Meta-analysis shows similar risk of thrombosis after drug-eluting stent, bare-metal stent, or angioplasty.
Coronary stent thrombosis remains an important problem after the implantation of different stent types. This study investigates the risk of stent thrombosis associated with the use of drug-eluting stents (DESs), bare-metal stents (BMSs) compared to balloon angioplasty. A meta-analysis of 28 randomized trials involving 5612 versus 7639 versus 2994 patients with coronary heart disease treated with DES, BMS, or balloon angioplasty was therefore performed. Comparing the implantation of DES versus BMS, DES was not found to increase the hazard for thrombosis up to 15 months (odds ratio [OR] = 0.86, 95% confidence interval [CI] 0.58 to 1.3, p < .48). There was also no significant difference in the hazard for subacute thrombosis (SAT) or late stent thrombosis (LST) in the DES versus BMSs group (OR = 0.86, 95% CI 0.50 to 1.5, p < .6 and OR = 0.92, 95% CI 0.50 to 1.68, p < .78, respectively). Comparing incidences of stent thromboses in patients receiving balloon angioplasty or implantation of BMS, the rate of SAT in the balloon angioplasty group (1.7% SAT) versus BMS group (1.8% SAT) was also similar (OR = 0.93, 95% CI 0.61 to 1.4, p < .71). Finally, there was no significant difference in the occurrence of stent thrombosis for the different coatings of DESs. In conclusion, the use of DES was not observed to have a significant effect on stent thrombosis events, compared with the implantation of BMS or balloon angioplasty.


[The role of macrolides in treatment of exacerbations of chronic obstructive pulmonary disease].
Exacerbations of chronic obstructive pulmonary disease (COPD) cause a lot of hospital admissions, mortality, and strongly influence health-related quality of life. Approximately half of COPD exacerbations are associated with bacterial infections and many patients have lower airways colonization. Current guidelines recommend antibotic therapy in course of COPD exacerbation for patients with sputum purulence and suggest correlation between severity of symptoms and the type of infecting pathogen. The most common bacterial pathogens isolated in COPD exacerbation are Haemophilus influenzae and parainfluenzae, Streptococcus pneumoniae and Moraxella catarrhalis. The presence of these bacteria are more common for mild and moderate exacerbations. More virulent organisms such as Staphylococcus aureus and Pseudomonas aeruginosa have been found in more severe cases. Atypical pathogens such Chlamydophila and Mycoplasma could cause exacerbation alone or they could coexist with typical pathogen. Rules of antibiotic therapy and usefulness of macrolides in treatment of COPD exacerbation has been described in the article.


Identification of defense-related genes newly-associated with tomato flower abscission.
The current abscission model suggests the formation of a post-abscission trans-differentiation of a protective layer as the last step of the process. The present report expands the repertoire of genes activated in the tomato flower abscission zone (AZ), which are likely to be involved in defense responses. We identified four different defense-related genes, including: Cysteine-type endopeptidase, α-Dioxygenase 1 (α-DOX1), HopW-1-1-Interacting protein2 (WIN2), and Stomatal-derived factor-2 (SDF2), that are newly-associated with the late stage of the abscission process. The late expression of these genes, induced at 8-14 h after flower removal when pedicel abscission was already in progress, was AZ-specific, and was inhibited by treatments that prevented pedicel abscission, including 1-methylcyclopropene pretreatment or IAA application. This information supports the activation of different defense responses and strategies at the late abscission stages, which may enable efficient protection of the exposed tissue toward different environmental stresses.


Synthesis and antiarrhythmic activity of substituted (2-pyrimidinylthio)acetamidoximes.
A series of (2-pyrimidinylthiomethyl)carbonitriles and -carboxamidoximes was synthesized and the antiarrhythmic effects were evaluated against ventricular arrhythmias as measured by the electrical fibrillatory threshold in the anesthetized dog. Structure-activity studies indicated 2-[4-(p-chlorobenzylamino)-6-methyl-2-pyrimidinylthio]acetamidoxime dihydrochloride (6a) and 2-[4-(1,3-benzodioxol-5-ylmethylamino-6-propyl-2-pyrimidinylthio]acetamidoxime (6g) to be the most potent members of the series.


The moral foreign language effect is stable across presentation modalities.
People's judgements and decisions often change when made in their foreign language. Existing research testing this foreign language effect has predominantly used text-based stimuli with little research focusing on the impact of listening to audio stimuli on the effect. The only existing study on this topic found shifts in people's moral decisions only in the audio modality. First, by reanalysing the data from this previous study and by collecting data in an additional experiment, we found no consistent effects of using foreign language on moral judgements. Second, in both data sets, we found no significant language by modality interaction. Overall, our results highlight the need for more robust testing of the foreign language effect, and its boundary conditions. However, modality of presentation does not appear to be a candidate for explaining its variability. Data and materials for this experiment are available at https://osf.io/qbjxn/.


Target-dependent enrichment of virions determines the reduction of high-throughput sequencing in virus discovery.
Viral infections cause many different diseases stemming both from well-characterized viral pathogens but also from emerging viruses, and the search for novel viruses continues to be of great importance. High-throughput sequencing is an important technology for this purpose. However, viral nucleic acids often constitute a minute proportion of the total genetic material in a sample from infected tissue. Techniques to enrich viral targets in high-throughput sequencing have been reported, but the sensitivity of such methods is not well established. This study compares different library preparation techniques targeting both DNA and RNA with and without virion enrichment. By optimizing the selection of intact virus particles, both by physical and enzymatic approaches, we assessed the effectiveness of the specific enrichment of viral sequences as compared to non-enriched sample preparations by selectively looking for and counting read sequences obtained from shotgun sequencing. Using shotgun sequencing of total DNA or RNA, viral targets were detected at concentrations corresponding to the predicted level, providing a foundation for estimating the effectiveness of virion enrichment. Virion enrichment typically produced a 1000-fold increase in the proportion of DNA virus sequences. For RNA virions the gain was less pronounced with a maximum 13-fold increase. This enrichment varied between the different sample concentrations, with no clear trend. Despite that less sequencing was required to identify target sequences, it was not evident from our data that a lower detection level was achieved by virion enrichment compared to shotgun sequencing.


Eikelboom filamentous morphotypes 0675 and 0041 embrace members of the Chloroflexi: resolving their phylogeny, and design of fluorescence in situ hybridisation probes for their identification.
Although the phylogeny of many of the filamentous bacteria responsible for bulking in activated sludge plants is now known, and fluorescence in situ hybridisation (FISH) probes have been designed for their in situ identification, there are some noticeable exceptions. This study reports the identification of the Eikelboom morphotypes 0041 and 0675. Because these morphotypes differ only in their filament diameters, they are often considered together in surveys based on microscopic identifications. Here we show that they are phylogenetically distinct, and so should be viewed no longer as morphological variants of a single population. Amplicon sequencing data of Australian EBPR plant biomass containing types 0041 and 0675, and phylogenetic analysis have revealed that both, like many other bulking filament morphotypes, are members of the phylum Chloroflexi and probably representatives of two different genera. FISH probes are described here targeting each. Surveys carried out on Australian activated sludge plants suggest that type 0675 occurs more in plants designed to remove phosphorus, while type 0041 shows no such preference, and was seen in biomass samples from a wide range of plant configurations.


Conditional deletion of Atoh1 using Pax2-Cre results in viable mice without differentiated cochlear hair cells that have lost most of the organ of Corti.
Atonal homolog1 (Atoh1, formerly Math1) is a crucial bHLH transcription factor for inner ear hair cell differentiation. Its absence in embryos results in complete absence of mature hair cells at birth and its misexpression can generate extra hair cells. Thus Atoh1 may be both necessary and sufficient for hair cell differentiation in the ear. Atoh1 null mice die at birth and have some undifferentiated cells in sensory epithelia carrying Atoh1 markers. The fate of these undifferentiated cells in neonates is unknown due to lethality. We use Tg(Pax2-Cre) to delete floxed Atoh1 in the inner ear. This generates viable conditional knockout (CKO) mice for studying the postnatal development of the inner ear without differentiated hair cells. Using in situ hybridization we find that Tg(Pax2-Cre) recombines the floxed Atoh1 prior to detectable Atoh1 expression. Only the posterior canal crista has Atoh1 expressing hair cells due to incomplete recombination. Most of the organ of Corti cells are lost in CKO mice via late embryonic cell death. Marker genes indicate that the organ of Corti is reduced to two rows of cells wedged between flanking markers of the organ of Corti (Fgf10 and Bmp4). These two rows of cells (instead of five rows of supporting cells) are positive for Prox1 in neonates. By postnatal day 14 (P14), the remaining cells of the organ of Corti are transformed into a flat epithelium with no distinction of any specific cell type. However, some of the remaining organ of Corti cells express Myo7a at late postnatal stages and are innervated by remaining afferent fibers. Initial growth of afferents and efferents in embryos shows no difference between control mice and Tg(Pax2-Cre)::Atoh1 CKO mice. Most afferents and efferents are lost in the CKO mutant before birth, except for the apex and few fibers in the base. Afferents focus their projections on patches that express the prosensory specifying gene, Sox2. This pattern of innervation by sensory neurons is maintained at least until P14, but fibers target the few Myo7a positive cells found in later stages.


The cardio-protective diet.
Globalization has made calorie rich, cheap, convenient marketed foods the main menu for the common man. Indians are particularly susceptible to the adverse outcomes of this dietary change because of ethnic, epigenetic reasons and sarcopenic adiposity (less muscle more fat for the same body weight). Children have smaller body frame making them more susceptible to adverse effects of hyperglycaemia leading to stress on beta cells and their damage. This has resulted in escalation of lifestyle diseases by three-fold, that too at our younger age group at lower body mass indices. Preventive measures are necessary in early life to protect the beta cells, to achieve a metabolically healthy society. This will help in sustaining optimal beta cell function throughout a person's life. Modification in dietary habits by educating the society, proper food labelling and legal regulation, restricting calorie, sugar, saturated fat, trans-fat and salt intake has proved its benefits in the developed world. Changes in the quality of food is as important as restricting calorie intake. This includes facilitation of increased consumption of dietary fiber, complex carbohydrates, nuts, fruits and vegetables. Restrictions are needed to reduce trans-fats, saturated fats and cooking habits such as deep frying which oxidizes cholesterol and lipids. Foods with long shelf-life shorten the life line because of their salt, sugar or trans-fat content. Individual meals need to be targeted in the general dietary guidelines, to minimize the post-prandial metabolic insult. In general, we need healthy start to early life particularly the first twenty years of life so that the habits cultured during childhood are sustained for the rest of productive years.


