The Discordance between G-Banding Karyotyping and Microarray in Structural Abnormality.
Cytomolecular genetic laboratory techniques have developed from conventional G-banding karyotyping to whole genome sequencing. Although resolution has greatly increased, various cytogenetic techniques have their advantages and limitations in detecting genomic variations. We compared the chromosomal abnormalities detected by G-banding karyotyping and SNP-based microarray testing in 62 patients from July 2020 to December 2022. We analyzed their difference according to chromosomal abnormalities, including numerical and structural and others. Of the 62 patients, 28 patients showed chromosomal aberration detected in one or more of the two test methods. Aneuploidy was detected in both methods, while gain and loss less than 3 Mb were only detectable by the microarray. G-banding karyotyping is fundamental to detect structural chromosome rearrangement such as inversions, ring chromosomes, and translocations, but additional breakpoint or unknown origin materials informa-tion obtained from microarray. Loss of heterozygosity was only detectable in microarray, and mosaicism had limitations in both G-banding karyotyping and microarray. Various disease cause genomic structural variants, it is very important to detect this. We showed discordance between G-banding karyotyping and SNP based microarray in clinical laboratory. It can be helpful to clinical physicians to decide which diagnostic tool to use.


Downregulation of mouse intestinal Na(+)-coupled glucose transporter SGLT1 by gum arabic (Acacia Senegal).
Intestinal Na(+)-coupled glucose transporter SGLT1 determines the rate of glucose transport, which in turn influences glucose-induced insulin release and development of obesity. The present study explored effects of Gum Arabic (GA), a dietary polysaccharide from dried exudates of Acacia Senegal, on intestinal glucose transport and body weight in wild-type C57Bl/6 mice. Treatment with GA (100 g/l) in drinking water for four weeks did not affect intestinal SGLT1 transcript levels but decreased SGLT1 protein abundance in jejunal brush border membrane vesicles. Glucose-induced jejunal short-circuit currents revealed that GA treatment decreased electrogenic glucose transport. Drinking a 20% glucose solution for four weeks significantly increased body weight and fasting plasma glucose concentrations, effects significantly blunted by simultaneous treatment with GA. GA further significantly blunted the increase in body weight, fasting plasma glucose and fasting insulin concentrations during high fat diet. In conclusion, the present observations disclose a completely novel effect of gum arabic, i.e. its ability to decrease intestinal SGLT1 expression and activity and thus to counteract glucose-induced obesity.


ANTI-DNA ANTIBODIES IN HYPERIMMUNIZED RABBITS.
Complement-fixing anti-DNA antibodies were detected in a minority of sera of rabbits hyperimmunized with killed Gram-negative bacteria. The C'-fixing property of DNA was lost after DNase treatment. Preferential reactivity with denatured DNA was observed. The antisera reacted with DNA preparations derived from rabbit bone marrow and thymus, calf thymus, pneumococci, salmon sperm, and Escherichia coli. E. coli DNA was less effective than preparations of mammalian and salmon sperm DNA in fixation of C'. Inhibition of DNA C' fixation by nucleotides and nucleosides was observed. The bulk of anti-DNA activity was associated with the low molecular weight antibody fraction.


Salmonella pathogenicity island 4-mediated adhesion is coregulated with invasion genes in Salmonella enterica.
Salmonella pathogenicity island 4 (SPI4) encodes a type I secretion system and the cognate substrate protein, SiiE. We have recently demonstrated that SiiE is a giant nonfimbrial adhesin involved in the adhesion of Salmonella enterica serovar Typhimurium to polarized epithelial cells. We also observed that under in vitro culture conditions, the synthesis and secretion of SiiE coincided with the activation of Salmonella invasion genes. These observations prompted us to investigate the regulation of SPI4 genes in detail. A novel approach for the generation of reporter gene fusions was employed to generate single-copy chromosomal fusions to various genes within SPI4, and the expression of these fusions was investigated. We analyzed the regulation of SPI4 genes and the roles of various regulatory systems for SPI4 expression. Our data show that the expression of SPI4 genes is coregulated with SPI1 invasion genes by the global regulator SirA. Expression of a SPI4 gene was also reduced in the absence of HilA, the central local regulator of SPI1 gene expression. Both SirA and HilA functions were required for the secretion of SiiE and the SPI4-mediated adhesion. Our data demonstrate that SPI4-mediated adhesion, as well as SPI1-mediated invasion, are tightly coregulated by the same regulatory circuits and induced under similar environmental conditions.


Expanding the toolset of fluorescent covalent staining of biological samples by labeling carboxylate and phosphate groups.
Recently, fluorescent covalent staining methods have been developed for visualization of anatomical structures in cells and tissues. Coupled with expansion microscopy, these stains revealed various ultrastructural details. However, the covalently stainable chemical groups have been limited to amines, carbohydrates, and thiols. Here, we developed procedures for covalently labeling tissues for carboxylate and phosphate groups, utilizing carbodiimide crosslinker chemistry. In porcine kidney tissues, the carboxylate and phosphate stain provides 1.8-4.8-fold higher signal intensity than those from the three existing stains. In cancer cells, such stain allows 2-8-fold more accurate identification of nucleoli than the amine stain. In expansion microscopy samples, such stain reveals a variety of sub-cellular structures in tissues when combined with the amine stain. Such stain also allows imaging of lipid-based structures in cultured cells. With these advantages, this new covalent staining method further expands the toolset for fluorescent visualization of histology.


Soy Consumption, but Not Dairy Consumption, Is Inversely Associated with Fatty Acid Desaturase Activity in Young Adults.
Past research using hepatic rat microsomes showed that soy protein suppressed delta-6 desaturase activity (D6D) compared to casein (a dairy protein). The effects of soy and dairy on desaturase pathway activity in humans remain poorly investigated. The objective of this analysis was to investigate the association between soy and dairy consumption with plasma fatty acids and estimate the desaturase pathway activity in a multiethnic Canadian population of young adults. We analyzed data from men (n = 319) and women (n = 764) previously collected for the Toronto Nutrigenomics and Health Study. Food frequency questionnaires and plasma fatty acids were assessed. Relationships between soy and dairy beverages and food consumption with estimated desaturase activities were assessed by regression models and by grouping participants according to beverage and food intake data. Weak inverse associations (p ≤ 0.05) were found between soy consumption and the overall desaturation pathway activity, specifically D6D activity. When participants were grouped based on soy and dairy consumption habits, omega-6 LC-PUFAs, as well as various estimates of the desaturase pathway activity, were significantly lower in individuals consuming soy (with or without dairy) compared to individuals consuming only fluid milk and dairy products. In conclusion, soy consumption, not dairy consumption, appears to suppress desaturase pathway activity.


Large-scale sequencing of the CD33-related Siglec gene cluster in five mammalian species reveals rapid evolution by multiple mechanisms.
Siglecs are a recently discovered family of animal lectins that belong to the Ig superfamily and recognize sialic acids (Sias). CD33-related Siglecs (CD33rSiglecs) are a subgroup with as-yet-unknown functions, characterized by sequence homology, expression on innate immune cells, conserved cytosolic tyrosine-based signaling motifs, and a clustered localization of their genes. To better understand the biology and evolution of CD33rSiglecs, we sequenced and compared the CD33rSiglec gene cluster from multiple mammalian species. Within the sequenced region, the segments containing CD33rSiglec genes showed a lower degree of sequence conservation. In contrast to the adjacent conserved kallikrein-like genes, the CD33rSiglec genes showed extensive species differences, including expansions of gene subsets; gene deletions, including one human-specific loss of a novel functional primate Siglec (Siglec-13); exon shuffling, generating hybrid genes; accelerated accumulation of nonsynonymous substitutions in the Sia-recognition domain; and multiple instances of mutations of an arginine residue essential for Sia recognition in otherwise intact Siglecs. Nonsynonymous differences between human and chimpanzee orthologs showed uneven distribution between the two beta sheets of the Sia-recognition domain, suggesting biased mutation accumulation. These data indicate that CD33rSiglec genes are undergoing rapid evolution via multiple genetic mechanisms, possibly due to an evolutionary "arms race" between hosts and pathogens involving Sia recognition. These studies, which reflect one of the most complete comparative sequence analyses of a rapidly evolving gene cluster, provide a clearer picture of the ortholog status of CD33rSiglecs among primates and rodents and also facilitate rational recommendations regarding their nomenclature.


Gut microbiota differences in elderly subjects between rural city Kyotango and urban city Kyoto: an age-gender-matched study.
Several outcomes have been reported on the role of gut microbiota in health promotion and disease prevention. Kyotango, one of the longevity areas with various centenarians, is a provincial city located in the northern part of Kyoto Prefecture in Japan. To understand the relationship between gut microbiota and urbanization, we compared the diversity, abundance, and function of gut microbiota in older healthy subjects between Kyotango and Kyoto cities; Kyoto is an urban city located in the southern part of Kyoto Prefecture. In total, 51 subjects at Kyotango and 51 subjects at Kyoto matched by age and gender were recruited, and their fecal samples were obtained to analyze the gut microbiota using 16S rRNA gene sequencing. Principal coordinate analysis for β-diversity revealed significant differences in the gut microbiota between two cities. In contrast, the analysis of α-diversity revealed no significant differences between the groups. On comparison at the phylum levels, the abundance of Firmicutes was decreased with the urbanization, whereas that of Proteobacteria and Bacteroidetes increased. On comparison at the genus levels, with urbanization, a significant decrease was observed in Lachnospiraceae families including genus Roseburia and Coprococcus, and significant increases was observed in Bacteroides, Oscillospira, Parabacteroides, and Ruminococcus. The most markedly increased functional pathway with urbanization was lipopolysaccharide biosynthesis proteins and lipopolysaccharide biosynthesis, and decreased pathway was transporters and ABC transporters. In conclusion, the present findings indicate significant differences in the gut microbiota between the provincial city and urban cities at Kyoto Prefecture. These alterations in the microbiota may provide new insights to consider the relationship between longevity and gut microbiota.


