Ratiometric NAD+ Sensors Reveal Subcellular NAD+ Modulators.
Mapping NAD+ dynamics in live cells and human is essential for translating NAD+ interventions into effective therapies. Yet, genetically encoded NAD+ sensors with better specificity and pH resistance are still needed for the cost-effective monitoring of NAD+ in both subcellular compartments and clinical samples. Here, we introduce multicolor, resonance energy transfer-based NAD+ sensors covering nano- to millimolar concentration ranges for clinical NAD+ measurement and subcellular NAD+ visualization. The sensors captured the blood NAD+ increase induced by NMN supplementation and revealed the distinct subcellular effects of NAD+ precursors and modulators. The sensors then enabled high-throughput screenings for mitochondrial and nuclear NAD+ modulators and identified α-GPC, a cognition-related metabolite that induces NAD+ redistribution from mitochondria to the nucleus relative to the total adenine nucleotides, which was further confirmed by NAD+ FRET microscopy.


Rho kinase activity controls directional cell movements during primitive streak formation in the rabbit embryo.
During animal gastrulation, the specification of the embryonic axes is accompanied by epithelio-mesenchymal transition (EMT), the first major change in cell shape after fertilization. EMT takes place in disparate topographical arrangements, such as the circular blastopore of amphibians, the straight primitive streak of birds and mammals or in intermediate gastrulation forms of other amniotes such as reptiles. Planar cell movements are prime candidates to arrange specific modes of gastrulation but there is no consensus view on their role in different vertebrate classes. Here, we test the impact of interfering with Rho kinase-mediated cell movements on gastrulation topography in blastocysts of the rabbit, which has a flat embryonic disc typical for most mammals. Time-lapse video microscopy, electron microscopy, gene expression and morphometric analyses of the effect of inhibiting ROCK activity showed - besides normal specification of the organizer region - a dose-dependent disruption of primitive streak formation; this disruption resulted in circular, arc-shaped or intermediate forms, reminiscent of those found in amphibians, fishes and reptiles. Our results reveal a crucial role of ROCK-controlled directional cell movements during rabbit primitive streak formation and highlight the possibility that temporal and spatial modulation of cell movements were instrumental for the evolution of gastrulation forms.


Hospital outcome after emergent vs elective revision total hip arthroplasty.
This is a retrospective review of inpatient outcomes, based upon emergent or elective admission for revision total hip arthroplasty (THA) procedures performed between 2000 and 2006. Three hundred forty-two revision THA procedures (291 elective, 51 emergent) were identified. Emergent revisions were more likely to be older (69.9 vs 62.7; P = .003), women (72% vs 54%), require longer hospitalization (8.3 vs 3.8 days), and require a skilled care facility at discharge. No significant difference was observed in mortality. We identified 2 basic outcome measures suggesting that patients undergoing emergent revision will have a more complex hospitalization and require more assistance at discharge. Clarifying emergent vs elective THA at admission may assist in better planning and assessment of patient needs regarding rehabilitation, hospital management, and discharge planning.


Cost and quality issues in establishing hematopoietic cell transplant program in developing countries.
The hematopoietic cell transplant (HCT) activity has grown significantly over the past two decades in both developing and developed countries. Many challenges arise in establishing new HCT programs in developing countries, due to scarcity of resources and manpower in expertise in HCT. While cost issues can potentially hinder establishment of new HCT programs in certain regions, the focus on quality and value should be included in the general vision of leadership before establishing an HCT program. The main challenge in most developing countries is the lack of trained/qualified personnel, enormous start-up costs for a tertiary care center, and quality maintenance. Herein, we discuss the main challenges from a cost and quality perspective which occur at initiation of a new HCT program. We give real world examples of two developing countries that have recently started new HCT programs despite significant financial constraints. We also portray recommendations from the Worldwide Network of Blood and Marrow Transplantation for levels of requirements for a new HCT program. We hope that this review will serve as a general guide for new transplant program leadership with respect to the concerns of balancing high quality with concurrently lowering costs.


Shortcuts to Adiabatic Pumping in Classical Stochastic Systems.
Adiabatic pumping is characterized by a geometric contribution to the pumped charge, which can be nonzero even in the absence of a bias. However, as the driving speed is increased, nonadiabatic excitations gradually reduce the pumped charge, thereby limiting the maximal applicable driving frequencies. To circumvent this problem, we here extend the concept of shortcuts to adiabaticity to construct a control protocol which enables geometric pumping well beyond the adiabatic regime. Our protocol allows for an increase, by more than an order of magnitude, in the driving frequencies, and the method is also robust against moderate fluctuations of the control field. We provide a geometric interpretation of the control protocol and analyze the thermodynamic cost of implementing it. Our findings can be realized using current technology and potentially enable fast pumping of charge or heat in quantum dots, as well as in other stochastic systems from physics, chemistry, and biology.


General Use of Chinese Herbal Products among Female Patients with Mastitis in Taiwan.
Little information is available regarding the use of Chinese herbal medicine to treat mastitis. This study evaluated the prescription patterns of Chinese herbal medicine products in women with mastitis in Taiwan. This is a population-based cross-sectional study. Setting. 8,531 women aged 20-49 years, who received a diagnosis of mastitis between 2004 and 2013, were identified from the Longitudinal Health Insurance Database in Taiwan. We collected data on demographic characteristics, including age, monthly insurance premium, and urbanization level. The ten most Chinese herbal medicines prescribed for mastitis were assessed, including frequency, percentage, average daily dose, and average duration of prescription. Main outcome measures. We analysed the ten most single Chinese herbs and Chinese herbal formulae prescribed for mastitis. Overall, 437 (5.1%) women received Chinese herbal medicine to treat mastitis. Mai Men Dong (Ophiopogon japonicus (Thunb.) Ker Gawl.; 22.3%), Pu Gong Yin (Taraxacum mongolicum Hand.-Mazz.; 7.8%), and Wang Bu Liu Xing (Vaccaria hispanica (Mill.) Rauschert; 3.5%) were three of the most commonly prescribed single Chinese herbs for mastitis. Xian-Fang-Huo-Ming-Yin (18.2%), Jia-Wei-Xiao-Yao-San (9.1%), and Chai-Hu-Shu-Gan-San (8.4%) were three of the most commonly prescribed Chinese herbal formulae. Xian-Fang-Huo-Ming-Yin can clear heat, detoxify body, alleviate swelling, activate blood, and relieve pain. It was the most frequently prescribed Chinese herbal formula in patients with mastitis.


Expression of neuronal nitric oxide synthase in the developing superficial layers of the rat superior colliculus.
We investigated the level of expression of neuronal nitric oxide synthase (nNOS) in the retinorecipient layers of the rat superior colliculus during early postnatal development. Male and female Lister rats ranging in age between the day of birth (P0) and the fourth postnatal week were used in the present study. Two biochemical methods were used, i.e., in vitro measurement of NOS specific activity by the conversion of [3H]-arginine to [3H]-citrulline, and analysis of Western blotting immunoreactive bands from superior colliculus homogenates. As revealed by Western blotting, very weak immunoreactive bands were observed as early as P0-2, and their intensity increased progressively at least until P21. The analysis of specific activity of NOS showed similar results. There was a progressive increase in enzymatic activity until near the end of the second postnatal week, and a nonsignificant tendency to an increase until the end of the third week was also observed. Thus, these results indicated an increase in the amount of nNOS during the first weeks after birth. Our results confirm and extend previous reports using histochemistry for NADPH-diaphorase and immunocytochemistry for nNOS, which showed a progressive increase in the number of stained cells in the superficial layers during the first two postnatal weeks, reaching an adult pattern at the end of the third week. Furthermore, our results suggested that nNOS is present in an active form in the rat superior colliculus during the period of refinement of the retinocollicular pathway.


Frequency of unexpected antibody and consideration during transfusion.
In this retrospective study, we measured the frequency of unexpected antibodies in the blood. Specific considerations for preoperative preparations were kept in mind for the patients undergoing surgery positive for these antibodies. After reviewing the results of antibody screening tests lasted for 2 years, the frequency of unexpected antibodies was determined. Surgical patients who were positive for unexpected antibodies were selected and divided into two groups based on their potential need for an intra-operative transfusion (groups with high versus low possibility of transfusion). Blood for the high possibility group was prepared before surgery. For the low possibility group for which preoperative blood preparation was not performed, cases of this group were reviewed whether a blood preparation was delayed or not in case of transfusion. Among a total 22,463 cases, 340 (1.52%) had positive results for antibody screening tests. Among the 243 patients who were positive for unexpected antibodies, Lewis, Rh, Xga, and mixed antibodies were found in 85, 25, five, and eight cases, respectively. Out of 243 patients, 117 patients, specificities of the unexpected antibodies were not determined and 125 (51.4%) had a history of pregnancy and delivery, and 49 (20.2%) had a history of transfusion. In the low probability group, transfusions were administered for nine patients; transfusion was delayed for two patients due to difficulties with obtaining matched blood. Patients with unexpected blood antibodies may be at increased risk for delayed transfusion. For rapid transfusion, it might be helpful to keep a record about blood antibodies and introduce a notification system such as medical alert cards. Preoperative blood preparation is needed for timely intraoperative transfusion.


[First trimester ultrasound: beyond nuchal translucency].
Pregnancy care has gradually evolved over the last two decades, with a trend towards earlier detection and diagnosis of both maternal and fetal pathologies. At the core of this process, antenatal ultrasound allows to identify a large number of congenital malformations as early as the end of the first trimester. It has also become an increasingly specialized procedure, requiring considerable material and human resources. In this article, we review the basic principles of first-trimester ultrasound, focusing on most recent screening recommendations.


