Feasibility and effect of aerobic exercise for lowering depressive symptoms among individuals with traumatic brain injury: a pilot study.
: To establish the feasibility and effect of an aerobic exercise intervention on symptoms of depression among individuals with traumatic brain injury. : A pre-post single group. : our community dwelling participants (>11 months postinjury) with residual physical impairment recruited from an outpatient clinic. : 12-week aerobic exercise program. : The Hamilton Rating Scale for Depression; aerobic capacity (cycle ergometer, heart rate at reference resistance, perceived exertion); Rosenberg Self-Esteem Scale and program perception (survey). : Descriptive statistics to depict change in outcome measure scores. Answers from the survey were collated and presented as summary statements. : All participants had fewer symptoms of depression, improved aerobic capacity and higher self esteem after the intervention. High satisfaction with the program was reported with no adverse effects. : The aerobic exercise program was feasible and effective for individuals with traumatic brain injury, leading to improved mood, cardiovascular fitness, and self-esteem. Future research is needed to determine the intensity, frequency, and duration required to reach and maintain improvement.


Effect of Fluosol-DA and hetastarch on local cerebral blood flow, cortical O2 availability and computerized EEG data during cerebral ischaemia.
This study was designed to assess the effects of volume expansion with Fluosol-DA and hetastarch on local cerebral blood flow (CBF), cortical O2 availability (O2a) and computerized EEG power data during cerebral ischaemia in a primate stroke model. Focal cerebral ischaemia was produced in 20 anaesthetized Macaca monkeys by right unilateral middle cerebral artery (MCA) occlusion by the transorbital technique. Following occlusion of the right MCA, monkeys were randomized into one of the following treatment groups: Group A--Fluosol-DA 15 ml kg-1 i.v. + 40% O2; Group B--Fluosol-DA 15 ml kg-1 i.v. + 100% O2; Group C--hetastarch 30 ml kg-1 i.v. + 40% O2; Group D--hetastarch 30 ml kg-1 i.v. + 100% O2. In Group A, local CBF increased and EEG power data improved while O2a showed no change in the right MCA territory. In Group B, local CBF increased from 84% (P less than 0.001), O2a improved significantly, and EEG power data showed significant improvement in the right hemisphere. Cardiac output did not change during the Fluosol-DA infusions. In Groups C and D, local CBF increased significantly, O2a did not change, and EEG power data improved significantly in the right hemisphere. Cardiac output also increased significantly during the hetastarch infusions. These results show that Fluosol-DA and hetastarch improve local CBF and EEG power data in ischaemic brain. Only the Fluosol-DA + 100% O2 increased the O2a in the ischaemic brain. We conclude that the benefits with Fluosol-DA are due to its ability to increase O2 delivery to ischaemic brain.


β-Glucan and Parasites.
Immunosuppression caused by parasitic infections represents the foremost way by which the parasites overcome or escape the host's immune response. Glucan is a well-established natural immunomodulator with the ability to significantly improve immune system, from innate immunity to both branches of specific immunity. Our review is focused on the possible role of glucan's action in antiparasite therapies and vaccine strategies. We concluded that the established action of glucan opens a new window in treatment and protection against parasitic infections.


Azapeptides as pharmacological agents.
Azapeptides, formed by replacing the C(alpha) of amino acid residues by nitrogen, are promising peptidomimetic compounds. Azaamino acids impart a unique conformational property to peptide structures because of the loss of chirality and reduction of flexibility of the parent linear peptide. The peculiar conformational properties make azaamino acids an attractive tool for drug design involving specific secondary structures in peptides and proteins. Additionally, since azapeptides are less susceptible to enzymatic breakdown by proteases, they may possibly lead to orally active drugs with longer duration of action. One of the advantages of azapeptides is their unproblematic synthesis allowing retention of the amino acid side chain. Azapeptides have been developed by several groups for the design of hormone analogues, protease inhibitors and active site titrants.


Evaluation of imaging studies for vesicoureteral reflux in infants with first urinary tract infection.
Routine imaging studies following first urinary tract infection(UTI) in infancy are clinically used to identify who has vesicoureteral reflux (VUR) and acute pyelonephritis or renal scars. The potential value of these images in avoiding children acquiring renal complication and whether the children benefited from these examinations were not well justified. Analysis was undertaken of 114 infants (228 renal units) at the time of first documented UTI. All underwent renal ultrasound, voiding cystourethrography (VCUG) and dimercaptosuccinic acid (DMSA) renal scan on admission and repeated follow-up VCUG, DMSA or both after 4-6 months if initial examinations showed abnormal at first time. The VUR on VCUG when UTI and its statistical correlations with both acute and follow-up DMSA renal scan revealing renal scar were calculated. Seventeen children (14.9%) had VUR detected by VCUG. Forty-six patients (40.4%) had abnormal findings on acute DMSA renal scans (acute pyelonephritis or renal scars). The sensitivity, specificity, positive prediction rate and negative prediction rates of DMSA for VUR were 63%, 82.6%, 32.7% and 94.3%, respectively. The initial identified VUR versus renal scarring on follow-up DMSA showed little correlation. There is limited effectiveness of routine investigation by VCUG in infants with first confirmed UTI. VCUG may be withheld in a child who presents with first UTI before the age of one year if there has been no demonstrable abnormal DMSA scan.


Ranolazine inhibition of hERG potassium channels: drug-pore interactions and reduced potency against inactivation mutants.
The antianginal drug ranolazine, which combines inhibitory actions on rapid and sustained sodium currents with inhibition of the hERG/IKr potassium channel, shows promise as an antiarrhythmic agent. This study investigated the structural basis of hERG block by ranolazine, with lidocaine used as a low potency, structurally similar comparator. Recordings of hERG current (IhERG) were made from cell lines expressing wild-type (WT) or mutant hERG channels. Docking simulations were performed using homology models built on MthK and KvAP templates. In conventional voltage clamp, ranolazine inhibited IhERG with an IC50 of 8.03μM; peak IhERG during ventricular action potential clamp was inhibited ~62% at 10μM. The IC50 values for ranolazine inhibition of the S620T inactivation deficient and N588K attenuated inactivation mutants were respectively ~73-fold and ~15-fold that for WT IhERG. Mutations near the bottom of the selectivity filter (V625A, S624A, T623A) exhibited IC50s between ~8 and 19-fold that for WT IhERG, whilst the Y652A and F656A S6 mutations had IC50s ~22-fold and 53-fold WT controls. Low potency lidocaine was comparatively insensitive to both pore helix and S6 mutations, but was sensitive to direction of K(+) flux and particularly to loss of inactivation, with an IC50 for S620T-hERG ~49-fold that for WT IhERG. Docking simulations indicated that the larger size of ranolazine gives it potential for a greater range of interactions with hERG pore side chains compared to lidocaine, in particular enabling interaction of its two aromatic groups with side chains of both Y652 and F656. The N588K mutation is responsible for the SQT1 variant of short QT syndrome and our data suggest that ranolazine is unlikely to be effective against IKr/hERG in SQT1 patients.


Interplay of Experiment and Theory in Elucidating Mechanisms of Oxidation Reactions by a Nonheme Ru(IV)O Complex.
A comprehensive experimental and theoretical study of the reactivity patterns and reaction mechanisms in alkane hydroxylation, olefin epoxidation, cyclohexene oxidation, and sulfoxidation reactions by a mononuclear nonheme ruthenium(IV)-oxo complex, [Ru(IV)(O)(terpy)(bpm)](2+) (1), has been conducted. In alkane hydroxylation (i.e., oxygen rebound vs oxygen non-rebound mechanisms), both the experimental and theoretical results show that the substrate radical formed via a rate-determining H atom abstraction of alkanes by 1 prefers dissociation over oxygen rebound and desaturation processes. In the oxidation of olefins by 1, the observations of a kinetic isotope effect (KIE) value of 1 and styrene oxide formation lead us to conclude that an epoxidation reaction via oxygen atom transfer (OAT) from the Ru(IV)O complex to the C═C double bond is the dominant pathway. Density functional theory (DFT) calculations show that the epoxidation reaction is a two-step, two-spin-state process. In contrast, the oxidation of cyclohexene by 1 affords products derived from allylic C-H bond oxidation, with a high KIE value of 38(3). The preference for H atom abstraction over C═C double bond epoxidation in the oxidation of cyclohexene by 1 is elucidated by DFT calculations, which show that the energy barrier for C-H activation is 4.5 kcal mol(-1) lower than the energy barrier for epoxidation. In the oxidation of sulfides, sulfoxidation by the electrophilic Ru-oxo group of 1 occurs via a direct OAT mechanism, and DFT calculations show that this is a two-spin-state reaction in which the transition state is the lowest in the S = 0 state.


Enteral Nutrition in Pediatric Short-Bowel Syndrome.
Pediatric intestinal failure (IF) is the critical reduction of intestinal mass or function below the amount necessary for normal growth in children. Short-bowel syndrome (SBS) is the most common cause of IF in infants and children and is caused by intestinal resection. Enteral autonomy and freedom from parenteral nutrition is the mainstay of nutrition management in SBS. The goal is to achieve intestinal adaptation while maintaining proper growth and development. Treatment is variable, and there remains a paucity of evidence to draw well-informed conclusions for the care of individuals in this complex population. Physiological principles of enteral nutrition and practical recommendations for advancing the diet of patients with pediatric SBS are presented. Emerging trends in nutrition management, such as the growing interest in blending diets and the impact on SBS, are reviewed. Finally, the influence of the microbiome on enteral tolerance and small bowel bacterial overgrowth are considered.


The group employed model as a foundation for health care delivery reform.
With a focus on delivering low-cost, high-quality care, several organizations using the group employed model (GEM)-with physician groups whose primary and specialty care physicians are salaried or under contract-have been recognized for creating a culture of patient-centeredness and accountability, even in a toxic fee-for-service environment. The elements that leaders of such organizations identify as key to their success are physician leadership that promotes trust in the organization, integration that promotes teamwork and coordination, governance and strategy that drive results, transparency and health information technology that drive continual quality improvement, and a culture of accountability that focuses providers on patient needs and responsibility for effective care and efficient use of resources. These organizations provide important lessons for health care delivery system reform.


