Complete Ring Artifacts Reduction Procedure for Lab-Based X-ray Nano CT Systems.
In this article, we introduce a new ring artifacts reduction procedure that combines several ideas from existing methods into one complex and robust approach with a goal to overcome their individual weaknesses and limitations. The procedure differentiates two types of ring artifacts according to their cause and character in computed tomography (CT) data. Each type is then addressed separately in the sinogram domain. The novel iterative schemes based on relative total variations (RTV) were integrated to detect the artifacts. The correction process uses the image inpainting, and the intensity deviations smoothing method. The procedure was implemented in scope of lab-based X-ray nano CT with detection systems based on charge-coupled device (CCD) and scientific complementary metal-oxide-semiconductor (sCMOS) technologies. The procedure was then further tested and optimized on the simulated data and the real CT data of selected samples with different compositions. The performance of the procedure was quantitatively evaluated in terms of the artifacts' detection accuracy, the comparison with existing methods, and the ability to preserve spatial resolution. The results show a high efficiency of ring removal and the preservation of the original sample's structure.


The impact of chronic orofacial pain on health-related quality of life.
Background and aims Health-related quality of life (HRQoL) assessments have been widely used in pain medicine as they are able to reflect the subjective and multidimensional nature of chronic pain. Studies have shown a consistent impairment in HRQoL in different chronic pain conditions. However, it is not known whether HRQoL is impaired in chronic orofacial pain (OFP). The generic 15D HRQoL instrument has been shown to fare as well as or better than other generic HRQoL instruments in the study of chronic pain. The aim was to investigate HRQoL in patients with chronic OFP using the generic 15D HRQoL instrument. The validity of the instrument was tested by studying the association of the 15D data with pain interference. Methods One hundred fifty-one patients (mean age 50 years, SD 15 years, 119 females) were recruited from three tertiary facial pain clinics. HRQoL data of the participants were contrasted with that of an age- and gender- standardized sample of general population by comparing the mean 15D scores and profiles. The data for the general population came from the National Health 2011 Survey representing Finnish population aged 18 years and older. Pain interference was assessed using Brief Pain Inventory. Based on pain interference distribution the participants were divided into tertiles. Statistical comparison between patient and population HRQoL values were performed using Monte-Carlo-type simulations. Statistical significance for the hypothesis of linearity was evaluated by using generalized linear models. Results The mean 15D score of OFP patients (0.824, SD 0.113) was statistically significantly lower than that of the age- and gender-standardized general population (0.929, SD 0.019) (p < 0.001). The difference between the patients and the general population was also clinically important, i.e. over the minimum clinically important difference in the 15D score. All mean 15D dimension values were significantly lower compared with the general population values (p < 0.001 for all dimensions). The largest differences were seen in the dimensions of discomfort and symptoms (0.418, SD 0.222 vs. 0.816, SD 0.027), sleeping (0.693, SD 0.258 vs. 0.838, SD 0.029), and vitality (0.702, SD 0.221 vs. 0.884 SD 0.026). There was a statistically significant linear decrease in the 15D dimension values (p < 0.001) with increasing pain interference. The greatest differences were found on the dimensions of discomfort and symptoms, sleeping and vitality. Conclusions HRQoL is significantly impaired in patients with chronic OFP. A decrease in the 15D dimension values with increasing pain interference indicated convergent validity between 15D and pain interference. Implications The findings suggest that 15D is an appropriate instrument for use in the assessment of HRQoL in OFP patients. By showing the usefulness of the 15D, the present study may encourage further use of generic HRQoL assessments in the study of chronic OFP, and contribute e.g. to the implementation of HRQoL as one of the core outcome measures in future treatment studies on chronic OFP.


[Knockdown of Larp4b in Lin(-) cells does not affect the colony forming ability of mouse hematopoietic cells].
Larp4b is a member of the LARP family, which can interact with RNA and generally stimulate the translation of mRNA. Abnormal expression of Larp4b can be found in leukemia patients in our previous study. This study was purposed to detect the relative expression of Larp4b mRNA in different subpopulations of mouse hematopoietic cells, to construct lentivirus vector containing shLarp4b targeting mouse gene Larp4b and to explore its effects on mouse Lin(-) cells infected with shLarp4b by lentivirus. SF-LV-shLarP4b-EGFP and control vectors were constructed and two-plasmid lentivirus packing system was used to transfect 293T cells. After 48 h and 72 h, lentivirus SF-LV-shLarp4b-EGFP was harvested and was used to infect Lin(-) cells. After 48 h, EGFP(+) cells was sorted by flow cytometry (FCM). Meanwhile, semi-quantitative real time-PCR, AnnexinV-PE/7-AAD staining, PI staining and colony forming cell assay (CFC) were performed to determine the expression of Larp4b and its effect on the proliferation of hematopoietic progenitor cells. The results showed that Larp4b was highly expressed in myeloid cells. SF-LV-shLarp4b-EGFP was successfully constructed according to the restriction endonuclease digestion assay. RT-PCR confirmed that Larp4b was efficiently knockdown in mouse Lin(-) cells. The low expression of Larp4b did not affect the colony forming number, the apoptosis and cell cycle of Lin(-) cells. It is concluded that knockdown of Larp4b in mouse Lin(-) cells do not contribute to the colony forming ability and the growth of Lin(-) cells in vitro. This useful knockdown system will be used to study in vivo Larp4b in future.


Preparation of alpha-emitting 213Bi-labeled antibody constructs for clinical use.
Preclinical evaluation of alpha particle-emitting 213Bi-labeled antibody constructs have demonstrated the specificity and potency of these agents in a variety of cancer systems. The transition of a 213Bi-radiolabeled antibody from a preclinical construct to a clinical drug represented a difficult task that involved development of reliable and validated methods to provide multiple MBq quantities of a pure, immunoreactive agent that met pharmaceutical standards to treat patients. The methods used for the preparation of (213Bi)CHX-A-diethylenetriamine pentaacetic acid (DTPA)-HuM195, an alpha particle-emitting anti-CD33 antibody construct for therapy of myeloid leukemias, is used as a specific example. This article describes methods for reagent purification, drug labeling, radioprotection and chromatographic purification. Quality of the drug is evaluated using radiochemical incorporation and purity assays with instant thin-layer chromatography (ITLC) and high-performance liquid chromatography (HPLC), determination of cell-based antibody total immunereactivity, small animal safety, pyrogen level, sterility and radionuclidic purity. Sixty-seven doses were prepared. Individual doses ranged from 148 to 814 MBq. Specific activities ranged from 329 to 766 MBq/mg. The radiolabeling efficiency (median +/- SD) of CHX-A-DTPA-HuM195 with 213Bi was 81% +/- 9% (n = 67) after 9 min. The construct was purified by size-exclusion chromatography and was found to be 99% +/- 2% pure (n = 67) by either ITLC or HPLC methods. The immunoreactivity of (213Bi)CHX-A-DTPA-HuM195 was 89% +/- 9% (n = 44) and was independent of the specific activity. The formulated pharmaceutical was found to contain < or =4 +/- 1 EU/mL pyrogens (n = 66); all samples examined were sterile. An 225Ac radionuclidic impurity was present at a level of 0.04 +/- 0.03 x 10(-6)/mL (n = 10) in a product volume of 7.4 +/- 0.5 mL (n = 67). Each of the 67 doses was injected intravenously into patients without complication as part of a phase I clinical trial. These data show that 213Bi-labeled antibody constructs can be prepared and administered safely to humans at a wide range of therapeutic levels.


Associations of symptoms of anxiety disorders and self-reported behavior problems in normal children.
61 children, aged between 14 and 18 years, completed the Screen for Child Anxiety Related Emotional Disorders, a scale of anxiety disorders symptoms, and the Youth Self-report, a measure of internalizing, i.e., emotional, and externalizing, i.e., behavioral, problems. Analysis showed that, with the exception of the Social Phobia and the Specific Phobia subscales, Screen total and subscale scores were significantly related to Internalizing problems (rs between .40 and .77). Thus, the more frequently children reported Anxiety Disorder symptoms, the more often they reported emotional problems. Furthermore, in particular, anxious-depressed problems as measured by the Youth Self-report were significantly associated with scores on Screen scales. These results further support the concurrent validity of the Screen.


Substrate recognition by mitochondrial processing peptidase toward the malate dehydrogenase precursor.
Mitochondrial processing peptidase (MPP) cleaves the extension peptides of precursor proteins newly imported into the mitochondria. Using synthetic oligopeptides modeled on the extension peptide of malate dehydrogenase, the critical elements of the substrate for the processing of MPP were determined [Niidome, T., Kitada, S., Shimokata, K., Ogishima, T., and Ito, A. (1994) J. Biol. Chem. 269, 24719-24722; Ogishima, T., Niidome, T., Shimokata, K., Kitada, S., and Ito, A. (1995) ibid. 270, 30322-30326]. In the present study, we constructed mutant precursors and compared the processing reaction with that of the peptide substrates to confirm the validity of use of peptide substrates. In both cases, the arginine residue presents at a proximal (-2) position relative to the processing site proved to be important for the processing. The distal arginine residue at position 7 was replaceable with alanine with no significant loss in cleavage efficiency if the precursor protein contained two consecutive arginine residues at a proximal position, although the arginine residue at a position 7 was indispensable in the model peptide. The proline residue, lying between the distal and proximal arginine residues, which is assumed to break a continuous alpha-helix region in the extension peptide, was needed for the processing. This peptidase has a preference for aromatic amino acids at the P1' site. These results were essentially the same as those obtained with model peptides except for the role of the distal arginine. We also found that amino acids at P2' and P3' sites had some effects on the processing. Thus we concluded that an effective combination of model peptides with precursor proteins is needed for the studies on MPP responsible substrate-recognition mechanisms.


Fcgamma receptors are crucial for the expression of acquired resistance to virulent Salmonella enterica serovar Typhimurium in vivo but are not required for the induction of humoral or T-cell-mediated immunity.
Antibodies play an important role in immunity to Salmonella enterica. Here we evaluated the requirement for Fcgamma receptors in host resistance to S. enterica using an in vivo model of systemic infection. We show that mice lacking FcgammaRI, II and III can control and clear a primary infection with S. enterica micro-organisms of low virulence, but are impaired in the expression of vaccine-induced acquired immunity to oral challenge with virulent bacteria. We also show that, in vivo, FcgammaRI, II, III(-/-) mice were able to mount efficient T-helper 1 type T-cell responses and antibody responses specific for S. enterica. The work indicates that targeting S. enterica to FcgammaR is needed for the expression of vaccine-induced acquired immunity, but is not essential for the engenderment of T- and B-cell immunity to the bacterium in vivo.


