Antioxidative efficacy of alkali-treated tilapia protein hydrolysates: a comparative study of five enzymes.
The antioxidant activities of alkali-treated tilapia protein hydrolysates were determined by their ability to inhibit the formation of lipid hydroperoxides (PV) and thiobarbituric acid reactive substances (TBARS) in a washed muscle model system and by their ability to inhibit DPPH free radicals and chelate ferrous ion in an aqueous solution. Protein isolates were prepared from tilapia white muscle using alkali solubilization at pH 11.0 and reprecipitation at pH 5.5. Protein hydrolysates were prepared by hydrolyzing the isolates using five different enzymes, Cryotin F, Protease A Amano, Protease N Amano, Flavourzyme, and Neutrase, to 7.5, 15, and 25% degrees of hydrolysis (DH). All of the protein hydrolysates significantly (p<0.05) inhibited the development of TBARS and PV. The antioxidant activity of the hydrolysates increased with the DH. Also, the antioxidant activity of the hydrolysates varied significantly (p<0.05) among the different enzymes. The ability of different enzyme-catalyzed protein hydrolysates to scavenge DPPH radicals was not reflected in their ability to inhibit oxidation in a washed tilapia model system. In a washed muscle model system, the hydrolysates prepared using Cryotin F were most effective and the hydrolysates prepared using Flavourzyme and Neutrase were least effective in inhibiting the development of TBARS and PV, whereas in an aqueous solution, hydrolysates prepared using Flavourzyme were most effective in scavenging DPPH radicals and chelating ferrous ions. Enzymatic hydrolysis decreased the size of tilapia protein hydrolysates and, in general, tilapia protein hydrolysates with low molecular weights were better antioxidants than those with high molecular weights.


Breast cancer survival in England, Norway and Sweden: a population-based comparison.
Several international studies have found that survival from breast cancer is lower in the United Kingdom than in some other European countries. We have compared breast cancer survival between the national populations of England, Norway and Sweden, with a view to identifying subsets of patients with particularly good or adverse survival outcomes. We extracted cases of breast cancer in women diagnosed 1996-2004 from the national cancer registries of the 3 countries. The study comprised 303,657 English cases, 24,919 Norwegian cases and 57,512 cases from Sweden. Follow-up was in 2001-2004. The main outcome measures were 5-year cumulative relative survival and excess death rates, stratified by age and period of follow-up. In comparison with Norway and Sweden, the excess mortality in England was particularly pronounced in the first month and in the first year after diagnosis, and generally more marked in the oldest age groups. Compared with Norwegian patients, 81% of the excess deaths in the English patients occurred in the first 2 years after diagnosis. Our findings emphasise the importance of awareness of symptoms and early detection as the main strategy to improve breast cancer survival in the United Kingdom.


Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease.
We used magnetic resonance imaging (MRI) measurements to determine whether persons in the prodromal phase of Alzheimer's disease (AD) could be accurately identified before they developed clinically diagnosed dementia. Normal subjects (n = 24) and those with mild memory difficulty (n = 79) received an MRI scan at baseline and were then followed annually for 3 years to determine which individuals subsequently met clinical criteria for AD. Patients with mild AD at baseline were also evaluated (n = 16). Nineteen of the 79 subjects with mild memory difficulty "converted" to a diagnosis of probable AD after 3 years of follow-up. Baseline MRI measures of the entorhinal cortex, the banks of the superior temporal sulcus, and the anterior cingulate were most useful in discriminating the status of the subjects on follow-up examination. The accuracy of discrimination was related to the clinical similarity between groups. One hundred percent (100%) of normal subjects and patients with mild AD could be discriminated from one another based on these MRI measures. When the normals were compared with the individuals with memory impairments who ultimately developed AD (the converters), the accuracy of discrimination was 93%, based on the MRI measures at baseline (sensitivity = 0.95; specificity = 0.90). The discrimination of the normal subjects and the individuals with mild memory problems who did not progress to the point where they met clinical criteria for probable AD over the 3 years of follow-up (the "questionables") was 85% and the discrimination of the questionables and converters was 75%. The apolipoprotein E genotype did not improve the accuracy of discrimination. The specific regions selected for each of these discriminations provides information concerning the hierarchical fashion in which the pathology of AD may affect the brain during its prodromal phase.


Illuminating membrane structural dynamics of fusion and endocytosis with advanced light imaging techniques.
Visualization of cellular dynamics using fluorescent light microscopy has become a reliable and indispensable source of experimental evidence for biological studies. Over the past two decades, the development of super-resolution microscopy platforms coupled with innovations in protein and molecule labeling led to significant biological findings that were previously unobservable due to the barrier of the diffraction limit. As a result, the ability to image the dynamics of cellular processes is vastly enhanced. These imaging tools are extremely useful in cellular physiology for the study of vesicle fusion and endocytosis. In this review, we will explore the power of stimulated emission depletion (STED) and confocal microscopy in combination with various labeling techniques in real-time observation of the membrane transformation of fusion and endocytosis, as well as their underlying mechanisms. We will review how STED and confocal imaging are used to reveal fusion and endocytic membrane transformation processes in live cells, including hemi-fusion; hemi-fission; hemi-to-full fusion; fusion pore opening, expansion, constriction and closure; shrinking or enlargement of the Ω-shape membrane structure after vesicle fusion; sequential compound fusion; and the sequential endocytic membrane transformation from flat- to O-shape via the intermediate Λ- and Ω-shape transition. We will also discuss how the recent development of imaging techniques would impact future studies in the field.


Impact of Obstructive Sleep Apnea on Health-Related Quality of Life in Patients With Partial Laryngectomy for Laryngeal Cancer.
Objectives: To evaluate the possible risk factors of obstructive sleep apnea (OSA) and its impact on the health-related quality of life (HRQoL) in patients with partial laryngectomy for laryngeal cancer. Methods: A cross-sectional method was used to carry out this study. Patients who underwent partial laryngectomy for laryngeal cancer completed overnight polygraphy (PG) home sleep tests and quality of life questionnaires. The Medical Outcome Study 36-item Short-Form Health Survey (SF-36) questionnaire was used to investigate the factors influencing HRQoL. Results: A total of 59 patients completed the PG tests and quality of life questionnaires, with 74.6% demonstrating evidence of OSA. There were significant differences in tumor area and neck dissection between OSA group and non-OSA groups. Based on sleep-related parameters, patients were divided into cluster 1 (n = 14) and cluster 2 (n = 45) using principal component analysis combined with K-means clustering. Two clusters had significantly different scores of body pain, general health, and health transition in SF-36 domains. Independent factors associated with general health were identified as tobacco use (OR = 4.716), alcohol use (OR = 3.193), and OSA-related condition (OR = 11.336). Conclusions: Larger tumor area and neck dissection might be associated with an increased risk for developing OSA in patients with partial laryngectomy for laryngeal cancer. OSA partially mediated the effect on physical health, including body pain, general health, and health transition. It is important to be aware of the potential impact of OSA on diminished HRQoL of these patients.


Materials with negative compressibilities in one or more dimensions
Rare crystal phases that expand in one or more dimensions when hydrostatically compressed are identified and shown to have negative Poisson's ratios. Some of these crystals (i) decrease volume and expand in two dimensions when stretched in a particular direction and (ii) increase surface area when hydrostatically compressed. Possible mechanisms for achieving such negative linear and area compressibilities are described for single crystals and composites, and sensor applications are proposed. Materials with these properties may be used to fabricate porous solids that either expand in all directions when hydrostatically compressed with a penetrating fluid or behave as if they are incompressible.


High-Performance Organic Solar Cells Based on a Non-Fullerene Acceptor with a Spiro Core.
Derived from perylenediimide (PDI) building blocks, 3D PDI molecules are considered as a type of promising structure to overcome molecular aggregation, thus improving the performance of organic solar cells. Herein, we report a novel PDI-based derivative, SCPDT-PDI4 , with four PDI units connected to a unique spiro core. Attributed to this novel molecular design, SCPDT-PDI4 exhibits a rigid 3D structure, in which the aggregation tendency of PDI chromophores could be effectively attenuated. Additionally, strong intramolecular charge transfer and high charge mobility are achieved due to the well-conjugated structure and electron-rich property of SCPDT. Therefore, fullerene-free organic solar cells based on SCPDT-PDI4 and PTB7-Th achieve a remarkable high efficiency of 7.11 %. Such an excellent result demonstrates the opportunity of SCPDT to be a promising building block for non-fullerene acceptors.


Influence of RET mutations on the expression of tyrosine kinases in medullary thyroid carcinoma.
The therapeutic options for patients with metastatic medullary thyroid carcinoma (MTC) have recently increased due to the development of tyrosine kinase inhibitors (TKIs), some of which have achieved remarkable clinical responses in MTC patients. However, the molecular basis for the large variability in TKI responses is unknown. In this exploratory study, we investigated the expression of eight key TKI target proteins (EGFR, KIT, MET, PDGFRB, VEGF (VEGFA), VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4)) by immunohistochemistry in 103 molecularly characterized MTC samples and identified the associated clinical and molecular features. A number of MTC samples exhibited a high expression of VEGFR2 and VEGFR3, which were overexpressed in 57 and 43% of the MTC samples respectively. VEGFR1, PDGFRB, VEGF, KIT, and MET were present in 34-20% of the cases, while EGFR was highly expressed in only 10% of the MTC samples. Some proteins exhibited large differences in expression between sporadic and familial cases, suggesting that different RET mutations may be associated with the immunohistochemical profiles. MTC samples with the C634 RET mutation exhibited a higher expression of VEGFR3 and KIT than the M918T RET-mutated and non-mutated RET tumor samples (P=0.005 and P=0.007 respectively) and a lower expression of VEGFR1 (P=0.04). Non-mutated RET MTC cases exhibited a lower expression of PDGFRB (P=0.04). Overall, this is the first study, to our knowledge, to show that multiple TKI targets are highly expressed in a subset of MTCs, suggesting that molecular stratification of patients may have the potential to improve TKI therapies for MTC.


