Developmental changes in IKr and IKs contribute to age-related expression of dofetilide effects on repolarization and proarrhythmia.
Clinical and experimental studies suggest that immature hearts are as or more sensitive than adult hearts to adverse effects of I(Kr) blocking drugs. We hypothesized that age-dependent changes in I(Kr) and I(Ks) contribute to the different repolarization reserves and proarrhythmic effects of I(Kr) blockers in the young and adult heart. Dogs aged 1-150 days and adults were used to study (1) proarrhythmic effects in situ of the I(Kr) blocker dofetilide; (2) dofetilide effects on action potential duration (APD) recorded with microelectrodes from left ventricular (LV) slabs; (3) I(Kr) and I(Ks) in single LV myocytes using whole-cell voltage clamp. In situ, dofetilide-induced proarrhythmia occurred in 40% of adults, 86% of young (20-150 day) dogs and 0% of neonatal (1-19 day) dogs (P<0.05). Isolated tissue experiments showed no transmural gradient for repolarization from neonate through 3 months of age, after which the gradient increased through adulthood. In the presence of dofetilide, the greatest APD prolongation occurred in neonates. Yet, transmural dispersion did not increase in neonates but significantly increased in young and adults. Dofetilide-induced early after depolarization (EAD) incidence was 23% in adults, 59% in young and 8% in neonates (P<0.05). I(Kr) but not I(Ks) was expressed at <30 days, whereas both currents were present in adult myocardium. Our data suggest that a lack of I(Ks) results in a greater dependence on I(Kr) for repolarization in neonates and is associated with exaggerated effects of I(Kr)-blockade on APD. However, APD prolongation alone is insufficient for expression of proarrhythmia, which also requires transmural dispersion of repolarization and EADs. The extent to which APD prolongation, transmural dispersion and EADs are manifested at various ages in the absence and presence of I(Kr) blocking drugs appears to be the ultimate determinant of proarrhythmia.


Prevalence of lumbar spinal stenosis, using the diagnostic support tool, and correlated factors in Japan: a population-based study.
Few studies have examined the prevalence of lumbar spinal stenosis (LSS) in the general population. The purposes of this study were to estimate the prevalence of LSS and to investigate correlated factors for LSS in Japan. A questionnaire survey was performed on 4,400 subjects selected from residents aged 40-79 years in Japan by stratified two-stage random sampling in 2010. The question items consisted of lower-limb symptoms suggestive of LSS, the diagnostic support tool for LSS (LSS-DST), demographic and lifestyle characteristics, comorbidities, the Japanese Perceived Stress Scale (JPSS), and the Mental Health Index 5 (MHI-5). Using the LSS-DST, the presence of LSS was predicted to estimate the prevalence of LSS. Logistic regression analysis was performed to examine the relationship between LSS and correlated factors. Questionnaires were obtained from 2,666 subjects (60.6 %), consisting of 1,264 males (47.4 %). The mean (standard deviation) age was 60.0 (10.9) years. According to the LSS-DST, 153 subjects were regarded as having LSS. The prevalence was estimated to be 5.7 %. When standardizing this value with the age distribution of the Japanese population, it was estimated that 3,650,000 Japanese subjects aged 40-79 years might have LSS using the LSS-DST. Prevalence increased with age and was particularly high in subjects aged 70-79 years, irrespective of gender. As correlated factors, an advanced age (60 years or older), diabetes mellitus, urological disorders, and osteoarthritis/fracture as comorbidities, and depressive symptoms, were associated with LSS. This study elucidated the prevalence of LSS and factors associated with LSS in Japan. This is the first report describing the estimated prevalence of LSS and associated factors using a strictly sampled representative population.


Heart rate and cardiovascular mortality: the Framingham Study.
The relation of resting heart rate on biennial ECG examinations to mortality rates over 30 years of follow-up of the Framingham cohort was examined based on 1876 total deaths and 894 cardiovascular deaths, evolving out of 5070 subjects free of cardiovascular disease at entry into the study. In both sexes, at all ages, all-cause, cardiovascular, and coronary mortality rates increased progressively in relation to antecedent heart rates determined biennially. A more impressive association to cardiovascular disease was observed in men than in women, which was independent of associated cardiovascular risk factors. Case fatality rates following coronary events also increased with antecedent heart rate and the fraction of coronary deaths as sudden death increased strikingly with heart rate in men 35 to 64 years of age. There was also a substantial excess of noncardiovascular deaths at high heart rates, and the proportion of all deaths resulting from cardiovascular disease did not increase with heart rate. The excess cardiovascular deaths with more rapid heart rates were also noted, excluding those with interim overt cardiovascular disease, suggesting an effect independent of preexisting cardiac damage.


How do patients perceive the benefits and risks of peripheral angioplasty? Implications for informed consent.
To explore perceptions of benefits and risks of patients undergoing peripheral angioplasty and to investigate factors that modify them. Two hundred patients undergoing peripheral angioplasty during a 12-month period (134 men and 66 women; mean age, 68.8 years; age range, 37-94 years) were interviewed by one interventional radiologist who asked 18 questions with regard to the risks and benefits of this procedure. The patients were randomly assigned into two groups of 100 patients. The first group answered questions with use of a recognized risk assessment chart. The other group answered without the aid. Depending on the referral pathway, patients received the institution's patient information sheet. Of the 200 patients, 178 (89%) thought that they would have at least a 75% (three in four) chance of benefiting from angioplasty. Eighty patients (40%) thought they would definitely benefit from angioplasty. One hundred one patients (50%) thought the test would be painful. Fifty-four patients (27%) thought there would be no radiation exposure. Forty-one patients (21%) realized there was a chance of needing emergency surgery. Sixty-seven patients (34%) thought the test was easier than anticipated. Previous peripheral angioplasty altered perceptions of benefit (P = .012), but not risk. The use of a risk assessment chart altered perceptions of benefit (P = .049). The use of a patient information sheet predicted (made more realistic) the patients' perceptions of risks (P = .012) and benefits (P = .001). Patients who undergo peripheral angiography tend to underestimate the risks and overestimate the benefits of peripheral angioplasty. The patient information sheet and risk assessment tool used in this study altered patient perceptions of risks and benefits of the procedure and, therefore, aid informed consent.


3D site specific sample preparation and analysis of 3D devices (FinFETs) by atom probe tomography.
With the transition from planar to three-dimensional device architectures such as Fin field-effect-transistors (FinFETs), new metrology approaches are required to meet the needs of semiconductor technology. It is important to characterize the 3D-dopant distributions precisely as their extent, positioning relative to gate edges and absolute concentration determine the device performance in great detail. At present the atom probe has shown its ability to analyze dopant distributions in semiconductor and thin insulating materials with sub-nm 3D-resolution and good dopant sensitivity. However, so far most reports have dealt with planar devices or restricted the measurements to 2D test structures which represent only limited challenges in terms of localization and site specific sample preparation. In this paper we will discuss the methodology to extract the dopant distribution from real 3D-devices such as a 3D-FinFET device, requiring the sample preparation to be carried out at a site specific location with a positioning accuracy ∼50 nm.


Chronic extradural hematomas of the posterior cranial fossa.
During the past 6 years, seven patients with chronic extradural hematomas have been observed at these hospitals. All had a history of occipital injury. Occipital fracture was demonstrated in five cases (by skull x-ray in three cases, at operation in two). The diagnosis was obtained by computed tomography scan in six cases and by iodoventriculography in one. One patient had an associated cerebral lesion, namely, a contralateral temporoparietal contusion. The interval between injury and operation ranged from 27 to 13 days with a mean of 19 days. Only one patient was not operated on, because he was free from symptoms and the hematoma was small. The course was excellent in all seven cases.


Diagnostic pitfalls in osteomyelitis of the odontoid process: case report.
Pyogenic osteomyelitis of the odontoid process is a very rare disease associated with a variety of clinical symptoms, and previous reports have stressed the difficulties inherent in making the diagnosis. The authors present a case of osteomyelitis of the odontoid process with epidural abscess in which magnetic resonance imaging (MRI) was used in the diagnosis, assessment of the extent of concomitant epidural abscess, treatment effect, and long-term follow-up. A 68-year-old male was admitted to our hospital with cervical pain, neck stiffness, and fever. Although the diagnosis was missed at the beginning, the patient was diagnosed with osteomyelitis of the odontoid process with a paravertebral epidural abscess by MRI. The patient became asymptomatic after 3 months of antibiotic therapy. Pyogenic osteomyelitis of the odontoid process is a rare condition requiring a high index of suspicion for diagnosis. MRI examination should be considered in the diagnosis in patients with neck pain combined with fever. Serial MRI during and after antibiotic therapy provided an objective assessment of the healing rate of the lesions.


Total disability days in interprovincial and home-province workers injured in Alberta, Canada: A mixed-methods study with matched-pair analysis of compensation data and participant interviews.
Workers moving between states or provinces to find employment are reported to take longer to return to work after the injury. The Alberta Workers Compensation Board (WCB) identified all workers from four Canadian Atlantic provinces who sustained a work injury in Alberta resulting in greater than 5 total temporary disability days (TTDDays) from January 2015 to June 2017. Each was matched on sex, age, and injury date with an Alberta claimant also with greater than 5 TTDDays. WCB information extracted included employment, injury, cost and place of treatment, and modified work. Cox regression identified factors associated with TTDDays. Semi-structured interviews were also undertaken. Two-hundred forty pairs were identified and 60 interviews completed. Those from the Atlantic provinces had more TTDDays (median 63 days) than Alberta (median 22 days) with an unadjusted hazard ratio (HR) 0.50 (95% confidence interval [CI], 0.42-0.61). When adjusted for all factors, the HR moved closer to unity (HR = 0.62; 95% CI, 0.50-0.76). Total health care costs were the strongest predictor, with modified work, injury type, and claim status also explanatory factors. Among the Atlantic workers, leaving Alberta for treatment was strongly related to a lower likelihood of ending wage replacement (HR = 0.45; 95% CI, 0.32-0.62). Participants in the interview study emphasized the importance of returning to the family after injury and the financial difficulties of maintaining a second home with reduced income after the injury. The higher costs of wage replacement associated with extended time off work may be inherent to the practice of employing out-of-province workers for jobs for which there is a shortage of local labor.


