Sex-specific patterns of discomfort in patients with restless legs syndrome.
Sex differences in the prevalence of restless legs syndrome (RLS) have been reported, with a higher prevalence in women than in men. However, sex differences in clinical presentation remain unclear. We aimed to investigate the phenotypic differences in patients with RLS between sexes by comparing clinical presentations, iron status, polysomnographic parameters, and treatment. We retrospectively evaluated 614 patients (225 men, 389 women) diagnosed with RLS. To enhance the robustness of the study, an age-matched control group of 179 men and 286 women without sleep disorders was also included. Information on demographics and sleep-related questionnaires were collected. Iron status was evaluated using blood samples, and polysomnography was performed to evaluate periodic leg movements and comorbid sleep disorders. Our analysis revealed no sex difference in the severity of RLS but a difference in the pattern of symptoms. Women had more frequent symptoms of pain and awakening during sleep, while men had more common motor symptoms (both subjective symptoms and periodic leg movement on polysomnography). Women with RLS also had lower iron parameters and received more frequent iron supplementation therapy than men. In contrast to women with RLS, who presented higher sleep disturbances and depressive mood, men with RLS had a higher risk of comorbidities such as hypertension and cardiovascular disease. These gender differences were notably more pronounced than in the control group. This study suggests that sex differences exist in RLS phenotypes, and clinicians should consider these differences for treatment.


Knowledge and risk of cardiovascular disease in rural Alabama women.
The purpose of this study was to describe rural women's knowledge of cardiovascular disease (CVD) and actual risk of CVD. The research question guiding this study was: "Are there relationships between demographic factors, women's knowledge of CVD, and women's CVD risk score?" Demographic data were collected from a convenience sample of 112 women at a full-service, rural medical clinic in Alabama. Two questions assessed women's knowledge of their risk factors for CVD. The Coronary Heart Disease Knowledge Test measured knowledge of coronary heart disease (CHD). Framingham CHD prediction scores were calculated to assess the actual heart disease risk of subjects. Knowledge of CVD in rural Alabama women is inadequate. The mean score for the knowledge test was 8.50 out of 20. This population of women has significant risk for CVD. Women recognized that smoking and obesity are issues, but are less aware of factors such as race, personality types, oral contraceptive use, hypertension, diabetes, age, hyperlipidemia, and family history. The majority of women in the study could list only one or two CVD risk factors. New strategies for educating women about CVD should be explored by nurse practitioners (NPs). For example, NPs interested in CVD in women could organize and offer to teach in local schools, colleges, universities, churches, and at sites where women work. Collaboration with the local American Heart Association and Health Department in educating women may be appropriate. By increasing women's knowledge, their actual risk may change and thus improve their chance to live free of CVD or have it later in life or to a lesser extent.


Thousand-year-long Chinese time series reveals climatic forcing of decadal locust dynamics.
For >1,000 years, Chinese officials have recorded the annual abundance of the oriental migratory locust Locusta migratoria manilensis, with the ultimate aim of predicting locust outbreaks. Linking these records with temperature and precipitation reconstructions for the period 957-1956, we show that decadal mean locust abundance is highest during cold and wet periods. These periods coincide with above-average frequencies of both floods and droughts in the lower Yangtze River, phenomena that are associated with locust outbreaks. Our results imply differential ecological responses to interdecadal and interannual climatic variability. Such frequency-dependent effects deserve increased attention in global warming studies.


Plant Cell-Cell Transport via Plasmodesmata Is Regulated by Light and the Circadian Clock.
Plasmodesmata (PD) are essential for plant development, but little is known about their regulation. Several studies have linked PD transport to chloroplast-centered signaling networks, but the physiological significance of this connection remains unclear. Here, we show that PD transport is strongly regulated by light and the circadian clock. Light promotes PD transport during the day, but light is not sufficient to increase rates of PD transport at night, suggesting a circadian gating mechanism. Silencing expression of the core circadian clock gene, LHY/CCA1, allows light to strongly promote PD transport during subjective night, confirming that the canonical plant circadian clock controls the PD transport light response. We conclude that PD transport is dynamically regulated during the day/night cycle. Due to the many roles of PD in plant biology, this discovery has strong implications for plant development, physiology, and pathogenesis.


Herpesvirus vaccines: challenges and future prospects.
Human herpes viruses are a family of large double stranded DNA viruses. Their life-cycle is characterized by an initial lytic cycle of infection in which large numbers of new virions are generated, followed by a pattern of lifelong latent infection with intermittent reactivation and viral shedding. Co-evolution over millennia has resulted in an interaction between host and pathogen which leads to the successful establishment of a lifelong latent infection with typically minimal impact upon the host, and subsequent maintenance and control of latently infected cells by the host immune system. Infection is usually asymptomatic or leads to an acute transient disease. However more severe disease can arise during primary infection, latency or upon reactivation; in both an immunocompromised and an immunocompetent setting, indicative of a need for the development of vaccine strategies which can either prevent infection or treat virally-associated diseases.


Human health risks from arsenic in soils: does one model fit all?
In the absence of a "soil model" on arsenic bioavailability, many investigators conducting baseline risk assessments of arsenic-enriched sites have assumed that all arsenic present in the soil is bioavailable. This assumption overestimates actual human health risk because various geochemical forms of arsenic are stable, or insoluble, in human digestive juices. The authors conducted a laboratory incubation study to analyze the in vitro bioavailability of arsenic in soils as a function of soil properties. Four different soil types were selected on the basis of their potential differences with respect to arsenic reactivity. Each soil was amended with sodium arsenite at a rate representative of a routine 1-yr application of arsenical pesticide in an agricultural system. The soils were incubated for 1 yr, after which the authors measured soil-specific total and bioavailable arsenic concentrations. Results demonstrated that soil physicochemical properties significantly affect arsenic bioavailability, and hence estimates of cancer risk, which in turn affect site cleanup cost projections.


Cutaneous side effects of TNF-alpha inhibitors.
Since the early 1990s, tumor necrosis factor alpha (TNF-alpha) inhibitors have been successfully used in the treatment of various immune-mediated inflammatory diseases. By now, comprehensive safety data has been compiled. While adverse reactions do occur, they are - in relation to the frequent use of these agents - rare and usually not serious. Cutaneous side effects include local injection site reactions, infections, immune-mediated reactions, and neoplasms. The most common serious adverse events are of an infectious nature. Mycobacteria but also non-mycobacterial pathogens, such as viruses and fungi, may cause serious, even lethal, systemic infections. The present article is meant to review current knowledge with respect to cutaneous side effects of TNF-alpha inhibitors.


DNA Breaks and End Resection Measured Genome-wide by End Sequencing.
DNA double-strand breaks (DSBs) arise during physiological transcription, DNA replication, and antigen receptor diversification. Mistargeting or misprocessing of DSBs can result in pathological structural variation and mutation. Here we describe a sensitive method (END-seq) to monitor DNA end resection and DSBs genome-wide at base-pair resolution in vivo. We utilized END-seq to determine the frequency and spectrum of restriction-enzyme-, zinc-finger-nuclease-, and RAG-induced DSBs. Beyond sequence preference, chromatin features dictate the repertoire of these genome-modifying enzymes. END-seq can detect at least one DSB per cell among 10,000 cells not harboring DSBs, and we estimate that up to one out of 60 cells contains off-target RAG cleavage. In addition to site-specific cleavage, we detect DSBs distributed over extended regions during immunoglobulin class-switch recombination. Thus, END-seq provides a snapshot of DNA ends genome-wide, which can be utilized for understanding genome-editing specificities and the influence of chromatin on DSB pathway choice.


Elimination of porcine heptadecapeptide gastrin (G17) and human leu big gastrin (G34) by the perfused pig liver.
In order to study some of the molecular events during the hepatic passage of gastrin, we perfused sulfated natural porcine gastrin (G17 II) through isolated pig livers. The disappearance half time of G17 II was about 20-30 min when the starting gastrin concentrations were greater than 100 pM; lower concentrations were reduced with half times of 40-100 min. Synthetic human leu-32 (G34) was not eliminated. The use of region-specific antibodies to gastrin indicated that degradation was more effective at the N-terminus of gastrin. Whereas Sephadex chromatography revealed no change of the molecular size, SDS-polyacrylamide gel electrophoresis showed the presence of smaller immunoreactive fragments of gastrin in addition to immunoreactive fragments of gastrin of the heptadecapeptide size. These findings indicate that the isolated porcine liver degrades porcine G17 to smaller fragments.


Contemporary treatment patterns in plaque psoriasis and psoriatic arthritis.
Psoriasis is a chronic inflammatory skin disease affecting about 2% of the general population. Although there are many treatment options, and new medications have been introduced, the disease is considered not curable, and it may seriously affect patients' quality of life. The authors present contemporary treatment patterns used by dermatologists in Poland to manage plaque psoriasis and psoriatic arthritis, particularly regarding systemic treatment. The authors also aimed to analyse how these treatment patterns are influenced by the guidelines of the Polish Dermatological Society. The author's questionnaire, consisting of 13 questions was used. It included demographic and professional characteristics of questioned dermatologists, as well as the assessment of the attitudes towards management of plaque psoriasis and psoriatic arthritis. A total of 132 dermatologists completed the questionnaire. Most of the specialists worked in out-patient clinics and private practices. The most commonly used topicals for psoriasis included: glucocorticosteroids, a combination of glucocorticosteroid and vitamin D analogue and salicylic acid. Regarding the treatment of psoriatic arthritis, most of the specialists declared using systemic therapy and a combination of systemic therapy and phototherapy. The majority of the respondents were particularly concerned with possible side effects or difficulties in qualifying and monitoring the patients, and less frequently on the cost of the therapy. Observations suggest that 60% of physicians have some reservation to initiate systemic treatment in outpatient clinics, and they admit that they lack additional training. On the other hand, it seems also that the organization of systemic treatment in psoriasis may generate these difficulties and thus necessitate additional effort. Another factor could be the budget - not only regarding healthcare professionals, but also the patient, sometimes financing various investigations from private resources.


[The significance of portal infusion chemotherapy for prevention of recurrence in residual liver after hepatectomy for metastases from colorectal cancer].
We performed portal infusion chemotherapy using a reservoir for prevention of recurrence in residual liver after hepatectomy for metastases from colo-rectal cancer. To study the usefulness of portal infusion chemotherapy, the period from hepatectomy to recurrence in residual liver was investigated by three treatment groups for H2 cases; (a) a group of systemic chemotherapy, (b) a group of arterial infusion chemotherapy and (c) a portal infusion chemotherapy group. Treatment in (a) group was for 204 +/- 98.2 days (n = 6), in (b) group for 343.0 +/- 238.3 days (n = 8) and in (c) group for 961.0 +/- 1,172.4 days (n = 5). There was no statistically significant difference in the three groups, but (c) group had a better result in recurrence in residual liver. As for prevention of recurrence in residual liver after re-hepatectomy, there was no significant difference in the three groups, but (c) group had the longest survival.


