Effects of respirators under heat/work conditions.
Physiological responses and perceived strain of five unacclimatized male subjects were studied. The subjects were exposed to heat during an exercise task and were evaluated while wearing half and full facepiece, cartridge-type, air-purifying respirators, and without a respirator. The exercise consisted of walking on a treadmill for a period of 1 hour in a controlled environmental chamber at each of two different energy expenditure levels (200 and 400 Kcal/hr) (approximately equal to 58 and 116 Watts) and two different heat exposures (air temperatures of 25 degrees C and 43.3 degrees C). The results indicated that wearing a full facepiece respirator imposed significant physiological strain added to that caused by the heat and workloads used in the study. Five of the six physiological measures show this increased physiological strain: heart rate; minute ventilation; oxygen consumption; energy expenditure; and oral temperature. There was no detectable effect on sweat rate. Although subjective ratings indicated more discomfort with increasing physiological strain, the observed correlations between such measures were low (Tb less than .60). The net consequence of the significant effects indicates that workers' tolerance to moderate or higher levels of work under hot conditions while wearing a respirator is reduced. The reduction is more pronounced when wearing a full mask than when wearing a half mask. Changes in respirator design which minimize respiratory dead space are suggested to alleviate this problem. Otherwise, prevention of excessive physiological strain from respirator use when working at moderate or higher levels at hot job sites could necessitate more rest breaks or limiting work time under such conditions.


[Genetic variations of membrane gene of infectious bronchitis virus strains isolated in China between 1995 and 2004].
Membrane (M) protein genes of 20 infectious bronchitis virus (IBV) strains isolated in China between 1995 and 2004 were sequenced and analyzed. The M genes of twenty isolates were composed of 672 to 681 nucleotides, encoding polypeptides of 223 to 226 amino acid residues. Variations of the deduced amino acids of M gene mainly occurred at positions 2 to 17 and 221 to 233, comparing with that of the IBV strain LX4. There were deletions or insertions in the M gene of Chinese isolates at amino acid position 2 to 6, leading to the loss or gain of a glycosylation site. Phylogenetic tree based on amino acid sequences of M genes from 20 Chinese isolates and 34 reference strains showed that they were classified into five distinct clusters. Most of the Chinese IBV strains were included in clusters II and IV, forming distinct groups. The isolates in cluster II showed a close evolutionary relationship with Taiwan isolates. Furthermore, recombination especially the recombination between field isolates and vaccine strains had been observed while comparing the phylogeny of M genes with those of S1 and N genes.


Medication Rules and Mechanism of Topical Traditional Chinese Medicine for Meibomian Gland Dysfunction-Related Dry Eye Disease.
To summarize the use of traditional Chinese medicine in the treatment of meibomian gland dysfunction-related dry eye disease through data mining. Additionally, it aims to explore the signaling pathways and mechanisms of critical drugs used in the treatment of this condition through network pharmacology analysis. Clinical trial literature on the topical application of traditional Chinese medicine for meibomian gland dysfunction-related dry eye disease in the past 20 years was collected from Chinese academic databases (Zhiwang, Wanfang Data, and Weipu). Association rule analysis and clustering analysis were performed using IBM SPSS. Active ingredients and target sites of critical drugs were obtained from the TCSMP and BATMAN-TCM databases. Disease target sites were sourced from databases such as DrugBank and OMIM. The drug-disease intersecting target genes were used to construct a protein-protein interaction (PPI) network in the String database. Common target genes were subjected to GO function and KEGG signaling pathway enrichment analyses using the DAVID platform. The molecular docking of active ingredients and key targets was validated using AutoDock Vina (1.1.2). A total of 93 Chinese herbal medicines in 56 prescriptions were collected. The critical drugs identified were flos chrysanthemi, flos lonicerae japonicae, fructus forsythiae, radix scrophulariae, radix rehmanniae recens, and radix ophiopogonis. There were 63 active ingredients and 905 potential targets. Key targets identified through PPI analysis included AKT1, TP53, TNF, EGFR, IL6, VEGFA, IL1B, INS, EGF, and CXCL8. GO function analysis revealed processes such as positive regulation of expression, positive regulation of cell proliferation, negative regulation of apoptosis, and inflammatory reactions. The main signaling pathways identified were the MAPK signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, and cytokine-cytokine receptor interactions. Molecular docking indicated relatively strong binding activity between the small molecules of the active ingredients and the target proteins. The critical drugs analyzed in this study potentially exert therapeutic effects on meibomian gland dysfunction-related dry eye disease by regulating related biological processes such as anti-inflammation and repairing the corneal epithelial barrier. These findings provide a theoretical basis for future research and development of new drugs and subsequent experimental investigations.


Sex differences in susceptibility to epinephrine-induced arrhythmias.
Gender differences in incidence of cardiac arrhythmias have been documented. It is generally believed that cardiac pathology provides an arrhythmogenic substrate but that a trigger such as sympathetic nervous system activation is required to initiate arrhythmias. This study was done to determine whether there is a sex difference in susceptibility to epinephrine-induced arrhythmias in healthy rats without preexisting pathology and to determine whether gonadal hormones play a role in development of arrhythmias. Untreated, sham-operated, and gonadectomized male and female rats were anesthetized and given IV boluses of epinephrine. ECG, heart rate, and blood pressure were measured continuously for 1 minute and intermittently over a period of 30 minutes. Male rat hearts have a higher occurrence and frequency of epinephrine-induced premature ventricular contractions, missed beats, and blocks than female rat hearts. Ovariectomy increases arrhythmias, thereby abolishing the female advantage. Castration has no effect on occurrence and frequency of premature ventricular contractions but attenuates missed beats and blocks. Sex differences and effect of gonadectomy on epinephrine-induced alterations in heart rate and blood pressure implicate baroreceptor reflex in the dimorphic arrhythmogenic response. Male rat hearts are more susceptible than female hearts to epinephrine-induced arrhythmias, and gonadal hormones play a role in this disparity.


Efficacy of guided tissue regeneration in the management of through-and-through lesions following surgical endodontics: a preliminary study.
The purpose of this prospective study was to assess the outcome of periradicular surgery with or without guided tissue regeneration (GTR) for the treatment of through-and-through lesions. Thirty-four teeth were included according to specific selection criteria. In the test group (using GTR), after root-end filling, the defects were filled with anorganic bovine bone and covered with a resorbable collagen membrane. Healing was assessed according to specific criteria and graded as successful, doubtful, or failed. In the control group, neither grafts nor membranes were used. After 1 year, 31 teeth were evaluated. Of these, 22 (71%) healed successfully, 6 (19%) showed doubtful healing, and 2 were recorded as failures. The outcomes of the defects treated with GTR (88% successful) were significantly better than those of the control group (57% successful). The present study showed that the use of GTR associated with anorganic bovine bone in the treatment of through-and-through lesions may positively affect the healing process.


Aging and Work Ability: The Moderating Role of Job and Personal Resources.
Objective: Demographic changes involving western countries and later retirements due to the recent pension reforms induce a gradual aging of the workforce. This imply an increasing number of workers with health problems and a decreasing of ability to work. In this direction, the present study aims at examining the role of job and personal resources between age and work ability within nurses. Method: The study was cross-sectional and not randomized; data were collected by a self-report questionnaire during a multi-center survey conducted in two Italian hospitals in 2016. In this way, 333 nurses were reached. Results: Multiple linear regression showed that age is significantly and negatively associated to work ability, and that job resources (e.g., decision authority and meaning of work) and personal resources (e.g., hope and resilience) moderate the relationship between age and work ability. Discussion: These results highlight that investing in work and personal resources to support WA is even more relevant for those professions where high physical effort is required.


Differential role of interleukin-6 in lung inflammation induced by lipoteichoic acid and peptidoglycan from Staphylococcus aureus.
Lipoteichoic acids (LTA) and peptidoglycans (PepG) are major components of the cell walls of gram-positive bacteria that trigger inflammatory responses in vitro. To study the in vivo effects of LTA and PepG from Staphylococcus aureus in lungs and to determine the role of interleukin (IL)-6 herein, these compounds were intranasally administered to IL-6 gene deficient (IL-6(-/-)) and wild type (IL-6(+/+)) mice. In IL-6(+/+) mice, LTA and PepG induced acute pulmonary inflammation in a dose-dependent way, characterized by neutrophilic influx and IL-6 production in the bronchoalveolar lavage fluid. Endogenously produced IL-6 attenuated inflammation induced by 10 microg LTA, as reflected by enhanced neutrophil influx, and increased tumor necrosis factor-alpha, macrophage inflammatory protein-1-alpha, and cytokine-induced neutrophil chemoattractant (KC) release into bronchoalveolar lavage fluid of IL-6(-/-) mice, compared with IL-6(+/+) mice. By contrast, pulmonary inflammation induced by 100 microg LTA was similar (neutrophil influx) or even tended to be attenuated (cytokine and chemokine release) in IL-6(-/-) mice. Endogenous IL-6 increased inflammation induced by PepG, as reflected by decreased neutrophil influx into lungs of IL-6(-/-) mice, compared with IL-6(+/+) mice. These data suggest that IL-6 plays an anti-inflammatory role during LTA-induced pulmonary inflammation, which is dependent on the severity of the inflammatory challenge, and a proinflammatory role in peptidoglycan-induced acute lung inflammation. Thus, the contribution of IL-6 to lung inflammation may vary with the stimulus used.


Regional localization of the human glutaminase (GLS) and interleukin-9 (IL9) genes by in situ hybridization.
Phosphate-activated glutaminase is found in mammalian small intestine, brain, and kidney, but not in liver. The enzyme initiates the catabolism of glutamine as the principal respiratory fuel in the small intestine, may synthesize the neurotransmitter glutamate in the brain, and functions in the kidney to help maintain systemic pH homeostasis. Interleukin-9 (IL9) is a relatively new cytokine that supports the growth of helper T-cell clones, mast cells, and megakaryoblastic leukemia cells. cDNA clones have recently been obtained for each of these genes. The human loci for phosphate-activated glutaminase (GLS) and IL9 have previously been mapped to chromosomes 2 and 5, respectively, by analysis of somatic cell hybrid DNAs. By using chromosomal in situ hybridization, we have regionally mapped GLS to 2q32----q34 and IL9 to 5q31----q35.