Analysis of causes of velocity spread during initial deceleration in the ascending aorta in children and young adults.
Factors that predict the magnitude of instantaneous systolic velocities within the Doppler sample volume in the ascending aorta have not been elucidated in normal persons. This study determines whether the magnitude of instantaneous velocity spread in the ascending aorta is related to ascending aortic diameter, Reynolds number or other factors. Ascending aortic velocity tracings and diameters were recorded for 77 normal subjects using a 25 degrees off-axis transducer that permitted beam-flow alignment. Percent instantaneous velocity spread at peak modal velocity, which corresponds temporally to initial deceleration, was determined by dividing instantaneous velocity spread by peak modal velocity. Using standard formulations, values were computed in the ascending aorta of each subject for Reynolds number using peak and mean velocity, Womersley's alpha, and critical oscillatory Reynolds number. The highest correlation occurred for percent instantaneous velocity spread and ascending aortic diameter (r = 0.54) (p less than 0.001). The second highest correlation occurred for percent instantaneous velocity spread and critical oscillatory Reynolds number (r = -0.47) (p less than 0.001). A low but significant correlation (r = 0.30) (p less than 0.05) was found between alpha and percent instantaneous velocity spread. No significant correlation was found between percent instantaneous velocity spread and heart rate (r = 0.23), Reynolds number (r = -0.11) or maximal ascending aortic velocity (r = 0.14). This study demonstrates that percent instantaneous velocity spread in the human aorta is most closely related to ascending aortic diameter, an increase of which will cause a higher percent instantaneous velocity spread at initial deceleration.(ABSTRACT TRUNCATED AT 250 WORDS)


Covariance Shrinkage for Dynamic Functional Connectivity.
The tracking of dynamic functional connectivity (dFC) states in resting-state fMRI scans aims to reveal how the brain sequentially processes stimuli and thoughts. Despite the recent advances in statistical methods, estimating the high dimensional dFC states from a small number of available time points remains a challenge. This paper shows that the challenge is reduced by linear covariance shrinkage, a statistical method used for the estimation of large covariance matrices from small number of samples. We present a computationally efficient formulation of our approach that scales dFC analysis up to full resolution resting-state fMRI scans. Experiments on synthetic data demonstrate that our approach produces dFC estimates that are closer to the ground-truth than state-of-the-art estimation approaches. When comparing methods on the rs-fMRI scans of 162 subjects, we found that our approach is better at extracting functional networks and capturing differences in rs-fMRI acquisition and diagnosis.


Decarbonizing real estate portfolios considering optimal retrofit investment and policy conditions to 2050.
Retrofitting existing buildings is crucial for achieving Net Zero emissions. Institutional real estate owners play a key role because of their significant ownership, especially of large buildings. We utilize an interdisciplinary approach to evaluate cost-optimal decarbonization conditions for three Swiss real estate portfolios owned by a global institutional investor. We leverage a bottom-up optimization framework for building asset retrofitting, scaled to the portfolio-level, to study the effect of policy scenarios and implementations. Results indicate that achieving Net Zero necessitates significant investments, largely through thermal energy efficiency measures and low-CO2 energy systems, as early as possible to avoid locked-in emissions. Owners will be challenged to smooth long-term capital investments, pointing to a potential liquidity crisis. Consequently, hard-to-decarbonize assets are unable to reach regulatory benchmarks largely because of lingering embodied emissions. To lower transition risk, we recommend that policymakers move toward average CO2 benchmarks at the real estate portfolio-level, emulating automotive fleets.


Composites of cellulose nanocrystals in combination with either cellulose nanofibril or carboxymethylcellulose as functional packaging films.
Cellulose nanocrystals (CNC) were mixed with either cellulose nanofibril (CNF) or carboxymethylcellulose (CMC) in variable proportions (0/100, 20/80, 40/60, 50/50, 60/40, 80/20 and 100/0) to obtain cast films with acceptable barrier and mechanical properties as replacements for food packaging plastics. Both CNF and CMC improved tensile strength, elongation, UV opacity, air resistance, hydrophobicity (WCA-water contact angle), water vapor transmission rate (WVTR) and oxygen impermeability in pure CNC. WVTR and oxygen permeability were strongly dependent on relative humidity (RH). Interestingly, the greatest effect on WVTR was observed at RH = 90% in films containing CMC in proportions above 60%. CMC- and CNF-containing films had oxygen impermeability up to an RH level of 80% and 60%, respectively. The previous effects were confirmed by food packaging simulation tests, where CMC-containing films proved the best performers. The composite films studied were biodegradable-which constitutes a major environmental related advantage-to an extent proportional to their content in CMC or CNF.


CE: Integrative Care: The Evolving Landscape in American Hospitals.
As the use of complementary and alternative medicine-CAM-has surged in popularity in the United States, many hospitals have begun integrating complementary services and therapies to augment conventional medical care. In this article, the first in a five-part series that will examine various aspects of holistic nursing and forms of complementary care currently in use, the authors provide an overview of some of the integrative care initiatives being introduced in hospitals throughout the United States and report on findings from a survey they conducted of nursing leaders at hospitals that have implemented integrative care programs.


Evaluation of Potential Neuroprotective Effects of Vanillin Against MPP+/MPTP-Induced Dysregulation of Dopaminergic Regulatory Mechanisms in SH-SY5Y Cells and a Mouse Model of Parkinson's Disease.
Parkinson's disease (PD) is a progressive neurodegenerative condition. The pathogenesis of PD is still unknown, and drugs available for PD treatment either have side effects or have suboptimal efficacy. Flavonoids are potent antioxidants having little toxicity with extended use, suggesting they might hold promising therapeutic potential against PD. Vanillin (Van) is a phenolic compound that has exhibited neuroprotective properties in various neurological disorders, including PD. However, the neuroprotective role of Van in PD and its underlying mechanisms are scarce and therefore need more exploration. Here, we evaluated the neuroprotective potential of Van and its associated mechanisms against MPP+/MPTP-induced neuronal loss in differentiated human neuroblastoma (SH-SY5Y) cells and the mouse model of PD. In the present study, Van treatment significantly enhanced the cell viability and alleviated oxidative stress, mitochondrial membrane potential, and apoptosis in MPP+-intoxicated SH-SY5Y cells. Moreover, Van significantly ameliorated the MPP+-induced dysregulations in protein expression of tyrosine hydroxylase (TH) and mRNA expressions of GSK-3β, PARP1, p53, Bcl-2, Bax, and Caspase-3 genes in SH-SY5Y cells. Similar to our in vitro results, Van significantly alleviated MPTP-induced neurobehavioral dysregulations, oxidative stress, aberrant TH protein expressions, and immunoreactivity in SNpc of mice brains. Treatment of Van also prevented MPTP-mediated loss of TH-positive intrinsic dopaminergic neurons to SNpc and TH-fibers projecting to the striatum of mice. Thus, Van exhibited promising neuroprotective properties in the current study against MPP+/MPTP-intoxicated SH-SY5Y cells and mice, indicating its potential therapeutic properties against PD pathology.


Genetic vaccination for production of DNA-designed antibodies specific to Hepadnavirus envelope proteins.
We propose a method of avian antibodies production based on DNA immunization of laying ducks with a plasmid encoding specified antigen, followed by egg collection and purification of egg yolk immunoglobulins (IgY). We have validated this approach in the Duck hepatitis B virus (DHBV) model. We report here that following immunization of female ducks with plasmids encoding DHBV envelope proteins, large amounts (at least 50 mg/egg) of specific antibodies can be obtained from eggs of these ducks. Interestingly, the comparison of different plasmid constructs showed the important differences in their efficacy of specific IgY antibodies induction in the sera and eggs of immunized ducks.


Tolypocladium cylindrosporum (Deuteromycotina: Moniliales), a fungal pathogen of the mosquito Aedes australis. II. Methods of spore propagation and storage.
A laboratory fermenter was used to produce up to 12 l of infective Tolypocladium cylindrosporum blastoconidia in Sabouraud dextrose broth. Two media derived from coconuts were also demonstrated as suitable alternative systems for the production of viable blastoconidia. T. cylindrosporum conidia when dried at 37 degrees C and stored at 4 degrees C retained their viability for 10 months, but, when stored at 25 degrees C, the conidia lost viability after 2 months and blastoconidia did not survive the drying process. Distilled water suspensions were a simple, economic technique for the long-term storage of spores at both 4 and 25 degrees C. The adsorption of conidia onto silica gel crystals was a very suitable technique for the storage of stock culture material at 4 degrees C. The virulence, production and storage capabilities of both spore types were examined.


Prevention of spontaneous leukemia in mice by oncornavirus immunization.
C57L, NIH, and SWR mice were immunized with inactivated Gross leukemia virus (GLV) and then mated with AKR males. Their F1 offspring were then immunized with the murine sarcoma virus pseudotype of GLV, MSV(GLV). The concentrations of infectious ecotropic AKR virus in tail extracts of immunized mice were 100- to 1,000-fold lower than in non-immunized controls when tested at 30--40 days of age. Although viral titers increased slightly with time, the titers remained at least one log10 lower in the immunized mice than in non-immunized F1 control mice at all times tested. The reduction in the level of expression of endogenous ecotropic virus showed a highly significant positive correlation with the reduction in incidence of spontaneous leukemia in these mice. These data thus show that successful immunoprevention of leukemia in mice can be achieved with viral vaccines.


Brucella suis S2, brucella melitensis Rev. 1 and Brucella abortus S19 living vaccines: residual virulence and immunity induced against three Brucella species challenge strains in mice.
Live attenuated Brucella suis S2 vaccine was compared to living vaccines B. abortus S19 and B. melitensis Rev. 1 in mice. Residual virulence was estimated by ability to multiply and persist in spleen and lymph nodes. Immunogenicity was estimated by spleen counts of control and vaccinated mice challenged either with the reference B. abortus 544 strain or with virulent B. melitensis H38 and B. suis 1330 strains. S2 vaccine had lower residual virulence; expressed as 50% recovery time, persistence was 4.3 weeks, compared to 7.1 and 9.0 weeks for S19 and Rev. 1 vaccines. Immunity induced by the three vaccines was similar 45 days after vaccination. At 150 days, immunity by S19 and Rev.1 was still similar against the three challenge strains. In contrast, immunity induced by S2 had declined against the B. melitensis strain. Thus, a recall vaccination may be required for vaccination of sheep to confer a long-lasting immunity.


Vessel density in endometrium of women with and without intrauterine contraceptive devices: a morphometric evaluation.
Increased vascularity was found in the endometrial functionalis in uteri of women wearing intrauterine contraceptive devices (IUDs) as compared to uteri of women without IUDs (control subjects). Vessel concentration was highest in endometrial tissue adjacent to that tissue which was depressed by the IUD. In control tissues there was a significant variation in vascularity according to geographic location in the following order of magnitude: fundus greater than corpus greater than cornua greater than isthmus. No significant variation was found, however, among different phases of the ovarian cycle in either control or IUD cases. Increased endometrial vascularity could be a reaction to vessel damage caused by the IUD and for several reasons may contribute to IUD-induced endometrial bleeding.


