Fertility-Sparing surgery for young women with ovarian endometrioid carcinoma: a multicenteric comparative study using inverse probability of treatment weighting.
The aim of this study was to evaluate the oncologic outcome of women with stage I ovarian endometrioid carcinoma (EC) who underwent fertility-sparing surgery (FSS). Between 1986 and 2017, a total of 3227 patients with epithelial ovarian carcinoma were retrospectively evaluated based on a central pathological review and search of the medical records from multiple institutions. We identified 24 and 54 patients with stage I EC who underwent FSS and conventional radical surgery (CRS), respectively. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox regression analyses were employed to compare OS between the two groups. With follow-up of a total of 78 patients, 9 patients (11.5%) developed recurrence. In addition, 5 patients (6.4%) died of the disease. Recurrence was noted in 3 (10.7%) patients in the FSS group and 6 (11.1%) patients in the CRS group. Death was noted in 2 (8.3%) patients in the FSS group and 3 (5.6%) patients in the CRS group. In the original cohort, there was no significant difference in overall survival (OS) or recurrence-free survival (RFS) between the FSS and RS groups {Log-rank: OS (P = 0.630), RFS (P = 0.757)}. In the IPTW-adjusted cohort, the 5-year OS rates were 96.6 and 92.4% in patients with FSS and CRS, respectively (P = 0.319). Furthermore, the 5-year RFS rate was 88.6% for the FSS group and 88.1% for the CRS group (Log-rank: P = 0.556). Young women with stage I EC undergoing FSS showed a relatively satisfactory prognosis, equal to those receiving CRC.


Whole blood selenium determination by inductively coupled plasma mass spectrometry.
To develop a sensitive method for accurately measuring whole blood selenium and determining an appropriate reference interval for the local Cleveland population. The assay was developed and validated on an inductively coupled plasma mass spectrometry (ICP-MS) with a collision cell. Whole blood trace element free EDTA tubes were used to collect samples for the reference interval study (n=50). Samples were collected after at least 8h fast from healthy adults (76% females) with ages between 19 and 64yr. Whole blood aliquots (1mL) in acid washed cryogenic vials were stored at -70°C until analysis. The method passed the matrix effect, interference (except for Gd), and carryover tests. The method had a linear range of 0.2-7.1μmol/L with accuracies of 87.1-118.1%. The total assay imprecision (CV) was <2.5% across the concentration levels tested. Comparison to another ICP-MS assay offered by an independent clinical lab yielded a Deming regression with a slope of 0.98, an intercept of 0.1μmol/L, a standard error of estimate of 0.1μmol/L, a correlation coefficient of 0.9846, and an average difference of 0.8%. The whole blood Se reference interval using a transformed parametric method was 2.2-3.5μmol/L. This whole blood Se ICP-MS methodology is sensitive and acceptable for patient testing.


Duration, recency, and type of hormonal contraceptive use and antimüllerian hormone levels.
To assess whether the duration, recency, or type of hormonal contraceptive used is associated with antimüllerian hormone (AMH) levels, given that the existing literature regarding the association between hormonal contraceptive use and AMH levels is inconsistent. Cross-sectional study. Baseline data from the Study of the Environment, Lifestyle and Fibroids Study, a 5-year longitudinal study of African American women. The patients were 1,643 African American women aged 23-35 years at the time of blood drawing (2010-2012). None. Serum AMH level was measured by an ultrasensitive enzyme-linked immunosorbent assay. Linear regression models were used to estimate percent differences in mean AMH levels and 95% confidence intervals (CIs) according to use of hormonal contraceptives, with adjustment for potential confounders. In multivariable-adjusted analyses, current users of hormonal contraceptives had 25.2% lower mean AMH levels than non-users of hormonal contraceptives (95% CI: -35.3%, -13.6%). There was little difference in AMH levels between former users and non-users of hormonal contraceptives (-4.4%; 95% CI: -16.3%, 9.0%). AMH levels were not appreciably associated with cumulative duration of use among former users or time since last use among non-current users. Current users of combined oral contraceptives (-24.0%; 95% CI: -36.6%, -8.9%), vaginal ring (-64.8%; 95% CI: -75.4%, -49.6%), and depot medroxyprogesterone acetate (-26.7%; 95% CI: -41.0%, -8.9%) had lower mean AMH levels than non-users. The present data suggest that AMH levels are significantly lower among current users of most forms of hormonal contraceptives, but that the suppressive effect of hormonal contraceptives on AMH levels is reversible.


Fatty acid hydroxylase system in the Japanese harvest mouse, Micromys minutus.
Liver microsomes of the Japanese harvest mouse (Micromys minutus), which is the smallest known mammal among rodents, catalyze the hydroxylation of various fatty acids (C8 to C18) to the corresponding omega-hydroxy and (omega-1)-hydroxy derivatives. Although laurate is most effectively hydroxylated among saturated fatty acids by liver microsomes of other species, harvest mouse liver microsomes most effectively catalyze the hydroxylation of decanoate. From inhibitor and cofactor studies, and from the substrate specificity for hydroxylation, it was concluded that omega- and (omega-1)-hydroxylation of fatty acids are catalyzed by different cytochrome P-450 species in the liver microsomes of the harvest mouse.


Significance of PML and p53 protein as molecular prognostic markers of gallbladder carcinomas.
Molecular markers for cancers are not only useful for cancer detection and prognostic prediction, but may also serve as potential therapeutic targets. In order to identify reliable molecular markers for prognostic prediction in gallbladder carcinoma (GBC), we evaluated the immunohistochemical expression of 15 proteins, namely p53, p27, p16, RB, Smad4, PTEN, FHIT, GSTP1, MGMT, E-cadherin, nm23, CD44, TIMP3, S100A4, and promyelocytic leukemia (PML) in 138 cases of GBC using the tissue microarray method. The prognostic significance was analyzed for each protein. Overexpression of p53 and S100A4, and loss of p27, p16, RB, Smad4, FHIT, E-cadherin and PML expression were associated with poor survival. In particular, PML and p53 showed considerable potential as independent prognostic markers. Patients with normal PML and p53 expression displayed favorable outcomes, compared to those showing abnormal expression of either or both proteins (49% vs. 23% in a 5-year survival rate; 60 months vs. 11 months in median survival, respectively; P=0.009). Thus, PML and p53 are potential candidates for development as clinically applicable molecular prognostic markers of GBC, and may be effective therapeutic targets for the disease in the future.


New opto-plasmonic tweezers for manipulation and rotation of biological cells--design and fabrication.
Opto-Plasmonic Tweezers are proposed as a new optical manipulator and rotator for biological cells. The approach utilizes polarized light to excite localized surface plasmon resonance (LSPR) on an array of Au nanostructure. Large dielectrophoretic trapping force is expected to be induced by the highly non-uniform scattering field from the resonant oscillating dipoles. Fine orientation control of the cells can be realized by tuning the polarization state of the input light.


Coronary tortuosity is negatively correlated with coronary atherosclerosis.
The impact of coronary tortuosity on coronary atherosclerosis remains unclear. This study was performed to determine to the relationship between coronary tortuosity and the presence of coronary atherosclerosis. Tortuosity and the presence of coronary atherosclerosis in the main coronary arteries were evaluated. The coronary artery was divided into non-tortuous and tortuous segments. The incidence of coronary atherosclerosis between the two segments was compared. The prevalence of coronary atherosclerotic stenosis was significantly lower in the tortuous than non-tortuous segment. The prevalence of coronary atherosclerotic stenosis is lower in the coronary tortuous than non-tortuous segment, indicating that coronary tortuosity might be considered a protective factor for atherosclerosis.


PHA-induced interferon in multiple sclerosis: association between gamma interferon and clinical and genetical variables.
Gamma interferon (INF-gamma) production, after PHA stimulation of peripheral blood mononuclear cells, from multiple sclerosis (MS) patients with the acute remitting and chronic progressive forms, in attack and remission phases, and from normal controls, was studied by immunoradiometric assay. MS patients in all these 4 clinical states of disease produced less INF-gamma (log value range from 2.55 to 2.65). MNC from the total MS patients produced significantly low levels of INF-gamma compared to the control group (log values 2.60 vs. 2.82; P = 0.001). No association between the interferon production and antigens at any HLA locus (A, B, C, Dw and Bf) was found. There was no correlation between IFN-gamma production and age, sex, duration of disease, or disability index. However there was a slight tendency to negative correlation with the progression index of the disease. The results suggest that this lower IFN-gamma production in MS may be secondary to the disease, and the primary defect may be a severe reduction of the essential lymphocyte populations required for an effective lymphokine cascade to produce the normal immune response against infection.


Recent advances in transdermal drug delivery.
Transdermal delivery of pharmacologically active agents has been extensively studied for the past 40 years. Despite the strong efforts, currently, only about 40 products are in market on about 20 drug molecules, due to the requirements that the patch area should be small enough for the patients to feel comfortable, and to the barrier properties of the stratum corneum. Various approaches to overcome the barrier function of skin through physical and chemical means have been broadly studied. The development of an effective transdermal delivery system is dictated by the unique physicochemical property each drug molecule possesses. In this review, we have summarized various physical and chemical approaches for transdermal flux enhancement, including the application of electricity, ultrasound, microneedle and chemical enhancers. Pressure sensitive adhesive such as acrylics, rubbers and silicones are described together with recent developments. Factors affecting dosage form design, particularly for drug in adhesive system, like adhesion and crystallization are also discussed.


Contribution of genetic polymorphisms of interleukins IL1B-511 C/T, IL1RN VNTR, IL6-174 G/C, and IL8-251 A/T in gastric lesions: gender and Helicobacter pylori genes matter.
Stomach pathologies develop in a complex interaction between the host's genetic background and H. pylori virulent genes. Thus, our study aimed to compare active chronic gastritis (ACG), and intestinal metaplasia (IM) with inactive chronic gastritis (ICG), according to interleukin polymorphisms of IL6-174 G/C, IL8-251 A/T, IL1β-511 C/T, and IL1RN VNTR taking into account patient gender and H. pylori genotypes. Interleukin polymorphisms were determined by RFLP-PCR and H. pylori genotype by PCR. IL6-174 GC and IL8-251 T allele showed a protective effect in women against ACG development and, conversely, IL8-251 polymorphism showed a risk for men. More virulent H. pylori strains were associated with the IL8-251 T allele and IL1β-511 T allele in the AGC, and the vacA m1 allele and cagE gene from H. pylori was associated with the IM. Analysis of the progression of gastric lesions must take into account host variability genetic associated with genes H. pylori due to the relation between the virulent H. pylori genes and more severe gastric lesions, besides the relevance to the gender to IL6-174 and IL8-251 polymorphisms.


