Combined effects off indomethacin and oxaliplatin on lymph node metastasis related factors in human lung cancerxenografts in nude mice.
To investigate the combined effects of indomethacin and oxaliplatin on expressions of epidermal growth factor receptor (EGFR), E-cadherin (E-cad), intercellular adhesion molecule-1 (ICAM-1) and CD44v6 related to lymph node metastasis of human lung cancer cell lines. Human lung adenocarcinoma A549 cells were inoculated subcutaneously into the left armpit of nude mice to establish human lung cancer xenografts. The mice were randomly divided into control group, indomethacin group, oxaliplatin group and combination therapy group, which were treated with sterile distilled water, indomethacin, oxaliplatin and indomethacin combined with oxaliplatin, respectively. After 42 days, the mice were sacrificed. The immunohistochemistry and reverse transcription polymerase chain reaction were used to detect the expressions of EGFR, E-cad, ICAM-1 and CD44v6 in tumor tissues. Compared to control group, the protein and mRNA expressions of EGFR, ICAM-1 and CD44v6 in the indomethacin, oxaliplatin, and combination therapy groups were significantly reduced (P<0.05) and the protein and mRNA expressions of E-cad expression were significantly increased (P<0.05). Compared to indomethacin group and oxaliplatin group, the protein and mRNA expressions of EGFR, ICAM-1 and CD44v6 in combination therapy groups were significantly reduced (P<0.05), and the protein and mRNA expressions of E-cad expression were significantly increased (P<0.05). There was no significant difference between indomethacin and oxaliplatin groups. Indomethacin and oxaliplatin have synergistic effect on expressions of lymph node metastasis related factors in lung cancer cell lines.


On illicit drug policies; methods of evaluation and comments on recent practices.
This contribution provides an overview of different approaches used to analyse drug policies within and across countries. Besides the great number of cost of illness studies which have contributed to the assessment of health harms and risks associated to the drug use, most of the recent efforts have focused on the creation of synthetic indices to classify countries around the world or to evaluate particular law enforcement policies in some countries. This is probably due to a general lack of comparable data across countries. The wide variety of budgetary practices in the drugs field in Europe contributes to the problems that exist in estimating drug-related public expenditure. These heterogeneous accounting practices, together with the complexity of the drug phenomenon and the multiplicity of perspectives on the issue, strongly constrains the possibility of economically evaluate and compare drug laws across countries.


Cell-specific CYP1A expression and benzo[a]pyrene adduct formation in gills of rainbow trout (Oncorhynchus mykiss) following CYP1A induction in the laboratory and in the field.
The effect of cytochrome P4501A (CYP1A) induction on cell-specific benzo[a]pyrene (BaP) adduct formation was studied in rainbow trout (Oncorhynchus mykiss) gills. Fish preexposed to beta-naphthoflavone (betaNF) or caged in a polluted river were exposed to waterborne 3H-benzo[a]pyrene (3H-BaP). The 3H-benzo[a]pyrene adducts in the gill filaments were localized by autoradiography and CYP1A protein by immunohistochemistry. Ethoxyresorufin O-deethylase (EROD) activity was measured using a gill filament-based ex vivo assay. Branchial 3H-BaP binding and EROD activity were enhanced by exposure to betaNF or to the river water, and completely blocked by the CYP1A inhibitor ellipticine. The predominant sites of adduct formation were in epithelium of the secondary lamellae and in epithelium of the efferent edge of the gill filament. In betaNF-exposed fish, the strongest CYP1A immunoreactivity was observed in differentiating cells and in pillar cells. In fish caged in the polluted river, strong CYP1A immunoreactivity was found in most cells in the secondary lamellae, whereas the primary lamellae were almost devoid of immunoreactivity. Our results reveal a discrepancy between the localization of CYP1A protein and BaP adducts in the gill. Consequently, other factors, such as bioavailability of waterborne polycyclic aromatic hydrocarbons (PAHs) to the target cells, are important for the localization of PAH adducts in the gill.


Long W tracts are over-represented in the Escherichia coli and Haemophilus influenzae genomes.
The occurrence of DNA tracts of the three binary base combinations: R.Y, K.M and W;S has been mapped in the complete genomes of Haemophilus influenzae and Escherichia coli. A highly significant over-representation of W tracts is observed in both bacteria. The excess of W tracts is particularly striking in the 10% intercoding regions. Subdivision of intercoding regions into divergent (promoting), convergent (terminating) and sequential subregions shows that the excess of W tracts is most concentrated in the promoter regions. A particularly high excess of W tracts is observed in the first 200 bases 5' upstream of coding start sites. The data suggest that W tracts have a role in promoter function. A function as unwinding centers, analogous to the role of R.Y tracts in eukaryotes, is proposed. R.Y and K.M tracts are only modestly over-represented in the two bacteria.


Genetic architecture of individual meiotic crossover rate and distribution in Atlantic Salmon.
Meiotic recombination through chromosomal crossovers ensures proper segregation of homologous chromosomes during meiosis, while also breaking down linkage disequilibrium and shuffling alleles at loci located on the same chromosome. Rates of recombination can vary between species, but also between and within individuals, sex and chromosomes within species. Indeed, the Atlantic salmon genome is known to have clear sex differences in recombination with female biased heterochiasmy and markedly different landscapes of crossovers between males and females. In male meiosis, crossovers occur strictly in the telomeric regions, whereas in female meiosis crossovers tend to occur closer to the centromeres. However, little is known about the genetic control of these patterns and how this differs at the individual level. Here, we investigate genetic variation in individual measures of recombination in > 5000 large full-sib families of a Norwegian Atlantic salmon breeding population with high-density SNP genotypes. We show that females had 1.6 × higher crossover counts (CC) than males, with autosomal linkage maps spanning a total of 2174 cM in females and 1483 cM in males. However, because of the extreme telomeric bias of male crossovers, female recombination is much more important for generation of new haplotypes with 8 × higher intra-chromosomal genetic shuffling than males. CC was heritable in females (h2 = 0.11) and males (h2 = 0.10), and shuffling was also heritable in both sex but with a lower heritability in females (h2 = 0.06) than in males (h2 = 0.11). Inter-sex genetic correlations for both traits were close to zero, suggesting that rates and distribution of crossovers are genetically distinct traits in males and females, and that there is a potential for independent genetic change in both sexes in the Atlantic Salmon. Together, these findings give novel insights into the genetic architecture of recombination in salmonids and contribute to a better understanding of how rates and distribution of recombination may evolve in eukaryotes more broadly.


Thermal fixing of 10,000 Holograms in LiNbO3:Fe.
We discuss thermal fixing as a solution to the volatility problem in holographic storage systems that use photorefractive materials such as LiNbO(3):Fe. We present a systematic study to characterize the effect of thermal fixing on the error performance of a large-scale holographic memory. We introduce a novel, to our knowledge, incremental fixing schedule to improve the overall system fixing efficiency. We thermally fixed 10,000 holograms in a 90 degrees -geometry setup by using this new schedule. All the fixed holograms were retrieved with no errors.


Prevalence of Diabetes Mellitus and Associated Factors in Addis Ababa Public Health Facilities, Addis Ababa, Ethiopia, 2016.
Diabetes mellitus is one of the most public health challenges of the twenty-first century. Globally, 382 million people had diabetes by the year 2013. The purpose of this study was to determine the prevalence of diabetes mellitus and identify its associated factors at public health institutions in Addis Ababa. An institution-based cross-sectional study was carried out from June to July 2016. A total of 758 participants were selected using a multistage sampling technique. Data were collected with a structured interviewer-administered questionnaire; a WHO STEPwise approach of NCDs risk factors identification, and the collected data were checked for completeness immediately following data collection and the filled questionnaires were entered into Epi-Info 3.5.1, and then exported to SPSS 23 for further analysis. Descriptive statistics such as mean, percentages, standard deviation, and ranges were determined. To identify factors associated with diabetes mellitus, binary logistics regression was used. The overall prevalence of diabetes mellitus was 14.8%, with a sex-specific prevalence of 18.35% and 16.62% for males and females, respectively. Older age participants had higher risks of developing diabetes mellitus than younger age individuals. Alcohol drinkers had more risks of developing diabetes mellitus than non-alcohol drinkers. Participants with plasma HDL-C ≥40mg/dl were more likely to develop diabetes mellitus than those with <40mg/dl. Participants with a higher level of plasma triglyceride ≥130mg/dl were found to be more exposed to the risks of developing diabetes mellitus than study participants with a low level of triglycerides. A higher prevalence of diabetes mellitus was observed in Addis Ababa public health institutions. Factors such as age, alcohol drinking, HDL, triglycerides, and vagarious physical activity were associated with diabetes mellitus. Concerned bodies need to work over the ever-increasing diabetes mellitus in Addis Ababa.


Gordona hirsuta sp. nov.
Bacterial strain K718aT (T = type strain), which was isolated from the packing material of a biofilter used for deodorization of animal-rendering plant emissions, was subjected to a polyphasic taxonomic study in which physiological, chemotaxonomic, and genomic methods were used. On the basis of the chemotaxonomic and physiological properties found and the results of 16S ribosomal DNA sequence comparisons, it was evident that strain K718aT belongs to a new species in the genus Gordona. We propose that strain K718a should be the type strain of the new species Gordona hirsuta.


