Environmental exposures to pesticides, phthalates, phenols and trace elements are associated with neurodevelopment in the CHARGE study.
To determine if higher exposures measured in early childhood to environmental phenols, phthalates, pesticides, and/or trace elements, are associated with increased odds of having a diagnosis of Autism Spectrum Disorder (ASD), Developmental Delay (DD), or Other Early Concerns (OEC) compared to typically developing children (TD). This study included 627 children between the ages of 2-5 who participated in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Urine samples were collected at the same study visit where diagnostic assessments to confirm diagnosis indicated during the recruitment process were performed. Adjusted multinomial regression models of each chemical with diagnosis as the outcome were conducted. Additionally, two methods were used to analyze mixtures: repeated holdout multinomial weighted quantile sum (WQS) regression for each chemical class; and a total urinary mixture effect was assessed with repeated holdout random subset WQS. Many urinary chemicals were associated with increased odds of ASD, DD or OEC compared to TD; however, most did not remain significant after false discovery rate adjustment. Repeated holdout WQS indices provided evidence for associations of both a phenol/paraben mixture effect and a trace element mixture effect on DD independently. In analyses adjusted for confounders and other exposures, results suggested an association of a pesticide mixture effect with increased risk for ASD. Results also suggested associations of a total urinary mixture with greater odds of both ASD and DD separately. Higher concentrations of urinary biomarkers were associated with ASD, DD, and OEC compared to TD, with consistency of the results comparing single chemical analyses and mixture analyses. Given that the biospecimens used for chemical analysis were generally collected many months after diagnoses were made, the direction of any causal association is unknown. Hence findings may reflect higher exposures among children with non-typical development than TD children due to differences in behaviors, metabolism, or toxicokinetics.


[Features of individual sympathetic preganglionic neurons and their axons in the superior thoracic portion of the spinal cord].
The existence of B- and C-preganglionic fibers in T3 spinal cord segment was shown with the aid of recording the antidromic waves in the ventral root filaments elicited by corresponding white ramus stimulation. Conduction velocity, excitability, and refractory period of these fibers were obtained. Antidromic discharges of sympathetic preganglionic neurons with high-speed B-axons were found in ventral horn. Sympathetic preganglionic neurons of the lateral horn have B-axons with slower conduction velocity, and those situated in lateral part of the intermediate zone have C-axons.


Self Representations and Music Performance Anxiety: A Study With Professional and Amateur Musicians.
Individual, social and situational factors might play an important role on the experience of anxiety during musical performances. The present research focused on the relationship between self-representations, including musical self, and performance anxiety among a sample of Italian professional and amateur musicians (N = 100; age, M = 23.40, 50% females). We predicted that higher self-discrepancies (actual vs. future self) would be associated with higher performance anxiety in a musical setting (vs. a non musical one), via musical self, and only in professional musicians. The results confirmed our hypothesis. Higher discrepancies between actual and future self-representations were positively associated with higher performance anxiety levels via the musical self only in participants who play instruments at a professional level. Furthermore, musical self influenced performance anxiety levels in a music related setting (i.e., a concert) but not in a non musical one (i.e., an exam).


In the Era of Shared Decision Making, How Would An Iranian Urologist Screen Himself For Prostate Cancer?
Prostate cancer (PCa) poses a significant health problem in developed countries. Prostate specific antigen (PSA) based screening for PCa is controversial and large trials have failed to show a significant reduction in prostate-specific mortality and all-cause mortality. Considering the contradictory data on PCa screening, current guidelines emphasize shared decision making. Physicians are the ones in charge of helping patients with informed decision making, so we conducted this study to find out what urologists would do for themselves as patients. Urologists attending the 15th congress of Iranian Urological Association were invited to participate in a questionnaire-based survey on PCa screening. A total of 184 physicians completed the questionnaire. Of participants 76.8% declared that they would like to be screened. 69.3% of those in favor of screening did not consider digital rectal examination (DRE) as part of their screening program. 62.8% of the urologists willing to be screened chose serial PSA as their follow up method in case their PSA level came above normal ranges, and 35.8% preferred to be biopsied. Urologists tend to prefer PSA screening despite the current controversy about its usefulness. Most of the urologists practicing in Iran do not choose DRE as part of their screening program. Large high quality studies conducted in other countries are needed to look into urologist's attitudes towards PCa screening, and to investigate their preferences in order to understand the rationale behind their decisions.


Evaluation of the recommended core components of cardiac rehabilitation practice: an opportunity for quality improvement.
Guidelines have been established that describe recommended core components for cardiac rehabilitation (CR) programs; yet, there are no national efforts to monitor the integration of the guidelines. The purpose of this research was to describe incorporation of core components in CR programs. This was a cross-sectional study using the Ohio Phase II Cardiac Rehabilitation Survey. Descriptive analyses were stratified on American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) certification, case management, and staff mix. Sixty-six percent (n = 94) of programs responded, 39% (n = 37) were AACVPR certified, 40% (n = 38) used case management, and 73% (n = 75) staffed an exercise physiologist. Notable findings included that only 44% of programs obtained/performed a 12-lead electrocardiogram and 36% screened for depression. AACVPR-certified programs compared with uncertified programs were more likely to manage overweight/obesity (100% vs 84% instruct on weight control, respectively, P = .02) and perform health assessments upon admission (89% vs 70% respectively, P = .04). Programs using case management when compared with programs that did not use case management were more likely to administer a health survey (92% vs 65%, respectively, P = .003) and risk stratify (100% vs 84%, respectively, P = .02). Programs with an exercise physiologist were more likely to administer/obtain a stress test when compared with those without an exercise physiologist (78% vs 56%, respectively, P = .04). There was a lack of consistency in the incorporation of core component guidelines; certification, case management, and staff mix offered little improvement. This study provides direction for statewide quality improvement initiatives to improve care delivered in CR programs.


Optimization of Golgi methods for impregnation of brain tissue from humans and monkeys.
Golgi impregnation is unique in its ability to display the dendritic trees of large numbers of individual neurons. However, its reputation for inconsistency leaves many investigators reluctant to embrace this methodology, particularly for the study of formalin-fixed human brain tissue. After reviewing the literature, testing a variety of technical variations, and discussing the procedure with experienced practitioners, we have concluded that much of the unpredictability can be removed by matching the Golgi technique to the conditions that were used for fixation of the tissue. Briefly fixed tissues worked best with the rapid Golgi technique, which includes osmium during the initial chromation step, and with the Golgi-Cox method, which includes mercuric chloride during chromation. For tissues that have been fixed for several years or even for several decades, superior results are obtained with the Golgi-Kopsch technique, using multiple changes of a chromation solution that contains paraformaldehyde. In the Golgi-Kopsch technique, pH should be used to monitor the reduction of Cr6+ to Cr3+, which is a crucial determinant of successful chromation. With any Golgi technique, agitation throughout the impregnation helps to avoid precipitates and to improve the quality of impregnation. When the appropriate method is chosen, Golgi impregnation is a useful technique for the neuropathologist.


PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication.
Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2). However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway. Based on a 7-Methylguanosine 5'-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells. This suggests that most mosquito proteins are synthesized via canonical cap-dependent translation. When the PERK signal pathway was inhibited, both accumulation of reactive oxygen species and changes in the mitochondrial membrane potential increased. This suggested that ER stress response was alleviated through the PERK-mediated shutdown of global proteins in DENV2-infected C6/36 cells. In the meantime, the activities of caspases-9 and -3 and the apoptosis-related cell death rate increased in C6/36 cells with PERK inhibition. This reflected that the PERK-signaling pathway is involved in determining cell survival, presumably by reducing DENV2-induced ER stress. Looking at the PERK downstream target, α-subunit of eukaryotic initiation factor 2 (eIF2α), an increased phosphorylation status was only shown in infected C6/36 cells. This indicated that recruitment of ribosome binding to the mRNA 5'-cap structure could have been impaired in cap-dependent translation. It turned out that shutdown of cellular protein translation resulted in a pro-survival effect on mosquito cells in response to DENV2 infection. As synthesis of viral proteins was not affected by the PERK signal pathway, an alternate mode other than cap-dependent translation may be utilized. This finding provides insights into elucidating how the PERK signal pathway modulates dynamic translation of proteins and helps mosquito cells survive continuous replication of the DENV2. It was ecologically important for virus amplification in mosquitoes and transmission to humans.


XRMA and ToF-SIMS Analysis of Normal and Hypomineralized Enamel.
Molar incisor hypomineralization (MIH) is a developmental disturbance of the enamel. This study presents analyses of hypomineralized and normal enamel in first molar teeth diagnosed with MIH, utilizing time-of-flight secondary ion mass spectrometry area analyses and X-ray microanalysis of area and spot profiles in uncoated samples between gold lines which provide electrical conductivity. Statistical analysis of mean values allows discrimination of normal from MIH enamel, which has higher Mg and lower Na and P. Inductive analysis using complete data sets for profiles from the enamel surface to the enamel-dentin junction found that Mg, Cl and position in the profile provide useful discrimination criteria. Element profiles provide a visual complement to the inductive analysis and several elements also provide insight into the development of both normal and MIH enamel. The higher Mg content and different Cl profiles of hypomineralized enamel compared with normal enamel are probably related to a relatively short period during the development of ameloblasts between birth and the 1st year of life.