Application of anthropometric indices in childhood obesity.
The purpose of this study was to determine which anthropometric index can best predict childhood obesity and to investigate the interrelationship between these anthropometric indices and metabolic abnormalities. This was a cross-sectional study. In March 2000, 2005 children aged 7 to 8 from the first grade of primary schools in Taichung City in Taiwan were enrolled in this study. Data were obtained on the children's anthropometry, blood pressure, and serum lipid profiles. Body mass index (cutoff points by international age- and sex-specific body mass index [BMI]) and weight-length index (WLI) were measured. The t test, the chi2 test, and stepwise multivariate logistic regression were used. All subjects were divided into four groups: Group 1, nonobese by BMI definition, WLI < 1.2; group 2, obese by BMI definition, WLI < 1.2; group 3, nonobese by BMI definition, WLI > or = 1.2; and group 4, obese by BMI definition, WLI > or = 1.2. There were 951 girls (47.43%) and 1,054 boys (52.57%). The mean age was 7.3 +/- 0.4 years. The prevalence of obesity was 4.21% in girls and 7.87% in boys using BMI definition, and 12.83% in girls and 14.14% in boys using WLI definition. The prevalence of obesity revealed an increased trend with age in both sexes, whether by BMI or WLI definition. Group 4 had the highest prevalence rate of all metabolic abnormalities, except hypertriglyceridemia. After controlling for age and sex, and with group 1 as a reference, odds ratios were considerably higher in group 3 for the risk of hypertension (2.73; 95% confidence interval [CI], 1.67-4.44) and hypertriglyceridemia (5.83; 95% CI, 1.42-23.95). Odds ratios were considerably higher in group 4 for the risk of hypertension (3.75; 95% CI, 2.31-6.07) and high level of low-density lipoprotein cholesterol (1.93; 95% CI, 1.32-2.82). The prevalence of obesity apparently differs depending on the definition of estimation. Childhood obesity exhibits significant correlation with some metabolic abnormalities. We hypothesize that, at present, both indices, BMI and WLI, should be used together to define childhood obesity in clinical practice until a more appropriate and excellent index can be established.


Frizzled gene expression and development of tissue polarity in the Drosophila wing.
Almost every cell in the Drosophila pupal wing forms a single, distally pointing cuticular hair. The function of the frizzled (fz) gene is essential for the elaboration of the normal wing hair pattern. In the absence of fz function hairs develop, but they display an abnormal polarity. We have examined the developmental expression of the fz gene at the RNA level via in situ hybridization and at the protein level via Western blotting. We have found that fz is expressed in all regions of the epidermis before, during, and after the fz cold sensitive period. We have also found that fz function is not required for normal fz expression. We have further found that mutations in several other tissue polarity genes do not noticeably alter the expression or the modification state of the Fz protein.


[Evaluation of an applied program for the prevention and control of tuberculosis].
To evaluate the efficacy of a tuberculosis prevention and control program applied in the health care area of Cadiz (Spain). Tuberculosis cases diagnosed by microbiological criteria (Ziehl-Neelsen/auramine smear and/or culture in Löwenstein-Jensen medium) from 1996 to 2000 were analyzed in relation to epidemiologic characteristics of the patients. Susceptibility studies were performed from 1997 onwards using the proportion method described by Canetti, Rist and Grosset. The rate of tuberculous infections gradually dropped from 38.4 cases/100,000 inhabitants in 1996 to 16.0 cases/100,000 inhabitants in 2000. Along the study period, the percentage of men affected by the disease ranged from 81.2% in 1996 to 70.0% in 2000. In 1996, 26.0% of tuberculous patients were HIV-positive, and in 2000, 27.5%. The sensitivity of microbiologic diagnosis increased considerably from 60.4% in 1996 to 67.5% in 2000. Multi-drug resistance (9.2% en 1997) has virtually disappeared in our area since 1998 (1.6%).CONCLUSIONS. Implementation of a plan for the prevention and control of tuberculosis in our geographic area was effective, resulting in a decrease in the infection rate to less than 25 cases/100,000 inhabitants, and improvements in microbiologic diagnosis and compliance with treatment. Tuberculous disease has affected an increasingly higher proportion of women, regardless of HIV status. Antimicrobial resistance, particularly multi-drug resistance is now low in our area.


Clinical Implications of Hedgehog Pathway Signaling in Prostate Cancer.
Activity in the Hedgehog pathway, which regulates GLI-mediated transcription, is important in organogenesis and stem cell regulation in self-renewing organs, but is pathologically elevated in many human malignancies. Mutations leading to constitutive activation of the pathway have been implicated in medulloblastoma and basal cell carcinoma, and inhibition of the pathway has demonstrated clinical responses leading to the approval of the Smoothened inhibitor, vismodegib, for the treatment of advanced basal cell carcinoma. Aberrant Hedgehog pathway signaling has also been noted in prostate cancer with evidence suggesting that it may render prostate epithelial cells tumorigenic, drive the epithelial-to-mesenchymal transition, and contribute towards the development of castration-resistance through autocrine and paracrine signaling within the tumor microenvironment and cross-talk with the androgen pathway. In addition, there are emerging clinical data suggesting that inhibition of the Hedgehog pathway may be effective in the treatment of recurrent and metastatic prostate cancer. Here we will review these data and highlight areas of active clinical research as they relate to Hedgehog pathway inhibition in prostate cancer.


Anti-babesial ellagic acid rhamnosides from the bark of Elaeocarpus parvifolius.
Bioassay-guided investigation of the bark of Elaeocarpus parvifolius led to the isolation of three new ellagic acid derivatives, 4-O-methylellagic acid 3'-alpha-rhamnoside (2), 4-O-methylellagic acid 3'-(3''-O-acetyl)-alpha-rhamnoside (3), and 4-O-methylellagic acid 3'-(4''-O-acetyl)-alpha-rhamnoside (4) in addition to the known ellagic acid derivative, 4-O-methylellagic acid 3'-(2'',3''-di-O-acetyl)-alpha-rhamnoside (1). Their structures were elucidated on the basis of analysis of 1H NMR, 13C NMR, HMQC, HMBC and MS spectroscopic data. Compounds 1-4 were evaluated for their growth-inhibitory effect on Babesia gibsoni in vitro. Compounds 2 and 4 showed very weak activity, while compounds 1 and 3 showed moderate activity, with IC50 values of 28.5 and 52.1 microg/ml, respectively.


Early antibody response against hypervariable region 1 is associated with acute self-limiting infections of hepatitis C virus.
Antibodies directed to hypervariable region 1 (HVR1) of hepatitis C virus (HCV) have recently been shown to neutralize the corresponding HCV isolate in vitro. We analyzed the appearance of antibodies directed to HVR1 during the course of infection in a large group of patients who have been infected by the same isolate of a HCV contaminated anti-D immunoglobulin (HCV-AD78). An enzyme-linked immunosorbent assay (ELISA) was established using a synthetic peptide to detect antibodies against the main HVR1 variant of HCV-AD78. 207 sera obtained at different time points post infection (p.i.) of 51 patients having either acute self-limiting (n = 28) or chronic infection (n = 23) were studied. Antibodies directed to HVR1 were found at least at one time point during the infection course in 15 of 28 patients (53%) having acute self-limiting infections and in 17 of 23 patients (74%) with chronic disease. The time of appearance of anti-HVR1 was significantly different between these two patient groups (P < .025) although appearance and titers of other HCV-specific antibodies were found to be similar at early time points p.i. In acute self-limiting infections 9 of 21 sera (43%) of respective patients with sera available within the first 6 months p.i. were anti-HVR1 positive. The highest prevalence of anti-HVR1 in this group of patients was within month 6 to 12 p.i. (64%). None of the sera available after 24 months p.i. had such antibodies. In contrast, only 2 of 15 sera (13%) of chronically infected patients with respective time points of sera were anti-HVR1 positive within the first 6 months p.i. and only 5 of 18 sera (28%) were positive within month 7 to 12 p.i. Seven patients with chronic HCV infections showed at least two consecutive anti-HVR1 negative early time points up to month 18 p.i. Prevalence of anti-HVR1 after 24 months p.i. was high (84%) in this group of patients and most of the patients maintained high levels of anti-HVR1 for up to 17 years p.i. Our findings suggest clearance of virus by respective neutralizing antibodies resulting in a self-limiting infection and may have implications for prognosis of the disease and also for any future vaccine development.


Spontaneous temperature-sensitive Pluronic(®) based niosomes: Triggered drug release using mild hyperthermia.
Inclusion of lipids or polymers with a transition temperature closer to physiological body temperature (40-42°C) is a strategy used in tumor therapy for more than 30 years, because it allows induction of drug release from delivery systems by mild hyperthermia. Unfortunately, most of these thermo-sensitive carriers are removed from circulation before completion of their function. Thus, novel multi-functional niosomes possessing spontaneous stealth and thermo-sensitive properties were developed from L64 Pluronic(®) and L64ox as its derivative, in presence or absence of cholesterol. The use of L64 both as amphiphilic constituent and thermo-sensitive molecule, gave the possibility to bypass the use of additional excipients and increased the system biocompatibility. Niosomes diameter ranged from 400 to 750nm and were long term stable. Calcein and 5-FU possess great affinity to niosomal matrices rich in PEO groups. Negative Z-potential values were attributed to the negative charges onto the niosomes surface and generally change according to the temperature. The in vitro drugs release studies were performed at 25°C, 37°C and 42°C, that are representative of certain conditions (storage, physiological condition and mild hyperthermia, respectively). Results showed that L64-based niosomes possess spontaneous thermo-sensitive properties: drugs releases were found to be more pronounced at 42°C. These early results are a promising first step for the development of multi-functional devices that combine several advantages such as stealth properties and temperature controllability at the desired location and time, for a more specific and efficient pharmacological therapy.


Draft Genome Sequence of Coralloluteibacterium stylophorae LMG 29479T.
Here, we report a draft genome sequence of the strain Coralloluteibacterium stylophorae LMG 29479T, acquired from the Belgian Coordinated Collections of Microorganisms. The genus Coralloluteibacterium currently includes only one species with a validly published name. These genome sequencing data are important for the phylogeny of the Lysobacteraceae family.


A procedure to detect and identify specific chemicals of potential inhalation toxicity concern in aerosols.
Understanding the potential inhalation toxicity of poorly characterized aerosols is challenging both because aerosols may contain numerous chemicals and because it is difficult to predict which chemicals may present significant inhalation toxicity concerns at the observed levels. We have developed a novel systematic procedure to address these challenges through non-targeted chemical analysis by two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS) and assessment of the results using publicly available toxicity data to prioritize the tentatively identified detected chemicals according to potential inhalation toxicity. The procedure involves non-targeted chemical analysis of aerosol samples utilizing GC × GC-TOFMS, which is selected because it is an effective technique for detecting chemicals in complex samples and assigning tentative identities according to the mass spectra. For data evaluation, existing toxicity data (e.g. from the U.S. Environmental Protection Agency CompTox Chemicals Dashboard) are used to calculate multiple toxicity metrics that can be compared among the tentatively identified chemicals. These metrics include hazard quotient, incremental lifetime cancer risk, and metrics analogous to hazard quotient that we designated as exposure-(toxicology endpoint) ratios. We demonstrated the utility of our procedure by detecting, identifying, and prioritizing specific chemicals of potential inhalation toxicity concern in the mainstream smoke generated from the machine-smoking of marijuana blunts. By designing a systematic approach for detecting and identifying numerous chemicals in complex aerosol samples and prioritizing the chemicals in relation to different inhalation toxicology endpoints, we have developed an effective approach to elucidate the potential inhalation toxicity of aerosols.


