of germination allowed us to identify a transient up-regulation of genes involved in protein folding and transport. We also identified a network of transcription factors that may be regulating the global response. While the expression outputs following stimulation by rich glucose medium or by glucose alone are qualitatively similar, the response to rich medium is stronger. Moreover, spores sense and react to amino acid starvation within the first 30 min after germination initiation, and this response can be linked to specific transcription factors. Resumption of growth in germinating spores is characterized by a highly synchronized temporal organisation of up- and down-regulated genes which reflects the metabolic reshaping of the quickening spores.


Improved glycemic control in patients with advanced type 2 diabetes mellitus taking Urtica dioica leaf extract: a randomized double-blind placebo-controlled clinical trial.
Advanced type 2 diabetes mellitus (T2DM) needing insulin therapy is common. Most conventional anti-hyperglycemic drugs have limited efficacies and significant side effects, so that better anti-hyperglycemic agents are needed. Urtica dioica L. (nettle) leaves have insulin secretagogue, PPARgamma agonistic, and alpha-glucosidase inhibitory effects. Moreover, nettle leaves are used in traditional medicine as an anti-hyperglycemic agent to treat diabetes mellitus. Thus, efficacy and safety of nettle in the treatment of patients with advanced type 2 diabetes mellitus needing insulin were studied. In this randomized double-blind placebo-controlled clinical trial, we evaluated the effects of taking nettle leaf extract (one 500 mg capsule every 8 hours for 3 months) combined with the conventional oral anti-hyperglycemic drugs on the blood levels of fasting glucose, postprandial glucose, glycosylated hemoglobin (HbA1c), creatinine and liver enzymes SGOT and SGPT, and systolic and diastolic blood pressures in 46 patients and compared with the placebo group (n = 46). At the endpoint, the extract lowered the blood levels of fasting glucose, 2 hours postprandial glucose, and HbA1c significantly (p < 0.001, p = 0.009, and p = 0.006, respectively) without any significant effects on the other parameters (p > 0.05) compared with placebo. Nettle may safely improve glycemic control in type 2 diabetic patients needing insulin therapy.


Clusterless Decoding of Position from Multiunit Activity Using a Marked Point Process Filter.
Point process filters have been applied successfully to decode neural signals and track neural dynamics. Traditionally these methods assume that multiunit spiking activity has already been correctly spike-sorted. As a result, these methods are not appropriate for situations where sorting cannot be performed with high precision, such as real-time decoding for brain-computer interfaces. Because the unsupervised spike-sorting problem remains unsolved, we took an alternative approach that takes advantage of recent insights into clusterless decoding. Here we present a new point process decoding algorithm that does not require multiunit signals to be sorted into individual units. We use the theory of marked point processes to construct a function that characterizes the relationship between a covariate of interest (in this case, the location of a rat on a track) and features of the spike waveforms. In our example, we use tetrode recordings, and the marks represent a four-dimensional vector of the maximum amplitudes of the spike waveform on each of the four electrodes. In general, the marks may represent any features of the spike waveform. We then use Bayes's rule to estimate spatial location from hippocampal neural activity. We validate our approach with a simulation study and experimental data recorded in the hippocampus of a rat moving through a linear environment. Our decoding algorithm accurately reconstructs the rat's position from unsorted multiunit spiking activity. We then compare the quality of our decoding algorithm to that of a traditional spike-sorting and decoding algorithm. Our analyses show that the proposed decoding algorithm performs equivalent to or better than algorithms based on sorted single-unit activity. These results provide a path toward accurate real-time decoding of spiking patterns that could be used to carry out content-specific manipulations of population activity in hippocampus or elsewhere in the brain.


Stereospecific mobilization of intracellular Ca2+ by inositol 1,4,5-triphosphate. Comparison with inositol 1,4,5-trisphosphorothioate and inositol 1,3,4-trisphosphate.
The stereo specificity of myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] to mobilize Ca2+ from an intracellular store has been examined in permeabilized rat pituitary-tumour GH3 and Swiss 3T3 cells. A comparison of D-Ins(1,4,5)P3 with the synthetic enantiomer L-Ins(1,4,5)P3 and the racemate DL-Ins(1,4,5)P3 clearly demonstrates the marked stereospecificity of the response. Whereas D-Ins(1,4,5)P3 released 30-50% of non-mitochondrially-bound Ca2+ with a EC50 (concentration producing 50% of maximal response) of 200 nM, the L isomer was both substantially less potent and efficacious. A high concentration of the L isomer (10 microM) did not significantly shift the dose-response curve for the D isomer in Swiss 3T3 cells, suggesting that the less active isomer is probably a very weak agonist. Other studies revealed, in contrast with previous work, that the other naturally occurring isomer, D-Ins(1,3,4)P3, was essentially inactive in releasing Ca+, whereas a novel 5-phosphatase-resistant analogue, DL-myo-inositol 1,4,5-trisphosphorothioate, was a relatively potent full agonist in GH3 cells. These data reveal, for the first time, the stereoselectivity of the intracellular receptor associated with Ca2+ release. They also provide evidence for the activity of the novel phosphorothioate analogue of Ins(1,4,5)P3, but suggest that D-Ins(1,3,4)P3 is not involved in cellular Ca2+ mobilization.


