Selection of resistance to gentamicin and netilmicin in the faecal flora following prophylaxis for colo-rectal surgery.
The selection of aminoglycoside-resistant bowel flora, following the administration of either gentamicin or netilmicin in combination with metronidazole for prophylaxis, during colo-rectal surgery in 88 patients has been examined. Both antibiotic regimens resulted in the selection of an aminoglycoside-resistant flora in a total of 57 (65%) of patients: in half of the patients there was a net gain in the aminoglycoside-resistant flora, and in 13 (15%) one aminoglycoside-resistant strain present prior to prophylaxis was displaced by another following operation. Three patients (3%) lost aminoglycoside-resistant strains after prophylaxis. Most of the resistant organisms selected were considered to be of little importance as potential pathogens, at least in the short term. In only a small minority (5%) of patients were aminoglycoside-resistant enterobacteria isolated. Aminoglycoside-resistant Staphylococcus aureus was not isolated. Of the resistant enterobacteria, only one strain, an isolate of Enterobacter cloacae selected in a patient receiving gentamicin, carried a resistance determinant which was self-transmissible to Escherichia coli.


Pivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes.
Various immune diseases are considered to be regulated by the balance of T helper (Th)1 and Th2 subsets. Although Th lymphocytes are believed to be generated in draining lymph nodes (LNs), in vivo Th cell behaviors during Th1/Th2 polarization are largely unexplored. Using a murine granulomatous liver disease model induced by Propionibacterium acnes, we show that retention of Th1 cells in the LNs is controlled by a chemokine, CXCL10/interferon (IFN) inducible protein 10 produced by mature dendritic cells (DCs). Hepatic LN DCs preferentially produced CXCL10 to attract 5'-bromo-2'-deoxyuridine (BrdU)+CD4+ T cells and form clusters with IFN-gamma-producing CD4+ T cells by day 7 after antigen challenge. Blockade of CXCL10 dramatically altered the distribution of cluster-forming BrdU+CD4+ T cells. BrdU+CD4+ T cells in the hepatic LNs were selectively diminished while those in the circulation were significantly increased by treatment with anti-CXCL10 monoclonal antibody. This was accompanied by accelerated infiltration of memory T cells into the periphery of hepatic granuloma sites, most of them were in cell cycle and further produced higher amount of IFN-gamma leading to exacerbation of liver injury. Thus, mature DC-derived CXCL10 is pivotal to retain Th1 lymphocytes within T cell areas of draining LNs and optimize the Th1-mediated immune responses.


Ordered subset linkage analysis supports a susceptibility locus for age-related macular degeneration on chromosome 16p12.
Age-related macular degeneration (AMD) is a complex disorder that is responsible for the majority of central vision loss in older adults living in developed countries. Phenotypic and genetic heterogeneity complicate the analysis of genome-wide scans for AMD susceptibility loci. The ordered subset analysis (OSA) method is an approach for reducing heterogeneity, increasing statistical power for detecting linkage, and helping to define the most informative data set for follow-up analysis. OSA assesses the linkage evidence in subsets of potentially more homogeneous families by rank-ordering family-specific lod scores with respect to trait-associated covariates or phenotypic features. Here, we present results of incorporating five continuous covariates into our genome-wide linkage analysis of 389 microsatellite markers in 62 multiplex families: Body mass index (BMI), systolic (SBP) and diastolic (DBP) blood pressure, intraocular pressure (IOP), and pack-years of cigarette smoking. Chromosome-wide significance of increases in nonparametric multipoint lod scores in covariate-defined subsets relative to the overall sample was assessed by permutation. Using a correction for testing multiple covariates, statistically significant lod score increases were observed for two chromosomal regions: 14q13 with a lod score of 3.2 in 28 families with average IOP </= 15.5 (p = 0.002), and 6q14 with a lod score of 1.6 in eight families with average BMI >/= 30.1 (p = 0.0004). On chromosome 16p12, nominally significant lod score increases (p </= 0.05), up to a lod score of 2.9 in 32 families, were observed with several covariate orderings. While less significant, this was the only region where linkage evidence was associated with multiple clinically meaningful covariates and the only nominally significant finding when analysis was restricted to advanced forms of AMD. Families with linkage to 16p12 had higher averages of SBP, IOP and BMI and were primarily affected with neovascular AMD. For all three regions, linkage signals at or very near the peak marker have previously been reported. Our results suggest that a susceptibility gene on chromosome 16p12 may predispose to AMD, particularly to the neovascular form, and that further research into the previously suggested association of neovascular AMD and systemic hypertension is warranted.


Relative risk and acceleration in lung cancer.
For a substance that increases the relative risk of disease, it does not necessarily follow that the proportion of cases due to exposure to the substance is the same as the attributable fraction in the exposed. An alternative explanation is that the substance has accelerated the occurrence of disease and, therefore, played a role in all cases. When the incidence of disease with time follows the Weibull distribution, it is well known that the proportional hazards model and the accelerated failure time model are equivalent. The purpose of this paper is to provide a numerical illustration of the relationship between the relative risk and the acceleration time of occurrence of cases. A Weibull distribution is a good approximation for lung cancer death rates up to the age of 80 years. The numerical relationship between the relative risk and the time by which cases are accelerated is given for lung cancer deaths occurring at ages of 40-75 years with relative risks of 1.01-3. As an example, for a death due to lung cancer at age 60 years in a smoker, relative risks of 2 and 1.1 due to occupational exposure to a substance correspond to accelerations of 5.2 years and 8 months, respectively.


Bite force production capability and efficiency in Neandertals and modern humans.
Although there is consensus that Neandertal craniofacial morphology is unique in the genus Homo, debate continues regarding the precise anatomical basis for this uniqueness and the evolutionary mechanism that produced it. In recent years, biomechanical explanations have received the most attention. Some proponents of the "anterior dental loading hypothesis" (ADLH) maintain that Neandertal facial anatomy was an adaptive response to high-magnitude forces resulting from both masticatory and paramasticatory activity. However, while many have argued that Neandertal facial structure was well-adapted to dissipate heavy occlusal loads, few have considered, much less demonstrated, the ability of the Neandertal masticatory system to generate these presumably heavy loads. In fact, the Neandertal masticatory configuration has often been simultaneously interpreted as being disadvantageous for producing large bite forces. With rare exception, analyses that attempted to resolve this conflict were qualitative rather than quantitative. Using a three-dimensional digitizer, we recorded a sequence of points on the cranium and associated mandible of the Amud 1, La Chapelle-aux-Saints, and La Ferrassie 1 Neandertals, and a sample of early and recent modern humans (n = 29), including a subsample with heavy dental wear and documented paramasticatory behavior. From these points, we calculated measures of force-production capability (i.e., magnitudes of muscle force, bite force, and condylar reaction force), measures of force production efficiency (i.e., ratios of force magnitudes and muscle mechanical advantages), and a measure of overall size (i.e., the geometric mean of all linear craniofacial measurements taken). In contrast to the expectations set forth by the ADLH, the primary dichotomy in force-production capability was not between Neandertal and modern specimens, but rather between large (robust) and small (gracile) specimens overall. Our results further suggest that the masticatory system in the genus Homo scales such that a certain level of force-production efficiency is maintained across a considerable range of size and robusticity. Natural selection was probably not acting on Neandertal facial architecture in terms of peak bite force dissipation, but rather on large tooth size to better resist wear and abrasion from submaximal (but more frequent) biting and grinding forces. We conclude that masticatory biomechanical adaptation does not underlie variation in the facial skeleton of later Pleistocene Homo in general, and that continued exploration of alternative explanations for Neandertal facial architecture (e.g., climatic, respiratory, developmental, and/or stochastic mechanisms) seems warranted.


Selective Window Application of Gentamicin+ Dexamethasone in Meniere's Disease.
The purpose of the study is to prevent hearing loss when using intratympanic (IT) gentamicin for intractable Meniere's disease. It is a retrospective case review study. Twenty five patients who had definite Meniere's disease and had either selective window application or weekly IT gentamicin were included into the study. First group (selective) had dexamethasone on the round window and gentamicin on oval window during exploratory tympanotomy procedure. The second group had IT gentamicin at weekly intervals. The degree of caloric weakness (CW), average hearing level in low pitch (HLP) (250, 500, 1000, 2000 Hz) and high pitch (HHP) (4000, 6000, 8000 Hz) were compared before and after treatment. The need for further treatment was noted. In the first group, the average HLP was increased from 51.6±7dB to 52.2±5.6 dB. The average HHP was increased 41.96±20.2 dB to 47.2±18.3 dB after treatment. The CW changed from 37.6±23.9 % to 54.6±30.6 %. In the second group, the average HLP was increased from 56.3±10.5 dB to 61.65±18.3 dB. The average HHP was increased 59.05±17.4 dB to 69.4±21.98 dB after treatment. The CW changed from 45.8±22.3% to 71.53±29.63 %. Both methods had statisticaly significant increase in caloric weakness. But only IT gentamicin led a significant hearing loss in HHP. The use of dexamethasone and gentamycin via different windows in the middle ear is safe and effective method for Meniere's disease in the short term. Application of dexamethasone protects not only the hearing cells but vestibular cells also.


Effectiveness of Acupuncture for Management in a Hospitalized Geriatric Patient with Constipation.
Background: Constipation is a gastrointestinal problem commonly found in clinical practice. The prevalence increases with age. Chronic constipation is associated with a decrease in patients' quality of life (QoL). Existing treatments cause side-effects and the positives effects are only short-term. Recently, acupuncture has been widely used to treat geriatric problems, and one of the problems being addressed is constipation. Case: An 85-year-old female, with hip fractures, had episodes of being unable to defecate and had stomach pain that was persistent due to this constipation. She was admitted to the hospital for her fractures, where manual acupuncture was used to treat her constipation. Results: The therapy was effective for relieving the patient's stomach pain and constipation, and increased the patient's appetite as well as improving her QoL. Conclusions: Stomach pain in geriatric patients with constipation can lead to difficulty in sleeping, loss of appetite, and persistent pain in the stomach. Constipation can be assessed by using posterior anterior and oblique views of the abdominal radiographic projection. Numerous modalities, including pharmacologic therapy (sodium lauryl sulfoacetate enema and lactulose syrup), have been used to treat constipation-related pain. Recently, acupuncture has also been used to treat stomach pain in geriatric patients with constipation. Acupuncture was effective for relieving the current patient's pain and constipation and also improved her QoL.