Design of an optically stable pH sensor based on immobilization of Giemsa on triacetylcellulose membrane.
In this work a simple, inexpensive, and sensitive optical sensor based on triacetylcellulose membrane as solid support was developed by using immobilization of Giemsa indicator for pH measurement. In this method, the influence variables on the membrane performance including pH concentration of indicator, response time, ionic strength, and reversibility were investigated. At optimum values of all variables the response of optical pH sensor is linear in the pH range of 3.0-12.0. This optical sensor was produced through simultaneous binding of the Giemsa on the activated triacetylcellulose membrane which responded to the pH changes in a broader linear range within less than 2.0 min and suitable reproducibility (RSD<5%). Stability results showed that this sensor was stable after 6 months of storage in the water/ethanol (50:50, v/v) solution without any measurable divergence in response properties (less than 5% RSD).


Systemic and local immune responses to enhanced-potency inactivated poliovirus vaccine in premature and term infants.
Serum neutralizing, nasopharyngeal neutralizing, and IgA antibodies to polioviruses 1, 2, and 3 were detected in preterm and term infants who had received three doses of an enhanced-potency inactivated poliovirus vaccine at 2, 4, and 12 months of age. After the third dose of this vaccine, 95% or more of the infants tested had detectable serum neutralizing antibodies to polioviruses types 1, 2, and 3. Nasopharyngeal neutralizing and IgA antibodies were detected in 43% to 91% of the infants. The peak geometric mean titers of serum and nasopharyngeal antibodies against polioviruses types 1, 2, and 3 were similar for both groups. These preliminary data indicate that preterm infants are capable of mounting systemic and local immune responses to enhanced-potency inactivated poliovirus vaccine that are comparable to those made by term infants.


Nitric oxide inhibits tissue factor synthesis, expression and activity in human monocytes by prior formation of peroxynitrite.
Nitric oxide (NO) has antithrombotic properties by regulating platelet function, whereas direct effects on plasmatic coagulation are rarely described. In sepsis and inflammation, when synthesis of NO, oxygen radicals and toxic metabolites is crucial, the expression of tissue factor (TF) on monocytes stimulated by lipopolysaccharides (LPS) induces intravascular coagulation. This study was performed to examine the influence of NO and the NO-dependent metabolite peroxynitrite on LPS-induced TF expression and activity in human monocytes. Experimental study. Laboratory for cell biology. Human peripheral blood mononuclear cells were isolated from buffy coats by gradient centrifugation. The NO-releasing compounds SIN1 and NOC18 were used under different conditions. TF antigen was assayed by flow cytometry, and its activity by a clotting assay. TF-mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR-ELISA). Whereas NOC18, a pure NO donor, had no effect, SIN1, releasing both NO and superoxide (O2-), reduced TF expression and activity in a dose- and time-dependent manner; superoxide dismutase (SOD) reversed the SIN1-mediated effect. Adding the O2(-)-deliberating system hypoxanthin/xanthin oxidase (which had no significant effect per se) to NOC18, or using the NO and O2- reaction product peroxynitrite resulted in a reduction of TF expression. RT-PCR-ELISA indicated upregulation of TF-mRNA by SIN1 with a peak at 500 microM; higher doses had less effect. These data demonstrate an influence of NO on LPS-induced TF expression in monocytes by prior formation of peroxynitrite; furthermore, the balance between NO and O2- seems to play a crucial role.


Immunogenicity and safety of an AS03(A)-adjuvanted H5N1 influenza vaccine in a Taiwanese population.
A multicenter study (NCT00449670) conducted across Taiwan, Singapore, Hong Kong and Thailand evaluated the safety and manufacturing consistency of four formulations of an AS03(A)-adjuvanted H5N1 vaccine in terms of immune response against the vaccine-homologous strain (A/Vietnam/1194/2004). This manuscript presents data from the Taiwanese population. A total of 400 individuals, aged 18-60 years, were randomized into six groups (2:2:2:2:1:1 ratio) to receive two doses (21 days apart) of one of the four adjuvanted formulations (H5N1-AS03(A)-groups) or one of the two nonadjuvanted formulations (H5N1-DIL-groups). Blood samples collected before vaccination (Day 0) and 21 days after each vaccine dose were analyzed using hemagglutination inhibition (HI) assay. Adverse events were recorded. All four AS03(A)-adjuvanted formulations induced comparable immune responses against the A/Vietnam/1194/2004 strain; following the second dose, immune response in terms of HI antibodies was higher in the H5N1-AS03(A)-groups {seroprotection rate=91.6% [95% confidence interval (CI): 87.9-94.4]; geometric mean titer (GMT)=177.6 (95% CI: 153.2-206.0)} compared with the H5N1-DIL-groups [seroprotection rates=5.0% (95% CI: 1.4-12.3); GMT=6.3 (95% CI: 5.4-7.4)]. Immune response against the heterologous A/Indonesia/05/2005 strain was also stronger in the H5N1-AS03(A)-groups [seroprotection rate=45.6% (95% CI: 40.0-51.4); GMT=20.5 (95% CI: 17.8-23.7)] compared with the H5N1-DIL groups [seroprotection rate=0.0% (95% CI: 0.0-4.5); GMT=5.0 (95% CI: 5.0-5.0)]. The overall reactogenicity profile of the adjuvanted formulations was clinically acceptable. The AS03(A)-adjuvanted H5N1 influenza vaccine formulations induced stronger immune response against the vaccine-homologous and heterologous strains than the nonadjuvanted formulations. The AS03(A)-adjuvanted H5N1 vaccine demonstrated a good immunogenicity and an acceptable safety profile in the Taiwanese population.


A comparison of transketolase assay and transketolase and lactate dehydrogenase activity levels in whole blood and red cell hemolysates and in leukocytes.
1. A study was made of transketolase activity in red and white blood cells and of conditions for assay for transketolase activity and for assessment of the "TPP effect" in human and rat blood. 2. The ratio of the transketolase activity in white cells to that in red cells varied between 23 and 93. 3. Red cells or white cells can both be used for assessment of transketolase activity and the "TPP effect", but the best source for evaluation of transketolase activity and the percent change on addition of thiamin diphosphate appears to be whole blood.


Diagnosis and treatment of uncommon wounds.
Uncommon wounds present unique challenges to plastic surgeons and other wound care providers in regard to their presentation, recognition, and ultimate treatment. This article presents an overview of diagnosis and actual case treatment of unusual wounds, a review of the literature, and case studies of interest. A systematic approach to diagnosis; careful review of history; and full understanding of topical, systemic, and surgical therapies is paramount to proper treatment recommendations, appropriate patient management, and successful wound-healing outcomes. The ability to identify and treat wounds caused by an unusual etiology or presentation is an important skill.


Death education in selected medical schools as related to physicians' attitudes and reactions toward dying patients.
These data obtained from 1093 recent graduates of five selected medical schools suggest that the physician who chose to take a medical school course on relating to dying patients tends to actually relate better to the dying patient than does the physician who did not take such a course.


Prevention of vasculitis and vascular pain by side route administration of vinorelbine: A case report.
A 49-year-old female with non-small-cell lung cancer was placed on adjuvant chemotherapy with vinorelbine (25 mg/m2: Day 1.8) and cisplatin (80 mg/m2: Day 1). The simultaneous intravenous infusion of vinorelbine from the side route and 500 mL of saline from the main route successfully prevented vasculitis and vascular pain.


The HOP1 gene encodes a meiosis-specific component of yeast chromosomes.
The HOP1 gene in Saccharomyces cerevisiae is important for meiotic chromosomal pairing, because hop1 diploids fail to form synaptonemal complex during meiosis and are defective in crossing over between, but not within, chromosomes. We demonstrate here that the HOP1 gene is transcriptionally regulated during sporulation and that the HOP1 protein is situated along the lengths of meiotic chromosomes. Furthermore, the HOP1 protein contains a Cys2/Cys2 zinc finger motif. A mutation within this motif that changes a cysteine to serine results in the hop1 phenotype, consistent with the possibility that the HOP1 gene product acts in chromosome synapsis by directly interacting with DNA. These observations demonstrate that HOP1 encodes a component of meiotic chromosomes, perhaps serving as a constituent of the synaptonemal complex.


Construction of a Mutant in Prevotella melaninogenica Using the Conjugation Transfer Method with Escherichia coli.
Prevotella melaninogenica is a bacterium that is resident in the oral cavity and upper respiratory tract and is associated with periodontal disease and aspiration pneumonia. Prevotella mutants are difficult to produce and only few reports have been reported. We examined several methods and many strains and succeeded in producing mutants in Prevotella melaninogenica GAI 07411. In this chapter, we will describe how to create a mutation of a target gene by carrying out conjugation transfer using Escherichia coli S17-1 as a donor and introducing a plasmid into P. melaninogenica.


Agreement of specific IgE and skin prick test in an unselected cohort of two-year-old children.
The objective of this study was to evaluate the agreement between specific IgE (sIgE) and skin prick test (SPT), and the possible association between total IgE concentration and allergy-related disorders, when performed in an unselected cohort of 353 two-year olds. Median total IgE was within the reference value for two-year-old children regardless of the presence or absence of allergy-related disorders. 18.7% of the children had one or more positive reactions to SPT and/or sIgE in a panel of 12 allergens. Agreement between SPT and sIgE was variable, being best for peanut and poorest for milk. In young children total IgE is of limited value when evaluating allergy-related disorder. The lack of agreement among the positive tests of the sIgE and SPT for some allergens imply that these tests should not be used interchangeably, and both tests should probably be used complementarily when diagnosing atopic sensitization in small children.


Up-regulation of Smurf1 after spinal cord injury in adult rats.
Smad ubiquitination regulatory factor 1 (Smurf1) is one of members of the Hect family of proteins, which also includes the ubiquitin E3-type ligases Nedd3 and E6-AP. As an E3 ligase, Smurf1 selectively interacts with receptor-regulated Smads to trigger their ubiquitination and degradation. Recently, a report indicates that Smurf1 can inhibit apoptosis by regulating p53 negatively, which depends on the effect of Smurf1 stabilizing the MDM2-MDMX complex. However, the roles of Smurf1 in central nervous system injury remain to be unknown. In our study, we finished acute spinal cord injury (SCI) in adult rats to research the protein expression and cellular localization of Smurf1 in spinal cord. Western blot analysis showed that Smurf1 was low expressed in normal spinal cord. It was increased at 6 h after SCI, peaked at 1 day, remained for 3 days, and then declined gradually during the following days. Immunohistochemistry further confirmed that Smurf1 immunoactivity was expressed at low levels in the gray matter and white matter in normal condition and increased after SCI. Double immunofluorescence staining showed that Smurf1 was co-expressed NeuN (neuronal marker), CNPase (oligodendroglial marker), and active caspase-3 at 1 day post-injury. Additionally, p53 and MDM2 levels were up-regulated after SCI consistently. All these findings suggest that Smurf1 might be involved in the pathophysiology of spinal cord after SCI.