The influence of ABO blood group on mortality in major trauma.
ABO blood group has a profound influence on hemostasis as it is a major determinant of plasma levels of von Willebrand Factor. In vitro studies suggest that blood group O is a risk factor for increased severe bleeding while blood group non-O is a risk factor for thromboembolic events. Yet, the impact of ABO blood group outcome after multiple trauma is unknown. Retrospective multicenter case-control study from three level-1 trauma centers in Germany from 2012-2015. Inclusion criteria were severe trauma with an Injury severity score ≥9 and admission to an intensive care unit. 1281 patients (69.5% male) were included. Mean Injury Severity Score (ISS) was 21.1±12.4; mean age was 50.2±22.4 years. Distribution of blood groups was: O: 37.4%; A: 44%, B: 12.7 and AB: 5.8%. Hospital mortality depending on blood group was 9.7 (A), 10.4 (B), 6.8 (AB) and 12.7 (O) %. Multivariant logistic regression for mortality revealed an Odds ratio of 0.79 (A), 0.60 (B) and 0.54 (AB) without statistical significance (P=0.35 (A), 0.17 (B), 0.33 (AB)). Thromboembolic events (blood group O vs. others) occurred in 2.8 (O) vs. 3.3 (others) %, P=0.619. In this retrospective study on 1281 multiple injured patients, no relevant influence of ABO blood group on hemorrhage, thromboembolic events and mortality could be found.


Update on kidney transplantation in HIV-infected recipients.
HIV infection has historically been a contraindication to kidney transplantation. Prior to the era of potent antiretroviral therapy, the survival of HIV-infected patients was too poor to justify transplantation. In the last 15 years there has been substantial improvement in antiretroviral medications, such that HIV-positive patients are living longer and developing chronic diseases such as end-stage renal disease. The improvement in survival of HIV-positive patients has resulted in transplant centers increasingly considering infected patients appropriate for kidney transplantation. Recently, the results of the first prospective multicenter trial of kidney transplantation into HIV-positive candidates were released, showing the success and challenges of transplantation into this population. In light of the multicenter findings as well as national registry data, kidney transplantation should be considered the standard-of-care renal replacement therapy for HIV-positive end-stage renal disease patients and they should be referred and evaluated for kidney transplantation accordingly.


HIV prevalence among clients attending a sexually transmitted diseases clinic in Amsterdam: the potential risk for heterosexual transmission.
Patients attending a clinic for sexually transmitted diseases (STD) in general have engaged in at risk sexual behaviour. Therefore they are at increased risk of acquiring HIV through sexual contact. To determine the HIV prevalence among patients attending a STD clinic in Amsterdam. An anonymous cross sectional study was conducted in two 5-week periods in Spring and Autumn 1991. Of the 2362 patients attending the clinic during the study period, 2292 (97%) consented to participate; of these, 2138 (93%) were interviewed and anonymously tested, while 154 (7%) consented to be interviewed but refused HIV antibody testing. The HIV prevalence was 4.2% (90/2138); 93% of seropositive participants reported homosexual contacts and/or intravenous use of drugs (IVDU). HIV prevalence among heterosexual non-IVDU men was 0.5% and among non-IVDU women 0.1%. Among all heterosexually active participants, including IVDU and bisexual men, the HIV prevalence was 1.5%. The 28 of 90 HIV infected participants that were heterosexually active reported together approximately 135 heterosexual partners in the six months preceding the study; 13 of these 28 heterosexually active participants had a STD diagnosed at their present clinic visit, while four (30%) of them already knew they were HIV infected. From these data we conclude that there is a substantial risk of further transmission of HIV through heterosexual contact. In order to try to reduce this potential for further sexual transmission of HIV, services offered by the STD clinic should not only include voluntary confidential counselling and HIV testing, but also notification of partners of HIV infected clinic-attendants. Finally, we conclude that anonymous HIV prevalence studies that link HIV test results to risk behaviour for HIV infection can be performed with a high rate of participation. Repeating such prevalence studies in time can help in monitoring the HIV incidence in the heterosexually active population.


Quantitative stable isotope probing with H218O reveals that most bacterial taxa in soil synthesize new ribosomal RNA.
Most soil bacterial taxa are thought to be dormant, or inactive, yet the extent to which they synthetize new rRNA is poorly understood. We analyzed 18O composition of RNA extracted from soil incubated with H218O and used quantitative stable isotope probing to characterize rRNA synthesis among microbial taxa. RNA was not fully labeled with 18O, peaking at a mean of 23.6 ± 6.8 atom percent excess (APE) 18O after eight days of incubation, suggesting some ribonucleotides in soil were more than eight days old. Microbial taxa varied in the degree they incorporated 18O into their rRNA over time and there was no correlation between the APE 18O of bacterial rRNA and their rRNA to DNA ratios, suggesting that the ratios were not appropriate to measure ribonucleotide synthesis. Our study indicates that, on average, 94% of soil taxa produced new rRNA and therefore were metabolically active.