[Indoleamine 2, 3-dioxygenase activity for breast cancer patients with recurrence 5 or more years after surgery].
We evaluated the significance of indoleamine 2, 3-dioxygenase( IDO) in breast cancer patients with recurrence 5 or more years after surgery. IDO activity can be measured by the tryptophan (Trp)/kynurenine (Kyn) ratio. Trp and Kyn were measured by high-performance liquid chromatography( HPLC). We encountered 32 patients in whom breast cancer recurred 5 or more years after surgery. The mean age of the patients was 56.8 years. The mean duration of years since the initial treatment for breast cancer was 9.3±3.8 years. The rate of hormone receptor positivity was 93.8%. Twelve patients were suitable for locoregional therapy and the remaining 20 patients required chemotherapy. The patients suitable for locoregional therapy had a better prognosis than those who required chemotherapy. The correlation of the Trp/Kyn ratio between these 2 groups (locoregional therapy group and chemotherapy group) was studied. The Trp/Kyn ratio was higher in patients suitable for locoregional therapy than in those who received chemotherapy. The prognosis was better in patients with a high Trp/Kyn ratio than in those with a low Trp/Kyn ratio. These results suggest that determining the Trp/Kyn ratio was useful in the prognosis of patients with breast cancer that recurred 5 or more years after surgery.


Histological and anatomical variations of septomarginal trabecula in bovine hearts.
The use of hearts from different animals as models in the experimental pharmacology and surgical clinic has led, in recent years, to an increase on interest of research with this organ. The heart's conducting system, from the septomarginal trabecula, presents several variations, which generates numerous controversies in the literature. So, the objective of the present study is to analyse the morphology of the septomarginal trabecula of bovine hearts, identifying possible macro- and microscopic variations. Thirty-four bovine hearts were analysed. Each trabecula was analysed macroscopically to obtain an anatomical description and measurements of its length and thickness. For histological and morphometric analysis, the samples were fixed in Bouin's solution and then subjected to histological processing. In all the analysed bovine hearts, the septomarginal trabecula presented itself as a smooth, tubular meaty structure of muscular consistency, with variable length and diameter. The anatomical variations observed included a trabecula with forked marginal fixation, and single septal fixation, in addition to a trabecula with extremely reduced or excessively thick caliber. The septomarginal trabecula consists of cardiac muscle fibres, connective tissue, vascular tissue and conduction myofibrils or Purkinje fibres. In the samples of smaller thicknesses, there was a predominance of connective tissue and scarce cardiac muscle tissue, whereas in the thicker samples the predominance was of cardiac striated muscle tissue. Therefore, there are significant macro- and microscopic differences between the bovine septomarginal trabecula concerning their diameter and constituent tissue, and that can lead to possible changes in cardiac physiology.


Production of antibodies against glycolipids from the Mycobacterium tuberculosis cell wall in aerosol murine models of tuberculosis.
Evolution of antibodies against glycolipids from the Mycobacterium tuberculosis cell wall has been studied for the first time in experimental murine models of tuberculosis induced by aerosol, in which infection, reinfection, reactivation, prophylaxis and treatment with antibiotics have been assayed. Results show a significant humoral response against these antigens, where diacyltrehaloses (DAT) and sulpholipid I (SL-I) elicited higher antibody levels than protein antigens like antigen 85 protein complex (Ag85), culture filtrate proteins (CFP) and purified protein derivative (PPD). Only immunoglobulin M (IgM) antibodies have been detected against DAT and SL-I. Their evolution has a positive correlation with bacillary concentration in tissues.


The Incremental Prognostic Value of Hepatocyte Growth Factor in First-Ever Acute Ischemic Stroke: An Early Link Between Growth Factor and Interleukins.
Hepatocyte growth factor (HGF) is a potential prognostic factor for acute ischemic stroke (AIS). In this study, we sought to validate its earlier predictive accuracy within 24 h for first-ever AIS. Moreover, as HGF interacts with interleukins, their associations may lead to novel immunomodulatory therapeutic strategies. Patients with first-ever AIS (n = 202) within 24 h were recruited. Plasma HGF and related interleukin concentrations were measured by multiplex immunoassays. The primary and secondary outcomes were major disability (modified Rankin scale score ≥3) at 3 months after AIS and death, respectively. Elastic net regression was applied to screen variables associated with stroke outcome; binary multivariable logistic analysis was then used to explore the relationship between HGF level and stroke outcome. After multivariate adjustment, upregulated HGF levels were associated with an increased risk of the primary outcome (odds ratio, 7.606; 95% confidence interval, 3.090-18.726; p < 0.001). Adding HGF to conventional risk factors significantly improved the predictive power for unfavorable outcomes (continuous net reclassification improvement 37.13%, p < 0.001; integrated discrimination improvement 8.71%, p < 0.001). The area under the receiver operating characteristic curve value of the traditional model was 0.8896 and reached 0.9210 when HGF was introduced into the model. An elevated HGF level may also be a risk factor for mortality within 3 months poststroke. The HGF level was also positively correlated with IL-10 and IL-16 levels, and HGF before interaction with all interleukins was markedly negatively correlated with the lymphocyte/neutrophil ratio. HGF within 24 h may have prognostic potential for AIS. Our findings reinforce the link between HGF and interleukins.


An Efficient Iron(III)-Catalyzed Aerobic Oxidation of Aldehydes in Water for the Green Preparation of Carboxylic Acids.
The first example of a heterogeneous iron(III)-catalyzed aerobic oxidation of aldehydes in water was developed. This method utilizes 1 atmosphere of oxygen as the sole oxidant, proceeds under extremely mild aqueous conditions, and covers a wide range of various functionalized aldehydes. Chromatography is generally not necessary for product purification. Its operational simplicity, gram-scale oxidation, and the ability to successively reuse the catalyst, make this new methodology environmentally benign and cost effective. The generality of this methodology gives it the potential to be used on an industrial scale.


[Ophthalmology in Greenland from the year 1000 until the year 2000].
The superstition of the Eskimoes exists even today also with regard to disease and treatment. The author has experienced this himself as ophthalmologist in Greenland. Snow blindness is a common complaint in Greenland and different types of primitive snowglasses to protect the eyes are described. Primitive eye operations were performed by the Eskimoes as long as 250 years ago. In 1721 Denmark commenced a colonization of Greenland when the missionary Hans Egede was sent there. The first physician arrived in Greenland in 1742 but was only there for 2 years. The next one was sent 18 years later. Since then innummerable physicians have worked for Greenland for shorter and longer periods. The observations of several doctors who have seen eye diseases among the Eskimoes are mentioned. During the past 70 years eye specialists have regularly visited the country and by screening and the following treatment helped many with eye lesions.


Lopinavir/ritonavir is associated with pneumonia resolution in COVID-19 patients with influenza coinfection: A retrospective matched-pair cohort study.
During the early stages of the pandemic, some coronavirus disease (COVID-19) patients were misdiagnosed as having influenza, which aroused the concern that some deaths attributed to influenza were actually COVID-19-related. However, little is known about whether coinfection with influenza contributes to severity of COVID-19 pneumonia, and the optimal therapeutic strategy for these patients. We retrospectively studied 128 hospitalized patients with COVID-19 pneumonia. All patients were positive severe acute respiratory syndrome coronavirus 2 positive by nucleic acid detection. Sixty-four cases were coinfected with influenza A/B and the other 64 were influenza negative, matched by age, sex, and days from onset of symptoms. Among the 64 coinfected patients, 54 (84.4%) were coinfected with influenza A, and 10 (15.6%) with influenza B. The median duration of viral shedding time from admission was longer for patients with influenza coinfection (17.0 days) than for those without influenza coinfection (12.0 days) (P < .001). The multivariable Cox proportional hazards model showed that the hazards ratio of resolution in lung involvement was 1.878 (P = .020) for patients administered lopinavir/ritonavir, compared with those not administered lopinavir/ritonavir (95% confidence interval: 1.103-3.196). Among influenza coinfected patients, those treated with lopinavir/ritonavir exhibited faster pneumonia resolution within 2 weeks after symptom onset (37% vs 1%; P = .001). There was no difference in lung involvement between influenza coinfected and noninfected groups. Lopinavir/ritonavir eliminated the difference of lung involvement between influenza coinfected and noninfected groups, indicating that lopinavir/ritonavir is associated with pneumonia resolution in COVID-19.


An enzymatic ion exchange model for active sodium transport.
An enzymatic ion exchange model for active sodium transport is described. Kinetic equations relating net flux to time, and to concentration difference across the actively transporting membrane are derived. The second of these equations is tested, using the isolated frog skin in the "short-circuit" apparatus of Ussing. Reasonable linearity, as predicted by this equation, is observed. The passive permeability coefficient for Na(+), is calculated as 5.3 x 10(-4) +/- 5.3 x 10(-4) cm./hr. If cholinesterase is assumed to be the enzyme responsible for transport, the activity required to account for the observations reported here is 17.7 x 10(-4) mmoles/cm.(2)/hr.


Improvements in Patient-Reported Outcomes Following Initiation of Dolutegravir-Based or Low-Dose Efavirenz-Based First-Line Antiretroviral Therapy: A Four-Year Longitudinal Analysis in Cameroon (NAMSAL ANRS 12313 Trial).
We provide new and comprehensive evidence on the evolution of a wide range of patient-reported outcomes (PROs) in the NAMSAL ANRS 12313 trial in Cameroon (2016-2021)-the first randomized comparison of dolutegravir 50 mg (DTG) and low-dose efavirenz (ie, 400 mg; EFV400) in treatment-naive adults living with HIV-1 in sub-Saharan Africa. We first described the evolution of PROs between baseline and week 192. Then, we used random-effects models to measure the effect of time since the initiation of antiretroviral therapy and the differential effect of DTG versus EFV400 on each PRO, adjusting for clinical, demographic, and socioeconomic factors, while accounting for unobserved heterogeneity and missing data. Among the 613 patients randomized (DTG arm, n = 310; EFV400 arm, n = 303), (1) physical and mental health-related quality of life improved by 13.3% and 6.8%, respectively, (2) the percentage of patients with depression, anxiety, and stress decreased from 23.3%, 23.0%, and 7.7% to 3.1%, 3.5%, and 0.4%, respectively, and (3) the mean number of HIV-related symptoms decreased from 7.2 to 3.0 ( P < 0.001). For most PROs, no significant difference was found between both arms, even when accounting for the effect of DTG on weight gain. Nevertheless, our results suggest smaller improvements in mental health outcomes in the DTG arm, with a 5 percentage point higher adjusted probability of having anxiety at week 192 ( P < 0.01). Although supporting the current World Health Organization guidelines recommending DTG-based and EFV400-based regimens as preferred and alternative first-line antiretroviral therapy, further studies should investigate medium-term mental health outcomes in patients on DTG. ClinicalTrials.gov : NCT02777229.


