Influence of Horizontal Centrifugation Processes on the Content of Phenolic Secoiridoids and Their Oxidized Derivatives in Commercial Olive Oils: An Insight by Liquid Chromatography-High-Resolution Mass Spectrometry and Chemometrics.
Reversed-phase liquid chromatography with electrospray ionization-high-resolution/accuracy Fourier transform mass spectrometry (RPC-ESI-FTMS) and chemometrics were exploited to evaluate the influence of horizontal centrifugation by two- or three-phase decanters on the content of major phenolic secoiridoids in extravirgin olive oils (EVOOs). Despite the occurrence of other potential sources of variability typical of commercial olive oils, horizontal centrifugation was found to play a primary role, with a general increase of secoiridoid content occurring when two-phase decanters were used. As emphasized by principal component analysis (PCA), the increase involved preferentially oleacin and oleocanthal, when oxidative deterioration was purposely minimized during and/or after production, and oleuropein and ligstroside aglycones, when no vertical centrifugation was performed at the end of the productive cycle. The influence of the type of horizontal centrifugation was also emphasized by the elaboration of RPC-ESI-FTMS data based on hierarchical cluster analysis (HCA) and linear discriminant analysis (LDA).


"Union is strength": how weak hydrogen bonds become stronger.
Recently reported rotational spectroscopic studies on small dimers and oligomers bound by weak hydrogen bonds show that the driving forces, the spatial arrangement and the dynamical features displayed are very different from those involved in stronger and conventional hydrogen bonds. The very small binding energies (similar to those of van der Waals interactions) imply that the stabilization of the dimer is often obtained by networks of weak hydrogen bonds. Even in the presence of multiple bonds the partner molecules show a high degree of internal freedom within the complex. This paper analyses several examples of molecular adducts bound by weak hydrogen bonds formed in free jet expansions and recently characterized by rotational spectroscopy. They include weakly bound complexes of weak donors with strong acceptors (C-H···O,N, S-H···O,N), strong donors (O-H, N-H) with weak acceptors such as the halogen atoms and π systems but also the elusive interactions between weak donors and weak acceptors (C-H···π and C-H···halogen). Examples are also given where rotational spectroscopy highlights that weak hydrogen bonds are extremely important in chiral recognition phenomena and as driving forces of the conformational landscape of important biomolecules.


Expert consensus workshop report: Guideline for three-dimensional printing template-assisted computed tomography-guided 125I seeds interstitial implantation brachytherapy.
Radioactive 125I seeds (RIS) interstitial implantation brachytherapy has been a first-line treatment for early-stage cancer of the prostate gland. However, its poor accuracy and homogeneity has limited its indication and hampered its popularization for a long time. Intriguingly, scholars based in China introduced computed tomography (CT)-guided technology to improve the accuracy and homogeneity of RIS implantation and broadened the indications. Then, they creatively designed and introduced three-dimensional printing coplanar template (3D-PCT) and 3D printing noncoplanar template (3D-PNCT) into the practice of RIS implantation. Use of such templates makes RIS implantation more precise and efficacious and aids preoperative planning, real-time dose optimization, and postoperative planning. However, studies on the standard workflow for 3D-PT-assisted CT-guided RIS implantation have not been published. Therefore, the China Northern Radioactive Seeds Brachytherapy Group organized multidisciplinary experts to formulate the guideline for this emerging treatment modality. This guideline aims at standardizing 3D-PT-assisted CT-guided RIS implantation procedures and criteria for selecting treatment candidates and assessing outcomes and for preventing and managing postoperative complications.


Spinal blockage of CXCL1 and its receptor CXCR2 inhibits paclitaxel-induced peripheral neuropathy in mice.
Painful peripheral neuropathy is the most dose-limiting side effect of paclitaxel (PTX), a widely used anti-cancer drug to treat solid tumours. The understanding of the mechanisms involved in this side effect is crucial to the development of new therapeutic approaches. CXCL1 chemokine and its receptor CXCR2 have been pointed as promising targets to treat chronic pain. Herein, we sought to evaluate the possible involvement of CXCL1 and CXCR2 in the pathogenesis of PTX-induced neuropathic pain in mice. PTX treatment led to increased levels of CXCL1 in both dorsal root ganglion and spinal cord samples. Systemic treatment with the anti-CXCL1 antibody (10 μg/kg, i.v.) or the selective CXCR2 antagonist (SB225002, 3 mg/kg, i.p.) had minor effect on PTX-induced mechanical hypersensitivity. On the other hand, the intrathecal (i.t.) treatment with anti-CXCL1 (1 ng/site) or SB225002 (10 μg/site) consistently inhibited the nociceptive responses of PTX-treated mice. Similar results were obtained by inhibiting the PI3Kγ enzyme a downstream pathway of CXCL1/CXCR2 signalling with either the selective AS605240 (5 μg/site, i.t.) or the non-selective wortmannin PI3K inhibitor (0.4 μg/site, i.t.). Overall, the data indicates that the up-regulation of CXCL1 is important for the development and maintenance of PTX-induced neuropathic pain in mice. Therefore, the spinal blockage of CXCL1/CXCR2 signalling might be a new innovative therapeutic approach to treat this clinical side effect of PTX.


SNOT-22 validation in greek patients.
Chronic rhinosinusitis (CRS) with or without nasal polyps is a frequent and significant health problem. The 22-item Sinonasal Outcome Test (SNOT-22) is a valid, disease-specific health status instrument translated into several languages. The translation into Greek has been considered essential for the individual assessment of the patients' symptoms and a reliable tool for quality of life evaluation. Our study included 40 patients with CRS without nasal polyps and 40 healthy individuals as control group recruited from the ENT Allergy and Endoscopy Clinic of Chania General Hospital. Assessment included full ENT examination and nasal endoscopy. In the study, we compared the patients' examination and reexamination results with the results of the control group, and thus estimated test-retest reliability, internal consistency (determined by Cronbach's alpha) and validity. The statistical significance level calculated by the paired t test was p < 0.05 for all questions, which proves the questionnaire's consistency. The kappa value was estimated for each symptom, with an average value of 0.94. Cronbach's alpha was 0.934 in the test and 0.856 in the retest. The p value was <0.05 between both the control group and the test group and between the control group and the retest group. Our study certifies the existence of a valid, reproducible Greek version of SNOT-22, which overcomes limitations of use, allows to answer the questionnaire in Greek, and thus makes it highly recommended for Greek clinicians.


Effects of antiresorptive treatment on nonvertebral fracture outcomes.
Various definitions of nonvertebral fracture have been used in osteoporosis trials, precluding comparisons of efficacy. Using only subgroups of nonvertebral fractures for trial outcomes may underestimate the benefits and cost-effectiveness of treatments. The objectives of this study were to determine (1) the effect of antiresorptive treatment on various nonvertebral fracture outcomes, (2) whether risk reduction from antiresorptive treatment is greater for nonvertebral fractures that have stronger associations with low BMD, and (3) sample size estimates for clinical trials of osteoporosis treatments. Study-level data were combined from five randomized fracture-prevention trials of antiresorptive agents that reduce the risk of nonvertebral fracture in postmenopausal women: alendronate, clodronate, denosumab, lasofoxifene, and zoledronic acid. Pooled effect estimates were calculated with random-effects models. The five trials included 30,118 women; 2997 women had at least one nonvertebral fracture. There was no significant heterogeneity between treatments for any outcome (all p > 0.10). Antiresorptive treatment had similar effects on all fractures (summary hazard ratio [HR] = 0.76, 95% CI 0.70-0.81), high-trauma fractures (HR = 0.74, 95% CI 0.57-0.96), low-trauma fractures (HR = 0.77, (95% CI 0.71-0.83), nonvertebral six (ie, hip, pelvis, leg, wrist, humerus, and clavicle) fractures (HR = 0.73, 95% CI 0.66-0.80), other than nonvertebral six fractures (HR = 0.78, 95% CI 0.70-0.87), and all fractures other than finger, face, and toe (HR = 0.75, 95% CI 0.70-0.81). Risk reduction was not greater for fractures with stronger associations with low BMD (p = 0.77). A trial of all nonvertebral fractures would require fewer participants (n = 2641 per arm) than one of a subgroup of six fractures (n = 3289), for example. In summary, antiresorptive treatments reduced all nonvertebral fractures regardless of degree of trauma or special groupings, supporting the use of all nonvertebral fractures as a standard endpoint of osteoporosis trials and the basis for estimating the benefits and cost-effectiveness of treatments.


Scanning electron microscopy of evaporating ice.
Direct observation of evaporating ice with a scanning electron microscope indicates that the surfaces of single-crystal and polycrystalline ice are markedly different. In specimens of single-crystal ice the crystal planes are revealed by evaporation, whereas polycrystalline ice develops a fibrous surface.


A genetic upper limit to whole-body protein deposition in a strain of growing pigs.
The genetic upper limit to daily whole-body protein deposition (Pdmax) is an important constraint on pig growth. The Pdmax was determined for a specified pig genotype using N balance and serial slaughter techniques. A traditional N-balance study, involving 36 and 90 kg of BW Large White x (Landrace x Large White) entire male pigs, was first conducted to demonstrate that a highly digestible, nutrient-dense diet (1.54% Lys; 18 MJ of DE/kg, air-dried basis) was able to support the attainment of Pdmax within the constraints of pig appetite. Animals were allocated to set levels of feed intake [set proportions of ad libitum DE intake (DEi), 50 to 100%]. Nitrogen retention increased linearly with DEi up to 25.3 and 35.2 MJ of DE/d for the 36 and 90 kg of BW pigs, respectively, then showed a departure (P < 0.05) from linearity. For DEi of the experimental diet above the latter intakes, which were approximately 80% of a determined ad libitum DEi, the pigs deposited protein at a rate approaching Pdmax. When a linear plateau response model (accepted a priori) was fitted, Pdmax values of 189.9 g/d at a DEi breakpoint of 28.3 MJ of DE/d at 36 kg of BW and 186.4 g/d at a DEi breakpoint of 37.3 MJ of DE/d at 90 kg of BW were found. In the serial slaughter study, 18 female and 18 entire male pigs were allocated to 5 slaughter BW (25, 45, 65, 85, and 110 kg) such that there were 5, 3, 3, 3, and 4 animals of each sex at each slaughter weight, respectively. Animals were fed the experimental diet ad libitum, and whole-body protein was determined at slaughter. Growth data were analyzed by differentiating and combining continuous mathematical functions for BW and body composition. The ad libitum DEi were 27.4 and 50.7 MJ/d at 36 and 90 kg of BW for the entire males and were assumed, based on the N-balance results, sufficiently high to allow expression of Pdmax. There was an effect (P < 0.05) of sex on Pdmax vs. time (days on trial). Over the BW range of 25 to 85 kg, Pdmax was constant for the entire male and female pigs at 170 and 147 g/d, respectively. Above 85 kg of BW, Pdmax was no longer constant for either sex.