Effect of particle size and heat treatment of soybean meal on standardized ileal digestibility of amino acids in growing pigs.
A study with growing barrows was conducted to evaluate of variations in particle size and degree of heat treatment during processing on standardized ileal digestibility (SID) of AA in soybean (Glycine max) meal (SBM). A commercial SBM batch was visually identified as being overtoasted due to its brownish color and was separated into small and large particles using a 1-mm sieve. In addition, 3 SBM were produced from 1 batch of soybean and exposed to different processing conditions (temperature and direct steam contact) referred to as mild (105°C; 34 min), medium (115°C; 45 min), and strong (139°C; 7 min). In total, 5 SBM-corn (Zea mays) starch-based diets were formulated to contain SBM as the sole protein source. This experiment was conducted according to a 6 × 6 Latin square design using 6 barrows (23 kg initial BW) fitted with a T-cannula at the distal ileum. With increasing particle size, SID of His and some dispensable AA increased (P < 0.05). Lower SID values in small compared to large SBM particles indicate more pronounced heat damage possibly due to increased surface area. The SID of CP and AA was lowest in the mild, intermediate in the strong, and highest in the medium toasted SBM (P < 0.001). These differences in SID are reflected in varying contents of trypsin inhibitors, Lys, reactive Lys, and NDF. In conclusion, both differences in particles size and variations in thermal processing conditions of SBM may affect SID of CP and AA.


The OPTIS Integrated System: real-time, co-registration of angiography and optical coherence tomography.
The efficacy of an IVUS-guided stent implantation strategy to improve acute results and clinical outcome has been described previously. OCT is another technique which allows high-resolution intracoronary imaging. However, the use of invasive imaging modalities to guide PCI has, as yet, played a limited role in current clinical practice. This may be partly explained by the expertise required for interpretation and clinical decision making. We present a novel technology which enables real-time co-registration of OCT images with angiography. This will simplify matching cross-sectional images to their geographic position on the angiogram, thereby facilitating imaging-guided PCI.


The regulation of explicit and implicit race bias: the role of motivations to respond without prejudice.
Three studies examined the moderating role of motivations to respond without prejudice (e.g., internal and external) in expressions of explicit and implicit race bias. In all studies, participants reported their explicit attitudes toward Blacks. Implicit measures consisted of a sequential priming task (Study 1) and the Implicit Association Test (Studies 2 and 3). Study 3 used a cognitive busyness manipulation to preclude effects of controlled processing on implicit responses. In each study, explicit race bias was moderated by internal motivation to respond without prejudice, whereas implicit race bias was moderated by the interaction of internal and external motivation to respond without prejudice. Specifically, high internal, low external participants exhibited lower levels of implicit race bias than did all other participants. Implications for the development of effective self-regulation of race bias are discussed.


Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA) as a recently emerged anti-neoplastic histone deacetylase (HDAC) inhibitor and pioglitazone (PGZ) as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies. Here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human Jurkat cells. Treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and MTT viability assay. Real-time RT-PCR was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. Our findings illustrated that both VPA and PGZ can inhibit Jurkat E6.1 cells in vitro after 24 hr; however, PGZ 400 μM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G2/M with deregulated cell division cycle 25A (Cdc25A) phosphatase and cyclin-dependent kinase inhibitor 1B (CDKN1B or p27) expression. Expression of cyclin D1 gene was inhibited when DNA synthesis entry was declined. Cell cycle deregulation in PGZ and VPA-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. These findings define that anti-proliferative effects of PGZ and VPA on Jurkat cell line are mediated by cell cycle deregulation. Thus, we suggest PGZ and VPA may relieve potential therapeutic application against apoptosis-resistant malignancies.


[Effect of different tests with physical exercise to change of the ankle-brachial index in aged patients].
The aim was to study the dynamics of ankle-brachial index (ABI) after treadmill test, after six-minute walk test (SWT) and after electric muscle stimulation (EMS) in aged patients. We conducted a survey of 80 aged patients (73,0 +/- 16,0 years). ABI was determined at rest and immediately after the following tests: 1) treadmill-test for five minutes, 2) SWT, and 3) EMS for five minutes. Atherosclerotic lesions of lower limb arteries was absent only in 21,3% of patients according to color duplex scanning. ABI significantly decreased on both limbs after treadmill-test ant after SWT. During EMS, in contrast, ABI was increased. Thus, you can use SWT in the diagnosis of subclinical atherosclerosis in a general clinical practice as an alternative to treadmill-tests. Good tolerability of EMS patients and ABI increase show the availability of EMS in physical rehabilitation of aged patients with peripheral atherosclerosis.


Physiological responses of the European cockle Cerastoderma edule (Bivalvia: Cardidae) as indicators of coastal lagoon pollution.
Physiological responses can be used as effective parameters to identify environmentally stressful conditions. In this study, physiology changes such as oxygen consumption, clearance rate, survival in air, condition index and energy reserves were measured on natural populations of cockles collected from different sites at Ria de Aveiro, Portugal. At those sites, sediment samples were collected for Hg concentration analysis. Cockles were used for the evaluation of both the Hg concentration and physiological response. Mercury was detected in the cockle tissue and in the sediment collected from the sampling points both nearby and distant from the main mercury contamination source. The energy content was negatively correlated with both Hg concentration in cockle tissues and survival in air. Nonetheless, the energy content was positively correlated with the condition index, and there was a positive correlation between the survival in air test and the tissue mercury concentration. A PCA-factor analysis explained 86.8% of the total variance. The principal factor (62.7%) consisted of the air survival, the Hg in soft tissues (positive) and the condition index (negative). The second factor (24.1%) consisted of a negative correlation between the oxygen consumption and the clearance rate. Due to their sensitivity to environmental conditions, the physiological responses of cockles can be used to assess the ecological status of aquatic environments. More effort should be invested in investigating the effects of environmental perturbations on cockle health once they are a good reporter organism.


Effects of oral intake of nitrates on reproductive functions of bulls.
Effects of oral intake of nitrates on selected biochemical and endocrinological indices and its impact on reproductive functions were investigated in five feeder bulls aged 16-18 months. The bulls were tested prior to (30 days), during (30 days) and after (35 days) the period of the nitrate administration. The initial dose of 100 g potassium nitrate per day was increased at weekly intervals by 50 g up to 250 g per day. The administration of nitrates resulted in a highly significant (P < 0.01) increase in methaemoglobin concentration and a non-significant decrease in the concentration of beta-carotene and a highly significant (P < 0.01) decrease in the concentration of E vitamin in blood serum. A significant (P < 0.01) increase in blood serum concentration of bile acids and prolonged biological half-life of progesterone were suggestive of an impairment of liver metabolism. Prolonged intake of excessive doses of nitrates resulted in a significant (P < 0.05) increase in cortisol concentration during and after the administration period, while depressed thyroid gland activity was evident from a significant (P < 0.05) decrease in thyroxin concentration during the administration period. A suppression of hypothalamic functions after the administration period was documented by non-detectable levels (< 0.001 microgram/ml) of thyrotropin in TRH test. Depressive effects of nitrates on the function of Leydig cells during and particularly after the administration period were apparent from weakening testicular responses to a treatment with GnRH. Biochemical analyses of seminal plasma revealed a highly significant (P < 0.01) increase in total acid phosphatase activity and a significant (P < 0.05) decrease in the concentration of fructose. No other significant changes in seminal plasma components were observed. Adverse effects of excessive intake of nitrates were also evident from reduced sperm motility in the 120-min thermal test. While no difference was found in the frequency of primary morphological abnormalities, the number of secondary abnormalities rose by 115% in the post-administration period and was suggestive of damaged membrane integrity. Histological examinations revealed degenerative lesions in cells of the spermiocyte and spermatid layers.


Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline phosphatase gene in neonatal hypophosphatasia associated with convulsions.
We describe a patient diagnosed with lethal perinatal hypophosphatasia with a unique clinical presentation of convulsions that responded to vitamin B6. Genomic DNA sequence analysis of the tissue-nonspecific alkaline phosphatase (TNSALP) gene revealed two missense mutations: a G-to-A transition resulting in a Glu to Lys at codon 274 (E274K), and a G-to-C transversion resulting in a Gly to Arg at codon 309 (G309R). The first mutation was maternally transmitted and was previously characterized as a moderate one, whereas the latter was paternally transmitted and has not been previously reported. Phenotype/genotype correlation indicates that G309R is a deleterious mutation that can lead to seizures and a lethal outcome, as was demonstrated in our patient.


The role of cigarette smoking and statins in the development of postmenopausal osteoporosis: a pilot study utilizing the Marshfield Clinic Personalized Medicine Cohort.
A cohort of postmenopausal osteoporotic females and controls with normal bone mineral density, the interleukin 6 (IL6) -634G > C (rs1800796) C allele of the promoter region showed association with osteoporosis. The lipoprotein receptor-related protein 5 (LRP5) gene showed association between C135242T C/T alleles and osteoporosis only in smokers, suggesting a role for environmental interaction. A nested case-control study within a population-based cohort was undertaken to assess the relative impact of cigarette smoking, statin use, genetic polymorphisms, and one-way interaction of these factors on development of osteoporosis in postmenopausal women. Genotyping of 14 single-nucleotide polymorphisms (SNPs) corresponding to vitamin D receptor gene, estrogen receptor 1, collagen type 1 alpha 1, IL6, transcription growth factor beta, apolipoprotein E, and LRP5 genes was performed in cases (n = 309) with osteoporosis and controls (n = 293) with normal bone mineral density drawn from a homogeneous Caucasian population. SNPs were chosen based on known functional consequences or prior evidence for association and genotyped using matrix-assisted laser desorption ionization time-of-flight technology. Cases differed from controls relative to body mass index, age, and smoking but not statin use. After adjusting for age, the IL6 -634G > C (rs1800796) allele showed association with osteoporosis (odds ratio (OR) for CC + CG = 2.51, p = 0.0047)), independent of statin use or smoking status. On stratification for smoking, association with LRP5 C135242T (rs545382) and osteoporosis emerged (OR 2.8 in smokers for CT alleles, p = 0.03)), suggestive of potential environmental interaction. Evidence suggested a role for genetic variation in IL6 and LRP5 in conferring risk for osteoporosis in Caucasian women, with the latter manifest only in smokers.