Site- and species-specific hydrolysis rates of cocaine.
The hydroxide-catalyzed non-enzymatic hydrolysis of cocaine is quantified in terms of ten site- and species-specific rate constants in connection with also ten site- and species-specific acid-base equilibrium constants, comprising all the twelve coexisting species in solution. This characterization involves the major and minor decomposition pathways via benzoylecgonine and ecgonine methyl ester, respectively, leading to ecgonine, the final product. Hydrolysis has been found to be 10-330 times faster at site 2 than at site 3, depending on the ionization status of the amino moiety and the rest of the molecule. Nitrogen protonation accelerates the hydrolyses approximately ten times both at site 2 and site 3.


Pediatric Blepharoptosis.
Congenital blepharoptosis, caused by levator muscle dysgenesis, presents at birth and may lead to disturbed visual development and function. Other causes of ptosis in pediatric patients can be myogenic, neurogenic, mechanical, or traumatic. Timely correction is, therefore, critical, and careful preoperative planning and intraoperative considerations are crucial to achieve optimal outcomes and minimize potential complications. The various surgical techniques, including the frontalis suspension or sling, levator resection and advancement, Müller's muscle conjunctival resection (the Putterman procedure), and modified Fasanella-Servat procedure are each associated with distinct indications, benefits, and drawbacks, necessitating a unique tailored approach to each surgical candidate.


Space-time stereo analysis combining local structure and modulation features in the monogenic wavelet domain.
A multimodal cost function, based on the local multimodal image descriptors that combine local structure features (orientation, coherency) and modulation/localization information (amplitude, phase, and spatial frequency) of the monogenic wavelet transform, is proposed to estimate the time-varying disparity maps in the space-time stereo framework. The proposed cost function makes use of a constraint of local orientation, phase, and amplitude congruencies with the weighted coefficients, which are adapted to local image features and are insusceptible to level shift, scaling, and rotation and lighting invariance. Experiments on the synthetic and natural stereo sequences show the estimated results are more robust than the intensity-based sum of standard sum of squared difference cost function.


Characterization of a novel two-component system response regulator involved in biofilm formation and a low-iron response of Burkholderia pseudomallei.
Two-component systems (TCSs) regulate an adaptive response to environmental conditions, leading to changes in bacterial cellular processes. In this study, we identified a novel TCS response regulator gene, designated as bfmR (biofilm formation-associated regulator) that regulates biofilm formation by Burkholderia pseudomallei (Bp). An insertion mutant of the Bp bfmR gene resulted in a significant decrease in expression of fimbriae chaperone-usher assembly genes (BPSL2O28 and BPSL22 7), leading to suppression of assembly of fimbriae on the cell surface and reduced biofilm formation. The defective phenotypes of the mutant strain were restored by introducing a complementing plasmid having an intact bfmR gene. Using RT-PCR analyses, we found that bfmR gene expression was upregulated under low-iron growth conditions. In addition, the bfmR mutant strain showed retarded growth in low-iron medium and in phagocytic cells compared to the wild-type strain. These results indicate that bfmR is a novel positive regulator for controlling assembly of fimbriae and biofilm formation, and is upregulated under low-iron conditions.


Impairment in task-specific modulation of muscle coordination correlates with the severity of hand impairment following stroke.
Significant functional impairment of the hand is commonly observed in stroke survivors. Our previous studies suggested that the inability to modulate muscle coordination patterns according to task requirements may be substantial after stroke, but these limitations have not been examined directly. In this study, we aimed to characterize post-stroke impairment in the ability to modulate muscle coordination patterns across tasks and its correlation with hand impairment. Fourteen stroke survivors, divided into a group with severe hand impairment (8 subjects) and a group with moderate hand impairment (6 subjects) according to their clinical functionality score, participated in the experiment. Another four neurologically intact subjects participated in the experiment to serve as a point of comparison. Activation patterns of nine hand and wrist muscles were recorded using surface electromyography while the subjects performed six isometric tasks. Patterns of covariation in muscle activations across tasks, i.e., muscle modules, were extracted from the muscle activation data. Our results showed that the degree of reduction in the inter-task separation of the multi-muscle activation patterns was indicative of the clinical functionality score of the subjects (mean value = 26.2 for severely impaired subjects, 38.1 for moderately impaired subjects). The values for moderately impaired subjects were much closer to those of the impaired subjects (mean value = 46.1). The number of muscle modules extracted from the muscle activation patterns of a subject across six tasks, which represents the degree of motor complexity, was found to be correlated with the clinical functionality score (R = 0.68). Greater impairment was also associated with a change in the muscle module patterns themselves, with greater muscle coactivation. A substantial reduction in the degrees-of-freedom of the multi-muscle coordination post-stroke was apparent, and the extent of the reduction, assessed by the stated metrics, was strongly associated with the level of clinical impairment.


In vivo replication and reversion to wild type of a neutralization-resistant antigenic variant of hepatitis A virus.
Six seronegative owl monkeys were intravenously inoculated with an antigenic variant (S18) of hepatitis A virus that is highly adapted to growth in cell culture and resists neutralization by monoclonal antibodies due to replacement of aspartic acid 70 of capsid protein VP3 with histidine. Each developed hepatitis 22-33 days after inoculation. Virus in feces, serum, and liver was quantified by radioimmunofocus assay. Viremia developed 7-11 days after inoculation, in parallel with fecal shedding of virus, and persisted for a mean of 20.5 days. Although the antigenic variant was recovered from feces or liver of three animals, virus in liver at the time of enzyme elevations was predominantly wild-type antigenic phenotype. Virus was not recovered from liver 96 days after challenge. These studies further define virologic events in hepatitis A and show that in vivo replication of an antigenic variant was restricted compared with that of wild-type virus.


Systemic Regulators of Skeletal Muscle Regeneration in Obesity.
Skeletal muscle maintenance is a dynamic process and undergoes constant repair and regeneration. However, skeletal muscle regenerative capacity declines in obesity. In this review, we focus on obesity-associated changes in inflammation, metabolism, and impaired insulin signaling, which are pathologically dysregulated and ultimately result in a loss of muscle mass and function. In addition, we examine the relationships between skeletal muscle, liver, and visceral adipose tissue in an obese state.


Structural, Optical, and Electrical Characterization of Yttrium-Substituted BiFeO3 Ceramics Prepared by Mechanical Activation.
Ceramics of Bi(1-x)Y(x)FeO3 solid solutions (x = 0.02, 0.07, and 0.10) have been prepared by mechanical activation followed by sintering. The effect of yttrium content on the structural, electrical, and optical properties of the materials has been studied. Thus, single-phase solid solutions with rhombohedral R3c structure have been achieved for x = 0.02 and 0.07, while for x = 0.10 the main R3c phase has been detected together with a small amount of the orthorhombic Pbnm phase. Multiferroic properties of the samples, studied by differential scanning calorimetry (DSC), showed that both T(N) and T(C) (temperatures of the antiferromagnetic-paramagnetic and ferroelectric-paraelectric transitions, respectively) decrease with increasing yttrium content. The nature of the ferroelectric-paraelectric transition has been studied by temperature-dependent X-ray diffraction (XRD), which revealed rhombohedral R3c to orthorhombic Pbnm phase transitions for x = 0.07 and 0.10. On the other hand, for x = 0.02 the high-temperature phase was indexed as Pnma. Optical properties of the samples, as studied by diffuse reflectance spectroscopy, showed low optical band gap that decreases with increasing yttrium content. Prepared ceramics were highly insulating at room temperature and electrically homogeneous, as assayed by impedance spectroscopy, and the conductivity increased with x.


[A trial to study the effect of influenza vaccination in the elderly: ethical, feasible and badly needed].
Based on current research, there are no valid reasons to assume that influenza vaccination of people aged 60 and over without any other medical indications, in the context of the national programme of influenza prevention, leads to significant, relevant and cost-effective health benefits. In view of the pressure on health care budgets and the decreasing social willingness to vaccinate, it is of great and urgent importance that the actual effect of influenza vaccination is quantified in a double-blind placebo-controlled randomized trial (RCT) with relevant outcome measures, which does not suffer from the methodological shortcomings of the few previous studies. In order to demonstrate a 10% reduction in hospitalisation for respiratory infections, this RCT should include approximately 100,000 subjects and follow these participants for three years. We consider such a trial feasible in the Dutch situation.


Transfusion-transmitted hepatitis E: What we know so far?
Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. There is growing concern about transfusion-transmitted HEV (TT-HEV) as an emerging global health problem. HEV can potentially result in chronic infection in immunocompromised patients, leading to a higher risk of liver cirrhosis and even death. Between 0.0013% and 0.281% of asymptomatic blood donors around the world have HEV viremia, and 0.27% to 60.5% have anti-HEV immunoglobulin G. HEV is infectious even at very low blood concentrations of the virus. Immunosuppressed patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced; ribavirin may be considered as treatment. Pegylated interferon can be considered in those who are refractory or intolerant to ribavirin. Sofosbuvir, a nucleotide analog, showed modest antiviral activity in some clinical studies but sustained viral response was not achieved. Therefore, rescue treatment remains an unmet need. The need for HEV screening of all blood donations remains controversial. Universal screening has been adopted in some countries after consideration of risk and resource availability. Various pathogen reduction methods have also been proposed to reduce the risk of TT-HEV. Future studies are needed to define the incidence of transmission through transfusion, their clinical features, outcomes and prognosis.


Analysis of the Hessburg-Barron vacuum trephine.
We tested the Hessburg-Barron vacuum trephine on 23 human cadaver eyes for accuracy and quality of cut. The trephine was found to make accurate, spherical cuts in the anterior corneal stroma. With penetration, the cut became beveled, leaving the posterior corneal button diameter larger than the anterior diameter especially if the trephine was lifted. The results are discussed relative to conventional techniques.