Fluid and Salt Balance and the Role of Nutrition in Heart Failure.
The main challenges in heart failure (HF) treatment are to manage patients with refractory acute decompensated HF and to stabilize the clinical status of a patient with chronic heart failure. Beyond the use of medications targeted in the inhibition of the neurohormonal system, the balance of salt and fluid plays an important role in the maintenance of clinical compensation in respect of renal function. In the case of heart failure, a debate of opinion exists on salt restriction. Restricted dietary sodium might lead to worse outcomes in heart failure patients due to the activation of the neurohormonal system and malnutrition. On the contrary, positive sodium balance is the primary driver of water retention and, ultimately, volume overload in acute HF. Some recent studies reported associations of decreased salt consumption with higher readmission rates and increased mortality. Thus, the usefulness of salt restriction in heart failure management remains debated. The use of individualized nutritional support, compared with standard hospital food, was effective in reducing these risks, particularly in the group of patients at high nutritional risk.


Skull base osteomyelitis in the emergency department: a case report.
Skull base osteomyelitis (SBO) is a rare clinical presentation and usually occurs as a complication of trauma or sinusitis. A 5-year-old child presented to the emergency department with a three-week history of fever associated with drowsiness and left parietal headache, and a week's history of swelling on the left frontoparietal soft tissue. He had suffered a penetrating scalp injury four month ago. On physical examination, there was a tender swelling with purulent stream on the lateral half of his scalp. His vital signs are within normal limits. Plain X-ray of the skull showed a lytic lesion on the left frontoparietal bone. A cranial computed tomography (CT) scan demonstrated a large subgaleal abscess at the left frontoparietal region. SBO possesses a high morbidity and mortality; therefore, prompt diagnosis and appropriate treatment are mandatory to prevent further complications and to reduce morbidity and mortality significantly.


Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.
SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.


In vitro production of interferon-gamma by peripheral blood from patients with Graves' disease, Hashimoto's thyroiditis and rheumatoid arthritis.
The production of interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells (PBMC), CD4 cells, or CD8 cells in response to interleukin-2 (IL-2) stimulation has been studied; the samples were obtained from 12 healthy control subjects, 19 patients with Graves' disease (10 hyperthyroid and nine euthyroid), 13 patients with Hashimoto's thyroiditis (four hypothyroid and nine euthyroid), and 15 patients with rheumatoid arthritis (11 active and four inactive). A dose of IL-2 (25 U/ml) was utilized to induce IFN-gamma by PBMC from all four groups. The incremental increase in IFN-gamma values (with IL-2 stimulation minus without stimulation) was significantly less in PBMC from patients with Graves' disease, Hashimoto's thyroiditis, and rheumatoid arthritis than that in PBMC from control subjects. The values from PBMC in patients with Graves' disease in a euthyroid state were below normal but greater than those from patients with Graves' disease in a hyperthyroid state. The incremental increase in IFN-gamma values from Graves' disease PBMC correlated with the serum TSH values (r = 0.622, P less than 0.01), but not with thyroid autoantibodies (anti-thyroid microsomal antibodies, anti-thyroid microsomal antibodies, nor TSH-binding inhibitory immunoglobulin activities). The incremental increase in IFN-gamma from PBMC from both control subjects and Graves' disease was correlated with that from CD4 cells (r = 0.711, P less than 0.01), but not with that from CD8 cells. The production of IFN-gamma in response to IL-2 from PBMC in Graves' disease correlated inversely with thyroid function, appearing to reflect the very effect of hyperthyroidism in this process. The precise explanation of these phenomena remains unclear. The decreased response of IFN-gamma to IL-2 stimulation by PBMC from patients with Graves' disease, Hashimoto's thyroiditis, and rheumatoid arthritis seems to be a non-specific phenomenon occurring in both organ specific autoimmune disease and systemic autoimmune disease. It may be due to a down-regulation in autoimmune disease of CD4 cells in response to IL-2, a decreased level of IL-2 cellular receptors or a decreased receptor affinity, associated increased soluble IL-2 receptors, or a defect of the intra-CD4 cellular IL-2 signal to produce or release IFN-gamma in the conditions studied.


A culture of genius: how an organization's lay theory shapes people's cognition, affect, and behavior.
Traditionally, researchers have conceptualized implicit theories as individual differences-lay theories that vary between people. This article, however, investigates the consequences of organization-level implicit theories of intelligence. In five studies, the authors examine how an organization's fixed (entity) or malleable (incremental) theory of intelligence affects people's inferences about what is valued, their self- and social judgments, and their behavioral decisions. In Studies 1 and 2, the authors find that people systematically shift their self-presentations when motivated to join an entity or incremental organization. People present their "smarts" to the entity environment and their "motivation" to the incremental environment. In Studies 3a and 4, they show downstream consequences of these inferences for participants' self-concepts and their hiring decisions. In Study 3b, they demonstrate that the effects are not due to simple priming. The implications for understanding how environments shape cognition and behavior and, more generally, for implicit theories research are discussed.


In vitro characterization of the metabolism of haloperidol using recombinant cytochrome p450 enzymes and human liver microsomes.
A systematic in vitro study was carried out to elucidate the enzymes responsible for the metabolism of haloperidol (HAL) using human liver microsomes and recombinant human cytochrome P450 isoenzymes. In the first series of experiments, recombinant cytochrome P450 (P450) isoenzymes were used to evaluate their catalytic involvement in the metabolic pathways of HAL. Recombinant CYP3A4, CYP3A5, and CYP1A1 were shown to be able to catalyze the metabolism of HAL to its pyridinium analog (HP(+)) and the oxidation of reduced HAL (RH) back to HAL; Recombinant CYP3A4, CYP3A5, CYP1A1, CYP2C19, CYP2C8, CYP2C9, and CYP2D6 were able to catalyze the dealkylation of HAL to 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP). CYP3A4 was capable of metabolizing HAL to its tetrahydropyridine analog 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydropyridine and metabolizing to CPHP; CYP3A4 and CYP3A5 were able to metabolize RH to its pyridinium analog (RHP(+)); CYP1A1, CYP1A2, and CYP3A4 were able to catalyze the oxidation of RHP(+) to HP(+). In the second series of experiments, the metabolic activities of human liver microsomes from 12 donors were correlated with catalytic activities of selective substrates of different P450 isoenzymes and immuno-reactivities toward different P450 isoenzymes. CYP3A4 activities were found to correlate to all the seven metabolic pathways of HAL mentioned above. This suggests a prominent role for CYP3A4 in the metabolism of HAL. Interestingly, it was found that recombinant CYP1A1 has the highest activity for oxidizing RHP(+) to HP(+). The activity of recombinant CYP1A1 was 50 times higher than CYP1A2 and 220 times higher than CYP3A4.


BCL7B, a predictor of poor prognosis of pancreatic cancers, promotes cell motility and invasion by influencing CREB signaling.
The functions of B-cell CLL/lymphoma 7B (BCL7B) are unknown and the protein lacks any known functional domains. The aim of this study was to investigate the role of BCL7B in the motility and invasiveness of pancreatic cancer cells. Immunohistochemistry was performed to determine whether high BCL7B expression in human pancreatic cancer tissues is correlated with poor prognosis. High BCL7B expression was an independent predictor of worse overall survival of pancreatic cancer patients. Immunocytochemistry showed that BCL7B was accumulated in cell protrusions of migrating pancreatic cancer cells. Knockdown of BCL7B inhibited the motility and invasiveness of pancreatic cancer cells through a decrease in cell protrusions. Phosphoprotein array analysis was performed to determine BCL7B-associated intracellular signaling pathways. Suppression of BCL7B increased phosphorylated CREB expression in pancreatic cancer cells, and knockdown of CREB promoted the motility and invasiveness by increasing cell protrusions. The combined data suggest that BCL7B promotes pancreatic cancer cell motility and invasion through a signaling pathway that involves dephosphorylation of CREB.


A neural mechanism for exacerbation of headache by light.
The perception of migraine headache, which is mediated by nociceptive signals transmitted from the cranial dura mater to the brain, is uniquely exacerbated by exposure to light. We found that exacerbation of migraine headache by light is prevalent among blind individuals who maintain non-image-forming photoregulation in the face of massive rod/cone degeneration. Using single-unit recording and neural tract tracing in the rat, we identified dura-sensitive neurons in the posterior thalamus whose activity was distinctly modulated by light and whose axons projected extensively across layers I-V of somatosensory, visual and associative cortices. The cell bodies and dendrites of such dura/light-sensitive neurons were apposed by axons originating from retinal ganglion cells (RGCs), predominantly from intrinsically photosensitive RGCs, the principle conduit of non-image-forming photoregulation. We propose that photoregulation of migraine headache is exerted by a non-image-forming retinal pathway that modulates the activity of dura-sensitive thalamocortical neurons.


Ponatinib for the treatment of adult patients with resistant or intolerant Chronic-Phase Chronic Myeloid Leukemia.
Patients with chronic myeloid leukemia in chronic phase (CP-CML) who are resistant or intolerant to second-generation tyrosine kinase inhibitors (TKIs) may benefit from treatment with a third-generation TKI, like ponatinib. In this review, the authors discuss the role of ponatinib, an oral pan-inhibitor of BCR-ABL1, with potent activity in heavily pretreated patients, including T315I mutation. In the long-term follow-up of the PACE trial, 60% of patients with prior TKIs exposure achieved a major cytogenetic response with ponatinib and 40% a major molecular response; 5-year overall survival was 73%. Cardiovascular adverse events represent the major toxicity associated with ponatinib. Adopting a dose-reduction approach appeared to be safe: starting with 45 or 30 mg and decreasing to 15 mg once BCR-ABL1/ABL1≤1% is achieved. In patients who are not candidates for ponatinib therapy, asciminib or other novel TKIs like HQP1351, represent alternative options. In patients with CP-CML resistant or intolerant to second-generation TKIs, we favor using a third-generation TKI such as ponatinib. Although we initiate a donor search as soon as a patient fails a second-generation TKI, we still prefer treating patients with ponatinib and will only consider transplantation in the event of no response or disease progression.


