Physiologic correlates of intraoperative blood transfusion among patients undergoing major gastrointestinal operations.
Guidelines for transfusion focus on nadir levels of hemoglobin. Hemoglobin triggers may not be helpful, however, in defining appropriate intraoperative use of packed red blood cells. We sought to define the use of intraoperative packed red blood cells relative to quantitative physiologic factors at the time of operation. Prospective intraoperative data on patients undergoing a major gastrointestinal operation between 2010 and 2014 were analyzed. Risk of intraoperative transfusion was assessed with multivariable extended Cox models using baseline clinical covariates and time-varying intraoperative covariates. Among 2,316 patients, the mean preoperative hemoglobin was 12.6 g/dL (standard deviation = 2.0 g/dL), while the median estimated blood loss was 200 mL (interquartile range: 100-55 mL). Overall, 357 (15.4%) patients received a transfusion intraoperatively. A greater hazard of transfusion was associated with a greater American Society of Anesthesiologists class (ref: American Society of Anesthesiologists class I-II; American Society of Anesthesiologists class III-IV; hazard ratio = 1.44, 95% confidence interval, 1.18-1.77, P < .001), and a lesser preoperative hemoglobin level (per 1 g/dL increase; hazard ratio = 0.70, 95% confidence interval, 0.65-0.74, P < .001). In addition, an increase in heart rate of 10 beats/min above the cumulative average at any measurement was associated with up to a 30% increased probability of transfusion (hazard ratio = 1.30, 95% confidence interval, 1.15-1.47, P < .001); similarly, an increase in mean arterial pressure of 10 mm Hg was associated with an 8% decreased likelihood of transfusion (hazard ratio = 0.92, 95% confidence interval, 87-0.99, P = .017). In contrast, nadir hemoglobin was not associated with the risk of receiving a transfusion (hazard ratio = 1.10, 95% confidence interval, 0.97-1.23, P = .129). Among patients who received an intraoperative transfusion, 9.2% (n = 33) never had a hemoglobin nadir below 10 g/dL, nor an average mean arterial pressure less than 65 mm Hg or a heart rate greater than 100 beats/min around the time of transfusion. Among the intraoperative factors, heart rate, and mean arterial pressure were strongly associated with the likelihood of receiving a transfusion, despite the observation that 9.2% of patients never had a physiologic indicator for transfusion or a nadir hemoglobin below 10 g/dL, suggesting a subset of patients could benefit from a decrease in intraoperative rate of transfusion.


Pharmacokinetics and bioequivalence evaluation of leflunomide tablets in Korean healthy volunteers.
Leflunomide is a disease-modifying antirheumatic drug. The purpose of this study was to evaluate the bioequivalence of a test drug (CJ leflunomide) and a commercially available reference drug (Arava®) at 2 doses (10 and 20 mg) in healthy Korean volunteers. This was a single-dose (28 individuals enrolled at each dose group), randomized, open-label, 2-way crossover study. The 2 treatment periods were separated by a 56-day wash-out interval. Blood sampling was conducted until 672 h after drug administration. Plasma teriflunomide (active metabolite of leflunomide) concentrations were determined, and pharmacokinetic parameters were calculated. Bioequivalence was evaluated using an ANOVA model, based on the AUCt and the Cmax after administration of leflunomide tablets. Bioequivalence was defined as the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUCt and Cmax for the test and reference drugs being within the range of 0.80-1.25. The GMRs (90% CI) for AUCt and Cmax were 0.9506 (0.9091-0.9941) and 0.9861 (0.9360-1.0389), respectively, in the 10 mg study, and 0.9524 (0.9101-0.9968) and 0.9740 (0.9314-1.0186), respectively, in the 20 mg study. The 90% CIs of AUCt and Cmax at each dose were within the accepted range for bioequivalence. Based on the results, the test drug (CJ leflunomide) was bioequivalent to the commercially available reference drug (Arava®) at both doses.


A missing piece in the puzzle: the presence of Euglossa viridissima in the Baja California Peninsula (Hymenoptera, Apidae).
Orchid bees are a conspicuous component of the neotropical bee fauna, with a few species reaching the northernmost natural distribution for the group in northwestern continental Mexico. Among them, Euglossa viridissima Friese is here reported for the first time in the Cape Region of the Baja California peninsula, Mexico, where no species of the group have been found previously. These records are presented, their biogeographical implications discussed, and some interpretations of the local factors that influence the bees is presented.


Acute and Subacute Triggers of Cardiovascular Events.
Inability to predict short-term cardiovascular (CV) events and take immediate preemptive actions has long been the Achilles heel of cardiology. However, certain triggers of these events have come to light. Although these triggers are nonspecific and are part of normal life, studying their temporal relationship with the onset of CV events provides an opportunity to alert high-risk atherosclerotic patients who may be most vulnerable to such triggers, the "vulnerable patient". Herein, we review the literature and shed light on the epidemiology and underlying pathophysiology of different triggers. We describe that certain adrenergic triggers can precipitate a CV event within minutes or hours; whereas triggers that elicit an immune or inflammatory response such as infections may tip an asymptomatic "vulnerable patient" to become symptomatic days and weeks later. In conclusion, healthcare providers should counsel high-risk CV patients (e.g., in secondary prevention clinics or those with coronary artery Calcium >75th percentile) on the topic, advise them to avoid such triggers, take protective measures once exposed, and seek emergency care immediately after becoming symptomatic after such triggers. Furthermore, clinical trials targeting triggers (prevention or intervention) are needed.


Energy Landscapes in Photochemical Dissociation of Small Peroxides.
Organic peroxides are known to have important roles in many chemical and biochemical processes such as intermediates in the oxidation of various hydrocarbons, as initiators of free-radical polymerization and cross-linking agents, etc. Consequently, the study of the organic peroxides and their radicals are of fundamental interest and importance. Although several reaction pathways after dissociation of organic peroxides have been successfully identified using time-resolved optical absorption spectroscopy, interpretation of the data can be complicated due to spectral overlap of parent molecules, intermediates, and products. Therefore, a reliable theoretical framework is necessary in case of complex or less studied systems. In this study, we investigated the plausible thermal dissociation pathways of diethyl peroxide, ditert butyl peroxide, and dicumyl peroxide by density functional theory with M06-2X hybrid functional and compared its results to coupled cluster single double and perturbative triple, CCSD(T), level energies. Our results indicate that methyl radical elimination is the main dissociation mechanism for all of the studied peroxides after O-O bond cleavage which has been also observed in experiments. The resulting relative energies of the M06-2X functional were found to have reasonable accuracy in comparison with the CCSD(T) method. We also show that time-dependent density functional theory (TD-DFT) with the M06-2X functional provides a suitable guide for interpretation of time-resolved optical absorption spectra of peroxides. The experimental transient absorption spectra of dicumyl peroxide are interpreted using the theoretically predicted pathways and transient radical species. Both results agree within experimental resolution and accuracy. We propose that the traditionally assigned visible absorption is not due to the cumuloxyl radical and the photodissociation of dicumyl peroxide involves other pathways with extremely short-lived radicals.


[Boxer's fracture: Cost evaluation orthopaedic or surgical treatment].
Many methods of treatment have been proposed for fractures of the neck of the fifth metacarpal ranging from early mobilization to various surgical techniques. The aim of this retrospective study was to evaluate the functional results and the costs of closed as opposed to open treatment (Foucher's K-Wire technique). We conducted a retrospective study on all fractures without rotational deformity and with a palmar angulation less than 40 degrees C. Details of the patients, the fractures, functional results and the cost of management were analyzed. The functional results were similar between the two groups, but surgical treatment increased the cost of treatment to 1100 euros. We advocate the use of closed treatment for these fractures. The functional results are the same as with surgical management, but the costs are much reduced.


Structure and function of the vertebrate magnetic sense.
Some vertebrates can navigate over long distances using the Earth's magnetic field, but the sensory system that they use to do so has remained a mystery. Here we describe the key components of a magnetic sense underpinning this navigational ability in a single species, the rainbow trout (Oncorhynchus mykiss). We report behavioural and electrophysiological responses to magnetic fields and identify an area in the nose of the trout where candidate magnetoreceptor cells are located. We have tracked the sensory pathway from these newly identified candidate magnetoreceptor cells to the brain and associated the system with a learned response to magnetic fields.


[Tumoral development of prolactin-secreting pituitary adenomas during pregnancy. Therapeutic approaches (author's transl)].
During pregnancy the volume of prolactin-secreting pituitary adenomas tends to increase dangerously for surrounding structures, especially the optic chiasma. When rapid growth occurs, at least three therapeutic approaches are possible: resection of the adenoma, temporization under monitoring and administration of bromocriptine. The latter treatment, which seems to be of particular value, was applied to a female patient and was followed by prompt regression of optic chiasma compression. However, as bromocriptine was given concurrently with chlormadinone acetate, this excellent result cannot be ascribed to bromocriptine alone.


[Thrombolytic therapy of acute myocardial infarct: which drugs? Which patients?].
The efficiency of thrombolytic therapy in acute myocardial infarction has been documented in a large number of studies. The reduction of mortality has been shown for streptokinase (SK) and APSAC and various combinations (SK and aspirin). The recanalisation-rate is higher for rtPA as is the reocclusion-rate. Major bleeding complications are similar for all agents. However, the incidence of intracranial bleedings seems to be higher with rtPA; thus the cost-effectiveness for the tissue plasminogen activators is questionable. Attempts are made to focus on the implications of the major clinical trials for the therapeutic strategy in different patient-groups.


Collagenase: a key enzyme in collagen turnover.
The primary agents responsible for cartilage and bone destruction in joint diseases are active proteinases that degrade collagen and proteoglycan. All four main classes of proteolytic enzymes are involved in either the normal turnover of connective tissue or its pathological destruction. These proteinases are made by different cells found within the joints. Both extracellular and intracellular pathways exist and individual enzymes can be inhibited by specific proteinaceous inhibitors that block their activity. Recent research has implicated the matrix metalloproteinases (MMPs) in many of the processes involved in joint diseases. The metalloproteinases are capable of degrading all components of the extracellular matrix. This family of proteinases contains a group of at least three collagenases that are capable of degrading native fibrillar collagen. Collagen degradation within joint disease is recognized as the irreversible step in the destruction of cartilage that leads to a failure in joint function. The collagenases are the enzymes necessary to initiate collagen turnover in normal connective tissue turnover and in disease.