Appendectomy and Risk of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: A Nationwide Population-based Cohort Study.
The aim of this study was to examine the association between appendectomy and advanced colorectal neoplasia (aCRN) in patients with inflammatory bowel disease (IBD). Inflammatory bowel disease patients diagnosed in Denmark in the period 1977 to 2017 were identified from the Danish National Patient Registry. Inflammatory bowel disease patients who underwent appendectomy were matched with up to 10 IBD patients without appendectomy and followed until aCRN, death, or emigration. Absolute risks of aCRN were calculated, treating death and bowel resections as competing risks. Stratified Cox regression was used to calculate adjusted hazard ratios (aHRs) of aCRN, comparing IBD patients with appendectomy to IBD patients without appendectomy. We identified 3789 IBD patients with appendectomy and 37 676 IBD patients without appendectomy. A total of 573 patients (1.4%) developed aCRN, with an absolute risk of aCRN at 20 years of 4.9% (95% confidence interval [CI], 2.9%-7.7%) for ulcerative colitis (UC) patients with appendectomy after UC diagnosis compared with 2.8% (95% CI, 2.3%-3.3%) for UC patients without appendectomy. Appendectomy after UC was associated with an increased rate of aCRN 5 to 10 years (aHR, 2.5; 95% CI, 1.1-5.5) and 10 to 20 years after appendectomy (aHR, 2.3; 95% CI, 1.0-5.5). Appendectomy prior to UC diagnosis was not associated with an increased rate of aCRN, and Crohn's disease was not associated with the rate of aCRN, regardless of timing or histological diagnosis of the appendix specimen. Although appendectomy may have a positive effect on the clinical course of UC, our study suggests that this may come at the expense of a higher risk of aCRN.


Investigation of Copy Number Variation by arrayCGH in Turkish Children and Adolescents Diagnosed with Autism Spectrum Disorders.
The development of whole-genome screening methodologies for the detection of copy number variations (CNVs), such as array-based comparative genomic hybridization (aCHG), provides a much higher resolution than karyotyping leading to the identification of novel microdeletion and microduplication syndromes often associated with an autism spectrum disease (ASD) phenotype. The aim of the study was to determine CNVs of patients with ASD by using array-based comparative genomic hybridization. Fifty-three patients diagnosed with ASD between 20.01.2014 and 14.01.2015 were included in the study. Chromosome analysis of the patients was performed from peripheral blood cultures and analysed as normal. All patients were evaluated with P064C1 and P096A2 MLPA probes in terms of 16 mental retardation related syndromes. For aCGH method, SurePrint G3 Human microarrays 8x60K were used with genomic DNA isolated from peripheral blood. According to results of 53 patients who were included in and performed with arrayCGH, 8 (15%) patients had CNVs classified as pathogenic or variant of unknown significance (VOUS) in the study. We detected a pathogenic NRXN1 gene partial CNV deletion (2p16.3) in two patients. Also we identified a 900 kb duplication of 4p15.31 including SLIT2 gene, and a 245 kb duplication of 15q11.2 including PWRN1 gene in one patient. Our other findings are considered to be a variant of unknown significance (VOUS). The results of the study support the literature knowledge, where the copy number variations that cannot be detected with conventional cytogenetics methods in terms of size may happen in patients with ASD.


Philadelphia negative BCR-ABL positive chronic myeloid leukemia mimicking juvenile chronic myeloid leukemia in a 2-year-old child.
We present the case of a two-year-old child with an atypical presentation of chronic myeloid leukemia. At diagnosis, he showed clinical and biological features of juvenile chronic myeloid leukemia (CML). However, eosinophilia was observed in blood and bone marrow. The bone marrow karyotype did not demonstrate the Philadelphia chromosome but BCR-ABL rearrangement was shown to be present by reverse transcriptase polymerase chain reaction (RT-PCR) analysis and confirmed by fluorescent in situ hybridization (FISH) analysis. Discussion centres on the differentiation between juvenile CML and childhood chronic myelogenous Leukemia and the importance of carrying out RT PCR for all juvenile CML cases.


Ethinylestradiol/cyproterone acetate in polycystic ovary syndrome: lipid and carbohydrate changes.
Ethinylestradiol (EE) combined with the antiandrogenic progestin cyproterone acetate (CPA) is a possible treatment in polycystic ovary syndrome (PCOS). We investigated the impact of EE/CPA on lipid and carbohydrate metabolism in women with PCOS,who were otherwise healthy. The 31 women were separated into two groups paired by body mass index (BMI): Group A (control, n = 15) were cycled with 10 mg medroxyprogesterone acetate (MPA) x 10 days (Provera, Pharmacia & Upjohn) every month for 3 months; Group B (n = 16) were treated with 35 microg EE/2 mg CPA (Diane 35, Schering) for 3 months. Metabolic and hormonal conditions were similar in both groups. Group A showed no change in any hormone or metabolic parameter. Group B showed a significant decrease in free androgen index (-81%) and increase in sex hormone binding globulin (+ 639%), a decrease in low density lipoprotein cholesterol (-14%) and total cholesterol/high density lipoprotein (HDL) cholesterol index (-19%), and increases in HDL cholesterol (+ 23%) and triglycerides (+ 82%) (p < 0.001). Fasting insulin increased in 18%, the glucose/insulin index worsened in 8%, and the plasma glucose disappearance worsened in 12%, with no statistical significance (p= 0.092, p=0.308 and p= 0.237, respectively). Treatment of PCOS with EE/CPA induces important favorable changes regarding hormone parameters associated with hyperandrogenism, significant favorable changes in lipid profile except for triglyceride increase, and no significant change in carbohydrate metabolism (measured by fasting insulin, glucose/insulin index and plasma glucose disappearance). MPA cycling does not change any of these parameters.


Assessing the ability of white-rot fungi to tolerate polychlorinated biphenyls using predictive mycology.
The aim of the present study was to assess the ability of different white-rot fungi to tolerate polychlorinated biphenyls (PCBs) using predictive mycology, by relating fungal growth inhibition to ligninolityc enzyme secretion. Fungal strains were grown in the presence of PCBs in solid media and their radial growth values were modelled through the Dantigny-logistic like function in order to estimate the time required by the fungal colonies to attain half their maximum diameter. The principal component analysis (PCA) revealed an inverse correlation between strain tolerance to PCBs and the laccase secretion over time, being laccase production closely associated with fungal growth capacity. Finally, a PCA was run to regroup and split between resistant and sensitive fungi. Simultaneously, a function associated with a model predicting the tolerance to PCBs was developed. Some of the assayed isolates showed a promising capacity to be applied in PCB bioremediation. Abbreviations: Polychlorinated biphenyls (PCBs), white-rot fungi (WRF).


Associations between stool micro-transcriptome, gut microbiota, and infant growth.
Rapid infant growth increases the risk for adult obesity. The gut microbiome is associated with early weight status; however, no study has examined how interactions between microbial and host ribonucleic acid (RNA) expression influence infant growth. We hypothesized that dynamics in infant stool micro-ribonucleic acids (miRNAs) would be associated with both microbial activity and infant growth via putative metabolic targets. Stool was collected twice from 30 full-term infants, at 1 month and again between 6 and 12 months. Stool RNA were measured with high-throughput sequencing and aligned to human and microbial databases. Infant growth was measured by weight-for-length z-score at birth and 12 months. Increased RNA transcriptional activity of Clostridia (R = 0.55; Adj p = 3.7E-2) and Burkholderia (R = -0.820, Adj p = 2.62E-3) were associated with infant growth. Of the 25 human RNAs associated with growth, 16 were miRNAs. The miRNAs demonstrated significant target enrichment (Adj p < 0.05) for four metabolic pathways. There were four associations between growth-related miRNAs and growth-related phyla. We have shown that longitudinal trends in gut microbiota activity and human miRNA levels are associated with infant growth and the metabolic targets of miRNAs suggest these molecules may regulate the biosynthetic landscape of the gut and influence microbial activity.


Increased levels of surgical adhesions in TGFbeta1 heterozygous mice.
Adhesion formation and fibrosis represent a major complication of surgical intervention. Reducing the morbidity associated with adhesions requires an understanding of the mechanisms underlying their formation. Since increased levels of transforming growth factor-beta1 (TGFbeta1) have been associated with inflammation and adhesion production, we investigated the requirement of TGFbeta1 in peritoneal adhesion formation utilizing mice carrying a targeted disruption of the TGFbeta1 allele. Mice that were either wild-type (+/+), containing two normal alleles of TGFbeta1, or heterozygous (+/-) for the TGFbeta1 null allele received injections of magnesium silicate (talc), and the extent of abdominal adhesions was determined utilizing a standard grading score. Wild-type (+/+) animals had at least twofold more TGFbeta1 protein in peritoneal fluids at 2 h posttrauma compared to heterozygous (+/-) mice (727 vs. 243 pg TGFbeta1/mg protein by enzyme-linked immunosorbent assay (ELISA) in +/+ and +/- mice, respectively), and had significantly less scar and adhesion formation (p < .05) at 7 days posttrauma (1.8 +/- 0.8 vs. 3.4 +/- 1.4, graded from 0 to 5, in +/+ and +/- mice, respectively). These results demonstrate that haploid insufficiency in TGFbeta1 levels can lead to inappropriate matrix and adhesion production during inflammation, and together with previous studies suggest that any perturbation of normal TGFbeta1 levels can modulate the injury response that regulates the extent of adhesion formation.


Non-catalytic motor domains enable processive movement and functional diversification of the kinesin-14 Kar3.
Motor proteins of the conserved kinesin-14 family have important roles in mitotic spindle organization and chromosome segregation. Previous studies have indicated that kinesin-14 motors are non-processive enzymes, working in the context of multi-motor ensembles that collectively organize microtubule networks. In this study, we show that the yeast kinesin-14 Kar3 generates processive movement as a heterodimer with the non-motor proteins Cik1 or Vik1. By analyzing the single-molecule properties of engineered motors, we demonstrate that the non-catalytic domain has a key role in the motility mechanism by acting as a 'foothold' that allows Kar3 to bias translocation towards the minus end. This mechanism rivals the speed and run length of conventional motors, can support transport of the Ndc80 complex in vitro and is critical for Kar3 function in vivo. Our findings provide an example for a non-conventional translocation mechanism and can explain how Kar3 substitutes for key functions of Dynein in the yeast nucleus.