Ficolin-2 Gene rs7851696 Polymorphism is Associated with Delayed Graft Function and Acute Rejection in Kidney Allograft Recipients.
Ficolin-2 is an activator of the complement system that acts via the lectin pathway. Complement activation plays a substantial role in the renal injury inherent to kidney transplantation. In this study, we examined the associations between ficolin-2 gene polymorphisms in exon 8 and kidney allograft function. This study comprised 270 Caucasian deceased-donor renal transplant recipients. The following parameters were recorded in each case: delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction. Among patients with DGF, we observed a significantly increased frequency of rs7851696 GT and TT genotypes as well as T allele (TT + GT vs GG OR 1.98, 95% CI 1.12-3.48, p = 0.02; T vs G OR 2.08, 95% CI 1.27-3.41, p = 0.005). There was also an increased frequency of rs4521835 GG and TG genotypes as well as G alleles; however, these differences were on the borderline of statistical significance (GG + TG vs TT, OR 1.75, 95% CI 0.98-3.12, p = 0.07; G vs T OR 1.45, 95% CI 1.00-2.09, p = 0.050). In addition, we observed an increased frequency of acute allograft rejection in carriers of ficolin-2 rs7851696 T alleles on the borderline of statistical significance (TT + GT vs GG OR 1.75, 95% CI 0.97-3.16, p = 0.08), but the frequency of T allele was significantly higher in patients with AR (T vs G OR 1.71, 95% CI 1.02-2.87, p = 0.048). The results of our study suggest that ficolin-2 rs7851696 gene polymorphism influences kidney allograft functions, with T allele increasing the risk of DGF and AR.


Newborn screening for sickle cell disease: A 1988-2003 Quebec experience.
Sickle cell disease (SCD) is associated with significant mortality and morbidity that can be decreased by neonatal diagnosis. Although 44 American states have implemented such programs, there are no provincially funded universal or targeted newborn screening programs for SCD in Canada. To report a critical appraisal of a hospital-based neonatal screening program targeting at-risk infants over a 15-year period. The cord blood of infants born at Sainte-Justine University Health Centre (Sainte-Justine UHC, Montreal, Quebec) whose mother or father was black was collected at birth and analyzed for the presence of hemoglobin (Hb) S by liquid chromatography or isoelectric focusing. Samples with positive results underwent confirmatory testing. A total of 9619 infants were screened: 8142 (84.6%) had a normal phenotype, 1012 (10.5%) had sickle cell trait and 386 (4.0%) had HbC trait. Seventy-two infants were diagnosed with SCD: 37 (0.4%) were classified as HbSS or HbS-beta-thalassemia and 35 (0.4%) had HbSC disease. Of these 72 infants, 67 (93.1%) were immediately enrolled in a multidisciplinary SCD follow-up clinic. The five remaining children not initially enrolled were later referred to the clinic. A chart study revealed that six patients with SCD born at Sainte-Justine UHC were not identified by neonatal screening. The screening program was clinically effective because it identified 92.3% of at-risk patients born at Sainte-Justine UHC. These infants received appropriate medical care before 10 weeks of age as opposed to a median of 12 months for infants not identified by the screening program. It is proposed that either a targeted or a universal neonatal screening for SCD should be available in Canada.


Blue light-regulated molecular switch of Ser/Thr kinase in phototropin.
Phototropin is a blue light photoreceptor for tropic responses, relocation of chloroplasts, and stomata opening in plants. Phototropin has two chromophoric domains named light-oxygen-voltage-sensing (LOV) 1 and 2 in the N-terminal half, and a serine/threonine (Ser/Thr) protein kinase motif in the C-terminal half. Concerning the kinase activity of phototropin, only autophosphorylation has been detected so far. However, we found that phototropin can phosphorylate a protein other than phototropin itself. Bacterially expressed Arabidopsis phototropin 2 kinase domain (KD) with GST-tag showed a constitutive kinase activity on casein, a common in vitro substrate of Ser/Thr protein kinase. By using this in vitro assay system, the roles of each LOV domain were studied. Addition of LOV2 to KD (GST-L2-KD) inhibits the kinase activity that is canceled by light. This light activation of kinase disappeared on introduction of a mutation blocking photochemical reaction in the LOV2 domain. Accordingly, LOV2 domain acts as a major light-regulated molecular switch of casein phosphorylation. Interestingly, isolated LOV2 from the KD still binds to the KD in a light-dependent manner and functions in similar ways, indicating the role of LOV2 domain as an inhibitor of the kinase activity in the substrate phosphorylation. LOV1, in contrast, contributes little to the photoactivation in GST-L1-L2-KD; however, it acts as an attenuator of the light activation of the kinase by LOV2.


An empirical comparison of combinations of evolutionary algorithms and neural networks for classification problems.
There are numerous combinations of neural networks (NNs) and evolutionary algorithms (EAs) used in classification problems. EAs have been used to train the networks, design their architecture, and select feature subsets. However, most of these combinations have been tested on only a few data sets and many comparisons are done inappropriately measuring the performance on training data or without using proper statistical tests to support the conclusions. This paper presents an empirical evaluation of eight combinations of EAs and NNs on 15 public-domain and artificial data sets. Our objective is to identify the methods that consistently produce accurate classifiers that generalize well. In most cases, the combinations of EAs and NNs perform equally well on the data sets we tried and were not more accurate than hand-designed neural networks trained with simple backpropagation.


Accurate HIV viral load measurement in primary health care settings using the cobas® plasma separation card.
Plasma is considered the gold standard for HIV viral load (VL) testing, however its use is challenging due to the need for phlebotomy and centrifugation services, as well as cold chain for transporting to laboratories for testing. The use of Dried Blood Spot (DBS) specimen has allowed a rapid expansion of antiretroviral therapy (ART) monitoring in remote areas in many African countries, however, the VL in DBS may overestimate the copies of viral RNA result at the clinically relevant range of 1000 copies/ml, due to proviral DNA and intracellular RNA. The characteristics of the cobas® Plasma Separation Card (PSC) specimen are similar to fresh plasma (gold standard), so a better performance of HIV VL is expetected in PSC specimen and can be an alternative to DBS. This study aims to evaluate the performance of cobas® PSC for VL testing at primary health care facilities in Mozambique. HIV-1 infected adults on ART were enrolled consecutively in two health facilities in Mozambique, between August 2018 and October 2018. Capillary and venous cobas® PSC, DBS and fresh plasma specimens were collected from each patient. All specimens were tested for VL using CAP/CTM v2.0. Sensitivity and specificity of viral load using DBS, capillary and venous PSC specimens were estimated. Viral load obtained in fresh plasma specimen was used as reference and a threshold of 1000 copies/ml was considered for the analyses. From the total 613 patients included for the study, 2444 specimens including DBS (613), plasma (613), venous cobas® PSC (609) and capillary cobas® PSC (609) were collected and 2407 results were obtained. Sensitivity and specificity of the VL using venous cobas®PSC specimen at 1000 copies/ml threshold were 99.8% and 98.1% respectively, whereas for capillary cobas® PSC sensitivity was 99.6% and specificity was 97.2%. For DBS VL, sensitivity was 96.9% and specificity was 81.8%. Misclassification rate was more prominent in DBS specimens (5.9%), but lower in venous and capillary cobas®PSC with a rate of 0.3% and 0.7% respectively. The cobas® PSC specimen has improved performance over DBS for more accurate VL testing aligned with plasma testing. The use of this specimen type can increase the rates of reliable VL results and this will improve the quality of VL monitoring of HIV-positive patients in low-income settings.


Increase in Peripheral Blood Intermediate Monocytes is Associated with the Development of Recent-Onset Type 1 Diabetes Mellitus in Children.
Monocytes play important roles in antigen presentation and cytokine production to achieve a proper immune response, and are therefore largely implicated in the development and progression of autoimmune diseases. The aim of this study was to analyze the change in the intermediate (CD14+CD16+) monocyte subset in children with recent-onset type 1 diabetes mellitus (T1DM) and its possible association with clinical parameters reflecting islet β-cell dysfunction. Compared with age- and sex-matched healthy controls, intermediate monocytes were expanded in children with T1DM, which was positively associated with hemoglobin A1C and negatively associated with serum insulin and C-peptide. Interestingly, the intermediate monocytes in T1DM patients expressed higher levels of human leukocyte antigen-DR and CD86, suggesting better antigen presentation capability. Further analysis revealed that the frequency of CD45RO+CD4+ memory T cells was increased in the T1DM patients, and the memory T cell content was well correlated with the increase in intermediate monocytes. These results suggest that expanded intermediate monocytes are a predictive factor for the poor residual islet β-cell function in children with recent-onset T1DM.


[Postprandial plasma variations of 3-methylhistidine compared to those of lysine, homoarginine and xylose on the normal conditions and in malabsorption in the suckling calf].
We have studied the absorption of 3-methylhistidine (3MH) in vitro and changes in its plasma concentration in preruminant calves after ingestion of milk containing 3MH under normal and malabsorptive conditions. Changes in 3MH concentration were compared to those in lysine, homoarginine (as a component of guanidinated caseine) and xylose, also added to milk. The absorption of 3MH in vitro was dose-dependent and was inhibited by leucine, indicating that 3 MH was transported in the same manner as neutral amino acids. After the ingestion of milk supplying 2.5-20 mumols (3MH)/kg body weight, 3MH increased dose-dependently within 1.75 h and reached maximal levels between 3 and 8 h. Lysine concentration initially parallelled the course of blood 3MH levels but dropped sooner. Homoarginine concentration did not increase until 2-4 h postprandially, probably as a consequence of the time needed for casein degradation. Xylose concentration increased as rapidly as 3MH and lysine concentration. Feeding a diet containing soybean protein for 36 d and administration of neomycine for 5 d to newborn calves induced malabsorption of xylose. However, 3MH absorption and caseine digestion, which increased after homoarginine absorption were not reduced.


Antihyperglycemic effects of N-containing sugars from Xanthocercis zambesiaca, Morus bombycis, Aglaonema treubii, and Castanospermum australe in streptozotocin-diabetic mice.
The aqueous MeOH extract of the leaves and root of Xanthocercis zambesiaca (Leguminosae) and eight structurally related nitrogen-containing sugars, fagomine (1), 4-O-beta-D-glucopyranosylfagomine (2), 3-O-beta-D-glucopyranosylfagomine (3), 3-epifagomine (4), 2,5-dideoxy-2,5-imino-D-mannitol (5), castanospermine (6), alpha-homonojirimycin (7), and 1-deoxynojirimycin (8) were evaluated for antihyperglycemic effects in streptozotocin (STZ)-diabetic mice. The insulin-releasing effects of 1 were also investigated. The blood glucose level fell after i.p. injection of the extract (50 mg/kg). Compounds 1, 2, 5, and 6 reduced the blood glucose level after i.p. injection of 150 mumol/kg. Compound 1 increased plasma insulin level in STZ-diabetic mice and potentiated the 8.3-mM glucose-induced insulin release from the rat isolated-perfused pancreas. The 1-induced potentiation of insulin release may partly contribute to antihyperglycemic action.