Modification of the synaptic cleft under excitatory conditions.
The synaptic cleft is the extracellular part of the synapse, bridging the pre- and postsynaptic membranes. The geometry and molecular organization of the cleft is gaining increased attention as an important determinant of synaptic efficacy. The present study by electron microscopy focuses on short-term morphological changes at the synaptic cleft under excitatory conditions. Depolarization of cultured hippocampal neurons with high K+ results in an increased frequency of synaptic profiles with clefts widened at the periphery (open clefts), typically exhibiting patches of membranes lined by postsynaptic density, but lacking associated presynaptic membranes (18.0% open clefts in high K+ compared to 1.8% in controls). Similarly, higher frequencies of open clefts were observed in adult brain upon a delay of perfusion fixation to promote excitatory/ischemic conditions. Inhibition of basal activity in cultured neurons through the application of TTX results in the disappearance of open clefts whereas application of NMDA increases their frequency (19.0% in NMDA vs. 5.3% in control and 2.6% in APV). Depletion of extracellular Ca2+ with EGTA also promotes an increase in the frequency of open clefts (16.6% in EGTA vs. 4.0% in controls), comparable to that by depolarization or NMDA, implicating dissociation of Ca2+-dependent trans-synaptic bridges. Dissociation of transsynaptic bridges under excitatory conditions may allow perisynaptic mobile elements, such as AMPA receptors to enter the cleft. In addition, peripheral opening of the cleft would facilitate neurotransmitter clearance and thus may have a homeostatic and/or protective function.


Manipulation of Promoter-Associated Noncoding RNAs in Mouse Early Embryos for Controlling Sequence-Specific Epigenetic Status.
In mammals, transcription in the zygote begins after fertilization. This transcriptional wave is called zygotic gene activation (ZGA). During ZGA, epigenetic modifications, such as DNA methylation and histone modifications, are dynamically and drastically reconstructed in a sequence-specific manner. However, how such orchestrated gene upregulation is regulated remains unknown. Recently, using microinjection techniques, we have revealed that a class of long noncoding RNAs, named promoter-associated noncoding RNAs (pancRNAs), mediates specific gene upregulation through promoter DNA demethylation during ZGA. Here, we describe the experimental methods available to control the expression levels of pancRNAs and to evaluate epigenetic status after pancRNA manipulation.


Predictive equations for the estimation of basal metabolic rate in Malaysian adults.
In the field of human energy expenditure, the measurement of basal metabolic rate (BMR) is an essential element to derive energy requirement estimates for any given population. Besides basic anthropometrics data, this paper reports the generation of predictive equation for basal metabolic rates of healthy Malaysian adult from prospective measurements on 307 male and 349 females aged 18-60 years, using the Douglas bag technique. These new equations based on body-weight reveal that the current FAO/WHO/UNU (1985) predictive equations overestimate BMR of adult Malaysian by an average of 13% in males and 9% in female subjects while differences of between 4-5% were observed when compared to Henry and Rees (1991) equations for tropical people. There is a good reason to believe that the capacity to slow down metabolism amidst the hot and humid climate experience throughout the year as a genuine phenomenon for Malaysians. Similarly, these findings suggest that at equal energy intake recommendation for similar body weight, the lower energy needs of Malaysian could put them at greater risk for developing obesity. These observed deviations must be taken into account in formulating energy requirements of the population.


Expanding the genetic code of Escherichia coli with phosphotyrosine.
Protein phosphorylation is one of the most important post-translational modifications in nature. However, the site-specific incorporation of O-phosphotyrosine into proteins in vivo has not yet been reported. Endogenous phosphatases present in cells can dephosphorylate phosphotyrosine as a free amino acid or as a protein residue. Therefore, we deleted the genes of five phosphatases from the genome of Escherichia coli with the aim of stabilizing phosphotyrosine. Together with an engineered aminoacyl-tRNA synthetase (derived from Methanocaldococcus jannaschii tyrosyl-tRNA synthetase) and an elongation factor Tu variant, we were able to cotranslationally incorporate O-phosphotyrosine into the superfolder green fluorescent protein at a desired position in vivo. This system will facilitate future studies of tyrosine phosphorylation.


Extrinsic sialylation is dynamically regulated by systemic triggers in vivo.
Recent reports have documented that extracellular sialyltransferases can remodel both cell-surface and secreted glycans by a process other than the canonical cell-autonomous glycosylation that occurs within the intracellular secretory apparatus. Despite association of the abundance of these extracellular sialyltransferases, particularly ST6Gal-1, with disease states such as cancer and a variety of inflammatory conditions, the prevalence of this extrinsic glycosylation pathway in vivo remains unknown. Here we observed no significant extrinsic sialylation in resting mice, suggesting that extrinsic sialylation is not a constitutive process. However, extrinsic sialylation in the periphery could be triggered by inflammatory challenges, such as exposure to ionizing radiation or to bacterial lipopolysaccharides. Sialic acids from circulating platelets were used in vivo to remodel target cell surfaces. Platelet activation was minimally sufficient to elicit extrinsic sialylation, as demonstrated with the FeCl3 model of mesenteric artery thrombosis. Although extracellular ST6Gal-1 supports extrinsic sialylation, other sialyltransferases are present in systemic circulation. We also observed in vivo extrinsic sialylation in animals deficient in ST6Gal-1, demonstrating that extrinsic sialylation is not mediated exclusively by ST6Gal-1. Together, these observations form an emerging picture of glycans biosynthesized by the canonical cell-autonomous glycosylation pathway, but subjected to remodeling by extracellular glycan-modifying enzymes.


Molecular cross-talk between the NFkappaB and STAT3 signaling pathways in head and neck squamous cell carcinoma.
The development of head and neck squamous cell carcinoma (HNSCC) involves the accumulation of genetic and epigenetic alterations in tumor-suppressor proteins, together with the persistent activation of growth-promoting signaling pathways. The activation of epidermal growth factor receptor (EGFR) is a frequent event in HNSCC. However, EGFR-independent mechanisms also contribute to the activation of key intracellular signaling routes, including signal transducer and activator of transcription-3 (STAT3), nuclear factor kappaB (NFkappaB), and Akt. Indeed, the autocrine activation of the gp130 cytokine receptor in HNSCC cells by tumor-released cytokines, such as IL-6, can result in the EGFR-independent activation of STAT3. In this study, we explored the nature of the molecular mechanism underlying enhanced IL-6 secretion in HNSCC cells. We found that HNSCC cells display an increased activity of the IL-6 promoter, which is dependent on the presence of an intact NFkappaB site. Furthermore, NFkappaB inhibition downregulated IL-6 gene and protein expression, and decreased the release of multiple cytokines. Interestingly, interfering with NFkappaB function also prevented the autocrine/paracrine activation of STAT3 in HNSCC cells. These findings demonstrate a cross-talk between the NFkappaB and the STAT3 signaling systems, and support the emerging notion that HNSCC results from the aberrant activity of a signaling network.


[The role of cognitive emotional self-regulation in adolescence in levels of depression, psychosomatic symptoms and subjective well-being].
More and more studies suggest that mental health may be determined by processes of emotional self-regulation. Emotion regulation is a complex concept which can be explicit and implicit and includes different cognitive and behavioral processes: evaluation, modifying of emotional reaction to accomplish goals. Our research aim was to explore the use of cognitive emotional self-regulation strategies related to mental health indicators among adolescents. The youth study was performed with a sample size of 1245 participants in Makó, in 2016. Data collection was based on self-administrated questionnaries that contained items on mental health, subjective well-being and background of sociodemographics. The data were compared on the basis of gender differences and tested by multiple linear regression analysis to map associations between the regulation strategies and mental health indicators: depression, psychosomatic symptoms, satisfaction with life. Girls reported higher levels of depression and psychosomatic symptoms and lower satisfaction with life than boys. Significant differences were observed between boys and girls in using rumination, positive refocusing, selfblame, others-blame and putting into perspective regulation strategy. In addition the nonadaptive strategies were proved to be related to higher depression and psychosomatic symptom scores, whereas adaptive strategies to higher level of satisfaction with life in both boys and girls. The study draws attention to the importance of cognitive emotion regulation strategies from the point of view of mental health and to explore the background factors of cognitive processes of emotional self-regulation.


Information engineering for molecular diagnostics.
Clinical laboratories are beginning to apply the recent advances in molecular biology to the testing of patient samples. The emerging field of Molecular Diagnostics will require a new Molecular Diagnostics Laboratory Information System which handles the data types, samples and test methods found in this field. The system must be very flexible in regards to supporting ad-hoc queries. The requirements which are shaping the developments in this field are reviewed and a data model developed. Several queries which demonstrate the data models ability to support the information needs of this area have been developed and run. These results demonstrate the ability of the purposed data model to meet the current and projected needs of this rapidly expanding field.


Radiologic staging of primary bone sarcoma: MR imaging, scintigraphy, angiography, and CT correlated with pathologic examination.
The relative value of magnetic resonance (MR) imaging, computed tomography (CT), technetium-99m bone scintigraphy, and angiography in local tumor staging was prospectively evaluated in 56 patients with primary bone sarcoma. The results of imaging were correlated with findings at surgery and at dissection of the resected specimens. MR imaging was significantly superior to CT and scintigraphy in defining intraosseous tumor length and was as accurate as CT in demonstrating cortical bone and joint involvement. It was definitely superior to CT in demonstrating involvement of muscle compartments. MR imaging was also the best modality in exhibiting the relationship between tumor and major neurovascular bundles; however, these differences were not significant. It is concluded that MR imaging is the modality of choice for local staging of primary bone sarcoma.


Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone.
Fluoroquinolones have been associated with collagen degradation, raising safety concerns related to more serious collagen disorders with use of these antibiotics, including aortic aneurysm and dissection. To examine the relationship between fluoroquinolone therapy and the risk of developing aortic aneurysm and dissection. We conducted a nested case-control analysis of 1477 case patients and 147 700 matched control cases from Taiwan's National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011. Cases patients were defined as those hospitalized for aortic aneurysm or dissection. One hundred control patients were matched for each case based on age and sex. Current, past, or any prior-year use of fluoroquinolone. Current use was defined as a filled fluoroquinolone prescription within 60 days of the aortic aneurysm or dissection; past use refers to a filled fluoroquinolone prescription between 61 and 365 days prior to the aortic aneurysm; and any prior-year use refers to having a fluoroquinolone prescription filled for 3 or more days any time during the 1-year period before the aortic aneurysm or dissection. Risk of developing aortic aneurysm or dissection. A total of 1477 individuals who experienced aortic aneurysm or dissection were matched to 147 700 controls. After propensity score adjustment, current use of fluoroquinolones was found to be associated with increased risk for aortic aneurysm or dissection (rate ratio [RR], 2.43; 95% CI, 1.83-3.22), as was past use, although this risk was attenuated (RR, 1.48; 95% CI, 1.18-1.86). Sensitivity analysis focusing on aortic aneurysm and dissection requiring surgery also demonstrated an increased risk associated with current fluoroquinolone use, but the increase was not statistically significant (propensity score-adjusted RR, 2.15; 95% CI, 0.97-4.60). Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.