Healthy Aging and Dementia: Two Roads Diverging in Midlife?
Dementia, particularly Alzheimer's disease (AD), is a growing pandemic that presents profound challenges to healthcare systems, families, and societies throughout the world. By 2050, the number of people living with dementia worldwide could almost triple, from 47 to 132 million, with associated costs rising to $3 trillion. To reduce the future incidence of dementia, there is an immediate need for interventions that target the disease process from its earliest stages. Research programs are increasingly starting to focus on midlife as a critical period for the beginning of AD-related pathology, yet the indicators of the incipient disease process in asymptomatic individuals remain poorly understood. We address this important knowledge gap by examining evidence for cognitive and structural brain changes that may differentiate, from midlife, healthy aging and pathological AD-related processes. This review crystallizes emerging trends for divergence between the two and highlights current limitations and opportunities for future research in this area.


Neuroprotection and neurogenesis: modulation of cornus ammonis 1 neuronal survival after transient forebrain ischemia by prior fimbria-fornix deafferentation.
Severe transient forebrain ischemia causes selective neuronal death in the hippocampal cornus ammonis 1 region. We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. Temperature was regulated and rats survived for 7, 14 or 28 days. Immunofluorescent bromodeoxyuridine and neuron specific nuclear protein staining and immunochemistry terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining were performed. At 7 days after ischemia, 73%+/-14% of cornus ammonis 1 neurons were damaged, while deafferentation reduced the injury to 36%+/-17% of cornus ammonis 1 neurons. This protection persisted for at least 28 days. Ischemia significantly increased the number of bromodeoxyuridine-positive cells (85-90 cells/section in stroke group vs. 6 to 11 cells/section in normal or sham stroke group), with very few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-stained cells adjacent to the hippocampal cornus ammonis 1. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults.


Beyond regulations: industry voluntary ban in arsenic use.
Firms play a key role in pollution abatement and control by engaging in beyond-compliance actions without the force of law in voluntary programs. This study examines the effectiveness of a bilateral voluntary agreement, one type of voluntary programs, negotiated between the U.S. Environmental Protection Agency (EPA) and the pressure-treated wood industry to phase-out the use of chromated copper arsenate (CCA), a poisonous arsenic compound. Arsenic is ranked number one on the EPA's priority list of hazardous substances. Unlike a majority of earlier studies on voluntary programs, dynamic panel estimation and structural break analysis show that while a technological innovation in semiconductors is associated with arsenic use increases, the CCA voluntary agreement is associated with a reduction in arsenic use to levels not seen since the 1920s. A voluntary ban in arsenic acid by pesticide manufacturers in the agriculture sector has also contributed to arsenic reductions. Furthermore, the results suggest that environmental activism has played a role in curbing arsenic use. Increasing stakeholder pressures, as measured by membership in the Sierra Club, improves voluntary agreement effectiveness.


Dendritic cell-based assays, but not mannosylation of antigen, improves detection of T-cell responses to proinsulin in type 1 diabetes.
In vitro detection of T-cell responses to autoantigens in type 1 diabetes is recognized as being technically challenging. We aimed to accurately measure cellular responses to proinsulin in patients with diabetes, and speculated that presentation of antigen by dendritic cells (DCs) would enhance the sensitivity of the peripheral blood assay. Antigen was mannosylated to facilitate uptake through DC surface mannose receptors to further improve the assay. Whole proinsulin, as well as mannosylated peptides of proinsulin, were combined with peripheral T cells and autologous immature DCs in a proliferative assay in a panel of newly diagnosed type 1 diabetic patients. The DC-based assay detected responses to proinsulin in five of 15 diabetic patients compared to one of 15 diabetic patients detected using the standard mononuclear cell assay. When the results of all patients were combined, the DC assay, but not the mononuclear cell assay, had a proinsulin response that was significantly higher than background (P < 0.001). The DC assay was, however, associated with high autologous mixed lymphocyte reactions that possibly masked responses in individual patients. Mannosylated antigen was taken up in larger quantities than non-mannosylated antigen, but not presented any more powerfully. Our data suggest that autologous DC-based assays are more powerful than standard peripheral blood mononuclear cell assays. However, they are compromised by high autologous mixed lymphocyte reactions and this requires addressing before they can be used as a routine readout of in vitro peripheral T-cell responses.