The relation between scabies and hypersensitivity to antigens of house dust mites and storage mites.
Twenty five non-atopic scabietic patients were examined to estimate their reaction to crude house dust mite Dermatophagoides farinae (D. farinae) and storage mite Tyrophagus putrescentia (T. putrescentiae) antigens. Skin prick testing (SPT) by extracts of both mites antigens showed significant higher positive results in scabietics when compared to non-scabietic control subjects. Moreover, 60% and 56% of scabietic patients showed positive levels of specific anti-D. farinae and T. putrescentia IgE respectively in comparison to 13.4% & 20% of control subjects. A significant difference has been obtained when the total number of positive results were compared to the total number of negative ones. The results revealed that there is an evidence of cross reactivity between Sarcoptes scabiei antigens and extracts of D. farinae and T. putrescentiae, and the hypersensitivity to house dust mite and storage mite antigens was significantly higher in scabietics than in controls. It could be concluded that there is some proof that other mites rather than Sarcoptes scabiei may have a role in the pathogenesis of scabies and the cross reactivity between S. scabiei and house dust mite and storage mite may explain the persistence of symptoms in some cases even after proper treatment of the disease.


Immunosuppressive and Prometastatic Functions of Myeloid-Derived Suppressive Cells Rely upon Education from Tumor-Associated B Cells.
Myeloid-derived suppressive cells (MDSC) have been reported to promote metastasis, but the loss of cancer-induced B cells/B regulatory cells (tBreg) can block metastasis despite MDSC expansion in cancer. Here, using multiple murine tumor models and human MDSC, we show that MDSC populations that expand in cancer have only partially primed regulatory function and limited prometastatic activity unless they are fully educated by tBregs. Cancer-induced tBregs directly activate the regulatory function of both the monocyte and granulocyte subpopulations of MDSC, relying, in part, on TgfβR1/TgfβR2 signaling. MDSC fully educated in this manner exhibit an increased production of reactive oxygen species and NO and more efficiently suppress CD4(+) and CD8(+) T cells, thereby promoting tumor growth and metastasis. Thus, loss of tBregs or TgfβR deficiency in MDSC is sufficient to disable their suppressive function and to block metastasis. Overall, our data indicate that cancer-induced B cells/B regulatory cells are important regulators of the immunosuppressive and prometastatic functions of MDSC.


[Lattice degeneration of the retina].
Lattice degeneration of the retina is a clinically important type of peripheral retinal dystrophies due to its participation in the pathogenesis of rhegmatogenous retinal detachment. In spite of extensive epidemiological, morphological, and clinical data, the question on causes of this particular type of retinal dystrophies currently remains debatable. Existing hypotheses on pathogenesis of retinal structural changes in lattice degeneration explain it to a certain extent. In clinical ophthalmology it is necessary to pay close attention to this kind of degenerations and distinguish between cases requiring preventive treatment and those requiring monitoring.


Gamma Ray Glow Observations at 20-km Altitude.
In the spring of 2017 an ER-2 aircraft campaign was undertaken over continental United States to observe energetic radiation from thunderstorms and lightning. The payload consisted of a suite of instruments designed to detect optical signals, electric fields, and gamma rays from lightning. Starting from Georgia, USA, 16 flights were performed, for a total of about 70 flight hours at a cruise altitude of 20 km. Of these, 45 flight hours were over thunderstorm regions. An analysis of two gamma ray glow events that were observed over Colorado at 21:47 UT on 8 May 2017 is presented. We explore the charge structure of the cloud system, as well as possible mechanisms that can produce the gamma ray glows. The thundercloud system we passed during the gamma ray glow observation had strong convection in the core of the cloud system. Electric field measurements combined with radar and radio measurements suggest an inverted charge structure, with an upper negative charge layer and a lower positive charge layer. Based on modeling results, we were not able to unambiguously determine the production mechanism. Possible mechanisms are either an enhancement of cosmic background locally (above or below 20 km) by an electric field below the local threshold or an enhancement of the cosmic background inside the cloud but then with normal polarity and an electric field well above the Relativistic Runaway Electron Avalanche threshold.


The impending peak and decline of petroleum production: an underestimated challenge for conservation of ecological integrity.
In the last few decades petroleum has been consumed at a much faster pace than new reserves have been discovered. The point at which global oil extraction will attain a peak ("peak oil") and begin a period of unavoidable decline is approaching. This eventuality will drive fundamental changes in the quantity and nature of energy flows through the human economic system, which probably will be accompanied by economic turmoil, political conflicts, and a high level of social tension. Besides being a geological and economic issue, peak oil is also a fundamental concern as it pertains to ecological systems and conservation because economics is a subsystem of the global ecosystem and changes in human energy-related behaviors can lead to a broad range of effects on natural ecosystems, ranging from overuse to abandonment. As it becomes more difficult to meet energy demands, environmental considerations may be easily superseded. Given the vital importance of ecosystems and ecosystem services in a postpetroleum era, it is crucially important to wisely manage our ecosystems during the transition period to an economy based on little or no use of fossil fuels. Good policies can be formulated through awareness and understanding gained from scenario-based assessments. Presently, most widely used global scenarios of environmental change do not incorporate resource limitation, including those of the Millennium Ecosystem Assessment and the Intergovernmental Panel on Climate Change. Considering the potential magnitude of the effects of peak oil on society and nature, the development of resource-constrained scenarios should be addressed immediately. Ecologists and conservation biologists are in an important position to analyze the situation and provide guidance, yet the topic is noticeably absent from ecological discussions. We urge politicians, corporate chief executives, thought leaders, and citizens to consider this problem seriously because it is likely to develop into one of the key environmental issues of the 21st century.


Mortality after first myocardial infarction. Search for a secular trend.
Two earlier studies of prognosis of coronary heart disease among men enrolled in the Health Insurance Plan in the 1960s and 1970s permitted us to examine whether prognosis had improved over this ten-year period. The new comparison involved 1,133 men aged 35 to 64 years who had survived a first acute myocardial infarction and were followed up for mortality after a baseline examination. Mortality estimates were controlled for clinical and demographic differences between the two cohorts by multivariate methods and by comparing subgroups. The analyses showed no difference in long-term prognosis between patients in the two decades. The observations in this population suggest that any contribution of improved medical care to the nationally observed secular decline in mortality from coronary heart disease in the time period studied was probably restricted to the acute stage of myocardial infarction.


Laboratory quality improvement in Thailand's northernmost provinces.
In Thailand nearly 1000 public health laboratories serve 65 million people. A qualified indicator of a good quality laboratory is Thailand Medical Technology Council certification. Consequently, Chiang Rai Regional Medical Sciences Center established a development program for laboratory certification for 29 laboratories in the province. This paper seeks to examine this issue. The goal was to improve laboratory service quality by voluntary participation, peer review, training and compliance with standards. The program consisted of specific activities. Training and workshops to update laboratory staffs' quality management knowledge were organized. Staff in each laboratory performed a self-assessment using a standard check-list to evaluate ten laboratory management areas. Chiang Rai Regional Medical Sciences Center staff supported the distribution of quality materials and documents. They provided calibration services for laboratory equipment. Peer groups performed an internal audit and successful laboratories received Thailand Medical Technology Council certification. By December 2007, eight of the 29 laboratories had improved quality sufficiently to be certified. Factors that influenced laboratories' readiness for quality improvement included the number of staff, their knowledge, budget and staff commitment to the process. Moreover, the support of each hospital's laboratory working group or network was essential for success. There was no clear policy for supporting the program. Laboratories voluntarily conducted quality management using existing resources. A bottom-up approach to this kind of project can be difficult to accomplish. Laboratory professionals can work together to illustrate and highlight outcomes for top-level health officials. A top-down, practical approach would be much less difficult to implement. Quality certification is a critical step for laboratory staff, which also encourages them to aspire to international quality standards like ISO. The certification program is an important mechanism for addressing inadequate knowledge, budget, planning, policy and staff required to improve laboratory services.


Recent advances in plasma modification of 2D transition metal dichalcogenides.
Two-dimensional (2D) transition metal dichalcogenide (TMDC) materials have recently attracted great interest because of their tantalising prospects for a broad range of applications including electronics, optoelectronics, and energy storage. Unlike bulk materials, the device performance of atomically thin 2D materials is determined by the interface, thickness and defects. Plasma processing is very effective for diverse modifications of nanoscale 2D TMDC materials, owing to its uniquely controllable, effective processes and energy efficiency. Herein, we critically discuss selected recent advances in plasma modification of 2D TMDC materials and their optical and electronic (including optoelectronic) properties of relevance to applications in hydrogen production, gas sensing and energy storage devices. Challenges and future research opportunities in the relevant research field are presented. This review contributes to directing future advances of plasma processing of TMDC materials for targeted applications.


Wireless transmission of neural signals using entropy and mutual information compression.
Two of the most critical tasks when designing a portable wireless neural recording system are to limit power consumption and to efficiently use the limited bandwidth. It is known that for most wireless devices the majority of power is consumed by the wireless transmitter and it often represents the bottleneck of the overall design. This paper compares two compression techniques that take advantage of the sparseness of the neural spikes in neural recordings using an information theoretic formalism to enhance the well-established vector quantization (VQ) algorithm. The two discriminative VQ algorithms are applied to neuronal recordings proving their ability to accurately reconstruct action potential (AP) regions of the neuronal signal while compressing background activity without using thresholds. The two operational modes presented offer distinct characteristics to lossy compression. The first approach requires no preprocessing or prior knowledge of the signal while the second requires a training set of spikes to obtain AP templates. The compression algorithms are implemented on an on-board digital signal processor (DSP) and results show that power consumption is decreased while the bandwidth is more efficiently utilized. The compression algorithms have been tested in real time on a hardware platform (PICO DSP ) enhanced with the DSP which runs the algorithm before sending the compressed data to a wireless transmitter. The compression ratios obtained range from 70:1 and 40:1 depending on the signal to noise ratio (SNR) of the input signal. The spike sorting accuracy in the reconstructed data is 95% compatible to the original neural data.


