Needs of caregivers of clinic and hospice cancer patients.
This prospective correlational study compared the self-identified needs of 55 caregivers of clinic (n = 25) and hospice (n = 30) cancer patients. Patients identified their family caregivers who filled out the Home Caregiver Need Survey (HCNS) and a demographic data form. The HCNS measures the importance and satisfaction of needs on two seven-point Likert-type scales. Descriptive statistics and t tests were used to analyze the data. Caregivers of both clinic and hospice cancer patients ranked the needs items in the Information and Spiritual categories as most important. Variation in types of information occurred between the groups. Clinic caregivers were less satisfied with how well their needs in the Information category were met. Differences between the groups in the importance scores were significant at the 0.001 level for the needs in the Patient Care and Personal Care categories. Differences in the satisfaction scores between the groups were significant at the 0.001 level for needs in the Household and Patient Care categories. The HCNS is helpful for assessing and screening caregiver needs and identifying differences in needs between groups. Health care providers in clinics and hospices must individualize teaching to meet the specific needs of caregivers, particularly those needs related to information.


The use of inhaled formoterol in the treatment of asthma.
To discuss the clinical efficacy and safety of formoterol when used to relieve symptoms of asthma and prevent exercise-induced bronchoconstriction (EIB). A PubMed search was performed for articles published between 1997 and 2005 with the keywords formoterol, asthma, and long-acting beta2-adrenergic agonist, with cross-referencing to identify peer-reviewed journal articles. Published articles on the clinical use of formoterol for asthma or EIB were included as well as articles detailing the pharmacologic properties of the drug. To present a thorough review of the literature, published studies based on patient number, study design, or other measures of study quality were not excluded. Formoterol is the only long-acting beta2-adrenergic agonist that combines a rapid onset of action (within 3 minutes) with a long duration of effect (approximately 12 hours). Clinically, as recommended by asthma treatment guidelines, formoterol in conjunction with inhaled corticosteroids (ICSs) is a preferred treatment for moderate to severe persistent asthma. Significant clinical data support the use of formoterol in combination with ICSs for the treatment of asthma, with studies demonstrating improved pulmonary function and symptom scores and decreased need for maintenance ICSs and short-acting beta2-adrenergic agonists (SABAs) as relief medication. Recent studies also demonstrate that use of formoterol as needed as relief medication is associated with a prolonged time to exacerbation, improved pulmonary function, and decreased asthma symptoms. When used as monotherapy, formoterol provides protection against EIB. Clinical data also demonstrate that formoterol is safe and well tolerated even in high doses, with an adverse event profile similar to that of SABAs. Overall, formoterol is safe and effective as adjunct controller therapy for moderate and severe persistent asthma and as monotherapy for EIB.


Functional assessment of nursing home patients. Reliability and relevance.
Functional assessment of patients for resource allocation or staffing requires a higher level of interrater reliability than functional assessment in normal clinical settings. Although many functional assessment instruments are available, interrater reliability of these items has frequently not been reported. An assessment instrument based on the Long Term Care Minimum Data Set format was used for 290 patients in six wards in two Veterans Administration nursing homes. Each patient was assessed independently by two nurse caregivers to obtain reliability information. Different reliability measures yielded differing evaluations of the reliability of the instrument. Absolute agreement rates combined with Kendall's tau-b were most useful in deciding on the reliability of items in the instrument.


Back-mutation of the V-Ets to the C-Ets carboxy-terminal amino acids in the P135gag-myb-ets results in chicken neuroretina cells transformation and loss of basic fibroblast growth factor responsiveness.
The v-Myb, v-Ets containing E26 retrovirus (called in this work E26ABC) induces the proliferation of chicken neuroretina (CNR) cells in minimal medium, strongly stimulated by basic Fibroblast Growth Factor (bFGF) which confers on them the ability to form colonies in soft agar. V-Ets differs from its cellular counterpart c-Ets-1 by two point mutations and by the replacement of the 13 last C-terminal amino acids by 16 unrelated residues as a consequence of DNA segment inversion in the viral sequence. It has been documented that this different C-terminal sequence influences DNA binding activity and specificity. Replacement in E26ABC virus of the sequence encoding the 16 v-Ets last C-terminal amino acids by the sequence encoding the 13 c-Ets-1 derived C-terminus (virus E26ABO), results in the production of a P135gag-myb-ets with modified biological properties on CNR cells. E26ABO infected CNR cells proliferate in minimal medium more efficiently than E26ABC, are unresponsive to bFGF and able to grow in soft agar. In contrast, CNR cells infected by viruses encoding Myb and Ets proteins either in the E26ABO or in the E26ABC configuration are bFGF responsive. Since Myb alone is sufficient to induce bFGF responsiveness on CNR cells, these results suggest that the c-Ets-1 C-terminus interferes with the Myb activity of the E26ABO P135gag-myb-ets protein in CNR cells.