Automated QuantMap for rapid quantitative molecular network topology analysis.
The previously disclosed QuantMap method for grouping chemicals by biological activity used online services for much of the data gathering and some of the numerical analysis. The present work attempts to streamline this process by using local copies of the databases and in-house analysis. Using computational methods similar or identical to those used in the previous work, a qualitatively equivalent result was found in just a few seconds on the same dataset (collection of 18 drugs). We use the user-friendly Galaxy framework to enable users to analyze their own datasets. Hopefully, this will make the QuantMap method more practical and accessible and help achieve its goals to provide substantial assistance to drug repositioning, pharmacology evaluation and toxicology risk assessment. http://galaxy.predpharmtox.org firstname.lastname@example.com or firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Evaluation of pediatric rheumatology telehealth satisfaction during the COVID-19 pandemic.
During the Coronavirus disease 2019 pandemic, ambulatory pediatric rheumatology healthcare rapidly transformed to a mainly telehealth model. However, pediatric patient and caregiver satisfaction with broadly deployed telehealth programs remains largely unknown. This study aimed to evaluate patient/caregiver satisfaction with telehealth and identify the factors associated with satisfaction in a generalizable sample of pediatric rheumatology patients. Patients with an initial telehealth video visit with a rheumatology provider between April and June 2020 were eligible. All patients/caregivers were sent a post-visit survey to assess a modified version of the Telehealth Usability Questionnaire (TUQ) and demographic and clinical characteristics. TUQ total and sub-scale (usefulness, ease of use, effectiveness, satisfaction) scores were calculated and classified as "positive" based on responses of "agree" or "strongly agree" on a 5-point Likert scale. Results were analyzed using standard descriptive statistics and Wilcoxon signed rank testing. The association between demographic and clinical characteristics with TUQ scores was assessed using univariate linear regression. 597 patients/caregivers met inclusion criteria, and the survey response rate was 42% (n = 248). Juvenile idiopathic arthritis was the most common diagnosis (33.5%). The majority of patients were diagnosed greater than 6 months previously (72.6%) and were prescribed chronic medications (59.7%). The median total TUQ score was 4 (IQR: 4-5) with positive responses in 81% of items. Of the subscales, usefulness scores were lowest (median: 4, p < 0.001). Telehealth saves time traveling was the highest median item score (median = 5, IQR: 4-5). Within subscales, items that scored significantly lower included convenience, providing for needs, seeing rheumatologist as well as in person, and being an acceptable way to receive rheumatology services (all p < 0.001). There were no significant demographic or clinical features associated with TUQ scores. Our results suggest telehealth is a promising mode of healthcare delivery for pediatric rheumatic diseases but also identifies opportunities for improvement. Innovation and research are needed to design a telehealth system that delivers high quality and safe care that improves healthcare outcomes. Since telehealth is a rapidly emerging form of pediatric rheumatology care, improved engagement and training of patients, caregivers, and providers may help improve the patient experience in the future.


Standard endovascular aneurysm repair in patients with wide infrarenal aneurysm necks is associated with increased risk of adverse events.
Endovascular aneurysm repair (EVAR) has progressively expanded to treat more challenging anatomies. Although EVAR in patients with wide infrarenal necks has been reported with acceptable results, there is still controversy regarding the longer-term outcomes. Our aim is to determine the impact of infrarenal neck diameter on midterm outcome following EVAR with a single endograft with suprarenal fixation. A retrospective case-control study was designed using data from a prospective multicenter database. Patients who electively underwent standard EVAR with an Endurant stent graft (Medtronic Ave, Santa Rosa, Calif) for a degenerative abdominal aortic aneurysm from January 2008 to December 2012 in three high-volume centers in The Netherlands were included. All measurements were obtained using dedicated reconstruction software and center-lumen line reconstruction. Patients with an infrarenal neck diameter of ≥30 mm were compared with patients with a neck diameter of <30 mm. The primary end point was freedom from neck-related adverse events (a composite of type Ia endoleak, neck-related secondary intervention, and endograft migration). Secondary end points were primary clinical success, type Ia endoleak, neck-related reinterventions, endoleaks, and aneurysm-related secondary interventions. Four-hundred twenty-seven patients were included. Seventy-four patients (17.3%) with a neck diameter of ≥30 mm were compared with a control group of 353 patients. There were no significant differences at baseline between groups including demographics, comorbidities, baseline aneurysm diameter, infrarenal neck length, suprarenal angulation, or infrarenal neck angulation. Median stent graft oversizing was 12.5% (7.9-16.1) and 16.6% (12.0-23.1) in the ≥30-mm neck-diameter and control groups, respectively (P < .001). Median follow-up was 3.1 years (1.2-4.7) and 4.1 years (2.7-5.6) for the large neck and control groups, respectively (P < .001). Type Ia endoleaks occurred in 17 patients (4.0%) and were significantly more frequent in patients with ≥30-mm neck diameter (9.5% vs 2.8%; P = .005). Neck-related secondary interventions were performed in 20 patients (4.7%) and were also more common among patients with neck diameters of ≥30 mm (9.5% vs 3.7%; P = .04). The 4-year freedom from neck-related adverse events were 75% and 95% for the large neck and control groups, respectively (P < .001). On multivariable regression analysis, infrarenal neck diameter of ≥30 mm was an independent risk factor for neck-related adverse events (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.6-9.1), type Ia endoleak (OR, 2.7; 95% CI, 1.0-8.3), and neck-related secondary interventions (OR, 3.2, 95% CI, 1.1-9.2). EVAR in patients with large diameter necks is associated with an increased risk of neck-related adverse events in midterm follow-up. This may influence the clinical decision regarding choice of repair and toward a more intensive surveillance following EVAR in these patients in the long term.