Effect of varying UAV height on the precise estimation of potato crop growth.
A phenotyping pipeline utilising DeepLab was developed for precisely estimating the height, volume, coverage and vegetation indices of European and Japanese varieties. Using this pipeline, the effect of varying UAV height on the precise estimation of potato crop growth properties was evaluated. A UAV fitted with a multispectral camera was flown at a height of 15 m and 30 m in an experimental field where various varieties of potatoes were grown. The properties of plant height, volume and NDVI were evaluated and compared with the manually obtained parameters. Strong linear correlations with R2 of 0.803 and 0.745 were obtained between the UAV obtained plant heights and manually estimated plant height when the UAV was flown at 15 m and 30 m respectively. Furthermore, high linear correlations with an R2 of 0.839 and 0.754 were obtained between the UAV-estimated volume and manually estimated volume when the UAV was flown at 15 m and 30 m respectively. For the vegetation indices, there were no observable differences in the NDVI values obtained from the UAV flown at the two heights. Furthermore, high linear correlations with R2 of 0.930 and 0.931 were obtained between UAV-estimated and manually measured NDVI at 15 m and 30 m respectively. It was found that UAV flown at the lower height had a higher ground sampling distance thus increased resolution leading to more precise estimation of both the height and volume of crops. For vegetation indices, flying the UAV at a higher height had no effect on the precision of NDVI estimates.


Second trimester amniotic fluid endothelin concentration. A possible predictor for pre-eclampsia.
The mechanism of pre-eclampsia is still an enigma. There is now some evidence that amniotic concentrations of endothelin is elevated in pregnancies associated with pre-eclampsia. The aim of this prospective observational study was to record the concentration of amniotic fluid endothelin and compare this in women who develop pre-eclampsia and women who do not develop pre-eclampsia. Amniotic fluid concentration of endothelin is elevated by the second trimester in women who later develop pre-eclampsia.


Self-assembly and chemical reactivity of alkenes on platinum nanoparticles.
Stable platinum nanoparticles were synthesized by the self-assembly of alkene derivatives onto the platinum surface, possibly forming platinum-vinylidene (Pt═C═CH-) or -acetylide (Pt-C≡) interfacial bonds as a result of dehydrogenation and transformation of the olefin moieties catalyzed by platinum. Transmission electron microscopic measurements showed that the nanoparticles were well-dispersed without apparent agglomeration, indicating effective passivation of the nanoparticles by the ligands, and the average core was estimated to be 1.34 ± 0.39 nm. FTIR measurements showed the emergence of a new vibrational band at 2023 cm(-1), which was ascribed to the formation of Pt-H and C≡C from the dehydrogenation of alkene ligands on platinum surfaces. Consistent behaviors were observed in photoluminescence measurements, where the emission profiles were similar to those of alkyne-functionalized Pt nanoparticles that arose from intraparticle charge delocalization between the particle-bound acetylene moieties. Selective reactivity with imine derivatives further confirmed the formation of Pt═C═CH- or Pt-C≡ interfacial linkages, as manifested in NMR and electrochemical measurements. Further structural insights were obtained by X-ray absorption near-edge spectroscopy and extended X-ray absorption fine structure analysis, where the coordinate numbers and bond lengths of the Pt-Pt and Pt-C linkages suggested that the metal-ligand interfacial bonds were in the intermediate between those of Pt-C≡ and Pt-Csp(2).


Women's perceptions of personal cardiovascular risk and their risk-reducing behaviors.
Coronary heart disease is the leading cause of death in women. Risk factors include smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity. Without an understanding of these riskfactors, women are poorly prepared to carry out preventive self-care actions to reduce their risk. To describe perceptions of cardiovascular risk factors and risk-reducing behaviors among women with newly diagnosed coronary heart disease. A descriptive study was done in a large midwestern suburban hospital. A nonprobability sample of 33 women with coronary heart disease completed a mail questionnaire. Data were collected by using the Coronary Heart Disease Knowledge Test, the Health-Promoting Lifestyle Profile II, and questions developedfor the study. Thirty-three women responded. Mean age was 65.64 years (range, 36-85 years; SD, 11.32 years); mean educational level was 12.67 years (range, 8-18 years; SD, 1.79 years). Most of the respondents could not identify personal cardiovascular risk factors; the risks identified were considerably fewer and differed from those documented in the women's medical records. Women reported moderate levels of most risk-reducing behaviors and low levels ofphysical activity. Women with coronary heart disease may not know what risk factors they have. Women must have their risk factors assessed and should be counseled about those risks.


Paired development of hair cells in neuromasts of the teleost lateral line.
Lateral line neuromasts of the bullseye Parapriacanthus ransonetti and the cardinal fish Apogon cyanosoma were examined by scanning electron microscopy. Neuromasts showed large numbers of degenerating hair cells and immature hair cells, suggesting a high degree of hair cell turnover. New hair cells were mainly produced in pairs (fewer than 5% appear singly), the two cells of a pair having opposite but parallel orientations of their mechanosensitive axes. It is suggested that each pair results, directly or indirectly, from a single mitosis. The results further suggest that the axis of mitosis is one of the factors which determine the direction of the hair cell axis of mechanosensitivity.


Physalis alkekengi and Alhagi maurorum ameliorate the side effect of cisplatin-induced nephrotoxicity.
Cisplatin is frequently being used for the treatment of different tumors, although the application of this agent is associated with nephrotoxicity. Here, we explored the antioxidant and anti-inflammatory activities of Physalis alkekengi and Alhagi maurorum; 400 mg kg(-1) per day P. alkekengi and 100 mg kg(-1) per day A. maurorum were administered in rats, orally for 10 days after a single dose of 7 mg kg(-1) intraperitoneal cisplatin. The concentrations of creatinine, urea-nitrogen, and relative and absolute excretion of sodium/potassium were evaluated before/after therapy. Levels of malondialdehyde (MDA) and ferric-reducing antioxidant power (FRAP) were measured to assess the oxidative stress induced by cisplatin. Moreover, tissues sections were used for histological analyses and evaluation of the degree of tissue damage. Cisplatin increased serum levels of creatinine and urea-nitrogen, relative/absolute excretion of sodium/potassium, and MDA, whereas decreased FRAP level. Interestingly, P. alkekengi or A. maurorum were able to reduce the level of the renal function markers as well as the levels of sodium/potassium. This effect was more pronounced by P. alkekengi. Moreover, cisplatin induced pathological damage in kidney, whereas treatment with these agents improved this condition. Our findings demonstrate the potential therapeutic impact of P. alkekengi and A. maurorum for improving cisplatin-induced nephrotoxicity, supporting further investigations on the novel potential clinical application of these agents for patients being treated with cisplatin to ameliorate cisplatin-induced nephrotoxicity.


[Could apoptotic markers help the exploration of male infertility?].
Apoptosis is a cell death program involved in different steps of spermatogenesis, first at puberty, at the beginning of spermatogenesis, then in adult testicles by controlling normal spermatogenesis. As a result, apoptosis deregulation can affect spermatogenesis. Many studies have provided evidence that apoptosis deregulation in germinal cells resulted in male infertility. In addition, apoptosis detection in ejaculated spermatozoa arouses a growing interest in research as a reliable marker of spermatozoon quality. The aim of this review is to summarize our knowledge on physiological apoptosis during spermatogenesis, and then analyse the possibility of using apoptotic markers as selective markers of spermatozoon quality to optimize the rate of success of in vitro fertilization.


Evaluation of the One-Step ELISA kit for the detection of buprenorphine in urine, blood, and hair specimens.
A solid-phase enzyme immunoassay involving microtiter plates was recently proposed by International Diagnostic Systems corporation (IDS) to screen for buprenorphine in human serum. The performance of the kit led us to investigate its applicability in other biological matrices such as urine or blood, and also hair specimens. Low concentrations of buprenorphine were detected with the ELISA test and confirmed by HPLC/MS (buprenorphine concentrations measured by HPLC/MS: 0.3 ng/mL in urine, 0.2 ng/mL in blood, and 40 pg/mg in hair). The intra-assay precision values were 8.7% at 1 ng/mL of urine (n = 8), 11.5% at 2 ng/mL in serum (n = 8), and 11.5% at 250 pg/mg of hair (n = 8), respectively. The immunoassay had no cross-reactivity with dihydrocodeine, ethylmorphine, 6-monoacetylmorphine, pholcodine, propoxyphene, dextromoramide, dextrometorphan at 1 and 10 mg/L, or codeine, morphine, methadone, and its metabolite EDDP. A 1% cross-reactivity was measured for a norbuprenorphine concentration of 50 ng/mL. Finally, the immunoassay was validated by comparing authentic specimens results with those of a validated HPLC/MS method. From the 136 urine samples tested, 93 were positive (68.4%) after the ELISA screening test (cutoff: 0.5 ng/mL) and confirmed by HPLC/MS (buprenorphine concentrations: 0.3-2036 ng/mL). From the 108 blood or serum samples screened, 27 were positive (25%) after the ELISA test with a cutoff value of 0.5 ng/mL (buprenorphine concentrations: 0.2-13.3 ng/mL). Eighteen hair specimens were positive (72%) after the screening (cutoff: 10 pg/mg) and confirmed by LC/MS (buprenorphine concentrations: 40-360 pg/mg). The ELISA method produced false positive results in less than 21% of the cases, but no false negative results were observed with the immunological test. Four potential adulterants (hypochloride 50 mL/L, sodium nitrite 50 g/L, liquid soap 50 mL/L, and sodium chloride 50 g/L) that were added to 10 positive urine specimens (buprenorphine concentrations in the range 5.3-15.6 ng/mL), did not cause a false negative response by the immunoassay.


