The Influence of Emotional Regulation and Cognitive Flexibility on Sleep Habits in Spanish Children and Adolescents through the Lens of Parents.
Previous research studies have suggested the importance of studying the relationship between emotional regulation and sleep habits. Some investigations have especially focused on how emotional regulation could impact sleep habits in children and adolescents. Therefore, these researchers have stated there exists a two-way direction in this relationship. This study aimed to analyze the influence of emotional regulation on sleep habits in Spanish children and adolescents and the mediating role of anxiety in this relationship. Participants were 953 Spanish parents who completed the assessment protocol according to their children and adolescents' information. The results revealed moderate-strong correlations between emotional regulation problems and sleep habit disturbances (r = 0.375, p < 0.001), trait (r = 0.488, p < 0.001) anxiety, and state (r = 0.589, p < 0.001) anxiety. Additionally, emotional regulation showed a direct impact on sleep habits (β = 0.011, p = 0.005). Trait and state anxiety demonstrated a significant mediating role in the relationship between emotional regulation and sleep habits. Emotional regulation may have an impact on sleep habits during childhood and adolescence, suggesting the importance of early intervention focused on the emotions management and the prevention of sleep habit disturbances.


[Use of electrolyte solutions in surgery (author's transl)].
The use of isotonic saline and Ringer's lactate in surgery has become widespread following the work of Shires on the sequestration of extra-cellular fluid in hemorrhagic shock. Their use both in military and civilian practice and during hemodilutions in cardiac surgery have shown their efficacy. During intensive care, the risk of pulmonary edema is insignificant when less than 4 liters are given daily. Apart from cases of severe renal failure, they increase diuresis and reduce post-operative renal failure. Their use in appropriate cases permits economies in blood transfusion.


Complete genome sequence of a novel fusarivirus from the phytopathogenic fungus Corynespora cassiicola.
Corynespora cassiicola is an important phytopathogenic fungus that severely impairs crop production. Here, we report the molecular characterization of a novel positive-sense single-stranded RNA (+ssRNA) mycovirus, Corynespora cassiicola fusarivirus 1 (CcFV1), isolated from C. cassiicola strain 20200826-3-1. Excluding the poly(A) tail, the genome of the virus is 6491 nt in length and contains three putative open reading frames (ORFs). The large ORF1 encodes a polypeptide of 1524 aa with a conserved RNA-dependent RNA polymerase (RdRp) domain and a helicase (Hel) domain. BLASTp analysis showed that CcFV1 ORF1 has the highest similarity to Setosphaeria turcica fusarivirus 1 (StFV1, 50.45% identity, E-value 0.0). ORF2 encodes a polypeptide with a conserved chromosome segregation ATPase (Smc) domain. The smaller ORF3 encodes a polypeptide with an unknown function. Phylogenetic analysis based on the ORF1- encoded polypeptide showed that CcFV1 is phylogenetically related to members of the newly proposed family "Fusariviridae". Thus, we suggest that CcFV1 might be a novel member of the family "Fusariviridae", and is the first to be discovered in C. cassiicola.


Polyethylene materials with in-chain ketones from nonalternating catalytic copolymerization.
The world's most abundantly manufactured plastic, polyethylene, consists of inert hydrocarbon chains. The introduction of reactive polar groups in these chains could help overcome problematic environmental persistence and enhance compatibility with other materials. We show that phosphinophenolate-coordinated nickel complexes can catalyze nonalternating copolymerization of ethylene with carbon monoxide to incorporate a low density of individual in-chain keto groups in polyethylene chains with high molecular weight while retaining desirable material properties. After processing by conventional injection molding techniques, tensile properties remain on par with those of standard high-density polyethylene while also imparting photodegradability.


Adjustable gastric banding, sleeve gastrectomy or gastric bypass. Can evidence-based medicine help us to choose?
Dietary management of obesity, based on modification of eating patterns, increased physical activity and psychological and social support has provided inconsistent and disappointing results. Surgery is an invasive and often irreversible alternative that offers substantial and durable weight loss at the price of non-negligible morbidity and mortality. Three procedures account for almost all bariatric surgical procedures in France: adjustable gastric banding (AGB), vertical or sleeve gastrectomy (SG), and gastric bypass (GBP). The goal of this review is to help the surgeon make the best choice among these procedures, depending on his surgical convictions, abilities, and habits. Evidence-based data were extracted from the literature using the major data-base resources (Medline, Web of knowledge, Scopus); as well the most recent recommendations from relevant learned societies and health care organisms were analyzed. In 2010, 26,558 bariatric operations were performed in France; these were more or less equally distributed between AGB, SG and GBP. In 2011, the proportion of SG increased enormously and represented 43.9% of all bariatric procedures. In terms of weight loss and perioperative morbidity/mortality, SG tends to stand midway between AGB and GBP.


Organophilic treatments of bentonite increase the adsorption of aflatoxin B1 and protect stem cells against cellular damage.
Bentonite clays exhibit high adsorptive capacity for contaminants, including aflatoxin B1 (AFB1), a mycotoxin responsible for causing severe toxicity in several species including pigs, poultry and man. Organophilic treatments is known to increase the adsorption capacity of bentonites, and the primary aim of this study was to evaluate the ability of Brazilian bentonite and two organic salts - benzalkonium chloride (BAC) and cetyltrimethylammonium bromide (CTAB) to adsorb AFB1. For this end, 2(2) factorial designs were used in order to analyze if BAC or CTAB was able to increase AFB1 adsorption when submitted in different temperature and concentration. Both BAC and CTAB treatment (at 30°C and 2% of salt concentration) were found to increase the adsorption of AFB1 significantly compared with untreated bentonite. After organophilic bentonite treatments with BAC or CTAB, a vibration of CH stretch (2850 and 2920cm(-1)) were detected. A frequency of the SiO stretch (1020 and 1090cm(-1)) was changed by intercalation of organic cation. Furthermore, the interlayer spacing of bentonite increases to 1.23nm (d001 reflection at 2θ=7.16) and 1.22 (d001 reflection at 2θ=7.22) after the addition of BAC and CTAB, respectively. Another aim of the study was to observe the effects of these two bentonite salts in neural crest stem cell cultures. The two materials that were created by organophilic treatments were not found to be toxic to stem cells. Furthermore the results indicate that the two materials tested may protect the neural crest stem cells against damage caused by AFB1.


Bimetallic nanoporous Pd-Ag prepared by dealloying with polyvinylpyrrolidone and their electrocatalytic properties.
Bimetallic nanoporous Pd-Ag solid solution alloys with hierarchical structure were prepared by dealloying melt-spun Al-Pd-Ag ribbons in a 10 wt% H3PO4 solution. Electrocatalytic properties of nanoporous Pd-Ag alloys were measured in comparison with the nanoporous Pd without Ag. Experimental results showed that the nanoporous Pd-Ag alloys displayed electrocatalytic properties superior to their Ag-free counterparts. In particular, the optimised composition was revealed to be Pd/Ag = 3/2 in atomic ratio in the precursor with fixed 85 at% Al alloys, which yielded in a peak current density in the nanoporous Pd-Ag alloy two times that of the pure Pd one. The electrocatalytic activity of nanoporous Pd-Ag alloy with refined microstructure was further increased up to three times of the pure Pd one by adding 1 mM polyvinylpyrrolidone (PVP) into the H3PO4 solution. The underlying mechanism of refinement was related to a restriction effect on the free diffusion of Pd and Ag under adsorption of the PVP macromolecules. The significant improvement in the electrocatalytic properties was attributed to the dual promotion by the electron transfer from PVP to Pd-Ag and by a synergistic effect between Pd and Ag.


Pharmacological treatment of social anxiety disorder: a meta-analysis.
Placebo-controlled trials have evaluated the efficacy of several medications in the treatment of social anxiety disorder but information regarding their relative efficacy is lacking. We compared the efficacy of medications systematically studied for the treatment of social anxiety disorder using meta-analytic techniques. The methodology included a database search of articles published between January 1980 and June 2001 and manual searches of bibliographies in published manuscripts. Trials were included if they reported outcome data on the Liebowitz Social Anxiety Scale (LSAS) or a categorical measure of responder status. Data were extracted independently by two authors. The Q statistic was used to assess homogeneity across trials. All analyses were conducted using intent-to-treat data. There was substantial heterogeneity across trials. The medications with largest effect sizes were phenelzine [effect size, 1.02; 95% Confidence Interval (CI), 0.52-1.52], clonazepam (effect size, 0.97; 95% CI, 0.49-1.45), gabapentin (effect size, 0.78; 95% CI, 0.29-1.27), brofaromine (effect size, 0.66; 95% CI, 0.38-0.94), and the selective serotonin reuptake inhibitors (SSRIs; effect size, 0.65; 95% CI, 0.50-0.81). There were no statistically significant differences between medications or medication groups. However, formal methods of interim monitoring adapted for meta-analyses suggested strongest evidence of efficacy for SSRIs and brofaromine. Several medications are efficacious for the treatment of social anxiety disorder. The stability of the SSRI effect size estimate in conjunction with other evidence for safety and tolerability and their ability to treat comorbid conditions supports the use of SSRIs as the first-line treatment. Direct comparisons of SSRIs vs. other promising medications deserve consideration.


The glp-1 locus and cellular interactions in early C. elegans embryos.
Interactions between the early blastomeres in a C. elegans embryo are required for the specification of certain cell fates. Blastomeres that produce neurons and skin cells when cultured in isolation are induced to also produce pharyngeal cells in intact embryos. We have identified maternal effect lethal mutations that, on the basis of phenotype and temperature-sensitive period, appear to disrupt this inductive interaction. These mutations are all alleles of glp-1, a gene also involved in the control of germ cell proliferation during postembryonic development of C. elegans.


Effects of pH changes on systems ASC and B in rabbit ileum.
Influx of D-aspartate (D-Asp), L-glutamate (L-Glu), and serine (Ser) across the brush-border membrane of the intact mucosa from rabbit ileum has been examined. L-Glu influx is chloride independent and completely sodium dependent. D-Asp and L-Glu share a transport system with a maximum transport rate of 1 micromol. cm-2. h-1 and an apparent affinity constant (K1/2) of approximately 0.3 mM. The function of this transport system is pH insensitive between pH 5.65 and 8.2, and bipolar amino acids do not affect the way in which the transport system handles D-Asp and L-Glu. The characteristics of this transport system match those of system X-AG. L-Glu and Ser share a transporter for which the inhibitor constant (Ki) of L-Glu against Ser decreases from 54 to 10 mM when pH is reduced from 7.2 to 5.65, while the maximum rate of transport remains unaffected at approximately 10 micromol. cm-2. h-1. The Ki values (5 mM) of Ser against L-Glu influx and the L-Glu-sensitive contribution to Ser influx (0.8 micromol. cm-2. h-1 at 1 mM Ser) are the same at both pH values. The L-Glu-sensitive transport of Ser together with the contribution of system bo,+ account for approximately 50% of Ser influx at pH 7.2. The remaining 50% can be ascribed to system B. Transport of Ser by system B is reduced by >95% at pH 5.65. At pH 7. 2 Ki of Ser against transport of leucine (Leu) by system B is 18 mM and Ki of Leu against transport of Ser is 1.7 mM. The low-affinity transport of L-Glu and the L-Glu-sensitive transport of Ser are performed by an equivalent of system ASC. Supplementary experiments using the jejunum confirm the validity of these results for a major portion of the rabbit small intestine.