Yield of Investigations in Young Patients Presenting With Transient Monocular Vision Loss: A Prospective Study.
It is unclear whether transient monocular vision loss (TMVL) warrants the same thorough systemic evaluation for potential embolic sources in young adults as it does in older adults. The objective of the present study was to evaluate the yield of investigations in patients under 45 years of age presenting with TMVL. Prospective cohort study. Young adult patients with TMVL presenting to a university-affiliated neuro-ophthalmology clinic were included. All included patients were referred for neuroimaging (computed tomography or magnetic resonance angiography of entire carotid tree and magnetic resonance imaging of the brain) and cardiac investigations (transesophageal echocardiography and 2 weeks of Holter monitoring). A total of 20 participants with TMVL were included in the study. The mean age was 33.1 ± 8.2 years, and 16 of the 20 participants were women. The most common finding on past medical history was migraines, in 5 of 20 cases (25%), and 25% of patients had headaches during their visual loss. Of 17 participants who completed neuroimaging, 1 had fibromuscular dysplasia (this patient also experienced headaches during their symptoms). Two of 13 patients who completed echocardiography had patent foramen ovale. Overall, 3 of 20 participants (15%, 95% CI 3%-38%) had abnormal findings associated with their TMVL. Aspirin treatment was initiated in 2 of 3 patients following investigations. In our cohort of young patients presenting with TMVL, 15% of patients had abnormal findings on further investigations. We recommend that young patients presenting with TMVL be referred for neuroimaging and cardiac workup so that appropriate treatments can be initiated to prevent future complications. Headaches during vision loss may not always indicate a benign cause, and retinal migraine should be a diagnosis of exclusion.


Abernethy malformation with portal vein aneurysm.
We present the case of a 24-year-old man who was incidentally diagnosed with congenital extrahepatic portosystemic shunt with portal vein aneurysm during an investigation for non-specific abdominal pain. These are rare anomalies, and to the best of our knowledge, this is the first case reported with both anomalies associated together. Ultrasound, including color Doppler, computed tomography, and magnetic resonance imaging were performed which revealed a side-to-side shunt between the extrahepatic portal vein and the inferior vena cava, with aneurysmal fusiform dilatation of the proximal intrahepatic portal vein which ended abruptly. Etiology, clinical significance, and management strategies with regard to these abnormalities are discussed.


Demographic and ecological effects on patterns of parasitism in eastern chimpanzees (Pan troglodytes schweinfurthii) in Gombe National Park, Tanzania.
From January 2006 to January 2008, we collected 1,045 fecal samples from 90 individually-recognized, free-ranging, eastern chimpanzees (Pan troglodytes schweinfurthii) inhabiting Gombe National Park, Tanzania to determine how patterns of parasitism are affected by demographic and ecological covariates. Seventeen parasite species were recovered, including eight nematodes (Oesophagostomum sp., Necator sp., Probstmayria gombensis, Strongyloides fulleborni, Ascaris sp., Trichuris sp., Abbreviata caucasica, and an unidentified strongyle), 1 cestode (Bertiella sp.), 1 trematode (Dicrocoeliidae), and 7 protozoa (Entamoeba coli, Entamoeba histolytica/dispar, Iodamoeba bütschlii, Troglodytella abrassarti, Troglocorys cava, Balantidium coli, and an unidentified protozoa). Significant differences were observed in interannual infection prevalence and parasite richness between 2006 and 2007. Intercommunity comparisons demonstrated higher prevalence of parasites for the Mitumba compared with Kasekela chimpanzee community. Prevalence of several parasites was strongly correlated with monthly rainfall patterns for both 2006 and 2007. Subadult chimpanzees had lower prevalence for most parasite species compared with adults in both years and also yielded a lower average parasite species richness. No significant differences were observed between males and females in prevalence in 2006. However, in 2007 the prevalence of S. fulleborni and I. bütschlii were higher in males than in females. Parasite prevalence and richness were substantially higher in this multiyear study compared with previous short-term studies of the gastrointestinal parasites of Gombe chimpanzees. This coupled with the significant interannual and interseasonal variation, demonstrated in this study, emphasizes the importance of multiyear monitoring with adequate sample size to effectively determine patterns of parasitism in wild primate populations.


Phylogenomics resolves evolutionary relationships among ants, bees, and wasps.
Eusocial behavior has arisen in few animal groups, most notably in the aculeate Hymenoptera, a clade comprising ants, bees, and stinging wasps [1-4]. Phylogeny is crucial to understanding the evolution of the salient features of these insects, including eusociality [5]. Yet the phylogenetic relationships among the major lineages of aculeate Hymenoptera remain contentious [6-12]. We address this problem here by generating and analyzing genomic data for a representative series of taxa. We obtain a single well-resolved and strongly supported tree, robust to multiple methods of phylogenetic inference. Apoidea (spheciform wasps and bees) and ants are sister groups, a novel finding that contradicts earlier views that ants are closer to ectoparasitoid wasps. Vespid wasps (paper wasps, yellow jackets, and relatives) are sister to all other aculeates except chrysidoids. Thus, all eusocial species of Hymenoptera are contained within two major groups, characterized by transport of larval provisions and nest construction, likely prerequisites for the evolution of eusociality. These two lineages are interpolated among three other clades of wasps whose species are predominantly ectoparasitoids on concealed hosts, the inferred ancestral condition for aculeates [2]. This phylogeny provides a new framework for exploring the evolution of nesting, feeding, and social behavior within the stinging Hymenoptera.


Role of B cell receptor signaling in IL-10 production by normal and malignant B-1 cells.
B-1 cells are considered innate immune cells, which produce the majority of natural antibodies. B-1 cell responses to B cell receptor (BCR) and Toll-like receptor ligation are tightly regulated owing to the cross-reactivity to self-antigens. CD5 has been shown to play a major role in downregulation of BCR responses in B-1 cells. Here, we provide evidence for another mechanism by which BCR response is regulated in B-1 cells. B-1 cells, as well as their malignant counterpart, B cell chronic lymphocytic leukemia (B-CLL) cells, produce interleukin-10 (IL-10) constitutively. IL-10 secretion by normal B-1 cells downregulates their proliferation responses to BCR ligation. However, we found that CLL cells appear to be unique in not responding to IL-10-mediated feedback-suppressive effects in comparison to normal B-1 cells. In addition, we describe a novel role of the BCR signaling pathway in constitutive IL-10 secretion by normal and malignant B-1 cells. We found that inhibition of Src family kinases, spleen tyrosine kinase, Syk, or Bruton's tyrosine kinase reduces constitutive IL-10 production by both normal and malignant B-1 cells.


Enhanced malignant tumorigenesis in Cdk4 transgenic mice.
In a previous study, we reported that overexpression of cyclin-dependent kinase-4 (CDK4) in mouse epidermis results in epidermal hyperplasia, hypertrophy and severe dermal fibrosis. In this study, we have investigated the susceptibility to skin tumor formation by forced expression of CDK4. Skin tumors from transgenic mice showed a dramatic increase in the rate of malignant progression to squamous cell carcinomas (SCC) in an initiation-promotion protocol. Histopathological analysis of papillomas from transgenic mice showed an elevated number of premalignant lesions characterized by dysplasia and marked atypia. Interestingly, transgenic mice also developed tumors in initiated but not promoted skin, demonstrating that CDK4 replaced the action of tumor promoters. These results suggest that expression of cyclin D1 upon ras activation synergizes with CDK4 overexpression. However, cyclin D1 transgenic mice and double transgenic mice for cyclin D1 and CDK4 did not show increased malignant progression in comparison to CDK4 transgenic mice. Biochemical analysis of tumors showed that CDK4 sequesters the CDK2 inhibitors p27Kip1 and p21Cip1, suggesting that indirect activation of CDK2 plays an important role in tumor development. These results indicate that, contrary to the general assumption, the catalytic subunit, CDK4, has higher oncogenic activity than cyclin D1, revealing a potential use of CDK4 as therapeutic target.


[Radiation-population monitoring of Pinus sylvestris L. in the zone of the Chernobyl power plant].
Cytogenetic and genetic effects in populations of Pinus sylvestris L. suffered wiak, average, strong and sublethal radiation damage after the Chernobyl accident in 1986 were studied. The absorbed dozes for trees in these plantings were from 0.1 up to 20 Gy. It was shown that the amount of cells with chromosome aberrations in sprouts of seeds of a crop of 1993, are comparable with effects marked at once after accident in 1986. In 1997 and in 1998 the amount of cells with chromosome aberrations in sprouts of seeds in majority inspected plantings decreased to control values. The effect of adaptation was detected, when seeds of Pinus sylvestris L., gathered in 1997 from inspected trees, were exposed to additional 4 Gy gamma-radiation.


[A look on a half century of activity of the Wrocław Division of the Polish Society of History of Medicine and Pharmacy].
The Wrocław division of the Polish Society of the History of Medicine was founded on 16th June 1957 as one of the seven branches of the Society. In its history one can distinguish three main stages of activity, comprising the years 1957-1972, 1976-1990 and since 1991 up to the present. In the years 1973-1976 some disagreements between the General Board of the Society and the local authorities of the Society led to a temporary break in its activity. The most frequently appearing issues during the meetings of the Society comprised first of all biographies of famous physicians since Renessaince up to the present, issues related to the history of medicine in the Lower Silesia and history of the Lvowian school of medicine, the so called nazi medicine as well as history of pharmacy. The members of the Wrocław Division of the Society took part in numerous conferences both in the country and abroad.


The structural validity of the IKDC and its relationship with quality of life following ACL reconstruction.
The purpose of this study was to (a) examine the structural validity of the International Knee Documentation Committee Subjective Knee Form in light of previously reported dimensionality issues, and (b) examine the relationships between the IKDC and patients' knee-related quality of life 2-9 years after anterior cruciate ligament (ACL) reconstruction. A prospective research design was employed, wherein 319 patients (mean age = 29.07, SD = 9.03) completed the IKDC before surgery, 191 patients (mean age = 29.71, SD = 9.36) completed the IKDC at 6 months post-surgery, and 132 patients (mean age = 34.34, SD = 7.89) completed the IKDC and the Anterior Cruciate Ligament Quality of Life Survey (ACL-QOL) at 2-9 years post-surgery. Bayesian structural equation modeling analysis confirmed the two-factor structure (symptom & knee articulation and activity level) represented the most accurate conceptualization of perceived knee function across the three time-points. Moreover, findings revealed that of the two IKDC subscales pre-operatively, activity level was most strongly associated with long-term quality of life at 2-9 years following surgery, whereas 2-9 years post-operatively, symptoms and knee articulation was most strongly associated with long-term quality of life. The IKDC provides clinicians with a convenient total score to assess patients' perceived knee function, but its unidimensional factor structure is a poor representation of its items and fails to detect discrepancies in patients' post-operative quality of life, such as the relative importance of perceived knee activity level before reconstructive surgery.


