Computational Analysis of Cytokine Release Following Bispecific T-Cell Engager Therapy: Applications of a Logic-Based Model.
Bispecific T-cell engaging therapies harness the immune system to elicit an effective anticancer response. Modulating the immune activation avoiding potential adverse effects such as cytokine release syndrome (CRS) is a critical aspect to realizing the full potential of this therapy. The use of suitable exogenous intervention strategies to mitigate the CRS risk without compromising the antitumoral capability of bispecific antibody treatment is crucial. To this end, computational approaches can be instrumental to systematically exploring the effects of combining bispecific antibodies with CRS intervention strategies. Here, we employ a logical model to describe the action of bispecific antibodies and the complex interplay of various immune system components and use it to perform simulation experiments to improve the understanding of the factors affecting CRS. We performed a sensitivity analysis to identify the comedications that could ameliorate CRS without impairing tumor clearance. Our results agree with publicly available experimental data suggesting anti-TNF and anti-IL6 as possible co-treatments. Furthermore, we suggest anti-IFNγ as a suitable candidate for clinical studies.


Rabies in the Americas: 1998-2014.
Through national efforts and regional cooperation under the umbrella of the Regional Program for the Elimination of Rabies, dog and human rabies have decreased significantly in Latin America and Caribbean (LAC) countries over the last three decades. To achieve this decline, LAC countries had to develop national plans, and consolidate capabilities such as regular mass dog vaccination, opportune post-exposure prophylaxis and sensitive surveillance. This paper presents longitudinal data for 21 LAC countries on dog vaccination, PEP and rabies surveillance collected from the biannual regional meeting for rabies directors from 1998-2014 and from the Regional Epidemiologic Surveillance System for Rabies (SIRVERA). Differences in human and dog rabies incidence rates and dog vaccination rates were shown between low, middle and high-income countries. At the peak, over 50 million dogs were vaccinated annually in national campaigns in the countries represented. The reported number of animal exposures remained fairly stable during the study period with an incidence rate ranging from 123 to 191 reported exposures per 100,000 people. On average, over 2 million doses of human vaccine were applied annually. In the most recent survey, only 37% of countries reported that they had sufficient financial resources to meet the program objectives. The data show a sufficient and sustained effort of the LAC countries in the area of dog vaccination and provide understanding of the baseline effort required to reduce dog-mediated rabies incidence.


Nonergodicity of the motion in three-dimensional steep repelling dispersing potentials.
It is demonstrated numerically that smooth three degrees of freedom Hamiltonian systems that are arbitrarily close to three-dimensional strictly dispersing billiards (Sinai billiards) have islands of effective stability, and hence are nonergodic. The mechanism for creating the islands is corners of the billiards domain.


Double-Barrier Memristive Devices for Unsupervised Learning and Pattern Recognition.
The use of interface-based resistive switching devices for neuromorphic computing is investigated. In a combined experimental and numerical study, the important device parameters and their impact on a neuromorphic pattern recognition system are studied. The memristive cells consist of a layer sequence Al/Al2O3/Nb x O y /Au and are fabricated on a 4-inch wafer. The key functional ingredients of the devices are a 1.3 nm thick Al2O3 tunnel barrier and a 2.5 mm thick Nb x O y memristive layer. Voltage pulse measurements are used to study the electrical conditions for the emulation of synaptic functionality of single cells for later use in a recognition system. The results are evaluated and modeled in the framework of the plasticity model of Ziegler et al. Based on this model, which is matched to experimental data from 84 individual devices, the network performance with regard to yield, reliability, and variability is investigated numerically. As the network model, a computing scheme for pattern recognition and unsupervised learning based on the work of Querlioz et al. (2011), Sheridan et al. (2014), Zahari et al. (2015) is employed. This is a two-layer feedforward network with a crossbar array of memristive devices, leaky integrate-and-fire output neurons including a winner-takes-all strategy, and a stochastic coding scheme for the input pattern. As input pattern, the full data set of digits from the MNIST database is used. The numerical investigation indicates that the experimentally obtained yield, reliability, and variability of the memristive cells are suitable for such a network. Furthermore, evidence is presented that their strong I-V non-linearity might avoid the need for selector devices in crossbar array structures.


Ligand-field and ligand-binding analysis of the active site of copper-bound Aβ associated with Alzheimer's disease.
Alzheimer's disease (AD) patients show abnormally high concentrations of Cu(2+) in the amyloid β plaques. This invokes that Cu(2+) might play a crucial role in the onset of AD. The last few decades of research have also shown that Cu(2+) plays a significant role in the aggregation of Aβ plaques in the brain and the generation of oxidative stress. Because the crystal structures of Cu-Aβ are yet to be obtained, there are various proposed models for the Cu(2+) coordination environment of Aβ peptides. In this study, we have used the truncated hydrophilic part of the native Aβ peptide to probe the Cu(2+) coordination site of the peptide, using a combination of spectroscopy and exogenous ligand-binding studies. It is evident from our study that Aβ(1-16) binds 1 equiv of Cu(2+) and yet shows an equilibrium between two species with a pK(a) of ~8.1. Ligand-field analysis of absorption and circular dichroism spectroscopy data indicates five-coordinate geometry for both components. We investigate the effect of azide and 8-hydroxyquinoline binding to Cu-Aβ and demonstrate the presence of a water-derived ligand and a second exchangeable ligand coordinated to copper at physiological pH, along the equatorial plane of a square-pyramidal active site.


A Formative Program Evaluation of Electronic Clinical Tracking System Documentation to Meet National Core Competencies.
Electronic clinical tracking systems are used in many educational institutions of higher learning to document advanced practice registered nursing students' clinical experiences. Students' clinical experiences are constructed according to the National Organization of Nurse Practitioner Faculties core competencies. These competencies form a basis for evaluation of advanced practice registered nursing programs. However, no previous studies have evaluated the use of electronic clinical tracking systems to validate students' clinical experiences in meeting national core competencies. Medatrax, an electronic clinical tracking system, is evaluated using a formative program evaluation approach to determine if students' clinical documentations meet Family/Across the Lifespan Nurse Practitioner Competencies in a midsouthern family nurse practitioner program. This formative program evaluation supports the use of an electronic clinical tracking system in facilitating accreditation and program outcome goals. The significance of this study is that it provides novel evidence to support the use of an electronic clinical tracking system to assist a midsouthern school of nursing in meeting national core competencies.


Mutation analysis of Drosophila dikar/CG32394, homologue of the chromatin-remodelling gene CECR2.
The mammalian CECR2 protein contains a highly conserved bromodomain and forms a chromatin-remodelling complex with the ISWI homologue SNF2L. Mutation of the mouse CECR2 homologue results in a neural tube defect. Here we describe the characterization of the Drosophila melanogaster homologue of CECR2. Originally annotated as 2 genes, dikar and CG32394 now appear to encode both a long dikar/CG32394 transcript homologous to CECR2 and a truncated transcript missing the bromodomain. This truncated transcript may be specific to Diptera, as it is predicted from the genomic sequences of several other dipteran species but it is not predicted in the honey bee, Apis mellifera, and it is not found in mammals. Five different P element-mediated 5' deletions of the Drosophila dikar gene were generated. All mutants were homozygous-viable and the 3 mutants examined further displayed continued, albeit aberrant, transcription of dikar/CG32394. In a previous study, a dikar insertion mutation was associated with long-term memory deficits. However, the 2 deletion mutants tested here showed normal long-term memory, suggesting that the memory deficit associated with the dikar P element insertion is not due to disruption of dikar. No genetic interaction was seen between Iswi and dikar mutations. This study therefore suggests that the lack of a visible phenotype in dikar mutants is due to compensation by a second gene, possibly acf1.


Starch-based biodegradable hydrogels with potential biomedical applications as drug delivery systems.
The design and preparation of novel biodegradable hydrogels developed by the free radical polymerization of acrylamide and acrylic acid, and some formulations with bis-acrylamide, in the presence of a corn starch/ethylene-co-vinyl alcohol copolymer blend (SEVA-C), is reported. The redox system benzoyl peroxide (BPO) and 4-dimethylaminobenzyl alcohol (DMOH) initiated the polymerization at room temperature. Xerogels were characterized by 1H NMR and FTIR spectroscopies. Swelling studies were performed as a function of pH in different buffer solutions determining the water-transport mechanism that governs the swelling behaviour. Degradation studies of the hydrogels were performed in simulated physiological solutions for time up to 90 days, determining the respective weight loss, and analyzing the solution residue by 1H NMR. The mechanical properties of the xerogels were characterized by tensile and compressive tests, as well as by dynamo-mechanical analysis (DMA). Dynamo-mechanical parameters are also reported for hydrated samples.


Current practice of thoracic outlet decompression surgery in the United States.
Thoracic outlet syndrome (TOS) and its management are relatively controversial topics. Most of the literature reporting the outcomes of surgical decompression for TOS derives from single-center experiences. The objective of our study was to describe the current state of TOS surgery among hospitals that participate in the American College of Surgeons National Surgical Quality Improvement Program database. Our study sample consisted of patients from the 2005 to 2014 American College of Surgeons National Surgical Quality Improvement Program database who underwent first or cervical rib resection as their index procedure and whose constellation of diagnosis and procedure codes identified them as having neurogenic, arterial, or venous TOS. Patient and procedure characteristics were determined, as were the 30-day incidence of specific complications including nerve injury. Multimodel inference was used for multivariable analysis of the composite outcome of readmission or reoperation ≤30 days. We identified 1431 patients undergoing operation for TOS: 83% for neurogenic TOS, 3% for arterial TOS, and 12% for venous TOS. Vascular surgeons performed 90% of procedures. Only four patients (0.3%) demonstrated evidence of nerve injury. The rate of bleeding complication requiring transfusion was also quite low, at 1.4%. The 30-day incidence of readmission or reoperation, or both, in our study cohort was 8.6%. The risk of this outcome was increased in patients with a higher American Society of Anesthesiologists Physical Status Classification, those whose procedure was for non-neurogenic symptoms, and those whose procedure took longer to complete. The findings of our study will provide surgeons who advocate for the surgical management of TOS with reassurance that such intervention is associated with an extremely low risk of disability resulting from iatrogenic nerve injury and major bleeding events.