Quo vadis chimerism?
Although immunity in multicellular organisms is efficient in dealing with alien agents, it may fail for allogeneic chimerism. Natural chimerism is widely documented in nature, distributed in at least ten phyla of protists, invertebrates and plants, vertebrates and mammals, including humans; it is an important ecological/evolutionary tool manipulating metazoans' life history portraits. Instead of purging allogeneic nascent selfish cells, a 'double edged sword' chimerism emerges, displaying environmental dictated costs and benefits for the genotypes involved. Benefits include the development of synergistic complementation, the increase of genetic variability, the assurance of mate location, improved size-dependent ecological qualities (growth rates, reproduction, survivorship, competition, environmental tolerance) and more. Costs include the threat of somatic and germ cell parasitism, developmental instability, death, diseases, autoimmunity, sexual sterility and organ malformations, which develop as well in mammalian natural chimerism, including humans. Because of its importance, medical sciences should study and harness natural chimerism properties for clinical purposes.


Nanohexaconazole: synthesis, characterisation and efficacy of a novel fungicidal nanodispersion.
Here, the authors describe a simple method to formulate the nanodispersion of hexaconazole (hexa); henceforth, referred to as nanohexaconazole (N-hexa) that is water soluble and effective against several species of Aspergillus. Size and shape of the prepared nanocomposite was determined with high-resolution transmission electron microscopy and field-emission scanning electron microscopy. Nanohexaconazole structure was further confirmed by Fourier-transform infrared spectroscopy and gas chromatography-mass spectrometry. The antifungal efficacy of nanohexaconazole (N-hexa) was studied in vitro, compared with micronised hexaconazole (M-hexa) at different doses (5 ppm, 10 ppm and control) against two food pathogenic fungi: Aspergillus niger (MTCC 282, MTCC 2196 and BDS 113) and Aspergillus fumigatus through poisoned food technique. A dose-dependent significant growth inhibition was observed in nanohexaconazole (N-hexa) treated fungal sample compared with that of micronised hexaconazole (M-hexa). Micrographic studies for the morphological analysis of control and nanohexaconazole (N-hexa) treated fungal samples were done, exhibited an alternation in fungal morphology. Results showed that nanohexaconazole (N-hexa) is more efficacious than commercially available micronised hexaconazole (M-hexa). In future nanohexaconazole (N-hexa) could be a possible candidate for modern medical science and also reduce damage to the environment from injudicious use of pesticides.


Eliminating untimely deaths of women from heart disease: highlights from the Minnesota Women's Heart Summit.
Despite national campaigns to increase awareness and reduce cardiovascular disease (CVD) mortality in women, CVD remains their leading cause of death, annually killing more women than men. Although some progress has been made in our understanding and treatment of CVD in women, the causes, extent, and demographic trends of observed sex differences and disparities remain uncertain, and the growing burden of CVD and its risk factors among younger women is concerning. The Minnesota Women's Heart Summit was convened to chart a course to eliminate premature deaths of women from heart disease. The multidisciplinary summit was hosted by the Minneapolis Heart Institute, Minneapolis Heart Institute Foundation, University of Minnesota, and Mayo Clinic. Presentations highlighted sex-based differences in symptoms, treatment, and outcomes, and panel experts provided commentary. Invited faculty and summit participants worked in small-group sessions to identify strategies to dissolve barriers, improve primary and secondary prevention, and enhance women's care and outcomes. This report summarizes strategies identified during the conference to serve as springboards for more substantive future initiatives. These include, for example, standardized data collection and use of existing data sets to inform perspectives on sex-related cardiovascular issues, mandatory reporting of sex-specific data, and increased attention to underserved/high-risk women. Participants acknowledged that implementing these ideas would be challenging and recommended key priorities/next action steps such as providing services close to "point-of-life" rather than "point-of-care" and creation of policies and regulations so that resources and environmental modifications encouraging healthier lifestyle choices are promoted. Additional research is needed to improve identification, treatment, and health behaviors and to address continued lack of awareness, symptom recognition delays, barriers to care, and outcome disparities-especially in diverse populations.


Interplay of cell motility and self-secreted extracellular polymeric substance induced depletion effects on spatial patterning in a growing microbial colony.
Reproducing bacteria self-organize to develop patterned biofilms in various conditions. Various factors contribute to the shaping of a multicellular bacterial organization. Here we investigate how motility force and self-secreted extracellular polymeric substances (EPS) influence bacterial cell aggregation, leading to phase-separated colonies using a particle-based/individual-based model. Our findings highlight the critical role of the interplay between motility force and depletion effects in regulating phase separation within a growing colony under far-from-equilibrium conditions. We observe that increased motility force hinders depletion-induced cell aggregation and phase segregation, necessitating a higher depletion effect for highly motile bacteria to undergo phase separation within a growing biofilm. We present a phase diagram illustrating the systematic variation of motility force and repulsive mechanical force, shedding light on the combined contributions of these two factors: self-propulsive motion and aggregation due to the depletion effect, resulting in the presence of small to large bacterial aggregates. Furthermore, our study reveals the dynamic nature of clustering, marked by changes in cluster size over time. Additionally, our findings suggest that differential dispersion among the components can lead to the localization of EPS at the periphery of a growing colony. Our study enhances the understanding of the collective dynamics of motile bacterial cells within a growing colony, particularly in the presence of a self-secreted polymer-driven depletion effect.


A chemical strategy for the cell-based detection of HDAC activity.
A strategy for activity-based enzyme detection using a novel enamide-based chemical strategy is described. Enzymatic cleavage of an amide bond results in the formation of an aldehyde. The interaction of this aldehyde with proteins increases retention in cells that express the enzyme. Proof of concept for this enamide-based strategy is demonstrated by detecting histone deacetylase (HDAC) activity in HeLa cells. The modular design of this strategy makes it amenable to in vitro and in vivo detection.


CYP4V2 rs56413992 C > T was associated with the risk of coronary heart disease in the Chinese Han population: a case-control study.
The research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk. This case-control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection. As a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09-1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06-1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN). This study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.


Current progress in computational metabolomics.
Being a relatively new addition to the 'omics' field, metabolomics is still evolving its own computational infrastructure and assessing its own computational needs. Due to its strong emphasis on chemical information and because of the importance of linking that chemical data to biological consequences, metabolomics must combine elements of traditional bioinformatics with traditional cheminformatics. This is a significant challenge as these two fields have evolved quite separately and require very different computational tools and skill sets. This review is intended to familiarize readers with the field of metabolomics and to outline the needs, the challenges and the recent progress being made in four areas of computational metabolomics: (i) metabolomics databases; (ii) metabolomics LIMS; (iii) spectral analysis tools for metabolomics and (iv) metabolic modeling.


[Aggregation of membrane proteins of E. coli cells after treatment with singlet oxygen].
It was found that interaction of 1O2 with bacterial membranes of E. coli cells results in covalent binding and aggregation of membrane proteins. This process was shown to be inhibited by water-soluble free radical scavengers, e. g., 1O2 quenchers (cysteine, sodium azide, histidine), of which the latter afforded the strongest inhibition. No protective effect of the fat-soluble free radical scavenger ionol (BHT) on membrane protein aggregation was observed. It was assumed that the main role in oxidative destruction of bacterial membranes (in contrast to membranes from animal sources) is ascribed to processes which are not coupled to lipid peroxidation.


Psycholinguistic changes in athletes' grief response to injury after written emotional disclosure.
Grief can be a common psychological characteristic of long-term injury, but few athletes are taught how to effectively deal with these intense emotions. To examine the effectiveness of Pennebaker's standard writing paradigm in improving athletes' psychological response to injury after engaging in written disclosure. Repeated-measures design with 6 data-collection time points. Sport-injury clinics. 9 elite long-term-injured athletes. MEASURES AND INTERVENTION: Participants were administered the Psychological Responses to Sport Injury Inventory and the Rehabilitation Beliefs Survey at 3 times preintervention and postintervention. Intervention comprised three 20-min writing sessions. Linguistic analyses were carried out using the Linguistic Inquiry Word Count to determine whether changes in word categories would be associated with postintervention changes in grief characteristics and rehabilitation-belief subscales. There were significant differences in athletes' grief characteristics postintervention, with athletes feeling less devastated, dispirited, cheated, and restless by their injury and increasing the reorganization of their thoughts. Corresponding evidence from text analyses further supported these changes, with athletes linguistically demonstrating that they were actively working through their grief-related response using improved cognitive processing (F2,16=5.15, P=.019, Eta2=.39) and the disinhibition of positive and negative affect (F2,16=4.05, P=.038, Eta2=.34). There were no significant changes in athletes' rehabilitation beliefs, which remained high throughout the testing period. Overall, the findings demonstrated that written emotional disclosure was effective in enhancing psychological rehabilitation by contributing to a greater personal understanding of the injury event and attenuating athletes' grief-related response.


Effect of Behavioral and Pelvic Floor Muscle Therapy Combined With Surgery vs Surgery Alone on Incontinence Symptoms Among Women With Mixed Urinary Incontinence: The ESTEEM Randomized Clinical Trial.
Mixed urinary incontinence, including both stress and urgency incontinence, has adverse effects on a woman's quality of life. Studies evaluating treatments to simultaneously improve both components are lacking. To determine whether combining behavioral and pelvic floor muscle therapy with midurethral sling is more effective than sling alone for improving mixed urinary incontinence symptoms. Randomized clinical trial involving women 21 years or older with moderate or severe stress and urgency urinary incontinence symptoms for at least 3 months, and at least 1 stress and 1 urgency incontinence episode on a 3-day bladder diary. The trial was conducted across 9 sites in the United States, enrollment between October 2013 and April 2016; final follow-up October 2017. Behavioral and pelvic floor muscle therapy (included 1 preoperative and 5 postoperative sessions through 6 months) combined with midurethral sling (n = 209) vs sling alone (n = 207). The primary outcome was change between baseline and 12 months in mixed incontinence symptoms measured by the Urogenital Distress Inventory (UDI) long form; range, 0 to 300 points; minimal clinically important difference, 35 points, with higher scores indicating worse symptoms. Among 480 women randomized (mean [SD] age, 54.0 years [10.7]), 464 were eligible and 416 (86.7%) had postbaseline outcome data and were included in primary analyses. The UDI score in the combined group significantly decreased from 178.0 points at baseline to 30.7 points at 12 months, adjusted mean change -128.1 points (95% CI, -146.5 to -109.8). The UDI score in the sling-only group significantly decreased from 176.8 to 34.5 points, adjusted mean change -114.7 points (95% CI, -133.3 to -96.2). The model-estimated between-group difference (-13.4 points; 95% CI, -25.9 to -1.0; P = .04) did not meet the minimal clinically important difference threshold. Related and unrelated serious adverse events occurred in 10.2% of the participants (8.7% combined and 11.8% sling only). Among women with mixed urinary incontinence, behavioral and pelvic floor muscle therapy combined with midurethral sling surgery compared with surgery alone resulted in a small statistically significant difference in urinary incontinence symptoms at 12 months that did not meet the prespecified threshold for clinical importance. ClinicalTrials.gov Identifier: NCT01959347.