[Age-related characteristics of insulin regulation of the physico-chemical properties of liver membranes].
Alterations in physico-chemical properties of rat liver plasmatic membranes induced by insulin were shown to be age-dependent The experiments showed also that high doses of the hormone impaired distinctly the membranes in old animals. The relationship between structural alterations in plasmatic membranes and the rate of lipid peroxidation was observed.


[Mechanisms of formation of chronic low back pain relapse and their correction in patients with dorsopathy].
A clinical-neurological, psychological, biochemical and electromyographic study of 40 operated and 40 non-operated patients with chronic low back pain syndrome was conducted before and after treatment. The authors used various modes of administration of xydifonum, a chelate from the group of bisphosphonates, including electrophoretic, peroral and administration in the form of ointment, administered in turn with heparin one to improve the antiplatelet effect, using photopheresis the with the help of the state-of-the art photomatrix LED equipment. The application of Ca2+-modulating properties of xydifonum demonstrate its universality in achieving of analgesic, muscle-relaxing, anxiolytic and antidepressant effects thus allowing to exclude polypragmasy. This is a main difference between this drug and other medications with limited effects. Based on the results obtained, the authors propose a scheme of development of chronic low back pain.


Patient response to PMMA contact lenses.
This study was designed to determine patient response to hard (PMMA) contact lenses and evaluate how lens modifications and refitting affect success. The subjects of this study were 178 randomly selected contact lens patients fitted at the University of California School of Optometry. Six to nine months after the patients were examined and fitted, their response to contact lenses was evaluated using the standard of Sarver and Harris. 44.4% of the patients were successful with the initial lenses while an additional 35.4% of the patients became successful after appropriate lens changes were made. The majority of the changes made were to eliminate ocular tissue changes. Our results indicate that lens modifications or refittings are often necessary to achieve a successful response to contact lenses.


Inhibition by etomoxir of rat liver carnitine octanoyltransferase is produced through the co-ordinate interaction with two histidine residues.
Rat peroxisomal carnitine octanoyltransferase (COT), which facilitates the transport of medium-chain fatty acids through the peroxisomal membrane, is irreversibly inhibited by the hypoglycaemia-inducing drug etomoxir. To identify the molecular basis of this inhibition, cDNAs encoding full-length wild-type COT, two different variant point mutants and one variant double mutant from rat peroxisomal COT were expressed in Saccharomyces cerevisiae, an organism devoid of endogenous COT activity. The recombinant mutated enzymes showed activity towards both carnitine and decanoyl-CoA in the same range as the wild type. Whereas the wild-type version expressed in yeast was inhibited by etomoxir in an identical manner to COT from rat liver peroxisomes, the activity of the enzyme containing the double mutation H131A/H340A was completely insensitive to etomoxir. Individual point mutations H131A and H340A also drastically reduced sensitivity to etomoxir. Taken together, these results indicate that the two histidine residues, H131 and H340, are the sites responsible for inhibition by etomoxir and that the full inhibitory properties of the drug will be shown only if both histidines are intact at the same time. Our data demonstrate that both etomoxir and malonyl-CoA inhibit COT by interacting with the same sites.


Nanojets, electrospray, and ion field evaporation: molecular dynamics simulations and laboratory experiments.
The energetics, interfacial properties, instabilities, and fragmentation patterns of electrosprays made from formamide salt solutions are investigated in a mass spectrometric vacuum electrospray experiment and using molecular dynamics (MD) simulations. The electrospray source is operated in a Taylor cone-jet mode, with the nanojet that forms being characterized by high surface-normal electric field strengths in the vicinity of 1 V/nm. Mass-to-charge ratios were determined for both positive and negative currents sprayed from NaI-formamide solutions with solute-solvent mole ratios of 1:8.4 and 1:36.9, and from KI-formamide solutions with mole ratios of 1:41 and 1:83. The molecular dynamics simulations were conducted on isolated 10 nm NaI-formamide droplets at mole ratios of 1:8 and 1:16. The droplet was subjected to a uniform electric field with strengths ranging between 0.5 and 1.5 V/nm. Both the experiments and simulations demonstrate a mixed charge emission regime where field-induced desorption of solvated ions and charged droplets occurs. The macroscopic parameters, such as average mass-to-charge ratio and maximum surface-normal field strengths deduced from the simulations are found to be in good agreement with the experimental work and consistent with electrohydrodynamic theory of cone-jets. The observed mass spectrometric Na (+) and I (-) solvated ion distributions are consistent with a thermal evaporation process, and are correctly reproduced by the simulation after incorporation of the different flight times and unimolecular ion dissociation rates in the analysis. Alignment of formamide dipoles and field-induced reorganization of the positive and negative ionic charges in the interfacial region are both found to contribute to the surface-normal field near the points of charge emission. In the simulations the majority of cluster ions are found to be emitted from the tip of the jet rather than from the neck region next to the Taylor cone. This finding is consistent with the experimental energy distributions of the solvated ions which demonstrate that indeed most ions are emitted closer to the jet region, that is, beyond the cone-neck region where ohmic losses occur. This observation is also consistent with continuum electrohydrodynamic predictions of cluster-ion evaporation at surface regions of high curvature and therefore maximum surface electric field strengths, which may be the cone-neck region, the breakup region of the jet (usually near the tip of the jet), or the emitted charged droplets. In the nanoscale jets observed in this study, the regions of highest spatial curvature are at the ends of the jets where nascent drops either are forming or have just detached.


Strain differences in pH-sensitive K+ channel-expressing cells in chemosensory and nonchemosensory brain stem nuclei.
The ventilatory CO2 chemoreflex is inherently low in inbred Brown Norway (BN) rats compared with other strains, including inbred Dahl salt-sensitive (SS) rats. Since the brain stem expression of various pH-sensitive ion channels may be determinants of the CO2 chemoreflex, we tested the hypothesis that there would be fewer pH-sensitive K(+) channel-expressing cells in BN relative to SS rats within brain stem sites associated with respiratory chemoreception, such as the nucleus tractus solitarius (NTS), but not within the pre-Bötzinger complex region, nucleus ambiguus or the hypoglossal motor nucleus. Medullary sections (25 μm) from adult male and female BN and SS rats were stained with primary antibodies targeting TASK-1, Kv1.4, or Kir2.3 K(+) channels, and the total (Nissl-stained) and K(+) channel immunoreactive (-ir) cells counted. For both male and female rats, the numbers of K(+) channel-ir cells within the NTS were reduced in the BN compared with SS rats (P < 0.05), despite equal numbers of total NTS cells. In contrast, we found few differences in the numbers of K(+) channel-ir cells among the strains within the nucleus ambiguus, hypoglossal motor nucleus, or pre-Bötzinger complex regions in both male and female rats. However, there were no predicted functional mutations in each of the K(+) channels studied comparing genomic sequences among these strains. Thus we conclude that the relatively selective reductions in pH-sensitive K(+) channel-expressing cells in the NTS of male and female BN rats may contribute to their severely blunted ventilatory CO2 chemoreflex.


Effects of a ZnCuO-Nanocoated Ti-6Al-4V Surface on Bacterial and Host Cells.
This study aims to investigate the effects of a novel ZnCuO nanoparticle coating for dental implants-versus those of conventional titanium surfaces-on bacteria and host cells. A multispecies biofilm composed of Streptococcus sanguinis, Actinomyces naeslundii, Porphyromonas gingivalis, and Fusobacterium nucleatum was grown for 14 days on various titanium discs: machined, sandblasted, sandblasted and acid-etched (SLA), ZnCuO-coated, and hydroxyapatite discs. Bacterial species were quantified with qPCR, and their viability was examined via confocal microscopy. Osteoblast-like and macrophage-like cells grown on the various discs for 48 h were examined for proliferation using an XTT assay, and for activity using ALP and TNF-α assays. The CSLM revealed more dead bacteria in biofilms grown on titanium than on hydroxyapatite, and less on sandblasted than on machined and ZnCuO-coated surfaces, with the latter showing a significant decrease in all four biofilm species. The osteoblast-like cells showed increased proliferation on all of the titanium surfaces, with higher activity on the ZnCuO-coated and sandblasted discs. The macrophage-like cells showed higher proliferation on the hydroxyapatite and sandblasted discs, and lower activity on the SLA and ZnCuO-coated discs. The ZnCuO-coated titanium has anti-biofilm characteristics with desired effects on host cells, thus representing a promising candidate in the complex battle against peri-implantitis.


Acute Pulmonary Exacerbations in Cystic Fibrosis.
With the improving survival of cystic fibrosis (CF) patients and the advent of highly effective cystic fibrosis transmembrane conductance regulator therapy, the clinical spectrum of this complex multisystem disease continues to evolve. One of the most important clinical events for patients with CF in the course of this disease is an acute pulmonary exacerbation. Clinical and microbial epidemiology studies of CF pulmonary exacerbations continue to provide important insight into the disease course, prognosis, and complications. This work has now led to a number of large scale clinical trials with the goal of improving the treatment paradigm for CF pulmonary exacerbation. The primary goal of this review is to provide a summary of the pathophysiology, the clinical epidemiology, microbial epidemiology, outcome and the treatment of CF pulmonary exacerbation.