Training and Competency Strategies for Point-of-Care Testing.
The increased availability and use of POCT are being influenced by many factors, such as; industry trends to move towards patient-centered care and healthcare decentralization, the increasing prevalence of infectious diseases also including the current use of Rapid SARS-CoV-2 Testing, a growing incidence of lifestyle diseases such as diabetes, heart disease, and hypertension, as well as advances in in-vitro diagnostic medical technologies. The use of POCT can increase the efficiency of services and improve outcomes for patients. However, the variability of the testing environment and conditions as well as the competency of staff performing the tests may have a significant impact on the quality and accuracy of POCT results. A majority of the staff who perform POCT are not trained laboratory staff and may not be as knowledgeable about the processes involved in testing, such as patient preparation, sample collection, management of equipment and supplies, instrument calibration and maintenance, the performance of the test, quality control, interpretation of the results, and reporting/documentation of results in each patient's context. Therefore, staff performing POCT must have the proper training and experience to ensure test results are accurate and reliable. This short communication outlines the specific requirements for staff training based on international standards which need to be considered to ensure the quality of test results and describes competency criteria required for compliance with POCT.


Clinical evaluation of therapeutic cancer vaccines.
Therapeutic cancer vaccines are an immunotherapy that targets tumor antigens to induce an active immune response. To date, Provenge® is the only therapeutic cancer vaccine approved by the United States Food and Drug Administration. Although therapeutic cancer vaccines have not been approved by the European Medicines Agency (EMA), they have been approved in several countries other than the United States (US) and the European Union (EU). Provenge® is the only approved cancer vaccine that showed significant primary endpoint efficacy in a phase III study at the time of approval. Retrospective analysis of 23 completed or terminated phase III studies showed that 74% (17/23) failed to demonstrate significant efficacy in the primary endpoint. The reasons for failure were surveyed in 13 of the 17 studies. Despite efforts to minimize tumor burden, including surgery and induction chemotherapy before therapeutic cancer vaccine therapy, 69% (9/13) of the phase III studies failed. These findings indicate that tumor burden may not be the only prognostic factor. Immunological response has often been used as a predictive factor, and a small number of sub-group analyses have succeeded in showing that immunological response is associated with the efficacy of therapeutic cancer vaccines. Being a prognostic factor, inclusion of immunological response in addition to tumor stage in the eligibility criteria or sub-group analysis may minimize study population heterogeneity, a key factor in the success of phase III studies.


Transport of plasma free fatty acids and triglycerides in man: a theoretical analysis.
Three different multicompartmental models of free fatty acid (FFA) and very low density lipoprotein triglyceride fatty acid (VLDL-TGFA) transport in man are formulated from plasma FFA and VLDL-TGFA tracee and tracer data collected over a 24 hr interval after the injection of palmitate-(14)C. All modeling and data fitting were performed on a digital computer using the SAAM program. Structural differences in the three models relate to the position of the slowly turning over compartment required to generate the late portion of the plasma VLDL-TGFA tracer data. The positions of this slow compartment are along the hepatic pathway from FFA to VLDL-TGFA (model A) or in the distribution system of VLDL-TGFA (model B) or in the distribution system of FFA (model C). Although all three models are equally consistent with our experimental data and are supported by observations of others, each reveals inconsistency with some data obtained from the literature. Consequently, a combination model of FFA-TGFA transport, incorporating properties of models A, B, and C would be more consistent with all available data. Experiments that would help to determine the quantitative significance of each of the slow compartments in the combination model are suggested. Several other models suggesting recycling of plasma VLDL-TGFA through the plasma FFA pool, kinetic heterogencity of the plasma VLDL-TGFA pool, and contamination of plasma VLDL-TGFA radioactivity with low density lipoprotein (LDL) TGFA radioactivity were tested. The first model does not explain the late portion of the plasma VLDL-TGFA tracer data. The second and third models, while consistent with our tracee and tracer data, have steady-state implications with respect to the extent of kinetic heterogeneity and size of the LDL-TGFA contaminant that make them unlikely. Assumptions underlying other investigator's models of FFA and TGFA transport in man are reviewed within the logical framework of our models. Quantitative differences among the various models are shown by evaluating all of the models with respect to a common set of plasma FFA and VLDL-TGFA data.


Fascination with the conformational analysis of succinic acid, as evaluated by NMR spectroscopy, and why.
A serendipitous effort to use NMR spectroscopy to determine the conformational preferences of succinate monoanion opened a Pandora's box of unexpected uncertainties as to what influences such preferences of succinic acid in its various ionization states, not only in water but also in other less polar protic solvents, as well as a range of aprotic solvents. The dianion in aprotic solvents shows substantial gauche preferences, which give the appearance of violating Coulomb's law.


Survival after self-poisoning with sodium nitrite: A case report.
Sodium nitrite ingestion poses a considerable public health threat. The incidence of sodium nitrite self-poisoning in the United States has been trending upward since 2017. Our case report describes an intentional sodium nitrite ingestion with favorable outcomes. We highlight the proper treatment of this ingestion with intravenous methylene blue. Sodium nitrite is an oxidizing agent that is commonly found in processed meats, fish, and cheeses as a preservative, antimicrobial, and food coloring agent. It is an odorless, white crystalline powder that has been confused for table salt or granulated sugar. It has become more readily available in large quantities online. Unfortunately, online forums exist that detail how to dose sodium nitrite for suicide. Furthermore, it has been recently discussed in popular news streams after a celebrity died of an overdose. Sodium nitrite toxicity is capable of causing severe methemoglobinemia with high mortality. Prompt identification is crucial. We discuss the important implications in regard to media coverage, imitative suicide, and accessibility of sodium nitrite.


[Optical coherence tomography and coronary artery ectasia: the critical role of intracoronary imaging for optimal results of percutaneous coronary intervention].
Percutaneous coronary intervention (PCI) in coronary artery ectasia is technically challenging, particularly regarding appropriate stent sizing, and it is associated with a higher incidence of adverse events. In this case report, a 63-year-old male patient, heart transplant recipient, underwent elective follow-up coronary angiography in the absence of clinical symptoms. Five years previously the patient was treated with coronary angioplasty and drug-eluting stent implantation for critical lesions of the left anterior descending coronary artery. Angiographic images showed a focal in-stent haziness at the level of an ectatic segment. To elucidate this finding, optical coherence tomography (OCT) was performed. Intracoronary imaging showed severe malapposition of the proximal end of the stent, with an intraluminal signal-rich structure, suggestive of organized stent thrombosis. Stent dilation was performed to maximal recommended diameter, with significant reduction of the malapposed area, as shown by repeated OCT pullbacks. Intracoronary imaging is particularly valuable in PCI of ectatic vessels to guide appropriate stent sizing and avoid stent malapposition. OCT, thanks to its superior spatial resolution in comparison with other intravascular imaging techniques, provides advantages for stent optimization and evaluation of stent failure causes. However, its limited imaging area and possible incomplete blood clearance may limit its usefulness in severely ectatic vessels.


Multidrug resistance phenotype associated with selection of an aminopterin resistant dog kidney cell line.
A determination of the mechanisms of drug resistance in tumour cells is important for developing strategies to combat such resistance in persons receiving chemotherapy. This report describes a combined cellular, biochemical, and molecular analysis of a dog kidney cell line selected for resistance to increasing levels of the hydrophilic antifolate, aminopterin. Three distinct drug resistance phenotypes were observed in cells exhibiting high levels of aminopterin resistance. Two of these phenotypes were decreased aminopterin accumulation and increased levels of dihydrofolate reductase specific activity. The third drug resistance phenotype was noted initially as cross resistance to a variety of hydrophobic drugs indicating multidrug resistance. Biochemical assays demonstrated reduced accumulation of the hydrophobic fluorescent drug daunorubicin and of 3H-colchicine in the aminopterin resistant cells. These results were then correlated with increased levels of the multidrug resistance (mdr) gene product, P-glycoprotein, and mdr mRNA levels in the aminopterin resistant cells. However, experiments designed to prove a role for expression of the mdr gene in providing a degree of aminopterin resistance were unsuccessful. It is concluded that aminopterin selection in these dog kidney cells resulted in expression of at least three distinct drug resistance phenotypes and that one of these phenotypes, multidrug resistance, represented a secondary response to the aminopterin selection.


[The Tugela-Vaal state water scheme as a bilharzia risk].
The Tugela-Vaal River water scheme constitutes a possible source for the introduction of bilharziasis into an area where the disease is at present not endemic. A survey was made of the snail species in the area encompassed by the scheme. Although Bulinus (Physopsis) africanus (a host of Schistosoma species responsible for urinary bilharziasis) was found in the proposed source area of the water scheme, it is not possible at this stage to determine with certainty whether this host will be introduced over the Drakensberg escarpment into the Orange Free State. However, this is a distinct possibility, and it is discussed in relation to ecological factors.


CARE CR-Cardiovascular and cardiorespiratory Adaptations to Routine Exercise-based Cardiac Rehabilitation: a study protocol for a community-based controlled study with criterion methods.
Cardiac rehabilitation (CR) reduces all-cause and cardiovascular mortality in patients with coronary heart disease (CHD). Much of this improvement has been attributed to the beneficial effects of structured exercise training. However, UK-based studies have not confirmed this. Improvements in survival and cardiovascular health are associated with concurrent improvements in cardiorespiratory fitness (CRF). It is therefore concerning that estimated CRF improvements resulting from UK-based CR are approximately one-third of those reported in international literature. Modest improvements in CRF suggest that UK CR exercise training programmes may require optimisation if long-term survival is to be improved. However, contemporary UK studies lack control data or use estimates of CRF change. Cardiovascular and cardiorespiratory Adaptations to Routine Exercise-based CR is a longitudinal, observational, controlled study designed to assess the short-term and long-term effect of CR on CRF, as well cardiovascular and cardiometabolic health. Patients will be recruited following referral to their local CR programme and will either participate in a routine, low-to-moderate intensity, 8-week (16 sessions) exercise-based CR programme or freely abstain from supervised exercise. Initial assessment will be conducted prior to exercise training, or approximately 2 weeks after referral to CR if exercise training is declined. Reassessment will coincide with completion of exercise training or 10 weeks after initial assessment for control participants. Participants will receive a final follow-up 12 months after recruitment. The primary outcome will be peak oxygen consumption determined using maximal cardiopulmonary exercise testing. Secondary outcomes will include changes in subclinical atherosclerosis (carotid intima-media thickness and plaque characteristics), body composition (dual X-ray absorptiometry) and cardiometabolic biomarkers. Ethical approval for this non-randomised controlled study has been obtained from the Humber Bridge NHS Research Ethics Committee-Yorkshire and the Humber on the 27th September 2013, (12/YH/0278). Results will be presented at national conferences and published in peer-reviewed journals.