Angiolymphoid hyperplasia with eosinophilia that was possibly induced by vaccination in a child.
Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign vasoproliferative disease of an unknown cause involving the skin or subcutaneous tissue of the head and neck, and particularly around the ear. It predominantly affects Caucasian adults during the third and fourth decades and it very rarely occurs in children. We experienced a case of ALHE in a 2-year-old Korean boy who had a firm, pruritic, skin-colored, subcutaneous nodule on his right upper arm. The histopathological findings were compatible with ALHE and they showed prominent vascular changes with epitheloid or histiocytoid endothelial cells surrounded by inflammatory cells, including a large proportion of eosinophils. This unusual distribution of the lesion and the young age of the patient may be associated with vaccination.


Hafnium (Hf)-Chelating Porphyrin-Decorated Gold Nanosensitizers for Enhanced Radio-Radiodynamic Therapy of Colon Carcinoma.
X-ray-induced radiodynamic therapy (RDT) that can significantly reduce radiation dose with an improved anticancer effect has emerged as an attractive and promising therapeutic modality for tumors. However, it is highly significant to develop safe and efficient radiosensitizing agents for tumor radiation therapy. Herein, we present a smart nanotheranostic system FA-Au-CH that consists of gold nanoradiosensitizers, photosensitizer chlorin e6 (Ce6), and folic acid (FA) as a folate-receptor-targeting ligand for improved tumor specificity. FA-Au-CH nanoparticles have been demonstrated to be able to simultaneously serve as radiosensitizers and RDT agents for enhanced computed tomography (CT) imaging-guided radiotherapy (RT) of colon carcinoma, owing to the strong X-ray attenuation capability of high-Z elements Au and Hf, as well as the characteristics of Hf that can transfer radiation energy to Ce6 to generate ROS from Ce6 under X-ray irradiation. The integration of RT and RDT in this study demonstrates great efficacy and offers a promising therapeutic modality for the treatment of malignant tumors.


Ab initio quantum-chemical computations of the absorption cross sections of HgX2 and HgXY (X, Y = Cl, Br, and I): molecules of interest in the Earth's atmosphere.
The electronic-structure properties of the low-lying electronic states and the absorption cross sections (σ(E)) of mercury halides HgCl2, HgBr2, HgI2, HgBrCl, HgClI, and HgBrI have been determined within the UV-vis spectrum range (170 nm ≤ λphoton ≤ 600 nm) by means of the DKH3-MS-CASPT2/SO-RASSI quantum-chemical methodology (with the ANO-RCC basis set) and a semi-classical computational strategy based on nuclear sampling for simulating the band shapes. Computed band energies show a good agreement with the available experimental data for HgX2 with errors around 0.1-0.2 eV; theoretical and σ(E) are within the same order of magnitude. For the mixed HgXY compounds, the present computed data allow us to interpret previously proposed absorption bands estimated from the spectra of the parent molecules HgX2 and HgY2, measured in methanol solution. The analyses performed on the excited-state electronic structure and its changes around the Franck-Condon region provide a rationale on the singlet-triplet mixing of the absorption bands and the heavy-atom effect of the Hg compounds. Furthermore, the present benchmark of HgX2 and HgXY absorption σ values together with the previous benchmark of the electronic-structure properties of HgBr2 [see S. P. Sitkiewicz, et al., J. Chem. Phys., 2016, 145, 244304] has been helpful to set up a methodological and computational protocol which shall be used for predicting the atmospheric absorption and photolysis properties of several Hg compounds present in the atmospheric cycle of Hg.


The interaction of obesity with susceptible gene polymorphisms in the relationship with mild cognitive impairment.
Mild cognitive impairment (MCI) in the elderly is threatening the mental health of the elderly, and the interaction of some factors is worth exploring. This study aims to explore the interactions of obesity and gene polymorphisms in the relationship with MCI. A total of 2555 community resident dwellings include 444 participants who met MCI criteria recruited from the Ningxia province of China. Fourteen MCI-susceptible single nucleotide polymorphisms were detected using a high-throughput mass spectrometer. The interaction was examined by performing the multifactor dimensionality reduction model and unconditional logistic regression model. Logistic regression showed that obesity (OR = 1.42, 95%CI: 1.04-1.94), rs2075650G allele carrying (OR = 17.95, 95%CI: 1.32-244.95), rs11556505T allele carrying (OR = 0.06, 95%CI: 0.01-0.87) were statistically associated with MCI. Multifactor dimensionality reduction analysis showed a strong antagonistic effect between obesity and rs4402960 (Interaction dendrogram between obesity and rs4402960 is red) and a weak synergy effect on rs7901695 (Interaction dendrogram between obesity and rs7901695 is green). The hierarchical analysis showed obesity is a risk factor for MCI in the non-rs4402960T allele carrier group (OR = 1.55, 95%CI: 1.02-2.35). This study found that obesity is an independent risk factor for MCI, and the interactions with MCI-susceptible gene polymorphisms suggest a possible precision preventive intervention program should be developed to reduce the risk of MCI among individuals with obesity in the community.


Comparison of Stent-Assisted Coil Embolization Versus Coil Embolization Alone for Ruptured Cerebral Aneurysms with Mild Symptoms: A Single-Clinic Experience.
To evaluate the safety and efficacy of stent-assisted coil embolization (SAC) in acutely ruptured cerebral aneurysms without severe symptoms, and thus, the usefulness of the stent itself in patients with subarachnoid hemorrhages. From January 2017 to June 2019, 118 patients were treated with coil embolization for acutely ruptured cerebral aneurysms without severe symptoms (Hunt & Hess grade ≤ 3). The periprocedural complications, six-month modified Rankin scores (mRS), and six-month radiologic outcomes were compared between 56 patients with SAC and 62 patients without SAC (non-SAC). The rate of good clinical outcomes (mRS ≤ 2), as well as the rate of hemorrhagic and ischemic complications, showed no significant difference between the SAC and non-SAC groups. Moreover, compared to the non-SAC group, the SAC group showed a lower recanalization rate on the six-month follow-up angiogram (20% vs. 39.3%, p = 0.001). Although stent use was not significantly associated with clinical outcomes in coil embolization of ruptured cerebral aneurysms with non-severe symptoms (Hunt & Hess grade ≤ 3), it significantly decreased the rate of recanalization on follow-up cerebral angiograms.


Implantable device therapy for the treatment of resistant hypertension.
The prevalence of resistant hypertension continues to increase and the standard approaches of therapeutic lifestyle changes and drug therapy are ineffective in bringing many of these patients to goal blood pressure. Electrical stimulation of the carotid sinus baroreceptor through a surgically implanted device is presently under clinical investigation and is showing some encouraging early results. This review discusses the evolution of this therapy including a review of the current data available from the early stages of ongoing clinical trials.


Kidney-Metabolic Factors Associated with Cognitive Impairment in Chronic Kidney Disease: A Pilot Study.
The associations of kidney-metabolic biomarkers with cognitive impairment (CI) beyond the estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) and albuminuria levels are not well understood. In exploratory analysis, our objective was to determine the extent that three kidney-metabolic factors, previously proposed as mechanisms of CI and commonly abnormal in chronic kidney disease (CKD), were associated with prevalent CI in CKD participants, adjusted for kidney function measures. The study cohort included community-dwelling individuals aged ≥45 years with CKD (eGFR <60), not requiring dialysis, recruited from four health systems. We examined the serum biomarkers bicarbonate (CO2), TNFαR1, and cholesterol as primary exposures. A structured neuropsychological battery conducted by trained staff measured global and domain-specific cognitive performance. Logistic regression analyses estimated the cross-sectional associations between kidney-metabolic measures and global and cognitive domain-specific moderate/severe (Mod/Sev) CI, adjusted for the eGFR, urinary albumin-creatinine ratio (UACR, mg/g), demographics, comorbid conditions, and other kidney-metabolic biomarkers commonly abnormal in CKD. Among 436 CKD participants with mean age 70 years, 16% were Black, the mean eGFR was 34, and the median [IQR] UACR was 49 [0.0, 378] mg/g. In adjusted models, increased TNFαR1 was associated with global Mod/Sev CI (odds ratio [95% confidence interval] = 1.40 [1.02, 1.93]; p = 0.04); low bicarbonate (CO2 <20 mEq/L) with Mod/Sev memory impairment (3.04 [1.09, 8.47]; p = 0.03), and each 10-mg/dL lower cholesterol was associated with Mod/Sev executive function/processing speed impairment (1.12 [1.02, 1.23]; p = 0.02). However, after adjustment for multiple comparisons, these associations were no longer significant nor were any other kidney-metabolic factors significant for any CI classification. In exploratory analyses in a CKD population, three kidney-metabolic factors were associated with CI, but after adjustment for multiple comparisons, were no longer significant. Future studies in larger CKD populations are needed to assess these potential risk factors for CI.