Anticipating future actions: Motor planning improves with age in wild bearded capuchin monkeys (Sapajus libidinosus).
Self-directed object manipulation tasks illuminate development of motor planning. Grasping strategies that lead to good object control to perform the following action(s) reveal second-order motor planning. Motor planning for efficient grips develops slowly in children. Age-related differences in other primates have been poorly investigated. Here, we investigated anticipatory motor planning of infant, juvenile and adult wild capuchin monkeys grasping a horizontally positioned stick baited to the left or right side (a version of the elevated spoon task). We recorded the grasps capuchins used to bring the baited end of the stick to the mouth. The percentage of efficient radial grips positively correlated with age and adults used efficient grips significantly more frequently than infants. Adult wild capuchins' use of radial grips was higher than that reported for adult captive capuchins in similar tasks, suggesting that experience throughout life may influence motor anticipation. Self-directed object manipulation tasks will be useful to compare this aspect of cognition across primates. A video abstract of this article can be viewed at https://youtu.be/a1Zbr_AQkb8.


Dynamic evolution of brain structural patterns in liver transplantation recipients: a longitudinal study based on 3D convolutional neuronal network model.
To evaluate the dynamic evolution process of overall brain health in liver transplantation (LT) recipients, we employed a deep learning-based neuroanatomic biomarker to measure longitudinal changes of brain structural patterns before and 1, 3, and 6 months after surgery. Because of the ability to capture patterns across all voxels from a brain scan, the brain age prediction method was adopted. We constructed a 3D-CNN model through T1-weighted MRI of 3609 healthy individuals from 8 public datasets and further applied it to a local dataset of 60 LT recipients and 134 controls. The predicted age difference (PAD) was calculated to estimate brain changes before and after LT, and the network occlusion sensitivity analysis was used to determine the importance of each network in age prediction. The PAD of patients with cirrhosis increased markedly at baseline (+ 5.74 years) and continued to increase within one month after LT (+ 9.18 years). After that, the brain age began to decrease gradually, but it was still higher than the chronological age. The PAD values of the OHE subgroup were higher than those of the no-OHE, and the discrepancy was more obvious at 1-month post-LT. High-level cognition-related networks were more important in predicting the brain age of patients with cirrhosis at baseline, while the importance of primary sensory networks increased temporarily within 6-month post-LT. The brain structural patterns of LT recipients showed inverted U-shaped dynamic change in the early stage after transplantation, and the change in primary sensory networks may be the main contributor. • The recipients' brain structural pattern showed an inverted U-shaped dynamic change after LT. • The patients' brain aging aggravated within 1 month after surgery, and the subset of patients with a history of OHE was particularly affected. • The change of primary sensory networks is the main contributor to the change in brain structural patterns.


High dose estrogen response of the hormone independent R3327-At Copenhagen rat prostatic tumor.
In studies with the hormone independent R3327-At prostatic tumor, relatively high doses of estrogen were inhibitory to the growth of the R3327-At rat prostatic tumor were observed. It was further observed that although tumor growth was inhibited, an increase in the [3H]thymidine labelling of the DNA of the tumor cells of the estrogen treated group relative to the castrate control was apparent.


Chagas' disease: IgG isotypes against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive antigens of Trypanosoma cruzi in chronic Chagasic patients.
The wide range of clinical Chagas' disease manifestations, of which heart involvement is the most significant, because of its characteristics, frequency and consequences, and lack of treatment and cure, justify research in this area. Specific immunoglobulin G (IgG) antibody subclasses have been associated with human Chagas' disease. Thus, in this study, the profile of IgG subclasses against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive T. cruzi-specific antigens was correlated with cardiac (CARD, n=33), cardiodigestive (CD, n=7), and indeterminate (IND, n=20) forms of Chagas' disease by indirect enzyme-linked immunosorbent assay (ELISA). IgG subclasses were detected in almost all Chagas patients studied. Nevertheless, only specific IgG2 isotype FRA was found with a significant statistical difference in CARD patients when compared to IND patients. This result suggests the potential use of this isotype for prognostic purposes, for monitoring the progression of chronic Chagas' disease, and for predicting the risk of CARD damage. This is important information, as it could help physicians to evaluate and manage the treatment of their patients. However, a follow-up study is necessary to confirm our result.


Attitudes towards disclosing a mental illness: impact on quality of life and recovery.
The decision whether to disclose a mental illness has individual and social consequences. Secrecy may protect from stigma and discrimination while disclosure can increase social support and facilitate help-seeking. Therefore, disclosure decisions are a key reaction to stigma. The first aim of this study was to test a newly developed scale to measure disclosure attitudes, the Attitudes to Disclosure Questionnaire (AtDQ). The second aim was to examine the impact of attitudes towards disclosing a mental illness on quality of life and recovery. Among 100 participants with mental illness, disclosure attitudes, quality of life, recovery, benefits of disclosure, secrecy, social withdrawal, self-stigma, and depressive symptoms were assessed at weeks 0, 3 and 6. Psychometric properties of the AtDQ were analysed. Longitudinal associations between disclosure attitudes at baseline and quality of life and recovery after 6 weeks were examined in linear regressions. The analyses of the AtDQ indicated one-factor solutions, high acceptability, high internal consistency, and good retest reliability for the total scale and the subscales as well as high construct validity of the total scale. Results provided initial support for sensitivity to change. More positive disclosure attitudes in general and in particular regarding to family at baseline predicted better quality of life and recovery after 6 weeks. The current study provides initial support for the AtDQ as a useful measure of disclosure attitudes. Disclosing a mental illness, especially with respect to family, may improve quality of life and recovery of people with mental illness.


Bis{2-meth-oxy-6-[(4-methyl-phen-yl)iminiometh-yl]phenolato-κO,O}tris-(nitrato-κO,O')methano-lsamarium(III).
The asymmetric unit of the title compound, [Sm(NO(3))(3)(C(15)H(15)NO(2))(2)(CH(3)OH)], contains two Schiff base 2-meth-oxy-6-[(4-methyl-phen-yl)iminiometh-yl]phenolate (HL) ligands, three nitrate ions and one methanol mol-ecule that binds to the nine-coordinate samarium(III) ion via its O atoms. The HL ligands chelate with a strong Sm-O(deprotonated phenolic) bond and a weak Sm-O(meth-oxy) contact. The latter can be inter-preted as the apices of the bicapped square-anti-prismatic Sm(III)O(9) polyhedron. The Schiff base ligands are in a zwitterionic state with the phenolic H atom transferred to the imine N atom. O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds lend stability to the structure. One O atom of one nitrate group is equally disordered over two positions.


Neutralizing the pathological effects of extracellular histones with small polyanions.
Extracellular histones in neutrophil extracellular traps (NETs) or in chromatin from injured tissues are highly pathological, particularly when liberated by DNases. We report the development of small polyanions (SPAs) (~0.9-1.4 kDa) that interact electrostatically with histones, neutralizing their pathological effects. In vitro, SPAs inhibited the cytotoxic, platelet-activating and erythrocyte-damaging effects of histones, mechanistic studies revealing that SPAs block disruption of lipid-bilayers by histones. In vivo, SPAs significantly inhibited sepsis, deep-vein thrombosis, and cardiac and tissue-flap models of ischemia-reperfusion injury (IRI), but appeared to differ in their capacity to neutralize NET-bound versus free histones. Analysis of sera from sepsis and cardiac IRI patients supported these differential findings. Further investigations revealed this effect was likely due to the ability of certain SPAs to displace histones from NETs, thus destabilising the structure. Finally, based on our work, a non-toxic SPA that inhibits both NET-bound and free histone mediated pathologies was identified for clinical development.


Treatment of postvitrectomy fibrin pupillary block with tissue plasminogen activator.
We injected 25 micrograms of recombinant tissue plasminogen activator into the anterior chamber or the vitreous cavity in seven aphakic patients for pupillary block caused by a complete fibrin pupillary membrane that formed after vitrectomy with fluid-gas exchange. Progressive fibrin deposition resulted in pupillary block by three days after vitrectomy surgery in six patients, and seven days after vitrectomy in one patient. The pupillary block was associated with increased intraocular pressure in six patients. Tissue plasminogen activator was injected via the corneoscleral limbus in five patients and via the pars plana in two patients. In all patients, injection of tissue plasminogen activator resulted in complete fibrinolysis of the fibrin pupillary membrane within four hours, associated with a deepening of the anterior chamber. In the six patients with increased intraocular pressure at the time of tissue plasminogen activator injection, dissolution of the fibrin membrane was associated with a decrease in pressure. In all patients, intraocular pressure had returned to normal by three days after the injection. No complications were associated with the injection.


Graphene nanopore devices for DNA sensing.
We describe here a method for detecting the translocation of individual DNA molecules through nanopores created in graphene membranes. The devices consist of 1-5-nm thick graphene membranes with electron-beam sculpted nanopores from 5 to 10 nm in diameter. Due to the thin nature of the graphene membranes, and the reduced electrical resistance, we observe larger blocked currents than for traditional solid-state nanopores. We also show how ionic current noise levels can be reduced with the atomic-layer deposition of a few nanometers of titanium dioxide over the graphene surface. Unlike traditional solid-state nanopore materials that are insulating, graphene is an excellent electrical conductor, and its use opens the door to a new future class of nanopore devices in which electronic sensing and control is performed directly at the pore.


Maternal vitamin B3 and C intake in pregnancy influence birth weight at term.
The objective of this study was to examine the influence of maternal nutrient intake during pregnancy on the baby's birth weight at term. A cross-sectional study design was used to evaluate a sample of women aged 18 to 44 y in the postpartum period in a public maternity department (2018-2019), with dietary intake collected by a validated food frequency questionnaire (n = 626 mother-offspring pairs). A multivariable linear regression model was used to identify the influence of nutrient intake during pregnancy on the baby's birth weight at term. The model was adjusted for maternal energy intake, education level, gestational age, physical activity, and supplementation during pregnancy. Maternal intake of vitamins B3 and C was associated with an increase in birth weight (respectively, β = 0.01; 95% confidence interval [CI], 0.01-0.02; P = 0.01; and β = 0.01; 95% CI, 0.01-0.02; P = 0.02). Prepregnancy body mass index (β = 0.01; 95% CI, 0.01-0.02; P = 0.001), gestational weight gain (β = 0.02; 95% CI, 0.01-0.02; P < 0.001), parity (β = 0.05; 95% CI, 0.02-0.09; P = 0.001), and male babies (β = 0.08; 95% CI, 0.01-0.02; P = 0.02) also contributed to increase birth weight. These variables explained about 27% of the variation of this outcome (adjusted R2 = 0.27, P < 0.001). Our findings provide evidence that maternal intake of vitamins B3 and C influences increased birth weight. In addition, prepregnancy body mass index, gestational weight gain, parity, and male babies contribute to the same outcome.


