Association of influenza virus infection and inflammatory cytokines with acute myocardial infarction.
To explore the potential relationship between previous influenza virus (IV) infection and acute myocardial infarction (AMI), and the mechanism of atherosclerosis, we conducted a case-control study and examined inflammatory cytokines to assess the association of previous IV infection and AMI. A questionnaire-based survey was conducted to collect information about demographic characteristics and heart disease risk factors. Fasting blood samples were obtained to measure immunoglobulin (Ig) G antibodies to influenza virus A (IV-A), influenza virus B (IV-B), cytomegalovirus, herpes simplex virus type-1 and type-2, adenovirus, rubella virus and Chlamydia pneumoniae, and to measure the level of certain biochemistry markers: interleukin-2, 6, 10 and 18 (IL-2, 6, 10 and 18), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), endothelin-1 (ET-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). Compared with the controls, the cases were more likely to have positive IgG antibodies to IV-A and IV-B [IV-A: odds ratio (OR): 3.1, 95% confidence interval (CI): 1.5-6.4; IV-B: OR: 10.2, 95% CI: 5.7-20.0]. After adjustment for potential confounding variables, the risk of AMI was still associated with the presence of IgG antibodies to IV-A (adjusted OR: 5.5, 95% CI: 1.3-23.0) and IV-B (adjusted OR: 20.3, 95% CI: 5.6-40.8). The levels of IL-2, 6, 10 and18, TNF-α, IFN-γ, ET-1, sICAM-1 and sVCAM-1 in patients with AMI were significantly higher than those of the controls (P < 0.01). Our study supports the hypothesis that previous IV infection is associated with AMI. Inflammatory cytokines may take part in the development of atherosclerosis and trigger the occurrence of AMI.


Evaluation of developmental neurotoxicity of polysorbate 80 in rats.
The developmental neurotoxicity of polysorbate 80 (PS80) was evaluated in rats. Crl:CD(SD) rats were given drinking water containing PS80 at 0, 0.018, 0.13, 1.0, or 7.5% (0, 0.035, 0.245, 1.864, or 16.783ml/kgbw/day) on day 0 of pregnancy through day 21 after delivery. Pregnant rats were allowed to deliver spontaneously. Potential adverse effects of pre- and post-natal exposure on the development and function of the nervous system in offspring of rats given PS80 were examined. Maternal body weight was lowered at 7.5%. Number of pups born was lowered at 7.5%. There were no compound-related effects on locomotor activity of offspring on postnatal days (PNDs) 14-15, 17-18, 20-21 and 33-37. No compound-related changes were found in developmental landmarks, sexual maturation, or reflex responses. Although decreased rate of avoidance responses was noted on PNDs 23-27 in male and female offspring at 7.5%, no compound-related changes were found in performance in the conditioned avoidance response on PNDs 60-67. Histopathological examinations of the brain revealed no toxicological changes. Lowered body weight was observed in male and female offspring at 7.5%. The NOAEL in this study was considered to be 1.0% (1.864ml/mg/kgbw/day).


[The role of systemic therapy of lung metastases with lymph node involvement].
Modern systemic therapy with chemotherapy, targeted therapy and immunotherapy has led to a significant improvement in the overall survival in many tumor diseases over the past 15 years. Thus, the surgical treatment of lung metastases and lymph node metastases is not only valuable to achieve a cure for selected tumors but it can and must be used to eliminate tumor growth peaks in the case of a circumscribed progression. These can be an expression of tumor heterogeneity that cannot be achieved by systemic therapy. Depending on the dynamics and extent of the metastasis, the therapeutic approach must be individually decided in the tumor board.


The potential prolonged effect at one-year follow-up after 18-month randomized controlled trial of a 90 g/day low-carbohydrate diet in patients with type 2 diabetes.
To evaluate the effect at a one-year follow-up after an 18-month randomized controlled trial (RCT) of 90 gm/day low-carbohydrate diet (LCD) in type 2 diabetes. Eighty-five poorly controlled type 2 diabetic patients with an initial HbA1c ≥ 7.5% who have completed an 18-month randomized controlled trial (RCT) on 90 g/day low-carbohydrate diet (LCD) were recruited and followed for one year. A three-day weighted food record, relevant laboratory tests, and medication effect score (MES) were obtained at the end of the previous trial and one year after for a total of 30 months period on specific diet. 71 (83.5%) patients completed the study, 35 were in TDD group and 36 were in LCD group. Although the mean of percentage changes in daily carbohydrate intake was significantly lower for those in TDD group than those in LCD group (30.51 ± 11.06% vs. 55.16 ± 21.79%, p = 0.0455) in the period between 18 months and 30 months, patients in LCD group consumed significantly less amount of daily carbohydrate than patients in TDD group (131.8 ± 53.9 g vs. 195.1 ± 50.2 g, p < 0.001). The serum HbA1C, two-hour serum glucose, serum alanine aminotransferase (ALT), and MES were also significantly lower for the LCD group patients than those in the TDD group (p = 0.017, p < 0.001, p = 0.017, and p = 0.008 respectively). The mean of percentage changes of HbA1C, fasting serum glucose, 2 h serum glucose, as well as serum cholesterol, triglyceride, low-density lipoprotein, ALT, creatinine, and urine microalbumin, however, were not significantly different between the two groups (p > 0.05). The one-year follow-up for patients on 90 g/d LCD showed potential prolonged and better outcome on glycaemic control, liver function and MES than those on TDD for poorly controlled diabetic patients.


Hospital volume allocation: integrating decision maker and patient perspectives.
Planning problems in healthcare systems have received greater attention in the last decade, especially because of the concerns recently raised about the scattering of surgical interventions among a wide number of different facilities that can undermine the quality of the outcome due to the volume-outcome association. In this paper, an approach to plan the amount of surgical interventions that a facility has to perform to assure a low adjusted mortality rate is proposed. The approach explicitly takes into account the existing interaction among patients' choices and decision makers' planning decisions. The first objective of the proposed approach is to find a solution able to reach quality in health outcomes and patients' adherence. The second objective is to investigate the difference among solutions that are identified as optimal by either only one of the actors' perspective, i.e., decision makers and patients, or by considering both the perspectives simultaneously. Following these objectives, the proposed approach is applied to a case study on Italian colon cancer interventions performed in 2014. Results confirm a variation in the hospital planned volumes when considering patients' behaviour together with the policy maker plan, especially due to personal preferences and lack of information about hospital quality.


Classifying diseases by using biological features to identify potential nosological models.
Established nosological models have provided physicians an adequate enough classification of diseases so far. Such systems are important to correctly identify diseases and treat them successfully. However, these taxonomies tend to be based on phenotypical observations, lacking a molecular or biological foundation. Therefore, there is an urgent need to modernize them in order to include the heterogeneous information that is produced in the present, as could be genomic, proteomic, transcriptomic and metabolic data, leading this way to more comprehensive and robust structures. For that purpose, we have developed an extensive methodology to analyse the possibilities when it comes to generate new nosological models from biological features. Different datasets of diseases have been considered, and distinct features related to diseases, namely genes, proteins, metabolic pathways and genetical variants, have been represented as binary and numerical vectors. From those vectors, diseases distances have been computed on the basis of several metrics. Clustering algorithms have been implemented to group diseases, generating different models, each of them corresponding to the distinct combinations of the previous parameters. They have been evaluated by means of intrinsic metrics, proving that some of them are highly suitable to cover new nosologies. One of the clustering configurations has been deeply analysed, demonstrating its quality and validity in the research context, and further biological interpretations have been made. Such model was particularly generated by OPTICS clustering algorithm, by studying the distance between diseases based on gene sharedness and following cosine index metric. 729 clusters were formed in this model, which obtained a Silhouette coefficient of 0.43.


Omega-3 polyunsaturated fatty acids and corneal nerve health: Current evidence and future directions.
Corneal nerves play a key role in maintaining ocular surface integrity. Corneal nerve damage, from local or systemic conditions, can lead to ocular discomfort, pain, and, if poorly managed, neurotrophic keratopathy. Omega-3 polyunsaturated fatty acids (PUFAs) are essential dietary components that play a key role in neural development, maintenance, and function. Their potential application in modulating ocular and systemic inflammation has been widely reported. Omega-3 PUFAs and their metabolites also have neuroprotective properties and can confer benefit in neurodegenerative disease. Several preclinical studies have shown that topical administration of omega-3 PUFA-derived lipid mediators promote corneal nerve recovery following corneal surgery. Dietary omega-3 PUFA supplementation can also reduce corneal epithelial nerve loss and promote corneal nerve regeneration in diabetes. Omega-3 PUFAs and their lipid mediators thus show promise as therapeutic approaches to modulate corneal nerve health in ocular and systemic disease. This review discusses the role of dietary omega-3 PUFAs in maintaining ocular surface health and summarizes the possible applications of omega-3 PUFAs in the management of ocular and systemic conditions that cause corneal nerve damage. In examining the current evidence, this review also highlights relatively underexplored applications of omega-3 PUFAs in conferring neuroprotection and addresses their therapeutic potential in mediating corneal nerve regeneration.


Purification and characterization of an organic solvent-tolerant alkaline cellulase from a halophilic isolate of Thalassobacillus.
An extracellular cellulase from Thalassobacillus sp. LY18 was purified 4.5-fold with a recovery of 21 % and a specific activity of 52.4 U mg(-1) protein. Its molecular mass was 61 kDa estimated by SDS-PAGE. It was an endoglucanase for soluble cellulose with optimal activity was at 60 °C and pH 8 with 10 % (w/v) NaCl. It was stable from 30 to 80 °C and from pH 7 to 11 with NaCl from 5 to 17.5 % (w/v). EDTA inhibited activity indicating it was a metalloenzyme. Inhibition by diethyl pyrocarbonate and β-mercaptoethanol suggested that histidine residues and disulfide bonds may play important roles in its catalytic function. The cellulase was highly active in non-ionic surfactants and was stable in water-insoluble organic solvents with log P (ow) ≥ 2.13.