Juvenile aggressive fibromatosis.
A case study of a fibromatosis occurring in a 3 year old male is discussed, where a clinical diagnosis of juvenile aggressive fibromatosis was reached after correlating clinical and histopathological findings.


Racial differences in the distribution of anterior circulation occlusive disease.
We compared clinical and angiographic features of 26 white and 45 black patients with symptomatic occlusive cerebrovascular disease. White patients had more transient ischemic attacks, carotid bruits, and more severe occlusive disease of the internal carotid artery origin. Blacks had more severe disease of the middle cerebral artery stem and supraclinoid internal carotid arteries. Differences were not explained by racial differences in the prevalence of hypertension, diabetes, hypercholesterolemia, or ischemic heart disease. Since the middle cerebral artery lesions in blacks do not correlate with other accepted epidemiologic, clinical, and laboratory markers of atherosclerosis, the lesions may arise from a disorder that differs from atherosclerosis.


A novel motion tracking system for evaluation of functional rehabilitation of the upper limbs.
Upper limb function impairment is one of the most common sequelae of central nervous system injury, especially in stroke patients and when spinal cord injury produces tetraplegia. Conventional assessment methods cannot provide objective evaluation of patient performance and the tiveness of therapies. The most common assessment tools are based on rating scales, which are inefficient when measuring small changes and can yield subjective bias. In this study, we designed an inertial sensor-based monitoring system composed of five sensors to measure and analyze the complex movements of the upper limbs, which are common in activities of daily living. We developed a kinematic model with nine degrees of freedom to analyze upper limb and head movements in three dimensions. This system was then validated using a commercial optoelectronic system. These findings suggest that an inertial sensor-based motion tracking system can be used in patients who have upper limb impairment through data integration with a virtual reality-based neuroretation system.


A Study of the Discharge Mechanism of ZnO.
The discharge of negatively charged ZnO powder samples has been measured. The shape of the recorded discharge curves predicts a charge decay which is governed by two different mechanisms. Experiments with a point counter indicate that there is emission of negative charge during the first minutes of the discharge in the dark, as well as under illumination. When, simultaneously with the latter experiments, the discharge curve of the sample is recorded, it can be seen that emission of negative charge cannot be responsible for the complete discharge of the sample. Evidence is presented that there is a second mechanism which corresponds to the final part of the recorded decay curve. A study of the light decay curves of ZnO layers indicates that this second discharge mechanism is very sensitive to light in the fundamental absorption edge (380 nm). Even so, yellow ZnO seems to be very sensitive to illumination in the b band (400 nm). We observed the spectral sensitivity of the slope of the final part of the decay curves. As a result of these experiments, we concluded that, in the second mechanism, the negative surface charge is neutralized by means of positive charges present in the surface zone of ZnO. Finally, the complete discharge in the dark as well as under illumination can be described as follows: after the height of the potential barrier has been decreased considerably as the result of discharge by emission, a second mechanism becomes important. In this mechanism, electrons from the negative surface charge can easily pass the surface barrier and recombine with positive charges in the surface zone of ZnO.


Chromosome breakage syndromes and cancer.
There exist numerous genetic disorders, marked by chromosome instability, that are strikingly associated with various cancers. Both the chromosomal instabilities and neoplastic outcomes are related to abnormalities of DNA metabolism, DNA repair, cell-cycle governance, or control of apoptosis. Among these diseases are ataxia telangectasia and Nijmegen breakage syndrome, with increased incidences of lymphomas. Bloom syndrome, Werner syndrome, and Rothmund-Thompson syndrome, each characterized by a DNA helicase defect, are associated with early incidences of different cancers. Other diseases combining the phenotype of chromosomal instabilities and neoplastic development are Fanconi anemia and breast cancers associated with mutant BRCA1 and BRCA2 genes. The cloning of the encoding genes and the characterization of their products have resulted in partial understanding of the pathways of cellular DNA surveillance and maintenance of genomic rectitude. The exact pathways fully linking the genetic defect mechanisms to the eventual development of various neoplasias remain to be elucidated, but progress in defining the molecular genetics of these entities suggests that many of them are disorders of DNA recombination. Each defect involves a separate protein in these complex pathways.


Guide wire thrombogenicity measured by fibrinopeptide A radioimmunoassay.
A radioimmunoassay for measurement of canine fibrinopeptide A, which provides a quantitative index of thrombin action on canine fibrinogen, was applied to measurements of the thrombogenicity of angiographic guide wires. Benzalkonium-heparin-treated Teflon-coated, untreated Teflon-coated, and uncoated stainless steel wires were compared in an experiment in dogs which closely simulated the use of these wires in humans. During the first 4 min after insertion, the benzalkonium-heparin-treated Teflon-coated wire was associated with significantly greater systemic levels of fibrinopeptide A than were either Teflon-coated or stainless steel wires. Beyond 10 min, markedly increased levels of fibrinopeptide A were measured in association with these latter two wires compared to the benzalkonium-heparin-treated Teflon-coated wire. Both the early rises in fibrinopeptide A associated with the benzalkonium-heparin-treated Teflon-coated wire and the late increases in fibrinopeptide A associated with the Teflon-coated and uncoated stainless steel wires could be eliminated by prior systemic administration of low dose heparin (40U/kg). These studies suggest that, at least in regard to activation of the plasma clotting system, the benzalkonium-heparin treatment offered no advantages over the other wires tested in terms of reduced thrombogenicity within the critical 10 min following insertion. No difference could be discerned between uncoated stainless steel wires and Teflon-coated stainless steel guide wires in this test.


Isolation and multiplex genotyping of polymorphic microsatellite DNA markers in the snakehead murrel, Channa striata.
Seven polymorphic microsatellite loci were isolated and characterized for the snakehead murrel, Channa striata (Channidae), a valuable tropical freshwater fish species. Among 25 specimens collected from Kedah state in Malaysia, the number of alleles per locus ranged from 2 to 7. Observed and expected heterozygosities ranged from 0.120 to 0.880 and 0.117 to 0.698, respectively. A single locus (CS1-C07) was significantly deviated from Hardy-Weinberg equilibrium after Bonferroni correction. These novel markers would be useful for population genetic studies of the C. striata.


Effect of estrogen on melanocortin-3 receptor mRNA expression in mouse pituitary glands in vivo and in vitro.
Alpha-melanocyte-stimulating hormone (alpha-MSH) stimulates prolactin (PRL) release and mammotrope proliferation in mouse anterior pituitary glands. The present study investigated the regulation of melanocortin-3 receptor (MC3-R) mRNA levels in mice using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Relative MC3-R mRNA levels in the anterior lobes of female mice increased between 20 and 45 days of age, and a significant difference in MC3-R mRNA expression between sexes was seen at 45 days. Ovariectomy decreased MC3-R mRNA expression in the female anterior lobes, and estradiol-17beta (E(2)) treatment increased MC3-R mRNA levels in ovariectomized mouse anterior lobes and cultured anterior pituitary cells. E(2) treatment increased proopiomelanocortin (POMC) mRNA levels in ovariectomized mouse neurointermediate lobes and cultured neurointermediate pituitary cells. On the other hand, E(2) treatment did not affect POMC mRNA expression in mouse anterior lobes or cultured anterior pituitary cells. These results suggest that alpha-MSH directly stimulates PRL release and mammotrope proliferation through MC3-Rs expressed in mammotropes, while estrogen stimulates MC3-R gene transcription in the anterior pituitary cells and POMC gene transcription in the intermediate lobes. In lactating mice, POMC mRNA levels in the neurointermediate lobes were elevated compared with in non-lactating mice. The present study suggests that alpha-MSH is involved in augmented PRL secretion by estrogen and during lactation.


ICAM-1 triggers liver regeneration through leukocyte recruitment and Kupffer cell-dependent release of TNF-alpha/IL-6 in mice.
Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mediate hepatocyte proliferation in vivo, suggesting that local and systemic inflammatory reactions may trigger hepatic regeneration after major tissue loss. Wild-type, intercellular adhesion molecule (ICAM)-1-/-, and neutropenic-induced mice were subjected to 70% hepatectomy. Three different approaches to block and/or deplete liver macrophages (Kupffer cells) were used. We found that liver from ICAM-1-deficient mice exhibited impaired regeneration after partial hepatectomy. This finding is associated with dramatic decrease in leukocyte recruitment and tissue TNF-alpha and IL-6 levels. All markers of hepatocyte proliferation were restored in ICAM-/- mice by injections of recombinant IL-6. Neutropenic animals and liver macrophage (Kupffer cell) depletion resulted in similar failure of regeneration with low levels of TNF-alpha and IL-6. The data suggest a novel pathway in which ICAM-1 binds to leukocytes after hepatectomy, triggering hepatocyte proliferation through Kupffer cell-dependent release of TNF-alpha and IL-6.


Nck adaptor proteins link Tks5 to invadopodia actin regulation and ECM degradation.
Invadopodia are actin-based projections enriched with proteases, which invasive cancer cells use to degrade the extracellular matrix (ECM). The Phox homology (PX)-Src homology (SH)3 domain adaptor protein Tks5 (also known as SH3PXD2A) cooperates with Src tyrosine kinase to promote invadopodia formation but the underlying pathway is not clear. Here we show that Src phosphorylates Tks5 at Y557, inducing it to associate directly with the SH3-SH2 domain adaptor proteins Nck1 and Nck2 in invadopodia. Tks5 mutants unable to bind Nck show reduced matrix degradation-promoting activity and recruit actin to invadopodia inefficiently. Conversely, Src- and Tks5-driven matrix proteolysis and actin assembly in invadopodia are enhanced by Nck1 or Nck2 overexpression and inhibited by Nck1 depletion. We show that clustering at the plasma membrane of the Tks5 inter-SH3 region containing Y557 triggers phosphorylation at this site, facilitating Nck recruitment and F-actin assembly. These results identify a Src-Tks5-Nck pathway in ECM-degrading invadopodia that shows parallels with pathways linking several mammalian and pathogen-derived proteins to local actin regulation.