Evidence of angiogenesis and microvascular regression in autosomal-dominant polycystic kidney disease kidneys: a corrosion cast study.
Autosomal-dominant polycystic kidney disease (ADPKD) accounts for about 10% of all cases of chronic renal failure requiring dialysis. The disease is characterized by proliferation of renal epithelial cells and formation of cysts that expand over years and replace the normal parenchyma of the kidney. As the cysts grow, the volume of the kidney can increase by more than 10-fold, implying that remodeling and expansion of the vasculature must occur to provide oxygenation and nutrition to the cyst cells. Our previous studies support the notion that there is angiogenesis in ADPKD. We report here results from resin casting of ADPKD kidneys vasculature. In this study, the corrosion-casting method was used in conjunction with scanning electron microscopy to study the vascular architecture and the evidence for angiogenesis in ADPKD kidneys. We found a well-defined vascular network around the cysts forming a 'vascular capsule' somewhat similar to that described in avascular leiomyomata. We also found that the normal vascular architecture is lost and replaced by an assortment of capillaries of larger size than those in the normal kidney, mixed with flattened and spiral arterioles, damaged glomeruli, and atresic venules, indicative of regression of the microvasculature. In the same areas, there was capillary sprouting, considered the hallmark of angiogenesis. The present study documents regression changes of the vasculature and confirms the existence of angiogenesis in ADPKD kidneys, and suggests the use of inhibitors of angiogenesis as a possible avenue for the treatment of the disease.


[Influence of magnetic field on hydrogen peroxide decomposition by catalase].
The rate constants of H2O2 decomposition equal to 0.45 X 10(7) M-1S-1 per hem and Michaelis constants higher than 0.3 M were found by gas volume meter and spectrophotometer methods for purified preparations of catalase from bovine liver. Unlike the results obtained earlier the magnetic field with induction 0.65 T and 0.012 T does not affect the constant rate within 3%. It was found with the substrate concentration less than 0.01 M when the classical catalase mechanism was observed and with higher concentration of the substrate up to 0.7 M when the catalase inhibition by H2O2 played an important role.


Prolactin serum level in patients with breast cancer.
Previous studies have suggested that prolactin may serve as an indicator of disease progression in breast cancer. To evaluate the use of PRL as a serum tumor marker in patients with breast cancer. PRL serum level was determined in 99 breast cancer patients and compared with CA 15-3 serum level. Elevated serum level of PRL (> 20 ng/ml) was found in 8 of 99 patients (8.1%). A stratified analysis of prolactin levels according to therapy revealed that PRL levels was increased in 8 of 55 untreated patients (14.5%), but not in patients who received hormonal or chemotherapy in the 3 months preceding the test (0/42 patients, P = 0.009). However, mean PRL level was similar in patients with no evidence of disease activity and in patients with active disease (10.2 vs. 8.2 ng/ml, NS). In comparison, CA 15-3 mean level was significantly lower in patients with no evidence of disease as compared to patients with active disease (18.2 vs. 144.7 units/ml, P < 0.001). PRL level was increased in 6 of 60 patients (10%) with no evidence of disease and in 2 of 39 (5.2%) with active disease (NS). In comparison, CA 15-3 level was increased in 3 of 60 patients (5%) with no evidence of disease and in 24 of 39 (61.5%) with active disease (P < 0.001). PRL levels are decreased following hormonal or chemotherapy in patients with breast cancer and there is no correlation between PRL serum level and the state of disease. Further studies are needed to clarify a possible clinical significance of hyperprolactinemia in a subset of patients with breast cancer.


A first phylogenetic study on stoloniferous octocorals off the coast of Kota Kinabalu, Sabah, Malaysia, with the description of two new genera and five new species.
Sabah, Malaysia, is well known for its extensive and diverse coral reefs. It is located on the northwestern edge of the Coral Triangle, the region with the highest marine biodiversity. Much of the marine fauna here is still unknown, especially inconspicuous animals, such as small stoloniferous octocorals, which are common on coral reefs. Here, we describe two new monospecific genera of the family Arulidae found off the coast of Kota Kinabalu, Sabah, East Malaysia; Bunga payung gen. nov. et sp. nov. and Laeta waheedae gen. nov. et sp. nov. As well, the stoloniferan genus Phenganax Alderslade & McFadden, 2011 belonging to the family Clavulariidae is expanded with three new species, P. marumi sp. nov., P. subtilis sp. nov., and P. stokvisi sp. nov., which are all sclerite-free. Additionally, we report a possibly undescribed species, closely related to the clavulariid genera Azoriella Lopez-Gonzalez & Gili, 2001 and Cervera Lopez-Gonzalez et al., 1995. As this and other recent studies have shown, discoveries of small stoloniferous octocorals are helping to fill gaps in our knowledge of the overall systematics of Octocorallia.


Self-management of type 1 diabetes in young adults: Is it impeded by aspects of everyday life? A scoping review.
For people with type 1 diabetes, self-management is a necessity. However, self-management can be impeded by aspects of everyday life, which may impact young adults moving to independence. However, it is not yet clear which aspects are most relevant, nor what knowledge gaps remain. An established scoping review methodology was used to select and synthesise the existing literature. Sixteen peer reviewed articles were included for analysis. Type 1 diabetes self-management exists within a disordered space, impeded by aspects of everyday life, while simultaneously impeding daily living. Negative attitudes, concealment, non-adherence, Diabetes Distress, and mental illness were each associated with difficulty in self-management. A cyclical relationship between these characteristics emerged: they are obstacles to self-management yet also result from poor self-management. Young adults were identified as a vulnerable demographic: they tend to perceive type 1 diabetes more negatively and have additional life priorities (e.g., education/work) that lead to suboptimal self-management, including non-adherence behaviours, which can reduce quality of life. Several gaps in the literature were found, notably around psychological experiences, employment, and effective interventions. Few studies involved in-depth exploration of lived experiences. There is a need to develop novel interventions to support self-management of type 1 diabetes that target the obstacles identified here. Furthermore, experiential research into younger adults' experiences of life and work with type 1 diabetes will help fill the knowledge gap for this demographic.


Impact of Short-Range Forces on Defect Production from High-Energy Collisions.
Primary radiation damage formation in solid materials typically involves collisions between atoms that have up to a few hundred keV of kinetic energy. During these collisions, the distance between two colliding atoms can approach 0.05 nm. At such small atomic separations, force fields fitted to equilibrium properties tend to significantly underestimate the potential energy of the colliding dimer. To enable molecular dynamics simulations of high-energy collisions, it is common practice to use a screened Coulomb force field to describe the interactions and to smoothly join this to the equilibrium force field at a suitable interatomic spacing. However, there is no accepted standard method for choosing the parameters used in the joining process, and our results prove that defect production is sensitive to how the force fields are linked. A new procedure is presented that involves the use of ab initio calculations to determine the magnitude and spatial dependence of the pair interactions at intermediate distances, along with systematic criteria for choosing the joining parameters. Results are presented for the case of nickel, which demonstrate the use and validity of the procedure.


The effect of human antiendotoxin monoclonal antibodies on endotoxin-induced lung injury in the rat.
A model of endotoxin-induced lung injury was developed in the rat. We found that 24 h after intravenously administered endotoxin (3 mg/kg) there was increased clearance of the isotope 99mTcDTPA from the lung to blood, increased neutrophils in the lung in bronchoalveolar lavage, and increased levels of products of peroxidation of lipids and nucleic acid in the serum. Using this model, we evaluated the effect of pretreatment of rats with a human monoclonal antibody specific to the core glycolipid that is common to all endotoxins. We found that pretreatment prevented the increased clearance of 99mTcDTPA from the lung, as well as the increase in lipid peroxidation products in the serum. The antibody did not prevent increased neutrophil accumulation in the lung. The findings suggest that the administration of human antiendotoxin monoclonal antibodies prior to endotoxemia may prevent some of the changes in the lung associated with endotoxin.


Evolution of drift robustness in small populations.
Most mutations are deleterious and cause a reduction in population fitness known as the mutational load. In small populations, weakened selection against slightly-deleterious mutations results in an additional fitness reduction. Many studies have established that populations can evolve a reduced mutational load by evolving mutational robustness, but it is uncertain whether small populations can evolve a reduced susceptibility to drift-related fitness declines. Here, using mathematical modeling and digital experimental evolution, we show that small populations do evolve a reduced vulnerability to drift, or 'drift robustness'. We find that, compared to genotypes from large populations, genotypes from small populations have a decreased likelihood of small-effect deleterious mutations, thus causing small-population genotypes to be drift-robust. We further show that drift robustness is not adaptive, but instead arises because small populations can only maintain fitness on drift-robust fitness peaks. These results have implications for genome evolution in organisms with small effective population sizes.


Trauma Exposure and Posttraumatic Stress Disorder in the Canadian Military.
To estimate the lifetime prevalence of trauma exposure and posttraumatic stress disorder (PTSD) among a representative, active military sample, and to identify demographic and military variables that modulate rates of trauma exposure as well as PTSD rates and duration. A cross-sectional weighted sample of 5155 regular members and 3957 reservists (n = 8441) of the Canadian Armed Forces (CAF) was face-to-face interviewed using a lay-administered structured interview that generates Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, psychiatric diagnoses. Within this sample, 85.6% reported 1 or more trauma exposure, with a median number of 3 or more exposures. Compared with males, females were less likely (P < 0.05) to be exposed to warlike trauma (adjusted odds ratio [AOR] 0.40), disasters (AOR 0.43), assaultive violence (AOR 0.52), and witnessing trauma (AOR 0.75). However, they were more likely to report sexual assault (AOR 7.36). The lifetime prevalence of PTSD was 6.6% and the conditional rate was 7.7%. Both lifetime and conditional PTSD rates were higher among female soldiers, but lower among the reserve forces, both male and female. Finally, the median duration of PTSD was negatively influenced by younger age of onset, but not influenced by whether the event occurred during deployment. Active members of the CAF report a high degree of trauma exposure but a moderate rate of lifetime PTSD.