Rank tests for clustered survival data when dependent subunits are randomized.
In clustered survival data, subunits within each cluster share similar characteristics, so that observations made from them tend to be positively correlated. In clinical trials, the correlated subunits from the same cluster are often randomized to different treatment groups. In this case, the variance formulas of the standard rank tests such as the logrank, Gehan-Wilcoxon or Prentice-Wilcoxon, proposed for independent samples, need to be adjusted for intracluster correlations both within and between treatment groups for testing equality of marginal survival distributions. In this paper we derive a general form of simple variance formulas of the rank tests when subunits from the same cluster are randomized into different treatment groups. Extensive simulation studies are conducted to investigate small sample performance of the variance formulas. We compare our non-parametric rank tests based on the adjusted variances with one from a shared frailty model, which is an optimal semi-parametric testing procedure when the intracluster correlations within and between groups are the same.


Qualitative and quantitative changes in beta-1,4-glucosidase accompanying growth of Aspergillus nidulans.
A comparative study of the wild type A. nidulans and a mutant strain aco-T69 (lacking conidia and cleistothecia) revealed the better production of beta-1,4-glucosidase in the former. The relative distribution of the enzyme levels in various morphological structures viz. somatic hyphae, spores and cleistothecia also showed a variation. Highest specific activity was found in the cleistothecial extracts. The electrophoretic analysis of the wild type strain demonstrated the presence of three isoenzymes of beta-1,4-glucosidase i.e. beta-GLU I, beta-GLU II and beta-GLU III, the number of which varies from one to three during the growth of the organism. The parallel study of the mutant strain showed complete absence of beta-GLU II. All three forms were present in the somatic hyphae and cleistothecial extracts while spore extracts depicted the absence of beta-GLU III in the wild type.


Gestational weight gain in insulin-resistant pregnancies.
To examine the Institute of Medicine (IOM) guidelines for gestational weight gain (GWG) in insulin-resistant pregnancy. Secondary analysis of a prospective cohort of 435 women with type 2 or gestational diabetes from 2006 to 2010. The exposure was categorized as GWG less than, within or greater than the IOM recommendations for body mass index. The maternal outcome was a composite of preeclampsia, eclampsia, third- to fourth-degree laceration, readmission or wound infection. The neonatal outcome was a composite of preterm delivery, level 3 nursery admission, oxygen requirement >6 h, shoulder dystocia, 5-min Apgar3, umbilical cord arterial pH<7.1 or base excess <-12. Secondary outcomes were cesarean delivery (CD), macrosomia and small for gestational age (SGA). Incidence of the maternal outcome did not differ with GWG (P=0.15). Women gaining more than recommended had an increased risk of CD (relative risk (RR) 1.31, 95% confidence interval (CI) 1.01 to 1.69) and the neonatal outcome (RR 1.40, 95% CI 1.01 to 1.95) compared with women gaining within the IOM recommendations. Women gaining less than recommended had an increased risk of SGA (RR 3.29, 95% CI 1.09 to 9.91) without a decrease in the risk of the maternal outcome (RR 0.93, 95% CI 0.49 to 1.78) or CD (RR 0.74, 95% CI 0.40 to 1.37) compared with women gaining within the IOM recommendations. Women with insulin resistance should be advised to gain within the current IOM guidelines.


Ionic Liquid Treatment for Highest-Efficiency Ambient Printed Stable All-Inorganic CsPbI3 Perovskite Solar Cells.
All-inorganic cesium lead triiodide (CsPbI3 ) perovskite is well known for its unparalleled stability at high temperatures up to 500 °C and under oxidative chemical stresses. However, upscaling solar cells via ambient printing suffers from imperfect crystal quality and defects caused by uncontrollable crystallization. Here, the incorporation of a low concentration of novel ionic liquid is reported as being promising for managing defects in CsPbI3 films, interfacial energy alignment, and device stability of solar cells fabricated via ambient blade-coating. Both theoretical simulations and experimental measurements reveal that the ionic liquid successfully regulates the perovskite thin-film growth to decrease perovskite grain boundaries, strongly coordinates with the undercoordinated Pb2+ to passivate iodide vacancy defects, aligns the interface to decrease the energy barrier at the electron-transporting layer, and relaxes the lattice strain to promote phase stability. Consequently, ambient printed CsPbI3 solar cells with power conversion efficiency as high as 20.01% under 1 sun illumination (100 mW cm-2 ) and 37.24% under indoor light illumination (1000 lux, 365 µW cm-2 ) are achieved; both are the highest for printed all-inorganic cells for corresponding applications. Furthermore, the bare cells show an impressive long-term ambient stability with only ≈5% PCE degradation after 1000 h aging under ambient conditions.


Knotted urethral catheter in an 80-year-old woman: prevention and management of this unusual complication.
Intravesical catheter knotting represents a rare event, especially described in paediatric literature. We report a case of a catheter knot, occurring in an 80-year-old woman, managed by means of sustained traction.


Adverse effects of praziquantel treatment of Schistosoma japonicum infection: involvement of host anaphylactic reactions induced by parasite antigen release.
The present study using a murine model heavily infected with Schistosoma japonicum aimed to elucidate the pathogenesis of adverse effects of praziquantel treatment of schistosome-infected subjects. Inbred BALB/c mice were infected with S. japonicum (Yamanashi strain) before being treated with a single dose of praziquantel at 4 or 8 weeks p.i. All the mice treated at 8 weeks p.i. exhibited signs typical of systemic anaphylaxis until half of them died shortly after praziquantel administration. At autopsy, these mice exhibited remarkable intestinal alterations characterised by increased mucosal permeability, mucosal oedema and petechial haemorrhage, which are changes typical of immediate intestinal anaphylaxis. In these mice treated at 8 weeks p.i., degranulation of intestinal mast cells was frequently observed, which was particularly remarkable around S. japonicum eggs hatched as an effect of praziquantel. Furthermore, the plasma histamine concentration just after praziquantel treatment was much higher in mice at 8 weeks p.i. than that in uninfected mice or in S. japonicum-infected mice without drug treatment. In contrast, none of these intestinal changes was observed in untreated or uninfected control mice, or in mice administered praziquantel at 4 weeks p.i., in which worm pairs had just reached sexual maturation and begun egg-laying. The finding by ELISA that serum IgM and IgA levels specific to S. japonicum eggs decreased immediately after praziquantel treatment, together with the results of immunohistochemistry, revealed the sudden release of parasite antigens from the eggs hatched by praziquantel treatment. The results of this study demonstrate that adverse effects of praziquantel treatment of schistosomiasis characterised by abdominal signs depend on anaphylactic reactions due to parasite antigens, especially antigens from eggs hatched as an effect of praziquantel.


The Expression of Notch 1 and Notch 3 in Gallbladder Cancer and Their Clinicopathological Significance.
Gallbladder cancers (GBCs) are highly malignant gastrointestinal cancers. The biological makers for the prognosis and targeting therapy of GBCs have not been established. The protein expression of Notch 1 and Notch 3 in 46 squamous cell/adenosquamous carcinomas (SC/ASCs) and 80 adenocarcinomas (AC) was measured using immunohistochemistry. Positive Notch 1 and Notch 3 expression in both SC/ASC and AC was significantly associated with large tumor size, invasion, metastasis, and low surgical curability (P < 0.05 or P < 0.01). Univariate Kaplan-Meier analysis showed that positive Notch 1 and Notch 3 expression was significantly associated with mean survival of SC/ASC and AC patients (P < 0.01 or P < 0.001). Multivariate Cox regression analysis showed that positive Notch 1 and Notch 3 expression, as well as low differentiation, large tumor size, high TNM stage, invasion, lymph node metastasis, and surgical curability are independent poor-prognostic factors in both SC/ASC and AC patients. Positive Notch 1 and Notch 3 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in both SC/ASC and AC patients.


The mitotic apparatus-associated 51-kDa protein from sea urchin eggs is a GTP-binding protein and is immunologically related to yeast polypeptide elongation factor 1 alpha.
We investigated the biochemical characteristics of the 51-kDa protein that is a major mitotic apparatus-associated basic protein of sea urchin eggs (Toriyama, M., Ohta, K., Endo, S., and Sakai, H. (1988) Cell Motil. Cytoskeleton 9, 117-128). The amino acid composition of the 51-kDa protein was apparently different from those of tubulin, actin, histones, and myelin basic protein; yet it was similar to those of polypeptide elongation factors 1 alpha (EF-1 alpha). In addition, antibody to EF-1 alpha from yeast cross-reacted with the 51-kDa protein. [3H] GTP binding activity was detected in the phosphocellulose-purified fraction (PC fraction) which predominantly contained the 51-kDa protein and was shown to be specific to GTP, GDP, guanylyl imidodiphosphate, and ITP. Photo-affinity labeling using [alpha-32P]8-azidoguanosine triphosphate (8-azido-GTP) demonstrated that a 51-kDa polypeptide in the PC fraction specifically bound 8-azido-GTP. This GTP-binding polypeptide was bound to a GTP affinity column, could be eluted by the addition of GTP, and was immunoreactive with anti-51-kDa protein antibodies. When the PC fraction was applied to a gel filtration chromatography column, GTP binding activity was completely coeluted with the 51-kDa protein. Furthermore, the PC fraction and the gel filtration-purified fraction had EF-1 alpha activity: [14C]Phe-tRNA transferring activity to ribosomes in the presence of poly(U) and ribosome-dependent GTPase activity. The results indicate that the mitotic apparatus-associated 51-kDa protein is a GTP-binding protein and suggest that it is structurally and functionally related to yeast EF-1 alpha.


[Spirometry and veloergometry in evaluating physical performance of individuals exposed to organic solvents].
Increased length of service in house-painters causes longer half-periods of adaptation and recovery, larger their total, lower coefficient of recovery and lower coefficient of myocardial resources expenditure. That indicates lower efficiency of heart action under exertion, poor adaptive reactions to physical exertion and latent heart failure formation.