Keeping an eye on environmental quality in Tanzania as trade, industrialization, income, and urbanization continue to grow.
By applying the ARDL (autoregressive distributed lag) bounds testing method, this study examines the short- and long-term dynamic relationship between carbon dioxide (CO2) emissions, economic growth (gross domestic product), industrialization, trade, and urban population in Tanzania from 1990 to 2020. The study found that economic growth, trade, industrialization, and the urban population all contributed to the increase in environmental degradation (i.e., carbon dioxide emissions). However, we found that financial credit (i.e., domestic credit to the private sector) reduces carbon dioxide emissions, and its effects are significant in EKC (environmental Kuznets curve) model. Our findings revealed that economic growth (i.e., income) was responsible for both short- and long-term increases in carbon dioxide emissions in Tanzania. Economic growth is harmful to the environmental quality above a threshold value of 6.23%. Furthermore, the environmental Kuznets curve hypothesis is confirmed for Tanzania. Our findings suggest that policymakers should monitor and use the threshold levels to manage carbon dioxide emissions and to protect the environmental quality. Further, a strong focus should be placed on formulating environmental policies (i.e., carbon tax policy) as industrialization, urban population, economic growth, and trade continue to grow in future, restricting carbon dioxide emissions and safeguarding the environment.


Hormone-stimulated phosphorylation of liver phosphofructokinase in vivo.
The effect of glucagon on the phosphorylation and the enzymic activity of phosphofructokinase in rat liver in vivo was investigated. Glucagon stimulated the phosphorylation of liver phosphofructokinase approximately 3- to 5-fold and increased cAMP levels 5-fold and blood glucose levels 2-fold over the values obtained for control animals. The specific radioactivity of ATP isolated from liver was the same in both control and hormone-treated animals. During the purification of the 32P-labeled enzyme from both animals, no difference was observed in the total or specific enzyme activities of the enzymes from the various fractions. Thus, phosphofructokinase appears to be phosphorylated in vivo by a cyclic AMP-dependent protein kinase. Although phosphorylation does not affect the maximum catalytic activity of the enzyme, it does render the enzyme significantly more sensitive to ATP inhibition. Thus, at a given concentration of ATP, the phosphorylated phosphofructokinase exhibits considerably lower activity than the unphosphorylated enzyme. The possible relationship between our observations and glucagon-mediated control of glycolysis is discussed.


Neuro-ophthalmological consequences of acute influenza A encephalitis in a genetically predisposed child.
Acute necrotising encephalopathy (ANE) is a rare disease that corresponds to a rapidly progressive encephalopathy induced by a viral infection. It is frequently associated with a mutation on the RAN-binding protein 2 (RANBP2) gene-ANE1. We present a case of a 5-year-old boy with a clinical picture of influenza aggravated to an acute encephalopathy picture after the 3rd day. Complementary examinations came back positive for the influenza A virus, and MRI showed aspects compatible with ANE. He was treated accordingly with subsequent improvement of the clinical picture. During ambulatory follow-up, a mutation was detected on the RANBP2 gene and, at the ophthalmological level, bilateral peripheral constriction on the campimetry and a significant reduction of bilateral peripapillary retinal nerve fibre layer was reported. Our case contributes to the enrichment of the neuro-ophthalmological literature and expands the spectrum of sequelae of this rare entity in the Caucasian population.


Effects of bonding agent types and incremental techniques on minimizing contraction gaps around resin composites.
In this in vitro study, large rectangular cavities were prepared on the proximal surfaces of human premolars with cervical margins placed beyond the cemento-enamel junction. Before the insertion of resin composite, the cavity walls were treated with Bowen's system, Scotchbond, or Gluma combined with different bonding agents. Various incremental techniques were tested. The contraction gap was determined by use of the resin impregnation technique: After polymerization shrinkage, a low-viscosity resin with a fluorescent additive was applied to the cervical and occlusal margins to penetrate the contraction gap. After being ground, the width of fluorescent resin could be measured with a microscope. All combinations of materials and techniques produced contraction gaps at the cervical wall. The range for mean width of the impregnated gap at the cervical wall was from 5 to 13 microns. The lowest mean value was obtained for Gluma in combination with Clearfil Bonding Agent. Placement of the composite in two increments significantly reduced the gap width. No reduction was achieved when a three-step insertion technique was used.


Extra-osseous osteochondroma-like soft tissue mass of the patello-femoral space.
Extraskeletal cartilaginous tumors are uncommon. Osteochondromas usually arise from the metaphyseal region of the growing skeleton. A 53 year old man presented with a three years history of anterior knee pain and inability to flex his knee more than 90 degrees . Clinical examination and imaging studies revealed a nodular calcific mass in the anterior portion of the knee, displacing the medial portion of the patellar tendon. Following excision, histopathology confirmed the diagnosis of extra-osseous osteochondroma-like soft tissue mass, with no recurrence 24 months after surgery. An integrated clinical-pathologic diagnosis helps to clarify the nature of extraskeletal cartilaginous tumors that can arise at unusual anatomic site. Complete local surgical excision is the management of choice.


Targeting the phosphoserine phosphatase MtSerB2 for tuberculosis drug discovery, an hybrid knowledge based /fragment based approach.
Tuberculosis is currently still one of the leading causes of death from a treatable pathogen. The proportion of cases of resistance to common antibiotics is frequently increasing and the development of new drugs with new therapeutic targets is becoming necessary. The Mycobacterium tuberculosis phosphoserine phosphatase MtSerB2 is an interesting enzyme to target in drug design because of its ability to allow immune evasion of the bacteria. Research has already been carried out on this protein both from a mechanistic point of view and from the point of view of its inhibition by trisubstituted harmine derivatives. Based on this work, a new approach based on virtual screening is presented in the selection of fragment-sized harmine-derived compounds as well as chelators to target the catalytic magnesium of MtSerB2. The selection of a minimum list of fragments is explained as well as the screening cascade (DSF, Ligand-based NMR, High concentration enzymatic assay) to characterise their affinity for MtSerB2. Crystallogenesis assays have provided structural information on some promising fragments and the development of a pharmacophore model with the structural elements necessary for the development of more complex inhibitors. Ultimately, this work on fragment growth would allow the development of antimycobacterial molecules inhibiting MtSerB2 as well as the growth of the pathogen.


[Influences of portal pressure change on intestinal permeability in patients with portal hypertension].
To investigate intestinal permeability in patients with portal hypertension and to search for a relationship with portal pressure. Twenty patients with portal hypertension were divided two groups (A, B), 10 patients per group. In group A patients were treated with combined TIPS and modified Sugiura. In group B, patients were treated with modified Sugiura only. Intestinal permeability was assessed before operation, two weeks after TIPS, and two weeks after modified Sugiura, and 20 healthy control subjects were also assessed. Intestinal permeability was significantly higher in patients with portal hypertension than in healthy controls (0.132 +/- 0.110 vs. 0.032 +/- 0.018, P < 0.01). In group A, portal pressure and intestinal permeability decreased two weeks after TIPS (P < 0.05) and no obvious change was noted two weeks after modified Sugiura; but they were significantly lower than those before TIPS (P < 0.05). In group B intestinal permeability was not different before and after operation. Intestinal permeability in group A was not different from that in group B before treatment, but significantly lower after modified Sugiura (P < 0.05). Portal pressure was significantly correlated with intestinal permeability (r = 0.627, P < 0.01). This study shows that combined TIPS and modified Sugiura can lower portal pressure and intestinal permeability, and enhance the therapeutic efficacy on portal hypertension.


Spontaneous charged lipid transfer between lipid vesicles.
An assay to study the spontaneous charged lipid transfer between lipid vesicles is described. A donor/acceptor vesicle system is employed, where neutrally charged acceptor vesicles are fluorescently labelled with the electrostatic membrane probe Fluoresceinphosphatidylethanolamine (FPE). Upon addition of charged donor vesicles, transfer of negatively charged lipid occurs, resulting in a fluorescently detectable change in the membrane potential of the acceptor vesicles. Using this approach we have studied the transfer properties of a range of lipids, varying both the headgroup and the chain length. At the low vesicle concentrations chosen, the transfer follows a first-order process where lipid monomers are transferred presumably through the aqueous solution phase from donor to acceptor vesicle. The rate of transfer decreases with increasing chain length which is consistent with energy models previously reported for lipid monomer vesicle interactions. Our assay improves on existing methods allowing the study of a range of unmodified lipids, continuous monitoring of transfer and simplified experimental procedures.


Adsorption properties of hollow carbon spheres to gaseous cyclohexane using DFT simulation and experiments.
The cyclohexane is the common toxic volatiles emitted from the various industry in worldwide leading to environmental degradation and human illnesses. Hence, there is a requirement for an efficient and stable adsorbent for adsorbing these toxic molecules to safeguard human health and the air atmosphere. Hollow carbon spheres (HCS) are a new type of carbon nanomaterial with large specific surface area, low density, and good chemical and thermal stability. In this study, DFT simulations and static-dynamic adsorption studies of cyclohexane were carried out using HCS as the adsorbent material. Among them, static adsorption focuses on adsorption/desorption isotherm, adsorption isotherm model fitting and isosteric heat of adsorption. Dynamic adsorption was mainly studied the effect of initial concentrations, gas flow rate, and ambient temperature on adsorption performance. The results showed that HCS exhibited very good performance in cyclohexane adsorption.


Low Case Finding Among Men and Poor Viral Load Suppression Among Adolescents Are Impeding Namibia's Ability to Achieve UNAIDS 90-90-90 Targets.
In 2015, Namibia implemented an Acceleration Plan to address the high burden of HIV (13.0% adult prevalence and 216 311 people living with HIV [PLHIV]) and achieve the UNAIDS 90-90-90 targets by 2020. We provide an update on Namibia's overall progress toward achieving these targets and estimate the percent reduction in HIV incidence since 2010. Data sources include the 2013 Namibia Demographic and Health Survey (2013 NDHS), the national electronic patient monitoring system, and laboratory data from the Namibian Institute of Pathology. These sources were used to estimate (1) the percentage of PLHIV who know their HIV status, (2) the percentage of PLHIV on antiretroviral therapy (ART), (3) the percentage of patients on ART with suppressed viral loads, and (4) the percent reduction in HIV incidence. In the 2013 NDHS, knowledge of HIV status was higher among HIV-positive women 91.8% (95% confidence interval [CI], 89.4%-93.7%) than HIV-positive men 82.5% (95% CI, 78.1%-86.1%). At the end of 2016, an estimated 88.3% (95% CI, 86.3%-90.1%) of PLHIV knew their status, and 165 939 (76.7%) PLHIV were active on ART. The viral load suppression rate among those on ART was 87%, and it was highest among ≥20-year-olds (90%) and lowest among 15-19-year-olds (68%). HIV incidence has declined by 21% since 2010. With 76.7% of PLHIV on ART and 87% of those on ART virally suppressed, Namibia is on track to achieve UNAIDS 90-90-90 targets by 2020. Innovative strategies are needed to improve HIV case identification among men and adherence to ART among youth.