Cyanobacteria - insidious foe of the skin?
Cyanobacteria are ancient photosynthetic microorganisms that shaped today's atmosphere. Anthropocentric and irresponsible activities are changing the atmosphere which favor the frequent occurrence and mass development of cyanobacteria. Extensive cyanobacterial blooming causes numerous problems, including negative effects on human skin. Climate change, depletion of ozone layer, and the increased ultraviolet radiation also affect the skin and lead to more frequent occurrence of skin cancer. This research, for the first time, attempts to establish a connection between these two factors, or whether, in addition to ultraviolet radiation, cyanobacteria can influence the incidence of melanoma. With this objective in mind, an epidemiological investigation was conducted in Vojvodina, Serbia. It was observed that the incidence of melanoma was higher in municipalities where water bodies used for recreation, irrigation and fishing are blooming; however, results could be considered as inconclusive, because of the restrictions in the cancer database. Nevertheless, results gathered from the reviewed literature support the hypothesis that cyanobacteria could be a new potential risk factor for melanoma, while climate change could be a catalyst that converts these potential risk factors into cofactors, which act synergistically with the main risk factor - ultraviolet radiation - and induce an increase of melanoma incidence.


LUBAC determines chemotherapy resistance in squamous cell lung cancer.
Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10+, but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-κB signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-κB activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.


The effects of dyphylline [7-(2,3-dihydroxypropyl) theophylline] on the toxicity of hycanthone on the frog's heart.
The effects of the topical application of Dyphylline in concentrations of 1.0 mg/1.0 ml and 10 mg/1.0 ml Ringer's solution and 25 mg/1.0 ml, 0.065% NaCl solution (the content of ampoules in clinical use) were investigated on frog's heart in situ. Dyphylline in all of the above concentrations had a stimulatory effect on the frog's heart. Hycanthone methanesulphonate in concentration of 1.0 ml/1.0 ml when topically applied to the frog's heart had a depressant effect on both of the contractility and rhythmicity. The depressant effects of Hycanthone in concentration of 1:1 were compared before and after the topical application of Dyphylline in the above mentioned concentrations. It was found that Dyphylline in concentration of 1.0 mg/1.0 ml could partially antagonize the depressant effect of Hycanthone on the heart rate but not on the force of contraction. Dyphylline in concentration of 10 mg/1.0 ml could partially antagonize the depressant effects of Hycanthone on both of the heart rate and the force of contraction. Dyphylline in concentration of 25 mg/1.0 ml could completely antagonize the depressant effects of hycanthone on both of the heart rate and the force of contraction.


Exsolution in clinoamphiboles.
Ten amphibole specimens from a variety of metamorphic rocks such as talc schists, eclogites, and metamorphosed iron formations contain lamellae of a second amphibole oriented parallel to ([unknown]101) or (100), or both, of the host. Tremolites, actinolites, and hornblendes commonly have lamellae of a calcium-poor clinoamphibole with P2(1)/m space-group symmetry, or lamellae of cummingtonite with C2/m space-group symmetry. Likewise cummingtonites and P2(1)/m clinoamphiboles commonly contain lamellae of calcium-rich C2/m amphiboles such as tremolite. Results of x-ray diffraction, electron-probe, and microscope studies indicate that most lamellae result from unmixing of a homogeneous amphibole. The P2(1)/m clinoamphibole is analogous to the clinopyroxene pigeonite in agreement with the results of M. G. Bown.


Mec1/Tel1-dependent phosphorylation of Slx4 stimulates Rad1-Rad10-dependent cleavage of non-homologous DNA tails.
Budding yeast Slx4 interacts with the Rad1-Rad10 endonuclease that is involved in nucleotide excision repair (NER), homologous recombination (HR) and single-strand annealing (SSA). We previously showed that Slx4 is dispensable for NER but is essential for SSA. Slx4 is phosphorylated by the Mec1 and Tel1 kinases after DNA damage on at least six Ser/Thr residues, and mutation of all six residues to Ala reduces the efficiency of SSA. In this study, we further investigated the role of Slx4 phosphorylation in SSA, specifically in regulating cleavage of 3' non-homologous (NH) DNA tails by Rad1-Rad10 during SSA and HR. Slx4 became phosphorylated after induction of a single double-strand break (DSB) during SSA and dephosphorylation coincided approximately with completion of repair. Slx4 is recruited to 3' NH tails during DSB repair, but this does not require phosphorylation of Slx4. However, we identified a specific damage-dependent Mec1/Tel1 site of Slx4 phosphorylation, Thr 113, that is required for efficient cleavage of NH tails by Rad1-Rad10. Consistent with these data, deletion of both Mec1 and Tel1 severely reduces the efficiency of NH DNA tail cleavage during HR. These data show that phosphorylation of Slx4 by Mec1 and Tel1 plays an important role in facilitating NH DNA tail cleavage during HR.


[Cocaine and psychiatric comorbidity].
A bibliographic review of psychiatric comorbidity in cocaine users was done in last ten years (Medline, IME, HealthSTAR, Cinahl). It was valued the prevalence of psychiatric disorders in cocaine users and that of consume of this substance in-patients with psychiatric disorders. Their relationship, influence over the evolution and consequences on the treatment were studied as well. Epidemiologic studies showed an increase of affective disorders, anxiety disorders and personality disorders in cocaine users and an increase of consume of this substance in those patients who are presented psychosis and anxiety disorders. The relationship of these disorders was analysed, as well as the influence oh the comorbidity in the evolution and repercussion on the treatment.


Central nervous system involvement in ALK-rearranged NSCLC: promising strategies to overcome crizotinib resistance.
ALK rearranged Non Small Cell Lung Cancers (NSCLCs) represent a distinct subgroup of patients with peculiar clinic-pathological features. These patients exhibit dramatic responses when treated with the ALK tyrosine kinase inhibitor Crizotinib, albeit Central Nervous System (CNS) activity is much less impressive than that observed against extracranial lesions. CNS involvement has become increasingly observed in these patients, given their prolonged survival. Several novel generation ALK inhibitors have been developing to increase CNS penetration and to provide more complete ALK inhibition.. The CNS activity of Crizotinib and novel generation ALK inhibitors will be summarized in this review, evaluating the strengths and weaknesses of the therapeutic strategies developed to date in this specific subgroup of NSCLCs with a look towards the future. Expert commentary: In the next few years, the results of ongoing comparative head-to-head trials will provide the definitive conclusions on the optimal treatment sequence in ALK-rearranged NSCLCs. Moreover, ongoing clinical trials with novel-generation ALK inhibitors will produce more evidences on the best approach in the growing number of ALK-positive NSCLCs with CNS involvement.


Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets.
High rates of vancomycin failure in methicillin-resistant Staphylococcus aureus (MRSA) infections have been increasingly reported over time. The primary objective of our study was to determine the impact of vancomycin exposure and outcomes in patients with MRSA bacteremia initially treated with vancomycin. This was a single-center retrospective analysis of 320 patients with documented MRSA bacteremia initially treated with vancomycin from January 2005 through April 2010. Two methods of susceptibility, Etest and broth microdilution, were performed for all isolates to determine the correlation of susceptibility testing to patient outcomes. Among a cohort of 320 patients, more than half (52.5%) experienced vancomycin failure. Independent predictors of vancomycin failure in logistic regression included infective endocarditis (adjusted odds ratio [AOR], 4.55; 95% confidence interval [CI], 2.26-9.15), nosocomial-acquired infection (AOR, 2.19; 95% CI, 1.21-3.97), initial vancomycin trough <15 mg/L (AOR, 2.00; 95% CI, 1.25-3.22), and vancomycin minimum inhibitory concentration (MIC) >1 mg/L by Etest (AOR, 1.52; 95% CI, 1.09-2.49). With use of Classification and Regression Tree (CART) analysis, patients with vancomycin area under the curve at 24 h (AUC(24h)) to MIC ratios <421 were found to have significantly higher rates of failure, compared with patients with AUC(24h) to MIC ratios >421 (61.2% vs 48.6%; P = .038). In light of the high failure rates associated with this antimicrobial, optimizing the pharmacokinetic/pharmacodynamic properties of vancomycin by targeting higher trough values of 15-20 mg/L and AUC(24h)/MIC ratios ≥400 in selected patients should be considered.


Total Osseous Calcification of the Prostate Gland.
Prostatic calculi are commonly seen in older men as their incidence increases with age. They are associated with prostate hypertrophy, chronic inflammation of the gland, prostate cancer, and rarely with other pathological conditions such as granulomatous diseases. Although typical small in size, they can seldom become giant and replace the entire prostate gland with only few cases reported in literature. We present one such rare case of a young male who presented to the emergency department with clinical manifestations of sepsis and no relevant past medical history. The patient was ultimately treated with open simple retropubic prostatectomy as a surgical stone extraction method.


False belief and sentence complement performance in children with specific language impairment.
Children with specific language impairment (SLI) have language abilities not commensurate with other cognitive abilities. This pattern makes the SLI population of interest when investigating the relationship between language and theory of mind. One view regarding this relationship is that theory of mind develops independently of language, but certain language skills are required to meet the demands of tasks used to measure theory of mind, such as false belief. Another view is that language development facilitates theory of mind development, and specifically, that mastery of sentence complement structures is necessary for false belief. The study asked (1) if children with SLI can succeed on false belief, despite their language deficits, when the linguistic demands of the false belief task are low, and (2) if performance on sentence complement structures predicts false belief performance. Fifteen children with SLI, 15 children matched for age and 15 children matched for language comprehension level participated in a false belief task with four conditions of differing linguistic complexity, and a test of sentence complementation understanding. Spontaneous production of sentence complements was also measured. Group differences for false belief and sentence complementation, and condition differences for false belief, were tested non-parametrically. Partial correlation analysis, log-linear analysis, and Wilcoxon-Mann-Whitney tests were used to explore relationships among the complementation and false belief measures for all children and for each group. Children with SLI performed similarly to age-matched peers on false belief when linguistic complexity of the task was low, and performed more poorly than age-matched peers on understanding of sentence complements. For all children, sentence complement performance was correlated with false belief (controlling for age), and those who performed well on sentence complements had higher mean rates of false belief success. Log-linear analysis showed the sentence complement-false belief relationship to hold for a condition with relatively low linguistic demands. The study provides evidence that children with SLI can perform at age-appropriate levels when false belief tasks are less demanding, and that mastery of sentence complementation is a predictor of false belief ability.


