Examining Transdiagnostic Factors among Firefighters in Relation to Trauma Exposure, Probable PTSD, and Probable Alcohol Use Disorder.
Firefighters represent a distinct group of first responders that are at heightened risk of developing posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). Assessing the role of transdiagnostic factors that underlie PTSD-AUD associations can inform specialized interventions among this population. This study included urban firefighters (N = 657) with probable PTSD-AUD (n = 27), probable PTSD-alone (n = 35), probable AUD-alone (n = 125), and trauma-exposure-only (n = 470). Methods: All firefighters completed a self-report, online questionnaire battery. Between group differences in anxiety sensitivity (AS), distress tolerance (DT), mindfulness, and emotional regulation difficulties (ERD) were assessed. It was hypothesized that firefighters with probable PTSD-AUD would endorse elevated AS and ERD, and reduced DT and mindfulness in comparison to all other diagnostic groups. Relationship status was included as a covariate in all comparisons. Results: Firefighters with probable PTSD-AUD endorsed elevated AS and ERD, and reduced DT and mindfulness in comparison to firefighters with trauma-exposure-only and probable AUD-alone. Firefighters with probable PTSD-AUD and probable PTSD-alone did not significantly differ. Conclusions: Given these findings, this line of inquiry has great potential to inform specialized, evidence-based mental health programming among firefighter populations, who represent a unique population susceptible to trauma-exposure, PTSD symptomology, and problematic alcohol use.


In vitro susceptibilities of Leptospira spp. and Borrelia burgdorferi isolates to amoxicillin, tilmicosin, and enrofloxacin.
Antimicrobial susceptibility testing was conducted with 6 different spirochetal strains (4 strains of Leptospira spp. and 2 strains of Borrelia burgdorferi) against 3 antimicrobial agents, commonly used in equine and bovine practice. The ranges of MIC and MBC of amoxicillin against Leptospira spp. were 0.05 - 6.25 microgram/ml and 6.25 - 25.0 microgram/ml, respectively. And the ranges of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of amoxicillin against B. burgdorferi were 0.05 - 0.39 microgram/ml and 0.20 - 0.78 microgram/ml, respectively. The ranges of MIC and MBC of enrofloxacin against Leptospira spp. were 0.05 - 0.39 microgram/ml and 0.05 - 0.39 microgram/ml, respectively. Two strains of B. burgdorferi were resistant to enrofloxacin at the highest concentration tested for MBC (>or=100 microgram/ml). Therefore, the potential role of tilmicosin in the treatment of leptospirosis and borreliosis should be further evaluated in animal models to understand whether the in vivo studies will confirm in vitro results. All spirochetal isolates were inhibited (MIC) and were killed (MBC) by tilmicosin at concentrations below the limit of testing (<or=0.01 microgram/ml).


[Laparoscopic biliary surgery].
Laparoscopic cholecystectomy has become the standard treatment for patients with symptomatic gallbladder disease. However, there is a substantial proportion of patients in whom laparoscopic cholecystectomy cannot be successfully performed, and conversion to open surgery is required because of technical difficulties or complications. The incidence of bile duct injury has increased in laparoscopic cholecystectomy. Meticulous dissection and intraoperative cholangiography could significantly reduce the rate of that injury. Laparoscopic cholecystectomy for acute cholecystitis is still controversial because of surgical difficulty. In our experience, early laparoscopic cholecystectomy is a beneficial option for patients with acute cholecystitis, and it may even be safe in the acute stage. A better alternative for high-risk early operation and septic cases is percutaneous transhepatic gallbladder drainage. The coexistence of gallbladder cancer should be ruled out and preoperative diagnosis should be done carefully. Laparoscopic management of common bile duct (CBD) stones has many advantages. However it has been reported to be demanding and time-consuming to perform, which limits its widespread adoption. In our experience with 258 patients, laparoscopic CBD exploration was feasible for almost all CBD stones. The technical difficulties associated with laparoscopic CBD exploration could be overcome with the development of suitable equipment and increased expertise.


Forensic investigation of a 1986 outbreak of osteopetrosis in commercial brown layers reveals a novel avian leukosis virus-related genome.
Avian leukosis virus (ALV) is known to cause several neoplastic conditions in chickens, such as B-cell lymphomas, myelocytomas, erythroblastosis, and other types of neoplasia including osteopetrosis. We describe herein the identification of unique ALV-related proviral DNA sequences in an archived chicken bone affected with osteopetrosis. The osteopetrotic bone was obtained from an affected 46-week-old brown layer during an outbreak of osteopetrosis in Costa Rica in 1986. Analysis of proviral DNA in the 23-year-old osteopetrotic bone revealed unique exogenous ALV-related sequences that were named CR-1986 (Costa Rica, 1986). The 5' and 3' long terminal repeats (LTR) in the proviral DNA were identical to each other. The U3 regions in the LTRs were most similar to equivalent sequences in ALV-J, while U5 was identical to known endogenous ALV-E sequences. The predicted CR-1986 envelope protein was most similar to the envelope of myeloblastosis associated virus type 1 (MAV-1), although the percentage of amino acid sequence similarity to MAV-1 was low (90.4%). The variable and hypervariable regions of gp85 displayed several mutations compared to representative strains of ALV. The gp37 (transmembrane or TM) envelope protein showed three leucine to serine mutations that may represent important changes in the conformation of this protein, a finding that is currently being investigated. Several recombination events may have contributed to the emergence of CR-1986 because each analyzed segment was similar to a different ALV. CR-1986 may represent a unique ALV based on distinctive characteristics of its predicted envelope protein in comparison to previously reported ALVs.


Current role of semen storage and artificial insemination in the turkey industry.
The turkey industry is moving towards the development of stud farms, but an essential condition is the existence of efficient methods to store semen. Much research has been done recently to determine the number of viable spermatozoa in an insemination dose needed for maintaining optimum fertility. Practical methods to determine the number of intact spermatozoa in semen, both before and after storage, are under development. It is now possible to store turkey semen for 6 to 24 h without appreciable loss in fertility and hatchability. Ideal experimental conditions for 48 h storage have not yet been fully determined. Development of new storage media, allowing the insemination of very low numbers of spermatozoa, may provide interesting possibilities regarding the use of elite sires.


Magnetic resonance imaging of the shoulder: rotator cuff.
Magnetic resonance imaging has proven to be useful in the assessment of rotator cuff injuries. Improvements in magnetic resonance techniques, including fast spin-echo imaging and fat saturation, have facilitated demonstration of tendinous abnormalities of the rotator cuff. Rotator cuff disease is multifactorial. Primary impingement within the coracoacromial arch, degeneration of the rotator cuff tendons, trauma, and glenohumeral instability may be contributing factors. Shoulder pain in athletes can be related to acute myotendinous and muscle injuries, which can be easily detected using magnetic resonance imaging.


Differential Recognition of Diet-Derived Neu5Gc-Neoantigens on Glycan Microarrays by Carbohydrate-Specific Pooled Human IgG and IgA Antibodies.
Sialic acids (Sias) cover vertebrate cell surface glycans. N-Acetylneuraminic acid (Neu5Ac) and its hydroxylated form N-glycolylneuraminic acid (Neu5Gc) are common Sia in mammals. Humans cannot synthesize Neu5Gc but accumulate it on cells through red-meat rich diets, generating numerous immunogenic Neu5Gc-neoantigens. Consequently, humans have diverse anti-Neu5Gc antibodies affecting xenotransplantation, cancer, atherosclerosis, and infertility. Anti-Neu5Gc antibodies circulate as IgG, IgM, and IgA isotypes; however, repertoires of the different isotypes in a large population have not been studied yet. Here, we used glycan microarrays to investigate anti-Neu5Gc IgGs and IgAs in intravenous immunoglobulin (IVIG) or pooled human IgA, respectively. Binding patterns on microarrays fabricated with Neu5Gc- and Neu5Ac-glycans, together with inhibition assays, revealed that different IVIG preparations have highly specific anti-Neu5Gc IgG reactivity with closely related repertoires, while IgAs show cross-reactivity against several Neu5Ac-glycans. Such different anti-Neu5Gc IgG/IgA repertoires in individuals could possibly mediate distinctive effects on human diseases.


Dishware size and snack food intake in a between-subjects laboratory experiment.
The use of smaller dishware as a way of reducing food consumption has intuitive appeal and is recommended to the general public. Recent experimental studies have failed to find an effect of plate size on food intake, although the methods used across studies have varied. The aim of the present study was to examine the effect that bowl size had on snack food consumption in a 'typical' snacking context (snacking while watching television). Between-subjects. Laboratory experiment. Sixty-one adult participants served themselves and ate popcorn while watching television. Participants were randomly assigned to serve themselves with and eat from either a small or a large bowl. The use of a smaller bowl size did not reduce food consumption. Unexpectedly, participants in the small bowl condition tended to consume more popcorn (34·0 g) than participants in the large bowl condition (24·9 g; 37 % increase, d=0·5), although the statistical significance of this difference depended on whether analyses were adjusted to account for participant characteristics (e.g. gender) associated with food intake (P=0·02) or not (P=0·07). Counter to widely held belief, the use of a smaller bowl did not reduce snack food intake. Public health recommendations advising the use of smaller dishware to reduce food consumption are premature, as this strategy may not be effective.


STAG2 deficiency induces interferon responses via cGAS-STING pathway and restricts virus infection.
Cohesin is a multi-subunit nuclear protein complex that coordinates sister chromatid separation during cell division. Highly frequent somatic mutations in genes encoding core cohesin subunits have been reported in multiple cancer types. Here, using a genome-wide CRISPR-Cas9 screening approach to identify host dependency factors and novel innate immune regulators of rotavirus (RV) infection, we demonstrate that the loss of STAG2, an important component of the cohesin complex, confers resistance to RV replication in cell culture and human intestinal enteroids. Mechanistically, STAG2 deficiency results in spontaneous genomic DNA damage and robust interferon (IFN) expression via the cGAS-STING cytosolic DNA-sensing pathway. The resultant activation of JAK-STAT signaling and IFN-stimulated gene (ISG) expression broadly protects against virus infections, including RVs. Our work highlights a previously undocumented role of the cohesin complex in regulating IFN homeostasis and identifies new therapeutic avenues for manipulating the innate immunity.