[Quantitative analysis of pulegone in Herba Schizonepetae].
To establish the determination method of pulegone in Herba Schizonepetae. HPLC method was developed for the determination of pulegone in Herba Schizonepetae. The separation was performed on C18 column with MeOH-H2O (80:20) as a mobile phase. The detection wavelength was set at 252 nm. The quantitation of pulegone in Herba Schizonepetae varied from 0.2-0.7 mg x g(-1). The average recovery is 96.2%, RSD 0.81%. The method is simple, rapid and accurate.


Effect of oxygen concentration on production of ethane and thiobarbituric acid-reactive substances by peroxidizing lung and liver homogenates and formation of ethanol by peroxidizing docosahexaenoic acid preparations under hyperoxic conditions.
The oxygen dependence of ethane formation was investigated in rat lung and liver homogenates, incubated in sealed flasks, in which the peroxidation was stimulated by the addition of ferrous ions. For both tissues, the production of ethane was maximal under a 20% oxygenated gas phase, while hyperoxic conditions led to a decreased ethane in the gas phase. The formation of thiobarbituric acid-reactive substances (TBA-RS), another marker of the lipid peroxidation process, in the homogenates of lung and liver was strongly stimulated at 100% compared to 20% oxygen. Experiments were also carried out on iron-stimulated peroxidation of pure docosahexaenoic acid preparations, which under air led to a large production of ethane. As for tissue homogenates, the TBA-RS content was increased in the presence of 100% oxygen. Those conditions, however, did not induce an increase in ethane production but led to the formation of ethanol. Therefore, the quenching of ethyl radical by molecular oxygen seems to be a very attractive hypothesis to explain the lack of increased ethane production in favor of ethanol when iron-induced lipid peroxidation was stimulated by oxygen.


Distinct guanine nucleotide binding and release properties of the three Gi proteins.
The native pertussis toxin sensitive GTP-binding proteins (Gi proteins) were individually resolved, and their guanine nucleotide binding and release properties were studied. Gi2 and Gi3, the two major GTP-binding proteins of human erythrocytes, were purified to apparent homogeneity by fast protein liquid chromatography. Gi1 was purified from bovine brain. The three proteins bound 0.6-0.85 mol of guanosine 5'-O-(thio-triphosphate (GTP gamma S)/mol of protein with similar affinities (KD(app) = 50-100 nM). The rate of [35S]GTP gamma S binding to Gi2 was 5-8-fold faster than to Gi1 or Gi3 at 2 mm Mg2+. There were no observable differences in the binding characteristics between bovine brain Gi1 and human erythrocyte Gi3. At 50 mM Mg2+, all three Gi proteins exhibited fast binding, although Gi1 and Gi3 were marginally slower than Gi2. All three Gi proteins exhibited different rates of [32P]GDP release at 2 mM Mg2+. GDP release from Gi2 was severalfold faster than that from Gi1 or Gi3. GDP release rates from Gi1 and Gi3 were similar, although Gi3 was somewhat (60-80%) faster than Gi1. These data indicate that rates of GDP release and GTP binding may be independently regulated for these three proteins and that the relative proportions of Gi2/Gi1 or Gi2/Gi3 will be a crucial factor in determining the kinetics of signal transduction through Gi-coupled effectors.


Rate of Heart Failure Following Atrial Fibrillation According to Presence of Family History of Dilated Cardiomyopathy or Heart Failure: A Nationwide Study.
Background It is poorly understood why some patients with atrial fibrillation develop heart failure (HF) and others do not. We examined the rate of developing HF in patients with atrial fibrillation with and without first-degree family members with HF or dilated cardiomyopathy (DCM). Methods and Results Using Danish nationwide registries, patients born after 1942 diagnosed with atrial fibrillation in the period 2005 to 2015 were identified and followed for up to 5 years. Patients with pre-existing HF, DCM, and/or ischemic heart disease diagnoses were excluded. Exposure was defined as a first-degree relative with HF or DCM. The rate of developing the composite end point of HF or death, and the components, was estimated with multivariable Cox proportional hazard regression models. We included 10 605 patients. A total of 17% had a family member with DCM/HF. Having a family member with HF/DCM was associated with an increased 5-year risk of the composite of HF/death (cumulative incidence, 9.2% [95% CI, 7.8-10.7] versus 5.6% [95% CI, 5.0-6.1]; adjusted hazard ratio [HR] 1.36 [95% CI, 1.13-1.64]). (HF 8.4% [95% CI, 7.0-9.8] versus 4.5% [95% CI, 4.1-5.0]); (adjusted HR, 1.49 [95% CI, 1.22-1.82]). However, familial HF/DCM was not significantly associated with an increased 5-year risk and rate of death (0.8% [95% CI, 0.4-1.2] versus 1.1% [95% CI, 0.8-1.3]); (adjusted HR, 0.80 [95% CI, 0.46-1.39]). Conclusions In patients with incident atrial fibrillation without prior ischemic heart disease or HF diagnoses, 1 of 6 had a first-degree relative with HF, and having such a family history of HF/DCM was associated with an 87% increase in 5-year incidence of HF compared with those without.


trans-Cinnamaldehyde stimulates mitochondrial biogenesis through PGC-1α and PPARβ/δ leading to enhanced GLUT4 expression.
Type 2 diabetes is characterized by insulin resistance and chronic hyperglycemia, and is increasing in incidence and severity. This work explored the effects of trans-cinnamaldehyde (CA) on carbohydrate metabolism, mitochondrial content, and related metabolic gene and protein expression in cultured myotubes treated with various concentrations of CA for up to 24 h. CA treatment increased myotube myocyte enhancer factor 2 (MEF2) along with glucose transporter 4 (GLUT4) content. CA treatment also significantly increased expression of markers of improved oxidative metabolism including 5' adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), cytochrome c (CytC), as well as peroxisome proliferator-activated receptor α (PPARα) and PPARβ/δ. Despite increased expression of proteins associated with improved oxidative metabolism and glucose uptake, CA-treated myotubes exhibited significantly reduced oxidative metabolism compared with controlled cells. Additionally, CA treatment increased markers of glucose-mediated lipid biosynthesis without elevated PPARγ and sterol receptor element binding protein 1c (SREBP-1c) expression. The ability of CA to stimulate mitochondrial biogenesis and GLUT4 expression suggests CA may offer possible benefits for metabolic disease. However, increases in markers of fatty acid synthesis with simultaneously reduced oxidative metabolism suggest CA may have counterproductive effects for metabolic disease, warranting a need for further investigation.


Angiographic assessment of sequential and individual coronary artery bypass grafting.
In trying to answer the question about the controversial use of sequential grafts, we determined the mid-term angiographic outcome of patients in whom coronary artery bypass was performed with different types of vein grafts. A total of 1034 coronary anastomoses on 724 saphenous vein grafts (SVGs) (apart from 497 left internal mammarian artery (LIMA) anastomoses) were assessed in 509 patients in an average of 55.4 +/- 17.6 months after coronary artery bypass grafting. The patency rates of sequential conduits were markedly higher than those of individual ones (86.6% vs 69.6%, p = 0.0001). Also, the anastomoses on the sequential conduits had better patency rates (80.6% vs 69.6%, p = 0.0001). This difference was even more pronounced in coronary arteries of poor quality/small (< 1.5 mm) diameter (68.9% vs 51.6%) for the sequential and individual grafts, respectively (p = 0.03). Also, the patency of the entire sequential conduit was lower when most distally located anastomosis was of poor runoff (45.2%). The patency of a sequential vein conduit is generally superior than that of an individual one, especially for poor runoff coronary vessels, provided that the most distally located anastomosis is performed on a good coronary artery in terms of quality and diameter. Using a minimal length of SVG is another advantage. However, failure of a single sequential conduit jeopardizes all of the anastomoses along that graft segment. Besides, being technically more demanding, technical expertise in performing a sequential anastomosis is probably among the important predictors of patency.


Controlling anisotropic thermal properties of graphene aerogel by compressive strain.
Materials with adjustable wide-ranging thermal conductivity are desired to tackle the problem of thermal management for electronic devices operating in an extended range of temperature. In this study, graphene aerogels (GAs) are fabricated and transformed from thermal insulators to thermal conductors by high-temperature annealing. The highest through-plane and in-plane thermal conductivity of annealed GA reaches 3.3 and 96 W/m·K, respectively, under 95% compressive strain. Using the annealed GA as thermal interface material leads to superior performance than commercially available products that have higher through-plane thermal conductivity in dissipating heat for high-power electronic devices (e.g., LED lamp). Furthermore, due to excellent elasticity, the thermal resistance of annealed GAs can be reversibly tuned about six-fold by compressive strain. This paves a novel venue in designing thermal management system for devices, which not only need excellent heat dissipation but also good thermal insulation at various operating environments.


Standards for evaluating proposals to develop ethics curricula.
A focus on standards for assessing proposals for online teaching of practical and professional ethics provides an approach to standards for raising the level of online teaching. Intellectual merit, broad impact, and integration of research and teaching featuring a high level of interactivity are key criteria for evaluation. Especially noted is research that can serve to prepare instructors, to enrich the content of courses, and to stimulate further research. Yet raising the level of online teaching hinges on developing easy access and navigability in an online curriculum.


Optical isomers of the hepatocarcinogenic beta-blocker ZAMI 1305: influence on nucleic acids synthesis and DNA integrity.
The influence on nucleic acids synthesis and DNA integrity of the D-isomer and of the DL-racemic form of the oncogenic beta-blocker 1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1305) and of the non-oncogenic beta-blocker propranolol was tested in vitro and in vivo. Both D- and DL-ZAMI 1305, when added in vitro to nuclei isolated from rat liver, cause inhibition of DNA and RNA synthesis and DNA fragmentation, as evaluated by alkaline sucrose gradient analysis, in a similar dose-dependent fashion. D- and DL-ZAMI 1305 also inhibit to a similar extent the activity of DNA polymerase alpha and beta from regenerating rat liver. When administered in vivo to female rats both D and DL-ZAMI 1305 cause a dose-dependent fragmentation of liver DNA. The D-isomer and DL-racemic form of the non-oncogenic beta-blocker propranolol inhibit DNA and RNA synthesis and cause DNA fragmentation when added in vitro to isolated liver nuclei, being instead without effect when administered in vivo.