[Current state and problems in the microbiology laboratory--organizing the laboratory].
The microbiological laboratory in the hospital has many roles including the rapid and precise identification of pathogenic bacteria in specimens, their antimicrobial susceptibility tests, microbial antigen detection using immunological methods and DNA hybridization methods, surveillance of bacterial milieu of the hospital environment, monitoring quality control of microbiological methods, to educate microbiological skills of staffs, the economical management of laboratory and so on. The last two issues are our major concerns. Improvement of the microbiological skills of the staff is most important in the laboratory, but is a time-consuming. From our experience, a technical expert, intermediately skilled technicians and beginners should always work in the laboratory, together. On the other hand, the economical management of the microbiological laboratory is also another concern. Although the mechanization of procedures comes to mind, it is hard to improve the economical conditions in the laboratory. Because of the control of the machines is not completely automatic and requires the knowledges and decisions of technical experts, the work force and running cost can not be reduced. As the technical expert can economize in the use of media or tests for identification of pathogens, good training of beginners into skillful successors, is important.


Effects of voluntarily-ingested buprenorphine on plasma corticosterone levels, body weight, water intake, and behaviour in permanently catheterised rats.
This study investigated the peri- and postoperative effect of pre-emptive analgesia through voluntary ingestion of buprenorphine in Nutella, in male Sprague-Dawley rats. An arterial catheter was inserted and the rats were connected to an automated blood sampling device (AccuSampler). Blood samples were drawn up to 18 h after surgery and the plasma concentrations of corticosterone were quantified. Postoperative changes in water intake and body weight were recorded, and the behaviour of the rats was analysed during two 30-min periods. Pre-emptive oral buprenorphine treatment reduced the plasma corticosterone levels in the postoperative period, compared to controls treated with local anaesthetics. Buprenorphine-treated rats consumed more water and maintained body weight better. Behavioural observations indicated that buprenorphine changed the behaviour in non-operated rats but there was no difference in the operated rats. The present study strengthens the hypothesis that pre-emptive oral buprenorphine in Nutella is suitable for treatment of postoperative pain in rats.


Boric ester-type molten salt via dehydrocoupling reaction.
Novel boric ester-type molten salt was prepared using 1-(2-hydroxyethyl)-3-methylimidazolium chloride as a key starting material. After an ion exchange reaction of 1-(2-hydroxyethyl)-3-methylimidazolium chloride with lithium (bis-(trifluoromethanesulfonyl) imide) (LiNTf2), the resulting 1-(2-hydroxyethyl)-3-methylimidazolium NTf2 was reacted with 9-borabicyclo[3.3.1]nonane (9-BBN) to give the desired boric ester-type molten salt in a moderate yield. The structure of the boric ester-type molten salt was supported by 1H-, 13C-, 11B- and 19F-NMR spectra. In the presence of two different kinds of lithium salts, the matrices showed an ionic conductivity in the range of 1.1 × 10⁻⁴-1.6 × 10⁻⁵ S cm⁻¹ at 51 °C. This was higher than other organoboron molten salts ever reported.


Gender disparities in quality of life and psychological disturbance in patients with implantable cardioverter-defibrillators.
Implantable cardioverter-defibrillator (ICD) has improved prognosis in fatal arrhythmia and the number of ICD implantations has increased. ICD-related psychological problems and impaired quality of life (QOL), however, have been observed. This study examined whether gender differences exist in QOL and psychological disturbances in ICD patients. Consecutive outpatients (n=179; mean age, 60.5±15.9 years; 81% male) with ICD implantations completed questionnaires consisting of the Short Form-8 (SF-8), Beck Depression Inventory, Impact of Event Scale-Revised (IES-R), State-Trait Anxiety Inventory, and Worries about ICD. One-way multivariate analysis of variance (MANOVA) showed women to have impaired QOL on the role physical functioning (F15,157=4.57, P<0.05) and bodily pain (F15,157=5.26, P<0.05) subscales of the SF-8. More women reported depression (F15,157=5.37, P<0.05) and worry about ICD than men (F15,157=6.62, P<0.05). Moreover, women also had higher IES-R scores indicating post-traumatic stress disorder (PTSD) than men (F15,157=5.87, P<0.05). Women reported poorer QOL on 2 subscales: role physical functioning and bodily pain. There was a significant relationship between gender and depression, worry about ICD, and PTSD, but not for anxiety. Female patients need more psychological interventions following ICD implantation.


Consensus viewpoint on management of urinary infections.
Twenty-four general practitioners completed a questionnaire on behalf of their partners in the practices before attending the symposium. The main points that emerged were that trimethoprim was the most popular antibiotic for treatment of acute urinary infection and that the most common duration of treatment was 5 to 7 days. A panel discussion, with audience participation, covered duration of treatment, antibiotic resistance, specimen collection, management of different patient groups and availability of information concerning resistance patterns. Nineteen of the original 24 general practitioners returned the post-meeting questionnaire, and stated that, as a result of what they had heard at the symposium, they were contemplating changing the way in which they managed urinary infections. Information concerning bacteriuria in pregnancy and changing patterns of bacterial resistance to antibiotics were of particular interest.


Consumption of yacon flour improves body composition and intestinal function in overweight adults: A randomized, double-blind, placebo-controlled clinical trial.
Yacon root is a natural source of fructooligosaccharides (FOS), and it has been studied for its potential effect as a functional food. However, FOS in the in natura root are rapidly hydrolyzed. Thus, the use of dehydrated products such as flour ensures stability of FOS. The effect of chronic consumption of yacon flour on body composition, food intake and of biochemical variables concentration has not yet been evaluated in humans. Thus, we evaluated the effects of yacon flour consumption on these variables associated with excess body weight. Twenty-six adults (31.3 ± 8.5 years) with excess weight (30.4 ± 2.4 kg/m2, 40.16 ± 6.7% body fat) participated in this randomized, double-blind, six-week study. Subjects were randomly allocated to one of the experimental groups (control (n = 13) or yacon flour (n = 13)), received the prescription of energy-restricted diets (- 500 kcal/day) and daily consumed a breakfast drink not containing or containing 25 g of yacon flour (0.1 g of FOS/kg body weight). At the beginning and at the end of the study, biochemical analyses (glycemia, insulinemia, lipid profile and liver function markers), anthropometrics (weight, waist, hip and neck circumference and sagittal abdominal diameter), body composition (lean mass, total body fat, trunk fat, android fat and gynoid fat), blood pressure, intestinal function, and food intake were assessed. Daily yacon flour consumption was well tolerated, did not cause adverse gastrointestinal effects, increased dietary fiber consumption, promoted greater body weight, waist circumference, waist to height index, sagittal abdominal diameter, and body fat reduction, besides improving bowel function in comparison to the control group. Yacon flour served as a natural fiber supplement and proved to be an effective adjuvant to be used in nutritional strategies to control excess body weight.


Novel retinal findings in peroxisomal biogenesis disorders.
Peroxisomal biogenesis disorders are caused by disruption of long chain fatty acid metabolism due to mutations in PEX genes. Individuals with these disorders often have vision loss due to optic atrophy and pigmentary retinopathy. We report an unusual retinal manifestation of peroxisomal biogenesis disorder.


Pulmonary irradiation-induced expression of VCAM-I and ICAM-I is decreased by manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) gene therapy.
Pulmonary toxicity is a major complication of total body irradiation used in preparation of patients for bone marrow transplantation. The mechanism of the late pulmonary damage manifested by fibrosis is unknown. In C57BL/6NHsd mice, manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) intratracheal injection 24 hours prior to 20 Gy single-fraction irradiation to both lungs significantly reduced late irradiation damage. Single intratracheal injections of MnSOD-PL, at concentrations as low as 250 microg of plasmid DNA, in a constant volume of 78 microL of liposomes, reduced late damage. To determine whether a slowly proliferating population of cells in the lung was responsible for initiation of fibrosis and was altered by MnSOD-PL therapy, 20 Gy total lung-irradiated mice were examined at serial time points for bromodeoxyuridine (BrdU) uptake in sites of cell division. There was low-level, but nonsignificant, increased cell proliferation detected at 80 days, with a significant increase at 100 days, 120 days, and at the time of death. Immunohistochemical assay for up-regulation of adhesion molecules associated with recruitment, transendothelial migration, and proliferation of bronchoalveolar macrophages revealed significant up-regulation of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) at 100 days with further increases up to the time of death. Increases were first detected in endothelin-positive endothelial cells. MnSOD-PL administration prior to irradiation decreased both BrdU incorporation and delayed expression of VCAM-1 and ICAM-1. The data indicate that the appearance of late irradiation-induced pulmonary fibrosis is associated with the up-regulation of adhesion molecules and suggest that potential targets for intervention may focus on the pulmonary vascular endothelium.


Dynamics of a colloidal particle driven by continuous time-delayed feedback.
We perform feedback experiments and simulations in which a colloidal dumbbell particle, acting as a particle on a ring, is followed by a repulsive optical trap controlled by a continuous-time-delayed feedback protocol. The dynamics are described by a persistent random walk similarly to that of an active Brownian particle, with a transition from predominantly diffusive to driven behavior at a critical delay time. We model the dynamics in the short and long delay regimes using stochastic delay differential equations and derive a condition for stable driven motion. We study the stochastic thermodynamic properties of the system, finding that the maximum work done by the trap coincides with a local minimum in the mutual information between the trap and the particle position at the onset of stable driven dynamics.