[A study on latex agglutination for serological diagnosis of brucellosis].
A latex agglutination test was first used for the serological diagnosis of Brucellosis. Results of tested sera obtained from patients with a clinical diagnosis of Brucellosis and cows infected with Brucella showed that this test was specific and sensitive. Meantime the procedure of this test was easily and rapidly to perform. In addition, preparation of immuno-latex, the procedure of this test and some factors which affected the result of this test were also described in the paper.


Income-related health inequalities associated with the coronavirus pandemic in South Africa: A decomposition analysis.
The coronavirus disease 2019 (COVID-19) has resulted in an enormous dislocation of society especially in South Africa. The South African government has imposed a number of measures aimed at controlling the pandemic, chief being a nationwide lockdown. This has resulted in income loss for individuals and firms, with vulnerable populations (low earners, those in informal and precarious employment, etc.) more likely to be adversely affected through job losses and the resulting income loss. Income loss will likely result in reduced ability to access healthcare and a nutritious diet, thus adversely affecting health outcomes. Given the foregoing, we hypothesize that the economic dislocation caused by the coronavirus will disproportionately affect the health of the poor. Using the fifth wave of the National Income Dynamics Study (NIDS) dataset conducted in 2017 and the first wave of the NIDS-Coronavirus Rapid Mobile Survey (NIDS-CRAM) dataset conducted in May/June 2020, this paper estimated income-related health inequalities in South Africa before and during the COVID-19 pandemic. Health was a dichotomized self-assessed health measure, with fair and poor health categorized as "poor" health, while excellent, very good and good health were categorized as "better" health. Household per capita income was used as the ranking variable. Concentration curves and indices were used to depict the income-related health inequalities. Furthermore, we decomposed the COVID-19 era income-related health inequality in order to ascertain the significant predictors of such inequality. The results indicate that poor health was pro-poor in the pre-COVID-19 and COVID-19 periods, with the latter six times the value of the former. Being African (relative to white), per capita household income and household experience of hunger significantly predicted income-related health inequalities in the COVID-19 era (contributing 130%, 46% and 9% respectively to the inequalities), while being in paid employment had a nontrivial but statistically insignificant contribution (13%) to health inequality. Given the significance and magnitude of race, hunger, income and employment in determining socioeconomic inequalities in poor health, addressing racial disparities and hunger, income inequality and unemployment will likely mitigate income-related health inequalities in South Africa during the COVID-19 pandemic.


PML Body Biogenesis: A Delicate Balance of Interactions.
PML bodies are subnuclear protein complexes that play a crucial role in various physiological and pathological cellular processes. One of the general structural proteins of PML bodies is a member of the tripartite motif (TRIM) family-promyelocytic leukemia protein (PML). It is known that PML interacts with over a hundred partners, and the protein itself is represented by several major isoforms, differing in their variable and disordered C-terminal end due to alternative splicing. Despite nearly 30 years of research, the mechanisms underlying PML body formation and the role of PML proteins in this process remain largely unclear. In this review, we examine the literature and highlight recent progress in this field, with a particular focus on understanding the role of individual domains of the PML protein, its post-translational modifications, and polyvalent nonspecific interactions in the formation of PML bodies. Additionally, based on the available literature, we propose a new hypothetical model of PML body formation.


Bacterial CD1d-restricted glycolipids induce IL-10 production by human regulatory T cells upon cross-talk with invariant NKT cells.
Invariant NKT (iNKT) cells and CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) are important immune regulatory T cells with Ag reactivity to glycolipids and peptides, respectively. However, the functional interplay between these cells in humans is poorly understood. We show that Tregs suppress iNKT cell proliferation induced by CD1d-restricted glycolipids, including bacterial-derived diacylglycerols, as well as by innate-like activation. Inhibition was related to the potency of iNKT agonists, making diacylglycerol iNKT responses very prone to suppression. Cytokine production by iNKT cells was differentially modulated by Tregs because IL-4 production was reduced more profoundly compared with IFN-γ. A compelling observation was the significant production of IL-10 by Tregs after cell contact with iNKT cells, in particular in the presence of bacterial diacylglycerols. These iNKT-primed Tregs showed increased FOXP3 expression and superior suppressive function. Suppression of iNKT cell responses, but not conventional T cell responses, was IL-10 dependent, suggesting that there is a clear difference in mechanism between the Treg-mediated inhibition of these cell types. Our data highlight a physiologically relevant interaction between human iNKT and Tregs upon pathogen-derived glycolipid recognition that has a significant impact on the design of iNKT cell-based therapeutics.


Protein Intake, Protein Mealtime Distribution and Seafood Consumption in Elderly Norwegians: Associations with Physical Function and Strength.
Protein intake is considered important in the maintenance of muscle health in ageing. However, both the source and mealtime distribution of protein might affect the intake of protein and its effect on muscle protein synthesis. In this study, protein intake, mealtime distribution of protein, and seafood consumption were assessed in 92 older adults (aged 65+), and associations with physical performance (Short Physical Performance Battery (SPPB)), grip strength and gait speed were assessed in a multiple linear regression analysis. The participants had a mean age of 73 ± 8.9 years. Mean protein intake was 1.1 g/kg body weight. Protein intake was well distributed, with coefficient of variance between meals (CV meals) 0.6 ± 0.3. However, dinner had the highest protein intake. No associations were found between the nutrition factors and physical performance or strength; however, this result might have been caused by a ceiling effect in the chosen test batteries, as the mean score on SPPB was 10.3 ± 2.7, and 48.9% of the participants reached the top score of 12 points. Mean grip strength was 44.4 ± 9.4 kg (men) and 26.2 ± 6.8 kg (women). Mean gait speed was 1.0 ± 0.3 m/s. The interaction analysis suggests that there might be gender differences in the effect of seafood consumption on gait speed.


Alcohol and health: a drink a day won't keep the doctor away.
We should not advise patients to start drinking alcohol for its alleged cardiovascular benefits. The negative effects of alcohol are well established, and the evidence of alcohol's benefits comes mainly from epidemiologic studies that were not well controlled for other influences, such as lifestyle factors. Moreover, we have other means of lowering cardiovascular risk that are safe and proven. Those who are healthy and whose drinking history shows little risk of developing alcohol dependency may continue to drink moderate amounts. Heavy drinkers should be advised to quit.


Aedes aegypti container preference for oviposition and its possible implications for dengue vector surveillance in Delhi, India.
Dengue is a mosquito-borne viral disease globally transmitted by Aedes aegypti. The most effective method to prevent the transmission of the disease is proficient vector control. Understanding the breeding behaviour of the responsible vectors is very pertinent in this regard; therefore, the present study was conducted to understand Ae. aegypti behaviour regarding the selection of containers for oviposition in the megacity of Delhi. A household survey in different localities within Delhi was carried out during 2018-2019. All available containers were inspected for the presence of immature Ae. aegypti. In entomological surveillance, the ovipositional preference of Aedes was computed using the breeding preference ratio, container index in the field, and laboratory settings, and associations of dengue cases with monthly variation in environmental factors and container type were also calculated. The household larval survey in 40 localities showed that 40% of 27,776 water-holding containers in 3,400 houses were plastic, followed by overhead tanks (26.2%), and coolers (12.1%). The most preferred breeding habitat was clay pots (9.3%), followed by metallic containers (8.5%) and solid waste (7.1%). A laboratory-based study showed that Aedes preferred clay containers (81.8%) over 4 other types of containers (plastic, paper, metal, and glass). The present study provides a rationale for using clay containers as a possible surveillance tool (ovitraps) or as a vector control tool. This information might aid researchers in developing novel traps and targeting preferred containers for larval control activities during transmission and non-transmission seasons.


Mature teratoma of liver in an adult male patient.
Teratomas are germ cell tumors occurring usually in gonadal organs. They are neoplasms composed of one or more of the three germ layers. Extragonadal teratomas are uncommonly reported in the literature. The liver is an extremely rare site for teratoma, constituting < 1% of all teratomas. The majority of the liver teratomas are found in the pediatric population with only a dozen cases reported in adults to the best of our knowledge. We present a case of a 27-year-old male with a history of abdominal pain of 5 months duration. CT scan revealed liver mass suggesting teratoma. The patient underwent cholecystectomy and segmental liver resection. Histopathology revealed mature cystic teratoma. Complete resection remains the best treatment option. Teratomas of the liver are extremely rare, constituting < 1% of all teratomas. An extensive review of the literature yielded < 50 cases of primary hepatic teratomas with only a dozen cases in adults and only two cases in males.


Biology of metastatic renal cell carcinoma.
In the past ten years we have made exceptional progresses in the understanding of RCC biology, particularly by recognizing the crucial pathogenetic role of activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful clinical development of anti-angiogenic and mTOR-targeted drugs, which have profoundly impacted on the natural history of the disease and have improved the duration and quality of RCC patient lives. However, further improvements are still greatly needed: 1) even in patients who obtain striking clinical responses early in the course of treatment, disease will ultimately escape control and progress to a treatment-resistant state, leading to therapeutic failure; 2) prolonged disease control usually requires 'continuous' treatment, even across different treatment lines, making the impact of chronic, low-grade, toxicities on quality of life greater and precluding, for most patients, the possibility of experiencing 'drug-free holidays'; 3) although we have successfully identified classes of drugs (or molecular mechanisms of action) that are effective in a substantial proportion of patients, we still fall short of molecular predictive factors that identify individual patients who will (or will not) benefit from a specific intervention and still proceed on a trial-and-error basis, far from a truly 'personalized' therapeutic approach; 4) finally (and perhaps most importantly), even in the best case scenario, currently available treatments inevitably fail to definitively 'cure' metastatic RCC patients. In this review we briefly summarize recent developments in the understanding of the molecular pathogenesis of RCC, the development of resistance/escape mechanisms, the rationale for sequencing agents with different mechanisms of action, and the importance of host-related factors. Unraveling the complex mechanisms by which RCC shapes host microenvironment and immune response and therapeutic treatments, in turn, shape both cancer cell biology and tumor-host interactions may hold the key to future advances in such a complex and challenging disease.