Construction of Oxadiazepines via Lewis Acid-Catalyzed Tandem 1,5-Hydride Shift/Cyclization.
Expeditious access to oxadiazepines via 1,5-hydride shift/cyclization of pyrrolidine- or tetrahydroisoquinoline-containing nitrones has been developed. With 1,3-dipole nitrones serving as the hydride acceptors, this transformation was promoted by a Lewis acid, providing access to structurally diverse oxadiazepines in good yields. A one-pot process for in situ nitrone formation, a 1,5-hydride shift, and ring cyclization was also realized.


Reduced osteoblastic population and defective mineralization in osteopetrotic (op/op) mice.
Osteopetrotic (op/op) mice fail to exhibit bone remodeling because of a defective osteoclast formation due to a lack of macrophage colony-stimulating factor. In this study, we investigated the femora of op/op mice to clarify whether the osteoblastic population and bone mineralization are involved in osteoclasts or their bone resorption. The op/op mice extended the meshwork of trabecular bones from the chondro-osseous junction to the diaphyseal region. In the femoral metaphyses of op/op mice, intense alkaline phosphatase (ALPase)-positive osteoblasts were observed on the metaphyseal bone in close proximity to the erosion zone of the growth plates. Von Kossa's staining revealed scattered mineralized nodules and a fine meshwork of mineralized bone matrices while the wild-type littermates developed well-mineralized trabeculae parallel to the longitudinal axis. In contrast to the metaphysis, some op/op diaphyses showed flattened osteoblasts with weak ALPase-positivity, and the other diaphyses displayed bone surfaces without a covering by osteoblasts. It is likely, therefore, that the osteoblastic population and activity were lessened in the op/op diaphyses. Despite the osteopetrotic model, von Kossa's staining demonstrated patchy unmineralized areas in the op/op diaphyses, indicating that a lower population and/or the activity of osteoblasts resulted in defective mineralization in the bone. Transmission electron microscopy disclosed few osteoblasts on the diaphyseal bones, and instead, bone marrow cells and vascular endothelial cells were often attached to the unmineralized bone. Osteocytes were embedded in the unmineralized bone matrix. Thus, osteoclasts appear to be involved in the osteoblastic population and activity as well as subsequent bone mineralization.


Computational Study of Selected Amine and Lactam N-Oxides Including Comparisons of N-O Bond Dissociation Enthalpies with Those of Pyridine N-Oxides.
A computational study of the structures and energetics of amine N-oxides, including pyridine N-oxides, trimethylamine N-oxide, bridgehead bicyclic amine N-oxides, and lactam N-oxides, allowed comparisons with published experimental data. Most of the computations employed the B3LYP/6-31G* and M06/6-311G+(d,p) models and comparisons were also made between the results of the HF 6-31G*, B3LYP/6-31G**, B3PW91/6-31G*, B3PW91/6-31G**, and the B3PW91/6-311G+(d,p) models. The range of calculated N-O bond dissociation energies (BDE) (actually enthalpies) was about 40 kcal/mol. Of particular interest was the BDE difference between pyridine N-oxide (PNO) and trimethylamine N-oxide (TMAO). Published thermochemical and computational (HF 6-31G*) data suggest that the BDE of PNO was only about 2 kcal/mol greater than that of TMAO. The higher IR frequency for N-O stretch in PNO and its shorter N-O bond length suggest a greater difference in BDE values, predicted at 10-14 kcal/mol in the present work. Determination of the enthalpy of sublimation of TMAO, or at least the enthalpy of fusion and estimation of the enthalpy of vaporization might solve this dichotomy. The "extra" resonance stabilization in pyridine N-oxide relative to pyridine was consistent with the 10-14 kcal/mol increase in BDE, relative to TMAO, and was about half the "extra" stabilization in phenoxide, relative to phenol or benzene. Comparison of pyridine N-oxide with its acyclic model nitrone ("Dewar-Breslow model") indicated aromaticity slightly less than that of pyridine.


Calcium pyrophosphate crystal deposition with rotator cuff tear-A case report.
Calcium pyrophosphate dihydrate (CPPD) deposition disease is an inflammatory arthritis induced by calcium pyrophosphate (CPP) crystals and clinically it is called pseudogout. It usually deposits in articular cartilage and in periarticular soft tissues. But no cases of pseudogout in the rotator cuff without cartilage deposition or destruction have been reported so far. We present a case of a 57-year-old woman who was diagnosed as pseudogout with rotator cuff tear.


Blood feeding habits of mosquitoes: hardly a bite in South America.
Mosquito blood feeding plays a key role in epidemiology. Despite its importance and large number of studies worldwide, less attention has been paid in South America. We summarized some general concepts and methodological issues related to the study of mosquito blood feeding habits, and compiled and analyzed all published information regarding the subject in the continent until 2020. Available literature comprised 152 scientific studies, that pursued different approaches: human landing catches (102 studies), baited trap (19), and blood meal analyses of collected specimens (38). Among the latter, 23 used serological and 15 molecular techniques. Species most frequently studied were those incriminated in malaria transmission, whereas relevant vectors such as Aedes aegypti, Ae. albopictus, and Haemagogus janthinomys were surprisingly neglected. Brazil was the leading country both in number of works and species studied. For over 70% of the species and three out of 13 South American countries there is no single information on mosquito blood feeding habits. Data from baited traps included 143 mosquito species, 83.9% of which were attracted to humans, either exclusively (10.5%) or in combination with other vertebrates (73.4%). Host blood identification of field collected specimens provided data on 102 mosquito species, and 60.8% of these fed on humans (55.9% combined with other vertebrates). Only 17 of the 73 species assessed by both methods yielded similar feeding patterns. Finally, supplementary tables are provided in a comprehensive summary of all information available and information gaps are highlighted for future research in the continent.


Polarizability of the Active Site in Enzymatic Catalysis: Cytochrome c.
Anisotropic polarizability of the heme in cytochrome c is found to be a major factor in suppressing the activation barrier of protein electron transfer (catalytic effect). Polarizability couples to the electric field of protein and water to enhance fluctuations of the electron-transfer energy gap and the corresponding variance reorganization energy λvar. The reorganization energy observable by kinetic measurements λr = (λSt)2/λvar is composed of λvar and the Stokes-shift reorganization energy λSt. It is lowered compared to the usually reported λSt due to polarizability of the active site leading to λvar > λSt. The coupling of electrostatic protein-water fluctuations to the polarizable active site is accounted for here by empirical valence-bond diagonalization of the active-site Hamiltonian along the simulation trajectory. We show that recent simulations employing this technique, which failed to find the effect of polarizability on electron-transfer kinetics, were erroneous in neglecting the diagonal dipole moments in the Hamiltonian matrix and failing to rotate the electric field produced by the protein-water medium into the molecular frame of the active site. We find that anisotropy of the tensor of polarizability difference in the two oxidation states of the heme matches anisotropy of the second-rank tensor constructed from the electric field at the active site. Exposure of the heme to water from only one side carries significant catalytic function, directly leading to the field anisotropy and the corresponding depression of the activation barrier.


The French OQALI survey on dairy products: comparison of nutrient contents and other nutrition information on labels among types of brands.
Depending on their spending power, consumers may choose foodstuffs from more or less expensive types of brands (national, retailer, economy-line retailer or discount brands). The present study, on dairy products, assesses the nutritional composition and the frequencies of labelled nutrition parameters, according to types of brands. The 1646 most consumed dairy products were collected. Nutrient contents and other labelled nutrition parameters provided on the packaging (i.e. nutrition and health claims, nutrition guidelines such as guideline daily amounts, consumption advice and information on added vitamins and minerals) were captured in the French branded product composition database (OQALI). Significant differences between brands were found for energy, protein, fat, saturates, carbohydrate, sugars, dietary fibre, calcium and sodium, in four of six dairy groups studied, but not systematically. National brands and retailer brands provided more detailed nutrition labelling and more frequent nutrition claims than cheaper brands. More retailer brand products provided nutrition guidelines and consumption advice than the other branded products. National brand products more frequently contained added vitamins and minerals and more frequently bore health claims. Nutrient contents of the cheaper brands of dairy products did not vary systematically from more expensive ones. However, national brands and retailer brands products provided more nutrition information on labels than the cheaper ones. There should be more detailed studies comparing different types of brands regarding labelling practices for nutrient contents and other nutrition information about foodstuffs to help prepare public health recommendations, adapted to all consumers, regardless of their income.


Diaph3 underlines tumor cell heterogeneity in glioblastoma with implications for treatment modalities resistance.
Glioblastoma (GBM) is the most aggressive central nervous system (CNS) tumor with astrocytic differentiation. The growth pattern of GBM mimics that of the precursor cell migration during the fetal development of the brain. Diaphanous homolog (Diaph3) has been established to play a role in both CNS maturation and cancer progression as it is required both for cell migration and division. Furthermore, Diaph3 has been shown to play a role in malignant disease progression through hyperactivation of the EGFR/MEK/ERK in loss of expression and its overexpression correlating to hyperactivity of the mTOR pathway, both of which are with a well-established role in GBM. Herein, we aimed at establishing the diagnostic role of Diaph3 immunohistochemistry expression patterns in GBM and their possible implications for molecular response to different therapies. The study utilized a retrospective nonclinical approach. Results of Diaph3 immunohistochemical expression were compared to healthy controls and reactive gliosis and statistically analyzed for correlation with neuroradiological tumor parameters and patient survival. Healthy controls showed individual weakly positive cells, while reactive gliosis controls showed a strong expression in astrocytic projections. GBM samples showed a heterogeneous positive reaction to Diaph3, mean number of positive cells 62.66%, median 61.5, range 12-96%. Areas of migrating cells showed a strong diffuse cytoplasmic reaction. Cells located in the tumor core and those in areas of submeningeal aggregation had no antibody expression. Statistical analysis revealed no correlation with tumor size or patient survival. The different expression pattern of Diaph3 in healthy controls, reactive gliosis and GBM shows promise as a clinical differentiating marker. Despite Diaph3 expression not correlating with survival and tumor size in GBM, there is an accumulating body of evidence that Diaph3 correlates with mTOR activity and can thus be used as a predictor for response to rapamycin and taxanes, clinical studies of which have shown promising, if mixed results in GBM.


The implementation of clinical practice guidelines for venous leg ulcers.
Since publishing its guidelines on the management of venous leg ulcers last year, the RCN has worked steadily to implement and audit both the guidelines, and their impact.