Temporary cognitive impairment related to administration of newly developed anticholinergic medicines for overactive bladder: two case reports.
Cognitive impairment is one of the side effects of using anticholinergic medicines for overactive bladder; however, its incidence has not been fully reported. We experienced two elderly Japanese patients with overactive bladder who had temporary cognitive impairment caused by anticholinergic medicines. The first case was a 79-year-old female patient to whom imidafenacin (0.2 mg) was administered daily to control her frequent micturition and urgency. She was taking the following medicines: etizolam, triazolam, captopril, bisoprolol, and amlodipine besylate. Her Hasegawa dementia rating scale-revised was impaired from 26/30 to 17/30 and recovered to 25/30 after the imidafenacin treatment was stopped. The second case was an 82-year-old female patient to whom imidafenacin (0.2 mg) was administered daily for frequent micturition and urgency. She was taking the following medicines: losartan potassium and clenbuterol. Her Hasegawa dementia rating scale-revised decreased from 28/30 to 19/30 and recovered to 24/30 after the imidafenacin treatment was stopped. In our patients who were taking multiple medicines, there is a possibility that medicines other than anticholinergics may have caused cognitive impairment. We need to keep in mind that many elderly people take multiple medicines because of comorbidity. Anticholinergic medicines can cause cognitive impairment in elderly people, and attention should be paid to cognition when elderly overactive bladder patients are treated with anticholinergic medicines.


Effects of Dietary Supplementation with Bilberry Extract on Growth Performance, Immune Function, Antioxidant Capacity, and Meat Quality of Yellow-Feathered Chickens.
The experiment was conducted to investigate the effects of bilberry extract on growth performance, meat quality, antioxidant status, and immune function of yellow-feathered chickens. A total of 360 female hatchling Lingnan chickens were randomly allocated to three treatments with 6 replicates of 20 chickens per replicate. Birds were fed a basal diet supplemented with 0 (the control group), 100 (B100), and 400 (B400) mg/kg of bilberry extract for 63 d. Compared with the controls, (1) dietary supplementation with bilberry extract did not affect the growth performance of chickens from 1 to 63 d. (2) At 21 d, the relative weight of the bursa of Fabricius was increased (p < 0.05) by dietary supplementation with 400 mg/kg bilberry extract. Bilberry extract decreased the concentrations of IgY and IgM in blood plasma of 63-d chickens (p < 0.05). (3) For 21-d chickens, dietary supplementation with 400 mg/kg bilberry extract increased (p < 0.05) the activity of GSH-Px in blood plasma and jejunal mucosa (p < 0.05). Supplementation with 100 mg/kg bilberry extract increased (p < 0.05) the activities of T-SOD in jejunal mucosa and GSH-Px in the liver and decreased (p < 0.05) the MDA concentration in the liver. For chickens at the age of 63 d, both levels of bilberry extract increased activity of T-SOD in blood plasma (p < 0.05) and reduced MDA concentration in the jejunum (p < 0.05). (4) Supplementation with bilberry extract in the diet decreased the MDA concentration (B100) in muscle of 63-d chickens at 45 min postmortem and increased (p < 0.05) the activity of T-SOD (B400) at 4 d postmortem. (5) In breast muscle at 63 d, birds supplemented with bilberry extract (B400) had increased pH and drip loss while drip loss was reduced in the B100 treatment (p < 0.05); treatments did not affect inosinic acid or intramuscular fat contents. In conclusion, dietary supplementation of yellow-feathered chickens with bilberry extract enhanced the relative weight of the bursa of Fabricius, and broadly increased activities of antioxidant enzymes; indices of meat quality were improved without impact on growth performance. Considering the results in the current research, 100 mg/kg bilberry extract was recommended when supplemented in chickens.


The commercial and agricultural applications of animal transgenesis.
The potential for commercial application of transgenic technologies in domestic animals is discussed in relation to the areas where a significant impact on agriculture might be expected. These are the endocrine system, novel biochemical pathways, structural proteins of milk and of textile fibers, and the immune system. Manipulation of the endocrine system has been investigated for some years and it is clear that very accurate control is needed over gene expression if this approach is to prove commercially useful. The area most advanced in commercial application is the production of high-value pharmaceutical proteins in the mammary glands of domestic animals. Other applications that are discussed remain to be proven in larger animals despite being demonstrated laboratory test animals. These include a functional cysteine biosynthetic pathway and a functional glyoxylate cycle transferred from bacteria to mice, and alterations to the proteins of hair that change the physical properties of the resultant fibers. Research is also actively directed toward novel approaches for providing domestic animals with resistance to insects.


Naked Gene Salmon: Debating Fish, Genes, and the Politics of Science in the "Age of Publics".
This article follows what was supposed to become a new salmon for the aquaculture industry on its travels through Norwegian society during the 1980s. This is a history of a new animal technology that was born out of the biotechnology hype of the 1980s. The article takes Edmund Russell's claim that the tools of historians of technology can be utilized for investigating animals as technologies as a point of departure. However, instead of investigating the construction of the fish, the article focuses on how the new creature was integrated into society through controversy.


Monte Carlo simulation of molecular and structural properties of random copolymer thin films.
Molecular and structural properties of random copolymer thin films were studied by Monte Carlo simulation of coarse-grained copolymer model on the high coordination lattice. Random copolymer thin films with 50% comonomer fraction with varied interaction strength between comonomer units were studied. Intramolecular interaction was represented by Flory's rotational isomeric state (RIS) model of polyethylene (PE). The non-bonded interactions were treated by Lennard-Jones potential with different parameter sets for comonomer units. When the interaction strength of comonomer is increased, the density of thin films is higher in the inner region and significantly dropped near the free surface along the normal direction of the film. Higher bulk densities and narrower interfacial thicknesses are observed for random copolymer with stronger bead interaction. End beads were segregated at the free surface region and tend to orient perpendicularly to the surface. Copolymer size and shape were significantly changed as a function of bead interaction. For orientation of the whole chain, the largest molecular axis tends to orient along the film surface, but changed toward random orientation for weaker bead interaction. The intra-chain energies were decreased at the surface region while the non-bonded energies were increased. The stronger the comonomer bead attraction, the more change in energetics across the thin film.


Evaluating Standard of Care and Obstetrical Outcomes in a Reduced Contact Prenatal Care Model in the COVID-19 Pandemic.
We aimed to investigate the impact of reduced contact prenatal care necessitated by the COVID-19 pandemic on meeting standards of care and perinatal outcomes. This was a retrospective case-control study of patients in low-risk obstetrics clinic at a tertiary care county facility serving solely publicly insured patients comparing reduced in-person prenatal care (R) over 12 weeks with a control group (C) receiving traditional prenatal care who delivered prior. Total 90 patients in reduced contact (R) cohort were matched with controls (C). There were similar rates of standard prenatal care metrics between groups. Gestational age (GA) of anatomy ultrasound was later in R (p = 0.017). Triage visits and missed appointments were similar, though total number of visits (in-person and telehealth) was higher in R (p = 0.043). R group had higher GA at delivery (p = 0.001). Composite neonatal morbidity and length of stay were lower in R (p = 0.017, p = 0.048). Maternal and neonatal outcomes did not otherwise differ between groups. Using Kotelchuck Adequacy of Prenatal Care Utilization index, R had higher rates of adequate prenatal care (45.6% R vs. 24.4% C, p = 0.005). Our study demonstrates the non-inferiority of a hybrid, reduced schedule prenatal schedule to traditional prenatal scheduling. In a reduced contact prenatal care model, more patients met criteria for adequate prenatal care, likely due to higher attendance of telehealth visits. These findings raise the question of revising the prenatal care model to mitigate disparities in disadvantaged populations.


Current practices for QSP model assessment: an IQ consortium survey.
Quantitative Systems Pharmacology (QSP) modeling is increasingly applied in the pharmaceutical industry to influence decision making across a wide range of stages from early discovery to clinical development to post-marketing activities. Development of standards for how these models are constructed, assessed, and communicated is of active interest to the modeling community and regulators but is complicated by the wide variability in the structures and intended uses of the underlying models and the diverse expertise of QSP modelers. With this in mind, the IQ Consortium conducted a survey across the pharmaceutical/biotech industry to understand current practices for QSP modeling. This article presents the survey results and provides insights into current practices and methods used by QSP practitioners based on model type and the intended use at various stages of drug development. The survey also highlights key areas for future development including better integration with statistical methods, standardization of approaches towards virtual populations, and increased use of QSP models for late-stage clinical development and regulatory submissions.


Pulmonary embolus originating from renal vein stump thrombus after laparoscopic living donor nephrectomy: case report.
Pulmonary embolism (PE) is an uncommon, life-threatening complication after living donor nephrectomy (LDN), and is considered among the most common causes for donor mortality. Most cases of postoperative PEs are thought to originate in deep venous thrombosis (DVT) of the lower extremities. A 56-year-old, healthy woman underwent laparoscopic left LDN. Her postoperative course was complicated by PE, presenting at postoperative day 7. Doppler ultrasonography of her lower extremities did not demonstrate DVT. Both transthoracic echocardiogram and contrast-enhanced computed tomography demonstrated a floating thrombus within the inferior vena cava (IVC) originating from a thrombus in the left renal vein stump. Symptoms resolved with systemic anticoagulation. Repeat transesophageal echocardiography demonstrated resolution of the IVC thrombus. Thrombus originating in left renal vein stump should be considered in patients who develop PE after LDN, especially when lower extremity DVT is not demonstrated.