Scaffold topologies. 1. Exhaustive enumeration up to eight rings.
Mapping the chemical space of small organic molecules is approached from a theoretical graph theory viewpoint, in an effort to begin the systematic exploration of molecular topologies. We present an algorithm for exhaustive generation of scaffold topologies with up to eight rings and an efficient comparison method for graphs within this class. This method uses the return index, a topological invariant derived from the adjacency matrix of the graph. Furthermore, we describe an algorithm that verifies the adequacy of the comparison method. Applications of this method for chemical space exploration in the context of drug discovery are discussed. The key result is a unique characterization of scaffold topologies, which may lead to more efficient ways to query large chemical databases.


Use of quality indicators to compare point-of-care testing errors in a neonatal unit and errors in a STAT central laboratory.
Point-of-care testing (POCT), like other laboratory tests, can be affected by errors throughout the total testing process. To evaluate quality error rates, the use of quality indicators (QIs) is recommended; however, little information is available on the quality error rate associated with POCT. The objective of this study was to investigate quality error rates related to POCT and compare them with central laboratory (CL) testing. We studied standardized QIs for POCT in comparison to CL testing. We compared error rates related to requests, collection, and handling of samples and results from external quality assessment program (EQAP) and internal quality control (IQC). The highest difference between POCT and CL testing was observed for QI related to patient identification, 45.3% vs. 0.02% (p<0.001). Regarding specimen collection and handling, the QI related to samples without results was also higher in POCT than in CL testing, 15.8% vs. 3.3% (p<0.001). For the QI related to insufficient sample volume, we obtained 2.9% vs. 0.9% (p=0.27). Unlike QIs for the preanalytical phase, QIs for the analytical phase had better results in POCT than CL testing. We obtained 8.3% vs. 16.6% (p=0.13) for QI related to unacceptable results in EQAP and 0.8% vs. 22.5% (p<0.001) for QI related to unacceptable results in IQC. Our results show that the preanalytical phase remains the main problem in POCT like in CL testing and that monitoring of quality indicators is a very valuable tool in reducing errors in POCT.


Relaxed predation risk reduces but does not eliminate sociality in birds.
Disentangling the relative contribution of predation avoidance and increased foraging efficiency in the evolution of sociality in animals has proven difficult given that the two types of benefits often operate concurrently. I identified different types of refuges from predation in birds related to morphological and ecological traits, providing an opportunity to examine concomitant changes in sociality over evolutionary times. Results of a matched-species comparative analysis indicated a reduction in the size of foraging or non-foraging groups but not complete disappearance under negligible predation risk. The results suggest that while predation avoidance is an important component in the evolution of sociality in birds, it is most probably not acting alone but rather in conjunction with other benefits such as increased foraging efficiency.


Chemokine decoy receptor d6 plays a negative role in human breast cancer.
Chemokine binding protein D6 is a promiscuous decoy receptor that can inhibit inflammation in vivo; however, the role it plays in cancer is not well known yet. In this study, we showed for the first time that human breast cancer differentially expressed D6 and the expression could be regulated by some cytokines. More importantly, overexpression of D6 in human breast cancer cells inhibits proliferation and invasion in vitro and tumorigenesis and lung metastasis in vivo. This inhibition is associated with decreased chemokines (e.g., CCL2 and CCL5), vessel density, and tumor-associated macrophage infiltration. Furthermore, D6 expression is inversely correlated to lymph node metastasis as well as clinical stages, but positively correlated to disease-free survival rate in cancer patients. Therefore, D6 plays a negative role in the growth and metastasis of breast cancer.


Lotus japonicus symRK-14 uncouples the cortical and epidermal symbiotic program.
SYMRK is a leucine-rich-repeat (LRR)-receptor kinase that mediates intracellular symbioses of legumes with rhizobia and arbuscular mycorrhizal fungi. It participates in signalling events that lead to epidermal calcium spiking, an early cellular response that is typically considered as central for intracellular accommodation and nodule organogenesis. Here, we describe the Lotus japonicus symRK-14 mutation that alters a conserved GDPC amino-acid sequence in the SYMRK extracellular domain. Normal infection of the epidermis by fungal or bacterial symbionts was aborted in symRK-14. Likewise, epidermal responses of symRK-14 to bacterial signalling, including calcium spiking, NIN gene expression and infection thread formation, were significantly reduced. In contrast, no major negative effects on the formation of nodule primordia and cortical infection were detected. Cumulatively, our data show that the symRK-14 mutation uncouples the epidermal and cortical symbiotic program, while indicating that the SYMRK extracellular domain participates in transduction of non-equivalent signalling events. The GDPC sequence was found to be highly conserved in LRR-receptor kinases in legumes and non-legumes, including the evolutionarily distant bryophytes. Conservation of the GDPC sequence in nearly one-fourth of LRR-receptor-like kinases in the genome of Arabidopsis thaliana suggests, however, that this sequence might also play an important non-symbiotic function in this plant.


Analysis of a Charcot-Marie-Tooth disease mutation reveals an essential internal ribosome entry site element in the connexin-32 gene.
A mutation located in the 5'-untranslated region (5'-UTR) of the nerve-specific connexin-32 mRNA, previously found in a family with Charcot-Marie-Tooth disease (CMTX), was analyzed for its effect on the expression of a reporter gene (luciferase) in transgenic mice and in transfected cells. Whereas both mutant and wild-type genes appeared to be transcribed and spliced efficiently, no luciferase was detected from the mutant in either system, suggesting that the mutation affects translation of the mRNA. When the 5'-UTR of nerve-specific connexin-32 mRNA was inserted between the two genes of a bicistronic vector and transfected into various cell lines, expression of the second gene was significantly increased. Because the mutant did not facilitate translation of the second gene in the bicistronic mRNA system, this result suggested that the CMTX mutation abolished function of an internal ribosome entry site (IRES) in the 5'-UTR of the wild-type connexin-32 mRNA. The CMTX phenotype of the mutant 5'-UTR further suggested that the wild-type IRES was essential for the translation of the connexin-32 mRNA in nerve cells. In addition, other sequence elements of the connexin-32 IRES were characterized by mutation analysis. A mutation in either of the first two elements investigated showed loss of IRES function, whereas mutation of a third element showed gain of function.


Plasmid partitioning in Escherichia coli.
The mechanisms by which plasmids are stably maintained in bacterial populations are not yet completely understood. However, it is apparent that interactions with the cell envelope, site-specific recombination and modulation of the host cell's division process may be involved in plasmid maintenance.


Family presence during cardiopulmonary resuscitation.
The effect of family presence during cardiopulmonary resuscitation (CPR) on the family members themselves and the medical team remains controversial. We enrolled 570 relatives of patients who were in cardiac arrest and were given CPR by 15 prehospital emergency medical service units. The units were randomly assigned either to systematically offer the family member the opportunity to observe CPR (intervention group) or to follow standard practice regarding family presence (control group). The primary end point was the proportion of relatives with post-traumatic stress disorder (PTSD)-related symptoms on day 90. Secondary end points included the presence of anxiety and depression symptoms and the effect of family presence on medical efforts at resuscitation, the well-being of the health care team, and the occurrence of medicolegal claims. In the intervention group, 211 of 266 relatives (79%) witnessed CPR, as compared with 131 of 304 relatives (43%) in the control group. In the intention-to-treat analysis, the frequency of PTSD-related symptoms was significantly higher in the control group than in the intervention group (adjusted odds ratio, 1.7; 95% confidence interval [CI], 1.2 to 2.5; P=0.004) and among family members who did not witness CPR than among those who did (adjusted odds ratio, 1.6; 95% CI, 1.1 to 2.5; P=0.02). Relatives who did not witness CPR had symptoms of anxiety and depression more frequently than those who did witness CPR. Family-witnessed CPR did not affect resuscitation characteristics, patient survival, or the level of emotional stress in the medical team and did not result in medicolegal claims. Family presence during CPR was associated with positive results on psychological variables and did not interfere with medical efforts, increase stress in the health care team, or result in medicolegal conflicts. (Funded by Programme Hospitalier de Recherche Clinique 2008 of the French Ministry of Health; ClinicalTrials.gov number, NCT01009606.).


Patient education in high-tech home care.
High-tech home care requires that nurses have intricate knowledge and skills to care for patients with complicated treatments and equipment. Yet the need for teaching skills is often overlooked. Home care professionals can teach patients to help in their own care if the professionals assess that patients are ready to learn and incorporate principles of adult teaching and learning.


A critical review of the role of milk and other dairy products in the development of obesity in children and adolescents.
Existing reviews suggest that milk and other dairy products do not play a role in the development of obesity in childhood, but they do make an important contribution to children's nutrient intake. It is thus curious that public health advice on the consumption of dairy products for children is often perceived as unclear. The present review aimed to provide an overview of the totality of the evidence on the association between milk and other dairy products, and obesity and indicators of adiposity, in children. Our search identified forty-three cross-sectional studies, thirty-one longitudinal cohort studies and twenty randomised controlled trials. We found that milk and other dairy products are consistently found to be not associated, or inversely associated, with obesity and indicators of adiposity in children. Adjustment for energy intake tended to change inverse associations to neutral. Also, we found little evidence to suggest that the relationship varied by type of milk or dairy product, or age of the children, although there was a dearth of evidence for young children. Only nine of the ninety-four studies found a positive association between milk and other dairy products and body fatness. There may be some plausible mechanisms underlying the effect of milk and other dairy products on adiposity that influence energy and fat balance, possibly through fat absorption, appetite or metabolic activity of gut microbiota. In conclusion, there is little evidence to support a concern to limit the consumption of milk and other dairy products for children on the grounds that they may promote obesity.


Tocilizumab for the treatment of patients with refractory Takayasu arteritis.
Treatment of refractory Takayasu arteritis (TA) remains an unresolved clinical issue. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose. The aim of the present study was to assess the safety and efficacy of the interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) in patients with TA refractory to conventional therapies including GC. Four patients with TA who had shown GC resistance received TCZ infusions (8 mg/kg) every 4 weeks a total of at least 24 times (range, 24 to 51). Clinical symptoms, the serum levels of acute phase proteins and IL-6, GC dosage necessary to maintain remission, and cross-sectional imaging by enhanced CT and MRI were assessed. All patients achieved good clinical response and rapid normalization of the acute phase proteins such as C-reactive protein and serum amyloid A during the therapy with TCZ. The mean dosage of prednisolone could be reduced from 21.3 mg/day to 1.5 mg/day. Although the serum IL-6 level was transiently elevated in all patients after several TCZ infusions, it gradually recovered to the initial level. Along with the decrease of serum IL-6, two patients exhibited significant reduction in thickened arterial lesions. No drug-related adverse effects were noted. In this small group of patients with refractory TA, TCZ therapy was effective and well-tolerated. Further larger studies should be conducted to confirm this finding.