Minimum-Norm Estimation of Motor Representations in Navigated TMS Mappings.
Navigated transcranial magnetic stimulation (nTMS) can be applied to locate and outline cortical motor representations. This may be important, e.g., when planning neurosurgery or focused nTMS therapy, or when assessing plastic changes during neurorehabilitation. Conventionally, a cortical location is considered to belong to the motor cortex if the maximum electric field (E-field) targeted there evokes a motor-evoked potential in a muscle. However, the cortex is affected by a broad E-field distribution, which tends to broaden estimates of representation areas by stimulating also the neighboring areas in addition to the maximum E-field location. Our aim was to improve the estimation of nTMS-based motor maps by taking into account the E-field distribution of the stimulation pulse. The effect of the E-field distribution was considered by calculating the minimum-norm estimate (MNE) of the motor representation area. We tested the method on simulated data and then applied it to recordings from six healthy volunteers and one stroke patient. We compared the motor representation areas obtained with the MNE method and a previously introduced interpolation method. The MNE hotspots and centers of gravity were close to those obtained with the interpolation method. The areas of the maps, however, depend on the thresholds used for outlining the areas. The MNE method may improve the definition of cortical motor areas, but its accuracy should be validated by comparing the results with maps obtained with direct cortical stimulation of the cortex where the E-field distribution can be better focused.


Relationship between Keloid Formation and YAP/TAZ Signaling.
YAP (yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are part of a classical pathway that controls contact inhibition in the Hippo pathway. YAP and TAZ were recently reported to act as nuclear relays of mechanical signals that communicate extracellular matrix rigidity and cell shape. However, the role of YAP/TAZ signaling in keloid formation is unclear. Here, we used immunohistochemistry to investigate YAP/TAZ expression in keloid and nonaffected lesions. YAP/TAZ expression in keloid fibroblasts had a greater tendency to localize to the nucleus relative to that seen in fibroblasts from unaffected tissues. Meanwhile, keratinocytes or endothelial cells from either keloid or unaffected tissues showed no significant differences in YAP/TAZ expression patterns. These results suggest that YAP/TAZ nuclear localization in keloid fibroblasts might activate Hippo signaling and may play an important role in gene expression that affects keloid formation and stiffness.


From pollutant gas to biological messenger: the diverse actions of nitric oxide in cancer.
Nitric oxide (NO) has undergone an image change in recent years. Previously regarded as a toxic pollutant gas, it has now become the subject of intense research in many fields of medicine and science. It is a free radical, with a diverse range of actions in both physiological and pathological processes. Although over 44,000 research papers have now been written on NO, only a small number have originated from the surgical specialties. Its role in tumour biology remains incompletely understood. NO is known to have both tumour promoting and inhibitory effects, presumed to be dependent on its local concentration within the tumour. NO appears to be pivotal in the angiogenic process, and the p53 tumour suppressor gene may influence its production. This review summarises the brief history of this molecule, gives an overview of its many effects in the common solid tumours and discusses how targeting of NO production may have possible future therapeutic benefit.


Reducing nutritional risk in hospital: the red tray.
Malnutrition in hospital is too common. During the patient's stay, many factors influence their nutritional state. Several reports have drawn attention to the removal of patients' food before they have had an opportunity to eat it (ACHC 1997, Horan and Coad 2000). A lack of assistance at meal times can also be a factor. This article describes the introduction of a simple innovation that has concentrated attention on patient nutrition in one clinical setting. Red trays were used as a visible indicator of vulnerable patients who needed help and support from all staff. The system was part of a total strategy implemented in a trauma rehabilitation unit for mainly older adults. The results of an audit undertaken one month after implementation of the red trays showed that use of the system had transformed nutritional assessment from a paper exercise to a practical tool that enabled patients at risk to be identified and supported with their meals.


Application of P450 reporter gene system (RGS) in the analysis of sediments near pulp and paper mills.
Cytochrome P4501A (CYP1A) induction in fish and other animals has been reported following exposure to pulp and paper mill effluent. Dioxins and furans as well as polycyclic aromatic hydrocarbons (PAH) are known inducers of CYP1A and have been found in sediments near pulp and paper mills. Retene (7-isopropyl-1-methylphenanthrene), an alkyl-substituted phenanthrene, has been recently associated with effluent and found to induce CYP1A in fish. This study utilized an in vitro assay, P450 Reporter Gene System (RGS), to assess the transcriptional activation of human CYP1A by retene after short (6 h) and long (16 h) exposures. Retene was as potent as benzo[a]pyrene in inducing RGS, but was not as readily biotransformed by the cells. Extracts of sediments collected near a pulp and paper mill were analysed, and RGS-derived toxic equivalencies (TEQ) were strongly correlated with Chemical TEQ analysis of dioxins and furans determined by EPA Method 8290 using high-resolution gas chromatography/mass spectrometry. RGS 6-h responses indicated the presence of PAH in the extracts, which was confirmed by GC/MS analysis. Retene was detected at considerably higher concentrations than other PAH. These data support the use of the RGS assay to detect the presence of CYP1Ainducing compounds, including retene as well as dioxins and furans, in sediments near pulp mills.


Jimmy's baby doll and Jenny's truck: young children's reasoning about gender norms.
To assess the flexibility of reasoning about gender, children ages 4, 6, and 8 years (N = 72) were interviewed about gender norms when different domains were highlighted. The majority of participants at all ages judged a reversal of gender norms in a different cultural context to be acceptable. They also judged gender norms as a matter of personal choice and they negatively evaluated a rule enforcing gender norms in schools. Older children were more likely to show flexibility than younger children. Justifications obtained from 6- and 8-year-olds showed that they considered adherence to gender norms a matter of personal choice and they viewed the rule enforcing gender norms as unfair.


The Essential Oil-Bearing Plants in the United Arab Emirates (UAE): An Overview.
Essential Oils (EOs) are expensive hydrocarbons produced exclusively by specific species in the plant kingdom. Their applications have deep roots in traditional herbal medicine, which lacks scientific evidence. Nowadays, more than ever, there is a growing global interest in research-based discoveries that maintain and promote health conditions. Consequently, EOs became a much attractive topic for both research and industry, with revenues reaching billions of dollars annually. In this work, we provide key guidance to all essential oil-bearing plants growing in the United Arab Emirates (UAE). The comprehensive data were collected following an extensive, up-to-date literature review. The results identified 137 plant species, including indigenous and naturalized ones, in the UAE, citing over 180 published research articles. The general overview included plant botanical names, synonyms, common names (Arabic and English), families and taxonomic authority. The study acts as a baseline and accelerator for research, industry and discoveries in multiple disciplines relying on essential oil-bearing plants.


A simple strategy based on upconversion nanoparticles for a fluorescent resonant energy transfer biosensor.
A novel aptasensor was fabricated for the detection of lysozyme and DNA based on the fluorescence resonance energy transfer (FRET) technique between upconversion nanoparticles (UCNPs) and a dye labeled aptamer. UCNPs can act as excellent emitters due to their low autofluorescence and high penetration depth of biosamples. NaYF4:Yb, Er nanoparticles as UCNPs were synthesized and attached with a dye labeled aptamer through a cationic polymer as an electrostatic linker to quench the upconversion fluorescence intensity. The intensity can be restored after the addition of lysozyme or the complementary DNA (target DNA) because of their strong interaction with the aptamer. The sensor provided a linear concentration range from 30 to 210 nM for lysozyme and 40 to 200 nM for the target DNA, the limit of detection was 2.5 nM and 2.8 nM, respectively. The sensor was also used to monitor the lysozyme level in both human saliva and serum samples, and the results were consistent with the reported values. The method was simple and convenient without the extra procedure of bioconjugation, and could be put to use for the determination of various targets in the future.


Outcomes of a quality improvement project for educating nurses on medication administration and errors in nursing homes.
The Institute of Medicine has provided recommendations for preventing medication errors in nursing homes that include nursing education. Support for education on medication administration is derived from evidence, primarily in settings other than nursing homes. This quality improvement project implemented an educational program for licensed nurses to increase knowledge of medication administration and to decrease medication-related errors. A descriptive study of 72 licensed nurses in two nursing homes was used for this project. Medication resources were provided at nursing stations in both facilities. Licensed nurses took a pretest and then watched a 35-minute education presentation. One month later, they took a posttest. Percentage scores on the tests were calculated. Paired t tests demonstrated an increase in nursing knowledge in one facility (p = 0.04) and no significant increase in nursing knowledge in the second. Mandatory participation by all staff members who administer medications would increase participation in the project. Multiple factors influence knowledge and medication administration in nursing homes and need further study.


Novel Gold Nanorods@Thiolated Pectin on the Killing of HeLa Cells by Photothermal Ablation.
Gold nanorods (AuNRs) have attracted attention in the field of biomedicine, particularly for their potential as photothermal agents capable of killing tumor cells by photothermic ablation. In this study, the synthesis of novel AuNRs stabilized with thiolated pectin (AuNR@SH-PEC) is reported. To achieve this, thiolated pectin (SH-PEC) was obtained by chemically binding cysteamine motifs to the pectin backbone. The success of the reaction was ascertained using FTIR-ATR. Subsequently, the SH-PEC was used to coat and stabilize the surface of AuNRs (AuNR@SH-PEC). In this context, different concentrations of SH-PEC (0.25, 0.50, 1.0, 2.0, 4.0, and 8.0 mg/mL) were added to 0.50 mL of AuNRs suspended in CTAB, aiming to determine the experimental conditions under which AuNR@SH-PEC maintains stability. The results show that SH-PEC effectively replaced the CTAB adsorbed on the surface of AuNRs, enhancing the stability of AuNRs without affecting their optical properties. Additionally, scanning electron and atomic force microscopy confirmed that SH-PEC is adsorbed into the surface of the AuNRs. Importantly, the dimension size (60 × 15 nm) and the aspect ratio (4:1) remained consistent with those of AuNRs stabilized with CTAB. Then, the photothermal properties of gold nanorods were evaluated by irradiating the aqueous suspension of AuNR@SH-PEC with a CW laser (808 nm, 1 W). These results showed that photothermal conversion efficiency is similar to the photothermal conversion observed for AuNR-CTAB. Lastly, the cell viability assays confirmed that the SH-PEC coating enhanced the biocompatibility of AuNR@SH-PEC. Most important, the viability cell assays subjected to laser irradiation in the presence of AuNR@SH-PEC showed a decrease in the cell viability relative to the non-irradiated cells. These results suggest that AuNRs stabilized with thiolated pectin can potentially be exploited in the implementation of photothermal therapy.