Profiling the jasmonic acid responses by nuclear magnetic resonance-based metabolomics.
Metabolomics based on nuclear magnetic resonance (NMR) can be used to monitor the metabolite response of plants to jasmonic acid. Metabolomics experiments consist of three important steps: sample preparation, NMR analysis, and data mining. In sample preparation, a very critical factor is the selection of a proper solvent for plant material extraction because the presence of metabolites will vary according to the solvent used. For NMR analysis, an intermediate-to-polar solvent, such as a mixture of methanol and water, is a good choice. In general, (1)H-NMR spectroscopy is the standard method for metabolite profiling, whereas two-dimensional spectroscopy provides more detailed information on the metabolites. Finally, various chemometric methods can be used for data mining. Here, we describe all three steps of metabolomic analysis by means of NMR spectroscopy.


Evidence of recombination and positive selection in cetacean papillomaviruses.
Papillomaviruses (PVs) are small DNA viruses that have been associated with increased epithelial proliferation. Over one hundred PV types have been identified in humans; however, only three have been identified in bottlenose dolphins (Tursiops truncatus) to date. Using rolling circle amplification and degenerate PCR, we identified four novel PV genomes of bottlenose dolphins. TtPV4, TtPV5 and TtPV6 were identified in genital lesions while TtPV7 was identified in normal genital mucosa. Bayesian analysis of the full-length L1 genes found that TtPV4 and TtPV7 group within the Upsilonpapillomavirus genus while TtPV5 and TtPV6 group with Omikronpapillomavirus. However, analysis of the E1 gene did not distinguish these genera, implying that these genes may not share a common history, consistent with recombination. Recombination analyses identified several probable events. Signals of positive selection were found mostly in the E1 and E2 genes. Recombination and diversifying selection pressures constitute important driving forces of cetacean PV evolution.


Investigation of coagulation and serum biochemistry profiles in dairy cattle with different degrees of fatty liver.
Das Ziel der vorliegenden Arbeit war es, Blutgerinnungsprofile, biochemische und hämatologische Parameter bei Kühen mit unterschiedlichen Schweregraden der Leberverfettung zu untersuchen. Der Schweregrad der Leberverfettung wurde mittels histologischer Untersuchung von Leberbiopsien ermittelt. Fünfzig Kühe, die wegen linksseitiger Labmagenverlagerung überwiesen wurden und verschiedene Schweregrade einer Leberverfettung aufwiesen wurden untersucht. Ein Gerinnungsprofil einschliesslich Prothrombinzeit, Thrombinzeit, partieller Thromboplastinzeit und Fibrinogen konnte nicht zwischen Kühen mit oder ohne Leberverfettung unterscheiden. Die Aspartat Aminotransferase (ASAT) war der einzige Parameter, der bei Kühen mit Leberverfettung signifikant verändert war, jedoch nicht verschiedene Schweregrade der Leberverfettung unterscheiden konnte. Die Ergebnisse zeigen, dass Gerinnungsfaktoren durch eine Leberverfettung nicht beeinflusst werden. Die routinemässig gemessenen biochemischen Parameter sind nicht geeignet um den Schweregrad einer Leberverfettung bestimmen zu können.


A modelling study on transmission of the central oscillator in tremor by a motor neuron pool.
In spite of decades of intense research, pathological tremors still constitute unknown disorders. This study addresses, based on a multi-scale model, the behavior of an entire pool of motor neurons in tremor, under the hypothesis that tremor is an oscillation of central origin commonly projected to all motor neurons that innervate a muscle. Our results show that under such conditions both paired discharges and enhanced motor neuron synchronization, two of the characteristic landmarks of tremor, emerge. Moreover, coherence and correlation analyses suggest that the central tremor oscillator is transmitted linearly by the motor neuron pool given that a small set (7 or 8) of motor neurons are sampled.


Structure Analysis of Proteins and Peptides by Difference Circular Dichroism Spectroscopy.
Difference circular dichroism (CD) spectroscopy was used here to characterize changes in structure of flexible peptides upon altering their environments. Environmental changes were introduced by binding to a large target structure, temperature shift (or concentration increase) or so-called membrane-mimicking solvents. The first case involved binding of a largely disordered peptide to its target structure associated with chromatin remodeling, leading to a transition into a highly helical structure. The second example was a short 8HD (His-Asp) repeat peptide that can bind metal ions. Both Zn and Ni at μM concentrations resulted in different type of changes in secondary structure, suggesting that these metal ions provide different environments for the peptide to assume unique secondary structures. The third case is related to a few short neuroprotective peptides that were largely disordered in aqueous solution. Increased temperature resulted in induction of significant, though small, β-sheet structures. Last example was the induction of non-helical structures for short neuroprotective peptides by membrane-mimicking solvents, including trifluoroethanol, dodecylphosphocholine and sodium dodecylsulfate. While these agents are known to induce α-helix, none of the neuropeptides underwent transition to a typical helical structure. However, trifluoroethanol did induce α-helix for the first peptide involved in chromatin remodeling described above in the first example.


Pregnancy in the underweight woman. Course, outcome, and growth patterns of the infant.
The obstetric performance and pregnancy outcome of 354 underweight patients were compared with matched control subjects of normal weight. The growth patterns of their infants were also compared. The underweight women had significantly higher rates of cardiac/respiratory problems, anemia, PROM, and endometritis but were less prone to develop pre-eclampsia. Prematurity and low Apgar scores were significantly more frequent in the infants of underweight women. There was no difference in the frequency of IUGR and in perinatal mortality rates. The mean birth weight of the infants of underweight women was 231 grams less than that of infants of control subjects. Underweight women, particularly if they were anemic, had a higher incidence of low-birth-weight infants despite adequate weight gain. AGA infants of underweight women were more likely to be below the twenty-fifth percentile for weight correlated with length by 12 months of age.


Fusion of the HSV-1 tegument protein vp22 to cytosine deaminase confers enhanced bystander effect and increased therapeutic benefit.
A major limitation in cancer gene therapy, specifically gene-dependent enzyme prodrug therapy (GDEPT), is inefficient gene delivery and expression. The suicide gene cytosine deaminase (CD) and its substrate, 5-fluorocytosine (5-FC), have been extensively explored due to the inherent 'bystander' effect achieved through diffusion of the toxic metabolite 5-fluorouracil (5-FU). In this study, we aimed to enhance this 'bystander' effect by fusing the Saccharomyces cerevisiae CD to the HSV-1 tegument protein vp22, a novel translocating protein. Two constructs were created: one with vp22 fused to CD (vp22CD) and a second wherein a truncated vp22, lacking the necessary residues for trafficking, fused to CD (delvp22CD). The generated 9L stable lines exhibited similar growth rates, enzyme expression, CD activity, and sensitivity to 5-FC and 5-FU. However, mixed population colony formation assays demonstrated greater bystander effect with the vp22CD fusion as compared to delvp22CD. This enhancement was maintained in vivo where 9L tumors expressing 20 or 50% vp22CD exhibited increased growth delay compared to the respective delvp22CD tumors. Moreover, adenoviral transduction of established wild-type 9L tumors showed increased growth delay with vp22CD (Ad-EF_vp22CD) as compared to equivalent CD (Ad-EF_CD) transduced tumors. Finally, confirming the increased efficacy, (19)F magnetic resonance spectroscopy (MRS) of vp22CD-expressing tumors demonstrated increased 5-FU levels as compared to tumors expressing the nontranslocating CD. These results together demonstrated that fusion of vp22 to CD resulted in CD translocation, which in turn amplified conversion of 5-FC to 5-FU in vivo and enhanced the therapeutic benefit of this GDEPT strategy.


Age and sex hormones modulate left ventricle regional response to angiotensin II in male and female mice.
Age, hypertension, and the female sex are among the risk factors in the development of heart failure with preserved ejection fraction. We studied by standard and speckle-tracking echocardiography (STE), the response of the left ventricle (LV) to aging and angiotensin II continuous infusion (ANG II; 1.5 mg/kg/day for 28 days) in 2- and 12-mo-old male and female C57Bl6/J mice. We also investigated the effects of the loss of sex steroids by gonadectomy (GDX). To do so, we used STE data from 48 points or regions of interest (ROIs) around the LV endocardium from B-mode images and generated profiles of maximal strain, strain rate (SR), and reverse SR for each experimental group of mice. In young mice, LV strain, strain rate (SR), and reverse SR profile levels were higher in females than in males. Aging was characterized by concentric LV remodeling and a decrease of strain, SR, and reverse SR. GDX at 6 wk of age slowed normal cardiac growth in male mice. In females, GDX reduced LV strain, SR, and reverse SR but did not influence cardiac growth. ANG II caused similar levels of hypertrophy in young and older mice. In young mice, ANG II had little effect on STE parameters, whereas in older animals, strain, SR, and reverse SR were reduced, mainly for the LV posterior wall. In older GDX mice, hypertrophic response to ANG II was decreased compared with intact animals. Generating detailed STE profile for the LV wall can help detect differences linked to sex, age, or a stressor better than global strain measurements.NEW & NOTEWORTHY We propose a new method for the study of regional strain data by analyzing individually the software-generated 48 regions of interest (ROI) from an LV wall tracing in B-mode. This helps obtain a more comprehensive profile of strain data. Using these new tools, we studied in mice how sex, sex hormones, age, or a pathological stress influenced strain parameters. We show that for similar cardiac hypertrophy, regional strain shows important differences related to sex, sex hormones, and age.


Intranuclear filaments in a soft tissue sarcoma.
Intranuclear filaments aggregating into rodlike structures were found in cells of an undifferentiated soft tissue sarcoma in a child. Similar structures have been uncommonly described in human neoplasms, and uncertainties exist concerning the nature of the inclusion bearing cells in previous reports. The filaments were found to be resistant to mild trypsin digestion. Review of the pertinent literature indicates that these structures may represent the structural manifestation of a highly specialized functional state, rather than a degenerative phenomenon or an artifact. A certain selectivity of occurrence has also been noted. It is therefore plausible to speculate that intranuclear filaments may eventually constitute a morphologic criterion of interest for new tumor classifications.