Development of a nested polymerase chain reaction method to detect oncogenic Marek's disease virus from feather tips.
For the easy survey of Marek's disease virus (MDV), feather tip-derived DNA from MDV-infected chickens can be used because feather tips are easy to collect and feather follicle epithelium is known to be the only site of productive replication of cell-free MDV. To develop a diagnostic method to differentiate highly virulent strains of MDV from the attenuated MDV vaccine strain, CVI988, which is widely used, nested polymerase chain reaction (PCR) was performed to detect a segment of the meq gene in feather tip samples of chickens experimentally infected with MDV. In chickens infected with Md5, a strain of oncogenic MDV, the meq gene was consistently detected, whereas the L-meq gene, in which a 180-base pair (180-bp) sequence is inserted into the meq gene, was detected in CVI988-infected chickens. Moreover, the meq gene was mainly detected even in chickens co-infected with both Md5 and CVI988. These results suggest that this method is appropriate for the surveillance of the highly virulent MDV infection in the field.


What scans see when patients see defects: neuroimaging findings in body dysmorphic disorder.
Body dysmorphic disorder (BDD) is characterized by an individual's preoccupation with a perceived defect in their appearance which to others may be barely noticeable or even completely unnoticed. It confers significant disturbances of everyday functioning in affected persons. The present review study provides an overview of neuroimaging findings on BDD. Literature on three platforms, PubMed, Google Scholar and PsycArticles of APA PsycNet, was searched for studies on patients with BBD compared with healthy controls (HCs), with a focus on neuroimaging findings. Out of an initial yield of 414 articles, 23 fulfilled inclusion criteria and were reviewed. Among the most remarkable findings were functional abnormalities in visual processing, frontostriatal and limbic systems, reduced global efficiency of White Matter (WM) connectivity, reduced cortical thickness in temporal and parietal lobes, and correlations between these neuroimaging findings and clinical variables such as symptom severity and degree of insight. Structural, volumetric and functional neuroimaging findings in BDD affected persons may help shed light on the pathophysiology and neurobiological underpinnings of this condition. Future studies should further investigate the use of imaging findings as potential prognostic biomarkers of treatment efficacy and disease outcome.


How can eHealth enhance adherence to cancer therapy and supportive care?
eHealth is currently a hot topic, but is certainly not a new one. The use of communications technology to relay health-related information or provide medical services has been around since the advent of this technology. It has been primarily over the last decade that eHealth has seen a global expansion, due to the far-reaching capabilities of the Internet and the widespread use of wireless technology. This paper will outline what eHealth is, what adherence is, and how eHealth can help with adherence, in cancer and supportive care particularly. It will discuss the current state of the art, and project into the future. Keywords: telemedicine; compliance; use of electronic media for health


Investigation of malaria sporozoites by immunoradiometric assay.
Two-site immunoradiometric assay (IRMA) (Zavala et al., 1982) using monoclonal antibodies to P. falciparum and P. vivax was applied to detect sporozoites in laboratory-maintained An. dirus and also mosquitoes collected from endemic areas of malaria in Thailand. Study in P. falciparum infected mosquitoes revealed that the circumsporozoite (CS) antigen was first found in the abdominal portion on day 10 post-infection, while it could be observed in the salivary glands from day 15 onwards. The head-thorax portion of wild-caught mosquitoes were investigated by IRMA compared with the dissection technique. The results showed that none of the mosquitoes collected from Phrae was positive for malaria. The mosquitoes collected from Chantaburi showed 4 out of 1243 An. dirus that were positive for P. falciparum by IRMA, with sporozoites ranging from 207 to 3875. Among 3123 An. minimus collected from Kanchanaburi, 3 were positive by IRMA, 2 for P. falciparum and one P. vivax with sporozoites found in head-thorax portion were 1880, 2380 and 1026 respectively. Not a single sporozoite was found in the mosquitoes collected from these areas by the dissection technique. However 7 out of 1219 An. minimus from Kanchanaburi were found to possess undeveloped oocysts in the stomach wall. It is evident that the IRMA is efficient, convenient and suitable for the investigation of sporozoites in this region. The application of this technique in further epidemiological study of malaria is in progress.


Role of the dipolar interaction on the macroscopic state of magnetic nanoparticle systems: a Monte Carlo study.
We have performed Monte Carlo simulations to treat the effect of the dipolar interaction in assemblies of superparamagnetic nanoparticles. Our simulations reproduce correctly the increase of the blocking temperature (T(B)) as the concentration increases, as observed experimentally. Interestingly, we have observed a progressive displacement of the M2 versus H/M isotherms (Arrott plots) from the origin as the concentration of nanoparticles increases. Moreover, the curvature of the isotherms at T > T(B) changes from positive to negative slope at high sample concentrations, resembling the shape of a first order phase transition. These results are surprisingly similar to that found in a conventional magnetic phase transition under the effect of a random anisotropy or a random field.


Chiropractic management of a patient with symptoms of attention-deficit/hyperactivity disorder.
The purpose of this study is to report a case of a child with attention-deficit/hyperactivity disorder (ADHD) who was treated with chiropractic care. Parents of a 5-year-old boy with diagnosed ADHD brought him for chiropractic care to address his subjective signs (acting out, ability to follow instructions, and poor home and school performance), which also included waking at night due to asthmatic symptoms and low self-esteem. Palpation revealed hypertonicity and trigger points in the paraspinal muscles at the thoracolumbar region with local pain. A preliminary diagnosis included cervical and thoracolumbar facet joint irritation with concurrent muscle hypertonicity. Treatment including spinal manipulative therapy, soft tissue therapy, and stretching was provided. Treatment began on a thrice-weekly basis and declined to twice weekly over the course of approximately 12 weeks. After 1 year of treatment, subjective improvements were noted in episodes of acting out, ability to follow instructions, and general home and school performance. The patient improved over 1 year in which he received chiropractic care, including manual treatments such as spinal manipulative therapy and soft tissue therapies. This suggests that there may be a role for doctors of chiropractic in the management of patients with ADHD.


[carbonyl-11C]Desmethyl-WAY-100635 (DWAY) is a potent and selective radioligand for central 5-HT1A receptors in vitro and in vivo.
[carbonyl-11C]Desmethyl-WAY-100635 (DWAY) is possibly a low-level metabolite appearing in plasma after intravenous administration of [carbonyl-11C]WAY-100635 to human subjects for positron emission tomographic (PET) imaging of brain 5-HT1A receptors. In this study we set out to assess the ability of DWAY to enter brain in vivo and to elucidate its possible interaction with 5-HT1A receptors. Desmethyl-WAY-100635 was labelled efficiently with carbon-11 (t1/2 = 20.4 min) in high specific radioactivity by reaction of its descyclohexanecarbonyl analogue with [carbonyl-11C]cyclohexanecarbonyl chloride. The product was separated in high radiochemical purity by high-performance liquid chromatography (HPLC) and formulated for intravenous injection. Rats were injected intravenously with DWAY, sacrificed at known times and dissected to establish radioactivity content in brain tissues. At 60 min after injection, the ratios of radioactivity concentration in each brain region to that in cerebellum correlated with previous in vitro and in vivo measures of 5-HT1A receptor density. The highest ratio was about 22 in hippocampus. Radioactivity cleared rapidly from plasma; HPLC analysis revealed that DWAY represented 55% of the radioactivity in plasma at 5 min and 33% at 30 min. Only polar radioactive metabolites were detected. Subsequently, a cynomolgus monkey was injected intravenously with DWAY and examined by PET. Maximal whole brain uptake of radioactivity was 5.7% of the administered dose at 5 min after injection. The image acquired between 9 and 90 min showed high radioactivity uptake in brain regions rich in 5-HT1A receptors (e.g. frontal cortex and neocortex), moderate uptake in raphe nuclei and low uptake in cerebellum. A transient equilibrium was achieved in cortical regions at about 60 min, when the ratio of radioactivity concentration in frontal cortex to that in cerebellum reached 6. The corresponding ratio for raphe nuclei was about 3. Radioactive metabolites appeared rapidly in plasma, but these were all more polar than DWAY, which represented 52% of the radioactivity in plasma at 4 min and 20% at 55 min. In a second PET experiment, in which a cynomolgus monkey was pretreated with the selective 5-HT1A receptor antagonist, WAY-100635, at 25 min before DWAY injection, radioactivity in all brain regions was reduced to that in cerebellum. Autoradiography of post mortem human brain cryosections after incubation with DWAY successfully delineated 5-HT1A receptor distribution. Receptor-specific binding was eliminated in the presence of the selective 5-HT1A receptor agonist, 8-OH-DPAT [(+/-)-8-hydroxy-2-dipropylaminotetralin]. These findings show that: (a) intravenously administered DWAY is well able to penetrate brain in rat and monkey, (b) DWAY is a highly effective radioligand for brain 5-HT1A receptors in rat and monkey in vivo and for human brain in vitro, and (c) the metabolism and kinetics of DWAY appear favourable to successful biomathematical modelling of acquired PET data. Thus, DWAY warrants further evaluation as a radioligand for PET studies of 5-HT1A receptors in human brain.