DNA translocation in inorganic nanotubes.
Inorganic nanotubes were successfully integrated with microfluidic systems to create nanofluidic devices for single DNA molecule sensing. Inorganic nanotubes are unique in their high aspect ratio and exhibit translocation characteristics in which the DNA is fully stretched. Transient changes of ionic current indicate DNA translocation events. A transition from current decrease to current enhancement during translocation was observed on changing the buffer concentration, suggesting interplay between electrostatic charge and geometric blockage effects. These inorganic nanotube nanofluidic devices represent a new platform for the study of single biomolecule translocation with the potential for integration into nanofluidic circuits.


Understanding the determinants of under-five child mortality in Uganda including the estimation of unobserved household and community effects using both frequentist and Bayesian survival analysis approaches.
Infant and child mortality rates are among the health indicators of importance in a given community or country. It is the fourth millennium development goal that by 2015, all the United Nations member countries are expected to have reduced their infant and child mortality rates by two-thirds. Uganda is one of those countries in Sub-Saharan Africa with high infant and child mortality rates, therefore it is important to use sound statistical methods to determine which factors are strongly associated with child mortality which in turn will help inform the design of intervention strategies The Uganda Demographic Health Survey (UDHS) funded by USAID, UNFPA, UNICEF, Irish Aid and the United Kingdom government provides a data set which is rich in information on child mortality or survival. Survival analysis techniques are among the well-developed methods in Statistics for analysing time to event data. These methods were adopted in this paper to examine factors affecting under-five child mortality rates (UMR) in Uganda using the UDHS data for 2011 in R and STATA software. Results obtained by fitting the Cox-proportional hazard model with frailty effects and drawing inference using both the frequentists and Bayesian approaches at 5 % significance level, show evidence of the existence of unobserved heterogeneity at the household level but there was not enough evidence to conclude the existence of unobserved heterogeneity at the community level. Sex of the household head, sex of the child and number of births in the past one year were found to be significant. The results further suggest that over the period of 1990-2015, Uganda reduced its UMR by 52 % . Uganda has not achieved the MDG4 target but the 52 % reduction in the UMR is a move in the positive direction. Demographic factors (sex of the household head) and Biological determinants (sex of the child and number of births in the past one year) are strongly associated with high UMR. Heterogeneity or unobserved covariates were found to be significant at the household but insignificant at the community level.


[Analysis of causes of death of patients with chronic circulatory insufficiency].
The presented analysis is based on the case reports of 166 patients who had been treated in the A. L. Myasnikov Cardiology Institute, USSR Academy of Medical Sciences, for rheumatic heart diseases (97), postinfarction cardiosclerosis (35), myocardiopathies (24) complicated by Stage III or IIB circulatory insufficiency. Chronic circulatory insufficiency free of complications was the cause of death of only 1/3 of the mortality cases. The rest of the patients' death was considered to be caused by thromboembolism, predominantly to the pulmonary artery system, pneumonias, haemorrhages from acute and subacute gastric ulcers, etc. The factors most frequently complicating the chronic circulatory insufficiency in patients suffering either from heart diseases, cardiosclerosis, or myocardiopathy, were thromboembolisms.


Developing a Research Strategy for Suicide Prevention in the Department of Defense: Status of Current Research, Prioritizing Areas of Need, and Recommendations for Moving Forward.
In response to the elevated rate of suicide among U.S. service members, a congressionally mandated task force recommended that the U.S. Department of Defense (DoD) create a unified, comprehensive strategic plan for suicide prevention research to ensure that DoD-funded studies align with DoD's goals. To help meet this objective, a RAND study cataloged the research funded by DoD and other entities that is directly relevant to military personnel, examined the extent to which current research maps to DoD's strategic research needs, and provided recommendations to ensure that proposed research strategies align with the national research strategy and integrate with DoD's data collection and program evaluation strategies. The study found that although DoD is one of the largest U.S. funders of research related to suicide prevention, its current funding priorities do not consistently reflect its research needs. The study indexed each of 12 research goals according to rankings of importance, effectiveness, cultural acceptability, cost, and learning potential provided by experts who participated in a multistep elicitation exercise. The results revealed that research funding is overwhelmingly allocated to prevention goals already considered by experts to be effective. Other goals considered by experts to be important and appropriate for the military context receive relatively little funding and have been the subject of relatively few studies, meaning that there is still much to learn about these strategies. Furthermore, DoD, like other organizations, suffers from a research-to-practice gap. The most promising results from studies funded by DoD and other entities do not always find their way to those responsible for implementing suicide prevention programs that serve military personnel. The RAND study recommended approaches to thoughtfully integrate the latest research findings into DoD's operating procedures to ensure that evidence-based approaches can benefit suicide prevention programs and prevent the further loss of lives to suicide.


Solvent- and Pressure-Induced Phase Changes in Two 3D Copper Glutarate-Based Metal-Organic Frameworks via Glutarate (+gauche ⇄ -gauche) Conformational Isomerism.
Two isoreticular three-dimensional copper(II) glutarate-based pillared-layered metal-organic frameworks (MOFs) with flexible pillars, [Cu2(glu)2(bpa)] and [Cu2(glu)2(bpp)] (bpa = 1,2-bis(4-pyridyl)ethane; bpp = 1,3-bis(4-pyridyl)propane), undergo spontaneous phase changes upon solvent loss at room temperature. Using single-crystal X-ray diffraction analysis (SCXRD), we show that the phase changes result in new narrow-channel forms that experience a large reduction in solvent-accessible volume. Moreover, the [Cu2(glu)2(bpa)] MOF displays a stepped sorption isotherm for the uptake of CO2 at room temperature. This is indicative of reversion of the framework to the wide-channel form under CO2 pressure. Supercritical CO2 was used to isolate the gas-included structures, and by means of SCXRD we were able to determine the positions of the CO2 molecules in the channels of the frameworks. Finally, we report the use of molecular modeling simulations to elucidate the phase-change mechanism, including the energetic changes involved. Structural limitations in both MOFs allow for only direct gauche-gauche enantiomeric interconversion of the glutarate moieties.


Dihydropyridazinone cardiotonics: synthesis and inotropic activity of 5'-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)spiro[cycloalkane- 1,3'-[3H]indol]-2'(1'H)-ones.
In the 1,3-dihydro-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one series of cardiotonics, we found that a spirocycloalkyl ring may be annealed to the 3-position of the indolone moiety while retaining inotropic activity. An inverse relationship was found between spirocyloalkyl ring size and inotropic potency. ED50 values of the spirocyclopropane 10, spirocyclobutane 12, and spirocyclopentane 13 were 2.7, 35, and 133 micrograms/kg, respectively, following iv administration to pentobarbital-anesthetized dogs. The most potent compound prepared was 11 (5'-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)spiro[cyclopropane- 1,3'-[3H]indol]-2'(1'H)-one), the 4-methyl analogue of 10. This compound had an iv ED50 of 1.5 microgram/kg. Oral activity was evaluated by administering 50 micrograms/kg of 10 to conscious, chronically instrumented dogs. A 39% increase in LV dP/dt60 was observed, and an inotropic effect was demonstrable in excess of 7 h. Thus, the spirocyclic dihydropyridazinone inotropes are potent, long-acting, orally effective cardiotonics. Compound 11 was a potent inhibitor (IC50 = 13 nM) of cAMP phosphodiesterase derived from canine cardiac sarcoplasmic reticulum (SR-PDE). Importantly, -log IC50 values for inhibition of SR-PDE for this entire series of compounds were highly correlated (r = 0.949, p less than 0.02) with their inotropic -log ED50 values, supporting the hypothesis that inhibition of this enzyme contributes to the mechanism of action of the spirocyclic dihydropyridazinones.


Aging Affects Insulin Resistance, Insulin Secretion, and Glucose Effectiveness in Subjects with Normal Blood Glucose and Body Weight.
Several studies have demonstrated that factors including diabetes, including insulin resistance (IR), glucose effectiveness (GE), and the first and second phase of insulin secretion (FPIS, SPIS) could easily be calculated using basic characteristics and biochemistry profiles. Aging is accompanied by deteriorations of insulin resistance (IR) and insulin secretion. However, little is known about the roles of aging in the different phases of insulin secretion (ISEC), i.e., the first and second phase of insulin secretion (FPIS, SPIS), and glucose effectiveness (GE). In total, 169 individuals (43 men and 126 women) recruited from the data bank of the Meei-Jaw (MJ) Health Screening Center and Cardinal Tien Hospital Data Access Center between 1999 and 2008, with a similar fasting plasma glucose (FPG: 90 mg/dL) and BMI (men: 23 kg/m2, women 22 kg/m2) were enrolled. The IR, FPIS, SPIS, and GE were estimated using our previously developed equations shown below. Pearson correlation analysis was conducted to assess the correlations between age and four diabetes factors (DFs: IR, FPIS, SPIS, and GE). The equations that are used to calculate the DF in the present study were built and published by our group. The age of the participants ranged from 18 to 78 years. Men had higher FPIS but lower HDL-C levels than women (2.067 ± 0.159, 1.950 ± 0.186 μU/min and 1.130 ± 0.306, 1.348 ± 0.357 mmol/dl, accordingly). The results of the Pearson correlation revealed that age was negatively related to the IR and GE in both genders (IR: r = -0.39, p < 0.001 for men, r = -0.24, p < 0.003 for women; GE: r = 0.66, p < 0.001 for men, r = 0.78, p < 0.001 for women). At the same time, the FPIS was also only found to be negatively correlated with age in females (r = -0.238, p = 0.003), but there was no difference in the SPIS and age among both genders. We have found that in Chinese subjects with a normal FPG level (90 mg/dL) and body mass index (men: 23 kg/m2, women: 22: kg/m2), age is negatively related to the IR and GE among both genders. Only the FPIS was found to be negatively related to age in women. The tightness of their relationships, from the highest to the lowest, are GE, FPIS, and IR. These results should be interpreted with caution because of the small sample size.