Intensify3D: Normalizing signal intensity in large heterogenic image stacks.
Three-dimensional structures in biological systems are routinely evaluated using large image stacks acquired from fluorescence microscopy; however, analysis of such data is muddled by variability in the signal across and between samples. Here, we present Intensify3D: a user-guided normalization algorithm tailored for overcoming common heterogeneities in large image stacks. We demonstrate the use of Intensify3D for analyzing cholinergic interneurons of adult murine brains in 2-Photon and Light-Sheet fluorescence microscopy, as well as of mammary gland and heart tissues. Beyond enhancement in 3D visualization in all samples tested, in 2-Photon in vivo images, this tool corrected errors in feature extraction of cortical interneurons; and in Light-Sheet microscopy, it enabled identification of individual cortical barrel fields and quantification of somata in cleared adult brains. Furthermore, Intensify3D enhanced the ability to separate signal from noise. Overall, the universal applicability of our method can facilitate detection and quantification of 3D structures and may add value to a wide range of imaging experiments.


Drug-delivering nerve conduit improves regeneration in a critical-sized gap.
Autologous nerve grafts are the current "gold standard" for repairing large nerve gaps. However, they cause morbidity at the donor nerve site and only a limited amount of nerve can be harvested. Nerve conduits are a promising alternative to autografts and can act as guidance cues for the regenerating axons, without the need to harvest donor nerve. Separately, it has been shown that localized delivery of GDNF can enhance axon growth and motor recovery. FK506, an FDA approved small molecule, has also been shown to enhance peripheral nerve regeneration. This paper describes the design of a novel hole-based drug delivery apparatus integrated with a polytetrafluoroethylene (PTFE) nerve conduit for controlled local delivery of a protein such as GDNF or a small molecule such as FK506. The PTFE devices were tested in a diffusion chamber, and the bioactivity of the released media was evaluated by measuring neurite growth of dorsal root ganglions (DRGs) exposed to the released drugs. The drug delivering nerve guide was able to release bioactive concentrations of FK506 or GDNF. Following these tests, optimized drug releasing nerve conduits were implanted across 10 mm sciatic nerve gaps in a BL6 yellow fluorescent protein (YFP) mouse model, where they demonstrated significant improvement in muscle mass, compound muscle action potential, and axon myelination in vivo as compared with nerve conduits without the drug. The drug delivery nerve guide could release drug for extended periods of time and enhance axon growth in vitro and in vivo.


The effects of actomyosin disruptors on the mechanical integrity of the avian crystalline lens.
Actin and myosin within the crystalline lens maintain the structural integrity of lens fiber cells and form a hexagonal lattice cradling the posterior surface of the lens. The actomyosin network was pharmacologically disrupted to examine the effects on lenticular biomechanics and optical quality. One lens of 7-day-old White Leghorn chickens was treated with 10 µM of a disruptor and the other with 0.01% dimethyl sulfoxide (vehicle). Actin, myosin, and myosin light chain kinase (MLCK) disruptors were used. The stiffness and the optical quality of the control and treated lenses were measured. Western blotting and confocal imaging were used to confirm that treatment led to a disruption of the actomyosin network. The times for the lenses to recover stiffness to match the control values were also measured. Disruptor-treated lenses were significantly less stiff than their controls (p≤0.0274 for all disruptors). The disruptors led to changes in the relative protein amounts as well as the distributions of proteins within the lattice. However, the disruptors did not affect the clarity of the lenses (p≥0.4696 for all disruptors), nor did they affect spherical aberration (p = 0.02245). The effects of all three disruptors were reversible, with lenses recovering from treatment with actin, myosin, and MLCK disruptors after 4 h, 1 h, and 8 min, respectively. Cytoskeletal protein disruptors led to a decreased stiffness of the lens, and the effects were reversible. Optical quality was mostly unaffected, but the long-term consequences remain unclear. Our results raise the possibility that the mechanical properties of the avian lens may be actively regulated in vivo via adjustments to the actomyosin lattice.


Clinical utility of HIV-IgA immunoblot assay in the early diagnosis of perinatal HIV infection.
To ascertain the sensitivity, specificity, predictive value, and clinical use of a human immunodeficiency virus (HIV)-IgA immunoblot assay for diagnosing perinatal HIV infection in infants tested at birth to 1 month, 3 months, and 6 months of age. Prospective, longitudinal cohort study of children born to HIV-infected and noninfected women. The HIV-IgA immunoblot assays were performed at birth to 1 month, 3 months, and 6 months of age and compared with the Centers for Disease Control's classification system of HIV infection in the children. Children were followed up for at least 15 months to ensure accuracy of infection status. Municipal hospital in central Brooklyn, NY, where the prevalence of HIV infection is high. Serum samples from 58 children, 22 with documented HIV infection, 18 noninfected children born to seropositive women, and 18 children born to noninfected women, were studied. Diagnosis of HIV infection using the Centers for Disease Control's classification scheme was compared with diagnosis using the HIV-IgA immunoblot assay for children 6 months of age or younger. The HIV-IgA immunoblot assay yielded negative results at 3 and 6 months of age for all 18 infants born to seronegative women; for the 18 seroreverting, noninfected children born to infected women, the assay yielded negative results at 1 month, 3 months, and 6 months of age. The positive predictive value of the assay was 100%--no false-positive results were identified in the 88 serum samples obtained from noninfected infants. For the HIV-infected children, sensitivity was a function of age: one (5.9%) of 17 infants had an assay that yielded positive results at birth to 1 month of age, 13 (62%) of 21 infants had assays that yielded positive results at 3 months of age, and 17 (77%) of 22 infants had assays that yielded positive results at 6 months of age. The presence or absence of symptoms did not affect the sensitivity. The HIV-IgA immunoblot assay can detect a significant proportion of infected children during an early asymptomatic period of their life. This relatively inexpensive, easily standardized assay may allow for institution of therapy before the onset of clinical symptoms.


Quantitative relations between noxious stimulus intensity and magnitude of central afferent evoked responses in rat.
Relations between intensities of electrical noxious stimulus applied to the tooth pulp and magnitudes of evoked responses at various relay stations of tooth pulp afferents were investigated with lightly anesthetized rats. The stimulus-response function in each relay station and the cerebral cortex follows the power function only in the range of lower, but noxious, stimulus intensities; however, it deviates from it in the range of higher ones, the exponent of the function becoming smaller. The higher the relay station locates, the smaller the exponent value is.


Establishment of the Western Japan Psoriasis Registry and first cross-sectional analysis of registered patients.
The efficacy and safety of new psoriatic treatments are confirmed in clinical trials, but such clinical trial data are limited by the number and heterogeneity of patients. Furthermore, the prevalence and characteristics of psoriasis differ among racial groups. Therefore, it is important to obtain real-world evidence in specific regions. To identify the optimal systemic treatment for psoriatic patients in Western Japan, we established the Western Japan Psoriasis Registry (WJPR). This registry is led by a neutral physicians' league associated with university hospitals, general hospitals, and clinics that specialize in treatment of psoriasis. Systemically treated psoriatic patients who provided written informed consent were enrolled, and data were collected on their background information, several patient-reported outcomes, dermatologists' objective evaluations, and treatment regimens. Patient enrollment began in 2019, and 1394 patients had been recruited by the end of 2020. The prevalence of psoriatic arthritis was 27.2% and that of pustular psoriasis was 7.5%. The mean body mass index was 24.1 kg/m2 , and 12% of patients had severe obesity (body mass index ≥30 kg/m2 ). Major comorbidities were hypertension (35.0%), diabetes (14.1%), and hyperlipidemia (12.2%). Serological data showed that hepatitis B virus surface antigen, anti-hepatitis B virus core antibody, anti-hepatitis C virus antibody, and human T-cell leukemia virus type 1 antibody were detected in 1.1%, 18.0%, 3.1%, and 3.7% of patients, respectively. The most frequently used small-molecule-systemic intervention was apremilast (18.0%), followed by methotrexate (7.7%), etretinate (4.2%), and cyclosporin (3.7%). The most frequently used biologics were interleukin (IL)-17 inhibitors (31.8%), followed by IL-23 inhibitors (including IL-12/23 inhibitors) (26.7%), and tumor necrosis factor inhibitors (11.1%). The WJPR is the first Japanese prospective observational cohort of psoriatic patients. Annual WJPR updates may provide the incidences of comorbidities such as cardiovascular events or onset of arthritis in systemically treated patients, identify rare complications, and identify the optimal treatment regimens for various psoriatic patients.


Effectiveness and legitimacy of forest carbon standards in the OTC voluntary carbon market.
In recent years, the voluntary over-the-counter (OTC) carbon market has reached a significant market volume. It is particularly interesting for forest mitigation projects which are either ineligible in compliance markets or confronted with a plethora of technical and financial hurdles and lacking market demand. As the OTC market is not regulated, voluntary standards have been created to secure the social and environmental integrity of the traded mitigation projects and thus to ensure the quality of the resulting carbon credits. Building on a theoretical efficiency-legitimacy framework, this study aims to identify and analyse the characteristics and indicators that determine the efficiency and organisational legitimacy of standards for afforestation/reforestation carbon projects. All interviewed market actors consider third-party certification and standards as a crucial component of market functionality, which provide quality assurance mechanisms that reduce information asymmetries and moral hazard between the actors regarding the quality of carbon credits, and thus reduce transaction costs. Despite this development, the recent evolution of many new and differing standards is seen as a major obstacle that renders it difficult for project developers and buyers to select an appropriate standard. According to the interviewed experts the most important legitimating factors of standards are assurance of a sufficient level of quality of carbon credits, scientifically substantiated methodological accounting and independent third-party verification, independence of standard bodies, transparency, wide market acceptance, back-up of the wider community including experts and NGOs, rigorous procedures, and the resemblance to the Afforestation/Reforestation (A/R) CDM due to its international policy endorsements. In addition, standards must provide evidence that projects contribute to a positive social and environmental development, do no harm as a minimum requirement and build a strong track record of successful projects. Project developers require clear, easily and practically applicable standards at lowest possible costs with a high potential in order to achieve good carbon prices, while buyers require that standards are legitimate, credible and that no public criticism arises when carbon credits are purchased from projects certified by a certain standard. Despite the fragmented and immature state of the OTC market, standards act as 'market-making' intermediaries and contribute to the quality and transparency of the OTC market. However, the variety of different standards imposes new hurdles for their efficiency and often creates confusion instead of confidence among potential buyers. Despite the lacking legitimacy of the standards, pressures from the institutional environment on standards ensure a minimum quality of carbon credits (including positive social and environmental impacts of carbon credits) that serves as an insurance mechanism for the integrity of standards. Its unregulated nature and the pressure from an increasingly competitive environment provides innovative space to deliver efficient certification procedures without imposing unreasonably high transaction costs on market actors. Furthermore, voluntary standards imply a more innovative certification approach, as one legal authority could do, because standards have to compete for adopters backed by civil society organisations. Thereby, the forest sector in OTC voluntary market bears great opportunities to provide the forest sector with crucial lessons for international climate policy and governmental institutions when designing regulation for forest regulation such as international and national REDDplus schemes.