Nutritional Factors, DNA Methylation, and Risk of Type 2 Diabetes and Obesity: Perspectives and Challenges.
A healthy diet improves life expectancy and helps to prevent common chronic diseases such as type 2 diabetes (T2D) and obesity. The mechanisms driving these effects are not fully understood, but are likely to involve epigenetics. Epigenetic mechanisms control gene expression, maintaining the DNA sequence, and therefore the full genomic information inherited from our parents, unchanged. An interesting feature of epigenetic changes lies in their dynamic nature and reversibility. Accordingly, they are susceptible to correction through targeted interventions. Here we will review the evidence supporting a role for nutritional factors in mediating metabolic disease risk through DNA methylation changes. Special emphasis will be placed on the potential of using DNA methylation traits as biomarkers to predict risk of obesity and T2D as well as on their response to dietary and pharmacological (epi-drug) interventions.


Situating mobile health: a qualitative study of mHealth expectations in the rural health district of Nouna, Burkina Faso.
The implementation of mobile health (mHealth) projects in low- and middle-income countries raises high and well-documented expectations among development agencies, policymakers and researchers. By contrast, the expectations of direct and indirect mHealth users are not often examined. In preparation for a proposed intervention in the Nouna Health District, in rural Burkina Faso, this study investigates the expected benefits, challenges and limitations associated with mHealth, approaching these expectations as a form of situated knowledge, inseparable from local conditions, practices and experiences. The study was conducted within the Nouna Health District. We used a qualitative approach, and conducted individual semi-structured interviews and group interviews (n = 10). Participants included healthcare workers (n = 19), godmothers (n = 24), pregnant women (n = 19), women with children aged 12-24 months (n = 33), and women of childbearing age (n = 92). Thematic and content qualitative analyses were conducted. Participants expect mHealth to help retrieve patients lost to follow-up, improve maternal care monitoring, and build stronger relationships between pregnant women and primary health centres. Expected benefits are not reducible to a technological realisation (sending messages), but rather point towards a wider network of support. mHealth implementation is expected to present considerable challenges, including technological barriers, organisational challenges, gender issues, confidentiality concerns and unplanned aftereffects. mHealth is also expected to come with intrinsic limitations, to be found as obstacles to maternal care access with which pregnant women are confronted and on which mHealth is not expected to have any significant impact. mHealth expectations appear as situated knowledges, inseparable from local health-related experiences, practices and constraints. This problematises universalistic approaches to mHealth knowledge, while nevertheless hinting at concrete, expected benefits. Findings from this study will help guide the design and implementation of mHealth initiatives, thus optimising their chances for success.


Long-term evaluation of required coursework in palliative and end-of-life care for medical students.
In response to the nationwide need for improved care of patients at end of life, our medical school implemented approximately 20 hours of mandatory coursework on the care of dying patients for all students, with satisfactory completion required for graduation. We now report a long-term evaluation of this coursework. DESIGN/SUBJECTS/MEASUREMENTS: A 74-item questionnaire concerning attainment of palliative care and other medical school course objectives, postgraduate practice encounters with patients at end of life, and postgraduate behaviors in palliative care was mailed to all students who graduated from our medical school in 2000, 2001, and 2002. Responses were graded by a Likert-type scale. Additionally, the Association of American Medical Colleges Medical School Graduation Questionnaire (AAMC/GQ) reports for all schools and for our medical school were queried for data regarding palliative care. The return rate of the questionnaire was 54%. The respondents perceived the training to be valuable and effective. They displayed good postgraduate palliative care practices such as choosing to use opiates other than meperidine for pain in the end-of-life setting. Fifty-three percent of the respondents reported that dying patients were often or frequently under their care since graduation. Despite evidence for the efficacy of the training, the respondents perceived that preparedness in certain palliative care domains was somewhat below preparedness in benchmark medical school competencies such as assessment/management of hypertension and diabetes. The AAMC/GQ surveys indicated that for the years 2000-2002, at least 20% more of our graduates perceived that their training in pain management and palliative care was adequate than did all other medical students graduating nationwide. The evaluation provides support for the conclusion that mandatory training in palliative and end-of-life care is effective, perceived to be valuable, and contributes to good palliative and end-of-life care practices in our graduates. Furthermore, the training meets a significant demand in our graduates' clinical practice: end-of-life care. However, expanded medical school emphasis and curriculum hours are still needed for palliative care topics, because preparedness in palliative care skills was perceived to be inferior to benchmark medical skills. To our knowledge, this is the first report of a rigorous summative evaluation of the efficacy of required coursework in palliative and end-of-life care in a U.S. medical school curriculum.


Prevalence of Metabolic Syndrome in Middle School Children and Evaluation of Components of Metabolic Syndrome.
This study was designed to determine the prevalence of metabolic syndrome (MS) in Turkish children and to examine the relationship between MS components in this age group. A total of 395 students in Istanbul aged 10 to 14 years in the 2004-2005 school year were enrolled in the study. Body weight, height, waist circumference, hip circumference, and systolic-diastolic blood pressure were measured. Of the total, 353 provided blood samples for analysis of fasting glucose level, basal insulin, total cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) levels. Modified World Health Organization criteria were used for the diagnosis of MS. In this study, 44.5% of the children were female and 55.5% were male. The mean body mass index (BMI) was 20.57±3.48 kg/m², 10.4% (n=41) were overweight, and 12.7% (n=50) were obese. MS was diagnosed in 0.85% of the entire study group and in 6% of the obese children. There was a positive correlation between BMI and waist circumference (p<0.001), waist/hip ratio (p<0.001), systolic blood pressure (p<0.001), diastolic blood pressure (p<0.001), basal insulin level (p<0.001), homeostasis model assessment of insulin resistance (p<0.001), triglyceride value (p<0.001), total cholesterol level (p<0.05), LDL (p<0.001), and VLDL level (p<0.001), and a negative correlation with HDL level (p<0.001). The study results confirmed that MS is present in children and not limited to adults, and this is an important health problem. The prevalence of MS is more common in obese children. Therefore, early diagnosis of obese children and examination of cardiovascular risk factors and metabolic syndrome criteria is very important.


The quadriceps insertion of the medial patellofemoral complex demonstrates the greatest anisometry through flexion.
A comprehensive understanding of the biomechanical properties of the medial patellofemoral complex (MPFC) is necessary when performing an MPFC reconstruction. How components of the MPFC change over the course of flexion can influence the surgeon's choice of location for graft fixation along the extensor mechanism. The purpose of this study was to (1) determine native MPFC length changes throughout a 90° arc using an anatomically based attachment and using Schöttle's point, and (2) compare native MPFC length changes with different MPFC attachment sites along the extensor mechanism. Eight fresh-frozen (n = 8), cadaveric knees were dissected of all soft tissue structures except the MPFC. The distance between the femoral footprint (identified through anatomical landmarks and Schottle's point) and the MPFC was calculated at four attachment sites along the extensor mechanism [midpoint of the patella [MP], the center of the osseous footprint of the MPFC (FC), the superomedial corner of the patella at the quadriceps insertion (SM), and the proximal extent of the MPFC along the quadriceps tendon (QT)] at 0°, 20°, 40°, 60°, and 90° of flexion. Length changes were investigated between the MPFL femoral attachment site and the radiographic surrogate of the MPFL attachment site, Schottle's Point (SP). Paired t tests at each of the four components showed no differences in length change from 0° to 90° when comparing SP to the anatomic MPFC insertion. MPFL length changes from 0° to 90° were greatest at the QT point (13.9 ± 3.0 mm) and smallest at the MP point (2.7 ± 4.4 mm). The FC and SM points had a length change of 6.6 ± 4.2 and 9.0 ± 3.8, respectively. Finally, when examining how the length of the MPFC components changed through flexion, the greatest differences were seen at QT where all comparisons were significant (p < 0.01) except when comparing 0° vs 20° (n.s.). The MPFC demonstrates the most significant length changes between 0° and 20° of flexion, while more isometric behavior was seen during 20°-90°. The attachment points along the extensor mechanism demonstrate different length behaviors, where the more proximal components of the MPFC display greater anisometry through the arc of motion. When performing a proximal MPFC reconstruction, surgeons should expect increased length changes compared to reconstructions utilizing distal attachment sites.


Sphingoaurantiacus polygranulatus gen. nov., sp. nov., isolated from high-Arctic tundra soil, and emended descriptions of the genera Sandarakinorhabdus, Polymorphobacter and Rhizorhabdus and the species Sandarakinorhabdus limnophila, Rhizorhabdus argentea and Sphingomonas wittichii.
An orange, Gram-reaction-negative and aerobic bacterium, designated MC 3718T, was isolated from a tundra soil near Ny-Ålesund, Svalbard archipelago, Norway (78° N). The cells were motile with either a polar or a subpolar flagellum and reproduced by budding or asymmetrical cell division. Growth occurred at 4-37 °C (optimum 28-30 °C) and at pH 6.0-10.0 (optimum pH 9.0). Many cells accumulated poly-β-hydroxybutyrate granules and contained a single large polyphosphate granule at a pole or in the middle of the cell. Cell walls contained meso-diaminopimelic acid as the diagnostic diamino acid, and ubiquinone 10 was the main respiratory quinone. Strain MC 3718T contained summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c; 29.49 %), summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c; 29.38 %), C17 : 1ω6c (10.15 %), C14 : 0 2-OH (9.05 %) and C16 : 0 (6.84 %) as the major cellular fatty acids. The main polar lipids were two sphingoglycolipids, phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, three unknown phospholipids and two unknown polar lipids. Carotenoids were detected. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain MC 3718T belonged to the family Sphingomonadaceae. The DNA G+C content was 67.2 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain MC 3718T is considered to represent a novel genus and species in the family Sphingomonadaceae, for which the name Sphingoaurantiacus polygranulatus gen. nov., sp. nov. is proposed. The type strain of Sphingoaurantiacus polygranulatus is MC 3718T ( = CCTCC AB 2014274T = LMG 28636T). Emended descriptions of the genera Sandarakinorhabdus, Polymorphobacter and Rhizorhabdus and the species Sandarakinorhabdus limnophila, Rhizorhabdus argentea and Sphingomonas wittichii are also provided.


Caffeine reduction as an adjunct to anxiety management.
A reduction in tea and coffee drinking is popularly advocated for the relief of tension and anxiety symptoms, and it was decided to collect empirical data on this matter in the course of normal clinical practice. It was found that patients who made substantial reductions in caffeine drinking also made the greatest improvements in anxiety, irritability, sleep disturbance, headaches and abdominal symptoms. The methodology leaves an ambiguity in the interpretation of this result, but the data provide a useful basis for the design of further studies.