Measuring the x-ray resolving power of bent potassium acid phthalate diffraction crystals.
This report presents the results from measuring the X-ray resolving power of a curved potassium acid phthalate (KAP(001)) spectrometer crystal using two independent methods. It is part of a continuing effort to measure the fundamental diffraction properties of bent crystals that are used to study various characteristics of high temperature plasmas. Bent crystals like KAP(001) do not usually have the same diffraction properties as corresponding flat crystals. Models that do exist to calculate the effect of bending the crystal on the diffraction properties have simplifying assumptions and their accuracy limits have not been adequately determined. The type of crystals that we measured is being used in a spectrometer on the Z machine at Sandia National Laboratories in Albuquerque, New Mexico. The first technique for measuring the crystal resolving power measures the X-ray spectral line width of the characteristic lines from several metal anodes. The second method uses a diode X-ray source and a double crystal diffractometer arrangement to measure the reflectivity curve of the KAP(001) crystal. The width of that curve is inversely proportional to the crystal resolving power. The measurement results are analyzed and discussed.


Effect of Korean red ginseng on the rabbit corpus cavernosal smooth muscle.
The extracts of Korean red ginseng (EKG) is a complex mixture containing ginsenosides, polysaccharides, and several other products. Animal experiments have shown that the intravenous administration of extract of ginseng reduces blood pressure. Recently, it has been reported that ginseng has a relaxing effect on vascular smooth muscle and that the relaxation is associated with nitric oxide (NO) released from the vascular endothelium. The present study was undertaken to investigate the effects of EKG on isolated rabbit corpus cavernosal smooth muscle for evaluation of the possibility of developing EKG as an pharmacoerecting agent. Strips of rabbit corpus cavernosum were mounted in organ chambers to measure isometric tension. On the precontracted muscle strip with phenylephrine (PHE; 5 x 10(-6) M), EKG began to exert a relaxing effect at the concentration of 1 mg/ml and the maximal relaxation effect was reached at 40 mg/ml in a dose-dependent manner. EKG was inhibited significantly by endothelial disruption and by pretreatment with methylene blue, pyrogallol, L-NNA or atropine. EKG partially inhibited the PHE (5 x 10(-6) M) induced contraction up to 45.67% of the control in a dose-dependent fashion. EKG decreased basal tension as well as inhibited the contraction induced by addition of CaCl2 (10(-3) M) dose-dependently in muscle strips at basal equilibrated state in Ca2+ free, high K+ depolarizing solution. EKG also inhibited the contraction induced by depolarization with 20, 40 and 60 mM of KCl. However, this inhibitory effect did not occur with high concentrations of KCl (80 and 120 mM). EKG has a relaxing effect on the rabbit corpus cavernosal tissue in a dose dependent manner. The relaxation action of EKG is mediated by multiple action mechanisms that include increasing the release of NO from the corporal sinusoids, increasing intracellular calcium sequestration, and a hyperpolarizing action.


Interfacial oxygen stabilizes composite silicon anodes.
Silicon can store Li(+) at a capacity 10 times that of graphite anodes. However, to harness this remarkable potential for electrical energy storage, one has to address the multifaceted challenge of volume change inherent to high capacity electrode materials. Here, we show that, solely by chemical tailoring of Si-carbon interface with atomic oxygen, the cycle life of Si/carbon matrix-composite electrodes can be substantially improved, by 300%, even at high mass loadings. The interface tailored electrodes simultaneously attain high areal capacity (3.86 mAh/cm(2)), high specific capacity (922 mAh/g based on the mass of the entire electrode), and excellent cyclability (80% retention of capacity after 160 cycles), which are among the highest reported. Even at a high rate of 1C, the areal capacity approaches 1.61 mAh/cm(2) at the 500th cycle. This remarkable electrochemical performance is directly correlated with significantly improved structural and electrical interconnections throughout the entire electrode due to chemical tailoring of the Si-carbon interface with atomic oxygen. Our results demonstrate that interfacial bonding, a new dimension that has yet to be explored, can play an unexpectedly important role in addressing the multifaceted challenge of Si anodes.


Establishment and characterization of a human gastric carcinoma cell line TMC-1.
Established cancer cell lines are useful in the study of various cancers. We established a human gastric carcinoma cell line TMC-1 derived from the lymph node of a moderately differentiated adenocarcinoma of the stomach. TMC-1 cells grew in vitro as a mixture of attached and suspension cells, and exhibited spindle or ovoid morphology. They had a population doubling time of 15 h, a plating efficiency of 61%, formed colonies in semisolid agar, secreted the tumor marker CA 19-9, and were tumorigenic in athymic nude mice. The cells expressed E-cadherin and beta-catenin. The karyotypic analysis demonstrated hyperdiploid features with a modal chromosome of 53. The cell had the deletion at chromosome 18q and gains at chromosome 2p13-25, 5p15, 5q21-35, 7, 8q24, 9q, 11, 12p, 14q24-32 and 20. Analysis by fluorescence in situ hybridization showed the deletion at 7qtel and duplication at 7q11.2 at the rearranged chromosome 7. Growth of TMC-1 cells was inhibited by 27-32% by interferon-alpha (2,000 U/ml) and by interferon-gamma with an IC50 of 125 U/ml. The cell line is tumorigenic in vivo, and its growth is moderately inhibited by interferon-alpha and interferon-gamma. It can be used to develop new modalities of human gastric cancer treatment.


CRISPR-targeted genome editing of mesenchymal stem cell-derived therapies for type 1 diabetes: a path to clinical success?
Due to their ease of isolation, differentiation capabilities, and immunomodulatory properties, the therapeutic potential of mesenchymal stem cells (MSCs) has been assessed in numerous pre-clinical and clinical settings. Currently, whole pancreas or islet transplantation is the only cure for people with type 1 diabetes (T1D) and, due to the autoimmune nature of the disease, MSCs have been utilised either natively or transdifferentiated into insulin-producing cells (IPCs) as an alternative treatment. However, the initial success in pre-clinical animal models has not translated into successful clinical outcomes. Thus, this review will summarise the current state of MSC-derived therapies for the treatment of T1D in both the pre-clinical and clinical setting, in particular their use as an immunomodulatory therapy and targets for the generation of IPCs via gene modification. In this review, we highlight the limitations of current clinical trials of MSCs for the treatment of T1D, and suggest the novel clustered regularly interspaced short palindromic repeat (CRISPR) gene-editing technology and improved clinical trial design as strategies to translate pre-clinical success to the clinical setting.


Dynamics of Soil Bacterial Communities Over a Vegetation Season Relate to Both Soil Nutrient Status and Plant Growth Phenology.
Soil microorganisms regulate element cycling and plant nutrition, mediate co-existence of neighbors, and stabilize plant communities. Many of these effects are dependent upon environmental conditions and, in particular, on nutrient quality and availability in soils. In this context, we set up a pot experiment in order to examine the combined effects of soil nutrient availability and microbial communities on plant-soil interactions and to investigate assemblage rules for soil bacterial communities under changed nutrient conditions. Four gamma-sterilized soils, strongly differing in their nutrient contents, were obtained from different fertilization treatments of a centenary field experiment and used to grow communities of grassland plants. The sterilized soils were either self- or cross-inoculated with microbial consortia from the same four soils. Molecular fingerprinting analyses were carried out at several time points in order to identify drivers and underlying processes of microbial community assemblage. We observed that the bacterial communities that developed in the inoculated sterilized soils differed from those in the original soils, displaying dynamic shifts over time. These shifts were illustrated by the appearance of numerous OTUs that had not been detected in the original soils. The community patterns observed in the inoculated treatments suggested that bacterial community assembly was determined by both niche-mediated and stochastic-neutral processes, whereby the relative impacts of these processes changed over the course of the vegetation season. Moreover, our experimental approach allowed us not only to evaluate the effects of soil nutrients on plant performance but also to recognize a negative effect of the microbial community present in the soil that had not been fertilized for more than 100 years on plant biomass. Our findings demonstrate that soil inoculation-based approaches are valid for investigating plant-soil-microbe interactions and for examining rules that shape soil microbial community assemblages under variable ecological conditions.


Fast and Noninvasive Characterization of Suspicious Lesions Detected at Breast Cancer X-Ray Screening: Capability of Diffusion-weighted MR Imaging with MIPs.
To evaluate the ability of a diagnostic abbreviated magnetic resonance (MR) imaging protocol consisting of maximum intensity projections (MIPs) from diffusion-weighted imaging with background suppression (DWIBS) and unenhanced morphologic sequences to help predict the likelihood of malignancy on suspicious screening x-ray mammograms, as compared with an abbreviated contrast material-enhanced MR imaging protocol and a full diagnostic breast MR imaging protocol. This prospective institutional review board-approved study included 50 women (mean age, 57.1 years; range, 50-69 years), who gave informed consent and who had suspicious screening mammograms and an indication for biopsy, from September 2014 to January 2015. Before biopsy, full diagnostic contrast-enhanced MR imaging was performed that included DWIBS (b = 1500 sec/mm(2)). Two abbreviated protocols (APs) based on MIPs were evaluated regarding the potential to exclude malignancy: DWIBS (AP1) and subtraction images from the first postcontrast and the unenhanced series (AP2). Diagnostic indexes of both methods were examined by using the McNemar test and were compared with those of the full diagnostic protocol and histopathologic findings. Twenty-four of 50 participants had a breast carcinoma. With AP1 (DWIBS), the sensitivity was 0.92 (95% confidence interval [CI]: 0.73, 0.98), the specificity was 0.94 (95% CI: 0.77, 0.99), the negative predictive value (NPV) was 0.92 (95% CI: 0.75, 0.99), and the positive predictive value (PPV) was 0.93 (95% CI: 0.75, 0.99). The mean reading time was 29.7 seconds (range, 4.9-110.0 seconds) and was less than 3 seconds (range, 1.2-7.6 seconds) in the absence of suspicious findings on the DWIBS MIPs. With the AP2 protocol, the sensitivity was 0.85 (95% CI: 0.78, 0.95), the specificity was 0.90 (95% CI: 0.72, 0.97), the NPV was 0.87 (95% CI: 0.69, 0.95), the PPV was 0.89 (95% CI: 0.69, 0.97), and the mean reading time was 29.6 seconds (range, 6.0-100.0 seconds). Unenhanced diagnostic MR imaging (DWIBS mammography), with an NPV of 0.92 and an acquisition time of less than 7 minutes, could help exclude malignancy in women with suspicious x-ray screening mammograms. The method has the potential to reduce unnecessary invasive procedures and emotional distress for breast cancer screening participants if it is used as a complement after the regular screening clarification procedure.