[Pharmacological correction of hypoxia in patients with severe carbon monoxide poisoning].
The article deals with the materials, which have been received in the process of the examination and treatment of 44 patients with acute severe methadone poisonings. It has been revealed, that gravity of these patients' condition depends on the intensity of hypoxia due to breath deficiency because of methadone. The development of hypoxia, in its turn, causes violations of antiradical protection system and intensification of processes of peroxide lipid oxidation. It has been registered that the including of reamberin into the complex program of the intensive therapy of acute severe methadone poisonings leads to a more rapid restoration of antiradical protection system and to a decrease of activity of processes of peroxide lipid oxidation. The correction of hypoxia and free-radical violations led to the improvement of the acute poisonings clinics, what was characterized by a decrease of coma-period duration, duration of treatment with artificial lung ventilation, a decrease of secondary lung complications and a decrease of lethality.


Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure.
A sustained viral response (SVR) after interferon-based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work-up with highly sensitive HCV RNA detection, and the determination of immune responses. To determine clinical, histological, virological and immunological markers 5-20 years after SVR. In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV-specific T-cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3-specific antibodies and virus neutralisation. Liver disease regressed significantly in all patients, and 51 were HCV RNA-negative in all tissues tested. There was an inverse association between liver disease, HCV-specific T-cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5-9 years after SVR. All three had HCV-specific T cells and NS3 antibodies, but no cross-neutralising antibodies. Our combined data confirm that a SVR corresponds to a long-term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.


Direct costs of asthma in Brazil: a comparison between controlled and uncontrolled asthmatic patients.
Asthma is a common chronic illness that imposes a heavy burden on all aspects of the patient's life, including personal and health care cost expenditures. To analyze the direct cost associated to uncontrolled asthma patients, a cross-sectional study was conducted to determine costs related to patients with uncontrolled and controlled asthma. Uncontrolled patient was defined by daytime symptoms more than twice a week or nocturnal symptoms during two consecutive nights or any limitations of activities, or need for relief rescue medication more than twice a week, and an ACQ score less than 2 points. A questionnaire about direct cost stratification in health services, including emergency room visits, hospitalization, ambulatory visits, and asthma medications prescribed, was applied. Ninety asthma patients were enrolled (45 uncontrolled/45 controlled). Uncontrolled asthmatics accounted for higher health care expenditures than controlled patients, US$125.45 and US$15.58, respectively [emergency room visits (US$39.15 vs US$2.70) and hospitalization (US$86.30 vs US$12.88)], per patient over 6 months. The costs with medications in the last month for patients with mild, moderate and severe asthma were US$1.60, 9.60, and 25.00 in the uncontrolled patients, respectively, and US$6.50, 19.00 and 49.00 in the controlled patients. In view of the small proportion of uncontrolled subjects receiving regular maintenance medication (22.2%) and their lack of resources, providing free medication for uncontrolled patients might be a cost-effective strategy for the public health system.


Three-dimensional in vitro co-culture model of breast tumor using magnetic levitation.
In this study, we investigate a novel in vitro model to mimic heterogeneous breast tumors without the use of a scaffold while allowing for cell-cell and tumor-fibroblast interactions. Previous studies have shown that magnetic levitation system under conventional culturing conditions results in the formation of three-dimensional (3D) structures, closely resembling in vivo tissues (fat tissue, vasculature, etc.). Three-dimensional heterogeneous tumor models for breast cancer were designed to effectively model the influences of the tumor microenvironment on drug efficiency. Various breast cancer cells were co-cultured with fibroblasts and then magnetically levitated. Size and cell density of the resulting tumors were measured. The model was phenotypically compared to in vivo tumors and examined for the presence of ECM proteins. Lastly, the effects of tumor stroma in the 3D in vitro model on drug transport and efficiency were assessed. Our data suggest that the proposed 3D in vitro breast tumor is advantageous due to the ability to: (1) form large-sized (millimeter in diameter) breast tumor models within 24 h; (2) control tumor cell composition and density; (3) accurately mimic the in vivo tumor microenvironment; and (4) test drug efficiency in an in vitro model that is comparable to in vivo tumors.


Bucket and straw technique to facilitate passage of a ventriculoperitoneal shunt through the distal tunneling sheath.
Placement of a ventriculoperitoneal shunt (VPS) is a procedure comprising many small steps. Difficulties and delays can arise when passing the distal shunt tubing down the distal tunneling sheath during surgery. The authors of this report describe a simple technique for quickly passing the distal catheter of a VPS through the tunneler sheath, whereby the sheath is used as a fluid tube to allow the distal catheter to be drawn through the fluid tube under suction pressure. The plastic sheath that surrounds the shunt tunneler device is used as a fluid tube, or "straw," with the proximal aperture submerged into a bucket of sterile irrigation liquid containing the distal catheter. Suction pressure is placed against the distal aperture of the tunneler, and the shunt catheter is quickly drawn through the sheath. No special equipment is required. In time trials, the bucket and straw technique took an average of 0.43 seconds, whereas traditional passage methods took 32.3 seconds. The "bucket and straw" method for passing distal shunt tubing through the tunneler sheath is a technique that increases surgical efficiency and reduces manual contact with shunt hardware.


Increased levels of oxidative stress markers detected in the brains of mice devoid of prion protein.
Although minor abnormalities have been reported in prion protein (PrP) knock-out (Prnp-/-) mice, the normal physiological function of PrP, the causative agent implicated in transmissible spongiform encephalopathies (TSE), remains unresolved. Since there are increasing correlations between oxidative stress and amyloidoses, we decided to investigate whether PrP plays a role in oxidative modulation. We found higher levels of oxidative damage to proteins and lipids in the brain lysates of Prnp-/- as compared to wild-type (WT) mice of the same genetic background. These two indicators, protein oxidation and lipid peroxidation, are hallmarks of cellular oxidative damage. Elevated levels of ubiquitin-protein conjugates were also observed in Prnp-/- mice, a probable consequence of cellular attempts to remove the damaged proteins as indicated by increased proteasome activity. Taken together, these findings are indicative of a role for PrP in oxidative homeostasis in vivo.


[Congenital muscular dystrophies: muscle-eye-brain disease].
Three rare autosomal recessive disorders share the combination of congenital muscular dystrophy and brain malformations including a neuronal migration defect: muscle-eye-brain disease (MEB), Walker-Warburg syndrome (WWS), and Fukuyama congenital muscular dystrophy (FCMD). In addition, ocular abnormalities are a constant feature in MEB and WWS. We report on two brothers with MEB. The clinical and radiological characteristics are demonstrated.


Evaluation of Holmium Laser Enucleation of the Prostate Learning Curves with and without a Structured Training Programme.
To evaluate perioperative parameters, early functional outcomes, and the safety profile of holmium laser enucleation of the prostate learning curves with and without mentoring. The learning curves of 2 surgeons of their first 100 consecutive patients treated with holmium laser enucleation of the prostate were retrospectively analyzed. We analyzed demographic parameters, clinical outcomes, adverse events, and the progress during each learning experience. The only statistically significant differences between the two learning curves were found for operation time (138.2 ± 60.7 vs. 98.2 ± 37.7 min; p < 0.001) in favor of the supervised approach, the total weight of resected prostatic tissue (81.5 ± 50.5 vs. 65.0 ± 6.7 g; p < 0.001) with more tissue removal by the surgeon without guidance, and the perioperative hemoglobin drop (1.9 ± 1.4 vs. 1.1 ± 1.0 g/dl; p < 0.001) in favor of the learning curve with a training programme. In multivariate logistic regression, the time factor was independently associated with a higher drop in hemoglobin levels (OR 1.015; 95% CI 1.000-1.023; p = 0.001). The improvements of clinical outcomes as determined by International Prostate Symptom Score, quality of life, peak urinary flow rate and postvoid residual volume were comparable. After the first 50 procedures the mean operation time significantly improved from 147 to 107.5 minutes for the learning curve without supervision (p < 0.001), whereas the surgical time was consistent throughout the 100 cases with a mentoring programme. The overall incidence of treatment-related adverse events was significantly higher without the training programme (16 vs. 5%; p = 0.008). Our study clearly showed the benefits of a structured training programme to overcome the steep learning curve.


The effect of supplementing microbial phytase and organic acids to a corn-soybean based diet fed to early-weaned pigs.
The effect of microbial phytase (MP) and organic acids (OA) supplementation in diets for early-weaned pigs was investigated in an in vitro assay and a growth performance and digestibility trial involving 96 pigs (18 d old). The experimental diets were: 1) a control (C) formulated according to NRC (1998); 2) a negative control (NC) that was similar to diet C except that available P was reduced by 0.19%; 3) NC plus MP (500 U/kg); and 4) NC+MP and OA (NC+MPOA). In the in vitro assay, the four diets were incubated under simulated gut conditions. Addition of MP increased (P = 0.003) phytate hydrolysis from 34 (NC) to 87.5% (NC+MP); this was further increased to 90.1% due to the addition of OA (NC+MPOA). In the 4-wk growth trial, each diet was randomly assigned to six pens each with four pigs. At the end of wk 3, a mobility test was conducted on one pig randomly selected from each pen. Pigs fed the NC diet tended to have a lower (P = 0.06) mobility score compared with those fed the other diets. At the end of wk 4, six pigs per treatment were killed and samples of digesta from different sections of the gut and the third metatarsal bone were collected for nutrient digestibility and bone ash measurements, respectively. There were no differences in ADFI, ADG, and gain:feed ratio among treatments (P > 0.05); however, ADG was 6.5% higher in piglets fed the NC+MPOA diet compared with those fed the C diet. Bone ash content was lower (P = 0.003) in NC fed pigs than in those fed the other treatments. Supplementing NC with MP and MP+OA improved bone ash content to the same level as C. Apparent ileal digestibility (AID) of DM and CP did not differ (P > 0.10) among treatments and averaged 80.7 and 79.4%, respectively. Of all AA, only AID of isoleucine, histidine, and aspartic acid was increased (P < 0.05) by MP+OA supplementation. Overall, there were slight numerical improvements in AID of AA due to MP and OA supplementation, with AID of essential AA averaging 79.4, 77.7, 80.1, and 81.6% for C, NC, NC+MP, and NC+MPOA, respectively. The AID of P was increased (P = 0.0001) by 21 percentage units, and the amount of P excreted was decreased (P = 0.03) by 19.4% as a result of MP+OA supplementation compared with C. In conclusion, addition of MP and OA to pig starter diets improved P digestion and utilization, thereby leading to a reduction in P excretion. Addition of MP and OA to corn-soybean meal diets fed to young pigs had only a slight effect on ileal amino acid digestibilities.


Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.
Disturbances in the circadian pacemaker system are commonly found in individuals with depression and sleep-related problems. We hypothesized that some of the canonical circadian clock genes would be associated with depression accompanied by signs of disturbed sleep, early morning awakening, or daytime fatigue. We tested this hypothesis in a population-based sample of the Health 2000 dataset from Finland, including 384 depressed individuals and 1270 controls, all with detailed information on sleep and daytime vigilance, and analyzed this set of individuals with regard to 113 single-nucleotide polymorphisms of 18 genes of the circadian system. We found significant association between TIMELESS variants and depression with fatigue (D+FAT+) (rs7486220: pointwise P = 0.000099, OR = 1.66; corrected empirical P for the model of D+FAT+ = 0.0056; haplotype 'C-A-A-C' of rs2291739-rs2291738-rs7486220-rs1082214: P = 0.0000075, OR = 1.72) in females, and association to depression with early morning awakening (D+EMA+) (rs1082214: pointwise P = 0.0009, OR = 2.70; corrected empirical P = 0.0374 for the model D+EMA+; haplotype 'G-T' of rs7486220 and rs1082214: P = 0.0001, OR = 3.01) in males. There was significant interaction of gender and TIMELESS (for example with rs1082214, P = 0.000023 to D+EMA+ and P = 0.005 to D+FAT+). We obtained supported evidence for involvement of TIMELESS in sleeping problems in an independent set of control individuals with seasonal changes in mood, sleep duration, energy level and social activity in females (P = 0.036, = 0.123 for rs1082214) and with early morning awakening or fatigue in males (P = 0.038 and P = 0.0016, respectively, for rs1082214). There was also some evidence of interaction between TIMELESS and PER1 in females to D+FAT+ as well as between TIMELESS and ARNTL, RORA or NR1D1 in males to D+EMA+. These findings support a connection between circadian genes and gender-dependent depression and defective sleep regulation.


Expectancies, evaluations and attitudes: prediction of college student drinking behavior.
The goal of this study was to investigate a model of college student alcohol use that not only included primary demographic and social factors shown to influence college student drinking behavior but also measured the influence of expectancies, evaluations of expectancies, and attitudes in prospectively predicting drinking behavior. Participants (N = 17) were recruited from an introductory psychology course subject pool and were asked to complete several questionnaires, including a modified Alcohol Expectancy Questionnaire, an attitude questionnaire and a modified timeline follow-back measure. These measures were completed at baseline and at a 1-month follow-up assessment. The study was then replicated with a separate sample (N = 162). The results of a series of mixed regression analyses indicated that, after accounting for demographic variables, social norms and a college lifestyle attitude variable, the only significant predictor consistent across drinking measures was the general attitude variable. This was true for both the prospective and concurrent analyses of alcohol use. The evaluations of expectancies did account for a significant portion of the variance but appeared secondary to the general attitude measure. The results of the study were replicated in a separate sample. Contrary to previous research, the results of this study suggest that attitudes toward alcohol use account for more variance in predicting drinking behavior than both alcohol expectancies and evaluations of those expectancies. The results of this study are also consistent with findings that evaluations of alcohol-related expectancies predict drinking behavior.


Processing Chain for Localization of Magnetoelectric Sensors in Real Time.
The knowledge of the exact position and orientation of a sensor with respect to a source (distribution) is essential for the correct solution of inverse problems. Especially when measuring with magnetic field sensors, the positions and orientations of the sensors are not always fixed during measurements. In this study, we present a processing chain for the localization of magnetic field sensors in real time. This includes preprocessing steps, such as equalizing and matched filtering, an iterative localization approach, and postprocessing steps for smoothing the localization outcomes over time. We show the efficiency of this localization pipeline using an exchange bias magnetoelectric sensor. For the proof of principle, the potential of the proposed algorithm performing the localization in the two-dimensional space is investigated. Nevertheless, the algorithm can be easily extended to the three-dimensional space. Using the proposed pipeline, we achieve average localization errors between 1.12 cm and 6.90 cm in a localization area of size 50cm×50cm.


Ultrathin zirconium disulfide nanodiscs.
We present a colloidal route for the synthesis of ultrathin ZrS(2) (UT-ZrS(2)) nanodiscs that are ~1.6 nm thick and consist of approximately two unit cells of S-Zr-S. The lateral size of the discs can be tuned to 20, 35, or 60 nm while their thickness is kept constant. Under the appropriate conditions, these individual discs can self-assemble into face-to-face-stacked structures containing multiple discs. Because the S-Zr-S layers within individual discs are held together by weak van der Waals interactions, each UT-ZrS(2) disc provides spaces that can serve as host sites for intercalation. When we tested UT-ZrS(2) discs as anodic materials for Li(+) intercalation, they showed excellent nanoscale size effects, enhancing the discharge capacity by 230% and greatly improving the stability in comparison with bulk ZrS(2). The nanoscale size effect was especially prominent for their performance in fast charging/discharging cycles, where an 88% average recovery of reversible capacity was observed for UT-ZrS(2) discs with a lateral diameter of 20 nm. The nanoscale thickness and lateral size of UT-ZrS(2) discs are critical for fast and reliable intercalation cycling because those dimensions both increase the surface area and provide open edges that enhance the diffusion kinetics for guest molecules.


The Effects of Natural Epigenetic Therapies in 3D Ovarian Cancer and Patient-Derived Tumor Explants: New Avenues in Regulating the Cancer Secretome.
High mortality rates in ovarian cancer have been linked to recurrence, metastasis, and chemoresistant disease, which are known to involve not only genetic changes but also epigenetic aberrations. In ovarian cancer, adipose-derived stem cells from the omentum (O-ASCs) play a crucial role in supporting the tumor and its tumorigenic microenvironment, further propagating epigenetic abnormalities and dissemination of the disease. Epigallocatechin gallate (EGCG), a DNA methyltransferase inhibitor derived from green tea, and Indole-3-carbinol (I3C), a histone deacetylase inhibitor from cruciferous vegetables, carry promising effects in reprograming aberrant epigenetic modifications in cancer. Therefore, we demonstrate the action of these diet-derived compounds in suppressing the growth of 3D ovarian cancer spheroids or organoids as well as post-treatment cancer recovery through proliferation, migration, invasion, and colony formation assays when compared to the synthetic epigenetic compound Panobinostat with or without standard chemotherapy. Finally, given the regulatory role of the secretome in growth, metastasis, chemoresistance, and relapse of disease, we demonstrate that natural epigenetic compounds can regulate the secretion of protumorigenic growth factors, cytokines, extracellular matrix components, and immunoregulatory markers in human ovarian cancer specimens. While further studies are needed, our results suggest that these treatments could be considered in the future as adjuncts to standard chemotherapy, improving efficiency and patient outcomes.


[Klippel-Trenaunay, syndrome or disease].
Two cases which were clinically typical of the Klippel Trenaunay syndrome and in which the integrity of the deep venous system demonstrated by phlebography form the basis for the author's discussion of the various theories and classifications which have been put forward up to now. The authors favour Schobinger's opinion, according to which three varieties of the Klippel Trenaunay syndrome are recognised. Malan's anatomoclinical classification has been adopted : this permits the grouping together of the numerous variations possible in this type of dysplasia.


Comparison of Spinal Block Levels between Laboring and Nonlaboring Parturients Using Combined Spinal Epidural Technique with Intrathecal Plain Bupivacaine.
Background. It was suggested that labor may influence the spread of intrathecal bupivacaine using combined spinal epidural (CSE) technique. However, no previous studies investigated this proposition. We designed this study to investigate the spinal block characteristics of plain bupivacaine between nonlaboring and laboring parturients using CSE technique. Methods. Twenty-five nonlaboring (Group NL) and twenty-five laboring parturients (Group L) undergoing cesarean delivery were enrolled. Following identification of the epidural space at the L3-4 interspace, plain bupivacaine 10 mg was administered intrathecally using CSE technique. The level of sensory block, degree of motor block, and hemodynamic changes were assessed. Results. The baseline systolic blood pressure (SBP) and the maximal decrease of SBP in Group L were significantly higher than those in Group NL (P = 0.002 and P = 0.03, resp.). The median sensory level tested by cold stimulation was T6 for Group NL and T5 for Group L (P = 0.46). The median sensory level tested by pinprick was T7 for both groups (P = 0.35). The degree of motor block was comparable between the two groups (P = 0.85). Conclusion. We did not detect significant differences in the sensory block levels between laboring and nonlaboring parturients using CSE technique with intrathecal plain bupivacaine.