An acidic modification of the cytoplasmic domain contributes to the charge heterogeneity of the MHC class I antigens.
Polypeptide phosphorylation and sialylation of the glycan moieties contribute to the charge heterogeneity of the class I major histocompatibility complex glycoproteins. The present study demonstrates that a unique acidic modification unrelated to phosphorylation or glycosylation also affects the charge heterogeneity of the H2-Kk heavy chain of BW5147 lymphoma cells. In vitro cultivation of BW5147 cells results in changes in charge heterogeneity of the H2-Kk heavy chains due to the unique acidic modification. Sequential papain digestion of the 45 000 Mr H2-Kk glycoprotein yields a 42 500 Mr glycopolypeptide initially, followed by production of a 39 000 Mr glycopolypeptide. Results from experiments designed to localize and characterize the novel acidic modification suggest that the modification resides in the segment of the H2-Kk polypeptide located between the two papain cleavage sites. This portion of the polypeptide consists of the transmembrane region and part of the cytoplasmic domain of the H2-Kk heavy chain. At steady state, 25% of the total cell surface H2-Kk possesses this modification. In addition, the modification is mutually exclusive with the phosphorylation of the H2-Kk heavy chain at Ser-333. The possible biological significance of the novel modification of class I antigens is discussed.


[Lithium and cerebral functions].
Two cases, sustaining the possible part of long term lithium therapy in progressive intellectual deterioration, are submitted. Arguments clinic as well as paraclinical and fundamental, supporting the idea of insidious lithium's neurotoxicity are discussed. Most recent findings about drug's incidence on the cerebral functioning are reviewed. The study of the erythroplasmatic ratio and the analysis of several factors implied in its variations seem to back up our hypothesis.


The Gray Lecture 2001: coming technical advances in radiation oncology.
To review the current limits on the efficacy of radiotherapy (RT) due to technical factors and to assess the potential for major improvements in technology. The method of this review was to assess the efficacy of current RT in general terms; strategies for improving RT; historical record of technological advances; rationale for further reductions of treatment volume; and importance of defining and excluding nontarget tissues from the target volume. The basis for the interest in proton beam RT is developed, and the relative dose distributions of intensity-modulated radiotherapy (IMRT) and intensity-modulated proton RT (IMPT) are discussed. The discovery of the proton and the first proposal that protons be used in RT is described. This is followed by a brief mention of the clinical outcome studies of proton RT. Likely technical advances to be integrated into advanced proton RT are considered, specifically, four-dimensional treatment planning and delivery. Finally, the increment in cost of some of these developments is presented. For definitive RT, dose limits are set by the tolerance of normal tissues/structures adjacent or near to the target. Using imaging fusion of CT, MRI, positron emission tomography, magnetic resonance spectroscopic imaging, and other studies will result in improved definition of the target margins. Proton beams are likely to replace photon beams because of their physical characteristics. Namely, for each beam path, the dose deep to the target is zero, across the target it is uniform, and proximal to the target it is less. Proton therapy can use as many beams, beam angles, noncoplanar, and dynamic, as well as static, intensity modulation, as can photon plans. The ability for much greater accuracy in defining the target position in space and then maintaining the target in a constant position in the radiation beam despite target movement between and during dose fractions will be possible. The cost of proton RT will be modestly higher than comparable high technology photon therapy. The technology of RT is clearly experiencing intense and rapid technical developments as pertains to treatment planning and dose delivery. It is predicted that radical dose RT will move to proton beam technology and that the treatment will be four dimensional (the fourth dimension is time). The impact will be higher tumor control probability and reduced frequency and severity of treatment-related morbidity.


Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors.
The simultaneous inhibition of polo-like kinase 1 (PLK1) and BRD4 bromodomain by a single molecule could lead to the development of an effective therapeutic strategy for a variety of diseases in which PLK1 and BRD4 are implicated. Compound 23 has been found to be a potent dual kinase-bromodomain inhibitor (BRD4-BD1 IC50 = 28 nM, PLK1 IC50 = 40 nM). Compound 6 was found to be the most selective PLK1 inhibitor over BRD4 in our series (BRD4-BD1 IC50 = 2579 nM, PLK1 IC50 = 9.9 nM). Molecular docking studies with 23 and BRD4-BD1/PLK1 as well as with 6 corroborate the biochemical assay results.


Characterization of the electrophysiological effects of metoprolol on isolated feline ventricular myocytes.
Metoprolol is considered to be a class II antiarrhythmic agent that is highly specific for cardiac beta-1 adrenergic receptors, yet long-term administration can produce prolongation of the rate-corrected Q-T interval in humans. Action potentials and sodium (INa), "L"-type calcium (ICa) and transient outward (Ito) or inward rectifying potassium (IKl) currents were recorded from isolated cat ventricular myocytes using the whole-cell-patch technique to determine if metoprolol can directly affect cellular electrophysiological activity. External and pipette solutions, holding potentials and voltage-clamp protocols appropriate to isolate and examine INa, IKl, Ito and ICa were used. Metoprolol reversibly decreased both the duration and voltage of the action potential plateau but had no effect on upstroke velocity, the repolarization rate during phase 3 or the resting potential. Confirming previous reports suggesting that metoprolol appears to have little or no local anesthetic activity, INa was not affected by metoprolol at concentrations up to 100 microM during voltage-clamp pulses applied at less than 1 Hz when holding potential was negative to -110 mV. However, when trains of pulses to -10 mV from a holding potential of -110 mV were applied at 1 to 5 Hz, use-dependent inhibition of INa occurred, suggesting that 100 microM metoprolol may interact with inactivated Na channels to inhibit INa. Metoprolol (10 and 100 microM) also caused a concentration-dependent decrease in peak inward IKl elicited in response to hyperpolarizing from -40 mV to potentials negative to the IKl reversal potential. In addition, during strong hyperpolarizations (i.e., less than or equal to -150 mV) an inward (i.e., downward) droop in current was observed during the inactivation phase approximately 20 to 30 msec after pulse onset. Metoprolol (10 microM) also reduced peak Ito and ICa without altering the time courses of inactivation of either current or the level of the steady-state outward current elicited positive to -40 mV; steady-state ICa, on the other hand, was reduced. The sensitivity to block by metoprolol was: IKl greater than ICa greater than or equal to Ito greater than INa.


[Metalloproteinases in tumor progression. Review].
The two biological characteristics that determine the malignancy of cancer are infiltration and metastasis. The study of these mechanisms is related to the invasion of tumoral cells and the relationship of these cells with their stroma, which interact producing the movement and accumulation of inflammatory cells, the formation of new blood vessels, multiplication of fibroblasts and the synthesis of the components of the extra cellular matrix production. Tumoral invasion is conditioned through various enzyme activities, in particular proteases which degrade the matrix, thus facilitating the progression of the tumor. The metalloproteinases (MMP) are a family of proteinases that play an important role in cancer as well as in numerous other diseases. MMP are, therefore, a potential factor in cancer therapy. Several synthetic MMP inhibitors have been developed and have shown successful anti-tumor activity in a variety of animal species, but in clinical studies of patients with advanced forms of cancer, this therapeutic strategy has not resulted as effective. In this article, due to the biological and clinical importance of this therapy, we summarize the current views on the role of metalloproteinases (MMP) in tumor promotion, proliferation, invasion, metastasis and angiogenesis.


Time-based measures of treatment effect: reassessment of ticagrelor and clopidogrel from the PLATO trial.
Treatment effects to binary endpoints using time-to-event data in randomised controlled trials are typically summarised by reporting HRs derived with Cox proportional hazard models. Alternative and complementary methods include summarising the between-treatment differences on the metric time scale, quantifying the effect as delay of the event (DoE). The aim of this study was to reassess data from the PLATO study expressing the effects as the time by which the main outcomes are delayed or hastened due to treatment. PLATO was a randomised controlled double-blind multicentre study (n=18,624), conducted between 2006 and 2008, which demonstrated superiority of the antiplatelet treatment ticagrelor over clopidogrel in reducing risk of several cardiovascular events. In the present study, four of the main PLATO outcomes were reassessed by calculating the time by which an event may be delayed due to the treatment. The effects of ticagrelor, as compared with clopidogrel, consisted of a substantial delay of the evaluated outcomes, ranging from 83 to 98 days over 400-day follow-up. The Delay of Events Curves showed that the effects progressively increased over time, and the significant findings were concordant with those presented in the original PLATO study. This study confirmed evidence of a beneficial effect of ticagrelor over clopidogrel, and provided the magnitude of such effects in terms of delayed event time. Investigating time-to-event data with a percentile approach allows presenting treatment effects from randomised controlled studies as absolute measures of the time by which an event may be delayed due to the treatment. PLATO (www.clinicaltrials.gov; NCT00391872); Results.


Evaluating the feasibility and outcomes of a resident-led school-based pediatric clinic.
A resident-led school-based clinic to serve low-income populations was established in 2019 and served as a continuity clinic for pediatric residents at a single university. Our aim was to assess the feasibility, clinic outcomes, and resident experience of a resident-led school-based clinic (RLSBC), established in an elementary school that serves an underserved population. A retrospective chart review for the first 6 months (October 2019 to March 2020) of clinic operations was conducted. Feasibility metrics included the number of patients, visits and planned follow-ups; clinic outcomes included the number and type of presenting complaint, new diagnoses and interventions. Residents were also surveyed to assess their satisfaction and perceived learning in training at the school-based clinic. Over the first 19 clinic days, 48 children were seen at the school-based clinic. Of the clinic users, 60% did not have a primary care physician, 46% received a new diagnosis, 46% received an intervention in the form of medication prescription, laboratory/imaging requisitions or referrals, and 96% received a treatment plan. Residents positively rated the experience of staffing the school-based clinic in all aspects, including learning environment, clinic and team environment, teaching obtained, practice management, and overall experience. A RLSBC is feasible and our outcomes suggest that such clinics may address health care needs of low-income families and children, while being a positively rated educational experience for pediatric residents.