Rational social distancing policy during epidemics with limited healthcare capacity.
Epidemics of infectious diseases posing a serious risk to human health have occurred throughout history. During recent epidemics there has been much debate about policy, including how and when to impose restrictions on behaviour. Policymakers must balance a complex spectrum of objectives, suggesting a need for quantitative tools. Whether health services might be 'overwhelmed' has emerged as a key consideration. Here we show how costly interventions, such as taxes or subsidies on behaviour, can be used to exactly align individuals' decision making with government preferences even when these are not aligned. In order to achieve this, we develop a nested optimisation algorithm of both the government intervention strategy and the resulting equilibrium behaviour of individuals. We focus on a situation in which the capacity of the healthcare system to treat patients is limited and identify conditions under which the disease dynamics respect the capacity limit. We find an extremely sharp drop in peak infections at a critical maximum infection cost in the government's objective function. This is in marked contrast to the gradual reduction of infections if individuals make decisions without government intervention. We find optimal interventions vary less strongly in time when interventions are costly to the government and that the critical cost of the policy switch depends on how costly interventions are.


Evaluating healthy cities: A scoping review protocol.
The Healthy Cities project supports municipal policymakers in the struggle to safeguard the health of urban citizens around the world (and in other limited geographies such as islands). Although Healthy Cities has been implemented in thousands of settings, no synthesis of implementation experiences have been conducted. In this article, we develop a scoping review protocol that can be applied to collect evidence on process evaluations of Healthy Cities. To develop a scoping review protocol that could identify experiences evaluating the Healthy Cities project, we followed the PRISMA guidelines for Scoping Reviews (PRISMA-ScR). We applied these guidelines in consultation with a research librarian to design a search of the peer-reviewed literature, specifically Ovid Medline, Ovid Embase, Web of Science Core Collection, and Scopus databases, and a grey literature search. In addition to the aim of collecting evidence on Healthy Cities process evaluation experiences, the broader goal is to spark discussions and inform future evaluations of Healthy Cities. This work can also inform other evaluations of initiatives seeking to raise socio-political change, such as those focused on enhancing intersectoral and multisectoral action.


Uptake of myocardial imaging agents by rejected hearts.
Technetium 99 m pyrophosphate, Gallium 67 and Thallium 201 uptakes were measured in heterotopically transplanted rat hearts. Five days after transplantation, Technetium 99 m pyrophosphate, and Gallium 67 uptakes were significantly higher in allogeneic grafts than in syngeneic grafts. At an early stage of rejection (three days after transplantation), only Technetium 99 m pyrophosphate uptake in the left ventricle of allogeneic grafts showed a significant difference (p less than 0.04). At five days, Thallium 201 uptake was significantly lower in allo- than syngeneic grafts. There was a positive correlation between radionuclide uptake and histologic degree of rejection for Technetium 99 m pyrophosphate and Gallium 67 while Thallium 201 uptake correlated negatively. Analysis of variance revealed that hearts with no or minimal rejection had statistically different uptakes than hearts with mild to moderate rejection. These results suggest that uptake of imaging agents might be useful in the diagnosis of rejection of the transplanted heart.


Stepwise activation of "non-innocent" Cp* substituents--a Cp* based cascade reaction.
Reactions of Cp* substituted pentelidene complexes with the primary phosphine Cp*PH(2) yield novel polycyclic phosphorus/arsenic and carbon containing cage compounds via cascade-like reactions. These reactions include a sequence of nucleophilic addition reactions, intramolecular hydrophosphination (partially hydroarsination) reactions, retro-Diels-Alder reactions with Cp*H elimination and subsequent [2+4]-cycloadditions.


[DRESS syndrome in paediatrics: Clinical case].
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially life-threatening, drug-induced hypersensitivity reaction that includes skin eruption, haematological abnormalities, lymphadenopathy, and internal organ involvement. Presenting a rare condition in children, to facilitate a rapid diagnostic suspicion and recognition by doctors. An 9 months old infant admitted due to a severe viral pneumonia, managed with non-invasive ventilation and ceftriaxone. Five days after stopping antibiotics, a confluent maculopapular rash appeared, which was predominantly in the trunk, face and upper extremities, combined with a fever, eosinophilia, and elevated serum levels of transaminase. She received treatment with oral prednisone and topical corticosteroids for 6 weeks, with a good outcome after 3 months. The diagnosis of DRESS syndrome is made using clinical criteria, laboratory values, and histopathology, if there is any query. Although it is classically caused by anticonvulsants and sulphonamides, many other drugs have been implicated. The offending drug should be immediately discontinued and the patient given supportive treatment, and systemic corticosteroids for long periods of treatment.


A Rare Case of Extra-Pulmonary Sarcoidosis With Only Initial Presentation of Hypercalcemia.
Sarcoidosis is a systemic disorder characterized by the aberrant development of granulomatous inflammation within various organs in the body. In over 90% of cases, sarcoidosis typically manifests initially in the intra-thoracic region, characterized by pulmonary involvement or mediastinal lymphadenopathy. It is rare for sarcoidosis to manifest exclusively as extra-thoracic involvement and even more rarely for hypercalcemia to be the only initial sign. We present a case of a 70-year-old female with hypercalcemia and elevated 1,25-dihydroxyvitamin D3 (1,25(OH)2 D) which raised the suspicion of a granulomatous disease. Granulomatous diseases increase levels of 1,25(OH)2 D via the abnormal expression of 1 alpha-hydroxylase enzyme; therefore, these conditions should be considered in the differential diagnosis when encountered with hypercalcemia. PET-CT showed increased FDG uptake in the reticuloendothelial system. An easily accessible inguinal lymph node biopsy was performed which revealed non-necrotizing granulomatous inflammation. Other causes of non-necrotizing granulomatous diseases, cancer, and lymphoma were ruled out, leading to sarcoidosis being considered as a possible diagnosis. When diagnosing sarcoidosis, other potential causes of granulomatous inflammation need to be ruled out definitively via laboratory findings, imaging, and tissue histopathology before initiation of treatment with steroids. Treatment with glucocorticoids remains the mainstay therapy of 1,25(OH)2 D-mediated hypercalcemia associated with sarcoidosis. The patient was accordingly treated with prednisone which led to the normalization of calcium and 1,25(OH)2 D levels within three weeks. Here, we discuss the clinical features and investigations of extra-pulmonary sarcoidosis for early diagnosis and management.


A Novel Pan-Genome Reverse Vaccinology Approach Employing a Negative-Selection Strategy for Screening Surface-Exposed Antigens against leptospirosis.
Reverse vaccinology (RV) has been widely used for screening of surface-exposed proteins (PSEs) of important pathogens, including outer membrane proteins (OMPs), and extracellular proteins (ECPs) as potential vaccine candidates. In this study, we applied a novel RV negative strategy and a pan-genome analysis for screening of PSEs from 17 L. interrogans strains covering 11 predominately epidemic serovars and 17 multilocus typing (MLST) sequence types (STs) worldwide. Our results showed, for instance, out of a total of 633 predicted PSEs in strain 56601, 92.8% were OMPs or ECPs (588/633). Among the 17 strains, 190 core PSEs, 913 dispensable PSEs and 861 unique PSEs were identified. Of the 190 PSEs, 121 were further predicted to be highly antigenic and thus may serve as potential vaccine candidates against leptospirosis. With the exception of LipL45, OmpL1, and LigB, the majority of the 121 PSEs were newly identified antigens. For example, hypothetical proteins BatC, LipL71, and the OmpA family proteins sharing many common features, such as surface-exposed localization, universal conservation, and eliciting strong antibody responses in patients, are regarded as the most promising vaccine antigens. Additionally, a wide array of potential virulence factors among the predicted PSEs including TonB-dependent receptor, sphingomyelinase 2, leucine-rich repeat protein, and 4 neighboring hypothetical proteins were identified as potential antigenicity, and deserve further investigation. Our results can contribute to the prediction of suitable antigens as potential vaccine candidates against leptospirosis and also provide further insights into mechanisms of leptospiral pathogenicity. In addition, our novel negative-screening strategy combined with pan-genome analysis can be a routine RV method applied to numerous other pathogens.


Transcription of genes coding for metabolic key functions in Nitrosomonas europaea during aerobic and anaerobic growth.
Nitrosomonas europaea can grow under conditions of chemolithoautotrophic aerobic (oxygen as oxidant) as well as anaerobic [nitrogen dioxide (NO(2)) as oxidant] nitrification or chemoorganotrophic anaerobic pyruvate-dependent denitrification. In this study, the adaptation of the transcription (mRNA synthesis/concentration) of N. europaea to aerobic and anaerobic growth conditions was evaluated and the transcription of genes coding for metabolic key functions was analyzed: nitrogen and energy metabolism (amoA, hao, rh1, nirK, norB, nsc, aceE, ldhA, ppc, gltA, odhA, coxA), carbon dioxide fixation (cbbL), gluconeogenesis (ppsA), cell growth (ftsZ), and oxidative stress (sodB). During aerobic ammonia oxidation the specific activities of ammonia oxidation, nitrite reduction, and the growth rates correlated with the transcription level of the corresponding genes amoA/hao, nirK/norB/nsc, and cbbL/ftsZ. In anaerobically ammonia-oxidizing cells of N. europaea, the cellular mRNA concentrations of amoA, hao, rh1,coxA, cbbL, ftsZ, and sodB were reduced compared with aerobically nitrifying cells, but the mRNA levels of nirK, norB, and nsc were significantly increased. During anaerobic pyruvate-dependent denitrification, the mRNA abundance of nirK, norB, nsc, aceE, gltA, and odhA was increased, while the concentrations of amoA,hao, rh1, coxAcbbL, ftsZ, and sodB were significantly reduced. Temperature, pH value, and NH(4)(+), O(2), NO, and NO(2) concentrations had comparatively small effects on the transcription of the studied genes.


[Symptomatology of dyscalculia in the presence of cortical lesions (author's transl)].
The authors examine the function of calculation in 26 patients presenting lateral local cortical lesions. They analyse the symptomatology of acalculia in relation to the location and lateral position of the lesion, and define the influence of concomitant constructive apraxia or aphasia before proposing a method for the classification of calculating disorders.


Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of ATLL patients.
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with very poor prognosis and short survival, caused by the human T-lymphotropic virus type-1 (HTLV-1). The HTLV-1 biomarkers trans-activator x (TAX) and HTLV-1 basic leucine zipper factor (HBZ) are main oncogenes and life-threatening elements. This study aimed to assess the role of the TAX and HBZ genes and HTLV-1 proviral load (PVL) in the survival of patients with ATLL. Forty-three HTLV-1-infected individuals, including 18 asymptomatic carriers (AC) and 25 ATLL patients (ATLL), were evaluated between 2011 and 2015. The mRNA expression of TAX and HBZ and the HTLV-1 PVL were measured by quantitative PCR. Significant differences in the mean expression levels of TAX and HBZ were observed between the two study groups (ATLL and AC, P=0.014 and P=0.000, respectively). In addition, the ATLL group showed a significantly higher PVL than AC (P=0.000). There was a significant negative relationship between PVL and survival among all study groups (P=0.047). The HTLV-1 PVL and expression of TAX and HBZ were higher in the ATLL group than in the AC group. Moreover, a higher PVL was associated with shorter survival time among all ATLL subjects. Therefore, measurement of PVL, TAX, and HBZ may be beneficial for monitoring and predicting HTLV-1-infection outcomes, and PVL may be useful for prognosis assessment of ATLL patients. This research demonstrates the possible correlation between these virological markers and survival in ATLL patients.


A simplistic approach to structural dysplasia assessment: description and validation.
The purpose of this study was to formulate a simplistic method of assessing human structural dysplasia and to validate a classification system that would objectively categorize the type and extent of such dysplasia through the use of indices. Anthropometric measurements were taken from a sample of 222 male college students, length/breadth ratios were formulated, and upper/lower body classifications were made in terms of type and subtype dysplasia. Correlation validation results were highly significant. Body composition data information was also provided for descriptive purposes.


[Histopathologic studies in dementia--comparison with clinical findings].
This paper compares the clinical diagnosis of dementia with the result of the neuropathological brain examination in 23 patients. Aim of this investigation was a verification of the clinical diagnosis. The diagnosis was based on the clinical findings, the Mini Mental State Examination, DSM-III-R classification of dementia, the NINCDS-ADRDA-criteria, results of laboratory tests, EEG, CCT and sonography. A total of 70% of the clinical diagnosis corresponded to the neuropathological results. In 25% of these cases which clinically showed the characteristics of Alzheimer's disease histopathological findings delineated dementia of non-Alzheimer-type. These results underline the importance of additional histopathological investigations in the diagnosis of dementia.


Thermo- and pH-responsive nano-in-micro particles for combinatorial drug delivery to cancer cells.
Drug combinatorial therapy has been gaining the scientific community attention as a suitable approach to increase treatments efficacy and promote cancer eradication. In this study, a new pH- and thermo- responsive carrier was developed by combining doxorubicin-loaded gold-core silica shell nanorods with salicylic acid loaded poly (lactic-co-glycolic acid) based microparticles (NIMPS). The obtained results showed that the drugs and nanorods release could be triggered by the near-infrared (NIR) laser irradiation or by the exposition to an acidic environment. The in vitro 2D cell studies showed that the NIMPS are biocompatible and easily uptaken by HeLa cells. In addition, 3D cell culture models revealed that the NIMPS administration, combined with the NIR laser irradiation, was capable of reducing the size of the HeLa spheroids up to 48%. Overall, the attained data support the application of the nano-in-micro spheres as a dual stimuli responsive drug carrier system for the local administration of combined therapies to cervical cancer cells.


Behavior problems of young girls with fragile X syndrome: factor scores on the Conners' Parent's Questionnaire.
Mothers of 60 girls with fragile X [fra(X)] and 58 controls were asked to fill out the Conners' Parent's Questionnaire to determine if this commonly used checklist would detect behavior problems in young girls with fra(X). The mean T-scores were significantly different between the 2 groups of girls on 5 of the 6 factors on the Conners' Parent's Questionnaire and the girls with fra(X) had mean T-scores that were above the average range on both the Anxiety factor and the Hyperactivity Index factor. Significantly more girls had T-scores greater than 70 (> 98th centile) on 3 of the 6 factors. Twenty-three percent of the girls had T-scores greater than 70 on the Anxiety factor and 38% of the girls had T-scores greater than 70 on the Hyperactivity Index factor. This study suggests that some behavior problems will be reported frequently in young girls with fra(X) and should not be difficult for clinicians to detect.


Aberrant memory system connectivity and working memory performance in subjective cognitive decline.
Subjective cognitive decline, a perceived worsening of cognitive functioning without objective deficit on assessment, could indicate incipient dementia. However, the neural correlates of subjective cognitive decline as assessed by magnetic resonance imaging remain somewhat unclear. Here, we evaluated differences in functional connectivity across memory regions, and cognitive performance, between healthy older adults aged 50 to 85 with (n = 35, Age = 68.5 ± 7.7, 22 female), and without (n = 48, Age = 67.0 ± 8.8, 29 female) subjective cognitive decline. We also evaluated neurite density, fractional anisotropy, and mean diffusivity of the parahippocampal cingulum, cingulate gyrus cingulum, and uncinate fiber bundles in a subsample of participants (n = 37). Participants with subjective cognitive decline displayed lower average functional connectivity across regions of a putative posterior memory system, and lower retrosplenial-precuneus functional connectivity specifically, than those without memory complaints. Furthermore, participants with subjective cognitive decline performed poorer than controls on visual working memory. However, groups did not differ in cingulum or uncinate diffusion measures. Our results show differences in functional connectivity and visual working memory in participants with subjective cognitive decline that could indicate potential incipient dementia.


Fuel oxidation efficiencies and exhaust composition in solid oxide fuel cells.
Solid oxide fuel cells (SOFCs) are electrochemical devices that rely on ion migration through a solid-state electrolyte to oxidize fuel and produce electricity. The present study employs Fourier transform infrared spectroscopy to quantify the exhaust of an SOFC operating with fuel flows of methane over Ni/YSZ cermet anodes and butane over Ni/YSZ and Cu/CeO2/YSZ cermet anodes. Data show that hydrocarbon fuels can participate in a variety of different reactions including direct electrochemical oxidation, various reforming processes, and surface-catalyzed carbon deposition. These findings have direct consequences for assessing the environmental impact of SOFCs in terms of the exhaust discharged from devices operating with common hydrocarbon fuel feeds. In the work presented below, a measure of fuel oxidation efficiency is found by comparing the partial pressure of CO2 (P(CO2)) in the SOFC exhaust to the partial pressure of CO (P(CO)). The fuel anode combination with the largest P(CO2)/P(CO) ratio is the C4H10 over Cu/CeO2 combination (0.628 +/- 0.016). The CH4 over Ni cell type has the second highest ratio (0.486 +/- 0.023). The C4H10 over Ni cell type gives a ratio of 0.224 +/- 0.001. Attempts to balance the carbon content of the fuel feed and exhaust lead to predictions of SOFC fuel oxidation mechanisms.


Simulation of Nonlinear Resonance, Amplitude-Frequency, and Harmonic Generation Effects in SAW and BAW Devices.
Nonlinearly coupled sets of piezoelectric field equations in the frequency domain were derived for the nonlinear propagation of finite-amplitude waves in piezoelectric bulk acoustic wave (BAW) and surface acoustic wave (SAW) devices. To verify their accuracy, we have embedded these sets of equations in the finite-element method (FEM) of COMSOL Multiphysics software and compared the FEM results with both the analytical and experimental results found in the published literature. The nonlinear frequency responses for both plano- and contoured-plate resonators of AT-cut quartz were investigated under various voltage drives, circuit resistances, and quality factors. The proposed equations with FEM have also been employed to study 33.3-MHz very-high-frequency (VHF) quartz resonators, showing that under different conditions of how well the third overtone mode (f3) matches the third harmonic (3f) and how the fractional frequency shift of the third overtone mode (f3) occurs as a function of the fundamental mode current. Furthermore, we have studied the nonlinear harmonic generation of an 840-MHz 128° Y-cut X-propagating (128° YX) LiNbO3 SAW resonator. The second-harmonic (H2) and third-harmonic (H3) modes were observed to occur, respectively, at two-time (2f) and three-time (3f) frequencies of fundamental frequency (f) when such resonators were driven with high power. The effects of substrate thickness, bottom surface conditions of the substrate, and different circuit connections on the H2 and H3 generations were simulated and compared with available measurements. Current proposed sets of equations are general and could be used for the study of nonlinear resonance, amplitude-frequency effect, and harmonic generation in any piezoelectric devices, provided that the necessary nonlinear material constants are known.


Metabolism of lipid-linked oligosaccharide intermediates in rat spleen lymphocytes. Evidence for ectoglycosyltransferase activities.
Double-labelling experiments show that intact lymphocytes as well as lymphocyte homogenates can utilize GDP-[14C]mannose and UDP-N-[3H]acetylglucosamine to synthesize lipid-linked oligosaccharide intermediates. However, the intermediates formed are quantitatively and qualitatively different in the two systems. The amount of dolichyl diphosphate oligosaccharides synthesized in both cases was calculated by using external labelling by sodium boro[3H]hydride reduction of the glycan moiety obtained after mild acid treatment of [14C]mannose-labelled dolichyl diphosphate oligosaccharides. This showed that, due to the liberation of intracellular enzymes, a larger amount of dolichyl diphosphate oligosaccharides was synthesized by homogenate. However, this higher glycosyltransferase activity was not detected by the direct measurement of incorporation of labelled GDP-[14C]mannose and UDP-N-[3H]acetylglucosamine, due to isotopic dilution caused by both endogenous soluble UDP-N-acetylglucosamine and membrane-bound dolichyl phosphate mannose accumulated during the homogenization process. In addition, endogenous UDP-glucose allowed the formation, by homogenate, of glucosylated dolichyl diphosphate oligosaccharides which were not observed with intact cells unless exogenous UDP-glucose was added. These striking differences between the lipid intermediates synthesized by homogenate or by intact cells exclude the possibility that intracellular glycosyltransferases could account for the glycosyltransferase activities observed with whole lymphocyte suspensions. This allows us to conclude that ectoglycosyltransferases involved in the dolichol cycle are present at the outer surface of lymphocytes.


CYP2D6 Genotype and Risk of Recurrence in Tamoxifen Treated Breast Cancer Patients.
Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen exposure, there is considerable controversy regarding the validity of CYP2D6 as a predictor of tamoxifen outcome. Understanding the current state of evidence in this area and its limitations is important for the care of patients who require endocrine therapy for breast cancer. A total of 101 patients with breast cancer who received tamoxifen therapy for at least 3 years, were genotyped for common alleles of the CYP2D6 gene by nested-PCR and restriction fragment length polymorphism PCR. Patients were classified as extensive or poor metabolizers (PM) based on CYP2D6*4 alleles in 3 different groups according to the menopause, Her2-neu status, and stage 3. The mean age of the patients with the disease recurrence was 50.8±6.4 and in non recurrent patients was 48.2±6.8. In this study 63.3% (n=64) patients were extensive metabolizers and 36.6% (n=37) were poor metabolizers. Sixty four of the 101 patients (63.3%) were Her2-neu positive. For tamoxifen- treated patients, no statistically significant difference in rate of recurrence observed between CYP2D6 metabolic variants in stage 3 and post-menopausal patients. However, there was a significant association between CYP2D6 genotype and recurrence in tamoxifen-treated Her2-neu positive patients. Compared with other women with breast cancer, those with Her2-neu positive breast cancer and extensive metabolizer alleles had a decreased likelihood of recurrence. This study for the first time demonstrated significant effects of CYP2D6 extensive metabolizer alleles on risk of recurrence in Her2-neu positive breast cancer patients receiving adjuvant tamoxifen therapy. Therefore, CYP2D6 metabolism, as measured by genetic variation, can be a predictor of breast cancer outcome in Her2-neu positive women receiving tamoxifen.