Bullying among immigrant and non-immigrant early adolescents: School- and student-level effects.
We examined the association between school immigrant concentration and bullying among immigrant and non-immigrant early adolescents, and identified potential explanatory factors. First generation immigrant students had reduced odds of victimization and perpetration in schools with high (20-60%), compared to low, levels of immigrant concentration. Second generation immigrant students had reduced odds of ethnic/racial victimization in moderately concentrated schools; while non-immigrants had increased odds in the same schools. Non-white students had increased odds of ethnic/racial victimization compared to White students. While students' sense of school belonging and perceived teacher cultural sensitivity were negatively associated with bullying, they did not account for the differential associations noted above. Results demonstrate the importance of immigrant density as a protective school characteristic for immigrant and ethnic minority youth. Additional social processes operating in schools that may explain bullying behaviors among immigrant and non-immigrant youth should be explored to inform programs for promoting inclusion in schools.


[Paracoccidioidomycosis at Brasilias university hospital].
Seventy-six paracoccidioidomycosis patients attended at the university hospital of Brasília from 1984 to 2005 were studied. 82.9% were male and the mean age was 42 years. 54.9% of the patients were engaged in farming activities. Among the patients with the chronic form, 87% were smokers and 55.3% consumed alcohol. Among 71 patients without HIV/AIDS coinfection: a) paracoccidioidomycosis was recurrent in 21 (29.6%); b) the chronic or mixed form affected 77.5% of patients, predominantly in the oropharynx (70.9%) and lungs (67.3%), with lymph node lesions in 29.8%, laryngeal lesions in 27.3% and cutaneous lesions in 16.4%; c) in the acute/subacute form, lymph node lesions predominated (81.3%), followed by cutaneous lesions in 43.8%, which resulted in severe disease in 62.5% and moderate disease in 37.5%. Five patients had HIV/AIDS coinfection and three of them presented disseminated fungal infection together with marked immunosuppression.


Health data ecosystem in Pakistan: a multisectoral qualitative assessment of needs and opportunities.
Data are essential for tracking and monitoring of progress on health-related sustainable development goals (SDGs). But the capacity to analyse subnational and granular data is limited in low and middle-income countries. Although Pakistan lags behind on achieving several health-related SDGs, its health information capacity is nascent. Through an exploratory qualitative approach, we aimed to understand the current landscape and perceptions on data in decision-making among stakeholders of the health data ecosystem in Pakistan. We used an exploratory qualitative study design. This study was conducted at the Aga Khan University, Karachi, Pakistan. We conducted semistructured, in-depth interviews with multidisciplinary and multisectoral stakeholders from academia, hospital management, government, Non-governmental organisations and other relevant private entities till thematic saturation was achieved. Interviews were recorded and transcribed, followed by thematic analysis using NVivo. Thematic analysis of 15 in-depth interviews revealed three major themes: (1) institutions are collecting data but face barriers to its effective utilisation for decision-making. These include lack of collection of needs-responsive data, lack of a gender/equity in data collection efforts, inadequate digitisation, data reliability and limited analytical ability; (2) there is openness and enthusiasm for sharing data for advancing health; however, multiple barriers hinder this including appropriate regulatory frameworks, platforms for sharing data, interoperability and defined win-win scenarios; (3) there is limited capacity in the area of both human capital and infrastructure, for being able to use data to advance health, but there is appetite to improve and invest in capacity in this area. Our study identified key areas of focus that can contribute to orient a national health data roadmap and ecosystem in Pakistan.


[Sonography as a screening examination method of the venous system in pregnancy. Comparative studies of the arm and leg vein system].
Comparative studies were conducted during the third trimenon of pregnancy between the 36th and 40th weeks of gestation and on the seventh day after delivery, at the venous system of the legs (vena iliaca, v. femoralis and v. poplitea) and at the venous system of the arms (v. brachialis). A marked reduction of the venous diameters was seen on the legs, whereas no difference was found in the venous system of the arms between both times of measurement. This points to the haemodynamic effect of the pregnant uterus, providing an obstacle to the flow of blood from the venous system of the legs. After delivery there is a relatively higher extensibility of the veins of the leg compared with the measurements in the third trimenon. This may be due on the one hand to the long-lasting overextension during pregnancy, and on the other hand also to the hormonal and enzymochemical changes that take place even during the puerperium. Doppler sonography of the v. femoralis showed clearly that the foetus obstructs blood flow from the venous system of the legs. Sonography seems to be able to visualise direct the changed morphology of the veins during pregnancy and to indirectly yield information on the extensibility of the venous system eg during standing, thus demonstrating in what way the venous system functions in a particular condition. Hence, sonography of the venous system of the legs during pregnancy should be used as a screening method wherever it is essential to discover extreme venous dilatations well in time and to initiate compression treatment.


Dissociations among the anxiolytic effects of septal, hippocampal, and amygdaloid lesions.
Fear reactions of rats given bilateral lesions to the septum, hippocampus, or amygdala were compared with those of rats given sham lesions, in 2 animal models of anxiety: the shock-probe burying test and the elevated plus-maze test. Septal lesions produced anxiolytic effects in both tests (i.e., an increase in open-arm activity and a decrease in burying), whereas hippocampal and amygdaloid lesions produced neither of these effects. On the other hand, hippocampal and amygdaloid lesions impaired rats' passive avoidance of the electrified shock-probe, whereas septal lesions did not. These dissociations suggest that limbic structures such as the septum, amygdala, and hippocampus exert parallel but distinct control over different fear reactions.


Visualization of nucleosomes in thin sections by stereo electron microscopy.
Nucleosomes (approximately diameter) were clearly visualized in thin sections (approximately 0.1 micrometer thick) of isolated chicken erythrocytes. The cells were lysed and fixed in low ionic strength buffers that maintained the chromatin as dispersed filaments and prevented the reformation of supranucleosomal structures. Stereo electron micrographs at high magnification demonstrate the stability of nucleosome structure in the dispersed chromatin state during fixation, dehydration, and embedding.


[Evaluation of the effectiveness of a specific immunoglobulin against hepatitis A].
The present work deals with the controlled trial aimed at the study of the effectiveness of specific immunoglobulin against hepatitis A, developed in the USSR. This immunoglobulin is prepared from carefully selected blood sera from persons who have had hepatitis A. In accordance with the program approved by the USSR Ministry of Health, two trials were organized among the most susceptible groups of the population: organized groups of preschool children and young adults. During 6 months of the subsequent surveillance carried out in both age groups, the highest morbidity rate in hepatitis A was registered among the nonimmunized subjects. Morbidity rate among the subjects immunized with common commercial immunoglobulin was 3-7 times higher than among those immunized with the specific preparation, but a small size of the groups and a low morbidity level prevented the statistically significant confirmation of this higher effectiveness. Specific immunoglobulin produced a statistically significant (t = 2.72 and 2.4) decrease in morbidity rate among the immunized subjects in both age groups in comparison with morbidity rate among the nonimmunized ones.


Identification of a bidirectional splicing enhancer: differential involvement of SR proteins in 5' or 3' splice site activation.
The adenovirus E1A pre-mRNA undergoes alternative splicing whose modulation occurs during infection, through the use of three different 5' splice sites and of one major or one minor 3' splice site. Although this pre-mRNA has been extensively used as a model to compare the transactivation properties of SR proteins, no cis-acting element has been identified in the transcript sequence. Here we describe the identification and the characterization of a purine-rich splicing enhancer, located just upstream of the 12S 5' splice site, which is formed from two contiguous 9-nucleotide (nt) purine motifs (Pu1 and Pu2). We demonstrate that this sequence is a bidirectional splicing enhancer (BSE) in vivo and in vitro, because it activates both the downstream 12S 5' splice site through the Pu1 motif and the upstream 216-nt intervening sequence (IVS) 3' splice site through both motifs. UV cross-linking and immunoprecipitation experiments indicate that the BSE interacts with several SR proteins specifically, among them 9G8 and ASF/SF2, which bind preferentially to the Pu1 and Pu2 motifs, respectively. Interestingly, we show by in vitro complementation assays that SR proteins have distinct transactivatory properties. In particular, 9G8, but not ASF/SF2 or SC35, is able to strongly activate the recognition of the 12S 5' splice site in a BSE-dependent manner in wild-type E1A or in a heterologous context, whereas ASF/SF2 or SC35, but not 9G8, activates the upstream 216-nt IVS splicing. Thus, our results identify a novel exonic BSE and the SR proteins which are involved in its differential activity.


Prolonged continuous versus intermittent oral acyclovir treatment in normal adults with frequently recurring genital herpes simplex virus infection.
In Year 1 of this two-year trial, patients with six or more genital herpes recurrences in the past year received suppressive treatment with either acyclovir, 400 mg, or placebo, orally twice daily for one year, and physician-documented recurrences were treated with open-labeled acyclovir, 200 mg, orally five times per day for five days (acute treatment). In Year 2, patients received open-labeled acyclovir treatment either with daily suppressive therapy or intermittent acute therapy. Among 683 patients who completed two years of treatment, 348 received continuous suppressive treatment for two years, 276 received acute treatment in Year 1 and suppressive treatment in Year 2, 24 received suppressive treatment in Year 1 and acute treatment in Year 2, and 35 received acute treatment for two years. Patient groups receiving intermittent acute acyclovir treatment experienced means of 7.0 to 12.6 recurrences/year during treatment as compared with 1.4 to 1.9 recurrences/year among groups receiving continuous suppressive treatment. No patients who received acute treatment remained recurrence-free for two years as compared with 29 percent of patients receiving continuous acyclovir suppression for two years. There was no evidence of cumulative toxicity detected by clinical, hematologic, or blood chemistry evaluations performed monthly in Year 1 and quarterly in Year 2. Suppressive oral acyclovir therapy remained effective and well-tolerated in this two-year trial.