Measurement of thin filament lengths by distributed deconvolution analysis of fluorescence images.
The lengths of the actin (thin) filaments in sarcomeres directly influence the physiological properties of striated muscle. Although electron microscopy techniques provide the highest precision and accuracy for measuring thin filament lengths, significant obstacles limit their widespread use. Here, we describe distributed deconvolution, a fluorescence-based method that determines the location of specific thin filament components such as tropomodulin (Tmod) or probes such as phallacidin (a phalloidin derivative). Using Tmod and phallacidin fluorescence, we were able to determine the thin filament lengths of isolated chicken pectoralis major myofibrils with an accuracy and precision comparable to electron microscopy. Additionally, phallacidin fluorescence intensity at the Z line provided information about the width of Z lines. Furthermore, we detected significant variations in thin filaments lengths among individual myofibrils from chicken posterior latissimus dorsai and embryonic chick cardiac myocytes, suggesting that a ruler molecule (e.g., nebulin) does not strictly determine thin filament lengths in these muscles. This versatile method is applicable to myofibrils in living cells that exhibit significant variation in sarcomere lengths, and only requires a fluorescence microscope and a CCD camera.


Spleen volume is a predictor of posthepatectomy liver failure and short-term mortality for hepatocellular carcinoma.
The study aimed at retrospectively assessing the impact of spleen volume (SpV) on the development of posthepatectomy liver failure (PHLF) in patients who underwent hepatectomy for hepatocellular carcinoma (HCC). 152 patients with primary HCC who underwent hepatectomy (sectionectomy or more) were classified into PHLF and non-PHLF groups, and then the relationship between PHLF and SpV was assessed. SpV (cm3) was obtained from preoperative CT and standardized based on the patient's body surface area (BSA, m2). PHLF was observed in 39 (26%) of the 152 cases. SpV/BSA was significantly higher in the PHLF group, and the postoperative 1-year survival rate was significantly worse in the PHLF group than that in the non-PHLF group (p = 0.044). Multivariable analysis revealed SpV/BSA as a significant independent risk factor for PHLF. Using the cut-off value (160 cm3/m2), the 152 cases were divided into small SpV and large SpV groups. The incidence of PHLF was significantly higher in the large SpV group (p = 0.002), the liver failure-related mortality rate was also significantly higher in the large SpV group (p = 0.007), and the 1-year survival rate was significantly worse in the large SpV group (p = 0.035). These results suggest SpV as a predictor of PHLF and short-term mortality in patients who underwent hepatectomy for HCC. Moreover, SpV measurement is a simple and potentially useful method for predicting PHLF in patients with HCC.


COPD Maintenance Therapy with Tiotropium/Olodaterol Compared with Tiotropium: An Analysis in the Absence of Additional ICS Therapy.
The American Thoracic Society guidelines recommend long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilation over LAMA or LABA monotherapy as maintenance therapy for patients with chronic obstructive pulmonary disease suffering from dyspnea or exercise intolerance. Previous studies, which included patients receiving background inhaled corticosteroids (ICS), have shown the benefits of dual bronchodilation over monotherapy. This analysis aimed to confirm the benefits of LAMA/LABA over LAMA alone, without any confounding effects from ICS use. This pooled post hoc analysis compared the efficacy of tiotropium/olodaterol with tiotropium alone in patients from the TONADO® and OTEMTO® clinical trials who were not receiving ICS at study entry or during the studies. We analyzed change from baseline in trough forced expiratory volume in 1 s (FEV1), St. George's Respiratory Questionnaire (SGRQ) score and Transition Dyspnea Index (TDI) score in all patients, by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, baseline SGRQ score, and Baseline Dyspnea Index score. In this analysis of 1596 patients, tiotropium/olodaterol improved trough FEV1, SGRQ and TDI compared with tiotropium alone. The observed mean differences were: trough FEV1, 0.054 L (95% confidence interval [CI] 0.036, 0.073; p < 0.001); SGRQ, -1.918 (95% CI -2.994, -0.843; p < 0.001); and TDI, 0.575 (95% CI 0.301, 0.848; p < 0.001). Similar improvements were seen in each of the subgroup analyses. Tiotropium/olodaterol therapy significantly improved lung function, symptoms and health status compared with tiotropium alone. In a population free from ICS treatment, these data confirm the benefits of dual bronchodilation versus monotherapy.


Prevalence of Human papillomavirus (HPV) and Epstein-Barr virus (EBV) in oral and oropharyngeal squamous cell carcinoma in south-eastern Poland.
The aim of this study was to analyze the prevalence of HPV and EBV in oral and oropharyngeal squamous cell carcinoma in south-eastern Poland. The correlation between viral infection, OSCC, alcohol use, tobacco smoking, demographic data (gender, age, place of residence), anatomic location, pre-treatment staging, evidence of metastases to lymph nodes, and grading was also investigated. The examination samples were collected from paraffin tissue blocks, from 154 patients. Viral DNA was amplified by the nested-PCR method. HPV DNA was detected in 29.2 % of the tested samples (in 27.4 % of oropharyngeal and in 30.4 % of oral cavity). The HPV type 16 was detected in 15.6 % of all samples, and in 53.3 % of HPV-positive group. In HPV-positive samples from oropharyngeal HPV 16 constitute 76.5 %, and in HPV-positive samples from oral cavity HPV 16 constitute 39.3 %. Mixed infection (more than one type of HPV) was observed in 23.5 and 60.7 %, respectively, and in 46.7 % of all HPV-positive samples, and in 12.3 % of the whole study group. EBV DNA was detected in 27.3 % of the cases and HPV-EBV co-infection in 7.8 % of samples. In major patients from Southeastern region of Poland with oropharyngeal cancer HPV type 16 was detected but in oral cavity cancer other mixed infections were observed (i.e. 51, 52, 59, 66, 68, 71, 74). HPV 16 was detected more often among patients younger than 50 years of age, whereas the mixed HPV in the group aged 50-59. The pathogenesis of oral squamous cell carcinoma may be connected with EBV infection. Future studies on the mechanisms of HPV/EBV co-infection and/or superinfection and their role in oral squamous cell carcinoma are necessary.


Determination and antioxidant activity evaluation of etodolac, an anti-inflammatory drug, by sequential injection analysis.
A robust, accurate and sensitive automated procedure for the determination of etodolac, an anti-inflammatory drug, in pharmaceutical formulas by sequential injection analysis, is reported. The same system was also applied to evaluate the antioxidant activity of the drug expressed as Trolox equivalent antioxidant capacity (TEAC). The methodology is based on measuring at 734 nm the decay of absorbance of a solution with the radical 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) after its reduction by etodolac. Optimum ABTS*+-etodolac reaction was achieved with 0.329 mL of sample and 0.205 mL of ABTS*+ solution. Etodolac was determined at concentrations up to 4.5 x 10(-5) mol L(-1). A solution detection limit of 6.6 x 10(-6) mol L(-1) was obtained under the optimised experimental conditions. A relative standard deviation (n=10) lower than 4.7% with a sample throughput of more than 21 samples/h was obtained. No interference from excipients was observed. The developed methodology was applied in the analysis of pharmaceutical preparations and the obtained results were in good agreement with those furnished by the reference procedure with relative deviations lower than 1.4%.


Influence of deoxynivalenol and zearalenone on the immunohistochemical expression of oestrogen receptors and liver enzyme genes in vivo in prepubertal gilts.
Deoxynivalenol (DON) and zearalenone (ZEN) are often detected in plant materials used to produce feed for pre-pubertal gilts. Daily exposure to small amounts of these mycotoxins causes subclinical conditions in pigs and affects various biological processes (e.g. mycotoxin biotransformation). The aim of this preclinical study was to evaluate the effect of low monotonic doses of DON and ZEN (12 µg/kg body weight-BW-and 40 µg/kg BW, respectively), administered alone or in combination to 36 prepubertal gilts for 42 days, on the degree of immunohistochemical expression of oestrogen receptors (ERs) in the liver and the mRNA expression of genes encoding selected liver enzymes during biotransformation processes. The level of expression of the analysed genes proves that the tested mycotoxins exhibit variable biological activity at different stages of biotransformation. The biological activity of low doses of mycotoxins determines their metabolic activity. Therefore, taking into account the impact of low doses of mycotoxins on energy-intensive processes and their endogenous metabolism, it seems that the observed situation may lead to the activation of adaptation mechanisms.


Controlling energy conservation in quantum dynamics with independently moving basis functions: Application to multi-configuration Ehrenfest.
Application of the time-dependent variational principle to a linear combination of frozen-width Gaussians describing the nuclear wavefunction provides a formalism where the total energy is conserved. The computational downside of this formalism is that trajectories of individual Gaussians are solutions of a coupled system of differential equations, limiting implementation to serial propagation algorithms. To allow for parallelization and acceleration of the computation, independent trajectories based on simplified equations of motion were suggested. Unfortunately, within practical realizations involving finite Gaussian bases, this simplification leads to breaking the energy conservation. We offer a solution for this problem by using Lagrange multipliers to ensure the energy and norm conservation regardless of basis function trajectories or basis completeness. We illustrate our approach within the multi-configurational Ehrenfest method considering a linear vibronic coupling model.


Developing a Genetic Biomarker-based Diagnostic Model for Major Depressive Disorder using Random Forests and Artificial Neural Networks.
The clinical diagnosis of major depressive disorder (MDD) mainly relies on subjective assessment of depression-like behaviors and clinical examination. In the present study, we aimed to develop a novel diagnostic model for specially predicting MDD. The human brain GSE102556 DataSet and the blood GSE98793 and GSE76826 Data Sets were downloaded from the Gene Expression Omnibus (GEO) database. We used a novel algorithm, random forest (RF) plus artificial neural network (ANN), to examine gene biomarkers and establish a diagnostic model of MDD. Through the "limma" package in the R language, 2653 differentially expressed genes (DEGs) were identified in the GSE102556 DataSet, and 1786 DEGs were identified in the GSE98793 DataSet, and a total of 100 shared DEGs. We applied GSE98793 TrainData 1 to an RF algorithm and thereby successfully selected 28 genes as biomarkers. Furthermore, 28 biomarkers were verified by GSE98793 TestData 1, and the performance of these biomarkers was found to be perfect. In addition, we further used an ANN algorithm to optimize the weight of each gene and employed GSE98793 TrainData 2 to build an ANN model through the neural net package by R language. Based on this algorithm, GSE98793 TestData 2 and independent blood GSE76826 were verified to correlate with MDD, with AUCs of 0.903 and 0.917, respectively. To the best of our knowledge, this is the first time that the classifier constructed via DEG biomarkers has been used as an endophenotype for MDD clinical diagnosis. Our results may provide a new entry point for the diagnosis, treatment, outcome prediction, prognosis and recurrence of MDD.