Habitual physical activity can be increased in people with cerebral palsy: a systematic review.
To determine if habitual physical activity could be increased in people with cerebral palsy. We searched electronic databases until February 2010 using key words related to concepts of cerebral palsy and physical activity. This search was supplemented with citation tracking. Studies had to include participants with cerebral palsy who have habitual physical activity measured over at least one day after a therapy intervention. Two reviewers independently assessed study quality with the PEDro scale (quantitative studies) and Critical Appraisal Checklist for Qualitative Research (qualitative studies). For quantitative studies standardized mean differences were calculated and meta-analysis conducted. Qualitative data were synthesized thematically. Three randomized controlled trials (96 participants) and two qualitative studies (21 participants) were reviewed. Four studies evaluated exercise programmes, and one study an online educational and support programme. Meta-analysis showed that exercise programmes could increase habitual physical activity (δ = 1.0; 95% confidence interval (CI) 0.28 to 1.72). This result was reinforced by reports of increased daily activity in two qualitative studies. The online programme increased weekly minutes of moderate to vigorous physical activity (d = 0.81; 95% CI 0.17 to 1.45), and weekly step counts (d = 0.62; 95% CI 0.0 to 1.25). Positive effects were not maintained after programmes stopped. There was insufficient evidence to determine if demographic factors or programme characteristics, such as intensity and setting, were associated with outcomes. Preliminary evidence suggests that exercise programmes and online support programmes can increase habitual physical activity in people with cerebral palsy, but effects are not maintained when programmes stop.


Antilymphocyte serum produced by immunization with purified mouse thymocyte plasma membrane.
A predominantly plasma membrane fraction was isolated from mouse thymocytes and characterised. Immunization of rabbits with this material yielded highly potent antilymphocyte sera as measured by prolongation of skin allograft survival. Potency was maintained after repeated boosting of the rabbits, yet the generation of irrelevant antibodies was contained. Binding of antilymphocyte sera to lymphocytes was studied by immunofluorescence using the analytical facility of a fluorescence activated cell sorter (FACS-1). The results demonstrated that these anti-membrane sera recognise antigens common to thymocytes and spleen lymphocytes, bind more to T-cells and thymocytes than to B-cells and bind more avidly than antisera raised with intact cells. It was concluded that this thymocyte plasma membrane preparation is highly effective in raising powerful antilymphocyte serum.


Can NbO Keep nbo Topology under Electrons? -Unveiling Novel Aspects of Niobium Monoxide at the Atomic Scale.
A precise investigation of NbO has been carried out by advanced electron microscopy combined with powder and single crystal X-ray diffraction (XRD). The structure of pristine NbO has been determined as Pm-3 m space group (SG) with a = 4.211 Å and the positions of Nb and O at the 3c and 3d Wyckoff positions, respectively, which is consistent with previous report based on powder XRD data. Electron beams induced a structural transition, which was investigated and explained by combining electron diffraction and atomic-resolution imaging. The results revealed that the electron beam stimulated both Nb and O atom-migrations within each fcc sublattice, and that the final structure was SG Fm-3 m with a = 4.29 Å, Nb and O at the 4a and 4b with 75 % occupancy and same chemical composition. Antiphase planar defects were discovered in the pristine NbO and related to the structural transformation. Theoretical calculations performed by density functional theory (DFT) supported the experimental conclusions.


Significance of serum neuron-specific enolase in transient global amnesia.
Neuron-specific enolase (NSE) is a glycolytic enzyme, which is associated with neuronal cell dysfunction in the brain. This study evaluated the role of serum NSE levels of patients with transient global amnesia (TGA). In addition, the relationship between serum NSE levels and the clinical features of TGA was explored. Forty-eight patients with TGA were prospectively included, and their serum NSE levels were measured. We investigated serum NSE levels in patients with TGA. In addition, we analyzed the differences in clinical characteristics between patients with elevated and normal serum NSE levels. Of the 48 patients with TGA, 16 patients (33.3%) had elevated serum NSE levels (25.0 ± 11.5 ng/mL), whereas 32 patients (66.7%) showed normal serum NSE levels (12.8 ± 2.1 ng/mL). The patients with elevated serum NSE levels exhibited higher levels of cognitive impairment than those with normal serum NSE levels (4/16 vs. 1/32, p = 0.036). The serum NSE levels showed a relatively high discrimination (AUC 0.684) between patients with and without cognitive impairment, with 80.0% sensitivity and 74.4% specificity at a cut-off value 17.3 ng/mL. A third of all patients with TGA carry elevated serum NSE levels, which suggests that the neuronal cell dysfunction could be associated with TGA pathogenesis. In addition, it might be correlated with cognitive impairment.


[Genetics of pheochromocytoma and the relevance in surgery].
Chromaffin tumors, e.g. pheochromocytomas and paragangliomas are caused by germline mutations of several susceptibility genes in 30-40% of the patients. The corresponding syndromes are multiple endocrine neoplasia type 2 (MEN2, RET gene), von Hippel-Lindau disease (VHL), neurofibromatosis type 1 (NF1), paraganglioma syndrome types 1-5 (PGL1-5, SDHx gene) and familial pheochromocytoma due to mutations in the MAX and TMEM127 genes. Clinically, screening for such diseases should be carried out by clinical symptoms and mutation analyses. Important indications can be found in the history of patients and their families, young age of manifestation (<30 years), extra-adrenal localization and the presence of metastatic pheochromocytomas. Organ-preserving endoscopic adrenal operations are nowadays standard for hereditary pheochromocytomas. Previous studies have shown that the reoccurrence of tumors in residual tissue is rare and can occur many years later and that metastatic tumors arising from such recurrences are very rare. When a mutation is detected in a susceptibility gene, a multidisciplinary follow-up care tailored to each individual syndrome is essential.


Binding of the ATP-dependent DNase from Hemophilus influenzae to duplex DNA molecules.
Using a membrane filter assay, we have studied the binding reaction between the ATP-dependent DNase from Hemophilus influenzae and duplex DNA under conditions where the degradative reaction is not allowed to proceed. Experiments with three forms of SV40 DNA. Complex formation between enzyme and DNA requires neither DNA or enzyme concentration is fixed while the other is varied reveal that binding is noncooperative and that there are two binding sites per linear DNA molecule. These binding sites probably correspond to the two termini of the molecule.


The Ubiquitination of Spinal MrgC Alleviates Bone Cancer Pain and Reduces Intracellular Calcium Concentration in Spinal Neurons in Mice.
Mas-related G-protein-coupled receptor subtype C (MrgC) has been shown to play an important role in the development of bone cancer pain. Ubiquitination is reported to participate in pain. However, whether MrgC ubiquitination plays a role in bone cancer pain remains unclear. To answer this question, we designed and performed this study. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer pain. MrgC agonist bovine adrenal medulla 8-22 (BAM 8-22) or MrgC antagonist anti-MrgC antibody were injected intrathecally on day 14 after bone cancer pain was successfully induced. The pain behaviors, the MrgC ubiquitination levels and intracellular calcium concentration in spinal neurons were measured before and after injection, respectively. With comparison to normal and sham group, mice in tumor group exhibited serious bone cancer pain on day 14, and the level of MrgC ubiquitination and intracellular calcium concentration in spinal neurons was significantly higher. Intrathecal injection of BAM 8-22 significantly alleviated bone cancer pain, increased the MrgC ubiquitination level and decreased intracellular calcium concentration in spinal neurons; however, these effects were reversed by administration of anti-MrgC antibody. Our study reveals that MrgC ubiquitination participates in the production and maintenance of bone cancer pain in mice, possibly through the regulation of intracellular calcium concentration in mice spinal neurons.


Photosensitivity of Dispersing Cryptic Date Stone Beetles Coccotrypes dactyliperda (Coleoptera, Curculionidae, Scolytinae)-A Pilot Study.
The date stone beetle, Coccotrypes dactyliperda, is a cryptic spermatophagus species that spends almost its entire life cycle inside the seeds of palms, esp. Phoenix sp. Only during dispersal, when the host seed has been largely eaten out, do females emerge for a short period of time in search of a fresh seed in which to establish new brood galleries. Previous work indicated that C. dactyliperda might be photophobic, preferring to emerge from seeds during night hours, whereas anecdotal evidence suggested that the beetles might be photophilic in terms of their movements post emergence. This paper examines the photosensitivity of the species under controlled laboratory conditions. The results show that C. dactyliperda, once removed from the brood chamber, is attracted by and moves faster to a light source, but that the color of the lit surface (red, blue, green, black) has no influence on either direction or crawl speed.


Total body protein turnover and growth in children: is it a futile cycle?
Rates of total body protein turnover during growth greatly exceed those necessary for net protein deposition. The excess protein synthesis would appear to be energy wasteful. However, a constant relationship is noted between whole body protein synthesis and basal energy needs, except during periods of rapid growth and development (newborn and adolescence). We suggest that whole body protein turnover is regulated by basal energy needs. The excess synthesis seen during periods of rapid growth is probably necessary to permit development and remodelling of tissues and organs to take place coincident with a mere increase in size.


Cardiac surgery in the presence of dialysis: effect on mid-term outcomes and quality of life.
this study evaluates the impact on short and mid-term outcomes and quality of life of dialysis dependent patients undergoing cardiac surgery. The benefit to patients from a bio-psycho-social perspective is put into context via an inter-personal patient interview. the study period was from February 1999 to February 2009. Data on 45 dialysis dependent patients undergoing cardiac surgery was prospectively collected and analysed retrospectively. The mean age was 59.9 years and sex ratio (M:F) of 32:13. All patients were New York Heart Association (NYHA) class >2 preoperatively. Fifty-five percent (25/45) of these patients had coronary artery bypass graft surgery (CABG) and 28% (12/45) aortic valve replacement surgery alone. Forty-two variables were studied to define predictors of outcome. Follow-up was 100% (18/18) with a mean follow-up time of 48.1 months (0-124 months). They were followed up with quality of life and functional coping score surveys (SF-36). the main postoperative morbidities were pulmonary complications 20% (9/45), multi-organ failure 11% (5/45) and blood transfusion rates 40% (18/45). The 30 day mortality of the dialysis patients was 13.3% (6/45) and late death was 54% (21/39). Increasing age, pulmonary complications and blood product usage were the significant predictors of both 30 day mortality (age: p=0.02, pulmonary: p=0.003, blood product usage: p=0.03) and late death (age: p=0.008, pulmonary: p=0.02, blood product usage: p=0.02). New York Heart Association class was I-II in 83% (15/18) on long term follow up. All five patients awaiting renal transplants received their transplant in the first six months post-operatively. The overall survival at one year was 78% and five years was 40%. On SF-36 health questionnaire all patients scored less on physical functioning than the Australian norms (24.89 ± 4.10). cardiac surgery in the presence of renal failure is associated with significant morbidity and mortality. The overall survival and quality of life of dialysis patients undergoing cardiac surgery is poor.