Well-designed two-fold crosslinked biological valve leaflets with heparin-loaded hydrogel coating for enhancing anticoagulation, endothelialization, and anticalcification.
Commercial biological valve leaflets (BVLs) crosslinked with glutaraldehyde (GA) are at risk of accelerating damage and even failure, owing to the high cell toxicity of GA, acute thrombosis, and calcification in clinical applications. In this study, a novel joint strategy of double crosslinking agents (dialdehyde pectin (AP) and carbodiimide) and heparin-loaded hydrogel coating was developed, endowing BVLs with excellent mechanical properties and multiple performances. Herein, AP played two essential roles, the crosslinking agent and the main component of the hydrogel coating. Both experimental and theoretical results indicated that the mechanical properties and stability of double-crosslinked BVLs were comparable to those of GA, and heparin loaded in hydrogel coating could improve the hemocompatibility of AP + EDC/NHS-PP. Further, cytocompatibility and in vivo tests showed that compared with GA-PP, AP + EDC/NHS + CS + Hep-PP has exhibited good endothelialization ability, mild immune response and anti-calcification performance and therefore prompts it to be an extremely valuable candidate for more durable and multifunctional BVLs.


Perforin-dependent killing of tumor cells by Vgamma1Vdelta1-bearing T-cells.
The T-cell subset expressing Vdelta2 paired primarily with Vgamma2 comprises a majority of gammadelta T-cells in human adult peripheral blood and expands significantly during a variety of infectious diseases. In contrast, the other subset of gammadelta T-cells that express Vdelta1 is rare among circulating T-cells and its function is poorly understood. Here, we show that a Vgamma1Vdelta1(+) T-cell line, 3-D, established from human peripheral blood by immortalization with Herpesvirus saimiri was able to specifically recognize tumor cells, such as K562 cells, and release cytotoxic granules containing perforin for target cell killing. Some tumor cells, including Daudi cells that are known to be susceptible to killing by Vdelta2(+) T-cells, were resistant to 3-D killing, implicating distinct pathways for tumor cell control by Vdelta1(+) and Vdelta2(+) T-cells. The 3-D T-cell receptor (TCR):CD3 complex reconstituted in TCR-deficient Jurkat cells was capable of transmitting signals, evidenced by activation of the interleukin 2 (IL-2) gene following ligation with anti-CD3 antibody, yet the TCR-reconstituted cells failed to produce IL-2 in response to the target cells. Thus, these results raise the possibility that some Vgamma1Vdelta1(+) T-cells could potentially be stimulated and lyse tumor cells via ligation of TCR/CD3-unassociated molecules.


Car-surfing in southwest Ohio: incidence and injuries.
A local increasing prevalence of injuries due to the unusual mechanism of "car-surfing," during which youths ride on the hood or roof of a vehicle, led us to review our experience with these injuries with the goal of designing an effective prevention program. Patient information from the trauma registry at our Level I trauma center was abstracted and analyzed to determine the characteristics of injuries due to this unusual mechanism. Thirty-five patients were identified over a 15-year period. The average age was 19.5 +/- 5.2 years (mean +/- S.D.); 69% were young men. The number of injuries is increasing, with nine injuries identified during the first 5 years, 10 during the next 5 years, and 16 patients during the most recent 5-year period. Fifty-seven percent of the injuries occurred in a rural area and 43% in an urban area. Blood alcohol levels were tested in 29 patients--18 were negative and 11 were positive. Alcohol was more likely to be a factor in older patients with 77.8% (7/9) of those > or = 21 years old having a positive blood alcohol but only 20% (4/20) < or = 20 years old. The most severe injuries were due to head trauma (82.9%), and five patients died. This high risk behavior is becoming more prevalent in our region. The information gained from this study will be valuable to our Injury Prevention Center in designing an effective program to reduce such injuries.


Highly Diastereoselective One-Pot Synthesis of 4,5-Dihydrofuro[2,3-b]azocin-6-one Derivatives through Cyclization/[4+4] Annulation Reactions.
A variety of 4,5-dihydrofuro[2,3-b]azocin-6-one derivatives were expediently assembled through Au(I)-catalyzed cyclization and 2-(tert-butyl)-1,1,3,3-tetramethylguanidine (BTMG)-mediated [4+4] annulation reactions of enyne-amides and ynones. The reactions exhibit high efficiency with excellent regio- and diastereoselectivity. A broad spectrum of substrates was utilized. The products with an eight-membered ring might be useful in biological chemistry and medicinal science. Furthermore, the products could be facilely converted into various derivatives.


Lessons for Robotics From the Control Architecture of the Octopus.
Biological and artificial agents are faced with many of the same computational and mechanical problems, thus strategies evolved in the biological realm can serve as inspiration for robotic development. The octopus in particular represents an attractive model for biologically-inspired robotic design, as has been recognized for the emerging field of soft robotics. Conventional global planning-based approaches to controlling the large number of degrees of freedom in an octopus arm would be computationally intractable. Instead, the octopus appears to exploit a distributed control architecture that enables effective and computationally efficient arm control. Here we will describe the neuroanatomical organization of the octopus peripheral nervous system and discuss how this distributed neural network is specialized for effectively mediating decisions made by the central brain and the continuous actuation of limbs possessing an extremely large number of degrees of freedom. We propose top-down and bottom-up control strategies that we hypothesize the octopus employs in the control of its soft body. We suggest that these strategies can serve as useful elements in the design and development of soft-bodied robotics.


Improving carbon monoxide tolerance of Cupriavidus necator H16 through adaptive laboratory evolution.
Background: The toxic gas carbon monoxide (CO) is abundantly present in synthesis gas (syngas) and certain industrial waste gases that can serve as feedstocks for the biological production of industrially significant chemicals and fuels. For efficient bacterial growth to occur, and to increase productivity and titres, a high resistance to the gas is required. The aerobic bacterium Cupriavidus necator H16 can grow on CO2 + H2, although it cannot utilise CO as a source of carbon and energy. This study aimed to increase its CO resistance through adaptive laboratory evolution. Results: To increase the tolerance of C. necator to CO, the organism was continually subcultured in the presence of CO both heterotrophically and autotrophically. Ten individual cultures were evolved heterotrophically with fructose in this manner and eventually displayed a clear growth advantage over the wild type strain. Next-generation sequencing revealed several mutations, including a single point mutation upstream of a cytochrome bd ubiquinol oxidase operon (cydA2B2), which was present in all evolved isolates. When a subset of these mutations was engineered into the parental H16 strain, only the cydA2B2 upstream mutation enabled faster growth in the presence of CO. Expression analysis, mutation, overexpression and complementation suggested that cydA2B2 transcription is upregulated in the evolved isolates, resulting in increased CO tolerance under heterotrophic but not autotrophic conditions. However, through subculturing on a syngas-like mixture with increasing CO concentrations, C. necator could also be evolved to tolerate high CO concentrations under autotrophic conditions. A mutation in the gene for the soluble [NiFe]-hydrogenase subunit hoxH was identified in the evolved isolates. When the resulting amino acid change was engineered into the parental strain, autotrophic CO resistance was conferred. A strain constitutively expressing cydA2B2 and the mutated hoxH gene exhibited high CO tolerance under both heterotrophic and autotrophic conditions. Conclusion: C. necator was evolved to tolerate high concentrations of CO, a phenomenon which was dependent on the terminal respiratory cytochrome bd ubiquinol oxidase when grown heterotrophically and the soluble [NiFe]-hydrogenase when grown autotrophically. A strain exhibiting high tolerance under both conditions was created and presents a promising chassis for syngas-based bioproduction processes.


Searching for Alternatives to the Savitzky-Golay Filter in the Spectral Processing Domain.
An elegant, well-established effective data filter concept, proposed originally by Abraham Savitzky and Marcel J.E. Golay, is undoubtedly a very effective tool, however not free from limitations and drawbacks. Despite the latter, over the years it has become a "monopolist" in many fields of spectra processing, claiming a "commercial" superiority over alternative approaches, which would potentially allow to obtain equivalent or in some cases even more reliable results. In order to show that basic operations performed on spectral datasets, like smoothing or differentiation, do not have to be equated to the application of the one particular single algorithm, several of such alternatives are briefly presented within this paper and discussed with regard to their practical realization. A special emphasis is put on the fast Fourier methodology (FFT), being widespread in the general domain of signal processing. Finally, a user-friendly Matlab routine, in which the outlined algorithms are implemented, is shared, so that one can select and apply the technique of spectral data processing more adequate for their individual requirements without the need to code it prior to use.


Welsh Onion (Allium fistulosum L.) Seed Physiology, Breeding, Production and Trade.
In the coming years, it is expected that the European Union countries will increase their interest in the use of the Welsh onion (Allium fistulosum L.). It is a little-known vegetable from the Far East. Consequently, growers might be asking their extension advisors increasingly about its seed physiology and commercial production. This article provides basic information on the origin of the species, its botanical characteristics, the main breeding directions and achievements, seed production methods and areas, main plant breeding and seed production companies, seed dormancy and the best methods for seed storage, use of the crop and market responses to promotion activities.


[Results of rubella prevention in Austria (1988 status)].
The aim of any rubella eradication programme is the prevention of rubella embryopathy. In Austria, every girl aged 13 years is vaccinated without prior antibody testing. In addition, all pregnant women are tested for antibodies and vaccinated post partum, if necessary. As in other European countries, this policy has not (yet) led to the elimination of rubella embryopathies. In 1987 and 1988, 3 embryopathies as well as 16 and 17, respectively, rubella infections in pregnant women were diagnosed. In order to monitor the effectiveness of the vaccination in 13 years old girls, we tested 325 sera from student nurses (mean age 15.6 years) as well as 895 sera from pregnant women (mean age 23.1 years). In the 1st group, only 2.2% had a titer of less than or equal to 16 in hemagglutination inhibition test and therefore were not unequivocally protected. In the pregnant women, this ratio was 6.1%. We therefore draw the conclusion that in some cases the protection afforded by the vaccination begins to decrease after 10 years. At the same time, we also tested the sera of 4186 pregnant women who claimed they never had been vaccinated. Their mean age was higher (26 years) and 11.1% were not unequivocally protected. In addition, we tested 28 women who had been vaccinated 3 to 6 months previously due to negative serology. Of these, 6 (21.4%) did not produce antibodies with a titer of at least 32. Many European countries had the same experience and therefore began vaccinations of all children in the 2nd year, using the trivalent vaccine (mumps, measles, rubella) instead of the bivalent one (without rubella).(ABSTRACT TRUNCATED AT 250 WORDS)


[Thinking and challenge induced by the hypothesis of breaking stagnant and eliminating blood stasis in Treating acute cerebral hemorrhage by rF VII a].
Definite therapeutic effect has obtained by TCM in treating acute cerebral hemorrhage (ACH) according the TCM theory of "blood circulating outside the vessels is the stasis" using breaking stagnant and eliminating blood stasis (Poxue Zhuyu) method, but no material involving the natural development of stoke in superacue stage (0 - 4 hrs after onset of the disease) being presented so far. It has been proved by randomized, double-blinded multi-centeric clinical trials that recombinant activated factor VII (rF VII a) could decreased the morbidity and disability of patients suffered from ACH, suggesting that use hemostasis treatment in ACH during superacu stage should be stressed, and the drugs for Poxue Zhuyu should be used cautiously in the period of 0 - 4 hrs after onset. The hemorrhagic disorder could be eliminated by using drugs for Poxue Zhuyu and other medicines in rational combination.