[Does annual simulation training influence the safety climate of a university hospital? : Prospective 5‑year investigation using dimensions of the safety attitude questionnaire].
Simulation-based training with a focus on non-technical skills can have a positive influence on safety relevant attitudes of participants. If an organization succeeds in training sufficient staff, it may experience a positive change in the safety climate. As the effects of a single training are of a transient nature, annual training sessions may lead to an incremental improvement of safety relevant attitudes of employees over time. In spring 2012 the Department of Anesthesia at the University Hospital of Erlangen established an annual simulation-based training for staff members (e.g. consultants, trainee anesthetists and nurse anesthetists). The study aimed to test whether an annual simulation-based training would result in an incremental longitudinal improvement in attitudes towards teamwork, safety and stress recognition. A survey comprising three domains (teamwork climate, safety climate and stress recognition) of the safety attitudes questionnaire (SAQ) and items addressing briefing and speaking up was distributed to all participants in an annual in-house simulation training. Participants filled out the questionnaire in the morning of each training day. The attitudes were measured before the first training series in 2012, 6 months after the first training and then every year (2013-2016). Participants generated a personalized identification code which allowed individuals to be anonymously tracked over time. Results of the 5‑point Likert scale were transformed to a 100-point scale. Results were calculated at the group level and at the individual level. Univariable linear regression was used to calculate mean changes per year. Over a period of 5 years (2012-2016) a total of 255 individuals completed the questionnaire. Each year, 14-20% of all nurse anesthetists and 81-90% of all anesthetists participated in the simulation-based training. As a result of annual staff turnover 16-24% of participants were new staff members. A personalized code allowed the before and after comparison of 99 staff members who had participated twice or more. Physicians had a higher mean score for teamwork climate before the first training (+8.7 p < 0.001). Mean teamwork climate and safety climate scores before the first training increased over a period of 5 years (3.11 for teamwork climate, p < 0.001 and 2.73 for safety climate, p < 0.001). Repeat participation led to a bigger mean change of individual attitudes in nurse anesthetists: teamwork climate 5.2 (nurses) vs. 1.4 (physicians) and safety climate 5.3 (nurses) vs. 2.8 (physicians) without reaching significance. Participants acknowledged the importance of briefings but confirmed their existence in less than half of the cases. The frequency of briefings increased over the 5‑year period. There were no changes in attitude towards speaking up. Over a 5-year period, small positive changes in attitudes towards teamwork and safety occurred. Low participation of nurse anesthetists as well as personnel turnover may have weakened the impact of simulation-based training on the safety climate.


Lung Function and CT Densitometry in Subjects with alpha-1-Antitrypsin Deficiency and Healthy Controls at 35 Years of Age.
Alpha-1-antitrypsin (AAT) deficiency is a genetic risk factor for pulmonary emphysema. In 1972-74 all 200,000 Swedish new-born infants were screened for AAT deficiency. The aim of the present study was to investigate whether the PiZZ and PiSZ individuals identified by this screening have signs of emphysema and the role of smoking in this, compared with a random sample of control subjects at 35 years of age. The study participants underwent complete pulmonary function tests (PFT) and CT densitometry. The fifteenth percentile density (PD15) and the relative area below -910 HU (RA-910) were analyzed. Fifty-four PiZZ, 21 PiSZ and 66 PiMM control subjects participated in the study. No significant differences were found in lung function between the never-smoking AAT-deficient and control subjects. The 16 PiZZ ever-smokers had significantly lower carbon monoxide transfer coefficient (KCO) than the 20 PiSZ never-smokers (p = 0.014) and the 44 PiMM never-smokers (p = 0.005). After correction for the CT derived lung volume, the PiZZ ever-smokers had significantly lower PD15 (p = 0.046) than the ever-smoking controls. We conclude that 35-year-old PiZZ and PiSZ never-smokers have normal lung function when compared with never-smoking control subjects. The differences in KCO and CT densitometric parameters between the PiZZ ever-smokers and the control subjects may indicate early signs of emphysema.


Emerging Technologies in Algal Biotechnology: Toward the Establishment of a Sustainable, Algae-Based Bioeconomy.
Mankind has recognized the value of land plants as renewable sources of food, medicine, and materials for millennia. Throughout human history, agricultural methods were continuously modified and improved to meet the changing needs of civilization. Today, our rapidly growing population requires further innovation to address the practical limitations and serious environmental concerns associated with current industrial and agricultural practices. Microalgae are a diverse group of unicellular photosynthetic organisms that are emerging as next-generation resources with the potential to address urgent industrial and agricultural demands. The extensive biological diversity of algae can be leveraged to produce a wealth of valuable bioproducts, either naturally or via genetic manipulation. Microalgae additionally possess a set of intrinsic advantages, such as low production costs, no requirement for arable land, and the capacity to grow rapidly in both large-scale outdoor systems and scalable, fully contained photobioreactors. Here, we review technical advancements, novel fields of application, and products in the field of algal biotechnology to illustrate how algae could present high-tech, low-cost, and environmentally friendly solutions to many current and future needs of our society. We discuss how emerging technologies such as synthetic biology, high-throughput phenomics, and the application of internet of things (IoT) automation to algal manufacturing technology can advance the understanding of algal biology and, ultimately, drive the establishment of an algal-based bioeconomy.


[Fulminant hepatic failure of neoplastic origin].
The case of a 59-year-old woman, hospitalised for a degradation of her health status which evolved within 10 days in fatal liver failure is reported. Although acute yellow atrophy was diagnosed, its origin remained elusive. Post-mortem examination of the liver disclosed massive hepatic infiltration by a breast adenocarcinoma. The causes of acute hepatic failure are reviewed and, particularly, the neoplastic ones.


[Risk management at an Intensive Care Department: conciliation of medication].
To explain the implementation process of conciliation of medication as one measure included in the risk management program at an Intensive Care department. A multidisciplinary team was put together to work on a risk management program. Work meetings were held from January to December of 2011. The development of the risk management program was done in sequential stages; identification of potential risks; analysis and assessment, management, set-up, implementation, follow-up, and reassessment. In total, 17 potential risks were identified, of which those with the highest scores given by the working group were analyzed and managed. Conciliation of medication was included. For managing this particular risk, conciliation of medication was proposed as an improvement measure, for which the pharmacist was in charge of its implementation. Besides, he also was in charge of the follow-up and reassessment process to assure its efficacy by designing indicators allowing periodic monitoring. The implementation of a clinical risks management program aims at reducing the errors and consequently improving the patient's safety. The inclusion of the pharmacist in the Intensive Care units contributes to achieving this goal and therefore we should accept our duties in the implementation of this kind of measures, such as conciliation of medication.


Simultaneous injection effective mixing flow analysis of urinary albumin using dye-binding reaction.
A new four-channel simultaneous injection effective mixing flow analysis (SIEMA) system has been assembled for the determination of urinary albumin. The SIEMA system consisted of a syringe pump, two 5-way cross connectors, four holding coils, five 3-way solenoid valves, a 50-cm long mixing coil and a spectrophotometer. Tetrabromophenol blue anion (TBPB) in Triton X-100 micelle reacted with albumin at pH 3.2 to form a blue ion complex with a λ(max) 625nm. TBPB, Triton X-100, acetate buffer and albumin standard solutions were aspirated into four individual holding coils by a syringe pump and then the aspirated zones were simultaneously pushed in the reverse direction to the detector flow cell. Baseline drift, due to adsorption of TBPB-albumin complex on the wall of the hydrophobic PTFE tubing, was minimized by aspiration of Triton X-100 and acetate buffer solutions between samples. The calibration graph was linear in the range of 10-50μg/mL and the detection limit for albumin (3σ) was 0.53μg/mL. The RSD (n=11) at 30μg/mL was 1.35%. The sample throughput was 37/h. With a 10-fold dilution, interference from urine matrix was removed. The proposed method has advantages in terms of simple automation operation and short analysis time.


Approaches to inhibiting oncogenic K-Ras.
Activating somatic K-Ras mutations are associated with >15% all human tumors and up to 90% of specific tumor types such as pancreatic cancer. Successfully inhibiting abnormal K-Ras signaling would therefore be a game changer in cancer therapy. However, K-Ras has long been considered an undruggable target for various reasons. This view is now changing by the discovery of allosteric inhibitors that directly target K-Ras and inhibit its functions, and by the identification of new mechanisms to dislodge it from the plasma membrane and thereby abrogate its cellular activities. In this review, we will discuss recent progresses and challenges to inhibiting aberrant K-Ras functions by these two approaches. We will also provide a broad overview of other approaches such as inhibition of K-Ras effectors, and offer a brief perspective on the way forward.


Plant ABC proteins--a unified nomenclature and updated inventory.
The ABC superfamily comprises both membrane-bound transporters and soluble proteins involved in a broad range of processes, many of which are of considerable agricultural, biotechnological and medical potential. Completion of the Arabidopsis and rice genome sequences has revealed a particularly large and diverse complement of plant ABC proteins in comparison with other organisms. Forward and reverse genetics, together with heterologous expression, have uncovered many novel roles for plant ABC proteins, but this progress has been accompanied by a confusing proliferation of names for plant ABC genes and their products. A consolidated nomenclature will provide much-needed clarity and a framework for future research.