Reward Devaluation in Autistic Children and Adolescents with Complex Needs: A Feasibility Study.
Rewards act as a motivator for positive behavior and learning. Although compounding evidence indicates that reward processing operates differently in autistic individuals who do not have co-occurring learning disabilities, little is known about individuals who have such difficulties or other complex needs. This study aimed first to assess the feasibility of using an adapted reward devaluation paradigm to examine basic reward processes in this underrepresented population, and second to investigate whether autistic children and adolescents with complex needs would show dynamic behavioral changes in response to changes in the motivational value of a reward. Twenty-seven autistic children and adolescents with complex needs and 20 typically developing 5-year-old children took part in the study. Participants were presented with two visual cues on a touchscreen laptop, which triggered the delivery of a video, music, or physical reward. One of the rewards was then presented in abundance to decrease its motivational value. Participants showed decreased interest in the video and music rewards after devaluation. The experimental setup was found to be suitable to test individuals with complex needs, although recommendations are made for the use of physical rewards. The results suggest that autistic participants with complex needs demonstrate goal-directed behavior and that it is feasible to develop experimental paradigms that can shed important light on learning processes that are fundamental to many education and intervention strategies for this population. Autism Res 2020, 13: 1915-1928. © 2020 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC. LAY SUMMARY: We adapted an experimental task to conduct research with autistic children and adolescents with complex needs, who remain grossly underrepresented in autism research. We found that once a reward was presented in great quantity, participants were less motivated to obtain it, showing that they adapted their behavior to changes in the value of that reward. This is an important finding to help promote learning and design better interventions for this population.


Clip-assisted endoloop ligation of the mucosal defect after resection of colorectal polyps decreased postprocedural delayed bleeding.
Postprocedural delayed bleeding (PDB) remains the most common major complication of colorectal polypectomy. Incomplete clip closure of mucosal defect and unclosed injured blood vessels in gaps between clips may be the risk factors for PDB. To observe whether completely no-gap closure of mucosal defect after polypectomy can reduce PDB occurrence. Single-center, retrospective case-control study. In this study based on historical comparisons of patients in 2 time periods, only the patients with polyps sized between 6 and 15 mm were included. A new clip-assisted endoloop ligation (CAEL, treatment group) method was used between January 2019 and December 2020, and a traditional simple clip closure (SCC, control) was used Between January 2017 and December 2018 to prevent PDB after polypectomy. The rate of PDB of two groups and risk factors for PDB were evaluated. Totally 4560 patients were included in the study; 2418 patients belong to CAEL group, and 2142 patients belong to SCC group. The overall rate of PDB was significantly lower in CAEL group compared to SCC group (0.6% versus 1.5%, p < 0.00). On multivariate logistic analysis, CAEL was a significant independent preventive factor for PDB (odds ratio (OR), 0.092; 95% confidence interval (CI), 0.029-0.3335; p = 0.000). Polyps located at rectum (colon versus rectum) represented a significant independent risk factor for PDB (OR, 11.888; 95% CI, 3.343-42.269; p = 0.001). Completely no-gap closure of mucosal defect after polypectomy further reduced the rate of PDB for polyps sized between 6 and 15 mm. CAEL may be a significant independent preventive factor for PDB. Polyps located at the rectum may be a significant independent risk factor for PDB.


Low-temperature hydrogen peroxide gas plasma--atomic age sterilization technology.
The combined use of hydrogen peroxide vapor and plasma sterilizes most medical instruments and material without leaving toxic residues. Patients and personnel are not in jeopardy of exposure to an inadequately aerated instrument this this sterilization method.


New regression formulas for sonographic weight estimation within 10, 7, and 3 days of delivery.
The purpose of this study was to develop new regression formulas based on large numbers of sonographic examinations performed within 10, 7, and 3 days of delivery. Sonographic fetal biometric measurements and delivery ward data for an unselected population were analyzed. Multivariate linear regression models were fitted to the sonographic data to predict the actual birth weight (BW) within 10, 7, and 3 days. The analyses included 6289, 5449, and 4007 patients who underwent sonographic examinations within 10, 7, and 3 days of delivery, respectively. All models yielded very high correlation coefficients (r = 0.927-0.958; R(2) = 0.859-0.918), low mean deviations between the calculated and actual BWs (6.4%-6.6% +/- 1 SD of 5.5%-5.9%), and high percentages of the calculated BW within 10% of the actual BW (78.5%-80.4%). Estimated fetal weight analyses made within 3 days of delivery yielded slightly better results than within 7 and 10 days. The new regression formulas yielded overall similar results, with a small advantage for estimates calculated within 3 days of delivery. Further prospective studies are needed to compare the accuracy of these formulas with those used to date.


Impact of implementing pathogen reduction technologies for platelets on reducing outdates.
Applying pathogen reduction technologies (PRT) to platelets can extend their shelf life from 5 to 7 days, but there have been few systematic studies of the repercussions of such technologies on outdate rates. The benefits in terms of outdate rates of applying PRT to platelets are studied via a mathematical simulation. Specifically, statistical methods are used to determine the daily production rate needed to meet demand while not exceeding a maximum amount set as a result of limitations on donations and while assuring a minimum daily stock. The results show that a 2-day extension in the shelf life of platelet concentrates (PC) results in reductions in outdates ranging from 88·4% to 100% at the production centres analysed. It may be the case for budgetary reasons that only part of the PCs produced can be treated. This being so, we show that if the proportion treated per annum exceeds 25% the best option is to treat part of the output every day, otherwise, it is preferable to concentrate treatment on the last two production days of the week. Extending the shelf life of PC from five to seven days and setting up suitable production logistics can drastically reduce outdates at production centres. If only a part of all PCs is treated, the best choices are to distribute PRT overall production days or, if the percentage of PCs treated is very low, to apply PRT on the days preceding the weekend break.


Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium: A Network Meta-analysis.
Although several pharmacological interventions for delirium have been investigated, their overall benefit and safety remain unclear. To evaluate evidence regarding pharmacological interventions for delirium treatment and prevention. PubMed, Embase, ProQuest, ScienceDirect, Cochrane Central, Web of Science, ClinicalKey, and ClinicalTrials.gov from inception to May 17, 2018. Randomized clinical trials (RCTs) examining pharmacological interventions for delirium treatment and prevention. To extract data according to a predetermined list of interests, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were applied, and all meta-analytic procedures were conducted using a random-effects model. The primary outcomes were treatment response in patients with delirium and the incidence of delirium in patients at risk of delirium. A total of 58 RCTs were included, in which 20 RCTs with 1435 participants (mean age, 63.5 years; 65.1% male) compared the outcomes of treatment and 38 RCTs with 8168 participants (mean age, 70.2 years; 53.4% male) examined the prevention of delirium. A network meta-analysis demonstrated that haloperidol plus lorazepam provided the best response rate for delirium treatment (odds ratio [OR], 28.13; 95% CI, 2.38-333.08) compared with placebo/control. For delirium prevention, the ramelteon, olanzapine, risperidone, and dexmedetomidine hydrochloride groups had significantly lower delirium occurrence rates than placebo/control (OR, 0.07; 95% CI, 0.01-0.66 for ramelteon; OR, 0.25; 95% CI, 0.09-0.69 for olanzapine; OR, 0.27; 95% CI, 0.07-0.99 for risperidone; and OR, 0.50; 95% CI, 0.31-0.80 for dexmedetomidine hydrochloride). None of the pharmacological treatments were significantly associated with a higher risk of all-cause mortality compared with placebo/control. This network meta-analysis demonstrated that haloperidol plus lorazepam might be the best treatment and ramelteon the best preventive medicine for delirium. None of the pharmacological interventions for treatment or prophylaxis increased the all-cause mortality.


The endophytome (plant-associated microbiome): methodological approaches, biological aspects, and biotech applications.
Similar to other organisms, plants establish interactions with a variety of microorganisms in their natural environment. The plant microbiome occupies the host plant's tissues, either internally or on its surfaces, showing interactions that can assist in its growth, development, and adaptation to face environmental stresses. The advance of metagenomics and metatranscriptomics approaches has strongly driven the study and recognition of plant microbiome impacts. Research in this regard provides comprehensive information about the taxonomic and functional aspects of microbial plant communities, contributing to a better understanding of their dynamics. Evidence of the plant microbiome's functional potential has boosted its exploitation to develop more ecological and sustainable agricultural practices that impact human health. Although microbial inoculants' development and use are promising to revolutionize crop production, interdisciplinary studies are needed to identify new candidates and promote effective practical applications. On the other hand, there are challenges in understanding and analyzing complex data generated within a plant microbiome project's scope. This review presents aspects about the complex structuring and assembly of the microbiome in the host plant's tissues, metagenomics, and metatranscriptomics approaches for its understanding, covering descriptions of recent studies concerning metagenomics to characterize the microbiome of non-model plants under different aspects. Studies involving bio-inoculants, isolated from plant microbial communities, capable of assisting in crops' productivity, are also reviewed.


Soluble Receptor for advanced glycation end products (RAGE) is a prognostic factor for heart failure.
We recently reported that serum levels of pentosidine, one of the well-defined advanced glycation end products (AGE), was an independent prognostic factor for heart failure. Receptor for AGEs (RAGE) is expressed in a variety of tissues, and RAGE has a C-truncated secretory isoform of the receptor protein, termed soluble RAGE. In the present study, we measured serum soluble RAGE levels in patients and examined whether serum soluble RAGE predicts prognosis in patients with heart failure. Serum soluble RAGE concentration was measured in 160 patients with heart failure by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 872 days with end points of cardiac death or rehospitalization. Serum soluble RAGE level increased with advancing New York Heart Association functional class. Serum soluble RAGE level was also higher in patients with cardiac events than in event free patients. From the receiver operating characteristic curve analysis, the cutoff value of serum soluble RAGE level was determined as 1220 pg/mL. Kaplan-Meier analysis clearly demonstrated that the high soluble RAGE group had a significantly higher incidence of cardiac events than occurred in the low serum soluble RAGE group (P = .0004). In the multivariate Cox proportional hazard analysis, soluble RAGE and serum pentosidine were independent risk factors for cardiac events (soluble RAGE: HR 1.90, 95% CI 1.16-3.09, P = .010; pentosidine: HR 1.59, 95% CI 1.11-2.29, P = .012). Serum soluble RAGE level is an independent prognostic factor for heart failure, and this novel marker may be useful for risk stratification of patients with heart failure.