Cell survival effect of activin against heat shock stress on OVCAR3.
Activin has been known as the hormone protein which regulates either cell proliferation or cell differentiation. Recently, it has also been reported that activin may have cell survival function. In this study, we have investigated, 1) the expression of inhibin subunits and activin receptors (ActRs) in ovarian carcinoma cell line (OVCAR3), 2) the binding property between activin and its receptors under the exposure to stress, and 3) the effect of activin on cell proliferation. All of inhibin subunits and ActR Ia, IIa and IIb mRNA were amplified by RT-PCR in OVCAR3. By Western blot analysis, ActR IIa and IIb proteins were detected. The binding property between activin and ActRs was analyzed with the fixed complex, using chemical cross linker. The bigger molecular weight signals, which had been shown to form the heterotrimeric complex among activin, ActR type I and ActR type II were detected after cross linking. These upper signals were apparently increased by rh-Activin and decreased by rh-Follistatin. Therefore, it was suggested that they were resultant from activin and Act-R complex. OVCAR3 was exposed to the stress (42C, 1 hour heat shock), the protein level of ActR IIa increased and ActR IIb decreased from about 3 h to 24 h after the exposure to the heat stress (HS). On the other hand, the complex between activin and ActR IIa and IIb increased from 3 h after the exposure to HS. To investigate the effect of activin and follistatin on OVCAR3 proliferation after the exposure to HS, we counted the cell number at 96 h after the treatment with activin or follistatin in the condition either with or without HS. Proliferation of the cell in the presence of HS was stimulated by rh-Activin and inhibited by rh-Follistatin. These data suggest that activin might have the function to survive and to proliferate OVCAR3, due to, at least in part the increase in its binding capacity to ActRs through either autocrine or paracrine manner.


Mothers' caries increases odds of children's caries.
There are many determinants of children's dental caries. We hypothesized that a mother's untreated caries was associated with increased likelihood of her children's untreated caries, after controlling for other factors. This population-based study was conducted in a rural, primarily Hispanic, California community. Interview and dental examination data for mother-child (children < 18 yrs old) dyads were analyzed. In a Generalized Estimation Equation (GEE) logit model for mothers (n = 179) and children (n = 387), maternal untreated caries was a statistically significant correlate of child's untreated caries, odds ratio (OR) = 1.76 (95%CI: 1.10, 2.70), adjusted for demographic factors. This relationship did not change when behavioral and dental utilization factors were added to the model, OR = 1.85 (95% CI: 1.12, 3.07). Maternal untreated caries almost doubled the odds of children's untreated caries and significantly increased child's caries severity by about 3 surfaces. Caries prevention and dental utilization programs for mothers and their children should be increased.


European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment.
In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed. Recommendations were based on evidence-based literature review, guidelines and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable) and distant metastatic cSCC. For common primary cSCC (the most frequent cSCC type), first-line treatment is surgical excision with postoperative margin assessment or microscopically controlled sugery. Safety margins containing clinical normal-appearing tissue around the tumour during surgical excision and negative margins as reported in the pathology report are necessary to minimise the risk of local recurrence and metastasis. In case of positive margins, a re-excision shall be done, for operable cases. Lymph node dissection is recommended for cSCC with cytologically or histologically confirmed regional nodal involvement. Radiotherapy should be considered as curative treatment for inoperable cSCC, or for non-surgical candidates. Anti-PD-1 antibodies are the first-line systemic treatment for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drug Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiation therapy. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Patients should be engaged with informed decisions on management and be provided with best supportive care to optimise symptom management and improve quality of life. Frequency of follow-up visits and investigations for subsequent new cSCC depend on underlying risk characteristics.


[A nematode parasite of the penguin Spheniscus magellanicus (Forster) (Ascaridoidea, Anisakidae)].
The nematodes were collected from the penguin Spheniscus magellanicus (Forster) (Sphenisciformes). A study from the main species of Contracaecum that occur in penguins and piscivorous birds from the south hemisphere is made, more specifically the C. eudyptulae Johnston & Mawson, 1942a, C. eudyptes Johnston & Mawson, 1953, C. heardi Mawson, 1953, C. antarcticum Johnston, 1938, C. prevosti Tchéprakoff, 1966, C. spiculigerum (Rudolphi, 1809), C. osculatum (Rudolphi, 1802), C. scotti (Leiper & Atkinson, 1914) and C. pelagicum Johnston & Mawson, 1942b. C. pelagicum is redescribed and turns to be a new reference for Spheniscus magellanicus (Forster).


Species-specific usage of sleeping sites in two sympatric mouse lemur species (Microcebus murinus and M. ravelobensis) in northwestern Madagascar.
We investigated the sleeping site ecology of two sympatric mouse lemur species (Microcebus murinus and M. ravelobensis) in northwestern Madagascar during the second half of the dry season with respect to the type, quality, and usage pattern of the sleeping sites, as well as to social sleeping habits and response to potential threats. The type and quality of the sleeping sites differed between the two species. M. murinus used protected wooden shelters (tree holes) more frequently than M. ravelobensis, and M. ravelobensis used a broader variety of less protected sites (e.g., branches, lianas, and leaves) than M. murinus. Whereas male M. murinus usually slept alone, and female M. murinus mostly slept in groups, both sexes of M. ravelobensis slept in mixed-sex sleeping groups. M. murinus relied on crypsis in their sleeping sites, whereas M. ravelobensis regularly showed a flight response to the approach of an observer. This behavioral difference could indicate an adaptation to a higher predation risk in less protected sleeping sites. Whereas female M. murinus showed a high site fidelity, male M. murinus and both sexes of M. ravelobensis frequently changed their sleeping sites, which may also be interpreted as an antipredator strategy. The results are discussed with respect to three possible ecological explanations: interspecies competition, restricted resource availability, and niche differentiation. The latter is the most likely explanation for these interspecific differences.


Sex-ratio evolution in sex changing animals.
Sex allocation theory is often able to make clear predictions about when individuals should facultatively adjust their offspring sex ratio (proportion male) in response to local conditions, but not the consequences for the overall population sex ratio. A notable exception to this is in sex changing organisms, where theory predicts that: (1) organisms should have a sex ratio biased toward the "first" sex: (2) the bias should be less extreme in partially sex changing organisms, where a proportion of the "second" sex matures directly from the juvenile stage; and (3) the sex ratio should be more biased in protogynous (female first) than in protandrous (male first) species. We tested these predictions with a comparative study using data from 121 sex changing animal species spanning five phyla, covering fish, arthropods, echinoderms, molluscs, and annelid worms. We found support for the first and third predictions across all species. The second prediction was supported within the protogynous species (mainly fish), but not the protandrous species (mainly invertebrates).


Alpha 1 adrenoceptor mediated signal transduction in neonatal rat ventricular myocytes: effects of prolonged hypoxia and reoxygenation.
The aim was to study the effects of prolonged hypoxia and reoxygenation on alpha 1 adrenoceptors and inositol phosphate accumulation in neonatal rat ventricular myocytes maintained in culture for 6-8 d. Neonatal rat ventricular myocytes were subjected to 2 h hypoxia followed by 2 h reoxygenation. Cells were harvested at various times during hypoxia and after reoxygenation and measurements of alpha 1 adrenoceptor density and affinity and determinations of basal and (-)-noradrenaline stimulated inositol phosphate accumulation were carried out. A neonatal rat ventricular myocyte preparation almost completely free of contaminating non-myocytes was used. Cells were grown in serum containing medium for 5 d before experiments were performed. alpha 1 Adrenoceptors were measured using the radioligand 125I-HEAT and inositol phosphates were measured by anion exchange chromatography after incubation with 1 microM (-)-noradrenaline for 5 min. Hypoxia resulted in an increase in alpha 1 adrenoceptor density which was reversed by reoxygenation. There were no changes in antagonist affinity. (-)-Noradrenaline stimulated inositol phosphate production was increased at 1 h hypoxia but declined to control levels after 2 h hypoxia, while basal levels increased significantly at this time. This pattern was similar for all inositol phosphates measured: inositol-1-phosphate, inositol bisphosphate, and the putative second messenger, inositol trisphosphate. Displacement by (-)-noradrenaline of 125I-HEAT binding was significantly shifted to the right after 2 h hypoxia. Prolonged hypoxia in neonatal rat ventricular myocytes increases alpha 1 adrenoceptor density without change in antagonist affinity. Inositol phosphates follow a biphasic response, increasing after 1 h and decreasing after 2 h hypoxia in response to (-)-noradrenaline stimulation. This second messenger response and the rightward shift of the (-)-noradrenaline displacement curve suggests that after 2 h hypoxia there is a decrease in agonist affinity for the alpha 1 adrenoceptor consistent with uncoupling of the alpha 1 adrenoceptor from its effector.


Observation of hydrofluoric acid burns on osseous tissues by means of terahertz spectroscopic imaging.
Terahertz technologies have gained great amount of attention for biomedical imaging and tissue analysis. In this study, we utilize terahertz imaging to study the effects of hydrofluoric acid on both compact bone tissue and cartilage. We compare the differences observed in the exposure for formalin fixed and raw, dried, tissue as well as those resulting from a change in hydrofluoric (HF) concentration. Measurements are performed with THz-TDS, and a variety of spectroscopic-based image reconstruction techniques are utilized to develop contrast in the features of interest.


Active manganese oxide: a novel adsorbent for treatment of wastewater containing azo dye.
A new variety of active manganese oxide was prepared, characterized, and tested for its potential of adsorbing Congo Red, a dis-azo dye, from aqueous solutions. Both equilibrium and kinetics were investigated over different values of process parameters such as temperature (25-45 degrees C), adsorbent loading (0.4-0.6%), initial dye concentration (50-500 mg/L), presence of salts (sodium sulphate, 500 mg/L) and the oxygen content (MnO(x), x=1.2, 1.33 and 2) of the adsorbent. The equilibrium adsorption data were fitted to Langmuir and Freundlich isotherms. Langmuir adsorption capacity of the sorbent (x=1.33) for Congo Red was 38.6 mg/g at room temperature which is substantially higher than those for commercial manganese dioxide, red mud, coir pith, activated carbon, and fly ash. The kinetic data were best interpreted using a pseudo-second order model. The results show that the active manganese oxide used in this work removes the dye by reversible adsorption and has the potential for practical use for remediation of textile industry effluents.