The Oxygen quantum yield in diverse algae and cyanobacteria is controlled by partitioning of flux between linear and cyclic electron flow within photosystem II.
We have measured flash-induced oxygen quantum yields (O2-QYs) and primary charge separation (Chl variable fluorescence yield, Fv/Fm) in vivo among phylogenetically diverse microalgae and cyanobacteria. Higher O2-QYs can be attained in cells by releasing constraints on charge transfer at the Photosystem II (PSII) acceptor side by adding membrane-permeable benzoquinone (BQ) derivatives that oxidize plastosemiquinone QB(-) and QBH2. This method allows uncoupling PSII turnover from its natural regulation in living cells, without artifacts of isolating PSII complexes. This approach reveals different extents of regulation across species, controlled at the QB(-) acceptor site. Arthrospira maxima is confirmed as the most efficient PSII-WOC (water oxidizing complex) and exhibits the least regulation of flux. Thermosynechococcus elongatus exhibits an O2-QY of 30%, suggesting strong downregulation. WOC cycle simulations with the most accurate model (VZAD) show that a light-driven backward transition (net addition of an electron to the WOC, distinct from recombination) occurs in up to 25% of native PSIIs in the S2 and S3 states, while adding BQ prevents backward transitions and increases the lifetime of S2 and S3 by 10-fold. Backward transitions occur in PSIIs that have plastosemiquinone radicals in the QB site and are postulated to be physiologically regulated pathways for storing light energy as proton gradient through direct PSII-cyclic electron flow (PSII-CEF). PSII-CEF is independent of classical PSI/cyt-b6f-CEF and provides an alternative proton translocation pathway for energy conversion. PSII-CEF enables variable fluxes between linear and cyclic electron pathways, thus accommodating species-dependent needs for redox and ion-gradient energy sources powered by a single photosystem.


Clusters of Factors Identify A High Prevalence of Pregnancy Involvement Among US Adolescent Males.
The study purpose was to use recursive partitioning analysis (RPA) to identify factors that, when clustered, are associated with a high prevalence of pregnancy involvement among US adolescent males. The National Survey of Family Growth is a nationally representative survey of individuals 15-44 years old. RPA was done for the 2002 and 2006-2010 cycles to identify factors which, when combined, identify adolescent males with the highest prevalence of pregnancy involvement. Pregnancy-involvement prevalence among adolescent males was 6 %. Two clusters of adolescent males have the highest pregnancy-involvement prevalence, at 84-87 %. In RPA, the highest pregnancy-involvement prevalence (87 %) was seen in adolescent males who ever HIV tested, had >4 lifetime sexual partners, reported less than an almost certain chance of feeling less physical pleasure with condom use, had an educational attainment of <11th grade, and had ≤2 sexual partners in the past 12 months. Adolescent males who ever HIV tested, had >4 lifetime sexual partners, reported less than an almost certain chance of feeling less physical pleasure with condom use, had an educational attainment ≥11th grade, were >17 years old, and had their first contraceptive education ≥10th grade, had a pregnancy-involvement prevalence of 84 %. Pregnancy-prevention efforts among adolescent males who have been involved in a pregnancy may need to target risk factors identified in clusters with the highest pregnancy prevalence to prevent subsequent pregnancies in these adolescent males and improve their future outcomes.


Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in prevention of autoimmune diabetes in non-obese diabetic mice treated with alpha-galactosylceramide.
CD1d-restricted natural killer T (NKT) cells and CD4+CD25+ regulatory T (Treg) cells are two thymus-derived subsets of regulatory T cells that play an important role in the maintenance of self-tolerance. Yet the functional changes of the two subsets of regulatory T cells in the development of diabetes in non-obese diabetic (NOD) mice remain unclear, and how NKT cells and CD4+CD25+ Treg cells cooperate functionally in the regulation of autoimmune diabetes is also uncertain. We provide evidence that in NOD mice, an animal model of human type 1 diabetes, the functions of both NKT cells and CD4+CD25+ Treg cells decrease in an age-dependent manner. We show that treatment with alpha-galactosylceramide increases the size of the CD4+CD25+ Treg cell compartment in NOD mice, and augments the expression of forkhead/winged helix transcription factor and the potency of CD4+CD25+ Treg cells to inhibit proliferation of CD4+CD25- T cells. Our data indicate that NKT cells and CD4+CD25+ Treg cells might cooperate in the prevention of autoimmune diabetes in NOD mice treated with alpha-galactosylceramide. Induced cooperation of NKT cells and CD4+CD25+ Treg cells could serve as a strategy to treat human autoimmune disease, such as type 1 diabetes.


Mechanism of La Crosse virus inhibition by ribavirin.
The effect of ribavirin on the growth and replication of La Crosse virus was examined. The data suggest that low concentrations of ribavirin have a marked effect on the initial steps of La Crosse virus transcription. The therapeutic potential of ribavirin in the treatment of human California encephalitis serotype infections is discussed in light of these findings.


Affective mechanisms linking dysfunctional behavior to performance in work teams: a moderated mediation study.
The present study examines the association between dysfunctional team behavior and team performance. Data included measures of teams' dysfunctional behavior and negative affective tone as well as supervisors' ratings of teams' (nonverbal) negative emotional expressivity and performance. Utilizing a field sample of 61 work teams, the authors tested the proposed relationships with robust data analytic techniques. Results were consistent with the hypothesized conceptual scheme, in that negative team affective tone mediated the relationship between dysfunctional team behavior and performance when teams' nonverbal negative expressivity was high but not when nonverbal expressivity was low. On the basis of the findings, the authors conclude that the connection between dysfunctional behavior and performance in team situations is more complex than was previously believed--thereby yielding a pattern of moderated mediation. In sum, the findings demonstrated that team members' collective emotions and emotional processing represent key mechanisms in determining how dysfunctional team behavior is associated with team performance.


The Overtraining Syndrome in Soldiers: Insights from the Sports Domain.
Soldiers are exposed to extreme training regimens in order to optimally prepare for real battle. High attrition rates are a known issue during training courses, especially for elite troops. An underlying factor might be the disbalance between stress/strain and recovery. The aim of this review is to give insight in the current knowledge about functional overreaching (FOR), non-FOR (NFOR), and the overtraining syndrome (OTS) in the military. A systematic literature review was conducted. PubMed, IngentaConnect, Science Direct, and Web of Science were screened for the following keywords and combinations of search terms; military, personnel, OT, soldier. Seven studies investigating the effects of OT during training courses were selected. The definitions used for OT varied widely and there is no systematic use of markers to determine FOR, NFOR, or the OTS in the military. Much research on NFOR/OTS has been conducted in the sports domain and the military could make use of these insights to promote a more efficient balance between training load and recovery. It is suggested to regularly test soldiers on physical performance, psychomotor speed and mood using ideally a military-specific test or the 1.5-mile run, psychomotor vigilance test and Profile of Mood States. The two-bout exercise test can be used as a specific test if previous testing indicates the development of NFOR/OTS and can be combined with metabolic and immunological testing to exclude pathological causes.


Th1 and Th2 cytokine responses after measles antigen stimulation in vitro in bone marrow transplant patients: response to measles vaccination.
In seronegative autologous bone marrow transplanted (ABMT) patients, a sustained cell-mediated immunity (CMI) has been shown to impair the antibody response after measles vaccination. To investigate if this might be caused by a preferential Th1 cytokine response, interferon (IFN)-gamma and interleukin (IL)-10 production of peripheral blood mononuclear cells (PBMC) was analyzed after measles antigen (M-ag) stimulation in vitro. The non-specific immune response was measured by IFN-alpha, and IL-12 analyses. Fifty non-vaccinated patients following ABMT or allogeneic bone marrow transplantation (BMT) were included. IFN-gamma production was significantly higher in patients with a retained CMI to measles than in patients without (2.3 vs 0.8 IU/ml; P = 0.01). Only a non-significant tendency was seen in IL-10 production (48.6 vs 26.7 pg/ml; NS), whereas no difference was found in IFN-alpha or IL-12 production. A positive correlation between IFN-gamma and IL-10 production was found (r(s) = 0.49; P < 0.001). After vaccination of 14 ABMT children, there was an increase in PBMC IFN-gamma production in vitro (2.5 vs <0.1 IU/ml; P < 0.05), whereas no changes were seen in the IL-10, IFN-alpha, or antibody levels. These results suggest that both Th1 and Th2 cytokine production are increased by M-ag stimulation in patients with a retained CMI to measles, but the Th1 response seems to be stronger. The preferential Th1 stimulation and increase in IFN-gamma production after vaccination may lead to a reduction in the humoral immune response which may explain the negative correlation between antibody production and T cell reactivity prior to vaccination.


IFI16 in human prostate cancer.
Increased expression of IFI16 protein (encoded by the IFI16 gene) in normal human prostate epithelial cells is associated with cellular senescence-associated cell growth arrest. Consistent with a role for IFI16 protein in cellular senescence, the expression of IFI16 protein is either very low or not detectable in human prostate cancer cell lines. We now report that treatment of DU-145 and LNCaP prostate cancer cell lines with histone deacetylase inhibitor trichostatin A (TSA) or CGK1026 resulted in transcriptional activation of the IFI16 gene. The induction of IFI16 protein in LNCaP cells was dependent on the duration of TSA treatment. Furthermore, TSA treatment of LNCaP cells up-regulated the expression of Janus-activated kinase 1 protein kinase and modulated the transcription of certain IFN-activatable genes. However, overexpression of exogenous Janus-activated kinase 1 protein in LNCaP cells and treatment of cells with IFNs (alpha and gamma) did not increase the expression of IFI16. Instead, the transcriptional activation of IFI16 gene by TSA treatment of LNCaP cells was dependent on transcriptional activation by c-Jun/activator protein-1 transcription factor. Importantly, increased expression of IFI16 in LNCaP cells was associated with decreases in the expression of androgen receptor and apoptosis of cells. Conversely, knockdown of IFI16 expression in TSA-treated LNCaP cells increased androgen receptor protein levels with concomitant decreases in apoptosis. Together, our observations provide support for the idea that histone deacetylase-dependent transcriptional silencing of the IFI16 gene in prostate epithelial cells contributes to the development of prostate cancer.