Ischiofemoral impingement syndrome: a case report and review of literature.
The etiology of ischiofemoral impingement (IFI) syndrome, an unusual and uncommon form of hip pain, remains uncertain. Some patients demonstrate narrowing of the space between the ischial tuberosity and lesser trochanter from trauma or abnormal morphology of the quadratus femoris muscle. Combined clinical and imaging aid in the diagnosis. A 32-year-old female presented with a 3 years history of pain over the lower aspect of the right buttock, aggravated by movements of the right hip, and partially relieved with rest and medications. The right hip showed extreme restriction of abduction and external rotation. MRI of the right hip showed reduced ischiofemoral space and quadratus femoris space when compared to the left hip. The patient underwent endoscopic resection of the right lesser trochanter, with no recurrence of pain at 2 years. An unusual cause of hip pain, IFI syndrome, should be suspected when hip pain at extremes of movement is associated with signal abnormality of quadratus femoris muscle. Management is tailored to address the inciting factors that precipitated the IFI syndrome.


Projected lifetime risks and hospital care expenditure for traumatic injury.
The lifetime risk and expected cost of trauma care would be valuable for health policy planners, but this information is currently unavailable. The cumulative incidence rates methodology, based on a cross-sectional population analysis, offers an alternative approach to prohibitively costly prospective cohort studies. Retrospective analysis of the California Office of Statewide Health Planning and Development (OSHPD) database was performed for 2008. Trauma admissions were identified by ICD-9 primary diagnosis codes 800-959, with certain exclusions. Cumulative incidence rates were calculated as the cumulative summation of incidence risks sequentially across age groups. A total of 2.2 million admissions were identified, with mean age of 63.8 y, 49.6% men, 82.8% Whites, 5.7% Blacks, 11.3% Hispanics, and 3.1% Asians. The cumulative incidence rate for patients older than age 85 y was 1119 per 10,000 people, with the majority of risk in the elderly, compared with 24,325 per 10,000 people for all-cause hospitalizations. The rates were 946 for men, 1079 for women, 999 for non-Hispanic Whites, 568 for Blacks, 577 for Hispanics, and 395 for Asians, per 10,000 population. The cumulative expected hospital charge was $6538, compared with $81,257 for all-cause hospitalizations. The cumulative lifetime risk of trauma/injury requiring hospitalization for a person living to age 85 y in California is 11.2%, accounting for 4.6% of expected lifetime hospitalizations, but accounting for 8.0% of expected lifetime hospital expenditures. Risk of trauma is significant in the elderly. The total expenditure for all trauma hospitalizations in California was $7.62 billion in 2008.


Metacognitive Domains Are Not Aligned along a Dimension of Internal-External Information Source.
It is still debated whether metacognition, or the ability to monitor our own mental states, relies on processes that are "domain-general" (a single set of processes can account for the monitoring of any mental process) or "domain-specific" (metacognition is accomplished by a collection of multiple monitoring modules, one for each cognitive domain). It has been speculated that two broad categories of metacognitive processes may exist: those that monitor primarily externally generated versus those that monitor primarily internally generated information. To test this proposed division, we measured metacognitive performance (using m-ratio, a signal detection theoretical measure) in four tasks that could be ranked along an internal-external axis of the source of information, namely memory, motor, visuomotor, and visual tasks. We found correlations between m-ratios in visuomotor and motor tasks, but no correlations between m-ratios in visual and visuomotor tasks, or between motor and memory tasks. While we found no correlation in metacognitive ability between visual and memory tasks, and a positive correlation between visuomotor and motor tasks, we found no evidence for a correlation between motor and memory tasks. This pattern of correlations does not support the grouping of domains based on whether the source of information is primarily internal or external. We suggest that other groupings could be more reflective of the nature of metacognition and discuss the need to consider other non-domain task-features when using correlations as a way to test the underlying shared processes between domains.


Outcomes of Patients Initially Treated with Intravitreal Bevacizumab for Central Retinal Vein Occlusion: Long-Term Follow-Up.
To assess outcomes of visual acuity (VA) and central retinal thickness (RT) in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO) who were initially treated with bevacizumab and followed for up to four years. In this observational case series, 51 patients with non-ischemic and ischemic CRVO who had initial treatment with bevacizumab were included. Main outcome measures were VA and RT at one year, with follow-up of up to four years. Mean VA improved from 20/214 at baseline to 20/107 at one year (p = 0.0009) and this improvement was maintained clinically at four years. RT decreased from 595 μm to 339 μm at one year (p = 0.0027) and this was maintained at four years. Patients who received bevacizumab as initial therapy for ME from CRVO maintained VA and RT improvement for up to four years.


Axial ligand effects on myoglobin stability.
Reversible guanidine hydrochloride denaturation has been applied to obtain the first quantitative estimate of ligand-induced changes in hemoprotein conformational free energy. It is found that strong field (low spin) complexes, e.g. cyanometmyoglobin (MbCN) and azido metmyoglobin (MbN3), are 1.0 +/- 0.1 kcal/mol more stable than the high spin analogs aquometmyoglobin (MbH2O) and fluorometmyoglobin (MbF). This observed stability increment is essentially independent of the model chosen for data analysis. These results demonstrate the value of denaturation titration in measuring the stabilization of hemoprotein conformation by ligand binding. The denaturation of MbN3 appears complex. This complexity may be quantitatively accounted for by considering spin state equilibria. Applying this correction, MbCN and MbN3 have essentially the same stability in spite of steric differences in the two proteins. This result implies metal spin state is more important than ligand stereochemistry in determining the conformational free energy of myoglobin.


Endoscopic holmium:YAG laser ablation of early gastrointestinal intramucosal cancer.
Various endoscopic techniques are being increasingly used in early gastrointestinal (GI) cancer. The holmium: yttrium-aluminum-garnet (Ho:YAG) laser has precise tissue cutting ability and good hemostatic properties and has been widely applicated to soft tissue, but the use of endoscopic Ho:YAG laser ablation for early gastrointestinal cancer has not been reported. Twenty patients with biopsy-proven early GI cancer who had a high surgical risk or refused surgery were treated by endoscopic Ho:YAG laser ablation. The tumors of all patients were confined to the mucosal layer without ulceration and without lymph node metastasis. The tumor diameter was not more than 2.5 cm. Endoscopy, endoscopic ultrasound, and computed tomography scan were performed 1-3 months after the treatment, and a biopsy was performed to evaluate the effects of the therapy. Long-term endoscopic follow-up was maintained. Complete eradication was achieved in all the 20 patients, including four patients with high-grade dysplasia associated with focal canceration, seven patients with well-differentiated squamous cell cancer, and nine patients with well-differentiated adenocarcinoma, resulting in a complete response rate of 100% at 1-3 months after treatment. No recurrence was found during 36-73 months of follow-up in all 20 patients. No operative or delayed complications were observed in any of the 20 patients. Preliminary study shows that endoscopic Ho:YAG laser ablation may be an effective, safe, and minimally invasive method for selected patients with early GI intramucosal cancer. Further research is required to confirm the safety and efficacy of this technique compared to its alternative techniques in a multicenter randomized controlled trial.


Prospective evaluation of external ocular microbial growth and aqueous humor contamination during cataract surgery.
To analyze the route of aqueous humor contamination leading to the development of postoperative endophthalmitis. Department of Ophthalmology, University of Helsinki, Finland. Forty-nine eyes of 49 patients (31 having phacoemulsification and 18 extracapsular cataract extraction [ECCE]) participated in the study. Four bacterial cultures were taken: preoperative conjunctival swab, lid margin culture, intraoperative lacrimal lake sample, and immediate postoperative anterior chamber fluid sample. Preoperative lid margin cultures were positive in 59.2% of eyes, conjunctival cultures in 69.4%, and lacrimal lake cultures in 24.9%. Four aqueous humor samples (8.2%) showed bacterial growth in the anterior chamber aspirate: 3 in the phacoemulsification and 1 in the ECCE group. The bacteria isolated in this study, Staphylococcus epidermidis and Propionibacterium acnes (2 positive isolates each) were sensitive to the preoperative topical antibiotics used. No aqueous humor sample or any from other locations showed gram-negative microbe growth. The most frequently recovered microbes in all samples collected from the 3 other sources were S epidermidis and other coagulase-negative staphylococcus species, followed by P acnes and other propionibacterium species. Staphylococcus aureus, and diptheroids. The ocular surface significantly contributed to the transmission of microbes into the eye during cataract surgery. These microbes could not be eradicated by topical preoperative antibiotics. However, no patient developed postoperative endophthalmitis. Natural defense mechanisms appear to fend off a minor inoculum with these microbes of relatively low pathogenicity.


Impact of Heat and Cold on Total and Cause-Specific Mortality in Vadu HDSS--A Rural Setting in Western India.
Many diseases are affected by changes in weather. There have been limited studies, however, which have examined the relationship between heat and cold and cause-specific mortality in low and middle-income countries. In this study, we aimed to estimate the effects of heat and cold days on total and cause-specific mortality in the Vadu Health and Demographic Surveillance System (HDSS) area in western India. We used a quasi-Poisson regression model allowing for over-dispersion to examine the association of total and cause-specific mortality with extreme high (98th percentile, >39 °C) and low temperature (2nd percentile, <25 °C) over the period January 2003 to December 2012. Delays of 0 and 0-4 days were considered and relative risks (RR) with 95% confidence intervals (CI) were calculated. Heat was significantly associated with daily deaths by non-infectious diseases (RR = 1.57; CI: 1.18-2.10). There was an increase in the risk of total mortality in the age group 12-59 years on lag 0 day (RR = 1.43; CI: 1.02-1.99). A high increase in total mortality was observed among men at lag 0 day (RR = 1.38; CI: 1.05-1.83). We did not find any short-term association between total and cause-specific mortality and cold days. Deaths from neither infectious nor external causes were associated with heat or cold. Our results showed a strong and rather immediate relationship between high temperatures and non-infectious disease mortality in a rural population located in western India, during 2003-2012. This study may be used to develop targeted interventions such as Heat Early Warning Systems in the area to reduce mortality from extreme temperatures.


Aggressive osteoblastoma of the mandible.
We report a case of aggressive osteoblastoma of the mandible, an extremely rare primary bone tumor of the maxillofacial skeleton. Although osteoblastomas are benign tumors requiring only curettage for cure, there is a small subset of tumors that exhibit locally aggressive behavior and have atypical histopathologic features. Differentiation from low-grade osteosarcoma is often difficult. There is some disagreement as to the proper classification of these tumors. The correct diagnosis must be based on clinical, radiographic and pathologic features. Surgical resection and reconstruction is the recommended treatment for these invasive lesions.


Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics.
Brain 18F-FDG PET imaging has the potential to provide an objective assessment of brain involvement in post-COVID-19 conditions but previous studies of heterogeneous patient series yield inconsistent results. The current study aimed to investigate brain 18F-FDG PET findings in a homogeneous series of outpatients with post-COVID-19 conditions and to identify associations with clinical patient characteristics. We retrospectively included 28 consecutive outpatients who presented with post-COVID-19 conditions between September 2020 and May 2022 and who satisfied the WHO definition, and had a brain 18F-FDG PET for suspected brain involvement but had not been hospitalized for COVID-19. A voxel-based group comparison with 28 age- and sex-matched healthy controls was performed (p-voxel at 0.005 uncorrected, p-cluster at 0.05 FWE corrected) and identified clusters were correlated with clinical characteristics. Outpatients with post-COVID-19 conditions exhibited diffuse hypometabolism predominantly involving right frontal and temporal lobes including the orbito-frontal cortex and internal temporal areas. Metabolism in these clusters was inversely correlated with the number of symptoms during the initial infection (r = - 0.44, p = 0.02) and with the duration of symptoms (r = - 0.39, p = 0.04). Asthenia and cardiovascular, digestive, and neurological disorders during the acute phase and asthenia and language disorders during the chronic phase (p ≤ 0.04) were associated with these hypometabolic clusters. Outpatients with post-COVID-19 conditions exhibited extensive hypometabolic right fronto-temporal clusters. Patients with more numerous symptoms during the initial phase and with a longer duration of symptoms were at higher risk of persistent brain involvement.


Purification and characterization of a novel laccase from the edible mushroom Hericium coralloides.
A novel laccase from the edible mushroom Hericium coralloides was purified by ion exchange chromatography on diethylaminoethyl (DEAE) cellulose, carboxymethyl (CM) cellulose, and Q-Sepharose columns followed by fast protein liquid chromatography gel filtration on a Superdex 75 column. Analysis by gel filtration and SDS-PAGE indicated that the protein is a monomer in solution with a molecular mass of 65 kDa. Its N-terminal amino acid sequence was AVGDDTPQLY, which exhibits partial sequence homology to previously isolated laccases. Optimum activity was observed at pH 2.2 and at 40°C. The enzyme showed activity toward a variety of substrates, the most sensitive of which was 2,2'-azinobis [3-ethylbenzothiazolone-6-sulfonic acid] diammonium salt (ABTS). The degradation activity toward substrates was ABTS > N,N-dimethyl-1,4-phenylenediamine > catechol > 2-methylcatechol > pyrogallol. The laccase did not exert any antiproliferative activity against Hep G2 or MCF 7 tumor cell lines at a concentration of 60 μM, unlike some previously reported mushroom proteins, but showed significant activity toward human immunodeficiency virus-1 (HIV-1) reverse transcriptase with an IC(50) of 0.06 μM.


[An investigation on dental bio-tribological characteristics of prosthesis made of titanium material].
This study aimed at investigating bio-tribological property of titanium opposite to teeth as a base of clinical application. Under a modified fretting machine, wear tests on human natural teeth were carried out in artificial saliva conditions against to pure titanium. The dynamic frictional process and wear mechanisms were investigated by means of Nene-2, MVK-H12, TALYSURF6, OM, LSM, SEM, EDX. The coefficient of friction exhibited a variation pattern of longs. The wear mechanism of natural tooth was detected as micro-cut and denaturation of dental texture and the wear depth of Ti/teeth was 20.33 + 2.86 microm, the wear depth of Ti/Ti being 38.00 + 5.88 microm (P < 0.05). The natural tooth has a good tribological behavior, matching the friction behavior of pure titanium. Over occlusal force during masticate process and para-function should be avoided. When we chose dental materials, wear resistance should be taken into account.


Preparation and evaluation of bombesin peptide derivatives as potential tumor imaging agents: effects of structure and composition of amino acid sequence on in vitro and in vivo characteristics.
Among the many clinically relevant peptide receptor systems, bombesin (BN) receptors have attracted enormous attraction due to their overexpression in various frequently occurring human tumors including breast and prostate, thus making such receptors promising targets with radiolabeled BN analogs. The present study describes the preparation and evaluation of a series of new BN derivatives as potential tumor imaging agents. Several new BN derivatives with the common structure MAG(3)-X-BN(1-14 or 6-14), where X=Asp or Asp-Asp, were synthesized by solid-phase peptide synthesis. S-benzoylmercaptoacetic acid was incorporated at the end of synthesis via manual conjugation to yield MAG(3)-BN conjugates. Radiolabeling with (99m)Tc was accomplished by ligand exchange method. The receptor-binding affinity assays were performed in MDA-MB-231, MCF-7, T47-D and PC-3 cancer cell lines. In vivo biodistribution and clearance kinetics were assessed in Balb/c mice, and tumor targeting efficacy was determined in nude mice bearing breast tumor xenografts. The peptides were prepared conveniently and radiolabeled efficiently with (99m)Tc (up to 95% labeling efficiency). In vitro cell binding assays demonstrated high affinity (values in the nanomolar range) of (99m)Tc peptides towards breast and prostate cancer cell lines. In addition, the radioconjugates displayed significant internalization (values ranged between 19% and 35%) in tumor cells. In vivo biodistribution and biokinetics are characterized by efficient clearance from the blood and variable degrees of excretion through the renal pathway. In vivo tumor targeting studies displayed variable uptake capacity of different BN derivatives, underlining the influence of specific amino acid sequence on tumor targeting profiles. Tumor uptake was always higher than the radioactivity in the blood and muscle, with good tumor retention and good tumor-to-blood and tumor-to-muscle ratios, indicating the potential of these agents for targeting tumors in vivo. The combination of favorable in vitro and in vivo properties may render these BN peptides as potential candidates for targeting BN/GRP receptor-positive tumors. They deserve further evaluation to determine their real strength. The present data indeed provide useful information regarding peptide structure-pharmacologic activity relationship, which might be useful in designing and developing new BN-like peptides for efficient targeting of tumors in vivo.


Fast developing Russian wheat aphid biotypes remains an unsolved enigma.
Diuraphis noxia, commonly known as the Russian wheat aphid, is an economically important cereal pest species, highly invasive and reproduces mostly asexually. Remarkably, many new virulent populations continue to develop, despite the lack of genetic diversity in the aphid. Russian wheat aphid is a phloem feeder and is therefore engaged in a continuous arms battle with its cereal host, with the acquisition of virulence central to the breakdown of host resistance. In the review, most attention is given to recent topics about mechanisms and strategies whereby the aphid acquires virulence against its host, with special reference given to the role of noncoding RNA elements, bacteria, and the epigenetic pathway in possibly directing virulence.


Repeatability and robustness of MP-GRASP T1 mapping.
To demonstrate the repeatability of fast 3D T1 mapping using Magnetization-Prepared Golden-angle RAdial Sparse Parallel (MP-GRASP) MRI and its robustness to variation of imaging parameters including flip angle and spatial resolution in phantoms and the brain. Multiple imaging experiments were performed to (1) assess the robustness of MP-GRASP T1 mapping to B1 inhomogeneity using a single tube phantom filled with uniform MnCl2 liquid; (2) compare the repeatability of T1 mapping between MP-GRASP and inversion recovery-based spin-echo (IR-SE; over 12 scans), using a commercial T1MES phantom; (3) evaluate the longitudinal variation of T1 estimation using MP-GRASP with varying imaging parameters, including spatial resolution, flip angle, TR/TE, and acceleration rate, using the T1MES phantom (106 scans performed over a period of 12 months); and (4) evaluate the variation of T1 estimation using MP-GRASP with varying imaging parameters in the brain (24 scans in a single visit). In addition, the accuracy of MP-GRASP T1 mapping was also validated against IR-SE by performing linear correlation and calculating the Lin's concordance correlation coefficient (CCC). MP-GRASP demonstrates good robustness to B1 inhomogeneity, with intra-slice variability below 1% in the single tube phantom experiment. The longitudinal variability is good both in the phantom (below 2.5%) and in the brain (below 2%) with varying imaging parameters. The T1 values estimated from MP-GRASP are accurate compared to that from the IR-SE imaging (R2 = 0.997, Lin's CCC = 0.996). MP-GRASP shows excellent repeatability of T1 estimation over time, and it is also robust to variation of different imaging parameters evaluated in this study.


Identification of IL-40, a Novel B Cell-Associated Cytokine.
We describe a novel B cell-associated cytokine, encoded by an uncharacterized gene (C17orf99; chromosome 17 open reading frame 99), that is expressed in bone marrow and fetal liver and whose expression is also induced in peripheral B cells upon activation. C17orf99 is only present in mammalian genomes, and it encodes a small (∼27-kDa) secreted protein unrelated to other cytokine families, suggesting a function in mammalian immune responses. Accordingly, C17orf99 expression is induced in the mammary gland upon the onset of lactation, and a C17orf99-/- mouse exhibits reduced levels of IgA in the serum, gut, feces, and lactating mammary gland. C17orf99-/- mice have smaller and fewer Peyer's patches and lower numbers of IgA-secreting cells. The microbiome of C17orf99-/- mice exhibits altered composition, likely a consequence of the reduced levels of IgA in the gut. Although naive B cells can express C17orf99 upon activation, their production increases following culture with various cytokines, including IL-4 and TGF-β1, suggesting that differentiation can result in the expansion of C17orf99-producing B cells during some immune responses. Taken together, these observations indicate that C17orf99 encodes a novel B cell-associated cytokine, which we have called IL-40, that plays an important role in humoral immune responses and may also play a role in B cell development. Importantly, IL-40 is also expressed by human activated B cells and by several human B cell lymphomas. The latter observations suggest that it may play a role in the pathogenesis of certain human diseases.