Radiofrequency-Driven and Slow-Magic-Angle-Sample-Spinning Polarization-Transfer Techniques: A Comparative Study
The rate constant of radiofrequency-driven (RF-driven) polarization transfer and that of polarization transfer under slow-magic-angle sample spinning (S-MAS) are compared using a model system, polycrystalline alpha-alpha'-13C2-phthalic acid. While the rate constant under RF irradiation in static samples strongly depends on the orientation of the internuclear vector, the rate constant under S-MAS is hardly sensitive to that orientation and, thus, depends almost exclusively on the internuclear distance. Consequently, polarization-transfer rate constants obtained under S-MAS can be interpreted more simply when used to study local order in polycrystalline or amorphous solids. Copyright 1998 Academic Press.


The ultimate curse: the doctor as patient.
Doctors may be thrust into the difficult situation of treating friends and colleagues. A doctor's response to this situation is strongly influenced by his or her emotions and by medical tradition. Such patients may be treated as 'special cases' but the 'special' treatment can backfire and lead to an adverse outcome. Why does this happen and can doctors avoid it happening? These issues are discussed in this commentary on Dr. Crisci's paper, 'The ultimate curse.'


Validation of ten-year fracture risk prediction: a clinical cohort study from the Manitoba Bone Density Program.
Absolute 10-year fracture risk is the preferred method for fracture risk assessment. The validity of applying published fracture rates from one population to another population is uncertain. 20,579 women age 47.5 years or older at the time of baseline femoral neck bone mineral density (BMD) were identified in a database containing all clinical DXA results for the Province of Manitoba, Canada. Individual 10-year fracture risk was predicted from age-only and age plus femoral neck T-score using published 10-year fracture risk for Swedish women. Health service records were assessed for the presence of non-trauma 'osteoporotic' fracture codes (hip, clinical spine, wrist, humerus) subsequent to BMD testing (86,447 person-y follow up, 1173 patients with osteoporotic fractures). Fracture rates were derived for subgroups stratified by age (5-year strata) and estimated risk (5% strata). 10-year fracture rates were computed directly by the Kaplan-Meier method (10-year continuous data) and by the actuarial method (two 5-year periods with adjustments for aging, death and expected BMD loss). Direct and actuarial methods gave nearly identical point estimates, but the latter were more precise. There was a strong linear correlation between predicted and observed fracture rates based upon age-only (r = 0.95) and age plus BMD (r = 0.99). For age strata 50 to 75, and for estimated risk strata from 0-5% to 20-25%, the confidence intervals overlapped the line of identity. For women age >77.5 or estimated risk >25%, observed exceeded estimated fracture rates. This is explained by healthy selection bias whereby elderly women referred for BMD testing have lower mortality than expected, hence more years at risk for fracture. Corrected for survival bias, women age >77.5 had observed fracture rates no different than predicted. Swedish 10-year fracture risk data are generally applicable to the Canadian female population referred for clinical BMD testing, though fracture rates were underestimated in the oldest and highest risk subgroups due to healthy selection bias.


Which axial and bending stiffnesses of posterior implants are required to design a flexible lumbar stabilization system?
Dynamic stabilization devices have been introduced to clinics as an alternative to rigid fixation. The stiffness of these devices varies widely, whereas the optimal stiffness, achieving a predefined stabilization of the spine, is unknown. This study was focused on the determination of stiffness values for posterior stabilization devices achieving a flexible, semi-flexible or rigid connection between two vertebrae. An extensively validated finite element model of a lumbar spinal segment L4-5 with an implanted posterior fixation device was used in this study. The model was exposed to pure moments of 7.5 and 20Nm around the three principal anatomical directions, simulating flexion, extension, lateral bending and axial rotation. In parametrical studies, the influence of the axial and bending fixator stiffness on the spinal range of motion was investigated. In order to examine the validity of the computed results, an in-vitro study was carried out. In this, the influence of two posterior stabilization devices (DSS and rigidly internal fixator) on the segmental stabilization was investigated. The finite element (FE)-model predicted that each load direction caused a pairing of stiffness relations between axial and bending stiffness. In flexion and extension, however, the bending stiffness had a neglectable effect on the segmental stabilization, compared to the axial stiffness. In contrast, lateral bending and axial rotation were influenced by both stiffness parameters. Except in axial rotation, the model predictions were in a good agreement with the determined in-vitro data. In axial rotation, the FE-model predicted a stiffer segmental behavior than it was determined in the in-vitro study. It is usually expected that high stiffness values are required for a posterior stabilization device to stiffen a spinal segment. We found that already small stiffness values were sufficient to cause a stiffening. Using these data, it may possible to develop implants for certain clinical indications.


Population genetic structure and Wolbachia infection in an endangered butterfly, Zizina emelina (Lepidoptera, Lycaenidae), in Japan.
Zizina emelina (de l'Orza) is listed on Japan's Red Data List as an endangered species because of loss of its principal food plant and habitat. We compared parts of the mitochondrial and nuclear genes of this species to investigate the level of genetic differentiation among the 14 extant populations. We also examined infection of the butterfly with the bacterium Wolbachia to clarify the bacterium's effects on the host population's genetic structure. Mitochondrial and nuclear DNA analyses revealed that haplotype composition differed significantly among most of the populations, and the fixation index F ST was positively correlated with geographic distance. In addition, we found three strains of Wolbachia, one of which was a male killer; these strains were prevalent in several populations. There was linkage between some host mitochondrial haplotypes and the three Wolbachia strains, although no significant differences were found in a comparison of host mitochondrial genetic diversity with nuclear genetic diversity in Wolbachia-infected or -uninfected populations. These genetic analyses and Wolbachia infection findings show that Z. emelina has little migratory activity and that little gene flow occurs among the current populations.


Importance of heart rate response during exercise in patients using atrioventricular synchronous and ventricular pacemakers.
Atrioventricular synchronous pacing offers advantages over fixed-rate ventricular (VVI) pacing both at rest and during exercise. This study compared the hemodynamic effects at rest and exercise of ventricular pacing at a rate of 70 beats/min, ventricular pacing where the rate was increased during exercise and dual chamber pacing. Ten patients, age 63 +/- 8 years, with multiprogrammable DDD pacemakers were studied using supine bicycle radionuclide ventriculography. Radionuclide data during dual chamber pacing was acquired at rest and during a submaximal workload of 200-400 kpm/min. The pacemakers were then programmed to VVI pacing at a rate of 70 beats/min, and 1 week later, studies were repeated in the VVI mode at rest, during exercise at a rate of 70 beats/min, and during exercise with the VVI pacemaker programmed to a rate adapted to the DDD pacing exercise rate. At rest, the cardiac output was lower in the VVI compared with the AV sequential mode (4.1 +/- 1.1 vs 5.7 +/- 1.1 1/min, P less than 0.01). During exercise, the cardiac output increased from resting values in the DDD and VVI pacing modes, however cardiac output in the rate-adapted VVI mode was higher than in the VVI mode with the rate maintained at 70 beats/min (8.1 +/- 1.5 vs 6.3 +/- 1.1 1/min, P = 0.02). Three patients completed lower workloads with VVI pacing at 70 beats/min compared with AV synchronous pacing. At rest, AV sequential pacing was superior to VVI pacing, suggesting the importance of the atrial contribution to ventricular filling. With VVI pacing during exercise, cardiac output was improved with an increased pacemaker rate, suggesting that the heart rate response during exercise was the major determinant of the higher cardiac output.


Erection hardness: a unifying factor for defining response in the treatment of erectile dysfunction.
The extensive sildenafil citrate erectile dysfunction (ED) database of double-blind, placebo-controlled clinical trials was examined to determine the relation between erection hardness graded on the Erectile Hardness Grading Scale (EHGS) and (1) erectile function (EF), as assessed by the EF domain of the International Index of Erectile Function (IIEF); (2) frequency of erections hard enough for penetration, as assessed by IIEF Q2; and (3) the percentage of successful sexual intercourse attempts according to patient event logs. Pooled data from 6549 men with ED provided strong proof and improved characterization of the response to sildenafil. Almost half of men with ED and a baseline IIEF EF domain score classified as "severe ED" (< or = 10) shifted to a score classified as "no ED" (> or = 26). Sildenafil recipients showed greater mean improvement from baseline to end point in IIEF Q2 scores versus placebo, regardless of baseline ED severity, and a higher mean percentage of successful sexual intercourse attempts occurred during the last 4 weeks of treatment versus placebo (5.4-fold vs 2.0-fold increase from baseline). At end point, 95% of men who scored "no ED" on the IIEF EF domain and 92% of men who reported "almost always/always" achieving an erection hard enough for penetration (IIEF Q2) had graded their erections hard (rigid) enough for penetration (grade 3) or completely hard and fully rigid (grade 4) during the last 4 weeks of treatment, suggesting that the IIEF EF domain and IIEF Q2 may be good surrogate end points for erection hardness. Furthermore, during the last 4 weeks of treatment, the percentage of grade 3 and/or 4 erections correlated positively with the percentage of successful sexual intercourse attempts. Hence, hard erections may be considered a unifying factor that defines response to ED treatment. Completely hard and fully rigid erections (grade 4) should be recognized as the optimal goal of an ED therapy. Evidence presented here demonstrates that sildenafil significantly improved EF as assessed by the IIEF EF domain and assessments of erection hardness in patients with ED; a dose-response relation was observed in the proportions of men with ED who graded their erections hard (rigid) enough for sexual penetration or completely hard and fully rigid.


Sol-gel dip coating of yttria-stabilized tetragonal zirconia dental ceramic by aluminosilicate nanocomposite as a novel technique to improve the bonding of veneering porcelain.
The aim of this in vitro study was to evaluate the effect of silica and aluminosilicate nanocomposite coating of zirconia-based dental ceramic by a sol-gel dip-coating technique on the bond strength of veneering porcelain to the yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) in vitro. Thirty Y-TZP blocks (10 mm ×10 mm ×3 mm) were prepared and were assigned to four experimental groups (n=10/group): C, without any further surface treatment as the control group; S, sandblasted using 110 μm alumina powder; Si, silica sol dip coating + calcination; and Si/Al, aluminosilicate sol dip coating + calcination. After preparing Y-TZP samples, a 3 mm thick layer of the recommended porcelain was fired on the coated Y-TZP surface. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray analysis were used to characterize the coating and the nature of the bonding between the coating and zirconia. To examine the zirconia-porcelain bond strength, a microtensile bond strength (μTBS) approach was chosen. FT-IR study showed the formation of silica and aluminosilicate materials. XRD pattern showed the formation of new phases consisting of Si, Al, and Zr in coated samples. SEM showed the formation of a uniform coating on Y-TZP samples. Maximum μTBS values were obtained in aluminosilicate samples, which were significantly increased compared to control and sandblasted groups (P=0.013 and P<0.001, respectively). This study showed that aluminosilicate sol-gel dip coating can be considered as a convenient, less expensive reliable method for improving the bond strength between dental Y-TZP ceramics and veneering porcelain.


