The antimicrobial peptide LL-37 induces synthesis and release of cysteinyl leukotrienes from human eosinophils--implications for asthma.
Eosinophils and their products, including leukotrienes and eosinophil cationic protein (ECP), are well-known mediators of inflammation and tissue damage in asthma. The antimicrobial peptide LL-37 exhibits a variety of immunomodulatory activities. However, the role of LL-37 in asthma has not been fully addressed. Here, we aim to investigate the effect of LL-37 on inducing inflammatory mediators in human eosinophils, probe the underlying mechanisms, and search for a clinical correlate. Primary eosinophils were isolated from peripheral blood. Leukotriene and ECP levels were measured using EIAs or ELISAs. Activation of leukotriene-synthesizing enzymes and signaling kinases was analyzed by Western blot or immunofluorescent imaging. LL-37/its proform hCAP18 expression was analyzed by Western blot. LL-37, via formyl peptide receptor-2 (FPR-2), triggered the release of cysteinyl leukotrienes (cys-LTs) from eosinophils. The release was more prominent in cells primed with the eosinophilopoietic cytokine GM-CSF or IL-5 or cells from asthmatic patients. LL-37 stimulates lipid body formation and activates cys-LT-synthesizing enzymes by multiple mechanisms: enhancing cPLA(2) activity by pERK1/2-mediated phosphorylation and inducing intracellular translocation and assembly of 5-LO and LTC(4) S at perinuclear locations and lipid bodies. In addition to cys-LTs, LL-37 enhances ECP release from eosinophils via pERK1/2. The expression of hCAP18 and its release following leukotriene stimulation are significantly higher in eosinophils from asthmatics. This study identifies LL-37 as an eosinophil-activating peptide that triggers release of inflammatory mediators. The clinical correlation suggests that LL-37/hCAP18 and its signaling pathway represent potential therapeutic targets for this disease.


A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP.
A female offspring of consanguineous parents, showed features of Wiskott-Aldrich syndrome (WAS), including recurrent infections, eczema, thrombocytopenia, defective T cell proliferation and chemotaxis, and impaired natural killer cell function. Cells from this patient had undetectable WAS protein (WASP), but normal WAS sequence and messenger RNA levels. WASP interacting protein (WIP), which stabilizes WASP, was also undetectable. A homozygous c.1301C>G stop codon mutation was found in the WIPF1 gene, which encodes WIP. Introduction of WIP into the patient's T cells restored WASP expression. These findings indicate that WIP deficiency should be suspected in patients with features of WAS in whom WAS sequence and mRNA levels are normal.


Methods to account for attrition in longitudinal data: do they work? A simulation study.
Attrition threatens the internal validity of cohort studies. Epidemiologists use various imputation and weighting methods to limit bias due to attrition. However, the ability of these methods to correct for attrition bias has not been tested. We simulated a cohort of 300 subjects using 500 computer replications to determine whether regression imputation, individual weighting, or multiple imputation is useful to reduce attrition bias. We compared these results to a complete subject analysis. Our logistic regression model included a binary exposure and two confounders. We generated 10, 25, and 40% attrition through three missing data mechanisms: missing completely at random (MCAR), missing at random (MAR) and missing not at random (MNAR), and used four covariance matrices to vary attrition. We compared true and estimated mean odds ratios (ORs), standard deviations (SDs), and coverage. With data MCAR and MAR for all attrition rates, the complete subject analysis produced results at least as valid as those from the imputation and weighting methods. With data MNAR, no method provided unbiased estimates of the OR at attrition rates of 25 or 40%. When observations are not MAR or MCAR, imputation and weighting methods may not effectively reduce attrition bias.


Deep peroneal nerve palsy with isolated lateral compartment syndrome secondary to peroneus longus tear: a report of two cases and a review of the literature.
Drop foot is typically caused by neurologic disease such as lumbar disc herniation, but we report two rare cases of deep peroneal nerve palsy with isolated lateral compartment syndrome secondary to peroneus longus tears. Both patients developed mild pain in the lower legs while playing sport, and were aware of drop foot. As compartment pressures were elevated, fasciotomy was performed immediately, and the tendon of the peroneus longus was completely detached from its proximal origin. The patients were able to return their original sports after 3 months, and clinical examination revealed no hypesthesia or muscle weakness in the deep peroneal nerve area at the time of last follow-up. The common peroneal nerve pierced the deep fascia and lay over the fibular neck, which formed the floor of a short tunnel (the so-called fibular tunnel), then passed the lateral compartment just behind the peroneus longus. The characteristic anatomical situation between the fibular tunnel and peroneus longus might have caused deep peroneal nerve palsy in these two cases after hematoma adjacent to the fibular tunnel increased lateral compartment pressure.


Continuous regional myocardial blood flow measurement: validation of a near-infrared laser Doppler device in a porcine model.
RMBF measurement is a major concern in various clinical and experimental settings, but no validated device for RMBF is currently available. An LVP-triggered laser Doppler to measure RMBF was validated by simultaneous fluorescent MS RMBF in a porcine LAD flow reduction model (n = 10 pigs). The laser probe was positioned on the left ventricle's anterior wall. LAD blood flow reduction was achieved by a shaft-driven occluder positioned proximal to the transit-time flow meter measuring coronary blood flow. RMBF was measured at baseline; after the reduction of LAD blood flow to 70% and 30% of baseline; at 20 and 120 minutes of reperfusion; and, finally, 15 minutes after LAD occlusion. Laser Doppler RMBF (LDU) correlated strongly with MS RMBF under all tested conditions: baseline (epicardial 194.7 ± 41.9, endocardial 130.2 ± 29.2); 70% baseline-flow (epicardial 160.4 ± 27.7, endocardial 112.1 ± 15.1); 30% baseline-flow (epicardial 44.3 ± 5.5, endocardial 32.9 ± 9); 20 minutes reperfusion (epicardial 175.8 ± 33.6, endocardial 126.5 ± 30); 120 minutes reperfusion (epicardial 146.3 ± 31.1, endocardial 107.1 ± 29.7); and complete LAD occlusion (epicardial 10.5 ± 5.8 endocardial 1.4 ± 0.3) (r = 0.986-0.962, p < 0.001). This new blood pressure waveform-triggered laser Doppler probe is able to measure RMBF at different depths online in the beating heart.


Tuned normalization explains the size of attention modulations.
The effect of attention on firing rates varies considerably within a single cortical area. The firing rate of some neurons is greatly modulated by attention while others are hardly affected. The reason for this variability across neurons is unknown. We found that the variability in attention modulation across neurons in area MT of macaques can be well explained by variability in the strength of tuned normalization across neurons. The presence of tuned normalization also explains a striking asymmetry in attention effects within neurons: when two stimuli are in a neuron's receptive field, directing attention to the preferred stimulus modulates firing rates more than directing attention to the nonpreferred stimulus. These findings show that much of the neuron-to-neuron variability in modulation of responses by attention depends on variability in the way the neurons process multiple stimuli, rather than differences in the influence of top-down signals related to attention.


A meta-analysis of the effects of UV radiation on the plant carotenoid pool.
Induction of metabolite biosynthesis and accumulation is one of the most prominent UV-mediated changes in plants, whether during eustress (positive response) or distress (negative response). However, despite evidence suggesting multiple linkages between UV exposure and carotenoid induction in plants, there is no consensus in the literature concerning the direction and/or amplitude of these effects. Here, we compiled publications that characterised the relative impact of UV on the content of individual carotenoids and subjected the created database to a meta-analysis in order to acquire new, fundamental insights in responses of the carotenoid pool to UV exposure. Overall, it was found that violaxanthin was the only carotenoid compound that was significantly and consistently induced as a result of UV exposure. Violaxanthin accumulation was accompanied by a UV dose dependent decrease in antheraxanthin and zeaxanthin. The resulting shift in the state of the xanthophyll cycle would normally occur when plants are exposed to low light and this is associated with increased susceptibility to photoinhibition. Although UV induced violaxanthin accumulation is positively linked to the daily UV dose, the current dataset is too small to establish a link with plant stress, or even experimental growth conditions. In summary, the effects of UV radiation on carotenoids are multifaceted and compound-specific, and there is a need for a systematic analysis of dose-response and wavelength dependencies, as well as of interactive effects with further environmental parameters.


Nasal augmentation in the problem nose.
The author emphasizes that nasal implants made of pierced silicone material, or conchal cartilage, are extremely satisfactory in selected cases. Their use should be restricted to dorsal implants, and the type of implant individually adapted to each case. The implant used should be made of solid silicone with numerous large holes piercing its form to create a natural fixation. In addition, the author stresses that cartilage grafts are very satisfactory, especially for small depressions or tip augmentation.


In vivo quantitative ultrasonic evaluation of neonatal brain with a real time integrated backscatter imaging system.
We applied the integrated backscatter (IBS) imaging system to the evaluation of the normal neonatal brain of different birth-weights: extremely low-birth-weight (N=13), very-low-birth-weight (N=14), low-birth weight (N=14), and normal birth weight (N=19). The IBS values in six regions of interest, the deep white matter, subcortical white matter, choroid plexus, thalamus, lateral ventricle, and occipital bone, were compared among groups of different birth weights, gestational age, and postnatal age: at the date of birth and 28 approximately 30 days after birth. The IBS values were higher in the order of bone>choroid plexus>deep white matter>subcortical white matter>thalamus>lateral ventricle and were significantly different except for the lateral ventricle in all the groups at days 0 and 28 approximately 30. The IBS values increased with the decrease of birth weight and gestational age. There was a decrease of IBS values at day 28 compared to that of day 0 in the extremely low birth weight and very low birth weight groups; however, they remained the same in infants with low birth weights and in the normal birth weight group. Further studies to evaluate the significance of this technique for the objective diagnosis of brain insults in neonates are necessary.


Does ragging play a role in medical student depression - cause or effect?
Medical students experience a lot of stress what may contribute to symptoms of depression. In this study we set out to look at the environmental factors which may be contributing in one medical school in Brazil. We assessed depressive symptoms using Beck's Depression Inventory in 465 and 267 medical students in 2001 and 2006 respectively. We explored possible social and environmental causes using qualitative data. Nearly 15% scored above the cut off for depression in both the samples. Males in the pre-clinical stage in 2006 showed an increase in depressive symptoms than males in the same cycle in 2001 (aOR=7.36 [95% CI=0.85-63.5] p=0.07). Qualitative data confirmed that factors such as ragging and low social involvement were correlated with depressive symptoms in pre-clinical stage males. The sample size was small both for quantitative and qualitative aspects of the study. It appears that ragging plays an important role in the genesis of depressive symptoms in medical students.