Development of a 'mechano-active' scaffold for tissue engineering.
In this study. we investigate the potential for manipulating bone cell mechanotransducers in tissue engineering. Membrane ion channels such as voltage operated calcium channels (VOCC) have been shown to be a critical component of the bone cell transduction pathway with agonists and inhibitors of this pathway having profound effects on the load signal. By encapsulating a calcium channel agonist with slow release within a poly(L-lactide) (PLLA) scaffold, we can generate a 'mechano-active' scaffold for use in skeletal tissue engineering. PLLA scaffolds with and without a calcium channel agonist, BAY K8644, were seeded with primary human bone cells or the human MG63 bone cell line and cultured for 13 weeks followed by mechanical stimulation with a four-point bending model. Our results show that addition of the agonist for slow release is sufficient to enhance the load-related responses in bone cells within the scaffolds. Specifically, collagen type I expression and the ratio of alkaline phosphatase to protein are elevated in response to cyclical mechanical stimulation of approximately 1000 microstr which is then further enhanced in the mechano-active' scaffolds. As the agonists only act when the calcium channels are open by attenuating the calcium flux, the stimulation is specifically targeted to scaffolds subjected to load either in vitro or ultimately in vivo. Our results suggest that manipulating the VOCC and attenuating the opening of the calcium channels may be an effective technique to amplify matrix production via mechanical stimulation which may be applied to bone tissue engineering and potentially engineering of other load-bearing connective tissues.


Comparison of the discriminative stimulus properties of cocaine and amphetamine in rats.
1. Water-deprived rats were trained to press either the left or the right bar in a test chamber according to whether they were injected with a central nervous system stimulant or 0.9% w/v NaCl solution (saline). Correct responses were reinforced with water. 2. Different groups of rats learned to discriminate amphetamine or cocaine from saline. Dose-response curves and ED50 values were then determined in brief test sessions when no responses were reinforced. 3. In a crossover study, cocaine was tested in the rats trained to discriminate amphetamine from saline, and vice versa. The two drugs were largely interchangeable, but the ED50 values were increased, indicating a possible, subtle difference in their discriminative stimulus properties. 4. The results indicate the importance of complete crossover designs in combination with dose response determinations when attempting to classify drugs according to their discriminable properties.


Optimizing resource allocation for breast cancer prevention and care among Hong Kong Chinese women.
Recommendations about funding of interventions through the full spectrum of the disease often have been made in isolation. The authors of this report optimized budgetary allocations by comparing cost-effectiveness data for different preventive and management strategies throughout the disease course for breast cancer in Hong Kong (HK) Chinese women. Nesting a state-transition Markov model within a generalized cost-effectiveness analytic framework, costs and quality-adjusted life-years (QALYs) were compared to estimate average cost-effectiveness ratios for the following interventions at the population level: biennial mass mammography (ages 40-69 years or ages 40-79 years), reduced waiting time for postoperative radiotherapy (by 15% or by 25%), adjuvant endocrine therapy (either upfront aromatase inhibitor [AI] therapy or sequentially with tamoxifen followed by AI) in postmenopausal women with estrogen receptor-positive disease, targeted immunotherapy in those with tumors that over express human epidermal growth factor receptor 2, and enhanced palliative services (either at home or as an inpatient). Usual care for eligible patients in the public sector was the comparator. In descending order, the optimal allocation of additional resources for breast cancer would be the following: a 25% reduction in waiting time for postoperative radiotherapy (in US dollars: $5000 per QALY); enhanced, home-based palliative care ($7105 per QALY); adjuvant, sequential endocrine therapy ($17,963 per QALY); targeted immunotherapy ($62,092 per QALY); and mass mammography screening of women ages 40 to 69 years ($72,576 per QALY). Given the lower disease risk and different age profiles of patients in HK Chinese, among other newly emergent and emerging economies with similar transitioning epidemiologic profiles, the current findings provided direct evidence to support policy decisions that may be dissimilar to current Western practice.


Separation of triacylglycerols in a complex lipidic matrix by using comprehensive two-dimensional liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometric detection.
The present investigation describes the employment of a comprehensive 2-D HPLC system, based on the combination of a silver ion and an RP column, for the characterization of the triacylglycerol (TAG) fraction of a very complex lipidic sample: donkey milk fat. The TAGs were grouped on the resulting bidimensional contour plot according to their double bond numbers (aligned along vertical bands) and according to their partition numbers (aligned along horizontal bands). Peak assignment was supported by using atmospheric pressure chemical ionization mass spectrometric (APCI-MS) detection. The combination of the enhanced resolving power of comprehensive multidimensional LC, the formation of ordered 2-D patterns, and APCI-MS detection proved to be an effective tool for the characterization of the complex matrix, enabling the separation and identification of nearly 60 TAGs.


Interaction of 125I-labeled Ca2+-dependent regulator protein with cyclic nucleotide phosphodiesterase and its inhibitory protein.
The Ca2+-dependent regulator protein of cyclic nucleotide phosphodiesterase was labeled with 125I to the extent of 1 mol of monoiodotyrosine per mol. The iodinated protein showed a small decrease in affinity for phosphodiesterase but gave the same maximal level of activation of the enzyme as did the unmodified regulator protein. Iodinated regulator protein formed complexes with both highly purified cyclic nucleotide phosphodiesterase and phosphodiesterase inhibitory protein in the presence but not in the absence of Ca2+ as demonstrated by ultracentrifugation in glycerol gradients. Cross-linking experiments indicate that the Ca2+-dependent regulator protein interacts with the large subunit of the inhibitory protein.


Decreased Serum Netrin-1 as a Predictor for Post-Stroke Depression in Chinese Patients with Acute Ischemic Stroke.
Experimental studies demonstrated that netrin-1 (NT-1) is an important factor influencing the recovery after ischemic stroke. However, whether NT-1 levels were associated with the post-stroke depression (PSD) remains unclear. We aimed to evaluate the relationship between NT-1 levels and PSD at 3 months in patients with ischemic stroke. From January 2018 to December 2019, consecutive Chinese patients with first-ever ischemic stroke were prospectively recruited. Serum NT-1 levels were measured at admission. Patients with a 17-item Hamilton Depression Scale score of ≥7 were given the Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for diagnosis of PSD. A total of 238 patients (mean age, 62.5 years; 45.4% female) were enrolled. The median NT-1 concentrations were 467.8 pg/mL (interquartile range, 351.8-581.0 pg/mL). During the 3-month follow-up period, 64 patients (26.9%) experienced PSD. Serum NT-1 levels were significantly lower in PSD patients than in patients without PSD (median, 380.3 pg/mL versus 478.5 pg/mL; P = 0.001). After adjusting for demographic characteristic, National Institutes of Health stroke score, and other potential confounders by multiple logistic regression analysis, patients with NT-1 levels in the first quartile were more likely to have 3-month PSD (as compared with the fourth quartile, odds ratio 3.83, 95% confidence intervals, 1.53-9.63, P = 0.004). Similar significant findings were observed when the NT-1 levels were added as a continuous variable. Our data demonstrated that decreased serum NT-1 levels, in a Chinese population, were significantly associated with PSD at 3 months.


Fabrication of hydrogen peroxide biosensor based on Ni doped SnO2 nanoparticles.
Ni doped SnO(2) nanoparticles (0-5 wt%) have been prepared by a simple microwave irradiation (2.45 GHz) method. Powder X-ray diffraction (XRD) and transmission electron microscopy (TEM) studies confirmed the formation of rutile structure with space group (P(42)/mnm) and nanocrystalline nature of the products with spherical morphology. Direct electrochemistry of horseradish peroxidase (HRP)/nano-SnO(2) composite has been studied. The immobilized enzyme retained its bioactivity, exhibited a surface confined, reversible one-proton and one-electron transfer reaction, and had good stability, activity and a fast heterogeneous electron transfer rate. A significant enzyme loading (3.374×10(-10) mol cm(-2)) has been obtained on nano-Ni doped SnO(2) as compared to the bare glassy carbon (GC) and nano-SnO(2) modified surfaces. This HRP/nano-Ni-SnO(2) film has been used for sensitive detection of H(2)O(2) by differential pulse voltammetry (DPV), which exhibited a wider linearity range from 1.0×10(-7) to 3.0×10(-4)M (R=0.9897) with a detection limit of 43 nM. The apparent Michaelis-Menten constant (K(M)(app)) of HRP on the nano-Ni-SnO(2) was estimated as 0.221 mM. This excellent performance of the fabricated biosensor is attributed to large surface-to-volume ratio and Ni doping into SnO(2) which facilitate the direct electron transfer between the redox enzyme and the surface of electrode.


Free Desmosine is a Sensitive Marker of Smoke-Induced Emphysema.
While the elastin-specific crosslinks, desmosine and isodesmosine (DID), are increased in blood, urine, and sputum of patients with clinically documented pulmonary emphysema, the usefulness of DID in detecting early lung injury remains untested. To this end, our laboratory has measured DID in a hamster model of smoke-induced emphysema, involving only minimal alveolar wall damage. Animals were either treated with cigarette smoke for 2 h/day, 5 days/week, or exposed only to room air (controls) for a period of 3 months. DID levels in bronchoalveolar lavage fluid (BALF) and whole lungs were determined at monthly intervals, using liquid chromatography and tandem mass spectrometry. Lung surface area was also determined, as a measure of airspace enlargement. The portion of BALF DID not bound to peptides (free DID) was significantly higher in smoke-exposed animals at 2 months (9.2 vs 4.4 pg/mg protein; p < 0.05), whereas total BALF DID showed no significant increases over the course of the study, and total lung DID remained unchanged. There was a mild, but significant, loss of lung surface area in the smoke-exposed group at 2 months (28.8% vs 25.2%, p < 0.05), which showed no further progression, consistent with the return of free DID to control levels at 3 months. These findings support the hypothesis that free DID are sensitive indicators of smoke-induced lung injury. Measurement of free DID in smokers with minimally decreased lung mass may help determine the utility of this parameter as a test for incipient pulmonary emphysema.


Carotid ultrasound and systematic coronary risk assessment 2 in the prediction of cardiovascular events.
Subclinical carotid atherosclerosis adds predictive value to traditional risk factors for cardiovascular diseases (CVDs). Systematic Coronary Risk Assessment 2 (SCORE2), an algorithm composed of traditional risk factors, is a state-of-the-art to estimate the 10-year risk of first-onset CVDs. We aim to investigate whether and how subclinical carotid atherosclerosis affects the performance of SCORE2. Carotid plaque presence and intima media thickness (IMT) were measured with ultrasound. The SCORE2 was calculated in 4588 non-diabetic participants aged 46-68 years. The incremental value for predicting CVD events of adding carotid plaque or IMT to SCORE2 was evaluated using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The predicted 10-year CVD risk by SCORE2 and the observed event rate were compared between participants with and without carotid plaque. Adding plaque or IMT to SCORE2 significantly improved performance for predicting CVDs. The improvements in C-statistics, IDI, and NRI of adding plaque to SCORE2 for events occurring during the first 10 years were 2.20%, 0.70%, and 46.1%, respectively (all P < 0.0001). The SCORE2 over-predicted the 10-year CVD risk in those without carotid plaque (3.93% observed vs. 5.89% predicted, P < 0.0001) while under-predicted the risk in those with carotid plaque (9.69% observed vs. 8.12% predicted, P = 0.043). Carotid ultrasound adds predictive performance to SCORE2 for assessment of CVD risk. Using SCORE2 without considering carotid atherosclerosis could under- or over-estimate the risk. Subclinical carotid atherosclerosis is an important consideration in cardiovascular risk estimation by Systematic Coronary Risk Assessment 2 (SCORE2). Carotid ultrasound adds predictive performance to SCORE2 for assessment of cardiovascular risk. SCORE2 over-predicted the 10-year cardiovascular risk in those without carotid plaque while under-predicted the risk in those with carotid plaque.