Treatment of hepatic epithelioid hemangioendothelioma with liver transplantation.
Ten patients received liver transplants for unresectable epithelioid hemangioendothelioma (EHE). At the time of transplantation, four patients had microscopic metastases to the hilar lymph nodes, and one of the four also had metastases to a rib. The fifth patient had metastases to the lung, pleura, and diaphragm. The remaining five patients were believed to be free of metastatic disease. Two of these five patients died of metastatic disease at 3 and 16 months, respectively, after transplantation. Interestingly, all five patients with metastatic involvement are currently alive 40.6 +/- 22 months (mean +/- standard error of mean [SEM]) after transplantation, although one of these patients currently has metastatic disease to the lungs and mediastinum. Thus, the projected 5-year actuarial survival rate is 76%, with two patients at risk after the third year. In conclusion, liver transplantation is a reasonable procedure for bulky, otherwise unresectable, EHE even in the presence of metastatic disease.


Why 21? The significance of selenoproteins for human health revealed by inborn errors of metabolism.
Selenocysteine is the 21st proteinogenic amino acid in mammals. The human genome contains 25 genes encoding selenoproteins, and their significance for human health is increasingly recognized through the identification of patients with inborn errors in selenoprotein biosynthetic factors or in individual selenoproteins. Mutations in selenoprotein N (SEPN1) lead to a spectrum of disorders collectively called SEPN1-related myopathy, and mutations in glutathione peroxidase 4 (GPX4) cause respiratory failure and bone defects, and mutations in thioredoxin reductase 2 (TXNRD2) are associated with familial glucocorticoid deficiency. Pathogenic mutations in selenocysteine synthase (SEPSECS) cause neurodevelopmental disorders, but also other factors epistatic to selenoprotein biosynthesis, such as SECIS-binding protein 2 (SECISBP2) and tRNA[Ser]Sec, are known to cause complex disorders. Mutations in the latter 2 genes involve impaired metabolism and action of thyroid hormones, which lead to delayed bone growth and maturation. Mutations in SECISBP2 sometimes affect nervous system development, muscle, inner ear, skin, and immune system function, underlining the significance of selenoproteins for the organism. Mouse models helped to delineate the functions of selenoproteins and explain pathomechanisms. For brevity, this review is focused on human genetic disorders associated with selenoprotein deficiency and only briefly touches on health effects of nutritional selenium deficiency.-Schweizer, U., Fradejas-Villar, N. Why 21? The significance of selenoproteins for human health revealed by inborn errors of metabolism.


Kaniuwatewara (when we get sick): understanding health-seeking behaviours among the Shawi of the Peruvian Amazon.
Detailed qualitative information regarding Indigenous populations' health-seeking behaviours within Peru's plural healthcare system is lacking. Such context-specific information is prerequisite to developing evidence-based health policies and programs intended to improve health outcomes for Indigenous populations. To this end, this study aimed to characterize health-seeking behaviours, factors affecting health-seeking behaviours, and barriers to obtaining healthcare in two Indigenous Shawi communities in Peru. Community-based approaches guided this work, and included 40 semi-structured interviews and a series of informal interviews. Data were analysed thematically, using a constant comparative method; result authenticity and validity were ensured via team debriefing, member checking, and community validation. Shawi health-seeking behaviours were plural, dynamic, and informed by several factors, including illness type, perceived aetiology, perceived severity, and treatment characteristics. Traditional remedies were preferred over professional biomedical healthcare; however, the two systems were viewed as complementary, and professional biomedical healthcare was sought for illnesses for which no traditional remedies existed. Barriers impeding healthcare use included distance to healthcare facilities, costs, language barriers, and cultural insensitivity amongst professional biomedical practitioners. Nevertheless, these barriers were considered within a complex decision-making process, and could be overridden by certain factors including perceived quality or effectiveness of care. These findings emphasize the importance of acknowledging and considering Indigenous culture and beliefs, as well as the existing traditional medical system, within the professional healthcare system. Cultural competency training and formally integrating traditional healthcare into the official healthcare system are promising strategies to increase healthcare service use, and therefore health outcomes.


Chemical Composition and Biological Activity of Allium cepa L. and Allium × cornutum (Clementi ex Visiani 1842) Methanolic Extracts.
Here, we report a comparative study of the phytochemical profile and the biological activity of two onion extracts, namely Allium cepa L. and Allium × cornutum (Clementi ex Visiani 1842), members of the family Amaryllidaceae. The identification of flavonoids and anthocyanins, and their individual quantities, was determined by high-performance liquid chromatography (HPLC). The potency of both extracts to scavenge free radicals was determined by the DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical-scavenging activity and oxygen radical absorbance capacity (ORAC) methods. The DNA protective role was further tested by the single-cell gel electrophoresis (COMET) assay and by Fenton's reagent causing double-strand breaks on the closed circular high copy pUC19 plasmid isolated from Escherichia coli. In the presence of both extracts, a significant decrease in DNA damage was observed, which indicates a protective role of Allium cepa and Allium × cornutum on DNA strand breaks. Additionally, cytotoxicity was tested on glioblastoma and breast cancer cell lines. The results showed that both extracts had antiproliferative effects, but the most prominent decrease in cellular growth was observed in glioblastoma cells.


Nrf-2/Gst-α mediated imatinib resistance through rapid 4-HNE clearance.
The advent of imatinib mesylate (IM) has dramatically improved the outcome of patients with chronic myeloid leukemia, but drug resistance, particularly in advanced stage of disease, portents eventual relapse and progression. To identify the candidate molecule responsible for resistance during IM treatment, an IM-resistant K562 cell line was generated by culturing in gradually increasing dose of IM. The expression of Nrf-2 and its downstream target, Gst-α, were significantly induced in these cells. GST-α, in turn, mediated cell survival by maintaining intracellular low level of 4-HNE. Inhibition of Nrf-2 effectively reduced the expression of Gst-α, resulting in accumulation of 4-HNE and elevated sensitiveness to IM. Moreover, in IM-sensitive K562 cells enforced Gst-α expression strikingly protected cells from the insult of IM. Finally, we also examined the levels of Nrf-2 in clinical bone morrow samples. Nrf-2 and Gst-α were more abundant in bone morrow of CML patients compared with that of healthy donors. In addition, Nrf-2 and Gst-α were further up-regulated in samples of patients with weak response to IM. In conclusion, our study shows that rapid clearance of 4-HNE by Nrf-2/GST may represents a novel molecular basis of IM resistance in CML.


A Novel Procedure for the Immediate Reconstruction of Severely Resorbed Alveolar Sockets for Advanced Periodontal Disease.
Background. Several clinical techniques and a variety of biomaterials have been introduced over the years in an effort to overcome bone remodeling and resorption after tooth extraction. However, the predictability of these procedures in sockets with severely resorbed buccal/lingual plate due to periodontal disease is still unknown. Case Description. A patient with advanced periodontitis underwent extraction of upper right lateral and central incisors. The central incisor exhibited complete buccal bone plate loss and a 9 mm vertical bone deficiency on its palatal side. The alveolar sockets were filled with collagen sponge and covered with a nonresorbable high-density PTFE membrane. Primary closure was not attained and any rigid scaffold material was not used. Histologic analysis provided evidence of new bone formation. At 12 months a cone-beam computed tomographic scan revealed enough bone volume to insert two conventional dental implants in conjunction with minor horizontal bone augmentation procedures. Clinical Implications. This case report would seem to support the potential of the proposed reconstructive approach in changing the morphology of severely resorbed alveolar sockets, minimizing the need for advanced bone regeneration procedures during implant placement.


[Study of diphtheria anatoxins in immunochemical and tissue culture assays].
Equine diphtheria antitoxins from different manufacturers were studied. Their immunochemical interaction with diphtheria toxin, toxoid, and antigens of Corynebacterium diphtheriae in ELISA and immunoblotting assays as well as biological activity in CHO cell assay were compared. The discovered differences between antitoxin samples with stated equal activity in IU/ml point to heterogeneity of antigen composition in preparations used for immunization. Mentioned methods allow to standardize antitoxins basing on their biological activity and immunochemical characteristics.


Characterization of a thermo-alkali-stable laccase from Bacillus subtilis cjp3 and its application in dyes decolorization.
In this work, a novel bacterial strain exhibiting laccase activity was isolated from black liquor and identified as Bacillus subtilis cjp3. The CotA-laccase gene was cloned from strain cjp3 and expressed in Escherichia coli. The purified recombinant laccase has a maximum activity of 7320 U/L, maintaining high stabilities under a wide pH range and high temperature conditions. Nearly no loss of laccase activity was observed even at pH 9.0 after 10 h of incubation. Reactive blue 19, reactive black 5 and indigo carmine could be efficiently decolorized by the purified laccase in the presence of a mediator ABTS. More than 86% of tested dyes were removed in 4 h at pH = 9.0. The recombinant laccase can work well in a broad range of temperatures of 20-80°C(>80% relative activity). These special properties indicated the potential use of the CotA-laccase in treating wastewater containing synthetic dyes.


The AGTR2 rs11091046 (A>C) polymorphism and power athletic status in top-level Brazilian athletes.
The main purpose of this study was to investigate if the rs11091046 (A>C) polymorphism in AGTR2 gene is associated with athletic status in top-level athletes from Brazil. Since the AGTR2 gene is located on the X chromosome, the case-control association study was done separately for women and men. The female cohort was composed of 205 athletes and 241 non-athletes, and the male cohort was composed of 419 athletes and 490 non-athletes. We did not identify an association between the C-allele and the endurance phenotype. However, power athletes had a higher frequency of the A-allele. In women, A/A genotype was overrepresented in international-level power group compared with non-athletes or international-level endurance athletes (23.2% vs. 16.6% or 8.8%, respectively; p < 0.05). In men, the A-allele frequency observed in power athletes or international-level power athletes was statistically different from that observed in non-athletes (51.6% or 57.8% vs. 40.4%; p < 0.009). Furthermore, men sprinters with the A-allele showed significantly faster personal best times for the 100 m than those with the C-allele (10.56 ± 0.32 s vs. 10.93 ± 0.49 s; p < 0.02). In conclusion, it was found that the AGTR2 A-allele is a candidate genetic marker for top-level power athletes.