Detection of extended-spectrum β-lactamases producing Enterobacteriaceae using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry based MBT STAR-BL software module with β-lactamase inhibition assay depends on the bacterial strains.
Rapid and sensitive detection of extended-spectrum β-lactamases (ESBLs) is essential for infection control and antimicrobial treatment. Recently, a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based MBT STAR-BL software module has been used for detecting β-lactamase activity; however, this system cannot differentiate ESBL producing bacteria from other third-generation cephalosporin-resistant strains. In this study, we utilized a MALDI-TOF MS-based MBT STAR-BL method to identify ESBL activity with β-lactamase inhibitors. A cefotaxime (CTX) hydrolysis assay, β-lactamase inhibition, clavulanic acid (CVA), and sulbactam (SBT) were used for detecting ESBL producers with the MBT STAR-BL software module. This software module automatically calculated the logRQ values in each assay. logRQ is the logarithm of the ratio of the summed hydrolyzed peak intensities to the summed non-hydrolyzed peak intensities and measured the efficiency of antibiotic hydrolysis. We divided the logRQ level of the β-lactamase inhibition assay by the logRQ value in the CTX hydrolysis assay, and we used this logRQ ratio as a measure of β-lactamase inhibition efficiency. We assessed the logRQ ratio calculated by this novel method for detecting ESBL producers in 132 Enterobacteriaceae. We performed the MALDI-TOF MS-based MBT STAR-BL approach with β-lactamase inhibitors for detecting ESBL producers and showed that the results of the inhibition assay with β-lactamase inhibitors depended on types of bacterial species. Furthermore, we improved elapsed times and accuracy in MBT STAR-BL methods by using proper β-lactamase inhibitors against specific bacterial strains to compare with the conventional standard lab method. The results suggest that the target bacterial species and β-lactamase inhibitors used were important for the utility of the MALDI-TOF MS-based MBT STAR-BL software module.


Comparison of three stationary phases in the separation of polyphenyls by liquid chromatography.
We present herein new analytical protocols for the separation and structural elucidation of polyphenyls. Three commercially available chromatographic stationary phases are compared in the separation of these non-polar, unfunctionalized, positional isomers. Baseline separation of nine terphenyl and quaterphenyl isomers is achieved in under ten minutes using a rapid gradient elution HPLC method. Complete separation of these, and a further five polyphenyls, is demonstrated. We finally present a linear correlation between solvent accessible surface area and the retention times of these closely related compounds.


Anaerobic biotransformation of dinitrotoluene isomers by Lactococcus lactis subsp. lactis strain 27 isolated from earthworm intestine.
Dinitrotoluenes are widely used as solvents and are intermediates in the synthesis of dyes, explosives, and pesticides. Environmental concerns regarding DNTs have increased due to their widespread use and their discharge into the environment. In this study, the anaerobic biodegradation of four dinitrotoluene isomers, 2,3-, 2,4-, 2,6- and 3,4-DNT, was investigated using Lactococcus lactis subsp. lactis strain 27, which was isolated from the intestines of earthworms. Liquid chromatography/mass spectrometry and NMR spectroscopy showed that L. lactis strain 27 non-specifically reduced the nitro groups on the tested dinitrotoluenes to their corresponding aminonitrotoluenes. L. lactis strain 27, however, did not reduce either sequentially or simultaneously two nitro groups of the dinitrotoluenes, resulting in the formation of the corresponding diaminotoluenes. In vitro formation of dinitroazoxytoluenes suggested the presence of oxygen-sensitive hydroxylaminonitrotoluenes. L. lactis strain 27 was capable of reducing 2,4-, 2,6-, 2,3-, and 3,4-dinitrotoluenes up to 173.6, 66.6, 287.1, and 355 microM, respectively in 12 h incubation. A relatively rapid reduction was observed in the case of the 2,3-, and 3,4-dinitrotoluenes, which have vicinal nitro groups on their arene structure. Non-specific anaerobic reduction of dinitrotoluenes by the intestinal bacterium L. lactis strain 27 differentiated the extent of reduction of DNTs according to the substitutional position of the nitro groups and produced in vitro more toxic dinitroazoxytoluenes, suggesting that anaerobic biotransformation of dinitrotoluenes could increase environmental risk.


A new method for precise determination of iron, zinc and cadmium stable isotope ratios in seawater by double-spike mass spectrometry.
The study of Fe, Zn and Cd stable isotopes (δ(56)Fe, δ(66)Zn and δ(114)Cd) in seawater is a new field, which promises to elucidate the marine cycling of these bioactive trace metals. However, the analytical challenges posed by the low concentration of these metals in seawater has meant that previous studies have typically required large sample volumes, highly limiting data collection in the oceans. Here, we present the first simultaneous method for the determination of these three isotope systems in seawater, using Nobias PA-1 chelating resin to extract metals from seawater, purification by anion exchange chromatography, and analysis by double spike MC-ICPMS. This method is designed for use on only a single litre of seawater and has blanks of 0.3, 0.06 and <0.03 ng for Fe, Zn and Cd respectively, representing a 1-20 fold reduction in sample size and a 4-130 decrease in blank compared to previously reported methods. The procedure yields data with high precision for all three elements (typically 0.02-0.2‰; 1σ internal precision), allowing us to distinguish natural variability in the oceans, which spans 1-3‰ for all three isotope systems. Simultaneous extraction and purification of three metals makes this method ideal for high-resolution, large-scale endeavours such as the GEOTRACES program.


Positional transient loss of consciousness and hemispheric deficits in the setting of severe four-vessel extracranial cerebrovascular disease.
Carotid artery stenosis typically causes hemispheric neurologic effects by atheroembolism. Nonhemispheric symptoms, such as syncope, are generally not attributable to extracranial carotid disease. This report describes a 62-year-old woman with severe bilateral carotid artery stenosis, right vertebral artery occlusion, and severe left vertebral artery stenosis who presented with transient loss of consciousness and unilateral weakness when upright. Her symptoms resolved after right carotid endarterectomy. Whereas vertebrobasilar insufficiency alone can cause syncope, in the case of severe multivessel cerebrovascular disease, unilateral carotid revascularization was successful in treating the patient's transient loss of consciousness, suggesting global cerebral hypoperfusion as the cause.


Clavicular periostitis: an unusual complication of percutaneous subclavian venous catheterization.
The first three cases, to the authors' knowledge, of benign clavicular periostitis resulting from percutaneous subclavian venous catheterization in children and the mechanism of this iatrogenic trauma are discussed.


Global correlation analysis for micro-RNA and mRNA expression profiles in human cell lines.
Microribonucleic acids (miRNAs) are small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level. Although considerable progress has been made in studying the function of miRNAs, they still remain largely unclear, mainly because of the difficulty in identifying target genes for miRNA. We performed a global analysis of both miRNAs and mRNAs expression across 16 human cell lines and extracted negatively correlated pairs of miRNA and mRNA which indicate miRNA-target relationship. The many of known-target of miR-124a showed negative correlation, suggesting our analysis were valid. We further extracted physically relevant miRNA-target gene pairs, applying computational target prediction algorithm with inverse correlations of miRNA and messenger RNA (mRNA) expression. Furthermore, gene-ontology-based annotation and functional enrichment analysis of the extracted miRNA-target gene pairs made it possible to indicate putative functions of miRNAs. The data collected here will be of value for further studies into the function of miRNA.


Integrin signaling gene alterations and outcomes of cancer patients receiving immune checkpoint inhibitors.
Immune evasion is a hallmark of cancer and is associated with resistance to PD-1/PD-L1 and CTLA-4 inhibitors. Several interactions between tumor and immune cells within the tumor microenvironment are effected through integrin signaling; however the latter has been underrecognized as a pathway that could have an impact on oncological outcomes after treatment with immune checkpoint inhibitors (ICIs). This study aimed to assess the clinical relevance of genomic alterations in the integrin signaling pathway in ICI-treated patients with advanced cancers. Next generation sequencing (NGS) data from tumor samples of patients with advanced cancers treated with ICIs (anti-PD-1/PD-L1, anti-CTLA4 or both) were queried from four independent publicly available cohorts for mutations and structural variations in 72 integrin signaling pathway genes (Gene Set: GOBP_CELL_ADHESION_MEDIATED_BY_INTEGRIN). The Kaplan Meier method was used to assess the association between mutated and unmutated genes with overall (OS) and progression-free survival (PFS). All results were reported at the 0.05 significance level. The largest cohort included 1662 patients (discovery set) and comprised 350 non-small cell lung cancer (NSCLC), 321 melanoma, 214 bladder, 151 renal cell carcinoma (RCC), 138 head neck (HN), 126 esophageal/gastric (EG), 117 glioma, 110 colorectal (CRC), 90 cancer of unknown primary (CUP), and 45 breast cancer patients. ICI treatments included PD-1 or PD-L1 inhibitors (n=1256), anti-CTLA4 inhibitors (n=146) or both (n=260). 170 patients (10% of the entire cohort) harbored mutations in PIK3CG (6%), RET (3%), SYK (1.4%), LYN (1.4%), PTPN11 (1.3%), and CRKL (0.1%) genes. Presence of these mutations was more frequent in melanoma (18%), followed by CRC (14.5%), CUP (11%), and NSCLC (11%). Patients with mutated tumors experienced a significantly longer median OS (41 months) compared to those without alterations (16 months, log-rank P<0.001). The favorable prognostic value of PIK3CG, RET, SYK, LYN, PTPN11, and CRKL alterations was confirmed in three melanoma cohorts (validation set, n=212, P=0.024). Assessment of mutation status of these genes in a fourth cohort of NSCLC patients (n=75) revealed a predictive significance as well, with regard to PFS after treatment with ipilimumab and nivolumab combination (P=0.048). Mutations and/or structural variations in integrin signaling genes may have prognostic and predictive value in patients with metastatic malignancies who receive ICIs. Although confirmation in larger studies with concurrent investigation of underlying immunologic mechanisms is needed, these findings pose therapeutic implications for co-targeted approaches to overcome immune evasion and resistance.


The charge of technology.
Science policies based on techno-nationalist thinking and fantasies about the past technological revolutions will get us nowhere fast, says David Edgerton.


A nonsynonymous functional variant of the ITGAM gene is not involved in biopsy-proven giant cell arteritis.
To investigate whether a functional integrin alpha M (ITGAM) variant is involved in susceptibility to and clinical manifestations of giant cell arteritis (GCA). A Spanish cohort of 437 white patients with biopsy-proven GCA and 1388 healthy controls were genotyped using the TaqMan allele discrimination technology. No association was observed between ITGAM rs1143679 and GCA (p = 0.80, OR 0.97). Similarly, subphenotype analyses did not yield significant differences between the case subgroups and the control set or between GCA patients with or without the main specific features of GCA. Our results suggest that the ITGAM rs1143679 variant does not play an important role in the pathophysiology of GCA.


Prosocial behavior as sexual signaling.
Maestripieri et al. provide an important service in highlighting prosocial biases toward attractive people from a cross-disciplinary perspective. Here I comment on the conceptual and critical side of their review of evolutionary psychology studies. I propose that further work should be focused on understanding the role of signaling in prosocial behavior.