The prevalence of musculoskeletal pain among above 50-year-old population referred to the Kermanshah-Iran health bus in 2016.
Musculoskeletal disorders are one of the most important causes of disability. The aim of this study was to evaluate the prevalence of musculoskeletal disorders among the above 50-year-old population who referred to the health bus in Kermanshah. A questionnaire was used to collect data regarding musculoskeletal disorders of 589 people who voluntarily referred to the health bus. Means (SD) and range were used in descriptive statistics. The most prevalence of musculoskeletal complaints was related to the knee (338, 57.4%). After that, the low back pain had the most frequency (319, 54.3%). The lowest prevalence of musculoskeletal complaints was related to the thighs with a frequency of 95 (16.1%). The highest rate of musculoskeletal complaints over the past week in both genders with a frequency of 251 (59.3%) among women and 68 (41%) among men was related to the low back region The highest rate of musculoskeletal complaints over the past year was also related to the low back region, with a frequency of 220 (41%) among women and 61 (36.7%) among men. Concerning the physical health of the elderly, special attention is required for the knee joint and the low back region.


[Analysis of arrhythmia and recovering in early stage pregnancy of older pregnant women].
To observe the abnormality of the electrocardiogram (ECG) and the characteristics of arrhythmia in the early stage of older pregnant women and to record the late outcome of atrial and ventricular arrhythmia. Two hundrend and ninty pregnant women were divided into 3 groups by age under 35 group, 35~39 group and 40~45 group. The ECG waveform was analyzed systematically when the patients were subjected to routine ECG examination and abnormal changes of ECG were collected and recorded, including ST segment changes, various arrhythmias, etc. Then the recovery and deterioration rate of atrial, ventricular arrhythmia was recorded. The incidence of arrhythmia in 35~39 group and 40~45 group was significantly higher than under 35 group (P<0.05); the incidence of abnormal ST section in 35~39 group and 40~45 group was significantly higher than under 35 group(P<0.05); and the incidence of widened QRS wave in 40~45 group was higher than under 35 group (P<0.05). The incidence of sinus tachycardia, sinus irregularityand atrial premature beats in 35~39 group and 40~45 group was obviously lower than that under 35 group (P<0.05); the incidence of Paroxysmal supraventricular tachycardia in 40~45 group was obviously higher than under 35 group (P<0.05) and the incidence of ventricular premature beat and atrial fibrillation in 35~39 group and 40~45 group was significantly higher than under 35 group (P<0.05). The recovery rate of atrial arrhythmia in 40~45 group was obviously lower than under 35 group (P<0.05);the exacerbation rate of trial and ventricular arrhythmia in 40~45 group was obviously higher than over 35 group (P<0.05). The incidences of IUGR in 35~39 group and 40~45 group with abnormal ECG was obviously higher than under 35 group and 35~39 group with normal ECG; The incidences of fetal distress in 35~39 year-old group and 40~45 year-old group with abnormal ECG was obviously higher than under 35 group(P<0.05). There is a positive correlation between the old age and the incidence of arrhythmia in the early stage of pregnancy, and old age factors can reduce the recovery rate but increase the incidence of deterioration of arrhythmia. And older pregnant women with abnormal ECG have undesirable effect to perinatal infant.


Treatment of radiation-induced cystitis and vulvodynia via a ganglion impar block using a lateral approach under computed tomography guidance: a case report.
Adjuvant radiation therapy (RT) after colorectal cancer surgery can prevent local recurrence, but has several side effects. Precise injection of drugs into the affected areas is complicated by radiation-induced fibrosis of soft or connective tissue. A 48-year-old woman experienced severe intractable perineal pain, dysuria, urinary urgency, and frequent urination after rectal cancer surgery and adjuvant RT, and was diagnosed with radiation-induced cystitis and vulvodynia. Her symptoms persisted despite two fluoroscopy-guided ganglion impar blocks. Fluoroscopy revealed atypical needle tip positioning and radiolucent dye distribution, presumably due to radiation-induced fibrosis in the target region. We performed two computed tomography (CT)-guided ganglion impar blocks by using a lateral approach, which allowed more accurate po-sitioning of the needle tip. Her pain visual analog score decreased from 9 to 3, and she recently resumed sexual intimacy. CT guidance is a viable alternative to fluoroscopy guidance when performing ganglion impar blocks in fibrotic areas.


α-1,3-Fucosyltransferase-VII siRNA inhibits the expression of SLex and hepatocarcinoma cell proliferation.
The increased expression of sialyl-Lewisx (SLex) epitope on the surface of tumor cells has been known for decades. However, genetic manipulation of the expression of SLex and the role of SLex in cancer cell proliferation remains to be fully elucidated. The present study suggested that the monoclonal antibody of SLex (KM93) significantly inhibited the proliferation of human hepatocarcinoma (HCC) cells. The expression levels of three sialyl‑Lewis oligosaccharide antigens, SLex, SLea and dimeric SLex (SDLex), were determined on the cell surface of the MHCC97 human HCC cell line. The expression of SLex was markedly higher in MHCC97 cells than in normal liver cells. The expression of SDLex was also relatively high, however, no significant difference was observed between normal liver cells and HCC cells. The expression of SLea was only detected in trace quantities. Fucosyltransferase (FUT) is the key enzyme of the fucosylation step in the biosynthesis of sialyl‑Lewis oligosaccharide antigens. Therefore, the present study investigated the expression of FUTs. It was found that the mRNA and protein expression levels of FUT7 were high in the MHCC97 HCC cell line compared with levels in normal liver cells. FUT6 was also expressed at a high level, although the difference was not statistically significant between MHCC97 cells and normal liver cells. No expression of FUT3 was detected. The results were consistent with the change insialyl‑Lewis antigens. The effects of FUT7 small interfering (si)RNA transfection on the expression of FUT7, expression of SLex and MHCC97 cell proliferation were also examined. Following FUT7 siRNA transfection, the expression of FUT7 was markedly downregulated, as determined by western blot and reverse transcription‑quantitative polymerase chain reaction methods. The results from flow cytometry showed that the synthesis of SLex was also inhibited, which was consistent with the downregulated expression of FUT7. MHCC97 cell proliferation was also significantly inhibited following FUT7 siRNA transfection, which was correlated with suppression of the S‑phase in cell cycle progression. By using inhibitors of various signaling pathways, it was found that the knockdown of FUT7 inhibited the activation of phospholipase Cγ (PLCγ) by inhibiting the translocation and phosphorylation of PLCγ. In conclusion, the results suggested that FUT7 has animportant functional role in human HCC cell proliferation by controlling cell cycle progression via the PLCγ/extracellular signal‑regulated kinase signaling pathway. The inhibition of SLex and FUT7 siRNA transfection may provide a novel therapeutic methodology to treat tumors that express SLex glycoconjugates.


ECS-NL: An Enhanced Cuckoo Search Algorithm for Node Localisation in Wireless Sensor Networks.
Node localisation plays a critical role in setting up Wireless Sensor Networks (WSNs). A sensor in WSNs senses, processes and transmits the sensed information simultaneously. Along with the sensed information, it is crucial to have the positional information associated with the information source. A promising method to localise these randomly deployed sensors is to use bio-inspired meta-heuristic algorithms. In this way, a node localisation problem is converted to an optimisation problem. Afterwards, the optimisation problem is solved for an optimal solution by minimising the errors. Various bio-inspired algorithms, including the conventional Cuckoo Search (CS) and modified CS algorithm, have already been explored. However, these algorithms demand a predetermined number of iterations to reach the optimal solution, even when not required. In this way, they unnecessarily exploit the limited resources of the sensors resulting in a slow search process. This paper proposes an Enhanced Cuckoo Search (ECS) algorithm to minimise the Average Localisation Error (ALE) and the time taken to localise an unknown node. In this algorithm, we have implemented an Early Stopping (ES) mechanism, which improves the search process significantly by exiting the search loop whenever the optimal solution is reached. Further, we have evaluated the ECS algorithm and compared it with the modified CS algorithm. While doing so, note that the proposed algorithm localised all the localisable nodes in the network with an ALE of 0.5-0.8 m. In addition, the proposed algorithm also shows an 80% decrease in the average time taken to localise all the localisable nodes. Consequently, the performance of the proposed ECS algorithm makes it desirable to implement in practical scenarios for node localisation.


Comprehensive expression analysis of FSHD candidate genes at the mRNA and protein level.
In facioscapulohumeral muscular dystrophy (FSHD) the majority of patients carry a D4Z4 macrosatellite repeat contraction in the subtelomere of chromosome 4q. Several disease mechanisms have been proposed to explain how repeat contraction causes muscular dystrophy. All proposed mechanisms foresee a change from a closed to a more open chromatin structure followed by loss of control over expression of genes in or proximal to D4Z4. Initially, a distance and residual repeat size-dependent upregulation of the candidate genes FRG2, FRG1 and ANT1 was observed, but most successive expression studies failed to support transcriptional upregulation of 4qter genes. Moreover, chromatin studies do not provide evidence for a cis-spreading mechanism operating at 4qter in FSHD. In part, this inconsistency may be explained by differences in the techniques used, and the use of RNA samples obtained from different muscle groups. The aim of this study is to comprehensively and uniformly study the expression of the FSHD candidate genes FRG1, FRG2, CRYM, ANT1, ALP, PITX1 and LRP2BP at the RNA and protein level in identically processed primary myoblasts, myotubes and quadriceps muscle. Expression was compared between samples obtained from FSHD patients and normal controls with samples from myotonic dystrophy type 1 patients as disease controls. No consistent changes in RNA or protein expression levels were observed between the samples. The one exception was a selective increase in FRG2 mRNA expression in FSHD myotubes. This study provides further evidence that there is no demonstrable consistent, large magnitude, overexpression of any of the FSHD candidate genes.