Pursuing the structure and function of voltage-gated channels.
A cyclical process of experimentation and theoretical analysis is being used to develop increasingly precise models of the structure and functional mechanisms of membrane proteins. Nucleic acid sequences have been determined for several voltage-gated sodium, calcium and potassium channels from invertebrates and vertebrates and from nerve and muscle tissues. Some of these sequences have been altered using site-directed mutagenesis. Properties of channels expressed after injection of normal and altered mRNA into Xenopus oocytes have been analysed by a variety of patch-clamp techniques. Preliminary structural models based on the first sequence information on sodium channels need to be modified to account for a large amount of new data. Here, Robert Guy and Franco Conti present their current view of the activation mechanism and ion selectivity of the voltage-gated channels.


Surgical Therapy of Temporal Triggered Migraine Headache.
The auriculotemporal and zygomaticotemporal nerves are the 2 primary trigger points in the temporal area of migraine headache. Different surgical approaches are described in literature, either open or endoscopic ones. We described and delineated the currently adopted strategies to treat temporal trigger points in migraine headache. Furthermore, we reported our personal experience in the field. Regardless of the type of approach, outcomes observed were similar and ranged from 89% to 67% elimination / >50% reduction rates. All procedures are minimally invasive and only minor complications are reported, with an incidence ranging from 1% to 5%. Just like upper limb compressive neuropathies, migraine headache is believed to be caused by chronic compression of peripheral nerves (ie, the terminal branches of trigeminal nerve) caused by surrounding structures (eg, muscles, vessels, and fascial bands) the removal of which eventually results in improvement or elimination of migraine attacks. Particular attention should be paid to the close nerve/artery relationship often described in anatomical studies and clinical reports.


Methoxylation of Acyl Fluorides with Tris(2,4,6-trimethoxyphenyl)phosphine via C-OMe Bond Cleavage under Metal-Free Conditions.
Acyl fluorides are subjected to methoxylation with tris(2,4,6-trimethoxyphenyl)phosphine (TMPP) to afford the corresponding methyl esters in good to excellent yields. This transformation is featured by C(sp2)-OMe bond cleavage under metal-free conditions. Unprecedented utilization of TMPP as a methoxylating agent realized the installation of an OMe group into the desired products.


Identification of Disease-Associated MicroRNAs Via Locality-Constrained Linear Coding-Based Ensemble Learning.
Clinical trials indicate that the dysregulation of microRNAs (miRNAs) is closely associated with the development of diseases. Therefore, predicting miRNA-disease associations is significant for studying the pathogenesis of diseases. Since traditional wet-lab methods are resource-intensive, cost-saving computational models can be an effective complementary tool in biological experiments. In this work, a locality-constrained linear coding is proposed to predict associations (ILLCEL). Among them, ILLCEL adopts miRNA sequence similarity, miRNA functional similarity, disease semantic similarity, and interaction profile similarity obtained by locality-constrained linear coding (LLC) as the priori information. Next, features and similarities extracted from multiperspectives are input to the ensemble learning framework to improve the comprehensiveness of the prediction. Significantly, the introduction of hypergraph-regular terms improves the accuracy of prediction by describing complex associations between samples. The results under fivefold cross validation indicate that ILLCEL achieves superior prediction performance. In case studies, known associations are accurately predicted and novel associations are verified in HMDD v3.2, miRCancer, and existing literature. It is concluded that ILLCEL can be served as a powerful tool for inferring potential associations.


Effect of Silane Heat Treatment by Laser on the Bond Strength of a Repair Composite to Feldspathic Porcelain.
Ceramic restoration fracture may occur in the oral cavity. Intraoral repair of fractured porcelain could be advantageous to both patient and dentist. The aim of this study was to evaluate the effect of heat treatment of the silane coupling agent by Er:YAG and CO2 lasers on the microshear bond strength of a repair composite to feldspathic porcelain. Sixty ceramic blocks were prepared and randomly divided into six groups (n = 10): (i) HF + silane (HS); (ii) silane + CO2 laser (SC); (iii) CO2 laser + silane (CS); (iv) silane + Er:YAG laser (SE); (v) Er:YAG laser + silane (ES); (vi) bur + HF + silane (BuHS). An adhesive resin was applied to the prepared ceramic surfaces and light-cured. Two transparent plastic tubes were placed perpendicularly to each ceramic block. The composite resin was then placed on the treated ceramic surface and light-cured for 40 seconds. The bonded blocks were stored in distilled water at 37°C for 24 hours and subjected to 3000 thermocycles. Microshear bond strength (μSBS) tests were performed using a wire and loop method. Data were analyzed using one-way ANOVA and Duncan's multiple range tests (p ≤ 0.05). The comparison of the mean μSBS values showed no significant differences between the ES and HS groups (p = 0.914). On the other hand, the specimens in these groups exhibited significantly higher bond strengths than those in the other groups (p < 0.01). The mean μSBS of the BuHS group was statistically similar to that of CS and SE groups (p > 0.05). The μSBS for the SC group was significantly lower than that of the other groups (p < 0.01), with the exception of the CS group (p = 0.674). Treatment with Er:YAG laser prior to silane application can be as effective as HF etching. Heat treatment of silane by CO2 or Er:YAG lasers does not improve the bond strength between feldspathic porcelain and composite resin.


Protein restriction, blood pressure and the progression of diabetic nephropathy.
Diabetic nephropathy is the long-term complication of diabetes responsible for the greatest increased mortality. Clinical nephropathy is characterised by a triad consisting of persistent proteinuria (total urinary protein greater than 0.5 g/24 h), rising arterial pressure and declining renal function. The role of treatment of raised blood pressure and the influence of dietary protein restriction on the established progressive phase of the disease are discussed. Subclinical elevations of urinary albumin excretion rates (greater than 30 micrograms/min; microalbuminuria), glomerular hyperfiltration and marginal elevations of arterial pressure are early markers of later clinical nephropathy which appear to respond to strict blood glucose control, blood pressure treatment and lowered dietary protein intake. Recent evidence to suggest that an inherited predisposition to raised arterial pressure may confer the susceptibility to diabetic nephropathy is presented.


EXpectation Propagation LOgistic REgRession on permissioned blockCHAIN (ExplorerChain): decentralized online healthcare/genomics predictive model learning.
Predicting patient outcomes using healthcare/genomics data is an increasingly popular/important area. However, some diseases are rare and require data from multiple institutions to construct generalizable models. To address institutional data protection policies, many distributed methods keep the data locally but rely on a central server for coordination, which introduces risks such as a single point of failure. We focus on providing an alternative based on a decentralized approach. We introduce the idea using blockchain technology for this purpose, with a brief description of its own potential advantages/disadvantages. We explain how our proposed EXpectation Propagation LOgistic REgRession on Permissioned blockCHAIN (ExplorerChain) can achieve the same results when compared to a distributed model that uses a central server on 3 healthcare/genomic datasets, and what trade-offs need to be considered when using centralized/decentralized methods. We explain how the use of blockchain technology can help decrease some of the problems encountered in decentralized methods. We showed that the discrimination power of ExplorerChain can be statistically similar to its counterpart central server-based algorithm. While ExplorerChain inherited some benefits of blockchain, it had a small increased running time. ExplorerChain has the same prerequisites as a distributed model with a centralized server for coordination. In a manner similar to secure multi-party computation strategies, it assumes that participating institutions are honest, but "curious." When evaluated on relatively small datasets, results suggest that ExplorerChain, which combines artificial intelligence and blockchain technologies, performs as well as a central server-based method, and may avoid some risks at the cost of efficiency.


Structural-electronic correlation in the first-order phase transition of [FeH2L2-Me](ClO4)2 (H2L2-Me = bis[((2-methylimidazol-4-yl)methylidene)-3- aminopropyl]ethylenediamine).
The synthesis and detailed study of the new mononuclear spin crossover complex [Fe(II)H2L(2-Me)](ClO4)2 (where H2L(2-Me) = bis[((2-methylimidazol-4-yl)methylidene)-3-aminopropyl]ethylenediamine) are reported. Variable-temperature magnetic susceptibility measurements show the occurrence of a steep spin crossover centered at 171.5 K with a hysteresis loop of ca. 5 K width (T(/2)(increasing) = 174 K and T(1/2)(decreasing) = 169 K, for increasing and decreasing temperatures, respectively). The crystal structure has been resolved for the high-spin (HS) and low-spin (LS) states at 200 and 123 K, respectively, revealing a crystallographic phase transition that occurs concomitantly to the spin crossover: at 200 K, the complex crystallizes in the monoclinic system, space group P2(1)/n, while the space group is P2(1) at 123 K. The mean Fe-N distances are shortened by 0.2 A, but the thermal spin crossover is accompanied by significant structural changes: the rearrangement of the central atom C12 of a six-membered chelate ring of [Fe(II)H2L(2-Me)]2+ to two positions (C12A and C12B) and, consequently, the lack of an inversion center at 123 K (P2(1) space group). Both HS and LS supramolecular structures involve all possible hydrogen bonds between imidazole and amine NH functions, and perchlorate anions; however, the HS supramolecular structure is a one-dimensional (1D) network, and the LS phase may better be described as a two-dimensional (2D) extended structure of A and B molecules. The structural phase transition of [FeH2L(2-Me)](ClO4)2 seems to trigger the steep and hysteretic spin crossover. Discontinuities in the temperature dependence of the Mössbauer parameters (isomer shift and quadrupole splitting) at the spin crossover temperature confirmed the occurrence of a structural phase transition. The experimental enthalpy and entropy variations were determined by differential scanning calorimetry (DSC) as 7.5 +/- 0.4 kJ/mol and 45 +/- 3 J K(-1) mol(-1), respectively. The regular solution theory was applied to the experimental data, yielding an interaction parameter of Gamma = 3.36 kJ/mol, which is larger than 2RT(1/2), which fulfills the condition for observing hysteresis.