The separate and interactive effects of drinking motives and social anxiety symptoms in predicting drinking outcomes.
Our goal was to test the separate and interactive effects of drinking motives and social anxiety symptoms in predicting drinking-related consumption and problems. Participants (N=730; 59.7% female) were undergraduate college students who completed measures of social anxiety symptoms, drinking motives, alcohol consumption, and drinking problems. Greater social anxiety symptoms were significantly associated with less alcohol consumption, and there was some evidence that greater social anxiety symptoms were also associated with greater alcohol-relevant problems. Significant interactions between social anxiety and motives indicated that a) alcohol use was most pronounced for individuals high in enhancement motives and low in social anxiety symptoms; and b) among participants low in coping motives, drinking problems were greater for individuals high (vs. low) in social anxiety symptoms. More fully identifying the individual difference factors that link social anxiety symptoms with drinking outcomes is important for informing prevention and intervention approaches.


PIWIL2 promotes progression of non-small cell lung cancer by inducing CDK2 and Cyclin A expression.
PIWI proteins have important roles in tumorigenesis due to their interaction with piRNAs. Recent studies suggest that PIWI proteins affect prognosis of various cancers. In the present study, PIWI genes expression was assayed in non-small cell lung cancer (NSCLC). To determine the effects of PIWIL2 on NSCLC cells, overexpression and interference assays were performed using the A549 and H460 cell lines. The tumor formation model was performed to demonstrate the effects of PIWIL2 on tumor formation in vivo. PIWIL2 was increased both at the RNA and protein level in malignant cancer tissues compared with adjacent normal tissue. Moreover, increased PIWIL2 gene expression was negatively correlated with prognosis in NSCLC patients. Overexpression and interference of PIWIL2 promoted and depressed cell proliferation, respectively. Meanwhile, PIWIL2 interference arrested cells at the G2/M stage. In addition, we found that CDK2 and Cyclin A expression were correlated with PIWIL2 expression. Moreover, transfection of PIWIL2 promoted tumor growth in nude mice. Our findings shed light on the function of PIWIL2 in NSCLC and suggest potential prognostic and therapeutic value.


Effect of low-temperature conditioning combined with methyl jasmonate treatment on the chilling resistance of eggplant (Solanum melongena L.) fruit.
Chilling injury (CI) can injure harvested eggplants and lead to a reduction in postharvest quality. The present study examined the effect of low-temperature conditioning (LTC) combined with a methyl jasmonate (MeJA) treatment on CI by analyzing the visual appearance and physiology of eggplants stored at 4 °C. Results indicated that treatment of eggplants with LTC + MeJA effectively maintained the visual quality of eggplants, inhibited a decline in chlorophyll and total phenolics, delayed the accumulation of malondialdehyde (MDA), decreased polyphenol oxidase (PPO) gene expression and enzyme activity, and enhanced the activity of the antioxidant enzymes, catalase (CAT) and peroxidase (POD), as well as the expression of their corresponding genes. Collectively, the data indicate that LTC combined with MeJA effectively improves the CI tolerance of postharvest eggplant fruit stored at 4 °C, by enhancing the activity and relative gene expression of antioxidant enzymes.


2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters intrathymic T-cell development in mice.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was administered to 2-4-week-old mice (5, 25, and 50 micrograms/kg body wt.) and to in vitro cultures (10(-9) M) of fetal thymi. By monitoring thymocyte populations with respect to the differentiation antigens CD4 and CD8, it was found that the cell number in all thymocyte populations except for CD8+ decreased significantly compared with controls. In vivo the most marked decrease occurred among double negative (DN) and double positive (DP) cells, whereas in vitro, the DP cells were most severely affected. The cell number had already decreased to some extent by day 1 after a dose of 50 micrograms/kg body wt. of TCDD, although a severe reduction did not become apparent until day 4. There was a clear dose/response relationship between 5 and 50 micrograms/kg body wt. Autoradiography and liquid scintillation counting studies showed that incorporation of [3H]thymidine in the thymus had already decreased 24 h after TCDD treatment, with the decrease being even more pronounced at 48 h. By 96 h, the rate of cell proliferation had returned to approximately normal values. The results show that TCDD has a long-lasting effect on thymocyte abundance together with a transient effect on cell proliferation. This indicates that in addition to the initial effects of TCDD on cell proliferation, it may also more permanently disturb the normal process of elimination by means of selection.


Extending the prescribing framework to nurses: lessons from the past.
This paper highlights the parallels between the journey to prescribing for nurse practitioners when the role was initially introduced in New Zealand and the journey now towards extending the prescribing framework to registered nurses. Nurse practitioners are the only nurses who can prescribe medicines, and their numbers are few. There are several thousand experienced registered nurses who meet the education requirements to be a nurse practitioner but who have not applied to the regulatory body for registration. Attention has begun to turn from this model, in which nurse practitioners are the only category of nurse who can prescribe, towards independent and supplementary nurse prescribing models. The New Zealand government is yet to fully commit to a specific plan for extending prescribing responsibilities to registered nurses, but feedback has been sought on two different proposals. Dependent prescribing arrangements used elsewhere appear to disregard the implications for professional autonomy. The proposed models of nurse prescribing for New Zealand impose oppressive restrictions, which nurse leaders over the last decade have fought hard to resist. Regulations are needed to allow nurses who have the appropriate education to be designated prescribers in their named area of specialisation. The difference between advanced practice nurses with prescribing rights and nurse practitioners must be clarified to minimise the impact of other prescribers on the nurse practitioner role. Lessons from the past and from the United Kingdom's experience could be drawn upon in order to better utilise the existing well-educated nursing workforce.


Determination of Cu, Fe, Mn and Zn by flame atomic absorption spectrometry in multivitamin/multimineral dosage forms or tablets after an acidic extraction.
This work presents the development of a methodology for the determination of Cu, Fe, Mn and Zn in samples of multivitamin/multimineral tablets, by flame atomic absorption spectrometry (FAAS), after extraction of the analytes with diluted hydrochloric acid solution. Several parameters that could influence the extraction process such as acid extraction solution concentration and nature, mixing mode (ultrasonic or magnetic stirring), extraction time and sample composition were evaluated. The obtained results showed that Fe, Mn and Zn were easily extracted with 1 mol/L HCl solution after 5 min of mixing with either ultrasonic or magnetic stirring for all studied samples. On the other hand, Cu extraction appeared to be more complex since it could only be extracted at the same conditions for silicate-free samples. For samples containing silicates the time of contact between solid sample and extraction solution presented remarkable influence, being necessary up to 12 h to achieve quantitative recovery with 1 mol/L HCl solution. The developed methodology was applied in the determination of Cu, Fe, Mn and Zn in seven commercially available multivitamin/multimineral tablets. The results obtained with the developed method were compared with those obtained after total digestion of samples using a closed-vessel microwave oven device.


Synthesis and incorporation of human ribosomal protein S14 into functional ribosomes in human-Chinese hamster cell hybrids containing human chromosome 5: human RPS14 gene is the structural gene for ribosomal protein S14.
In Chinese hamster ovary cells, mutations in the RPS14 gene (which was previously designated emtB) render cells resistant to normally cytotoxic concentrations of the protein synthesis inhibitor, emetine. Several lines of evidence indicate the RPS14 gene in Chinese hamster is the structural gene for ribosomal protein S14, including the finding that mutants with alterations in this gene produce an electrophoretically altered form of this protein. A human gene which complements the defect in CHO RPS14 mutants and renders them sensitive to emetine has previously been assigned to the long arm of chromosome 5. The analysis of ribosomal proteins extracted from CHO Emtr X human cell hybrids, which contain human chromosome 5 and are emetine sensitive, demonstrated the presence of both the normal human and altered hamster forms of ribosomal protein S14. Human chromosome 5, the emetine-sensitive phenotype, and the human form of ribosomal protein S14 segregate concordantly from hybrids, confirming that the human gene in question is the structural gene for this protein. In addition, the results indicate that in interspecific cell hybrids, the human form of S14 is either incorporated into functional ribosomes more efficiently than the altered hamster protein or the human gene is overexpressed relative to the corresponding hamster gene.


Effects of anger awareness and expression training versus relaxation training on headaches: a randomized trial.
Stress contributes to headaches, and effective interventions for headaches routinely include relaxation training (RT) to directly reduce negative emotions and arousal. Yet, suppressing negative emotions, particularly anger, appears to augment pain, and experimental studies suggest that expressing anger may reduce pain. Therefore, we developed and tested anger awareness and expression training (AAET) on people with headaches. Young adults with headaches (N = 147) were randomized to AAET, RT, or a wait-list control. We assessed affect during sessions, and process and outcome variables at baseline and 4 weeks after treatment. On process measures, both interventions increased self-efficacy to manage headaches, but only AAET reduced alexithymia and increased emotional processing and assertiveness. Yet, both interventions were equally effective at improving headache outcomes relative to controls. Enhancing anger awareness and expression may improve chronic headaches, although not more than RT. Researchers should study which patients are most likely to benefit from an emotional expression or emotional reduction approach to chronic pain.


Traffic injuries of the pregnant women and fetal or neonatal outcomes.
To investigate the relationship between pregnancy outcome and injury severity of pregnant woman in traffic accidents. We reviewed insurance reports of traffic accidents and collected data on injuries of pregnant women and outcomes of their pregnancies. A total of 135 pregnant women, with a mean injury severity score of 1.8+/-4.0, were involved in traffic accidents from 1994 through 2003. Injury severity score, abdominal abbreviated injury scale score were significantly higher in women whose neonates died than in women with healthy newborns. However, neither the likelihood of having been subjected to direct external forces during the accident nor injury severity differed between women with spontaneous abortions and woman with healthy newborns. Predicting abortion on the basis of maternal injury severity is difficult. Because unknown variables may contribute to fetal loss, further studies of traffic injuries are needed.