A Pilot Intervention to Promote Safer Sex in Heterosexual Puerto Rican Couples.
Although the sexual transmission of HIV occurs in the context of an intimate relationship, preventive interventions with couples are scarce, particularly those designed for Hispanics. In this article, we present the effect of a pilot intervention directed to prevent HIV/AIDS in heterosexual couples in Puerto Rico. The intervention was theory-based and consisted of five three-hour group sessions. Primary goals included increasing male condom use and the practice of mutual masturbation as a safer sex method, and promoting favorable attitudes toward these behaviors. Twenty-six couples participated in this study. Fifteen were randomly assigned to the intervention group and eleven to a control group. Retention rates at post-intervention and follow-up were 82% for the whole sample. Results showed that there was a significant increase in the use of male condoms with main partners in the intervention group when compared with the control group. Couples in the intervention group also had better scores on secondary outcomes, such as attitudes toward condom use and mutual masturbation, HIV information, sexual decision-making, and social support. We found that these effects persisted over the three month follow up. A significant effect was also observed for the practice of mutual masturbation, but not for sexual negotiation. These results showed that promoting male condom use in dyadic interventions among heterosexual couples in Puerto Rico is feasible. Our findings suggest that because vaginal penetration has been constructed as the sexual script endpoint among many Hispanic couples, promoting other non-penetrative practices, such as mutual masturbation, may be difficult.


Dyslipidemia modulates Müller glial sensing and transduction of ambient information.
Unesterified cholesterol controls the fluidity, permeability and electrical properties of eukaryotic cell membranes. Consequently, cholesterol levels in the retina and the brain are tightly regulated whereas depletion or oversupply caused by diet or heredity contribute to neurodegenerative diseases and vision loss. Astroglia play a central role in the biosynthesis, uptake and transport of cholesterol and also drive inflammatory signaling under hypercholesterolemic conditions associated with high-fat diet (diabetes) and neurodegenerative disease. A growing body of evidence shows that unesterified membrane cholesterol modulates the ability of glia to sense and transduce ambient information. Cholesterol-dependence of Müller glia - which function as retinal sentinels for metabolic, mechanical, osmotic and inflammatory signals - is mediated in part by transient receptor potential V4 (TRPV4) channels. Cholesterol supplementation facilitates, whereas depletion suppresses, TRPV4-mediated transduction of temperature and lipid agonists in Müller cells. Acute effects of cholesterol supplementation/depletion on plasma membrane ion channels and calcium homeostasis differ markedly from the effects of chronic dyslipidemia, possibly due to differential modulation of modality-dependent energy barriers associated with the functionality of polymodal channels embedded within lipid rafts. Understanding of cholesterol-dependence of TRP channels is thus providing insight into dyslipidemic pathologies associated with diabetic retinopathy, glaucoma and macular degeneration.


Albumin, bilirubin, and activated carbon: new edges of an old triangle.
The problem of interaction of human serum albumin (HSA), unconjugated bilirubin (UB) and high porosity activated HSGD carbons is investigated in this study. The decrease of UB to HSA molecular ratio by more than 300 times was demonstrated while the batch experiments in HSA-UB admixtures after contact with HSGD. HSGD carbons express extremely high activity for the removal of UB from HSA containing solutions (more than 100 mg of UB per 1 g of activated carbon). Ex-tempore albumin-coating of carbon surface decreases adsorbent capacity by bilirubin on 21%. At the same time ex-tempore albumin-coating of HSGD carbon surface as well as blood citratization prevent platelet and leukocytes loss and clotting inside of the column. Pharmacopoeia solution of HSA containing acetyl-tryptophan or octanoate used for albumin-coating of HSGD adsorbents, becomes ligand-free and rather more active in complexing with protein-bound substances. Combination of albumin-coated HSGD carbon as haemosorbent with HSA ligand-free solution as a transfusion media seems a new prospective modality of the extracorporeal removal of protein-bound toxins.


Contagious flexibility? A study on whether schedule flexibility facilitates work-life enrichment.
Schedule flexibility defines an important generating resource for work-life enrichment; however, our knowledge about how such spillovers take place is limited. This multiple case study examines how workers from different working time contexts with varying levels of schedule flexibility experience work-life interplay. Given the adopted explorative design, it is important to interpret the findings in a tentative light. Nonetheless, the study offers important insight into work-life enrichment that may guide future research in this field. The findings indicate that schedule flexibility may act as a boundary-spanning resource owing to the agency potential it offers workers. Thus, it seemed that flexible schedule opportunities enabled workers to engage more fully in personal life activities, which in turn had a positive influence on their work involvement through positive affect. Such positive role engagements appeared, however, to be greatly determined by workers' boundary management and by time conditions of work and family. In conclusion, the major findings and limitation of the study are discussed against existing research and theory.


Resistant hypertension? Assessment of adherence by toxicological urine analysis.
Uncontrolled hypertension under antihypertensive multidrug regimen is not necessarily always true resistance. Incomplete adherence is one of several possible causes of uncontrolled hypertension. Nonadherence remains largely unrecognized and is falsely interpreted as treatment resistance, as it is difficult to confirm or exclude objectively. This is the first study assessing adherence in patients with apparent resistant hypertension systematically via toxicological urine screening. All patients referred from primary care physicians because of uncontrolled hypertension between 2004 and 2011 were analysed. Adherence was assessed in all patients with uncontrolled hypertension despite the concurrent use of at least four antihypertensive agents by using liquid chromatography-mass spectrometry analysis for antihypertensive drugs or their corresponding metabolites in urine. A total of 375 patients with uncontrolled hypertension were referred. After optimization of drug therapy and exclusion of white coat hypertension, 108 patients met criteria for resistant hypertension. Of those, 15 patients had secondary causes of hypertension and 17 achieved goal blood pressure with quadruple antihypertensive therapy. Of the remaining 76 patients, 40 patients (53%) were found to be nonadherent. Among nonadherent patients, 30% had complete and 70% had incomplete adherence; 85% of the latter had taken less than 50% of drugs prescribed. Lack of adherence was almost evenly distributed between different classes of antihypertensive drugs. Low adherence was the most common cause of poor blood pressure control in patients with apparent resistant hypertension, being twice as frequent as secondary causes of hypertension. Incomplete adherence was far more common than complete nonadherence; thus, assessment of adherence in patients on multiple drug regime is only reliable when all drugs are included in assessment. Assessing adherence by toxicological urine screening is a useful tool in detecting low adherence, especially in the setting of multidrug regimen as a cause of apparently resistant hypertension.


Impact of Interfacial Layers in Perovskite Solar Cells.
Perovskite solar cells (PCSs) are composed of organic-inorganic lead halide perovskite as the light harvester. Since the first report on a long-term-durable, 9.7 % efficient, solid-state perovskite solar cell, organic-inorganic halide perovskites have received considerable attention because of their excellent optoelectronic properties. As a result, a power conversion efficiency (PCE) exceeding 22 % was certified. Controlling the grain size, grain boundary, morphology, and defects of the perovskite layer is important for achieving high efficiency. In addition, interfacial engineering is equally or more important to further improve the PCE through better charge collection and a reduction in charge recombination. In this Review, the type of interfacial layers and their impact on photovoltaic performance are investigated for both the normal and the inverted cell architectures. Four different interfaces of fluorine-doped tin oxide (FTO)/electron-transport layer (ETL), ETL/perovskite, perovskite/hole-transport layer (HTL), and HTL/metal are classified, and their roles are investigated. The effects of interfacial engineering with organic or inorganic materials on photovoltaic performance are described in detail. Grain-boundary engineering is also included because it is related to interfacial engineering and the grain boundary in the perovskite layer plays an important role in charge conduction, recombination, and chargecarrier life time.


[Antitumor spectrum of aclacinomycin A, MA 144 N 1 and MA 144 S 1 on the rat ascitic hepatoma (author's transl)].
Antitumor activity of new anthracycline antibiotics aclacinomycin A, MA 144 N1 and MA 144 S 1 was studied on 11 cell lines of ascitic hepatoma in Donryu rats. These compounds showed similar antitumor spectrum against AH hepatoma; moderate effect on AH 13, 44, 66, 66F, 7974 and 60 C in the ip inoculation-ip treatment system. Aclacinomycin A showed a marked antitumor effect on AH 41 C in the iv-iv system, and AH 44 in the iv-ip and iv-po systems. The antitumor spectrum of aclacinomycin A seems to be different from that of adriamycin.


Survival of a GFP-Labeled Polychlorinated Biphenyl Degrading Psychrotolerant Pseudomonas spp. in 4 and 22 degrees C Soil Microcosms.
The green fluorescent protein gene (gfp) was inserted into the chromosome of Pseudomonas spp. Cam-1 and Sag-50G, two psychrotolerant polychlorinated biphenyl (PCB)-degrading bacteria. The gfp-transformed microorganisms, designated Cam-1-gfp1, Cam-1-gfp2, Sag-50G-gfp1, and Sag-50G-gfp2, exhibited green fluorescence under an epifluorescent microscope. The gfp was inserted into the chromosome of each psychrotolerant strain and was stable with no apparent adverse affects on the metabolism and growth of each organism. Activity of gfp-transformed microorganisms against biphenyl and 2,3-dichlorobiphenyl was determined by assaying for BphC activity and by resting cell assays. The patterns of BphC activity at two different growth temperatures in batch cultures were similar for each of the gfp-transformed microorganisms. Resting cell assays of both the parent strains (Cam-1, Sag-50G) and the gfp-transformed strains (Cam-1-gfp1, Cam-1-gfp2, Sag-50G-gfp1, Sag-50G-gfp2), grown on glycerol or glucose, exhibited BphC activity to a lesser extent and at a slower rate than those observed for biphenyl grown cells. In addition, all gfp-transformed microorganisms degraded 2,3-dichlorobiphenyl (2,3-DCB) in broth to the same extent as the parent strains. When Cam-1-gfp1 and Sag-50G-gfp1 were used as a bioremediation amendment in soil microcosms spiked with 2,3-DCB, both strains survived in high numbers (5.6 to 7.9 log cfu g?1 and 5.6 to 8.0 log cfu g?1) when inoculated into nonsterilized soil over 16 weeks at 22 degrees C and 18 weeks at 4 degrees C, respectively. Biodegradation of 2,3-DCB was enhanced with the microbial amendment; however, the addition of sunflower oil did not help the PCB degrading bacteria and may have enhanced the growth of the indigenous population, thereby decreasing the amended PCB-degrading population.