Ultrasound assisted synthesis of 5,9-dimethylpentadecane and 5,9-dimethylhexadecane--the sex pheromones of Leucoptera coffeella.
Racemic 5,9-dimethylpentadecane and 5,9-dimethylhexadecane, the major and minor constituents, respectively, of the sex pheromone of Leucoptera coffeella, have been synthesized from citronellol in 56-58% overall yield through six steps. Ultrasound irradiation efficiently supported tosylation of alcohols (two steps) as well as the subsequent cross coupling reactions with the pertinent Grignard reagents (also two steps).


Clinical outcomes of conduction system pacing versus biventricular pacing for cardiac resynchronization therapy: A systematic review and meta-analysis.
Conduction system pacing (CSP) is observed to produce greater improvements in echocardiographic and hemodynamic parameters as compared to conventional biventricular pacing (BiVP). However, whether these surrogate endpoints directly translate to improvements in hard clinical outcomes such as death and heart failure hospitalization (HFH) with CSP remains uncertain as studies reporting these outcomes are scarce. The aim of this meta-analysis was to analyze the existing data to compare the clinical outcomes of CSP versus BiVP. A systematic search of the Embase and PubMed database was performed for studies comparing CSP and BiVP for patients indicated to receive a CRT device. The coprimary endpoints were all-cause mortality and HFH. Other secondary outcomes included change in left ventricular ejection fraction (LVEF), change in NYHA class, and increase in NYHA class ≥1. A random-effects model was chosen a priori to analyze the composite effects given the anticipated heterogeneity of included trials. Twenty-one studies (4 randomized and 17 observational) were identified reporting either primary outcome and were included in the meta-analysis. In total 1960 patients were assigned to CSP and 2367 to BiVP. Median follow-up time was 10.1 months (ranging 2-33 months). CSP was associated with a significant reduction in all-cause mortality (odds ratio [OR] 0.68, 95% confidence interval [CI]: 0.56-0.83) and HFH (OR 0.52, 95% CI: 0.44-0.63). Mean improvement in LVEF was also greater with CSP (mean difference 4.26, 95% CI: 3.19-5.33). Reduction in NYHA class was significantly greater with CSP (mean difference -0.36, 95% CI: -0.49 to -0.22) and the number of patients with an increase in NYHA class ≥1 was significantly greater with CSP (OR 2.02, 95% CI: 1.70-2.40). CSP was associated with a significant reduction in all-cause mortality and HFH when compared to conventional BiVP for CRT. Further large-scale randomized trials are needed to verify these observations.


Synthesis and SAR of novel oxazolidinones: discovery of ranbezolid.
Novel oxazolidinones were synthesized containing a number of substituted five-membered heterocycles attached to the 'piperazinyl-phenyl-oxazolidinone' core of eperezolid. Further, the piperazine ring of the core was replaced by other diamino-heterocycles. These modifications led to several compounds with potent activity against a spectrum of resistant and susceptible gram-positive organisms, along with the identification of ranbezolid (RBx 7644) as a clinical candidate.


ThrR, a DNA-binding transcription factor involved in controlling threonine biosynthesis in Bacillus subtilis.
The threonine dehydratase IlvA is part of the isoleucine biosynthesis pathway in the Gram-positive model bacterium Bacillus subtilis. Consequently, deletion of ilvA causes isoleucine auxotrophy. It has been reported that ilvA pseudo-revertants having a derepressed hom-thrCB operon appear in the presence of threonine. Here we have characterized two classes of ilvA pseudo-revertants. In the first class the hom-thrCB operon was derepressed unmasking the threonine dehydratase activity of the threonine synthase ThrC. In the second class of mutants, threonine biosynthesis was more broadly affected. The first class of ilvA pseudo-revertants had a mutation in the Phom promoter (P*hom ), resulting in constitutive expression of the hom-thrCB operon. In the second class of ilvA pseudo-revertants, the thrR gene encoding a putative DNA-binding protein was inactivated, also resulting in constitutive expression of the hom-thrCB operon. Here we demonstrate that ThrR is indeed a DNA-binding transcription factor that regulates the hom-thrCB operon and the thrD aspartokinase gene. DNA binding assays uncovered the DNA-binding site of ThrR and revealed that the repressor competes with the RNA polymerase for DNA binding. This study also revealed that ThrR orthologs are ubiquitous in genomes from the Gram-positive phylum Firmicutes and in some Gram-negative bacteria.


Corneal thickness. II. Environmental and genetic factors.
In a material of 839 Greenland Eskimos with no corneal abnormalities, the variations of central corneal thickness (CT) were analysed from a genetic point of view. Environmental factors were suggested by a town-village difference in mean CT level (excess in town), by a higher CT level in families with an indoor occupation, and by a nearly significant husband-wife CT correlation. Using an age-sex-location-independent CT deviation score (CTDS) the family variations were studied in 86 families with two parents and one to seven children, and in 187 sibships with two to seven sibs. The first degree relationships showed a fairly high level of resemblance, which seems to indicate a major genetic influence on CT, with heritability estimates about 0.6--0.7. In men an association was found between CT and Caucasian admixture, which also suggested genetic factors. However, both findings call for reservation because of the socioeconomic environmental influence.


Imaging of Congenital/Childhood Central Nervous System Infections.
This article highlights the changing profile of the pediatric patient with central nervous system infection as countries develop and the roles of different imaging modalities such as cranial ultrasound, MR imaging, and computed tomography. It discusses the commonly encountered congenital toxoplasmosis, rubella, cytomegalovirus, herpes simplex (TORCH) infections, Group B Streptococcal and Escherichia coli infections in the neonatal period, and disease outbreaks affecting children. Iatrogenic, opportunistic, and immune-mediated changes as well as long-term effects of infection and mimics of infection are also discussed. Variety of images is provided to show the range of neuroimaging findings encountered, particularly on cranial ultrasound and MR imaging.


Net photosynthetic recovery in subarctic lichens with contrasting water relations.
The rates of net photosynthetic recovery after wetting for six subarctic lichens were related to their drying rates under laboratory conditions. Net photosynthetic recovery was described by the three parameters of the Von-Bertalanffy equation: T o and K, related to the rates of resaturation respiration and gross photosynthetic recovery, and P max, the photosynthetic maximum attained at full recovery. The time to full photosynthetic recovery ranged from 143 to 510 min and was positively correlated with the drying rate of the thallus. In order from most to least rapid recovery, the species are Coelocaulon divergens, Cetraria cucullata, Alectoria ochroleuca, Cladina stellaris, Nephroma arcticum, and Cladonia sulphurina.In nature the high evaporative resistance or low waterholding capacity characterizing fast-drying species will result in short, frequent cycles of wetting and drying which induce carbon losses. In such situations a rapid photosynthetic recovery should be adaptive since it increases photosynthetic carbon gain during a period of metabolic activity. We hypothesize that fast-drying species achieve their rapid photosynthetic recovery by an increased desiccation-tolerance which has a metabolic cost associated with it. In slowdrying species a rapid recovery is not favored by natural selection since these species can take advantage of longer photosynthetic activity periods and are exposed less frequently to deleterious wetting and drying cycles. Future studies of lichen distribution and productivity should take into account the recovery phenomena.


Leukotriene B4 generation by blood polymorphonuclear leukocytes after incubation in urine.
To investigate the capacity of leukocytes in urine to produce leukotriene B4 (LTB4), we evaluated calcium ionophore A23187-induced LTB4 generation by human blood polymorphonuclear leukocytes (PMNL) after these cells were incubated in urine under various conditions. LTB4 production was markedly reduced after incubation of PMNL in urine of high or low pH and high osmolarity. The production was also inhibited by a prolonged incubation period. There was a significant correlation (r = 0.82, p < 0.01) between LTB4 production and PMNL viability. Our results indicate that it is possible to evaluate the LTB4 production capacity of urinary PMNL by determining PMNL viability only. Furthermore acidification of urine hamper the LTB4 generation which might be unfavorable in vivo.


The case against secondary epileptogenesis.
Secondary epileptogenesis is a theory that hypothesizes that uncontrolled seizures in people with epilepsy lead to the development of new sites of seizure onset. This process has often been cited when people experience a new seizure type after a period of poor seizure control. The theory proposes that repeated seizures induce changes in regions of the brain that are regularly recruited into the seizure. These hypothetical changes can then lead to a new, independent seizure onset zone. The concept is based on a number of clinical observations which secondary epileptogenesis could explain. However there are alternative explanations from the clinic as well as from the laboratory that call the process into question. In this review some of the observations that have been used to support the theory will be reviewed, and the many counterarguments will be presented. At this time there is little evidence to support secondary epileptogenesis and much to refute it.


Prognostic implications of DNA index in patients with stage III cutaneous melanoma.
DNA flow cytometry of the lymph node metastases from 56 patients was used to retrospectively evaluate the prognostic significance of DNA ploidy in patients with stage III melanoma. The findings were correlated with traditional prognostic factors and patient survival. Multivariate regression analysis revealed that, in addition to the number of positive lymph nodes and patient gender, the DNA index was a significant predictor of patient survival (all p < 0.03). Within this cohort of patients, the patients with the poorest prognoses were those with DNA indices greater than 2 (at least tetraploid), more than three positive lymph nodes, and male gender. There was a significant survival difference among the patients having zero, one, or two of these risk factors (p < 0.001). Our results indicate that DNA analysis of melanoma metastases by flow cytometry provides an additional discriminating factor for predicting patient outcome after therapeutic lymph node dissection. This information may be useful in directing patients with stage III melanoma at higher risk for recurrence into clinical trials of more aggressive systemic adjuvant therapy.