Potential target of infliximab in autoimmune and inflammatory diseases.
Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine produced by many cell types (blood monocytes, macrophages, mast cells and endothelial cells), that play a key role in the pathogenesis of multiple autoimmune and nonautoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-alpha, is effective and well tolerated in patients with Crohn's disease, rheumatoid arthritis and spondiloarthritides and has become a widely used treatment for these diseases. Preliminary data suggest that several forms of vasculitis appear responsive to TNF antagonists: Behçet's disease, Churg-Strauss vasculitis, polyarteritis nodosa, and giant cell arteritis, among others. Wegener's granulomatosis and sarcoidosis have been shown to improve with infliximab. Polymyositis/dermatomyositis may also be responsive to TNF blockade. TNF likely plays little role in Sjögren's syndrome as evidenced by the lack of efficacy of TNF antagonists. There is a rationale for using TNF blockade even in systemic lupus erythematosus, a prototype of autoantibody-mediated disease, and a pilot study seems to confirm this potential effective approach. A number of other more rare disorders also may be responsive to TNF blockade. We here review the current and prospective roles of infliximab in the treatment of autoimmune diseases and other conditions.


Transfilter analysis of the inductive influence of proventricular mesenchyme on stomach epithelial differentiation of chick embryos.
To clarify the precise conditions under which chick embryonic proventricular mesenchyme can induce proventricular epithelial differentiation, transfilter experiments were carried out. Six-day proventricular epithelium formed glands and expressed pepsinogen when a Nucleopore filter with a pore size of more than 0.6 μm, but not 0.2 μm, was inserted between the epithelium and the proventricular mesenchyme. The larger the pore size of the filter, the more elongated the glands and the more pepsinogen was induced in the explants. The quail nuclear marker and scanning electron microscopy were used to examine penetration of mesenchymal cells through the Nuclepore filter. The filter of more than 0.2 μm pore size allowed cell processes of mesenchymal cells to pass through. However, only the filter with a pore size of more than 0.6 μm allowed actual migration of mesenchymal cells through the filter, and the larger the pore size of the filter, the more mesenchymal cells passed through. Under the same conditions 6-day and 4.5-day gizzard epithelium formed glands and expressed pepsinogen. These results indicate that a flow of diffusible substances through a Nuclepore filter and even direct contact of a few short cell processes of mesenchymal cells with epithelial cells are not sufficient for induction, and that direct contact of mesenchymal cell processes and/or mesenchymal cells with epithelial cells over a considerably wide area may be prerequisite for the induction.


Gd-EDDA/HYNIC-RGD as an MR molecular probe imaging integrin alphanubeta3 receptor-expressed tumor-MR molecular imaging of angiogenesis.
The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin alphanubeta3 receptor-expressed tumor. Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd(3+), and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA/HYNIC-RGD. Human hepatocellular carcinoma (HHCC) cell line BEL-7402 was cultured and the cells harvested and suspended in serum-free Dulbecco's modified Eagle medium (DMEM) were subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin alphanubeta3 receptor and cell viability experiments were conducted. The in vivo imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at time points of 0, 30, 60, 90min and 24-h post-intravenous injection (p.i.). Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Gd-EDDA/HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The nude mice model bearing HHCC was well established. There was approx. 30% signal enhancement on T1WI FSE images at 90min post-intravenous injection of the Gd-EDDA/HYNIC-RGD compared with baseline, and the signal to time curve is straightforward over time in the span of 0-90min p.i., while the control arms do not show this tendency. Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin alphanubeta3 receptor-expressed tumor.


Cytoplasmic modification of nuclear gene expression.
A review is presented on 1) the autonomous nature of mammalian cell cytoplasm and 2) the cytoplasmic modification of nuclear gene expression. Topics include a discussion of cytoplasmic suppression of tumorigenicity. It is proposed that alterations in DNA methylation patterns may be a possible mechanism to explain cytoplasmic modification of nuclear gene expression.


Mechanisms of regulation of G protein-coupled receptor kinases (GRKs) and cardiovascular disease.
The G protein-coupled receptor kinases (GRKs) participate with arrestins in the regulation and signal propagation of multiple G protein-coupled receptors (GPCR) of key physiological and pharmacological relevance in the cardiovascular system. The complex mechanisms of regulation of GRK expression, degradation and function are being unveiled gradually. The levels of these kinases are known to change in pathological situations such as heart failure, hypertrophy and hypertension, and in animal models of these diseases. A better understanding of the mechanisms underlying these changes and of how these alterations participate in the triggering or progression of cardiovascular disease may contribute to the design of novel diagnostic and therapeutic strategies.


Use of intravenous acetaminophen in the treatment of postoperative pain.
Pain management is a crucial component in the care of the postoperative patient. Although there have been innovative advances in pain management and new analgesic modalities, a need still exists for safer and more tolerable analgesics for the management of pain in the postoperative setting. An intravenous formulation of acetaminophen has been available in Europe for more than 20 years and may soon be reaching the US market. Intravenous acetaminophen may help reduce the consumption of opioid analgesics and has a safety and tolerability profile comparable to placebo. This review will discuss the novel characteristics of intravenous acetaminophen that may make it an attractive choice for the management of acute pain in the postoperative period.


Interactions between Casein kinase Iepsilon (CKIepsilon) and two substrates from disparate signaling pathways reveal mechanisms for substrate-kinase specificity.
Members of the Casein Kinase I (CKI) family of serine/threonine kinases regulate diverse biological pathways. The seven mammalian CKI isoforms contain a highly conserved kinase domain and divergent amino- and carboxy-termini. Although they share a preferred target recognition sequence and have overlapping expression patterns, individual isoforms often have specific substrates. In an effort to determine how substrates recognize differences between CKI isoforms, we have examined the interaction between CKIepsilon and two substrates from different signaling pathways. CKIepsilon, but not CKIalpha, binds to and phosphorylates two proteins: Period, a transcriptional regulator of the circadian rhythms pathway, and Disheveled, an activator of the planar cell polarity pathway. We use GST-pull-down assays data to show that two key residues in CKIalpha's kinase domain prevent Disheveled and Period from binding. We also show that the unique C-terminus of CKIepsilon does not determine Dishevelled's and Period's preference for CKIepsilon nor is it essential for binding, but instead plays an auxillary role in stabilizing the interactions of CKIepsilon with its substrates. We demonstrate that autophosphorylation of CKIepsilon's C-terminal tail prevents substrate binding, and use mass spectrometry and chemical crosslinking to reveal how a phosphorylation-dependent interaction between the C-terminal tail and the kinase domain prevents substrate phosphorylation and binding. The biochemical interactions between CKIepsilon and Disheveled, Period, and its own C-terminus lead to models that explain CKIepsilon's specificity and regulation.


Serum concentration of copper, zinc, iron, and cobalt and the copper/zinc ratio in horses with equine herpesvirus-1.
The serum concentrations of copper, zinc, iron, and cobalt and copper/zinc ratio were investigated in horses infected with equine herpesvirus-1 (EHV-1). Nine horses were naturally infected with the virus and nine healthy horses served as controls. The concentrations of copper, zinc, iron, and cobalt were determined spectrophotometrically in the blood serum of all horses. The results were (expressed in micrograms per deciliters) copper 2.80 +/- 0.34 vs 1.12 +/- 0.44, zinc 3.05 +/- 0.18 vs 0.83 +/- 0.06, iron 2.76 +/- 0.17 vs 3.71 +/- 0.69, cobalt 0.19 +/- 0.37 vs 0.22 +/- 0.45, and copper/zinc ratio 0.72 +/- 0.38 vs 1.41 +/- 0.36 for control vs infected group, respectively. In conclusion, copper and zinc concentrations of the infected group were lower than the control group (p < 0.001), whereas iron concentration and the copper/zinc ratio of the infected group were higher than the control group (p < 0.05 and p < 0.001). The cobalt concentration was not found to be statistically different between two groups. It might be emphasized that copper/zinc ratio was significantly affected by the EHV-1 infection, so it could be taken into consideration during the course of infection.


Treatment of Persistent Postural-Perceptual Dizziness (PPPD) and Related Disorders.
Persistent postural-perceptual dizziness (PPPD) is a newly defined disorder of functional dizziness that in the International Classification of Diseases in its 11th revision (ICD-11) supersedes phobic postural vertigo and chronic subjective dizziness. Despite efforts to unify the diagnosis of functional (somatoform) dizziness, patients will present with a variety of triggers, perpetuating factors, and comorbidities, requiring individualized treatment. This article will review different treatment strategies for this common functional neurological disorder and provide practical recommendations for tailored therapy. An emerging understanding of the underlying pathophysiology that considers vestibular, postural, cognitive, and emotional aspects can enable patients to profit from vestibular rehabilitation, as well as cognitive-behavioral therapy (CBT). Crucially, approaches from CBT should inform and augment physiotherapeutic techniques, and, on the other hand, vestibular exercises or relaxation techniques can be integrated into CBT programs. Antidepressant medication might further facilitate rehabilitation, though the mechanisms are yet to be elucidated, and the level of evidence is low. In PPPD and related disorders, vestibular rehabilitation combined with CBT, and possibly supported by medication, can help patients escape a cycle of maladaptive balance control, recalibrate vestibular systems, and regain independence in everyday life.


The cell type-specific octamer transcription factor OTF-2 has two domains required for the activation of transcription.
Many studies indicate that the cell type-specific transcription factor OTF-2 plays a central role in the lymphoid-specific transcription of immunoglobulin genes. In order to better understand the mechanisms regulating transcriptional selectivity, we have initiated a functional dissection of OTF-2. By mutagenesis of an OTF-2 cDNA and by subsequent transfection into non-lymphoid cells we have defined two domains that are required jointly for high levels of transcription from a lymphoid-specific target promoter. One of these domains, located at the extreme carboxy-terminus, is rich in proline. The other domain, which appears to represent a novel type, is located upstream of the POU-specific box and contains clusters of intermingled proline, glutamine and leucine residues. Point mutations that change either groups of glutamine or groups of leucine show that both types of amino acids are required for function. Our data indicate that a high content in a particular amino acid does not necessarily suffice to generate a potent activation domain but that severe structural constraints may also play a major role.