Increased exposure of plankton to arsenic in contaminated weakly-stratified lakes.
Arsenic, a priority Superfund contaminant and carcinogen, is a legacy pollutant impacting aquatic ecosystems in urban lakes downwind of the former ASARCO copper smelter in Ruston, WA, now a Superfund site. We examined the mobility of arsenic from contaminated sediments and arsenic bioaccumulation in phytoplankton and zooplankton in lakes with varying mixing regimes. In lakes with strong seasonal thermal stratification, high aqueous arsenic concentrations were limited to anoxic bottom waters that formed during summer stratification, and arsenic concentrations were low in oxic surface waters. However, in weakly-stratified lakes, the entire water column, including the fully oxic surface waters, had elevated concentrations of arsenic (up to 30μgL-1) during the summer. We found enhanced trophic transfer of arsenic through the base of the aquatic food web in weakly-stratified lakes; plankton in these lakes accumulated up to an order of magnitude more arsenic on multiple sampling days than plankton in stratified lakes with similar levels of contamination. We posit that greater bioaccumulation in weakly-stratified lakes was due to elevated arsenic in oxic waters. Aquatic life primarily inhabits oxic waters and in the oxic water column of weakly-stratified lakes arsenic was speciated as arsenate, which is readily taken up by phytoplankton because of its structural similarities to phosphate. Our study indicates that mobilization of arsenic from lake sediments into overlying oxic water columns in weakly-stratified lakes leads to increased arsenic exposure and uptake at the base of the aquatic food web.


Global trends toward urban street-network sprawl.
We present a global time series of street-network sprawl-that is, sprawl as measured through the local connectivity of the street network. Using high-resolution data from OpenStreetMap and a satellite-derived time series of urbanization, we compute and validate changes over time in multidimensional street connectivity measures based on graph-theoretic and geographic concepts. We report on global, national, and city-level trends since 1975 in the street-network disconnectedness index (SNDi), based on every mapped node and edge in the world. Streets in new developments in 90% of the 134 most populous countries have become less connected since 1975, while just 29% show an improving trend since 2000. The same period saw a near doubling in the relative frequency of a street-network type characterized by high circuity, typical of gated communities. We identify persistence in street-network sprawl, indicative of path-dependent processes. Specifically, cities and countries with low connectivity in recent years also had relatively low preexisting connectivity in our earliest time period. We discuss implications for policy intervention in road building in new and expanding cities as a top priority for sustainable urban development.


Origins and insights into the historic Judean date palm based on genetic analysis of germinated ancient seeds and morphometric studies.
Germination of 2000-year-old seeds of Phoenix dactylifera from Judean desert archaeological sites provides a unique opportunity to study the Judean date palm, described in antiquity for the quality, size, and medicinal properties of its fruit, but lost for centuries. Microsatellite genotyping of germinated seeds indicates that exchanges of genetic material occurred between the Middle East (eastern) and North Africa (western) date palm gene pools, with older seeds exhibiting a more eastern nuclear genome on a gradient from east to west of genetic contributions. Ancient seeds were significantly longer and wider than modern varieties, supporting historical records of the large size of the Judean date. These findings, in accord with the region's location between east and west date palm gene pools, suggest that sophisticated agricultural practices may have contributed to the Judean date's historical reputation. Given its exceptional storage potentialities, the date palm is a remarkable model for seed longevity research.


Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B.
There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE). We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV). Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females (p < 0.05). Patients with HBV had lower liver stiffness than those with HCV and NAFLD. After adjustment for age, gender, smoking, alcohol consumption, M or XL probe, and disease state (NAFLD, HCV, and HBV status), those who drank 2 or more cups of coffee per day had a lower liver stiffness (p = 0.044). Tea consumption had no effect (p = 0.9). Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease.


Ion strength and pH sensitive phase transition of N-isobutyryl-L-(D)-cysteine monolayers on Au(111) surfaces.
Self-assembled monolayers (SAMs) of N-isobutyryl-L-(D)-cysteine (NIBC) on Au(111) surfaces were successfully prepared by immersing the Au(111) surfaces in the preheated pure NIBC aqueous solutions for a certain time and characterized by means of scanning tunneling microscopy. Close-packed lamellar structures with a rectangular (4 x radical3) lattice were found both in the SAMs of L-NIBC and D-NIBC. The pH value of the aqueous solutions was found to be sensitive to adjust the SAM structures during the assembly. Changing the pH value from 5 to 7 may completely shift the SAM structures from close-packed lamellar phase to loose-packed perpendicular phase. Combined with density functional theory calculations, such kind of phase transition was explained by the breaking of hydrogen bonds between carboxylic groups and the formation of extra interactions between COO(-) and Au.


Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells.
Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser) to severe (Tyr1680Phe, Ser2119Tyr) VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo.


HIV infection does not prevent the metabolic benefits of diet-induced weight loss in women with obesity.
To test the hypothesis that HIV infection impairs the beneficial effects of weight loss on insulin sensitivity, adipose tissue inflammation, and endoplasmic reticulum (ER) stress. A prospective clinical trial evaluated the effects of moderate diet-induced weight loss on body composition, metabolic function, and adipose tissue biology in women with obesity who were HIV-seronegative (HIV-) or HIV-positive (HIV+). Body composition, multiorgan insulin sensitivity (assessed by using a two-stage hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions), and adipose tissue expression of markers of inflammation, autophagy, and ER stress were evaluated in 8 HIV- and 20 HIV+ women with obesity before and after diet-induced weight loss of 6% to 8%. Although weight loss was not different between groups (∼7.5%), the decrease in fat-free mass was greater in HIV+ than HIV- subjects (-4.4 ± 0.7% vs. -1.7 ± 1.0%, P < 0.05). Weight loss improved insulin sensitivity in adipose tissue (suppression of palmitate rate of appearance [Ra]), liver (suppression of glucose Ra), and muscle (glucose disposal) similarly in both groups. Weight loss did not affect adipose tissue expression of markers of inflammation or ER stress in either group. Moderate diet-induced weight loss improves multiorgan insulin sensitivity in HIV+ women to the same extent as women who are HIV-. However, weight loss causes a greater decline in fat-free mass in HIV+ than HIV- women.


Quality of Life: A Nurse-Led Physical Activity Coaching Program to Improve the Quality of Life of Patients With Cancer During the COVID-19 Pandemic.
Physical activity has been shown to mitigate many of the effects of cancer treatment, yet it often is not embraced by the patient or made part of the nursing standard of care. This pilot study evaluates the impact of the Oncology Nursing Society's Get Up, Get Moving program, a personalized, home-based, nurse-led physical activity coaching program. Patients with cancer in the intervention and control groups completed the SF-36® and the Godin Leisure-Time Exercise Questionnaire at weeks 1 and 12. All patients were initially counseled on exercise. A nurse called each member of the intervention group weekly to encourage physical activity and asked about fatigue, nausea, and step count. The control group was contacted at 6 weeks and 12 weeks only. The program, coupled with nurse telephone calls, increased steps, decreased fatigue, and maintained health-related quality of life among patients in the intervention group. The control group had a decrease in steps, a decline in their SF-36 general health score, and an increase in fatigue. Nurse coaching positively affects physical activity, which may help to decrease cancer treatment side effects.


A 56-year mortality follow-up of Texas petroleum refinery and chemical employees, 1948-2003.
To further investigate the mortality risk of employees who worked in the petroleum refinery industry, we updated an earlier investigation by extending the mortality follow-up by an additional 14 years through 2003. The cohort consisted of 10,621 employees with an average follow-up of 34 years. We used the standardized mortality ratio (SMR) adjusted for age, race, and calendar years as a measure of risk. Overall mortality (SMR=0.77, 95% confidence interval [CI], 0.74-0.79), all cancer mortality (SMR=0.87, 95% CI=0.82-0.93), and most cause-specific mortalities for the total study population were lower than or similar to that of the population of Harris County, Texas. This study did not show a significant increase in leukemia in the total population or in any of the subgroups. The only statistically significant excess of mortality found in this study was an increase in mesothelioma among maintenance employees; the SMR was 4.78 (95% CI=2.54-8.17) among employees who worked for a minimum of one year and was 7.51 (95% CI=3.75-13.45) among those with 10 or more years of employment and 20 or more years of latency. After more than half a century of follow-up, employees at this facility continue to show more favorable mortality outcomes than the general local population. Overall, no statistically significant increase of leukemia or of any of the specific cell types was found. The increased mesothelioma is likely related to past exposure to asbestos.