Dentists and AIDS: a survey of knowledge, attitudes, and behavior in Italy.
Italy, together with Spain, is second only to France in the total number of AIDS cases in Europe, with over 16,800 as of March 1993. The purpose of this study was to evaluate knowledge, attitudes, and behavior concerning AIDS and infection control among Italian dentists. A questionnaire was mailed to 1,000 dentists randomly selected from the Italian Dental and Maxillo-Facial Association's register of dentists. Of the 715 dentists responding, 70.7 percent of dentists knew all the main risk groups able to transmit the infection and that semen is a biologic fluid potentially contaminated by HIV virus. This knowledge was greater if the number of patients per week was not higher than 55 and if the dentist had had a previous contact with an HIV-seropositive patient. Only a few (21.1%) knew all the oral manifestations of AIDS. Over 65 percent of the dentists indicated that they would treat HIV-seropositive patients (71.9%) or those with AIDS (66.8%). Dentists were more willing to care for an HIV-seropositive patient if they were involved in specialties with high blood contact, if they had a previous contact with an HIV patient, as the average number of patients per week increased, and if they did not consider saliva as a possible route of transmission of HIV. A small percentage of dentists who had the opportunity to treat patients at risk for AIDS (12.1%) or HIV seropositive (9.4%) refused to treat them. Willingness to treat was the most significant predictor of actual treatment of an infected patient. Only 24.4 percent routinely used all barrier techniques (gloves, masks, and protective eyewear). Predictors of routine use of all barrier techniques were specialties with high blood contact, considering saliva a possible route of transmission of HIV infection, average number of patients per week fewer than 40, and number of years of practice. Educational efforts for improving knowledge and finding and implementing ways to motivate dentists to the correct and routine use of infection control procedures are needed.


The Impact of Body Mass Index on Perioperative Outcomes of Robotic Adrenalectomy: An Update.
Background. Robotic surgery has gained increasing popularity over the past 2 decades. However, factors including patient comorbidities and tumor characteristics are still crucial factors for outcomes of surgery. In this study, we evaluated the impact of body mass index (BMI) on perioperative outcomes in patients who underwent robotic adrenal surgery. Methods. Between May 2012 and November 2017, 66 consecutive patients who underwent robotic adrenalectomy were included in this study. Patients were divided into 2 groups based on their BMI: nonobese (<30 kg/m2) and obese (≥30 kg/m2). Additionally, patient demographics, tumor size, total operative time, docking time, console time, estimated blood loss, conversion to open, complications, additional analgesia requirement, length of hospital stay, and rough costs were evaluated. Results. Of the 66 patients, a total of 26 patients were obese (30%). Between study groups, the median BMI was calculated as 26 (18-29) and 33 (30-57). The groups were similar in terms of age, gender, American Society of Anesthesiologists scores, and previous history of abdominal surgery. Likewise, there were no significant differences between groups regarding total operative time (P = .085), docking time (P = .196), console time (P = .211), estimated blood loss (P = .180), complications (P = .991), length of hospital stay (P = .598), and rough costs (P = .468). Five cases were converted to open surgery. Nonobese cases required additional analgesia (P = .007). We had no unexpected hospitalizations in either group. Conclusion. Guidelines express the advantages of robotic surgery in obese patients. No statistically significant differences were detected between the 2 groups except for the additional analgesia required in nonobese patients.


Occupational hazard evaluation of working population in a select automotive industrial plant.
The research was conducted in the selected vehicle industry plant. Work conditions were assessed on the assembly line by measuring chemical and physical factors. Exposure to noise in the investigated plant exceeded the values of permissible standards. The pollution on the posts did not exceed the standards except singular concentrations. While assessing the values of chemical factors concentration, no toxicological danger was revealed in the investigated population. The work conditions of the investigated plant did not create the danger of professional diseases.


The effect of high fat diet on daily rhythm of the core clock genes and muscle functional genes in the skeletal muscle of Chinese soft-shelled turtle (Trionyx sinensis).
In the present study, we sought to investigate the influence of high fat diet on the core clock genes and the muscle functional genes daily expression in the skeletal muscle of Chinese soft-shelled turtle. The turtles were fed by two diets including a control fat diet (the CON treatment, 7.98% lipid) and a high fat diet (the HFD treatment, 13.86% lipid) for six weeks and administrated by the photophase regimen of 24h light/dark (12L:12D) cycle. After the feeding trial experiment, we measured the daily expression levels of 17 core clock genes (Clock, Bmal1/2, NPAS2, Tim, Cry1/2, Per1/2, DBP, AANAT, NIFL3, BHLHE40, NR1D2, RORA, RORB, RORC) and 12 muscle functional genes (FBXO32, MBNL1, MSTN, Myf5, Myf6, MyoD, MyoG, MyoM1, PPARa, PDK4, Trim63, UCP3) in the skeletal muscle of the two treatments. The results showed that except for Bmal1, NPAS2, Per2 and RORB, the expression of the other 13 core clock genes exhibited circadian oscillation in the CON treatment. Among the 12 muscle functional genes, MBNL1, PDK4 and MyoM1 did not exhibit circadian oscillation in the CON treatment. In the HFD treatment, the circadian rhythms expressional patterns of the 8 core clock genes (Clock, Bmal2, Cry2, Per1, DBP, NFIL3, BHLHE40 and RORA) and 6 muscle functional genes (MSTN, Myf5, MyoD, MyoG, PPARa and Trim63) were disrupted. In addition, compared with the CON treatment, the circadian expression of the 5 core clock genes (Tim, Cry1, AANAT, NR1D2, RORC) and the 3 muscle functional genes (FBXO32, Myf6, UCP3) showed the advanced or delayed expression peaks in the HFD treatment. In CON treatment, the circadian expression of the MyoG, MyoD, Myf6, FBXO32 and PPARa showed positive or negative correlation with the transcription pattern of Clock, Bmal2, Cry1/2, Per1/2. However, only the FBXO32 and Myf6 presented positive or negative correlation with the circadian expression of Cry1, RORB, AANAT and Tim in HFD treatment. In summary, these results demonstrate that the disruption of the circadian rhythm of the core clock genes and muscle functional genes in the skeletal muscle is closely associated with feeding high fat diet to Chinese soft-shelled turtle.


Properties of nanocrystalline Fe75Si15M10 (M-Cr and Al) powders prepared by mechanical alloying.
We report the structural and magnetic properties of the nanocrystalline Fe75Si15M10 (M-Al and Cr) powders prepared by mechanical alloying. The milling process produced a non-equilibrium solid solutions of bcc alpha-Fe(Si,Cr) and alpha-Fe(Si,Al). The average dislocation density increases and the average crystallite size decreases with increasing milling time. Magnetic property studies show that the coercivity of the sample increases and magnetization of the sample decreases with increasing milling time. The evolution of a non-equilibrium solid solution and the resulting magnetic properties of nanocrystalline powders are explained on the basis of Neel theory and modified random anisotropy model proposed by Shen et al.


Relationship between left ventricular mass and endothelium-dependent vasodilation in never-treated hypertensive patients.
Hypertensive patients are characterized by development of both left ventricular hypertrophy (LVH) and endothelial dysfunction We enrolled 65 never-treated hypertensive patients (36 men and 29 women aged 45.6+/-6.0 years) to assess the possible relationship between echocardiographic left ventricular mass (LVM) and endothelium-dependent vasodilation. Left ventricular measurements were performed at end diastole and end systole according to the recommendations of the American Society of Echocardiography and the Penn Convention. LVM was calculated with the Devereux formula and indexed by body surface area and height raised to the 2.7th power. The endothelial function was tested as responses of forearm vasculature to acetylcholine (ACh), an endothelium-dependent vasodilator (7.5, 15, and 30 microg. mL-1. min-1, each for 5 minutes), and sodium nitroprusside (SNP), an endothelium-independent vasodilator (0.8, 1.6, and 3.2 microg. mL-1. min-1, each for 5 minutes). Drugs were infused into the brachial artery, and forearm blood flow (FBF) was measured by strain-gauge plethysmography. A negative significant relationship between indexed LVM and peak of increase in FBF was found during ACh infusions (r=-0. 554; P<0.0001). In addition, hypertrophic patients had a significantly lower responsive to ACh than patients without LVH (the peak increase in FBF was 9.9+/-3.7 versus 16.1+/-8.1 mL per 100 mL of tissue per minute; P<0.0001). No significant correlation was observed between LVM and FBF during SNP infusion. Our data provide the first evidence that echocardiographic LVM in hypertensive patients is inversely related to FBF responses to the endothelium-dependent vasodilating agent ACh, but it is likely that both endothelium and LVM are damaged by hypertension.


Cyclosporin A inhibits the propagation of influenza virus by interfering with a late event in the virus life cycle.
Influenza is a global public health problem that causes a serious respiratory disease. Influenza virus frequently undergoes amino acid substitutions, which result in the emergence of drug-resistant viruses. To control influenza viruses that are resistant to currently available drugs, it is essential to develop new antiviral drugs with a novel molecular target. Here, we report that cyclosporin A (CsA) inhibits the propagation of influenza virus in A549 cells by interfering with a late event in the virus life cycle. CsA did not affect adsorption, internalization, viral RNA replication, or synthesis of viral proteins in A549 cells, but inhibited the step(s) after viral protein synthesis, such as assembly or budding. In addition, siRNA-mediated knockdown of the expression of the major CsA targets, namely cyclophilin A (CypA), cyclophilin B (CypB), and P-glycoprotein (Pgp), did not inhibit influenza virus propagation. These results suggest that CsA inhibits virus propagation by mechanism(s) independent of the inhibition of the function of CypA, CypB, and Pgp. CsA may target an unknown molecule that works as a positive regulator in the propagation of influenza virus. Our findings would contribute to the development of a novel anti-influenza virus therapy and clarification of the regulatory mechanism of influenza virus multiplication.


Forced Spreading of Aqueous Solutions on Zwitterionic Sulfobetaine Surfaces for Rapid Evaporation and Solute Separation.
Solute separation of aqueous mixtures is mainly dominated by water vaporization. The evaporation rate of an aqueous drop grows with increasing the liquid-gas interfacial area. The spontaneous spreading behavior of a water droplet on a total wetting surface provides huge liquid-gas interfacial area per unit volume; however, it is halted by the self-pinning phenomenon upon addition of nonvolatile solutes. In this work, it is shown that the solute-induced self-pinning can be overcome by gravity, leading to anisotropic spreading much faster than isotropic spreading. The evaporation rate of anisotropic spreading on a zwitterionic sulfobetaine surface is 25 times larger as that on a poly(methyl methacrylate) surface. Dramatic enhancement of evaporation is demonstrated by simultaneous formation of fog atop liquid film. During anisotropic spreading, the solutes are quickly precipitated out within 30 s, showing the rapid solute-water separation. After repeated spreading process for the dye-containing solution, the mean concentration of the collection is doubled, revealing the concentration efficiency as high as 100%. Gravity-enhanced spreading on total wetting surfaces at room temperature is easy to scale-up with less energy consumption, and thus it has great potentials for the applications of solute separation and concentration.