Picogram quantities of anti-Ig antibodies coupled to dextran induce B cell proliferation.
To investigate the properties which enable type 2 Ag, as exemplified by dextran and Ficoll, to stimulate high levels of antibody responses in the relative absence of T cells, we conjugated anti-IgD and anti-IgM mAb to both dextran and Ficoll and examined their B cell-activating properties. Such conjugated anti-Ig antibodies stimulated both early and later stages of B cell activation at picogram concentrations, which are at least 1000-fold lower than that required for B cell stimulation by unconjugated anti-Ig antibodies, and the level of proliferation they stimulated was on average 10-fold greater. Furthermore, concentrations of anti-Ig dextran (100 pg/ml) which modulated little sIgD from the B cell surface were strong inducers of enhanced B cell expression of MHC class II molecules. Conjugation of Fab fragments of anti-IgD or nonmitogenic anti-IgM mAb to dextran rendered them as mitogenic as dextran conjugated to strongly stimulatory anti-IgD or anti-IgM antibodies. The ability of dextran and Ficoll to serve as effective carrier molecules for anti-IgD was not related solely to their large m.w., because anti-IgD coupled to polymerized BSA (m.w. 1.5 X 10(6), was only 10- to 50-fold more potent than unconjugated anti-IgD antibodies at stimulating B cell DNA synthesis. These results suggest, therefore, that the unique ability of picogram concentrations of haptenated type 2 Ag to stimulate Ig secretion in the absence of T cells may be a function of their ability to promote effective cross-linking without resulting in the modulation of sIg. This would enable such Ag to mediate repetitive B cell signaling, a situation that cannot be achieved by unconjugated anti-Ig antibodies which result in modulation of sIg at their mitogenic concentrations. These compounds therefore may be employed to study B cell activation stimulated by sIg cross-linking at concentrations that may more closely reflect those which are achieved under physiologic conditions by type 2 Ag.


Role of physical exercise in Alzheimer's disease.
The benefits of physical exercise on the brain and general wellness are well recognised, but not particularly well known to the general public. Understanding the importance of integrating active behavior for overall health is crucial at any age and particularly for the elderly who are at risk of developing Alzheimer's disease (AD), a disease mainly affecting individuals aged >65 years. AD is a neurodegenerative disease characterized by extracellular senile plaques of amyloid-β, intracellular neurofibrillary tangles of the protein tau, brain atrophy and dementia. The beneficial effects of physical exercise have been observed on the maintenance of brain size and efficiency for the prevention of AD risks, such as obesity, hypertension and stroke. These effects are extended to individuals with, or at risk of dementia and other age-related neurodegenerative disorders. Accordingly, although extensive studies are required to fully understand the mechanisms by which physical exercise procures beneficial effects, data suggest the relevance of integrating physical exercise in the prevention and/or cure of AD, disease whose incidence is predicted to increase in the future. Such an increase, may pose medical, social and economical challenges for populations and the health care system worldwide. In the present review we assess the positive aspects of physical exercise with regard to prevention and cure of AD.


Assessment of Risk for Ventricular Tachycardia based on Extensive Electrophysiology Simulations.
Patients that have suffered a myocardial infarction are at high risk of developing ventricular tachycardia. Patient stratification is often determined by characterization of the underlying myocardial substrate by cardiac imaging methods. In this study, we show that computer modeling of cardiac electrophysiology based on personalized fast 3D simulations can help to assess patient risk to arrhythmia. We perform a large simulation study on 21 patient digital twins and reproduce successfully the clinical outcomes. In addition, we provide the sites which are prone to sustain ventricular tachycardias, i.e, onset sites around the scar region, and validate if they colocalize with exit sites from slow conduction channels.Clinical relevance- Fast electrophysiological simulations can provide advanced patient stratification indices and predict arrhythmic susceptibility to suffer from ventricular tachycardia in patients that have suffered a myocardial infarction.


Reducing the risk of infection in vascular access patients: an in vitro evaluation of an antimicrobial silver nanotechnology luer activated device.
Luer-activated devices (LAD) have been designed to reduce the risk of sharps injury; however, published reports suggest that internal fluid path contamination occurs in selected devices. The present in vitro study compares the antimicrobial property of a silver-nanotechnology LAD to 8 nonantimicrobial LADs. A laboratory reference strain of methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 33592) was used to prepare a standardized microbial challenge, 3.73- to 3.86-log(10) colony-forming units (cfu)/mL, adjusted for fluid path volume for 9 commercially available LAD (1 sliver nanotechnology LAD and 8 non-antimicrobial LADs). Following incubation (15 hours at 30 degrees C), each device was flushed, serially diluted, and plated in triplicate to trypticase soy agar for microbial recovery, expressed as log(10) cfu/mL. Comparison of fluid path volumes documented a wide variation between the 9 commercial devices (range, 0.025-0.359 mL). Log(10) microbial recovery were shown to increase on average 1.5 to 3.0 logs in the 8 non-antimicrobial LADs, whereas S aureus recovery in the silver-nanoparticle LAD demonstrated a 2.6-log decrease following incubation (P < or = .05). These findings suggest that, under in vitro conditions, a silver nanotechnology was effective in reducing the risk of fluid path colonization when the LAD was challenged using a standardized inoculum of a laboratory reference strain of MRSA. Further studies are warranted to assess the clinical efficacy of an antimicrobial LAD technology for reducing the risk of vascular access (catheter associated) infections.


[Subclinical atherosclerosis in young patients with rheumatoid arthritis and low disease activity].
There is an increasing body of evidence suggesting that subjects with rheumatoid arthritis (RA) are characterized by acceleration of atherosclerotic process of arterial wall. However, all investigations performed so far to evaluate subclinical atherosclerosis in RA included subjects without selection for age and degree of disease activity that may represent confounding factors in such an evaluation. To verify signs of accelerated subclinical atherosclerosis in young subject suffering from RA but with low disease activity. Thirty-two patients with RA and 28 age- and sex-matched control subjects with non-inflammatory rheumatic diseases were enrolled. Inclusion criteria were age less than 60 and low disease activity with score < or =3.2 according to DAS28, while subjects with traditional risk factors for and/or overt cardiovascular disease were ruled out from the study. Both patients and controls underwent evaluation of carotid and femoral artery intima-media thickness by ultrasounds. Patients had higher intima-media thickness than controls of all the sites evaluated at carotid artery level, whereas there were no differences at the comparison of the superficial and common femoral artery wall. At the univariate analysis, a positive correlation between LDL cholesterol levels and intima-media thickness at the carotid bifurcation was found. Young patients with RA and low disease activity have acceleration of atherosclerosis development as shown by increased intima-media thickness of carotid artery with respect to subjects without inflammatory rheumatic disease. It is conceivable that the organic damage of arterial wall could be the result of persistent endothelial dysfunction induced by chronic inflammation and immune dysregulation which characterize RA.


Blockade of Glutamatergic Neurotransmission in the Suprachiasmatic Nucleus Prevents Cellular and Behavioural Responses of the Circadian System to Light.
The aim of this study was to test the role of glutamatergic neurotransmission in photic entrainment of the circadian oscillator of the suprachiasmatic nuclei (SCN) in the Syrian hamster. The response of the oscillator to a brief pulse of light was assessed using two independent indices, the phase shift of the free-running activity rhythm, and the photically induced expression of the immediate-early gene c-fos within neurons of the SCN. The behavioural and the cellular responses to light were compared in animals which received intracerebroventricular (icv) infusions into the region of the SCN of either a vehicle solution or a solution of gammad-glutamyl-glycine (DGG), a competitive antagonist at both N-methyl-d-aspartate (NMDA) and non-NMDA types of glutamate receptor. Infusions of vehicle or DGG (200 nmol) were given 10 min before presentation of a 15-min light pulse at either circadian time (CT) 14 or CT20 (onset of activity defined as CT12). As anticipated, animals treated with vehicle and light at CT14 exhibited phase delays in the activity rhythm, whereas animals treated at CT20 exhibited phase advances. Central infusion of DGG prior to a light pulse at CT14 blocked the phase-delaying effect of light, and DGG delivered before a light pulse at CT20 markedly attenuated the phase-advancing effect of light. In a separate group of animals, the expression of the immediate-early gene c-fos was assessed by immunocytochemical staining for its protein product Fos. Exposure of vehicle-infused animals to light at CT14 caused extensive expression of c-fos throughout the retinorecipient region of the SCN. However, when the light pulse was preceded by icv fusion of DGG at a dose which would block the phase-shifting response to light, the total number of neurons immunopositive for Fos was significantly reduced ( approximately 50%) and the expression was confined to a restricted area of the dorsolateral SCN. The precise correlation between the effects of glutamatergic blockade upon both the behavioural and the cellular responses of the circadian system to light demonstrates that effective glutamatergic neurotransmission within or adjacent to the SCN is a necessary component of the mechanism which mediates photic entrainment of the circadian clock. The results further demonstrate a pharmacological and anatomical compartmentalization of the retinorecipient zone of the SCN, consistent with the view that retinal afferents to the ventral region employ glutamate as a transmitter, whereas more dorsal input may be dependent upon non-glutamatergic (DGG-insensitive) pathways.