Modeled effectiveness of ventilation with contaminant control devices on indoor air quality in a swine farrowing facility.
Because adverse health effects experienced by swine farm workers in concentrated animal feeding operations (CAFOs) have been associated with exposure to dust and gases, efforts to reduce exposures are warranted, particularly in winter seasons when exposures increase due to decreased ventilation. Simulation of air quality and operating costs for ventilating swine CAFO, including treating and recirculating air through a farrowing room, was performed using mass and energy balance equations over a 90-day winter season. System operation required controlling heater operation to achieve room temperatures optimal to ensure animal health (20 to 22.5 °C). Five air pollution control devices, four room ventilation rates, and five recirculation patterns were examined. Inhalable dust concentrations were easily reduced using standard industrial air pollution control devices, including a cyclone, filtration, and electrostatic precipitator. Operating ventilation systems at 0.94 m3 s(-1) (2000 cfm) with 75 to 100% recirculation of treated air from cyclone, electrostatic precipitator, and shaker dust filtration system achieves adequate particle control with operating costs under $1.00 per pig produced ($0.22 to 0.54), although carbon dioxide (CO2) concentrations approach 2000 ppm using in-room ventilated gas fired heaters. In no simulation were CO2 concentrations below industry recommended concentrations (1540 ppm), but alternative heating devices could reduce CO2 to acceptable concentrations. While this investigation does not represent all production swine farrowing barns, which differ in characteristics including room dimensions and swine occupancy, the simulation model and ventilation optimization methods can be applied to other production sites. This work shows that ventilation may be a cost-effective control option in the swine industry to reduce exposures.


Cost of Operating Central Cancer Registries and Factors That Affect Cost: Findings From an Economic Evaluation of Centers for Disease Control and Prevention National Program of Cancer Registries.
The Centers for Disease Control and Prevention (CDC) evaluated the economics of the National Program of Cancer Registries to provide the CDC, the registries, and policy makers with the economics evidence-base to make optimal decisions about resource allocation. Cancer registry budgets are under increasing threat, and, therefore, systematic assessment of the cost will identify approaches to improve the efficiencies of this vital data collection operation and also justify the funding required to sustain registry operations. To estimate the cost of cancer registry operations and to assess the factors affecting the cost per case reported by National Program of Cancer Registries-funded central cancer registries. We developed a Web-based cost assessment tool to collect 3 years of data (2009-2011) from each National Program of Cancer Registries-funded registry for all actual expenditures for registry activities (including those funded by other sources) and factors affecting registry operations. We used a random-effects regression model to estimate the impact of various factors on cost per cancer case reported. The cost of reporting a cancer case varied across the registries. Central cancer registries that receive high-quality data from reporting sources (as measured by the percentage of records passing automatic edits) and electronic data submissions, and those that collect and report on a large volume of cases had significantly lower cost per case. The volume of cases reported had a large effect, with low-volume registries experiencing much higher cost per case than medium- or high-volume registries. Our results suggest that registries operate with substantial fixed or semivariable costs. Therefore, sharing fixed costs among low-volume contiguous state registries, whenever possible, and centralization of certain processes can result in economies of scale. Approaches to improve quality of data submitted and increasing electronic reporting can also reduce cost.


Metabolic syndrome predicts vascular changes in whole body magnetic resonance imaging in patients with long standing diabetes mellitus.
Although diabetic patients have an increased rate of cardio-vascular events, there is considerable heterogeneity with respect to cardiovascular risk, requiring new approaches to individual cardiovascular risk factor assessment. In this study we used whole body-MR-angiography (WB-MRA) to assess the degree of atherosclerosis in patients with long-standing diabetes and to determine the association between metabolic syndrome (MetS) and atherosclerotic burden. Long standing (> or = 10 years) type 1 and type 2 diabetic patients (n = 59; 31 males; 63.3 +/- 1.7 years) were examined by WB-MRA. Based on the findings in each vessel, we developed an overall score representing the patient's vascular atherosclerotic burden (MRI-score). The score's association with components of the MetS was assessed. The median MRI-score was 1.18 [range: 1.00-2.41] and MetS was present in 58% of the cohort (type 2 diabetics: 73%; type 1 diabetics: 26%). Age (p = 0.0002), HDL-cholesterol (p = 0.016), hypertension (p = 0.0008), nephropathy (p = 0.0093), CHD (p = 0.001) and MetS (p = 0.0011) were significantly associated with the score. Adjusted for age and sex, the score was significantly (p = 0.02) higher in diabetics with MetS (1.450 [1.328-1.572]) compared to those without MetS (1.108 [0.966-1.50]). The number of MetS components was associated with a linear increase in the MRI-score (increase in score: 0.09/MetS component; r2 = 0.24, p = 0.038). Finally, using an established risk algorithm, we found a significant association between MRI-score and 10-year risk for CHD, fatal CHD and stroke. In this high-risk diabetic population, WB-MRA revealed large heterogeneity in the degree of systemic atherosclerosis. Presence and number of traits of the MetS are associated with the extent of atherosclerotic burden. These results support the perspective that diabetic patients are a heterogeneous population with increased but varying prevalence of atherosclerosis and risk.


Collagen type IX from human cartilage: a structural profile of intermolecular cross-linking sites.
Type IX collagen, a quantitatively minor collagenous component of cartilage, is known to be associated with and covalently cross-linked to type II collagen fibrils in chick and bovine cartilage. Type IX collagen molecules have also been shown to form covalent cross-links with each other in bovine cartilage. In the present study we demonstrate by structural analysis and location of cross-linking sites that, in human cartilage, type IX collagen is covalently cross-linked to type II collagen and to other molecules of type IX collagen. We also present evidence that, if the proteoglycan form of type IX collagen is present in human cartilage, it can only be a minor component of the matrix, similar to findings with bovine cartilage.