Collo-diaphysial angle of the femur in East African subjects.
The collo-diaphysial angle of East African subjects was investigated using 860 unilateral anteroposterior radiographs of the hip from 400 Ugandan and 460 Kenyan subjects, aged between 18 and 65 years using the standard techniques of Singh and Singh (1975). The angle ranged from 125-144 degrees with a mean of 133.3 degrees and a standard deviation (SD) of 5.3 degrees for Ugandan males; and 119-139 degrees, mean 123.4 degrees, SD 5.8 degrees for Ugandan females. The Kenyan values were 125-159 degrees, mean 140.2 degrees, SD 6.2 degrees for males; and 117-134 degrees, mean 125.7 degrees, SD 5.1 degrees for females, respectively. There were significant differences between males and females in both groups as well as between Ugandan and Kenyan males (P < 0.05). Using the demarking points method, only 19.0% of male Ugandans, 41.7% of male Kenyans, and 18.2% of female Kenyans could be identified by gender. This study documents for the first time the collo-diaphysial angle of East African subjects and has further confirmed that the angle is wider in men than women.


Grip surface affects maximum pinch force.
The aim of this study was to investigate whether people change their isometric pinch grip generation depending on the surface they gripped. Specifically, the effect of grip surface friction condition on (a) maximum force produced in the direction normal to the contact surface, (b) fluctuation of normal force, and (c) the digit force's angular deviation from the direction normal to the grip surface was quantified. Isometric pinch grip has been traditionally thought to be independent from the friction condition between the finger and gripped surface, which may be questionable. For this study, 12 healthy participants performed maximum isometric pinch grip exertion on high-friction rubber and low-friction paper surfaces. Maximum normal force, normal force variance,and digit force's angular deviation from the normal direction were quantified. Pinch grip on the high-friction rubber surface was associated with 10% greater maximum normal force and 50% reduced normal force variance, compared with the low-friction paper surface (p < .05). Digit force's angular deviation was not significantly different between the two surface friction conditions. The data support that people do change their pinch grip generation (maximum normal force and normal force variance) depending on the surface they gripped, potentially by using sensory feedback. The results of this study demonstrate that even a simple isometric pinch grip (no lifting associated) is affected by grip surface friction. Grip surface condition should be considered for clinical assessments, biomechanical investigation, and motor control studies to ensure consistency in measurements and validity of comparisons.


[Preparation of antibodies against o-aminoazotoluene using chemically and enzymatically synthesized conjugated antigens].
Two methods are developed for synthesis of conjugated antigens to o-aminoazotoluene (o-AAT)-albumin: the enzymatic method--using horseradish peroxidase (HP) and the chemical one--diazomethod. A possible mechanism is suggested for the covalent binding of o-AAT to albumin which is catalyzed by HP. Antibodies to o-AAT are obtained by immunization of animals. An essential difference is established for antigenic o-AAT determinants in conjugates synthesized by the enzymatic and chemical methods.


Fluid management in acute lung injury and ards.
ARDS is particularly characterized by pulmonary edema caused by an increase in pulmonary capillary permeability. It is considered that limiting pulmonary edema or accelerating its resorption through the modulation of fluid intake or oncotic pressure could be beneficial. This review discusses the principal clinical studies that have made it possible to progress in the optimization of the fluid state during ARDS. Notably, a randomized, multicenter study has suggested that fluid management with the goal to obtain zero fluid balance in ARDS patients without shock or renal failure significantly increases the number of days without mechanical ventilation. On the other hand, it is accepted that patients with hemodynamic failure must undergo early and adapted vascular filling. Liberal and conservative filling strategies are therefore complementary and should ideally follow each other in time in the same patient whose hemodynamic state progressively stabilizes. At present, although albumin treatment has been suggested to improve oxygenation transiently in ARDS patients, no sufficient evidence justifies its use to mitigate pulmonary edema and reduce respiratory morbidity. Finally, the resorption of alveolar edema occurs through an active mechanism, which can be pharmacologically upregluated. In this sense, the use of beta-2 agonists may be beneficial but further studies are needed to confirm preliminary promising results.


Effect of ions on phospholipid layer structure as indicated by Raman spectroscopy.
Various anions and cations are found to induce changes in the layered structure of phosphatidylcholine-water systems as indicated by Raman Spectroscopy. From the ratio of Raman intensities, I1064/I1089, it is inferred that dipositive ions decrease the proportion of gauche character in the hydrocarbon chains, with the relative influence being: Ba2+ less than Mg2+ less than Ca2+ similar to Cd2+. Unipositive ions (Li+, K+ and Na+) produce no observed changes in the Raman spectrum of the lecithin dispersion. The proportion of gauche character of the hydrocarbon chains is found to be nearly independent of the anion for: Br-, Cl-, acetate-, I-, ClO4-, CNS- and SO42-. Dispersions prepared with a solution of KI+I2 produced Raman spectra in which the 1089cm-1 peak, which is characteristic of random lipid chains, was greatly intensified, presumably because of the presence of I3- which is known to penetrate the lipid lamellae. The observed trends are discussed.


Influence of early defibrillation on the survival rate and quality of life after CPR in prehospital emergency medical service in a German metropolitan area.
Early defibrillation by emergency medical personnel has been shown to improve survival in patients suffering from out-of-hospital cardiac arrest with ventricular fibrillation. Due to organisational differences it is difficult to compare results in various studies. Comparison of studies has been simplified by introduction of the Utstein template. After introduction of an early defibrillation program in Hamburg, we compared the patients being treated with early defibrillation by emergency medical technicians (EMTs) with patients being defibrillated by physicians in an out-of-hospital emergency service in a prospective study. All patients suffered from non EMT-witnessed ventricular fibrillation of cardiac origin. During 1 year, 103 patients were analyzed with respect to survival rate and quality of life. Of the 53 patients in the early defibrillation group (G1) 11 regained a palpable pulse at physicians' arrival, whereas all patients of the control group (G2) showed ventricular fibrillation. More patients treated with early defibrillation regained sinus rhythm without antiarrhythmics in the prehospital phase (G1: n=43 (86%); G2: n=32 (60%); P<0.05) and had a shorter in-hospital stay (G1: median, 23 days; range 5-51 days; G2: median 39, range 15-88 days; P<0.05). Twelve patients in G1 and 16 in G2 were discharged from hospital. The survival rate was similar in both groups (after 6 months G1: n=12; G2: n=14, after 12 months G1: n=10; G2: n=13 and after 24 months G1: n=9; G2: n=10), and the quality of life according to Glasgow-Pittsburgh Cerebral Performance Category (CPC) and Overall Performance Category (OPC) scores also was comparable between groups. We conclude that early defibrillation provides a higher incidence of return of a spontaneous circulation, a reduced need for antiarrhythmics and shorter in-hospital treatment times in patients with out-of-hospital ventricular fibrillation.


Structure-activity relationships of novel anti-malarial agents. Part 3: N-(4-acylamino-3-benzoylphenyl)-4-propoxycinnamic acid amides.
We have described 5-(4-propoxycinnamoylamino)-2-(4-tolylacetylamino)benzophenone 6e as a novel lead for anti-malarial agents. Anti-malarial activity of these 5-(4-propoxycinnamoylamino)benzophenones proved to be quite sensitive against variations of the acyl substituent at the 2-amino group. Best activity was obtained with phenylacetic acid moieties carrying small substituents in the para-position. From the para-substituents evaluated, the trifluoromethyl group yielded the most active compound (6j) in this series (IC50=120 nM). Deviations from the phenylacetic acid substructure, shifting the substituent into the ortho-position or bulkier para-substituents resulted in a significant reduction in anti-malarial activity.


[Acute aortic syndrome].
Acute aortic syndrome is the common denominator for acute events to the aortic wall and encompasses dissection of the aorta, intramural hematoma, formation of aortic ulcers and trauma to the aorta with an annual incidence of up to 35 cases/100.000 between 65 and 75 years of age. Both, inflammation and/or microtrauma at the level of the aortic media layer, and a genetic disposition are promoting elements of AAS, while the extent and anatomic involvement of the ascending aorta call for either surgical resection/repair in the proximal part of the aorta, or an endovascular solution for pathologies in the distal aorta; in all cases of dissection (regardless of location) reconstruction/realignment has been proven to portend better long-term outcomes (in addition to medical management of blood pressure).


Is there an association between advanced stage of renal cell carcinoma and paraneoplastic syndrome?
To investigate any association between renal cell carcinoma (RCC) and paraneoplastic syndromes (PNS). The retrospective analysis included 1,028 patients of Chinese Han nationality with resectable RCC and PNS. The PNS included elevated erythrocyte sedimentation rate (ESR), hypertension, cachexia, anemia, pyrexia, abnormal liver function, hypercalcemia, polycythemia, varicocele and neuromyopathy. Staging was categorized as local (T1-2N0M0) and locally advanced (T3-4NxM0). Among patients with at least one PNS, elevated ESR (p = 0.008), cachexia (p = 0.000), varicocele (p = 0.000) and pyrexia (p = 0.021) were related to advanced stage of RCC. Among patients with only one PNS, hypertension (p = 0.012) and hypercalcemia (p = 0.000) were related to advanced stage. The remaining PNS were not associated with tumor stage. Pyrexia, elevated ESR, cachexia and varicocele were related to advanced RCC. Hypertension and hypercalcemia occurring as single PNS, although also correlated with advanced stage, require further investigation.


Estimating the global burden of Epstein-Barr virus-related cancers.
More than 90% of the adult population globally is chronically infected by the Epstein-Barr virus (EBV). It is well established that EBV is associated with a number of malignancies, and advances in knowledge of EBV-related malignancies are being made every year. Several studies have analysed the global epidemiology and geographic distribution of EBV-related cancers. However, most have only described a single cancer type or subtype in isolation or limited their study to the three or four most common EBV-related cancers. This review will present an overview on the spectrum of cancers linked to EBV based on observations of associations and proportions in the published literature while also using these observations to estimate the incidence and mortality burden of some of these cancers. We have reviewed the literature on defining features, distribution and outcomes across six cancers with a relatively large EBV-related case burden: Nasopharyngeal carcinoma (NPC), Gastric carcinoma (GC), Hodgkin lymphoma (HL), Burkitt lymphoma (BL), Diffuse large B-cell lymphoma (DLBCL) and Extranodal NK/T-cell lymphoma, Nasal type (ENKTL-NT). We retrieved published region-specific EBV-related case proportions for NPC, GC, HL and BL and performed meta-analyses on pooled region-specific studies of EBV-related case proportions for DLBCL and ENKTL-NT. We match these pooled proportions with their respective regional incidence and mortality numbers retrieved from a publicly available cancer database. Additionally, we also reviewed the literature on several other less common EBV-related cancers to summarize their key characteristics herein. We estimated that EBV-related cases from these six cancers accounted for 239,700-357,900 new cases and 137,900-208,700 deaths in 2020. This review highlights the significant global impact of EBV-related cancers and extends the spectrum of disease that could benefit from an EBV-specific therapeutic.