Repetitive Transcranial Magnetic Stimulation in the Treatment of Bipolar Disorder.
Bipolar disorder (BD) is a debilitating mood disorder marked by manic, hypomanic and/or mixed or depressive episodes. It affects approximately 1-2% of the population and is linked to high rates of suicide, functional impairment and poorer quality of life. Presently, treatment options for BD are limited. There is a strong evidence base for pharmacological (e.g., lithium) and psychological (e.g., psychoeducation) treatments; however, both of these pose challenges for treatment outcomes (e.g., non-response, side-effects, limited access). Repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, is a recommended treatment for unipolar depression, but it is unclear whether rTMS is an effective, safe and well tolerated treatment in people with BD. This article reviews the extant literature on the use of rTMS to treat BD across different mood states. We found 34 studies in total (N = 611 patients), with most assessing bipolar depression (n = 26), versus bipolar mania (n = 5), mixed state bipolar (n = 2) or those not in a current affective episode (n = 1). Across all studies, there appears to be a detectable signal of efficacy for rTMS treatment, as most studies report that rTMS treatment reduced bipolar symptoms. Importantly, within the randomised controlled trial (RCT) study designs, most reported that rTMS was not superior to sham in the treatment of bipolar depression. However, these RCTs are based on small samples (NBD ⩽ 52). Reported side effects of rTMS in BD include headache, dizziness and sleep problems. Ten studies (N = 14 patients) reported cases of affective switching; however, no clear pattern of potential risk factors for affective switching emerged. Future adequately powered, sham-controlled trials are needed to establish the ideal rTMS treatment parameters to help better determine the efficacy of rTMS for the treatment of BD.


A call to excellence.
Health care improvement affects us all and is not optional. For change to occur, consumers must demand excellence from their providers and clinicians. Patient safety is part of a broader set of health care quality issues. Championing this view will not be easy, for it means fundamental change to the myriad interrelated systems that make up U.S. health care. HHS is taking the lead on patient safety through a number of initiatives and activities.


Histological control of tumor surgical margins with three-dimensional histology.
Three-dimensional (3D) histology provides a complete 3D representation of the margins of a tumor specimen on histological slides. This eliminates diagnostic gaps and provides maximum sensitivity in identifying tumor outgrowths. The method is used to confirm tumor-free margins or, in case of an incomplete tumor resection, to make even very small infiltrated areas visible with topographic orientation. The basic principle of 3D histology is the conversion from the 3D structure of the tumor-specimen margins into a two-dimensional view of histological sections. The 3D margins are flattened with their outside down and then cut into pieces, suitable for histopathological procedures of cryo or paraffin sections. The management of a full 3D histology needs a tight communication between the surgeon and the pathologist. Clear and safe rules are necessary to enable both the surgeon and the pathologist to point out areas of incomplete tumor excisions very precisely. Using a circle as representation of the separation between tumor base and margin, the pathologist can point out the exact position of an outgrowth by referring to different positions on the circle in clock times. This system will be sufficient to point out tumor outgrowths. The advantage is that it is very simple to communicate and easy implemented in any electronic communication.


In vivo confocal microscopy of corneal microscopic foreign bodies in horses.
To describe in vivo corneal confocal microscopy of horses with microscopic corneal foreign bodies and to correlate findings with clinical, cytological, and histopathologic evaluations of clinical cases and foreign body morphologies observed in vitro with the confocal microscope. Five horses with microscopic corneal foreign bodies. Sedated and anesthetized horses were examined with a modified Heidelberg Retina Tomograph II and Rostock Cornea Module. Confocal microscopy images were compared with images from cytologic and histopathologic corneal samples. To establish microscopic morphologic features, confocal microscopy images of burdock pappus bristles and surgical glove powder were obtained by in vitro examination. Horses were examined by in vivo confocal microscopy to assist in identifying corneal opacities detected by slit-lamp biomicroscopy, to determine the etiology of clinically idiopathic keratitis, or to localize corneal opacities presumed to be foreign bodies for surgical planning. Corneal foreign bodies presumptively identified by confocal microscopy included burdock pappus bristles, other plant foreign materials, and surgical glove powder. The corneal foreign bodies appeared as moderately or hyper-reflective linear, circular, or oval structures by confocal microscopy and did not resemble any normal anatomic structures. The confocal microscopic identification of the foreign bodies was corroborated by cytologic and histopathologic findings in some horses. The in vivo confocal microscopic appearance of the foreign bodies was consistent with morphologies observed during examination of foreign bodies in vitro. In vivo corneal confocal microscopy provides a noninvasive method for the detection, characterization, and localization of microscopic foreign bodies in the equine cornea.


Resolving Cytosolic Diffusive States in Bacteria by Single-Molecule Tracking.
The trajectory of a single protein in the cytosol of a living cell contains information about its molecular interactions in its native environment. However, it has remained challenging to accurately resolve and characterize the diffusive states that can manifest in the cytosol using analytical approaches based on simplifying assumptions. Here, we show that multiple intracellular diffusive states can be successfully resolved if sufficient single-molecule trajectory information is available to generate well-sampled distributions of experimental measurements and if experimental biases are taken into account during data analysis. To address the inherent experimental biases in camera-based and MINFLUX-based single-molecule tracking, we use an empirical data analysis framework based on Monte Carlo simulations of confined Brownian motion. This framework is general and adaptable to arbitrary cell geometries and data acquisition parameters employed in two-dimensional or three-dimensional single-molecule tracking. We show that, in addition to determining the diffusion coefficients and populations of prevalent diffusive states, the timescales of diffusive state switching can be determined by stepwise increasing the time window of averaging over subsequent single-molecule displacements. Time-averaged diffusion analysis of single-molecule tracking data may thus provide quantitative insights into binding and unbinding reactions among rapidly diffusing molecules that are integral for cellular functions.


Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens.
Emergence of antibiotic resistant pathogenic bacteria poses a serious public health challenge worldwide. However, antibiotic resistance genes are not confined to the clinic; instead they are widely prevalent in different bacterial populations in the environment. Therefore, to understand development of antibiotic resistance in pathogens, we need to consider important reservoirs of resistance genes, which may include determinants that confer self-resistance in antibiotic producing soil bacteria and genes encoding intrinsic resistance mechanisms present in all or most non-producer environmental bacteria. While the presence of resistance determinants in soil and environmental bacteria does not pose a threat to human health, their mobilization to new hosts and their expression under different contexts, for example their transfer to plasmids and integrons in pathogenic bacteria, can translate into a problem of huge proportions, as discussed in this review. Selective pressure brought about by human activities further results in enrichment of such determinants in bacterial populations. Thus, there is an urgent need to understand distribution of resistance determinants in bacterial populations, elucidate resistance mechanisms, and determine environmental factors that promote their dissemination. This comprehensive review describes the major known self-resistance mechanisms found in producer soil bacteria of the genus Streptomyces and explores the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates. Specific examples highlighting potential pathways by which pathogenic clinical isolates might acquire these resistance determinants from soil and environmental bacteria are also discussed. Overall, this article provides a conceptual framework for understanding the complexity of the problem of emergence of antibiotic resistance in the clinic. Availability of such knowledge will allow researchers to build models for dissemination of resistance genes and for developing interventions to prevent recruitment of additional or novel genes into pathogens.


Singlet oxygen is the major reactive oxygen species involved in photooxidative damage to plants.
Reactive oxygen species act as signaling molecules but can also directly provoke cellular damage by rapidly oxidizing cellular components, including lipids. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry-based quantitative method that allowed us to discriminate between free radical (type I)- and singlet oxygen ((1)O(2); type II)-mediated lipid peroxidation (LPO) signatures by using hydroxy fatty acids as specific reporters. Using this method, we observed that in non-photosynthesizing Arabidopsis (Arabidopsis thaliana) tissues, nonenzymatic LPO was almost exclusively catalyzed by free radicals both under normal and oxidative stress conditions. However, in leaf tissues under optimal growth conditions, (1)O(2) was responsible for more than 80% of the nonenzymatic LPO. In Arabidopsis mutants favoring (1)O(2) production, photooxidative stress led to a dramatic increase of (1)O(2) (type II) LPO that preceded cell death. Furthermore, under all conditions and in mutants that favor the production of superoxide and hydrogen peroxide (two sources for type I LPO reactions), plant cell death was nevertheless always preceded by an increase in (1)O(2)-dependent (type II) LPO. Thus, besides triggering a genetic cell death program, as demonstrated previously with the Arabidopsis fluorescent mutant, (1)O(2) plays a major destructive role during the execution of reactive oxygen species-induced cell death in leaf tissues.


Improving mental health capacity in rural communities: mental health first aid delivery in drought-affected rural New South Wales.
To assess the effectiveness of mental health first aid (MHFA) training in drought-affected rural and remote Australia, as part of a strategy to improve capacity among farming communities to provide early intervention for mental health problems. Data were obtained from 99 participants recruited across 12 New South Wales towns, before and after delivery of MHFA seminars emphasising the role of front-line workers from agricultural-related services. Surveys assessed knowledge of, confidence in dealing with, and attitude towards people experiencing mental illness, along with the impact of training on response to mental health problems among target population of farmers and farming families. Rural support workers and community volunteers attended MHFA seminars because of perceived mental health needs in the workplace. A majority of responses reflect a concern with giving appropriate advice and support well outside narrow job definitions. Participants' ability to identify high prevalence disorders and endorse evidence-based interventions for both high and low prevalence disorders increased following MHFA training, as did their confidence in their ability to provide appropriate help. MHFA training can form an effective part of a strategy to improve systems of care and pathways to early intervention in rural communities by using local networks to provide mental health support.