Recognizing the need for evidence-based macro practices in organizational and community settings.
The need for using evidence-based macro practices is examined. EBP is viewed as practitioners recognizing client values and then using the most promising research to guide programmatic, organizational, community, and policy activities to facilitate change. There are multiple ways to search for evidence. The nature of evidence in macro practice will look different depending on the practice situation. Being able to assess the situation and recognize the context in which one is practicing will set the stage for how EBP should be defined. A set of questions are suggested to guide decision-making regarding the use and the management of evidence.


Ultrasound of sacroiliac joints in spondyloarthritis: a systematic review.
Ultrasound (US) is an accessible imaging technique with a possible role to diagnose active sacroiliitis, so this technique is projected as a promising diagnostic tool for the diagnosis of SpA. We analyse the available evidence about the use of US as a diagnostic tool in sacroiliitis in patients with SpA, by a systemic review of the literature fulfilling OMERACT criteria. A systematic literature search for original articles was carried out using four databases (Medline, Embase, Scopus and Web of Science). Data from studies were included only if participants had SpA and a US examination of sacroiliac joint (SIJ) was performed. The methodological quality of the studies was assessed using QUADAS-2 tool. Thirteen studies were included. All studies were observational, prospective and cross-sectional. In most articles (76.9%), the main US finding compatible with sacroiliitis evaluated was the presence of vascularisation (Doppler signals) with measurements of the resistive index (RI). The sensitivity and specificity analysis were performed in seven studies (58.8%) and were good, with a median of 90 and 89.2%, respectively. The studies showed a positive to moderate a strong correlation between the US and the gold standard but this was optimal only in four studies. In general, the agreement was good in all studies (≥ 0.80). The methods of evaluation of sacroiliitis vary between the studies included. To date, there is not enough evidence to support the use of ultrasound as a diagnostic method for sacroiliitis but it has potential to identify structural lesions at SIJ's level.


Recent progress in synchrotron radiation 3D-4D nano-imaging based on X-ray full-field microscopy.
The advent of high-flux, high-brilliance synchrotron radiation (SR) has prompted the development of high-resolution X-ray imaging techniques such as full-field microscopy, holography, coherent diffraction imaging and ptychography. These techniques have strong potential to establish non-destructive three- and four-dimensional nano-imaging when combined with computed tomography (CT), called nano-tomography (nano-CT). X-ray nano-CTs based on full-field microscopy are now routinely available and widely used. Here we discuss the current status and some applications of nano-CT using a Fresnel zone plate as an objective. Optical properties of full-field microscopy, such as spatial resolution and off-axis aberration, which determine the effective field of view, are also discussed, especially in relation to 3D tomographic imaging.


Developing immunotherapeutic strategies to target brain tumors.
Recent years have seen rapid growth in cancer treatments that enhance the anti-tumor activities of the immune system. Collectively known as immunotherapy, modulation of the immune system has shown success treating some hematological malignancies, but has yet to be successfully applied to the treatment of patients with brain tumors. This review highlights mechanistic insights from murine studies and compiled recent clinical trial data, focusing on the most aggressive brain tumor, glioblastoma (GBM). The field has recently accumulated a critical mass of data, and we discuss past treatment failures in the context of newly developed approaches now entering clinical trials. This article provides an overview of the immunotherapeutic armamentarium currently in development for the treatment of patients with GBM, who are in dire need of safe and effective therapies. Expert commentary: Themes that emerge include the importance of mitigating the effects of an immunosuppressive tumor microenvironment and the potential for innate immune cell activation to enhance cytotoxic anti-tumor activity. Consideration of these studies as a collective may inform the design of new immunotherapies, as well as the immune monitoring protocols for patients participating in clinical trials.


Nuclear origins of brainstem reticulocortical systems in the rat.
Stereotaxic injections of 5% Fast Blue or 1% horseradish peroxidase-wheat germ agglutinin conjugate (HRP-WGA) were made into various cytoarchitectonic or functional regions of the cerebral cortex of anesthetized adult albino or hooded rats. Sections through the brainstems of these animals were then scrutinized for the presence of retrogradely labeled neurons. The data generated by this study indicate that at least 33 distinct nuclei or subnuclei within the brainstem reticular formation of the rat project directly to the cerebral cortex. More than half of these ascending reticulocortical systems are probably aminergic. The strongest reticulocortical projections emanate from presumed aminergic reticular-cell groups located at isthmic levels: specifically, the rostral serotonin-containing cell groups, as well as the noradrenergic locus coeruleus. However, relatively strong direct reticulocortical projections also originate from lower medullary cell groups which are probably catecholaminergic. Moderately strong reticulocortical projections emanate from cholinergic cell groups located at isthmic levels (the pars compacta of the pedunculopontine nucleus and the X area of Sakai). The most surprising finding in this study was that the classic isodendritic, nonaminergic central core of the brainstem gives rise to direct reticulocortical projections. The ventromedial areas of the medullary brainstem reticular formation give rise to the strongest nonaminergic ascending reticular projections, but all levels of the classic isodendritic reticular core give rise to direct reticulocortical projections. As a whole, cortically projecting reticular neurons are mostly small (10-25 microns in greatest diameter) or medium sized (26-35 microns in greatest diameter) neurons. Previous studies have shown that many of the cortically projecting reticular nuclei also project to the spinal cord, and within these nuclei, reticulocortical neurons often strongly resemble their reticulospinal counterparts with respect to details of neuronal morphology. This in turn suggests that some reticulocortical neurons may also project to spinal levels.


Purification of Gnathostoma spinigerum larval antigens by monoclonal antibody affinity chromatography.
An immunoaffinity column was prepared by coupling a partially purified Gnathostoma spinigerum-specific IgG1, MAb SK-6C4 (5 mg/ml) to CNBr-activated Sepharose 4B. Ten milliliters of approximately 0.3 mg/ml of crude soluble G. spinigerum larval antigens (GsAL3) were loaded onto the affinity column at a flow rate of about 5 ml/hour. Elution of the bound antigens was accomplished using 50 mM diethylamine-HCI containing 0.15 M NaCL, pH 11.5. The average amount of eluted antigens obtained by one passage of crude GsAL3 (1-4 mg) through 4 to 8 ml of column matrix was 143 micrograms (range, 67 - 414 micrograms). The minimal amount of purified GsAL3 detectable by ELISA using MAb SK - 6C4 (100 micrograms/ml) was 50 ng/ml. The SK - 6C4 affinity-purified GsAL3 was found to be relatively pure and immunologically specific as determined by SDS-PAGE and Western blotting, respectively.


Overview of boosted protease inhibitors in treatment-experienced HIV-infected patients.
Antiretroviral drug combinations that include two nucleoside reverse transcriptase inhibitors and a protease inhibitor (PI) can suppress HIV replication to undetectable levels, improving the prognosis of HIV-infected individuals. The aim of therapy is complete virological suppression, with a current goal of <50 copies/mL HIV-1 RNA, in order to minimize the occurrence of drug resistance. Improved understanding of the pharmacology of PIs, primarily the importance of adequate drug exposure, has led to the widespread administration of PIs combined with a low 'boosting' dose of ritonavir. The combination of PIs with ritonavir can improve treatment responses in both treatment-naive and -experienced patients. Boosted PIs are an important therapeutic option for HIV and extensive data exist supporting their use. Use of individual agents should be guided by a resistance test at all stages of treatment from naive through to highly treatment-experienced patients. Currently, seven boosted PIs have both US and European licensing approval: indinavir, saquinavir, lopinavir, fosamprenavir, atazanavir, tipranavir and darunavir (formerly TMC114). The preferred first-line option in the USA is lopinavir. Many of the older PIs are less effective and/or have less favourable tolerability profiles. Emergent PI resistance is a major challenge in treatment, and it can be accelerated by partial suppression of viral load through inappropriate therapy combinations. Using the newer boosted PIs, which have more robust resistance profiles, with an optimized background regimen may increase the likelihood of complete viral suppression. This review discusses the relative strengths and weaknesses of boosted PIs in current practice.


Photochromic Crystalline Systems Mimicking Bio-Functions.
Photoresponsive crystalline systems mimicking bio-functions are prepared using photochromic diarylethenes. Upon UV irradiation of the diarylethene crystal, the photogenerated closed-ring isomers self-aggregate to form needle-shaped crystals on the surface. The rough surface shows the superhydrophobic lotus effect. In addition, the rose-petal effects of wetting, the anti-reflective moth-eye effect, and a double-roughness structure mimicking the surface of a lotus leaf are observed by controlling the heating procedures, UV irradiation processes, and molecular structural modification. By changing the molecular structure, a superhydrophilic surface mimicking a snail shell can be generated. We also find the crystal of a diarylethene derivative that shows a photosalient effect. The effect is observed partly due to the hollow structure of the crystal. It is demonstrated that a photo-response similar to the response of impatiens plant to stimulation is observed by packing small beads in the hollow. These photoresponsive functions are unique, and they demonstrate a macroscopic response by means of microscopic molecular movement induced by light. In the future, such a molecular assembly system will be a promising candidate for fabricating photoresponsive architectures and soft robots.


Role of plasmids in Lactobacillus brevis BSO 464 hop tolerance and beer spoilage.
Specific isolates of lactic acid bacteria (LAB) can grow in the harsh beer environment, thus posing a threat to brew quality and the economic success of breweries worldwide. Plasmid-localized genes, such as horA, horC, and hitA, have been suggested to confer hop tolerance, a trait required for LAB survival in beer. The presence and expression of these genes among LAB, however, do not universally correlate with the ability to grow in beer. Genome sequencing of the virulent beer spoilage organism Lactobacillus brevis BSO 464 revealed the presence of eight plasmids, with plasmids 1, 2, and 3 containing horA, horC, and hitA, respectively. To investigate the roles that these and the other five plasmids play in L. brevis BSO 464 growth in beer, plasmid curing with novobiocin was used to derive 10 plasmid variants. Multiplex PCRs were utilized to determine the presence or absence of each plasmid, and how plasmid loss affected hop tolerance and growth in degassed (noncarbonated) beer was assessed. Loss of three of the eight plasmids was found to affect hop tolerance and growth in beer. Loss of plasmid 2 (horC and 28 other genes) had the most dramatic effect, with loss of plasmid 4 (120 genes) and plasmid 8 (47 genes) having significant, but smaller, impacts. These results support the contention that genes on mobile genetic elements are essential for bacterial growth in beer and that beer spoilage ability is not dependent solely on the three previously described hop tolerance genes or on the chromosome of a beer spoilage LAB isolate.