Genetics and evolution of Neisseria meningitidis: importance for the epidemiology of meningococcal disease.
Meningococcal disease is a life-threatening illness occurring worldwide with incidence rates varying from 1 to 1000 cases per 100,000. The causative organism, Neisseria meningitidis, is a normal commensal of humans. While strains associated with asymptomatic carriage are highly diverse, a few hyper-invasive genetic clones of the species may spread rapidly through human populations, resulting in countrywide epidemics of meningococcal meningitis. N. meningitidis fitness for spread and colonization is directly linked to the capability of the bacterium to change its genome and adapt to its environment, by means of a variety of genetic mechanisms. This review addresses some of the impacts of the evolutionary potential of N. meningitidis on the occurrence of meningococcal disease.


Sanitary installations and wastewater plumbing as reservoir for the long-term circulation and transmission of carbapenemase producing Citrobacter freundii clones in a hospital setting.
Accumulating evidence shows a role of the hospital wastewater system in the spread of multidrug-resistant organisms, such as carbapenemase producing Enterobacterales (CPE). Several sequential outbreaks of CPE on the geriatric ward of the Ghent University hospital have led to an outbreak investigation. Focusing on OXA-48 producing Citrobacter freundii, the most prevalent species, we aimed to track clonal relatedness using whole genome sequencing (WGS). By exploring transmission routes we wanted to improve understanding and (re)introduce targeted preventive measures. Environmental screening (toilet water, sink and shower drains) was performed between 2017 and 2021. A retrospective selection was made of 53 Citrobacter freundii screening isolates (30 patients and 23 environmental samples). DNA from frozen bacterial isolates was extracted and prepped for shotgun WGS. Core genome multilocus sequence typing was performed with an in-house developed scheme using 3,004 loci. The CPE positivity rate of environmental screening samples was 19.0% (73/385). Highest percentages were found in the shower drain samples (38.2%) and the toilet water samples (25.0%). Sink drain samples showed least CPE positivity (3.3%). The WGS data revealed long-term co-existence of three patient sample derived C. freundii clusters. The biggest cluster (ST22) connects 12 patients and 8 environmental isolates taken between 2018 and 2021 spread across the ward. In an overlapping period, another cluster (ST170) links eight patients and four toilet water isolates connected to the same room. The third C. freundii cluster (ST421) connects two patients hospitalised in the same room but over a period of one and a half year. Additional sampling in 2022 revealed clonal isolates linked to the two largest clusters (ST22, ST170) in the wastewater collection pipes connecting the rooms. Our findings suggest long-term circulation and transmission of carbapenemase producing C. freundii clones in hospital sanitary installations despite surveillance, daily cleaning and intermittent disinfection protocols. We propose a role for the wastewater drainage system in the spread within and between rooms and for the sanitary installations in the indirect transmission via bioaerosol plumes. To tackle this problem, a multidisciplinary approach is necessary including careful design and maintenance of the plumbing system.


The enigmatic fast leaflet rotation in Desmodium motorium: butterfly mimicry for defense?
I propose that the enigmatic leaflet movements in elliptical circles every few minutes of the Indian telegraph (semaphore) plant Desmodium motorium ( = D. gyrans = Hedysarum gyrans = Codariocalyx motorius), which has intrigued scientists for centuries, is a new type of butterfly or general winged arthropod mimicry by this plant. Such leaflet movement may deceive a passing butterfly searching for an un-occupied site suitable to deposit its eggs, that the plant is already occupied. It may also attract insectivorous birds, reptiles or arthropods to the plant because it looks as if it is harboring a potential prey and while they patrol there, they can find insects or other invertebrates that indeed attack the plant. The possibility that diurnal mammalian herbivores may also be deterred by these movements should not be dismissed.


Impact of transesophageal electrophysiological study on midterm management of pediatric tachyarrhythmias.
Transesophageal electrophysiological study (TEEPS) is a minimally invasive procedure that helps in evaluating the risk of recurrence of supraventricular tachycardia based on the inducibility of the tachycardia. The purpose of this study was to evaluate the diagnostic capability, negative predictive value of noninducibility of tachycardia and safety of TEEPS among the Indian pediatric population. It is a retrospective single-center observational study of all patients who underwent TEEPS from January 01, 2014, to December 31, 2020. Twenty-two TEEPS procedures were done in eighteen children with three children undergoing more than one procedure. The median duration of follow-up was 42.97 months (8.52-82.12 months). Out of the 22 procedures, four were conducted for acute tachycardia termination, two for tachycardia suppression assessment, and sixteen to assess tachycardia inducibility off medications. Tachycardia was noninducible in nine children and inducible in six children. Two children had clinical recurrence of tachycardia on follow-up. Out of these two children, one had noninducibility of tachycardia on TEEPS. The negative predictive value of TEEPS was 88.89% in this study. None of the children had any postprocedure complication. TEEPS is a safe procedure. It is used to assess the efficacy of medication in the suppression of arrhythmia. The noninducibility of tachycardia has a high negative predictive value and is a good indicator of nonrecurrence of clinical tachycardia on midterm follow-up.


Electrophysiological analysis of the trigemino-olivo-cerebellar (crura I and II, lobulus simplex) projection in the rat.
In albino rats the whisker area was electrically stimulated while climbing fiber responses were surveyed in the cerebellar hemisphere on the ipsilateral side. They were identified both deep in the intercrural sulcus, and in the posterior superior fissure. Histological examination has revealed that the response areas extend longitudinally from the dorsal surface of crus II to the ventral surface of crus I in the intercrural sulcus, and from the rostral surface of crus I to the caudal surface of lobulus simplex in the posterior superior fissure. These are supposed to be transmitted through direct trigemino-olivary projections.


Robust immune response stimulated by in situ injection of CpG/αOX40/cGAMP in αPD-1-resistant malignancy.
Recently, the emergence of immunotherapy has revolutionized traditional tumour treatment. However, effective treatments for patients exhibiting αPD-1 resistance are still lacking. In our study, a combination of cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODNs), anti-OX40 and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) injection in situ systematically generated a robust antitumour immune response in TC1 and B16 cells, which are αPD-1-resistant malignancies. More precisely, this method activates both adaptive and innate immunity. Additionally, in situ vaccination with CpG/αOX40/cGAMP fully activates the production of cytokines. However, the combination of αPD-1 does not improve the efficacy of triple therapy, prompting further questions. Collectively, the combination of CpG/αOX40/cGAMP causes the regression of various αPD-1-resistant tumours through the full mobilization of innate and adaptive immunity. In addition, we explored the therapeutic effect of triple therapy on the αPD-1-sensitive cell line CT26. The results showed that triple therapy could significantly enhance the therapeutic effect of αPD-1, and some mice even achieved complete tumour regression after the combined application of αPD-1 and triple treatment.


Management of proximal humerus fractures utilizing reverse total shoulder arthroplasty.
The increased incidence of proximal humerus fractures has resulted in a thoughtful evolution of treatment options in order to optimize clinical outcomes. Complex three- and four-part fractures present a treatment challenge, particularly in elderly patients with significant medial comorbidities and poor bone quality. While open reduction and internal fixation is a reasonable surgical option in some patients with acceptable bone quality and simple fracture patterns that are not susceptible to avascular necrosis, shoulder hemiarthroplasty is a well-established procedure for many elderly patients (i.e., >70 years). Historically, hemiarthroplasty has provided reliable pain relief, but outcomes with regard to function, motion, and strength have varied. Ultimately, successful outcomes are dependent upon tuberosity healing, since an intact rotator cuff is required to restore function. With the advent of reverse total shoulder arthroplasty (RTSA) and increased familiarity with the surgical technique, successful outcomes have been achieved in older patients with poor potential for tuberosity healing. In this review, we discuss the recent role of RTSA in the setting of proximal humerus fractures, including surgical indications, preferred operative technique, and recent literature that supports its use.


Differential Expression of Cancer-Associated Fibroblast-Related Proteins in Ductal Carcinoma in situ According to Molecular Subtype and Stromal Histology.
The purpose of this study is to investigate the expression of cancer-associated fibroblast (CAF)-related proteins and their implication in ductal carcinoma in situ (DCIS). We constructed a tissue microarray of 223 cases of DCIS and examined immunohistochemical staining for the 7 CAF-related proteins. We classified DCIS into luminal type, human epidermal growth factor receptor-2 (HER-2) type, and triple negative breast cancer (TNBC) according to the immunohistochemical results for estrogen receptor, progesterone receptor, and HER-2. We also classified DCIS into desmoplastic, normal-like, and inflammatory type according to stromal histology. There were significant differences in the expression of S100A4, podoplanin, prolyl 4-hydroxylase subunit alpha 3, NG2, and PDGFRα in stromal cells of DCIS when classified according to molecular subtype. The expression rate of all CAF-related proteins in stromal cells was higher in the HER-2 type and TNBC than in the luminal type (p < 0.001). When classified according to stromal subtype, there were significant differences in the expression of all CAF-related proteins in stromal cells, with the inflammatory stromal type showing higher expression of CAF-related proteins than other stromal types. The expression of CAF-related proteins in stromal cells of DCIS varies according to molecular subtype and stromal type.


Oxygen mass transfer enhancement by activated carbon particles in xylose fermentation media.
In this work, the effect of activated carbon particles on the production of xylonic acid from xylose by Gluconobacter oxydans in a stirred tank bioreactor was investigated. The enhancement of the oxygen transfer coefficient by activated carbon particles was experimentally evaluated under different solids volume fractions, agitation and aeration rates conditions. The experimental conditions optimized by response surface methodology (agitation speed 800 rpm, aeration rate 7 L min-1, and activated carbon 0.002%) showed a maximum oxygen transfer coefficient of 520.7 h-1, 40.4% higher than the control runs without activated carbon particles. Under the maximum oxygen transfer coefficient condition, the xylonic acid titer reached 108.2 g/L with a volumetric productivity of 13.53 g L-1 h-1 and a specific productivity of 6.52 g/gx/h. In conclusion, the addition of activated carbon particles effectively enhanced the oxygen mass transfer rate. These results demonstrate that activated carbon particles enhanced cultivation for xylonic acid production an inexpensive and attractive alternative.