The evolution of phenotypes and genetic parameters under preferential mating.
This article extends and adds more realism to Lande's analytical model for evolution under mate choice by using individual-based simulations in which females sample a finite number of males and the genetic architecture of the preference and preferred trait evolves. The simulations show that the equilibrium heritabilities of the preference and preferred trait and the genetic correlation between them (r G), depend critically on aspects of the mating system (the preference function, mode of mate choice, choosiness, and number of potential mates sampled), the presence or absence of natural selection on the preferred trait, and the initial genetic parameters. Under some parameter combinations, preferential mating increased the heritability of the preferred trait, providing a possible resolution for the lek paradox. The Kirkpatrick-Barton approximation for r G proved to be biased downward, but the realized genetic correlations were also low, generally <0.2. Such low values of r G indicate that coevolution of the preference and preferred trait is likely to be very slow and subject to significant stochastic variation. Lande's model accurately predicted the incidence of runaway selection in the simulations, except where preferences were relative and the preferred trait was subject to natural selection. In these cases, runaways were over- or underestimated, depending on the number of males sampled. We conclude that rapid coevolution of preferences and preferred traits is unlikely in natural populations, but that the parameter combinations most conducive to it are most likely to occur in lekking species.


Reflecting on Leadership Development through Community Based Participatory Action Research.
The need for leadership in nursing is well-documented and Domain Six of the doctoral section of the National Nursing Education Framework of the Canadian Association of Schools of Nursing (CASN) is Leadership. While there are likely many paths to achievement of these leadership components, the intent of this paper is to share my journey through iteration of and reflection on my PhD dissertation research focused on a four-cycle community-based participatory action research study (CBPR) related to clinical teaching in Ghana. The focus of CBPR is to engage the researcher and the participant group (community) in collaborative, and egalitarian processes to assess and problem solve an issue in the community. Similarly, leadership promotes collaborative interpersonal relationships among leaders and followers to address issues and institutes change strategies in policies. This paper presents my experiences in building leadership capacity through this scholarly endeavor (PhD thesis) in relation to the CASN guideline.


Atorvastatin and rosuvastatin do not prevent thioacetamide induced liver cirrhosis in rats.
To examine whether the administration of atorvastatin and rosuvastatin would prevent experimentally-induced hepatic cirrhosis in rats. Liver cirrhosis was induced by injections of thioacetamide (TAA). Rats were treated concurrently with TAA alone or TAA and either atorvastatin (1,10 and 20 mg/kg) or rosuvastatin (1, 2.5, 5, 10 and 20 mg/kg) given daily by nasogastric gavage. Liver fibrosis and hepatic hydroxyproline content, in the TAA-treated group was significantly higher than those of the controls [11.5 ± 3.2 vs 2.6 ± 0.6 mg/g protein (P = 0.02)]. There were no differences in serum aminotransferase levels in the TAA controls compared to all the groups treated concomitantly by statins. Both statins used in our study did not prevent liver fibrosis or reduce portal hypertension, and had no effect on hepatic oxidative stress. Accordingly, the hepatic level of malondialdehyde was not lower in those groups treated by TAA + statins compared to TAA only. In vitro studies, using the BrdU method have shown that atorvastatin had no effect of hepatic stellate cells proliferation. Nevertheless, statin treatment was not associated with worsening of liver damage, portal hypertension or survival rate. Atorvastatin or rosuvastatin did not inhibit TAA-induced liver cirrhosis or oxidative stress in rats. Whether statins may have therapeutic applications in hepatic fibrosis due to other etiologies deserve further investigation.


Elevated serum soluble Fas levels in the various stages of hepatitis C virus-induced liver disease.
We aimed to determine serum soluble Fas antigen (sFas) levels at various stages of hepatitis C virus (HCV)-induced liver disease, and investigate correlations between serum sFas levels and clinical, biochemical and pathologic features. Sixty-five patients were categorized into five groups: 1, chronic active hepatitis C, elevated alanine aminotransferase (ALT), HCV-polymerase chain reaction (PCR) positive; 2, responders to interferon + ribavirin therapy; 3, cirrhosis; 4, chronic hepatitis C, normal ALT, HVC-PCR positive; and 5, sustained responders. Group 6 comprised 15 control individuals. Serum sFas levels were measured by enzyme-linked immunosorbent assay. Significant differences in serum sFas levels were found between the following groups: 1 and 2; 1 and 3; 1 and 4; 1 and 6; and 3 and 6. Serum sFas levels did not correlate with ALT, histological activity or HCV-PCR positivity within group 1. Serum sFas levels appear to increase in advanced stages of HCV-induced liver disease, as a result of host-related immunological factors.


Raman spectroscopic analysis of skin as a diagnostic tool for Human African Trypanosomiasis.
Human African Trypanosomiasis (HAT) has been responsible for several deadly epidemics throughout the 20th century, but a renewed commitment to disease control has significantly reduced new cases and motivated a target for the elimination of Trypanosoma brucei gambiense-HAT by 2030. However, the recent identification of latent human infections, and the detection of trypanosomes in extravascular tissues hidden from current diagnostic tools, such as the skin, has added new complexity to identifying infected individuals. New and improved diagnostic tests to detect Trypanosoma brucei infection by interrogating the skin are therefore needed. Recent advances have improved the cost, sensitivity and portability of Raman spectroscopy technology for non-invasive medical diagnostics, making it an attractive tool for gambiense-HAT detection. The aim of this work was to assess and develop a new non-invasive diagnostic method for T. brucei through Raman spectroscopy of the skin. Infections were performed in an established murine disease model using the animal-infective Trypanosoma brucei brucei subspecies. The skin of infected and matched control mice was scrutinized ex vivo using a confocal Raman microscope with 532 nm excitation and in situ at 785 nm excitation with a portable field-compatible instrument. Spectral evaluation and Principal Component Analysis confirmed discrimination of T. brucei-infected from uninfected tissue, and a characterisation of biochemical changes in lipids and proteins in parasite-infected skin indicated by prominent Raman peak intensities was performed. This study is the first to demonstrate the application of Raman spectroscopy for the detection of T. brucei by targeting the skin of the host. The technique has significant potential to discriminate between infected and non-infected tissue and could represent a unique, non-invasive diagnostic tool in the goal for elimination of gambiense-HAT as well as for Animal African Trypanosomiasis (AAT).


Linear energy transfer (LET) distribution outside small radiotherapy field edges produced by 6 MV X-rays.
In modern radiotherapy with photons, the absorbed dose outside the radiation field is generally investigated. But it is well known that the biological damage depends not only on the absorbed dose but also on LET. This work investigated the dose-average LET (LΔ,D) outside several small radiotherapy fields to provide information that can help for better evaluating the biological effect in organs at risk close to the tumour volume. The electron fluences produced in liquid water by a 6 MV X-rays Varian iX linac were calculated using the EGSnrc Monte Carlo code. With the electron spectra, LΔ,D calculations were made for eight open small square fields and the reference field at water depths of 0.15 cm, 1.35 cm, 9.85 cm and 19.85 cm and several off-axis distances. The variation of LΔ,D from the centre of the beam to 2 cm outside the field's edge depends on the field size and water depth. Using radiobiological data reported in the literature for chromosomal aberrations as an endpoint for the induction of dicentrics determined in Human Lymphocytes, we estimated the maximum low-dose relative biological effectiveness, (RBEM) finding an increase of up to 100% from the centre of the beam to 2 cm from the field's edge.


Status epilepticus after intracranial neurosurgery: incidence and risk stratification by perioperative clinical features.
Status epilepticus (SE) is associated with significant mortality, cost, and risk of future seizures. In one of the first studies of SE after neurosurgery, the authors assess the incidence, risk factors, and outcome of postneurosurgical SE (PNSE). Neurosurgical admissions from the MarketScan Claims and Encounters database (2007 through 2015) were assessed in a longitudinal cross-sectional sample of privately insured patients who underwent qualifying cranial procedures in the US and were older than 18 years of age. The incidence of early (in-hospital) and late (postdischarge readmission) SE and associated mortality was assessed. Procedural, pathological, demographic, and anatomical covariates parameterized multivariable logistic regression and Cox models. Multivariable logistic regression and Cox proportional hazards models were used to study the incidence of early and late PNSE. A risk-stratification simulation was performed, combining individual predictors into singular risk estimates. A total of 197,218 admissions (218,217 procedures) were identified. Early PNSE occurred during 637 (0.32%) of 197,218 admissions for cranial neurosurgical procedures. A total of 1045 (0.56%) cases of late PNSE were identified after 187,771 procedure admissions with nonhospice postdischarge follow-up. After correction for comorbidities, craniotomy for trauma, hematoma, or elevated intracranial pressure was associated with increased risk of early PNSE (adjusted OR [aOR] 1.538, 95% CI 1.183-1.999). Craniotomy for meningioma resection was associated with an increased risk of early PNSE compared with resection of metastases and parenchymal primary brain tumors (aOR 2.701, 95% CI 1.388-5.255). Craniotomies for infection or abscess (aHR 1.447, 95% CI 1.016-2.061) and CSF diversion (aHR 1.307, 95% CI 1.076-1.587) were associated with highest risk of late PNSE. Use of continuous electroencephalography in patients with early (p < 0.005) and late (p < 0.001) PNSE rose significantly over the study time period. The simulation regression model predicted that patients at high risk for early PNSE experienced a 1.10% event rate compared with those at low risk (0.07%). Similarly, patients predicted to be at highest risk for late PNSE were significantly more likely to eventually develop late PNSE than those at lowest risk (HR 54.16, 95% CI 24.99-104.80). Occurrence of early and late PNSE was associated with discrete neurosurgical pathologies and increased mortality. These data provide a framework for prospective validation of clinical and perioperative risk factors and indicate patients for heightened diagnostic suspicion of PNSE.