High frequency jet ventilation and intermittent positive pressure ventilation. Effect of cerebral blood flow in patients after open heart surgery.
Attenuation of ventilator-synchronous pressure fluctuations of intracranial pressure has been demonstrated during high frequency ventilation in animal and human studies, but the consequences of this effect on cerebral blood flow have not been investigated in man. We compared the effects of high frequency jet ventilation and intermittent positive pressure ventilation on CBF in 24 patients investigated three hours after completion of open-heart surgery. The patients were investigated during three consecutive periods with standard sedation (morphine, pancuronium): a. IPPV; b. HFJV; c. IPPV. Partial pressure of arterial CO2 (PaCO2: 4.5-5.5 kPa) and rectal temperature (35.5 to 37.5 degrees C) were maintained constant during the study. The CBF was measured by intravenous 133Xe washout technique. The following variables were derived from the cerebral clearance of 133Xe: the rapid compartment flow, the initial slope index, ie, a combination of the rapid and the slow compartment flows, and the ratio of fast compartment flow over total CBF (FF). Compared to IPPV, HFJV applied to result in the same mean airway pressure did not produce any change in pulmonary gas exchange, mean systemic arterial pressure, and cardiac index. Similarly, CBF was not significantly altered by HFJV. However, important variations of CBF values were observed in three patients, although the classic main determinants of CBF (PaCO2, cerebral perfusion pressure, Paw, temperature) remained unchanged. Our results suggest that in patients with normal systemic hemodynamics, the effects of HFJV and IPPV on CBF are comparable at identical levels of mean airway pressure.


Prkra Mutation Alters circRNA Expression During Embryonic External Ear Development.
The changes in circRNA expression profile in the mouse external ear tissue during embryonic development to E15.5 and E17.5 can provide clues for the study of the regulation of external ear embryonic development. To understand the changes in gene regulation and expression of circRNA involved in mouse external ear embryonic development, a Prkra Little ear mouse model was used, and the changes in circRNA expression profiles were detected using next-generation sequencing. The changes in the expression of circRNA in the experimental group compared with those in the control group were identified using the find_circ and CiRi2 software, and the differentially expressed circRNAs were annotated via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The results show that the development of mouse external ear embryos is regulated by circRNA expression.


PBX3 Promotes Tumor Growth and Angiogenesis via Activation of AT1R/VEGFR2 Pathway in Papillary Thyroid Carcinoma.
PBX3 (Pre-B-cell leukemia homeobox 3) had been considered to be a multifunctional oncogene which involved in tumor growth, invasion, and metastasis in leukemia and some solid tumors. However, the contribution of PBX3 to papillary thyroid carcinoma (PTC) remains unclear. In this study, we found that PBX3 expression was significantly upregulated in PTC tissues compared to adjacent normal tissues, and high levels of PBX3 were correlated with tumor size, lymphatic metastasis, TMN stage, and poor prognosis of PTC patients. Overexpression of PBX3 in PTC cell lines promoted cell proliferation. Consistently, knockdown of PBX3 by shRNA induced cell cycle arrest at G0/G1 phase, and inhibited angiogenesis and tumor growth in vitro and in vivo. Furthermore, PBX3 promoted PTC cell proliferation and angiogenesis through activation of AT1R/VEGFR2 pathway while overexpression of AT1R and treatment with VEGFA reversed PBX3-shRNA-induced decreased phosphorylation of VEGFR2 and its downstream (ERK1/2, AKT and Src). It demonstrated that PBX3 could be used as a potential prognostic biomarker and therapeutic target for PTC.


CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies.
Unmethylated cytosine-guanine dinucleotide-containing oligodeoxynucleotides (CpG ODNs), which are synthetic agonists of Toll-like receptor 9 (TLR9), activate humoral and cellular immunity and are being developed as vaccine adjuvants to prevent or treat cancers, infectious diseases, and allergies. Free CpG ODNs have been used in many clinical trials implemented to verify their effects. However, recent research has reported that self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes demonstrate higher adjuvant effects than free CpG ODNs, owing to their improved uptake efficiency into cells expressing TLR9. Moreover, protein/peptide-CpG ODN conjugates and nanomaterial-CpG ODN complexes are able to deliver CpG ODNs and antigens (or allergens) to the same types of cells, which enables a higher degree of prophylaxis or therapeutic effect. In this review, the author describes recent trends in the research and development of CpG ODN nanomedicines containing self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes, focusing mainly on the results of preclinical and clinical studies.


Layer-by-layer-assembled microfiltration membranes for biomolecule immobilization and enzymatic catalysis.
Multilayer assemblies of polyelectrolytes, for protein immobilization, have been created within the membrane pore domain. This approach was taken for two reasons: (1) the high internal membrane area can potentially increase the amount of immobilized protein, and (2) the use of convective flow allows uniform assembly of layers and eliminates diffusional limitations after immobilization. To build a stable assembly, the first polyelectrolyte layer was covalently attached to the membrane surface and inside the pore walls. Either poly(L-glutamic acid) (PLGA) or poly(L-lysine) (PLL) was used in this step. Subsequent deposition occurs by multiple electrostatic interactions between the adsorbing polyelectrolyte [poly(allylamine) hydrochloride (PAH) or poly(styrenesulfonate) (PSS)] and the oppositely charged layer. Three-layer membranes were created: PLL-PSS-PAH or PLGA-PAH-PSS, for an overall positive or negative charge, respectively. The overall charge on both the protein and membrane plays a substantial role in immobilization. When the protein and the membrane are oppositely charged, the amount immobilized and the stability within the polyelectrolyte assembly are significantly higher than for the case when both have similar charges. After protein incorporation in the multilayer assembly, the active site accessibility was comparable to that obtained in the homogeneous phase. This was tested by affinity interaction (avidin-biotin) and by carrying out two reactions (catalyzed by glucose oxidase and alkaline phosphatase). Besides simplicity and versatility, the ease of enzyme regeneration constitutes an additional benefit of this approach.


Telomeres, Reproductive Aging, and Genomic Instability During Early Development.
Implantation rate decreases and miscarriage rate increases with advancing maternal age. The oocyte must be the locus of reproductive aging because donation of oocytes from younger to older women abrogates the effects of aging on fecundity. Nuclear transfer experiments in a mouse model of reproductive aging show that the reproductive aging phenotype segregates with the nucleus rather than the cytoplasm. A number of factors within the nucleus have been hypothesized to mediate reproductive aging, including disruption of cohesions, reduced chiasma, aneuploidy, disrupted meiotic spindles, and DNA damage caused by chronic exposure to reactive oxygen species. We have proposed telomere attrition as a parsimonious way to explain these diverse effects of aging on oocyte function. Telomeres are repetitive sequences of DNA and associated proteins, which form a loop (t loop) at chromosome ends. Telomeres prevent the blunt end of DNA from triggering a DNA damage response. Previously, we showed that experimental telomere shortening phenocopies reproductive aging in mice. Telomere shortening causes reduced synapsis and chiasma, chromosome fusions, embryo arrest and fragmentation, and abnormal meiotic spindles. Telomere length of polar bodies predicts the fragmentation of human embryos. Telomerase, the reverse transcriptase capable of reconstituting shortened telomeres, is only minimally active in oocytes and preimplantation embryos. Intriguingly, during the first cell cycles following activation, telomeres robustly elongate via a DNA double-strand break mechanism called alternative lengthening of telomeres (ALTs). Alternative lengthening of telomere takes place even in telomerase-null mice. This mechanism of telomere elongation previously had been found only in cancer cells lacking telomerase activity. We propose that ALT elongates telomeres across generations but does so at the cost of extensive genomic instability in preimplantation embryos.


Partial splenic embolization. An effective alternative to splenectomy for hypersplenism.
Splenectomy for massive splenomegaly and hypersplenism carries a significant morbidity and mortality. We have used partial splenic embolization (PSE) as an effective alternative to splenectomy. Ten PSE procedures were performed on nine patients without mortality and with minimal morbidity. The age of the patients ranged from 8 months to 32 years (mean 14 years). The causes of splenomegaly and hypersplenism included cystic fibrosis with cirrhosis (2), tyrosinemia and cirrhosis (1); thalassemia (1), hemophilia with Human Immune Deficiency Virus infection (2), chronic hepatitis with portal hypertension (1), malignant histiocytosis (1), and Wiskott-Aldrich Syndrome (1). All procedures were performed under local anesthesia with sedation. A percutaneous femoral artery approach to the splenic artery was used to deliver Ivalon sponge particles (280-800 microns) into the spleen. Splenic infarction was assessed by postembolization angiograms. All of the patients except one demonstrated improvement of hematologic parameters. In one patient, however, cytopenia improved only after a second embolization. In the total series, there was an early mean rise of 8,600/mm3 in the leukocyte count (range 2,900-14,900) and 212,000/mm3 in the platelet count (range 30,000-718,000). Follow-up ranged from 4 months to 7 years. Improvement of the blood picture has been persistent in seven of the eight patients who showed initial improvement. Transient procedural complications included fever (5), pleural effusion (2), pneumonia (1), and splenic abscess (1). One patient had paralytic ileus lasting for 10 days and one patient developed a streptococcal peritonitis 3 weeks after embolization. No patient developed pancreatitis or vascular compromise of other abdominal viscera.(ABSTRACT TRUNCATED AT 250 WORDS)


The Role of Attachment Behaviors in the Link between Relationship Satisfaction and Depression in Clinical Couples: Implications for Clinical Practice.
Using dyadic, clinical data from 104 couples in committed relationships, the purpose of this study was to determine whether relationship satisfaction was associated with depression through perceived partner attachment behaviors-accessibility, responsiveness, and engagement-for both men and women. We found that one's satisfaction in the relationship was the lens through which they viewed their partner's attachment behaviors and-women's relationship satisfaction was the lens through which her male partner viewed her attachment behaviors. Finally, women's relationship satisfaction is associated with both individuals' depression through her perceived partner's accessibility, responsiveness, and engagement. The findings from this study are important because they provide clinically relevant and mutable constructs in which clinicians can intervene at an attachment level in distressed marriages with depressed partners.


Trivalent rare-earth metal cyclic (alkyl)(amino)carbene complexes.
Coordination chemistry of cyclic (alkyl)(amino)carbene (CAAC) ligands has blossomed in recent years, exemplified by their strong σ-donating and π-accepting ability. However, trivalent rare-earth metal CAAC complexes remain elusive. By using M(CH2SiMe3)3(THF)2 (M = Sc, Y and Lu) as precursors, we synthesized mono CAAC coordinated rare-earth metal trisalkyl complexes, (RCAAC)M(CH2SiMe3)3 (R = Me and Et, M = Sc, Y and Lu). In addition, when MI3(Et2O)n (M = Y and Yb) were employed as metal precursors, bis(CAAC)-stabilized rare-earth metal triiodide complexes (MeCAAC)2MI3 (M = Y and Yb) could be obtained. All new compounds were characterized by X-ray crystallography, elemental analysis and NMR spectroscopy. Density functional theory calculations were conducted for these rare-earth metal CAAC complexes to gain insight into their electronic structures and bonding interactions. The bonding analysis unveils that the CAAC ligands act as σ donors to trivalent rare-earth metal ions and may be involved in π-bonding upon reduction.