The binding of cupric ions to 1-carboxymethylhistidine-119-ribonuclease.
Binding of Cu(2+) by 1-carboxymethylhistidine-119-ribonuclease was investigated by using diligand metal ion buffers. A single Cu(2+)-binding site was found over the Cu(2+) concentration range studied. The binding constants for this site were 8.33x10(5) (+/-2%)m(-1) and 1.57x10(4) (+/-6%)m(-1) at pH7.0 and 6.1 respectively. An estimate of the pH-independent Cu(2+)-binding constant suggests that the most avid Cu(2+)-binding site has disappeared after carboxymethylation. This is consistent with an earlier report that binding of Cu(2+) at the most avid site is associated with the loss of enzymic activity.


Modeling the fringe field of permanent magnet multipoles using numerical simulations.
Permanent magnet multipoles (PMMs) are widely used in accelerators to either focus particle beams or confine plasma in ion sources. The real magnetic field created by PMMs is calculated by magnetic field simulation software and then used in particle tracking codes by means of a three dimensional magnetic field map. A common alternative is to use the so-called "hard-edge" model, which gives an approximation of the magnetic field inside the PMM assuming a null fringe field. This work proposes an investigation of the PMM fringe field properties. An analytical model of the PMM magnetic field is developed using the Fourier multipole expansion. A general axial potential function with a unique parameter λ, able to reproduce the actual PMM magnetic field (including its two fringe fields) with an explicit dependence on the PMM length, is proposed. An analytical first order model including the axial fringe field is derived. This simple model complies with the Maxwell equations [curl(B) = 0 and div(B) = 0] and can replace advantageously the "hard-edge" model when fast analytical calculations are required. The higher order analytical multiple expansion model quality is assessed by means of χ2 estimators. The general dependence of the potential function parameter λ is given as a function of the PMM geometry for quadrupole, hexapole, and multipole, allowing one to use the developed model in simulation programs where the multipole geometry is an input parameter.


[Traffic-related air pollution at the place of residence and risk of cancer among children].
The hypothesis that exposure to traffic-related air pollution increases the risk of cancer developing during childhood was investigated. We enrolled 1,989 children notified to the Danish Cancer Registry with a diagnosis of leukaemia, tumour of the central nervous system (CNS), or malignant lymphoma during 1968-1991, and 5,506 control children selected at random from the entire childhood population. The residential histories of the children were traced from nine months before birth up to the time of diagnosis, as was a similar period for the controls. Information on traffic and the configuration of streets and buildings was collected for each of the 18,440 identified addresses. Concentrations of benzene and nitrogen dioxide (indicators of traffic-related air pollution) were calculated for the relevant residential periods, and combined into exposures to air pollution during pregnancy and childhood, respectively. The risks of leukaemia, CNS tumours, and all selected cancers combined were not related to exposure to benzene or nitrogen dioxide during either period. The risk of lymphomas increased by 25% (p for trend = 0.06) and 51% (p for trend = 0.05) for a doubling of the concentration of benzene and nitrogen dioxide, respectively, during the pregnancy. The association was restricted to Hodgkin's disease. On the basis of a low potential for selection bias, information bias, and confounding factors, we conclude that traffic-related air pollution at the residence of children is not linked to the risk of leukaemia or CNS tumour, which are the two major types of childhood cancer. The results indicated a possible association between air pollution and the risk of Hodgkin's disease, but the evidence allows of no firm conclusion at present.


Selective multi-electron aggregation at a hypervalent iodine center by sequential disproportionation.
We demonstrate that sequential disproportionation reactions can enable selective aggregation of two- or four electron-holes at a hypervalent iodine center. Disproportionation of an anodically generated iodanyl radical affords an iodosylbenzene derivative. Subsequent iodosylbenzene disproportionation can be triggered to provide access to an iodoxybenzene. These results demonstrate multielectron oxidation at the one-electron potential by selective and sequential disproportionation chemistry.


Regulation of thyroid hormone sensitivity by differential expression of the thyroid hormone receptor during Xenopus metamorphosis.
During amphibian metamorphosis, a series of dynamic changes occur in a predetermined order. Hind limb morphogenesis begins in response to low levels of thyroid hormone (TH) in early prometamorphosis, but tail muscle cell death is delayed until climax, when TH levels are high. It takes about 20 days for tadpoles to grow from early prometamorphosis to climax. To study the molecular basis of the timing of tissue-specific transformations, we introduced thyroid hormone receptor (TR) expression constructs into tail muscle cells of Xenopus tadpoles. The TR-transfected tail muscle cells died upon exposure to a low level of thyroxine (T4). This cell death was suggested to be mediated by type 2 iodothyronine deiodinase (D2) that converts T4 to T3-the more active form of TH. D2 mRNA was induced in the TR-overexpressing cells by low levels of TH. D2 promoter contains a TH-response element (TRE) with a lower affinity for TR. These results show that the TR transfection confers the ability to respond to physiological concentrations of TH at early prometamorphosis to tail muscle cells through D2 activity and promotes TH signaling. We propose the positive feedback loop model to amplify the cell's ability to respond to low levels of T4.


Equilibrium and Dynamical Characteristics of Imidazole Langmuir Monolayers on Graphite Sheets.
Using molecular dynamics techniques, we examine structural and dynamical characteristics of liquid-like imidazole (Im) monolayers physisorbed onto a planar graphite sheet, at T = 384 K. Our simulations reveal that molecular orientations in the saturated monolayer exhibit a bistable distribution, characterized by an inner parallel arrangement of the molecules in close contact with the substrate and a slanted alignment, in those lying in adjacent, outer locations. Compared to the results found in three-dimensional, bulk phases, the analysis of the spatial correlations between sites participating in hydrogen bonding shows a clear enhancement of the intermolecular interactions, which also leads to stronger dipolar correlations. As a result, the gross structural features of the monolayer can be cast in terms of mesoscopic domains, comprising units articulated via winding hydrogen bonds, that persist along typical time intervals of a few tens of picoseconds. On the dynamical side, a similar comparison of the characteristic decorrelation time for orientational motions shows a 4-fold increment. Contrasting, the reduction of the system dimensionality leads to a larger diffusion constant. Possible substrate-induced anisotropies in the diffusive motions are also investigated.


Speciation of Gold Nanoparticles by Ex Situ Extended X-ray Absorption Fine Structure and X-ray Absorption Near Edge Structure.
A combined X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) methodology is here presented on a series of partially and fully reduced Au(III) samples. This allows monitoring the relative fraction of Au(III) and Au(0) in the studied samples, displaying a consistent and independent outcome. The strategy followed is based, for the first time, on two structural models that can be fitted simultaneously, and it evaluates the correlation among strongly correlated parameters such as coordination number and the Debye-Waller factor. The results of the present EXAFS and XANES approach can be extended to studies based on X-ray absorption spectroscopy experiments for the in situ monitoring of the formation of gold nanoclusters.


The marula and elephant intoxication myth: assessing the biodiversity of fermenting yeasts associated with marula fruits (Sclerocarya birrea).
The inebriation of wild African elephants from eating the ripened and rotting fruit of the marula tree is a persistent myth in Southern Africa. However, the yeasts responsible for alcoholic fermentation to intoxicate the elephants remain poorly documented. In this study, we considered Botswana, a country with the world's largest population of wild elephants, and where the marula tree is indigenous, abundant and protected, to assess the occurrence and biodiversity of yeasts with a potential to ferment and subsequently inebriate the wild elephants. We collected marula fruits from over a stretch of 800 km in Botswana and isolated 106 yeast strains representing 24 yeast species. Over 93% of these isolates, typically known to ferment simple sugars and produce ethanol comprising of high ethanol producers belonging to Saccharomyces, Brettanomyces, and Pichia, and intermediate ethanol producers Wickerhamomyces, Zygotorulaspora, Candida, Hanseniaspora, and Kluyveromyces. Fermentation of marula juice revealed convincing fermentative and aromatic bouquet credentials to suggest the potential to influence foraging behaviour and inebriate elephants in nature. There is insufficient evidence to refute the aforementioned myth. This work serves as the first work towards understanding the biodiversity marula associated yeasts to debunk the myth or approve the facts.


Interleukin-13 and interleukin-4 induce vascular endothelial growth factor release from airway smooth muscle cells: role of vascular endothelial growth factor genotype.
Th2 cytokines induce the release of vascular endothelial growth factor (VEGF) from cultured human airway smooth muscle cells. The objective of this study was to examine the mechanistic basis for IL-4- and IL-13-induced VEGF release and to determine whether genetic differences are responsible for donor-to-donor variability in VEGF release. We measured VEGF mRNA expression by real-time PCR, mRNA stability using actinomycin D, and promoter activity with a VEGF-promoter luciferase reporter construct. We measured IL-4- and IL-13-induced VEGF release in cells from 21 donors by ELISA, genotyped the cells for common single nucleotide polymorphisms in the IL-4R alpha (Ile50Val, Ser478Pro, and Gln551Arg) and VEGF (-460T/C, -160C/T, -152G/A, +405C/G and +936 C/T) genes, and stratified the data by IL-4R alpha and VEGF genotype. IL-4 and IL-13 increased VEGF release and VEGF mRNA expression. IL-4 also increased mRNA stability but did not affect VEGF promoter activity. There was marked donor-to-donor variability in VEGF release from smooth muscle cells. The presence of Val50, Pro478/Arg551, or the Val50/Pro478/Arg551 IL-4R alpha haplotype had little effect on VEGF release. VEGF genotype at +405 or +936 alone had no effect on VEGF release, whereas cells bearing at least one -460C/-152A/+405G VEGF allele had lower release of VEGF in response to IL-13 or IL-4 than cells with other genotypes. Our data suggest that IL-4 and IL-13 mediate their effects on VEGF expression post-transcriptionally and indicate that polymorphisms in the VEGF, but not the IL-4R alpha, gene affect VEGF release from smooth muscle cells.