Social support and recovery from surgery.
This study examined the relationship of naturally occurring social support from the spouse with the preoperative anxiety and postoperative recovery of 56 male coronary-bypass patients. Patients were divided into groups based on whether the overall quality of their marital relationship was perceived to be relatively good or bad at the time of surgery and on whether they received relatively high or low spouse support in the hospital (defined in terms of frequency of visits). A fifth group (n = 16), consisting of unmarried patients, enabled additional comparisons. The results indicated that, although groups were essentially equivalent in preoperative physical status, married patients who received higher hospital support took less pain medication and recovered more quickly than their low-support counterparts. In contrast, perceived quality of the marital relationship was a relatively insignificant factor. Speed of recovery for unmarried patients was generally slower than for married, high-support patients and faster than for married, low-support patients.


The effect of anthropogenic drivers on spatial patterns of mangrove land use on the Amazon coast.
Mangroves play an essential ecological role in the maintenance of the coastal zone and are extremely important for the socioeconomics of coastal communities. However, mangrove ecosystems are impacted by a range of anthropogenic pressures, and the loss of this habitat can be attributed primarily to the human occupation of the coastal zone. In the present study, we analyzed the spatial patterns of land use in the mangrove of the Brazilian Amazon coast, and evaluated the anthropogenic drivers of this impact, using a remote sensing approach. We mapped the road network using RapidEye images, and human settlements using global data. The results of these analyses indicate that the Brazilian Amazon coast has a low population density and low rates of anthropogenic impact in most of the coastal microregions investigated, factors that contribute to the maintenance and conservation of the region's mangrove. The study also revealed that the paved road network is one of the principal drivers of land use in the mangrove, whereas other factors, such as population density, urban centers, and the number of settlements are much less important. While the region has 2024 km of paved highways, unpaved roads (17,496 km) facilitate access to the mangrove, with approximately 90% of anthropogenic impact being recorded within a 3 km radius of these roads. While the network of paved highways is relatively reduced in extension, preventive measures are urgently required to impede any major shift in the current scenario, caused by the expansion of major development programs. The results of the study indicate that biophysical, economic, and political factors may also contribute to the reduction, stability, and development of one of the world's largest areas of mangrove forest.


Is early gastric cancer, diffuse type, a forerunner of advanced gastric cancer.
Gastric cancer (GC) represents one of the most important causes of death by malignancy world wide. Our retrospective study was carried out on surgical stomach specimens obtained from a series of 552 consecutive cases of GC observed in the Departments of Surgical Pathology of the Public Hospitals of L'Aquila and Atri which cover the 17% of the entire population of the Italian Region Abruzzo. The aim of the study was to compare the anatomo-clinical characteristics of early GC (EGC) and advanced GC (AGC). The diagnosis was achieved by the criteria of the Lauren's histopathological classification (intestinal and diffuse types). Our study also stratified the cases by sex, age, lymph node metastases and associated lesions such as chronic atrophic gastritis, intestinal metaplasia and dysplasia. On an average, patients affected by EGC were 8.1 years younger than those with AGC. This age gap could support the hypothesis that early lesions represent the first stage of AGC. However, when patients were subdivided according to Lauren's classification, the mean age of patients with EGC, diffuse type, was 12.2 years less than that of AGC patients of the corresponding histological type. Furthermore, the subset of patients with EGC, diffuse type, and lymph node metastases was 17.8 years younger than patients affected by AGC diffuse type, with lymph node metastases. The present study offers an original survey on GC in a defined Italian population. As far as the intestinal histotype is concerned, the slight age difference between EGC and AGC suggests that these tumors are different steps of the same process. On the contrary, the age distribution suggests that EGC, diffuse type, has a different biological behaviour.


Beyond Beer's Law: Spectral Mixing Rules.
Based on Beer's law, it is assumed that the absorbance of a mixture is that of the neat materials weighted by their relative amounts (linear mixing rule). In this contribution, we show that this is an assumption that holds only under various approximations for which no change of the chemical interactions is just one among several. To understand these approximations, which lead incrementally to different well known mixing rules, we finally derive the linear mixing rule from the Lorentz-Lorenz relation, with the first approximation that the local electric field is correctly described in this relation. Further levels of approximation are that the local field equals the applied field (Newton-Laplace mixing rule) and that the change of the index of refraction and, equivalently, absorption is weak (Gladstone-Dale/Arago-Biot mixing rule). Even then the linear mixing rule is only strictly valid if the indices of refraction in the transparency region at higher frequency than the absorption have the same value and the mixing is homogeneous relative to the resolving power of the light ("micro-homogeneous"). Under these preconditions, linear mixing of the individual absorbances is established. We illustrate the spectral differences between the different mixing rules, all of which are based on volume and not on mass fractions, with examples. For micro-heterogeneous samples, a different linear mixing rule governs the optical properties, which refers to the experimental quantities, reflectance, and transmittance. As a result, for such samples, mixtures of already comparably high content give only weak signals due to band flattening, which are hard to distinguish from baseline effects.


Crystal structure of the peroxisome proliferator-activated receptor gamma (PPARgamma) ligand binding domain complexed with a novel partial agonist: a new region of the hydrophobic pocket could be exploited for drug design.
The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors regulating glucose and lipid metabolism. The search for new PPAR ligands with reduced adverse effects with respect to the marketed antidiabetic agents thiazolidinediones (TZDs) and the dual-agonists glitazars is highly desired. We report the crystal structure and activity of the two enantiomeric forms of a clofibric acid analogue, respectively complexed with the ligand-binding domain (LBD) of PPARgamma, and provide an explanation on a molecular basis for their different potency and efficacy against PPARgamma. The more potent S-enantiomer is a dual PPARalpha/PPARgamma agonist which presents a partial agonism profile against PPARgamma. Docking of the S-enantiomer in the PPARalpha-LBD has been performed to explain its different subtype pharmacological profile. The hypothesis that partial agonists show differential stabilization of helix 3, when compared to full agonists, is also discussed. Moreover, the structure of the complex with the S-enantiomer reveals a new region of the PPARgamma-LBD never sampled before by other ligands.


Different genotypes of Trypanosoma cruzi produce distinctive placental environment genetic response in chronic experimental infection.
Congenital infection of Trypanosoma cruzi allows transmission of this parasite through generations. Despite the problematic that this entails, little is known about the placenta environment genetic response produced against infection. We performed functional genomics by microarray analysis in C57Bl/6J mice comparing placentas from uninfected animals and from animals infected with two different T. cruzi strains: K98, a clone of the non-lethal myotropic CA-I strain (TcI), and VD (TcVI), isolated from a human case of congenital infection. Analysis of networks by GeneMANIA of differentially expressed genes showed that "Secretory Granule" was a pathway down-regulated in both infected groups, whereas "Innate Immune Response" and "Response to Interferon-gamma" were pathways up-regulated in VD infection but not in K98. Applying another approach, the GSEA algorithm that detects small changes in predetermined gene sets, we found that metabolic processes, transcription and macromolecular transport were down-regulated in infected placentas environment and some pathways related to cascade signaling had opposite regulation: over-represented in VD and down-regulated in K98 group. We also have found a stronger tropism to the placental organ by VD strain, by detection of parasite DNA and RNA, suggesting living parasites. Our study is the first one to describe in a murine model the genetic response of placental environment to T. cruzi infection and suggests the development of a strong immune response, parasite genotype-dependent, to the detriment of cellular metabolism, which may contribute to control infection preventing the risk of congenital transmission.


Tissue plasminogen activator and plasminogen activator inhibitor-1 levels in patients with acute myocardial infarction and unstable angina.
To compare levels of tissue plasminogen activator and plasminogen activator inhibitor-1 levels in patients with acute myocardial infarction and unstable angina in order to understand the use of high sensitivity C-reactive protein (hsCRP), coagulation and fibrinolysis markers for cardiovascular risk assessment. The cross-sectional case-control study compared circulating concentrations of high sensitivity C reactive protein (hsCRP), fibrinogen, tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) between patients of acute myocardial infarction (AMI) (n = 67), Unstable Angina Pectoris (UA) (n = 35) and healthy control subjects (n = 39) at the King Khalid University Hospital, Riyadh, Saudi Arabia, from June 2006 to August 2007. The patients had significantly higher hsCRP (1.06 +/- 0.11 vs 0.52 +/- 0.14, p < 0.01), fibrinogen (426.21 +/- 24.09 vs 329.32 +/- 13.93, p < 0.05), PAL-1 (44.02 +/- 6.05 vs 19.35 +/- 3.94, p < 0.01) and tPA (12.31 +/- 1.16 vs 9.49 +/- 0.86, p < 0.05) compared to the controls. Fibrinogen (329.32 +/- 13.93) and PAL-1 (19.35 +/- 3.94) were higher in both angina and infarction groups compared to the healthy subjects (p < 0.01). Between the two categories of patients the difference between Fibrinogen (449.60 +/- 52.98 vs 419.46 +/- 23.42) and PAL-1 (52.00 +/- 17.34 vs 43.19 +/- 6.10) levels were non-significant. Also, the difference in tPA levels between the controls and angina patients was nonsignificant (9.49 +/- 0.86 vs 9.91 +/- 1.24 p > 0.05). It was higher in infarction patients (14.79 +/- 3.14) compared to angina patients and the controls, (p < 0.05). Compared to the controls, hsCRP levels were significantly higher in both the patient groups (0.52 +/- 0.14, 1.05 +/- 0.28, 1.40 +/- 0.20, p < 0.01). Moreover, they were significantly higher in infarction patients than those suffering from angina (p < 0.05). CAD patients had a procoagulant state and presented with higher levels of hsCRP compared to the healthy individuals. Moreover, there were significant differences in coagulation markers and hsCRP between angina and infarction patients.


Graphene Oxide⁻PEG⁻Protocatechuic Acid Nanocomposite Formulation with Improved Anticancer Properties.
The treatment of cancer through chemotherapy is limited by its toxicity to healthy tissues and organs, and its inability to target the cancer site. In this study, we have designed an anticancer nanocomposite delivery system for protocatechuic acid (PCA) using graphene oxide⁻polyethylene glycol as the nanocarrier, and coated with folic acid (GO⁻PEG⁻PCA⁻FA) for targeting the cancer cells. The designed anticancer delivery system was found to show much better anticancer activity than the free drug PCA against liver cancer HEP-G2 cells and human colon cancer HT-29 cells; at same time, it was found to be less toxic to normal fibroblast 3T3 cells. The folate-coated anticancer delivery system was found to show better activity then the free drug and the uncoated anticancer delivery system. The in vitro release of the PCA was found to be sustained in human physiological pHs, i.e., blood pH 7.4 and intracellular lysosomal pH 4.8. These in vitro findings are highly encouraging for further in vivo evaluation studies.