Behavior of Hexanal, (E)-Hex-2-enal, 4-Hydroxyhex-2-enal, and 4-Hydroxynon-2-enal in Oil-in-Water Emulsions.
The reactivity of hexanal, (E)-hex-2-enal, 4-hydroxyhex-2-enal, and 4-hydroxynon-2-enal in oil-in-water emulsions and their respective compartments, in the presence and absence of protein, was studied at 40 °C. In aqueous buffer, hexanal oxidized to hexanoic acid. In the presence of protein, an additional loss occurred, presumably as a result of adduct formation with cysteine. Similarly, (E)-hex-2-enal oxidized to (E)-hex-2-enoic acid in aqueous buffer, and the results suggested that this acid is also able to form adducts with proteins. 4-Hydroxyalk-2-enals showed the highest reactivity in all models evaluated. Especially in protein-containing systems, they were not detectable anymore or their initial concentration was seriously reduced. 4-Hydroxynon-2-enal was the most reactive of the substances studied. The reactivity of the aldehydes was influenced by their partition within emulsions, which was remarkably not correlated with their hydrophobicity. These findings need to be considered when using these aldehydes as lipid oxidation markers in foods.


Unexpected Fe-enriched compounds observed in Mg-Ce alloy: An atomic-scale STEM investigation.
This paper investigates into the unexpected nanosize Fe-enriched particles with defects incorporated, using EDS under STEM mode and atomic-resolution HAADF. The particle that locates between eutectic Mg12 Ce phase and α-Mg phase is identified as CeFe2 Si2 compound. Two types of defects are incorporated: Type-I defect is Ce-Si in a simple cubic lattice; Type-II defect is Ce in a FCC lattice. The interface between the defect-free CeFe2 Si2 and the defects is fully coherent. In addition, another two Ce/Fe/Si-enriched particles are observed, proving that the enrichment of Ce, Fe, and Si is not an accidental phenomenon. The observed formation of Ce/Fe/Si-enriched particles provides a possible explanation for the improvement in corrosion resistance and the purification effect induced by addition of rare earth elements into alloys. In addition, the present study demonstrates an advanced application of Cs-corrected HAADF by successfully directly imaging the dislocation and complex defects incorporated in the compound and by achieving a one-angstrom resolution. SCANNING 38:783-791, 2016. © 2016 Wiley Periodicals, Inc.


Readiness for employment: perceptions of mental health service users.
Work is good for both physical and mental health, and access to work is a basic human right. People with mental health conditions want to work and with the right support can work but are often excluded from the workplace. We explored factors influencing individual's perceptions of their readiness for employment. Participants' narratives focused particularly on personal causation and it's inter-reactions with other aspects of volition, habituation and the environment and highlight a number of key areas, which are discussed in relation to service provision. Sheltered workshops offer support and some structure and routine but may limit an individual's readiness for employment. Services should be evidence based and focused on real work opportunities which fit with individual's interests and values. Occupational therapy theory offers a unique and valuable perspective in understanding perceptions of readiness for employment and occupational therapists offer valid and useful assessments and interventions for vocational rehabilitation.


Serum levels of VEGF and basic FGF in the subacute phase of myocardial infarction.
We examined serial changes in serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) measured by ELISAs in 45 patients with acute myocardial infarction (AMI) who received heparin intravenously for 3 to 5 days after the onset and in 30 control subjects with an old myocardial infarction. To evaluate the effect of heparin on these serum levels, heparin was administered intravenously in 10 patients with AMI on day 21. Blood samples were obtained from all AMI patients on days 1, 2, 3, 7, 14, 21, and 28 and from 10 AMI patients before and 1 h after heparin administration. Serum VEGF level was significantly reduced after heparin administration (P<0.001). Serum samples from day 1 to 3 were therefore excluded from the subsequent analysis. Serum VEGF level in AMI patients was significantly higher on day 7 than in the control subjects (P<0.0001), and then decreased over time (P<0.0001). The serum VEGF level on day 7 was independently associated with the peak serum CK level (P<0.05). The serum bFGF level did not differ significantly between the AMI patients and the control subjects. In conclusion, the serum VEGF level may be selectively elevated during the healing process after AMI.


A GIS-based method for modeling methane emissions from paddy fields by fusing multiple sources of data.
Quantification of regional methane (CH4) gas emission in the paddy fields is critical under climate warming. Mechanism models generally require numerous parameters while empirical models are too coarse. Based on the mechanism and structure of the widely used model CH4MOD, a GIS-based Regional CH4 Emission Calculation (GRMC) method was put forward by introducing multiple sources of remote sensing images, including MOD09A1, MOD11A2, MOD15A2H as well as local water management standards. The stress of soil moisture condition (f(water)) on CH4 emissions was quantified by calculating the redox potential (Eh) from days after flooding or falling dry. The f(water)-t curve was calculated under different exogenous organic matter addition. Combining the f(water)-t curve with local water management standards, the seasonal variation of f(water) was obtained. It was proven that f(water) was effective in reflecting the regulation role of soil moisture condition. The GRMC was tested at four Eddy Covariance (EC) sites: Nanchang (NC) in China, Twitchell (TWT) in the USA, Castellaro (CAS) in Italy and Cheorwon (CRK) in Korea and has been proven to well track the seasonal dynamics of CH4 emissions with R2 ranges of 0.738-0.848, RMSE ranges of 31.94-149.22 mg C/m2d and MBE ranges of -66.42- -14.79 mg C/m2d. The parameters obtained in Nanchang (NC) site in China were then applied to the Ganfu Plain Irrigation System (GFPIS), a typical rice planting area of China, to analyse the spatial-temporal variations of CH4 emissions. The total CH4 emissions of late rice in the GFPIS from 2001 to 2013 was in the range of 14.47-20.48 (103 t CH4-C). Ts caused spatial variation of CH4 production capacity, resulting in the spatial variability of CH4 emissions. Overall, the GRMC is effective in obtaining CH4 emissions from rice fields on a regional scale.


The expanding field of poly(ADP-ribosyl)ation reactions. 'Protein Modifications: Beyond the Usual Suspects' Review Series.
Poly(ADP-ribosyl)ation is a post-translational modification of proteins that is mediated by poly(ADP-ribose) polymerases (PARPs). Although the existence and nature of the nucleic acid-like molecule poly(ADP-ribose) (PAR) has been known for 40 years, understanding its biological functions--originally thought to be only the regulation of chromatin superstructure when DNA is broken--is still the subject of intense research. Here, we review the mechanisms controlling the biosynthesis of this complex macromolecule and some of its main biological functions, with an emphasis on the most recent advances and hypotheses that have developed in this rapidly growing field.


[The physician's attitudes toward venereal diseases: a survey in the district of Parma (author's transl)].
Stated that official data by large under-report the prevalence of the sexually transmitted diseases a survey questionnaire was mailed to every physician of the district of Parma. The results and the pros and cons of the method are discussed.


Microalgae Bioactive Carbohydrates as a Novel Sustainable and Eco-Friendly Source of Prebiotics: Emerging Health Functionality and Recent Technologies for Extraction and Detection.
There is a global interest in the novel consumption, nutritional trends, and the market of new prebiotic sources and their potential functional impacts. Commercially available nutritional supplements based on microalgae that are approved to be edible by FDA, like Arthrospira platensis (Cyanobacteria) and Chlorella vulgaris (Chlorophyta) become widely attractive. Microalgae are rich in carbohydrates, proteins, and polyunsaturated fatty acids that have high bioactivity. Recently, scientists are studying the microalgae polysaccharides (PS) or their derivatives (as dietary fibers) for their potential action as a novel prebiotic source for functional foods. Besides, the microalgae prebiotic polysaccharides are used for medication due to their antioxidant, anticancer, and antihypertensive bioactivities. This review provides an overview of microalgae prebiotics and other macromolecules' health benefits. The phytochemistry of various species as alternative future sources of novel polysaccharides were mentioned. The application as well as the production constraints and multidisciplinary approaches for evaluating microalgae phytochemistry were discussed. Additionally, the association between this potential of combining techniques like spectroscopic, chromatographic, and electrochemical analyses for microalgae sensation and analysis novelty compared to the chemical methods was emphasized.


Identifying cues of distorted memories in intensive care by focus group interview of nurses.
To determine cues to identify intensive care unit patients with distorted memories and related practices. Qualitative descriptive study. Twenty nurses were included in semi-structured focus groups. Qualitative content analysis was conducted. Cues and nursing practices related to distorted memories emerged under the following categories: "Get to know daily life before admission," "Facial expressions and behaviour are different from usual," "Pay close attention to the treatment outcome," "Notice it after the fact," "Sharing patients' intensive care unit experiences" and "Creates a new life." Nurses tried to detect distorted memories by observing the patients' facial expressions, medication effects and delirium presence during their normal lives and treatments, while trying to understand the patients' intensive care unit experiences and provide care that promotes autonomous living. This study emphasizes the importance of support for reconstructing ordinary life through communication and rehabilitation, in addition to support for medical care for distorted memories.


Amoxicillin Is the Most Effective Oral Antibiotic Prophylaxis Regimen for Reducing Post-Invasive Dental Procedure Bacteremia.
Prevention of Postdental Procedure Bacteremia: A Network Meta-analysis. Zeng BS, Lin SY, Tu YK, et al. J Dent Res 2019 Oct;98(11):1204-1210. There were no sources of funding associated with the work. Systematic review with meta-analysis of data.


Survey of primary care physicians and home care clinicians.
Providing home care in the United States is expensive, and significant geographic variation exists in the utilization of these services. However, few data exist on how well physicians and home care providers communicate and coordinate care for patients. To assess communication and collaboration between primary care physicians (PCPs) and home care clinicians (HCCs) within 1 primary care network. Mail survey. Boston. Sixty-seven PCPs from 1 academic medical center-affiliated primary care network and 820 HCCs from 8 regional home care agencies. Provider responses Ninety percent of PCPs and 63% of HCCs responded. The majority (54%) of PCPs reported that they only "rarely" or "occasionally" read carefully the home care order forms sent to them for signature. Further, when asked to rate their prospective involvement in the decision making about home care, only 24% of PCPs and 25% of HCCs rated this as "excellent" or "very good." Although more HCCs (79%) than PCPs (47%) reported overall satisfaction with communication and collaboration, 28% of HCCs felt they provided more services to patients than clinically necessary. PCPs from 1 provider network and the HCCs with whom they coordinate home care were both dissatisfied with many aspects of communication and collaboration regarding home care services. Moreover, neither group felt in control of home care decision making. These findings are of concern because poor coordination of home care may adversely affect quality and contribute to inappropriate utilization of these services.