Three-Dimensional Printing Bioceramic Scaffolds Using Direct-Ink-Writing for Craniomaxillofacial Bone Regeneration.
Defects characterized as large osseous voids in bone, in certain circumstances, are difficult to treat, requiring extensive treatments which lead to an increased financial burden, pain, and prolonged hospital stays. Grafts exist to aid in bone tissue regeneration (BTR), among which ceramic-based grafts have become increasingly popular due to their biocompatibility and resorbability. BTR using bioceramic materials such as β-tricalcium phosphate has seen tremendous progress and has been extensively used in the fabrication of biomimetic scaffolds through the three-dimensional printing (3DP) workflow. 3DP has hence revolutionized BTR by offering unparalleled potential for the creation of complex, patient, and anatomic location-specific structures. More importantly, it has enabled the production of biomimetic scaffolds with porous structures that mimic the natural extracellular matrix while allowing for cell growth-a critical factor in determining the overall success of the BTR modality. While the concept of 3DP bioceramic bone tissue scaffolds for human applications is nascent, numerous studies have highlighted its potential in restoring both form and function of critically sized defects in a wide variety of translational models. In this review, we summarize these recent advancements and present a review of the engineering principles and methodologies that are vital for using 3DP technology for craniomaxillofacial reconstructive applications. Moreover, we highlight future advances in the field of dynamic 3D printed constructs via shape-memory effect, and comment on pharmacological manipulation and bioactive molecules required to treat a wider range of boney defects.


Echocardiographic assessment of right ventricular functions in healthy subjects who migrated from the sea level to a moderate altitude.
The aim of this study was to evaluate right ventricle (RV) functions using echocardiography in healthy subjects who migrated from the sea level to moderate altitude (1890 m). The prospective observational in this study population consisted of 33 healthy subjects (23 men; mean age 20.4±3.2 years) who migrated from the sea level to a moderate altitude (Erzurum city centre, 1890 m above sea level) for long-term stay. Subjects underwent echocardiographic evaluation within the first 48 h of exposure to the moderate altitude and at the sixth month of arrival. Conventional echocardiographic parameters such as RV sizes and areas, systolic, and diastolic functional indices [fractional area change (FAC), tricuspid flow velocities, myocardial performance index (MPI), and tricuspid annular plane systolic excursion (TAPSE)] were obtained. Systolic (S) and diastolic (E', A') velocities were acquired from the apical fourchamber view using tissue Doppler imaging. Kolmogorov-Smirnov test, student's t-test, Wilcoxon test, and chi-square test were used in this study. There were no significant changes in RV size, FAC, MPI, TAPSE, inferior inspiratory vena cava collapse, tricuspid E velocity, and tricuspid annulus E' velocity. Compared with the baseline, there was a significant increase in mean pulmonary artery pressure (p=0.001); RV end systolic area (p=0.014); right atrial end diastolic area (p=0.021); tricuspid A velocity (p=0.013); tricuspid annulus S and A' velocity (p=0.031 and p=0.006, respectively); and RV free wall S, E', and A' velocity (p=0.007, p<0.001, and p=0.007 respectively) at the sixth month. Also, there was a significant decrease in tricuspid E/A ratio (1.61±0.3 vs. 1.45±0.2, p=0.038) and tricuspid annulus E'/A' ratio (1.52±0.5 vs. 1.23±0.4, p=0.002) at the sixth month. Our study revealed that right ventricular diastolic function was altered while the systolic function was preserved in healthy subjects who migrated from the sea level to a moderate altitude.


Reply to "Comment on 'Analytical investigation of the open boundary conditions in the Nagel-Schreckenberg model' ".
Recent reports [N. Jia and S. Ma, Phys. Rev. E 79, 031115 (2009); T. Neumann and P. Wagner, Phys. Rev. E 80, 013101 (2009)] have different opinions on the exact analytical solution of the inflow in the Nagel-Schreckenberg model with expanded left boundary condition. In the current study, the different implementations of the "expanded left boundary" are proven to cause the confliction. Detailed analyses show that both reports are reasonable, depending on whether the rule "clear the minisystem first" is applied.


[Obesity in sculptures of the paleolithic era].
In this paper I present 100 neolithic figurines (97 female and 3 male) made of ivory, mammuth bone, limestone and other substances. The sculptures were found on the Eurasian continent, from the Pirenees to Lake Baikal and the river Amur. More than half (57.3%) of the idols show various types of female obesity. However, they are named ironically "Venus"-es. The figurines are described and speculation underlying the reason for such depictions and their uses are presented.


Validation of a Dietary Questionnaire to Screen Omega-3 Fatty Acids Levels in Healthy Adults.
To facilitate a clinical observational study to identify healthy volunteers with low (defined as ≤4%) and high (defined as ≥5.5%) omega-3 indices, a dietary questionnaire to rapidly assess habitual dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was developed. This study aimed to determine the validity of this newly developed dietary questionnaire. One hundred and eight volunteers were included and were assessed for habitual dietary intake of EPA and DHA using the questionnaire. The United States Department of Agriculture food products database and nutrition fact label was referenced for calculation. Blood samples were collected for the analysis of fatty acids in whole blood specimens and to derive omega-3 indices. A linear correlation was observed between reported dietary consumption of EPA, DHA, EPA+DHA and the whole blood levels of EPA, DHA, and the omega-3 indices (r = 0.67, 0.62, 0.67, respectively, p < 0.001 for all). The findings also suggested that the questionnaire was substantially better at identifying volunteers with high omega-3 indices (sensitivity 89%, specificity 84%, and agreement 86%) compared to volunteers with low omega-3 indices (sensitivity 100%, specificity 66%, and agreement 42%). In conclusion, this newly developed questionnaire is an efficient tool for the assessment of omega-3 indices in study populations and is particularly effective in identifying individuals with high omega-3 indices.


Effect of surface capping with poly(vinyl alcohol) on the photocarrier relaxation of ZnO nanowires.
The effect of surface capping with poly(vinyl alcohol) (PVA) on the photocarrier relaxation of the aqueous chemically grown ZnO nanowires (NWs) has been investigated. The decay in the photocurrent during steady ultraviolet illumination due to the photocarrier relaxation has been reduced in the capped NWs, as evidenced from a decrease in the photocurrent only by 12% of its maximum value under steady illumination for 15 min and a decrease in the photocurrent by 49% of its maximum value during the same interval of time in the as-grown NWs. The surface modification is confirmed from the FESEM, HRTEM, and FTIR results. The photoluminescence spectrum shows an enhanced ultraviolet emission and a reduced defect-related emission in the capped ZnO NWs compared to bare ZnO.


Fungal isolation from disinfectant solutions of contact lens storage cases among asymptomatic users.
To investigate the incidence of fungal contamination of store disinfectant solutions contained in contact lens storage cases belonging to asymptomatic contact lens users. Asymptomatic contact lens users were asked to bring their storage cases, lenses included, without having opened the lid of the cup after placing lenses inside. The following information was recorded: age, sex, type of refractive error, contact lens material, schedule of wear, and brand of disinfectant solution. Included subjects had to comply with lens handling, cleaning, and replacement instructions given by the manufacturer or their attending optometrist. One sample per cup of contact lens case was collected using a sterile syringe. Samples were cultured on proper media for 96 hr at 35°C. Fungi were identified to species level by standard methodology. A total of 216 samples were collected from 117 contact lens storage cases. All participants were using monthly disposable hydrogel lenses on a daily wear basis. Seven fungal species were isolated from 15 specimens (6.9%) collected from 12 storage cases (10.2%). These included one Fusarium solani, four Aspergillus niger, two Aspergillus fumigatus, five Candida parapsilosis, one Candida tropicalis, one Rhodotorula rubra, and one F. solani in combination with Candida guilliermondii. Disinfectant solutions containing hydrogen peroxide were found to be less effective than various alternative solutions in eliminating fungal species. The results of this study show that even when contact lens users report compliance for handling, cleaning, and replacement according to the manufacturer's instructions, the potential risk of contact lens-related fungal keratitis still remains.


Infliximab therapy in pediatric patients 7 years of age and younger.
Infliximab (IFX) is efficacious for induction and maintenance of remission in pediatric patients with moderate-to-severe inflammatory bowel disease (IBD). It has, however, not been studied in patients 7 years old and younger. Our aim was to characterize efficacy and safety of IFX therapy in this cohort. This was a retrospective study of patients with IBD ages 7 years and younger, treated with IFX between 1999 and 2011. Medical records were reviewed for age of diagnosis, disease phenotype, therapy, surgery, IFX infusion dates, dose, and intervals. Outcome measures included physician global assessment, corticosteroid requirement, and adverse events. Thirty-three children (ages 2.4-7 years) were included. Twenty patients had Crohn disease, 4 had ulcerative colitis, and 9 had indeterminate colitis. Maintenance of IFX therapy at 1, 2, and 3 years was 36%, 18%, and 12%, respectively. Patients of age 5 years and younger had the lowest rates of maintenance of therapy at 25% at year 1, and 10% at years 2 and 3 combined. Nine percent of all of the patients demonstrated response measured by the physician global assessment and were steroid free at 1 year. There were 8 infusion reactions. There were no malignancies, serious infections, or deaths. IFX demonstrated a modest response rate and a low steroid-sparing effect in patients with IBD 7 years old and younger. Although this is a limited study, there appears to be a trend for decreased sustained efficacy with IFX in this age group, particularly in children 5 years old and younger, when compared with the previously published literature in older children.


[Neonatal endocarditis due to staphylococcus aureus as a complication of neonatal sepsis].
We present the case of a newborn with bacterial endocarditis with mitral valve involvement as a complication of late-onset sepsis due to Staphylococcus aureus with associated pyelonephritis and meningitis. The diagnosis was confirmed by echocardiogram and blood culture with growth of S. aureus. Treatment was medical and surgical. Neonatal bacterial endocarditis is extremely difficult to diagnose. The signs and symptoms are usually nonspecific and cannot be distinguished from those of sepsis or congenital heart disease. Consequently, a high degree of suspicion is needed for the early diagnosis of this condition. Echocardiography should be performed in children who present sepsis and heart murmur and even in those with staphylococcemia (sepsis due to S. aureus) without associated heart murmur. This investigation enables an early diagnosis of endocarditis to be made and appropriate treatment to be given without having to wait for the development of signs and symptoms that frequently go undetected.