The gene order for rubella virus structural proteins is NH2-C-E2-E1-COOH.
The order of translation in vivo of the genes coding for rubella virus structural proteins was studied in infected B-Vero cells. The proteins were sequentially pulse-chase labeled with [35S]methionine after synchronization of translation initiation with hypertonic salt treatment. A sequential labeling procedure ("window-labeling") to specifically label defined segments of the structural proteins was also used. The labeled proteins were identified by sodium dodecyl sulfate-gel electrophoresis after immunoprecipitation with specific antisera directed against the two virion glycoproteins (E1 and E2a/E2b) and the nucleocapsid (C) protein. The order of translation was found to be NH2-C-E2-E1-COOH. We have previously shown that the structural proteins are synthesized in vitro from a cytoplasmic 24S subgenomic mRNA as a 110,000-dalton (p110) precursor (Oker-Blom et al., J. Virol. 49:403-408, 1984). Here, it is shown that p110 is precipitated with anti-C, anti-E2, and anti-E1 sera, indicating that p110 is the precursor of all three structural proteins. Two major in vitro translation products (Mrs, 66,000 and 62,000) that could represent preterminated polypeptide chains or proteolytic cleavage products were precipitated with anti-C and anti-E2 sera, but not with anti-E1 serum, indicating, in conformity with the in vivo results, that the genes for the C and E2 proteins are adjacent to each other. Using these specific antisera, we have also confirmed the identity of the unglycosylated forms of E1 (Mr, 53,000) and E2 (Mr, 30,000) immunoprecipitated from tunicamycin-treated infected cells.


Intersex patients in military service.
The term "intersex" describes a variety of medical conditions in which sex determination is atypical. One of its most severe forms is an inadequate response to androgens due to mutations in the androgen receptor gene, which may manifest as a complete androgen insensitivity syndrome (CAIS). In this form of intersex condition, genetically male individuals do not form masculine genitalia, but have a female phenotype. Officially, Israel Defense Forces policy does not prohibit intersex patients' draft. However, it is uncommon to encounter intersex patients in the military setting. In this report, we describe a case of a combat Israeli Defense Forces female soldier, whose CAIS diagnosis was not reported to the military health authorities before her recruitment, but was revealed only during active service. Medical and other professional issues were discreetly handled, permitting her to successfully fulfill her 2 years of duty service. Although CAIS is a rare entity, it should be appropriately addressed in medical, psychological, social, and command aspects in the unique military setting. Our recommendation is to allow intersex patients military service, but not in combat units.


Nonsteroidal anti-inflammatory drug-induced visible and invisible small intestinal injury.
Permeation of the small intestinal mucosa is a key mechanism in the induction of enteropathy. We investigated the effect of rebamipide in healthy subjects with diclofenac-induced small intestinal damage and permeability. In this crossover study, each treatment period was 1 week with a 4-week washout period. Diclofenac (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo were administered. Capsule endoscopy and a sugar permeability test were performed on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups. Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the initial dose during the first treatment period in the placebo group, and from 0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal mucosal damage, the increased permeability in both groups resulted in sustained high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12% in the rebamipide group) through the 4-week washout period. Diclofenac administration induced enteropathy and hyperpermeability of the small intestine. The sustained hyperpermeability during the washout period may indicate the presence of invisible fragility.


Treatment of aerodigestive fistulas with a novel covered metallic Y-shaped segmented airway stent customized with the assistance of 3D printing.
The management of aerodigestive fistula remains challenging. An airway stent that matches well with the individual geometry of the airway is needed for the treatment of the aerodigestive fistula. This study aimed to evaluate the feasibility of a novel covered metallic segmented Y-shaped airway stent customized with the assistance of 3D printing in aerodigestive fistulas involving the carina and distal bronchi and to compare the flexibility of the novel stent with the conventional wholly knitted stent. In the flexibility study, we measured the longitudinal bending force and spring-back force of the segmented stent and wholly knitted stent. Patient-specific stents that were individually customized with the assistance of 3D printing technology were implanted in 26 patients with aerodigestive fistulas. The technical success, clinical success, Karnofsky performance status (KPS), and stent-related complications were recorded. The bending force and spring-back force of the segmented stent were significantly lower than those of the wholly knitted stent. Stent deployment was technically successful in all patients. Clinical success was obtained in 21 patients. The KPS of patients after the stenting procedure improved significantly compared with that before stenting (P<0.001). During follow-up, granulation tissue proliferation, sputum retention, stent migration, and intolerance of the stent were found in 2, 5, 1, and 1 patient, respectively. The segmented metallic Y-shaped airway stent had greater flexibility than the wholly knitted stent in an ex vivo setting. Implantation of the segmented stent individually customized with the aid of 3D printing is feasible in treating aerodigestive fistulas involving the carina and bronchi distal to the carina.


Supported Rhodium Catalysts for Ammonia-Borane Hydrolysis: Dependence of the Catalytic Activity on the Highest Occupied State of the Single Rhodium Atoms.
Supported metal nanocrystals have exhibited remarkable catalytic performance in hydrogen generation reactions, which is influenced and even determined by their supports. Accordingly, it is of fundamental importance to determine the direct relationship between catalytic performance and metal-support interactions. Herein, we provide a quantitative profile for exploring metal-support interactions by considering the highest occupied state in single-atom catalysts. The catalyst studied consisted of isolated Rh atoms dispersed on the surface of VO2 nanorods. It was observed that the activation energy of ammonia-borane hydrolysis changed when the substrate underwent a phase transition. Mechanistic studies indicate that the catalytic performance depended directly on the highest occupied state of the single Rh atoms, which was determined by the band structure of the substrates. Other metal catalysts, even with non-noble metals, that exhibited significant catalytic activity towards NH3 BH3 hydrolysis were rationally designed by adjusting their highest occupied states.


[Biochemical indicators in the blood and liver in rats after administration of beta-escin].
The effect of beta-escin on selected parameters of carbohydrate and lipid metabolism was studied in blood and liver tissue. The aim was to established whether its administration would result in steatosis of the liver. Rats were given sodium salt of beta-escin in water solution orally by gavage in the dose of 10 mg/kg or 70 mg/kg. Analysis of blood samples and liver tissue showed that administration of beta-escin to healthy rats did not induce any substantial changes in the metabolic parameters studied. The rats did not develop steatosis. The biological half-life of antipyrine was only sightly prolonged. (Tab. 3, Fig. 1, Ref. 10.)


Visual working memory performance is intact across development in autism spectrum disorder.
Autism spectrum disorder (ASD) is associated with atypical visual processing and deficits in working memory (WM). Visual WM performance typically improves between childhood and adulthood, but such improvement may be atypical in ASD. To better understand how visual WM develops, we used a well-established change detection task across multiple visual features. We examined visual WM for color, shape, and pattern in children, adolescents, and adults with and without ASD. VWM capacity and performance for all visual features improved across age similarly for both the TD and ASD groups. While performance was better on set size 4 trials than set size 8 trials for color, shape, and no change trials, such an effect was not evident for pattern change trials. Overall, the present findings suggest that VWM for different visual features may be intact across development in ASD. The ability to hold multiple objects in mind (WM) improves across typical development, but it remains unclear whether such improvement occurs in ASD. We found that developmental improvements in WM for different types of object details (e.g., color, shape, and pattern) is generally similar for both ASD and typical development. LAY SUMMARY: The ability to hold multiple objects in mind (working memory [WM]) improves across typical development, but it remains unclear whether such improvement occurs in autism spectrum disorder (ASD). We found that developmental improvements in WM for different types of object details (e.g., color, shape, pattern) is generally similar for both ASD and typical development.


Analyzing SNOMED CT's Historical Data: Pitfalls and Possibilities.
SNOMED CT's Release Format 2 (RF2) has been announced as an improvement over its predecessor, for instance because of its more consistent and almost formal approach towards describing changes in components over different versions, as well as changes in the structure of SNOMED CT itself. We explore two sorts of changes that are only partially formalized in RF2: the relationships between associative relations and reasons for inactivations as expressed in Association Reference Sets and Attribute Value Reference Sets on the one hand, and the various patterns according to which semantic tags appearing in fully specified names change over subsequent versions with or without being related to inactivations. We propose a data conversion methodology that combines assertions about SNOMED CT components into history profiles and use elements of these profiles to build Formal Concept Analysis contexts to discover valid implications that can render implicit assumptions hidden in SNOMED CT's structure explicit.


Toward Improving the Thermal Stability of Negative Electrode Materials: Differential Scanning Calorimetry and In Situ High-Temperature X-ray Diffraction/X-ray Absorption Spectroscopy Studies of Li2ZnTi3O8 and Related Compounds.
Negative electrode materials with high thermal stability are a key strategy for improving the safety of lithium-ion batteries for electric vehicles without requiring built-in safety devices. To search for crucial clues into increasing the thermal stability of these materials, we performed differential scanning calorimetry (DSC) and in situ high-temperature (HT)-X-ray diffraction (XRD)/X-ray absorption (XAS) up to 450 °C with respect to a solid-solution compound of Li4/3-2x/3ZnxTi5/3-x/3O4 with 0 ≤ x ≤ 0.5. The DSC profile of fully discharged x = 0.5 (Li2ZnTi3O8) with a LiPF6-based electrolyte could be divided into three temperature (T) regions: (i) T ≤ 250 °C for ΔHaccumi, (ii) 250 °C < T ≤ 350 °C for ΔHaccumii, and (iii) T > 350 °C for ΔHaccumiii, where ΔHaccumn is the accumulated change in enthalpy in region n. The HT-XRD/XAS analyses clarified that ΔHaccumi and ΔHaccumii originated from the decomposition of solid electrolyte interphase (SEI) films and the formation of a LiF phase, respectively. Comparison of the DSC profiles with x = 0 (Li[Li1/3Ti5/3]O4) and graphite revealed the operating voltage, i.e., amount of SEI films, and stability of the crystal lattice play significant roles in the thermal stability of negative electrode materials. Indeed, the highest thermal stability was attained at x = 0.25 using this approach.