Early response to interferon alpha treatment and long-term clinical outcome in Japanese patients with chronic HBV genotype C infection.
Genotype C of hepatitis B virus (HBV) has been shown to be associated with a poor clinical outcome and less favorable response to interferon (IFN) alpha therapy compared to genotype B. We evaluated the response to IFN alpha therapy and long-term clinical outcome in Japanese patients with chronic active HBV genotype C infection. Thirty Japanese patients with chronic active hepatitis who received natural IFN alpha therapy were followed for 2-12 years (mean 5.9 years). Twenty-four patients were treated short-term (daily for 4 weeks at a mean total dosage of 174 million units) and 6 patients were treated long-term (total of 26 weeks at a mean total dosage of 687 million units). Twelve of 30 (40%) patients had an antiviral response at 6 months after therapy. Clinical data before treatment in both responders and non-responders were comparable. Although not significant, responders tended to have younger age, a higher serum transaminase level, a lower frequency of precore mutation (G1896A) (67% vs. 92%) and a higher frequency of core promoter mutation (A1762T/G1764A) (89% vs. 58%) than non-responders. The patients treated long-term responded significantly better than those treated short-term (83% vs. 29%, P=0.026). Up to 12 years after therapy, a higher percentage of responders than non-responders had sustained clearance of HBeAg with seroconversion and normalization of transaminase concentration at the followed end point (83% vs. 17%, P<0.001). Two non-responder patients had cirrhosis after long-term follow-up. One non-responder patient died of hepatocellular carcinoma 8 years after IFN therapy; except in this patient there was no development of decompensated cirrhosis. Early responsiveness to IFN alpha therapy in Japanese patients with chronic active HBV genotype C infection improves the long-term clinical outcome.


Ionic liquids induced structural changes of bovine serum albumin in aqueous media: a detailed physicochemical and spectroscopic study.
Structural changes of a globular protein, bovine serum albumin (BSA), as a consequence of interaction with the surface active ionic liquids (ILs)-3-methyl-1-octylimidazolium chloride, [C(8)mim][Cl], and 1-butyl-3-methylimidazolium octylsulfate, [C(4)mim][C(8)OSO(3)]-have been investigated using various physicochemical and spectroscopic techniques such as tensiometry, conductometry, steady-state fluorescence, far-UV circular dichroism spectroscopy (CD), and dynamic light scattering (DLS). The interactional behavior of ILs (monomers and self-assembled structures) toward BSA in different IL concentration regimes at the air/solution interface as well as in the bulk is investigated and discussed depending upon the nature of ions of ILs. CD combined with the steady state fluorescence spectroscopy provided valuable insights into the unfolding of BSA as a consequence of IL binding. The complementary results obtained from the multitechnique approach proved very useful in drawing out the mechanism of interaction between ILs and BSA in different IL concentration regimes.


Parathyroid response to EDTA in hypoparathyroidism and in tetany.
The parathyroid response to an EDTA infusion was measured in 11 patients with hypoparathyroidism and 22 patients with normocalcaemic tetany, and compared to that of normal controls and of 23 patients with primary hyperparathyroidism. Despite comparable basal PTH values, the patients with hypoparathyroidism and the normocalcaemic patients, with tetany following thyroid surgery, responded less than normals to EDTA, while normocalcaemic patients with tetany due to psychogenic hyperventilation responded more than normals. In hypoparathyroidism, mainly three types of results were observed: no response (total hypoparathyroidism), diminished or delayed response (partial hypoparathyroidism), and discrepant results using different antisera in cases of idiopathic hypoparathyroidism, suggesting the secretion of immunologically abnormal PTH. In tetany due to psychogenic hyperventilation, parathyroid hyperreactivity might be explained by repeated stimulation through respiratory alkalosis. Although the EDTA test rarely improved the diagnostic accuracy of basal PTH measurements in primary hyperparathyroidism, it was useful for differentiating between latent hypoparathyroidism and tetany due to psychogenic hyperventilation, both presenting with normal plasma calcium.


Equipartition of rotational and translational energy in a dense granular gas.
Experiments quantifying the rotational and translational motion of particles in a dense, driven, 2D granular gas floating on an air table reveal that kinetic energy is divided equally between the two translational and one rotational degrees of freedom. This equipartition persists when the particle properties, confining pressure, packing density, or spatial ordering are changed. While the translational velocity distributions are the same for both large and small particles, the angular velocity distributions scale with the particle radius. The probability distributions of all particle velocities have approximately exponential tails. Additionally, we find that the system can be described with a granular Boyle's law with a van der Waals-like equation of state. These results demonstrate ways in which conventional statistical mechanics can unexpectedly apply to nonequilibrium systems.


SARS-CoV-2 Infection and Placental Pathology.
Placental pathophysiology in SARS-CoV-2 infection can help researchers understand more about the infection and its impact on the maternal/neonatal outcomes. This brief review provides an overview about some aspects of the placental pathology in SARS-CoV-2 infection. In total, 11 papers were included. The current literature suggests that there are no specific histopathological characteristics in the placenta related to SARS-CoV-2 infection, but placentas from infected women are more likely to show findings of maternal and/or fetal malperfusion. The most common findings in placentas from infected women were fibrin deposition and intense recruitment of inflammatory infiltrates. The transplacental transmission of this virus is unlikely to occur, probably due to low expression of the receptor for SARS-CoV-2 in placental cell types. Further studies are needed to improve our knowledge about the interaction between the virus and the mother-fetus dyad and the impact on maternal and neonatal/fetal outcomes.


Polyhydroxylated steroids from the bamboo coral Isis hippuris.
In previous studies on the secondary metabolites of the Taiwanese octocoral Isis hippuris, specimens have always been collected at Green Island. In the course of our studies on bioactive compounds from marine organisms, the acetone-solubles of the Taiwanese octocoral I. hippuris collected at Orchid Island have led to the isolation of five new polyoxygenated steroids: hipposterone M-O (1-3), hipposterol G (4) and hippuristeroketal A (5). The structures of these compounds were determined on the basis of their spectroscopic and physical data. The anti-HCMV (human cytomegalovirus) activity of 1-5 and their cytotoxicity against selected cell lines were evaluated. Compound 2 exhibited inhibitory activity against HCMV, with an EC(50) value of 6.0 μg/mL.


Physician marriages.
A questionnaire study of physicians' ratings of various aspects of their marriage, was sent to 100 randomly selected physicians in Ramsey County (St. Paul, Minnesota). Eighty per cent of the sample responded. All 80 had been married at least once. There were fewer divorces reported compared with the general population. The group of 80 rated their marriages above average. Spouses who were considered extroverted correlated very significantly with a good marriage rating. The educational level of the spouse did not correlate with the marriage rating. Working long hours was not associated with poor marriage ratings or divorce. No significant relationship was revealed in examining the study variables for grouped medical specialties.


Altered electroencephalography functional connectivity in depression during the emotional face-word Stroop task.
Depression is a severe mental disorder. However, the neural mechanisms underlying affective interference (difficulties in directing attention away from negative distractors) in depression patients are still not well-understood. In particular, the connections between brain regions remain unclear. Using the emotional face-word Stroop task, we aimed to reveal the altered electroencephalography (EEG) functional connectivity in patients with depression, using concepts from event-related potentials (ERPs) and time series clustering. In this study, the EEG signals of ten healthy participants and ten depression patients were collected from a 64-sensor cap. Subsequently, EEG signals were segmented into temporal windows corresponding to the ERPs. For each duration, the dynamic time warping algorithm was used to calculate the similarities between EEG signals from different electrodes, and differences of these similarities were compared between the groups. Finally, hierarchical clustering was used to identify functionally connected regions and examine changes in depression. It was observed that during the time interval of 400-600 ms (N450 components), depression patients had more long-range connections than did healthy control patients and exhibited abnormal functional connectivity via the superior and middle frontal gyrus, specifically, the dorsolateral prefrontal cortex (DL-PFC, Brodmann's area 8 and 9), which is related to the control and resolution of affective interference. Moreover, the functionally connected region of depression patients was much larger than that of healthy participants, which is caused by brain resource reorganization. These findings thus provide new insights into the neural mechanisms of depression and further identify the DL-PFC and connections between certain electrodes as quantitative indicators of depression.


Hearing Surveillance Chart--a tool for tracking serial audiometry results and predicting future hearing impairment.
High frequency hearing loss is related to noise-induced deafness. We decided to develop a method of recording serial audiogram results that would provide an accessible overview of trends for an individual. Health & Safety Executive (HSE) warning and referral levels for high frequency hearing losses were plotted against age. A third line was added to indicate a level of 'significant' handicap. This graph is inserted in each individual's hearing surveillance record. High frequency hearing loss results are plotted for each ear over time. Someone with known hearing loss but minimal deterioration will exceed the HSE warning level at every review, whereas someone with perfect hearing suffering a significant deterioration may not exceed the warning level initially. The latter should be of more concern to their current employer.


Circulating levels of 3-hydroxymyristate, a direct quantification of endotoxaemia in noninfected cirrhotic patients.
The quantification of lipopolysaccharide (LPS) in biological fluids is challenging. We aimed to measure plasma LPS concentration using a new method of direct quantification of 3-hydroxymyristate (3-HM), a lipid component of LPS, and to evaluate correlations between 3-HM and markers of liver function, endothelial activation, portal hypertension and enterocyte damage. Plasma from 90 noninfected cirrhotic patients (30 Child-Pugh [CP]-A, 30 CP-B, 30 CP-C) was prospectively collected. The concentration of 3-HM was determined by high-performance liquid chromatography coupled with mass spectrometry. 3-HM levels were higher in CP-C patients (CP-A/CP-B/CP-C: 68/70/103 ng/mL, P = 0.005). Patients with severe acute alcoholic hepatitis (n = 16; 113 vs 74 ng/mL, P = 0.012), diabetic patients (n = 22; 99 vs 70 ng/mL, P = 0.028) and those not receiving beta blockers (n = 44; 98 vs 72 ng/mL, P = 0.034) had higher levels of 3-HM. We observed a trend towards higher baseline levels of 3-HM in patients with hepatic encephalopathy (n = 7; 144 vs 76 ng/mL, P = 0.45) or SIRS (n = 10; 106 vs 75 ng/mL, P = 0.114). In multivariate analysis, high levels of 3-HM were associated with CP (OR = 4.39; 95%CI = 1.79-10.76) or MELD (OR = 8.24; 95%CI = 3.19-21.32) scores. Patients dying from liver insufficiency (n = 6) during a 12-month follow-up had higher baseline levels of 3-HM (106 vs 75 ng/mL, P = 0.089). In noninfected cirrhotic patients, 3-HM arises more frequently with impairment of liver function, heavy alcohol consumption, diabetic status, nonuse of beta blockers and a trend towards poorer outcome is also observed. The direct mass measurement of LPS using 3-HM appears reliable to detect transient endotoxaemia and promising to manage the follow-up of cirrhotic patients.