Mode of action of nitrofurazone.
When Escherichia coli strain B/r is exposed to 10 to 20 mug of nitrofurazone per ml, mutants with roughly threefold resistance are obtained. Treatment of these mutants with higher concentrations of nitrofurazone yields strains with six- to seven-fold resistance over strain B/r. Each of these steps toward nitrofurazone resistance is accompanied by loss of soluble nitrofurazone reductase activity. When sensitive bacteria are exposed to labeled nitrofurazone or labeled 2-nitrofuran, a considerable amount of radioactivity becomes bound to the cold trichloroacetic acid-insoluble fraction. Very little activity becomes bound in the mutants with six- to seven-fold resistance; mutants with intermediate resistance show intermediate levels of binding. Partially purified nitrofurazone reductase preparations catalyze the conversion of nitrofurazone to compounds which bind to protein and are not removed by prolonged dialysis against 8 m urea or by cold acid. Nitrofurazone reduced by xanthine oxidase or electrolytically reduced also yields compounds which react with protein to form stable derivatives.


Effects of two physical education programmes on health- and skill-related physical fitness of Albanian children.
This study aims to evaluate the effectiveness of two school-based physical education (PE) programmes (exercise-based and games-based) compared with traditional PE, on health- and skill-related physical fitness components in children in Tirana, Albania. Participants were 378 first-grade (6.8 years) and 389 fourth-grade (9.8 years) children attending four randomly selected schools in Tirana. Twenty-four school classes within these schools were randomly selected (stratified by school and school grade) to participate as exercise group (EG), games group (GG) and control group (CG). Both EG and GG intervention programmes were taught by professional PE teachers using station/circuit teaching framework while CG referred to traditional PE school lessons by a general teacher. All programmes ran in parallel and lasted 5 months, having the same frequency (twice weekly) and duration (45 min). Heart rate (HR) monitoring showed that intensity during PE lessons was significantly higher in the intervention groups compared with control (P < 0.001). Both PE exercise- and games programmes significantly improved several health- and skill-related fitness indicators compared with traditional PE lessons (e.g. gross motor skill summary score: 9.4 (95% CI 7.9; 10.9) for exercise vs. control and 6.5 (95% CI 5.1; 8.1) for games vs. control, cardiorespiratory fitness: 2.0 ml O2 · min(-1) · kg(-1) (95% CI 1.5; 2.4) for exercise vs. control and 1.4 ml O2 · min(-1) · kg(-1) (95% CI 1.0; 1.8) for games vs. control). Furthermore, compared to games-based PE, exercise-based PE showed more positive changes in some gross motor coordination skills outcomes, coordination skills outcomes and cardiorespiratory fitness. The results from this study show that exercise- and games-based PE represents a useful strategy for improving health- and skill-related physical fitness in Albanian elementary school children. In addition, the study shows that exercise-based PE was more effective than games-based PE in improving gross motor function and cardiorespiratory fitness.


Antibodies to HLA-E in nonalloimmunized males: pattern of HLA-Ia reactivity of anti-HLA-E-positive sera.
Natural anti-HLA Abs found in sera of healthy nonalloimmunized males recognize HLA-Ia alleles parallel to those recognized by anti-HLA-E mAbs (MEM-E/02/06/07). Therefore, some of the HLA-Ia Abs seen in healthy males could be due to anti-HLA-E Abs cross-reacting with HLA-Ia. If anti-HLA-E Abs occur in healthy nonalloimmunized males, it can be assessed whether they evoke HLA-Ia reactivity as do mouse HLA-E mAbs. IgG and IgM Abs to HLA-E and HLA-Ia alleles are identified in sera of healthy males using microbeads coated with recombinant denatured HLA-E or a panel of rHLA-Ia alleles. The pattern of allelic recognition is comparable to that of anti-HLA-E mAbs. Sixty-six percent of the sera with HLA-E IgG have a high level of HLA-Ia IgG, whereas 70% of those with no anti-HLA-E Abs have no HLA-Ia Abs. HLA-E IgM/IgG ratios of sera are divided into four groups: IgM(Low)/IgG(Low), IgM(High)/IgG(Low), IgM(High)/IgG(High), and IgM(Low)/IgG(High). These groups correspond to anti-HLA-Ia IgM/IgG ratio groups. When HLA-E IgM and IgG are absent or present in males, the IgM or IgG of HLA-Ia are similarly absent or present. The mean fluorescent intensity of HLA-Ia Abs correlates with that of anti-HLA-E Abs. Most importantly, HLA-E and HLA-Ia reactivities of the sera are inhibited by the shared, but cryptic, peptide sequences (117)AYDGKDY(123) and (137)DTAAQIS(143). Therefore, Abs to the H chain of HLA-E may be responsible for some of the HLA-Ia allele reactivity of the natural HLA-Ia Ab in human sera. Absence of any anti-HLA-Ia Abs in 112 nonvegans and the presence of the same in vegans suggest that dietary meat proteins might not have induced the natural allo-HLA Abs.


[Influence of alpha-lipoic acid on liver glutathione system of healthy and Ehrlich ascites carcinoma transplanted mice].
Influence of alpha-lipoic acid (LA) on liver glutathione system of Ehrlich ascites carcinoma (EAC) transplanted mice was studied. LA causes multidirectional influence on glutathione system of healthy mice. EAC transforms LA influence, strengthening prooxidative effects more expressed at introduction in early terms after inoculation of the tumor. The mechanism explaining realization of LA prooxidative effects as a result of interaction with glutathione system is suggested.


Characteristics of African American adolescent females who perceive their current boyfriends have concurrent sexual partners.
Perceived partner concurrency, reporting that a current sexual partner has other sexual partners, may pose sexual health risks to adolescents. We examined the contextual characteristics of African American female adolescents who reported their current boyfriend was having concurrent sexual relationships. Participants were African American adolescent females (N = 511; mean age = 17.6) recruited from sexual health clinics. Before participating in an STD/HIV prevention trial, the participants completed audio computer-assisted self-interviews with measures of perceived partner concurrency and individual- (e.g., depression, substance use), interpersonal- (e.g., social support, interpersonal stress), and community-level factors (i.e., neighborhood quality). Twenty-seven percent of participants reported their belief that their current boyfriend had concurrent sexual partners during their relationship. In a logistic regression analysis, participants endorsing perceived partner concurrency reported less relational power (adjusted odds ratio [AOR] = .94, 95% confidence interval [CI] = .89-.98, p < .01), decreased relationship commitment (AOR = .88, 95% CI = .80-.96, p < .01), elevated perceived interpersonal stress (AOR = 1.02, 95% CI = 1.003-1.04, p < .05), and previous STD diagnoses (AOR = 2.07, 95% CI = 1.31-3.28, p < .01; overall model: χ(2) = 67.25; p < .001). Results suggest that the efficacy of sexual risk reduction interventions may be improved by emphasizing the increased HIV/STD risks associated with having a boyfriend with concurrent sex partners. In addition, interventions may benefit from incorporating stress management training and addressing key relationship dynamics, particularly among adolescents with a history of STDs.


Lymphatic microvessels in the rat remnant kidney model of renal fibrosis: aminopeptidase p and podoplanin are discriminatory markers for endothelial cells of blood and lymphatic vessels.
ABSTRACT. Rat remnant kidney is an established model of renal tubulointerstitial fibrosis and progression to end-stage renal failure. The morphologic lesions comprise nephron loss and regeneratory tubular hypertrophy, interstitial infiltration, predominately by macrophages, and progressive fibrosis. A critical role in this complex pathology was assigned to tubulointerstitial blood microvessels that regulate the supply of oxygen and nutrients of tubuli. Whereas some investigations reported a rarefaction of the vascular network in association with the degenerative cortical changes, others observed an increase in vascularization. Here these discrepant findings are addressed by reinvestigation of the vascularization of rat remnant kidneys by the use of two novel endothelial lineage specific, discriminatory markers, i.e., the membrane mucoprotein podoplanin with specificity for lymphatic endothelia, and the glycosyl-phosphatidylinositol (GPI)-anchored membrane enzyme aminopeptidase P that is recognized by a monoclonal antibody designated JG12 and that is specifically expressed by endothelial cells of blood vessels only. The results obtained confirm a regional rarefaction of aminopeptidase P-positive blood microvessels; they also establish major changes in the renal lymphatic vasculature. Massive proliferation of lymphatic vessels was observed in fibrotic tubulointerstitial regions, whereas in kidneys of sham-operated rats, only a few lymphatic vessels were found adjoined with arteries. The lymphatic vessels frequently contained mononuclear cells that were also encountered in the interstitial spaces and expressed relative large amounts of vascular endothelial growth factor-C mRNA by in situ hybridization. Collectively, these results indicate that a large proportion of the microvessels encountered in the cortex of remnant kidneys are of lymphatic origin and cannot be discriminated by common endothelial markers, such as CD34, that are expressed by both lymphatic and blood endothelia cells. As lymphatic endothelial cells secrete chemokines that attract dendritic cells, it is possible that the increase in lymphatic vascularization could enhance the immunologic surveillance of remnant kidneys.


Mechanistic Insights into Co and Fe Quaterpyridine-Based CO2 Reduction Catalysts: Metal-Ligand Orbital Interaction as the Key Driving Force for Distinct Pathways.
Both [CoII(qpy)(H2O)2]2+ and [FeII(qpy)(H2O)2]2+ (with qpy = 2,2':6',2″:6'',2‴-quaterpyridine) are efficient homogeneous electrocatalysts and photoelectrocatalysts for the reduction of CO2 to CO. The Co catalyst is more efficient in the electrochemical reduction, while the Fe catalyst is an excellent photoelectrocatalyst ( ACS Catal. 2018, 8, 3411-3417). This work uses density functional theory to shed light on the contrasting catalytic pathways. While both catalysts experience primarily ligand-based reductions, the second reduction in the Co catalyst is delocalized onto the metal via a metal-ligand bonding interaction, causing a spin transition and a distorted ligand framework. This orbital interaction explains the experimentally observed mild reduction potential and slow kinetics of the second reduction. The decreased hardness and doubly occupied dz2-orbital facilitate a σ-bond with the CO2-π* in an η1-κC binding mode. CO2 binding is only possible after two reductions resulting in an EEC mechanism (E = electron transfer, C = chemical reaction), and the second protonation is rate-limiting. In contrast, the Fe catalyst maintains a Lewis acidic metal center throughout the reduction process because the metal orbitals do not strongly mix with the qpy-π* orbitals. This allows binding of the activated CO2 in an η2-binding mode. This interaction stabilizes the activated CO2 via a π-type interaction of a Fe-t2g orbital and the CO2-π* and a dative bond of the oxygen lone pair. This facilitates CO2 binding to a singly reduced catalyst resulting in an ECE mechanism. The barrier for CO2 addition and the second protonation are higher than those for the Co catalyst and rate-limiting.