A randomized trial of aspirin and sulfinpyrazone in patients with threatened stroke. Results and methodologic issues.
In the Canadian Cooperative Study of aspirin and sulfinpyrazone in patients with threatened stroke, there was no demonstrable benefit of sulfinpyrazone but there was a significant overall risk reduction in stroke or death of 31% with aspirin (p less than 0.05). This benefit of aspirin was restricted to males, in whom the risk reduction in stroke or death was 48% (p less than 0.005). As with a large-scale clinical trials, questions have been raised about the methodology of the study, including the type of patient included, the choice of outcome measures, the factorial design and the analysis of subgroups. In this report, the design and principal results of the study are summarized and the above methodologic concerns are discussed.


From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study.
Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS.


Survey of atmospheric pollen allergens in Delhi: seasonal periodicity.
Atmospheric pollen surveys were conducted at four different zones within the metropolitan capital city of India, Delhi, for a period of three years (1973-1975). Durham's Gravity Sampling Device was employed for sampling airborne pollen. Altogether 86 pollen types were identified from the atmosphere of Delhi; 22 types are new records for the atmosphere of Delhi. Two major pollen seasons--February to April and August to October--are recognized for Delhi. The atmosphere pollen concentration of different types as well as of the total counts showed significant annual and seasonal variations and also revealed marked differences in the quality and quantity of the pollen from site to site. Habitat factors seem to be the causal agents for the wide range of variations in the pollen content of the atmosphere of Delhi. The results of the survey are discussed in the light of relevant published literature.


[Adult-onset Still disease as the cause of fever of unknown origin].
Fever of unknown origin remains a diagnostic challenge with up to 50% of unexplained cases. Adult-onset Still disease typically present high fever, arthralgia, rash, pharyngitis and serositis, lymphadenopathy and hepatosplenomegaly, inflammatory markers and hepatic enzymes elevation and negative immunological study. The authors present a 46-year old man with previous admissions for fever of unknown origin with a 3-week history of fever and systemic symptoms. The study disclosed anaemia, inflammatory markers and hepatic enzymes elevation, splenomegaly and negative serological and immunological studies. The patient posteriorly presented polyarthralgias and cutaneous rash. The introduction of corticotherapy resolved symptoms and laboratories alterations. Adult-onset Still disease is a heterogeneous and rare disease and the lack of serologic markers as a true gold standard makes diagnosis difficult.


Latent structure of negative valence measures in childhood.
Internalizing disorders (IDs), consisting of the syndromes of anxiety and depression, are common, debilitating conditions often having onsets in adolescence. Scientists have developed dimensional self-report instruments that assess putative negative valence system (NVS) trait-like constructs as complimentary phenotypes to clinical symptoms. These include various measures that index temperamental predispositions to IDs and correlate with neural substrates of fear, anxiety, and affective regulation. This study sought to elucidate the overarching structure of putative NVS traits and their relationship to early manifestations of ID symptomatology. The sample consisted of 768 juvenile twin subjects ages 9-13. Together with ID symptoms, extant validated instruments were chosen to assess a broad spectrum of NVS traits: anxiety sensitivity, irritability, fearfulness, behavioral activation and inhibition, and neuroticism and extraversion. Exploratory and confirmatory factor analyses (EFA/CFA) were used to investigate the latent structure of the associations among these different constructs and ID symptoms. Bifactor modeling in addition to standard correlated-factor analytic approaches were applied. Factor analyses produced a primary tripartite solution comprising anxiety/fear, dysphoria, and positive affect among all these measures. Competing DSM-like correlated factors and an RDoC-like NVS bifactor structure provided similar fit to these data. Our findings support the conceptual organization of a tripartite latent internalizing domain in developing children. This structure includes both clinical symptoms and a variety of self-report dimensional traits currently in use by investigators. These various constructs are, therefore, most informatively investigated using an inclusive, integrated approach.


Proliferative breast disease: epidemiologic aspects, and cytologic diagnosis.
The aim of the present study is to describe the prevalence of proliferative breast lesions in cases of benign and malignant tumors of the breast as well as to assess the contribution of rapid intraoperative imprint cytology in the diagnosis of proliferative breast disease. Frozen section and intraoperative imprint cytology were performed on breast tissue biopsies from 486 breast cancer patients who underwent primary surgical treatment. Imprints were stained either by the Papanicolaou (Pap) or the May Grünwald-Giemsa (MGG) or the Hematoxylin eosin (HE) technique. Cytologic diagnoses were compared to the histopathologic ones from paraffin sections. Sclerosing adenosis was the most common finding in benign breast biopsies while in breast cancer the prevalence of the lesion was reduced by half. On the other hand, atypical hyperplasias in malignant biopsies were almost twice as many as in benign ones. Imprint cytology presented high sensitivity and specificity (99% and 96% respectively) in distinguishing benign proliferative from malignant lesions as a whole, but regarding atypical hyperplasias the specificity was significantly reduced (76% vs 96%). Clarification of cytologic diagnostic criteria and expertise in cytologic interpretation could show off intraoperative imprint cytology as a useful and inexpensive diagnostic tool providing the surgeon with prompt and accurate information regarding the nature of breast lesions.


Apolipoprotein D Internalization Is a Basigin-dependent Mechanism.
Apolipoprotein D (apoD), a member of the lipocalin family, is a 29-kDa secreted glycoprotein that binds and transports small lipophilic molecules. Expressed in several tissues, apoD is up-regulated under different stress stimuli and in a variety of pathologies. Numerous studies have revealed that overexpression of apoD led to neuroprotection in various mouse models of acute stress and neurodegeneration. This multifunctional protein is internalized in several cells types, but the specific internalization mechanism remains unknown. In this study, we demonstrate that the internalization of apoD involves a specific cell surface receptor in 293T cells, identified as the transmembrane glycoprotein basigin (BSG, CD147); more particularly, its low glycosylated form. Our results show that internalized apoD colocalizes with BSG into vesicular compartments. Down-regulation of BSG disrupted the internalization of apoD in cells. In contrast, overexpression of basigin in SH-5YSY cells, which poorly express BSG, restored the uptake of apoD. Cyclophilin A, a known ligand of BSG, competitively reduced apoD internalization, confirming that BSG is a key player in the apoD internalization process. In summary, our results demonstrate that basigin is very likely the apoD receptor and provide additional clues on the mechanisms involved in apoD-mediated functions, including neuroprotection.


[Diagnostic algorithms in pulmonary hypertension].
Pulmonary hypertension is a serious disease with a poor prognosis. The diagnosis and assessment of pulmonary hypertension is evolving rapidly with changes in the definition of the disease, diagnostic techniques and follow-up assessment. Different conditions associated with pulmonary hypertension and new diagnostic techniques have led to a need for a systematic diagnostic approach. This review article presents an update on alterations in the diagnostic algorithm.


Two family studies on congenital dislocation of the hip after early orthopaedic screening Hungary.
Two family studies involving 1767 and 379 index patients in Budapest and Bekes county, respectively, were undertaken to examine the effect of early orthopaedic screening on the recurrence risk of congenital dislocation of the hip. About 14%, 2.1-2.3%,1.2-1.4%, and 4.7-6% of sibs, parents, uncles and aunts, and cousins, respectively, had congenital dislocation of the hip in these two surveys. The recurrence risks were eight-fold and four-fold higher in brothers and sisters, four times higher in parents, 2.5-fold higher in uncles and aunts, and 2.0-2.5 times higher in cousins, respectively, than in the general population. This family pattern seems to fit best with a model of polygenic-multifactorial inheritance. In earlier studies higher recurrence risks were found. These may be explained by the change of diagnosis due to early orthopaedic screening which may increase the possibility of over diagnosis and the treatment of mild cases which previously recovered spontaneously.


Complexity of the supertypic HLA-DRw53 specificity: two distinct epitopes differentially expressed on one or all of the DR beta-chains depending on the HLA-DR allotype.
The supertypic HLA-DRw53 specificity is associated with three allelic class II specificities defined by alloantisera: HLA-DR4, -DR7, and DRw9. The present study demonstrates the complexity of this supertypic DR specificity by comparing two DRw53-related determinants defined by the monoclonal antibodies PL3 and 109d6. For every HLA-DR4 cell line tested, both monoclonal antibodies were found to bind to the same subpopulation of DR molecules. This PL3+, 109d6+ DR subpopulation is also found on most, but not all, DR7+ cell lines with a beta-chain pattern that is identical to the beta-chain pattern of the PL3+, 109d6+ subpopulation on DR4 cell lines. However, some DR7+ cells which carry the HLA haplotype Bw57, DR7, DRw53, DQw3 were also found which completely lack the expression of the 109d6 determinant, but continue to express the PL3 determinant and some of the DRw53 determinants recognized by alloantisera. This results from the fact that the PL3 determinant is expressed on all of the DR molecules found on DR7 cells, including the distinct subpopulation of molecules that carry the HLA-DR7 determinant recognized by the monoclonal antibody SFR16-DR7. This PL3+, SFR16-DR7+ subpopulation does not carry the 109d6 determinant, demonstrating that the PL3 and 109d6 DRw53-related determinants are distinct and can be expressed on a different number of DR molecules, depending on the allotype of the cells. Blocking studies were also performed by using these monoclonal antibodies with alloreactive HLA-DR7-specific cytotoxic T cell clones. In these studies, the T cell-defined HLA-DR7 determinants were found to be carried by the same subpopulation of DR molecules recognized by the HLA-DR7-specific monoclonal antibody and not carried by the DR molecules recognized by 109d6. The DR7+ cell lines which do not express the 109d6 determinant also fail to express another supertypic determinant recognized by the monoclonal antibody IIIE3 carried on this molecule. Furthermore, no additional allelic forms of this unique DR beta-chain were found associated with the nonpolymorphic DR alpha-chain on these cells, suggesting that this DR beta-chain gene is not expressed. These cells also behave as homozygous typing cells for the Dw11 subtype of DR7 in HLA-D typing in the mixed lymphocyte culture assay. This suggests that the lack of expression of a specific class II gene may contribute additional genetic polymorphism within the known HLA-DR allotypes.