Side chain effect on the double helix formation of ethynylhelicene oligomers.
Three series of ethynylhelicene oligomers with different side chains were synthesized: (P)-bD-n (n = 2-6) with branched alkyloxycarbonyl side chains; (P)-S-n (n = 2-7) with decylsulfanyl side chains; and (P)-DF-n (n = 4, 6, 8, 10) with alternating decyloxycarbonyl and perfluorooctyl side chains. The double helix formation of these side chain derivatives was compared to that of (P)-D-n with decyloxycarbonyl side chains. CD, UV-vis, and vapor pressure osmometry (VPO) studies showed that (P)-bD-n formed double helices as well as (P)-D-n. CD studies in trifluoromethylbenzene at different temperatures and concentrations indicated that the stability of the aggregate of (P)-bD-6 was similar to that of (P)-D-6. Bulkiness of side chains had little effect on aggregation, which indicated that π-π interactions of the aromatic moiety were essential for double helix formation. (P)-S-n were random coils in all solvents examined except in trifluoromethylbenzene. Whereas (P)-D-7 formed a double helix at 1 × 10(-3) M in toluene, (P)-S-7 was a random coil. This result indicated that the double helix forming ability of (P)-S-n was substantially lower than that of (P)-D-n. Based on the previous observation that (P)-F-n formed a more stable double helix than (P)-D-n, the order of stability may be summarized as follows: (P)-F-n > (P)-D-n and (P)-bD-n >(P)-S-n. The lower stability of (P)-S-n compared to that of (P)-F-n was ascribed to the softness and/or the electron-rich nature at the m-phenylene moiety. (P)-DF-n did not form a stable double helix. It was speculated that a regular alternating arrangement of soft/hard or electron-rich/deficient moieties is important for stable double helix formation. Side chains of ethynylhelicene oligomers can play significant roles in determining the stability of double helices.


Phylogenetic analysis of Pseudomonas syringae pathovars suggests the horizontal gene transfer of argK and the evolutionary stability of hrp gene cluster.
Pseudomonas syringae are differentiated into approximately 50 pathovars with different plant pathogenicities and host specificities. To understand its pathogenicity differentiation and the evolutionary mechanisms of pathogenicity-related genes, phylogenetic analyses were conducted using 56 strains belonging to 19 pathovars. gyrB and rpoD were adopted as the index genes to determine the course of bacterial genome evolution, and hrpL and hrpS were selected as the representatives of the pathogenicity-related genes located on the genome (chromosome). Based on these data, NJ, MP, and ML phylogenetic trees were constructed, and thus 3 trees for each gene and 12 gene trees in total were obtained, all of which showed three distinct monophyletic groups: Groups 1, 2 and 3. The observation that the same set of OTUs constitute each group in all four genes suggests that these genes had not experienced any intergroup horizontal gene transfer within P. syringae but have been stable on and evolved along with the P. syringae genome. These four index genes were then compared with another pathogenicity-related gene, argK (the phaseolotoxin-resistant ornithine carbamoyltransferase gene, which exists within the argK-tox gene cluster). All 13 strains of pv. phaseolicola and pv. actinidiae used had been confirmed to produce phaseolotoxin and to have argK, whose sequences were completely identical, without a single synonymous substitution among the strains used (Sawada et al. 1997a). On the other hand, argK were not present on the genomes of the other 43 strains used other than pv. actinidiae and pv. phaseolicola. Thus, the productivity of phaseolotoxin and the possession of the argK gene were shown at only two points on the phylogenetic tree: Group 1 (pv. actinidiae) and Group 3 (pv. phaseolicola). A t test between these two pathovars for the synonymous distances of argK and the tandemly combined sequence of the four index genes showed a high significance, suggesting that the argK gene (or argK-tox gene cluster) experienced horizontal gene transfer and expanded its distribution over two pathovars after the pathovars had separated, thus showing a base substitution pattern extremely different from that of the noncluster region of the genome.


Depot-specific release of leptin from subcutaneous and omental adipocytes in suspension culture: effect of tumor necrosis factor-alpha and transforming growth factor-beta1.
Leptin, the product of the ob gene, is overexpressed in human obesity and increased serum leptin levels are closely correlated with adipose tissue mass, but the regulation of leptin production is not completely understood. The aim of this study was to characterize the role of tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 in depot-specific secretion of leptin from cultured human adipocytes. We measured the leptin concentrations in the culture medium of omental and subcutaneous abdominal adipocytes taken from severely obese individuals and kept in suspension culture, and studied the effect of TNF-alpha and TGF-beta1 on leptin release. Leptin protein was measured by radioimmunoassay, leptin mRNA was assessed by reverse transcriptase (RT)-PCR relative to a housekeeping gene. Leptin secretion from subcutaneous fat cells was 2- to 3-fold higher than that from omental fat cells after incubation for 2 and 24h respectively. A 2-h exposure of adipocytes to 1nmol/l TNF-alpha and 400pmol/l TGF-beta1 respectively did not significantly affect leptin secretion. Whereas a 24-h incubation with 1nmol/l TNF-alpha also did not influence leptin secretion from fat cells from both depots, exposure of omental fat cells to 400pmol/l TGF-beta1 for 24h resulted in a significant inhibitory effect (by 33%) on leptin secretion (P<0.05). A 24- and 48-h exposure of in vitro differentiated human adipocytes to TNF-alpha led to a significant decrease in leptin mRNA levels to 70 +/- 8% and 49 +/- 13% of controls respectively. Similarly, TGF-beta1 decreased leptin mRNA expression in newly differentiated human adipocytes to 77 +/- 12% after 24h and to 54 +/- 8% after 48h compared with control cultures. These data provide evidence that long-term exposure of human fat cells to TNF-alpha or TGF-beta1 may suppress leptin expression in human adipose tissue. The inhibitory effect of TGF-beta1 appears to be more pronounced in omental as compared with subcutaneous adipocytes.


Long-term follow up of patients with gastritis associated with Helicobacter pylori infection.
The aim of this study was to evaluate the long-term prognosis for patients suffering from gastritis associated with Helicobacter pylori infection, and in particular the proportion of cases progressing to peptic ulcer. The study was carried out in one urban general practice. One hundred and three patients who had presented with dyspepsia over the 1973-80 period and who were found to have a macroscopically normal endoscopy were reassessed between seven and 14 years later. Gastric antral biopsies had been taken routinely at endoscopy and were subsequently re-examined for the presence of H pylori. The patients' medical records were examined to establish their consulting rates over the follow-up period and whether they suffered from any other medical conditions. Patients were interviewed to assess the course of their dyspeptic symptoms. Comparison of patients who were unequivocally H pylori positive with those who were negative revealed no significant differences in the consultation rate for gastroenterological symptoms, in the proportion of patients referred to a hospital consultant or for further gastroenterological investigations or in the proportion reporting that their symptoms had improved. However, a statistically highly significant relationship was found between H pylori infection and hypertension. The results of this study have shown that there is a good prognosis for non-ulcer dyspepsia whether or not H pylori infection is present. The association between H pylori gastritis and hypertension clearly merits further investigation.


Systems pharmacology.
We examine how physiology and pathophysiology are studied from a systems perspective, using high-throughput experiments and computational analysis of regulatory networks. We describe the integration of these analyses with pharmacology, which leads to new understanding of drug action and enables drug discovery for complex diseases. Network studies of drug-target relationships can serve as an indication on the general trends in the approved drugs and the drug-discovery progress. There is a growing number of targeted therapies approved and in the pipeline, which meets a new set of problems with efficacy and adverse effects. The pitfalls of these mechanistically based drugs are described, along with how a systems view of drug action is increasingly important to uncover intricate signaling mechanisms that play an important part in drug action, resistance mechanisms, and off-target effects. Computational methodologies enable the classification of drugs according to their structures and to which proteins they bind. Recent studies have combined the structural analyses with analysis of regulatory networks to make predictions about the therapeutic effects of drugs for complex diseases and possible off-target effects.


Competition for intrathoracic space reduces lung capacity in patients with chronic heart failure: a radiographic study.
The purpose of this study was to determine the influence of changes in cardiac size on total lung volume in patients with chronic heart failure compared to control subjects. Forty-four patients and age-, gender-, and height-matched control participants were recruited. All participants underwent posteroanterior and lateral chest radiography for volumetric estimations of the total thoracic cavity (TTC), diaphragm, heart, and lungs. To assess the relationship between chronic heart failure severity and cardiac enlargement, patients with chronic heart failure were classified into groups based on New York Heart Association class, as follows: class I and II, n = 26 (group A); class III and IV, n = 18 (group B). There was no difference between the groups for TTC volume (TTCV) [p = 0.56]. Cardiac volumes were significantly different between all groups for both the absolute volumes (p < 0.001) were calculated as a percentage of TTCV (p < 0.001), with the largest cardiac volumes in group B (twice the volume of healthy control subjects). When expressed as a percentage of TTCV, there also was a clear reduction in lung volumes as a function of disease severity (p < 0.001). The present study demonstrates a close relationship between the severity of heart failure and cardiac size. These changes in cardiac size within a closed thoracic cavity may pose significant constraints on the lungs, resulting in reductions in lung volumes that likely play a major role in the restrictive breathing patterns often reported in patients with chronic heart failure.


Surface plasmon dynamics in an isolated metallic nanoslit.
We present an analytical study of the dynamic interplay among surface plasmon polarization charges, electromagnetic fields, and energy flow in the metal/dielectric interface and metal nanoslit structure. Particular attention is given to the regime where the energy flow in the metal side is significant compared to that in the dielectric side. The study reveals that a vortex-like circulation of energy is an intrinsic feature of surface plasmon propagation supported by a metal/dielectric interface, and, in general, a vortex can form when the permittivity and permeability values of the materials involved satisfy the following condition: {(epsilon(m)/epsilon(d)) < -1 and (mu(m)/mu(d)) > -1} or {(epsilon(m)/epsilon(d)) > -1 and (mu(m)/mu(d)) < -1}.


[Effectiveness and characteristics of the action of etmozin in treating extrasystole in middle-aged and elderly patients].
Antiarrhythmic efficiency and specific effects of ethmozine, taken alone in increasing oral doses from 300 to 450 mg daily, were evaluated in 48 elderly and old coronary patients with stable supraventricular and ventricular extrasystoles (SVES, VES). It was demonstrated clinically and instrumentally (ECG, rhythmography, bicycle ergometry with standard exercise, cardiac rhythm monitoring and computer analysis, polycardiography, tetrapolar chest rheography) that ethmozine's antiarrhythmic effect was marked (a more than 75% post-treatment decline in the frequency of extrasystoles at rest and during exercise, provided that paired polytopic extrasystoles and paroxysms of tachycardia are suppressed completely) in 52.1% of SVES patients and 60% of VES patients. Antiarrhythmic action of a 300 mg ethmozine load dose was particularly apparent within 2-7 hours after administration. Ethmozine treatment, as described above, delayed atrioventricular conduction, causing however no significant decrease in heart rate, nor depressing cardiac output and myocardial function; arterial blood pressure and myocardial oxygen requirement remained basically unchanged either. Unlike propranolol effect on cardiac rhythm undulating pattern, there is evidence that ethmozine mechanism of action involves sympathetic activation. Ethmozine had to be discontinued in 10.4% of the 35.4% of patients with side effects.