Late onset Descemet's membrane detachment 20 years after penetrating keratoplasty.
This paper reports a case of spontaneous Descemet's Membrane (DM ) detachment 20-years after penetrating keratoplasty (PK). The patient presented with acute onset blurred vision in the right eye associated with mild ocular discomfort. There was no prior history of trauma. The patient had undergone PK in the right eye 20 years back. Detailed ophthalmic examination showed best corrected visual acuity of hand movements close to face in the right eye and 20/80 in the left eye. The right eye showed diffuse graft edema but no congestion, epithelial defect, or loss of continuity of graft-host junction to suggest a traumatic etiology. Anterior segment optical coherence tomography showed DM break with a detachment in the right eye, which was treated with an intracameral C3F8 injection. DM break with detachment post-PK has been very sparsely reported in literature and is an important differential to remember when faced with an edematous graft, in addition to the diagnosis of graft rejection or failure.


Intussusceptive Angiogenesis in Human Metastatic Malignant Melanoma.
Angiogenesis supplies oxygen and nutrients to growing tumors. Inhibiting angiogenesis may stop tumor growth, but vascular endothelial growth factor inhibitors have limited effect in most tumors. This limited effect may be explained by an additional, less vascular endothelial growth factor-driven form of angiogenesis known as intussusceptive angiogenesis. The importance of intussusceptive angiogenesis in human tumors is not known. Epifluorescence and confocal microscopy was used to visualize intravascular pillars, the hallmark structure of intussusceptive angiogenesis, in tumors. Human malignant melanoma metastases, patient-derived melanoma xenografts in mice (PDX), and genetically engineered v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-induced, phosphatase and TENsin homolog deleted on chromosome 10 (PTEN)-deficient (BPT) mice (BrafCA/+Ptenf/fTyr-Cre+/0-mice) were analyzed for pillars. Gene expression in human melanoma metastases and PDXs was analyzed by RNA sequencing. Matrix metalloproteinase 9 (MMP9) protein expression and T-cell and macrophage infiltration in tumor sections were determined with multiplex immunostaining. Intravascular pillars were detected in human metastases but rarely in PDXs and not in BPT mice. The expression of MMP9 mRNA was higher in human metastases compared with PDXs. High expression of MMP9 protein as well as infiltration of macrophages and T-cells were detected in proximity to intravascular pillars. MMP inhibition blocked formation of pillars, but not tubes or tip cells, in vitro. In conclusion, intussusceptive angiogenesis may contribute to the growth of human melanoma metastases. MMP inhibition blocked pillar formation in vitro and should be further investigated as a potential anti-angiogenic drug target in metastatic melanoma.


Liposome-encapsulated amphotericin B: a promising new treatment for disseminated fungal infections.
Amphotericin B therapy is hampered by numerous adverse effects but remains the treatment of choice for disseminated fungal infections. A new form of amphotericin B delivery, which utilizes liposome vesicles, is currently under investigation. Preliminary evidence suggests that liposome-encapsulated amphotericin B has a wider therapeutic index than free amphotericin B and allows for the use of larger total doses. The mechanism of reduced toxicity and enhanced activity may be associated with a liposome donor effect, an erythrocyte protective effect, and a liposome-targeting ability. Liposome-encapsulated amphotericin B tends to be entrapped or taken up by organs rich in reticuloendothelial cells--a particular advantage since disseminated fungal infections localize in these areas. This liposome-encapsulated preparation appears to represent a promising new form of antifungal therapy that may reduce the dose-limiting toxicities of amphotericin B and improve treatment response.


Countertransference issues in group psychotherapy with HIV-positive and AIDS patients.
Mental health professionals are increasingly aware of the special difficulties encountered by therapists working with HIV-positive and AIDS patients. In this report, countertransference issues experienced by therapists leading a psychotherapy group for heterosexual, drug-using HIV-positive and AIDS patients in an inner city hospital are explored. Countertransference is discussed under the headings of helplessness, death anxiety, and anger.


Clinical study for the undercorrection factor in intermittent exotropia.
The surgical technique for intermittent exotropia [X(T)] is quite simple. However, in many cases, the condition recurs due to any one of a number of causes, including undercorrection. This study examined the factors associated with undercorrection on X(T) patients. The study examined 199 X(T) patients who underwent bilateral recession of the lateral rectus muscle or unilateral recession of the lateral rectus muscle and resection of the medial rectus muscle, and who were followed-up for more than a year. Patients whose near and far distance angles of deviation were 9 prism diopters (PD) or more at one year after surgery were designated as group 1. Those whose PD was 8 or below or who had orthophoria were assigned to group 2. Various factors were compared and analyzed. One day after surgery, group 1 showed an average overcorrection of 1.9 and 4.1 PD at near and far, respectively, and group 2 showed an average overcorrection of 6.3 and 7.6 PD at near and far, respectively. A statistically significant difference was observed between the two groups (p < 0.05). Factors such as the age of onset of strabismus, age at the time of surgery, the interval from the onset of strabismus to surgery, the preoperative angle of deviation, the dissociated vertical deviation, amblyopia, anisometropia and vertical strabismus had no influence on the undercorrection of X(T) patients (p > 0.05). Of the many factors that might influence the surgical results of X(T) patients, the angle of deviation during the initial postoperative period is the most important factor.


When Benign Behaves Badly: Atypical Hemangiomas on Contrast-Enhanced Ultrasonography.
Hemangioma is the most common benign liver tumor and is frequently encountered as an incidental finding on imaging. The classic enhancement pattern of hemangioma is diagnostic on contrast-enhanced ultrasound (CEUS), and it follows the same pattern of enhancement on computed tomography and magnetic resonance imaging. However, there is a subset of hemangiomas that demonstrate atypical enhancement patterns on CEUS. The ability to recognize the different enhancement patterns and discern when additional imaging or biopsy may be necessary is essential to accurately interpret an atypical hemangioma on CEUS. This article reviews various enhancement patterns of hemangioma on CEUS to avoid pitfalls in characterization of focal liver lesions on CEUS.


Regulation of calcium reabsorption along the rat nephron: a modeling study.
We expanded a mathematical model of transepithelial transport along the rat nephron to include the transport of Ca(2+) and probe the impact of calcium-sensing mechanisms on Ca(2+) reabsorption. The model nephron extends from the medullary thick ascending limb (mTAL) to the inner medullary collecting duct (IMCD). Our model reproduces several experimental findings, such as measurements of luminal Ca(2+) concentrations in cortical tubules, and the effects of furosemide or deletion of the transient receptor potential channel vanilloid subtype 5 (TRPV5) on urinary Ca(2+) excretion. In vitro microperfusion of rat TAL has demonstrated that activation of the calcium-sensing receptor CaSR lowers the TAL permeability to Ca(2+), PCa (TAL) (Loupy A, Ramakrishnan SK, Wootla B, Chambrey R, de la Faille R, Bourgeois S, Bruneval P, Mandet C, Christensen EI, Faure H, Cheval L, Laghmani K, Collet C, Eladari D, Dodd RH, Ruat M, Houillier P. J Clin Invest 122: 3355, 2012). Our results suggest that this regulatory mechanism significantly impacts renal Ca(2+) handling: when plasma Ca(2+) concentration ([Ca(2+)]) is raised by 10%, the CaSR-mediated reduction in PCa (TAL) per se is predicted to enhance urinary Ca(2+) excretion by ∼30%. If high [Ca(2+)] also induces renal outer medullary potassium (ROMK) inhibition, urinary Ca(2+) excretion is further raised. In vitro, increases in luminal [Ca(2+)] have been shown to activate H(+)-ATPase pumps in the outer medullary CD and to lower the water permeability of IMCD. Our model suggests that if these responses exhibit the sigmoidal dependence on luminal [Ca(2+)] that is characteristic of CaSR, then the impact of elevated Ca(2+) levels in the CD on urinary volume and pH remains limited. Finally, our model suggests that CaSR inhibitors could significantly reduce urinary Ca(2+) excretion in hypoparathyroidism, thereby reducing the risk of calcium stone formation.


Mathematical modeling of the effects of ammonium ion on the intracellular pH of hybridoma cells.
A mathematical model for the effects of NH(4)Cl addition to the growth medium on hybridoma cell intracellular pH (pH(i)) is presented which includes a detailed description of the properties of the Na(+)/H(+) exchanger. The model is used to calculate the steady-state value of pH(i) as a function of the extracellular NH(4)Cl concentration, employing parameter values taken from the literature except for the cell permeability to NH(4) (+) This parameter value, estimated to be 3.5 x 10(-7) cm/s, is obtained by fitting simulation results to experimental data obtained previously for the steady-state value of pH(i) in the presence of 10mM NH(4)Cl. The model simulates well the major features of previously observed experimental pH(i) changes following NH(4)Cl addition: the transient characteristics, dependence on the NH(4)Cl concentration, and lack of dependence on the external pH value. The effect of parameter variations on model results is also investigated in additional simulations. The general modeling framework employed here should be useful for other types of mammalian cells.


Laparoscopic versus open peritoneal dialysis catheter insertion: a meta-analysis.
Peritoneal dialysis is an effective treatment for end-stage renal disease. Key to successful peritoneal dialysis is a well-functioning catheter. The different insertion techniques may be of great importance. Mostly, the standard operative approach is the open technique; however, laparoscopic insertion is increasingly popular. Catheter malfunction is reported up to 35% for the open technique and up to 13% for the laparoscopic technique. However, evidence is lacking to definitely conclude that the laparoscopic approach is to be preferred. This review and meta-analysis was carried out to investigate if one of the techniques is superior to the other. Comprehensive searches were conducted in MEDLINE, Embase and CENTRAL (the Cochrane Library 2012, issue 10). Reference lists were searched manually. The methodology was in accordance with the Cochrane Handbook for interventional systematic reviews, and written based on the PRISMA-statement. Three randomized controlled trials and eight cohort studies were identified. Nine postoperative outcome measures were meta-analyzed; of these, seven were not different between operation techniques. Based on the meta-analysis, the proportion of migrating catheters was lower (odds ratio (OR) 0.21, confidence interval (CI) 0.07 to 0.63; P = 0.006), and the one-year catheter survival was higher in the laparoscopic group (OR 3.93, CI 1.80 to 8.57; P = 0.0006). Based on these results there is some evidence in favour of the laparoscopic insertion technique for having a higher one-year catheter survival and less migration, which would be clinically relevant.