Micronutrient intake in elderly living in nursing homes.
The aim of this study was to evaluate the ingestion of micronutrients in elderly living in nursing homes. This is a cross-sectional study, conducted with 216 individuals of both sexes, age equal or greater than 60 years, living in nursing homes for elderly in Salvador, Bahia, Brazil. Direct weighing of the food was used to get food intake, and prevalence of inadequacy was obtained using the software Multiple Source Method (MSM) and evaluated by estimated average requirement (EAR). A high prevalence of inadequate intake of micronutrients was observed, being over 90% for vitamins E, folate, pyridoxine and calcium, in both sexes and between 50 and 70% for selenium, retinol, riboflavin, cyanocobalamin and vitamin C. The high prevalence of inadequate intake of micronutrients in elderly living on nursing homes observed in this study may be used for planning public health strategies aiming to improve the nutritional context of this population and their quality of life, reducing the costs of health care.


HIV counseling for behavior change.
The purpose of this paper was to provide a framework for discussion in the working group on HIV Counseling for Behavior Change at the Third USAID HIV/AIDS Prevention Conference. The paper begins with a section defining HIV counseling and describing different types of HIV counseling. Next, points of consensus and controversy regarding the conduct and evaluation of HIV counseling are discussed. This is followed by a section outlining findings to date on the effectiveness of HIV counseling, and a discussion of methodological issues in evaluating counseling outcomes. Finally, the paper includes a list of key issues for further research.


The immunohistochemical molecular risk classification in endometrial cancer: A pragmatic and high-reproducibility method.
The aim of this study is to assess the clinical reproducibility and the potential oncological validity of the molecular information provided by the immunohistochemistry (IHC) to properly stratify the endometrial cancer patients. Retrospective IHC analyses were conducted in a large series of 778 pre-operative uterine-confined ECs, studying the presence/absence of MLH1, MSH2, MSH6 and PMS2 to define the mismatch repair (MMR) stable or instable phenotype; the presence of p53 mutations and other molecular features. The molecular profile was correlated with histological, clinical and prognostic data. Based on IHC assessment, we defined 3 EC populations: stable MMR patients (MMRs), instable patients (MMRi) and p53 mutated patients (p53+). Our result demonstrated that the IHC stratification statistically correlated with the most relevant pathologic-clinical features: FIGO stage (p < 0.001), grading (p < 0.001), histotype (p < 0.001), presence of LVSI (p < 0.001), myometrial invasion and tumor dimension (p = 0.003 for both). These 3 IHC populations statistically reflected the EC risk class ESGO-ESMO-ESP classification 2021 (p < 0.001). These results were also confirmed in the Kaplan-Meier curves in terms of overall survival (OS) and disease-free survival (DFS) (p < 0.0001). The multivariate analyses demonstrated that absence of estrogen receptor (ER) impacted the OS (p = 0.011) and, the Age > 60 years and the ER-status the DFS (p = 0.041 and p = 0.004). In this large series, we demonstrated that the pragmatic and systematic use of IHC may have an important role to properly stratify, in terms of histological features and clinical outcomes, the EC patients.


Individual Characteristics Influencing Physicians' Perceptions of Job Demands and Control: The Role of Affectivity, Work Engagement and Workaholism.
The first purpose of the present study was to investigate the role of individual characteristics, i.e., positive and negative affectivity, in explaining the different perception of job control and job demands in a particularly demanding environment such as the healthcare setting. In addition, we aimed to explore the mediational role of work engagement and workaholism using the Job Demands-Resources Model as a theoretical framework. Data were collected using a sample of 269 Italian head physicians working in nine general hospitals. To test our hypotheses, the collected data were analyzed with structural equation modeling. Moreover, Sobel Test and bootstrapping were employed to assess the mediating hypotheses. Our results indicated that positive affectivity is related to work engagement, which, in its turn, showed a positive association with job control. In addition, workaholism mediated the relationship between negative affectivity and job demands. All in all, this study represents a first attempt to explore the role of trait affectivity as a dispositional characteristic able to foster the level of work engagement and workaholism exhibited by employees and, in turn, to increase the perceived levels of job control and job demands.


The rate of increase in blood pressure in children 5 years of age is related to changes in aerobic fitness and body mass index.
To determine whether changes in aerobic fitness and body mass index are related to the age-related rise in blood pressure in healthy preschool children. Longitudinal analyses of 196 free-living children aged 5 years at baseline who were followed over a mean of 19.7 months. Aerobic fitness was assessed using a treadmill. All measures were obtained on multiple occasions at scheduled visits as part of a longitudinal cohort study. An inner-city medical center. Blood pressure was measured using an automated Dinamap device. Mean systolic blood pressure was 95.3 mmHg (SD 8.38) at baseline and increased by 4.46 mmHg per year. Mean diastolic blood pressure was 53.9 mmHg (SD 5.81) at baseline and did not change significantly. Children in the highest quintile of increase in fitness had a significantly smaller increase in systolic blood pressure compared to children in the lowest quintile (2.92 vs 5.10 mmHg/year; P = .03). Children in the lowest quintile of increase in body mass index did not differ significantly in rate of increase in systolic blood pressure compared to children in the highest quintile (3.92 vs 4.96 mmHg/year). In a multiple regression model including baseline systolic blood pressure, fitness, height, body mass index, and other covariates, greater increase in fitness (P = .03) and lesser increase in body mass index (P < .01) were associated with lower rates of increase in systolic blood pressure. In a similar multivariate analysis, an increase in fitness was also associated with a lower rate of increase in diastolic blood pressure (P = .02). Young children who increase their aerobic fitness or decrease their body mass index reduce the rate of the age-related increase in blood pressure. These observations may have implications for development of interventions directed at the primary prevention of hypertension.


Kostmann's syndrome.
Kostmann's syndrome is a rare congenital disorder of neutrophil production due to impairment of myeloid differentiation in the bone marrow, with the neutrophil count being characteristically less than 500 x 10(3) cells/l (normal: 2-7 x 10(9)/l). Severe persistent neutropenia results in an increased susceptibility to frequent bacterial infections. The condition can be treated with recombinant human granulocyte colony-stimulating factor (G-CSF). Although several articles have addressed the clinicopathological and haematological aspects of this disorder, little or no information has been available concerning the radiological findings in this disorder. This report summarizes the clinical features, radiological findings and management of a patient with Kostmann's syndrome.


Assessing fear of falling: Can a short version of the Activities-specific Balance Confidence scale be useful?
We present the process of further validation of the 16-item Activities-specific Balance Confidence scale (ABC-16) and a short version (ABC-6) derived by us, to assess balance confidence and fear of falling (FOF). The ABC-16 was administrated to three groups who were anticipated to have a range of balance confidence: 70 patients with higher level gait disorders (HLGDs), 68 healthy controls, and 19 patients with Parkinson's disease (PD). Item reduction was based on identifying items with the lowest scores (high FOF) among the patients. Internal consistency and discriminative validity were assessed using Cronbach's alpha and logistic regression, respectively. The intraclass correlation (ICC) between the short and long versions was assessed using a mixed model approach, accounting for the difference between the scores of the two versions. Six items were found to reflect the most frightening conditions, especially in the patient groups, and to form the short version (ABC-6). Internal consistency of the ABC-16 and ABC-6 were high in the three groups: Cronbach's alpha was between 0.83 and 0.91 and 0.81 and 0.90, respectively. Compared to the control group, the sensitivity of the ABC-16 was 96% for identification of patients with HLGDs (greatest FOF) and 58% for identification of PDs (moderate FOF), based only on the ABC scores. Similar values were obtained for the short version, i.e., 91% for HLGDs and 53% for PDs. ICCs between the short and the long versions was 0.88 (HLGDs), 0.83 (PDs), and 0.78 (Controls). To conclude, the short version of the ABC has properties analogous to the parent questionnaire and is apparently useful in assessing FOF.


Clinical implication of subcategorizing T2 category into T2a and T2b in TNM staging of breast cancer.
Regarding TNM staging in breast cancer, T2 category is currently not divided into subcategories even though it covers a wider range of tumor sizes than T1 category. Using Korean Breast Cancer Registry database, data of 41 071 women diagnosed as non-metastatic T2 breast cancer between 2001 and 2014 were analyzed. Cutoff value for optimal tumor size was approximated by receiver operating characteristic (ROC) curve to subcategorize T2 tumors. Overall survival (OS) was compared between two subcategories. Median follow-up period was 65 months. Of 41 071 patients, 4504 (11.0%) died. Based on ROC curve analysis, 3.0 cm was selected as the cutoff value. Five-year OS rate was 91% in patients with breast tumors ≤3.0 cm (T2a) and 86% in patients with breast tumors >3.0 cm (T2b) (log-rank P < 0.001). T2b subcategory showed worse OS than T2a subcategory regardless of node status (log-rank P < 0.001 for all node categories). Within every subgroup defined by primary OS analysis covariates, T2b subcategory consistently showed worse outcome compared to T2a subcategory. By multivariate analysis, T2b subcategory was a significant independent prognostic factor of OS (hazard ratio: 1.26, 95% CI = 1.18-1.34). T2 category of breast cancer could be subcategorized into T2a and T2b with a cutoff value of 3 cm. These subcategories definitely showed different OSs even after adjusted for known prognostic factors. Subcategorization of T2 category might be useful for predicting prognosis more accurately and tailoring adjuvant therapy.


Characteristics of falls with damage to hospitalized patients.
Describe the characteristics of falls in patients with damage, their risk factors and injuries. Retrospective and longitudinal study of 260 records of falls with damage of adult patients in clinical and surgical units of a general hospital, from September 2012 to June 2017. Data were collected in May 2018 from the electronic fall and electronic record research instrument, and the statistical analysis was described. There were 260 falls with damage, mostly in the elderly (78%), female (55%), in clinical treatment (68%) and unaccompanied (59.4%). The falls occurred at the same height (63.4%) and in the patient's room (67.3%). The severity of the damage was mild in 80.8% of cases, severe in 11.9% and moderate in 7.3%. Improving understanding of falls and their consequences can assist professionals in identifying and assessing risks and in establishing preventive measures.


Morphological changes of Paulownia seedlings infected phytoplasmas reveal the genes associated with witches' broom through AFLP and MSAP.
Paulownia witches' broom (PaWB) caused by phytoplasma might result in devastating damage to the growth and wood production of Paulownia. To study the effect of phytoplasma on DNA sequence and to discover the genes related to PaWB occurrence, DNA polymorphisms and DNA methylation levels and patterns in PaWB seedlings, the ones treated with various concentration of methyl methane sulfonate (MMS) and healthy seedlings were investigated with amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP). Our results indicated that PaWB seedlings recovered a normal morphology, similar to healthy seedlings, after treatment with more than 20 mg · L-1 MMS; Phytoplasma infection did not change the Paulownia genomic DNA sequence at AFLP level, but changed the global DNA methylation levels and patterns; Genes related to PaWB were discovered through MSAP and validated using quantitative real-time PCR (qRT-PCR). These results implied that changes of DNA methylation levels and patterns were closely related to the morphological changes of seedlings infected with phytoplasmas.