Polymorphism at the alpha-glycerophosphate dehydrogenase locus in Drosophila melanogaster. I. Properties of adult allozymes.
A biochemical comparison was made between alpha-glycerophosphate dehydrogenase allozymes from Drosophila melanogaster. Enzymes extracted from the three major genotypes were indistinguishable in terms of their pH optima and thermal stabilities. Distinctive differences were observed for three parameters; temperature dependence of specific activity, temperature dependence of K-m, and reaction rate constancy over a physiological temperature range. These results are discussed in terms of a model of balancing selection and the existence of spatial and temporal allele frequency clines in natural populations.


Comparison of smear cytology and liquid-based cytology in EUS-guided FNA of pancreatic lesions: experience from a large tertiary center.
Studies comparing the diagnostic efficacy of liquid-based cytology (LBC) and smear cytology (SC) of pancreatic tissue sampling obtained via EUS-guided FNA (EUS-FNA) are still insufficient, mainly because results were controversial. We compared the diagnostic efficiency of LBC and SC of EUS-FNA of pancreatic lesions in one of the largest tertiary hospitals in China. A retrospective database search (January 2015 to January 2019) was performed for patients who underwent EUS-FNA with both LBC and SC. Demographic, cytologic, and endosonographic data were collected from 819 patients; 514 cases met the inclusion criteria. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were compared. Rapid on-site evaluation was not available in all cases. Three hundred eighty-five cases (74.90%) had confirmed malignancy, and 40 cases (7.78%) confirmed benign neoplasm. Adequate tissue sampling rates showed no significant difference between the 2 groups. The sensitivity, accuracy, and negative predictive value (NPV) of LBC were higher than those of SC with statistical significance (71.4% vs 55.1%, 76.1% vs 61.6%, and 40.6% vs 27.7%, respectively). The sensitivity, accuracy, and NPV of combined SC and LBC were higher than those of LBC alone with statistical significance (83.9% vs 71.4%, 86.5% vs 76.1%, and 56.8% vs 40.6%, respectively). Multivariate analysis revealed that pancreatic neck/body/tail lesions (P = .003), solid lesions (P < .001), 22-gauge needle size (P < .001), and number of needle passage >3 (P = .041) were associated with higher diagnostic sensitivity in all participants using LBC, whereas number of needle passage >3 (P = .017) was associated with higher diagnostic sensitivity using SC. LBC was more accurate and sensitive than SC in EUS-FNA of pancreatic lesions with higher NPV when rapid on-site evaluation is unavailable. Pancreatic neck/body/tail lesions, solid lesions, 22-gauge needle, and more than 3 passes were associated with higher sensitivity when using LBC. Performing more than 3 passes is associated with higher sensitivity when using SC.


Renin inhibitors as an example of presumptive irrelevant positive findings in the Salmonella/mammalian microsome assay (Ames test).
An increase in the number of mutant colonies in the Ames test is generally taken as a strong indication for a genotoxic (e.g., DNA damaging) property of the test compound or its metabolites. However, a few examples are known in which mechanisms usually related to some sort of growth enhancement will lead to increases in mutant frequencies of spontaneous origin. The renin inhibitor Ro 42-5892 increased the number of mutant colonies of strain TA1538 and to a lesser degree of TA98 in the standard plate incorporation assay (Ames test). Since there is no chemical basis for a 'DNA reactivity' of this compound, experiments were performed to obtain information about possible indirect mechanisms of enhancing the number of spontaneous mutant colonies. Circumstantial evidence is presented to attribute the weak activity not to an inherent genotoxic property but rather to an as yet undefined indirect effect on the expression of spontaneous mutants. Since Ro 42-5892 contains a histidine residue it was a reasonable assumption to suspect a growth enhancing property of the test compound. However, none of the strains showed an elevation of the number of revertant colonies or an increase in the density of the background growth. In addition, structurally related non-histidine containing renin inhibitors showed absolutely no increase in the number of revertant colonies. Furthermore, no growth induction (either in liquid or under selective conditions) and no histidine cleave off by a TA1538/TA98 specific metabolism could be shown. A second line of evidence showing parallelism to growth enhancing compounds concerns the comutagenicity of histidine containing renin inhibitors. When Ro 42-5892 was tested in combination with established mutagens, a multiplicative synergism was found. This effect was observed not only in strains TA1538 and TA98 but also in the standard Salmonella tester strains where the spontaneous mutant frequency was not increased by Ro 42-5892. Analogous effects were previously shown for free histidine, isohistidine, phenobarbital and tetracycline and in part explained by molecular mechanisms.


In ovo inhibition of fowlpoxvirus replication by a gall extract from Guiera senegalensis.
Several field isolates of fowlpoxvirus (FPV) from Burkina Faso, West Africa, were isolated and partly evaluated by molecular analysis. In addition, the in ovo antiviral activity against FPV of a gall extract from Guiera senegalensis was determined. Three viral isolates were obtained from suspected fowlpox cases after passage in embryonating chicken eggs and their poxviral identity confirmed by electron microscopy. All isolates were found to be pathogenic for chicks and all grew well in cell culture. Polymerase chain reaction and sequencing of amplicons revealed sequences identical with those of other FPV strains. The most studied isolate was then employed for use in an antiviral assay. An aqueous acetone extract from the galls of G. senegalensis was found to inhibit both virus-induced pock formation and to reduce viral titre in embryonating chicken eggs. The suggested mechanism of action is the activation of the alternative complement pathway and the inhibition of FPV-induced cholesterogenesis in ovo by constituents of the gall extract.


Diagnostic procedures in vaginitis.
Ninety-seven vaginitis patients underwent a standardized direct method of examination. Bacterial vaginosis was found in 38.1%, Candida albicans in 24.7% and Trichomonas vaginalis in 13.4%. Low secretional pH values were never met in bacterial vaginosis and T. vaginalis cases. A fishy odor, present in bacterial vaginosis, was also found in almost half of the T. vaginalis cases. Endocervical bacteriological cultures are probably insufficient with respect to the detection of C. albicans and Gardnerella vaginalis. However, we found 12.4% Chlamydia trachomatis, which indicates that endocervical bacteriology may be indicated in vaginitis patients.


Chronic flupentixol treatment potentiates the reinforcing properties of systemic heroin administration.
The behavioral effects of systemic heroin administration were examined in rats subjected to flupentixol impregnation prior to and during behavioral testing. In the first experiment, the dose of heroin required to produce a place preference was determined in two groups of rats, one of which had received chronic flupentixol decanoate (12 mg/kg, sc, every 10 days for 6 weeks) and the other which had received the palm oil vehicle during the same time period. It was found that whereas 60 micrograms/kg of heroin was required to produce a place preference in control rats, only 7.5 micrograms/kg was sufficient to do so in chronic neuroleptic-treated rats. In a second experiment, the locomotor activating effect of heroin was evaluated in two groups of rats that had been subjected to the same chronic regimen as in Experiment 1. Locomotor activity was enhanced in both groups following 120 micrograms/kg heroin, whereas 30 micrograms/kg was ineffective in either group. Finally, it was found that neuroleptic-treated, but not control, rats rapidly learned to self-administer intravenous infusions of an unusually low dose of heroin (4 micrograms) and to discriminate these infusions from vehicle infusions. Together, these data show that chronic dopamine (DA) receptor blockade produces a marked increase in the sensitivity to the reinforcing and discriminative stimulus properties of systemic heroin administration and that this increase is not attributable to heroin-induced locomotor activation. The results are discussed in terms of the role of DA systems in opiate reinforcement processes.


Dose-finding studies in drug development for rare genetic diseases.
The small patient populations inherent to rare genetic diseases present many challenges to the traditional drug development paradigm. One major challenge is generating sufficient data in early phase studies to inform dose selection for later phase studies and dose optimization for clinical use of the drug. However, optimizing the benefit-risk profile of drugs through appropriate dose selection during drug development is critical for all drugs, including those being developed to treat rare diseases. Recognizing the challenges of conducting dose finding studies in rare disease populations and the importance of dose selection and optimization for successful drug development, we assessed the dose-finding studies and analyses conducted for drugs recently approved for rare genetic diseases. Of the 40 marketing applications for new molecular entity (NME) drugs and biologics approved by the United States Food and Drug Administration for rare genetic diseases from 2015 to 2020, 21 (53%) of the development programs conducted at least one dedicated dose-finding study. In addition, the majority of drug development programs conducted clinical studies in healthy subjects and included population pharmacokinetic and exposure-response analyses; some programs also conducted clinical studies in patient populations other than the disease for which the drug was initially approved. The majority of primary endpoints utilized in dedicated dose-finding studies were biomarkers, and the primary endpoint of the safety and efficacy study matched the primary endpoint used in the dose finding study in 9 of 13 (69%) drug development programs where primary study endpoints were assessed. Our study showed that NME drug development programs for rare genetic diseases utilize multiple data sources for dosing information, including studies in healthy subjects, population pharmacokinetic analyses, and exposure-response analyses. In addition, our results indicate that biomarkers play a key role in dose-finding studies for rare genetic disease drug development programs. Our findings highlight the need to develop study designs and methods to allow adequate dose-finding efforts within rare disease drug development programs that help overcome the challenges presented by low patient prevalence and other factors. Furthermore, the frequent reliance on biomarkers as endpoints for dose-finding studies underscores the importance of biomarker development in rare diseases.


Re-tensionable Quadriceps Tendon Repair Technique.
Quadriceps tendon rupture is a devastating injury that has traditionally been repaired using bone tunnels and knot tying. Recent innovations seeking to address persistent weakness and gap formation of repairs have used suture anchors and knotless technology. Despite these innovations, the clinical outcomes of these repairs continue to be mixed. We describe a technique that leverages a pre-tied knotted high-tension suture construct to allow for a re-tensionable quadriceps repair.


Endoscopic endonasal approach to the ventral cranio-cervical junction: anatomical study.
In order to develop an endoscopic endonasal approach to the ventral cranio-cervical junction and odontoid process under the concept of a minimally invasive surgical strategy, a cadaver study was performed. Sixteen artery-injected adult head specimens were used. Endonasal endoscopic approach was made through one- or two-nostril routes following the Jho's endonasal paraseptal technique. Rod-lens endoscopes, which were 2.7 or 4 mm in diameter, 18 cm in length with 0-, 30-, and 70-degree lenses, were used. Surgical landmarks leading to the craniocervical junction were the inferior margin of the middle turbinate, nasopharynx and Eustachian tube. The nasopharynx was readily identified following the inferior margin of the middle turbinate. The line drawn between the Eustachian tubes indicated the juncture between the clivus and atlas. With a midline mucosal incision, the ventral cranio-cervical junction was exposed. Odontoid resection was performed with removal of the anterior arch of the atlas. Clival resection can be performed as much rostral as required. Maneuverability of the surgical instruments was better with a two-nostril technique than with a one-nostril. Although the entire midline clivus was accessible rostrally, C-2 was the caudal limit through this endonasal route. A suturing device needed to be developed for mucosal or dural closure for live operations. This cadaver study demonstrates that an endoscopic endonasal approach to the ventral cranio-cervical junction and odontoid process can be a valid alternative to the conventional transoral approach.