Enhancing the performance of polymer solar cells using CuPc nanocrystals as additives.
There is an increasing interest in the use of different nanoparticles as additives in polymer solar cells for enhancing the light absorption of active layers as well as their power conversion efficiency (PCE). In this paper, we report a PCE enhancement by simply adding copper phthalocyanine (CuPc) nanocrystals into photovoltaic devices based on a poly(3-hexylthiophene) (P3HT): fullerene system. Two kinds of device structure were studied: the first one is a CuPc nanocrystal suspension spin coated on the poly(3,4-ethylenedioxythiophene) polystyrene sulfonate-coated substrate; the second one is the CuPc nanocrystal suspension added into the active layer solutions. It is proved that incorporating organic semiconductor nanocrystals into the active layer can help trap light and enhance the crystallinity of the active layers, thus improving the device performance. This strategy might be generally compatible with a broad range of organic photovoltaic materials and offers an effective approach to enhance the device performance.


Temporal and spatial expression pattern of the angiotensinogen gene in mice and rats.
In situ hybridization for mouse angiotensinogen (Ao) mRNA was performed using a Stu I-Pst I 0.43-kb fragment of exon 2 as a template to synthesize RNA probes. The mouse Ao mRNA expression patterns were different from those reported for rats. Ao mRNA was expressed in the fetal liver as early as 12.5 days postcoitus, and the liver remained the predominant organ of its expression in utero. Within the developing kidney, Ao mRNA was demonstrated at 17.5 days postcoitus in the proximal straight tubules undergoing loop formation in the medulla. In the matured mouse kidney, the expression site is within the outer stripe of outer medulla, hence identified as the pars recta, not proximal convoluted tubules. Additional studies revealed that, in rats also, Ao mRNA was localized in the pars recta. This was in contrast to previously published results that showed that Ao mRNA was localized primarily in the proximal convoluted tubules in rats. Thus the pars recta appears to be an important intrarenal source of Ao for both rats and mice throughout pre- and postnatal periods, whereas the liver can be the major extrarenal source in utero in mice, but not in rats.


Thyroidal extracellular glutathione peroxidase: a potential regulator of thyroid-hormone synthesis.
Human thyrocytes were found to synthesize and secrete the selenoenzyme extracellular glutathione peroxidase (E-GPX), a process which was controlled by the Ca2+/phosphoinositol second-messenger cascade. The potential involvement of thyroidal E-GPX in the regulation of thyroid-hormone synthesis and in the protection of the thyrocyte from peroxidative damage is discussed.


Nightmares and Insomnia in the US National Guard: Mental and Physical Health Correlates.
Nightmares and insomnia are significant concerns that commonly co-occur with each other and with other health disorders. Limited research has examined the unique and shared aspects of insomnia and nightmares, and little is known about sleep in US National Guard personnel. This study sought to determine the prevalence and psychosocial correlates of nightmares with and without insomnia in US National Guard personnel. National Guard personnel (N = 841) completed an online survey and were classified as having nightmares only, insomnia only, both, or neither, using a minimum nightmare frequency of "less than once a week" and an Insomnia Severity Index cutoff of ≥ 15. Analyses examined differences in demographics, physical health, and psychosocial variables and in the prevalence of nightmares and insomnia in personnel with physical and mental health problems. In this sample, 32% reported nightmares only, 4% reported insomnia only, and 12% reported both. Those in the youngest age group (18-21) were more likely to have no nightmares or insomnia. Those with both nightmares and insomnia had more deployments. Nightmares and insomnia were associated with poorer physical and mental health and greater prevalence of comorbid physical and mental health conditions. Personnel with both insomnia and nightmares reported the greatest severity of comorbid conditions. US National Guard personnel with nightmares and/or insomnia reported worse mental and physical health impairment than those without these conditions. Personnel may benefit from screening for nightmares and insomnia and referrals for evidence-based treatment.


Hidden Markov models reveal complexity in the diving behaviour of short-finned pilot whales.
Diving behaviour of short-finned pilot whales is often described by two states; deep foraging and shallow, non-foraging dives. However, this simple classification system ignores much of the variation that occurs during subsurface periods. We used multi-state hidden Markov models (HMM) to characterize states of diving behaviour and the transitions between states in short-finned pilot whales. We used three parameters (number of buzzes, maximum dive depth and duration) measured in 259 dives by digital acoustic recording tags (DTAGs) deployed on 20 individual whales off Cape Hatteras, North Carolina, USA. The HMM identified a four-state model as the best descriptor of diving behaviour. The state-dependent distributions for the diving parameters showed variation between states, indicative of different diving behaviours. Transition probabilities were considerably higher for state persistence than state switching, indicating that dive types occurred in bouts. Our results indicate that subsurface behaviour in short-finned pilot whales is more complex than a simple dichotomy of deep and shallow diving states, and labelling all subsurface behaviour as deep dives or shallow dives discounts a significant amount of important variation. We discuss potential drivers of these patterns, including variation in foraging success, prey availability and selection, bathymetry, physiological constraints and socially mediated behaviour.


Management of massive haemoptysis with the rigid bronchoscope and cold saline lavage.
Twelve successive patients with massive haemoptysis were treated by emergency rigid bronchoscopy and lavage of the bleeding lung with cold saline. All patients stopped bleeding during the procedure and all blood and clot was evacuated from the accessible airways. The bleeding source was localised to a lobe in seven cases, and lateralised in the remaining five patients. Five patients had a second haemorrhage during that hospital stay and cold saline lavage again terminated it. Further therapy, either surgical or medical was based on information obtained during the respite from haemorrhage achieved with this technique. There was no hospital mortality in the series.


Abdominal ultrasonography in the diagnosis of extrinsic endoscopic compressions of stomach and duodenum.
Extrinsic compressions of stomach or duodenum (ECSD) are occasionally found during endoscopic examination. Ultrasonography is usually performed in order to explain the significance of this feature. We have prospectively assessed the prevalence of ECSD and the diagnostic role of US in this context. ECSD were found in 37 out of 6604 gastroduodenoscopies. An abdominal US was performed after endoscopy in all these patients. The extrinsic compressions were in the gastric anterior wall in 7 patients in the gastric posterior wall in 10 patients, and in the lesser curvature in 9 patients and in the duodenum in 11 patients. In 20 patients the compression was due to neoplastic lesions, in another 15 non neoplastic conditions were found (hepatomegaly, splenomegaly, gallbladder hydrops, pancreatic pseudocyst, vascular malformations). Ultrasonography was demonstrated to have an elevated sensitivity (87.5%) and an elevated specificity (100%) when technically adequate. We conclude that extrinsic compressions of stomach and duodenum detected at endoscopy are frequently associated to neoplastic lesions. Abdominal ultrasonography is an accurate tool, when technically adequate, as an initial screening test for such lesions. Endosonography, CT scan or other invasive tests must be performed in doubtful cases.


Nanoparticles Containing Oxaliplatin and the Treatment of Colorectal Cancer.
Colorectal cancer (CRC) is a highly widespread malignancy and ranks as the second most common cause of cancer-related mortality. Cancer patients, including those with CRC, who undergo chemotherapy, are often treated with platinum- based anticancer drugs such as oxaliplatin (OXA). Nevertheless, the administration of OXA is associated with a range of gastrointestinal problems, neuropathy, and respiratory tract infections. Hence, it is necessary to devise a potential strategy that can effectively tackle these aforementioned challenges. The use of nanocarriers has shown great potential in cancer treatment due to their ability to minimize side effects, target drugs directly to cancer cells, and improve drug efficacy. Furthermore, numerous studies have been published regarding the therapeutic efficacy of nanoparticles in the management of colorectal cancer. In this review, we present the most relevant nanostructures used for OXA encapsulation in recent years, such as solid lipid nanoparticles, liposomes, polysaccharides, proteins, silica nanoparticles, metal nanoparticles, and synthetic polymer-carriers. Additionally, the paper provides a summary of the disadvantages and limits associated with nanoparticles. The use of different carriers for the delivery of oxaliplatin increased the efficiency and reduced the side effects of the drug. It has been observed that the majority of research investigations have focused on liposomes and polysaccharides. This potentially auspicious method has the potential to enhance results and enhance the quality of life for cancer patients undergoing chemotherapy. However, additional investigation is required to ascertain the most suitable medium for the transportation of oxaliplatin and to assess its efficacy through clinical trials.


One-pot sequential organocatalysis: highly stereoselective synthesis of trisubstituted cyclohexanols.
A highly diastereoselective (d.r. >99:1) and enantioselective (ee value up to 96%) synthesis of trisubstituted cyclohexanols was achieved by using a one-pot sequential organocatalysis that involved a quinidine thiourea-catalyzed tandem Henry-Michael reaction between nitromethane and 7-oxo-hept-5-en-1-als followed by a tetramethyl guanidine (TMG)-catalyzed tandem retro-Henry-Henry reaction on the reaction products of the tandem Henry-Michael reaction. Through a mechanistic study, it has also been demonstrated that similar results may also be achieved with this one-pot sequential organocatalysis by using the racemic Henry product as the substrate.


Secretion of endothelin converting enzyme-1a: the hydrophobic signal anchor domain alone is not sufficient to promote membrane localization.
Endothelin converting enzyme-1 (ECE-1) is a type II membrane protein that is important for the proteolytic activation of big endothelin-1 to endothelin-1. Although the highly conserved zinc-binding motif is known to be located in the extracellular domain, the role(s) of the N-terminal and membrane-spanning signal anchor domains in the biosynthesis and function of ECE-1 isoforms, ECE-1a, ECE-1b, and ECE-1c, remain undetermined. In this study, we provide evidence that the deletion of the cytoplasmic N-terminal tail (residues 1-55) of ECE-1a results in the cleavage of a potential signal peptide located in the signal anchor domain leading to the partial secretion of the recombinant enzyme into the media. However, the truncation of N-terminal and/or signal anchor domain does not affect the activity of ECE-1a. Therefore, our results demonstrate that the hydrophobic signal anchor domain alone is not sufficient for the membrane anchoring of ECE-1a and that the N-terminal domain of ECE-1a is important for membrane targeting as well as the intracellular localization of the enzyme.