Ionizing radiation and genetic risks. VI. Chronic multifactorial diseases: a review of epidemiological and genetical aspects of coronary heart disease, essential hypertension and diabetes mellitus.
This paper provides a broad overview of the epidemiological and genetical aspects of common multifactorial diseases in man with focus on three well-studied ones, namely, coronary heart disease (CHD), essential hypertension (EHYT) and diabetes mellitus (DM). In contrast to mendelian diseases, for which a mutant gene either in the heterozygous or homozygous condition is generally sufficient to cause disease, for most multifactorial diseases, the concepts of genetic susceptibility' and risk factors' are more appropriate. For these diseases, genetic susceptibility is heterogeneous. The well-studied diseases such as CHD permit one to conceptualize the complex relationships between genotype and phenotype for chronic multifactorial diseases in general, namely that allelic variations in genes, through their products interacting with environmental factors, contribute to the quantitative variability of biological risk factor traits and thus ultimately to disease outcome. Two types of such allelic variations can be distinguished, namely those in genes whose mutant alleles have (i) small to moderate effects on the risk factor trait, are common in the population (polymorphic alleles) and therefore contribute substantially to the variability of biological risk factor traits and (ii) profound effects, are rare in the population and therefore contribute far less to the variability of biological risk factor traits. For all the three diseases considered in this review, a positive family history is a strong risk factor. CHD is one of the major contributors to mortality in most industrialized countries. Evidence from epidemiological studies, clinical correlations, genetic hyperlipidaemias etc., indicate that lipids play a key role in the pathogenesis of CHD. The known lipid-related risk factors include: high levels of low density lipoprotein cholesterol, low levels of high density lipoprotein cholesterol, high apoB levels (the major protein fraction of the low density lipoprotein particles) and elevated levels of Lp(a) lipoprotein. Among the risk factors which are not related to lipids are: high levels of homocysteine, low activity of paraoxonase and possibly also elevated plasma fibrinogen levels. In addition to the above, hypertension, diabetes and obesity (which themselves have genetic determinants) are important risk factors for CHD. Among the environmental risk factors are: high dietary fat intake, smoking, stress, lack of exercise etc. About 60% of the variability of the plasma cholesterol is genetic in origin. While a few genes have been identified whose mutant alleles have large effects on this trait (e.g., LDLR, familial defective apoB-100), variability in cholesterol levels among individuals in most families is influenced by allelic variation in many genes (polymorphisms) as well as environmental exposures. A proportion of this variation can be accounted for by two alleles of the apoE locus that increase (ε4) and decrease (ε2) cholesterol levels, respectively. A polymorphism at the apoB gene (XbaI) also has similar effects, but is probably not mediated through lipids. High density lipoprotein cholesterol levels are genetically influenced and are related to apoA1 and hepatic lipase (LIPC) gene functions. Mutations in the apoA1 gene are rare and there are data which suggest a role of allelic variation at or linked LIPC gene in high density lipoprotein cholesterol levels. Polymorphism at the apoA1--C3 loci is often associated with hypertriglyceridemia. The apo(a) gene which codes for Lp(a) is highly polymorphic, each allele determining a specific number of multiple tandem repeats of a unique coding sequence known as Kringle 4. The size of the gene correlates with the size of the Lp(a) protein. The smaller the size of the Lp(a) protein, the higher are the Lp(a) levels. (ABSTRACT TRUNCATED)


A novel minimally invasive dynamic-shield, intensity-modulated brachytherapy system for the treatment of cervical cancer.
To present a novel, MRI-compatible dynamicshield intensity modulated brachytherapy (IMBT) applicator and delivery system using 192 Ir, 75 Se, and 169 Yb radioisotopes for the treatment of locally advanced cervical cancer. Needle-free IMBT is a promising technique for improving target coverage and organs at risk (OAR) sparing. The IMBT delivery system dynamically controls the rotation of a novel tungsten shield placed inside an MRI-compatible, 6-mm wide intrauterine tandem. Using 36 cervical cancer cases, conventional intracavitary brachytherapy (IC-BT) and intracavitary/interstitial brachytherapy (IC/IS-BT) (10Ci 192 Ir) plans were compared to IMBT (10Ci 192 Ir; 11.5Ci 75 Se; 44Ci 169 Yb). All plans were generated using the Geant4-based Monte Carlo dose calculation engine, RapidBrachyMC. Treatment plans were optimized then normalized to the same high-risk clinical target volume (HR-CTV) D90 and the D2cc for bladder, rectum, and sigmoid in the research brachytherapy planning system, RapidBrachyMCTPS. Plans were renormalized until either of the three OAR reached dose limits to calculate the maximum achievable HR-CTV D90 and D98 . Compared to IC-BT, IMBT with either of the three radionuclides significantly improves the HR-CTV D90 and D98 by up to 5.2% ± 0.3% (P < 0.001) and 6.7% ± 0.5% (P < 0.001), respectively, with the largest dosimetric enhancement when using 169 Yb followed by 75 Se and then 192 Ir. Similarly, D2cc for all OAR improved with IMBT by up to 7.7% ± 0.6% (P < 0.001). For IC/IS-BT cases, needle-free IMBT achieved clinically acceptable plans with 169 Yb-based IMBT further improving HR-CTV D98 by 1.5% ± 0.2% (P = 0.034) and decreasing sigmoid D2cc by 1.9% ± 0.4% (P = 0.048). Delivery times for IMBT are increased by a factor of 1.7, 3.3, and 2.3 for 192 Ir, 75 Se, and 169 Yb, respectively, relative to conventional 192 Ir BT. Dynamic shield IMBT provides a promising alternative to conventional IC- and IC/IS-BT techniques with significant dosimetric enhancements and even greater improvements with intermediate energy radionuclides. The ability to deliver a highly conformal, OAR-sparing dose without IS needles provides a simplified method for improving the therapeutic ratio less invasively and in a less resource intensive manner.


Parents' opinions about epilepsy surgery in children with epilepsy.
This survey aimed to investigate the opinions of the parents of children with epilepsy with regard to the application of epilepsy surgery for their children. We surveyed all the parents of children with epilepsy referred to our neurology clinic (Shiraz University of Medical Sciences) in April-July 2022. We collected their opinions about epilepsy surgery based on a predesigned questionnaire. The inclusion criteria included parents of all children with epilepsy (1 to 16 years of age, with at least one-year history of epilepsy, and with at least one drug used in the past 12 months). In total, 472 people participated in the study; 277 participants (58.7%) were willing to have epilepsy surgery for their child; the most common reason was to be able to discontinue the drugs. Sex (male), age (younger), and education (college) of the parents had significant associations with the parental willingness to have surgery for their children. The patient's drug regimen (polytherapy) and history of ictal injury (in the child) also had significant associations with the parental willingness to have surgery for the children. Most parents of children with epilepsy are willing to have epilepsy surgery for their children if their physician presents epilepsy surgery to them as an established, safe, and effective treatment option. Patient and parental-related factors should be considered when designing educational materials and programs for preoperative counseling for the parents of children with drug-resistant seizures.


A short period of hypoxia produces a rapid and transient rise in [K+]e in rat hippocampus in vivo which is inhibited by certain K(+)-channel blocking agents.
Extracellular potassium concentrations, [K+]e, were measured in vivo in the rat dorsal hippocampus using valinomycin-based double-barrelled ion-selective microelectrodes. Experiments were conducted under chloral hydrate anaesthesia. The microelectrodes were implanted stereotaxically, after which different gas mixtures were administered by inhalation. Transient hypoxia was induced by changing the inspired gas from 20% O2/80% N2 to 10-0% O2/90-100% N2 for 0.5-2 min. Resting [K+]e in the dorsal hippocampus was 3.4 +/- 0.09 mM; 0.5, 1 or 2 min of 100% N2 administration caused a rapid rise of [K+]e to 0.75, 1.9 and 15 mM, respectively. Following 0.5 min of 100% N2, the switch back to 20% O2/80% N2 produced an almost instantaneous return to normal levels. The return of [K+]e to basal levels was more delayed after 1 or 2 min of 100% N2 inhalation. The rise of hippocampal [K+]e induced by hypoxia was influenced by body temperature, the increase being five-fold higher in rats whose body temperature was raised from 33 to 37 degrees C using a heating blanket. Three potassium-channel blocking agents, quinine, 4-aminopyridine and gliquidone, were tested for their action on the increase in [K+]e, induced by inhalation of 100% N2 for 0.5 min. Both 4-aminopyridine and quinine, administered systemically, attenuated the anoxia-induced rise in [K+]e by 70 and 35%, respectively. In contrast, gliquidone, given by intracerebroventricular injection, had no effect, suggesting that ATP-sensitive potassium channels are not involved in this very early change in [K+]e.


Assessment of right ventricular free wall longitudinal myocardial deformation using speckle tracking imaging in normal subjects.
To assess right ventricular free wall longitudinal myocardium deformation and examine the changes with normal age by speckle tracking imaging (STI), myocardial systolic peak strain (epsilon), systolic peak strain rate (SRs), early diastolic peak strain rate (SRe), late diastolic peak strain rate (SRa), the ratio of SRe/SRa were measured in the basal, middle and apical segments of right ventricular free wall in 75 healthy volunteers (age range: 21-71 y) by STI from the apical 4-chamber view. RV longitudinal strain and strain rate were highest in the basal segment of the free wall. Older subjects had lower early diastolic strain rate (SRe) than younger subjects, but they had higher late diastolic strain rate (SRa). A negative correlation between age and the ratio of SRe/SRa was found in all RV free wall segments (r=-0.466 - -0.614, P<0.01). It is concluded that RV diastolic strain rate changes with age and STI can be used for the study of RV myocardial deformation.


Strong visible cooperative up-conversion emission in ZrO2:Yb3+ nanocrystals.
Blue, green, and red emission was observed under infrared excitation in ZrO2:Yb3+ nanocrystals prepared by the sol-gel process. The structural characterization was performed by using XRD and HRTEM, suggesting that the crystalline phase of the nanoparticles is controlled by the active ion concentration being mainly tetragonal for 2 mol% of dopant and mainly monoclinic for 0.5 mol%. The blue emission was explained in terms of the cooperative deexcitation of an Yb-Yb pair, while the green and red bands were associated with the up-conversion of traces of Er ion. The number of photons involved in the luminescence process is analyzed in order to confirm that cooperative emission is produced by the interaction of an Yb pair and that the green and red emission are the results of energy transfer between Yb-Er ions. The high efficiency of all bands is explained in terms of the high surface area of the nanoparticles.


Advanced Imaging Utilization Trends in Privately Insured Patients From 2007 to 2013.
The aim of the study was to investigate whether the increase in utilization of advanced diagnostic imaging for privately insured patients in 2011 was the beginning of a new trend in imaging utilization growth, or an isolated deviation from the declining trend that began in 2008. We extracted outpatient and inpatient CT, diagnostic ultrasound, MRI, and PET procedures from databases, for the years 2007 to 2013. This study extended previous work, covering 2012 to 2013, using the same methodology. For every year of the study period, we calculated the following: number of procedures per person-year covered by private health insurance; proportion of office and emergency visits that resulted in an imaging session; average payments per procedure; and total payments per person-year covered by private health insurance. Outpatient utilization of CT and PET decreased in both 2012 and 2013; outpatient utilization of MRI mildly increased in 2012, but then decreased in 2013. Outpatient utilization of diagnostic ultrasound showed a very different pattern, increasing throughout the study period. Inpatient utilization of all imaging modalities except PET decreased in both 2012 and 2013. Adjusted payments for all imaging modalities increased in 2012, and then dropped substantially in 2013, except the adjusted payments for diagnostic ultrasound that increased in 2013 again. The trend of increasing utilization of advanced diagnostic imaging seems to be over for some, but not all, imaging modalities. A combination of policy (eg, breast density notification laws), technologic advancement, and wider access seems to be responsible for at least part of an increasing utilization of diagnostic ultrasound.