Lacunae in International Federation of Gynecology and Obstetrics (FIGO) classification for cervical carcinoma: observational study using TNM classification as comparator.
International Federation of Gynecology and Obstetrics (FIGO) staging for cervical cancer does not yet consider findings of cross-sectional imaging unlike clinical tumor, node, and metastasis (TNM) staging system. We compare the two with regard to accuracy in pretreatment staging and their reliability in the prediction of prognosis. This was an observational study of patients with biopsy-proven nonmetastatic cervical carcinoma. Pretreatment evaluation of patients was done by clinical assessment and contrast-enhanced computed tomographic scan of the pelvis to stage the disease with FIGO and clinical TNM (cTNM) system, respectively. The extent of discordance between the 2 staging systems were studied in assessing stage of disease, correlation with histopathologic classification in patients who were operated on, and in prediction of prognosis. The study included 54 patients. Seventeen of 19 patients with early-stage disease underwent upfront radical surgery; and in 59% of these, FIGO did not match with final histopathologic TNM (pTNM), but only in 23% patients, cTNM did not match with histopathological TNM (P = 0.02). Sensitivity of computed tomographic scan to pick up lymph node metastasis was 85% in early disease. Stage migration rates to higher stage when considering imaging findings in stage I, stage IIA, and stage IIB were 25%, 71%, and 37%, respectively. Thirty-four percent of stage IIIB disease was downstaged with cTNM. Lymph node positivity by cTNM was a strong pointer of recurrence (P = 0.01). Pretreatment cross-sectional imaging may help avoid undue surgery in patients with cervical cancer with positive lymph nodes and may help in a more accurate assessment of prognosis.


The "Sweet Spot" Revisited: Optimal Recall Rates for Cancer Detection With 2D and 3D Digital Screening Mammography in the Metro Chicago Breast Cancer Registry.
OBJECTIVE. One central question pertaining to mammography quality relates to discerning the optimal recall rate to maximize cancer detection while minimizing unnecessary downstream diagnostic imaging and breast biopsies. We examined the trade-offs for higher recall rates in terms of biopsy recommendations and cancer detection in a single large health care organization. MATERIALS AND METHODS. We included 2D analog, 2D digital, and 3D digital (tomosynthesis) screening mammography examinations among women 40-79 years old performed between January 1, 2005, and December 31, 2017, with cancer follow-up through 2018. There were 36, 67, and 38 radiologists who read at least 1000 2D analog examinations, 2D digital examinations, and 3D tomosynthesis examinations, respectively, who were included in these analyses. Using logistic regression with marginal standardization, we estimated radiologist-specific mean recall (abnormal interpretations/1000 mammograms), biopsy recommendation, cancer detection (screening-detected in situ and invasive cancers/1000 mammograms), and minimally invasive cancer detection rates while adjusting for differences in patient characteristics. RESULTS. Among 1,060,655 screening mammograms, the mean recall rate was 10.7%, the cancer detection rate was 4.0/1000 mammograms, and the biopsy recommendation rate was 1.60%. Recall rates between 7% and 9% appeared to maximize cancer detection while minimizing unnecessary biopsies. CONCLUSION. The results of this investigation are in contrast to those of a recent study suggesting appropriateness of higher recall rates. The "sweet spot" for optimal cancer detection appears to be in the recall rate range of 7-9% for both 2D digital mammography and 3D tomosynthesis. Too many women are being called back for diagnostic imaging, and new benchmarks could be set to reduce this burden.


Effects of short-term oral vitamin A supplementation on the ocular tear film in patients with dry eye.
To investigate the effects of short-term oral vitamin A supplementation on the ocular tear film in patients with dry eye. In total, 30 male patients with dry eye (age range, 18-38 years; mean age, 25.2±2.8 years) who did not wear contact lenses or exhibit any ocular (other than dry eye) or systemic diseases were included, along with 30 age-matched men (control group; mean age, 24.5±2.3 years) with healthy eyes. Subject exclusion was based on the findings of the McMonnies questionnaire (cutoff score for dry eye: 14.5) and slit-lamp biomicroscopy. All subjects received an oral vitamin A supplement at a daily dose of 1,500 mg for 3 consecutive days. The phenol red thread (PRT) test was performed along with assessments of tear ferning (TF), tear osmolarity, and the tear break-up time (TBUT) before and 24 hours after the third dose of the vitamin A supplement. A 10-minute interval was observed between different tests. In the dry eye group, the TF grade (Wilcoxon test, P=0.01) exhibited a significant decrease, while the tear osmolarity value (t-test, P=0.01) exhibited a significant increase after vitamin A supplementation. The PRT test findings (P=0.17) and TBUT (P=0.49) showed no significant differences before and after vitamin A supplementation. In the control group, vitamin A supplementation showed no significant effects on TF (P=0.74), tear osmolarity (P=0.55), the TBUT (P=0.19), and the PRT test scores (P=0.48). Our findings suggest that short-term oral vitamin A supplementation improves the quality, but not quantity, of tears in patients with dry eye. Future studies should involve larger patient samples and longer periods of vitamin A supplementation.


[Selenium, glutathione peroxidase, peroxides and platelet functions].
In the last five years, there has been a renewal of interest in the protective role of selenium in vascular disorders, inspired by experimental evidence that this trace element could modulate leukotriene and prostaglandin synthesis in both endothelial cells and platelets. In people living in low-selenium areas, a relationship has been established between a decrease in plasma selenium and an increase in the risk of coronary disease, atherosclerosis, platelet hyperaggregability and synthesis of proaggregant and proinflammatory compounds like thromboxane A2 and leukotrienes. Selenium, as an essential part of glutathione peroxidase, takes part in the reduction of hydrogen peroxides and lipid peroxides. The concentration of these peroxides, in turn, regulates the activities of cyclooxygenase and lipooxygenase pathways, ultimately influencing the production of eicosanoids and modulating the balance between a proaggregatory and antiaggregatory state. Recent evidence shows that selenium, via its action on glutathione peroxidase activity, may be primarily responsible for the regulation of the endogenous hydroperoxide level. In human platelets, the activity of glutathione peroxidase is particularly high and is very sensitive to the requirement of selenium. This sensitivity could explain why platelets of selenium-deficient subjects show increased aggregation, thromboxane B2 production and synthesis of the lipoxygenase-derived compounds. In these deficient subjects, selenium administration increases platelet glutathione peroxidase activity and inhibits platelet hyperaggregation and leukotriene synthesis. These results support the hypothesis that selenium supplementation has a positive effect on platelet aggregation in selenium-deficient subjects. In France, more than 10% of the population is selenium-deficient and long-term supplementation with low doses of selenium could have a beneficial effect on the prevention of both thrombosis and coronary heart disease in these subjects.


The intestinal calcistat.
The main physiological function of vitamin D is maintenance of calcium homeostasis by its effect on calcium absorption, and bone health in association with parathyroid gland. Vitamin D deficiency (VDD) is defined as serum 25-hydroxy vitamin D (25OHD) levels <20 ng/ml. Do all subjects with VDD have clinical disease according to this definition? We hypothesize that there exist an intestinal calcistat, which controls the calcium absorption independent of PTH levels. It consists of calcium sensing receptor (CaSR) on intestinal brush border, which senses calcium in intestinal cells and vitamin D system in intestinal cells. CaSR dampens the generation of active vitamin D metabolite in intestinal cells and decrease active transcellular calcium transport. It also facilitates passive paracellular diffusion of calcium in intestine. This local adaptation adjusts the fractional calcium absorption according the body requirement. Failure of local adaptation due to decreased calcium intake, decreased supply of 25OHD, mutation in CaSR or vitamin D system decreases systemic calcium levels and systemic adaptations comes into the play. Systemic adaptations consist of rise in PTH and increase in active vitamin D metabolites. These adaptations lead to bone resorption and maintenance of calcium homeostasis. Not all subjects with varying levels of VDD manifest with secondary hyperparathyroidism and decreased in bone mineral density. We suggest that rise in PTH is first indicator of VDD along with decrease in BMD depending on duration of VDD. Hence, subjects with any degree of VDD with normal PTH and BMD should not be labeled as vitamin D deficient. These subjects can be called subclinical VDD, and further studies are required to assess beneficial effect of vitamin D supplementation in this subset of population.


A Satellite-Based Spatio-Temporal Machine Learning Model to Reconstruct Daily PM2.5 Concentrations across Great Britain.
Epidemiological studies on the health effects of air pollution usually rely on measurements from fixed ground monitors, which provide limited spatio-temporal coverage. Data from satellites, reanalysis, and chemical transport models offer additional information used to reconstruct pollution concentrations at high spatio-temporal resolutions. This study aims to develop a multi-stage satellite-based machine learning model to estimate daily fine particulate matter (PM2.5) levels across Great Britain between 2008-2018. This high-resolution model consists of random forest (RF) algorithms applied in four stages. Stage-1 augments monitor-PM2.5 series using co-located PM10 measures. Stage-2 imputes missing satellite aerosol optical depth observations using atmospheric reanalysis models. Stage-3 integrates the output from previous stages with spatial and spatio-temporal variables to build a prediction model for PM2.5. Stage-4 applies Stage-3 models to estimate daily PM2.5 concentrations over a 1 km grid. The RF architecture performed well in all stages, with results from Stage-3 showing an average cross-validated R2 of 0.767 and minimal bias. The model performed better over the temporal scale when compared to the spatial component, but both presented good accuracy with an R2 of 0.795 and 0.658, respectively. These findings indicate that direct satellite observations must be integrated with other satellite-based products and geospatial variables to derive reliable estimates of air pollution exposure. The high spatio-temporal resolution and the relatively high precision allow these estimates (approximately 950 million points) to be used in epidemiological analyses to assess health risks associated with both short- and long-term exposure to PM2.5.


[Influence of different copper and zinc supply on their concentrations in blood serum, liver and hair of dairy cows].
In a feeding trial at the Institute of Animal Nutrition of the Federal Research Institute of Animal Health (FLI) over 12 weeks with 20 cows of the German Holstein Breed the influence of different copper and zinc contents in the ration on their concentration in blood serum, liver and hair was tested. All animals received a diet based on maize- and grass silage ad libitum. The animals were divided in two groups with 10 cows each; group A received a concentrate according to their milk yield with a copper and zinc content as recommended (GfE 2001), whereas group B was offered a concentrate with roughly the double amount of copper and zinc. At the beginning and at the end of the trial a sample of blood, pigmented hair and a liver bioptate was taken from all animals to evaluate the incorporation of copper and zinc in these tissues. In serum and pigmented hair the copper concentrations did not differ between the two groups [13.4 for Group A and 12.5 micromol/L for Group B in serum respectively 6.8 (Group A) and 7.4 mg/kg DM (Group B) in pigmented hair]. Only the copper concentration in the liver was influenced by the different feeding. The higher copper content for group B resulted in a significantly higher copper concentration in the liver (506 mg/kg DM compared to 383 mg/kg DM). The liver is the best indicator organ for a sufficient copper supply. An increase in the zinc content in the ration resulted neither in higher zinc concentrations in serum (15.1 in Group B in comparison to 13.4 micromol/L for Group A) nor in higher zinc concentrations in liver (140 for Group B and 112 mg/kg DM for Group A) and pigmented hair (130 in Group A and 123 mg/kg DM in Group B). There is a significant correlation between copper intake and copper concentration in the liver (r = 0.46), whereas the correlation between zinc intake and zinc concentration in the liver is only tendencially (r = 0.23). The three tested samples serum, liver and cow hair are not qualified to reflect exactly a sufficient zinc supply.