Evolutionary Profile for (Host and Viral) MLKL Indicates Its Activities as a Battlefront for Extensive Counteradaptation.
Pathogen infection triggers host innate defenses which may result in the activation of regulated cell death (RCD) pathways such as apoptosis. Given a vital role in immunity, apoptotic effectors are often counteracted by pathogen-encoded antagonists. Mounting evidence indicates that programmed necrosis, which is mediated by the RIPK3/MLKL axis and termed necroptosis, evolved as a countermeasure to pathogen-mediated inhibition of apoptosis. Yet, it is unclear whether components of this emerging RCD pathway display signatures associated with pathogen conflict that are rare in combination but common to key host defense factors, namely, rapid evolution, viral homolog (virolog), and cytokine induction. We leveraged evolutionary sequence analysis that examines rates of amino acid replacement, which revealed: 1) strong and recurrent signatures of positive selection for primate and bat RIPK3 and MLKL, and 2) elevated rates of amino acid substitution on multiple RIPK3/MLKL surfaces suggestive of past antagonism with multiple, distinct pathogen-encoded inhibitors. Furthermore, our phylogenomics analysis across poxvirus genomes illuminated volatile patterns of evolution for a recently described MLKL viral homolog. Specifically, poxviral MLKLs have undergone numerous gene replacements mediated by duplication and deletion events. In addition, MLKL protein expression is stimulated by interferons in human and mouse cells. Thus, MLKL displays all three hallmarks of pivotal immune factors of which only a handful of factors like OAS1 exhibit. These data support the hypothesis that over evolutionary time MLKL functions-which may include execution of necroptosis-have served as a major determinant of infection outcomes despite gene loss in some host genomes.


Bidirectional temporal associations between sleep and affect and cognitive complaints among community-dwelling stroke survivors: An ecological momentary assessment study.
Sleep plays a critical role in daily functioning and stroke recovery but receives little attention in stroke rehabilitation. Sleep disturbances are linked to affective and cognitive impairments, but temporal associations between sleep and affect and cognitive complaints are less clear. Understanding these temporal associations may inform new directions in intervention and prevention to support continued stroke recovery. To examine the bidirectional temporal associations between sleep and affect and cognitive complaints among community-dwelling stroke survivors. A secondary analysis of a longitudinal observational studyinvolving 7 days of ecological momentary assessment (EMA), during which participants completed 8 EMA surveys and a sleep diary per day.Multilevel modeling was used to analyze data. Community. Community-dwelling stroke survivors (N=40). Not applicable. EMA measures of depressed affect, cheerful affect, and cognitive complaints. Sleep quality and duration as measured using a sleep diary. Between-personsleep quality was negatively associated with next-day depressed affect (B=-.16;p=.028) and positively associated with next-day cheerful affect (B=.63;p<.001). Inversely, between-person depressed affect was negatively associated with next night sleep quality (B=-.77;p=.015), and vice versa for cheerful affect (between-person: B=.45;p<.001; within-person: B=.09;p=.008). Long sleep (>9 hours) was positively associated with next-day cognitive complaints (B=.13;p=.002); whereas cognitive complaints were associated with higher odds of long sleep the following night (OR=.25;p=.047). This study identified the bidirectional associations of sleep with affect and cognitive complaints in the context of stroke survivors' everyday life. Findings suggest that interventions addressing sleep quality and duration may impactaffect and cognitive complaints, and vice versa. This article is protected by copyright. All rights reserved.


Brain preconditioning and obstructive sleep apnea syndrome.
Intermittent hypoxia stimulates the development of adaptive responses, called preconditioning. This process is partially mediated by genetic remodeling, via hypoxia inducible factor (HIF), which induces long-term adaptation processes and is responsible for the increase of levels of vascular endothelial growth factor (VEGF), erythropoietin (Epo), atrial natriuretic peptide (ANP), and nitric oxide (NO). The synthesis of brain-derived neurotrophic factor (BDNF) participates in the control of neural plasticity after hypoxia. The mechanisms of neuroprotection against hypoxia may be related to vascular adjustments and to central neurogenic neuroprotection. Some of the factors known to be involved in the development of the mechanism of neuroprotection are also present in the responses to repetitive apneas that occur during sleep in patients with obstructive sleep apnea (OSA) syndrome, who are frequently exposed to severe sleep hypoxemia. It appears that OSA syndrome represents a clinical example of preconditioning and the development of adaptive responses to intermittent hypoxia.


Monitoring the abundance of plastic debris in the marine environment.
Plastic debris has significant environmental and economic impacts in marine systems. Monitoring is crucial to assess the efficacy of measures implemented to reduce the abundance of plastic debris, but it is complicated by large spatial and temporal heterogeneity in the amounts of plastic debris and by our limited understanding of the pathways followed by plastic debris and its long-term fate. To date, most monitoring has focused on beach surveys of stranded plastics and other litter. Infrequent surveys of the standing stock of litter on beaches provide crude estimates of debris types and abundance, but are biased by differential removal of litter items by beachcombing, cleanups and beach dynamics. Monitoring the accumulation of stranded debris provides an index of debris trends in adjacent waters, but is costly to undertake. At-sea sampling requires large sample sizes for statistical power to detect changes in abundance, given the high spatial and temporal heterogeneity. Another approach is to monitor the impacts of plastics. Seabirds and other marine organisms that accumulate plastics in their stomachs offer a cost-effective way to monitor the abundance and composition of small plastic litter. Changes in entanglement rates are harder to interpret, as they are sensitive to changes in population sizes of affected species. Monitoring waste disposal on ships and plastic debris levels in rivers and storm-water runoff is useful because it identifies the main sources of plastic debris entering the sea and can direct mitigation efforts. Different monitoring approaches are required to answer different questions, but attempts should be made to standardize approaches internationally.


[Preparation and identification of monoclonal antibody against repression and activation protein 1].
To prepare and identify monoclonal antibody (mAb) against human telomere-associated repression and activation protein 1 (Rap1). BALB/c mice were immunized with recombinant Rap1 protein. The spleen cells of the immunized mice were fused with Sp2/0 cells. The positive clones were confirmed and selected by indirect ELISA for titer determination and specificity identification. One hybridoma cell strain secreting specific mAb against Rap1 was obtained, namely 6F11. ELISA showed that the titer of the ascites was 1:10 000. Western blotting, immunoprecipitation and immunofluorescence experiments demonstrated that the mAb could specifically recognize and bind Rap1. We have prepared mAb against human telomere-associated protein Rap1. The Rap1 mAb has a good binding ability and specificity.


Explaining neural signals in human visual cortex with an associative learning model.
"Predictive coding" models posit a key role for associative learning in visual cognition, viewing perceptual inference as a process of matching (learned) top-down predictions (or expectations) against bottom-up sensory evidence. At the neural level, these models propose that each region along the visual processing hierarchy entails one set of processing units encoding predictions of bottom-up input, and another set computing mismatches (prediction error or surprise) between predictions and evidence. This contrasts with traditional views of visual neurons operating purely as bottom-up feature detectors. In support of the predictive coding hypothesis, a recent human neuroimaging study (Egner, Monti, & Summerfield, 2010) showed that neural population responses to expected and unexpected face and house stimuli in the "fusiform face area" (FFA) could be well-described as a summation of hypothetical face-expectation and -surprise signals, but not by feature detector responses. Here, we used computer simulations to test whether these imaging data could be formally explained within the broader framework of a mathematical neural network model of associative learning (Schmajuk, Gray, & Lam, 1996). Results show that FFA responses could be fit very closely by model variables coding for conditional predictions (and their violations) of stimuli that unconditionally activate the FFA. These data document that neural population signals in the ventral visual stream that deviate from classic feature detection responses can formally be explained by associative prediction and surprise signals.


Morphological and molecular characterization of three Agaricus species from tropical Asia (Pakistan, Thailand) reveals a new group in section Xanthodermatei.
The genus Agaricus is known for its medicinal and edible species but also includes toxic species that belong to section Xanthodermatei. Previous phylogenetic reconstruction for temperate species, based on sequence data of nuc rRNA gene (rDNA) internal transcribed spacers (ITS), has revealed two major groups in this section and a possible third lineage for A. pseudopratensis. Recent research in Agaricus has shown that classifications need improving with the addition of tropical taxa. In this study we add new tropical collections to section Xanthodermatei. We describe three species from collections made in Pakistan and Thailand and include them in a larger analysis using all available ITS data for section Xanthodermatei. Agaricus bisporiticus sp. nov. and A. fuscopunctatus sp. nov. are introduced based on molecular and morphological studies, whereas A. microvolvatulus is recorded for the first time in Asia. Specimens from Thailand however have a much larger pileus than the type specimens from Congo. In maximum likelihood (ML) and maximum parsimony (MP) phylogenetic analyses these three species cluster with A. pseudopratensis from the Mediterranean area and A. murinocephalus recently described from Thailand. In Agaricus section Xanthodermatei this new group is monophyletic and receives low bootstrap support whereas the two previously known groups receive strong support. Within the new group, the most closely related species share some traits, but we did not find any unifying morphological character; however the five species of the group share a unique short nucleotide sequence. Two putatively toxic species of section Xanthodermatei are now recognized in Pakistan and six in Thailand.


Radicals from the gas-phase pyrolysis of a lignin model compound: p-coumaryl alcohol.
The intermediate radicals produced in the gas-phase pyrolysis of one of the main building blocks of lignin - p-coumaryl alcohol (p-CMA) - were investigated using the low temperature matrix isolation technique interfaced with electron paramagnetic resonance spectroscopy (LTMI-EPR). An anisotropic EPR spectrum characterized by a high g-value (>2.0080) and a relatively low saturation coefficient (∼1.40) throughout the high pyrolytic temperature region (700 to 1000 °C) was observed. Theoretical calculations revealed plausible decomposition pathways for p-CMA comprising highly delocalized aromatic radicals. The results provide evidence for a dominant role of oxygen-centered radicals during the pyrolysis of p-CMA.