Functional properties and fatty acids profile of different beans varieties.
Dried seeds of four varieties of Phaseolus vulgaris, three of Vigna unguiculata ssp. unguiculata and two of Vigna angularis grown and marketed in Italy, Mexico, India, Japan, Ghana and Ivory Coast were analysed for fatty acids content. In oils from seeds of P. vulgaris, the main fatty acids were linolenic (34.7-41.5%) and linoleic (30.7-40.3%), followed by palmitic (10.7-16.8%). The first three aforementioned fatty acids in the lipid fraction of V. unguiculata varieties were 28.4, 28.7 and 26.2%, respectively; while in V. angularis varieties, main fatty acids were linoleic (36.4-39.1%) and palmitic (26.9-33.3%), followed by linolenic (17.9-22.2%). Statistical analyses indicate that botanical species play a rule in bean fatty acids distribution, while the same was not verified for geographical origin. Furthermore, the atherogenic index (AI) and the thrombogenic index (TI) were investigated for health and nutritional information. The results showed that these wide spread legumes have functional features to human health.


Quantitative evaluation of somatostatin receptor subtype 2 expression in sporadic colorectal tumor and in the corresponding normal mucosa.
The somatostatin (SS) receptor subtype 2 (sst2) is the principal mediator of the antiproliferative effects of SS and has the highest affinity for the commercially available SS analogues. The purpose of this study was to evaluate sst2 mRNA expression by quantitative reverse transcription-PCR (RT-PCR) in colon cancers and in corresponding normal tissues. The expression of sst2 mRNA was measured with a quantitative method based on real time RT-PCR with TaqMan assay in 100 colon cancers and in the corresponding normal tissues. In a limited number of patients, these results were compared with those obtained by in situ hybridization (n = 26) and by in vivo imaging with (111)In-pentetreotide (n = 17). Results obtained by quantitative RT-PCR on sst2 expression in colorectal cancer were significantly related to those obtained by in situ hybridization and (111)In-pentetreotide scintigraphy. Sst2 was expressed in all of the tumors investigated without any relationship with localization, grading, and stage of disease. Although the paired, unaffected mucosa tends to express a higher abundance of sst2 than the corresponding cancer samples, this difference did not reach a statistical significance. However, in patients with elevated carcinoembryonic antigen levels (>5 ng/ml) there was a significant loss of sst2 mRNA in the tumor when compared with its paired normal tissue. In this study we confirmed, by a quantitative method, that colorectal cancer does not express higher concentrations of sst2 mRNA than the corresponding unaffected tissue. Conversely, a loss of sst2 was found in patients with elevated preoperative concentrations of carcinoembryonic antigen, an unfavorable prognostic marker for colorectal cancer.


Blood myeloid and lymphoid dendritic cells are stable during the menstrual cycle but deficient during mid-gestation.
The aim of this study was to estimate the populations of peripheral blood myeloid and lymphoid dendritic cells (CD1c(+), BDCA-2(+), BDCA-4(+)) and the CD1c(+):BDCA-2(+) ratio in phases of the ovarian cycle and in normal pregnant patients. 18 non-pregnant women and 17 normal pregnant women were included. Dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies (mAbs) against blood dendritic cell antigens (anti-BDCA-1, BDCA-2, BDCA-4) and estimated using flow cytometry. CD1c(+), BDCA-2(+) and BDCA-4(+) dendritic cells were present in the follicular and luteal phases of the ovarian cycle and in all trimesters of normal pregnancy. The percentages of CD1c(+) dendritic cells did not differ between the follicular and luteal phases of the ovarian cycle. The percentage of BDCA-2(+) dendritic cells was lower in the luteal phase of the ovarian cycle compared with the follicular phase, but the differences were not statistically significant. The CD1c(+):BDCA-2(+) cell ratio was significantly lower in the luteal phase compared with the follicular phase of the ovarian cycle. The numbers of dendritic cells were significantly lower in the second trimester when compared with the first and third trimesters of normal pregnancy. Furthermore, in the second trimester, the CD1c(+):BDCA-2(+) ratio was higher than in the other trimesters of normal pregnancy. All populations of dendritic cells and the CD1c(+):BDCA-2(+) ratio did not differ in the first and third trimesters of physiological pregnancy. Our results suggest that myeloid and lymphoid dendritic cells are not affected by steroid hormones during the menstrual cycle. The deficiency of peripheral blood dendritic cells observed during the second trimester of normal pregnancy can be associated with their migration to the uterus during the second physiological invasion by cytotrophoblast.


Effects of a vitamin-A-free diet on tissue vitamin A concentration and dark adaptation of aging rats.
Changes in serum, hepatic, and ocular vitamin A levels were followed in 9-month-old Long Evans rats fed either a vitamin-A-free or vitamin-A-sufficient diet for up to 18 months. After 18 months, hepatic total vitamin A fell exponentially from 2542 +/- 433 to 48 +/- 12 micrograms/g wet weight, but these stores maintained normal serum retinol and ocular total vitamin A concentrations in vitamin-A-deprived rats. However, retinal dark-adaptation time, a functional indicator of photoreceptor integrity, was prolonged in elderly vitamin-A-deprived rats as compared to vitamin-A-sufficient controls (p less than 0.05). Aging appeared to be the most important factor that depressed the rate of dark adaptation, with vitamin A status having a secondary effect. The proportion of total ocular retinaldehyde decreased (p less than 0.05) and the concentration of retinyl ester increased (p less than 0.05) in the eyes of 27-month-old vitamin-A-deprived rats compared to age-matched vitamin-A-sufficient animals. Possible mechanisms of visual dysfunction include abnormal retinal rhodopsin recycling caused by a dependence on newly absorbed dietary vitamin A (e.g., chylomicron). Alternatively, in the vitamin-A-deprived rat, decreased hepatic oxidation of pentobarbital (used for electroretinographic anesthesia) could prolong retinal anesthetic exposure and either directly depress neural transmission or indirectly alter transmission by affecting rhodopsin recycling.


[End-of-life predictive models: risk of prognostic persistence?]
Machine learning techniques, applied in the palliative field, are able to define an increasingly accurate prognosis in patients with advanced neoplasms and to identify patients at greater risk of functional decline or short-term mortality. The improvement of predictive abilities can allow an enhancement of prognostic abilities and also a more accurate detection of the most complex needs of patients. Moreover, data, even scientific data, are not values, any intervention based on them must be endowed with meaning. Predictive models can therefore be useful but only as a complementary and above all optional tool for the doctor, one of the parameters to evaluate the usefulness in different specific situations. Otherwise, the risk is to add a new type of persistence, the prognostic one.


Organocatalyzed cyclizations of pi-allylpalladium complexes: a new method for the construction of five- and six-membered rings.
Synergic combination of organotransition metal catalysis and organocatalysis allows, for the first time, the Tsuji-Trost cyclization of aldehydes. A catalytic asymmetric variant of the reaction is also possible.


Isolation and structural analysis of the rat MyoD gene.
We have cloned and determined the nucleotide (nt) sequence of a 6.5-kb genomic DNA fragment containing the rat MyoD gene (encoding a muscle regulatory factor, MyoD). Mouse fibroblasts transfected with this DNA display a high degree of conversion to a muscle phenotype, suggesting that this genomic clone contains sufficient sequence information to allow the production of the rat MyoD protein in these cells. The 6.5-kb genomic fragment contains the complete coding region of MyoD, distributed over three exons, plus 2.3 kb of 5'-noncoding sequence and 1.4 kb of 3'-noncoding sequence. Based on RNase protection assays, the major transcription start point of MyoD is located 210 nt 5' to a methionine start codon and 26 nt 3' to a TAAATA motif which bears similarity to a consensus recognition sequence (TATA) utilized by eukaryotic RNA polymerase II transcription complexes. The high degree of identity between the amino acid sequence of rat MyoD and the MyoD proteins isolated from other vertebrates indicates that this muscle regulatory protein has been evolutionarily conserved.


Everolimus- versus sirolimus-eluting stents for the treatment of unprotected left main coronary artery stenosis (results from the EXCELLENT registry).
Data concerning the results of 2nd generation DES in the treatment of unprotected left main coronary artery (ULMCA) stenosis are limited. The aim of this study was to evaluate the efficacy and safety of stenting with everolimus- (EES) with sirolimus-eluting stent (SES) for the treatment of ULMCA stenosis in the "real world" setting. In this multi-center all-comer registry, a total of 275 patients with ULMCA stenosis were analyzed; 160 receiving EES and 115 receiving SES. The primary endpoint was major adverse cardiac events (MACE), defined as death, myocardial infarction, and ischemia-driven target vessel revascularization at 1 year. Baseline characteristics were similar between the two stent groups. At 1 year, the rate of MACE was comparable between the two groups (7.5% for EES vs. 13.9% for SES, HR: 0.55 [0.26-1.17], p = 0.117). However, after multivariable or propensity score adjustment, the risk of MACE was significantly lower for EES compared with that for SES (multivariable adjusted HR: 0.42 [0.19-0.92], p = 0.030; propensity score-adjusted HR: 0.43 [0.20-0.95], p = 0.037). These results were mainly driven from the numerically lower rate of repeat revascularization in the EES group (2.5% for EES vs. 7.0% for SES, p = 0.096). As for hard endpoint (death or myocardial infarction) and stent thrombosis, no differences were found between the 2 groups. In a large cohort of patients receiving ULMCA stenting, the MACE rate was numerically lower in the EES compared with that in the SES (statistically significant only after adjustment), which was mainly driven by significantly lower rates of repeat revascularization.