Distinctive biochemistry profiles associated with hyperuricemia between Tibetans and Hans in China.
We sought to identify distinct risk factors for hyperuricemia in native Tibetan and immigrant Han populations in Tibet, China. Three cohorts of male participants aged between 20 and 40 years were enrolled in this study. Biochemical parameters including serum uric acid (UA), fasting plasma glucose, insulin, lactate dehydrogenase (LDH), thyroxin, blood cell count, aminotransferase, and lipid profiles were analyzed. The association of risk factors with UA levels was evaluated using a multivariable line regression model. The effect of UA level on the biochemical parameters between the Hans and Tibetans was evaluated by two-way ANOVA. The prevalence of hyperuricemia (≥420 μmol/L) was 24.8% (62/250) in the Hans, similar to 23.8% (29/136) in the Tibetans. In the regression analysis, the risk factors that were significantly associated with UA in Hans did not apply to Tibetans. Tibetans had higher fasting insulin (P<0.05) and LDH (P<0.01) levels, in contrast with lower levels of triglycerides (P<0.05), total cholesterol (P<0.01), and low-density lipoprotein-cholesterol (P<0.01) than Hans in normal UA populations. Biochemistry analysis revealed lower albumin levels (P<0.001) and higher levels of all aminotransaminase and especially alkaline phosphatase (P<0.01) in Tibetans than in Hans in both populations. Compared with Hans, Tibetans had lower serum levels of urea, creatinine, and electrolytes in the normal UA population, which were further exacerbated in the high UA population. Tibetans had comparable white blood cell counts as Hans in both normal and high UA populations. In contrast, the red blood cell count and hemoglobin concentration were much lower in Tibetans than in Hans under high UA conditions. The distinctive biochemistry between Tibetans and Hans may underlie the different etiologies of hyperuricemia in Tibet, China.


The activity of rifabutin against Mycobacterium leprae.
Minimal effective doses of rifabutin and rifampicin were determined in Mycobacterium leprae isolated from skin biopsies of newly diagnosed, previously untreated lepromatous leprosy patients. Rifabutin was more potent than rifampicin. Our previous report that rifabutin was fully active against rifampicin-resistant M. leprae could not be confirmed. Examination of two strains of rifampicin-resistant M. leprae from elsewhere, and a repeat experiment on our original strain of rifampicin-resistant bacilli, showed full cross-resistance between rifampicin and rifabutin. A clinical trial in three newly diagnosed, previously untreated lepromatous patients showed that rifabutin has rapid bactericidal activity.


Influence of Different Surface Treatments on the Shear Bond Strength of Resin Cement to Base Metal Alloys.
Introduction: This study aimed to investigate the effect of different surface treatments on the bond strength of resin cement to nickel-chrome (Ni-Cr) alloy. Methods: Forty disk-shaped specimens of Ni-Cr alloy were prepared and divided into 4 groups. In the first group, the specimens' surface was sandblasted with 50 µ Al2 O3 particles. In the second group, the specimens were prepared with the Er:YAG laser. In the third group, the specimens were prepared using the Er:YAG laser after sandblasting. In the fourth group, the specimens' surface was covered with a thin layer of MKZ metal primer after sandblasting. Then the cylinders of composite resin were bonded to the treated metal surfaces using Panavia F2.0 resin cement. All of the samples were subjected to 2000 thermal cycles. The shear bond strength was tested using a universal testing machine at the crosshead speed of 0.5 mm/min. The failure mode was also observed by a stereomicroscope. Data were analyzed using the one-way ANOVA and the Tukey HSD test at a significance level of 0.05. Results: The shear bond strength from the highest to the lowest were as follows: the Er:YAG laser group, the sandblast and MKZ primer combination group, the sandblast group, and the sandblast and Er:YAG laser combination group. The mean differences of shear bond strength between the Er:YAG laser group and the sandblast group (P=0.047) and also between the Er:YAG laser group and the sandblast and Er:YAG laser combination group (P=0.015) were statistically significant. Conclusion: Among the different surface treatments employed in this study, Er:YAG laser treatment increased the shear bond strength between the metal alloy and the resin cement (Pavnavia F2).


In vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease.
CD103 (alphaEbeta7) has been shown to be an excellent marker for identifying in vivo-activated FoxP3(+)CD4(+) regulatory T (Treg) cells. It is unknown whether reinfusion of in vivo-activated donor-type CD103(+) Treg cells from recipient can ameliorate ongoing chronic graft-versus-host disease (GVHD). Here, we showed that, in a chronic GVHD model of DBA/2 (H-2(d)) donor to BALB/c (H-2(d)) recipient, donor-type CD103(+) Treg cells from recipients were much more potent than CD25(hi) natural Treg cells from donors in reversing clinical signs of GVHD and tissue damage. Furthermore, in contrast to CD25(hi) natural Treg cells, CD103(+) Treg cells expressed high levels of CCR5 but low levels of CD62L and directly migrated to GVHD target tissues. In addition, the CD103(+) Treg cells strongly suppressed donor CD4(+) T-cell proliferation; they also induced apoptosis of in vivo-activated CD4(+) T and B cells and significantly reduced pathogenic T and B cells in GVHD target tissues. These results indicate that CD103(+) Treg cells from chronic GVHD recipients are functional, and reinfusion of the CD103(+) Treg cells can shift the balance between Treg cells and pathogenic T cells in chronic GVHD recipients and ameliorate ongoing disease.


[Legal aspects of urgent medical care for patients of elderly and old age].
The problem of equivalent valuation of health state and the ability to come to self decision is very important in case the urgent medical help for elderly and old people is necessary. The following medical legal forms can be offered: "Well-informed patient's consent to be medically examined and treated" and "Consultation decision to take medical measures (and to operate, too) without a patient's agreement". These forms could be used in geriatric practice. These forms of medical activity are the basis of medical staff reliable protection if patients or their relatives make a claim against them on the point of urgent and planned medical help.


Self-managed teams: the reality and the promise.
The success of self-managed teams depends on many factors. This article highlights issues related to effective team work in health care, including literature reports and interviews with nurse executives about the use of self-managed teams in health care. Challenges for the future are presented.


Properties of the descending limb of the spinobulbospinal micturition reflex pathway in the cat.
The micturition reflex is thought to be mediated by a spinobulbospinal reflex pathway passing through the rostral pons. This study examined the properties of the descending limb of the reflex pathway by monitoring the responses of the lower urinary tract to stimulation of the pons in the decerebrate cat. Electrical stimulation (300 microseconds pulses at 50 Hz intratrain frequencies, 300-500 ms trains, 0.5-15 V) in the region of the locus coeruleus (P 0.5-3.1/L 2-4/H to -2.75) was used to activate the descending excitatory pathway to the sacral parasympathetic nucleus. Low intensity stimulation induced small amplitude, short duration (14 +/- 11 cm H2O, 10 +/- 3 s) bladder contractions in a partially full bladder, whereas higher intensity stimulation induced large amplitude, long duration (69 +/- 29 cm H2O, 70 +/- 44 s) contractions which were similar to distension-induced reflex micturition contractions. The evoked bladder contractions coincided with a reduction in external urethral sphincter (EUS) EMG activity. Following bilateral L7-S3 dorsal root transection, electrical stimulation of the pons still elicited the small amplitude bladder contractions, but the larger amplitude, long duration micturition contractions were abolished. During these small evoked bladder contractions, a suppression of EUS activity still occurred following deafferentation, indicating a pontine mediated bladder/EUS synergy. It is concluded that the pons can initiate bladder contractions and coordinated bladder-sphincter activity, but that afferent feedback (via the dorsal roots) is needed to maintain the large amplitude micturition contractions.


The Role of Insulin and Insulin-like Growth Factors in the Increased Risk of Cancer in Diabetes.
Patients with type 2 diabetes (T2D) are at increased risk of developing cancer. This evidence arises from numerous epidemiologic studies that relate a positive association between T2D and cancer. In-vitro and several in-vivo experiments have attempted to discern the potential mechanistic factors involved in this relationship. Candidates include hyperinsulinemia, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-2 (IGF-2) signaling. These studies demonstrated that increased insulin, IGF-1, and IGF-2 signaling through the insulin receptor and IGF-1 receptor can induce cancer development and progression.


Estimations of linkage disequilibrium, effective population size and ROH-based inbreeding coefficients in Spanish Churra sheep using imputed high-density SNP genotypes.
In this study, the availability of the Ovine HD SNP BeadChip (HD-chip) and the development of an imputation strategy provided an opportunity to further investigate the extent of linkage disequilibrium (LD) at short distances in the genome of the Spanish Churra dairy sheep breed. A population of 1686 animals, including 16 rams and their half-sib daughters, previously genotyped for the 50K-chip, was imputed to the HD-chip density based on a reference population of 335 individuals. After assessing the imputation accuracy for beagle v4.0 (0.922) and fimpute v2.2 (0.921) using a cross-validation approach, the imputed HD-chip genotypes obtained with beagle were used to update the estimates of LD and effective population size for the studied population. The imputed genotypes were also used to assess the degree of homozygosity by calculating runs of homozygosity and to obtain genomic-based inbreeding coefficients. The updated LD estimations provided evidence that the extent of LD in Churra sheep is even shorter than that reported based on the 50K-chip and is one of the shortest extents compared with other sheep breeds. Through different comparisons we have also assessed the impact of imputation on LD and effective population size estimates. The inbreeding coefficient, considering the total length of the run of homozygosity, showed an average estimate (0.0404) lower than the critical level. Overall, the improved accuracy of the updated LD estimates suggests that the HD-chip, combined with an imputation strategy, offers a powerful tool that will increase the opportunities to identify genuine marker-phenotype associations and to successfully implement genomic selection in Churra sheep.


Surface octahedral distortions and atomic design of perovskite interfaces.
Atomic engineering of perovskite films and interfaces is significantly improved by in situ optimization of reflection high-energy electron diffraction (RHEED) features resulting from surface BO₆ octahedral rotations seen during molecular-beam epitaxy growth. This approach yields Sr-doped manganite films across the phase diagram with magnetotransport properties that are, for the first time, identical to bulk single crystals. Careful structural analysis of manganite/titanate interfaces shows that cation intermixing and unit cell dilations are eliminated, while BO₆ rotations and Jahn-Teller-type elongations are nearly completely suppressed at the interface.