Evaluation of megavoltage CT imaging protocols in patients with lung cancer.
Currently, megavoltage CT studies in most centres with tomotherapy units are performed prior to every treatment for patient set-up verification and position correction. However, daily imaging adds to the total treatment time, which may cause patient discomfort as well as results in increased imaging dose. In this study, four alternative megavoltage CT imaging protocols (images obtained: during the first five fractions, once per week, alternating fractions and daily on alternative weeks) were evaluated retrospectively using the daily position correction data for 42 patients with lung cancer. The additional uncertainty introduced by using a specific protocol with respect to the daily imaging, or residual uncertainty, was analysed on a patient and population bases. The impact of less frequent imaging schedules on treatment margin calculation was also analysed. Systematic deviations were reduced with increased imaging frequency, while random deviations were largely unaffected. Mean population systematic errors were small for all protocols evaluated. In the protocol showing the greatest error, the treatment margins necessary to accommodate residual errors were 1.2, 1.3 and 1.7 mm larger in the left-right, superior-inferior and anterior-posterior directions, respectively, compared with the margins calculated using the daily imaging data. The increased uncertainty because of the use of less frequent imaging protocols may be acceptable when compared with other sources of uncertainty in lung cancer cases, such as target volume delineation and motion because of respiration. Further work needs to be carried out to establish the impact of increased residual errors on dose distribution.


The case for simplifying and using absolute targets for viral hepatitis elimination goals.
The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries' progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100 000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100 000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.


Strelkovimermis amphidis n. sp. from chironomid adults emerging from Lake Itasca and Long Lake, Minnesota.
Mermithid nematodes, Strelkovimermis amphidis n. sp., emerged from chironomid imagos from Lake Itasca in Minnesota in the fall of 1996, 1997 and from Long Lake in the fall of 1998. The species is distinguished from the other 11 members of the genus by the long cephalic papillae, absence of an excretory pore, pointed termini in both sexes, large amphids, body diameter decrease at the vulva, long vagina, and the absence of lateral genital papillae. Strelkovimermis amphidis n. sp. is the fifth member of this genus recorded from Lake Itasca. The presence of and nature of the bursal sleeve is suggested as a useful distinguishing characteristic. The ratios involving spicule axis length, diameter of the body at the genital pore, and the length of the tail are also discussed in distinguishing species of Strelkovimermis. An expanded key to the species of Strelkovimermis is included.


Intimate relationships of Devadasi sex workers in South India: An exploration of risks of HIV/STI transmission.
Global literature on female sex workers suggests that being in an intimate relationship is associated with barriers to practising safe sex behaviours. Condom use within intimate relationships is often seen as a sign of infidelity and fosters mistrust which could affect longevity, trust and intimacy within partnerships. Using qualitative data from Devadasi sex workers and their intimate male partners in Bagalkot District, Karnataka, India, we examined both partners' perspectives to understand the quality and dynamics of these relationships and the factors that influence condom use in intimate relationships. Our thematic analysis of individual interviews conducted in May 2011 with 20 couples suggests that many Devadasi sex workers and their intimate partners define their relationships as 'like marriage' which reduced their motivation to use condoms. Evidence from this study suggests that active participation in sex workers' collectives (sanghas) can increase condom use, education and family planning services, among other things, and could be helpful for both Devadasis and their intimate partners to better understand and accept safer sexual practices. Our work has direct implications for designing couple-based health interventions for traditional Devadasi sex workers and their intimate partners in India.


Physical Activity and Exercise During Pregnancy and the Postpartum Period: ACOG Committee Opinion Summary, Number 804.
Exercise, defined as physical activity consisting of planned, structured, and repetitive bodily movements done to improve one or more components of physical fitness, is an essential element of a healthy lifestyle, and obstetrician-gynecologists and other obstetric care providers should encourage their patients to continue or to commence exercise as an important component of optimal health. Women who habitually engaged in vigorous-intensity aerobic activity or who were physically active before pregnancy can continue these activities during pregnancy and the postpartum period. Observational studies of women who exercise during pregnancy have shown benefits such as decreased gestational diabetes mellitus, cesarean birth and operative vaginal delivery, and postpartum recovery time. Physical activity also can be an essential factor in the prevention of depressive disorders of women in the postpartum period. Physical activity and exercise in pregnancy are associated with minimal risks and have been shown to benefit most women, although some modification to exercise routines may be necessary because of normal anatomic and physiologic changes and fetal requirements. In the absence of obstetric or medical complications or contraindications, physical activity in pregnancy is safe and desirable, and pregnant women should be encouraged to continue or to initiate safe physical activities. This document has been revised to incorporate recent evidence regarding the benefits and risks of physical activity and exercise during pregnancy and the postpartum period.