Detection of Melanoma Cancer Biomarker Dimethyl Disulfide Using Cavity Ringdown Spectroscopy at 266 nm.
Skin cells emit volatile organic compounds (VOCs), and some of them can be used as biomarkers for screening specific diseases. Dimethyl disulfide (DMDS) has been recently reported as a biomarker of melanoma skin cancer (Kwak et al. "Volatile Biomarkers from Human Melanoma Cells". J. Chromatogr. B. 2013. 931: 90-96.). With the motivation of diagnosing melanoma using DMDS as its biomarker, we explore the potential of measuring DMDS using an advanced laser spectroscopic technique as an alternative method. We report on the first DMDS measurements using an experimental system based on cavity ringdown spectroscopy (CRDS). The test samples were mixtures of DMDS vapor and nitrogen in different concentrations. Two sampling methods were investigated to dilute the DMDS sample to low concentrations for ringdown measurements. The results showed that the ringdown system responded to various DMDS concentrations linearly and a theoretical detection limit of sub-ppb (parts per billion) could be achieved at the absorption wavelength of 266 nm. This ringdown system exhibited a high dynamic range for DMDS measurements, from ppm (parts per million) to ppt (parts per trillion) levels, given different laser wavelengths used. The feasibility of developing a portable melanoma screening sensor using the CRDS technique was also demonstrated in this study.


Genetic and structural analyses of cytoplasmic filaments of wild-type Treponema phagedenis and a flagellar filament-deficient mutant.
Unique cytoplasmic filaments are found in the treponeme genus of spirochete bacteria. Their function is unknown, but their location underneath the periplasmic flagellar filaments (PFF) suggests a role in motility and/or cell structure. To better understand these unique structures, the gene coding for the cytoplasmic filaments, cfpA, was identified in various treponemal species. Treponema phagedenis cfpA was 2,037 nucleotides long, and the encoded polypeptide showed 78 to 100% amino acid sequence identity with the partial sequence of CfpA from T. denticola, T. vincentii, and T. pallidum subsp. pertenue. Wild-type T. phagedenis and a PFF-deficient isolate were analyzed by electron microscopy to assess the structural relationship of the cytoplasmic filaments and the PFF. The number of cytoplasmic filaments per cell of T. phagedenis (mean, 5.7) was compared with the number of PFF at each end of the cell (mean, 4.7); the results suggest that there is no direct one-to-one correlation at the cell end. Moreover, a structural link between these structures could not be demonstrated. The cytoplasmic filaments were also analyzed by electron microscopy at different stages of cell growth; this analysis revealed that they are cleaved before or during septum formation and before the nascent formation of PFF. A PFF-deficient mutant of T. phagedenis possessed cytoplasmic filaments similar to those of the wild type, suggesting that intact PFF are not required for their assembly and regulation. The extensive conservation of CfpA among pathogenic spirochetes suggests an important function, and structural analysis suggests that it is unlikely that the cytoplasmic filaments and the flagellar apparatus are physically linked.


Genome-based bioinformatic selection of chromosomal Bacillus anthracis putative vaccine candidates coupled with proteomic identification of surface-associated antigens.
Bacillus anthracis (Ames strain) chromosome-derived open reading frames (ORFs), predicted to code for surface exposed or virulence related proteins, were selected as B. anthracis-specific vaccine candidates by a multistep computational screen of the entire draft chromosome sequence (February 2001 version, 460 contigs, The Institute for Genomic Research, Rockville, Md.). The selection procedure combined preliminary annotation (sequence similarity searches and domain assignments), prediction of cellular localization, taxonomical and functional screen and additional filtering criteria (size, number of paralogs). The reductive strategy, combined with manual curation, resulted in selection of 240 candidate ORFs encoding proteins with putative known function, as well as 280 proteins of unknown function. Proteomic analysis of two-dimensional gels of a B. anthracis membrane fraction, verified the expression of some gene products. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analyses allowed identification of 38 spots cross-reacting with sera from B. anthracis immunized animals. These spots were found to represent eight in vivo immunogens, comprising of EA1, Sap, and 6 proteins whose expression and immunogenicity was not reported before. Five of these 8 immunogens were preselected by the bioinformatic analysis (EA1, Sap, 2 novel SLH proteins and peroxiredoxin/AhpC), as vaccine candidates. This study demonstrates that a combination of the bioinformatic and proteomic strategies may be useful in promoting the development of next generation anthrax vaccine.


Dap1p, a heme-binding protein that regulates the cytochrome P450 protein Erg11p/Cyp51p in Saccharomyces cerevisiae.
Alkylating agents chemically modify DNA and cause mutations that lead to cancer. In the budding yeast Saccharomyces cerevisiae, resistance to the alkylating agent methyl methanesulfonate (MMS) is mediated in part by Dap1p (damage resistance protein 1). Dap1p is related to cytochrome b5, which activates cytochrome P450 proteins, elevating the metabolism of lipids and xenobiotic compounds. We have found that Dap1p, like cytochrome b5, binds to heme and that Dap1p targets the cytochrome P450 protein Erg11p/Cyp51p. Genetic analysis indicates that Erg11p acts downstream of Dap1p. Furthermore, Dap1p regulates the stability of Erg11p, and Erg11p is stabilized in dap1Delta cells by the addition of heme. Thus, Dap1p utilizes heme to stabilize Erg11p, which in turn regulates ergosterol synthesis and MMS resistance. Dap1p homologues have been identified in numerous eukaryotes, including mammals, suggesting that the Dap1p-cytochrome P450 protein pathway is broadly conserved in eukaryotic species.


[Selective proximal vagotomy with excision of duodenal ulcer].
257 patients with duodenal ulcer and its complications underwent selective proximal vagotomy in combination with excision of duodenal ulcer without pyloric injury. Lethality rate was 0.78%. Long-term results of the operation by Visick's classification are evaluated as excellent and good in 105 (90.5%) patients, in 9 (7.8%) as satisfactory, in 2 (1.7%) as unsatisfactory. It is emphasized that operation saving the pylorus is optimal in such patients and can be performed almost in all patients irrespective of location of the ulcer, presence and tupe of its complications.


A homogalacturonan from Hippophae rhamnoides L. Berries enhance immunomodulatory activity through TLR4/MyD88 pathway mediated activation of macrophages.
Our previous study isolated a natural high-methoxyl homogalacturonan (HRWP-A) from Hippophae rhamnoides and showed antitumor activity in vivo. In this study, the immunomodulatory activity and mechanisms of action of HRWP-A were further investigated. Results showed that HRWP-A could recover the body condition and activated macrophage in Cyclophosphamide (CTX)-induced immunosuppressed mice. Further, we investigated the possible mechanism underlying the effects of HRWP-A on mouse peritoneal macrophages. qPCR and western blot revealed that HRWP-A upregulated the expression of TLR4 mRNA in vitro. This process was accompanied by a clear increase in MyD88 expression and p-IκB-α, but these effects were largely abrogated by pretreatment with anti-TLR4 antibodies. The effects of HRWP-A on macrophage NO, IL-1β and IL-6 production were also inhibited by anti-TLR4 antibodies and were greatly influenced by the NF-κB inhibitor PDTC. Moreover, HRWP-A failed to induce the production of NO, IL-1β and IL-6 in peritoneal macrophages prepared from C3H/HeJ mice, which have a point mutation in the Tlr4 gene, suggesting the involvement of the TLR4 molecule in HRWP-A-mediated macrophage activation. These results may have important implications for our understanding of the structure-activity relationship of immunopotentiating polysaccharides from medicinal herbs.


A patient with both narcolepsy and multiple sclerosis in association with Pandemrix vaccination.
Narcolepsy with cataplexy is caused by a selective loss of hypocretin-producing neurons, but symptomatic narcolepsy can also result from hypothalamic and brainstem lesions caused by multiple sclerosis (MS). We report a previously healthy man who developed clinical and laboratory verified narcolepsy without having any indication of hypothalamic lesions and MS after vaccination against the influenza H1N1 with Pandemrix. HLA typing showed both DRB1*15:01, associated with MS and DQB1*06:02, associated with narcolepsy. The genetic susceptibility in this patient makes it tempting to speculate upon an immune-mediated mechanism and a common etiology for both diseases in this patient.


Reduced cortical folding of the anterior cingulate cortex in obsessive-compulsive disorder.
Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysiology of obsessive-compulsive disorder (OCD), yet it remains unclear whether these abnormalities originated during early neurodevelopment. In this study, we examined the ACC sulcal/gyral patterns to investigate whether neurodevelopmental anomalies of the ACC were present in patients with OCD. We hypothesized that patients with OCD would show reduced cortical folding of the ACC compared with controls. We used magnetic resonance imaging (MRI) of 169 healthy volunteers and 110 patients with OCD to examine the paracingulate sulcus and cingulate sulcus. We assessed cortical folding patterns according to established classification criteria and constructed 3 categories of paracingulate sulcus morphology according to its presence and anteroposterior extent: "prominent," "present" and "absent." We classified the cingulate sulcus as "interrupted" or "continuous" according to the interruptions in its course. In addition, we evaluated ACC sulcal asymmetry based on interhemispheric comparisons of paracingulate sulcus morphology. Analyses revealed that patients with OCD were significantly less likely than controls to show a well-developed left paracingulate sulcus: 50.0% of patients and 65.1% of controls showed a "prominent" or "present" paracingulate sulcus in the left hemisphere. However, there were no differences in regard to cingulate sulcus continuity, and patients also showed the same leftward ACC sulcal asymmetry as controls. Our study was limited by the fact that we obtained the MRI scans from 2 different scanners, and we did not calculate cerebral fissurization as our study was restricted to 1 specific brain region. Moreover, patients and controls differed significantly in terms of sex ratio and IQ, although we controlled these variables as covariates. Our findings imply a subtle deviation in the early neurodevelopment of the ACC in patients with OCD, but the extent to which these anomalies contributed to the pathogenesis of OCD remains unclear. Further studies that link the ACC morphologic anomalies to the pathophysiology of OCD are recommended.