Plague in Mongolia.
Mongolia is a country of Central Asia that occupies 1,564,116 km(2) and has a population of 2.7 million people. The geography of Mongolia is varied and has a continental climate. Plague, caused by the bacterium Yersinia pestis, is enzootic in wild rodent populations over large rural areas of Mongolia. Natural plague foci have occurred over 28.3% of Mongolia, and 47.1% of these foci are highly active. Highly active plague foci exist mainly in the western part of Mongolia. A total of 27% of all plague cultures were isolated from ectoparasites of 12 species of endemic mammals and 1 species of bird. Most plague cultures isolated from ectoparasites of mammals were from fleas (91.5%). The majority of cultures isolated from fleas were from marmot fleas (64.5% of all fleas). The marmot flea (Oropsylla silantiewi) is considered the primary vector of plague. Human cases of plague have been recorded in Mongolia since 1897 and more than 3000 plague cultures were isolated from natural foci. Plague foci occur between 50 degrees 00-43 degrees 00 longitude and 88 degrees 00-120 degrees 00 latitude and at altitudes between 640 and 3500 m.


Longitudinal associations of long-term exposure to ultrafine particles with blood pressure and systemic inflammation in Puerto Rican adults.
Few longitudinal studies have examined the association between ultrafine particulate matter (UFP, particles < 0.1 μm aerodynamic diameter) exposure and cardiovascular disease (CVD) risk factors. We used data from 791 adults participating in the longitudinal Boston Puerto Rican Health Study (Massachusetts, USA) between 2004 and 2015 to assess whether UFP exposure was associated with blood pressure and high sensitivity C-reactive protein (hsCRP, a biomarker of systemic inflammation). Residential annual average UFP exposure (measured as particle number concentration, PNC) was assigned using a model accounting for spatial and temporal trends. We also adjusted PNC values for participants' inhalation rate to obtain the particle inhalation rate (PIR) as a secondary exposure measure. Multilevel linear models with a random intercept for each participant were used to examine the association of UFP with blood pressure and hsCRP. Overall, in adjusted models, an inter-quartile range increase in PNC was associated with increased hsCRP (β = 6.8; 95% CI = - 0.3, 14.0%) but not with increased systolic blood pressure (β = 0.96; 95% CI = - 0.33, 2.25 mmHg), pulse pressure (β = 0.70; 95% CI = - 0.27, 1.67 mmHg), or diastolic blood pressure (β = 0.55; 95% CI = - 0.20, 1.30 mmHg). There were generally stronger positive associations among women and never smokers. Among men, there were inverse associations of PNC with systolic blood pressure and pulse pressure. In contrast to the primary findings, an inter-quartile range increase in the PIR was positively associated with systolic blood pressure (β = 1.03; 95% CI = 0.00, 2.06 mmHg) and diastolic blood pressure (β = 1.01; 95% CI = 0.36, 1.66 mmHg), but not with pulse pressure or hsCRP. We observed that exposure to PNC was associated with increases in measures of CVD risk markers, especially among certain sub-populations. The exploratory PIR exposure metric should be further developed.


A New System for Periprosthetic Fracture Stabilization-A Biomechanical Comparison.
In recent years, an increase in periprosthetic femur fractures has become apparent due to the increased number of hip replacements. In the case of Vancouver type B1 fractures, locking plate systems offer safe procedures. This study compared the distal lateral femur plate (LOQTEQ®, aap Implantate AG) with a standard L.I.S.S. LCP® (DePuy Synthes) regarding their biomechanical properties in fixation of periprosthetic femur fractures after hip arthroplasty. We hypothesized that the new LOQTEQ system has superior stability and durability in comparison. Eighteen artificial left femurs were randomized in two groups (Group A: LOQTEQ®; Group B: L.I.S.S. LCP®) and tested until failure. Failure was defined as 10° varus deformity and catastrophic implant failure (loosening, breakage, progressive bending). Axial stiffness, loads of failure, cycles of failure, modes of failure were recorded. The axial stiffness in Group A with 73.4 N/mm (SD +/- 3.0) was significantly higher (p = 0.001) than in Group B (40.7 N/mm (SD +/- 2.8)). Group A resists more cycles than Group B until 10° varus deformity. Catastrophic failure mode was plate breakage in Group A and bending in Group B. In conclusion, LOQTEQ® provides higher primary stability and tends to have higher durability.


High-Efficiency Ion Enrichment inside Ultra-Short Carbon Nanotubes.
The ion-enrichment inside carbon nanotubes (CNTs) offers the possibility of applications in water purification, ion batteries, memory devices, supercapacitors, field emission and functional hybrid nanostructures. However, the low filling capacity of CNTs in salt solutions due to end caps and blockages remains a barrier to the practical use of such applications. In this study, we fabricated ultra-short CNTs that were free from end caps and blockages using ball milling and acid pickling. We then compared their ion-enrichment capacity with that of long CNTs. The results showed that the ion-enrichment capacity of ultra-short CNTs was much higher than that of long CNTs. Furthermore, a broad range of ions could be enriched in the ultra-short CNTs including alkali-metal ions (e.g., K+), alkaline-earth-metal ions (e.g., Ca2+) and heavy-metal ions (e.g., Pb2+). The ultra-short CNTs were much more unobstructed than the raw long CNTs, which was due to the increased orifice number per unit mass of CNTs and the decreased difficulty in removing the blockages in the middle section inside the CNTs. Under the hydrated-cation-π interactions, the ultra-short CNTs with few end caps and blockages could highly efficiently enrich ions.


Altered Left Ventricular Myocardial Deformation in Young Women With Borderline Personality Disorder: An Echocardiographic Study.
Borderline personality disorder (BPD) is characterized by intense mood swings, impulsivity, self-injurious behavior, poor anger control, fear of abandonment, and unstable interpersonal relationships. BPD is also associated with a heightened risk of cardiovascular disease, whereby the underlying mechanisms are insufficiently understood. Accordingly, the present study set out to examine whether individuals with BPD would show abnormal myocardial deformation and to explore the role of potential risk factors, including maladaptive stress responsivity, childhood trauma, and current stress exposure. Fifty female patients diagnosed with BPD and 50 controls matched for sex and age underwent echocardiography to determine the global longitudinal strain (GLS) of the left ventricle. In addition, childhood trauma, chronic stress, and "allostatic load" were determined, as well as borderline symptom severity and common risk factors for cardiovascular disease. Aside from a significantly greater GLS in BPD patients, a multivariable regression analysis revealed that allostatic load (β = 0.225, p = .048) was significantly associated with GLS, with childhood trauma (β = 0.279, p = .062) approaching significance. Conversely, smoking (p = .867), chronic stress (p = .193), and borderline symptom severity (p = .342) were not associated with GLS, even though bivariate correlations were significant. Somatically healthy women with BPD display subtle signs of increased GLS, which is associated with allostatic load as an indicator of the "wear-and-tear" of the body. The association between childhood trauma with GLS was of similar strength but did not reach the threshold for statistical significance. This finding may support the need for primary prevention of somatic consequences of maladaptive stress responsivity in psychiatric patients.


Blood flow and blood pressure in fingers in generalized scleroderma.
Sympathetic hyperactivity cannot be implicated in the peripheral vascular disturbances in patients with generalized scleroderma. On the contrary, there seems to be some evidence for a sympathetic hypoactivity in these patients and there seems to be good reason to abandon sympathectomy in the treatment. Vasodilator drugs can be hazardous in late-stage scleroderma due to the possibility of redistribution of blood flow and a decrease in systemic blood pressure. Even a small decrease in systemic blood pressure severely affects blood flow in the low pressure vascular bed found in fingertips of patients with generalized scleroderma.


CoQ10 and Resveratrol Effects to Ameliorate Aged-Related Mitochondrial Dysfunctions.
Mitochondria participate in the maintenance of cellular homeostasis. Firstly, mitochondria regulate energy metabolism through oxidative phosphorylation. In addition, they are involved in cell fate decisions by activating the apoptotic intrinsic pathway. Finally, they work as intracellular signaling hubs as a result of their tight regulation of ion and metabolite concentrations and other critical signaling molecules such as ROS. Aging is a multifactorial process triggered by impairments in different cellular components. Among the various molecular pathways involved, mitochondria are key regulators of longevity. Indeed, mitochondrial deterioration is a critical signature of the aging process. In this scenario, we will focus specifically on the age-related decrease in CoQ levels, an essential component of the electron transport chain (ETC) and an antioxidant, and how CoQ supplementation could benefit the aging process. Generally, any treatment that improves and sustains mitochondrial functionality is a good candidate to counteract age-related mitochondrial dysfunctions. In recent years, heightened attention has been given to natural compounds that modulate mitochondrial function. One of the most famous is resveratrol due to its ability to increase mitochondrial biogenesis and work as an antioxidant agent. This review will discuss recent clinical trials and meta-analyses based on resveratrol and CoQ supplementation, focusing on how these compounds could improve mitochondrial functionality during aging.


Siglec-10 expression is up-regulated in activated human CD4+ T cells.
Most sialic acid-binding immunoglobulin-like lectins (Siglecs) suppress immune cell function but are expressed at low levels on human T cells. We found that soluble CD52 inhibited T cell signalling by ligating Siglec-10, but the presence of Siglec-10 on human T cells has been questioned. To address this concern, we examined the expression of Siglec-10 at the RNA and protein level in human CD4+ T cells. Analysis by RNAseq, qPCR and flow cytometry demonstrated that, in contrast to other Siglecs, after activation of CD4+ T cells Siglec-10 was selectively upregulated in a subset of cells also high for CD52 expression. This observation is consistent with a homeostatic role for Siglec-10 in human CD4+ T cells.


Long term posttraumatic growth after breast cancer: prevalence, predictors and relationships with psychological health.
This study evaluated the prevalence and predictors of long term posttraumatic growth (PTG) after breast cancer, and relationships of PTG with psychological health in a random sample of 307 currently disease-free women 5-15 years after diagnosis. This cross-sectional study reveals long term posttraumatic growth scores comparable to those found in shorter term studies. Prevalence of a better appreciation of life is especially noteworthy. With the exception of perceived current sequelae of disease associated in a somewhat curvilinear fashion with PTG, demographic and medical variables are poor predictors of the issue. On the contrary, dispositional positive affectivity and adaptative coping of positive, active, relational, religious and to some extent denial coping have a strong effect on growth. Finally, PTG is slightly associated with mental quality of life and happiness. Findings are discussed in the light of posttraumatic growth theory.