Prevalence of zygomatic air cell defect: Panoramic radiographic study of a selected Esfehanian population.
The mastoid pneumatization begins on the 33(rd) week of embryonic life, and continuous up to 8-9 years of age. This air cells is important for surgical perspective. Inadvertent penetration through this anatomical feature during surgical procedures can be disastrous. Aim of this study is to determine the prevalence of zygomatic air cell defect (ZACD) in the Esfehanian population. This was a cross-sectional study. 2600 panoramic radiographs of patients aged between 3 and 90 years were evaluated retrospectively to establish dominant laterality, type and grade amongst these patients. The SPSS 11.5 program was used for the statistical analysis. Mean and standard deviation were used for statistical methods in this study. ZACD was found in 94 cases, representing a prevalence of 3.6%. 59 cases occurred in females (62.8%) and 35 cases occurred in males (37.2%). Most cases were in their twenties. Unilateral ZACD was found in 70 patients (74.5%) with the half occurring on the right side. In 24 cases (25.5%) was bilateral. 70 of the cases (59.3%) were multilocular type, while 45 (38.1) and 3 (2.6%) were unilocular and trabecular type, respectively. 59 cases were grade 2 (62.8%) and 35 were grade 3 (37.2%). The frequency of ZACD amongst Iranian population was more than previous studies. In addition younger population was involved in this group. So it is important for clinicians who are planning to perform temporomandibular joint surgery to assess radiographic imaging thoroughly before the surgery to avoid intraoperative complications.


CD4+ T lymphocyte-induced target cell detachment. A model for T cell-mediated lytic and nonlytic inflammatory processes.
We have been exploring the hypothesis that T lymphocytes have the potential to mediate immune damage through nonlytic disruption of tissue organization. In this report, we have examined the ability of purified, primary cultures of alloreactive CD4+ T cells to mediate Ag-specific target cell detachment and/or lysis of L cell lines transfected with MHC class II determinants. Using this model, we demonstrate that: 1) MHC class II-specific CD4+ T cells can cause detachment as a distinct event of the E:T interaction, although the pathways or mechanisms involved appear to be different from those utilized by MHC class I-specific CD8+ T cells; 2) detachment and lysis by CD4+ T cells are distinct activities that involve different functional requirements: 3) CD4+ T cell-induced detachment is initiated by direct cell-cell interaction, independent of TNF-alpha/beta; 4) CD4+ T cell-mediated lysis can be accomplished by TNF-alpha/beta-dependent and independent pathways; and 5) the nature of a particular target cell response to alloreactive CD4+ T cell attack reflects its intrinsic susceptibility to one or more potential effector mechanisms.


Mutations that affect the efficiency of translation of mRNA for the cII gene of coliphage lambda.
Starting with the lambda pRE-strain lambda ctr1 cy3008, which forms clear plaques, we have isolated two mutant strains, lambda dya2 ctr1 cy3008 and lambda dya3 ctr1 cy3008, that form plaques with very slightly turbid centers. The dya2 and dya3 mutations lie in the region of overlap between the PRE promoter and the ribosome recognition region of the cII gene, and have nucleotide alterations at positions -1 and +5 of pRE, and alterations in cII mRNA at -16 and -21 nucleotides before the initial AUG codon of the gene. Both mutations destabilize a stem structure that may be formed by cII mRNA, and dya2 also changes the sequence on cII mRNA that is complementary to the 3'-end of 16 S rRNA from 5'-UAAGGA-3' to 5'-UGAGGA-3'. --The dya2 and dya3 mutations, along with the ctr1 mutation, which destabilizes either of two alternate stem structures which may be formed by cII mRNA (these being more stable stem structures than the one affected by dya2 and dya3), were tested for their ability to reverse two cII-mutations that are characterized by inefficient translation of cII mRNA. These are cII3088, an A----G mutation four bases before the initial AUG codon, and cII3059, a GUU----GAU (Val2----Asp) second codon mutation. It was found that ctr1 completely reverses the translation defects of these two mutations, while dya2 partially reverses these translation defects. The dya3 mutation has no effect on translation efficiency under any condition tested.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of recG genetic interactions in Escherichia coli by transposon sequencing.
DNA damage and subsequent DNA repair processes are mutagenic in nature and an important driver of evolution in prokaryotes, including antibiotic resistance development. Genetic screening approaches, such as transposon sequencing (Tn-seq), have provided important new insights into gene function and genetic relationships. Here, we employed Tn-seq to gain insight into the function of the recG gene, which renders Escherichia coli cells moderately sensitive to a variety of DNA-damaging agents when they are absent. The reported recG genetic interactions can be used in combination with future screens to aid in a more complete reconstruction of DNA repair pathways in bacteria.


Including spatial information in nonlinear inversion MR elastography using soft prior regularization.
Tissue displacements required for mechanical property reconstruction in magnetic resonance elastography (MRE) are acquired in a magnetic resonance imaging (MRI) scanner, therefore, anatomical information is available from other imaging sequences. Despite its availability, few attempts to incorporate prior spatial information in the MRE reconstruction process have been reported. This paper implements and evaluates soft prior regularization (SPR), through which homogeneity in predefined spatial regions is enforced by a penalty term in a nonlinear inversion strategy. Phantom experiments and simulations show that when predefined regions are spatially accurate, recovered property values are stable for SPR weighting factors spanning several orders of magnitude, whereas inaccurate segmentation results in bias in the reconstructed properties that can be mitigated through proper choice of regularization weighting. The method was evaluated in vivo by estimating viscoelastic mechanical properties of frontal lobe gray and white matter for five repeated scans of a healthy volunteer. Segmentations of each tissue type were generated using automated software, and statistically significant differences between frontal lobe gray and white matter were found for both the storage modulus and loss modulus . Provided homogeneous property assumptions are reasonable, SPR produces accurate quantitative property estimates for tissue structures which are finer than the resolution currently achievable with fully distributed MRE.


Designer interphases for the lithium-oxygen electrochemical cell.
An electrochemical cell based on the reversible oxygen reduction reaction: 2Li+ + 2e - + O2↔ Li2O2, provides among the most energy dense platforms for portable electrical energy storage. Such Lithium-Oxygen (Li-O2) cells offer specific energies competitive with fossil fuels and are considered promising for electrified transportation. Multiple, fundamental challenges with the cathode, anode, and electrolyte have limited practical interest in Li-O2 cells because these problems lead to as many practical shortcomings, including poor rechargeability, high overpotentials, and specific energies well below theoretical expectations. We create and study in-situ formation of solid-electrolyte interphases (SEIs) based on bromide ionomers tethered to a Li anode that take advantage of three powerful processes for overcoming the most stubborn of these challenges. The ionomer SEIs are shown to protect the Li anode against parasitic reactions and also stabilize Li electrodeposition during cell recharge. Bromine species liberated during the anchoring reaction also function as redox mediators at the cathode, reducing the charge overpotential. Finally, the ionomer SEI forms a stable interphase with Li, which protects the metal in high Gutmann donor number liquid electrolytes. Such electrolytes have been reported to exhibit rare stability against nucleophilic attack by Li2O2 and other cathode reaction intermediates, but also react spontaneously with Li metal anodes. We conclude that rationally designed SEIs able to regulate transport of matter and ions at the electrolyte/anode interface provide a promising platform for addressing three major technical barriers to practical Li-O2 cells.


Ba(1.3)Ca(0.7)SiO4:Eu(2+),Mn(2+): a promising single-phase, color-tunable phosphor for near-ultraviolet white-light-emitting diodes.
In this paper, Eu(2+)-doped and Eu(2+)/Mn(2+)-codoped Ba1.3Ca0.7SiO4 phosphors were synthesized by means of a conventional solid-state reaction process. The single-phase purity was checked by means of X-ray diffraction and the Rietveld method. Under excitation at 390 nm, the emission spectra of the Eu(2+)-doped phosphors exhibit a broad-band emission centered at 500 nm caused by the electric dipole allowed transition of the Eu(2+) ions. The emission spectra of codoped phosphors show one more broad emission centered at 600 nm attributable to the transitions from the (4)T1((4)G) → (6)A1((6)S) of Mn(2+) ions. The luminescent color of the codoped phosphors can be easily adjusted from blue to red with variation of the Mn(2+) content. The energy transfer mechanism from the Eu(2+) to Mn(2+) ions in Ba1.3Ca0.7SiO4 phosphors has been confirmed to be the resonant type via dipole-quadrupole interaction, and the critical distance has been calculated quantitatively. All these results demonstrate that the Eu(2+)/Mn(2+)-codoped Ba1.3Ca0.7SiO4 phosphors can be a promising single-phase, color-tunable phosphor for near-UV white-light-emitting diodes after a further optimization process. Additionally, a great red shift from 593 to 620 nm has been observed following the increase of Mn(2+) content, and the phenomenon has been discussed in relation to the changes in the crystal field surrounding the Mn(2+) ions and the exchange interactions caused by the formation of Mn(2+) pairs.


Soluble CD40 ligand and soluble P-selectin in allergic asthma patients during exercise-induced bronchoconstriction.
The interactions between CD40 and its ligand, CD40L, control humoral and cell-mediated immune responses. CD40 ligation may promote asthma-associated inflammatory responses in the airways. Many reports confirm the inflammatory basis of exercise-induced bronchoconstriction (EIB) in asthmatics. The study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB) and 8 healthy volunteers. We analyzed the changes in plasma concentrations of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) induced by intensive exercise. We also studied possible correlations with the results of measurements commonly associated with asthmatic inflammation. The study revealed statistically significant higher baseline concentrations of sCD40L--but not sP-selectin--in the group of asthmatics with EIB than in those without. In the asthmatic patients with EIB, sCD40L and sP-selectin concentrations increased significantly 30 minutes after exercise and returned to baseline 24 hours after exercise. Baseline concentrations of sCD40L correlated with baseline sP-selectin or fractional exhaled nitric oxide concentration (FE(NO)), an increase in sP-selectin 30 minutes after exercise, and changes in FE(NO) or bronchial hyperresponsiveness 24 hours after exercise. A statistically significant correlation between an increase in sCD40L concentrations 30 minutes after exercise and an increase in FE(NO) 24 hours after exercise or baseline eosinophil cationic protein was observed. After exercise in the group of allergic asthmatics with EIB, upregulation of CD40L by increased expression of inflammatory molecules and improved sensitivity of CD40-responsive cell types to the effects of proinflammatory cytokines may play an important role in the increased airway inflammation observed after postexercise bronchoconstriction.