Exenatide Reverts the High-Fat-Diet-Induced Impairment of BDNF Signaling and Inflammatory Response in an Animal Model of Alzheimer's Disease.
Alzheimer's disease (AD) is a multifactorial condition in which, along with amyloid-β (Aβ) and tau-related pathology, the synergistic activity of co-morbidity factors promote the onset and progression of the disease. Epidemiological evidence indicates that glucose intolerance, deficits in insulin secretion, or type-2 diabetes mellitus (T2DM) participate in increasing cognitive impairment or dementia risk. Insulin plays a pivotal role in the process as the hormone critically regulates brain functioning. GLP-1, the glucagon-like peptide 1, facilitates insulin signaling, regulates glucose homeostasis, and modulates synaptic plasticity. Exenatide is a synthetic GLP-1 analog employed in T2DM. However, exenatide has also been shown to affect the signaling of the brain-derived neurotrophic factor (BDNF), synaptic plasticity, and cognitive performances in animal models. In this study, we tested whether exenatide exerts neuroprotection in a preclinical AD model set to mimic the clinical complexity of the human disease. We investigated the effects of exenatide treatment in 3xTg-AD mice challenged with a high-fat diet (HFD). Endpoints of the study were variations in systemic metabolism, insulin and neurotrophic signaling, neuroinflammation, Aβ and tau pathology, and cognitive performances. Results of the study indicate that exenatide reverts the adverse changes of BDNF signaling and the neuroinflammation status of 3xTg-AD mice undergoing HFD without affecting systemic metabolism or promoting changes in cognitive performances.


Measurement of urinary total desmosine and isodesmosine using isotope-dilution liquid chromatography-tandem mass spectrometry.
The current LC-MS based desmosine/isodesmosine (DES/IDS) assays may be unsatisfactory for clinical use due to lack of an appropriate internal standard or low throughput. A fast and reliable LC-MS method using a D(5)-DES as an internal standard for measuring urinary total DES/IDS was developed and validated in this study. The reportable range of this assay was 1.0 and 480.0 ng/mL. The intra- and interassay imprecision, accuracy, and recovery for quality control samples were within acceptable range (<25%). Urinary total DES/IDS level was stable at room temperature or 4 degrees C for 20 h, and for three freeze/thaw cycles. The assay was employed to measure urine samples from COPD patients and demographically matched healthy volunteers. The total urinary DES/IDS levels were approximately 3-fold higher in COPD patients compared to healthy volunteers. The suitability of using urinary free DES to estimate elastin degradation was also evaluated in a second cohort. Despite urinary free and total DES/IDS levels being highly correlated, our data suggest that urinary total DES/IDS level is a preferred biomarker for elastin degradation. These results demonstrate that the LC-MS/MS method provides sensitive, reproducible and accurate quantification of urinary total DES/IDS as a biomarker for monitoring elastin degradation in diseases such as COPD.


Employee assistance programs: history and program description.
1. The history and development of Employee Assistance Programs (EAPs) can be traced back to the 1800s. There are currently over 10,000 EAPs in the United States. 2. Standards for program accreditation and counselor certification have been established for EAPs. The "core technology of Employee Assistance Programs" includes identification of behavioural problems based on job performance issues, expert consultation with supervisors, appropriate use of constructive confrontation, microlinkages with treatment providers and resources, macrolinkages between providers, resources, and work organizations, focus on substance abuse, and evaluation of employee success based on job performance. 3. Some EAPs take a broad brush approach, and incorporate health promotion and managed care functions.


In situ hybridization for detection of chicken anaemia virus in peripheral blood smears.
Blood smears, obtained from chickens known to be infected with or free from chicken anaemia virus (CAV), were tested to detect CAV DNA by in situ hybridization (ISH). A double-stranded, 1485 base-pair (bp) DNA probe was prepared employing polymerase chain reaction (PCR). The probe was labelled with digoxigenin or biotin by nick translation. In situ hybridization employing simple specimen preparation, using both digoxigenin- and biotin-labelled probes, provided a rapid and inexpensive method for diagnosis of CAV infection. Infection with CAV was detected by ISH prior to seroconversion by indirect immunofluorescence assay.


Determination of Lead with a Copper-Based Electrochemical Sensor.
This work demonstrates determination of lead (Pb) in surface water samples using a low-cost copper (Cu)-based electrochemical sensor. Heavy metals require careful monitoring due to their toxicity, yet current methods are too complex or bulky for point-of-care (POC) use. Electrochemistry offers a convenient alternative for metal determination, but the traditional electrodes, such as carbon or gold/platinum, are costly and difficult to microfabricate. Our copper-based sensor features a low-cost electrode material-copper-that offers simple fabrication and competitive performance in electrochemical detection. For anodic stripping voltammetry (ASV) of Pb, our sensor shows 21 nM (4.4 ppb) limit of detection, resistance to interfering metals such as cadmium (Cd) and zinc (Zn), and stable response in natural water samples with minimum sample pretreatment. These results suggest this electrochemical sensor is suitable for environmental and potentially biological applications, where accurate and rapid, yet inexpensive, on-site monitoring is necessary.


Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice.
Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam cell formation and determine whether advanced atherosclerotic lesions develop in these animals. Special attention was given to the presence of oxidized lipoproteins and expression of lipoprotein receptors. Plasma cholesterol levels in apo E3-leiden mice on an atherogenic diet increased from 2 to 36 mmol/l in 4 months. At this time apo E3-leiden mice had developed lesions, which ranged from early fatty streaks in thoracic and abdominal aorta to advanced lesions in aortic arch. Early fatty streaks were entirely composed of macrophages which also expressed scavenger receptors. Epitopes characteristic of oxidized LDL were present in macrophage-rich foam cells. Advanced atherosclerotic lesions also developed in apo E3-leiden mice including smooth muscle cell cap formation and erosion of the media. Macrophages and epitopes characteristic of oxidized LDL were present in core and shoulder regions. Scavenger receptors were expressed in macrophages in advanced lesions, whereas LDL-receptor-related protein (LRP) was mainly expressed in smooth muscle cells. It is concluded that: (1) macrophages are the major cell type in both early and advanced atherosclerotic lesions; (2) scavenger receptors and oxidized lipoproteins are present in lesion macrophages; and (3) LRP is mostly expressed in smooth muscle cells. Thus, lesions in apo E3-leiden transgenic mice have features in common with human atherosclerosis. Since lesion macrophages also retain their ability to synthesize endogenous apo E, apo E3-leiden transgenic mouse may be a useful model for studies on the development and genetics of atherosclerosis.


Omeprazole Inhibits Cell Proliferation and Induces G0/G1 Cell Cycle Arrest through Up-regulating miR-203a-3p Expression in Barrett's Esophagus Cells.
Existing data suggest that proton pump inhibitors (PPIs), particularly omeprazole, have significant anti-tumor action in monotherapy and or combination chemotherapy. Hedgehog (Hh) signaling pathway represents a leading candidate as a molecular mediator of Barrett's esophagus (BE). Studies have indicated reduced miRNAs in BE progression, however, little is known about the latent anti-neoplasm effects of miRNAs in BE cells. Here, we investigated whether omeprazole could inhibit BE progression by regulating Hh pathway and explored the promising Hh-targeted miRNAs in BE cells. We conducted qRT-PCR and immunoblotting assay to evaluate the effects of omeprazole on the expression of Hh signaling components and miR-203a-3p in CP-A and CP-B cells. The promising target genes of miR-203a-3p were predicted by bioinformatics methods, and verified by luciferase assays and qRT-PCR. The effects of omeprazole on BE cell proliferation and cell cycle distribution were determined. The overexpression or silencing of miR-203a-3p was performed to test its anti-proliferative effects. Finally, rescue experiments that miR-203a-3p inhibitor alleviated the effects of omeprazole on decreasing the levels of Gli1 mRNA, protein and luciferase were performed. Mechanistic studies showed that omeprazole could inhibit the expression of Gli1 and the nuclear localization of Gli1. Moreover, we determined that omeprazole could selectively up-regulated the expression of miR-203a-3p, and Gli1 was a bona fide target of miR-203a-3p. miR-203a-3p inhibitor alleviated the suppressing effects of omeprazole on Gli1 luciferase activity, mRNA and protein level. The functional assay suggested that omeprazole could dose-dependently inhibit BE cell growth and induce cell cycle arrest in G0/G1 phase. Additionally, overexpression and silencing of miR-203a-3p in BE cells disrupted cell cycle progress, resulting in suppressing and accelerating cell proliferation, respectively. Taken together, these data provide a novel mechanism of potentially anti-neoplastic effects for omeprazole through modulation of miR-203a-3p expression and thus suppressing Hh/Gli1 signaling in BE cells.


Effects of the insecticide esfenvalerate on zooplankton in an indoor synthetic model ecosystem.
Effects of esfenvalerate on zooplankton and their recovery potential were studied using an indoor synthetic model ecosystem. Esfenvalerate was applied to the system by direct spiking to overlying water or the introduction of treated slurry soil to imitate drift and run-off exposure. Four zooplankton taxa, Daphnia magna (Cladocera), Heterocypris incongruens (Ostracoda), Cyclops sp. (Copepoda), and Brachionus calyciflorus (Rotifera), were exposed to esfenvalerate with Raphidocelis subcapitata (green alga). In a drift scenario, lower doses (0.02-0.5 µg/L) showed slight or negligible effects, but the results for the highest dose (5 µg/L) indicated direct effects, as remarkable population decreases were observed for three taxa (except rotifera). However, for the latter dose, results of weekly or single (Day-15) zooplankton re-introductions after dosing demonstrated resilient recovery. In a run-off scenario, a nominal dose of 20 µg/L, in which the measured water concentrations remained at 3-6%, had effects similar to those of the high drift exposure scenario for cladocera and ostracoda.


[Sexual and global health: the role of the general practitioner].
Erectile dysfunction, a global health problem, has to must be considered not only as a consequence of vascular and/or psychological and/or neurological but also as the cause of a psychobehavioural disorder. The general practitioner has to screen for erectile dysfunction, prescribe treatment and its follow-up (patient's compliance, check the efficacy and tolerance) and, when necessary, explain and show the patient how to self-administer the intracavernous injections of alprostadil alfadex, which are a safe and efficient alternative.


[An unusual parotid gland foreign body].
A foreign body in the parotid gland is extremely uncommon. It can penetrate to the parotid gland through the skin or from the oral cavity via the Stenonís duct. A case of 23-years-old man with the several pieces of glass within the superficial lobe of the right parotid gland was described. The surgical removal was performed and the diagnosis of the foreign body was quite easy.