Applications of economic models in healthcare: the introduction of pioglitazone in Sweden.
Type 2 diabetes mellitus (T2DM) is a common disorder that is estimated to affect approximately 100 million people worldwide. Forecasts have suggested a substantial increase in incidence, mainly in Asia, Africa and North America. Thus, an increasing number of people with diabetes-related complications will have to be cared for in the future. This development will be a major health problem for the people affected, as well as a major health economic challenge for many countries. Thiazolidinediones represent a new class of drugs with a novel mechanism of action that addresses the root cause of T2DM. Their mode of action targets the core defect of T2DM, namely, insulin resistance. One of these drugs, pioglitazone, was recently approved by the Swedish authorities. To evaluate the cost effectiveness of this new drug, a published mathematical simulation model was used. This model was adapted to Swedish conditions, and local Swedish unit costs were put into the model. Modelling is necessary when performing economic evaluations in diabetes because of the complexity of the disease and its long time horizon. The cost-effectiveness analyses showed that the cost per life-year gained with pioglitazone combination therapy compared with current treatment ranged from 37,000 Swedish kronor (SEK) to SEK149,000. Although there is no threshold value for cost effectiveness in Sweden, the values presented would normally be regarded as cost effective in the Swedish healthcare system. Modelling studies are a good starting point, but long-term naturalistic studies are needed to establish the cost effectiveness of these new drugs.


Cellular and Mitochondrial Dual-Targeted Organic Dots with Aggregation-Induced Emission Characteristics for Image-Guided Photodynamic Therapy.
Targeted delivery of drugs toward mitochondria of specific cancer cells dramatically improves therapy efficiencies especially for photodynamic therapy (PDT), as reactive oxygen species (ROS) are short in lifetime and small in radius of action. Different from chemical modification, nanotechnology has been serving as a simple and nonchemical approach to deliver drugs to cells of interest or specific organelles, such as mitochondria, but there have been limited examples of dual-targeted delivery for both cells and mitochondria. Here, cellular and mitochondrial dual-targeted organic dots for image-guided PDT are reported based on a fluorogen with aggregation-induced emission (AIEgen) characteristics. The AIEgen possesses enhanced red fluorescence and efficient ROS production in aggregated states. The AIE dot surfaces are functionalized with folate and triphenylphosphine, which can selectively internalize into folate-receptor (FR) positive cancer cells, and subsequently accumulate at mitochondria. The direct ROS generation at mitochondria sites is found to depolarize mitochondrial membrane, affect cell migration, and lead to cell apoptosis and death with enhanced PDT effects as compared to ROS generated randomly in cytoplasm. This report demonstrates a simple and general nanocarrier approach for cellular and mitochondrial dual-targeted PDT, which opens new opportunities for dual-targeted delivery and therapy.


No evidence of host-specific egg mimicry in Asian koels.
Avian brood parasitism is costly for the host, in many cases leading to the evolution of defenses like discrimination of parasitic eggs. The parasite, in turn, may evolve mimetic eggs as a counter-adaptation to host egg rejection. Some generalist parasites have evolved host-specific races (gentes) that may mimic the eggs of their main hosts, while others have evolved 'jack-of-all-trades' egg phenotypes that mimic key features of the eggs of several different host species. The Asian koel (Eudynamys scolopaceus) is a widely distributed generalist brood parasite that exploits a wide range of host species. Based on human vision, previous studies have described Asian koel eggs as resembling those of its main host, the house crow (Corvus splendens). Using measurements of egg length and breadth, digital image analysis, reflectance spectrophotometry and avian visual modelling, we examined Asian koel egg variation and potential mimicry in egg size and shape, and eggshell pattern and color in three sympatrically occurring host species in Bangladesh: the common myna (Acridotheres tristis), house crow, and long-tailed shrike (Lanius schach). We found some differences among Asian koel eggs laid in different host nests: a) Asian koel eggs in long-tailed shrike nests were larger than those laid in common myna and house crow nests, and b) Asian koel eggs in house crow nests were less elongated than those in common myna nests. However, these changes in Asian koel egg volume and shape were in the opposite direction with respect to their corresponding host egg characteristics. Thus, our study found no evidence for Asian koel host-specific egg mimicry in three sympatrically occurring host species.


Cytotoxic T lymphocytes directed to the preferentially expressed antigen of melanoma (PRAME) target chronic myeloid leukemia.
The cancer testis antigen (CTA) preferentially expressed antigen of melanoma (PRAME) is overexpressed in many hematologic malignancies, including chronic myeloid leukemia (CML). The sensitivity of CML to donor lymphocyte infusion after allogeneic stem cell transplantation suggests this tumor can be highly susceptible to cellular immunotherapy targeted to tumor associated antigens. We therefore tested whether functional PRAME-specific cytotoxic T lymphocytes (PRAME CTLs) could be generated and expanded from healthy donors and CML patients, or whether the limited immunogenicity of this CTA coupled with tumor-associated anergy would preclude this approach. Using optimized culture conditions and HLA-A*02-restricted PRAME-peptides, we have consistently generated PRAME CTLs from 8/9 healthy donors and 5/6 CML patients. These CTLs released IFNgamma in response to PRAME peptides (between 113 +/- 8 and 795 +/- 23 spot forming cells/10(5) T cells) and lysed PRAME peptide-loaded cells (45 +/- 19% at an effector:target [E:T] ratio of 20:1) in a MHC-restricted fashion. Importantly, these CTLs recognized and had cytotoxic activity against HLA-A*02(+)/PRAME(+) tumor cell lines, and could recognize and respond to primary CML cells. PRAME CTLs were generated almost exclusively from the naive T-cell compartment, and clonal analysis showed these cells could have high alphabetaTCR-peptide avidity. PRAME CTLs or vaccines may thus be of value for patients with CML.


Crotonaldehyde: a carcinogenic and mutagenic air, water and food pollutant.
Crotonaldehyde is mutagenic and carcinogenic and it is ubiquitous in our environment. The data base does, however, not allow an assessment of the carcinogenic risk. We have developed a sensitive 32P-postlabelling technique which allows the detection of specific DNA-adducts in animal tissues as markers for initiation of cancer cells. Adducts were found in several organs of F 344 rats after gavage and persisted to a certain extent. The determination of adduct levels in animal tissues after different exposure or even in human tissues can therefore be considered as an effect monitoring and would certainly improve the risk assessment.


Robustification of Linear Regression and Its Application in Genome-Wide Association Studies.
Regression analysis is one of the most popular statistical techniques that attempt to explore the relationships between a response (dependent) variable and one or more explanatory (independent) variables. To test the overall significance of regression, F-statistic is used if the parameters are estimated by the least-squares estimators (LSEs), while if the parameters are estimated by the maximum likelihood estimators (MLEs), the likelihood ratio test (LRT) statistic is used. However, both procedures produce misleading results and often fail to provide good fits to the reasonable space of the dataset in the presence of outlying observations. Moreover, outliers occur very frequently in any real datasets as well as in the molecular OMICS datasets. Hence, an effort is made in this study to robustify MLE based regression analysis by maximizing the β-likelihood function. The tuning parameter β is selected by cross-validation. For β = 0, the proposed method reduces to the classical MLE based regression analysis. We inspect the performance of the proposed method using both synthetic and real data analysis. The results of simulations indicate that the proposed method performs better than traditional methods in both outliers and high leverage points to estimate the parameters and mean square errors. The results of relative efficiency analysis show that the proposed estimator is relatively less affected than the popular estimators, including S, MM, and fast-S for normal error distribution in case high dimension and outliers. Also, real data analysis results demonstrated that the proposed method shows robust properties with respect to data contaminations, overcome the drawback of the traditional methods. Genome-wide association studies (GWAS) by the proposed method identify the vital gene influencing hypertension and iron level in the liver and spleen of mice. Furthermore, we have identified 15 and 21 significant SNPs for chalkiness degree and chalkiness percentage, respectively, by GWAS based on the proposed method. The variant of the SNPs might be provided the new resources for grain quality traits and could be used for further molecular and physiological analysis to enhance the better quality of rice grain. These results offer an important basis for further understanding of the robust regression analysis, which might be applied in various fields, including business, genetics, and bioinformatics.


Time is tissue. Want to save millions in wound care? Start early: a QI project to expedite referral of high-risk wound care patients to specialised care.
Wound care is a multibillion-dollar industry, and most research and treatment are geared towards late-stage or end-stage care. The longer a patient has a wound, the more likely it is that complications (like sepsis or vascular compromise) will occur that will both extend treatment and multiply costs. We postulated that much of the suffering and healthcare costs of chronic wounds could be avoided by early identification of high-risk patients and subsequent earlier intervention. In an established regional wound clinic, our aim was to decrease referral times by 50% within 1 year, and to demonstrate the beneficial outcomes on wound healing and total cost of care. A prospective interventional quality improvement study was performed between June 2017 and June 2018. We determined baseline referral times to the clinic and then performed three interventions. The effects on referral time, healing time and number of home care visits to achieve wound healing were collected and displayed on annotated control charts. The cost of care and potential for cost avoidance was determined by an analysis of the medical encounters of twenty chronic wound patients. We achieved a 53.6% reduction in average referral times to the clinic, a 59.6% reduction in average healing times and a 66.0% reduction in the average number of home care visits required to achieve healing. Our cost analysis suggested the potential for significant cost avoidance (87.7%) compared with delayed treatment outside the clinic. Early identification and treatment of patients at high risk for wound chronicity and complications, followed by early referral to and treatment at a specialised wound clinic, resulted in faster healing and reduced health system costs.


Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management.
The disease spectrum currently known as the proteasome-associated autoinflammatory syndromes (PRAAS) was first described in 1939 in patients who presented with recurrent fevers beginning in infancy or early childhood, which were accompanied by nodular erythema, a pernio-like rash, and joint contractures. Since then, several syndromes, such as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome, Nakajo-Nishimura syndrome (NNS), joint contractures, muscle atrophy, microcytic anemia and panniculitis-induced lipodystrophy (JMP) syndrome, and Japanese autoinflammatory syndrome with lipodystrophy (JASL), have been used to categorize patients with diseases within the same spectrum. Recently, independent studies have identified mutations in the human proteasome subunit β type 8 (PSMB8) gene, which result in a sustained inflammatory response in all syndromes. Further functional studies not only suggest a causative role of PSMB8 mutations but also imply that they represent one disease spectrum, referred to as PRAAS. In this paper, we review the clinical presentations and laboratory findings of PRAAS, as well as the most recent advances in pathogeneses, diagnosis, and treatment options for patients with diseases in this spectrum.


An update on internal mammary artery grafting for coronary artery disease.
To describe recent results regarding the use of the internal mammary artery for coronary artery bypass grafting with emphasis on bilateral internal mammary artery grafting, patency, resistance to atherosclerosis, skeletonisation, composite arterial grafts, flow measurement, vasodilatation, and non-invasive imaging techniques. Coronary artery bypass grafting plays an important part in coronary revascularisation and seems to be associated with a survival benefit in comparison with percutaneous coronary intervention. After 10 years, internal mammary arteries demonstrate better patency than vein grafts except when grafting moderately stenosed right coronary arteries. Bilateral internal mammary artery grafting increases survival further, but carries a higher risk of sternal complications. Skeletonisation may reduce this risk. The internal mammary arteries are used increasingly as composite arterial grafts and this technical solution should no longer be considered experimental. Perioperative flow measurement by the transit-time method is recommended while postoperative echocardiography represents an accurate method for evaluation of flow in internal mammary artery grafts. Multi-detector computed tomography allows for accurate assessment of all types of bypass conduits and native coronary arteries. At present, magnetic resonance imaging of internal mammary artery patency and flow is possible. Newer studies confirm earlier data with respect to improved long-term survival when using internal mammary artery grafting, and this survival benefit is superior to percutaneous coronary intervention treatment. Bilateral internal mammary artery grafting improves survival further. Skeletonisation of the internal mammary artery provides extra length of grafts for complete arterial revascularisation. Non-invasive imaging techniques are increasingly sophisticated and may change the referral pattern for patients with coronary artery disease to either percutaneous coronary intervention or coronary artery bypass grafting.


Croatian version of the neck disability index can distinguish between acute, chronic and no neck pain : Results of a validation study.
Longitudinal study to test the validity and reliability of the Croatian version of the neck disability index (NDI-CRO) for use in patients. Three groups were given NDI-CRO on two occasions, 48 h apart: acute whiplash neck injury group (n = 30), hospital physiotherapists-professional chronic neck pain group (n = 56) and control group (n = 65). To test validity, correlation between NDI-CRO and the pain VAS and PHQ‑9 questionnaire for depression was analyzed. Reliability testing was done using the test-retest experiment and item-total score correlation. Test-retest showed excellent correlation in all groups: whiplash 0.86, control 0.95 and physiotherapist 0.89 (Spearman r). Item-total score in the 3 analyzed groups showed positive correlation in all 10 categories, varying from 0.43-0.85. The NDI-CRO score showed significant difference between groups (median whiplash 38%, physiotherapist 12% and control 6%, p < 0.05). Validity testing showed positive correlation between NDI and pain VAS (control r = 0.63, physiotherapist r = 0.68 and whiplash r = 0.83, p < 0.05) and PHQ‑9 (control r = 0.49, physiotherapist r = 0.71 and whiplash r = 0.69, p < 0.05). No correlation was found between NDI-CRO and age, gender or radiographic findings. In the whiplash injury group 75% of patients showed moderate to severe disability. The majority of physiotherapists showed mild to moderate disability due to neck pain while 40% showed no disability. In the control group two out of three people reported no disability. The NDI-CRO is a valid index for measuring the degree of neck disability in people with acute and chronic neck pain and in control group. It is strongly correlated with pain VAS and PHQ‑9 index.


In silico prediction of the chemical block of human ether-a-go-go-related gene (hERG) K+ current.
A variety of compounds with different chemical properties directly interact with the cardiac repolarizing K(+) channel encoded by the human ether-a-go-go-related gene (hERG). This causes acquired forms of QT prolongation, which can result in lethal cardiac arrhythmias including torsades de pointes one of the most serious adverse effects of various therapeutic agents. Prediction of this phenomenon will improve the safety of pharmacological therapy and also facilitate the process of drug development. Here we propose a strategy for the development of an in silico system to predict the potency of chemical compounds to block hERG. The system consists of two sequential processes. The first process is a ligand-based prediction to estimate half-maximal concentrations for the block of compounds inhibiting hERG current using the relationship between chemical features and activities of compounds. The second process is a protein-based prediction that comprises homology modeling of hERG, docking simulation of chemical-channel interaction, analysis of the shape of the channel pore cavity, and Brownian dynamics simulation to estimate hERG currents in the presence and absence of chemical blockers. Since each process is a combination of various calculations, the criterion for assessment at each calculation and the strategy to integrate these steps are significant for the construction of the system to predict a chemical's block of hERG current and also to predict the risk of inducing cardiac arrhythmias from the chemical information. The principles and criteria of elemental computations along this strategy are described.


IFN-γ regulates cytochrome 3A29 through pregnane X receptor in pigs.
1. The expression and the activity of cytochromes P450 (CYPs) can be elevated by the activation of nuclear receptors. The pregnane X receptor (PXR, or nuclear receptor NR1I2) is a ligand-activated transcription factor that mediates responses to diverse xenobiotics and endogenous chemicals. Here we investigated the regulatory role of PXR in IFN-γ-mediated CYP3A29 expression in pig liver microsomes, primary porcine hepatocytes, and a cultured hepatocyte cell line. 2. IFN-γ significantly up-regulated CYP3A29 and PXR expressions at mRNA and protein levels in a dose-dependent manner. IFN-γ treatment significantly increased the metabolism of nifedipine. PXR and IFN-γ treatments significantly enhanced the activity of CYP3A29 promoter and the upstream region from -1473 to -1021 of CYP3A29 might be PXR-binding site. Moreover, the IFN-γ-induced CYP3A29 expression was blocked by PXR knockdown, whereas CYP3A29 mRNA and protein expression levels were dramatically elevated by PXR overexpression. 3. The regulatory effect of IFN-γ on CYP3A29 expression is mediated via PXR.


A Duplex Quantitative Real-Time Reverse Transcription-PCR for Simultaneous Detection and Differentiation of Flaviviruses of the Japanese Encephalitis and Ntaya Serocomplexes in Birds.
High impact, mosquito-borne flaviviruses such as West Nile virus (WNV), Usutu virus (USUV), Japanese encephalitis virus (JEV), Tembusu virus (TMUV), and Bagaza/Israel turkey meningoencephalomyelitis virus (BAGV/ITV) are emerging in different areas of the world. These viruses belong to the Japanese encephalitis (JE) serocomplex (JEV, WNV, and USUV) and the Ntaya serocomplex (TMUV and BAGV/ITV). Notably, they share transmission route (mosquito bite) and reservoir host type (wild birds), and some of them co-circulate in the same areas, infecting overlapping mosquito and avian population. This may simplify epidemiological surveillance, since it allows the detection of different infections targeting the same population, but also represents a challenge, as the diagnostic tools applied need to detect the whole range of flaviviruses surveyed, and correctly differentiate between these closely related pathogens. To this aim, a duplex real-time RT-PCR (dRRT-PCR) method has been developed for the simultaneous and differential detection of JE and Ntaya flavivirus serocomplexes. The method has been standardized and evaluated by analyzing a panel of 49 flaviviral and non-flaviviral isolates, and clinical samples of different bird species obtained from experimental infections or from the field, proving its value for virus detection in apparently healthy or suspicious animals. This new dRRT-PCR technique is a reliable, specific and highly sensitive tool for rapid detection and differentiation of JE and Ntaya flavivirus groups in either domestic or wild animals. This novel method can be implemented in animal virology diagnostic laboratories as screening tool in routine surveillance and in the event of bird encephalitis emergence.


Bottom-Up Strategy To Prepare Nanoparticles with a Single DNA Strand.
We describe the preparation of cross-linked, polymeric organic nanoparticles (ONPs) with a single, covalently linked DNA strand. The structure and functionalities of the ONPs are controlled by the synthesis of their parent linear block copolymers that provide monovalency, fluorescence and narrow size distribution. The ONP can also guide the deposition of chloroaurate ions allowing gold nanoparticles (AuNPs) to be prepared using the ONPs as templates. The DNA strand on AuNPs is shown to preserve its functions.


Psychotropic drug-induced neutropenia.
Psychotropic medications have been known to cause blood dyscrasias, including neutropenia, and since the advent of clozapine, this side effect is now increasingly being recognized. Almost all the major classes of psychotropic medications have been associated with neutropenia. Operational definitions for blood dyscrasias have allowed us to create an epidemiological database on this rare side effect of psychotropic medications. With increased awareness of drug-induced neutropenia among physicians, methods of early detection and treatment of this side effect have also been the focus of recent literature. Another area of active research has been identifying the risk factors and mechanism of drug-induced neutropenia. This article attempts to synthesize our current understanding of psychotropic drug-induced neutropenia and also provide insights into future research in this realm.


Characterizing discrete subsets of polycystic ovary syndrome as defined by the Rotterdam criteria: the impact of weight on phenotype and metabolic features.
The Rotterdam criteria for polycystic ovary syndrome (PCOS) defines discrete subgroups whose phenotypes are not yet clear. The phenotypic characteristics of women in the PCOS subgroups defined by the Rotterdam criteria were compared. The study was observational. Subjects were studied in an outpatient setting in Boston and Reykjavik. Four subgroups of subjects with PCOS defined by 1) irregular menses (IM), hyperandrogenism (HA), and polycystic ovary morphology (PCOM, n = 298); 2) IM/HA (n = 7); 3) HA/PCOM (n = 77); and 4) IM/PCOM (n = 36) and a group of controls (n = 64), aged 18-45 yr, were examined. Subjects underwent a physical exam; fasting blood samples for androgens, gonadotropins, and metabolic parameters; and a transvaginal ultrasound. The phenotype was compared between groups. Ninety-seven percent of women with IM/HA had PCOM. Therefore, the groups with and without PCOM were combined. The Ferriman-Gallwey score and androgen levels were highest in the hyperandrogenic groups (IM/HA and HA/PCOM), whereas ovarian volume was higher in all PCOS subgroups compared with controls, as expected based on the definitions of the PCOS subgroups. Body mass index and insulin levels were highest in the IM/HA subgroup. Subjects with PCOS defined by IM/HA are the most severely affected women on the basis of androgen levels, ovarian volumes, and insulin levels. Their higher body mass index partially accounts for the increased insulin levels, suggesting that weight gain exacerbates the symptoms of PCOS.