[Hemoglobin SD disease].
A 7 year old Kurdish girl presented with a cerebral infarction and a resulting hemiparesis following a blood transfusion. Examination of the blood film suggested sickle cell anaemia. However a simultaneously carried out haemoglobin electrophoresis showed haemoglobin S and haemoglobin D. The diagnosis of haemoglobin SD disease was thereby established. This kind of haemoglobin disorder usually shows a mild clinical manifestation. According to our knowledge such serious cases have not been published before. With this disease the main emphasis is on the prevention of recurrent cerebral infarctions bay a long-term transfusion programme whereas the effects of the cerebral infarction are treated in the usual way.


A central role of perforin in cytolysis?
Studies on the gene structure, on the transcript, and on perforin protein are reviewed, including intracellular trafficking. Perforin transcription is tightly regulated and specific for CTL and NK. Two independent pathways for perforin induction exist, only one of them being IL-2 independent. Perforin expression in vitro and in vivo correlates with the functional expression of cytotoxicity in viral infection, transplant and tumor rejection, and in autoimmunity. Perforin together with granzymes is localized in cytolytic granules. However, the trafficking of those two proteins is quite different. Since the properties of perforin containing granules encompass the characteristics of secretory granules and of lyzosomes, the term granulosomes is used to describe this unique organelle. Evidence is reviewed to refute the concept that the homologous restriction factors of complement also restrict the lysis of homologous cells by perforin.


Complement activation on neutrophils initiates endothelial adhesion and extravasation.
Neutrophils are essential to the pathogenesis of many inflammatory diseases. In the autoantibody-mediated K/BxN model of inflammatory arthritis, the alternative pathway (AP) of complement and Fc gamma receptors (FcγRs) are required for disease development while the classical pathway is dispensable. The reason for this differential requirement is unknown. We show that within minutes of K/BxN serum injection complement activation (CA) is detected on circulating neutrophils, as evidenced by cell surface C3 fragment deposition. CA requires the AP factor B and FcγRs but not C4, implying that engagement of FcγRs by autoantibody or immune complexes directly triggers AP C3 convertase assembly. The absence of C5 does not prevent CA on neutrophils but diminishes the upregulation of adhesion molecules. In vivo two-photon microscopy reveals that CA on neutrophils is critical for neutrophil extravasation and generation of C5a at the site of inflammation. C5a stimulates the release of neutrophil proteases, which contribute to the degradation of VE-cadherin, an adherens junction protein that regulates endothelial barrier integrity. C5a receptor antagonism blocks the extracellular release of neutrophil proteases, suppressing VE-cadherin degradation and neutrophil transendothelial migration in vivo. These results elucidate the AP-dependent intravascular neutrophil-endothelial interactions that initiate the inflammatory cascade in this disease model but may be generalizable to neutrophil extravasation in other inflammatory processes.


Sensitized room-temperature luminescence in reverse micelles using lanthanide counterions as acceptors.
The analytical usefulness of sensitized room-temperature luminescence in reverse micelles using lanthanide counterions is examined. The technique is based on the unique luminescent properties of tripositive lanthanide metal ions as counterions for the surfactant and the molecular organization produced by reverse micelles. After excitation, the analyte molecule transfers its triplet-state energy to an acceptor molecule (lanthanide), which subsequently emits luminescence. Two surfactants with different lanthanide counterions have been synthesized and characterized by spectroscopic and mass spectrometric techniques. When compared to the lanthanide salt, the sensitized luminescence of the lanthanide surfactant is substantially enhanced. The exact locations of the analyte and the counterion in the micellar system are discussed. The efficiencies of energy transfer for the two surfactants are compared.