Contribution of Mobile Group II Introns to Sinorhizobium meliloti Genome Evolution.
Mobile group II introns are ribozymes and retroelements that probably originate from bacteria. Sinorhizobium meliloti, the nitrogen-fixing endosymbiont of legumes of genus Medicago, harbors a large number of these retroelements. One of these elements, RmInt1, has been particularly successful at colonizing this multipartite genome. Many studies have improved our understanding of RmInt1 and phylogenetically related group II introns, their mobility mechanisms, spread and dynamics within S. meliloti and closely related species. Although RmInt1 conserves the ancient retroelement behavior, its evolutionary history suggests that this group II intron has played a role in the short- and long-term evolution of the S. meliloti genome. We will discuss its proposed role in genome evolution by controlling the spread and coexistence of potentially harmful mobile genetic elements, by ectopic transposition to different genetic loci as a source of early genomic variation and by generating sequence variation after a very slow degradation process, through intron remnants that may have continued to evolve, contributing to bacterial speciation.


Magnetic resonance imaging: fundamental safety issues.
Medical practitioners have a variety of imaging modalities at their disposal. The exquisite soft tissue delineation available with magnetic resonance imaging (MRI) has resulted in the rising utilization of this particular modality. Increasingly, physical therapists around the world are actively involved in not only referring patients with musculoskeletal conditions for MRI but also in the acquisition of MRI data in both the clinical and research arenas. The MRI process involves the use of a very strong static magnetic field, time-varying (gradient) fields, and radiofrequency energy. To ensure the well-being of patients, staff, and visitors, an understanding of the primary hazards of this environment and the rigorous safety procedures that must be followed is imperative to the clinician. This paper describes the basic components of an MRI system, discusses various MRI safety issues, and presents the screening procedure necessary prior to using MRI. Primary hazards associated with the imaging process are also reviewed. J Orthop Sports Phys Ther 2011;41(11):820-828. doi:10.2519/jospt.2011.3906.


Investigating Whether Bereavement by Suicide and Other Unnatural Causes Has a Deterrent Effect on Alcohol or Drug Use in Young Adults.
Bereavement by suicide and other unnatural causes is associated with suicide but evidence regarding risk of substance misuse is inconsistent. This may be due to heterogeneity in patterns of alcohol or drug use after traumatic bereavement; some increasing use to cope with the loss and others reducing use. To highlight the problems of focussing on diagnostic thresholds when investigating substance use after traumatic loss, we aimed to test whether people bereaved by suicide or other unnatural causes are more likely to reduce or stop their substance use than people bereaved by sudden natural causes. Using multivariable logistic regression and data from an online survey of 1854 UK-based bereaved adults, we tested the association between bereavement by suicide and other unnatural causes and post-bereavement reduction/cessation in (i) alcohol and (ii) drug use. There were no group differences in the proportions who reduced/stopped alcohol use, but a significantly greater proportion of people bereaved by sudden unnatural causes reduced/stopped drug use post-bereavement than people bereaved by sudden natural causes (AOR = 2.61; 95% CI = 1.44-4.71; p = 0.001; 4.1% versus 1.7%). In sub-group analyses this applied separately to people bereaved by suicide and non-suicide unnatural causes. Research into post-bereavement substance use should accommodate apparent divergent sub-diagnostic patterns.


Realization of quantum error correction.
Scalable quantum computation and communication require error control to protect quantum information against unavoidable noise. Quantum error correction protects information stored in two-level quantum systems (qubits) by rectifying errors with operations conditioned on the measurement outcomes. Error-correction protocols have been implemented in nuclear magnetic resonance experiments, but the inherent limitations of this technique prevent its application to quantum information processing. Here we experimentally demonstrate quantum error correction using three beryllium atomic-ion qubits confined to a linear, multi-zone trap. An encoded one-qubit state is protected against spin-flip errors by means of a three-qubit quantum error-correcting code. A primary ion qubit is prepared in an initial state, which is then encoded into an entangled state of three physical qubits (the primary and two ancilla qubits). Errors are induced simultaneously in all qubits at various rates. The encoded state is decoded back to the primary ion one-qubit state, making error information available on the ancilla ions, which are separated from the primary ion and measured. Finally, the primary qubit state is corrected on the basis of the ancillae measurement outcome. We verify error correction by comparing the corrected final state to the uncorrected state and to the initial state. In principle, the approach enables a quantum state to be maintained by means of repeated error correction, an important step towards scalable fault-tolerant quantum computation using trapped ions.


Fast neurotransmitter identity of MCH neurons: Do contents depend on context?
Hypothalamic melanin-concentrating hormone (MCH) neurons participate in many fundamental neuroendocrine processes. While some of their effects can be attributed to MCH itself, others appear to depend on co-released neurotransmitters. Historically, the subject of fast neurotransmitter co-release from MCH neurons has been contentious, with data to support MCH neurons releasing GABA, glutamate, both, and neither. Rather than assuming a position in that debate, this review considers the evidence for all sides and presents an alternative explanation: neurochemical identity, including classical neurotransmitter content, is subject to change. With an emphasis on the variability of experimental details, we posit that MCH neurons may release GABA and/or glutamate at different points according to environmental and contextual factors. Through the lens of the MCH system, we offer evidence that the field of neuroendocrinology would benefit from a more nuanced and dynamic interpretation of neurotransmitter identity.


Prevalence and Genotype Distribution of Hepatitis C Virus Infection among Patients with Type 2 Diabetes Mellitus.
This study was conducted to determine the prevalence and genotype distribution of hepatitis C virus (HCV) infection among patients with type 2 diabetes mellitus (DM). We included 556 consecutive patients with confirmed type 2 DM attending the Diabetic Clinic of the Bushehr University of Medical Sciences and 733 nondiabetic subjects as controls. Serum levels of fasting blood sugar (FBS), alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TCH), and triglycerides (TG) were measured by enzymatic colorimetric methods, and the presence of anti-HCV antibodies was determined by enzyme-linked immunosorbent assay. Semi-nested reverse transcriptase-polymerase chain reaction (RT-PCR) followed by sequencing was performed on all anti-HCV-seropositive samples. Data were analyzed using the Statistical Package for the Social Sciences 17, and descriptive statistics, χ2 test, Fisher exact test, and the Student t test were used for analysis. The seroprevalence of HCV in the diabetic patients was 1.98% (11/556), which was higher than HCV prevalence among the nondiabetic controls (4/733, 0.54%) (p = 0.032). No significant differences in ALT, AST, FBS, TG, and TCH levels were found between the HCV-seropositive and HCV-seronegative diabetic patients, although HCV-seropositive diabetic patients tended to have higher ALT, AST, and TCH levels, but lower TG and FBS levels than HCV-seronegative patients. In logistic regression analysis, only AST levels were significantly associated with HCV seropositivity among diabetic patients. The AST level of 41-80 IU/L was the only significant predictive variable for HCV seropositivity in the diabetic patients (odds ratio, 4.89; 95% CI: 1.06-22.49; p = 0.041). Of the 11 HCV-seropositive diabetic patients, 10 (91%) had HCV viremia with genotype 3a. Patients with type 2 DM had a higher prevalence of HCV infection than controls, and HCV seropositivity was independent of biochemical parameters.


[Diarrhea and vaccines: current developments].
Diarrhoea is a main concern for travellers, populations of developing countries and children. Causative pathogens are numerous. An efficient vaccine against cholera is available, also offering a 50% cross-protection against E. Coli enterotoxin (ETEC), however its efficacy is only 23% against all-causes traveller's diarrhoea. Rotavirus can be responsible for severe diarrhoea in infants but rarely causes traveller's diarrhoea. Two new vaccines being under development appear effective and well-tolerated but too expensive for developing countries which most need them. To date, the live oral Ty21a vaccine remains frequently prescribed in Switzerland, with limited indications and suboptimal efficacy. A new oral vaccine is under development.


Novel bisaryl substituted thiazoles and oxazoles as highly potent and selective peroxisome proliferator-activated receptor delta agonists.
The discovery, synthesis, and optimization of compound 1 from a high-throughput screening hit to highly potent and selective peroxisome proliferator-activated receptor delta (PPARdelta) agonists are reported. The synthesis and structure-activity relationship in this series are described in detail. On the basis of a general schematic PPAR pharmacophore model, scaffold 1 was divided into headgroup, linker, and tailgroup and successively optimized for PPAR activation using in vitro PPAR transactivation assays. A (2-methylphenoxy)acetic acid headgroup, a flexible linker, and a five-membered heteroaromatic center ring with two hydrophobic aryl substituents were required for efficient and selective PPARdelta activation. The fine-tuning of these aryl substituents led to an array of highly potent and selective compounds such as compound 38c, displaying an excellent pharmacokinetic profile in mouse. In an in vivo acute dosing model, selected members of this array were shown to induce the expression of pyruvate dehydrogenase kinase-4 (PDK4) and uncoupling protein-3 (UCP3), genes that are known to be involved in energy homeostasis and regulated by PPARdelta in skeletal muscle.


Atg1-mediated Atg11 phosphorylation is required for selective autophagy by regulating its association with receptor proteins.
Atg11 is an adaptor protein required for the induction of selective autophagy via receptor binding. However, our understanding of the molecular mechanisms by which it regulates selective autophagy remains incomplete. Here, we show that Atg11 is phosphorylated by Atg1. Rapamycin treatment or starvation conditions induced slower electrophoretic mobility of Atg11 in an Atg1 kinase activity-dependent manner. Through in vitro kinase assays combined with mutagenesis, we determined that Atg1 phosphorylates S949, S1057, and S1064 residues in CC4 domain of Atg11. Replacing the three residues with alanine suppressed the cleavage of selective autophagy substrates for the cytoplasm-to-vacuole targeting (Cvt) pathway, mitophagy, reticulophagy, and pexophagy. The Atg11 mutant was defective in binding to related selective autophagy receptors. These results demonstrate a previously unknown function of Atg1 in regulation of selective autophagy via Atg11 phosphorylation.Abbreviations: AMPK: AMP-activated protein kinase; ATG: autophagy-related; Cvt: cytoplasm-to-vacuole targeting; FUNDC1: FUN14 domain-containing protein 1; GFP: green fluorescent protein; MTOR: mechanistic target of rapamycin kinase; PAS: phagophore assembly site; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PRKAC/PKA: protein kinase cAMP-activated; SD-G: glucose starvation; SD-N: nitrogen starvation; ULK1: unc-51 like autophagy activating kinase 1; λ-PPase: lambda protein phosphatase.