Quantum flux densities for electronic-nuclear motion: exact versus Born-Oppenheimer dynamics.
We study the coupled electronic-nuclear dynamics in a model system to compare numerically exact calculations of electronic and nuclear flux densities with those obtained from the Born-Oppenheimer (BO) approximation. Within the adiabatic expansion of the total wave function, we identify the terms which contribute to the flux densities. It is found that only off-diagonal elements that involve the interaction between different electronic states contribute to the electronic flux whereas in the nuclear case the major contribution belongs to the BO electronic state. New flux densities are introduced where in both, the electronic and the nuclear case, the main contribution is contained in the component corresponding to the BO state. As a consequence, they can be determined within the BO approximation, and an excellent agreement with the exact results is found. This article is part of the theme issue 'Chemistry without the Born-Oppenheimer approximation'.


Surgical Instrument Signaling Gesture Recognition Using Surface Electromyography Signals.
Surgical Instrument Signaling (SIS) is compounded by specific hand gestures used by the communication between the surgeon and surgical instrumentator. With SIS, the surgeon executes signals representing determined instruments in order to avoid error and communication failures. This work presented the feasibility of an SIS gesture recognition system using surface electromyographic (sEMG) signals acquired from the Myo armband, aiming to build a processing routine that aids telesurgery or robotic surgery applications. Unlike other works that use up to 10 gestures to represent and classify SIS gestures, a database with 14 selected gestures for SIS was recorded from 10 volunteers, with 30 repetitions per user. Segmentation, feature extraction, feature selection, and classification were performed, and several parameters were evaluated. These steps were performed by taking into account a wearable application, for which the complexity of pattern recognition algorithms is crucial. The system was tested offline and verified as to its contribution for all databases and each volunteer individually. An automatic segmentation algorithm was applied to identify the muscle activation; thus, 13 feature sets and 6 classifiers were tested. Moreover, 2 ensemble techniques aided in separating the sEMG signals into the 14 SIS gestures. Accuracy of 76% was obtained for the Support Vector Machine classifier for all databases and 88% for analyzing the volunteers individually. The system was demonstrated to be suitable for SIS gesture recognition using sEMG signals for wearable applications.


Risk factors and outcome of PCR-detected Clostridium difficile infection in ileal pouch patients.
The clinical implication of Clostridium difficile infection (CDI) in patients with ileal pouch-anal anastomosis (IPAA) for underlying inflammatory bowel disease (IBD) has not been well studied. This study was designed to investigate the cumulative incidence, risk factors, and outcome of CDI in patients with ileal pouches. Consecutive IPAA patients (n = 196) from the subspecialty Pouchitis Clinic with an increase of at least three stools per day more from the postoperative baseline for more than 4 weeks were enrolled from October 2010 to December 2011. CDI was diagnosed based on the presence of symptoms and positive polymerase chain reaction (PCR)-based stool test for C. difficile toxin B. Risk factors for CDI were assessed with univariate and multivariate analyses. All patients with CDI (n = 21) were treated with oral vancomycin (500 - 1000 mg/day) for 2-4 weeks. The treatment outcome of these patients was documented. Twenty-one patients (10.7%) were diagnosed with CDI. On univariate analysis, patients with CDI had more stool frequency (P = 0.014) and significant current weight loss (P = 0.003) than patients with no CDI. In logistic regression analysis, there was a trend that recent hospitalization (odds ratio [OR] = 4.00, 95% confidence interval [CI], 0.95-16.84) might be associated with CDI. Of the 14 CDI patients with follow-up data, eight (57.1%) had either recurrent (n = 5) or refractory (n = 3) CDI after oral vancomycin therapy. A high index of suspicion for CDI in pouch patients should be given to those with recent hospitalization or constitutional symptoms, such as weight loss. Recurrent or refractory CDI is common, even with standard oral vancomycin therapy.


Demography and Population Projection of Aphis fabae (Hemiptera: Aphididae): with Additional Comments on Life Table Research Criteria.
We collected developmental, survival, and reproduction data for Aphis fabae Scopoli (Hemiptera: Aphididae) reared on faba bean, Vicia faba L. 'Sevilla' at four constant temperatures (15, 20, 25, and 30°C), 70% relative humidity, and a photoperiod of 16:8 (L:D) h. The highest intrinsic rate of increase (r = 0.4347 d(-1)) and finite rate (λ = 1.5445 d(-1)) were observed at 25°C. The population projection based on the age-stage, two-sex life table quantitatively revealed the growth potential and stage structure of the aphid. We have included the following suggestions to aid researchers in life table studies: 1) The bootstrap method should be used to estimate the variance and SEs of developmental time, survival rate, fecundity, and population parameters. 2) The required number of bootstraps is dependent on the life table data--the higher the variation among individuals, the higher the number of bootstraps should be. In most cases, we suggest that 100,000 bootstraps should be used to obtain a stable estimate of variance and SEs. 3) Computer projection based on the age-stage, two-sex life table should be used to reveal the stage structure during population growth. 4) We used a simple equation based on the total fecundity, survival rate to adult stage, and first reproductive age to detect possible errors in life table parameters. 5) To assist readers in comprehending results, life table studies should include the cohort size, preadult survival rate, number of emerged female adults, mean fecundity, survival and fecundity curves, and population parameters.


Elastin: relation of protein and gene structure to disease.
The elastic properties of many tissues such as the lung, dermis, and large blood vessels are due to the presence of elastic fibers in the extracellular space. These fibers have been shown by biochemical and ultrastructural analysis to be comprised of two distinct components, a more abundant amorphous component and the microfibrillar component. The microfibrillar component is found in 10- to 12-nm fibrils which are located primarily around the periphery of the amorphous component but, to some extent, interspersed within it. The protein, elastin, makes up the highly insoluble amorphous component and is responsible for the elastic properties. Elastin is found throughout the vertebrate kingdom except for very primitive fish and possesses an unusual chemical composition consonant with its characteristic physical properties. Elastin is composed largely of glycine, proline, and other hydrophobic residues and contains multiple lysine-derived cross-links, such as the desmosines, which link the individual polypeptide chains into a rubber-like network. The intervening, hydrophobic regions of the polypeptide chains between the cross-links are highly mobile, and the elastic properties of the fibers can be described in terms of the theory of rubber elasticity. Recent application of recombinant DNA techniques has led to further understanding of the structure of elastin. Analyses of the bovine and human elastin genes have demonstrated that the hydrophobic and cross-linking domains are encoded in separate exons. These exons tend to be small, varying from 27 to 114 base pairs, and are separated by large intervening sequences. Furthermore, DNA sequence analysis has demonstrated that the elastin molecule contains two cysteine residues which were not previously identified near the carboxy terminus and which may be important in the interaction of elastin with other extracellular matrix proteins. Further DNA sequencing should determine the complete amino acid sequence of elastin. Biosynthetic studies and in vitro translation of elastin mRNA have demonstrated that a 72,000-dalton polypeptide, designated tropoelastin, is the initial translation product. Analysis of several developing systems has demonstrated that elastin synthesis is controlled by the level of elastin mRNA. After packaging into membrane-bound vesicles in the Golgi apparatus, tropoelastin is secreted by exocytosis into the extracellular space where it is cross-linked by a copper-requiring extracellular enzyme, lysyl oxidase. Elastin can be solubilized only by proteases that have consequently been designated elastases, although these are general, powerful proteases that can hydrolyze numerous proteins.(ABSTRACT TRUNCATED AT 400 WORDS)


Optimization of deflection of a big NEO through impact with a small one.
Using a small near-Earth object (NEO) to impact a larger and potentially threatening NEO has been suggested as an effective method to avert a collision with Earth. This paper develops a procedure for analysis of the technique for specific NEOs. First, an optimization method is used to select a proper small body from the database. Some principles of optimality are achieved with the optimization process. Then, the orbit of the small body is changed to guarantee that it flies toward and impacts the big threatening NEO. Kinetic impact by a spacecraft is chosen as the strategy of deflecting the small body. The efficiency of this method is compared with that of a direct kinetic impact to the big NEO by a spacecraft. Finally, a case study is performed for the deflection of the Apophis NEO, and the efficiency of the method is assessed.


Enuresis in children with attention-deficit hyperactivity disorder.
We did a retrospective study of the prevalence of nocturnal and diurnal enuresis in patients with attention-deficit hyperactivity disorder (ADHD). Patients with ADHD were identified at a referral center for developmental pediatrics. Control patients were identified at a general pediatric and pediatric allergy clinic. Adjusting for differences in sex and current age, ADHD children at age 6 were 2.7 times more likely than controls to have nocturnal enuresis and 4.5 times more likely to have diurnal enuresis. Results at children's current age were consistent with results at age 6; however, these differences were not statistically significant. Nocturnal and diurnal enuresis was found to be significantly more common in children with ADHD than in control subjects. Physicians who treat patients with ADHD should routinely inquire about the presence of enuresis.


5 alpha-reductase activity in the human hair follicle concentrates in the dermal papilla.
Hair growth depends on a close interaction of different cell populations of the hair follicle. In certain regions of the body, androgens interfere with this highly regulated cooperation in a yet poorly understood manner. The response of hair follicles to androgens can be categorized as androgen-dependent, e.g. in the beard, androgen-sensitive, e.g. in the frontal scalp of affected individuals, or androgen-independent, e.g. in the occipital scalp. At the target cell level, the balance between 5 alpha-reductase, 17 beta-hydroxysteroid-dehydrogenase (17 beta-HSD) and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) yields metabolites with different androgenic potential. We examined this target cell-specific androgen metabolism in microdissected intact sub-units of dermal papillae, connective tissue sheaths (CTS) and root sheaths. In dermal papillae, 5 alpha-reductase predominated with an accumulation of the strong androgen 5 alpha-dihydrotestosterone. The specific activity of 5 alpha-reductase in the papillae exceeded those in the other hair follicle compartments by a factor of at least 14 in the scalp (5.4, 0.4 and 0.1 pmol/h per mm3 in the papilla, CTS and root respectively and at least 80 in the beard (16.0, 0.2 and 0.4 pmol/h per mm3 in the papilla, CTS and root respectively). The root sheath keratinocytes expressed low 5 alpha-reductase levels, but high 17 beta-HSD levels, with androstenedione as the major metabolite. The CTS expressed both 5 alpha-reductase and 17 beta-HSD, resulting in androstenedione, 5 alpha-androsterone and 5 alpha-androstanedione. In the CTS and the root sheath, only minor amounts of 5 alpha-DHT were found. In beard papillae, the 5 alpha-reductase activity was three times that in the occipital scalp papillae. These results indicate that the androgen response of hair follicles depends on a differentiated intrafollicular androgen metabolism and that the dermal papilla might be a primary target in this process.