Clinical relevance of the distribution of the lesions in 500 consecutive breast cancer cases documented in large-format histologic sections.
Breast carcinoma is a heterogeneous group of diseases deviating from each other not only in their clinical manifestations and outcome but also in their histologic appearance. The submacroscopic morphology of breast carcinomas, the distribution of the lesions, and the extent of the disease are seldom studied. Even more infrequently are these parameters included in surgical pathology reports. Conversely, the routine use of large-format histologic sections in workup of operated breast specimens provides better insight into the significance of these parameters. The aim of the study was to identify breast carcinoma growth patterns indicating increased metastatic potential of the tumor and a need for more aggressive therapy. In all, 500 consecutive breast cancer cases, all of which were documented on large-format histologic sections, were retrospectively analyzed. The distribution of both in situ and invasive components of the tumors (unifocal/multifocal/diffuse) was defined, determined, and compared with the type of surgical intervention performed and the frequency of ipsilateral lymph node metastasis as endpoints. The extent of the disease, the size of the tumor, the presence or absence of lymphovascular invasion (LVI), and the proportion of invasive lobular carcinomas in the categories with different distributions were also analyzed. Only 34% of the analyzed cases could be categorized as unifocal. This kind of tumor distribution was associated with lymph node metastasis in 28% of the cases, with LVI in 18%, with breast-conserving surgery in 67%, and with a proportion of 4% invasive lobular carcinomas. Tumors with a unifocal invasive component upgraded to multifocal or diffuse because of the distribution of the associated in situ component had similar characteristics. With their larger extent, tumors with a diffuse in situ component required mastectomy in 43% of cases. Multifocal distribution of the invasive component in the tumors was associated with higher frequency of LVI (42%) and lymph node metastases (48%), with a substantially lower number of cases undergoing breast-conserving surgery (33%) and with a higher proportion of lobular carcinomas (25%). If the multifocal invasive foci were associated with a diffuse in situ component, the proportion of invasive lobular carcinomas was only 5%. The extent of the lesions (defined as the area of breast tissue involved by in situ, invasive, and/or intravascular tumor foci) was >or=2 cm in >90% of multifocal cases and >or=4 cm in >70%. Diffusely growing invasive carcinomas were rare (only 20 cases), but were associated with lymph node metastasis in 60% of cases and resulted in mastectomy in 85% of the cases. Approximately two-thirds (65%) of these tumors belonged to invasive lobular carcinomas. The extent of diffusely growing invasive carcinomas was >or=4 cm in 75% of the cases. Although LVI was detected in only 10% of tumors with a diffusely growing invasive component, such tumors were found to have lymph node metastasis significantly more often (odds ratio of 2.33) and required mastectomy much more frequently (odds ratio of 2.58) compared with purely unifocal breast carcinomas. These results indicate that the distribution of invasive and in situ tumor structures in breast carcinomas as defined in the current study, together with the extent of disease, are important morphologic parameters which determine the required surgical intervention and are related to biologic factors such as metastatic capacity. The method of large-section histology allows the examiner to properly document and demonstrate these important parameters, thus facilitating understanding of their clinical relevance.


Reconstruction of traumatic defect of the lower third of the leg using a combined therapy: negative pressure wound therapy, acellular dermal matrix, and skin graft.
The reconstruction of lower third of the leg is one of the most challenging problems for plastic and reconstructive surgeons and current approaches are still disappointing. We show an easy option to obtain a coverage of traumatic pretibial defects with good aesthetic and functional results: the association of negative pressure wound therapy, acellular dermal matrix, and skin graft. The choice of this combined therapy avoids other surgical procedures such as local perforator flaps and free flaps that require more operating time, special equipment, and adequate training.


Comparative genetic studies on the APRR5 and APRR7 genes belonging to the APRR1/TOC1 quintet implicated in circadian rhythm, control of flowering time, and early photomorphogenesis.
In Arabidopsis thaliana, a number of circadian-associated factors have been identified. Among those, TOC1 (TIMING OF CAB EXPRESSION 1) is believed to be a component of the central oscillator. TOC1 is a member of a small family of proteins, designated as Arabidopsis PSEUDO-RESPONSE REGULATORS (APRR1/TOC1, APRR3, APRR5, APRR7, and APRR9). Nonetheless, it is not very clear whether or not the APRR family members other than APRR1/TOC1 are also implicated in the mechanisms underlying the circadian rhythm. To address this issue further, here we characterized a set of T-DNA insertion mutants, each of which is assumed to have a severe lesion in each one of the quintet genes (i.e. APRR5 and APRR7). For each of these mutants (aprr5-11 and aprr7-11) we demonstrate that a given mutation singly, if not directly, affects the circadian-associated biological events simultaneously: (i) flowering time in the long-day photoperiod conditions, (ii) red light sensitivity of seedlings during the early photomorphogenesis, and (iii) the period of free-running rhythms of certain clock-controlled genes including CCA1 and APRR1/TOC1 in constant white light. These results suggest that, although the quintet members other than APRR1/TOC1 may not be directly integrated into the framework of the central oscillator, they are crucial for a better understanding of the molecular mechanisms underlying the Arabidopsis circadian clock.


An unusual presentation of non pathological delayed splenic rupture: a case report.
The diagnosis of Delayed Splenic Rupture poses a major challenge to even the most astute clinician, as it can mimic other medical emergencies. We present a case of an unusual presentation of delayed splenic rupture in a 23-year-old Caucasian man, who presented to the emergency department with a 2 day history of left upper quadrant pain. He initially denied any history of trauma. There were no signs of generalized peritonisim on examination but his haemoglobin level was low (8.9 gm/dl) for which there was no obvious cause identified. He was resuscitated and a computed tomography of the abdomen was performed. This revealed complete rupture of the splenic capsule with haemorrhagic fluid in the abdomen. With the computed tomography abdomen findings and further questioning of the patient, the only potential precipitating event that he could remember was a minor kick to the left upper quadrant more than 2 weeks ago while playing football. An urgent splenectomy was performed and histology confirmed complete rupture of the splenic capsule with a large adherent haematoma to the capsule. This case illustrates the difficulty in diagnosing delayed splenic rupture especially when accurate history is not available. A high index of suspicion is essential as delay in diagnosis can be fatal. Early diagnosis in suspected cases can be achieved by performing computed tomography of the abdomen.


Global prevalence of cerebral palsy: A systematic analysis.
To determine trends and current estimates in regional and global prevalence of cerebral palsy (CP). A systematic analysis of data from participating CP registers/surveillance systems and population-based prevalence studies (from birth year 1995) was performed. Quality and risk of bias were assessed for both data sources. Analyses were conducted for pre-/perinatal, postnatal, neonatal, and overall CP. For each region, trends were statistically classified as increasing, decreasing, heterogeneous, or no change, and most recent prevalence estimates with 95% confidence intervals (CI) were calculated. Meta-analyses were conducted to determine current birth prevalence estimates (from birth year 2010). Forty-one regions from 27 countries across five continents were represented. Pre-/perinatal birth prevalence declined significantly across Europe and Australia (11 out of 14 regions), with no change in postneonatal CP. From the limited but increasing data available from regions in low- and middle-income countries (LMICs), birth prevalence for pre-/perinatal CP was as high as 3.4 per 1000 (95% CI 3.0-3.9) live births. Following meta-analyses, birth prevalence for pre-/perinatal CP in regions from high-income countries (HICs) was 1.5 per 1000 (95% CI 1.4-1.6) live births, and 1.6 per 1000 (95% CI 1.5-1.7) live births when postneonatal CP was included. The birth prevalence estimate of CP in HICs declined to 1.6 per 1000 live births. Data available from LMICs indicated markedly higher birth prevalence. • Birth prevalence of pre-/perinatal cerebral palsy (CP) in high-income countries (HICs) is decreasing. • Current overall CP birth prevalence for HICs is 1.6 per 1000 live births. • Trends in low- and middle-income countries (LMICs) cannot currently be measured. • Current birth prevalence in LMICs is markedly higher than in HICs. • Active surveillance of CP helps to assess the impact of medical advancements and social/economic development. • Population-based data on prevalence and trends of CP are critical to inform policy.


Increased hemoglobin levels in patients with early onset scoliosis: prevalence and effect of a treatment with Vertical Expandable Prosthetic Titanium Rib (VEPTR).
The medical records of 138 subjects with Early Onset Scoliosis (EOS) from 5 US institutions were reviewed to analyze their hemoglobin levels before and after surgery. Eighty-five subjects were operated with the Vertical Expandable Prosthetic Titanium Rib (VEPTR) and 53 with growing rods. To estimate the prevalence of hypoxia and thoracic insufficiency using hemoglobin as a surrogate marker for pulmonary function, and to measure the effect of spine surgery with expandable devices. An early intervention with expandable devices might improve pulmonary function. This hypothesis is difficult to test in young subjects because the standard pulmonary function tests require that the patient be at least 7-year old. Previous studies demonstrated that hemoglobin levels are correlated with chronic hypoxemia. Blood data were collected before and 6 to 24 months after surgery. The hemoglobin and hematocrit levels were converted into Z-scores, using age-adjusted references to perform t test paired comparisons. The prevalence of elevated hemoglobin and hematocrit levels in EOS was 23.2% and 22.5%, respectively. The mean hemoglobin Z-score decreased from 1.26 to 0.92 (P = 0.03) after surgery and the hematocrit Z-score changed from 0.90 to 0.88 (P = 0.90). In the VEPTR group, the mean hemoglobin Z-score decreased from 0.98 to 0.69 (P = 0.20) and in the subgroup of subjects who had an expansion thoracostomy, it decreased from 0.82 to 0.24 (P = 0.04). In the subjects operated with growing rods, the hemoglobin Z-score decreased from 1.75 to 1.32 (P = 0.83). Twenty-three percent of the patients with EOS showed signs of chronic hypoxia. The hemoglobin levels decreased significantly 6 to 24 months after surgery. The greatest effect was observed in subjects with congenital scoliosis and rib fusion and who had an expansion thoracostomy with implantation of VEPTR.