Investigation of hindered phenol antioxidant effects on the aging performance of cross-linked LDPE in the presence of copper.
In this study, LDPE materials with different kinds of antioxidants were prepared by melt-blending method. To reveal the aging mechanism and the anti-oxidation efficiency of LDPE in the presence of copper, series of characterizations including tensile testing, Fourier transform infrared spectra (FTIR), differential scanning calorimetry (DSC), scanning electronic microscopy (SEM) and computation simulation were performed. The experimental results indicated that the aging process significantly decreased the tensile strength and elongation of those aged samples except 1024, which retarded the aging degradation of LDPE at the same condition. These results were further confirmed by the FTIR analysis with the carbonyl index values. Additionally, the melting peaks of DSC plots became broader and shifted to the lower temperatures during the aging process for S-0, S-3114 and S-1010, whereas no obvious changes were observed for S-1024. Importantly, according to the results obtained from computation simulation, a strong metal-ligand interaction between hydrazide group and copper ions was formed to prevent the further oxidation, which accounted for the excellent anti-oxidation behavior of 1024 for LDPE in the presence of copper.


Vessel-based photographic assessment of beach litter in remote coasts. A wide scale application in Saronikos Gulf, Greece.
The abundance of marine debris was quantified for a total of sixty-two inaccessible beaches in the western Saronikos Gulf, Greece. High resolution images were obtained through vessel-based photography survey, merged into seamless photomosaics, and manually processed to quantify beach litter abundance. A sample of four selected beaches were subjected to detailed photography followed by beach macro-litter (≥ 2.5 cm) in-situ sampling surveys over a period of one year, to calibrate and validate the proposed method. Regression analysis between photographic and in-situ data showed a significant correlation, hence providing a highly accurate regression model to assess the real number of beach litter stranded on the rest of the investigated beaches, exhibiting clear correlations to the hydrodynamic status of the area and, provide an indication of the main litter sources. The proposed method is an easily applicable and useful tool for fast and low-cost macro-litter monitoring in extended, remote coastlines, when only photographic data are available.


An overview of immunoinformatics approaches and databases linking T cell receptor repertoires to their antigen specificity.
Recent advances in molecular and bioinformatic methods have greatly improved our ability to study the formation of an adaptive immune response towards foreign pathogens, self-antigens, and cancer neoantigens. T cell receptors (TCR) are the key players in this process that recognize peptides presented by major histocompatibility complex (MHC). Owing to the huge diversity of both TCR sequence variants and peptides they recognize, accumulation and complex analysis of large amounts of TCR-antigen specificity data is required for understanding the structure and features of adaptive immune responses towards pathogens, vaccines, cancer, as well as autoimmune responses. In the present review, we summarize recent efforts on gathering and interpreting TCR-antigen specificity data and outline the critical role of tighter integration with other immunoinformatics data sources that include epitope MHC restriction, TCR repertoire structure models, and TCR/peptide/MHC structural data. We suggest that such integration can lead to the ability to accurately annotate individual TCR repertoires, efficiently estimate epitope and neoantigen immunogenicity, and ultimately, in silico identify TCRs specific to yet unstudied antigens and predict self-peptides related to autoimmunity.


Hepatic venular stenosis after orthotopic liver transplantation.
Fibrous stenosis of hepatic venules and other features of venous outflow obstruction, including zone 3 congestion and hemorrhage, are sometimes seen after orthotopic liver transplantation. similar changes associated with endothelial damage have recently been ascribed to azathioprine toxicity and may be forerunners of chronic rejection. Other potential causative agents such as viral hepatitis have yet to be considered. We reviewed 49 liver biopsy specimens from 21 consecutive patients after orthotopic liver transplantation, in whom full data including further follow-up biopsy samples were available. Hepatic venous stenosis was identified in seven patients who had received azathioprine and two additional patients in whom this change could not be ascribed to azathioprine. Stenosis was always associated with zone 3 hemorrhage and congestion and was first noted between 5 and 30 days after transplantation in all but two cases; in these two patients they were first noted after 72 and 133 days. Cellular rejection, including endotheliitis involving terminal hepatic venules, was found in five of the seven patients who had received azathioprine. Chronic (ductopenic) rejection was not seen during a follow-up period of between 97 and 540 days. In three of the nine patients with hepatic venular stenosis, zone 3 changes persisted, and in two of these azathioprine could not be held responsible. Of the 12 patients without hepatic venular stenosis, 10 had received azathioprine. Two of these 12 patients had peliosis-like foci but no other vascular abnormalities. Both also had moderate cellular rejection. Hepatic venular stenosis was found in 43% of patients after liver transplantation; this was usually associated with azathioprine administration and concomitant cellular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)


A biaxial tensional model for early vertebrate morphogenesis.
We propose a simple biaxial tensional model which is able to reproduce at a qualitative level several aspects of early stages of vertebrate morphogenesis. The model is based on subsequent excitable contractions of an orthoradial and periclinal (radial) set of contracting lines, which generate first the basic embryonic pattern (a motile tube), and second the lateral orifices such as ears, eyes, mouth, gills, etc. An important aspect of the model is the self-arresting character of the process, akin to wound healing. At later stages, the biaxial lines may also work in extension, and this generates a developmental feedback which is quadratic with respect to curvature.


Improved stenosis outcome in stroke-free sickle cell anemia children after transplantation compared to chronic transfusion.
We report here the 3-year stenosis outcome in 60 stroke-free children with sickle cell anaemia (SCA) and an abnormal transcranial Doppler history, enrolled in the DREPAGREFFE trial, which compared stem cell transplantation (SCT) with standard-care (chronic transfusion for 1-year minimum). Twenty-eight patients with matched sibling donors were transplanted, while 32 remained on standard-care. Stenosis scores were calculated after performing cerebral/cervical 3D time-of-flight magnetic resonance angiography. Fourteen patients had stenosis at enrollment, but only five SCT versus 10 standard-care patients still had stenosis at 3 years. Stenosis scores remained stable on standard-care, but significantly improved after SCT (P = 0·006). No patient developed stenosis after SCT, while two on standard-care did, indicating better stenosis prevention and improved outcome after SCT.


Angelol-type coumarins from Angelica pubescence F. biserrata and their inhibitory effect on platelet aggregation.
An ethyl acetate-soluble root extract of Angelica pubescence f. biserrata afforded two new angelol-type coumarins, angelols K and L, in addition to angelols B, C, D and G. Some of the compounds were tested on human platelet aggregation and showed significant activity.


A potent noncompetitive angiotensin II antagonist induces only competitive inhibition of angiotensin III responses.
Sarcosyl1, cysteinyl-S-methyl8-angiotensin II [(Sar1, Cys-Me8) Ang II] was examined for antagonism of angiotensin (Ang) responses in isolated rabbit atrial and aortic tissues. (Sar1, Cys-Me8) Ang II competitively antagonized Ang II responses in aorta at a concentration of 5 nM. Concentrations of the antagonist greater than 5 nM resulted in noncompetitive antagonism of Ang II responses in cardiac and vascular smooth muscle. These actions of (Sar1, Cys-Me8) Ang II were significant (p less than 0.01) and depressed maximal responses to Ang II as much as 80%. In contrast, (Sar1, Cys-Me8) Ang II at concentrations up to 10(-6) M did not significantly alter maximal responses to Ang III at any concentration in any of the experimental preparations. The antagonist did competitively inhibit Ang III concentration-dependent responses in the aorta and, to a lesser extent, in isolated atria. Saralasin was a competitive antagonist of Ang II and III in atrial and aortic preparations. Norepinephrine responses in cardiac and vascular tissues were not altered by these antagonists. The different types of antagonism exhibited by (Sar1, Cys-Me8) Ang II against Ang II and III in identical preparations demonstrate the potential for the existence of separate Ang receptors.


Transcardiac 5-hydroxytryptamine release and impaired coronary endothelial function in patients with vasospastic angina.
1. The present study was designed to test the hypotheses whether platelet degranulation across the coronary bed is detectable during non-ischaemic periods in patients with vasospastic angina (VSA) and whether the exogenous nitric oxide (NO) donor nitroglycerin (GTN) is able to modify platelet degranulation, reflecting an impaired endothelial production of NO. 2. We studied 13 patients with VSA and 10 controls. The time course of coronary sinus (CS) plasma 5-hydroxytryptamine (5-HT) levels was evaluated every 4 h before and after intravenous infusion of GTN over a period of 40 h. Coronary sinus plasma 5-HT levels were significantly higher at any measured time point in patients with VSA compared with control and were significantly decreased in patients with VSA following treatment with GTN, but not in controls. Femoral artery plasma 5-HT levels remained almost constant throughout the study. The ratio of CS:aorta 6-keto-prostaglandin F1 alpha was significantly and inversely correlated with the transcardiac plasma 5-HT difference only in patients with VSA (r = -0.68; P < 0.02; n = 13). 3. The time course of CS 5-HT levels confirmed significant platelet degranulation across the coronary bed supplied by the spasming artery in patients with VSA and this was modified by GTN. The present data suggest that platelet degranulation occurs during non-ischaemic periods in patients with VSA and that prostacyclin biosynthesis may be a compensatory response to an impaired endothelial release of NO, limiting the degree of the effects of platelet degranulation.


Monitoring acute inflammatory processes in mouse muscle by MR imaging and spectroscopy: a comparison with pathological results.
We have studied an animal model of acute local inflammation in muscle induced by Aspergillus fumigatus by using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We have compared our data to those found using histopathology and segmentation maps obtained by the mathematical processing of three-dimensional T2-weighted MRI data via a neural network. The MRI patterns agreed satisfactorily with the clinical and biological evidence of the phases of acute local infection and its evolution towards chronicity. The MRS results show a statistically significant increase in inorganic phosphate and a significant decrease in phosphocreatine levels in the inflamed region. Image segmentation made with a self-organizing, neural-network map yielded a set of ordered representatives that remained constant for all animals during the inflammatory process, allowing a non-invasive, three-dimensional identification and quantification of the inflamed infected regions by MRI.


Transformed cells have lost control of ribosome number through their growth cycle.
Previous studies on the synthesis and function of the protein synthetic machinery through the growth cycle of normal cultured hamster embryo fibroblasts (HA) were extended here to a series of four different clonal lines of polyoma virus-transformed HA cells. Under our culture conditions, these transformed cells could enter a stationary phase characterized by no mitotic cells, very low rates of DNA synthesis, and arrest in a post-mitotic pre-DNA synthetic state. Cellular viability was initially high in stationary phase but, unlike normal cells, transformed cells slowly lost viability. The rate of protein synthesis in the stationary phase of the transformed cells fell to 25-30% of the exponential rate. Though this reduction was similar to that seen in normal cells, it was accomplished by different means. The specific reduction in the ribosome complement per cell to values below that of any cycling cell seen in normal cells, was not seen in any of the transformed lines. This observation, which implies a loss of normal control of ribisome synthesis through the growth cycle after transformation, was confirmed in normal Chinese hamster embryo fibroblasts and transformed CHO cell lines. Normal control of ribosome synthesis was restored in L-73 and LR-73, growth control revertants of one of the transformed CHO lines. The transformed lines reduced their protein synthetic rates in stationary phase either by a greater reduction in the proportion of functioning ribosomes than that seen in normal cells or by a decrease in the elongation rate of functioning ribosomes; the latter effect was not seen in the normal cells. A model for growth control of normal cells and its derangement in transformed cells is presented.