Exploring nursing students' use of the Fundamentals of Care framework in case-based work.
To explore how nursing students perceive and use the conceptual Fundamentals of Care framework in case-based work in nursing education and furthermore to describe influencing factors on perceptions and use of the framework. The Fundamentals of Care framework has been integrated in core courses in two Schools of Nursing in Region North Denmark in response to studies reporting that nursing students and newly graduated nurses lack the knowledge, skills and competencies to meet the challenges of delivering fundamental care in clinical practice. An integration of the framework in case-based work in nursing education has not previously been studied. The study design was focused ethnography. Data were collected using participant observations, focus group interviews and individual interviews. Four groups of four to five nursing students participating in case-based work sessions and three faculty members from two Schools of Nursing were included. The study adhered to COREQ. The results show an uncertainty among the students about how to understand and use the conceptual framework in case-based work. The uncertainties derive from diversities in faculty members' perceptions and curricular planning among others. However, the framework appears to support the students' learning about what nursing is and requires. The study indicates that integrating Fundamentals of Care framework in case-based work may be one way of teaching nursing students the complexities of integrated fundamental nursing care. However, there is a need to consider how to support students in articulating Fundamentals of Care, and to draw attention to the influence of role models and curricular planning. The study provides knowledge relevant when customising future educational interventions regarding the integration of Fundamentals of Care in nursing education and may provide valuable knowledge of evaluation strategies.


A qualitative study of Telehealth patient information leaflets (TILs): are we giving patients enough information?
The provision of patient information leaflets regarding telehealth has been perceived by potential consumers as a strategy to promote awareness and adoption of telehealth services. However, such leaflets need to be designed carefully if adoption and awareness among potential users is to be promoted. Therefore, the aims of this study were: first, to see how telehealth was portrayed in some of the existing telehealth leaflets (THLs). Second, to explore patients' perceptions of the existing THLs and their engagement with the concept and how THLs can be optimised. A two-step approach was employed to address the aims of this study. The first phase involved the use of discourse analysis to compare 12 electronically and publically available THLs, with the existing THL guidance "Involve Yorkshire and Humber". The second phase involved conducting 14 semi-structured interviews with potential telehealth users/patients to gauge their perception and engagement with the concept, using the two leaflets that were mostly matching with the guidance used. Six interviews were audio-recorded and eight had detailed jotted notes. The interviews were transcribed and thematically analysed to identify key themes. The discourse analysis showed certain gaps and variations within the screened leaflets when addressing the following aspects: cost of the telehealth service, confidentiality, patients' choices in addition to equipment use and technical support. Analysis of the interviews revealed patients' need for having clear and sufficient information about the telehealth service within the THLs; in addition to, patients' preference for the use of simpler terminologies for telehealth description and the provision of clear simple texts with pictorial presentations. The interviews also revealed certain limitations against adoption of telehealth by the participants, such as: lack of privacy and confidentiality of information, fear of technology breakdown and equipment failure, loss of face-to-face contact with healthcare professionals and being too dependent on the telehealth service. The current study showed a great variation among the screened THLs and highlighted certain gaps within the content and presentation of these leaflets. However, the study also highlighted certain key issues to be considered when designing THLs in the future to enhance telehealth uptake and use by patients.


Externally Acquired Radiological Image Data and Reporting for the Clinical Routine, Conference and Boards - Legal Aspects of the Second Opinion in Germany.
Because of an increasing number of boards and conferences, the number of second opinion readings of externally acquired image data is growing dramatically. In this review article we intend to give medical and legal recommendations for the documentation and interpretation of externally acquired radiological data for second opinions and board presentations based on German jurisdiction. Using the FAQ format as a dialog between radiologists and medical legal experts, we answer the most crucial questions regarding correct documentation and interpretation for externally acquired radiological image data based on an up-to-date literature search. Based on the unity of radiological image data and the corresponding written report according to the radiation protection law, the primary report should be present when composing a second opinion. If the primary external report is not present, this should be mentioned as a limitation. All radiological second opinions should be documented in written form. This is especially important in cases of discrepant findings. Legally, the attending physician is responsible for selecting the radiological opinion. The radiologist should not rely on the written primary report without personal reevaluation. Legally, it would be considered radiological malpractice if the external image data and previous image data are not evaluated personally. From a legal point of view, there are explicit recommendations regarding thorough documentation of a second opinion as an independent medical service in all cases. · The written external report should be present when composing a second opinion report or case presentation.. · Second opinions or external case interpretations should be documented in written form.. · It is considered malpractice to completely rely on the external written report for a second opinion.. · In discrepant radiological findings the treating physician is responsible for choosing the correct radiological interpretation.. · Schreyer AG, Rosenberg B, Steinhäuser RT. Externally Acquired Radiological Image Data and Reporting for the Clinical Routine, Conference and Boards - Legal Aspects of the Second Opinion in Germany. Fortschr Röntgenstr 2018; 190: 610 - 615.


Physical activity in patients with advanced-stage cancer actively receiving chemotherapy.
Exercise has mental and physical health benefits for patients with advanced stage cancer who actively receive chemotherapy, yet little is known about patients'levels of interest in becoming more active or their confidence in increasing their activity level. A convenience sample of 128 patients with advanced-stage cancer who were receiving chemotherapy completed self-report measures assessing physical activity level, mood, and quality-of-life variables. Qualitative data on patient-perceived benefits of, and barriers to, physical activity also were collected, coded by independent raters, and organized by predominant themes. Fatigue was the most frequently listed barrier to physical activity; improved physical strength and health were the most commonly listed benefits. Participants identified benefits related to both general health and cancer-symptom management that were related to exercise. Over 50% of participants reported that they were seriously planning to increase or maintain their physical activity level, and 47% reported having interest in receiving an intervention to become more active. Future research will investigate how these findings may be incorporated into physical activity interventions for advanced-stage oncology patients receiving medical treatment.


Positive association between arterial blood lactate level before extra-corporeal membrane oxygenation and 30-day mortality in pediatric patients with severe cardiopulmonary failure.
This study aimed to investigate the relationship between blood lactate level and mortality in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) for severe cardiopulmonary failure. A retrospective observational study was conducted on pediatric patients who received ECMO from January 2013 to December 2021 at the Seventh Medical Center of PLA General Hospital. Patient demographic characteristics, arterial blood lactate level prior to ECMO (pre-ECMO), ECMO settings, ECMO duration, and 30-days mortality were retrieved from patients' medical records. The relationships between pre-ECMO blood lactate level and mortality were interpreted using the logistic regression analysis and Kaplan-Meier survival analysis. A total of 160 pediatric patients who had either refractory respiratory failure (n = 89) or circulatory failure (n = 71) and received ECMO were included in this study. In both the respiratory failure and circulatory failure groups, the non-survivors showed a higher mean pre-ECMO arterial blood lactate level than the survivors. In the respiratory failure group, a pre-ECMO lactate concentration at ≥11.6 mmol/L had a sensitivity of 51% and a specificity of 82% for predicting mortality. In the circulatory failure group, a pre-ECMO lactate concentration at ≥7.2 mmol/L had a sensitivity of 90% and a specificity of 57% for predicting mortality. The Kaplan-Meier survival curves showed that respiratory failure patients with a pre-ECMO lactate level over 11.6 mmol/L or circulatory failure patients with a pre-ECMO lactate level over 7.2 mmol/L had a higher 30-days mortality rate than those with a lower lactate level. High pre-ECMO arterial blood lactate level serves as an independent risk factor for mortality in pediatric patients who receive ECMO for severe cardiopulmonary failure.


A novel investigation of placebo analgesia through social communication in mice.
In rodents, placebo analgesia is often investigated through direct conditioning of stimuli, but humans can experience placebo analgesia through expectation without experience. In this study, we sought to determine whether placebo analgesia could be elicited through social communication. Male and female mice were housed in pairs (designated "Active" and "Bystander") and tested for thermal thresholds on a hot plate (53 °C). Food restriction (1 hr/day) was implemented. The Active mouse was taken to a new cage with food dusted with cocoa (COC) or cinnamon (CINN). The Bystander mice were given regular chow in the home cage. After feeding, the Active mice were given morphine (5 mg/kg, SC) or saline and tested on the hot plate. After 5 pairings of a flavor and treatment (counterbalanced), Active mice were tested following access to a flavored food. Bystander mice were given their first direct exposure to a flavored food and tested on the hot plate. The protocol was repeated with naloxone (10 mg/kg, IP) administered prior to testing. Finally, mice were tested in a two-choice test with both flavored foods available. Active mice showed a conditioned analgesic response to the morphine-paired flavor that was reduced by naloxone. Bystander mice showed a placebo analgesic response to their cagemate's morphine-paired flavor that was not significantly impacted by naloxone. Bystander mice spent more time in the chamber associated with their cagemate's morphine-paired flavor. To our knowledge, this is the first investigation of placebo analgesia without direct conditioning, instead relying on social communication between mice. The lack of effect with naloxone pretreatment suggests an opioid-independent effect in the Bystander mice. Placebo analgesia in mice may be possible without direct conditioning to better model the effect of expectation of a novel analgesic in humans.