Neuroprotective efficacy of combination therapy with two different antioxidants in rats subjected to transient focal ischemia.
The vascular endothelium and parenchyma of the brain have both potential pathways to generate free radicals under pathological conditions. We evaluated the neuroprotective efficacy of two different antioxidants, a microvascularly acting 21-aminosteroid (U-74389G) and a brain-penetrating pyrrolopyrimidine (U-101033E) alone and in combination. Forty Sprague-Dawley rats were randomly assigned to one of four treatment groups: (1) vehicle-treated controls, (2) U-74389G, (3) U-101033E, (4) U-74389G+U-101033E. Drugs were administered in a dosage of 3x3 mg/kg i.v. before, during, and after ischemia. All animals were subjected to 90 min of middle cerebral artery occlusion. Local cortical blood flow (LCBF) was continuously recorded by bilateral laser Doppler flowmetry. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed after 7 days. There were no significant differences in LCBF among groups. U-101033E improved neurological function from postoperative day 4 to 7, while U-74389G did not improve neurological recovery. Animals treated with both drugs showed significantly less deficits from postoperative day 1 to 7. U-101033E and combination therapy reduced total infarct volume by 53% and 54% (P<0.05). U-74389G non-significantly reduced total infarct volume by 25%. Cortical infarct volume was significantly reduced in all treatment groups but only U-101033E and combination therapy protected the basal ganglia from infarction. In conclusion, brain-penetrating antioxidants have superior neuroprotective properties compared to microvascularly acting agents. Combination therapy, affording antioxidation plus radical scavenging in blood vessels and brain parenchyma, might yield the highest degree of neuronal protection from peroxidative damage. The neuroprotective efficacy seems to be independent of CBF.


A universal model for mobility and migration patterns.
Introduced in its contemporary form in 1946 (ref. 1), but with roots that go back to the eighteenth century, the gravity law is the prevailing framework with which to predict population movement, cargo shipping volume and inter-city phone calls, as well as bilateral trade flows between nations. Despite its widespread use, it relies on adjustable parameters that vary from region to region and suffers from known analytic inconsistencies. Here we introduce a stochastic process capturing local mobility decisions that helps us analytically derive commuting and mobility fluxes that require as input only information on the population distribution. The resulting radiation model predicts mobility patterns in good agreement with mobility and transport patterns observed in a wide range of phenomena, from long-term migration patterns to communication volume between different regions. Given its parameter-free nature, the model can be applied in areas where we lack previous mobility measurements, significantly improving the predictive accuracy of most of the phenomena affected by mobility and transport processes.


Recurrent and incompletely treated aneurysms.
Endovascular treatment of intracranial aneurysms has become an established technique that can provide stable permanent occlusion in over 85 % of the cases. Even those aneurysms considered untreatable by endovascular means can now often be managed by the use of adjunctive measures, e.g., balloon protection devices, intracranial stents, and semipermeable stents, i.e., "flow diverters." In those cases, in which relevant aneurysm recurrences are documented upon angiographic follow-up, both endovascular and surgical techniques can be employed. In rare cases, combined treatment strategies including parent artery occlusion under bypass protection can be performed. At our center, the majority of relevant aneurysm recurrences after initial coil embolization are managed by a second endovascular procedure. In some cases, e.g., aneurysm recurrences not feasible for endovascular re-treatment, documented aneurysmal growth, bleeding from a previously embolized aneurysm, and acute hemorrhagic or ischemic complications during endovascular procedures, surgical management may be necessary. This report briefly outlines the most frequent treatment scenarios.


Ethanol added to resuscitation improves survival in an experimental model of hemorrhagic shock.
Ethyl alcohol induces systemic vasodilation, decreases platelet aggregation, and inhibits neutrophil activation in vivo. Alcohol may thus be of potential benefit in resuscitation from shock by improving microcirculation. The purpose of this study was to test the effects of ethanol (ETOH) in resuscitation from hemorrhagic shock. Blood pressure, tissue pO2, white blood cell (WBC) and platelet adhesiveness, and survival were measured for 60 male Sprague-Dawley rats in a blinded and randomized study. Anesthetized animals were phlebotomized to 60 per cent of their blood volume, and maintained in shock for 45 minutes. Resuscitation was by continuous infusion of Lactated Ringers (LR) at 2 x shed blood volume over 1 hour. The experimental group received LR and ETOH (1.25 mL/kg). Control rats received LR and placebo. Mean arterial pressure was not significantly different, nor was WBC adhesiveness index different. However, postresuscitation platelet adhesiveness index was significantly higher in control rats than in ETOH rats. Postresuscitation total platelet arterial-venous difference was also greater in controls than in ETOH rats. Average tissue pO2 for ETOH rats (47 +/- 8.2 mm Hg) was significantly higher than controls (39.0 +/- 9.8 mm Hg) during resuscitation (P = 0.0001). Survival for ETOH rats (70%) was significantly higher than controls (20%) (P = 0.003). Our data suggests that ETOH added to resuscitation from shock improves survival by inhibiting platelet activation and increasing tissue perfusion.


Low AS160 and high SGK basal phosphorylation associates with impaired incretin profile and type 2 diabetes in adipose tissue of obese patients.
To compare basal insulin and mTOR signaling in subcutaneous fat of obese T2DM vs. obese subjects with normal glucose tolerance (NGT), and correlate it with clinical parameters of carbohydrate metabolism and incretin secretion profiles. Recruited were 22 patients with long (>10 years) and morbid (BMI > 35 kg/m2) obesity, 12 of which had NGT and 10 had T2DM. Hyperinsulinemic-euglycemic clamp test and HOMA-IR were used to measure insulin resistance. Blood samples taken at 0, 30 and 120 min of food load test were used to assess incretin profile, insulin and glucose levels. Amount of total and visceral fat was determined by bioelectrical impedance analysis. Subcutaneous fat biopsies were obtained during bariatric surgery for all patients and analyzed by western blots. As assessed by western blots of insulin receptor substrate (IRS), Akt, Raptor, Rictor, mTOR and S6K1, the basal insulin signaling and mTORC activities were comparable in NGT and T2DM groups, whereas phosphorylation of AS160 was significantly lower and that of serum and glucocorticoid-induced kinase (SGK) was significantly higher in T2DM group. Various correlations were found between the degree of insulin resistance and amount of visceral fat, changes in incretin profile, glucose metabolic parameters and phosphorylation level of AS160, incretin secretion profile and phosphorylated levels of AS160 or SGK1. Altered phosphorylation of AS160 and SGK1 is associated with obese T2DM phenotype.


Study on cellulose microfilaments based composite spheres: Microwave-assisted synthesis, characterization, and application in pollutant removal.
A novel study of synthesizing the temperature-responsive polymer grafted cellulose filaments/Poly (N-isopropylacrylamide) (NIPAM) spheres (P-MCCBs) was carried out for the removal of dyes and heavy metal ions. The novelty of the presented work consists of the application of the nano-sized pore-forming agent (Calcium Carbonate) and the introduction of a temperature-responsive monomer (NIPAM) while preparing the adsorbents. In addition, the spherical adsorbents were synthesized through an in-situ free radical polymerization using a microwave-assisted heating approach. The morphology, chemical structure, pH, and thermal sensitivity of P-MCCBs were characterized properly. The adsorption and desorption behaviors of dyes and heavy metal ions on P-MCCBs were also investigated. The results showed that P-MCCBs exhibited a fast adsorption rate, the adsorption equilibrium reached within 80 min and 40 min for MB and Pb2+, respectively (25 °C). Moreover, around 5-8% and 20% of adsorbed MB and Pb2+ were released at the temperature above 45 °C. The adsorption kinetics followed pseudo-second-order model, and the desorption process was fit well using Higuchi and Korsmeyer-Peppas models. These results indicated that P-MCCBs could be served as a novel material for controllable adsorption and desorption processes of various contaminants.


Pharmacokinetics of low-dose intravenous pethidine in patients with renal dysfunction.
The kinetics and elimination of pethidine (meperidine) after intravenous administration (150 micrograms/kg) to ten healthy volunteer subjects were compared with those obtained from 18 patients who suffered from varying degrees of renal dysfunction. In both groups of subjects, pethidine was eliminated triexponentially from plasma. However, plasma concentrations in the patients (who were subdivided into patients with severe dysfunction, moderate dysfunction, and mild dysfunction) were consistently higher. The mean +/- SEM elimination half-life (t1/2) of pethidine was significantly longer in the three groups of renal patients: 7.9 +/- 1.1, 20.2 +/- 13.6, 16.6 +/- 5.4, and 14.3 +/- 3.1 hr, respectively, for healthy volunteers, patients with severe, moderate, and mild dysfunction; their mean +/- SEM creatinine clearances were 97.3 +/- 7.5, less than 9.5, 30.0 (3.7), and 63.3 +/- 8.5 mL/min respectively. The mean plasma clearance of the drug was higher in healthy subjects (342.7 +/- 62.5 mL/min) than various groups of renal patients (99.9 +/- 11.6, 120.9 +/- 45.8, and 123.8 +/- 34.1, respectively, for patients with severe, moderate, and mild dysfunction). Impairment of renal function also reduced total plasma protein binding: 58.2 +/- 5.0% in healthy subjects and 31.8 +/- 3.9%, 44.5 +/- 5.0%, and 42.5 +/- 5.6%, respectively, for the three renal patient groups. The percentage of pethidine recovered in the urine was significantly lower in the severe dysfunction group while norpethidine recovery was significantly lower in all three groups of renal patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Flexion and extension radiography of the lumbar spine: a comparison with lumbar discography.
Four methods of quantifying relative intervertebral body movement from static flexion/extension radiographs are reviewed and the ability of each of these techniques to indicate the site(s) of disc degeneration is compared with that of lumbar discography. Of the methods examined, that of measuring the linear displacement of one vertebra in the antero-posterior plane was found to be the most accurate method of indicating disc degeneracy. None of the methods examined was free from artefacts. With regard to the clinical usefulness of flexion/extension radiography, we discuss two separate situations. Firstly, the taking of a single set of flexion/extension radiographs is concluded to be of little value in the management of patients with low back pain. Secondly, flexion/extension radiography, on a serial basis, is considered to be of possible value in specific situations (for example, follow-up of a spinal fusion).