Synchronous correction in secondary cleft deformities: a prospective cohort study.
Patients with cleft lip and palate deformities undergo multiple surgical procedures from infancy till adolescence. We hypothesized that combining these surgical procedures might offer a better quality of life without compromising on surgical outcomes. A prospective cohort study was conducted at our center including all adult patients who reported to us for the correction of secondary cleft deformities. All patients with secondary deformities associated with cleft lip palate and alveolus were enrolled in the study. Patients with medical issues who are not fit for general anesthesia, Bilateral Cleft deformities, and patients with gross skeletal deformity warranting surgical correction by Le fort I distraction were excluded from the study. All the patients who were included in the study underwent simultaneous lip revision, rhinoplasty and cleft alveolar bone grafting. The outcome lip nose profile was assessed using standardized patient photographs with Ascher Mcdade Scale and Aesthetic outcome index by 2 blinded maxillofacial surgeons and the bone grafting was assessed using Berglands grading system. Twenty-eight patients were enrolled in the study, 10 patients were excluded based on the exclusion criteria. Thus 18 patients planned for synchronous correction of unilateral secondary cleft deformities were included in the study The Ascher Mcdade Score improved from 15 (13-16), to 4 (4-5) in the post op. All the patients were totally satisfied with the surgical outcome. The aesthetic index showed excellent outcomes in all the lip-nose procedures, except for one case which showed a good outcome. The Bergland Scale showed normal bone height in all cases of alveolar bone grafting, except for one case, which showed less than 3/4th fill of bone. No complications were associated with any of the procedures. Simultaneous correction of multiple secondary cleft lip deformities should be considered when feasible, to improve the psychological benefit and reduce financial burden on these patients. However, careful planning and execution of the techniques is essential to avoid complications associated with vascular compromise.


Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells.
Analysis of the total base composition of DNA from seven different normal human tissues and eight different types of homogeneous human cell populations revealed considerable tissue-specific and cell-specific differences in the extent of methylation of cytosine residues. The two most highly methylated DNAs were from thymus and brain with 1.00 and 0.98 mole percent 5-methylcytosine (m5C), respectively. The two least methylated DNAs from in vivo sources were placental DNA and sperm DNA, which had 0.76 and 0.84 mole percent m5C, respectively. The differences between these two groups of samples were significant with p less than 0.01. The m5C content of DNA from six human cell lines or strains ranged from 0.57 to 0.85 mole percent. The major and minor base composition of DNA fractionated by reassociation kinetics was also determined. The distribution of m5C among these fractions showed little or no variation with tissue or cell type with the possible exception of sperm DNA. In each case, nonrepetitive DNA sequences were hypomethylated compared to unfractionated DNA.


Microbiological method for assaying lincomycin in animal feed: collaborative study.
A microbiological assay for determining lincomycin in swine feed, supplement, and a vitamin-mineral premix was studied collaboratively in 16 laboratories. The design of the study involved a complete feed, feed supplement, and a vitamin-mineral premix covering a range of fortification from 20 to 80 g/ton and 80 to 2600 g/ton. Two methods of sample preparation were used depending on the concentration of lincomycin in the sample. Statistical evaluation of the results from the 2 methods indicated that 10 and 11 collaborators, respectively, had mean recoveries which were not significantly different from one another. Ten laboratories obtained a mean recovery of 112.2% (range 102.3--123.5%) for the lower level, and 11 laboratories obtained a mean recovery of 104.4% (range 100.0--107.7%) for the higher level. The method has been adopted as official first action.


Biochemical and physiological mechanisms underlying effects of Cucumber mosaic virus on host-plant traits that mediate transmission by aphid vectors.
The transmission of insect-vectored diseases entails complex interactions among pathogens, hosts and vectors. Chemistry plays a key role in these interactions; yet, little work has addressed the chemical ecology of insect-vectored diseases, especially in plant pathosystems. Recently, we documented effects of Cucumber mosaic virus (CMV) on the phenotype of its host (Cucurbita pepo) that influence plant-aphid interactions and appear conducive to the non-persistent transmission of this virus. CMV reduces host-plant quality for aphids, causing rapid vector dispersal. Nevertheless, aphids are attracted to the elevated volatile emissions of CMV-infected plants. Here, we show that CMV infection (1) disrupts levels of carbohydrates and amino acids in leaf tissue (where aphids initially probe plants and acquire virions) and in the phloem (where long-term feeding occurs) in ways that reduce plant quality for aphids; (2) causes constitutive up-regulation of salicylic acid; (3) alters herbivore-induced jasmonic acid biosynthesis as well as the sensitivity of downstream defences to jasmonic acid; and (4) elevates ethylene emissions and free fatty acid precursors of volatiles. These findings are consistent with previously documented patterns of aphid performance and behaviour and provide a foundation for further exploration of the genetic mechanisms responsible for these effects and the evolutionary processes that shape them.


p73 is regulated by phosphorylation at the G2/M transition.
p73 is a p53 paralog that encodes proapoptotic (transactivation-competent (TA)) and antiapoptotic (dominant negative) isoforms. TAp73 transcription factors mediate cell cycle arrest and/or apoptosis in response to DNA damage and are involved in developmental processes in the central nervous system and the immune system. p73 proteins may also play a role in the regulation of cell growth. Indeed, p73 expression is itself modulated during the cell cycle and TAp73 proteins accumulate in S phase cells. In addition, the function of p73 proteins is also regulated by post-translational modifications and protein-protein interactions in different cellular and pathophysiological contexts. Here we show that p73 is a physiological target of the p34cdc2-cyclin B mitotic kinase complex in vivo. Both p73beta and p73alpha isoforms are hyperphosphorylated in normal mitotic cells and during mitotic arrest induced by microtubule-targeting drugs. p34cdc2-cyclin B phosphorylates and associates with p73 in vivo, which results in a decreased ability of p73 to both bind DNA and activate transcription in mitotic cells. Indeed, p73 is excluded from condensed chromosomes in meta- and anaphase, redistributes throughout the mitotic cytoplasm, and unlike p53, shows no association with centrosomes. Together these results indicate that M phase-specific phosphorylation of p73 by p34cdc2-cyclin B is associated with negative regulation of its transcriptional activating function.


Oral anticoagulation with edoxaban. Focus on current phase III clinical development.
Edoxaban (the former DU176b) an orally available direct factor Xa inhibitor has been engineered from DX-9065a, which was one of the first parenteral Xa inhibitors. Edoxaban has a time to peak plasma concentrations of 1-2 hours and a half-life of approximately 10 hours after multiple doses. Edoxaban is the third new oral anticoagulant in the group of direct factor Xa inhibitors that has gained clinical approval for the prevention of venous thromboembolism after major orthopaedic surgery. Currently, edoxaban is assessed in late stage clinical development for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (ENGAGE AF-TIMI 48, NCT00781391) and for the treatment and prevention of venous thromboembolism in patients with acute deep vein thrombosis and/or pulmonary embolism (HOKUSAI VTE, NCT00986154). Both clinical phase III trials represent the largest single clinical studies in their entity so far with an enrolment of 21107 patients in ENGAGE AF-TIMI 48 and a planned enrolment of 7500 patients in HOKUSAI VTE. The pharmacological properties of edoxaban will be discussed along with the current late stage clinical development focusing on the prevention of stroke and venous thromboembolism.


Damage signals in the insect immune response.
Insects and mammals share an ancient innate immune system comprising both humoral and cellular responses. The insect immune system consists of the fat body, which secretes effector molecules into the hemolymph and several classes of hemocytes, which reside in the hemolymph and of protective border epithelia. Key features of wound- and immune responses are shared between insect and mammalian immune systems including the mode of activation by commonly shared microbial (non-self) patterns and the recognition of these patterns by dedicated receptors. It is unclear how metazoan parasites in insects, which lack these shared motifs, are recognized. Research in recent years has demonstrated that during entry into the insect host, many eukaryotic pathogens leave traces that alert potential hosts of the damage they have afflicted. In accordance with terminology used in the mammalian immune systems, these signals have been dubbed danger- or damage-associated signals. Damage signals are necessary byproducts generated during entering hosts either by mechanical or proteolytic damage. Here, we briefly review the current stage of knowledge on how wound closure and wound healing during mechanical damage is regulated and how damage-related signals contribute to these processes. We also discuss how sensors of proteolytic activity induce insect innate immune responses. Strikingly damage-associated signals are also released from cells that have aberrant growth, including tumor cells. These signals may induce apoptosis in the damaged cells, the recruitment of immune cells to the aberrant tissue and even activate humoral responses. Thus, this ensures the removal of aberrant cells and compensatory proliferation to replace lost tissue. Several of these pathways may have been co-opted from wound healing and developmental processes.


Biological and clinical aspects of ABO blood group system.
The ABO blood group was discovered in 1900 by Austrian scientist, Karl Landsteiner. At present, the International Society of Blood Transfusion (ISBT) approves as 29 human blood group systems. The ABO blood group system consists of four antigens (A, B, O and AB). These antigens are known as oligosaccharide antigens, and widely expressed on the membranes of red cell and tissue cells as well as, in the saliva and body fluid. The ABO blood group antigens are one of the most important issues in transfusion medicine to evaluate the adaptability of donor blood cells with bone marrow transplantations, and lifespan of the hemocytes.This article reviews the serology, biochemistry and genetic characteristics, and clinical application of ABO antigens.


An information system for emergency and out-patient departments.
Diagnoses are seldom coded in Out-Patient and Emergency Departments (EDs) in Canada, due, in large part, to the cost of manual coding. The lack of such diagnosis coding limits the information available to patient demographics, arrival mode, times of visits, and disposition. In the absence of diagnoses in a retrievable form, little information is available on just why patients came and what was done for them.


Pathogenesis of achalasia cardia.
Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down's syndrome and Parkinson's disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus.


CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon.
The aim of this study was to compare computed tomography (CT) scans of chest and lung function among patients with Human T-Lymphotropic Virus Type 1 (HTLV) with and without HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this cross-sectional study performed between January 2013 and June 2016, we included 48 patients with HAM/TSP (19 women and 11 men) and without HAM/TSP (12 women and 6 men). We compared CT findings and lung functions of these groups. Patients who had HAM/TSP had abnormal CT findings (P = 0.000), including more frequent bronchiectasis (P = 0.049), parenchymal bands (P = 0.007), interlobular septal thickening (P = 0.035), and pleural thickening (P = 0.009). In addition, neither patients with HAM/TSP (9/30; 30%) nor the controls (0/18; 0%) had obstructive or restrictive lung disease (P = 0.009). HTLV diagnosis should be considered in all patients with abnormal CT findings in whom no other cause is apparent. It is important to remember that lung disease increases the rates of morbidity and mortality in developing countries.


Nanocarriers in Improving Chemotherapy of Multidrug Resistant Tumors: Key Developments and Perspectives.
The multidrug resistance (MDR) of tumor cells significantly reduces the efficiency of traditional anticancer therapy. Tumor MDR is complex and involves several mechanisms such as decreased drug uptake, increased drug efflux, enhanced drug exocytosis, increased drug detoxification and inactivation by drugmetabolizing enzymes, altered drug targets due to genetic and epigenetic modifications, altered DNA repair, and impaired apoptotic pathways. Implementation of nanoparticles can markedly improve drug delivery through increased stability in the plasma, prolonged half-life, enhanced specificity of transfer, and advanced drug accumulation and retention in the tumor cells. So far, many various types of nanocarriers have been used for the delivery of anticancer agents. These carriers greatly increase anti-tumor effects of cytotoxic agents since drug-carrying nanoparticles are able to reverse MDR. The promising integrative approach in cancer nanotherapy assumes the development of multifunctional delivery systems simultaneously transmitting various agents such as drugs, genes, imaging agents, and targeting ligands in order to enhance anti-tumor toxicity and nanoparticle tracking.


Individual differences in vagal regulation moderate associations between daily affect and daily couple interactions.
Previous research suggests that cardiac vagal regulation (indexed by respiratory sinus arrhythmia, or RSA) provides a physiological substrate for affect regulation, which presumably underlies adaptive interpersonal functioning.The authors tested these associations in the context of daily interactions between 68 cohabiting couples. Participants underwent a laboratory assessment of RSA during rest and also during a series of psychological stressors. Subsequently, they kept daily measures of affect and interaction quality for 21 days. Individual differences in baseline and stress levels of RSA moderated within-person associations between daily affect and the quality of couple interactions. The pattern of results differed for women versus men. Men with lower vagal tone or higher vagal reactivity had stronger associations between daily negative affect and daily negative interactions, and men with higher vagal tone had more positive daily interactions overall. Women with higher vagal tone had stronger associations between daily positive affect and daily positive interactions.


Dynamic Functional Assessment of Hand Motion Using an Animation Glove: The Effect of Stenosing Tenosynovitis.
The aim of the present study is to determine whether an animation glove can be utilized to provide a reliable and reproducible assessment of dynamic hand function and whether this assessment is altered in the setting of hand pathology. Ten subjects without known hand pathology and 11 subjects with known stenosing tenosynovitis were assessed on tasks involving hand function at varied speeds, including forceful and gradual making of a fist and the quick and slow grip of a baseball using an animation glove to record range of motion and measures of velocity (CyberGlove II). In normal subjects, peak extension and flexion velocity of the index and middle finger was highest in the metacarpophalangeal and lowest in the distal interphalangeal; however, the converse was true in the ring finger. In those subjects with stenosing tenosynovitis, the animation glove was able to detect a triggering event during assessment. Furthermore, there was a significant decrease in the maximum velocity of the proximal interphalangeal joint observed with the slow fist task in both flexion and extension (55%, P < .01) in the affected hand when compared with the unaffected hand. The CyberGlove II can be utilized in the dynamic functional analysis of the hand and is able to detect a triggering event in subjects with known stenosing tenosynovitis. Those subjects demonstrate a significant decrease in maximum velocity in slow fist tasks, highlighting the need for comprehensive assessment to ascertain the full extent of functional limitations that can occur in the setting of hand pathology.


Broad-range survey of vector-borne pathogens and tick host identification of Ixodes ricinus from Southern Czech Republic.
Ixodes ricinus ticks are vectors of numerous human and animal pathogens. They are host generalists able to feed on more than 300 vertebrate species. The prevalence of tick-borne pathogens is influenced by host-vector-pathogen interactions that results in spatial distribution of infection risk. Broad-range polymerase chain reaction electrospray ionization mass spectrometry (PCR/ESI-MS) was used to analyze 435 I. ricinus nymphs from four localities in the south of the Czech Republic for the species identification of tick-borne pathogens. Borrelia burgdorferi sensu lato spirochetes were the most common pathogen detected in the ticks; 21% of ticks were positive for a single genospecies and 2% were co-infected with two genospecies. Other tick-borne pathogens detected included Rickettsia helvetica (3.9%), R. monacensis (0.2%), Anaplasma phagocytophilum (2.8%), Babesia venatorum (0.9%), and Ba. microti (0.5%). The vertebrate host of the ticks was determined using PCR followed by reverse line blot hybridization from the tick's blood-meal remnants. The host was identified for 61% of ticks. DNA of two hosts was detected in 16% of samples with successful host identification. The majority of ticks had fed on artiodactyls (50.7%) followed by rodents (28.6%) and birds (7.8%). Other host species were wild boar, deer, squirrels, field mice and voles.


Response to infection control challenges in the deployed setting: Operations Iraqi and Enduring Freedom.
Infections caused by multidrug-resistant organisms (MDROs), including Acinetobacter, have complicated the care of military personnel injured in Operations Iraqi and Enduring Freedom. Cumulative data suggest that nosocomial transmission of MDROs in deployed medical treatment facilities (MTFs) has contributed to these infections. A 2008 review of deployed MTFs identified multiple factors impeding the performance of infection prevention and control (IC) practices. In response, efforts to emphasize IC basics, improve expertise, and better track MDRO colonization were pursued. Efforts to increase awareness and enhance IC in deployed MTFs were focused on educating leaders and deploying personnel, producing deployed IC resources, and standardizing level IV and V admission screening for MDRO colonization. A repeat mission in 2009 reviewed interval progress. Increased awareness and the need for emphasis on basic IC practice, including hand hygiene, use of transmission-based (isolation) precautions, and cohorting of patients, were imparted to leaders and deploying personnel through briefings, presentations, and an All Army Activities message. Enhancement of IC expertise was implemented through increased standardization of IC practice, establishment of a predeployment IC short course, an IC teleconsultation service, and dedicated Internet resources. Standardization of admission colonization screening of personnel evacuated from the combat theater was established to better define and respond to the MDRO problem. A repeat review of the deployed MTFs found overall improvement in IC practice, including clear command emphasis in the Iraqi theater of operations. Maintaining a strong IC effort in the deployed setting, even in a stabilized operational environment, is difficult. Use of innovative strategies to enhance expertise and practice were implemented to reduce MDRO infections.


Impact of disabled circadian clock on yellow fever mosquito Aedes aegypti fitness and behaviors.
Like other insects, Aedes aegypti displays strong daily patterns in host seeking and mating. Much of these behaviors are believed to be under the control of a circadian clock, an endogenous timekeeping mechanism relying on transcriptional/translational negative feedback loops that drive rhythmic physiology and behavior. To examine the connection between the circadian clock and various Ae. aegypti behaviors, we knocked out the core clock gene cycle using CRISPR/Cas9. We found that the rhythmic pattern and intensity of mRNA expression of seven circadian genes, including AeCyc-/-, were altered across the day/night cycle as well as in constant darkness conditions. We further show that the mutant CYC protein is incapable of forming a dimer with CLK to stimulate per expression and that the endogenous clock is disabled in AeCyc-/- mosquitoes. AeCyc-/- do not display the bimodal locomotor activity pattern of wild type, have a significantly reduced response to host odor, reduced egg hatching rates, delayed embryonic development and reduced adult survival and mating success. Surprisingly however, the propensity to blood feed in AeCyc-/- females is significantly higher than in wildtype females. Together with other recent work on the circadian clock control of key aspects of mosquito biology, our data on how cycle KO affects mosquito behavior and fitness provides a basis for further work into the pathways that connect the mosquito endogenous clock to its vector competence.


Functional properties of tumor-infiltrating and blood lymphocytes in patients with solid tumors: effects of tumor cells and their supernatants on proliferative responses of lymphocytes.
Tumor-infiltrating lymphocytes (TIL) were obtained from 22 humans with solid tumors. In three cases only, one colon and two lung carcinomas, TIL which contained from 3 to 10% of T cells expressing the interleukin 2 receptor (IL 2R) were obtained, and these proliferated in the presence of exogenous IL 2. In most TIL preparations, however, the T lymphocytes did not express the IL 2R and failed to proliferate in response to IL 2. In contrast, TIL were able to proliferate in response to irradiated allogeneic spleen cells in mixed lymphocyte culture. Proliferative responses of autologous PBL were not inhibited by the addition of TIL. In most tumors, the TIL showed no response or had significantly lower (p less than 0.01) responses to PHA, Con A, and the phorbol ester TPA than did autologous peripheral blood lymphocytes (PBL). A limiting-dilution microculture system which allows clonal growth of every T cell was used to demonstrate decreased responses of the TIL to PHA at a single-cell level. In contrast to normal PBL-T with proliferating frequencies from 0.46 to 1.0, those for T cells in three TIL preparations were zero, 0.005, and 0.01. Normal PBL exposed in vitro to tumor cells or their supernatants lost the ability to respond to mitogens and to clone normally (e.g., proliferating frequency of 0.147 vs 0.863 in control). The TIL isolated from solid tumors resemble normal PBL exposed in vitro to tumor cells or their supernatants in terms of decreased responses to mitogens and poor clonogenicity in the PHA-dependent microculture system. It is possible that tumor cells may inhibit certain functions of the TIL in human solid tumors.