Sense of coherence and its association with exposure to traumatic events, posttraumatic stress disorder, and depression in eastern Democratic Republic of Congo.
The Democratic Republic of Congo is the scene of some of the worst atrocities in recent history. However, in the face of traumatic experience, only a minority of people develops symptoms that impair their functioning. The sense of coherence proposed by Antonovsky (1987) is a theoretical construct reflecting an individual's overall wellbeing and ability to cope with stress. This study explores the relationships between sense of coherence, exposure to traumatic events, symptoms of posttraumatic stress disorder (PTSD), and depression. Results suggest an association between a high sense of coherence and high education levels, high income, and positive social relationships. Furthermore, the study found that sense of coherence is inversely correlated with cumulative exposure to violence and symptoms of PTSD and depression.


The association between metabolic syndrome and bladder cancer susceptibility and prognosis: an updated comprehensive evidence synthesis of 95 observational studies involving 97,795,299 subjects.
The association between metabolic syndrome (MS) and bladder cancer (BC) was not fully investigated, and most primary studies and pooled analyses were only focused on certain specific components. To further investigate this issue and obtain more precise findings, we conducted this updated evidence synthesis of published studies, which involved not only MS components but also the MS in its entirety. We searched the PubMed, EMBASE, and Web of Science databases for observational studies on the association between BC susceptibility and/or mortality, and MS and its components. We extracted data from included studies, evaluated heterogeneity, and performed meta-analytic quantitative syntheses. A total of 95 studies with 97,795,299 subjects were included in the present study. According to the results, MS significantly increased the risk of BC (risk ratio [RR]=1.11, 95% CI=1.00-1.23); diabetes significantly increased the risk of BC (RR=1.29, 95% CI=1.19-1.39) and associated with poor survival (RR=1.24, 95% CI=1.08-1.43). Excessive body weight was associated with increased susceptibility (RR=1.07, 95% CI=1.02-1.12), recurrence (RR=1.46, 95% CI=1.18-1.81), and mortality (RR=1.17, 95% CI=1.00-1.37). As indicated by cumulative meta-analysis, sample size was inadequate for the association between BC susceptibility and MS, the association between BC recurrence and excessive body weight, and the association between BC survival and diabetes. The sample size of the meta-analysis was enough to reach a stable pooled effect for other associations. Diabetes and excessive body weight as components of MS are associated with increased susceptibility and poor prognosis of BC. Uncertainty remains concerning the impact of overall MS, hypertension, and dyslipidemia on BC susceptibility and prognosis, for which further investigations are needed.


Expression of heat shock protein 70 and p53 in human lung cancer.
Bronchial biopsies of 21 patients with lung cancer were analyzed by Western blot for stress protein HSP70 and p53 proteins. Squamous carcinoma was the most common type found. The p53 protein was detectable in 14 cases. The HSP70 was detectable in 17 and overexpressed in 9 patients. Eleven patients showed positivity for both protein expressions, however no statistical significance was found (Kappa's test, p>0.05). Specific associations were not observed for HSP70 overexpression and p53 detection that could be related to clinical finds or tabagism. Our results indicate that the stress protein HSP70 is detectable and may be involved in the tumor development.


The gene related to anergy in lymphocytes, an E3 ubiquitin ligase, is necessary for anergy induction in CD4 T cells.
Acquisition of the anergy phenotype in T cells is blocked by inhibitors of protein synthesis and calcineurin activity, suggesting that anergic T cells may have a unique genetic program. Retroviral transduction of hemopoietic stem cells from TCR transgenic mice and subsequent reconstitution of syngeneic mice to express the E3 ubiquitin ligase, gene related to anergy in lymphocytes (GRAIL), or an enzymatically inactive form, H2N2 GRAIL, allowed analysis of the role of GRAIL in T cell anergy in vivo. Constitutive expression of GRAIL was sufficient to render naive CD4 T cells anergic, however, when the enzymatically inactive form H2N2 GRAIL was expressed, it functioned as a dominant negative of endogenous GRAIL and blocked the development of anergy. These data provide direct evidence that a biochemical pathway composed of GRAIL and/or GRAIL-interacting proteins is important in the development of the CD4 T cell anergic phenotype in vivo.


Highly Active and Water-Resistant Cu-Doped OMS-2 Catalysts for CO Oxidation: The Importance of the OMS-2 Synthesis Method and Cu Doping.
Porous cryptomelane-type Mn oxide (OMS-2) has an outstanding redox property, making it a highly desirable substitute for noble metal catalysts for CO oxidation, but its catalytic activity still needs to be improved, especially in the presence of water. Given the strong structure-performance correlation of OMS-2 for oxidation reactions, herein, OMS-2 is synthesized by solid state (OMS-2S), reflux (OMS-2R), and hydrothermal (OMS-2H) methods, aiming to improve its CO oxidation performance through manipulating synthesis parameters to tailor its particle size, morphology, and crystallinity. Characterization shows that OMS-2S has the highest CO oxidation activity in the absence of water due to its low crystallinity, high specific surface area, large oxygen vacancy content, and good redox property, but the presence of water can greatly reduce its CO oxidation activity. Doping Cu into an OMS-2 can not only improve its CO oxidation activity but also greatly improve its water tolerance. The Cu-doped OMS-2S catalyst with ∼4 wt % Cu can achieve a T90 of 49 °C (1% CO/10% O2/N2 and WHSV = 60,000 mL·g-1·h-1), ranking among the lowest reported T90 values for Mn oxide-based CO oxidation catalysts, and it can maintain nearly 100% CO conversion in the presence of 5 vol % water for over 50 h. In situ DRIFTs characterization indicates that the good water resistance of Cu-doped OMS-2S can be attributed to the significantly suppressed surface hydroxyl group generation because of Cu doping. This work demonstrates the importance of the synthesis method and Cu doping in determining the CO oxidation activity and water resistance of OMS-2 and will provide guidance for synthesizing highly active and water-resistant CO oxidation catalysts.


AD-5423 Dainippon Pharmaceutical Co Ltd.
AD-5423, a D(2)/5-HT2 antagonist, is in phase II clinical trials by Dainippon for the treatment of schizophrenia and other psychoses. In a phase I study of AD-5423 in eight healthy volunteers, it appeared to be well-tolerated and failed to induce extra pyramidal side effects, excessive sedation or hypotension [181465]. Analysts at Yamaichi estimate that AD-5423 will be launched in Japan in 1999 and annual sales will be less than five billion Yen [216018].


Optical imaging of surface chemistry and dynamics in confinement.
We imaged the interfacial structure and dynamics of water in a microscopically confined geometry, in three dimensions and on millisecond time scales, with a structurally illuminated wide-field second harmonic microscope. The second harmonic images reported on the orientational order of interfacial water, induced by charge-dipole interactions between water molecules and surface charges. The images were converted into surface potential maps. Spatially resolved surface acid dissociation constant (pKa,s) values were determined for the silica deprotonation reaction by following pH-induced chemical changes on the curved and confined surfaces of a glass microcapillary immersed in aqueous solutions. These values ranged from 2.3 to 10.7 along the wall of a single capillary because of surface heterogeneities. Water molecules that rotate along an oscillating external electric field were also imaged.


Absence of functional messenger RNA activity for beta globin chain synthesis in beta 0-thalassemia.
Functional human globin messenger RNA was isolated from reticulocytes of two patients with homozygous beta 0-thalassemia, three patients with sickle cell beta 0-thalassemia, and one patient doubly heterozygous for beta 0-thalassemia and hemoglobin Lepore. When incubated in the Krebs type II mouse ascites tumor-cell-free system, messenger RNA from these patients actively directed the synthesis of human beta s and/or alpha- and gamma-globin chains but failed to stimulate the synthesis of any beta A-chains, even though nonthalassemic human globin mRNA preparations consistently stimulated two to four times as much beta A- or beta S-globin chain synthesis as alpha-chain synthesis when incubated in the same system under the same conditions. These results strongly suggest that functional beta A-chain-specific globin mRNA is absent in beta 0-thalassemia.


Disease Relapse After Drug-Free Remission in Ocular Mucous Membrane Pemphigoid.
To quantitate the risk of relapse of ocular and extraocular disease among patients with mucous membrane pemphigoid (MMP) who had undergone drug-free remission. Retrospective, comparative, interventional case series. There were 167 patients with biopsy-proven MMP who were seen at the Wilmer Eye Institute between November 1984 and December 2019. Among the 167 patients, 119 patients had ocular involvement and 103 of those patients received systemic treatment for MMP. The main outcome measures were the incidence of ocular remission, incidence rate of disease relapse after remission, and risk factors for disease relapse. Over a median follow-up time of 7 years, 74 of 103 treated patients (71.8%) experienced drug-free remission (incidence rate = 0.28/person-year [PY], 95% confidence interval [CI] 0.22-0.35/PY). Most patients (80/103, 77.7%) received cyclophosphamide therapy. Thirteen of the 74 patients (17.6%) had disease relapse after remission: 4 with ocular disease only, 4 with extraocular disease only, and 5 with both. The rate relapse of ocular MMP was 0.020/PY (95% CI 0.009-0.038/PY), and the rate of relapse of MMP at any site (ocular or extraocular site) was 0.029/PY (95% CI 0.015-0.050/PY). The use of cyclophosphamide was associated with a greater chance of remission (hazard ratio [HR] = 3.84, P < .0001) and a lower risk of relapse (HR = 0.32, P = .05) compared with other immunosuppressive drugs except for rituximab. Five patients experienced drug-free remission after rituximab therapy and none of them had relapse (median follow-up after remission = 3.6 years). When use of cyclophosphamide or rituximab was compared with all other treatments, the risk of MMP relapse at any site (HR = 0.17, P = .02) and of ocular MMP (HR = 0.11, P = .007) were significantly lower. Rates of relapse of MMP after drug-free remission are low but not zero; therefore, monitoring of patients remains necessary. Relapses were not observed among those patients treated with rituximab who had remission; however, follow-up duration in those patients was shorter than the whole MMP cohort and the sample size was small.