The need for surgical revision after isolated valenti arthroplasty for hallux rigidus: a systematic review.
Isolated Valenti arthroplasty has been proposed for treatment of moderate to severe hallux rigidus because of the perceived safety and efficacy. Furthermore, it has been proposed that undergoing isolated Valenti arthroplasty does not prevent the ability to perform revision surgery consisting of Keller resection arthroplasty, prosthetic implant arthroplasty, or arthrodesis. The author undertook a systematic review of electronic databases and other relevant sources to identify material relating to the need for surgical revision after isolated Valenti arthroplasty for hallux rigidus. Information from peer-reviewed journals as well as non-peer-reviewed publications, abstracts, and posters was also considered. In an effort to procure the highest quality studies available, studies were eligible for inclusion only if they involved consecutively enrolled patients undergoing isolated Valenti arthroplasty, if they evaluated patients in person at mean follow-up > or = 12 months' duration, and if they included details of complications after Valenti arthroplasty requiring surgical intervention. Three studies involving isolated Valenti arthroplasty were identified that met the inclusion criteria. Therefore, a total of 44 isolated Valenti arthroplasties were identified that met the inclusion criteria, with 2 (4.6%) undergoing surgical revision in the form of Keller resection arthroplasty (n = 1) and 1 plantarflexory base osteotomy (n = 1). No studies provided detailed information regarding complications specific to the exact grade of hallux rigidus in patients who underwent isolated Valenti arthroplasty. The results of this systematic review make clear the low incidence of revision surgery required after isolated Valenti arthroplasty for hallux rigidus. However, there is still a need for methodologically sound prospective cohort studies that focus on the use of isolated Valenti arthroplasty for specific grades of hallux rigidus and compare this procedure with other accepted forms of surgical treatment for moderate to severe hallux rigidus.


[Paget's disease of the skeleton].
Paget's disease of bone is now regarded as a slow virus disease of the skeleton presenting with localized manifestation. The affected areas show increased turnover with irregular structure (mosaic pattern in histology). The bones are thickened but have decreased mechanical strength. The disease most frequently affects the pelvis, femora, and tibiae, followed by the calvarium, the lumbar vertebrae and others. Diagnosis is made by X-ray examination. The differential diagnosis is rarely so difficult that a bone biopsy is required. Bone scintigraphy reveals asymptomatic lesions. Alkaline serum phosphatase mirrors the activity of the disease. Indications for treatment are pains, bending, deformities, fractures, skull base involvement, nerve damage and very high alkaline phosphatase. Calcitonins and bisphosphonates are used for treatment. Single-agent therapy reduces alkaline phosphatase to 50% of the initial level. If more intensive treatment is desired, a combination of calcitonin and EHDP can be used. Paget's sarcoma develops in less than 1% of patients with Paget's disease of bone; it is uncertain whether this complication can be prevented or delayed by the therapeutic regimens currently in use.


Variants of the BMP15 gene in a cohort of patients with premature ovarian failure.
Bone morphogenetic protein 15 (BMP15) is an oocyte-derived growth factor acting as a major player in follicle differentiation in mammals. Mutations in the BMP15 gene, some of which lead to defective secretion of bioactive dimers, have been associated with premature ovarian failure (POF) in humans. Fifty patients diagnosed with POF with a normal karyotype were included in the study. After DNA extraction and amplification by PCR, the entire coding sequence and intron-exon junctions of BMP15 gene were analysed in the cohort of POF patients and in a control group of 214 patients. Nine variants of the BMP15 gene including six missense substitutions and one insertion of three nucleotides were identified in the POF group. Three of them were previously described as single nucleotide polymorphisms and were also found in the control group. Two variants (H81R and G199R) have not been previously described and were not identified among controls but were not predicted to be deleterious. One variant (A180T) was identified among two POF cases, and also in two controls. One variant (F194S), predicted as potentially deleterious, was identified for the first time in a POF patient but also identified in one control. One variant (L148P), potentially deleterious, previously reported in POF patients, was identified for the first time among controls. The variant 788insTCT, previously identified among POF patients, probably has a low biological impact as it was also found in control patients and is a common polymorphism in sub-Saharan African populations. Various missense variants of the BMP15 gene were identified among patients with POF. For most variants, the impact of the amino-acid substitution on the protein structure and function was predicted to be low. The two variants predicted as potentially deleterious were also identified among controls and could be considered as rare polymorphisms. Although some of these variants could contribute to the development of POF in a complex manner, the demonstration of their role in the pathogenesis of POF requires additional functional studies.


Isoniazid induced motor-dominant neuropathy.
Isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. A 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid treatment was continued. Her motor weakness gradually improved in a few months, but mild sensory impairment persisted even after two years. There is need for vigilance regarding neurological effects of isoniazid in seemingly low-risk individuals in whom development of symptoms should raise the suspicion about slow acetylator status. Timely therapeutic intervention with high-dose vitamin B6 can reduce the long-term morbidity associated with this easily reversible condition.


Invasive Cervical Cancer and Antidepressants: A Nationwide Population-Based Study.
To our knowledge, no prior population-based study has been published wherein the primary aim was to evaluate whether an association between psychotropic drug prescription and cervical cancer exists. Herein we have conducted the first study that primarily aimed to determine the association between antidepressants use and risk of invasive cervical cancer in the general population.This is a population-based study utilizing Taiwan's National Health Insurance Research Database. We identified 26,262 cases with invasive cervical cancer and 129,490 controls. We adopted the conditional logistic regression model as the statistical method and adjusted for potential confounding factors.The prescription of selective serotonin reuptake inhibitors (SSRIs) (adjusted OR = 0.93, 95% CI = 0.84-1.04), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), serotonin norepinephrine reuptake inhibitors (SNRIs), mirtazapine and bupropion, adjusting for cumulative dose, was not associated with an increased, or decreased, risk for invasive cervical cancer. An association between trazodone prescription and invasive cervical cancer was observed (adjusted OR = 1.22, 95% CI = 1.03-1.43).An association between the major classes of antidepressants and invasive cervical cancer was not observed herein. Our preliminary finding regarding a possible association between trazodone and cervical cancer requires replication.


Comments of Holmquist's theory for paleogenetics: the effect of multiple hits on nucleotide differences between homologous DNA's.
The notion of the probability of back mutation is introduced and the method of probability generating functions is used in order to simplify and unify the Holmquist's (1972) investigation of the effect of multiple hits on nucleotide differences between homologous DNAs. We obtain explicit expressions for the distribution of the number of hit nucleotide sites, the number of altered sites, and the number of differences between two homologous DNAs, as functions of the total number of hits. For the case where the hit rate is a known function of time, we derive a formula for extending these results as functions of time.


Brevetoxicosis in manatees (Trichechus manatus latirostris) from the 1996 epizootic: gross, histologic, and immunohistochemical features.
In 1996, at least 149 manatees (Trichechus manatus latirostris) died in an unprecedented epizootic along the southwest coast of Florida. At about the same time, a bloom of the brevetoxin-producing dinoflagellates, Gymnodinium breve, was present in the same area. Grossly, severe nasopharyngeal, pulmonary, hepatic, renal, and cerebral congestion was present in all cases. Nasopharyngeal and pulmonary edema and hemorrhage were also seen. Consistent microscopic lesions consisted of catarrhal rhinitis, pulmonary hemorrhage and edema, multiorgan hemosiderosis, and nonsuppurative leptomeningitis. Immunohistochemical staining using a polyclonal primary antibody to brevetoxin (GAB) showed intense positive staining of lymphocytes and macrophages in the lung, liver, and secondary lymphoid tissues. Additionally, lymphocytes and macrophages associated with the inflammatory lesions of the nasal mucosa and meninges were also positive for brevetoxin. These findings implicate brevetoxicosis as a component of and the likely primary etiology for the epizootic. The data suggest that mortality resulting from brevetoxicosis may not necessarily be acute but may occur after chronic inhalation and/or ingestion. Immunohistochemical staining with interleukin-1-beta-converting enzyme showed positive staining with a cellular tropism similar to GAB. This suggests that brevetoxicosis may initiate apoptosis and/or the release of inflammatory mediators that culminate in fatal toxic shock.


Carbohydrate binding module recognition of xyloglucan defined by polar contacts with branching xyloses and CH-Π interactions.
Engineering of novel carbohydrate-binding proteins that can be utilized in various biochemical and biotechnical applications would benefit from a deeper understanding of the biochemical interactions that determine protein-carbohydrate specificity. In an effort to understand further the basis for specificity we present the crystal structure of the multi-specific carbohydrate-binding module (CBM) X-2 L110F bound to a branched oligomer of xyloglucan (XXXG). X-2 L110F is an engineered CBM that can recognize xyloglucan, xylans and β-glucans. The structural observations of the present study compared with previously reported structures of X-2 L110F in complex with linear oligomers, show that the π-surface of a phenylalanine, F110, allows for interactions with hydrogen atoms on both linear (xylopentaose and cellopentaose) and branched ligands (XXXG). Furthermore, X-2 L110F is shown to have a relatively flexible binding cleft, as illustrated in binding to XXXG. This branched ligand requires a set of reorientations of protein side chains Q72, N31, and R142, although these residues have previously been determined as important for binding to xylose oligomers by mediating polar contacts. The loss of these polar contacts is compensated for in binding to XXXG by polar interactions mediated by other protein residues, T74, R115, and Y149, which interact mainly with the branching xyloses of the xyloglucan oligomer. Taken together, the present study illustrates in structural detail how CH-π interactions can influence binding specificity and that flexibility is a key feature for the multi-specificity displayed by X-2 L110F, allowing for the accommodation of branched ligands.