The use of telemedicine in cardiogenetics clinical practice during the COVID-19 pandemic.
The COVID-19 pandemic has necessitated the rapid and widespread adoption of novel mechanisms of service delivery, including the use of telemedicine. The aim of this study was to examine the impact of COVID-19 on cardiogenetics practices. We retrospectively analyzed the clinical characteristics of patients who were seen for cardiogenetics visits pre-pandemic (1 April-23 December 2019) and during the pandemic (1 April-23 December 2020) at Columbia University Irving Medical Center. Six percent (n = 6) of visits in 2019 were remote telemedicine encounters, whereas 80% (n = 106) of visits in 2020 were telemedicine encounters. In 2019, only 18% (n = 19) of the patients seen for genetic counseling were family members of probands; this percentage increased to 34% in 2020 (n = 45; p = .01). In 2020, the geographic reach of genetic counseling also extended far beyond New York State, reaching a total of 11 states as well as one patient in Puerto Rico. Genetic testing results were similar in 2019 and 2020. Despite the health-care delivery barriers created by the COVID-19 pandemic, the use of telemedicine allowed us to expand the reach of cardiovascular genetic counseling and testing.


Behavioral rehabilitation of the eye closure reflex in senescent rats using a real-time biosignal acquisition system.
In this paper the replacement of a lost learning function of rats through a computer-based real-time recording and feedback system is shown. In an experiment two recording electrodes and one stimulation electrode were implanted in an anesthetized rat. During a classical-conditioning paradigm, which includes tone and airpuff stimulation, biosignals were recorded and the stimulation events detected. A computational model of the cerebellum acquired the association between the stimuli and gave feedback to the brain of the rat using deep brain stimulation in order to close the eyelid of the rat. The study shows that replacement of a lost brain function using a direct bidirectional interface to the brain is realizable and can inspire future research for brain rehabilitation.


Social vulnerability indicators in pandemics focusing on COVID-19: A systematic literature review.
Social factors can affect the vulnerability of disaster-prone communities. This review aimed to identify and categorize social vulnerability indicators in the COVID-19 pandemic. This systematic review was conducted in February 2021. Bibliographies, citation databases, and other available records were investigated based on the aim of the study. The Joanna Briggs Institute (JBI) critical appraisal tools were applied for assessing the included articles retrieved through the comprehensive and systematic literature search. Descriptive and thematic analyses were done to extract the indicators affecting social vulnerability in the COVID-19 pandemic. Thirty-one eligible articles were included and 85 indicators of social vulnerability were extracted. The indicators were categorized in seven main categories, including; Household, community composition; Race, minority status and language; Socioeconomic status; Community health status; Public health infra-structures; Education; Information, technology and communication. Regions with higher social vulnerability experienced greater mortality rates during the COVID-19 pandemic. Additional research is needed to measure the social vulnerability index in pandemics to prioritize distribution of scarce resources and ensure effectiveness and equity for all regions of countries.


Perceived and Preferred Social Support in Patients Experiencing Weight Regain After Bariatric Surgery-a Qualitative Study.
While bariatric surgery generally shows successful weight loss outcomes in patients with obesity, weight regain exists. The aim of this qualitative study was to improve understanding of how patients with substantial weight regain after bariatric surgery experienced the support from family, friends, and healthcare providers, and what kind of support they had preferred. Qualitative data were collected from semi-structured interviews with 16 participants. Mean weight regain from surgery to interview was 36%. The transcribed interviews were analyzed with thematic analysis. Two main themes and seven sub-themes were formulated. The theme, A lonely struggle, illustrates patients' feelings of abandonment and struggle during weight regain due to lack of support or unfavorable treatment. Participants commonly blamed themselves for re-gaining weight, and shame made them reluctant to engage in social activities or seek medical care. The theme, Others as sources of compassion and control, covers what support they desired, as well as had perceived to be helpful. Exercising or eating healthy with others was appreciated and felt supportive. Pro-active healthcare support and access to dietitians, physiotherapists, and psychological support were desired. To optimize the effect of bariatric surgery, support may need to be individualized and lifelong. Since shame and self-blame in patients with weight regain may hinder seeking professional help, care providers may need to initiate follow-up visits. Empathetic and non-judgmental support, access to multidisciplinary healthcare team, as well as peer-support groups may be beneficial to counteract weight regain post-bariatric surgery.


Impact of separate concentrations of polyethylene microplastics on the ability of pollutants removal during the operation of constructed wetland-microbial fuel cell.
Microplastics (MPs) in water pose a great threat to the ecological environment, but the impact of MPs on constructed wetland microbial fuel cells (CW-MFCs) has not been studied, so in order to fill the research gap and enrich the research in the field of microplastics, a 360-day experiment was designed to determine the operating status of CW-MFCs at different concentrations (0, 10, 100 and 1000 μg/L) polyethylene microplastics (PE-MPs) at different times, focusing on the changes of the CW-MFCs' ability to handle pollutants, power production performance and microbial composition. The results showed that with the accumulation of PE-MPs, the removal effect of COD and TP did not change significantly, and that the removal rate was maintained at around 90% and 77.9% respectively, within 120 d of operation. What's more, the denitrification efficiency increased (from 4.1% to 19.6%), but with the passage of time, it decreased significantly (from 7.16% to 31.9%) at the end of the experiment, while oxygen mass transfer rate was significantly increased. Further analysis showed that the accumulation of PE-MPs did not affect the current power density significantly with the changes of time and concentration, but the accumulation of PE-MPs would inhibit the exogenous electrical biofilm and increase the internal resistance, thereby affecting the electrochemical performance of the system. In addition, the results of microbial PCA showed that the composition and the activity of the microorganisms were changed under the action of PE-MPs, that the microbial community in CW-MFC showed a dose effect on the input of PE-MPs, and that the relative abundance of nitrifying bacteria with time was significantly affected by PE-MPs concentration. The relative abundance of denitrifying bacteria decreased over time, but PE-MPs promoted the reproduction of denitrifying bacteria, which was consistent with the changes in nitrification and denitrification rates. The removal modes of EP-MPs by CW-MFC include the adsorption and the electrochemical degradation, with two isothermal adsorption models of Langmuir and Freundlich being constructed in the experiment, and the electrochemical degradation process of EP-MPs being simulated. In summary, the results show that the accumulation of PE-MPs can induce a series of changes in substrate, microbial species and activity of CW-MFCs, which in turn affects the pollutant removal efficiency and power generation performance during its operation.


The pathogenicity of four avian influenza viruses for fowls, turkeys and ducks.
Groups of 10 two-week-old chicks, turkey poults and ducklings were each infected by the intranasal route with one of four avian influenza viruses: a/fowl/Germany/34 (Hav 1N))--Rostock, A/FPV/Dutch/27 (Hav 1 Neq 1)--Dutch, A/fowl/Victoria/75 (Hav 1 Neq 1)--Australian, and A/parrot/Ulster/73 (Hav 1 N1)--Ulster. Eight hours after infection 10 birds of the same age and species were placed in contact with each group and allowed to mix. The clinical signs of disease and onset of sickness and death were recorded. Ulster virus was completely avirulent for all birds. Rostock, Dutch and Australian viruses were virulent for fowls and turkeys causing death in all birds with the exception of 3/10 in contact fowls from the Rostock virus group and 2/10 in contact fowls from the Australian virus group. Only Rostock virus caused sicked sickness or death in ducks, 9/10 intranasally infected and 6/7 in contact birds showed clinical signs and 2/10 intranasally infected and 3/7 in contact ducks died. Intranasal and in contact pathogenicity indices were calculated for each virus in each bird species and indicated quantitatively the differences in virulence of the four virus strains. Virus isolation and immune response studies indicated that surviving in contact fowls in the Rostock virus group had never been infected but that surviving Australian virus in contact fowls had recovered from infection. Infection was not established in Ulster virus in contact fowls and Australian virus intranasally infected and in contact ducks. The birds in all other groups showed positive virus isolations and a high incidence of positive immune response. The last virus isolation was made at 22 days after intranasal infection of ducks with Ulster virus.


Prefabrication decisions of the construction supply chain under government subsidies.
Prefabrication has been generating increasing interest as a cleaner production strategy to promote sustainable development. Alongside this trend, various subsidies have been set to improve prefabrication levels. This paper evaluates the prefabrication levels of buildings through the assembly rate. A series of models are established to investigate the optimal assembly rate under various government subsidies. The optimal assembly rate and subsidy revenue-sharing coefficient are analyzed in both decentralized and centralized scenarios. By comparing the optimal decisions in these two scenarios, a transfer payment contract is proposed that enables the overall coordination of the prefabricated construction supply chain (PCSC). The results show that the optimal assembly rate in the centralized scenario is higher than that in the decentralized one. When the revenue-sharing coefficient is 100%, the subsidy revenue-sharing contract can coordinate the PCSC system and realize the Pareto improvement. When certain conditions are satisfied in the transfer payment contract, business profits can achieve Pareto optimality. This research provides a reference for construction enterprises making decisions to promote the development of PCSC.