Synthesis and pharmacological evaluation of pyrrolidin-2-one derivatives as antiarrhythmic, antihypertensive and alpha-adrenolytic agents.
A series of novel arylpiperazines bearing a pyrrolidin-2-one fragment were synthesized and evaluated for their binding affinity for alpha1- and alpha2-adrenoceptors (ARs) as well as their antiarrhythmic and antihypertensive activities. The highest affinity for the alpha1-AR was displayed by 1-{3-[4-(2-chloro-phenyl)-piperazin-1-yl]-propyl}-pyrrolidin-2-one 7, which binds with a pKi = 7.13. The highest affinity for the alpha2-AR was shown by 1-{3-[4-(4-chloro-phenyl)-piperazin-1-yl]-propyl}-pyrrolidin-2-one 18, which binds with a pKi = 7.29. Among the compounds tested, 1-{3-[4-(2-ethoxy-phenyl)-piperazin-1-yl]-propyl}-pyrrolidin-2-one 13 had the highest prophylactic antiarrhythmic activity in epinephrine-induced arrhythmia in anesthetized rats. Its ED50 value was 1.0 mg/kg intravenously (iv). The compounds with a hydroxy group in the 4-position of the phenyl ring or two substituents such as fluorine atoms in the 2 and 4 positions of the phenyl ring significantly decreased systolic and diastolic pressure in normotensive anesthetized rats at a dose of 2.5 mg/ kg iv, and their hypotensive effects lasted for longer than an hour.


High-Throughput Data Reveals Novel Circular RNAs via Competitive Endogenous RNA Networks Associated with Human Intracranial Aneurysms.
BACKGROUND Little is known about epigenetic regulation of intracranial aneurysms (IAs). Circular non-coding RNAs (circRNAs) play crucial roles in cardiovascular diseases, but they have received scant research attention regarding their relationship with IAs. This study aimed to explore new pathological mechanisms of IA through circRNA expression profiles and to provide novel therapeutic strategies. MATERIAL AND METHODS The comprehensive circRNA and mRNA expression profiles were detected by RNA-Seq in human IA walls and superficial temporal arteries (STAs). The RNA-Seq findings were validated by qRT-PCR. GO and KEGG analyses indicated the functions of these circRNAs. A competing endogenous RNA (ceRNA) network was constructed to reveal the circRNA-miRNA-mRNA relationship. Two newly discovered circRNAs were further detected in peripheral blood of IA patients and healthy people to clarify their expression patterns in the periphery. RESULTS Many differentially expressed circRNAs are closely involved in immune/inflammatory response and cell adhesion/adherens junction. The novel circRNAs (hsa_circ_0072309 and hsa_circ_0008433) regulate DDR2 and MMP2, respectively, which are associated with SMC dysfunction and vascular injury through ceRNA. Moreover, we found differential expression of these 2 circRNAs in the peripheral blood of IA patients, and the expression pattern of hsa_circ_0072309 had central and peripheral consistency. CONCLUSIONS To the best of our knowledge, this is the first study to perform circRNA sequencing analysis of IAs. hsa_circ_0072309 and hsa_circ_0008433 are novel and pivotal circRNAs related to IAs. This study provides new insights into therapeutic targets and biomarkers for IA patients.


Mussel-Inspired Caries Management Strategy: Constructing a Tribioactive Tooth Surface with Remineralization, Antibiofilm, and Anti-inflammation Activity.
Dental caries is a common chronic oral disease in humans resulting from tooth demineralization caused by acid production of bacterial plaque, which leads to the destruction of enamel and dentin and oral inflammation. However, it is still a challenge that the function of natural active ingredients in currently available oral care products is not comprehensive, especially the lack of remineralization. Here, inspired by the strong biological adhesion ability of mussels and ancient oral disease plant therapy, a multifunctional strategy is proposed to construct a bioactive tooth surface to treat dental caries. It has been demonstrated that the Turkish gall extract (TGE) can inhibit adhesion of cariogenic bacteria Streptococcus mutans and Actinomyces viscosus and destroy biofilms on the tooth surface. Meanwhile, TGE can reduce the expression of inflammatory factors. Notably, the TGE coating can induce the growth of hydroxyapatite (HAP) crystals in vivo and in vitro, recovering the enamel mechanical properties under normal oral conditions. MD simulations interpreted the adsorption mechanism by which the hydroxyl groups in TGE bind to phosphate group (PO43-) on the tooth surface, attracting calcium ions (Ca2+) as nucleation sites for remineralization. This work underlines the importance of TGE coating in remineralization, antibiofilm, and anti-inflammation activity as a promising strategy for dental caries.


The effects of time frames on self-report.
The degree to which episodic and semantic memory processes contribute to retrospective self-reports have been shown to depend on the length of reporting period. Robinson and Clore (2002) argued that when the amount of accessible detail decreases due to longer reporting periods, an episodic retrieval strategy is abandoned in favor of a semantic retrieval strategy. The current study further examines this shift between retrieval strategies by conceptually replicating the model of Robinson and Clore (2002) for both emotions and symptoms and by attempting to estimate the exact moment of the theorized shift. A sample of 469 adults reported the extent to which they experienced 8 states (excited, happy, calm, sad, anxious, angry, pain, stress) over 12 time frames (right now to in general). A series of curvilinear and piecewise linear multilevel growth models were used to examine the pattern of response times and response levels (i.e., rated intensity on a 1-5 scale) across the different time frames. Replicating previous results, both response times and response levels increased with longer time frames. In contrast to prior work, no consistent evidence was found for a change in response patterns that would suggest a shift in retrieval strategies (i.e., a flattening or decrease of the slope for longer time frames). The relationship between the time frames and response times/levels was similar for emotions and symptoms. Although the current study showed a pronounced effect of time frame on response times and response levels, it did not replicate prior work that suggested a shift from episodic to semantic memory as time frame duration increased. This indicates that even for longer time frames individuals might attempt to retrieve episodic information to provide a response. We suggest that studies relying on self-report should use the same well-defined time frames across all self-reported measures.


Psychosurgery in Britain now.
Between 1979 and 1986 the number of psychosurgical operations carried out in Britain fell from 70 to 15 procedures annually. There are a number of possible reasons for this change of which increased experience with new regimes of psychotropic medication is perhaps the most important. The new Mental Health Act (1983) which brought psychosurgery under the direct jurisdiction of the law was followed by a sudden reduction in the number of patients treated but referals are now increasing. In current psychiatric practice, classification relies largely on description of syndromes, each characterised by a set of core symptoms. Schizophrenia and affective psychoses (endogenous depression, mania and obsessional illness of late onset) are characterised by disturbances of mood, thinking and perception often so profound as to impair the patient's contact with reality. In contrast, neuroses produce symptoms which are quantitatively, rather than qualitatively different from normal experience and psychosurgery has no place in their treatment. Following the introduction of phenothiazines in the early 1950's schizophrenia ceased to be an indication for psychosurgery. For a small group of severely disabled and distressed people suffering from endogenous depressive and obsessional illnesses, when other treatments have failed or ceased to be effective, psychosurgery remains an appropriate treatment. Just over half the patients treated at the Geoffrey Knight Unit are relieved to the extent that they are either free of symptoms or such symptoms that remain do not significantly impair social function. Following operation recovery is slow and progressive and a programme of rehabilitation is usually necessary. Personality which is often severely damaged by the effects of long illness returns towards normal. Neuropsychiatric evaluation has consistently failed to demonstrate adverse cognitive effects. Evaluation and selection of patients for operation should be done by a psychiatrist and neurosurgeon working in partnership. Stereotactic techniques have made it possible to produce precisely located lesions of consistent size, virtually eliminating side effects and reducing the epileptic risk to between two and three percent. The Mental Health Act, contrary to early expectations, has allowed that psychosurgery retains a place in the treatment of a small highly selected group of patients.


ATP6S1 elicits potent humoral responses associated with immune-mediated tumor destruction.
An important goal of cancer immunology is the identification of antigens associated with tumor destruction. Vaccination with irradiated tumor cells engineered to secrete granulocyte/macrophage colony-stimulating factor (GM-CSF) generates potent, specific, and long-lasting antitumor immunity in multiple murine tumor models. A phase I clinical trial of this vaccination strategy in patients with advanced melanoma demonstrated the consistent induction of dense CD4(+) and CD8(+) T lymphocyte and plasma cell infiltrates in distant metastases, resulting in extensive tumor destruction, fibrosis, and edema. Antimelanoma antibody and cytotoxic T cell responses were associated with tumor cell death. To characterize the targets of these responses, we screened an autologous cDNA expression library prepared from a densely infiltrated metastasis with postvaccination sera from a long-term responding patient. High-titer IgG antibodies detected ATP6S1, a putative accessory unit of the vacuolar H(+)-ATPase complex. A longitudinal analysis of this patient revealed an association between the vaccine-induced increase in antibodies to ATP6S1 and tumor destruction. Three additional vaccinated melanoma patients and three metastatic non-small cell lung carcinoma patients vaccinated with autologous GM-CSF-secreting tumor cells similarly showed a correlation between humoral responses to ATP6S1 and tumor destruction. Moreover, a chronic myelogenous leukemia patient who experienced a complete remission after CD4(+) donor lymphocyte infusions also developed high-titer antibodies to ATP6S1. Lastly, vaccination with GM-CSF-secreting B16 melanoma cells stimulated high-titer antibodies to ATPS1 in a murine model. Taken together, these findings demonstrate that potent humoral responses to ATP6S1 are associated with immune-mediated destruction of diverse tumors.


Salivary and gastric secretions in patients with tropical sprue.
Salivary secretions on mechanical stimulation with forced spitting method and on chemical simulation with 10% citric acid and gastric acid secretions on maximal histamine stimulation were studied in 20 adults with tropical sprue and 20 adult control subjects. It was observed that the chemical method provided a better stimulus than the mechanical one in both groups. The salivary flow rates as well as salivary amylase, pH, sodium and potassium were similar in both groups. Tropical sprue patients, however, had significantly lower maximal acid output as compared to normals. It was concluded that, although tropical sprue patients are known to have widespread damage to alimentary tract mucosa, salivary glands do not seem to be involved.