Study of 3D-printed chitosan scaffold features after different post-printing gelation processes.
3D biomaterial manufacturing strategies show an extraordinary driving force for the development of innovative therapies in the tissue engineering field. Here, the behaviour of 3D printed chitosan (CH)-based scaffolds was explored as a function of the post-printing gelation process. To this purpose, gel forming properties of different media were tested on their capability to retain 3D structure, water content, mechanical resistance and surface/internal porosity. Three different gelation media (i.e. KOH 1.5 M, Na2CO3 1.5 M, ammonia vapours) were selected and the 3D CH scaffolds were tested in terms of biocompatibility toward fibroblast as skin associated human cell line.


Immune response in aged mice exposed to lead.
Mice were exposed to 0, 13, or 1,300 ppm lead in drinking water for 18 months. The immunological assays examined were mitogen (lipopolysaccharide E. coli, concanavalin A, and phytohemagglutinin-P) stimulation of lymphocytes; erythrocyte-antibody (EA), erythrocyte-antibody-complement (EAC), and phagocytosis of macrophages; and EAC of splenic lymphocytes. As measured by the majority of these assays, the low dosage (13 ppm) of lead tended to stimulate certain immune responses (lymphocyte mitosis, EA, and EAC) while the high dosage (1,300 pm) did not provoke an appreciable alteration. The results were interpreted by comparing data on aged mice with data on young adult mice. It was apparent from this comparison that the aged mice were naturally immunosuppressed. Therefore, the results obtained from lead-exposed mice were unpredictable.


Electrochemical potassium-ion intercalation in NaxCoO2: a novel cathode material for potassium-ion batteries.
Reversible electrochemical potassium-ion intercalation in P2-type NaxCoO2 was examined for the first time. Hexagonal Na0.84CoO2 platelets prepared by a solution combustion synthesis technique were found to work as an efficient host for K+ intercalation. They deliver a high reversible capacity of 82 mA h g-1, good rate capability and excellent cycling performance up to 50 cycles.


Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated process involving the scavenger receptor class B type I (SR-BI).
The carotenoid lutein is thought to play a role in the human eye and to protect against age-related macular degeneration. Lutein transport in the human intestine has not been characterized. We examined lutein transport processes using Caco-2 TC-7 monolayers as a model for human intestinal epithelium. Purified lutein was mixed with phospholipids, lysophospholipids, cholesterol, mono-olein, oleic acid and taurocholate to obtain lutein-rich mixed micelles that mimicked those found under physiological conditions. The micelles were added to the apical side of Caco-2 TC-7 cell monolayers for 30 min or 3 h at 37 degrees C. Absorbed lutein, i.e. the sum of lutein recovered in the scraped cells and in the basolateral chamber, was quantified by HPLC. Transport rate was measured (i) as a function of time (from 15 to 60 min), (ii) as a function of micellar lutein concentration (from 1.5 to 15 microM), (iii) at 4 degrees C, (iv) in the basolateral to apical direction, (v) after trypsin pretreatment, (vi) in the presence of beta-carotene and/or lycopene, (vii) in the presence of increasing concentrations of antibody against SR-BI (scavenger receptor class B type 1) and (viii) in the presence of increasing concentrations of a chemical inhibitor of the selective transfer of lipids mediated by SR-BI, i.e. BLT1 (blocks lipid transport 1). The rate of transport of lutein as a function of time and as a function of concentration was saturable. It was significantly lower at 4 degrees C than at 37 degrees C (approx. 50%), in the basal to apical direction than in the opposite direction (approx. 85%), and after trypsin pretreatment (up to 45%). Co-incubation with beta-carotene, but not lycopene, decreased the lutein absorption rate (approx. 20%) significantly. Anti-SR-BI antibody and BLT1 significantly impaired the absorption rate (approx. 30% and 57% respectively). Overall, these results indicate that lutein absorption is, at least partly, protein-mediated and that some lutein is taken up through SR-BI.


[Primary posterior perineal hernia. Case report and review of the literature].
Perineal hernias may occur after the completion of surgery in this region, or may occur as a primary lesion. Among the less frequent are the perineal hernias. Female patient, 42 years old, with perineal tumor mass on the right of the anus, spontaneously occurring, five years of evolution, with dimensions of 6 × 10 cm, soft and reducible behind transverse perineal muscle. With dignosis of primary posterior perineal hernia, surgery was performed by the perineum with Mersilene mesh placement. There was no recurrence after 18 months follow-up. The perineal plasty can be a good alternative for the surgical treatment of primary perineal hernias, as it allows for a better seal, dissect the hernia sac and reduce it properly.


Hypnorelaxation as treatment for myofascial pain disorder: a comparative study.
Hypnorelaxation has a potentially beneficial effect in the treatment of masticatory myofascial pain disorders (MPD). However, there are no data regarding the efficacy of hypnorelaxation in the treatment of MPD compared with other accepted modes of treatment (such as occlusal appliance) or with the mere effect of time. The purpose of the present study was to evaluate the effectiveness of hypnorelaxation in the treatment of MPD compared with the use of occlusal appliance and/or to minimal treatment. The study population consisted of 40 female patients with myofascial pain who were allocated to 1 of 3 possible treatment groups: (1) hypnorelaxation (n = 15), (2) occlusal appliance (n = 15), and (3) minimal treatment group (n = 10). Both active treatment modes (hypnorelaxation and occlusal appliance) were more effective than minimal treatment regarding alleviating muscular sensitivity to palpation. However, only hypnorelaxation (but not occlusal appliance) was significantly more effective than minimal treatment with regard to the patient's subjective report of pain on the Visual Analog Scale. Hypnorelaxation is an effective mode of treatment in MPD, especially with regard to some of the subjective pain parameters.


A Highly Symmetric Bimetallic-Tetracarboxylate Framework: Two-Step Crystallization and Gas Separation Properties.
A novel noninterpenetrated MOF (NbU-2, NbU denotes Ningbo University) based on an enneanuclear bimetallic cluster was synthesized by postsynthetic uptake of Ni(II) ions of a sodium-based framework via two-step crystallization. This result demonstrated that the hydrolysis of metal ions in the step-by-step synthesis process is controllable and provided a new method for synthesizing high-nuclear metal cluster-based MOF materials. Note that the activated NbU-2 displays relatively high CO2/N2 selectivity, which was proved by breakthrough experiments of CO2/N2 mixtures.


[The mammographic images of the irradiated breast after conservative therapy for carcinoma].
The mammographic patterns of the patients treated with conservative surgery (quadrantectomy) plus radiotherapy for early breast carcinoma were evaluated to assess treatment-induced changes over time and to improve the differential diagnosis between postirradiation effects and possible tumor recurrences. The mammographic examinations of 79 patients who had undergone quadrantectomy and radiotherapy for breast carcinoma (stage T1-T2) were examined. Skin thickening, edema, fibrosis, distortion and calcifications were considered and classified by comparing the radiographic patterns of the treated breast with those of the contralateral and untreated one. Pattern changes over time were also evaluated and quantified by comparing serial follow-up examinations of the same breast. The percentage of patients with irradiation-induced skin thickening steadily reduced from 100% at 6 months to just above 50% at 4 years. The number of patients showing diffuse irradiation-induced edema decreased from 56% at 6 months to 15% at 1 year and to 0% at 2 years, while the number of cases with localized edema decreased more slowly. The incidence of localized postirradiation breast fibrosis increased to 74% at 4 years, while diffuse fibrosis stabilized around 14%. The patients with no postoperative breast distortion accounted for nearly 33% of the examined cases, while those with minimal distortion approximated 58% and those with gross distortion 9%. In conclusion, the overall results confirmed the value of mammography in the follow-up of the patients treated with QUART.


1-Acetyl-3-acetoxy-5'5-diphenylhydantoin has colchicine-like activity.
1-Acetyl-3-acetoxy-5'5-diphenylhydantoin (Ac-DPH) is a synthetic derivative of diphenylhydantoin with unusual properties: 1) it inhibits microtubular polymerization and depolymerizes established microtubules; 2) it blocks colchicine binding and displaces colchicine from microtubular protein, although it bears no resemblance to colchicine; and 3) it does not arrest human lymphocytes in metaphase, in contrast to diphenylhydantoin or its metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH).


Pd-Catalyzed Coupling of γ-C(sp(3))-H Bonds of Oxalyl Amide-Protected Amino Acids with Heteroaryl and Aryl Iodides.
Pd-catalyzed regioselective coupling of γ-C(sp(3))-H bonds of oxalyl amide-protected amino acids with heteroaryl and aryl iodides is reported. A wide variety of iodides are tolerated, giving the corresponding products in moderate to good yields. Various oxalyl amide-protected amino acids were compatible in this C-H transformation, thus representing a practical method for constructing non-natural amino acid derivatives.


Sequential therapy of anti-Nogo-A antibody treatment and treadmill training leads to cumulative improvements after spinal cord injury in rats.
Intense training is the most clinically successful treatment modality following incomplete spinal cord injuries (SCIs). With the advent of plasticity enhancing treatments, understanding how treatments might interact when delivered in combination becomes critical. Here, we investigated a rational approach to sequentially combine treadmill locomotor training with antibody mediated suppression of the fiber growth inhibitory protein Nogo-A. Following a large but incomplete thoracic lesion, rats were immediately treated with either anti-Nogo-A or control antibody (2weeks) and then either left untrained or step-trained starting 3weeks after injury for 8weeks. It was found that sequentially combined therapy improved step consistency and reduced toe dragging and climbing errors, as seen with training and anti-Nogo-A individually. Animals with sequential therapy also adopted a more parallel paw position during bipedal walking and showed greater overall quadrupedal locomotor recovery than individual treatments. Histologically, sequential therapy induced the greatest corticospinal tract sprouting caudally into the lumbar region and increased the number of serotonergic synapses onto lumbar motoneurons. Increased primary afferent sprouting and synapse formation onto lumbar motoneurons observed with anti-Nogo-A antibody were reduced by training. Animals with sequential therapy also showed the highest reduction of lumbar interneuronal activity associated with walking (c-fos expression). No treatment effects for thermal nociception, mechanical allodynia, or lesion volume were observed. The results demonstrate that sequential administration of anti-Nogo-A antibody followed in time with intensive locomotor training leads to superior recovery of lost locomotor functions, which is probably mediated by changes in the interaction between descending sprouting and local segmental networks after SCI.