The Impact of eHealth and mHealth on doctor behavior and patient involvement: an Israeli and Portuguese comparative approach.
Based on the experience of a Short Term Scientific Mission (STSM) promoted by COST Net and developed in CIES/ISCTE-IUL (Portugal), this paper presents a reflection about the implementation of Information & Communication Technologies (ICT) in the healthcare sector in Israel and Portugal. Specifically, we focus on the impacts of ICT or eHealth on patient empowerment, as perceived by doctors and managers in order to better comprehend the role of national policy and explore the options for building a national strategy regarding ICT in healthcare. The experience of the Portuguese healthcare system was selected and compared to the results found in a similar research in Israel. Methodologically, in-depth interviews with the Ministry of Health, the private sector, patients associations and researches were used to collect data. Purposeful sampling was used to select respondents, and secondary sources were used for triangulation. The findings of the research work show that the increased deployment of ICT has furthered patient empowerment (1). From the doctors' perspective, while ICT has provided more information in the long-run, changes of these magnitudes were not easy in the beginning. These findings were similar in both countries. The work concludes that ICT tools were successfully implemented and the general perception is that they have been beneficial. The work provides information in order to understand and improve ICT services. Additionally, the results suggest alternatives for future investments in these technologies.


Development of an enzyme-linked immunosorbent assay for the organophosphorus insecticide bromophos-ethyl.
A competitive enzyme-linked immunosorbent assay (ELISA) was developed for the quantitative detection of the organophosphorus insecticide bromophos-ethyl. Four bromophos-ethyl derivatives (haptens) were synthesized and were coupled to carrier proteins through the pesticide thiophosphate group to use as an immunogen or as a coating antigen. Rabbits were immunized with either one of two haptens coupled to bovine serum albumin for production of polyclonal antibodies, and the sera were screened against one of the haptens coupled to ovalbumin. Using the serum with highest titer, an antigen-coated ELISA was developed, which showed an IC(50) of 3.9 ng/mL with a detection limit of 0.3 ng/mL (20% inhibition). An antibody-coated ELISA using an enzyme tracer was also developed, which showed an IC(50) of 6.5 ng/mL with a detection limit of 1.0 ng/mL (20% inhibition). The antibodies showed negligible cross-reactivity with other organophosphorus pesticides except with the insecticides bromophos-methyl and chlorpyrifos in the antibody-coated assay only. Recoveries of bromophos-ethyl from fortified crop and water samples ranged from 82 to 128% and from 95 to 127%, respectively.


Bionic microenvironment-inspired synergistic effect of anisotropic micro-nanocomposite topology and biology cues on peripheral nerve regeneration.
Anisotropic topographies and biological cues can simulate the regenerative microenvironment of nerve from physical and biological aspects, which show promising application in nerve regeneration. However, their synergetic influence on injured peripheral nerve is rarely reported. In the present study, we constructed a bionic microenvironment-inspired scaffold integrated with both anisotropic micro-nanocomposite topographies and IKVAV peptide. The results showed that both the topographies and peptide displayed good stability. The scaffolds could effectively induce the orientation growth of Schwann cells and up-regulate the genes and proteins relevant to myelination. Last, three signal pathways including the Wnt/β-catenin pathway, the extracellular signal-regulated kinase/mitogen-activated protein pathway, and the transforming growth factor-β pathway were put forward, revealing the main path of synergistic effects of anisotropic micro-nanocomposite topographies and biological cues on neuroregeneration. The present study may supply an important strategy for developing functional of artificial nerve implants.


Characterization of two distinct liver progenitor cell subpopulations of hematopoietic and hepatic origins.
Despite extensive studies, the hematopoietic versus hepatic origin of liver progenitor oval cells remains controversial. The aim of this study was to determine the origin of such cells after liver injury and to establish an oval cell line. Rat liver injury was induced by subcutaneous insertion of 2-AAF pellets for 7 days with subsequent injection of CCl(4). Livers were removed 9 to 13 days post-CCl(4) treatment. Immunohistochemistry was performed using anti-c-kit, OV6, Thy1, CK19, AFP, vWF and Rab3b. Isolated non-parenchymal cells were grown on mouse embryonic fibroblast, and their gene expression profile was characterized by RT-PCR. We identified a subpopulation of OV6/CK19/Rab3b-expressing cells that was activated in the periportal region of traumatized livers. We also characterized a second subpopulation that expressed the HSCs marker c-kit but not Thy1. Although we successfully isolated both cell types, OV6/CK19/Rab3b(+) cells fail to propagate while c-kit(+)-HSCs appeared to proliferate for up to 7 weeks. Cells formed clusters which expressed c-kit, Thy1 and albumin. Our results indicate that a bona fide oval progenitor cell population resides within the liver and is distinct from c-kit(+)-HSCs. Oval cells require the hepatic niche to proliferate, while cells mobilized from the circulation proliferate and transdifferentiate into hepatocytes without evidence of cell fusion.


Strength and Power Characteristics in National Amateur Rugby Players.
Rugby players need muscular strength and power to meet the demands of the sport; therefore, a proper assessment of the performance in rugby players should include both variables. The purpose of this study was to examine the strength and power characteristics (SPC) during the squat (SQ) and bench press (BP) in national amateur rugby players and to analyze gender- and position-related differences. A total of 47 players (30 males and 17 females; age: 25.56 ± 1.14 and 23.16 ± 1.38 years, respectively) participated in the study. The one repetition-maximum (1-RM) and SPC in SQ and BP were obtained using a Smith Machine. Then, subjects performed one set of five repetitions on the SQ and BP against six relative loads (30-40-50-60-70-80% 1-RM) using a linear transducer. Differences between genders were found in 1-RM for maximal power, kilograms lifted at maximal power, maximal power, maximal strength and maximal speed in BP (p < 0.00) and 1-RM, kilograms lifted at maximal power, maximal power, maximal strength and maximal speed in SQ (p < 0.00). Comparisons between variables in SQ and BP present a significant relationship (p < 0.01) in SQ and BP 1-RM with kilograms lifted at maximal power (r = 0.86 and r = 0.84), maximal strength (r = 0.53 and r = 0.92) and maximal power (r = 0.76 and r = 0.93). This study confirms the importance of the SPC assessment for training prescription in rugby amateur players.


Obesity and iron-deficiency anemia in women of reproductive age in northern Iran.
Obesity and iron deficiency (ID) are two forms of the most usual nutritional disorders worldwide. Some studies have discovered a correlation between ID and obesity although more investigation is required. This study was aimed to determine the association between obesity and ID anemia (IDA) in Iranian childbearing age women. This cross-sectional study was done on 256 women of reproductive age in northern Iran. The anthropometric measurements including height and weight were measured, and body mass index (BMI) was calculated. Low blood index of the hemoglobin (Hb), mean cell volume (MCV), and mean corpuscular hemoglobin (MCH) were evaluated with ferritin, serum iron, and total iron-binding capacity. Baseline data were expressed as means ± standard deviations. Chi-square test was applied to compare the categorical variable. Differences between the two groups were evaluated with independent samples t-test. A value of P < 0.05 was considered as statistically significant. Obesity was in urban women higher than rural women (55.1% vs. 44.9%), and this difference was significant (P < 0.021). There was found no association between hematological characteristics and BMI. The data showed that only 13.4% of obese women and 17.1% of the women with normal weight had IDA (odds ratio = 0.75; 95% confidence interval: 0.39-1.49, P > 0.05). According to the results of this study, it seems that the relationship between obesity and IDA is controversial. Hence, further studies are needed to be done.


Management of metallic mercury injection in the hand.
This case report discusses a patient who injected 20 mL of metallic mercury subcutaneously in his left hand during an attempted suicide. The blood mercury level was 118 microg/L and the urinary mercury level was 43 microg/L, which confirmed the diagnosis of metallic mercury poisoning. A good result was obtained in this patient and the local and systemic toxicity and its management are discussed. A chelation therapy with dimercaprol and early surgical excision of injected material are recommended because this treatment effectively lowers mercury blood levels and controls the local inflammatory reaction. Intraoperative fluoroscopy is useful to confirm the extent of removal.


The influence of a colonic microbiota on HPMA copolymer lectin conjugates binding in rodent intestine.
Germ-free (GF) animals lack a colonic microflora like that seen in conventional (CV) animals. Bacterial presence plays a role in the development of glycoproteins in the gastrointestinal (GI) tract; the absence of a microbiota has been seen to suppress the production of certain glycoproteins and glycolipids. Binding patterns of lectins are modified when glycoprotein structures are altered (e.g., during development or disease). Little information on lectin binding patterns in mature GF animals is available. We examined the binding of free and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-conjugated fluorescein isothiocyanate (FITC)-labeled wheat germ agglutinin (WGA) [P(HPMA)-(WGA-FITC)] and FITC-labeled peanut agglutinin (PNA) [P(HPMA)-(PNA-FITC)] in CV and GF mouse colon with and without neuraminidase pretreatment. Anti-Thomsen-Friedenreich (TF) antigen (a development and disease-related glycoprotein) antibody binding was also examined in these tissues. Subtle differences were seen in the binding patterns between CV and GF animals. CV animals showed strong P(HPMA)-(WGA-FITC) binding in goblet cells, but minimal P(HPMA)-(PNA-FITC) binding was visible. In GF animals, luminal surface binding of P(HPMA)-(WGA-FITC) was visible, and goblet cell binding of P(HPMA)-(PNA-FITC) was seen. These subtle changes suggest that altered glycoprotein expression occurred under GF conditions.


Adsorption removal of arsenic from aqueous solutions and groundwater by isomeric FeOOH.
FeOOH as a naturally abundant, relatively low-cost and effective adsorbent have been gradually valued in wastewater field rich in arsenic pollution, which can make for environmental remediation. In this study, FeOOH samples included Gth1/Gth2 as goethite, Aka1/Aka2 as akaganéite, and Lep as lepidocrocite, were prepared and used as adsorbents, and adsorption kinetic and isotherm experiments of As(III) were analyzed. Meanwhile, the effects of pH, adsorbent content, arsenic initial concentration and electrolyte solutions on adsorption processes were also discussed in detail to study adsorption behaviors and mechanism. The results showed that As(III) could be effectively adsorbed on goethite, akaganéite and lepidocrocite, the adsorption equilibrium achieved after 24 h. When As(III) concentration ranged in 40 mg/L, the saturated adsorption amounts (mg/g) calculated by the Langmuir equation were 12.3 (Gth1), 7.50 (Gth2), 6.29 (Aka1), 23.4 (Aka2), and 17.7 (Lep). The increase of adsorbent and adsorbate levels was favorable to improve the adsorption capacities of As(III) within a certain range. Removal efficiency of As(III) with Na2SO4 and NaH2PO4 as electrolyte reduced by about 10% and 30%, respectively. Therefore, the appropriate parameters in the adsorption process for investigation were isomeric FeOOH of 1.0 g/L, pH 7.0 and NaNO3 as electrolyte. In simulated groundwater filter system initially with 200 μg/L of arsenic species at about pH 7.0, arsenic removal strength for five FeOOH adsorbents (0.8 g) was Aka2 > Aka1 and Gth1 > Lep and Gth2. Some differences were present in the infrared (IR) spectra of arsenic-loaded and original isomeric FeOOH. These outcomes could give the aim at seeking high efficient materials for the purification of arsenic contaminated groundwater and put out the suggestion.


Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study.
During in-hospital cardiac arrests, how long resuscitation attempts should be continued before termination of efforts is unknown. We investigated whether duration of resuscitation attempts varies between hospitals and whether patients at hospitals that attempt resuscitation for longer have higher survival rates than do those at hospitals with shorter durations of resuscitation efforts. Between 2000 and 2008, we identified 64,339 patients with cardiac arrests at 435 US hospitals within the Get With The Guidelines—Resuscitation registry. For each hospital, we calculated the median duration of resuscitation before termination of efforts in non-survivors as a measure of the hospital's overall tendency for longer attempts. We used multilevel regression models to assess the association between the length of resuscitation attempts and risk-adjusted survival. Our primary endpoints were immediate survival with return of spontaneous circulation during cardiac arrest and survival to hospital discharge. 31,198 of 64,339 (48·5%) patients achieved return of spontaneous circulation and 9912 (15·4%) survived to discharge. For patients achieving return of spontaneous circulation, the median duration of resuscitation was 12 min (IQR 6-21) compared with 20 min (14-30) for non-survivors. Compared with patients at hospitals in the quartile with the shortest median resuscitation attempts in non-survivors (16 min [IQR 15-17]), those at hospitals in the quartile with the longest attempts (25 min [25-28]) had a higher likelihood of return of spontaneous circulation (adjusted risk ratio 1·12, 95% CI 1·06-1·18; p<0·0001) and survival to discharge (1·12, 1·02-1·23; 0·021). Duration of resuscitation attempts varies between hospitals. Although we cannot define an optimum duration for resuscitation attempts on the basis of these observational data, our findings suggest that efforts to systematically increase the duration of resuscitation could improve survival in this high-risk population. American Heart Association, Robert Wood Johnson Foundation Clinical Scholars Program, and the National Institutes of Health.


Necrotic crescentic glomerulonephritis and IGA nephropathy: Lee-Haas classification revisited.
Capillary necrosis is frequently encountered in most forms of proliferative glomerulonephritis, and varies in severity from only occasional finding to severe form of glomerular vasculitis. We report a patient who presented with features of acute glomerulonephritis. Kidney biopsy showed crescents in 30% of the glomeruli, diffuse mesangial expansion and hypercellularity with IgA deposits on immunofluorescence. The relevance of the Lee-Haas classification is discussed in relation to assessing prognosis.


The effect of longitudinal EMR access on laboratory ordering.
A longitudinal electronic medical record (EMR) allows physicians to access laboratory results in the context of the patient's medical history. Daily lab order volumes were tracked for physicians with access to an EMR and physicians with no EMR access to assess whether physicians with EMR access changed their lab order habits significantly more than a matched set of controls. This study shows that physicians will change their ordering habits in order to access the lab results in the context of an EMR.


Determining the mobility of ions by transient current measurements at high voltages.
We present polarization and transient current experiments that allow an independent determination of the charge carrier density and the mobility of ions in polymer electrolytes at low charge carrier density. The method relies on a complete depletion of ions in the bulk electrolyte achieved by applying high voltages. Based on a qualitative model for the charge dynamics in this nonlinear regime, the method is exemplarily applied to a system of polymethylmethacrylate doped with small amounts of a lithium salt. The independently obtained values for the ionic mobility, the charge carrier density, and the conductivity are consistent for all salt concentrations studied. Criteria for the applicability of the method are discussed.


The Development and Application of a HPTLC-Derived Database for the Identification of Phenolics in Honey.
This study reports on the development and validation of a HPTLC-derived database to identify phenolic compounds in honey. Two database sets are developed to contain the profiles of 107 standard compounds. Rich data in the form of Rf values, colour hues (H°) at 254 nm and 366 nm, at 366 nm after derivatising with natural product PEG reagent, and at 366 nm and white light after derivatising with vanillin-sulfuric acid reagent, λ max and λ min values in their fluorescence and λ max values in their UV-Vis spectra as well as λ max values in their fluorescence and UV-Vis spectra after derivatisation are used as filtering parameters to identify potential matches in a honey sample. A spectral overlay system is also developed to confirm these matches. The adopted filtering approach is used to validate the database application using positive and negative controls and also by comparing matches with those identified via HPLC-DAD. Manuka honey is used as the test honey and leptosperine, mandelic acid, kojic acid, lepteridine, gallic acid, epigallocatechin gallate, 2,3,4-trihydroxybenzoic acid, o-anisic acid and methyl syringate are identified in the honey using the HPTLC-derived database.


Written simulation of patient-doctor encounters. 2. Assessment of the performance of general practitioners.
Two rating procedures were used to judge the performance of 19 general practitioners confronted with a written simulation of patient-doctor encounters. The simulation comprised five patients with vague complaints. A group of three 'expert' general practitioners judged the attention that the doctors paid to somatic aspects or to causes of the complaints. A second group of 18 experts judged the extent to which the therapeutic procedures of the general practitioners might induce a risk of unnecessary harm to the patient. Both rating procedures were shown to be reliable for three of the five simulated patients. A weak correlation between these issues was established for these three patients. The problems of judging the behaviour of the practitioners with the other two patients are discussed. The performance of the general practitioners was relatively constant. Variability between individuals substantially exceeded variability within an individual with respect to the attention given to somatic aspects, but these variabilities were roughly equal with respect to the risk of causing unnecessary harm.


The cost-effectiveness of intensive national school-based anti-tobacco education: results from the tobacco policy model.
School-based anti-tobacco education using the "social influences" model is known to reduce smoking among youth by 5-56%. Program effectiveness, however, dissipates in 1-4 years. Consequently, opinion leaders have questioned whether a more intensive national educational effort would be economically efficient. To address this question, we evaluated the cost-effectiveness of enhanced nationwide school-based anti-tobacco education relative to the status quo. To estimate cost-effectiveness, we created the Tobacco Policy Model, a system dynamics computer simulation model. The model relies on secondary data and is designed to calculate the expected costs and public health gains of any tobacco policy or intervention over any time frame. Over 50 years, cost-effectiveness is estimated to lie between $4,900 and $340,000 per quality-adjusted life-year (QALY), depending on the degree and longevity of program effectiveness. Assuming a 30% effectiveness that dissipates in 4 years, cost-effectiveness is $20,000/QALY. Sensitivity analysis reveals that cost-effectiveness varies with cost, survival, and quality-of-life estimates but cost-effectiveness ratios generally remain favorable. Although not cost saving, a much more intensive school-based anti-tobacco educational effort would be an economically efficient investment for the nation.


Palliation in cyanotic congenital heart disease. Fifteen years' experience of various shunt procedures.
During the past 15 years, 143 systemic pulmonary shunt procedures have been performed in 117 patients. These have been evaluated for their clinical effectiveness, the need for a repeat operation and the mortality; particular attention was paid to the Teflon shunt. Variations were found in shunt performance, depending on the primary defect, the type of shunt that was employed and the year of operation. The overall shunt patency after three years was 77% (85% with the Teflon shunt). Although, in our total experience, mortality at 30 days was 12%, with 16% late deaths, "modified Blalock" (Teflon) shunts had only a 5% hospital mortality and a 5% late mortality within three years. Pulmonary atresia, without a ventricular septal defect, is often insufficiently palliated by a shunt alone. Ten of 82 patients with variations of the tetralogy complex died within 30 days of operation, and a further 11 died in the late follow-up period. Six of these 21 shunts were patent at autopsy. Less common defects, such as univentricular heart, transposition and double-outlet right ventricular connections, that are associated with pulmonary stenosis had no early mortality but led to four late deaths among 27 patients. Two of the four patients had patent shunts. Results in the early part of this experience were less than acceptable owing to inferior shunting techniques, postoperative management errors and, particularly, inadequate follow-up surveillance. With correction of these factors we find that the modified Blalock shunt provides very good early and late mortality results, with excellent clinical palliation and patency rates.


Identification of the interaction network of hub genes for melanoma treated with vemurafenib based on microarray data.
The objective of this study was to identify possible biomarkers and to explore the mechanisms of suppression of vemurafenib on melanoma progression. GSE42872 affymetrix microarray data were downloaded from the Gene Expression Omnibus database for further analysis. Differentially expressed genes (DEGs) between vehicle-treated samples and vemurafenib-treated samples were identified. Gene ontology and pathway enrichment analysis of DEGs were performed, followed by protein-protein interaction (PPI) network construction. Furthermore, the functional modules of the PPI network were screened using BioNet analysis tool. Finally, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for DEGs in the module. In total, 794 upregulated transcripts corresponding to 214 genes and 977 downregulated transcripts corresponding to 325 genes were screened. The downregulated DEGs were significantly enriched in pathways such as cell cycle, DNA replication, and p53 signaling pathway. Upregulated DEGs were significantly enriched in phosphatidylinositol signaling system and inositol phosphate metabolism. Significantly enriched functions of downregulated DEGs were mitotic cell cycle, nuclear division, DNA metabolic process, cell cycle, and mitosis. Upregulated DEGs were mainly enriched in single multicellular organism process and multicellular organismal process. Moreover, cell division cycle 6, checkpoint kinase 1 (CHEK1), E2F transcription factor 1 (E2F1), epidermal growth factor receptor (EGFR), and phosphoinositide-3-kinase, regulatory subunit 1-α (PIK3R1) of the module were remarkably enriched in pathways such as cell cycle, apoptosis, focal adhesion, and DNA replication. Cell division cycle 6, CHEK1, E2F1, EGFR, and PIK3R1 of the module and their relative pathways, cell cycle, and focal adhesion might play important roles of suppression of vemurafenib on melanoma progression.