Galbibacter marinus sp. nov., isolated from deep-sea sediment.
A taxonomic study was carried out on a novel bacterium, designated strain ck-I2-15(T), which was isolated from deep-sea sediment collected from the South-west Indian Ocean Ridge. Cells of strain ck-I2-15(T) were Gram-reaction-negative, rod-shaped, non-motile, moderately halophilic and capable of denitrification. Growth was observed with 0-9 % (w/v) NaCl and at temperatures of 10-37 °C. The novel strain was unable to degrade gelatin. The dominant cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 9 (iso-C17 : 1ω9c and/or 10-methyl C16 : 0). The major respiratory quinone was MK6 and the polar lipid profile comprised phosphatidylethanolamine, one unidentified phospholipid, two unidentified aminolipids, one unidentified glycolipid and four other unidentified lipids. The G+C content of the genomic DNA was 38 mol%. 16S rRNA gene sequence comparison indicated that strain ck-I2-15(T) was most closely related to Galbibacter mesophilus Mok-17(T) (92.9 % sequence similarity), followed by 'Joostella atrarenae' M1-2 (92.8 %), Joostella marina En5(T) (92.7 %) and Zhouia amylolytica HN-171(T) (91.6 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain ck-I2-15(T) formed a clade with the genus Galbibacter, within the family Flavobacteriaceae. Several phenotypic properties allowed strain ck-I2-15(T) to be distinguished from its closest phylogenetic relatives. On the basis of the phenotypic and phylogenetic data, strain ck-I2-15(T) represents a novel species of the genus Galbibacter, for which the name Galbibacter marinus is proposed. The type strain is ck-I2-15(T) ( = CCTCC AB 209062(T) = LMG 25228(T) = MCCC 1A03044(T)).


Tetrahydrobiopterin: biochemistry and pathophysiology.
BH4 (6R-L-erythro-5,6,7,8-tetrahydrobiopterin) is an essential cofactor of a set of enzymes that are of central metabolic importance, including four aromatic amino acid hydroxylases, alkylglycerol mono-oxygenase and three NOS (NO synthase) isoenzymes. Consequently, BH4 is present in probably every cell or tissue of higher organisms and plays a key role in a number of biological processes and pathological states associated with monoamine neurotransmitter formation, cardiovascular and endothelial dysfunction, the immune response and pain sensitivity. BH4 is formed de novo from GTP via a sequence of three enzymatic steps carried out by GTP cyclohydrolase I, 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase. An alternative or salvage pathway involves dihydrofolate reductase and may play an essential role in peripheral tissues. Cofactor regeneration requires pterin-4a-carbinolamine dehydratase and dihydropteridine reductase, except for NOSs, in which the BH4 cofactor undergoes a one-electron redox cycle without the need for additional regeneration enzymes. With regard to the regulation of cofactor biosynthesis, the major controlling point is GTP cyclohydrolase I. BH4 biosynthesis is controlled in mammals by hormones and cytokines. BH4 deficiency due to autosomal recessive mutations in all enzymes, except for sepiapterin reductase, has been described as a cause of hyperphenylalaninaemia. A major contributor to vascular dysfunction associated with hypertension, ischaemic reperfusion injury, diabetes and others, appears to be an effect of oxidized BH4, which leads to an increased formation of oxygen-derived radicals instead of NO by decoupled NOS. Furthermore, several neurological diseases have been suggested to be a consequence of restricted cofactor availability, and oral cofactor replacement therapy to stabilize mutant phenylalanine hydroxylase in the BH4-responsive type of hyperphenylalaninaemia has an advantageous effect on pathological phenylalanine levels in patients.


Medicare program; revision to accrual basis of accounting policy. Health Care Financing Administration (HCFA), HHS. Final rule.
Medicare policy provides that payroll taxes that a provider becomes obligated to remit to governmental agencies are included in allowable costs only in the cost reporting period in which payment (upon which the payroll taxes are based) is actually made to an employee. Therefore, for payroll accrued in 1 year but not paid until the next year, the associated payroll taxes are not an allowable cost until the next year. This final rule provides for an exception when payment would be made to the employee in the current year but for the fact the regularly scheduled payment date is after the end of the year. In that case, the rule requires allowance in the current year of accrued taxes on payroll that is accrued through the end of the year but not paid until the beginning of the next year, thus allowing accrued taxes on end-of-the year payroll in the same year that the accrual of the payroll itself is allowed. The effect of this rule is not on the allowability of cost but rather only on the timing of payment; that is, the cost of payroll taxes on end-of-the-year payroll is allowable in the current period rather than in the following period.


A molecular dynamics study on magnetic imidazolium-based ionic liquids: the effect of an external magnetic field.
In this paper, we have reported a molecular dynamics (MD) study on the properties of three different magnetic imidazolium-based ionic liquids in the absence and presence of an external magnetic field. In this regard, the volumetric properties such as density and isobaric expansion coefficient, dynamical properties, namely, viscosity, mean square displacement of ions, diffusion coefficients, transport numbers of cations and anions, and electrical conductivity, and structural properties such as radial distribution function (RDF) and spatial distribution function (SDF) of [emim][FeCl4], [bmim][FeCl4] and [hmim][FeCl4] have been studied at different temperatures using molecular dynamics simulations. After studying the different volumetric, structural, and dynamical properties of the above-mentioned magnetic ILs in the absence of a magnetic field, we investigated the effect of an external magnetic field on the structural properties of one of these systems, i.e., [bmim][FeCl4]. In this regard, we established different contributions in the interactions between the external magnetic field and the studied magnetic ionic liquid (MIL). The number density profiles of the studied MIL before and after imposing an external magnetic field of 1.5 T showed a significant variation in the molecular distribution. The results indicated that the external magnetic field reduced the intensity of RDFs due to the reduction in the interactions between different ion sites as a result of changes in their orientations. After applying the external magnetic field, it was observed that due to the oppositely directed forces on the cations and anions, they moved in opposite directions. The snapshots showed that the static motion of the anion was smaller because of its small size. In the presence of an external magnetic field, the ions distributed more homogeneously compared to that observed in the absence of this field. The results of this study can be used in the rational and accurate design of viscomagnetic fluids and reaction systems in the presence and absence of magnetic fields.


Chronic threat and contingent belonging: protective benefits of values affirmation on identity development.
Two longitudinal field experiments in a middle school examined how a brief "values affirmation" affects students' psychological experience and the relationship between psychological experience and environmental threat over 2 years. Together these studies suggest that values affirmations insulate individuals' sense of belonging from environmental threat during a key developmental transition. Study 1 provided an analysis of new data from a previously reported study. African American students in the control condition felt a decreasing sense of belonging during middle school, with low-performing students dropping more in 7th grade and high-performing students dropping more in 8th grade. The affirmation reduced this decline for both groups. Consistent with the notion that affirmation insulates belonging from environmental threat, affirmed African American students' sense of belonging in Study 1 fluctuated less over 2 years and became less contingent on academic performance. Based on the idea that developmentally sensitive interventions can have long-lasting benefits, Study 2 showed that the affirmation intervention was more effective if delivered before any drop in performance and subsequent psychological toll could unfold. The role of identity threat and affirmation in affecting the encoding of social experience, and the corresponding importance of timing treatments to developmentally sensitive periods, are explored.


T-cell acute lymphoblastic leukemia in association with Börjeson-Forssman-Lehmann syndrome due to a mutation in PHF6.
Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked mental retardation syndrome that is caused by germline mutations in PHF6. We describe a 9-year-old male with BFLS, who developed T-cell acute lymphoblastic leukemia (T-ALL). The PHF6 gene is located on the X chromosome and encodes a protein with two PHD-type zinc finger domains and four nuclear localization sequences. Previously, overexpression of Phf6 was observed in murine T-cell lymphomas. Our observation indicates that BFLS may represent a cancer predisposition syndrome and that mutations of PHF6 contribute to T-ALL.


The potassium-glycogen interaction on force and excitability in mouse skeletal muscle: implications for fatigue.
A reduced muscle glycogen content and potassium (K+ ) disturbances across muscle membranes occur concomitantly during repeated intense exercise and together may contribute to skeletal muscle fatigue. Therefore, we examined whether raised extracellular K+ concentration ([K+ ]o ) (4 to 11 mM) interacts with lowered glycogen to reduce force production. Isometric contractions were evoked in isolated mouse soleus muscles (37°C) using direct supramaximal field stimulation. (1) Glycogen declined markedly in non-fatigued muscle with >2 h exposure in glucose-free physiological saline compared with control solutions (11 mM glucose), i.e. to <45% control. (2) Severe glycogen depletion was associated with increased 5'-AMP-activated protein kinase activity, indicative of metabolic stress. (3) The decline of peak tetanic force at 11 mM [K+ ]o was exacerbated from 67% initial at normal glycogen to 22% initial at lowered glycogen. This was due to a higher percentage of inexcitable fibres (71% vs. 43%), yet without greater sarcolemmal depolarisation or smaller amplitude action potentials. (4) Returning glucose while at 11 mM [K+ ]o increased both glycogen and force. (5) Exposure to 4 mM [K+ ]o glucose-free solutions (15 min) did not increase fatiguability during repeated tetani; however, after recovery there was a greater force decline at 11 mM [K+ ]o at lower than normal glycogen. (6) An important exponential relationship was established between relative peak tetanic force at 11 mM [K+ ]o and muscle glycogen content. These findings provide direct evidence of a synergistic interaction between raised [K+ ]o and lowered muscle glycogen as the latter shifts the peak tetanic force-resting EM relationship towards more negative resting EM due to lowered sarcolemmal excitability, which hence may contribute to muscle fatigue. KEY POINTS: Diminished muscle glycogen levels and raised extracellular potassium concentrations ([K+ ]o ) occur simultaneously during intense exercise and together may contribute to muscle fatigue. Prolonged exposure of isolated non-fatigued soleus muscles of mice to glucose-free physiological saline solutions markedly lowered muscle glycogen levels, as does fatigue then recovery in glucose-free solutions. For both approaches, the subsequent decline of maximal force at 11 mM [K+ ]o , which mimics interstitial [K+ ] levels during intense exercise, was exacerbated at lowered compared with normal glycogen. This was mainly due to many more muscle fibres becoming inexcitable. We established an important relationship that provides evidence of a synergistic interaction between raised [K+ ]o and lowered glycogen content to reduce force production. This paper indicates that partially lowered muscle glycogen (and/or metabolic stress) together with elevated interstitial [K+ ] interactively lowers muscle force, and hence may diminish performance especially during repeated high-intensity exercise.