Sequence analysis of ripening-related cytochrome P-450 cDNAs from avocado fruit.
The ripening of avocado fruit is associated with the expression of a number of mRNAs concomitant with overt changes in texture and flavor. Two overlapping cDNAs for a mRNA that accumulates during ripening were identified. Sequence analysis of these two cDNAs revealed a polypeptide of 471 amino acids with characteristics of a typical P-450: an N-terminal hydrophobic membrane anchor, a conserved heme-binding domain in the C-terminal region, and patches of similarity to various P-450 family members. Further evidence that this polypeptide represents a cytochrome P-450 oxidase comes from the recent isolation and characterization of a cytochrome P-450 from ripe avocado mesocarp [O'Keefe, D. P. & Leto, K. J. (1989) Plant Physiol. 89, 1141-1149]. The N terminus of the predicted polypeptide in the cDNAs is identical to the N terminus of the purified avocado P-450. Gel blot analysis of RNA from fruit at various stages of ripening showed the accumulation of an 1800-nucleotide P-450 mRNA that hybridized to the P-450 cDNA. The P-450 protein predicted by the avocado cDNA sequence shares less than 40% positional identity with any known P-450 gene family. We propose therefore that it be placed in a separate family, P450LXXI, and that the corresponding gene from avocado be named cyp71A1.


Posttranscriptional Regulation of the Inflammatory Marker C-Reactive Protein by the RNA-Binding Protein HuR and MicroRNA 637.
C-reactive protein (CRP), an acute-phase plasma protein, is a major component of inflammatory reactions functioning as a mediator of innate immunity. It has been widely used as a validated clinical biomarker of the inflammatory state in trauma, infection, and age-associated chronic diseases, including cancer and cardiovascular disease (CVD). Despite this, the molecular mechanisms that regulate CRP expression are not well understood. Given that the CRP 3' untranslated region (UTR) is long and AU rich, we hypothesized that CRP may be regulated posttranscriptionally by RNA-binding proteins (RBPs) and by microRNAs. Here, we found that the RBP HuR bound directly to the CRP 3' UTR and affected CRP mRNA levels. Through this interaction, HuR selectively increased CRP mRNA stability and promoted CRP translation. Interestingly, treatment with the age-associated inflammatory cytokine interleukin-6 (IL-6) increased binding of HuR to CRP mRNA, and conversely, HuR was required for IL-6-mediated upregulation of CRP expression. In addition, we identified microRNA 637 (miR-637) as a microRNA that potently inhibited CRP expression in competition with HuR. Taken together, we have uncovered an important posttranscriptional mechanism that modulates the expression of the inflammatory marker CRP, which may be utilized in the development of treatments for inflammatory processes that cause CVD and age-related diseases.


Therapeutic prostate cancer vaccines: a review of the latest developments.
Therapeutic cancer vaccines are well-tolerated immunotherapy modalities designed to activate the immune system to kill cancer cells without a significant effect on healthy cells. An improved understanding of tumor immunology has led to improved strategies in vaccine development, which in turn have resulted in improved outcomes. This review discusses different types of cancer vaccines, with a focus on prostate cancer vaccines because of the high prevalence of prostate cancer and the wide variety of approaches used in prostate cancer immunotherapy.


A genotypic mutation system measuring mutations in restriction recognition sequences.
The RFLP/PCR approach (restriction fragment length polymorphism/polymerase chain reaction) to genotypic mutation analysis described here measures mutations in restriction recognition sequences. Wild-type DNA is restricted before the resistant, mutated sequences are amplified by PCR and cloned. We tested the capacity of this experimental design to isolate a few copies of a mutated sequence of the human c-Ha-ras1 gene from a large excess of wild-type DNA. For this purpose we constructed a 272 bp fragment with 2 mutations in the PvuII recognition sequence 1727-1732 and studied the rescue by RFLP/PCR of a few copies of this 'PvuII mutant standard'. Following amplification with Taq-polymerase and cloning into lambda gt10, plaques containing wild-type sequence, PvuII mutant standard or Taq-polymerase induced bp changes were quantitated by hybridization with specific oligonucleotide probes. Our results indicate that 10 PvuII mutant standard copies can be rescued from 10(8) to 10(9) wild-type sequences. Taq polymerase errors originating from unrestricted, residual wild-type DNA were sequence dependent and consisted mostly of transversions originating at G.C bp. In contrast to a doubly mutated 'standard' the capacity to rescue single bp mutations by RFLP/PCR is limited by Taq-polymerase errors. Therefore, we assessed the capacity of our protocol to isolate a G to T transversion mutation at base pair 1698 of the MspI-site 1695-1698 of the c-Ha-ras1 gene from excess wild-type ras1 DNA. We found that 100 copies of the mutated ras1 fragment could be readily rescued from 10(8) copies of wild-type DNA.


A universal test to determine the integrity of RNA, and its suitability for reverse transcription, in animal tissue laboratory specimens.
Degradation of RNA in diagnostic specimens can cause false-negative test results and potential misdiagnosis when tests rely on the detection of specific RNA sequence. Current molecular methods of checking RNA integrity tend to be host species or group specific, necessitating libraries of primers and reaction conditions. The objective here was to develop a universal (multi-species) quality assurance tool for determining the integrity of RNA in animal tissues submitted to a laboratory for analyses. Ribosomal RNA (16S rRNA) transcribed from the mitochondrial 16S rDNA was used as template material for reverse transcription to cDNA and was amplified using polymerase chain reaction (PCR). As mitochondrial DNA has a high level of conservation, the primers used were shown to reverse transcribe and amplify RNA from every animal species tested. Deliberate degradation of rRNA template through temperature abuse of samples resulted in no reverse transcription and amplification. Samples spiked with viruses showed that single-stranded viral RNA and rRNA in the same sample degraded at similar rates, hence reverse transcription and PCR amplification of 16S rRNA could be used as a test of sample integrity and suitability for analysis that required the sample's RNA, including viral RNA. This test will be an invaluable quality assurance tool for determination of RNA integrity from tissue samples, thus avoiding erroneous test results that might occur if degraded target RNA is used unknowingly as template material for reverse transcription and subsequent PCR amplification.


Understanding the SERS Effects of Single Silver Nanoparticles and Their Dimers, One at a Time.
This perspective article highlights recent developments in a class of surface-enhanced Raman scattering (SERS) experiments that aim to correlate SERS enhancement factors with the physical parameters of metal nanostructures. In a typical study, the SERS substrate is fabricated by depositing colloidal nanoparticles on a silicon wafer to obtain individual particles isolated from each other, or small aggregates such as dimeric units. With the help of registration marks, the same nanoparticle, or dimer of nanoparticles, can be quickly located under a Raman microscope (for SERS spectra) and a scanning electron microscope (for structural characterization). The nanoscale characterization achieved by these studies has resulted in unparalleled investigations into the nature of polarization dependency for SERS, the hot spot nature of single nanoparticles and dimers, and the manipulation of hot spots through shape-controlled synthesis and self-assembly. We discuss the new insights these studies have offered, and the future progress they can deliver to the advancement of SERS.


Why do clinicians maintain antidepressants in some patients with acute mania? Hints from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), a large naturalistic study.
Antidepressants are supposed to be withdrawn during a manic episode. The aim of this study was to analyze the characteristics of manic patients who received antidepressants during a manic phase in a large, naturalistic study. The European Mania in Bipolar Longitudinal Evaluation of Medication was a 2-year prospective observational study of inpatients and outpatients with acute mania/mixed mania (DSM-IV or ICD-10 criteria) conducted in 14 European countries. Of 2,416 manic patients who continued into the maintenance phase of the study, 345 (14%) were taking an antidepressant and 2,071 (86%) were not taking an antidepressant at baseline, week 1, and/or week 2 postbaseline. Demographic and clinical variables were collected at baseline and each study visit up to 24 months. Outcome measures included the Clinical Global Impressions-Bipolar Disorder scale (CGI-BP overall, mania, and depression scores) at 12 weeks and 24 months, the 5-item Hamilton Depression Rating Scale (HDRS-5), and the Young Mania Rating Scale (YMRS) at 12 weeks only. The present study was conducted from December 2002 to June 2004. More antidepressant maintenance use was seen in patients with mixed episodes (P < .001), rapid cyclers (P < .02), patients with more previous depressive episodes (P < .001), and patients with higher mean HDRS-5 score at baseline (P < .001)-specifically patients with anxiety (P = .013). Patients in the antidepressant group had significantly higher CGI-BP depression scores (P < .001) and a significantly higher rate of depression relapse (P < .001) at both 12 weeks and 24 months. Patients with mania receiving antidepressants are more likely to be outpatients with mixed episodes, anxiety, or rapid cycling and have a higher risk of depression relapse during follow-up.


Bioactive polyphenols from grapes and wine emphasized with resveratrol.
Grape polyphenols are abundant. They play essential roles in the plant's life, particularly in defence mechanisms. Moreover, the grape, fresh or dried, is a widely consumed fruit by humans, as are its by-products, grape juice and wine. They also contain vast and highly varied quantities of polyphenols. Like other phytophenols, grape and wine resveratrol is considered a protective micronutrient. Resveratrol is a well known antioxidant, for example, a protector of low-density lipoproteins against oxidation. Its applications are therefore highly varied. Research supports the idea that wine consumed regularly, without excess, is a natural biological product possesses preventive properties, and not only well-known properties against vascular diseases (illustrated by the so-called French paradox). At least in experimental models so far, resveratrol prevents infections, inflammation, neurodegenerative diseases, and cancer. This review addresses whether the pro-longevity properties of resveratrol are preserved in the human species. If such is the case, it will be possible to imagine new ways of eating based on natural foods, with or without supplements, based on resveratrol. On the other hand, studies such as ours are investigating the synergies between resveratrol and some of the many polyphenols found in wine. These studies should fill in the gaps between the study of a molecule tested in isolation or in a binary system (e.g., with alcohol) and this same molecule in its biological context.