Cryo-EM structure of Vibrio cholerae aldehyde-alcohol dehydrogenase spirosomes.
Aldehyde-alcohol dehydrogenase (AdhE) is a metabolic enzyme and virulence factor in bacteria. E. coli AdhE (eAdhE) multimerizes into spirosomes that are essential for enzymatic activity. However, it is unknown whether AdhE structure is conserved in divergent bacteria. Here, we present the cryo-EM structure of AdhE (vAdhE) from Vibrio cholerae to 4.31 Å resolution. Overall, vAdhE spirosomes are similar to eAdhE with conserved subunit arrangement. However, divergences in key oligomerization residues cause vAdhE to form labile spirosomes with lower enzymatic activity. Mutating the vAdhE oligomerization interface to mimic eAdhE increases spirosome stability and enzymatic activity to levels comparable to eAdhE. These results support the generality of AdhE spirosome structures, and provide a structural basis to target vAdhE to attenuate bacterial virulence.


Internal rotation of the tibial component is frequent in stiff total knee arthroplasty.
Stiffness complicating TKA is a complex and multifactorial problem. We suspected internally rotated components compromised motion because of pain, patellar maltracking, a tight medial flexion gap, and limited femoral rollback on a conforming lateral tibial condyle. We sought to determine: (1) the incidence of internal rotation of the femoral and tibial components in stiff TKAs; (2) if revision surgery that included correction of rotational positioning improved pain, ROM, and patellar tracking; and (3) if revision altered nonrotational radiographic parameters. From a cohort of 52 patients with TKAs revised for stiffness, we performed CT scans of 34 before and 18 after revision to quantify rotational positioning of the femoral and tibial components using a previously validated scanning protocol. All 34 patients with TKAs had internal rotation of the summed values for tibial and femoral components (mean, 14.8°; range, 2.7°-33.7°) before revision for stiffness. The incidence of internal rotation was 24 of 34 femoral (mean, 3.1°; internal) and 33 of 34 tibial components (mean, 13.7° internal). Revision arthroplasty improved Knee Society function, knee, and pain scores. Mean extension improved from a contracture of 10.1° to 0.8° and flexion from 71.5° to 100°. Postrevision CT scans confirmed correction of component rotation. Nonrotational parameters were unchanged. We recommend CT scanning of patients with stiff TKAs before surgical intervention to identify the presence of internally rotated components. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Comparative development of the nervous, respiratory, and cardiovascular systems.
The timing of some key embryological events is given for man, rat, chick, and certain other animals. Such times, however, are approximations, and variations occur among members of the same strain and even among members of the same litter. Some differences in developmental patterns are indicated.


Clinical Correlates of Sports Betting: A Systematic Review.
Sports betting is becoming increasingly widespread, and a growing number of individuals, both adolescents and adults, participate in this type of gambling. The main aim of this systematic review was to assess correlates of sports betting (sociodemographic features, gambling-related variables, co-occurring psychopathologies, and personality tendencies) through a systematic review conducted following the PRISMA guidelines. Relevant studies were identified via searches of NCBI/PubMed and APA PsycInfo databases. Individuals from the general population and/or with a clinical diagnosis of gambling disorder (GD) were included, irrespective of gender and age. In addition, the studies needed to have administered at least one clinical interview/psychometric instrument to assess the presence of problematic gambling/GD, contain at least one group of participants with sports betting, and directly analyze the association between sports betting and any of the following features: sociodemographics, gambling-related variables, co-occurring psychopathologies, and/or personality tendencies. Fifty-four articles were included. Multiple sociodemographic variables have been studied in relation to sports betting. In general, males with high impulsivity have greater tendencies for sports betting. The co-occurrence of certain pathologies, especially substance use or other addictive disorders, was also suggested. Most studies were cross-sectional, assessed participants using self-administered instruments, recruited samples using non-probability online panels, included small samples, had unbalanced samples, and included samples from only one country. Impulsive males may be particularly prone to sports gambling and related problems. Future research should examine prevention strategies that may help prevent the development of sport-betting-related GD and other addictive behaviors in vulnerable individuals.


Pharmacotherapy for systolic dysfunction: a review of randomized clinical trials.
Chronic heart failure (HF) is a leading cause of morbidity and mortality in the United States, affecting >4 million people. The increasing prevalence of HF has placed an enormous burden on the US healthcare system. For many patients with cardiovascular disease, HF is the final common pathway. Treatment strategies for HF are aimed at preventing and delaying progression of the disease and ultimately improving survival. This article reviews recent clinical drug trials for HF, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin II antagonists, vasodilators, beta-adrenergic blockers, positive inotropic agents, calcium antagonists, and antiarrhythmics. The benefits and shortcomings of these agents and the study designs are discussed. For patients with left ventricular (LV) systolic dysfunction, ACE inhibitors are the only agents that consistently improved survival and decreased the rate of HF progression. It is likely that beta-adrenergic blockers have the same effect. The syndrome of HF is complex with both peripheral and cardiac factors contributing to disease progression. The addition of a diuretic and/or digoxin is often needed to prevent worsening heart failure. Although an angiotensin II antagonist may also be beneficial in the treatment of HF, further studies are needed to clarify their precise role in the management of this condition. Calcium anatagonists, antiarrhythmics excluding amiodarone, and positive inotropes other than digoxin do not appear to prevent progression of HF nor improve survival. The most common cause of HF in the United States is related to coronary artery disease. Reduction of cardiac risk factors, such as smoking cessation, lowering serum cholesterol with diet and a lipid lowering agent, and blood pressure control, is likely to prevent the development or progression of HF.


[Radiological and instrumental study of the colon in idiopathic constipation].
It has been demonstrated that it is not always possible to attribute to constipation a reduced colonic transit time as being evidenced by radiological studies using radiopaque markers. In fact, in constipated patients with a normal transit time, it was more reasonable to consider a recto-anal disorder as evidenced by defecography and manometry.


Megestrol acetate in neoplastic anorexia/cachexia: clinical evaluation and comparison with cytokine levels in patients with head and neck carcinoma treated with neoadjuvant chemotherapy.
The aim of our study (clinical phase II open pilot study) was to evaluate the toxicity of megestrol acetate and its ability to increase appetite and body weight in patients with advanced-stage (III-IV) primary head and neck squamous cell carcinoma treated with neoadjuvant (primary) chemotherapy. Serum levels of interleukin-1 alpha and beta, interleukin-2 and 6, tumor necrosis factor-alpha, and the soluble receptor for interleukin-2 were evaluated before and after megestrol acetate treatment. The same cytokines and soluble interleukin-2 receptor were also measured in culture medium of peripheral blood lymphocytes from the same patients after stimulation with phytohemagglutinin. From April 1993 to February 1994, 11 male patients were enrolled in our study: their mean age was 57.8 years (range 43-69 years). Megestrol acetate was administered at a dose of 320 mg/day in the interval between chemotherapeutic cycles for a total of three consecutive cycles; 9 of the 11 patients could be evaluated (81.8%). Except for the performance status according to Karnofsky, all parameters were increased after megestrol acetate treatment. The average weight increased by 6.3 kg (13.2%), appetite by a score of 2.4 (38.6%) and the Spitzer's quality of life index by a score of 2.4 (36.2%). The performance status according to Karnofsky decreased in only 1 patient, remained the same in most patients, and in 2 patients was slightly improved. No significant side effects were observed during treatment. Serum levels of interleukin-1 alpha and beta, interleukin-2 and 6, tumor necrosis factor-alpha, and soluble interleukin-2 receptor were significantly higher than in normal subjects, prior to treatment with megestrol acetate. These levels dropped after megestrol acetate treatment with a statistically significant decrease for interleukin-1 alpha and beta and tumor necrosis factor-alpha. There were no significant differences in the production of cytokines by peripheral blood lymphocytes stimulated with phytohemagglutinin from patients before megestrol acetate treatment and normal subjects, with the exception of interleukin-6 (higher in patients) and of soluble interleukin-2 receptor (lower in patients). There was no significant difference in the cytokines and soluble interleukin-2 receptor produced in culture before and after megestrol acetate treatment, except for interleukin-6 which decreased after treatment.


Kinetics of Influenza A/BANGKOK/1/1979(Н3N2) Virus Thermal Inactivation in the Presence of Polyallylamine.
Polyelectrolytes currently play an increasingly important role in antivirus therapy. Antiviral activity towards influenza virus, measles virus, herpes simplex virus type 1, and cytomegalovirus was demonstrated for the 6000 Da polyelectrolyte polyallylamine. A nontoxic polyallylamine concentration of 30 µM at which the compound retains its antiviral effect towards measles and influenza viruses but lacks any toxic effect on human cells was previously determined. It is well known, at the same time, that simultaneous virus exposure to physical environmental factors and chemical substances causes a more significant decrease in virus infectivity. Temperature is among these physical factors since thermal exposure causes virus inactivation. Analysis of virus thermal inactivation parameters is of high practical importance when it comes to the development of vaccines against influenza virus and to the study of how virus particles infectivity decreases on various surfaces. In this view, the study of kinetic and thermodynamical characteristics of influenza virus thermal inactivation in the presence of the antiviral preparation polyallylanime is of particular interest. The paper reports that thermal inactivation of influenza virus in the temperature range of 38-60°C in the presence of polyallylamine follows the first-order reaction kinetics. Thermodynamic parameters of influenza virus thermal inactivation evidence that influenza virus surface proteins are involved in the inactivation process as a result of their interaction with polyallylamine. The obtained results show that polyallylamine may be used to accelerate thermal inactivation of the influenza virus.


Novel immediate/sustained-release formulation of acetaminophen-ibuprofen combination (Paxerol®) for severe nocturia associated with overactive bladder: A multi-center, randomized, double blinded, placebo-controlled, 4-arm trial.
To determine short-term efficacy and safety of Paxerol®, novel immediate:sustained (50%:50%) release tablets containing 325 mg acetaminophen and 150 mg ibuprofen per tablet. One of three dose levels, corresponding to the amounts in 1, 2, and 3 tablets, of Paxerol and placebo were administered for 14 consecutive days to patients with severe nocturia (defined in this study as an average nocturnal voids [NV] ≥2.5) associated with overactive bladder (OAB). Changes in NV, as well as Nocturia Quality of Life (NQOL), duration of first uninterrupted sleep (DFUS), and total hours of nightly sleep (THNS) associated with treatment were assessed. Short-term safety/tolerability was assessed throughout the study and for at least 30 days post-treatment. Paxerol at all three doses reduced NV to a greater degree than placebo (average NV -1.1, -1.4, -1.3 voids for low, mid, and high doses, respectively, vs -0.3 void for placebo). NQOL and THNS were similar between baseline and treatment values in all four groups. There were also no between-group differences. Paxerol at high dose tended to (although not statistical significantly) increase DFUS to a greater degree than placebo (1.2 vs 0.4 h, P = 0.057). There were no treatment related adverse events in any of the four groups. This study demonstrates short-term efficacy and short-term safety of Paxerol in patients with severe nocturia associated with OAB. The results warrant further investigation of the long-term efficacy and safety of Paxerol in larger patient populations.