Cardiopulmonary interactions in patients with heart failure.
The purpose of this review was to summarize recent findings concerning the consequences of cardiopulmonary interactions in acute cardiogenic pulmonary edema, weaning from mechanical ventilation and fluid-responsiveness assessment by respiratory variations of stroke volume. The efficacy of continuous or bilevel positive airway pressure in patients with acute cardiogenic pulmonary edema was strongly suggested by two recent meta-analyses. There is growing evidence to suggest that weaning-induced cardiac dysfunction and acute cardiogenic pulmonary edema could explain a large amount of liberation failure from mechanical ventilation. Despite a potential role for echocardiography and plasma measurements of B-type natriuretic peptide in demonstrating a cardiac origin to weaning failure, the demonstration of a significant increase in pulmonary-artery occlusion pressure during the weaning trial remains the gold standard for this purpose. In patients with heart failure there is no evidence for revisiting the reliability of the respiratory variation of stroke-volume surrogates to predict fluid responsiveness. For clinical practice, the knowledge of cardiopulmonary interactions is of paramount importance in understanding the crucial role of mechanical ventilation for treating patients with heart failure and, by contrast, the deleterious cardiovascular effects of weaning in patients with overt or hidden cardiac failure.


CT demonstration of congenital pulmonary venolobar syndrome.
The congenital pulmonary venolobar syndrome comprises a spectrum of thoracic anomalies that are discussed. Computed tomography demonstrated findings not readily apparent on conventional posteroanterior and lateral views of the chest and offered an explanation different from that usually given for the retrosternal opacity that may be seen on the lateral chest radiographs of patients with this syndrome.


The quality of life of the dentist as perceived by society.
Research dealing with the public's perception of the quality of life of the dentist is not well developed. Generally, the approach of researchers to this topic has been to examine the public's image of the dental profession. Specifically, the degree of prestige attributed to the dental profession by the public has attracted major attention. A review of studies reveals that while the profession enjoys relatively high prestige, it is extrinsic factors rather than the intrinsic value of the service that determine the public's image. The dental health care system and dental education as presently structured do not appear to be serving the bast interest of the public. The paper concludes with a discussion of what are considered to be major issues that the dental profession both in Canada and elsewhere will have to deal with in the coming years, in order to bring about change both in its image and the generally low utilization of the services it provides.


[Spontaneous pneumomediastinum in an asthmatic patient].
Spontaneous pneumomediastinum is a rare disease. It especially affects young adults. The onset is usually sudden, involving chest pain, subcutaneous emphysema and dyspnea. We report the case of a 24-year old asthmatic patient with pneumomediastinum after coughing effort. The patient presented with acute respiratory failure associated with retrosternal chest pain. Chest X-ray confirmed the diagnosis of pneumomediastinum. The patient evolved favorably within 4 days after exsufflation, oxygen therapy and conventional medical treatment.


Immunological relationship among adenoviruses of humans, simians, and nonprimates as determined by the neutralization test.
98 antisera prepared against 25 simian adenoviruses and 31 adenovirus types from various nonprimate mammals and birds were tested for their ability to neutralize 35 human adenovirus prototypes. Antisera to these human adenovirus types were similarly tested against 25 simian adenovirus prototypes. Although very few reactions to the human adenoviruses were found in antisera to nonprimate viruses, cross-reactions among the simian and human adenoviruses were more frequent. The majority of these reactions, however, were of low titer and of questionable significance. Two chimpanzee adenovirus strains--Pan 9 and SAV 21 (C 1)--were found with an immunological relationship to human adenoviruses: Pan 9 strain showed a two-way cross relationship to human adenovirus 4, and SAV 21 (C 1) was neutralized by antisera prepared against human adenoviruses 14 and 16.


Bioremediation: an important alternative for soil and industrial wastes clean-up.
Industrial and environmental biotechnology are going to new paths, resulting in processes with "clean technologies", with the maximum production and the less residues. Technologies of remediation and bioremediation are continuously being improved using genetically modified microorganisms or those naturally occurring, to clean residues and contaminated areas from toxic organics. Bioremediation of soils, water and marine environments has many advantages but at the same time it is a challenge for the researchers and engineers. Consequently, it is extremely important to carry out feasibility study based on pilot-testing before starting a remediation project in order to determine the best conditions for the process. The article presents a brief review of bioremediation including the description of the different methods applied to soil and industrial wastes, and, finally, some experiences of solid-state fermentation in relation to bioremediation.


Credentialing specialty nursing practice: a dissenting view.
Orderly development of specialty practice has been a professional issue in Australian nursing since the 1991 visit of Dr Margretta Madden Styles of the International Council of Nurses. In response, the ANF established the National Nursing Organisations (NNOs)--leaders of about 60 national specialty groups who meet twice each year to ensure orderly development of specialty practice. The most recent issue raised in this forum was credentialing.


Feature Selection Pipelines with Classification for Non-targeted Metabolomics Combining the Neural Network and Genetic Algorithm.
Non-targeted metabolomics via high-resolution mass spectrometry methods, such as direct infusion Fourier transform-ion cyclotron resonance mass spectrometry (DI-FT-ICR MS), produces data sets with thousands of features. By contrast, the number of samples is in general substantially lower. This disparity presents challenges when analyzing non-targeted metabolomics data sets and often requires custom methods to uncover information not always accessible via classical statistical techniques. In this work, we present a pipeline that combines a convolutional neural network with traditional statistical approaches and an adaptation of a genetic algorithm. The developed method was applied to a lifestyle intervention cohort data set, where subjects at risk of type 2 diabetes underwent an oral glucose tolerance test. Feature selection is the final result of the pipeline, achieved through classification of the data set via a neural network, with a precision-recall score of over 0.9 on the test set. The features most relevant for the described classification were then chosen via a genetic algorithm. The output of the developed pipeline encompasses approximately 200 features with high predictive scores, providing a fingerprint of the metabolic changes in the prediabetic class on the data set. Our framework presents a new approach which allows to apply complex modeling based on convolutional neural networks for the analysis of high-resolution mass spectrometric data.


The polymerization of actin: extent of polymerization under pressure, volume change of polymerization, and relaxation after temperature jumps.
The protein actin can polymerize from monomeric globular G-actin to polymeric filamentary F-actin, under the regulation of thermodynamic variables such as temperature, pressure, and compositions of G-actin and salts. We present here new measurements of the extent of polymerization (phi) of actin under pressure (P), for rabbit skeletal muscle actin in H2O buffer in the presence of adenosine triposphate and calcium ions and at low (5-15 mM) KCl concentrations. We measured phi using pyrene-labeled actin, as a function of time (t) and temperature (T), for samples of fixed concentrations of initial G-actin and KCl and at fixed pressure. The phi(T,P) measurements at equilibrium have the same form as reported previously at 1 atm: low levels of polymerization at low temperatures, representing dimerization of the actin; an increase in phi at the polymerization temperature (Tp); a maximum in phi(T) above Tp) with a decrease in phi(T) beyond the maximum, indicating a depolymerization at higher T. From phi(T,P) at temperatures below Tp, we estimate the change in volume for the dimerization of actin, DeltaVdim, to be -307+/-10 ml/mol at 279 K. The change of Tp with pressure dTp/dP=(0.3015+/-0.0009) K/MPa=(30.15+/-0.09) mK/atm. The phi(T,P) data at higher T indicate the change in volume on propagation, DeltaVprop, to be +401+/-48 ml/mol at 301 K. The phi(t) measurements yield initial relaxation times rp(T) that reflect the behavior of phi(T) and support the presence of a depolymerization temperature. We also measured the density of polymerizing actin with a vibrating tube density meter, the results of which confirm that the data from this instrument are affected by viscosity changes and can be erroneous.


Does patchouli oil change blood platelet monoamine oxidase-A activity of adult mammals?
Patchouli oil, an essential aroma oil extracted from patchouli leaf during short-term exposure with five and ten drops either inhibited (at 1 or 2 h) or stimulated (at 4 h) the platelet MAO-A activity depending on the dosages of the aroma oil mainly due to inhibition or stimulation of its K m. The long-term 15 consecutive days exposure (with two or five drops) of patchouli oil, on the other hand, maximally stimulated the platelet MAO-A activity with five drops patchouli oil for 1 h exposure, but further continuation of its exposure with same doses (two or five drops) for 30 consecutive days significantly stimulated (with two drops) and inhibited (with five drops) the platelet MAO-A activity due to stimulation and inhibition respectively of its corresponding both K m and V max. These results thus suggest that this aroma oil exposure may modulate the blood platelet serotonergic regulation depending on the dose, duration, and conditions of exposure.


Circadian rhythms of arterial pressure, heart rate and oral temperature in truck drivers.
Circadian rhythms of arterial pressure (AP), heart rate (HR) and oral temperature (OT) were studied in healthy male truck drivers and in a control group of air traffic controllers. Twenty-four-hour records of systolic and diastolic AP and HR and of OT were obtained from 12 truck drivers both during the outward and homeward journey in Europe and Asia, and from 12 air traffic controllers during a morning shift. Data were analyzed by the cosinor method. The results obtained in the control group were as follows (mesor/amplitude/acrophase): systolic AP (mm Hg): 111.1/6.1/16.51 h; diastolic AP: 68.4%5.6/16.58 h; HR (b.p.m.): 77.07/7.6/17.46 h; OT (dg C): 36.74/0.21/17.26 h. Statistically significant acrophase advances were observed for the circadian rhythms of systolic, diastolic and mean AP and of HR in TD during the outward journey in comparison with the control ATC group. These differences were still present during the homeward journey, in combination with an acrophase delay of the circadian rhythm of OT. Our results supply grounds to suppose that extended working time combined with greater load during a long-lasting trip may act to generate an internal desynchronization of circadian rhythms in long-haul truck drivers.


[The mechanism of the anti-arrhythmia action of mu-opioid-receptor agonists in a model of CaCl2-induced arrhythmias: the role of the autonomic nervous system].
It was established that selective ligands of the mu-opioid receptors DAGO and DALDA exhibit antiarrhythmic activity on a model of CACl2-induced arrhythmias when infused intravenously in a dose of 0.2 mg/kg. The autonomic nervous system does not take part in realization of the antiarrhythmic effect of DAGO and DALDA. It is supposed that this effect of DAGO and DALDA is associated with activation of cardiac mu-opioid receptors.