Biological processing.
The organization of brain processes leading to language and movement show important parallels with one another and also express important aspects of biological organization in general. Four major differences between biological processes and their commonly proposed analogues, machine processes, are as follows. 1) Reduction is not simplification in biological analysis; rather the subsystems that result from separation of parts of a biological system are themselves complex, often potentially viable, systems. 2) Machine processes are typically generalized, or, if specialized, they are specialized by connecting general-type subsystems in special ways. But biological systems are typically specialized at many levels, both in subsystems and their connections. 3) The history of a biological system is often an intimate and inseparable part of its structure. Furthermore biological systems never develop alone or de novo. Not only do they develop in clusters of contemporaries, they also develop in the presence of an older generation and a "culture." 4) Not only do formal logics have some constraints that biological minds may not have (e.g., internal consistency and universality), formal logics require descriptions of qualitative phenomena in a language that is inadequate and (as a deeper issue) may always require parsing a meaningful whole into approximate parts (e.g., as in writing this abstract). Instances of contrasts between biological systems and machine-type systems are seen in language and movement phenomena, such as embodying a distinction between purposes and causes and having flexibly reorganizable subassemblies, multiple goals, and motor equivalence.


IgE-mediated food allergy diagnosis: Current status and new perspectives.
In June 2005, the work of the EU Integrated Project EuroPrevall was started. EuroPrevall is the largest research project on food allergy ever performed in Europe. Major aims of the project are to generate for the first time reliable data on the prevalence of food allergies across Europe and on the natural course of food allergy development in infants. Improvement of in vitro diagnosis of food allergies is another important aim of the project. The present review summarizes current knowledge about the clinical presentation of food allergy and critically reviews available diagnostic tools at the beginning of the project period. A major problem in diagnosis is a relatively poor 'clinical specificity', i. e. both positive skin tests and in vitro tests for specific IgE are frequent in sensitized subjects without food allergy symptoms. So far, no in vitro test reliably predicts clinical food allergy. EuroPrevall aims at improving the predictive value of such tests by proceeding from diagnosis based on allergen extracts to purified allergen molecules, taking into account the affinity of the IgE-allergen interaction, and evaluating the potential of biological in vitro tests such as histamine release tests or basophil activation tests including assays performed with permanently growing cell lines.


CancerLinQ: Origins, Implementation, and Future Directions.
Rapid-learning health systems have been proposed as a potential solution to the problem of quality in medicine, by leveraging data generated from electronic health systems in near-real time to improve quality and reduce cost. Given the complex, dynamic nature of cancer care, a rapid-learning health system offers large potential benefits to oncology practice. In this article, we review the rationale for developing a rapid-learning health system for oncology and describe the sequence of events that led to the development of ASCO's CancerLinQ (Cancer Learning Intelligence Network for Quality) initiative, as well as the current state of CancerLinQ, including its importance to efforts such as the Beau Biden Cancer Moonshot. We then review the considerable challenges facing optimal implementation of a rapid-learning health system such as CancerLinQ, including integration of rapidly expanding multiomic data, capturing big data from a variety of sources, an evolving competitive landscape, and implementing a rapid-learning health system in a way that satisfies many stakeholders, including patients, providers, researchers, and administrators.


Significance of the "acute phase" factors during delivery.
In the intrauterine, peripheral and umbilical cord blood oj parturients the levels of the following glycoproteid "acute phase" factors--sialic acid, seromucoid, and haptoglobin were determined. It was found that the levels of these factors, determined in peripheral and intrauterine blood samples, were approximate. The determinations made in the umbilical cord blood showed regularly significantly lower levels. The differences found in contents of the substances studied between maternal and newborn blood were statistically significant. The possible causes of these differences were discussed considering both the placental barrier and developmental factors. It was found that the "acute phase" factors might be of importance in obstetrical practice.


[Protective action of electromagnetic radiation (40.68 MHz) on Saccharomyces cerevisiae UCM Y-517].
Electromagnetic radiation (EMR) (40.68 MHz, 15 and 30 W) has been studied for its effect on survivability of cells of Saccharomyces cerevisiae UCM Y-517 under the extremal influence of the environment factors (pH, freezing-thawing, nistatin (1.0 microg/ml)). It is shown that even short-term irradiation of the yeast suspension (during 5 min) takes protective effect under the conditions of stress factors, displayed in the increase of the number of live intact cells. It was established by cytochemical methods that 50-70 % of cells were characterized as damaged and dead in the control samples after yeast exposition under the stress conditions. Such an effect was not observed in the samples of preliminary irradiated cells. The pool of extracellular nucleotides was shown to decrease as a result of the yeast cells irradiation; one could also observe the decrease of these cells ability to acidity the culture medium. The increase of activity of intracellular enzymes of dehydrogenase complex was noted as well. Stability of electrostatic characteristics of the cell surface (zeta-potential) and catalase activity under the effect of EMR of radio-frequency range has been demonstrated. The found effect of protective action of EMR of the above frequency is of nonspecific character, which allows its mechanism universality to be supposed.


Phosphorylation of MCM4 at sites inactivating DNA helicase activity of the MCM4-MCM6-MCM7 complex during Epstein-Barr virus productive replication.
Induction of Epstein-Barr virus (EBV) lytic replication blocks chromosomal DNA replication notwithstanding an S-phase-like cellular environment with high cyclin-dependent kinase (CDK) activity. We report here that the phosphorylated form of MCM4, a subunit of the MCM complex essential for chromosomal DNA replication, increases with progression of lytic replication, Thr-19 and Thr-110 being CDK2/CDK1 targets whose phosphorylation inactivates MCM4-MCM6-MCM7 (MCM4-6-7) complex-associated DNA helicase. Expression of EBV-encoded protein kinase (EBV-PK) in HeLa cells caused phosphorylation of these sites on MCM4, leading to cell growth arrest. In vitro, the sites of MCM4 of the MCM4-6-7 hexamer were confirmed to be phosphorylated with EBV-PK, with the same loss of helicase activity as with CDK2/cyclin A. Introducing mutations in the N-terminal six Ser and Thr residues of MCM4 reduced the inhibition by CDK2/cyclin A, while EBV-PK inhibited the helicase activities of both wild-type and mutant MCM4-6-7 hexamers, probably since EBV-PK can phosphorylate MCM6 and another site(s) of MCM4 in addition to the N-terminal residues. Therefore, phosphorylation of the MCM complex by redundant actions of CDK and EBV-PK during lytic replication might provide one mechanism to block chromosomal DNA replication in the infected cells through inactivation of DNA unwinding by the MCM4-6-7 complex.


Artificial urinary sphincter implantation in women with stress urinary incontinence: preliminary comparison of robot-assisted and open approaches.
We aimed to compare outcomes of open and robot-assisted artificial urinary sphincter (AUS) implantation in female patients. The charts of all female patients who underwent an AUS implantation between 2008 and 2014 in a single center were retrospectively reviewed. From 2008 to 2012, AUS were implanted using an open approach and from 2013 to 2014 using a robot-assisted approach. Perioperative and functional parameters were compared between groups. The primary endpoint was continence status. Twenty-four women were assessed: 16 in the open group and eight in the robot-assisted group. Three patients had neurogenic stress urinary incontinence. Most patients had undergone previous procedures for urinary incontinence (15 in the open group and seven in the robotic group). Mean operative time was similar in both groups (214 vs. 211 min; p = 0.90). Postoperative complicationsrate was lower in the robot-assisted group (25 vs. 75 %; p = 0.02). There was a trend toward a lower intraoperative complication rate (37.5 vs. 62.5 %; p = 0.25), decreased blood loss (17 ml vs. 275 ml; p = 0.22), and shorter length of stay (3.5 vs. 9.3 days; p = 0.09) in the robot-assisted group. Continence rates were comparable in both groups (75 vs. 68.8 %; p = 0.75). Three AUS explantations were needed in the open group (18.8 %) compared with one in the robot-assisted group (12.5 %; p = 0.70). In female patients, the robot-assisted approach compared with open AUS implantation could decrease intraoperative and postoperative complication rates, length of hospital stay, and blood loss.


Development of antibody diversity in single germinal centers: selective expansion of high-affinity variants.
In a T cell-dependent immune response the microenvironment of the germinal center plays a crucial role in the affinity maturation of the antigen-specific, immunoglobulins. In order to look at the development of antibody diversity we have isolated single germinal centers and sequenced light chains characteristic of 2-phenyl-oxazolone (phOx)-specific antibodies. Fourteen days after immunization we can demonstrate various stages of intraclonal diversity. There are germinal centers where B cells are practically unmutated, suggesting that in these cases a substantial clonal expansion has taken place prior to the activation of the hypermutation mechanism. In other germinal centers, sequences with a low number of randomly distributed somatic mutations were observed, indicating that these changes have been introduced recently and/or that they fail to generate high-affinity variants and hence provide no basis for affinity selection. Finally, germinal centers are found in which practically all sequences carry the amino acid substitutions characteristic of the high affinity phOx antibodies. In these latter cases the high-affinity variants have been preferentially expanded. We conclude that affinity selection is a process that operates right from the beginning of germinal center development. Those B cells with a relative high affinity for the antigen gain a proliferative advantage over other cells and will dominate the response and these are the cells which will be selected to differentiate into memory cells.


[Stroke prevention with a high risk strategy of treating hypertension in patients after a transient ischemic attack].
High-risk strategies represent important preventive measures that focus on individuals with a defined high risk of suffering a chronic disease. They are valuable in addition to measures of prevention within the general population. One example for a high-risk approach for stroke prevention is the treatment of hypertension in individuals that have previously suffered a transient ischemic attack (TIA). Data from the Klosterneuburg Stroke Data Bank and other sources enable an estimate of 2000 TIAs occurring in Austria each year, half of them being hypertensives that are mostly not treated or not sufficiently treated for their hypertension. A high-risk programme that implies forced and effective treatment of hypertension would prevent some 400 strokes or 3% of 16,000 first-ever strokes per year. Costs for preventing one stroke by means of Betablocker agents would amount to ATS 3500 and by ACE-inhibitor agents ATS 11,500, respectively. In addition to general preventive measures, such a programme would have an important impact on stroke incidence and public health.


Autophagic cell death is induced by acetone and ethyl acetate extracts from Eupatorium odoratum in vitro: effects on MCF-7 and vero cell lines.
Eupatorium odoratum (EO) contains many biologically active compounds, the anticancer effects of which are not well documented. This study evaluates the cytotoxic effects and mechanism of action of EO extracts on MCF-7 and Vero cell lines. Evaluation of the cytotoxic activity using MTT assay, morphological alterations, and apoptosis were carried out. Autophagy was evaluated by LC3-A protein expression. Cytotoxic activity, membrane blebbing and ballooning at 24 hours, replacement by mass vacuolation, and double membrane vesicles mimicking autophagy and cell death were observed in the cancer cells. No apoptosis was observed by DNA fragmentation assay. Overexpression of LC3-A protein indicated autophagic cell death. Cell cycle analysis showed G0 and G2/M arrest. The Vero cells did not show significant cell death at concentrations <100 μg/mL. These results thus suggest that acetone and ethyl acetate extracts of EO induce cell death through induction of autophagy and hold potential for development as potential anticancer drugs.