Prostaglandin E2 stimulates VEGF expression in primary rat gastric fibroblasts through EP4 receptors.
Vascular endothelial growth factor (VEGF), a fundamental regulator of angiogenesis, plays an important role in gastric ulcer healing. In addition, prostaglandin E2 (PGE2), derived from cyclooxygenase-2, stimulates VEGF release in gastric fibroblasts. In the present study, we examined which EP receptor subtype is involved in the expression of VEGF in primary rat gastric fibroblasts. PGE2 stimulated VEGF protein expression in the fibroblasts in a time- and dose-dependent manner. The up-regulation by PGE2 of VEGF expression was completely inhibited by a subtype selective EP4 receptor antagonist (AE3-208). Furthermore, the selective EP4 receptor agonist, AE1-329, promoted VEGF expression in the fibroblasts, and this effect was also totally antagonized by AE3-208. These results suggest that PGE2 stimulates VEGF expression in gastric fibroblasts through the activation of EP4 receptors, and this effect may be involved in the healing promoting action of PGE2 on gastric ulcers.


The 1,2-propanediol-sensing properties of one-dimension Tb2O3-modified ZnO nanowires synthesized by water-glycerol binary thermal route.
One-dimension Tb2O3-modified ZnO nanowires were synthesized via water-glycerol binary thermal route. The X-ray diffraction (XRD) patterns demonstrated that the Tb2O3-modified ZnO was pure phase with high crystallinity. The Energy Dispersive Spectrometer (EDS) and X-ray photoelectron spectroscopy (XPS) confirmed the chemical compositions of Tb2O3-modified ZnO. The images of field-emission electron microscopy (FESEM) indicated that the Tb2O3-modified ZnO was one-dimension nanowires with a diameter of ∼40-100 nm. N2 adsorption/desorption measurements and BET analysis were used to revealed the specific surface area and pore size of Tb2O3-modified ZnO. The images of Transmission Electron Microscope (TEM) and High-Resolution Transmission Electron Microscopy (HRTEM) further showed that the highly uniform heterojunctions had been successfully obtained. The sensitivity and response/recovery time of 3 at% Tb2O3-modified ZnO tested at 200 °C were ∼123 and 73s/50s to 50 ppm 1,2-propanediol, respectively. In addition, the detection limit was as low as 1 ppm. Under UV irradiation, the sensitivity was further improved to 152 while the response/recovery time was shortened to 67s/23s. The morphology of one-dimension Tb2O3-modified ZnO nanowires, the increase of oxygen-deficient region in ZnO and the formation of p-n heterojunction enhanced the properties of 1,2-propanediol-sensing synergistically.


Assault-related facial fractures: does the injury mechanism matter?
This study clarified the injury characteristics and occurrence of associated injuries in patients with assault-related facial fractures. Data from 840 assault-related facial fracture patients were included; demographic factors, facial fracture type, associated injuries, alcohol use, and injury mechanisms were recorded. Assault mechanisms most often included combinations of different mechanisms (57.5%) and resulted in the victim falling (50.1%). The perpetrator was most commonly a stranger (52.5%) and acted alone (57.7%). A total of 123 patients (14.6%) had associated injuries, with the most common being traumatic brain injury. Associated injuries occurred most frequently in patients with combined fractures of the facial thirds (24.2%) and upper third fractures (42.9%). The most significant differentiating factors for associated injuries were the number of perpetrators, falling, the use of an offensive weapon, and if the events of the assault remained unknown. In adjusted logistic regression analyses, statistically significant associations with associated injuries were found for age (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.03-1.07; P < 0.001), falling due to the assault (OR 2.87, 95% CI 1.49-5.50; P = 0.002), and upper third facial fractures (OR 6.93, 95% CI 2.06-23.33; P = 0.002). A single punch also caused severe injuries and should therefore not be overlooked, as this can be as dangerous as other assault mechanisms.


Eicosanoid production in human umbilical cord vessels: effect of 17 beta-estradiol.
This study was designed to investigate the effects of 17 beta-estradiol on prostanoid formation from exogenous arachidonic acid in homogenates of human umbilical cord vessels. The veins produced more prostanoids than the arteries and predominantly 6-keto-PGF1 alpha. 17 beta-estradiol had no effect on the rate of production of prostanoids in either vessels. Thus, at least in our in vitro system, the regulation of the vascular tone by prostanoids seems not to be altered by the addition of 17 beta-estradiol.


[Changes in the dietary regimen during treatment of type I diabetes mellitus with continuous insulin infusion. II. Omitting food].
The authors investigated in 11 type diabetics the effect of omission of a meal on the compensation of diabetes during treatment with an insulin pump IP 1003. After stabilization of treatment by the pump, the patients were left on the 5th day without breakfast, while the basal operation of the pump was maintained and the patient received their insulin bolus in the morning. The test was terminated as planned after 180 mins. in 6 patients, in 5 it was terminated early because of typical signs of clinical hypoglycaemia. The course of the blood sugar curves revealed differences between patients from abrupt drops of hyperglycaemic values to hypoglycaemia to balanced low blood sugar levels. For the rest of the day till the following morning after the test the blood sugar was elevated, as compared with the control level of the 4th day. the tests revealed the relatively small drop of the blood sugar level after omission of the meal, hypoglycaemia develops in the majority of diabetics only after 120 to 180 mins. The danger of early hypoglycaemia within 60 minutes was recorded only in patients with a known history of severe hypoglycaemic states. Posthypoglycaemic hyperglycaemia influences the compensation of diabetics during the rest of the day.


Parameters of transplant-mediated pupilloconstriction in rats with unilateral olivary pretectal lesions.
Embryonic retina, transplanted to the midbrain of neonatal rats, innervates the host brain and mediates a pupilloconstrictor response in the host eye. We hypothesise that there is a dynamic interaction between normal host and transplant photic input to the pupilloconstrictor centres. This study aims to characterise the nature of these interactions and determine the impact of experimental lesions on this reflex system. Pupillary diameter in normal rats is regulated by integration of intensity levels of the light delivered to the two eyes. The integration occurs at the primary input nucleus, the olivary pretectal nucleus, and at the output nucleus, the Edinger-Westphal nucleus. We have examined the pattern of integration of inputs delivered through the host eye and a retinal transplant placed over the midbrain at birth. Restriction of the site of integration to one olivary pretectal nucleus by ablating the contralateral nucleus causes a substantial enhancement of the transplant-mediated response and a major reduction in the host eye-mediated response. Although the pattern of change is quite similar to that seen between the two eyes of a normal animal after a similar lesion, the magnitude of improvement of the transplant response is much greater. The integration that occurs between transplant and host inputs is dynamic, and the efficacy of the transplant can be modulated by the competing host input. These results have implications for the use of neural transplants in degenerative diseases and might also offer insight into the limited functional recovery that occurs after neurological injury.


Diffusion-weighted MR imaging in assessing cervical tumour response to nonsurgical therapy.
This study was undertaken to assess whether there is a correlation between the response of cervical tumours to nonsurgical therapy (chemo- and/or radiotherapy) and apparent diffusion coefficient (ADC) values. Seventeen consecutive patients prospectively underwent pelvic magnetic resonance (MR) imaging including diffusion-weighted imaging (DWI) sequences before and after nonsurgical therapy for cervical cancer. A control group of 17 patients without cervical pathology was matched to the study group. Differences in baseline ADC maps between the two groups and within the study group before and after therapy were assessed by nonparametric tests. The diameter and volume of cervical cancers decreased after therapy in 14/17 lesions (responders) and increased in 3/17 lesions (nonresponders). The ADC values of responders increased significantly (p=0.0009). Percent changes in ADC values before and after therapy were higher in responders than nonresponders (p=0.04). There was no significant difference in ADC values between responders and nonresponders at the staging MR examination (p=0.09) and no significant correlation between pretreatment ADC values and percentage of tumour reduction. Tumours with higher percent ADC value increase showed higher tumour reduction volume, but this was not significant (p=0.12). ADC values of cervical cancer after therapy showed significant differences compared with pretherapy values, particularly for responders.


Tongue base varix as a source of oral bleeding: A case report.
Oral bleeding is usually diagnosed after by referral to other department for the differential diagnosis of hematemesis or hemoptysis. If a patient presents with blood in the oral cavity with no obvious source, generally upper airway, pulmonary, or gastroesophageal lesions are considered likely bleeding foci. The tongue base is an unusual site for laryngopharyngeal varices and only a few cases have been reported. Although varix at the tongue base in patients with liver cirrhosis has been rarely described, physicians must consider variceal bleeding from the tongue base when presented with oral bleeding. In such cases, bleeding foci can be identified and controlled by laryngoscopy. We describe the case of a 42-year-old woman complaining of small amount of hemoptysis with variceal bleeding at the tongue base controlled by laryngoscopic excision and cauterization. A diagnosis of tongue base varix was made based on medical history, clinical manifestations, laryngoscopic findings and pathologic features for the patient. The successful laryngoscopic procedures were performed. The patient has shown no recurrent oral bleeding during follow-up. Variceal bleeding in the tongue base is likely to cause serious massive hemorrhage. We need to consider this possibility when presented with a patient with intraoral bleeding but no evidence of hemoptysis or hematemesis.


From skin to nerve: flies, vertebrates and the first helix.
Vertebrate and invertebrate nervous tissue is derived from early embryonic ectoderm, which also gives rise to epidermal derivatives such as skin. Proneural basic helix-loop-helix (bHLH) transcription factors are the key players in the formation of peripheral nervous system (PNS) and central nervous system (CNS) from naïve ectoderm to differentiated postmitotic neurons. The comparative approach and the use of a wide range of animal models have led to increasingly comprehensive investigations of this issue in the last decade. This review will focus on current studies of neural development in vertebrate and invertebrate PNS and on understanding how the bHLH domain structure encodes multiple functions required for neural specification.