Effect of a 21-aminosteroid, U74006F, on lipid peroxidation and glomerulotubular function following experimental renal ischemia.
In order to investigate the capacity of the 21-amino-steroid, U74006F, to mitigate ischemic/reperfusion injury (IRI), we studied lipid peroxidation and glomerulotubular function in a rat model of IRI. U74006F, superoxide dismutase (SOD), and their respective vehicles were administered preischemia and prereperfusion to Brown Norway rats subjected to 45 or 60 min of bilateral normothermic ischemia. Lipid peroxidation was assessed by assay of thiobarbituric acid reactive products (TBA-RP) in a forced peroxidation reaction with t-butylhydroperoxide while renal function was assessed by timed determinations of serum creatinine, creatinine clearance, urine volume, and fractional excretion of sodium (FeNa+). Twenty-four hours following a 60-min ischemic insult and uninephrectomy, the glomerular filtration rate (GFR) was markedly reduced in the IRI + vehicle group compared to controls as reflected by a significant elevation in mean serum creatinine (0.138 +/- 0.018 vs 0.045 +/- 0.002 mumole/liter, P < 0.05) and a significant reduction in mean creatinine clearance (0.200 +/- 0.076 vs 1.130 +/- 0.153 ml/min, P < 0.05). Neither U74006F nor SOD afforded protection against this marked fall in GFR. In contrast, U74006F significantly attenuated both the diuresis (UVol) and the increase in fractional excretion of filtered sodium (FeNa+) seen post-IRI. At 24 hr post-IRI, mean UVol was 22.50 +/- 4.57 ml/day and FeNa+ 1.35 +/- 0.16% in the IRI+vehicle group compared to 11.48 +/- 2.00 ml/day and 0.82 +/- 0.22%, respectively, in the IRI+U74006F group (P < 0.05). While SOD also proved partially protective of tubular function, the effect was not as pronounced as that observed with U74006F.(ABSTRACT TRUNCATED AT 250 WORDS)


Bone mineral analysis in patients with biliary atresia after successful Kasai procedure.
Metabolism is probably disturbed in patients with abnormal liver function who have undergone a successful Kasai procedure. We examined bone mineral metabolism in patients who have successfully undergone Kasai procedure. Bone mineral metabolism was examined in 8 patients with biliary atresia after a successful Kasai procedure. Five patients were female and 3 were male. The ages at Kasai procedure ranged from 50 to 80 days, and the follow-up periods ranged from 3 to 27 years after the operation. All patients eat a normal oral diet. We examined plasma levels of 25-OH-D3, 1, 25-(OH)2-D3, Ca and phosphorus (P). Bone mineral content of the lumbar spine (L2-L4) was assessed by dual energy x-ray absorptiometry (DEXA), and the data were expressed as a bone mineral density (BMD). Two patients showed abnormal levels on hepatic function tests. Plasma levels of 1, 25-(OH)2-D3, Ca, and P were normal in all patients. The level of 25-OH-D3 was normal in 7 patients. BMD levels were normal in 6 patients, but low in 2 who had undergone partial splenic embolization and splenectomy, respectively, due to hypersplenism. In long-term survivors of Kasai procedure, measurement of BMD may detect bone mineral deficiency earlier than measurements of serum levels of 25-OH-D, 1, 25-(OH)2-D, Ca and P.


Aurora B: a new prognostic marker and therapeutic target in cancer.
Aurora B is a serine-threonine kinase belonging to the highly conserved Aurora family of mitotic kinases. Aurora B is a chromosomal passenger protein involved in chromosome segregation, spindle-checkpoint, and cytokinesis. Alteration of each of these steps could induce aneuploidy, one of main features, and driving force of cancer progression. The overexpression of Aurora B has been observed in several tumor types, and has been linked with a poor prognosis of cancer patients. In this review we will focus on the role of Aurora B in cancer development, its role as a prognostic marker, and the clinical outcome of recently developed Aurora(s) inhibitors.


Safety of multidetector computed tomography in calculating liver volume for living-donor liver transplantation.
Living-related liver transplantation was developed to overcome the organ shortage for both children and adults with end-stage liver disease. Because impaired liver function after resection and transplantation is caused by insufficient liver volume, the reliable volumetric assessment of the hepatic segments of potential living donors is a critical element in preoperative evaluation. In this study, we compared the results of multidetector computed tomographic (CT) volumetry with the intraoperative findings from 80 liver transplantations performed at our center. Resection borders were determined preoperatively with the aid of CT by manual delineation in which the hepatic vessels were used as guides. Resected liver grafts were weighed intraoperatively, and the calculation of their volume was based on the specific weight of 1 g/mL. Statistical analyses were performed with Pearson's correlation test; P < .05 was considered significant. The study subjects consisted of 48 women and 32 men (mean age, 35.6 +/- 9.7 years; range, 23-56 years). Forty-one donors underwent right lobectomy, 22 underwent left lobectomy, and 17 underwent left lateral segmentectomy. Manual volumetric measurement was completed within 15 minutes. No significant differences were found between the results of preoperative volumetry and the intraoperative measurement. We therefore concluded that manual CT volumetric calculation is a reliable method of calculating liver volume for living-donor liver transplantation.


Carotenoid-cleavage activities of crude enzymes from Pandanous amryllifolius.
Carotenoid degradation products, known as norisoprenoids, are aroma-impact compounds in several plants. Pandan wangi is a common name of the shrub Pandanus amaryllifolius. The genus name 'Pandanus' is derived from the Indonesian name of the tree, pandan. In Indonesia, the leaves from the plant are used for several purposes, e.g., as natural colorants and flavor, and as traditional treatments. The aim of this study was to determine the cleavage of β-carotene and β-apo-8'-carotenal by carotenoid-cleavage enzymes isolated from pandan leaves, to investigate dependencies of the enzymatic activities on temperature and pH, to determine the enzymatic reaction products by using Headspace Solid Phase Microextraction Gas Chromatography/Mass Spectrophotometry (HS-SPME GC/MS), and to investigate the influence of heat treatment and addition of crude enzyme on formation of norisoprenoids. Crude enzymes from pandan leaves showed higher activity against β-carotene than β-apo-8'-carotenal. The optimum temperature of crude enzymes was 70°, while the optimum pH value was 6. We identified β-ionone as the major volatile reaction product from the incubations of two different carotenoid substrates, β-carotene and β-apo-8'-carotenal. Several treatments, e.g., heat treatment and addition of crude enzymes in pandan leaves contributed to the norisoprenoid content. Our findings revealed that the crude enzymes from pandan leaves with carotenoid-cleavage activity might provide a potential application, especially for biocatalysis, in natural-flavor industry.


[Pragmatic diagnostic value of hepatobiliary echography in 193 consecutive jaundiced patients referred to an endoscopic retrograde cholangiography center].
The aim of this retrospective work was to study the reliability of hepatobiliary sonography (SG) in a population of 193 icteric patients referred to our endoscopic retrograde cholangiography pancreatography (ERCP) unit between January 1980 and January 1983. One hundred and eight patients were female (ages varying from 9 to 90 years, average: 61 years) and 85 were male (ages varying from 9 to 91 years, average: 55 years). This study's objective was purely pragmatic. The initial SG report served as a basis for assessment of the diagnostic value of ultrasound examination. According to the sonographic patterns observed (biliary dilatation or not), jaundice was classified as intra- or extrahepatic. The sonographic results were then compared to the definitive diagnosis as determined from clinical, biological and pathological data. In the case of an obstacle, the final diagnosis was confirmed by either ERCP or laparotomy. When ERCP showed no obstruction, the final diagnosis was based on either percutaneous hepatic biopsy or clinical and biological evolution and in two cases, an autopsy findings. In this population and considering the pragmatic context of the study, the effectiveness of SG in classifying jaundice as extra- or intrahepatic was 76 p. 100 (70-82), the sensitivity was 75 p. 100 (67-83), specificity, 81 p. 100 (72-89), positive predictive value, 87 p. 100 (81-93) and the negative predictive value, 66 p. 100 (56-76). Sixty-seven p. 100 of the 30 false negative diagnoses in 120 cases of obstructive jaundice corresponded to misdiagnosis of cholelithiasis. SG was able to suggest the etiology of jaundice in 94 cases; this was correct in 58 cases (61 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS)


Understanding Health Care Administrators' Data and Information Needs for Decision Making during the COVID-19 Pandemic: A Qualitative Study at an Academic Health System.
Objective. The COVID-19 pandemic created an unprecedented strain on the health care system, and administrators had to make many critical decisions to respond appropriately. This study sought to understand how health care administrators used data and information for decision making during the first 6 mo of the COVID-19 pandemic. Materials and Methods. We conducted semistructured interviews with administrators across University of Florida (UF) Health. We performed an inductive thematic analysis of the transcripts. Results. Four themes emerged from the interviews: 1) common types of health systems or hospital operations data; 2) public health and other external data sources; 3) data interaction, integration, and exchange; and 4) novelty and evolution in data, information, or tools used over time. Participants illustrated the organizational, public health, and regional information they considered essential (e.g., hospital census, community positivity rate, etc.). Participants named specific challenges they faced due to data quality and timeliness. Participants elaborated on the necessity of data integration, validation, and coordination across different boundaries (e.g., different hospital systems in the same metro areas, public health agencies at the local, state, and federal level, etc.). Participants indicated that even within the first 6 mo of the COVID-19 pandemic, the data and tools used for making critical decisions changed. Discussion. While existing medical informatics infrastructure can facilitate decision making in pandemic response, data may not always be readily available in a usable format. Interoperable infrastructure and data standardization across multiple health systems would help provide more reliable and timely information for decision making. Conclusion. Our findings contribute to future discussions of improving data infrastructure and developing harmonized data standards needed to facilitate critical decisions at multiple health care system levels. The study revealed common health systems or hospital operations data and information used in decision making during the first 6 mo of the COVID-19 pandemic.Participants described commonly used internal data sources, such as resource and financial reports and dashboards, and external data sources, such as federal, state, and local public health data.Participants described challenges including poor timeliness and limited local relevance of external data as well as poor integration of data sources within and across organizational boundaries.Results suggest the need for continued integration and standardization of health data to support health care administrative decision making during pandemics or other emergencies.