Genetic analysis of mating locus linked mutations in Chlamydomonas reinhardii.
The mating-type (mt) locus of Chlamydomonas reinhardii has been analyzed using four mutant strains (imp-1, imp-10, imp-11 and imp-12). All have been shown, or are shown here, to carry mutations linked to either the plus (mt+) or the minus (mt-) locus, and their behavior in complementation tests has allowed us to define several distinct functions for each locus. Specifically, we propose that the mt+ locus contains the following genes or regulatory elements: a locus designated sfu, which is necessary for sexual fusion between gametes; a locus designated upp (uniparental plus), which controls aspects of chloroplast gene inheritance and perhaps also zygote maturation; and a locus designated sad, which functions in sexual adhesion. The mt- locus also contains a sad locus as well as a gene or regulatory element designated mid, which is necessary for the minus dominance in mt+/mt- diploids.


Ferritin-based fusion protein shows octameric deadlock state of self-assembly.
Ferritin is a universal protein complex responsible for iron perception in almost all living organisms and has applications from fundamental biophysics to drug delivery and structure-based immunogen design. Different platforms based on ferritin share similar technological challenges limiting their development - control of self-assembling processes of ferritin itself as well as ferritin-based chimeric recombinant protein complexes. In our research, we studied self-assembly processes of ferritin-based protein complexes under different expression conditions. We fused a ferritin subunit with a SMT3 protein tag, a homolog of human Small Ubiquitin-like Modifier (SUMO-tag), which was taken to destabilize ferritin 3-fold channel contacts and increase ferritin-SUMO subunits solubility. We first obtained the octameric protein complex of ferritin-SUMO (8xFer-SUMO) and studied its structural organization by small-angle X-ray scattering (SAXS). Obtained SAXS data correspond well with the high-resolution models predicted by AlphaFold and CORAL software of an octameric assembly around the 4-fold channel of ferritin without formation of 3-fold channels. Interestingly, three copies of 8xFer-SUMO do not assemble into 24-meric globules. Thus, we first obtained and structurally characterized ferritin-based self-assembling oligomers in a deadlock state. Deadlock oligomeric states of ferritin extend the known scheme of its self-assembly process, being new potential tools for a number of applications. Finally, our results might open new directions for various biotechnological platforms utilizing ferritin-based tools.


High MET Overexpression Does Not Predict the presence of MET exon 14 Splice Mutations in NSCLC: Results From the IFCT PREDICT.amm study.
MET proto-oncogene (MET) exon 14 splice site (METex14) mutations were recently described in NSCLC and has been reported to correlate with efficacy of MET tyrosine kinase inhibitors. High diversity of these alterations makes them hard to detect by DNA sequencing in clinical practice. Because METex14 mutations induce increased stabilization of the MET receptor, it is anticipated that these mutations are associated with MET overexpression. We aim to determine whether NSCLC with high MET overexpression could define a subset of patients with a high rate of METex14 mutations. From The French Cooperative Thoracic Intergroup PREDICT.amm cohort of 843 consecutive patients with a treatment-naive advanced NSCLC who were eligible for a first-line therapy, 108 NSCLC samples with high MET overexpression defined by an immunochemistry score 3+ were tested for METex14 mutations using fragment length analysis combined with optimized targeted next-generation sequencing. MET copy number analysis was also derived from the sequencing data. METex14 mutations were detected in two patients (2.2%) who also displayed a TP53 mutation and a PIK3CA mutation, respectively. An MET gene copy number increase was observed in seven additional patients (7.7%). Next-generation sequencing analysis revealed inactivating mutations in TP53 (52.7%) and PTEN (1.1%), and oncogenic mutations in KRAS (28.6%), EGFR (7.7%), PIK3CA (4.4%), BRAF (4.4%), NRAS (2.2%), GNAS (1.1%), and IDH1 (1.1%). The rate of METex14 mutations in NSCLC with high MET overexpression was similar to that found in unselected NSCLC. Moreover, we observed a high frequency of driver alterations in other oncogenes. Consequently these findings do not support the use of MET immunohistochemistry as a surrogate marker for METex14 mutations.


Cell cycle block in anergic T cells during tolerance induction.
The induction of anergy, or T cell unresponsiveness to antigen, is preceded by T cell activation and cell division in response to fed antigens. These events parallel the activation observed in T cells following sensitization with antigen and adjuvant. The events that distinguish eventual sensitization versus tolerance remain unclear. Using a T lymphocyte transfer model specific to OVA, we demonstrated previously that oral encounter with antigen leads to functional anergy. Antigen-specific CD4+ T cells nevertheless become activated and cycle briefly after encounter with antigen. In this study, we measured the extent of cell cycling of antigen-specific T cells after oral encounter with their antigen. Whereas T cells cycle on the average of eight times in 4 days after conventional immunization, an abortive proliferation was observed in the draining LN T cells after oral encounter with antigen; OVA-specific T cells divided fewer times after exposure to fed OVA, compared to T cells in mice immunized with OVA. This abortive proliferation is antigen specific and not due to bystander suppression, as coadministration of an unrelated antigen that was previously used as a tolerogen does not alter the degree of abortive proliferation. Measurement of BrdU incorporation in mice that were previously fed ovalbumin indicates that up to 3 days following feeding, OVA-specific cells are actively cycling in vivo. However, by day 4, they have stopped cycling while identical T cells in OVA-sensitized mice continue to cycle. Our results indicate either that tolerance is a default pathway and a secondary stimulus is required at day 3 to progress to sensitization, or that elements that limit cell cycle progression are provided for tolerance induction.


Beyond the Diketopiperazine Family with Alternatively Bridged Brevianamide F Analogues.
A method for the preparation of 3,5-bridged piperazin-2-ones from a tryptophan-proline-based diketopiperazine is described using diphosgene to induce the ring closure. Density functional theory calculations were conducted to study the mechanism of this C-C bond formation. Several derivatives of the thus obtained α-chloroamine were synthesized by substitution of the chlorine atom using a range of O-, N-, S-, and C-nucleophiles. This novel class of brevianamide F analogues possess interesting breast cancer resistance protein inhibitory activity.


The Road to Hell Is Paved With Good Intentions: How Common Practices in Scale Construction Hurt Validity.
Sound scale construction is pivotal to the measurement of psychological constructs. Common item sampling procedures emphasize aspects of reliability to the disadvantage of aspects of validity, which are less tangible. We use a health knowledge test as an example to demonstrate how item sampling strategies that focus on either factor saturation or construct coverage influence scale composition and demonstrate how to find a trade-off between these two opposing needs. More specifically, we compile three 75-item health knowledge scales using Ant Colony Optimization, a metaheuristic algorithm that is inspired by the foraging behavior of ants, to optimize factor saturation, construct coverage, or a compromise of both. We demonstrate that our approach is well suited to balance out construct coverage and factor saturation when constructing a health knowledge test. Finally, we discuss conceptual problems with the modeling of declarative knowledge and provide recommendations for the assessment of health knowledge.


Epstein-Barr virus: inhibition of replication by three new drugs.
Epstein-Barr virus (EBV) is the cause of infectious mononucleosis and is associated with three human malignancies. Acyclovir [9-(2-hydroxyethoxymethyl)guanine], the first clinically useful drug effective against replication of EBV, is without effect against latent or persistent EBV infection. Three nucleoside analogs, E-5-(2-bromovinyl)-2'-deoxyuridine, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine, and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyluracil are potent inhibitors of EBV replication in vitro. Moreover, in contrast to the reversibility of viral inhibition by Acyclovir, these three drugs have prolonged effects in suppressing viral replication even after the drugs are removed from persistently infected cell cultures.


Deltorphin II-induced rapid desensitization of delta-opioid receptor requires both phosphorylation and internalization of the receptor.
Similar to other G protein-coupled receptors, rapid phosphorylation of the delta-opioid receptor in the presence of agonist has been reported. Hence, agonist-induced desensitization of the delta-opioid receptor has been suggested to be via the receptor phosphorylation, arrestin-mediated pathway. However, due to the highly efficient coupling between the delta-opioid receptor and the adenylyl cyclase, the direct correlation between the rates of receptor phosphorylation and receptor desensitization as measured by the adenylyl cyclase activity could not be established. In the current studies, using an ecdysone-inducible expression system to control the delta-opioid receptor levels in HEK293 cells, we could demonstrate that the rate of deltorphin II-induced receptor desensitization is dependent on the receptor level. Only at receptor concentrations </=90 fmol/mg of protein were rapid desensitizations (t(12) <10 min) observed. Apparently, deltorphin II-induced receptor desensitization involves cellular events in addition to receptor phosphorylation. Mutation of Ser(363) in the carboxyl tail of the delta-opioid receptor to Ala completely abolished the deltorphin II-induced receptor phosphorylation but not the desensitization response. Although the magnitude of desensitization was attenuated, the rate of deltorphin II-induced receptor desensitization remained the same in the S363A mutant as compared with wild type. Also, the S363A mutant could internalize in the presence of deltorphin II. Only when the agonist-induced clathrin-coated pit-mediated receptor internalization was blocked by 0.4 m sucrose that the deltorphin II-induced receptor desensitization was abolished in the S363A mutant. Similarly, 0.4 m sucrose could partially block the agonist-induced rapid desensitization in HEK293 cells expressing the wild type delta-opioid receptor. Taken together, these data supported the hypothesis that rapid desensitization of the delta-opioid receptor involves both the phosphorylation and the internalization of the receptor.


Prognostic indicators for survival in stage I carcinoma of the lung: a histologic study of 47 surgically resected cases.
In a previous study of 91 consecutive lung cancer cases, we reported that tumor stage was the only significant predictor of survival, with all 5-yr survivors having Stage I disease. Approximately half of the 47 Stage I cases survived 5 yr, so the present study was initiated to determine which histologic features were predictive of survival for Stage I cases. An average of 10 slides per case was evaluated independently by three pathologists, and each slide was subjectively scored using previously agreed criteria for the following parameters: vascular or lymphatic invasion; anaplasia; mitotic rate; inflammatory host response; and the presence or absence of necrosis, tumor giant cells, a central scar, mucin production, benign giant cell reaction, or desmoplasia. Survival was also correlated with patient's age, sex, tumor (T) and nodal (N) status, tumor cell type, and histologic heterogeneity. All three observers found the extent of tumor necrosis to be a significant negative predictor of survival (P less than 0.05). One observer found tumor giant cells to be an adverse factor, another observer found scar carcinomas to have worse survival, and a third observer found lymphocytic inflammatory host response to be a positive predictor and venous invasion to be a negative predictor of survival (P less than 0.05). All other parameters showed no significant correlation with survival. The finding of some parameters which correlated with survival according to one but not the other two observers indicates that the results of studies of histologic prognostic indicators by a single observer may not be valid for other pathologists attempting to use the same subjective criteria.