Investigation of the relationships between immune-mediated inhibition of mycobacterial growth and other potential surrogate markers of protective Mycobacterium tuberculosis immunity.
Tuberculosis (TB) vaccine development is hindered by the lack of clear surrogate markers of protective human immunity to Mycobacterium tuberculosis. This study evaluated the hypothesis that immune-mediated inhibition of mycobacterial growth would more directly correlate with protective TB immunity than other immunologic responses. Bacille Calmette-Guérin (BCG) vaccination, known to induce partial protection against TB, was used as a model system to investigate mechanistic relationships among different parameters of antigen-specific immunity. Effects of primary and booster intradermal BCG vaccinations were assessed in 3 distinct assays of mycobacterial inhibition. Correlations between vaccine-induced growth inhibition and other immune responses were analyzed. BCG significantly enhanced all antigen-specific responses. Peak responses occurred at 2 months after boosting. Statistical analyses suggested that each assay measured unique aspects of mycobacterial immunity. Despite previous evidence that type 1 immune responses are essential for TB immunity, interferon-gamma production did not correlate with mycobacterial inhibition. These results have important implications for TB vaccine development.


A prospective observational assessment of Surgical Safety Checklist use in Brasov Children's Hospital, barriers to implementation and methods to improve compliance.
The WHO surgical checklist is a universal tool which has been shown to reduce surgical morbidity and mortality and improve patient safety; however, simply implementing a checklist in a hospital may not lead to its utilisation. We aim to evaluate completion of this checklist, and to investigate problems in compliance and methods for improving these. In July 2015 data was recorded regarding compliance with each of the components of the Surgical Safety Checklist (SSC) in a Children's Hospital in Brasov. 40 surgeries were observed over 10 days, information was gathered as regards to the surgical speciality, the number of surgeries per day, the number of theatre staff present and whether it was elective or emergency. At the end of the 10 days questionnaires were given to 15 staff members to ask their opinions regarding the surgical checklist. Data analysis was performed using a chi-squared with p < 0.05 determining statistical significance. None of the checklists in the patient files were filled in; however, components of the SSC were completed, with an average of 55% of the checklist being performed. The percentage of the SSC completed was not statistically significant with different numbers of staff, theatre numbers of the day, speciality and whether it was elective or emergency. The success of the Surgical Safety Checklist implementation is dependent on the training of staff to improve knowledge and compliance. It cannot be assumed that the introduction of a checklist will automatically lead to improved outcomes and communication with staff is essential in order to improve and ensure compliance.


The use of therapist self-disclosure: clinical psychology trainees' experiences.
This qualitative study examined clinical psychology trainees' experiences of using, or not using, therapist self-disclosure and their experience of training and supervision on this issue. Fourteen trainees were interviewed and their accounts analyzed using interpretative phenomenological analysis, yielding nine themes organized into two domains. The first domain ("the decision in the moment") concerned participants' struggle with decision making about disclosure; the second ("the developing therapist") reflected their evolving ideas about disclosure over training and within the wider philosophical context of therapy. The dilemmas surrounding disclosure seemed to distill some central issues associated with participants' developing professional therapist identity. Working out one's position on self-disclosure is a challenge that trainee therapists may require support in mastering.


Precise Brain-shift Prediction by New Combination of W-Net Deep Learning for Neurosurgical Navigation.
Brain tissue deformation during surgery significantly reduces the accuracy of image-guided neurosurgeries. We generated updated magnetic resonance images (uMR) in this study to compensate for brain shifts after dural opening using a convolutional neural network (CNN). This study included 248 consecutive patients who underwent craniotomy for initial intra-axial brain tumor removal and correspondingly underwent preoperative MR (pMR) and intraoperative MR (iMR) imaging. Deep learning using CNN to compensate for brain shift was performed using the pMR as input data, and iMR obtained after dural opening as the ground truth. For the tumor center (TC) and the maximum shift position (MSP), statistical analysis using the Wilcoxon signed-rank test was performed between the target registration error (TRE) for the pMR and iMR (i.e., the actual amount of brain shift) and the TRE for the uMR and iMR (i.e., residual error after compensation). The TRE at the TC decreased from 4.14 ± 2.31 mm to 2.31 ± 1.15 mm, and the TRE at the MSP decreased from 9.61 ± 3.16 mm to 3.71 ± 1.98 mm. The Wilcoxon signed-rank test of the pMR TRE and uMR TRE yielded a p-value less than 0.0001 for both the TC and MSP. Using a CNN model, we designed and implemented a new system that compensated for brain shifts after dural opening. Learning pMR and iMR with a CNN demonstrated the possibility of correcting the brain shift after dural opening.


Relationship between muscle strength and fall episodes among the elderly: the Yilan study, Taiwan.
Fall episodes are not unusual among community residents, especially the elderly, and lower muscle strength is an important issue to address in order to prevent falls. A community health survey was conducted in a suburban area of Taiwan, and 1067 older adults were selected for enrollment in the present study. All the enrolled subjects had been visited at their homes; the subjects' strength of both hands and muscle mass of both legs were measured and well-established questionnaires were finished by certificated paramedic staffs. The incidence of fall episodes in the previous 1 year in the Yilan elderly population was 15.1%, and the female predominance was significant. A significantly higher prevalence of cataracts was found in group who experienced a fall in the past year (64% vs. 54.9% in the non-fall group). Mild or more severe dementia was much more prevalent in the group who experienced a recent fall (33.8% vs. 25.7% in the non-fall group). The strength of both hands tested as the physical function was 17.6 ± 8.0 kg in the recent fall group, significantly weaker than that in the non-fall group (20.7 ± 8.7 kg). Multivariate regression analysis revealed a greater weekly exercise duration and greater strength of both hands reduced the occurrence of falls among the whole and the female population. The standardized effect sizes of hand grip strength between both groups, not trivial, were 0.29 and 0.37 for the total population and the female subpopulation respectively. Less weekly exercise duration and weaker muscle strength were f ound to be independent risk factors of fall episode(s) in an elderly Taiwanese population, especially in the female sub-population. Muscle strength, measured by average of both hands grip strength, was the most significantly factor of one-year fall episode(s) accessed retrospectively.


Protein adsorption and zeta potentials of a biphasic calcium phosphate ceramic under various conditions.
An investigation on the relationship between protein adsorption and zeta potentials of a biphasic calcium phosphate (BCP) ceramic was carried out. Zeta potentials of the BCP ceramic particles were measured at various aqueous solutions. Bovine serum album (BSA) and its competitive adsorption with lysozyme (LSZ) on BCP were investigated using conventional protein adsorption and polyacrylamide gel electrophoresis (PAGE) methods. The results showed that zeta potential and the amount of adsorbed BSA were both influenced by pH, ionic strength, Ca2+ and PO4(3-) concentrations in the buffers. The variation tendencies of BSA adsorption were consistent with that of zeta potentials to some extent. The co-adsorption of BSA and LSZ on BCP was confirmed by the PAGE gel pattern. The semi-quantitative analysis for the detected protein bands proved that LSZ had higher affinity for BCP than BSA and would preferentially bind to the surface. Electrostatic interaction played an important role in protein adsorption on the surface of the BCP ceramic particles.


Role of integrated 18-fluorodeoxyglucose position emission tomography-computed tomography in patients surveillance after multimodality therapy of malignant pleural mesothelioma.
To investigate the role of 18-fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG-PET-CT) in the surveillance of patients after multimodality treatment of malignant pleural mesothelioma. Retrospective study of patients who had chemotherapy, radical surgery, extrapleural pneumonectomy or pleurectomy/decortication, and radiotherapy for mesothelioma in our unit. PET-CT was performed after multimodality therapy to evaluate response to treatment or when disease recurrence was suspected. 18-FDG-PET scans were acquired from skull base to upper thigh with low-dose CT scans for attenuation correction and image fusion. Forty-four patients had extrapleural pneumonectomy (21) or pleurectomy/decortication (23) between January 2004 and July 2008. Twenty-five patients had PET-CT performed after multimodality therapy. This was performed in 11 patients in whom disease recurrence was suspected at a median of 9 (range, 6-16) months after treatment. PET-CT correctly diagnosed recurrent disease in eight patients and missed microscopic recurrence in one. Surveillance PET-CT was performed in 14 asymptomatic patients at a median of 11 (range, 7-13) months after treatment. It showed unsuspected recurrences in four patients. The standard uptake value max of recurrent mesothelioma was 8.9 +/- 4.0 (4-18.4). PET-CT had a sensitivity of 94%, a specificity of 100%, and the positive and negative predictive values of 100 and 88%, respectively. 18-FDG-PET-CT is useful in diagnosing disease recurrence after multimodality therapy for malignant pleural mesothelioma. We propose a prospective study to fully assess its value in this group of patients.


A dissolving and glucose-responsive insulin-releasing microneedle patch for type 1 diabetes therapy.
Diabetes and its complications have become crucial public health challenges worldwide. In this study, we aim to develop a dissolving and glucose-responsive insulin-releasing microneedle (MN) patch system, for minimally invasive and glucose-responsive insulin delivery for type 1 diabetes therapy. The MNs were composed of dissolving and biodegradable gelatin and starch materials, which encapsulated glucose-responsive insulin-releasing gold nanocluster (AuNC) nanocarriers. The fabricated MNs had a complete and uniform structure, consisting of an array of 11 × 11 conical needles, with a needle height of 756 μm, a bottom diameter of 356 μm, a tip diameter of 10 μm, and a tip-to-tip distance of 591 μm. The encapsulated AuNC nanocarriers as additives in the MNs enhanced the mechanical strength of the MNs, and facilitated the penetration of the MNs into the skins of mice. Moreover, the AuNC nanocarrier drugs in the MNs enabled MN patches with a glucose-responsive insulin releasing behavior. With one transdermal application of MN patches on the dorsal skin of mice, the MN patches effectively regulated the BG levels of mice in normoglycemic ranges for 1 to 2 days, and effectively alleviated the diabetic symptoms in type 1 diabetic mice. This dissolving and glucose-responsive insulin-releasing MN patch system realized a closed-loop administration of insulin with minimal invasion, providing great potential applications for type 1 diabetes therapy.