Expression of a divergent expansin gene is fruit-specific and ripening-regulated.
Expansins are proteins that induce extension in isolated plant cell walls in vitro and have been proposed to disrupt noncovalent interactions between hemicellulose and cellulose microfibrils. Because the plant primary cell wall acts as a constraint to cell enlargement, this process may be integral to plant cell expansion, and studies of expansins have focused on their role in growth. We report the identification of an expansin (LeExp1) from tomato that exhibits high levels of mRNA abundance and is specifically expressed in ripening fruit, a developmental period when growth has ceased but when selective disassembly of cell wall components is pronounced. cDNAs closely related to LeExp1 were also identified in ripening melons and strawberries, suggesting that they are a common feature of fruit undergoing rapid softening. Furthermore, the sequence of LeExp1 and its homologs from other ripening fruit define a subclass of expansin genes. Expression of LeExp1 is regulated by ethylene, a hormone known to coordinate and induce ripening in many species. LeExp1 is differentially expressed in the ripening-impaired tomato mutants Nr, rin, and nor, and mRNA abundance appears to be influenced directly by ethylene and by a developmentally modulated transduction pathway. The identification of a ripening-regulated expansin gene in tomato and other fruit suggests that, in addition to their role in facilitating the expansion of plant cells, expansins may also contribute to cell wall disassembly in nongrowing tissues, possibly by enhancing the accessibility of noncovalently bound polymers to endogenous enzymic action.


Optimization Conditions of Ultrasound-Assisted Extraction for Phenolic Compounds and Antioxidant Activity from Rubus alceifolius Poir Leaves.
Rubus alceifolius Poir (R.A. Poir) leaves are rich in phenolic compounds, offering many health benefits due to their incredible antioxidant potential. In this study, conditions for the ultrasound-assisted extraction (UAE) of phenolic compounds and antioxidant activity from R.A. Poir leaves were optimized using response surface methodology (RSM). This methodology assessed the effects of ultrasound power (X1: 100-500 W), extraction temperature (X2: 30-60°C), and extraction time (X3: 5-55 min). The optimized UAE conditions were then compared with conventional extraction methods (Soxhlet extraction: SE and maceration extraction: ME) for extracting total phenolics. A phenolic profile using GC-MS and antioxidant activity (ABTS) was also compared. According to the RSM, the best conditions for UAE to extract the highest total polyphenol content and ABTS radical scavenging activity were 320 W ultrasound power, 40°C extraction temperature, and 35.5 min sonication duration. Under these optimal conditions, the TPC and antioxidant activity reached 16.68 mg GAE/g dm and 21.9 mg TE/g, respectively, closely aligning with the predicted values. The UAE extraction technique proved to be more efficient in extracting phenolics and antioxidant capacity (ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)) radical scavenging activity, and enzyme inhibition) compared to the conventional extraction methods (SE and ME). A GC-MS analysis identified 12 components, including 5 phenolics and 3 flavonoids, which likely contribute to the antioxidant activity. Consequently, the UAE method improved extraction efficiency within a shorter time frame, suggesting that UAE is a promising, efficient, and ecofriendly technology for extracting bioactive compounds from R.A. Poir leaves.


High intercontinental migration rates and population admixture in the sapstain fungus Ophiostoma ips.
Ophiostoma ips is a common fungal associate of various conifer-infesting bark beetles in their native ranges and has been introduced into non-native pine plantations in the Southern Hemisphere. In this study, we used 10 microsatellite markers to investigate the population biology of O. ips in native (Cuba, France, Morocco and USA) and non-native (Australia, Chile and South Africa) areas to characterize host specificity, reproductive behaviour, and the potential origin as well as patterns of spread of the fungus and its insect vectors. The markers resolved a total of 41 alleles and 75 haplotypes. Higher genetic diversity was found in the native populations than in the introduced populations. Based on the origin of the insect vectors, the populations of O. ips in Australia would be expected to reflect a North American origin, and those in Chile and South Africa to reflect a European origin. However, most alleles observed in the native European population were also found in the native North American population; only the allele frequencies among the populations varied. This admixture made it impossible to confirm the origin of the introduced Southern Hemisphere (SH) populations of O. ips. There was also no evidence for specificity of the fungus to particular bark beetle vectors or hosts. Although O. ips is thought to be mainly self-fertilizing, evidence for recombination was found in the four native populations surveyed. The higher genetic diversity in the North American than in the European population suggests that North America could be the possible source region of O. ips.


Case studies from morning report: librarians' role in helping residents find evidence-based clinical information.
In primary care specialties, Morning Report is a traditional vehicle for expanding medical residents' training in diagnosis and treatment. At one academic medical center, residents and faculty in the Department of Family and Community Medicine use case-based teaching, centered around planning and reviewing patient management, to review intriguing cases from patient encounters in the department's hospital service. Seeking to improve the level of evidence-based information exchanged at Morning Report, department leaders invited reference librarians from the health sciences library to attend weekly Morning Report. The librarians saw this as an opportunity not only to improve residents' information-seeking skills, but also to improve librarians' teaching skills and understanding of the needs of users in clinical settings. This paper describes the evolution of librarians' involvement in Morning Report, examples of the kinds of contributions librarians have made in this setting, and changes made in Morning Report sessions to facilitate this activity.


Post-Infarction Ventricular Septal Rupture Complicated by Cardiogenic Shock Requiring Mechanical Circulatory Support as a Bridge to Definitive Therapy During the COVID-19 Pandemic.
Ventricular septal rupture (VSR) is a devastating complication of acute myocardial infarction (MI) and is often associated with cardiogenic shock. Although considered to be very rare in the reperfusion era, recent reports have demonstrated an increased frequency of post-MI VSR cases during the COVID-19 pandemic. Despite advances in surgical repair and management strategies over the past decades, mortality rate has remained high, especially in hemodynamically unstable patients. In VSR patients with cardiogenic shock, the use of mechanical circulatory support (MCS) could be used as a bridge to surgical intervention. We report a patient with VSR complicated by cardiogenic shock secondary to late presenting MI, managed successfully with venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a bridge to surgical intervention.


Photodynamic opening of the blood-brain barrier and pathways of brain clearing.
A new application of the photodynamic treatment (PDT) is presented for the opening of blood-brain barrier (BBB) and the brain clearing activation that is associated with it, including the use of gold nanoparticles as emerging photosensitizer carriers in PDT. The obtained results clearly demonstrate 2 pathways for the brain clearing: (1) using PDT-opening of BBB and intravenous injection of FITC-dextran we showed a clearance of this tracer via the meningeal lymphatic system in the subdural space; (2) using optical coherence tomography and intraparenchymal injection of gold nanorods, we observed their clearance through the exit gate of cerebral spinal fluid from the brain into the deep cervical lymph node, where the gold nanorods were accumulated. These data contribute to a better understanding of the cerebrovascular effects of PDT and shed light on mechanisms, underlying brain clearing after PDT-related opening of BBB, including clearance from nanoparticles as drug carriers.


Antibodies and their receptors: different potential roles in mucosal defense.
Over recent years it has become increasingly apparent that mucosal antibodies are not only restricted to the IgM and IgA isotypes, but that also other isotypes and particularly IgG can be found in significant quantities at some mucosal surfaces, such as in the genital tract. Their role is more complex than traditionally believed with, among other things, the discovery of novel function of mucosal immunoglobulin receptors. A thorough knowledge in the source and function and mucosal immunoglobulins is particularly important in development of vaccines providing mucosal immunity, and also in the current climate of microbicide development, to combat major world health issues such as HIV. We present here a comprehensive review of human antibody mediated mucosal immunity.


Training Physicians in the Digital Health Era: How to Leverage the Residency Elective.
Digital health is an expanding field and is fundamentally changing the ways health care can be delivered to patients. Despite the changing landscape of health care delivery, medical trainees are not routinely exposed to digital health during training. In this viewpoint, we argue that thoughtfully implemented immersive elective internships with digital health organizations, including start-ups, during residency are valuable for residents, residency programs, and digital health companies. This viewpoint represents the opinions of the authors based on their experience as resident physicians working as interns within a start-up health navigation and telehealth company. First, residents were able to apply their expertise beyond the traditional clinical environment, use creativity to solve health care problems, and learn from different disciplines not typically encountered by most physicians in traditional clinical practice. Second, residency programs were able to strengthen their program's educational offerings and better meet the needs of a heterogenous group of residents who are increasingly seeking nontraditional ways to learn more about care delivery transformation. Third, digital health companies were able to expand their clinical team and receive new insights from physicians in training. We believe that immersive elective internships for physicians in training provide opportunities for experiential learning in a fast-paced environment within a field that is rapidly evolving. By creating similar experiences for other resident physicians, residency programs and digital health companies have a key opportunity to influence future physician-leaders and health care innovators.


Peroral endoscopic pyloromyotomy for gastroparesis: a systematic review and meta-analysis.
Background and aim Gastric peroral endoscopic pyloromyotomy (G-POEM) is a new therapeutic option for refractory gastroparesis (GP). A systematic review and meta-analysis was conducted to assess the effectiveness of G-POEM in refractory GP. For the quality of evidence, we used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Methods We performed a literature search using MEDLINE, Embase, Cochrane library, LILACS and the Science citation index for studies related to G-POEM from the inception of its technique through January 2019. We selected studies that analyzed the gastroparesis cardinal symptom index (GCSI) and 4-hour solid-phase gastric emptying scintigraphy (GES) before and after the procedure to verify the efficacy of G-POEM, the main outcome measured. An analysis was performed using RevMan 5.3. Results Ten studies comprising 281 patients were included in this systematic review. The pooled mean difference in GCSI following the procedure was 1.76 (95 % CI: [1.43, 2.08], I 2 = 72 %). We also performed GCSI subgroup analysis by follow-up duration that showed a pooled mean difference of 1.84 (95 % CI: [1.57, 2.12], I 2 = 71 %). The pooled mean difference in GES after the procedure was 26.28 (95 % CI: [19.74, 32.83], I 2 = 87 %), corresponding to a significant drop in percentage values of the gastric retention 4-hour scintigraphy. Conclusion This meta-analysis demonstrates that G-POEM is effective and shows promising outcomes in the clinical response and gastric emptying scintigraphy for gastroparesis. Therefore, it should be considered in the management of refractory gastroparesis.