Integrated transcriptomic and proteomic analyses of grass carp intestines after vaccination with a double-targeted DNA vaccine of Vibrio mimicus.
Intestinal mucosal immunity plays a vital role against Vibrio mimicus infection because it is an enteric pathogen causing serious vibriosis in fish. In the previous studies, we developed an oral double-targeted DNA vaccine of V. mimicus and demonstrated that the vaccine could elicit significantly higher intestinal mucosal immune response than did naked DNA vaccine. But, little is known underlying regulatory molecular mechanisms of the enhanced intestinal mucosal immunity. Here the transcriptome and proteome in the intestines of the grass carps immunized or not with the double-targeted DNA vaccine were investigated by using RNA-seq and iTRAQ-coupled LC-MS/MS. Compared with the control group, a total of 5339 differentially expressed genes (DEGs) and 1173 differentially expressed proteins (DEPs) were identified in the immunized fish intestines. Subsequently, the integrated analysis between transcriptome and proteome data revealed that 250 DEPs were matched with the corresponding DEGs (named associated DEPs/DEGs) at both transcriptome and proteome levels. Fifty of all the associated DEPs/DEGs were immune-related and mainly enriched in phagosome, antigen-processing and presentation, complement and coagulation cascades, NLRs and MAPK signaling pathways via Gene Ontology and KEGG pathway analyses, which suggested the coordination of the five activated pathways was essential to the enhanced intestinal mucosal immune response in the immunized fish. The protein-protein interaction analysis showed that 60 of the 63 immune-related DEPs to form an integrated network. Additionally, randomly selected DEGs and DEPs were respectively validated by quantitative real-time RT-PCR and multiple reaction monitoring (MRM) assay, indicating that the both RNA-Seq and iTRAQ results in the study were reliable. Overall, our comprehensive transcriptome and proteome data provide some key genes and their protein products for further research on the regulatory molecular mechanisms underlying the enhanced intestinal mucosal immunity.


Population abundance of two-patch competitive systems with asymmetric dispersal.
This paper considers two-species competitive systems with two patches, in which one of the species can move between the patches. One patch is a source where each species can persist alone, but the other is a sink where the mobile species cannot survive. Based on rigorous analysis on the model, we show global stability of equilibria and bi-stability in the first octant Int[Formula: see text]. Then total population abundance of each species is explicitly expressed as a function of dispersal rates, and the function of the mobile species displays a distorted surface, which extends previous theory. A novel prediction of this work is that appropriate dispersal could make each competitor approach total population abundance larger than if non-dispersing, while the dispersal could reverse the competitive results in the absence of dispersal and promote coexistence of competitors. It is also shown that intermediate dispersal is favorable, large or small one is not good, while extremely large or small dispersal will result in extinction of species. These results are important in ecological conservation and management.


Routine donor red cell antibody screening: Considering the alternate strategy.
Australian Red Cross Lifeblood (Lifeblood) performs red blood cell (RBC) antibody screening on every whole blood donation. An alternate strategy has been proposed whereby an antibody screen is performed on the first donation and only repeated following pregnancy, transfusion or a significant break between donations (>2 years). We assess the blood safety risks associated with removing antibody screening for every whole blood donation. A retrospective desktop analysis included all whole blood donations collected by Lifeblood between 01 May 2018 and 30 April 2019 to quantify the antibodies that would have been undetected with the alternate strategy. The strategy was further assessed using the Alliance of Blood Operators Risk-Based Decision-Making framework. One hundred and seventy-one routine donors had antibodies for the first time, but reported no sensitizing event since their last donation. Forty-seven of these had antibodies of a clinically significant specificity and titre that have the potential to cause a haemolytic transfusion reaction (HTR). The calculated risk of undetected antibodies being transfused to an incompatible recipient is 1 in 82,200. The estimated risk of HTRs with the alternate strategy results in an increased risk. While the alternate strategy is identified as the most cost-effective option within the Australian setting, this additional residual risk was not deemed to be acceptable. Blood services would need to determine whether the increase in residual risk stemming from implementation of such a strategy is tolerable.


Comparison of two types of alginate microcapsules on stability and biocompatibility in vitro and in vivo.
Transplantation of encapsulated living cells is a promising approach for the treatment of a wide variety of diseases, especially diabetes. Range-scale application of the technique, however, is hampered by insufficient stability of the capsules. It is difficult to find the optimal membrane to meet all the properties required for cell transplantation. To overcome these difficulties, it is necessary to compare characteristics such as mechanical strength, cell proliferation and biocompatibility of different membranes. We prepared Ca-alginate-poly-L-lysine-alginate (APA) and Ba-alginate-poly-L-lysine-alginate (BPA) microcapsules using the electrostatic droplet method. The integrity of the microcapsules was measured by suspending them in a saline buffer and shaking at 150 rpm for 48 h. The microcapsules were cultured in simulated body fluid to analyze the osmotic pressure stability and implanted in the leg muscle pouch of SD rats to test in vivo transplantation stability. The microcapsules were implanted in the intraperitoneal cavity; then the biocompatibility of microcapsules was identified through analyzing fibrosis formation of microcapsules. The proliferation of cells (Cos-7 and HL-60) cultured in the microcapsules was measured by MTT assay. After 48 h shaking at 150 rpm, the percentages of intact microcapsules of BPA and APA microcapsules were 98.5 +/- 0.248% and 95.7 +/- 0.221% (p < 0.05), respectively. The intact percentages of APA and BPA microcapsules were 96.9% and 97.7%, respectively, after being soaked in SBF at 37 degrees C for 15 days. The empty APA and BPA microcapsules were not adhered to the muscle and there was light cellular overgrowth. There is no difference on biocompatibility in implantation into peritoneal cavities. After the cells were cultured in microcapsules, A(490 nm) of the 8th week was significantly higher than that of 1 day, and the 4th week was at the peak of the cell proliferation curve. After culture for 2 to 6 weeks, spheroids started to develop gradually within the beads. The mechanical strength of BPA microcapsules was higher than that of APA microcapsules. However, there was no difference between the two kinds of capsules in biocompatibility. Microencapsulation did not affect cell proliferation or increase the quantity of cells. In conclusion, BPA microcapsules were more suitable for transplantation in vivo.


Cardiac magnetic resonance imaging derived quantification of myocardial ischemia and scar improves risk stratification and patient management in stable coronary artery disease.
Quantification of myocardial ischemia and necrosis might ameliorate prognostic models and lead to improved patient management. However, no standardized consensus on how to assess and quantify these parameters has been established. The aim of this study was to quantify these variables by cardiac magnetic resonance imaging (CMR) and to establish possible incremental implications in cardiovascular risk prediction. This study is a retrospective analysis of patients with known or suspected coronary artery disease (CAD) referred for adenosine perfusion CMR was performed. Myocardial ischemia and necrosis were assessed and quantified using an algorithm based on standard first-pass perfusion imaging and late gadolinium enhancement (LGE). The combined primary endpoint was defined as cardiac death, non-fatal myocardial infarction, and stroke. 845 consecutive patients were enrolled into the study. During the median follow-up of 3.64 [1.03; 10.46] years, 61 primary endpoints occurred. Patients with primary endpoint showed larger extent of ischemia (10.7 ± 12.25% vs. 3.73 ± 8.29%, p < 0.0001) and LGE (21.09 ± 15.11% vs. 17.73 ± 10.72%, p < 0.0001). A risk prediction model containing the extent of ischemia and LGE proved to be superior in comparison to all other models (χ² increase: from 39.678 to 56.676, integrated discrimination index: 0.3851, p = 0.0033, net reclassification index: 0.11516, p = 0.0071). The ben-eficial effect of revascularization tended to be higher in patients with greater extents of ischemia, though statistical significance was not reached. Quantification of myocardial ischemia and LGE was shown to significantly improve existing risk prediction models and might thus lead to an improvement in patient management.


Structure-activity relationships of the prototypical TRPM8 agonist icilin.
A series of structural analogues of the TRPM8 agonist icilin was prepared. The compounds were examined for their ability to exert agonist or antagonist effects in HEK-293 cells expressing the TRPM8 receptor. Most structural modifications of the icilin structure largely met with diminished TRPM8 agonist activity. Cinnamamide 'open-chain' analogs of icilin, however, demonstrated significant antagonistic actions at the TRPM8 receptor. Optimal potency (IC50=73 nM) was observed in the 3-iodo derivative 18l.


Randomized controlled trial of a ragweed allergy immunotherapy tablet in North American and European adults.
In North America and Europe, millions of patients experience symptoms of allergic rhinitis with or without conjunctivitis (AR/C) on exposure to ragweed pollen. The disease burden can be significant, with most patients relying on symptomatic medications without disease-modifying potential. However, novel sublingual immunomodulatory treatment options may potentially play an important role if efficacy and side effect profiles allow the convenience of self-administration. This study evaluated an allergy immunotherapy tablet (AIT; SCH 39641/MK-3641) for treatment of ragweed-induced AR/C in the first large randomized, double-blind multinational trial of this therapeutic modality for ragweed allergy. Adults (n = 784) with short ragweed-induced AR/C were randomly assigned to approximately 52 weeks of daily self-administered ragweed AIT of 1.5, 6, or 12 units of Ambrosia artemisiifolia major allergen 1 (Amb a 1-U) or placebo. Subjects could use as-needed allergy rescue medication. Symptoms and medications were recorded daily. The primary efficacy end point was total combined daily symptom/medication score (TCS) during peak ragweed season. Safety was monitored through adverse event diaries maintained through study duration. During peak ragweed season, ragweed AIT of 1.5, 6, and 12 Amb a 1-U reduced TCS by 9% (-0.76; P = .22), 19% (-1.58; P = .01), and 24% (-2.04; P = .002) compared with placebo. During the entire season, ragweed AIT of 1.5, 6, and 12 Amb a 1-U reduced TCS by 12% (-0.88; P = .09), 18% (-1.28; P = .01), and 27% (-1.92; P < .001) compared with placebo. Treatment was well tolerated; no systemic allergic reactions occurred. In this trial, ragweed AIT of 12 Amb a 1-U was effective and tolerable with a safety profile that permitted daily self-administration of ragweed allergen immunotherapy.


The occurrence of human wart-virus antibodies in dogs, pigs and cattle.
Using the immunodiffusion method, antibodies against human wart-virus were detected in dog, pig and cattle sera but not in horse and reindeer sera. Antibodies were found in 25 percent (28/114) of the dog sera, the prevalence of antibodies being fairly similar to that in children of the same age. By electron microscopy the antibodies in dog sera were shown to attach to and precipitate the human wart-virus particles, and in immunodiffusion the precipitation lines of human and dog sera were shown to be identical. Of the cattle sera studied, 10 percent (10/97) and of the pig sera 13 percent (5/40) gave a faint precipitation line, having identity with that given by the human sera, against human wart-virus. Conversely 18 percent (9/50) of adult human sera contained precipitating antibodies against a bovine papilloma antigen, probably bovine papilloma virus.