Synthesis, Crystal Structures and Catalytic Property of Dioxomolybdenum(VI) Complexes Derived from Tridentate Schiff Bases.
A pair of structurally similar new dioxomolybdenum(VI) complexes, [MoO2L1(EtOH)]·EtOH (1) and [MoO2L2(MeOH)] (2), where L1 and L2 are the dianionic form of 2-[(2-hydroxyphenylimino)methyl]-6-methoxyphenol (H2L1) and 2-ethoxy-6-[(2-hydroxyphenylimino)methyl]phenol (H2L2), respectively, were prepared and characterized by IR and UV-Vis spectroscopy, as well as single crystal X-ray diffraction. X-ray analyses indicate that the complexes are dioxomolybdenum(VI) species. Complex 1 contains ethanol as co-ligand, and complex 2 contains methanol as co-ligand. The coordination geometry around the Mo atoms can be described as distorted octahedron, with one imino-N and two phenolate-O of the Schiff base ligand, and one oxo group defining the equatorial plane, and with the other oxo group and one solvent-O occupying the axial positions. The catalytic oxidation property of the complexes with tert-butylhydroperoxide in CH2Cl2 was studied. Both complexes have excellent catalytic properties on cyclooctene and cyclohexene, and good properties on 1-hexene and 1-octene.


Poly-(ADP-ribose)-polymerase inhibitors as radiosensitizers: a systematic review of pre-clinical and clinical human studies.
Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality. Furthermore the replication-dependent activity of PARP inhibitor helps to maintain the differential effect between tumoral and healthy tissues. Inhibition of chromatin remodeling, G2/M arrest, vasodilatory effect induced by PARP inhibitor, also participate to their radio-sensitization effect. Here, after highlighting mechanisms of PARP inhibitors radiosensitization we methodically searched PubMed, Google Scholar, Cochrane Databases and meeting proceedings for human pre-clinical and clinical studies that evaluated PARP inhibitor radiosensitizing effect. Enhancement ratio, when available, was systematically reported. Sixty four studies finally met our selection criteria and were included in the analysis. Only three pre-clinical studies didn't find any radiosensitizing effect. Median enhancement ratio vary from 1,3 for prostate tumors to 1,5 for lung cancers. Nine phase I or II trials assessed safety data. PARP inhibitors are promising radiosensitizers, but need more clinical investigation. The next ten years will be determining for judging their real potential.


Towards the simulation of large scale protein-ligand interactions on NISQ-era quantum computers.
We explore the use of symmetry-adapted perturbation theory (SAPT) as a simple and efficient means to compute interaction energies between large molecular systems with a hybrid method combining NISQ-era quantum and classical computers. From the one- and two-particle reduced density matrices of the monomer wavefunctions obtained by the variational quantum eigensolver (VQE), we compute SAPT contributions to the interaction energy [SAPT(VQE)]. At first order, this energy yields the electrostatic and exchange contributions for non-covalently bound systems. We empirically find from ideal statevector simulations that the SAPT(VQE) interaction energy components display orders of magnitude lower absolute errors than the corresponding VQE total energies. Therefore, even with coarsely optimized low-depth VQE wavefunctions, we still obtain sub kcal mol-1 accuracy in the SAPT interaction energies. In SAPT(VQE), the quantum requirements, such as qubit count and circuit depth, are lowered by performing computations on the separate molecular systems. Furthermore, active spaces allow for large systems containing thousands of orbitals to be reduced to a small enough orbital set to perform the quantum portions of the computations. We benchmark SAPT(VQE) (with the VQE component simulated by ideal statevector simulators) against a handful of small multi-reference dimer systems and the iron center containing human cancer-relevant protein lysine-specific demethylase 5 (KDM5A).


[Macromolecular contrast media for MR mammography. A new approach to characterizing breast tumors].
The value of macromolecular contrast agents (MMCM) for the characterization of benign and malignant breast tumors will be demonstrated in this review. Animal studies suggest a high potential of MMCM to increase the specificity of MR-mammography. The concept of tumor differentiation is based on the pathological hyperpermeability of microvessels in malignant tumors. MMCM show a leak into the interstitium of carcinomas, whereas they are confined to the intravascular space in benign tumors. Capabilities and limitations of the MMCM-prototype. Albumin-Gd-DTPA, for breast tumor characterization will be summarized and compared to the standard low molecular weight contrast agent Gd-DTPA. Initial experience with new MMCM, such as Dendrimers, Gd-DTPA-Polylysine and MS-325 will be outlined. The potential of "blood-pool"-iron oxides, such as AMI-227 for the evaluation of tumor microvascular permeabilities will be discussed.


ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.
The ATR kinase, which coordinates cellular responses to DNA replication stress, is also essential for the proliferation of normal unstressed cells. Although its role in the replication stress response is well defined, the mechanisms by which ATR supports normal cell proliferation remain elusive. Here, we show that ATR is dispensable for the viability of G0-arrested naïve B cells. However, upon cytokine-induced proliferation, Atr-deficient B cells initiate DNA replication efficiently in early S phase, but by mid-S phase they display dNTP depletion, fork stalling, and replication failure. Nonetheless, productive DNA replication can be restored in Atr-deficient cells by pathways that suppress origin firing, such as downregulation of CDC7 and CDK1 kinase activities. Together, these findings indicate that ATR supports the proliferation of normal unstressed cells by tempering the pace of origin firing during the early S phase to avoid exhaustion of dNTPs and other replication factors.


The hedgehog target Vlk genetically interacts with Gli3 to regulate chondrocyte differentiation during mouse long bone development.
Endochondral bone development is orchestrated by the spatially and temporally coordinated differentiation of chondrocytes along the longitudinal axis of the cartilage anlage. Initially, the slowly proliferating, periarticular chondrocytes give rise to the pool of rapidly dividing columnar chondrocytes, whose expansion determines the length of the long bones. The Indian hedgehog (IHH) ligand regulates both the proliferation of columnar chondrocytes and their differentiation into post-mitotic hypertrophic chondrocytes in concert with GLI3, one of the main transcriptional effectors of HH signal transduction. In the absence of Hh signalling, the expression of Vlk (vertebrate lonesome kinase, also called Pkdcc) is increased. We now show that the shortening of limb long bones in Vlk-deficient mouse embryos is aggravated by additional inactivation of Gli3. Our analysis establishes that Vlk and Gli3 synergize to control the temporal kinetics of chondrocyte differentiation during long bone development. Whereas differentiation of limb mesenchymal progenitors into chondrocytes and the initial formation of the cartilage anlagen of the limb skeleton are not altered, Vlk and Gli3 are required for the temporally coordinated differentiation of periarticular into columnar and ultimately hypertrophic chondrocytes in long bones. In limbs lacking both Vlk and Gli3, the appearance of columnar and hypertrophic chondrocytes is severely delayed and zones of morphologically distinct chondrocytes are not established until E16.5. At the molecular level, these morphological alterations are reflected by delayed activation and lowered expression of Ihh, Pth1r and Col10a1 in long bone rudiments of double mutant limbs. In summary, our genetic analysis establishes that VLK plays a role in the IHH/GLI3 interactions and that Vlk and Gli3 cooperate to regulate long bone development by modulating the temporal kinetics of establishing columnar and hypertrophic chondrocyte domains.


Peritoneal dialysis in nondiabetic patients older than 70 years: comparison with patients aged 40 to 60 years.
In all industrial countries, the number of elderly patients who need dialysis has increased in recent years. In the present study, we retrospectively analyzed two different age groups of nondiabetic peritoneal dialysis patients treated at the same unit by the same team of physicians and nurses with the same protocols. However, our purpose was to study possible differences in technique and survival rates, causes of dropout, complications, hospitalization rate, and everyday needs between the two groups. The results of 63 consecutive nondiabetic patients older than 70 years treated with continuous ambulatory peritoneal dialysis (CAPD) were compared with those of 86 nondiabetic patients aged 40 to 60 years treated during the same period. Patient survival was significantly worse in the elderly patients, but the observed to expected survival ratio with respect to age was similar. Technique survival was comparable in the two groups. Total hospitalization was 5,501 days (32 d/yr) in the elderly patients and 4,511 days (18 d/yr; P < 0.05) in the younger group. The peritonitis rate was 0.52 episodes/patient-year in the elderly patients and 0.37 episodes/patient-year in the younger patients (P < 0.002). The exit site infection rate was similar in the two groups (0.30 episodes/yr v0.29 episodes/yr). Other complications related to CAPD did not differ between the elderly and younger patients. Rehabilitation and biochemical data after 1 year of CAPD were similar in the two groups of patients. After 1 year of treatment, 12% of the younger patients and 43% of the elderly patients (P < 0.005) needed a partner for dialysis. Twenty-nine of 39 (74%) of the elderly patients and 30 of 53 (57%) of the younger patients considered their lifestyle acceptable after 1 year of dialysis. Thirty-four of 39 (87%) of the elderly patients and 32 of 53 (60%) of the younger patients (P < 0.02) rated their physical and social state after rehabilitation as better or comparable to that they had before terminal uremia.


Reduction of urinary excretion of PGE2 and 6 keto PGF1 alpha by tiaprofenic acid.
Tiaprofenic acid (Surgam, Cassenne) was administered intravenously to saline-diuretic conscious rats, at doses of 2, 10 and 25 mg kg-1 body weight. Tiaprofenic acid significantly reduced urinary prostaglandin E2 (PGE2) and 6 keto PGF1 alpha excretion, at all three doses employed. The extent of the reduction was similar for both PGE2 and 6 keto PGF1 alpha output; hence no evidence of 'selectivity' (i.e. sparing of PGI2 synthesis) was observed. Tiaprofenic acid was also administered to rats receiving an infusion of 5% dextrose. The dose employed (0.5 or 1 mg kg-1 body weight) was submaximal and elicited reductions in PGE2 output to values still more than 60% of the control period values. In this group of animals, the percentage change in 6 keto PGF1 alpha excretion was again not significantly different from that of PGE2. The maximal extent of reduction in urinary PGE2 excretion with tiaprofenic acid (25 mg kg-1 body weight) was not significantly different from that elicited by indomethacin (10 mg kg-1 body weight), although the time course of the reduction was different.


Multiple factors affecting the efficiency of multiple ovulation and embryo transfer in sheep and goats.
This review offers an overview of the basic characteristics of in vivo embryo technologies, their current status, the main findings and the advances gained in recent years, and the outstanding subjects for increasing their efficiency. The use of superovulation and embryo transfer procedures remains affected by a high variability in the ovulatory response to hormonal treatment and by a low and variable number of transferable embryos and offspring obtained. This variability has been classically identified with both extrinsic (source, purity of gonadotrophins and protocol of administration) and intrinsic factors (breed, age, nutrition and reproductive status), which are reviewed in this paper. However, emerging data indicate that the main causes of variability are related to endocrine and ovarian factors, and so the number of studies and procedures addressing a better understanding and control of these factors may be increased in the future. The accomplishment of this objective, the improvement of procedures for embryo conservation and for the selection and management of recipient females, will allow further development and application of this technology.