Antipruritic Effects of Kappa Opioid Receptor Agonists: Evidence from Rodents to Humans.
Centrally administered bombesin induces scratching and grooming in rats. These behaviors were blocked by early benzomorphan kappa opioid receptor (KOR) agonists as reported by Gmerek and Cowan in 1984. This was the first evidence that KORs may be involved in the sensation of itch-like behaviors. Subsequent development of additional animal models for acute and chronic itch has led to important discoveries since then. For example, it was found that (a) gastrin-releasing peptide (GRP), natriuretic polypeptide b and their cognate receptors are keys for the transmission of itch sensation at the spinal cord level, (b) dynorphins (Dyns), the endogenous KOR agonists, work as inhibitory neuromodulators of itch at the spinal cord level, (c) in a mouse model for acute itch, certain KOR antagonists elicit scratching, (d) in mouse models of acute or chronic itch, KOR agonists (e.g., U50,488, nalfurafine, CR 845, nalbuphine) suppress scratching induced by different pruritogens, and (e) nalfurafine, CR 845, and nalbuphine are in the clinic or in clinical trials for pruritus associated with chronic kidney disease and chronic liver disease, as well as pruritus in chronic skin diseases.


Objectives: The COVID-19 lockdown may lead to rising numbers of domestic violence (DV), especially among previously victimized individuals. The aim of this study was to investigate the development and influential factors of DV during the early COVID-19 lockdown. Methods: In this telephone-based study, previous participants with (n = 34) and without (n = 33) DV completed questionnaires on DV, attachment and COVID-19 related stressors. Development of DV and influential factors were investigated with repeated measures ANOVAs and linear regression models. Results: Individuals with prior DV reported significantly higher DV than previously not affected individuals. However, a statistically significant decrease of DV was found in the group with prior DV. Past DV, childlessness and insecure attachment, but not COVID-19 related stressors predicted current DV. Conclusions: In light of an insecure attachment style lockdown measures may have led to a temporary relationship stabilization. However, a reassessment is necessary to evaluate whether this stabilization was a short-time trend only.


Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review.
Infants < 3 months of age are at highest risk for developing severe complications after pertussis. The majority of pregnant women has low concentrations of pertussis-specific antibodies and thus newborns are insufficiently protected by maternally transferred antibodies. Acellular pertussis vaccination during pregnancy was recently implemented in various countries. Here, we assessed the evidence for safety and effectiveness of pertussis vaccination during pregnancy. We searched Medline, Embase, and ClinicalTrials.gov from January 1st 2010 to January 10th 2019. We assessed risk of bias (ROB) using the Cochrane ROB tool and ROBINS-I. We evaluated the quality of evidence using the GRADE approach. We identified 1273 articles and included 22 studies (14 for safety; 8 for effectiveness), comprising 1.4 million pregnant women in safety studies and 855,546 mother-infant-pairs in effectiveness studies. No significant differences between vaccinated and unvaccinated women and their infants were observed for safety outcomes with the exception of fever and chorioamnionitis. Compared to no vaccination, three studies showed a significantly increased relative risk for the presence of the ICD-9 code for chorioamnionitis in electronic patient data after pertussis vaccination. However, no study reported an increased risk for clinical sequelae of chorioamnionitis after vaccination during pregnancy, such as preterm birth or neonatal intensive care unit admission. Vaccine effectiveness against pertussis in infants of immunized mothers ranged from 69 to 91% for pertussis prevention, from 91 to 94% for prevention of hospitalization and was 95% for prevention of death due to pertussis. Risk of bias was serious to critical for safety outcomes and moderate to serious for effectiveness outcomes. GRADE evidence quality was moderate to very low, depending on outcome. Although an increased risk for a diagnosis of fever and chorioamnionitis was detected in pregnant women after pertussis vaccination, there was no association with a higher frequency of clinically relevant sequelae. Vaccine effectiveness for prevention of infant pertussis, hospitalization and death is high. Pertussis vaccination during pregnancy has an overall positive benefit-risk ratio. In view of the overall quality of available evidence ongoing surveillance of chorioamnionitis and its potential sequelae is recommended when pertussis vaccination in pregnancy is implemented. PROSPERO CRD42018087814, CRD42018090357.


Report from the ASHP 36th Midyear Clinical Meeting.
The ASHP Midyear Clinical meeting continues to be the largest pharmacy meeting in the world. A broad range of topics was presented at hundreds of symposia and posters at the 2001 meeting in New Orleans, Louisiana, in December. Pain management, hospice care, evidence based medicine, safe medication practices and improved drug information services were among the many practice areas addressed and recognized at the meeting.


Iodide abundance in oilfield brines in oklahoma.
Samples of subsurface water, oil, and rock from strata of Mississippian and Pennsylvanian age in the Northern Oklahoma Platform area were analyzed. Several of the water samples contained iodide at more than 500 parts per million. Analyses of the brines and rock indicated that the iodide originated organically.


Bench to bedside: new approaches to the immunotherapy of uveitic disease.
Intraocular inflammatory disease, or uveitis, appears to be due in large part to non-infectious, cell-mediated mechanisms. Experimental autoimmune uveitis (EAU) has been a valuable tool to better understand underlying mechanisms of this disorder, and it provides the possibility to evaluate new approaches to immunotherapy as well. Two approaches described here are oral tolerance and anti-IL2 receptor therapy. Both therapies were evaluated in the animal model and showed positive therapeutic effects. Based on these observations, both approaches were used in the treatment of patients with uveitis. Oral tolerance showed initial promising results. Anti-IL2 receptor therapy has been used for over 4 years in uveitis patients with an additional study evaluating this therapy in Behçet's disease. Future plans are to expand this approach to a larger number of patients. The use of animal models has been very useful in better understanding mechanisms of ocular disease and bringing new therapeutic approaches to the clinic.


Efficacy of antiviral therapy in patients with post-hepatitis C liver cirrhosis: is hyperuricaemia a potential adverse effect?
Hepatitis C virus (HCV) related liver cirrhosis is considered a major health problem; sofosbuvir (SOF)/ledipasvir (LDV) and SOF/daclatsvir (DACLA) are very promising direct antiviral agents (DAAS) especially in treating HCV genotype 4 which is the main genotype in Egypt. Uric acid elevation was reported in many systemic diseases and might be elevated during direct antiviral therapy. The aim is to evaluate efficacy and safety of SOF/LDV and SOF/DACLA plus ribavirin in treating HCV related child A liver cirrhosis and assess hyperuricaemia as a potential adverse effect to this regimen. This prospective observatinal study included 128 HCV naive child A cirrhotic patients divided into two groups (77 patients were treated with SOF 400 mg, DACLA 60 mg and ribavirin 600 mg and 51 patients were treated with SOF 400 mg, LDV 90 mg and ribavirin 600 mg) for 12 weeks, during the treatment complete blood count, creatinine, bilirubin, alanine transaminase, aspartate transaminase and serum uric acid were monitored, HCV RNA quantitative PCR at 12 weeks after the end of treatment was done. Response to treatment in SOF/LDV (sof/led) group is about (98%), response to treatment in SOF/DACLA (sof/dacla) group is about (96%). Hyperuricaemia was noticed in 17.6% of patients received sof/led and in 15.5% of those received sof/dacla. SOF+LDV and SOF+DACLA plus ribavirin regimens are highly effective in treating chronic HCV patients with compensated liver cirrhosis. Hyperuricaemia is considered a potential adverse effect to DAAS containing ribavirin and may lead to serious side effects such as renal impairment.


Effect of de-phenolization on protein-phenolic interactions of sunflower protein isolate.
Proteins and phenolic compounds are significant components of foods that can interact, and this interaction can impact the functional properties of proteins and the bioactivity of phenolic compounds. Sunflower meal, which has a high potential to be an important alternative protein source, contains phenolic compounds mostly bonded with proteins. In this study, the interaction between proteins and phenolic compounds which naturally exist in sunflower and prone to oxidation during alkaline treatment (for protein isolation) was investigated. There was a significant decrease up to 96.21% in the content of total phenolics by methanol washing. Chlorogenic acid, cryptochlorogenic acid and caffeic acid were detected in the phenolic extract obtained from sunflower protein isolate, and they exhibited different levels of reduction after methanol washing. For the total antioxidant capacity analysis, a decrease by 50% was observed after 4hwashing with methanol solution, and there was no significant decrease afterwards. In addition, the fluorescence intensity of sunflower protein was diminished with reduced washing time, which was mostly attributed to the protein-phenolic interaction. According to hydrodynamic parameters, the main force of the sunflower protein-phenolic complex formation was assumed to be hydrophobic attraction. The Stern-Volmer plot indicated that the main quenching mechanism was only static at all temperature conditions.


Nutrient recovery from anaerobically digested chicken slurry via struvite: Performance optimization and interactions with heavy metals and pathogens.
The aim of this study was to assess the potential of struvite precipitation to recover nutrients from anaerobically-processed poultry slurry and struvite's interactions with heavy metals (Zn, Cu, Pb, Cr, and Ni) and pathogens (total coliforms and Escherichia coli). The impacts of pH, Mg, N, and P molar proportion, reaction time, and mixing rate and duration were explored to determine the optimal conditions for nutrient recovery through struvite precipitation. A pH range of 9.5 to 10.5, was ideal for P and N removal and recovery, with a molar ratio of 1:1:1 for Mg:N:P. A mixing rate of 150rpm for 10min could allow nutrient recovery with little loss (3.32%) of NH₃ through volatilization, and also achieve an optimal struvite crystal size (50-60μm). The results of X-ray diffractometry and scanning electron microscopy confirmed that the precipitates generated at pH9 and 10 were orthorhombic struvite. Moreover, along with the recovery of nutrients, 40, 45, 66, 30, and 20% of Zn, Cu, Pb, Cr, and Ni, respectively, and 70% total coliforms and E. coli were removed by struvite precipitation from poultry slurry. This was observed despite that the levels of contaminants (heavy metals) detected in struvite were well below the permissible limits and free of pathogens. Consequently, it was inferred that the struvite quality was reasonable by virtue of its heavy metal and pathogen content, and therefore appropriate for application in the field. Similarly, struvite precipitation has multiple benefits as it can effectively recover nutrients as well as reducing pathogenic populations.


A few important points about dopamine's role in neural network dynamics.
Dopamine modifies a large variety of cellular and synaptic biophysical parameters in a seemingly paradoxical manner. Predicting their implications for neural network dynamics and computation seems difficult. Here I briefly review experimental and simulation data which illustrate that the diverse ionic consequences may combine such that dopamine's overall effect strongly depends on the activity state of the postsynaptic network, potentially with a temporal profile. These properties could be crucial for understanding dopamine's functional role.