Indoor solid fuel use and renal function among middle-aged and older adults: A national study in rural China.
Solid fuel use is the main source of indoor air pollution, especially in rural areas of developing countries. Nevertheless, the evidence linking indoor solid fuel use and renal function is very limited. Therefore, we investigated the association between indoor solid fuel use and renal function among middle-aged and older adults in rural China. Cystatin C (CysC) concentration of each participant was used to calculate the estimated glomerular filtration rate (eGFR). We used the baseline data to investigate the associations between solid fuel use for cooking and heating and eGFR through a linear-mixed effects model. Then, we applied the generalized linear-mixed effects model with binary distribution to examine the relationship between renal function decline and cooking fuel switching from 2011 to 2015. A total of 4959 participants were included at baseline, and 3536 participants were included in the follow-up analysis. Compared to participants who used clean fuel for both cooking and heating, the eGFR was significantly lower among participants who cooked with solid fuel and heated with clean fuel (β: -2.81; 95% CI: -5.53, -0.09). In the follow-up analysis, the risks of renal function decline for participants using solid fuel for cooking were significantly higher in males (OR: 2.74; 95% CI: 1.68, 4.49), smokers (OR: 5.70; 95% CI: 2.82, 11.55), and drinkers (OR: 7.11; 95% CI: 3.15, 16.02) compared to females, non-smokers, and non-drinkers. Moreover, 45-65 years aged participants (OR: 0.54; 95% CI: 0.33, 0.89) and non-drinkers (OR: 0.61; 95% CI: 0.41, 0.92) who switched from solid to clean cooking fuel had a lower risk of renal function decline. In conclusion, our findings show that household solid fuel use is likely to be an important risk factor for renal function decline in rural China. And switching to cleaner fuel may provide significant public health benefits.


Aqueous extract of Lespedeza cuneata improves male menopause by increase of nitric oxide and dihydrotestosterone.
This study aimed to evaluate the effect of aqueous extract of Lespedeza cuneata (ALC) on men menopause induced erectile dysfunction (ED) and testosterone deficiency syndrome (TDS) in vitro and in vivo. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) have been fundamental factors of ED, and free testosterone such as dihydrotestosterone (DHT) has a crucial role in mitigation of TDS. ALC increased the production of NO in a dose-dependent manner in vitro and in vivo. The level of neuronal nitric oxide synthase and cGMP was increased in the ALC group. The level of DHT and 17-beta hydroxysteroid dehydrogenases (17β-HSD) was also increased in the ALC group. There was no significant change of hepatotoxicity, renal toxicity, lipid metabolism, and glucose. These results suggest that ALC enhanced NO, cGMP and free testosterone which could be developed as a health supplement for improving male menopause.


Surgical practice of UK gynaecological oncologists in the treatment of primary advanced epithelial ovarian cancer (PAEOC): a questionnaire survey.
To assess the routine surgical practices of consultant gynaecological oncologists (CGOs) in the United Kingdom in their management of primary advanced (FIGO stages III and IV) epithelial ovarian cancer (PAEOC). The same anonymised questionnaire was sent twice to all consultant gynaecological oncologists (CGOs) working in the UK. The questions enquired about surgical practice of the previous calendar year and the respondents were asked to describe their usual or typical management of patients with PAEOC. 45 of 85 CGOs responded (53%). The mean number of ovarian cancer cases operated on by an individual surgeon was 47 (range 6-100). 6% of the surgeons never perform pelvic lymphadenectomy, and 22% of the surgeons never perform para-aortic lymphadenectomy in the primary surgery (PS) group, compared to 8% and 30% in the neoadjuvant chemotherapy (NAC) group. In the PS group 17% of the respondents perform pelvic lymphadenectomy routinely (80% or more of patients) compared to 11% of the respondents in the NAC group. The rates of bowel surgery and surgery for upper abdominal disease were highly variable. The average operating time per case was less than 3h in 78% of the respondents. The mean operating times, caseload, and types of procedure undertaken in the management of advanced ovarian cancer provide compelling evidence that in many UK cancer centres the surgical goal has not been complete cytoreduction. These data have implications for the centralisation of surgical services, subspecialty training, and the lower survival of UK patients compared to other comparable countries.


Brown seaweed: Fucus vesiculosus as a feedstock for agriculture and environment protection.
A comprehensive approach to the management of brown seaweed-Fucus vesiculosus was presented. An algal extract, which served as a biostimulant of plant growth was produced using ultrasound-assisted extraction (UAE). The concentration of the extract (20, 40, 60, 80, 100%), which had the greatest influence on biometric parameters of radish, was determined in germination tests. The seaweed itself as well as the produced post-extraction residue were used in doses of 2 and 4 g/kg as soil additives, stimulating plant growth in the initial phase. Pot tests for sorghum carried out under optimal conditions (20% extract and 2 g/kg of soil additive) had a positive effect on the plant weight, length and the content of chlorophyll in comparison with the control group treated with distilled water. Additionally, preliminary studies on the bioremediation of soil contaminated with Zn(II) ions with the use of both soil additives were performed. It was shown that the immobilization of Zn(II) ions in the soil by the applied additives reduced the bioaccumulation of zinc in the aerial part of plants as compared with the group cultivated in the contaminated soil but without additive. Accordingly, by producing plant biostimulants by UAE it was also possible to successfully manage the post-extraction residue following the concept of a bio-based economy.


Influence of intestinal microflora on murine bone marrow and spleen macrophage precursors.
To investigate the adjuvant effect of intestinal flora on macrophage-colony-stimulating factor-responsive macrophage progenitors from spleen and bone marrow, we compared progenitor numbers and phenotypic characteristics of in vitro matured macrophages in germ-free and flora-associated mice (conventional, Escherichia coli-monoassociated and conventionalized mice). The data obtained show that the flora affected differentially bone marrow and spleen progenitors. It increased the numbers of progenitors in the spleen but not in the bone marrow. It did not modify the expression of F4/80, Mac-1 and major histocompatibility complex (MHC) class II on bone-marrow-derived macrophages (BMDM), while it clearly up-regulated MHC class II expression on spleen-derived macrophages (SDM). This effect was more pronounced in flora-associated ex germ-free mice than in conventional mice and it was greatly enhanced in the absence of M-CSF. In vitro stimulation by lipopolysaccharide had no effect on marker expression of BMDM, while it decreased F4/80 and enhanced MHC class II molecules on SDM from germ-free and flora-associated mice. However, the expression of MHC class II remained lower in germ-free mice. Enhancement of MHC class II molecule expression on SDM may contribute to the protective role of flora, because successful immune responses are dependent on the expression of these molecules.


Draft Genome Sequence of Delftia tsuruhatensis Strain 45.2.2, Colonizer of Zebrafish, Danio rerio, Skin Mucus.
Delftia tsuruhatensis strain 45.2.2 is a member of the zebrafish, Danio rerio, skin mucus microbiota. Its genome is similar in size and GC content to those of other Delftia strains.


Avinza - 24-h sustained-release oral morphine therapy.
Avinza is a once-daily, extended-release oral morphine preparation. It has a pharmacokinetic profile that exhibits less peak-to-trough fluctuations in plasma concentration whilst providing analgesia statistically identical to that produced by MS Contin (controlled-release morphine sulfate), Oxycontin (oxycodone HCl controlled-release) and six doses of oral morphine sulfate administered every 4 h. Avinza improves quality of sleep by several measures but interestingly gives the best sleep improvement when given in the morning rather than at night. It causes the same side effects of other opioids: constipation, nausea, vomiting, somnolence and mood swings. Doses of 30 - 60 mg/day have been shown to be well tolerated by patients with osteoarthritis (even in the elderly), who have failed other medications.


The effect of serum lipoproteins on cholesterol content and sterol exchange in cultured human endothelial cells.
Cultured human endothelial cells preincubated with the infranatant of human serum increased their content of cholesterol when subsequently exposed to low density lipoproteins (LDL) as compared to control cultures further incubated in the presence of infranatant only. Replacing LDL with high density lipoproteins (HDL) resulted in no change in the cellular cholesterol content compared to the control. The addition of HDL did not influence the increase in cellular cholesterol content mediated by LDL. HDL stimulated the efflux of endogenously synthesized 14C-labelled sterols compared to the infranatant fraction, whereas LDL had only a slight effect. Cells preincubated with whole serum did not change their cholesterol content when subsequently exposed to LDL, compared to cultures further incubated in presence of whole serum. Replacing whole serum (during the final incubation) with infranatant, resulted in a decrease of the cellular cholesterol content, which was not influenced by further addition of HDL.


Early diagnosis of glaucoma. II. The value of the initial examination in ocular hypertension.
In a group of 46 patients with moderately elevated intraocular pressure (22-30 mmHg), signs of early glaucoma were found in half of them after a follow-up of 5-7.5 years. Most of the patients showed only a small increase in optic disc cupping revealed by stereophotography. Initial IOP higher than 25 mmHg, large pressure differences between the two eyes, large diurnal pressure variation, occurrence of pseudoexfoliation, pressure drop of more than 8 mmHg after topical epinephrine, and a pressure rise of more than 4 mmHg after water loading were more frequent in the group of patients who developed signs of glaucoma. Age, a positive family history, occurrence of cardiovascular disease, and the cup/disc ratio did not differ in the two groups of patients. The pilocarpine test and steroid provocation had no predictive value. Surprisingly, there was a small drop of pressure after topical steroids in 6 of the 8 patients with pseudoexfoliation.


Grading of transitional cell tumours of the urinary tract by urinary cytology.
1122 cytological diagnoses have been made on 2500 Papanicolaou stained cytological slides from Patients with urothelial carcinomas. The cytological accuracy was 78% for G1 tumours, 94% for G2 and 96% for G3 carcinomas. A histologically diagnosed G1 carcinoma was cytologically G1 in 81% of cases, a G2 carcinoma was recognized in 64% and G3 carcinoma in 48%.


Radiovisiography versus conventional radiography for detection of small instruments in endodontic length determination. Part 1. In vitro evaluation.
Radiovisiography is a new intraoral radiographic imaging system. In this in vitro investigation, radiovisiography was compared with conventional radiographs viewed with x2 magnification. Twenty-five extracted maxillary molars were evaluated for clarity of size 8 and 10 endodontic file tips in relation to the radiographic apex. Five images of radiovisiography were compared with D-speed and E-speed radiographs: original, enhanced, negative-to-positive, standard zoom, and zoom in the negative-to-positive mode. D-speed radiographs were also compared with E-speed radiographs. Zoom in the negative-to-positive mode was statistically equivalent to D-speed radiographs (p = 0.264) and superior to E-speed radiographs (p < 0.001). The standard zoom was also superior to E-speed radiographs (p = 0.025). D-speed radiographs were statistically superior to E-speed radiographs; being judged better than E-speed 90% of the time. Accurate identification of the position of the tips of size 8 and 10 files was achieved on all D- and E-speed radiographs with the use of magnification.