DNA-directed in vitro synthesis of Escherichia coli beta-isopropylmalate dehydrogenase.
The in vitro synthesis of beta-isopropylmalate dehydrogenase (EC 22.214.171.124), an enzyme involved in leucine biosynthesis, has been obtained using as template DNA from the hybrid plasmid (pLC1) which contains the Escherichia coli leucine operon. Enzyme synthesis in vitro is stimulated about 2-fold by guanosine-5'-diphosphate-3'-diphosphate and inhibited about 60% by 2 X 10(-4) M L-leucine.


An MR-based radiomics model for differentiation between hepatocellular carcinoma and focal nodular hyperplasia in non-cirrhotic liver.
We aimed to develop and validate a radiomics model for differentiating hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH) in non-cirrhotic livers using Gd-DTPA contrast-enhanced magnetic resonance imaging (MRI). We retrospectively enrolled 149 HCC and 75 FNH patients treated between May 2015 and May 2019 at our center. Patients were randomly allocated to a training (n=156) and validation set (n=68). In total, 2260 radiomics features were extracted from the arterial phase and portal venous phase of Gd-DTPA contrast-enhanced MRI. Using Max-Relevance and Min-Redundancy, random forest, least absolute shrinkage, and selection operator algorithm for dimensionality reduction, multivariable logistic regression was used to build the radiomics model. A clinical model and combined model were also established. The diagnostic performance of the models was compared. Eight radiomics features were chosen for the radiomics model, and four clinical factors (age, sex, HbsAg, and enhancement pattern) were chosen for the clinical model. A combined model was built using the factors from the previous models. The classification accuracy of the combined model differentiated HCC from FNH in both the training and validation sets (0.956 and 0.941, respectively). The area under the receiver operating characteristic curve of the combined model was significantly better than that of the clinical model for both the training (0.984 vs. 0.937, p=0.002) and validation (0.972 vs. 0.903, p=0.032) sets. The combined model provided a non-invasive quantitative method for differentiating HCC from FNH in non-cirrhotic liver with high accuracy. Our model may assist clinicians in the clinical decision-making process.


Do Bariatric Patients Follow Dietary and Lifestyle Recommendations during the First Postoperative Year?
Data on adherence to postoperative lifestyle recommendations by bariatric patients are scarce. Thus, the aim of this study was to evaluate adherence to selected recommendations during the first year following laparoscopic sleeve gastrectomy (LSG) surgery. A prospective cohort study with 12 months of follow-up on 100 LSG patients was conducted. Data were collected at baseline and at 3 (M3), 6 (M6), and 12 (M12) months post-surgery and included anthropometrics, biochemical tests, food intake, food tolerance, common surgery-related side effects, physical activity (PA), supplementation, and number of follow-up meetings with a dietitian. Data were available for 77 patients (57.1% women, mean age 43.1 ± 9.3 years and preoperative BMI 42.1 ± 4.8 kg/m2). Only a minority of the patients adhered to the recommended protein intake ≥60 g/day at all time points (≤40.3%) and ≥6 meetings with a dietitian at M12 (41.6%). Half of the patients performed ≥150 min/week of PA at all time points (≤50.6%) as recommended. PA of ≥150 min/week was associated with better lipid and glucose changes at M6 and M12 (P ≤ 0.044). Most of the patients adhered to the recommended supplementation at all time points (≥57.1%). Adherence to supplementation at M12 was significantly associated with higher serum levels of folic acid, iron, hemoglobin, and vitamins D and B12 (P ≤ 0.056 for all). Adherence to all recommendations was not significantly associated with excess weight loss ≥60% at M12 (P ≥ 0.195 for all). Bariatric patients have medium to high adherence to the major lifestyle recommendations during the first year following LSG; however, adherence to those recommendations was not related to better weight loss at short-term follow-up. Adherence to recommended supplementation was associated with better micronutrient status 1 year postoperatively.


Effects of methylmalonate and propionate on uptake of glucose and ketone bodies in vitro by brain of developing rats.
Methylmalonate (MMA) and propionate effects on glucose and ketone body uptake in vitro by brain of fed and 30-hour-fasted 15-day-old rats were studied. In some experiments cerebrum prisms were incubated in the presence of glucose and either MMA or propionate in Krebs-Ringer bicarbonate buffer, pH 7.0. In others, the incubation medium contained beta-hydroxybutyrate (HBA) or acetoacetate (AcAc) instead of glucose. We verified that MMA increased glucose uptake by brain of fasting animals, whereas propionate had no effect. In addition, MMA diminished HBA but not AcAc incorporation into brain prisms, whereas propionate provoked a diminished utilization of both ketone bodies by brain. The in vitro effect of MMA and propionate on brain and liver beta-hydroxybutyrate dehydrogenase activity was also investigated. It was shown that MMA but not propionate significantly inhibited this activity. Rats were also injected subcutaneously three times with a MMA buffered solution, and the in vivo effects of MMA on the above-mentioned parameters assessed. Results from these experiments confirmed the previously found in vitro MMA effects. Methylmalonic acidemic patients accumulate primarily methylmalonate and secondarily propionate and other metabolites in their tissues at levels comparable to those we used in our assays. Most patients who survive early stages of the disease show a variable degree of neuromotor delay. Since glucose and sometimes ketones are the vital substrates for brain metabolism, it is possible that our findings may contribute to a certain extent to an understanding of the biochemical basis of mental retardation in these patients.


Prognostic value of carcinoembryonic antigen level in rectal cancer treated with neoadjuvant chemoradiotherapy.
The purpose of this study was to identify clinical and pathological parameters to improve prediction of disease-free survival (DFS) and overall survival (OS) in patients treated with neoadjuvant chemoradiotherapy for rectal cancer. Between July 1995 and May 2007, 148 patients with primary rectal adenocarcinoma received neoadjuvant chemoradiotherapy followed by mesorectal excision. Preoperative treatment included various protocols, UFT and leucovorin (28%) and oxaliplatin-based chemotherapy (72%). Clinical and pathological variables were evaluated in relation to patient outcomes. Thirteen percent of patients achieved a complete pathologic response. No response or minimal response as defined by Dworak (Tumor Regression Grade 0/1) was observed in 30 patients (20%). At a median follow-up of 37 months, the 3-year DFS and OS were 64% and 83%, respectively. Pre-treatment serum carcinoembryonic antigen (CEA) level </= 2.5 ng/ml was associated with higher DFS (74 vs. 53%; p = 0.018), higher complete pathologic responses (21 vs. 9%; p = 0.05), and less recurrences (24 vs. 44%; p = 0.014). The data suggest that a CEA level </= 2.5 ng/ml might be a predictor not only of tumor response, as has been suggested before, but also of DFS. This finding could be useful in the future to predict individual risk and to develop more aggressive or alternative strategies.


Exploration of phobic behavior in a small child.
Behavioral assessment is an area receiving ever increasing attention. In the present manuscript an attempt is made to expand the ways in which one problem area frequently addressed by behavior therapists, phobias, is assessed and evaluated. A number of overt behaviors and self reports of fear by a very young girl are described in a naturalistic setting and the implications of these data are presented.


Antibiotics in penetrating abdominal trauma. Comparison of ticarcillin plus clavulanic acid with gentamicin plus clindamycin.
A comparative trial of ticarcillin plus clavulanic acid with gentamicin plus clindamycin was conducted in 85 patients who sustained penetrating abdominal wounds. The antibiotic regimens were given for 24 hours. The overall wound and/or intra-abdominal infection rate was 5.9 percent. Patients who sustained gunshot wounds to hollow viscera were at highest risk. Infection developed in one of 53 (1.9 percent) patients who received ticarcillin plus clavulanic acid and in four of 32 (12 percent) patients who received gentamicin plus clindamycin. These differences were not statistically significant. These data support the use of short-course (24-hour) antibiotic therapy in this clinical setting and demonstrate that ticarcillin plus clavulanic acid is efficacious as a preventive antibiotic combination.


Biotinidase in the porcine cerebrum.
Biotinidase activities found in porcine brains (n = 3) were as follows: cerebrum, 4.4 +/- 0.2 pmol/min per milligram of protein; cerebellum, 7.6 +/- 0.3 pmol/min per milligram of protein; medulla, 2.9 +/- 0.3 pmol/min per milligram of protein. These values are relatively high compared with the activities in rat or guinea pig brains. Subcellular distribution of biotinidase was found mainly in the soluble cytoplasmic fraction (S3), i.e., in the supernatant of 0.32 M sucrose S2 solution after ultracentrifugation at 105,000g for 90 min. This is in contrast to the guinea pig livers, in which the subcellular distribution of biotinidase is mainly found in the microsomal fraction. After a seven-step purification (22,200-fold enrichment), porcine brain biotinidase is identified as a single polypeptide by the sodium dodecyl sulfate-polyacrylamide gel electrophoresis system, and its molecular weight is determined as 68,000 Da. The isoelectric point of the enzyme was 4.3. Sialidase treatment strongly suggests the presence of sialyl residues in this enzyme. Amino acid analysis indicates relatively high hydrophilicity and high content of glycine and serine. The enzyme activity is inhibited by organic mercurials, but not by diisopropylfluorophosphate. Abundant soluble biotinidase in brain cytoplasm may play an important role which has not been discovered yet.


Monetary incentives have only limited effects on auditory distraction: evidence for the automaticity of cross-modal attention capture.
The duplex-mechanism account of auditory distraction postulates that two distinct forms of auditory distraction can be distinguished by whether or not they can be cognitively controlled. While the interference-by-process component of auditory distraction is postulated to be automatic and independent of cognitive control, the stimulus-aspecific attention capture by auditory deviants and the stimulus-specific attentional diversion by auditorily presented distractor sentences should be suppressed by increased task engagement. Here we test whether incentive-induced changes in task engagement affect the disruption of serial recall by auditory deviants (Experiment 1) and distractor sentences (Experiment 2). Monetary incentives substantially affected recall performance in both experiments. However, the incentive-induced changes in task engagement had only limited effects on auditory distraction. In Experiment 2, increased task engagement was associated with a small decrease of distraction relative to a quiet condition, but strong effects of auditory distraction on performance persisted in conditions of high task engagement in both experiments. Most importantly, and in contrast to the predictions of the duplex-mechanism account, the effects of stimulus-aspecific attention capture (Experiment 1) and stimulus-specific attentional diversion (Experiment 2) remained unaffected by incentive-induced changes in task engagement. These findings are consistent with an automatic-capture account according to which only the processes responsible for the deliberate memorization of the target items are dependent on controlled mental effort while the attention capture by auditory deviants and the attentional diversion by distractor speech are largely automatic.