Expression of hepatic microsomal cholesterol 7 alpha-hydroxylase activity in lean and obese Zucker rats.
The activity of hepatic microsomal cholesterol 7 alpha-hydroxylase was studied in genetically obese and lean Zucker rats. The liver microsomal cholesterol 7 alpha-hydroxylase activity in fatty Zucker rats (fa/fa) is about 50% to 70% lower than that of the lean (Fa/-) rats of the same sex, when animals were sacrificed at the middle of the dark cycle. When rats were sacrificed at the middle of the light cycle, cholesterol 7 alpha-hydroxylase activity was the same as in the dark cycle in obese rats of both sexes, but was 65% lower in lean rats. However, cholesterol 7 alpha-hydroxylase activity was stimulated by the treatment with cholestyramine in both obese and lean rats. Our results suggested that the diurnal regulation of cholesterol 7 alpha-hydroxylase activity is lost in obese rats but was present under cholestyramine treatment in the genetically obese strain of rats.


Broad-range real-time PCR assay for the rapid identification of cell-line contaminants and clinically important mollicute species.
Polymerase chain reaction assays have become widely used methods of confirming the presence of Mollicutes species in clinical samples and cell cultures. We have developed a broad-range real-time PCR assay using the locked nucleic acid technology to detect mollicute species causing human infection and cell line contamination. Primers and probes specifically for the conserved regions of the mycoplasmal tuf gene (encoding elongation factor Tu) were designed. Cell culture supernatants, clinical specimens (vaginal swabs, sputum, cryopreserved heart valve tissues), and reference strains were tested for mollicute contamination as well as to exclude cross-reaction to human nucleic acids and other bacterial species. Nucleic acids were extracted using magnetic separation technology. The coamplification of the human beta2-microglobulin DNA served as an internal control. The PCR assay was highly specific and obtained an analytical sensitivity of one copy per microl sample. The 95% detection limit was calculated to 10 copies per microl sample for Mycoplasma pneumoniae and M. orale. No false-positive results were observed due to cross-reaction of walled bacterial, fungal, and human nucleic acids. To evaluate the PCR, we compared the results to two commercialized test systems. Moreover, in combination with a previously developed broad-range RT-PCR assay for the detection of bacteria in blood products, both mollicute and walled bacterial contamination can be detected simultaneously using multiplex real-time RT-PCR.


Urea Stress: Myo-inositol's efficacy to counteract destabilization of TIM-β-globin complex by urea is as good as that of the methylamine.
Do kidney osmolytes counteract the deleterious effects of urea on kidney proteins? To answer this question, we measured guanidinium chloride (GdmCl)-induced denaturation of triose phosphate isomerase-β-globin subunit complex (TIM-β-globin) from sheep kidney in the presence of various concentrations of urea and each of kidney osmolytes (glycine betaine, myo-inositol and sorbitol) alone and in combination at pH 7.5 and 25 °C. Analysis of GdmCl-induced denaturation curve at a given osmolyte (or urea) concentration gave ΔGD0 (Gibbs free energy change in the absence of GdmCl). For a co-solute (CO), a linear plot of ΔΔGD0 (difference between values of ΔGD0 in the presence and absence of CO) against [CO] (molar concentration of CO) yielded m-value (=δΔΔGD0/δ[CO]). m-value for urea (murea) and that for the osmolyte (mosm) were used to determine [urea]:[osmolyte], the molar ratio for the perfect counteraction of the denaturing effect of urea on the protein stability by an osmolyte. For each osmolyte, we tested this ratio for the perfect counteraction. It was observed that glycine betaine and myo-inositol provide perfect counteraction at the predicted molar ratio whereas sorbitol fails to do so. Furthermore, urea and GdmCl induced a two-state denaturation, and both TIM and β-globin have identical thermodynamic stability.


Feeding Vessel Ablation: A Novel Subsegmental Devascularization Technique for the Treatment of Hepatocellular Carcinoma Located at the Liver Marginal Angle.
This pilot clinical study evaluated primarily the efficacy of feeding vessel ablation (FVA) in the treatment of hepatocellular carcinoma (HCC) located at the liver marginal angle (LMA). Nine patients with nine unresectable HCC lesions were prospectively included in this study. The target tumors (mean: 3.0 cm, interquartile range: 2.4-3.6 cm) were located at the LMA (segment 2/3/6) and adjacent to the gastrointestinal tract. Artificial ascites was attempted and failed. Multimode ultrasound technologies, including 2-D and real-time 3-D contrast-enhanced ultrasound, were used to identify the morphology and structure of the feeding vessels for the target tumors. During the treatment, a unipolar cool-tip electrode was used to ablate the feeding vessels, and the target ablation point was set in subsegmental or more distal vessels to induce a downstream ischemia region. Therapeutic outcomes were assessed after FVA, including the rates of technical success, tumor response, local tumor progression (LTP), overall survival (OS) and major complications. Cumulative LTP and OS were estimated with the Kaplan-Meier method. The technical success rate determined immediately after radiofrequency ablation was 7 of 9 (77.8%). Complete response (CR) was achieved in 7 of 7 tumors (100%) at the 1-mo evaluation. During a median follow-up period of 15.6 mo (range: 4.3-53.3 mo), CR remained in 6 of 7 tumors (85.7%), with LTP observed in 1 of 7 tumors (14.3%) 4.7 mo after treatment. The cumulative 1-, 3- and 5-y LTP-free rates were all 83.3%, and the cumulative 1-, 3- and 5-y OS rates were 42.9%, 28.6% and 0%, respectively. No major complications occurred. We concluded that FVA can induce subsegmental devascularization and has the potential to serve as an effective and safe alternative technique for local control of unresectable HCC located at the LMA when artificial ascites fails.


Acropetal movement of auxin: dependence on temperature.
The amounts of radioactive indole-3-acetic acid that moved, both basipetally and acropetally, through short sections of bean epicotyl were measured at 15 degrees and 25 degrees C in the presence and absence of 2,3,5-triiodobenzoic acid. Low temperature and this second compound each inhibited acropetal efflux of indole 3-acetic acid more than they did the influx. Results are interpreted as supporting a metabolically dependent component of the acropetal movement of auxin in bean epicotyls.


Insulin-stimulated NAD(P)H oxidase activity increases migration of cultured vascular smooth muscle cells.
We reported that insulin stimulates NAD(P)H oxidase activity but not migration of cultured rat vascular smooth muscle cells (VSMCs). Because angiotensin II (Ang II) increases NAD(P)H oxidase activity in these cells, we wished to determine whether insulin stimulates migration of Ang II-treated VSMCs by synergistically stimulating enzyme activity. Cultured rat VSMC superoxide anion (O2-) production, cyclic GMP production, and migration were measured by lucigenin luminescence, immunoassay, and wound closure rate, respectively. Nitric oxide (NO) scavenging was measured by inhibition of NO-induced fluorescence of 4-5-diaminofluorescin. Insulin (1 nmol/L) did not affect and Ang II (100 nmol/L) stimulated VSMC migration by 65% (P < .05), but together stimulated it by 150% (P < .05 versus Ang II) by a mechanism inhibited by the NAD(P)H oxidase inhibitors, diphenyleneiodonium (DPI) or gp91ds-tat. Insulin and Ang II stimulated O2- production by 34% and 35%, respectively (both P < .05), but together synergistically stimulated it by 143% (P < .05 versus insulin or Ang II) in a DPI or gp91ds-tat-sensitive manner. Neither insulin nor Ang II measurably affected NO scavenging, but together reduced NO availability by 46% in a DPI-sensitive manner (P < .05) and significantly inhibited NO-stimulated cyclic GMP production. Insulin synergestically stimulates NAD(P)H oxidase activity in Ang II-treated cultured rat VSMCs causing increased migration.


Developmental toxicity studies of caprolactam in the rat and rabbit.
Caprolactam was evaluated for developmental toxicity potential in both rats and rabbits by the oral route. In rats dosed on days 6-15 of gestation with 100, 500 or 1000 mg/kg/day of caprolactam, the maternal survival rate was significantly lower in the high-dose group and implantation efficiencies were slightly lower in the 100 and 1000 mg/groups (but not the 500 mg/kg) than in the control. The incidence of fetal death was comparable for all groups, and the incidence of fetal viability was considerably lower in the high-dose group (but not the mid or low) than in the control group. Visceral anomalies and one visceral variant were observed in one 100 mg/kg and one 500 mg/kg pup, respectively. The anomalies included exencephaly, an incomplete left eyelid, microphthalmia (right), and a protruding tongue. No skeletal anomalies were observed. It was concluded that caprolactam at levels up to at least 500 mg/kg of body weight produced no teratogenic effects in the Fischer 344 rats. In rabbits receiving 50, 150 or 250 mg/kg caprolactam on days 6-28 of gestation, the pregnancy rate in all groups was at least 80%. The numbers of corpora lutea, live and dead fetuses, resorptions, the sex ratio and the pre- and post-implantation losses were not significantly different among the test and control groups. The incidence of major malformations and of minor skeletal anomalies was unaffected by treatment with caprolactam. Maternal weights were depressed in the group receiving 250 mg/kg. Treatment of a separate group with a positive control substance (6-aminonicotinamide) resulted in significantly (P less than 0.001) increased incidences of major malformations, minor visceral anomalies and minor skeletal anomalies. Maternal toxicity in terms of mortality was observed in pregnant rabbits treated with caprolactam at a dose of 250 mg/kg/day. Fetotoxicity was evidenced by lower fetal weights at the 150 and 250 mg/kg/day levels, and an increased incidence of thirteenth ribs was observed at the 250 mg/kg/day dose level. Neither embryotoxicity nor teratogenicity occurred at any dose level.


An evaluation of telephone versus videoconference consults for pre-treatment medication history taking by cancer pharmacists.
The primary aim was to compare the successful completion rates of pre-treatment medication history consults conducted by pharmacists with patients either via an unscheduled telephone consult (current standard care) or a scheduled videoconference consult model. Secondary aims were to examine pharmacist perceptions of the telephone and videoconference consults and explore patient (+/- support person) perceptions of videoconference consults. Completion data were collected and compared for the two modalities. In addition, pharmacists commented on any positive/negative factors impacting all consults. For the final 35 participants completing a videoconference consult, patients, support people, and pharmacists involved, completed a survey exploring perceptions and satisfaction. A significantly higher completion rate (p < 0.0001) was found for the videoconferencing model, with 94% (76 of 81) completed successfully compared to 72% (76 of 105) of the unscheduled telephone consults. Pharmacists reported multiple factors impacting the success of the telephone consults including scheduling issues and patient factors. Survey responses revealed that 100% of patients/support people and 82% of pharmacists reported satisfaction with videoconference consults. Surveyed participants noted some technical issues, however, the 'ability to show/view medication containers and/or labels' and 'convenience of scheduled time' were benefits of the videoconference model. Results indicate that pre-treatment medication history consults should be offered via videoconference to maximise success.