Amyand's hernia managed with open repair and laparoscopic appendicectomy.
We present a rare case of Amyand's hernia that was surgically managed using an open repair of hernia combined with laparoscopic appendicectomy. A 68-year-old man presented with an irreducible recurrent right-sided inguinal hernia and abdominal pain. This gentleman had undergone three previous inguinal hernia repairs on the right, and one on the left using the open mesh technique. Ultrasound suggested the possibility of the appendix within the hernial sac and clinical correlation was advised. An open groin approach was taken to repair the incarcerated hernia. This revealed an indirect inguinal hernia containing the appendix with signs of inflammation. The base of the appendix was not visible due to there being a long appendix with fixed cecum in the abdomen. To safely resect the appendix, a laparoscopy was performed and the appendix was successfully removed. The inguinal hernia was repaired using a sutured technique without mesh. There were no post-operative complications.


Dietary determinants of one-carbon metabolism and the risk of non-Hodgkin's lymphoma: NCI-SEER case-control study, 1998-2000.
The role of dietary one-carbon determinants remains largely unexplored for non-Hodgkin's lymphoma (NHL). In a population-based case-control study of non-African-American adult (aged 20-74 years) women and men from four US Surveillance, Epidemiology, and End Results study centers (Detroit, Michigan; Iowa; Los Angeles, California; and Seattle, Washington; 1998-2000), the authors examined folate; vitamins B2, B6, and B12; methionine; and a one-carbon antagonist, alcohol, in 425 incident NHL cases and 359 controls who completed a detailed food frequency questionnaire. Adjusted odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Higher intake of one-carbon determinants from food was associated with a lower risk of NHL, but that for only vitamin B6 (highest vs. lowest quartile: odds ratio = 0.57, 95% confidence interval: 0.34, 0.95; p trend = 0.01) and methionine (odds ratio = 0.49, 95% confidence interval: 0.31, 0.76; p trend = 0.002) reached statistical significance. Folate from food was inversely associated with diffuse subtype (odds ratio = 0.47, 95% confidence interval: 0.23, 0.94; p trend = 0.03). The authors found no association between total (food plus supplement) vitamins and NHL. Nonusers of alcohol had an elevated NHL risk compared with users, and alcohol did not modify other nutrient-NHL associations. Findings suggest that one-carbon nutrients, particularly vitamin B6 and methionine, may be protective against NHL.


Non-homologous end joining requires that the DNA-PK complex undergo an autophosphorylation-dependent rearrangement at DNA ends.
Repair of chromosome breaks by non-homologous end joining requires the XRCC4-ligase IV complex, Ku, and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). DNA-PKcs must also retain kinase activity and undergo autophosphorylation at six closely linked sites (ABCDE sites). We describe here an end-joining assay using only purified components that reflects cellular requirements for both Ku and kinase-active DNA-PKcs and investigate the mechanistic basis for these requirements. A need for DNA-PKcs autophosphorylation is sufficient to explain the requirement for kinase activity, in part because autophosphorylation is generally required for end-joining factors to access DNA ends. However, DNA-PKcs with all six ABCDE autophosphorylation sites mutated to alanine allows access to ends through autophosphorylation of other sites, yet our in vitro end-joining assay still reflects the defectiveness of this mutant in cellular end joining. In contrast, mutation of ABCDE sites to aspartate, a phosphorylation mimic, supports high levels of end joining that is now independent of kinase activity. This is likely because DNA-PKcs with aspartate substitutions at ABCDE sites allow access to DNA ends while retaining affinity for Ku-bound ends and stabilizing recruitment of the XRCC4-ligase IV complex. Autophosphorylation at ABCDE sites thus apparently directs a rearrangement of the DNA-PK complex that ensures access to broken ends and joining steps are coupled together within a synaptic complex, making repair more accurate.


Association of hippocampal sclerosis with cortical dysgenesis in patients with epilepsy.
The possible dual occurrence of hippocampal sclerosis (HS) and other structural lesions (especially cortical dysgenesis [CD]) is well established in patients with chronic partial epilepsy. We describe the frequency of additional CD in a series of 100 patients with evidence of HS, using volumetric MRI. Additional, often subtle, CD was present in 15 patients: subependymal heterotopia (six), forme fruste of tuberous sclerosis (two), focal macrogyria (two), focal cortical dysplasia (one), laminar heterotopia (one), bilateral schizencephaly (one), and simplified gyral patterns (two). In contrast, in 46 healthy volunteers, only one had possible CD (p < 0.05). Only 2 of 15 patients had a history of childhood febrile convulsions. HS is a heterogeneous condition; patients being evaluated for temporal lobe surgery should be carefully screened for additional CD using appropriate MR techniques.


Dynamic force spectroscopy: Analysis of reversible bond-breaking dynamics.
The problem of diffusive bond dissociation in a double well potential under application of an external force is scrutinized. We compute the probability distribution of rupture forces and present a detailed discussion of the influence of finite rebinding probabilities on the dynamic force spectrum. In particular, we focus on barrier crossing upon extension, i.e., under linearly increased load, and upon relaxation starting from completely separated bonds. For large loading rates the rupture force and the rejoining force depend on the loading rate in the expected manner determined by the shape of the potential. For small loading rates the mean forces obtained from pull and relax modes approach each other as the system reaches equilibrium. We investigate the dependence of the rupture force distributions and mean rupture forces on external parameters such as cantilever stiffness and influence of a soft linker. We find that depending on the implementation of a soft linker the equilibrium rupture force is either unaffected by the presence of the linker or changes in a predictable way with the linker compliance. Additionally, we show that it is possible to extract the equilibrium constant of the on and off rates from the determination of the equilibrium rupture forces.


Parental Health Literacy in the Pediatric Surgical Setting.
Health literacy (HL) in the pediatric setting has been associated with poor health outcomes and plays an important role in the existing health disparities. Low parents caregivers HL influences health outcomes mainly in chronically ill children. Trying to identify the role of HL in the pediatric surgical and dentistry setting, we conducted a review of the relevant literature. The paucity of studies and the heterogeneity of the methodology do not lead to specific results. The need for more and larger studies in the field is evident and crucial in order to ameliorate the quality of surgical care in pediatric patients.


[The dynamics of tuberculosis].
The dynamics of tuberculosis is decisively influenced by factors, such as demography, BCG-vaccinations, infection rate by mycobacteria, diseases, cures, relapses and death. With national combatting programmes it is possible to develop the epidemetrical models to a dynamic-prognostic system.


[Analysis of clinical characteristics and factors associated with short term outcomes in early term neonates].
Objective: To investigate the clinical characteristics of early term and full term neonates, and analyze the risk factors associated with short term outcomes in early term neonates. Method: Neonates with birth weight (BW) ≥2 500 g from year 2013 were analyzed retrospectively based on American Congress of Obstericians & Gynecologists (ACOG) latest definition of term infants. According to inclusion and exclusion criteria, early term (gestational age 37-38 weeks) and full term(gestational age 39-40 weeks) neonates were included, whose morbidity constituent proportion was analyzed by χ(2) test or Fisher accuracy test or t test or Wilcoxon test. Risk factors associated with short term outcomes in early term population were analyzed by Logistic regression analysis. Result: There were 3 002 discharged term infants being investigated, among whom 1 303 cases were included(768 males and 535 females), and 37, 38, 39 and 40 weeks' gestational age newborns were 160, 324, 450 and 369 respectively. Compared with full term neonates(n=819), early term neonates (n=484) had longer length of hospital stay (LOS)(6.0(5.0, 9.0) vs. 6.0(4.0, 8.0), Z=2.830, P=0.005), higher usage rate of intravenous antibiotics(86.4%(418/484) vs. 80.1%(656/819), χ(2)=8.009, P=0.005), higher assisted ventilation rate(9.5%(46/484) vs. 2.9%(24/819), χ(2)=25.528, P<0.01), higher pulmonary surfactant administration rate(4.3%(21/484) vs. 1.1%(9/819), χ(2)=14.006, P<0.01), as well as higher hypoglycemia incidence(3.9%(19/484) vs. 1.2%(10/819), χ(2)=10.226, P=0.001). There were no statistically significant differences in 1 min Apgar score (9(9, 10)vs. 9(9, 10), Z=0.860, P=0.390), 5 min Apgar score (10(9, 10) vs. 10(9, 10), Z=0.810, P=0.418), white blood cell count (15 (11, 21) ×10(9) /L vs.15 (11, 22) ×10(9) /L, Z=0.880, P=0.379), hemoglobin count(180 (159, 205) vs. 182 (160, 204) g/L, Z=0.560, P=0.576), or platelet count(303(234, 372) ×10(9)/L vs. 301(237, 391) ×10(9)/L, Z=0.550, P=0.584). BW between 2 500 g and 2 999 g(OR 1.69, 95% CI: 1.10-2.62, χ(2) =5.614, P=0.018), wet lung(OR=2.61, 95% CI: 1.61-4.24, χ(2)=15.023, P=0.000)and pneumonia(OR 1.88, 95% CI: 1.14-3.08, χ(2)=6.192, P=0.013) were risk factors in early term neonates' short term adverse outcomes. Conclusion: Early term newborns are still at their "immature" state, and respiratory disorders are major risk factors associated with short term outcomes. Hence, early delivery during 37-38 weeks should be avoided as possible as we can.