Effects of polarization state and scatterer concentration on optical imaging through scattering media.
The imaging resolution in turbid media is severely degraded by light scattering. Resolution can be improved if the unscattered or weakly scattered light is extracted. Here the state of polarization of the emerging light is used to discriminate photon path length, with the more weakly scattered photons maintaining their original polarization state. It is experimentally demonstrated that over a wide range of scatterer concentrations there exist three distinct imaging regimes. It is also shown that within the intermediate regime one of two distinct imaging techniques is appropriate, depending on the particle size.


Evolutionary analyses of KCNQ1 and HERG voltage-gated potassium channel sequences reveal location-specific susceptibility and augmented chemical severities of arrhythmogenic mutations.
Mutations in HERG and KCNQ1 potassium channels have been associated with Long QT syndrome and atrial fibrillation, and more recently with sudden infant death syndrome and sudden unexplained death. In other proteins, disease-associated amino acid mutations have been analyzed according to the chemical severity of the changes and the locations of the altered amino acids according to their conservation over metazoan evolution. Here, we present the first such analysis of arrhythmia-associated mutations (AAMs) in the HERG and KCNQ1 potassium channels. Using evolutionary analyses, AAMs in HERG and KCNQ1 were preferentially found at evolutionarily conserved sites and unevenly distributed among functionally conserved domains. Non-synonymous single nucleotide polymorphisms (nsSNPs) are under-represented at evolutionarily conserved sites in HERG, but distribute randomly in KCNQ1. AAMs are chemically more severe, according to Grantham's Scale, than changes observed in evolution and their severity correlates with the expected chemical severity of the involved codon. Expected chemical severity of a given amino acid also correlates with its relative contribution to arrhythmias. At evolutionarily variable sites, the chemical severity of the changes is also correlated with the expected chemical severity of the involved codon. Unlike nsSNPs, AAMs preferentially locate to evolutionarily conserved, and functionally important, sites and regions within HERG and KCNQ1, and are chemically more severe than changes which occur in evolution. Expected chemical severity may contribute to the overrepresentation of certain residues in AAMs, as well as to evolutionary change.


Repeatability and reliability of semi-automated anterior segment-optical coherence tomography imaging compared to manual analysis in normal and keratoconus eyes.
To assess the repeatability and reliability of semi-automated EyeMark Python program measurements compared to manual ImageJ image processing of anterior segment-optical coherence tomography (AS-OCT) structures in healthy and keratoconus eyes. Heidelberg AS-OCT was used to image 25 eyes from 14 healthy subjects and 25 eyes from 15 subjects with keratoconus between the ages of 20 and 80 years, collected prospectively, in this observational case-control study. Visual axis scan containing vertical fixation light beam was selected from the 15-line AS-OCT scan raster. Central corneal thickness (CCT), anterior corneal radius of curvature (ACRC), posterior corneal radius of curvature (PCRC), and truncated anterior vault (TAV) were measured using ImageJ software and the EyeMark Python program. MedCalc and R were used to calculate the intraclass correlation coefficient (ICC) and generate Bland-Altman plots (BAP). When comparing the measurements of CCT, ACRC, PCRC, and TAV between manual ImageJ analysis and the EyeMark Python program, ICC values were consistently greater than 0.9, indicating excellent agreement. BAPs comparing the ImageJ and Python measurements of anterior segment structures show no systematic proportional bias and the average differences were near zero and within 95% of the limits of agreement. Semi-automated tools may provide the necessary efficiency for point-of-care quantitative corneal analysis of raw AS-OCT images. The semi-automated EyeMark Python program offers a repeatable and reliable tool compared to manual ImageJ analysis for measuring anterior segment structures from AS-OCT images among individuals with keratoconus.


Evolution of the black muntjac (Muntiacus crinifrons) karyotype revealed by comparative chromosome painting.
The black muntjac (Muntiacus crinifrons) has an unusual karyotype of 2n = 8 in females and 2n = 9 in males. We have studied the evolution of this karyotype by hybridising chromosome-specific paints derived from flow-sorted chromosomes of the Chinese muntjac (M. reevesi, 2n = 46) to chromosomes of the black muntjac. The hybridisation pattern allowed us to infer chromosomal homologies between these two species. Tandem and centromeric fusions, reciprocal translocations, and insertions are involved in the reduction of the diploid number from 2n = 46 to 2n = 8, 9. The painting patterns further show complex chromosomal rearrangements in the male black muntjac which involve more than half the karyotype, including both sex chromosomes. Since early meiosis is reported to be normal without any visible inversion loops of the synaptonemal complex, the observed chromosomal rearrangements would lead to heterosynapsis and, therefore, leave a large fraction of the male black muntjac karyotype balanced between the two sexes.


Comparing sensitivity estimates from MLDS and forced-choice methods in a slant-from-texture experiment.
Maximum likelihood difference scaling (MLDS) is a method for the estimation of perceptual scales based on the judgment of differences in stimulus appearance (Maloney & Yang, 2003). MLDS has recently also been used to estimate near-threshold discrimination performance (Devinck & Knoblauch, 2012). Using MLDS as a psychophysical method for sensitivity estimation is potentially appealing, because MLDS has been reported to need less data than forced-choice procedures, and particularly naive observers report to prefer suprathreshold comparisons to JND-style threshold tasks. Here we compare two methods, MLDS and two-interval forced-choice (2-IFC), regarding their capability to estimate sensitivity assuming an underlying signal-detection model. We first examined the theoretical equivalence between both methods using simulations. We found that they disagreed in their estimation only when sensitivity was low, or when one of the assumptions on which MLDS is based was violated. Furthermore, we found that the confidence intervals derived from MLDS had a low coverage; i.e., they were too narrow, underestimating the true variability. Subsequently we compared MLDS and 2-IFC empirically using a slant-from-texture task. The amount of agreement between sensitivity estimates from the two methods varied substantially across observers. We discuss possible reasons for the observed disagreements, most notably violations of the MLDS model assumptions. We conclude that in the present example MLDS and 2-IFC could equally be used to estimate sensitivity to differences in slant, with MLDS having the benefit of being more efficient and more pleasant, but having the disadvantage of unsatisfying coverage.


Clinical outcomes of medial collateral ligament injury in total knee arthroplasty.
Intraoperative injury to the medial collateral ligament (MCL) during total knee arthroplasty (TKA) is a rare but severe complication. The main treatment methods are primary repair and revision with a more constrained implant; however, the clinical outcomes of primary reconstruction without a constrained implant have rarely been reported.A retrospective study was performed to evaluate the prevalence of iatrogenic injury to the MCL during primary TKA, and to report the clinical outcomes of MCL reconstruction without the use of a constrained device.A total of 1749 patients (2054 knees) underwent primary TKA between 2007 and 2013 and were retrospectively evaluated. Seventeen patients (0.83%) experienced an MCL injury intraoperatively, and the remaining 1732 patients (2037 knees) were considered as the controls. We attempted to reconstruct the MCL with an unconstrained prosthesis in all patients. The Knee Society Score (KSS) was used to evaluate knee function after an average 51-month follow-up (range, 36-72 months).No patients were lost during the follow-up period. In the MCL injury group, the mean KSS was 84.7 for function and 87.7 for pain, while the scores were 87.9 and 90.6, respectively, in the control group. No patient treated with MCL reconstruction without increased prosthetic constraint experienced knee instability requiring revision.MCL reconstruction without a constrained implant achieved excellent results for MCL injury during TKA. Level IV, therapeutic study.


Anomalous dynamics of binary colloidal mixtures over a potential barrier: effect of depletion interaction.
The dynamics of a binary colloidal mixture under the influence of an external potential barrier has been studied by molecular dynamics simulations. The attractive depletion interaction between the barrier and larger particles fastens the dynamics of the larger particles over the potential barrier. At low temperatures, depletion interactions cause the larger particles to diffuse faster than smaller particles, which is counterintuitive. The repulsive barrier leads the small particles to undergo an anomalous diffusion which resembles the dynamics of systems undergoing a glass transition, while the larger particles undergo normal diffusion even at very low temperature.


Feeding broiler breeders a reduced balanced protein diet during the rearing and laying period impairs reproductive performance but enhances broiler offspring performance.
Mammalian studies have shown that nutritional constraints during the perinatal period are able to program the progeny (metabolism, performance). The presented research aimed to investigate if broiler breeders and their offspring performance could be influenced by reducing the dietary crude protein (CP) level with 25%. A total of 160 day-old pure line A breeder females were randomly divided over 2 dietary treatments. The control group was fed commercial diets, whereas the reduced balanced protein (RP) breeders received an isoenergetic diet that was decreased with 25% in dietary CP and amino acid during their entire lifespan. The RP birds required an increased feed allowance, varying between 3 and 15%, to meet the same BW goals as their control fed counterparts. The difference in feed allocations and reduction of the dietary CP level resulted in a net protein reduction varying between 14 and 23%. At wk 27 and 40, the body composition of the breeders was changed as a result of the dietary treatment. At both ages, the proportional abdominal fat pad weight of the RP breeders was increased (P < 0.001), whereas the proportional breast muscle weight was only higher at wk 27 in the control group compared to the RP group (P < 0.001). Egg weight (P < 0.001) and egg production (P < 0.001) was decreased for the RP fed birds. The lower dietary CP level reduced the proportional albumen weight of the RP eggs (P = 0.006). Male offspring from RP breeders were characterized by an increase in BW from 28 d until 35 d of age (P = 0.015). Moreover, female progeny of RP breeders showed a reduced FCR (P = 0.025), whereas male progeny showed a tendency (P = 0.052) towards a lower FCR at 5 wk of age. In conclusion, lowering dietary CP levels in rearing and laying phase of breeders had a negative effect on breeder performance but enhanced live performance of the offspring.