[Prevalence of chronic kidney disease among HIV-infected individuals in Japan--a report from two tertiary hospitals].
The improved survival of subjects with human immunodeficiency virus (HIV) has been accompanied by an increased prevalence of chronic kidney disease (CKD). Epidemic of CKD among those with HIV has not yet been evaluated in multiple tertiary hospitals in Japan. A cross-sectional study was conducted in 2011 at Tokyo Metropolitan Komagome Hospital (TMKH) and Tokyo Medical University Hospital (TMUH). A total of 1482 HIV-infected subjects (1384 men, 98 female, mean age: 44.2 +/- 11.4 years old) were consecutively enrolled in the study. Random urine and blood samples were collected to study prevalence of CKD. CKD was diagnosed as a decrease in glomerular function and/or proteinuria and classified into 5 stages based on National Kidney Foundation guidelines. The estimated glomerular filtration rate based on serum creatinine was calculated using the 3-variable equation, constructed by the Japanese Society of Nephrology. Proteinuria was defined as > or = 1+ on urine dipstick examination. All electronic medical charts were reviewed to determine comorbidities, including hypertension and diabetes mellitus (DM). The proportion of subjects receiving tenofovir disoproxil fumarate (TDF) was investigated. Risk factors for CKD were determined using multivariate logistic regression analysis. The mean CD4 cell count was 487 +/- 216/microL and 80.5% had undetectable HIV-RNA level in the combined cohort. Of the 90.2% of subjects taking antiretroviral agents, 61.5% was using TDF. The prevalence of overall CKD and CKD > or = stage 3 was 12.9% and 6.7%, respectively, both of which were nearly 3-fold higher in the TMKH cohort (p < .0001). Mean age and proportional prevalent hypertension and DM were significantly higher in the TKMH cohort than in the TMUH cohort. Multivariate analysis showed significant CKD to be associated with age > or =50 years (odds ratio [OR], 2.81), hypertension (OR, 3.04), and DM (OR, 2.05). CKD prevalence was 12.9% among combined cohorts, but differed significantly between them. Differences in age distribution and the proportion of comorbidities, including hypertension and DM, are likely involved.


Crystal structure of a SFPQ/PSPC1 heterodimer provides insights into preferential heterodimerization of human DBHS family proteins.
Members of the Drosophila behavior human splicing (DBHS) protein family are nuclear proteins implicated in many layers of nuclear functions, including RNA biogenesis as well as DNA repair. Definitive of the DBHS protein family, the conserved DBHS domain provides a dimerization platform that is critical for the structural integrity and function of these proteins. The three human DBHS proteins, splicing factor proline- and glutamine-rich (SFPQ), paraspeckle component 1 (PSPC1), and non-POU domain-containing octamer-binding protein (NONO), form either homo- or heterodimers; however, the relative affinity and mechanistic details of preferential heterodimerization are yet to be deciphered. Here we report the crystal structure of a SFPQ/PSPC1 heterodimer to 2.3-Å resolution and analyzed the subtle structural differences between the SFPQ/PSPC1 heterodimer and the previously characterized SFPQ homodimer. Analytical ultracentrifugation to estimate the dimerization equilibrium of the SFPQ-containing dimers revealed that the SFPQ-containing dimers dissociate at low micromolar concentrations and that the heterodimers have higher affinities than the homodimer. Moreover, we observed that the apparent dissociation constant for the SFPQ/PSPC1 heterodimer was over 6-fold lower than that of the SFPQ/NONO heterodimer. We propose that these differences in dimerization affinity may represent a potential mechanism by which PSPC1 at a lower relative cellular abundance can outcompete NONO to heterodimerize with SFPQ.


A technique for kinematic modeling of anatomical joints.
This paper describes a general technique for fitting a spatial kinematic model to an in-vivo anatomical joint under typical physiological loading conditions. The method employs a nonlinear least squares algorithm to minimize the aggregate deviation between postulated model motion and experimentally measured anatomical joint motion over multiple joint positions. Estimation of the parameters of a universal joint with skew-oblique revolutes to best reproduce wrist motion was used as an example. Experimental motion data from the right wrists of five subjects were analyzed. The technique performed very well and produced repeatable results consistent with previous biomechanical wrist findings.


Insulin-like growth factor-I and its binding protein-3 in serum: are they good screening properties for the diagnosis of growth hormone deficiency?
Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 are simply-determined screening analytes if growth hormone deficiency is suspected. The analysis of growth hormone secretion using standardised stimulation tests and secretion profiles is complicated and expensive in comparison. In retrospect, we have examined the value of insulin-like growth factor-I and its binding protein-3 for the diagnostic clarification of patients with short stature (n = 117). In 39/117 patients growth hormone secretion was investigated as ward patients. Growth hormone deficiency was diagnosed in 10 patients, for 16 patients the diagnosis was neurosecretory dysfunction. For all patients (n = 7) with lowered insulin-like growth factor binding protein-3 and insulin-like growth factor-I values (insulin-like growth factor binding protein-3 < 5th percentile, insulin-like growth factor-I < 10th percentile) a growth hormone disorder was proven. Conversely, however, only 3/10 patients with classical growth hormone deficiency (n = 3) showed a lowering of both analytes. 8/10 patients with classical growth hormone deficiency and 8/16 patients with neurosecretory dysfunction had at least one lowered value. Two patients showed normal values for insulin-like growth factor-I and insulin-like growth factor binding protein-3 despite biochemically proven growth hormone deficiency. The combined determination of insulin-like growth factor-I and insulin-like growth factor binding protein-3 can provide valuable help during preliminary diagnosis of patients of short stature, indicating a disturbance of the growth hormone secretion if the values are lowered. Normal values do not, however, exclude the possibility of a growth hormone deficiency. Inpatient endocrinological testing is indispensible if growth hormone deficiency is suspected.


From Short Electrospun Nanofibers to Ultralight Aerogels with Tunable Pore Structure.
Nanofiber production by electrospinning has made great progress over the past two decades. Recently the research area was revolutionized by a novel post-processing approach. By cutting the endless and intertwined nanofibers into short pieces, it is now possible to reassemble them into interconnected 3D structures. Such highly porous structures are built from dispersed short nanofibers by freeze-casting. This solid templating process controls the structures' ultimate properties and architecture in terms of primary and secondary pores below 5 μm and between 10 and 300 μm, respectively. The objective of this review is to provide insight into this young field of research, in particular highlighting the processing steps, materials and current applications, from scaffolds for tissue engineering, acoustics, sensors and catalyst supports to filtration.


The role of hyperuricemia and gout in kidney and cardiovascular disease.
Elevated serum urate levels are recognized as leading to gouty arthritis, tophi formation, and uric acid kidney stones. While serum urate elevations have long been associated with renal disease, they are not usually considered to have a causal role in kidney dysfunction. However, recent epidemiologic studies have identified serum urate elevations as an independent risk factor for chronic kidney disease. Hyperuricemia has also been found to be an independent risk factor for cardiovascular disease and hypertension. An animal model of mild hyperuricemia has shed new light on a potential mechanism of microvascular changes leading to endothelial dysfunction, a precursor to both coronary artery disease and hypertension. Additional animal studies and recent epidemiologic findings have provided further evidence that soluble urate is a risk factor for nonarticular disease.


Translationally controlled tumor protein is a novel heat shock protein with chaperone-like activity.
Translationally controlled tumor protein (TCTP) is often designated as a stress-related protein because of its highly regulated expression in stress conditions. Following a thermal shock, TCTP expression is highly upregulated in a variety of cells. However, at present it is not known whether this upregulation has any cell protective function similar to other heat shock proteins. In this study human TCTP (HuTCTP) and a TCTP homolog (SmTCTP) from Schistosoma mansoni were evaluated for heat shock protein-like function and molecular chaperone activity. Our results show that similar to other molecular chaperones, both human and parasite TCTPs can bind to a variety of denatured proteins and protect them from the harmful effects of thermal shock. An important observation was the ability of both HuTCTP and SmTCTP to bind to native protein and protect them from thermal denaturation. Over expression of TCTP in bacterial cells protected them from heat shock-induced death. These findings suggest that TCTP may belong to a novel small molecular weight heat shock protein.


Chromatin-remodelling proteins of the pea aphid, Acyrthosiphon pisum (Harris).
Aphids display extraordinary developmental plasticity in response to environmental cues. These differential responses to environmental changes may be due in part to changes in gene expression patterns. To understand the molecular basis for aphid developmental plasticity, we attempted to identify the chromatin-remodelling machinery in the recently sequenced pea aphid genome. We find that the pea aphid possesses a complement of metazoan histone modifying enzymes with greater gene family diversity than that seen in a number of other arthropods. Several genes appear to have undergone recent duplication and divergence, potentially enabling greater combinatorial diversity among the chromatin-remodelling complexes. The abundant aphid chromatin modifying enzymes may facilitate the phenotypic plasticity necessary to maintain the complex life cycle of the aphid.


Nanostructured fumarate copolymer-chitosan crosslinked scaffold: An in vitro osteochondrogenesis regeneration study.
In the tissue engineering field, the design of the scaffold inspired on the natural occurring tissue is of vital importance. Ideally, the scaffold surface must promote cell growth and differentiation, while promote angiogenesis in the in vivo implant of the scaffold. On the other hand, the material selection must be biocompatible and the degradation times should meet tissue reparation times. In the present work, we developed a nanofibrous scaffold based on chitosan crosslinked with diisopropylfumarate-vinyl acetate copolymer using anodized aluminum oxide (AAO) templates. We have previously demonstrated its biocompatibility properties with low cytotoxicity and proper degradation times. Now, we extended our studies to demonstrate that it can be successfully nanostructured using the AAO templates methodology, obtaining a nanorod-like scaffold with a diameter comparable to those of collagen fibers of the bone matrix (170 and 300 nm). The nanorods obtained presented a very homogeneous pattern in diameter and length, and supports cell attachment and growth. We also found that both osteoblastic and chondroblastic matrix production were promoted on bone marrow progenitor cells and primary condrocytes growing on the scaffolds, respectively. In addition, the nanostructured scaffold presented no cytotoxicity as it was evaluated using a model of macrophages on culture. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 570-579, 2018.