Dynamically adjustable SVEIR(MH) model of multiwave epidemics: Estimating the effects of public health measures against COVID-19.
The COVID-19 pandemic was characterized by multiple subsequent, overlapping outbreaks, as well as extremely rapid changes in viral genomes. The information about local epidemics spread and the epidemic control measures was shared on a daily basis (number of cases and deaths) via centralized repositories. The vaccines were developed within the first year of the pandemic. New modes of monitoring and sharing of epidemic data were implemented using Internet resources. We modified the basic SEIR compartmental model to include public health measures, multiwave scenarios, and the variation of viral infectivity and transmissibility reflected by the basic reproduction number R0 of emerging viral variants. SVEIR(MH) model considers the capacity of the medical system, lockdowns, vaccination, and changes in viral reproduction rate on the epidemic spread. The developed model uses daily infection reports for assessing the epidemic dynamics, and daily changes of mobility data from mobile phone networks to assess the lockdown effectiveness. This model was deployed to six European regions Baden-Württemberg (Germany), Belgium, Czechia, Lombardy (Italy), Sweden, and Switzerland for the first 2 years of the pandemic. The correlation coefficients between observed and reported infection data showed good concordance for both years of the pandemic (ρ = 0.84-0.94 for the raw data and ρ = 0.91-0.98 for smoothed 7-day averages). The results show stability across the regions and the different epidemic waves. Optimal control of epidemic waves can be achieved by dynamically adjusting epidemic control measures in real-time. SVEIR(MH) model can simulate different scenarios and inform adjustments to the public health policies to achieve the target outcomes. Because this model is highly representative of actual epidemic situations, it can be used to assess both the public health and socioeconomic effects of the public health measures within the first 7 days of the outbreak.


Prevalence of Self-Reported Food Allergy in Six Regions of Inner Mongolia, Northern China: A Population-Based Survey.
BACKGROUND The aim of this study was to determine the prevalence of self-reported food allergy in 6 regions of Inner Mongolia, northern China. MATERIAL AND METHODS A random cluster sampling population study using a field questionnaire was distributed to 4714 individuals in 6 regions within Inner Mongolia, northern China; the study included ethnic Mongol minorities and Chinese Han populations. The questionnaire obtained data on ethnicity, age, sex, level of education, income, socioeconomic status, rural versus urban location, medical and family history, and food allergy. RESULTS There were 4441 (73.5%) completed questionnaires. The prevalence of self-reported food allergy was 18.0% (15.2% men; 20.6% women) and was age-related, being significantly greater in children compared with adults (38.7% vs. 11.9%) (P<0.001). There was a significant difference in self-reported food allergy between rural and urban populations (14.6% vs. 21.4%) (P<0.001) and between Mongolian and Han populations (20.8% vs. 15.8%) (P<0.001). Socioeconomic status, higher education level, and increased family income were significantly correlated with the prevalence of food allergy (P<0.001). Participants with allergic diseases and atopic family history were at increased risk (OR>1, P<0.001). There were no significant associations between the prevalence of food allergy and birth history, infant feeding, and duration of breastfeeding. CONCLUSIONS An increase in the prevalence of self-reported food allergy was found in the Inner Mongolia region of northern China, which was greater in urban areas compared with rural areas.


Perception of severity of disease and health locus of control in compliant and noncompliant diabetic patients.
Compliant and noncompliant obese, non-insulin-dependent diabetic subjects were assessed using a variety of demographic variables, the health locus of control scale (HLC), and the perception of severity of disease index based on the health belief model. The complaint subjects were significantly older and viewed their illness as significantly more severe than the noncompliant patients. Additionally, they tended to exhibit more of an internal locus of control that the noncompliant patients.


Effects of work zone configurations and traffic density on performance variables and subjective workload.
This paper investigates the effect of changing work zone configurations and traffic density on performance variables and subjective workload. Data regarding travel time, average speed, maximum percent braking force and location of lane changes were collected by using a full size driving simulator. The NASA-TLX was used to measure self-reported workload ratings during the driving task. Conventional lane merge (CLM) and joint lane merge (JLM) were modeled in a driving simulator, and thirty participants (seven female and 23 male), navigated through the two configurations with two levels of traffic density. The mean maximum braking forces was 34% lower in the JLM configuration, and drivers going through the JLM configuration remained in the closed lane longer. However, no significant differences in speed were found between the two merge configurations. The analysis of self-reported workload ratings show that participants reported 15.3% lower total workload when driving through the JLM. In conclusion, the implemented changes in the JLM make it a more favorable merge configuration in both high and low traffic densities in terms of optimizing traffic flow by increasing the time and distance cars use both lanes, and in terms of improving safety due to lower braking forces and lower reported workload.


Prevalence of enterotoxin genes in Aeromonas spp. isolated from children with diarrhea, healthy controls, and the environment.
Aeromonads are causative agents of a number of human infections. Even though aeromonads have been isolated from patients suffering from diarrhea, their etiological role in gastroenteritis is unclear. In spite of a number of virulence factors produced by Aeromonas species, their association with diarrhea has not been clearly linked. Recently, we have characterized a heat-labile cytotonic enterotoxin (Alt), a heat-stable cytotonic enterotoxin (Ast), and a cytotoxic enterotoxin (Act) from a diarrheal isolate of Aeromonas hydrophila. Alt and Ast are novel enterotoxins which are not related to cholera toxin; Act is aerolysin related and has hemolytic, cytotoxic, and enterotoxic activities. We studied the distribution of the alt, ast, and act enterotoxin genes in 115 of 125 aeromonads isolated from 1, 735 children with diarrhea, in all 27 aeromonads isolated from 830 control children (P = 7 x 10(-4) for comparison of rates of isolation of aeromonads from cases versus those from controls), and in 120 randomly selected aeromonads from different components of surface water in Bangladesh. Aeromonas isolates which were positive only for the presence of the alt gene had similar distributions in the three sources; the number of isolates positive only for the presence of the ast gene was significantly higher for the environmental samples than for samples from diarrheal children; and isolates positive only for the presence of the act gene were not found in any of the three sources. Importantly, the number of isolates positive for both the alt and ast genes was significantly higher for diarrheal children than for control children and the environment. Thus, this is the first study to indicate that the products of both the alt and ast genes may synergistically act to induce severe diarrhea. In 26 patients, Aeromonas spp. were isolated as the sole enteropathogen. Analysis of clinical data from 11 of these patients suggested that isolates positive for both the alt and ast genes were associated with watery diarrhea but that isolates positive only for the alt gene were associated with loose stools. Most of the isolates from the three sources could be classified into seven phenospecies and eight hybridization groups. For the first time, Aeromonas eucrenophila was isolated from two children, one with diarrhea and another without diarrhea.


The metabolic response during resistance training and neuromuscular electrical stimulation (NMES) in patients with COPD, a pilot study.
Resistance training and transcutaneous neuromuscular electrical stimulation (NMES) are new modalities in rehabilitation of severely disabled patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to compare the metabolic response during resistance training and during NMES of the quadriceps femoris muscles in patients with COPD entering pulmonary rehabilitation. Pulmonary function, body composition, peak aerobic capacity, the Medical Research Council dyspnoea grade, the one-repetition maximum strength assessment were evaluated in 13 COPD patients. Additionally, peak oxygen uptake, peak minute ventilation and Borg symptom scores were assessed during a resistance training session and a NMES session. The median peak oxygen uptake and median peak minute ventilation during the resistance training session were significantly higher compared to the NMES session. Additionally, these higher metabolic responses were accompanied by higher symptom Borg scores for dyspnoea and leg fatigue. To conclude, the metabolic response was significantly lower during a NMES session compared to a resistance exercise training session in patients with COPD. Nevertheless, both modalities seem to result in an acceptable metabolic response accompanied by a clinically acceptable sensation of dyspnoea and leg fatigue.


[Use of blue-green algae for biogas production].
Perspectives for nature protection and energy-saving, by using blue-green algae, are discussed. Utilization of their phyto biomass for biogas manufacture will lead to the environmental normalization of the Transdniestria and allow one to have about 19,000,000 m3 of methane only from the water area of only one Kremenchug water basin each vegetative period (70 days).


TACTICS, an interactive platform for customized high-content bioimaging analysis.
We describe a modular MATLAB® Toolbox named TACTICS for time-lapse image analysis that meets several requirements not generally offered by currently available software packages: (i) the ability to assess quality of extracted imaging information by directly linking data end points to the original position, (ii) massively parallel analysis of each parameter, for flow cytometry-like assessment of possible relationships between parameters within sub-populations of the images, (iii) options for user control of the tracking such as an interface to restrict the analysis region, (iv) manual correction of automated processes and (v) user interfaces for post-tracking analysis that is linked to the original images, including options to view cell pedigrees and normalized polarization ratios based on fluorescence ratiometric measurements.


Purpose and coping with adversity: A repeated measures, mixed-methods study with young adolescents.
Purpose in life is associated with positive outcomes following adversity, but the mechanisms of this relationship are unclear. In this repeated measures, mixed-methods study, we examined the relationship of purpose to coping with adversity among young adolescents. A sample of 1357 adolescents completed a survey about purpose, negative life events, and positive reframing coping four times at six month intervals. A sub-sample of 91 survey respondents participated in an interview. Surveys were analyzed using fixed-effects and mixed-effects modeling to test the relationship between purpose and coping over time. Interviews were analyzed for purpose, adversity, and coping to understand this relationship as perceived by the participant. Survey results indicate that purpose and positive reframing coping are related and change together over time. Interview results suggest that purpose can be a response to negative experiences. There are likely underlying factors or processes driving the relationship between purpose and positive reframing coping. Some of the potential underlying factors and processes are discussed.