Involvement of cannabinoid CB(2) receptor-mediated response and efficacy of cannabinoid CB(2) receptor inverse agonist, JTE-907, in cutaneous inflammation in mice.
Involvement of cannabinoid CB(2) receptor and effect of cannabinoid CB(2) receptor antagonist/inverse agonists on cutaneous inflammation were investigated. Mice ears topically exposed to an ether-linked analogue of 2-arachidonoylglycerol (2-AG-E) or selective cannabinoid CB(2) receptor agonist, {4-[4-(1,1-dimethylheptyl)-2,6-dimethoxy-phenyl]-6.6-dimethyl-bicyclo[3.1.1]hept-2-en-2-yl}-methanol (HU-308), had early and late ear swelling (0--24 h and 1--8 days after exposure, respectively). Both types of responses induced by 2-AG-E were significantly suppressed by oral administration of cannabinoid CB(2) receptor antagonist/inverse agonists, [N-(benzo[1,3]dioxol-5-ylmethyl)-7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxamide] (JTE-907) and {N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2 yl]5-(4-chloro-3-methyl-phenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide}} (SR 144528). In contrast, JTE-907 did not affect arachidonic acid-induced swelling. Orally administered JTE-907 (0.1-10 mg/kg) and SR 144528 (1 mg/kg) also produced significant inhibition of dinitrofluorobenzene-induced ear swelling, with increased cannabinoid CB(2) receptor mRNA expression observed in the inflamed ear. These results suggest that cannabinoid CB(2) receptor is partially involved in local inflammatory responses and cannabinoid CB(2) receptor antagonist/inverse agonist has beneficial effects on ear swelling.


Improved detection of gene-microbe interactions in the mouse skin microbiota using high-resolution QTL mapping of 16S rRNA transcripts.
Recent studies highlight the utility of quantitative trait locus (QTL) mapping for determining the contribution of host genetics to interindividual variation in the microbiota. We previously demonstrated that similar to the gut microbiota, abundances of bacterial taxa in the skin are significantly influenced by host genetic variation. In this study, we analyzed the skin microbiota of mice from the 15th generation of an advanced intercross line using a novel approach of extending bacterial trait mapping to both the 16S rRNA gene copy (DNA) and transcript (RNA) levels, which reflect relative bacterial cell number and activity, respectively. Remarkably, the combination of highly recombined individuals and 53,203 informative SNPs allowed the identification of genomic intervals as small as <0.1 megabases containing single genes. Furthermore, the inclusion of 16S rRNA transcript-level mapping dramatically increased the number of significant associations detected, with five versus 21 significant SNP-bacterial trait associations based on DNA- compared to RNA-level profiling, respectively. Importantly, the genomic intervals identified contain many genes involved in skin inflammation and cancer and are further supported by the bacterial traits they influence, which in some cases have known genotoxic or probiotic capabilities. These results indicate that profiling based on the relative activity levels of bacterial community members greatly enhances the capability of detecting interactions between the host and its associated microbes. Finally, the identification of several genes involved in skin cancer suggests that similar to colon carcinogenesis, the resident microbiota may play a role in skin cancer susceptibility and its potential prevention and/or treatment.


Diffuse interstitial pulmonary fibrosis and lung cancer.
Forty-two cases of lung cancer complicated with diffuse interstitial pulmonary fibrosis (DIPF) were selected from 13,056 autopsy cases. They were divided into primary (Group I and II) and secondary (Group III) DIPF, and histopathologic and clinicopathologic studies were made. The prevalence of lung cancer with primary DIPF was 17% (8/47) which was significantly (p less than 0.01) higher than that without DIPF (7% or 886/13,009). All eight cases of lung cancer in Group I and II were male, and 7 had cigarette-smoking history. The anatomical sites of lung cancer and DIPF were all peripheral in origin, and in 7 cases located primarily in the lower lobes (left:right = 6:1). Adenocarcinoma was the most common type. The study suggests that male DIPF patients with long clinical history should be followed thoroughly for lung cancer.


Regulation of transcription and translation by hypoxia.
The maintenance of oxygen (O2) homeostasis is critical for embryonic development and postnatal life. In response to hypoxia, higher eukaryotes have developed coordinated mechanisms at both the transcriptional and translational levels to cope with this stress. Transcription of genes controlling glycolysis, glucose transport, cell survival and death, angiogenesis and erythropoiesis are activated (primarily by the hypoxia-inducible factor [HIF]) to facilitate cell survival and restore O2 homeostasis. During hypoxia, global protein synthesis is reduced to conserve ATP, while translation of factors like HIF-1alpha and VEGF that are critical for the hypoxic response is maintained by initiation via an internal ribosomal entry mechanism. This review addresses the regulatory effects of hypoxia on mRNA transcription and translation. As hypoxia is induced by tumor growth and affects tumor progression and metastasis, unraveling the basis of hypoxic control of transcription and translation will provide a better understanding of cancer physiology and development of anti-tumor therapies.


Profiling of Sialylated Oligosaccharides in Mammalian Milk Using Online Solid Phase Extraction-Hydrophilic Interaction Chromatography Coupled with Negative-Ion Electrospray Mass Spectrometry.
Sialylated oligosaccharides are important components in mammalian milk. They play a key role in the health and growth of infants by helping to shape up infant's gastrointestinal microbiota and defense against infection by various pathogenic agents. A detailed knowledge of the structures, compositions, and quantities of the sialylated milk oligosaccharides (SMOs) is a prerequisite for understanding their biological roles. However, because of the presence of very large amounts of lactose and neutral oligosaccharides, accurate analysis of SMOs is difficult. A pretreatment step is required to remove lactose and neutral oligosaccharides but conventional off-line pretreatment methods are time-consuming and of poor reproducibility. In this presentation, we linked solid-phase extraction (SPE) with hydrophilic interaction chromatography (HILIC) followed by mass spectrometry (MS) identification for the analysis of SMOs. A SPE column with electrostatic repulsion function was used for removal of lactose and neutral oligosaccharides, a HILIC analytical column for separation of the SMOs, and negative-ion electrospray ionization tandem MS was used for their identification and sequencing. The success of the established online SPE-HILIC-MS method was demonstrated by profiling of SMOs in human to investigate detailed SMO changes during lactation period and in animals to compare the difference in SMO contents among the different species.


[Interchange of babies in Portugal by exclusions in the ADA, GPT, ESD and HLA systems (author's transl)].
The suspicion of an interchange of babies in two Portuguese families could not be dissipated in the first course of testing the following systems being considered: AB0, MNSs, Rhesus, Kell, Cellano, Duffy. Including further markers in an additional opinion, multiple father- and mother-exclusions could be made in the systems of ADA, GPT, EsD, and HLA. The suspicion thus showed to be justified and the children were given back to their natural parents.


Conserved residues within the HIV-1 Vpu transmembrane-proximal hinge region modulate BST2 binding and antagonism.
BST2 inhibits HIV-1 release by tethering nascent virions to the surface of infected cells. HIV-1 Vpu overcomes this restriction by removing BST2 from viral budding sites via BST2 intracellular trapping and sequestration, surface downregulation and/or displacement mechanisms. Vpu is composed of a short luminal tail, a transmembrane domain (TMD) and a cytoplasmic hinge region that is followed by two helices. BST2 counteraction relies on the ability of Vpu to physically bind BST2 through TMD interactions and recruit the clathrin-dependent trafficking machinery via a canonical acidic di-leucine signalling motif within the helix-2 of Vpu. The highly conserved Vpu transmembrane-proximal hinge region encompasses residues that resemble an acidic leucine-based trafficking motif, whose functional roles are currently ill-defined. In this study, we investigated the contribution of these residues towards Vpu-mediated BST2 antagonism. We show that while these conserved residues have no intrinsic activity on the cellular distribution of Vpu in the absence of BST2, they regulate the ability of Vpu to bind to BST2 and, consequently, govern both BST2-dependent trafficking properties of the protein as well as its co-localization with BST2. Moreover, these residues, particularly a glutamic acid residue positioned immediately following the TMD, are a determinant not only for efficient targeting of BST2, but also binding and degradation of CD4, another host membrane protein targeted by Vpu. Mechanistically, our data are consistent with a role of these residues in the maintenance of the Vpu TMD conformational configuration such that interactions with membrane-associated host targets are favoured. Altogether, this work demonstrates an important regulatory role of the transmembrane-proximal Vpu hinge region residues towards enabling the protein to efficiently engage its target host proteins. Thus, this highly conserved, cytosolic Vpu hinge region may represent an attractive target for the development of anti-Vpu inhibitors.


Comparison of True Ileal Amino Acid Digestibility between Adult Humans and Growing Pigs.
It is not feasible to determine the true ileal amino acid (AA) digestibility of protein sources in humans on a routine basis, and the growing pig has been recommended as an animal model for this purpose but requires further validation. To determine and compare true ileal AA digestibility between adult human ileostomates and growing cannulated pigs for a range of food proteins. Seven protein sources (black beans, bread, collagen, pigeon peas, wheat bran, whey protein isolate, and zein) that spanned the range of digestibilities typically seen in foods were evaluated. Six female growing pigs received each of the protein sources, as well as a protein-free diet, and digesta were collected via ileal T-cannula. Adult human ileostomates consumed the same protein sources (5-8 ileostomates, depending on the protein source), as well as a protein-free diet, and digesta were collected. Titanium dioxide and celite were included in the diets as indigestible markers. True ileal AA digestibility coefficients were determined. There was a significant effect of protein source (P ≤ 0.001) for all AAs. The effect of species was not significant (P > 0.05) except for total lysine (but not for available lysine). When analyzed within diets, the statistically significant species effect for true lysine digestibility was found for black beans only. Pig and human digestibility values were generally highly and significantly (P ≤ 0.05) correlated. A linear regression equation derived for true ileal AA digestibility (given as coefficients) determined in the human and pig for the overall mean of all AAs was (y = human, x = pig) y = 1.00x - 0.010, with the slope not statistically significant (P > 0.05) from unity and the intercept not different (P > 0.05) from zero. True ileal AA digestibility values determined in the growing pig can be directly used for predicting digestibility in adult humans.


Computer-enhanced surgical systems ("robotic surgery").
Computer-linked surgical systems allow surgeons to perform procedures without coming into contact with the patient. Indications for these robotic surgery systems are expanding. This technology offers potential advantages through enabling more precise surgery, which may lead to shorter patient recovery times, fewer complications and improved patient outcomes. Limited studies indicate the promise of these systems, which appear to be safe, but their efficacy is not fully established. In some procedures, the advantages they offer may also be achieved by newer non-computer assisted techniques. Capital costs are high and cost-effectiveness has not been demonstrated. Diffusion of these systems can be expected to continue, but their place in surgical practice is not yet clear. They are most likely to be of value for centres undertaking specialized surgical services.


[Mycoplasma pneumoniae encephalitis].
Clinical, CT and, in one case, autopsy findings indicated a diagnosis of a severe necrotising encephalitis in two patients. Although usually herpes simplex virus is blamed for this form of encephalitis, it was possible to prove in these two patients that Mycoplasma was the causative agent of the disease. It is concluded that this organism can produce a serious disease in the central nervous system similar to that caused by herpes simplex.