Low-field NMR relaxometry: a study of interactions of water with water-repellant soils.
Petroleum-induced water repellency in soils is a problem that has been thought to develop randomly following contamination and then remediation of a site with petroleum. The emergence of the phenomenon can occur within months or years of original contamination and with seemingly no warning. Low-field NMR has been used to study these soils and, specifically, the processes of water uptake that occur in them. Critical aspects in the development of this phenomenon have been identified as well--specifically, a dependence on climatic events in the area and contamination levels that contribute are suggested.


Object recognition in subband transform-compressed images by use of correlation filters.
We introduce subband correlation filters (SCFs) as a solution to the problem of object recognition at multiple resolution levels in quantized transformed imagery. The approach synthesizes correlation filters that operate directly on subband coefficients rather than on image data. We explore two techniques to accomplish the reduced-resolution recognition: (1) training the correlation filters to incorporate downsampling tolerance and (2) adaptation of the subband decomposition filters to accommodate the reduced resolutions. For compression ratios of 20:1, SCFs demonstrate recognition performance of at least 90%, 85%, and 75%, respectively, on 2-, 4-, and 8-ft-resolution synthetic aperture radar data.


Corn1: a mouse model for corneal surface disease and neovascularization.
To describe a new mouse model of corneal surface disease and neovascularization. Anatomic changes were demonstrated in corn1 and control A.By/SnJ mice from day 10 of gestation of 8 months of age by routine techniques of light microscopic and scanning electron microscopy. Corneal epithelial cell kinetics were evaluated by labeling cells in the "S" phase of the cell cycle by intraperitoneal injection of tritiated thymidine. Labeled cells were counted under 250X magnification, and the length of the corneal epithelial chord was measured by morphometric techniques. Results were expressed as labeled cells per linear millimeter of corneal epithelium. The corn1 locus was mapped using selected back-crosses. Corn1 is characterized by early, irregular thickening of the corneal epithelium, development of stromal neovascularization by 20 days of age, and cataract by 48 days of age. Corneal epithelial cell kinetics demonstrated prominent labelling of corn1 mice at 30 days of age compared to the control mice. Corn1 behaves as an autosomal recessive gene and is located on mouse chromosome 2, approximately 5.2 cM from the agouti locus. Heterozygotes have no corneal disease. Corn1 mice, with genetically determined corneal epithelial hyperplasia and stromal neovascularization, may be particularly useful in studies of neovascularization and corneal surface proliferative disease.


[Papillomavirus and cervix atypia. Retrospective histo-colposcopic study of 175 cases].
One hundred and seventy five CIN cases diagnosed during the years 1958-60 have been reviewed and histologic slides as well as colpographies have been reevaluated for the presence of Papillomavirus-related features. Histo-colposcopic features of HPV infection have been found in 70% of CIN cases, incidence comparable to the one actually observed. Thus, the relationship between HPVs and cervical cancer doesn't seem to be changed.


Isolation and chemical structure of the peptidoglycan of Spirillum serpens cell walls.
The peptidoglycan layer of Spirillum serpens cell walls was isolated from intact cells after treatment with sodium dodecylsulfate and digestion with Pronase. The isolated peptidoglycan contained glucosamine, muramic acid, alanine, glutamic acid, and meso-diaminopimelic acid in the approximate molar ratio of 1:1:2:1:1. Aspartic acid and glycine were the only other amino acids found in significant quantities. N-terminal amino acid analyses of the tetrapeptide amino acids in the peptidoglycan revealed that 54% of the diaminopimelic acid molecules are involved in cross-linkage between tetrapeptides. This amount of cross-linkage is greater than that found in the peptidoglycan of previously studied cell walls of gram-negative bacteria. The polysaccharide backbone was isolated, after myxobacter AL-1 enzyme digestion of the peptidoglycan, by fractionation with ECTEOLA-cellulose and Sephadex G-100. An average length of 99 hexosamines for the polysaccharide chains was found (ratio of total hexosamines to reducing end groups).


[Regional and local differences in the structural changes in arterial vessels in spontaneously hypertensive rats].
Structural changes of the wall of arteries with different caliber that nourish skeletal muscle, guts and cerebral cortex of 7 months spontaneously hypertensive rats (SHR) were studied. Vessels of ramification order I-II in which significant increase of thickness of media, internal elastic membrane and elastic and collagenic components of the wall occurred were shown to undergo greater changes as compared to normotensive rats (WKR). Popliteal artery displayed myocyte hypertrophy, while hypertrophy and hyperplasty of cells were seen in middle cerebral and anterior mesentric artery. In order III vessels media thickness increased only due to hyperplasty in all regions studied. In order IV vessels almost no prominent structural changes were observed. In was concluded that the nature of alterations in vascular wall of SHR is associated both with peculiarities of regional vascular bed and caliber of branches composing it.


Predicting secondary organic aerosol phase state and viscosity and its effect on multiphase chemistry in a regional-scale air quality model.
Atmospheric aerosols are a significant public health hazard and have substantial impacts on the climate. Secondary organic aerosols (SOAs) have been shown to phase separate into a highly viscous organic outer layer surrounding an aqueous core. This phase separation can decrease the partitioning of semi-volatile and low-volatile species to the organic phase and alter the extent of acid-catalyzed reactions in the aqueous core. A new algorithm that can determine SOA phase separation based on their glass transition temperature (T g), oxygen to carbon (O : C) ratio and organic mass to sulfate ratio, and meteorological conditions was implemented into the Community Multiscale Air Quality Modeling (CMAQ) system version 5.2.1 and was used to simulate the conditions in the continental United States for the summer of 2013. SOA formed at the ground/surface level was predicted to be phase separated with core-shell morphology, i.e., aqueous inorganic core surrounded by organic coating 65.4 % of the time during the 2013 Southern Oxidant and Aerosol Study (SOAS) on average in the isoprene-rich southeastern United States. Our estimate is in proximity to the previously reported ~ 70 % in literature. The phase states of organic coatings switched between semi-solid and liquid states, depending on the environmental conditions. The semi-solid shell occurring with lower aerosol liquid water content (western United States and at higher altitudes) has a viscosity that was predicted to be 102-1012 Pa s, which resulted in organic mass being decreased due to diffusion limitation. Organic aerosol was primarily liquid where aerosol liquid water was dominant (eastern United States and at the surface), with a viscosity < 102 Pa s. Phase separation while in a liquid phase state, i.e., liquid-liquid phase separation (LLPS), also reduces reactive uptake rates relative to homogeneous internally mixed liquid morphology but was lower than aerosols with a thick viscous organic shell. The sensitivity cases performed with different phase-separation parameterization and dissolution rate of isoprene epoxydiol (IEPOX) into the particle phase in CMAQ can have varying impact on fine particulate matter (PM2.5) organic mass, in terms of bias and error compared to field data collected during the 2013 SOAS. This highlights the need to better constrain the parameters that govern phase state and morphology of SOA, as well as expand mechanistic representation of multiphase chemistry for non-IEPOX SOA formation in models aided by novel experimental insights.


Dynamic compressibility and third-order optical nonlinearities in carbon/metal-based nanofluids.
The influence of the superposition of two high-irradiance optical beams on the mechanical properties exhibited by carbon nanotubes decorated with platinum nanoparticles was analyzed. The change in density, compressibility modulus and acoustic velocity in the samples suspended in acetone and ethanol was estimated by measuring the nonlinear refractive index tested by a two-wave mixing experiment. The nanotubes were prepared by a spray pyrolysis processing route and the metal decoration was carried by chemical vapor deposition. High-Resolution Transmission Electron Microscopy studies confirmed the multiwall nature of the carbon nanotubes; while energy-dispersive X-ray spectroscopy reveals the separated presence of platinum nanoparticles incorporated to the hybrid nanostructures. An Nd-YAG laser system emitting at 532 nm wavelength with 4 ns pulse duration was used for conducting the third-order nonlinear optical evaluations by a standard optical Kerr gate technique. Comparative experiments showed that the composition of the liquid solution plays an important role in the manipulation of the density exhibited by the nanofluids. Remarkably, the incorporation of Pt in the tubes originates stronger changes of the mechanical characteristics induced by optical nonlinearities in the nanofluids irradiated by nanosecond pulses. Within this work, it is highlighted that potential applications for developing multivalent logic operations by fuzzy mechano-optic effects exhibited by nanofluids can be contemplated.


Lower-extremity function for driving an automobile after operative treatment of ankle fracture.
The purpose of this study was to determine when patients recover the ability to safely operate the brakes of an automobile following operative repair of an ankle fracture. A computerized driving simulator was developed and tested. Eleven healthy volunteers were tested once to establish normal mean values (Group I), and a group of thirty-one volunteers with a fracture of the right ankle were tested at six, nine, and twelve weeks following operative repair (Group II). The subjects were tested with a series of driving scenarios (city, suburban, and highway). Scores on the Short Form Musculoskeletal Assessment were recorded at six, nine, and twelve weeks and were compared with the results of the driving test. We investigated the effect of the time of the visit and of the testing condition on the braking times. The total braking time was 1079 msec for Group I and 1330, 1172, and 1160 msec for Group II at six, nine, and twelve weeks, respectively, postoperatively (p = 0.0094). The total braking time consistently improved for each of the driving scenarios at each successive data point (p = 0.05). The increase in the total braking time at six weeks meant an increase in the distance traveled by the automobile before braking of 22 ft (6.7 m) at 60 mph (96.6 km/hr), and the increase at nine weeks meant an increase of 8 ft (2.4 m) at 60 mph. The functional outcome improved at each successive visit, although no significant association was found between the functional scores and normalization of total braking time. By nine weeks, the total braking time of patients who have undergone fixation of a displaced right ankle fracture returns to the normal, baseline value.