Anaerobic degradation of long-chain alkylamines by a denitrifying Pseudomonas stutzeri.
The anaerobic degradation of tetradecylamine and other long-chain alkylamines by a newly isolated denitrifying bacterium was studied. Strain ZN6 was isolated from a mixture of soil and active sludge and was identified as representing Pseudomonas stutzeri, based on partial 16S rRNA gene sequence analysis. Strain ZN6 was a mesophilic, motile, Gram-negative rod-shaped bacterium and was able to grow on a variety of compounds including even-numbered primary fatty amines with alkyl chains ranging from C(4) to C(18) coupled to nitrate reduction. Alkylamines were used as sole carbon, energy and nitrogen source and were completely mineralized. Nitrate was dissimilated by ZN6 to nitrite. When strain ZN6 was grown under nitrate limitation, nitrite was slowly dissimilated further. When cocultivated with the complete denitrifier Castellaniella defragens ZN3, anaerobic degradation under denitrifying of alkylamines by strain ZN6 was slightly faster. Strain ZN3 is a complete denitrifier, unable to convert tetradecylamine, and was copurified from the same enrichment culture as strain ZN6. The proposed pathway for the degradation of alkylamines in strain ZN6 starts with C-N cleavages to alkanals and further oxidation to the corresponding fatty acids.


Antibiotic prophylaxis in open and closed fractures: a controlled clinical trial.
The value of prophylactic antibiotics in fracture surgery was studied in a series of 90 patients with open fractures of various bones and 180 patients with closed malleolar fractures treated by open surgery. Dicloxacillin and benzyl penicillin were compared to saline (placebo). The soft tissue lesions of the open fractures were divided into Grade I wounds and Grade II & III wounds. Of the patients with Grade I wounds, 17 received dicloxacillin, 21 benzyl penicillin and 17 saline. No major infections occurred. Twelve patients with Grade II & III wounds were treated with dicloxacillin, 10 with benzyl penicillin and 13 with saline. In the saline group, 2 patients developed a deep infection. Fifty-eight patients with closed malleolar fractures received dicloxacillin, 59 benzyl penicillin and 63 saline. Two infections developed in the placebo group. A statistically significant difference was found between the number of infections in the antibiotic groups and the number in the placebo group. Superficial thromboplebitis following the antibiotic infusion occurred in 16 per cent of the dicloxacillin treated patients and in 1 per cent of those treated with benzyl penicillin or placebo.


[Empirical antibiotic therapy for febrile neutropenia].
Immediate broad-spectrum empirical antibacterial therapy is the key of management in febrile neutropenic patients. These patients can be stratified according to the risk of complications with the clinical MASCC score. Patients at low risk of complications can be efficaciously treated with oral antibiotics (e.g. fluoroquinolone and beta-lactam), provided that compliance and drug absorption are adequate. Early discharge is possible if clinical, logistic, and social criteria are fulfilled. Intravenous antibiotic therapy with broad-spectrum beta-lactam antibiotics in the hospital remains the standard in high-risk patients. The empirical addition of an aminoglycoside and/or a glycopeptide is recommended if the local incidence of infections due to beta-lactam resistant pathogens is high or in critically ill septic patients.


Giant Haemangioma Of Nasopharynx: A Rare Case Outcome.
A 60-year-old female presented to us with a 5-year history of progressive right sided nasal obstruction and recurrent epistaxis. On examination lesion was seen in the right nostril which was firm and bled on probing. CT-scan paranasal sinuses showed a right sided lesion of nose and naso-pharnyx obstructing posterior nasal choanae. Dimensions were reported to be 9×4.1×3.8 cm. A punch biopsy was taken in operating room under general anaesthesia which resulted in profuse bleeding. Suction cautery was used to control bleeding and the nose was packed. The mass was firm to hard and provided resistance during the time of biopsy. On second post-operative day, the mass visibly changed its colour and became blackish in appearance. Patient had an episode of cough in the evening and expelled out the entire mass orally.


When and how to use self (home) and ambulatory blood pressure monitoring.
This American Society of Hypertension position paper focuses on the importance of out-of-office blood pressure (BP) measurement for the clinical management of patients with hypertension and its complications. Studies have supported direct and independent associations of cardiovascular risk with ambulatory BP and inverse associations with the degree of BP reduction from day to night. Self-monitoring of the BP (or home BP monitoring) also has advantages in evaluating patients with hypertension, especially those already on drug treatment, but less is known about its relation to future cardiovascular events. Data derived from ambulatory BP monitoring (ABPM) allow the identification of high-risk patients, independent from the BP obtained in the clinic or office setting. While neither ABPM nor self-BP monitoring are mandatory for the routine diagnosis of hypertension, these modalities can enhance the ability for identification of white-coat and masked hypertension and evaluate the extent of BP control in patients on drug therapy.


Transmission electron microscopic study of the hemorrhagic spots in patients with epidemic hemorrhagic fever in the early stage.
Epidemic hemorrhagic fever (EHF) virus particles were found in the squamous epithelial cells and the capillary endothelial cells of the petechial spots located on the mucous membrane of the soft palate in 3 patients with severe early-stage EHF with transmission electron microscopy. The virus particles were round or oval in shape, about 100 nm in diameter, with a two-layer lipid envelope from which spikes were protruding. The nucleocapsid of the virus appeared to be hollow microfilamentoid or dense granules. Meanwhile, budding virus particles with a diameter of 80 nm were found in the enlarged Golgi apparatus. The infected cells displayed an enlarged and proliferating Golgi apparatus. The morphological characteristics of the viron mentioned above coincided with those of the virus particles of the family Bunyaviridae. This study is the first to demonstrate that the squamous epithelial cells on the mucous membrane of the soft palate are the target cells of EHF infection and to provide subcellular morphological evidence of petechial hemorrhage at the soft palate.


Castleman disease of the mesentery as the great mimic: Incidental finding of one case and the literature review.
Castleman disease is an uncommon benign lymphoproliferative disorder characterized by hyperplasia of lymphoid follicles. More commonly described in the mediastinum, its occurrence in the mesentery is exceedingly rare, which is easily to be ignored in differential diagnosis when an abdominal mass is found. We report the case of an asymptomatic 71-year-old woman with a homogenous and hypervascular mass at the inner side of duodenojejunal junction. Based on the clinical suspicion of a gastrointestinal stromal tumor, a surgical resection was performed. Final diagnosis of the mass was hyaline vascular variant of Castleman disease. Here, we summarize the clinicopathological and radiological features of this disease by literature review, which may be helpful to bring awareness of this entity and improve the clinical decision making when similar scenarios are encountered.


Gene expression profiles and molecular markers to predict recurrence of Dukes' B colon cancer.
The 5-year survival rate of patients with Dukes' B colon cancer is approximately 75%. Identification of the patients at high risk of recurrence in this group would allow better staging and more informed use of adjuvant chemotherapy. In this study, we used DNA chip technology to systematically identify new prognostic markers for tumor relapse in Dukes' B patients. Using Affymetrix U133a GeneChip containing approximately 22,000 transcripts (Affymetrix, Santa Clara, CA), RNA samples from 74 patients with Dukes' B colon cancer were analyzed. Thirty-one patients developed tumor relapse in less than 3 years, whereas 43 patients remained disease-free for more than 3 years after surgery. Two supervised class prediction approaches were used to identify gene markers that can best discriminate between patients who would experience relapse and patients who would remain disease-free. A multivariate Cox model was built to predict recurrence. Gene expression profiling identified a 23-gene signature that predicts recurrence in Dukes' B patients. This signature was validated in 36 independent patients. The overall performance accuracy was 78%. Thirteen of 18 relapse patients and 15 of 18 disease-free patients were predicted correctly, giving an odds ratio of 13 (95% CI, 2.6 to 65; P =.003). The log-rank test indicated a significant difference in disease-free time between the predicted relapse and disease-free patients (P =.0001). The clinical value of these markers is that the patients at a high predicted risk of relapse (13-fold risk) could be upstaged to receive adjuvant therapy, similar to Dukes' C patients. Our data highlight the feasibility of a prognostic assay that could focus more intensive treatment for localized colon cancer.


Root symbionts: Powerful drivers of plant above- and belowground indirect defenses.
Soil microbial mutualists of plants, including mycorrhizal fungi, non-mycorrhizal fungi and plant growth promoting rhizobacteria, have been typically characterized for increasing nutrient acquisition and plant growth. More recently, soil microbes have also been shown to increase direct plant defense against above- and belowground herbivores. Plants, however, do not only rely on direct defenses when attacked, but they can also recruit pest antagonists such as predators and parasitoids, both above and belowground, mainly via the release of volatile organic compounds (i.e., indirect defenses). In this review, we illustrate the main features and effects of soil microbial mutualists of plants on plant indirect defenses and discuss possible applications within the framework of sustainable crop protection against root- and shoot-feeding arthropod pests. We indicate the main knowledge gaps and the future challenges to be addressed in the study and application of these multifaceted interactions.


Basal cell carcinoma: stressful life events and the tumor environment.
Child emotional maltreatment can result in lasting immune dysregulation that may be heightened in the context of more recent life stress. Basal cell carcinoma (BCC) is the most common skin cancer, and the immune system plays a prominent role in tumor appearance and progression. To address associations among recent severe life events, childhood parental emotional maltreatment, depression, and messenger RNA (mRNA) coding for immune markers associated with BCC tumor progression and regression. We collected information about early parent-child experiences, severe life events in the past year as assessed by the Life Events and Difficulties Schedule, depression, and mRNA for immune markers associated with BCC tumor progression and regression from patients with BCC tumors. University medical center. Ninety-one patients with BCC (ages, 23-92 years) who had a previous BCC tumor. The expression of 4 BCC tumor mRNA markers (CD25, CD3ε, intercellular adhesion molecule 1, and CD68) that have been linked to BCC tumor progression and regression were assessed in BCC tumor biopsy specimens. Both maternal and paternal emotional maltreatment interacted with the occurrence of severe life events to predict the local immune response to the tumor (adjusted P = .009 and P = .03, respectively). Among BCC patients who had experienced a severe life event within the past year, those who were emotionally maltreated by their mothers (P = .007) or fathers (P = .02) as children had a poorer immune response to the BCC tumor. Emotional maltreatment was unrelated to BCC immune responses among those who did not experience a severe life event. Depressive symptoms were not associated with the local tumor immune response. Troubled early parent-child relationships, in combination with a severe life event in the past year, predicted immune responses to a BCC tumor. The immunoreactivity observed in BCCs and the surrounding stroma reflects an anti-tumor-specific immune response that can be altered by stress.