Effects of various pre-slaughter weights on the physico-chemical qualities of pig meat.
The article aimed to study the relationship between the physico-chemical qualities of pig meat and their pre-slaughter weights. In this study, 60 pigs were reared for fattening under the same conditions of keeping and feeding, slaughtered, and used to sample the longest back muscle meat with pre-slaughter weights of 110 and 130 kg. The samples were evaluated according to generally accepted methods for assessing the physico-chemical qualities in pig meat. Samples of meat from animals slaughtered at 130 kg had higher values for marbling - by 2.0 points or 5.24% (p < 0.01), active acidity pH in ham muscles - by 0.20 pH or 3.57% (p < 0.01), and the longest muscle of the back - by 0.10 pH or 1.82% (p < 0.001). The pre-slaughter weight factor substantially affected the pH of ham muscles at 10.35% and on the marbling of meat in the longest back muscle at 13.31%. Pigs slaughtered at 110 kg had a greater increase in the color intensity of the meat and an increase in its water holding capacity. At a pre-slaughter weight of 130 kg, increasing the marbling and decreasing the softness of the flesh demonstrated a modest, adverse relationship. The findings support the use of pre-slaughter weight management to enhance pork quality.


Making the most of medicaid: promoting the health of women and infants with preconception care.
This paper examines the evolution and current role of Medicaid in improving access to preconception care for low-income women. The authors review Medicaid's eligibility policy and benefits of relevance to women of reproductive age and discuss various approaches to promote preconception care in Medicaid. The challenges facing the program and potential opportunities to use the program to promote preconception care to low-income women are discussed.


Cardiac output and pulmonary gas exchange at maximal exercise after atrial redirection for complete transposition.
To assess the determinants of exercise capacity and exercise oxygenation after atrial redirection for complete transposition. At graded bicycle ergometry, including respiratory and arterial blood gas analyses, intra-arterial blood pressure recording, and cardiac output determination (dye-dilution technique), we tested 17 post-Mustard/Senning patients, 8.9-22.0 years old (mean 14.5, SD 4.0). Reference data were obtained by similar methods. At maximal exercise, oxygen uptake (29.6 ml x kg(-1) x min(-1)) and heart rate (167 beats x min(-1)) were low (P<0.001). Right-to-left shunts were detected in five patients. Arterial oxygen partial pressure and saturation fell in all subjects (P<0.0001). In 15/16 (94%) the alveolar-arterial oxygen partial pressure difference was > +2 SD. In 13/15 (87%) stroke volumes fell during exercise. Cardiac output per oxygen uptake was low (P<0.0001), which implies a high arteriovenous oxygen difference and a low mixed venous oxygen content at peak exercise. The low exercise capacity was caused by a combination of low maximally attained heart rate and falling stroke volumes. The impaired arterial oxygenation may be caused by a combination of pulmonary ventilation/perfusion mismatch, a low mixed venous content and atrial shunting in some patients.


Fellow-eye comparison of posterior capsule opacification between 2 aspheric microincision intraocular lenses.
To compare posterior capsule opacification (PCO) between 2 microincision hydrophilic intraocular lenses (IOLs) and with a conventional spherical hydrophobic IOL. St. Thomas' Hospital, London, United Kingdom. Prospective randomized comparative study. A microincision Acri.Smart 36A (negatively aspheric) or Akreos MI-60 (aspherically neutral) IOL was randomized to the first eye of patients with the alternative IOL implanted in the fellow eye within 3 weeks. Postoperatively, 100% and 9% logMAR corrected distance visual acuity (CDVA) were assessed. Retroillumination photographs were analyzed using the posterior capsule opacity software system. The data on PCO scores were compared with those of a conventional spherical hydrophobic IOL (Acrysof SN60AT). One hundred percent CDVA was significantly better at 12 months and 9% CDVA was better at 6, 12, and 24 months (P<.05) with the negatively aspheric IOL. One eye in each group with microincision IOLs developed capsule phimosis at 1 month. Neodymium:YAG capsulotomies were required by 2 years in 2 eyes with a negatively aspheric IOL and 8 eyes with an aspherically neutral IOL. At 24 months, the mean PCO score remained less than 10% with the conventional spherical IOL, whereas it increased with time in the negatively aspheric IOL (up to 16%) and the aspherically neutral IOL (up to 23%). The negatively aspheric IOL had a better PCO profile than the aspherically neutral IOL. This may be attributed to the difference in the edge design between the IOLs. The microincision IOLs had more PCO than the conventional 1-piece hydrophobic IOL.


[Genetic control of the number of copies of type K2 killer plasmids in Saccharomyces cerevisiae].
13 non-linked chromosomal mutations derepress the negative genetic control of copy number of K2 yeast killer plasmids and lead to 1.5-2-fold elevating of copy number of that type plasmids -L2A and M2 virus-like dsRNA. The content of both plasmids is increased 3-5-fold in cells with chromosomal ski5 mutation, as compared to the strains of wild type. Expression of ski5 allele is recessive. The dose effect of this allele is observed on haploid and diploid levels. Dominant ochre nonsense suppressors suppress the action of ski5 and the ski6 allele epistates that of ski5.


The complete mitochondrial genome of Plesiastrea versipora (Scleractinia, Plesiastreidae) sheds light on its phylogeny and taxonomy of the family Plesiastreidae.
The genus Plesiastrea used to be a member of the traditional family Faviidae, falling into the challenging 'Bigmessidae' clade, and was re-established until recent molecular phylogenies published. The entire mitogenome of the symbiotic coral Plesiastrea versipora (Lamarck, 1816), the type species of the family Plesiastreidae, was sequenced. The length of the mitochondrial genome is 15,320 bp and it includes thirteen protein-coding genes (PCGs), two rRNAs and two tRNAs. The nucleotide composition of GC is 32%. We perform phylogenetic reconstruction based on maximum likelihood (ML) and Bayesian analysis(BI) using all PCGs. Our result indicates that P. versipora clusters closely with species which belong to Mussidae, Merulinidae and Lobophylliidae. Our phylogenetic analyses provide solid evidence for phylogenetic placement of P. versipora and the evolutionary relationships among different families within the traditional robust clade of Scleractinia. In addition, the mitogenome data provide useful information for further molecular systematic investigations on Plesiastreidae as well as conservation biology research of P. versipora.


Enhanced expression of alkaline phosphatase in hybrids between neuroblastoma and embryonal carcinoma.
Three independent hybrid cell lines were isolated from the fusion of clonal lines of embryonal carcinoma and neuroblastoma. A series of subclones was subsequently derived from the original hybrid clones. In early hybrid generations all hybrid lines showed enhancement of alkaline phosphatase activity, expressing 2--8 times the activity of the teratoma parental line. The overexpression of APase appears to take place in the stationary phase of the growth cycle. Segregation for very high levels of APase activity was observed among subclones of one hybrid line. Specific activities of the segregants ranged from 0.1 to 133. Results of heat denaturation studies are consistent with the hypothesis that it is the embryonal carcinoma APase that is being expressed in the hybrids.


Study of spatiotemporal regulation of kinase signaling using genetically encodable molecular tools.
Precise spatiotemporal organization and regulation of signal transduction networks are essential for cellular response to internal and external cues. To understand how this biochemical activity architecture impacts cellular function, many genetically encodable tools which regulate kinase activity at a subcellular level have been developed. In this review, we highlight various types of genetically encodable molecular tools, including tools to regulate endogenous kinase activity and biorthogonal techniques to perturb kinase activity. Finally, we emphasize the use of these tools alongside biosensors for kinase activity to measure and perturb kinase activity in real time for a better understanding of the cellular biochemical activity architecture.


Cadaveric Study of an Endoscopic Keyhole Middle Fossa Craniotomy Approach to the Superior Semicircular Canal.
Demonstrate that an endoscopic keyhole approach to the middle cranial fossa is technically feasible for repair of semicircular canal dehiscence. Cadaveric technical feasibility/methods development study. Tertiary care military medical center. Three fresh cadaveric heads (six sides). Endoscopic minimally invasive approach to the middle cranial fossa using the Medtronic Fusion Guidance system. Ability to identify the surgical landmarks of the middle cranial fossa and successfully identify and instrument the superior semicircular canal. In every attempt, the arcuate eminence was successfully identified under endoscopic visualization and with the assistance of surgical navigation. The superior semicircular canal was unroofed, and its location confirmed visually and with the navigation system. The opened canal was then plugged with bone wax, bone pate, and covered with fascia. The 15-mm burr hole craniotomy provided ample room for one working instrument and a 4-mm 0-degree endoscope. The endoscopic keyhole approach to superior semicircular canal dehiscence is technically feasible in a human cadaveric model. Further studies will determine 1) if this approach is possible and safe in vivo, 2) is associated with improved surgical outcomes, and 3) if surgical navigation aids in this approach.


Pharmacokinetic and glucodynamic variability: assessment of insulin glargine, NPH insulin and insulin ultralente in healthy volunteers using a euglycaemic clamp technique.
This single-dose, double-blind, randomised, parallel-group study evaluated the reproducibility in systemic exposure and glucodynamic effect of insulin glargine, NPH insulin (NPH) and insulin ultralente (ultralente) using the manually adjusted euglycaemic clamp technique. In total, 36 healthy volunteers received two consecutive s.c. injections (0.4 IU/kg) of glargine, NPH or ultralente with a wash-out period of 7 days between treatments. In healthy volunteers, glargine presented well-reproduced flat concentration profiles and no pronounced peaks in activity. NPH, by contrast, showed well-defined peaks in concentration and glucose disposal, while ultralente had highly variable profiles. Within-subject variability (ANOVA) for insulin exposure over 24 h was 15% for glargine and 19% for NPH, compared with 67% for ultralente (p<0.05, glargine and NPH vs ultralente). The 49% within-subject variability in total glucose disposal (glucose infusion rate [GIR]-AUC0-24 h) with ultralente was about twice as large as the 22% with NPH (p<0.05), but was intermediate with glargine at 31% (p=NS). By contrast, variability in the diurnal time-action profile (SD of diurnal day-to-day differences in GIR) for glargine was 30% (p<0.05) and 50% (p<0.05) less than with NPH and ultralente, respectively. No serious adverse events were reported. Although representing insulins of different profiles, glargine and NPH showed a high and similar reproducibility of total absorption and glucodynamic effect, whereas ultralente proved to have poor reproducibility. However, while NPH yields peaks in concentration and activity, glargine shows flat and non-fluctuating profiles resulting in less variation in day-to-day 24-h activity.