First Report of Severe Acute Graft-Versus-Host Disease After Allogeneic Stem Cell Transplant in a Patient With Myelodysplastic Syndrome Treated With Atezolizumab: Literature Review.
Checkpoint inhibitors have become a widely used and available immunotherapy option for treating a variety of malignancies, including hematological malignancies. Patients receiving these therapies may go on to receive a curative allogeneic hematopoietic stem cell transplant (allo-HSCT). This presents a clinical challenge as the safety and efficacy of HSCT is not well reported in this subset of patients and residual programmed death-ligand 1 inhibition could potentially enhance allogeneic T-cell responses, improving the graft-versus-tumor effect, but also increasing the incidence and severity of immune complications such as graft-versus-host disease (GVHD). Here, this report includes a detailed literature review summarizing all available data on HSCT outcomes in the setting of using checkpoint inhibitor therapy pre-transplant. Moreover, we report a case of acute GVHD after allo-HSCT in a patient with high-risk myelodysplastic syndrome who received prior atezolizumab therapy, highlighting the importance of further research into this specific population in order to improve transplant-related outcomes.


Follicular Graft-versus-host Disease: A Rare Manifestation in a Patient with the Overlap Subtype of Chronic Graft-versus-host Disease.
Graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Although skin involvement is common, generalized follicular eruption as the major clinical manifestation is rare. However, it is important for clinicians to recognize it at the earliest to initiate an appropriate therapy. We report a case of a patient with multiple myeloma who developed extensive hyperkeratotic, lichenoid folliculocentric papules with perifollicular erythema on day 53 following an allogeneic HSCT. The overall clinical and histological findings were consistent with the overlap subtype of chronic follicular GVHD.


[Causes of mechanical afferent loop syndrome after stomach resection in peptic ulcer].
The author observed 27 patients with the adducent loop mechanic syndrome (ALMS), which was caused by scarring deformations, ulcerous and cancer process in the region of anastomosis, constructed after one of Billroth-2 technics, impairing evacuation of the adducent loop content. The diagnosis was established on the basis of clinical findings and pinpointed further by roentgenoscopy and fibrogastroscopy. The presence of helminthic invasion of the liver--opisthordiasis resulted in hepatitis, pancreatitis that would not respond to therapy in patients with ALMS. Conservative measures in this syndrome yield but only a provisional effect. Eighteen patients were operated upon.


Epigenetic resetting of human pluripotency.
Much attention has focussed on the conversion of human pluripotent stem cells (PSCs) to a more naïve developmental status. Here we provide a method for resetting via transient histone deacetylase inhibition. The protocol is effective across multiple PSC lines and can proceed without karyotype change. Reset cells can be expanded without feeders with a doubling time of around 24 h. WNT inhibition stabilises the resetting process. The transcriptome of reset cells diverges markedly from that of primed PSCs and shares features with human inner cell mass (ICM). Reset cells activate expression of primate-specific transposable elements. DNA methylation is globally reduced to a level equivalent to that in the ICM and is non-random, with gain of methylation at specific loci. Methylation imprints are mostly lost, however. Reset cells can be re-primed to undergo tri-lineage differentiation and germline specification. In female reset cells, appearance of biallelic X-linked gene transcription indicates reactivation of the silenced X chromosome. On reconversion to primed status, XIST-induced silencing restores monoallelic gene expression. The facile and robust conversion routine with accompanying data resources will enable widespread utilisation, interrogation, and refinement of candidate naïve cells.


Fruit quality and shelf-life of Sardinian tomato (Solanum lycopersicum L.) landraces.
The conservation and characterization of landraces have key roles in the safeguarding and valorization of agrobiodiversity. Indeed, these plant genetic resources represent an important crop heritage with quality and sensory characteristics that can be of great use to consumers and industry. In addition, the preservation of genetic resources from the risk of progressive genetic erosion, and the enhancement of their potential can contribute to food security and improve the nutritional value of food. Accordingly, this study aimed to investigate a collection of Sardinian tomato landraces for parameters that have determinant roles in evaluating their responses to conservation, and therefore to consumer acceptance. Six Sardinian landraces and two commercial varieties were cultivated in a two-years off-season trial, harvested at two different maturity stages (turning, red-ripe) and characterized using 14 fruit-related quality parameters that define the marketability, nutritional value, and flavor of the fruit. Data were collected at intervals of 10 days, starting from the harvest date and over 30 days of storage under refrigeration. The simultaneous analysis of all the qualitative characteristics for the different genotypes allowed to clearly differentiate the local varieties from the commercial varieties and a few landraces emerged for their satisfactory performances, e.g. "Tamatta kaki" ad "Tamatta groga de appiccai". In particular, the "Tamatta groga de appiccai" showed satisfactory lycopene content at marketable stages (average 5.65 mg 100g-1 FF), a peculiar orange-pink color with the highest hue angle values (range: H°T0 = 72.55-H°T30 = 48.26), and the highest firmness among the landraces of the red-ripe group (range: EpT0 = 1.64-EpT30 = 0.54 N mm-1). These results highlight the potential of some of the Sardinian tomato landraces for developing new varieties or promoting their direct valorization in local markets and could considerably increase the effectiveness and efficiency of agrobiodiversity conservation strategies.


A dual controllability analysis of influenza virus-host protein-protein interaction networks for antiviral drug target discovery.
Host factors of influenza virus replication are often found in key topological positions within protein-protein interaction networks. This work explores how protein states can be manipulated through controllability analysis: the determination of the minimum manipulation needed to drive the cell system to any desired state. Here, we complete a two-part controllability analysis of two protein networks: a host network representing the healthy cell state and an influenza A virus-host network representing the infected cell state. In this context, controllability analyses aim to identify key regulating host factors of the infected cell's progression. This knowledge can be utilized in further biological analysis to understand disease dynamics and isolate proteins for study as drug target candidates. Both topological and controllability analyses provide evidence of wide-reaching network effects stemming from the addition of viral-host protein interactions. Virus interacting and driver host proteins are significant both topologically and in controllability, therefore playing important roles in cell behavior during infection. Functional analysis finds overlap of results with previous siRNA studies of host factors involved in influenza replication, NF-kB pathway and infection relevance, and roles as interferon regulating genes. 24 proteins are identified as holding regulatory roles specific to the infected cell by measures of topology, controllability, and functional role. These proteins are recommended for further study as potential antiviral drug targets. Seasonal outbreaks of influenza A virus are a major cause of illness and death around the world each year with a constant threat of pandemic infection. This research aims to increase the efficiency of antiviral drug target discovery using existing protein-protein interaction data and network analysis methods. These results are beneficial to future studies of influenza virus, both experimental and computational, and provide evidence that the combination of topology and controllability analyses may be valuable for future efforts in drug target discovery.


Persistence of antifouling agents in the marine biosphere.
Risk indicators provide an interesting way to compare chemical substances with respect to the risks of their large-scaled release. The present study implies that, for antifouling agents used in commercial shipping, residence times in the marine biosphere are especially suitable to represent their inherent potential to cause exposure of organisms. A simple box model is described providing the possibility to estimate residence times in the marine biosphere from water-particle equilibrium partitioning constants and half-lives in water and sediment. Resulting residence times in the marine biosphere range from about 5 d (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) up to about 40,000 yr (copper). For an evaluation of the validity of the model, calculated values are compared with measured environmental concentrations. Remaining uncertainties are also discussed. The main purpose of the presented residence times is to serve as a basis for decisions in antifouling paint development or environmentally conscious purchasing of antifouling paints.


[Hyperosmolar diabetic coma without ketoacidosis in purulent meningitis (author's transl)].
Hyperosmolar diabetic coma without ketoacidosis was observed as a complication of purulent meningitis in 3 patients. Diagnostic difficulties arise due to slow onset of hyperosmolality and misinterpretation of organic cerebral fits and the increasing disturbance of consciousness. Therapy is complicated by the necessity of treatment with anticonvulsants and sodium containing antibiotics which affect sugar and sodium balance. Abrupt lowering of serum osmolality leads to further increase of cerebral oedema. Slow normalisation of blood sugar and sodium values over several days may lead to satisfactory outcome despite unconsciousness of long duration. These complications could be overcome with high doses of insulin and large amounts of hypotonic infusion in two patients, one female succumbed.


Therapeutic Effects of Curcumol in Several Diseases; An Overview.
Curcumae Rhizoma, also known as Ezhu is a traditional Chinese medicine that has been used for many centuries against several diseases. The rhizome of the plant is composed of curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin), and essential volatile oils including curcumol, curdione, and germacrone. While curcuminoids have been extensively studied for their antimicrobial, antioxidant, anti-inflammatory and anticancer properties, the therapeutic efficacy of curcumol is still emerging. Recent studies have shown anticancer properties of curcumol against multiple solid tumors such as breast, colorectal, head and neck, and lung adenocarcinomas. The underlying anti-tumor mechanisms revealed inhibition of several signaling pathways (NF-κB, MAPK, PI-3K/AKT, and GSK-3β) associated with cell proliferation, survival, anti-apoptosis, invasion and metastasis. Besides curcumol, extracts from the Curcumae Rhizoma roots possess many other terpenoids such as β-elemene, δ-elemene, germacrone, furanodiene and furanodienone with known anticancer properties. In this review, we comprehensively focused on the composition of Curcumae Rhizoma essential oils, their structure, isolation and therapeutic uses of curcumol to aid in the improvement and development of novel drugs with minimal cytotoxicity, enhanced efficacy, and less cost.


Superionic behavior in polyethylene-oxide-based single-ion conductors.
We demonstrate superionic ion conduction in simulations of a poly(ethylene oxide)-based polymer electrolyte. The superionic conduction uses cation hopping via chain-like ion aggregates, enabling long-range charge transfer while ions only move locally. The Na single-ion conductor achieves two essential features of superionic metal ion conductors: one-dimensional ion structure and immobile anions. The superionic conduction depends on the number and length of conduction pathways, the conduction pathway lifetime, and the rate at which end ions join and leave the pathway.