Bioreactors Design, Types, Influencing Factors and Potential Application in Dentistry. A Literature Review.
A variety of bioreactors and related approaches have been applied to dental tissues as their use has become more essential in the field of regenerative dentistry and dental tissue engineering. The review discusses the various types of bioreactors and their potential application in dentistry. Review of the literature was conducted using keywords (and MeSH) like Bioreactor, Regenerative Dentistry, Fourth Factor, Stem Cells, etc., from the journals published in English. All the searched abstracts, published in indexed journals were read and reviewed to further refine the list of included articles. Based on the relevance of abstracts pertaining to the manuscript, full-text articles were assessed. Bioreactors provide a prerequisite platform to create, test, and validate the biomaterials and techniques proposed for dental tissue regeneration. Flow perfusion, rotational, spinner-flask, strain and customize-combined bioreactors have been applied for the regeneration of bone, periodontal ligament, gingiva, cementum, oral mucosa, temporomandibular joint and vascular tissues. Customized bioreactors can support cellular/biofilm growth as well as apply cyclic loading. Center of disease control & dip-flow biofilm-reactors and micro-bioreactor have been used to evaluate the biological properties of dental biomaterials, their performance assessment and interaction with biofilms. Few case reports have also applied the concept of in vivo bioreactor for the repair of musculoskeletal defects and used customdesigned bioreactor (Aastrom) to repair the defects of cleft-palate. Bioreactors provide a sterile simulated environment to support cellular differentiation for oro-dental regenerative applications. Also, bioreactors like, customized bioreactors for cyclic loading, biofilm reactors (CDC & drip-flow), and micro-bioreactor, can assess biological responses of dental biomaterials by simultaneously supporting cellular or biofilm growth and application of cyclic stresses.


Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics.
A latent reservoir for HIV-1 in resting CD4+ T lymphocytes precludes cure. Mechanisms underlying reservoir stability are unclear. Recent studies suggest an unexpected degree of infected cell proliferation in vivo. T cell activation drives proliferation but also reverses latency, resulting in productive infection that generally leads to cell death. In this study, we show that latently infected cells can proliferate in response to mitogens without producing virus, generating progeny cells that can release infectious virus. Thus, assays relying on one round of activation underestimate reservoir size. Sequencing of independent clonal isolates of replication-competent virus revealed that 57% had env sequences identical to other isolates from the same patient. Identity was confirmed by full-genome sequencing and was not attributable to limited viral diversity. Phylogenetic and statistical analysis suggested that identical sequences arose from in vivo proliferation of infected cells, rather than infection of multiple cells by a dominant viral species. The possibility that much of the reservoir arises by cell proliferation presents challenges to cure.


A test for ancient selective sweeps and an application to candidate sites in modern humans.
We introduce a new method to detect ancient selective sweeps centered on a candidate site. We explored different patterns produced by sweeps around a fixed beneficial mutation, and found that a particularly informative statistic measures the consistency between majority haplotypes near the mutation and genotypic data from a closely related population. We incorporated this statistic into an approximate Bayesian computation (ABC) method that tests for sweeps at a candidate site. We applied this method to simulated data and show that it has some power to detect sweeps that occurred more than 10,000 generations in the past. We also applied it to 1,000 Genomes and Complete Genomics data combined with high-coverage Denisovan and Neanderthal genomes to test for sweeps in modern humans since the separation from the Neanderthal-Denisovan ancestor. We tested sites at which humans are fixed for the derived (i.e., nonchimpanzee allele) whereas the Neanderthal and Denisovan genomes are homozygous for the ancestral allele. We observe only weak differences in statistics indicative of selection between functional categories. When we compare patterns of scaled diversity or use our ABC approach, we fail to find a significant difference in signals of classic selective sweeps between regions surrounding nonsynonymous and synonymous changes, but we detect a slight enrichment for reduced scaled diversity around splice site changes. We also present a list of candidate sites that show high probability of having undergone a classic sweep in the modern human lineage since the split from Neanderthals and Denisovans.


Aspergillus prosthetic valve endocarditis.
The clinical, laboratory, and histopathological features of seven cases of Aspergillus fumigatus prosthetic valve endocarditis are presented. The exact nature of the lesion, a combination of infective fungal endocarditis and thrombosis on the prosthetic valve, is discussed and the difficulties in clinical diagnosis are emphasized. Helpful indications were sudden unexplained heart failure with the appearance of new murmurs, and emboli to large or medium-sized systemic arteries. Fever and anaemia were inconstant, and in no case was blood culture or precipitin investigation helpful. Spore contamination of operating theatre air was the likely source of infection, and measures taken to overcome this and other predisposing factors are discussed. Since medical diagnosis is usually late and the few reported cures in this condition have included replacement of the prosthesis, early surgical intervention combined with antifungal chemotherapy is advised.


Dietary patterns in India and their association with obesity and central obesity.
Obesity is a growing problem in India, the dietary determinants of which have been studied using an 'individual food/nutrient' approach. Examining dietary patterns may provide more coherent findings, but few studies in developing countries have adopted this approach. The present study aimed to identify dietary patterns in an Indian population and assess their relationship with anthropometric risk factors. FFQ data from the cross-sectional sib-pair Indian Migration Study (IMS; n 7067) were used to identify dietary patterns using principal component analysis. Mixed-effects logistic regression was used to examine associations with obesity and central obesity. The IMS was conducted at four factory locations across India: Lucknow, Nagpur, Hyderabad and Bangalore. The participants were rural-to-urban migrant and urban non-migrant factory workers, their rural and urban resident siblings, and their co-resident spouses. Three dietary patterns were identified: 'cereals-savoury foods' (cooked grains, rice/rice-based dishes, snacks, condiments, soups, nuts), 'fruit-veg-sweets-snacks' (Western cereals, vegetables, fruit, fruit juices, cooked milk products, snacks, sugars, sweets) and 'animal-food' (red meat, poultry, fish/seafood, eggs). In adjusted analysis, positive graded associations were found between the 'animal-food' pattern and both anthropometric risk factors. Moderate intake of the 'cereals-savoury foods' pattern was associated with reduced odds of obesity and central obesity. Distinct dietary patterns were identified in a large Indian sample, which were different from those identified in previous literature. A clear 'plant food-based/animal food-based pattern' dichotomy emerged, with the latter being associated with higher odds of anthropometric risk factors. Longitudinal studies are needed to further clarify this relationship in India.


[Phosphorescent analysis of lipid peroxidation products in isolated human erythrocyte membranes].
The room temperature phosphorescence of lipid peroxidation products in the composition of isolated human erythrocyte membranes was registered, and its kinetic parameters were determined. The excitation and emission spectra of phosphorescence of lipid peroxidation products in the composition of erythrocyte membranes at 0 degree C measured. The nature of lipid peroxidation products possessing the phosphorescencing capacity was discussed. Based on the analysis of temperature dependences of the intensity and lifetimes of phosphorescence of lipid peroxidation products in the range -2 divided by 26 degrees C, it is concluded that the deactivation of excited triplet states of lipid chromophores was realized by the dynamic type.


Performance of digital screening mammography in a population-based cohort of black and white women.
There is scarce information on whether digital screening mammography performance differs between black and white women. We examined 256,470 digital screening mammograms performed from 2005 to 2010 among 31,654 black and 133,152 white Carolina Mammography Registry participants aged ≥40 years. We compared recall rate, sensitivity, specificity, and positive predictive value (PPV1) between black and white women, adjusting for potential confounders using random effects logistic regression. Breast cancer was diagnosed in 276 black and 1,095 white women. Recall rates were similar for blacks and whites (8.6 vs. 8.5 %), as were sensitivity (83.7 vs. 82.4 %), specificity (91.8 vs. 91.9 %), and PPV1 (4.8 vs. 5.3 %) (all p values >0.05). Stratified and adjusted models showed similar results. Despite comparable mammography performance, tumors diagnosed in black women were more commonly poorly differentiated and hormone receptor negative. Equivalent performance of digital screening mammography by race suggests that efforts to understand tumor disparities should focus on etiologic factors that influence tumor biology.


Epidemiology of pediatric emergency department use at an urban medical center.
Dramatic increases in emergency department (ED) use contribute to rising healthcare costs and decrease continuity of care in the United States. Yet little is known about the acuity, frequency of visits, and demographic characteristics of children using the ED. This study examines general demographic trends over a 3-year period and examines whether there are factors associated with varying acuity at an urban academic pediatric ED. Analysis of administrative ED records from fiscal years (FY) 1999 to 2001 for children 0 to 18 years was performed to assess demographic characteristics, periodicity of ED use, and acuity level. Patient demographic characteristics, periodicity, and acuity were comparable for ED visits across each study year with approximately 25,000 annual visits. Among ED users in FY 2001, 42% sought urgent care exclusively, 12% received both urgent and nonurgent care, and 46% used the ED solely for nonurgent care. Of those with only nonurgent visits, 80% had 1 visit. In FY 2001, ED use was predominantly among patients who were black (77.3%) and were 1 to 4 years of age (35.4%). Relative to all patients, a greater percentage of those who used the ED exclusively for nonurgent care were black (87.2% vs. 76.0%, P < 0.05) and lived within 2 miles of the hospital (45.2% vs. 37.4%, P < 0.05). Nearly half of pediatric emergency visits are for nonurgent care. Racial disparities in use of the ED for nonurgent care may be related to patient's proximity to the hospital. Patterns of use are stable across the 3 years. Further study is needed to identify mutable factors in emergency care use.