[Full-length genome analysis of four genotype 3 letogenic Newcastle disease viruses isolated from different hosts].
The purpose of this study is trying to analysis the homology between four lentogenic Class I genotype 3 Newcastle disease virus isolates from different hosts with NDV strain NDV 08-004, which was the first obtained complete genome sequence virus of class I genotype 3. The full-length genome of NDV isolates, JS/3/09/Ch, ZJ/3/10/Ch, AH/2/10/Du and JS/9/08/Go,were determined by RT-PCR and then an alyzed. All the genomes are 15 198 nucleotides (nt) in length. Compared with the full genome sequences of Class II NDV stains (genotype IV-IX),four isolates has a 6-nt deletion in the non-coding region of nuclear phosphoprotein gene between nucleotides 1 640-1 641 and 12-nt insertion in the coding region of phospho protein gene between nucleotides 2 381-2 382. All the isolates have the motifs 112EQ/RQE/GRL117 at the cleavage site of the fusion protein, which is typical of lenogenic NDV strains, and it is in agreement with the result of pathogenic tests. The full-length genome of 4 genotype 3 NDV isolates shared 93% nucleotide identity with NDV08-004. The results of alignment of 6 viral genes showed that NP gene shared the highest identity (98.3%-96.4%) and P gene shared the lowest identity (96.1%-91.9%). The results show the following two points. First, it is concluded that the isolates from different hosts share the same genotype has the insignificant divergence in the genetic information. Second, it is proposed that the mutation rates of NP/F/L genes are lower than P/M/HN genes.


Non-undulatory locomotion in the lamprey.
The lamprey (a lower vertebrate, cyclostome), in addition to ordinary swimming, is also capable of crawling. Here we describe crawling forward in a narrow U-shaped tunnel. A rapid movement along the tunnel was evoked by stimulating the tail. The muscle activity responsible for propulsion was confined to the area around the body bend. Muscles on the inner (concave) side were activated when approaching the turn, and inactivated on the top of the arc. Muscles on the outer (convex) side were co-active with their antagonists, but also active in the area of straightening of the body bend. This pattern of muscle activity propagated along the body. The role of central and reflex mechanisms in the generation of locomotor movements is discussed.


Preparation and appraisal of self-assembled valsartan-loaded amalgamated Pluronic F127/Tween 80 polymeric micelles: Boosted cardioprotection via regulation of Mhrt/Nrf2 and Trx1 pathways in cisplatin-induced cardiotoxicity.
This study aimed to develop valsartan (VAL)-loaded mixed micelles and investigate their cardioprotective potential and molecular mechanisms through Mhrt/Nrf2 and Trx1 pathways. VAL-loaded mixed micelles have not been elaborated and their impact on Mhrt/Nrf2 and Trx1 pathways has not been yet inspected. VAL-loaded mixed micelles were prepared, incorporating Pluronic F127 and Tween 80, adopting thin-film hydration method. The micelles were evaluated for drug entrapment efficiency, loading characteristics, particle size, morphology, in vitro drug release and micelles storage stability. The pharmacokinetic studies were explored in rats. Also, VAL suspension and mixed micelles were tested in cisplatin-induced cardiotoxicity in rats either pre to or simultaneously with cisplatin. RNA expression of lnc Mhrt and protein expression of Nrf2, Trx1, Ask1, AMPK and caspase 3, oxidative stress and cardiac injury markers besides tailed DNA% by comet assay were assessed. Pharmacokinetic studies evoked a 3.75-fold increase in oral bioavailability as compared with VAL suspension. Overall, treatment with VAL-loaded mixed micelles was superior to VAL suspension in decreasing oxidative stress and cardiac injury markers and restoring the abnormalities occurred in Mhrt/Nrf2 and Trx1 pathways. Thus, mixed micelles would be promising nanocarrier for the engineering of VAL with reinforced pharmacokinetics and cardioprotection characteristics.


Sepiapterin ameliorates chemically induced murine colitis and azoxymethane-induced colon cancer.
The effects of modulating tetrahydrobiopterin (BH4) levels with a metabolic precursor, sepiapterin (SP), on dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)-induced colorectal cancer were studied. SP in the drinking water blocks DSS-induced colitis measured as decreased disease activity index (DAI), morphologic criteria, and recovery of Ca(2+)-induced contractility responses lost as a consequence of DSS treatment. SP reduces inflammatory responses measured as the decreased number of infiltrating inflammatory macrophages and neutrophils and decreased expression of proinflammatory cytokines interleukin 1β (IL-1β), IL-6, and IL-17A. High-performance liquid chromatography analyses of colonic BH4 and its oxidized derivative 7,8-dihydrobiopterin (BH2) are inconclusive although there was a trend for lower BH4:BH2 with DSS treatment that was reversed with SP. Reduction of colonic cGMP levels by DSS was reversed with SP by a mechanism sensitive to 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a specific inhibitor of the NO-sensitive soluble guanylate cyclase (sGC). ODQ abrogates the protective effects of SP on colitis. This plus the finding that SP reduces DSS-enhanced protein Tyr nitration are consistent with DSS-induced uncoupling of NOS. The results agree with previous studies that demonstrated inactivation of sGC in DSS-treated animals as being important in recruitment of inflammatory cells and in altered cholinergic signaling and colon motility. SP also reduces the number of colon tumors in AOM/DSS-treated mice from 7 to 1 per unit colon length. Thus, pharmacologic modulation of BH4 with currently available drugs may provide a mechanism for alleviating some forms of colitis and potentially minimizing the potential for colorectal cancer in patients with colitis.


DNA methylation and histone modification patterns during the late embryonic and early postnatal development of chickens.
Early mammalian embryonic cells have been proven to be essential for embryonic development and the health of neonates. A series of epigenetic reprogramming events, including DNA methylation and histone modifications, occur during early embryonic development. However, epigenetic marks in late embryos and neonates are not well understood, especially in avian species. To investigate the epigenetic patterns of developing embryos and posthatched chicks, embryos at embryonic day 5 (E5), E8, E11, E14, E17, and E20 and newly hatched chicks on day of life 1 (D1), D7, D14, D21 were collected. The levels of global DNA methylation and histone H3 at lysine 9 residue (H3K9) modifications were measured in samples of liver, jejunum, and breast skeletal muscles by Western blotting and immunofluorescence staining. According to our data, decreased levels of proliferating cell nuclear antigen expression were found in the liver and a V-shaped pattern of proliferating cell nuclear antigen expression was found in the jejunum. The level of proliferating cell nuclear antigen in muscle was relatively stable. Caspase 3 expression gradually decreased over time in liver, was stable in the jejunum, and increased in muscle. Levels of DNA methylation and H3K9 acetylation decreased in liver over time, while the pattern was N-shaped in jejunal tissue and W-shaped in pectoral muscles, and these changes were accompanied by dynamic changes of DNA methyltransferases, histone acetyltransferases 1, and histone deacetylase 2. Moreover, dimethylation, trimethylation, and acetylation of H3K9 were expressed in a time- and tissue-dependent manner. After birth, epigenetic marks were relatively stable and found at lower levels. These results indicate that spatiotemporal specific epigenetic alterations could be critical for the late development of chick embryos and neonates.


Effect of Phosphorus Precursor, Reduction Temperature, and Support on the Catalytic Properties of Nickel Phosphide Catalysts in Continuous-Flow Reductive Amination of Ethyl Levulinate.
Levulinic acid and its esters (e.g., ethyl levulinate, EL) are platform chemicals derived from biomass feedstocks that can be converted to a variety of valuable compounds. Reductive amination of levulinates with primary amines and H2 over heterogeneous catalysts is an attractive method for the synthesis of N-alkyl-5-methyl-2-pyrrolidones, which are an environmentally friendly alternative to the common solvent N-methyl-2-pyrrolidone (NMP). In the present work, the catalytic properties of the different nickel phosphide catalysts supported on SiO2 and Al2O3 were studied in a reductive amination of EL with n-hexylamine to N-hexyl-5-methyl-2-pyrrolidone (HMP) in a flow reactor. The influence of the phosphorus precursor, reduction temperature, reactant ratio, and addition of acidic diluters on the catalyst performance was investigated. The Ni2P/SiO2 catalyst prepared using (NH4)2HPO4 and reduced at 600 °C provides the highest HMP yield, which reaches 98%. Although the presence of acid sites and a sufficient hydrogenating ability are important factors determining the pyrrolidone yield, the selectivity also depends on the specific features of EL adsorption on active catalytic sites.


Soluble Epoxide Hydrolase Is Associated with Postprandial Anxiety Decrease in Healthy Adult Women.
The metabolism of bioactive oxylipins by soluble epoxide hydrolase (sEH) plays an important role in inflammation, and sEH may be a risk modifier in various human diseases and disorders. The relationships that sEH has with the risk factors of these diseases remain elusive. Herein, sEH protein expression and activity in white blood cells were characterized before and after a high-fat meal in healthy women (HW) and women with anorexia nervosa (AN). sEH expression and sEH activity were significantly correlated and increased in both groups two hours after consumption of the study meal. Fasting sEH expression and activity were positively associated with body mass index (BMI) in both groups, while an inverse association with age was found in AN only (p value < 0.05). sEH was not associated with anxiety or depression in either group at the fasting timepoint. While the anxiety score decreased after eating in both groups, a higher fasting sEH was associated with a lower postprandial anxiety decrease in HW (p value < 0.05). sEH characterization using direct measurements verified the relationship between the protein expression and in vivo activity of this important oxylipin modulator, while a well-controlled food challenge study design using HW and a clinical control group of women with disordered eating elucidated sEH's role in the health of adult women.


Assessment of Microbiological and Chemical Quality of Bubble Tea Beverages Vended in Taiwan.
Bubble tea beverages (n = 105) purchased from vendors in Taiwan were tested to determine their microbiological and chemical quality. Nearly half of the tested samples (48.6%, 51 of 105) had aerobic plate counts (APCs) higher than the Taiwan Food and Drug Administration guideline of 4.0 log CFU/mL, and 55 (52.4%) had coliform counts (most probable number [MPN]) higher than the 10 MPN/mL guideline. Escherichia coli, Salmonella, Staphylococcus aureus, sweeteners, preservatives, maleic acid, and coumarin were not detected in any sample. However, catechins were not detected to 188 mg/mL, and caffeine was 10.1 to 457.6 mg/mL. Bubble tea samples obtained from vendors in southern Taiwan had a mean APC of 2.6 log CFU/mL and a mean coliform count of 61.7 MPN/mL; these values were significantly lower (P < 0.05) than those from samples collected from vendors in northern, eastern, or central Taiwan. Samples obtained from southern Taiwan had the highest mean catechin concentrations of 21.3 mg/mL (P < 0.05). About 60% (63 of 105) of the bubble tea samples were not labeled with the origin of the tea leaves, which is in violation of Taiwanese food labeling regulations. In general, the bubble tea beverages tested had satisfactory microbial and chemical qualities.