Performance on Auditory and Visual Tasks of Inhibition in English Monolingual and Spanish-English Bilingual Adults: Do Bilinguals Have a Cognitive Advantage?
Bilingual individuals have been shown to be more proficient on visual tasks of inhibition compared with their monolingual counterparts. However, the bilingual advantage has not been evidenced in all studies, and very little is known regarding how bilingualism influences inhibitory control in the perception of auditory information. The purpose of the current study was to examine inhibition of irrelevant information using auditory and visual tasks in English monolingual and Spanish-English bilingual adults. Twenty English monolinguals and 19 early balanced Spanish-English bilinguals participated in this study. All participants were 18-30 years of age, had hearing thresholds < 25 dB HL from 250 to 8000 Hz, bilaterally (American National Standards Institute, 2003), and were right handed. Inhibition was measured using a forced-attention dichotic consonant-vowel listening task and the Simon task, a nonverbal visual test. Both groups of participants demonstrated a significant right ear advantage on the dichotic listening task; however, no significant differences in performance were evidenced between the monolingual and bilingual groups in any of the dichotic listening conditions. Both groups performed better on the congruent trial than on the incongruent trial of the Simon task and had significantly faster response times on the congruent trial than on the incongruent trial. However, there were no significant differences in performance between the monolingual and bilingual groups on the visual test of inhibition. No significant differences in performance on auditory and visual tests of inhibition of irrelevant information were evidenced between the monolingual and bilingual participants in this study. These findings suggest that bilinguals may not exhibit an advantage in the inhibition of irrelevant information compared with monolinguals.


Weak noncovalent interactions in two positional isomers of acrylonitrile derivatives: inputs from PIXEL energy, Hirshfeld surface and QTAIM analyses.
A single crystal X-ray diffraction analysis was performed on two positional isomers (m-tolyl and p-tolyl) of acrylonitrile derivatives, namely, (Z)-3-(4-(pyridin-2-yl) phenyl)-2-(m-tolyl) acrylonitrile (1) and (Z)-3-(4-(pyridin-2-yl)phenyl)-2-(p-tolyl) acrylonitrile (2). Compound 1 crystallized in the monoclinic P21/n space group with two crystallographically independent molecules. Compound 2 also possesses two crystallographically independent molecules and crystallized in the triclinic P-1 space group. The Hirshfeld surface analysis revealed that, in both isomers, intermolecular H⋅⋅⋅H/C/N contacts contribute significantly to the crystal packing. More than 40% of the contribution arises from intermolecular C-H⋅⋅⋅C(π) contacts. In both compounds, the relative contribution of these contacts is comparable, indicating that the positional isomeric effects are marginal. The structures in which these isomers are arranged in the solid state are very similar, and the lattice energies are also comparable between the isomers. The Coulomb-London-Pauli-PIXEL (CLP-PIXEL) energy analysis identified the energetically significant dimers. The strength of the intra- and intermolecular interactions was evaluated using the quantum theory of atoms in molecules approach. The UV-Vis absorbance in three different solvents (chloroform, ethanol, and ethyl acetate) for isomers 1 and 2 are very similar. This result is in good agreement with the time-dependent density-functional theory (TD-DFT) calculations.


Apolipoprotein E epsilon4 genotype and gender: effects on memory.
Episodic recognition memory for odors and visual was assessed in apolipoprotein E (ApoE) epsilon4-positive and epsilon4-negative men and women diagnosed with Alzheimer disease (AD) and a healthy age- and gender-matched comparison group. A total of 38 AD patients and 38 age- and gender-matched healthy older adults completed a recognition memory task involving three categories of stimuli: odors, faces, and symbols. In the healthy comparison group, men who were epsilon4 negative outperformed epsilon4-positive men in recognition memory for odors and committed fewer false-positive errors. However, there were no significant differences between epsilon4-negative and epsilon4-positive women in the comparison group. No significant gender or ApoE status differences were detected in recognition memory for faces or symbols in the comparison group. In patients with AD, epsilon4-negative women outperformed epsilon4-positive women in recognition memory for odors and committed significantly fewer false-positive errors. However, there were no significant differences between epsilon4-positive and epsilon4-negative men. There were no significant gender or ApoE status differences in recognition memory for faces or symbols in AD patients. The results demonstrate that recognition memory for olfactory stimuli may be particularly impaired in healthy older men with the epsilon4 allele. In patients with AD, odor memory impairments may be less severe in women who are negative for the epsilon4 allele. The results offer new insight into how recognition memory is affected by gender, the epsilon4 allele, and the modality of the stimulus to be remembered in healthy older adults and patients with AD.


Toxin-Pathogen Synergy Reshaping Detoxification and Antioxidant Defense Mechanism of Oligonychus afrasiaticus (McGregor).
Current study reveals the likelihood to use pathogen and toxin mutually as an effective and eco-friendly strategy for Oligonychus afrasiaticus (McGregor) management, which could reduce toxicant dose and host killing time. Therefore, phytol and Beauveria bassiana in different proportions were evaluated to determine their effectiveness. Prior to ascertaining host mortality and defense mechanisms, we have recorded in vitro action of phytol using different concentrations (0.70, 1.40, 2.10, 2.80, and 3.50 mg/mL) against B. bassiana suspension. In vitro compatibility assays revealed that growth parameters (vegetative growth, sporulation, and viability) of B. bassiana were least affected by the action of phytol at all tested concentrations. Biological Index of B. bassiana exhibited compatibility with phytol allowed us to conduct Joint toxicity bioassays in which phytol and spores mixed in different proportions in order to attain maximum treatment effect in terms of high mortality at low concentration under short time. Results revealed that joint-application exhibited both synergistic (treatments with higher proportions of phytol), and antagonistic interaction (treatments with higher proportions of spores) interactions. Biochemical mechanisms involved in host antioxidant and detoxification response were explored by quantifying their respective enzymatic activities. Lethality of different treatments induced different patterns of detoxification enzymes including glutathione S-transferase (GST) and acetylcholinesterase (AchE). Overall, the least potent treatments (20% phytol:80% spores, and 40% phytol:60% spores) established in the current study induced relatively higher GST and AchE activities. On the other hand, the most potent treatment (80% phytol:20% spores) at its maximum concentration exhibited negligible relative GST and AchE activities. Antioxidant enzyme activities of CAT and SOD measured in the current study showed moderate to complex interaction might because of toxin-pathogen remarkable synergy. This study suggested that joint application of phytol with B. bassiana spores have shown tremendous acaricidal potential and found to be promising new strategy for controlling old world date mites.


Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery.
Influenza A virus NS1 protein (NS1A protein) via its effector domain targets the poly(A)-binding protein II (PABII) of the cellular 3'-end processing machinery. In vitro the NS1A protein binds the PABII protein, and in vivo causes PABII protein molecules to relocalize from nuclear speckles to a uniform distribution throughout the nucleoplasm. In vitro the NS1A protein inhibits the ability of PABII to stimulate the processive synthesis of long poly(A) tails catalyzed by poly(A) polymerase (PAP). Such inhibition also occurs in vivo in influenza virus-infected cells, where the NS1A protein via its effector domain causes the nuclear accumulation of cellular pre-mRNAs which contain short ( approximately 12 nucleotide) poly(A) tails. Consequently, although the NS1A protein also binds the 30 kDa subunit of the cleavage and polyadenylation specificity factor (CPSF), 3' cleavage of some cellular pre-mRNAs still occurs in virus-infected cells, followed by the PAP-catalyzed addition of short poly(A) tails. Subsequent elongation of these short poly(A) tails is blocked because the NS1A protein inhibits PABII function. Nuclear-cytoplasmic shuttling of PABII, an activity implicating this protein in the nuclear export of cellular mRNAs, is also inhibited by the NS1A protein. In vitro assays suggest that the 30 kDa CPSF and PABII proteins bind to non-overlapping regions of the NS1A protein effector domain and indicate that these two 3' processing proteins also directly bind to each other.


Early life adversity diminishes the cortisol response to opioid blockade in women: Studies from the Family Health Patterns project.
Early life adversity (ELA) contributes to behavioral impulsivity along with risk for substance use disorders, both accompanied by blunted stress-axis reactivity. However, the biological contributors to blunted stress reactivity are not known. We took advantage of the fact that women have significant opioid inhibition of cortisol output by using the opioid antagonist, naltrexone, to unmask opioid interactions due to ELA. We administered 50 mg of naltrexone or placebo to 72 healthy women (23 years of age) in a double-blind crossover study and observed deviations in cortisol secretion from placebo over the next 180 minutes. ELA was assessed by reported exposure to physical and sexual abuse or neglect and low socioeconomic status and scored as Low, Medium, or High (0, 1-2, and 3+). The ELA groups all had identical placebo-day cortisol secretion, indicating normal basal regulation of the hypothalamic-pituitary-adrenocortical axis. Cortisol rises to naltrexone were largest in the Low-ELA group and strongly blunted in the High-ELA group (F = 3.51, p = 0.035), indicating a lack of opioid function in women with high degrees of ELA. The Low-ELA women reported dysphoric responses to naltrexone (F = 4.05, p = .022) indicating a mild opioid withdrawal, an effect that was absent in the High-ELA group. Women exposed to ELA have blunted cortisol responses to naltrexone, indicating reduced opioid regulation of the stress axis. Central opioid changes may be one pathway linking ELA to blunted stress reactivity in adulthood.


Imaging in inflammatory bowel disease mucosal healing in ulcerative colitis: relevance for clinical outcomes.
There is growing evidence of the importance of mucosal healing (MH) in ulcerative colitis, but whether or not it should be a future primary treatment goal is still under intense discussion. Within the last decade many clinical trials have focused not only on response and remission rates but also on achievement of MH, while in clinical practice we still make treatment decisions on the basis of clinical symptoms. There is so far no internationally accepted definition of MH and the tools for assessment of MH vary from biomarkers to endoscopy with histological evaluation on the basis of several different scores and indices. This review will focus on present data dealing with methods to assess MH and the importance of MH for the future course of disease, the need for colectomy or risk of developing colorectal cancer and the patient's quality of life. Many questions remain: How and when do we best assess MH? How rapidly do we need to achieve MH? What is the optimal time point to discontinue treatment after achieving MH? Well defined prospective studies are needed to address these important questions.