Persistence of HTLV-I in blood components after leukocyte depletion.
The human T-cell leukemia virus HTLV-I is a transfusion-transmissible retrovirus targeting T lymphocytes for which screening is not currently undertaken in United Kingdom blood donors. The introduction of universal leukocyte depletion (LD) of the United Kingdom blood supply raises the question as to the degree of protection afforded by this procedure against HTLV-I transmission by blood components. HTLV-I viral DNA removal by leukocyte-depleting filters was assessed in units of whole blood and platelets by real-time quantitative polymerase chain reaction (PCR) and by nested PCR for HTLV-I Tax DNA. We examined HTLV-I removal by LD filters using a model system of blood units containing exogenous spiked HTLV-I-positive MT-2 cells at a relevant concentration and whole blood donations from asymptomatic HTLV-I carriers. T-lymphocyte removal was assessed in parallel by measurement of endogenous subset-specific CD3 mRNA. In the MT-2 model system we observed 3.5 log(10) to 4 log(10) removal of HTLV-I Tax DNA by filtration of whole blood and 2 log(10) to 3 log(10) removal across platelet filters with 13 of 16 whole blood and 8 of 8 platelet units still positive after filtration. Despite 3 log(10) to 4 log(10) viral removal, HTLV-I Tax DNA could be detected after whole blood filtration in asymptomatic carriers with viral loads above 10(8) proviral DNA copies/L. T-lymphocyte removal was also between 3.5 log(10) and 4.5 log(10). HTLV-I provirus removal was incomplete in the model system and in asymptomatic carriers with viral loads greater than 10(8) copies/L. These results suggest that LD alone may not provide complete protection from HTLV-I transmission by transfusion.


Longitudinal amyloid and tau PET imaging in Alzheimer's disease: A systematic review of methodologies and factors affecting quantification.
Deposition of amyloid and tau pathology can be quantified in vivo using positron emission tomography (PET). Accurate longitudinal measurements of accumulation from these images are critical for characterizing the start and spread of the disease. However, these measurements are challenging; precision and accuracy can be affected substantially by various sources of errors and variability. This review, supported by a systematic search of the literature, summarizes the current design and methodologies of longitudinal PET studies. Intrinsic, biological causes of variability of the Alzheimer's disease (AD) protein load over time are then detailed. Technical factors contributing to longitudinal PET measurement uncertainty are highlighted, followed by suggestions for mitigating these factors, including possible techniques that leverage shared information between serial scans. Controlling for intrinsic variability and reducing measurement uncertainty in longitudinal PET pipelines will provide more accurate and precise markers of disease evolution, improve clinical trial design, and aid therapy response monitoring.


Ammonia stress on a resilient mesophilic anaerobic inoculum: Methane production, microbial community, and putative metabolic pathways.
Short term inhibition tests, 16S rRNA tag sequencing and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), were employed to visualise the effects of increasing total ammoniacal nitrogen (TAN) concentration (3400-10166 ppm TAN) on microbial community structure and metabolic pathways for acetate degradation. The rate of methane production on acetate was significantly reduced by TAN concentrations above 6133 ppm; however, methane continued to be produced, even at 10166 ppm TAN (0.026 ± 0.0003 gCOD.gVS-1inoculum.day-1). Hydrogenotrophic methanogenesis with syntrophic acetate oxidation (SAO) was identified as the dominant pathway for methane production. A shift towards SAO pathways at higher TAN concentrations and a decrease in the number of 'gene hits' for key genes in specific methanogenesis pathways was observed. Overall, the results highlighted potential for inhibition activity testing to be used together with PICRUSt, to estimate changes in microbial metabolism and to better understand microbial resilience in industrial AD facilities.


Widespread Distribution of Fungivorus Aphelenchoides spp. in Blight Cankers on American Chestnut Trees.
Previously we showed in laboratory studies that the fungivorus nematode, Aphelenchoides hylurgi, was attracted to and fed upon the chestnut blight fungus, Cryphonectria parasitica, from American chestnut bark cankers and was a carrier of biocontrol, white hypovirulent C. parasitica strains. In the present field study, we recovered Aphelenchoides spp. in almost all (97.0 %) of 133 blight canker tissue assays (three 5-g samples each) from four eastern states. High mean population densities (227 to 474 nematodes per 5 g tissue) of Aphelenchoides spp. were recovered from cankers in Virginia, West Virginia, and Tennessee but not from New Hampshire (mean = 75 nematodes per 5 g tissue). Overall, most canker assays yielded population densities less than 200 nematodes per 5 g tissue. All of 12 very small or young cankers yielded a few to many Aphelenchoides spp. Regression analysis indicated greatest recovery of Aphelenchoides spp. occurred in the month of May (r = 0.94). The results indicate that Aphelenchoides spp. appear to be widespread in blight cankers on American chestnut trees and could play a role in biocontrol of chestnut blight.


[Oridonin suppresses the effect of thioacetamide for promoting osteoclast differentiation of RAW264.7 cells and inhibiting osteoblast differentiation of bone mesenchymal stem cells].
To explore the effect of oridonin (ORI) for suppressing thioacetamide (TAA)-induced osteoclast differentiation of RAW264.7 cells and antagonizing the inhibitory effect of TAA on osteogenic differentiation of bone mesenchymal stem cells (BMSCs). The effects of TAA and ORI on the proliferation of RAW264.7 cells and SD rat BMSCs were examined using CCK-8 assay. TRAP staining and immunofluorescence staining were used to observe the effects of TAA and ORI on osteoclast differentiation in RAW264.7 cells. The expressions of osteoclast-specific proteins in the treated cells were detected using Western blotting, and p65 nuclear translocation and reactive oxygen species (ROS) production in the cells were assessed with immunofluorescence assay and flow cytometry. Alkaline phosphatase (ALP) staining and alizarin red staining were used to examine the effects of TAA and ORI on osteogenic differentiation of BMSCs, and the expressions of osteogenic and apoptosis-related proteins in the cells were detected with Western blotting. Compared with RAW264.7 cells treated with TAA alone, the cells with the combined treatment with TAA and ORI showed decreased osteoclast differentiation (P < 0.01) and significant inhibition of the MAPK/NF-κB pathway (P < 0.01) with reduced p65 nuclear translocation and intracellular ROS production (P < 0.01). In rat BMSCs, treatment with TAA alone significantly inhibited ALP activity and formation of calcified nodules (P < 0.01) and induced obvious cell apoptosis. Compared with TAA-treated BMSCs, the cells treated with both TAA and ORI showed upregulated expressions of the BMP-2/RUNX2 pathway with enhanced ALP activity (P < 0.01) and calcium deposition (P < 0.01) and a lowered cell apoptosis level. ORI inhibits TAA-induced osteoclast differentiation via regulating the MAPK/NF-κB pathway and antagonizes TAA-induced inhibition of bone formation by regulating the BMP-2/RUNX2 pathway.


Generalized and transferable patient language representation for phenotyping with limited data.
The paradigm of representation learning through transfer learning has the potential to greatly enhance clinical natural language processing. In this work, we propose a multi-task pre-training and fine-tuning approach for learning generalized and transferable patient representations from medical language. The model is first pre-trained with different but related high-prevalence phenotypes and further fine-tuned on downstream target tasks. Our main contribution focuses on the impact this technique can have on low-prevalence phenotypes, a challenging task due to the dearth of data. We validate the representation from pre-training, and fine-tune the multi-task pre-trained models on low-prevalence phenotypes including 38 circulatory diseases, 23 respiratory diseases, and 17 genitourinary diseases. We find multi-task pre-training increases learning efficiency and achieves consistently high performance across the majority of phenotypes. Most important, the multi-task pre-training is almost always either the best-performing model or performs tolerably close to the best-performing model, a property we refer to as robust. All these results lead us to conclude that this multi-task transfer learning architecture is a robust approach for developing generalized and transferable patient language representations for numerous phenotypes.


The role of stigma and trauma in hepatitis C virus treatment in veterans: Applying the common-sense model.
Hepatitis C Virus (HCV), a blood borne pathogen capable of causing severe liver disease, disproportionately affects veterans in the United States. While there are antiviral medications to treat HCV, stigma and trauma in this population may lead to avoidance of care. Those veterans who do undergo treatment have certain illness representations about HCV and its treatment. They undergo treatment even while facing stigma and trauma. The Common-Sense Model may be useful in elucidating how such representations, when matched to an appropriate illness prototype, may inform an action plan of how to respond to HCV. An exploration of the illness representations among veterans with HCV, and the effects of stigma and trauma on these representations, may help to explain how they exercise the choice to undergo treatment and may inform interventions to encourage treatment in veterans who have yet to do so.


Detection of Cyclospora cayetanensis in wastewater.
Cyclospora cayetanensis causes diarrheal disease worldwide without a confirmed mode of transmission. Wastewater was examined for the presence of this organism. Oocysts were detected microscopically, and their identity was confirmed by molecular techniques. These findings verify that current techniques can isolate Cyclospora oocysts and suggest that fecally contaminated water may act as a vehicle of transmission.


The Na/K-ATPase Oxidant Amplification Loop Regulates Aging.
As aging involves oxidant injury, we examined the role of the recently described Na/K-ATPase oxidant amplification loop (NKAL). First, C57Bl6 old mice were given a western diet to stimulate oxidant injury or pNaKtide to antagonize the NKAL. The western diet accelerated functional and morphological evidence for aging whereas pNaKtide attenuated these changes. Next, human dermal fibroblasts (HDFs) were exposed to different types of oxidant stress in vitro each of which increased expression of senescence markers, cell-injury, and apoptosis as well as stimulated the NKAL. Further stimulation of the NKAL with ouabain augmented cellular senescence whereas treatment with pNaKtide attenuated it. Although N-Acetyl Cysteine and Vitamin E also ameliorated overall oxidant stress to a similar degree as pNaKtide, the pNaKtide produced protection against senescence that was substantially greater than that seen with either antioxidant. In particular, pNaKtide appeared to specifically ameliorate nuclear oxidant stress to a greater degree. These data demonstrate that the NKAL is intimately involved in the aging process and may serve as a target for anti-aging interventions.


Low cost active-active oscillator utilizing loss feedback control.
We have constructed a low-cost, phosphate glass actively mode-locked, actively Q-switched oscillator that produces pulses from 150 to 1000 ps with high energy. This was accomplished by reducing the time required for relaxation oscillations to die out through the use of an acoustooptic feedback system. We describe system performance and construction details of this oscillator.