The histomorphological and stereological assessment of rat dorsal root ganglion tissues after various types of sciatic nerve injury.
Peripheral nerve injuries lead to significant changes in the dorsal root ganglia, where the cell bodies of the damaged axons are located. The sensory neurons and the surrounding satellite cells rearrange the composition of the intracellular organelles to enhance their plasticity for adaptation to changing conditions and response to injury. Meanwhile, satellite cells acquire phagocytic properties and work with macrophages to eliminate degenerated neurons. These structural and functional changes are not identical in all injury types. Understanding the cellular response, which varies according to the type of injury involved, is essential in determining the optimal method of treatment. In this research, we investigated the numerical and morphological changes in primary sensory neurons and satellite cells in the dorsal root ganglion 30 days following chronic compression, crush, and transection injuries using stereology, high-resolution light microscopy, immunohistochemistry, and behavioral analysis techniques. Electron microscopic methods were employed to evaluate fine structural alterations in cells. Stereological evaluations revealed no statistically significant difference in terms of mean sensory neuron numbers (p > 0.05), although a significant decrease was observed in sensory neuron volumes in the transection and crush injury groups (p < 0.05). Active caspase-3 immunopositivity increased in the injury groups compared to the sham group (p < 0.05). While crush injury led to desensitization, chronic compression injury caused thermal hyperalgesia. Macrophage infiltrations were observed in all injury types. Electron microscopic results revealed that the chromatolysis response was triggered in the sensory neuron bodies from the transection injury group. An increase in organelle density was observed in the perikaryon of sensory neurons after crush-type injury. This indicates the presence of a more active regeneration process in crush-type injury than in other types. The effect of chronic compression injury is more devastating than that of crush-type injury, and the edema caused by compression significantly inhibits the regeneration process.


Role of alkali metal promoter in enhancing lateral growth of monolayer transition metal dichalcogenides.
Synthesis of monolayer transition metal dichalcogenides (TMDs) via chemical vapor deposition relies on several factors such as precursor, promoter, substrate, and surface treatment of substrate. Among them, the use of promoter is crucial for obtaining uniform and large-area monolayer TMDs. Although promoters have been speculated to enhance adhesion of precursors to the substrate, their precise role in the growth mechanism has rarely been discussed. Here, we report the role of alkali metal promoter in growing monolayer TMDs. The growth occurred via the formation of sodium metal oxides which prevent the evaporation of metal precursor. Furthermore, the silicon oxide substrate helped to decrease the Gibbs free energy by forming sodium silicon oxide compounds. The resulting sodium metal oxide was anchored within such concavities created by corrosion of silicon oxide. Consequently, the wettability of the precursors to silicon oxide was improved, leading to enhance lateral growth of monolayer TMDs.


Evaluating the Effect of Pravastatin in Early-Onset Fetal Growth Restriction: A Nonrandomized and Historically Controlled Pilot Study.
This study aimed to analyze the effect of pravastatin on angiogenic factors, feto-maternal Doppler findings and pregnancy outcomes in women with early-onset fetal growth restriction (FGR) treated with pravastatin compared with nontreated controls. This was a pilot study conducted between March 2016 and September 2017. Women with single pregnancies and FGR diagnosed at ≤ 28 weeks of gestation were offered 40 mg of pravastatin daily. Doppler progression, soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) values, and pregnancy outcomes were assessed and compared with consecutive historical controls. Controls were matched to treated women for gestational age, maternal characteristics, maternal and obstetric history, Doppler severity classification, and angiogenic factors at diagnosis. The sFlt-1/PlGF was measured in maternal serum at two different times: before pravastatin was started (ratio M0) and during pravastatin treatment (ratio M1). Doppler severity was classified into four categories: normal, mild, moderate, and severe. A total of 38 women were enrolled in this study. No differences were observed in baseline characteristics between groups. However, when compared with the ratio M0, M1 was increased by a median (interquartile range) of 67.0 (-34.8 to 197.3) in the control group but decreased by a median (interquartile range) of -10.1 (-53.1 to -0.07) in the pravastatin treated group (p < 0.001). No significant differences were observed in Doppler progression throughout pregnancy. Median interval from diagnosis to delivery was extended by 16.5 days, the median newborn birthweight was increased from 1,040 to 1,300 g, and the number of women with preeclampsia decreased from 9 (47.4%) to 6 (31.6%) in treated women; however, these trends were not statistically significant. In women with early-onset FGR, treatment with pravastatin 40 mg daily was associated with significant improvement in the angiogenic profile. Additionally, median pregnancy duration and median birthweight increased and the incidence of PE was reduced in treated women. Nevertheless, since this pilot study was underpowered, none of these differences were statistically significant. · Pravastatin improves sFlt-1/PlGF in FGR.. · Pregnancy duration tended to be greater in treated women.. · Birthweight tended to be greater in treated women..


[A method for repeated chromatic duodenal intubation during sanatorium observation].
This method was used in examinations of 313 patients with the digestion organ diseases treated at a health resort. Dysfunction of the biliary tract, often combined with other organic dysfunctions, was detected in 52% of the examinees; in 34.6% of these gallbladder dyskinesia was diagnosed and in 17.4% abnormal secretion and sphincter dyssynergia. The author recommends a wider employment of multipoint duodenal intubation for the examination of patients with gastrointestinal diseases.


Spontaneous electromechanical activity in the rat duodenum in vitro.
Isolated rat duodenum shows spontaneous mechanical and electrical activities. Mechanical activity consists in changes both in endoluminal pressure and in isometric tension. Electrical activity is characterized by slow waves with superimposed bursts. This spontaneous activity is tetrodotoxin (TTX) resistant and therefore it is myogenic in origin. Indeed, TTX pretreatment, even in the presence of atropine and guanethidine, caused an increase in amplitude and in frequency of the electrical and mechanical activities. This finding indicates the presence of tonically active inhibitory intramural non adrenergic, non cholinergic (NANC) nerves. Duodenal longitudinal strips showed a spontaneous mechanical activity resembling that one recorded from isolated segment. Instead, circular strips are quiescent under resting condition and a contractile activity can be detected only after TTX pretreatment suggesting that: i) the circular smooth muscle layer is tonically inhibited by intramural NANC nerves and, ii) the contractions observed in the rat duodenum are due to the activity of the longitudinal one.


Lactic dehydrogenase virus (LDV) infection inhibits allergic eosinophil reaction in the airway.
The effects of interferon (IFN)-gamma induced by virus infection on eosinophil reaction in allergic airway inflammation are not yet clear. We investigated the effects of lactic dehydrogenase virus (LDV) infection, which increases IFN -gamma production with no viral infection or replication in respiratory epithelium, on allergic airway hypersensitivity. LDV infection suppressed antigen-induced eosinophil recruitment into the airway in sensitized mice. IL -5 gene expression in bronchoalveolar lavage (BAL) cells was significantly suppressed in LDV -infected mice compared with uninfected controls. The numbers of total T cells and CD 4+ T cells were significantly reduced in LDV -infected mice compared with controls. The present results suggested that the increase in production of IFN -gamma by viral infection suppresses the eosinophil reaction, and this suppressive effect may be mediated by inhibition of the recruitment of CD 4+ T cell and IL -5 production.


The Trk Potassium Transporter Is Required for RsmB-Mediated Activation of Virulence in the Phytopathogen Pectobacterium wasabiae.
Pectobacterium wasabiae (previously known as Erwinia carotovora) is an important plant pathogen that regulates the production of plant cell wall-degrading enzymes through an N-acyl homoserine lactone-based quorum sensing system and through the GacS/GacA two-component system (also known as ExpS/ExpA). At high cell density, activation of GacS/GacA induces the expression of RsmB, a noncoding RNA that is essential for the activation of virulence in this bacterium. A genetic screen to identify regulators of RsmB revealed that mutants defective in components of a putative Trk potassium transporter (trkH and trkA) had decreased rsmB expression. Further analysis of these mutants showed that changes in potassium concentration influenced rsmB expression and consequent tissue damage in potato tubers and that this regulation required an intact Trk system. Regulation of rsmB expression by potassium via the Trk system occurred even in the absence of the GacS/GacA system, demonstrating that these systems act independently and are both required for full activation of RsmB and for the downstream induction of virulence in potato infection assays. Overall, our results identified potassium as an essential environmental factor regulating the Rsm system, and the consequent induction of virulence, in the plant pathogen P. wasabiae. Crop losses from bacterial diseases caused by pectolytic bacteria are a major problem in agriculture. By studying the regulatory pathways involved in controlling the expression of plant cell wall-degrading enzymes in Pectobacterium wasabiae, we showed that the Trk potassium transport system plays an important role in the regulation of these pathways. The data presented further identify potassium as an important environmental factor in the regulation of virulence in this plant pathogen. We showed that a reduction in virulence can be achieved by increasing the extracellular concentration of potassium. Therefore, this work highlights how elucidation of the mechanisms involved in regulating virulence can lead to the identification of environmental factors that can influence the outcome of infection.


Dissociable Neural Representations of Adversarially Perturbed Images in Convolutional Neural Networks and the Human Brain.
Despite the remarkable similarities between convolutional neural networks (CNN) and the human brain, CNNs still fall behind humans in many visual tasks, indicating that there still exist considerable differences between the two systems. Here, we leverage adversarial noise (AN) and adversarial interference (AI) images to quantify the consistency between neural representations and perceptual outcomes in the two systems. Humans can successfully recognize AI images as the same categories as their corresponding regular images but perceive AN images as meaningless noise. In contrast, CNNs can recognize AN images similar as corresponding regular images but classify AI images into wrong categories with surprisingly high confidence. We use functional magnetic resonance imaging to measure brain activity evoked by regular and adversarial images in the human brain, and compare it to the activity of artificial neurons in a prototypical CNN-AlexNet. In the human brain, we find that the representational similarity between regular and adversarial images largely echoes their perceptual similarity in all early visual areas. In AlexNet, however, the neural representations of adversarial images are inconsistent with network outputs in all intermediate processing layers, providing no neural foundations for the similarities at the perceptual level. Furthermore, we show that voxel-encoding models trained on regular images can successfully generalize to the neural responses to AI images but not AN images. These remarkable differences between the human brain and AlexNet in representation-perception association suggest that future CNNs should emulate both behavior and the internal neural presentations of the human brain.