Pendulating-A grounded theory explaining patients' behavior shortly after having a leg amputated due to vascular disease.
Although the group of vascular leg amputated patients constitutes some of the most vulnerable and frail on the orthopedic wards, previous research of amputated patients has focused on patients attending gait training in rehabilitation facilities leaving the patient experience shortly after surgery unexplored. Understanding patients' behavior shortly after amputation could inform health professionals in regard to how these vulnerable patients' needs at hospital can be met as well as how to plan for care post-discharge. To construct a grounded theory (GT) explaining patients' behavior shortly after having a leg amputated as a result of vascular disease. In line with constructivist GT methodology, data from ethnographic observations and interviews were simultaneously collected and analyzed using the constant comparative method covering the patients' experiences during the first 4 weeks post-surgery. Data collection was guided by theoretical sampling and comprised 11 patients. A GT was constructed. Patients went through a three-phased process as they realized they were experiencing a life-changing event. The first phase was "Losing control" and comprised the sub-categories "Being overwhelmed" and "Facing dependency." The second phase was "Digesting the shock" and comprised the sub-categories "Swallowing the life-changing decision," "Detecting the amputated body" and "Struggling dualism." The third phase was "Regaining control" and comprised the sub-categories "Managing consequences" and "Building-up hope and self-motivation." "Pendulating" was identified as the core category describing the general pattern of behavior and illustrated how patients were swinging both cognitively and emotionally throughout the process. The theory of "Pendulating" offers a tool to understand the amputated patients' behavior and underlying concerns and to recognize where they are in the process. Concepts from the theory could be used by health professionals who support patients coping with the situation by offering terms to express and recognize patients' reactions.


Centrosomes in the zebrafish (Danio rerio): a review including the related basal body.
Ever since Edouard Van Beneden and Theodor Boveri first formally described the centrosome in the late 1800s, it has captivated cell biologists. The name clearly indicated its central importance to cell functioning, even to these early investigators. We now know of its role as a major microtubule-organizing center (MTOC) and of its dynamic roles in cell division, vesicle trafficking and for its relative, the basal body, ciliogenesis. While centrosomes are found in most animal cells, notably it is absent in most oocytes and higher plant cells. Nevertheless, it appears that critical components of the centrosome act as MTOCs in these cells as well. The zebrafish has emerged as an exciting and promising new model organism, primarily due to the pioneering efforts of George Streisinger to use zebrafish in genetic studies and due to Christiane Nusslein-Volhard, Wolfgang Driever and their teams of collaborators, who applied forward genetics to elicit a large number of mutant lines. The transparency and rapid external development of the embryo allow for experiments not easily done in other vertebrates. The ease of producing transgenic lines, often with the use of fluorescent reporters, and gene knockdowns with antisense morpholinos further contributes to the appeal of the model as an experimental system. The added advantage of high-throughput screening of small-molecule libraries, as well as the ease of mass rearing together with low cost, makes the zebrafish a true frontrunner as a model vertebrate organism. The zebrafish has a body plan shared by all vertebrates, including humans. This conservation of body plan provides added significance to the existing lines of zebrafish as human disease models and adds an impetus to the ongoing efforts to develop new models. In this review, the current state of knowledge about the centrosome in the zebrafish model is explored. Also, studies on the related basal body in zebrafish and their relationship to ciliogenesis are reviewed.


ABC-transporters are localized in caveolin-1-positive and reggie-1-negative and reggie-2-negative microdomains of the canalicular membrane in rat hepatocytes.
The canalicular plasma membrane is constantly exposed to bile acids acting as detergents. Bile acids are essential to mediate release of biliary lipids from the canalicular membrane. Membrane microdomains (previously called lipid rafts) are biochemically defined by their resistance to detergent solubilization at cold temperature. We aimed to investigate the canalicular plasma membrane for the presence of microdomains, which could protect this membrane against the detergent action of bile acids. Highly purified rat liver canalicular plasma membrane vesicles were extracted with 1% Triton X-100 or 1% Lubrol WX at 4 degrees C and subjected to flotation through sucrose step gradients. Both detergents yielded detergent-resistant membranes containing the microdomain markers alkaline phosphatase and sphingomyelin. However, cholesterol was resistant to Lubrol WX solubilization, whereas it was only marginally resistant to solubilization by Triton X-100. The microdomain marker caveolin-1 was localized to the canalicular plasma membrane domain and was resistant to Lubrol WX, but to a large extent solubilized by Triton X-100. The two additional microdomain markers, reggie-1 and reggie-2, were localized to the basolateral and canalicular plasma membrane and were partially resistant to Lubrol WX but resistant to Triton X-100. The canalicular transporters bile salt export pump, multidrug resistance protein 2, multidrug resistance-associated protein 2, and Abcg5 were largely resistant to Lubrol WX but were solubilized by Triton X-100. These results indicate the presence of two different types of microdomains in the canalicular plasma membrane: "Lubrol-microdomains" and "Triton-microdomains". "Lubrol-microdomains" contain the machinery for canalicular bile formation and may be the starting place for canalicular lipid secretion.


Clinical evaluation of melanomas and common nevi by spectral imaging.
A clinical trial on multi-spectral imaging of malignant and non-malignant skin pathologies comprising 17 melanomas and 65 pigmented common nevi was performed. Optical density data of skin pathologies were obtained in the spectral range 450-950 nm using the multispectral camera Nuance EX. An image parameter and maps capable of distinguishing melanoma from pigmented nevi were proposed. The diagnostic criterion is based on skin optical density differences at three fixed wavelengths: 540nm, 650nm and 950nm. The sensitivity and specificity of this method were estimated to be 94% and 89%, respectively. The proposed methodology and potential clinical applications are discussed.


The Asian American hepatitis B program: building a coalition to address hepatitis B health disparities.
Community coalitions are increasingly recognized as important strategies for addressing health disparities. By providing the opportunity to pool resources, they provide a means to develop and sustain innovative approaches to affect community health. This article describes the challenges and lessons learned in building the Asian American Hepatitis B Program (AAHBP) coalition to conduct a community-based participatory research (CBPR) initiative to address hepatitis B (HBV) among New York City Asian-American communities. Using the stages of coalition development as a framework, a comprehensive assessment of the process of developing and implementing the AAHBP coalition is presented. Findings highlight the importance of developing a sound infrastructure and set of processes to foster a greater sense of ownership, shared vision, and investment in the program. Grassroots community organizing and campus-community partnerships can be successfully leveraged to address and prevent a significant health disparity in an underserved and diverse community.


Recent developments in the treatment of gastric carcinoma.
Surgery remains the mainstay for the curative treatment of gastric carcinoma. However, despite adequate surgery, survival remains poor. The use of adjuvant chemotherapy and radiotherapy has been examined in multiple previous clinical trials without convincing evidence of efficacy. However, recently, a large randomized controlled Intergroup trial, INT 116, demonstrated a survival advantage with chemoradiotherapy following curative surgery for gastric cancer. This review discusses the merits of the Intergroup trial and the ways in which it should affect the treatment of gastric cancer in the United States. INT 116 provides a foundation on which we can build to improve the care of patients with gastric cancer. With the evaluation of potentially better chemotherapeutic agents and the advent of molecularly directed therapy, there is increasing hope for improving the care of patients with gastric carcinoma.


Risk of major congenital malformations associated with infertility and its treatment by extent of iatrogenic intervention.
Cumulative evidence from large cohort studies, multicenter studies, and meta-analyses suggests that assisted reproductive technologies are associated with an elevated risk of congenital malformations. Theoretically, there are several putative factors in infertility treatments which may be related to the development of congenital malformations. These include, in part, the exposure to gonadotrophin stimulation and the exposure to supra-physiological levels of E2; the altered physiological environment of implantation; the in-vitro culture conditions at early stages of embryonic development; the artificial selection of sperm for fertilization and the sperm injection process in ICSI and the process of embryo cryopreservation. However, it is also possible that the culprit is not the infertility treatment that leads to the increased risk of congenital malformations but a factor or factors inherent to infertile patients. The aim of this review is to present the current data, summarize it and define the association between major congenital malformation and different types of infertility treatments as well as to infertility per se. We conducted an extensive search of the medical literature (Pubmed, 1985-2006) to identify all data relating major congenital malformations to infertile couples, infertility treatments or to characteristics of the infertile population. The rates of congenital malformations associated with infertility were analyzed by the degree of iatrogenic intervention to better define the relative risks. The findings confirmed the increased risk of congenital malformations in relation to in vitro fertilization even in singleton infants. There was no difference in the occurrence of major congenital malformations by either the laboratory maneuvers of sperm or embryos of varying complexity or by the specific medications used for ovarian stimulation or luteal support. Increased risk for congenital malformations was also found in infertile couples in relation to infertility treatment with ovulation induction with or without intrauterine insemination and even in spontaneous conception. The data seems to indicate that infertile couples harbor an inherent, a priori risk for congenital malformations in their offspring. The risk increases in direct relation to the severity of infertility treatment in which the pregnancy was obtained. The question still remains if this direct relation reflects the severity of the infertility status of the couple or is related to an added value imposed by the infertility treatment.


In vitro effect of pH and glucose concentration on the antibacterial activity of norfloxacin in urine.
The in vitro effect of pH and glucose concentration on the antibacterial activity of norfloxacin in urine was studied. Norfloxacin effectively inhibited the growth of four gram-negative pathogens in urine in vitro at pH values of 6.0, 7.0, and 8.0. The antibacterial activity of norfloxacin in urine was reduced severalfold at pH 6, but minimum inhibitory concentrations (MICs) at this pH remained clinically significant. Glucose at concentrations of 200 mg/dl and 400 mg/dl (simulating glucosuria of diabetes) did not significantly affect the antibacterial activity of norfloxacin when tested against clinical isolates of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, or Pseudomonas aeruginosa. Norfloxacin appears to be a highly effective antibiotic in vitro under conditions which simulate normal and diabetic states.