A Gadolinium-Based Magnetic Ionic Liquid for Dispersive Liquid-Liquid Microextraction of Ivermectin from Environmental Water.
The recently introduced gadolinium-based magnetic ionic liquid (Gd-MIL) has been exploited as an extractant in dispersive liquid-liquid microextraction (DLLME) for preconcentration of ivermectin (IVR) from water samples followed by analysis using reversed-phase HPLC with UV detection at 245 nm. The utilized Gd-MIL extractant is hydrophobic with markedly high magnetic susceptibility. These features result in an efficient extraction of the lipophilic analyte and facilitate the phase separation under the influence of a strong magnetic field, thus promoting the method sensitivity and increasing the potential for automation. To maximize the IVR enrichment by DLLME, the procedure was optimized for extractant mass, dispersive solvent type/volume, salt addition and diluent pH. At optimized conditions, an enrichment factor approaching 70 was obtained with 4.0-mL sample sizes. The method was validated in terms of accuracy, precision, specificity and limit of quantitation. The method was successfully applied to the determination of IVR in river water samples with a mean relative recovery of 97.3% at a spiked concentration of 400 ng/mL. Compared with other reported methods, this approach used a simpler procedure with improved precision, lower amounts of safer solvents and a short analysis time.


Zolpidem for persistent insomnia in SSRI-treated depressed patients.
Depressed individuals effectively treated with selective serotonin reuptake inhibitors (SSRIs) often report persistent insomnia and require adjunctive sleep-promoting therapy. Men (N = 40) and women (N = 150) with a mean age of 41.6 years who had persistent insomnia in the presence of effective and stable treatment (at least 2 weeks) with fluoxetine (< or =40 mg/day), sertraline (< or =100 mg/day), or paroxetine (< or =40 mg/day) for DSM-IV major depressive disorder, dysthymic disorder, or minor depressive disorder of mild-to-moderate severity (and score of < or =2 on item 3 of the Hamilton Rating Scale for Depression [HAM-D]) participated in this randomized, double-blind, parallel-group study. At study entry, patients were required to score < or =12 on the HAM-D. During a 1-week single-blind placebo period, patients had to report on at least 3 nights a latency of > or =30 minutes or a sleep time of <6.5 hours and clinically significant daytime impairment. Patients received either placebo (N = 96) or zolpidem, 10 mg (N = 94) nightly, for 4 weeks and single-blind placebo for 1 week thereafter. Sleep was measured with daily questionnaires and during weekly physician visits. Compared with placebo, zolpidem was associated with improved sleep: longer sleep times (weeks 1 through 4, p<.05), greater sleep quality (weeks 1 through 4, p<.01), and reduced number of awakenings (weeks 1, 2, and 4; p<.05), together with feeling significantly more refreshed, less sleepy, and more able to concentrate. After placebo substitution, the zolpidem group showed significant worsening relative to pretreatment sleep on the first posttreatment night in total sleep time and sleep quality, reverted to pretreatment insomnia levels on the other hypnotic efficacy measures, or maintained improvement (fewer number of awakenings). There was no evidence of dependence or withdrawal from zolpidem (DSM-IV criteria). Incidence rates of adverse events were similar in both treatment groups (74% and 83% for placebo and zolpidem, respectively), but 7 zolpidem patients discontinued compared with 2 placebo patients. In this defined patient population, zolpidem, 10 mg, was effectively and safely co-administered with an SSRI, resulting in improved self-rated sleep, daytime functioning, and well-being.


When is enough, enough? Quantifying trade-offs between information quality and sampling effort for fishing gear selectivity data.
There is general pressure throughout the world's fisheries for the industry to have greater involvement not only in the development of fishing gears but also in the testing and documentation of their effect. In the European Union, the Common Fisheries Policy of 2013, together with the proposed reform of the technical measures regulation, highlights the need for greater flexibility in fisheries through increased stakeholder involvement. To achieve this flexibility, there is a need for additional fishing gears available to the fishermen. A way to facilitate this is to have the industry take part in the development and testing of fishing gears, as well as collect data on their performance. However, to have a successful industry-collected data programme, fishermen have to be able to collect data on the length of a portion of the catch. In this study, we determine how many individuals need to be measured to correctly evaluate the relative selective performance of a new gear compared to a standard gear. The evaluation was carried out by analysing catch ratio curves, their associated uncertainties, and the trade-offs between uncertainties and sampling effort. Results show that with relatively small sample sizes (500 to 1000 individuals) it is possible to correctly evaluate the performance of a gear for a given species. By having the industry develop and test their own gears, as well as being involved in the collection of data, the number of potential gear solutions available to address the different issues emerging in the fisheries is increased.


Mode-coupling analysis in axisymmetric birefringent waveguides.
Axisymmetric periodic media such as annular layers have axi-symmetric birefringence. I report the theoretical analysis of mode coupling in axisymmetric birefringent waveguides. Any of the LP(11) modes in a perturbed system can couple with a corresponding LP(11) mode that is orthogonal to the original mode with respect to both the polarization direction and the node line of an electric field. The coupling beat length depends on the amount of birefringence, which can be as short as 5 mm for a practical structure.


Radiology and social media: are private practice radiology groups more social than academic radiology departments?
This study assesses the prevalence of use of the most commonly used social media sites among private radiology groups (PRGs) and academic radiology departments (ARDs). The 50 largest PRGs and the 50 ARDs with the highest level of funding from the National Institutes of Health were assessed for presence of a radiology-specific social media account on Facebook, Twitter, Instagram, Pinterest, YouTube, and LinkedIn. Measures of organizational activity and end-user activity were collected, including the number of posts and followers, as appropriate; between-group comparisons were performed. PRGs adopted Facebook 12 months earlier (P = .02) and Twitter 18 months earlier (P = .02) than did ARDs. A total of 76% of PRGs maintained ≥1 account on the social media sites included in the study, compared with 28% of ARDs (P < .0001). The prevalence of having an account on the social media sites for PRGs was: Facebook, 66%; LinkedIn, 56%; Twitter, 42%; YouTube, 20%; Pinterest, 4%; and Instagram, 2%. The prevalence of radiology-specific social media accounts for ARDs was: Facebook, 18%; LinkedIn, 0%; Twitter, 24%; YouTube, 6%; Pinterest, 0%; and Instagram, 0%. There was no significant difference between ARDs and PRGs in measures of end-user or organizational activity on Facebook or Twitter. Use of social media in health care is emerging as mainstream, with PRGs being early adopters of Facebook and Twitter in comparison with ARDs. Competitive environments and institutional policies may be strong factors that influence how social media is used by radiologists at the group and department levels.


[Malaria in hominids].
Malaria parasites (Plasmodium spp) that infect great apes are very poorly documented Malaria was first described in gorillas, chimpanzees and orangutans in the early 20th century, but most studies were confined to a handful of chimpanzees in the 1930-1950s and a few orangutans in the 1970s. The three Plasmodium species described in African great apes were very similar to those infecting humans. The most extensively studied was P reichenowi, because of its close phylogenetic relation to P. falciparum, the predominant parasite in Africa and the most dangerous for humans. In the last three years, independent molecular studies of various chimpanzee and gorilla populations have revealed an unexpected diversity in the Plasmodium species they harbor, which are also phylogenetically close to P falciparum. In addition, cases of non human primate infection by human malaria parasites have been observed. These observations shed fresh light on the origin and evolutionary history of P. falciparum and provide a unique opportunity to probe the biological specificities of this major human parasite.


Three-component synthesis of fluorinated pyrazoles from fluoroalkylamines, NaNO2 and electron-deficient alkynes.
Three-component reaction between RCF2CH2NH2·HCl, NaNO2 and electron-deficient alkynes significantly depends on substituent "R". The reaction gives the fluorinated pyrazoles in high yields when "R" is a fluorine atom or a fluoroalkyl group. With other "R" unexpected products are formed.


Mechanosensitive mechanisms in transcriptional regulation.
Transcriptional regulation contributes to the maintenance of pluripotency, self-renewal and differentiation in embryonic cells and in stem cells. Therefore, control of gene expression at the level of transcription is crucial for embryonic development, as well as for organogenesis, functional adaptation, and regeneration in adult tissues and organs. In the past, most work has focused on how transcriptional regulation results from the complex interplay between chemical cues, adhesion signals, transcription factors and their co-regulators during development. However, chemical signaling alone is not sufficient to explain how three-dimensional (3D) tissues and organs are constructed and maintained through the spatiotemporal control of transcriptional activities. Accumulated evidence indicates that mechanical cues, which include physical forces (e.g. tension, compression or shear stress), alterations in extracellular matrix (ECM) mechanics and changes in cell shape, are transmitted to the nucleus directly or indirectly to orchestrate transcriptional activities that are crucial for embryogenesis and organogenesis. In this Commentary, we review how the mechanical control of gene transcription contributes to the maintenance of pluripotency, determination of cell fate, pattern formation and organogenesis, as well as how it is involved in the control of cell and tissue function throughout embryogenesis and adult life. A deeper understanding of these mechanosensitive transcriptional control mechanisms should lead to new approaches to tissue engineering and regenerative medicine.


Positive emotions in caring for a spouse: a literature review.
This article aimed at identifying the positive emotions connected to spouse caregiving and the advantages for spouse carers. Theoretically, the article is based on the concept of emotion and the assumptions of positive psychology. Data search is conducted via electronic literature databases and the analysis method is partly theory-driven and partly inductive content classification. Our analyses discover and clarify the concepts associated with positive emotions in caring, such as the gains of caregiving, benefit-finding, finding meaning, personal growth, post-traumatic growth and resilience. We also utilise a conceptual framework to describe positive emotions in caregiving, and the identified advantages of positive emotions in spouse caregiving include distress buffering, mediation in coping with stress, increased quality of life and well-being, and finding a sense of purpose. Finally, spouse care is seen in this article as a challenging life situation which at best can support personal growth, if the processing of both positive and negative emotions is included in daily life. Hence, the service and support system should be developed further by utilising the findings of positive psychology as well as studies of personal growth.


Exposure workups.
Exposure workups are an important responsibility for infection control personnel. A well-designed plan for investigating exposures, which includes appropriate algorithms, will enable infection control personnel to evaluate exposures rapidly and consistently so that nosocomial transmission is minimized. Infection control personnel should use their own data to develop policies and procedures that suit the needs of their facility. After they have implemented the plan, infection control personnel should continue to collect data on exposures so they can continuously improve their performance.