Reliable Interlayer Based on Hybrid Nanocomposites and Carbon Nanotubes for Lithium-Sulfur Batteries.
The future energy needs have triggered research interest in finding novel energy storage systems with high energy density. Lithium-sulfur batteries are regarded as one of the most promising options for the next-generation energy storage applications because of their high theoretical energy and low cost. However, the electrochemical performances of lithium-sulfur batteries are seriously compromised by the polysulfide (LiPS) shuttling and the insulating nature of sulfur. To overcome these issues, novel CoNi1/3Fe2O4 (CNFO) nanoparticles uniformly covered on the carbon nanotubes are now reported as an efficient functional interlayer. Benefiting from the sufficient sulfiphilic sites of the CNFO for chemically bonding with LiPSs, as well as the conductive interconnected skeleton of carbon nanotubes, this composite material showed great enhancement on the rate capability and cycle stability of Li-S batteries. The Li-S battery using this interlayer exhibited a high initial capacity of 897 mA h g-1 and a low capacity decay of 0.063% per cycle within 250 cycles at 2 C. Meanwhile, an reversible specific capacity of 869 mA h g-1 (at 0.5 C) with high Coulombic efficiency could be obtained over 100 cycles at an elevated temperature (60 °C). We speculated that the chemical adsorption of CNFO for polysulfide-anchoring is extremely critical for the performances of Li-S batteries under high temperature.


Characteristic cellular fatty acid composition and an ornithine-containing lipid as a new type of hemagglutinin in Bordetella pertussis.
The fatty acid composition of the total extractable cellular lipids of Bordetella pertussis was very characteristic and was mostly hexadecenoic and hexadecanoic acids (90%) in a ratio of about 1:1. The fatty acid composition of Bordetella parapertussis and Bordetella bronchiseptica differed from that of B. pertussis. The two species were distinguished by the fatty acid composition of cell-bound lipids. The ornithine-containing lipid was characteristic of the genus Bordetella and its main structure was 3-hydroxyhexadecanoic acid amide-linked to ornithine and esterified to the second hexadecanoic acid. The lipid agglutinated human and some animal erythrocytes. The lipid is a new type of hemagglutinin and we proposed that hemagglutination occurred mainly by the hydrophobic interaction between the lipid moiety of the ornithine-containing lipid and phosphatidylcholine in the cell membrane of the erythrocytes. A relatively high content of ornithine-containing lipid was also found in opportunistic pathogens such as Flavobacterium meningosepticum which causes meningitis in babies and children. As the pathogenicity of the opportunistic pathogens is unclear, the ornithine-containing lipid may have an important role in pathogenicity.


Curricular Development and Implementation of a Longitudinal Integrative Medicine Education Experience for Trainees and Health-Care Professionals at an Academic Medical Center.
A growing number of patients and consumers are seeking integrative medicine (IM) approaches as a result of increasing complex medical needs and a greater emphasis on prevention and health promotion. Health-care professionals need to have knowledge of the evidence-based IM resources that are safe and available to patients. Medical institutions have acknowledged the need for education and training in various IM modalities and whole-health approaches in medical curricula. There is a strong need to develop and incorporate well-structured IM curricula across all levels of learning and practice within medicine. This article provides an example of the development, implementation, impact, and assessment of IM education curricula across all learner levels at a large academic medical center.


The apical-basal cell polarity determinant Crumbs regulates Hippo signaling in Drosophila.
Defects in apical-basal cell polarity and abnormal expression of cell polarity determinants are often associated with cancer in vertebrates. In Drosophila, abnormal expression of apical-basal determinants can cause neoplastic phenotypes, including loss of cell polarity and overproliferation. However, the pathways through which apical-basal polarity determinants affect growth are poorly understood. Here, we investigated the mechanism by which the apical determinant Crumbs (Crb) affects growth in Drosophila imaginal discs. Overexpression of Crb causes severe overproliferation, and we found that loss of Crb similarly results in overgrowth of imaginal discs. Crb gain and loss of function caused defects in Hippo signaling, a key signaling pathway that controls tissue growth in Drosophila and mammals. Manipulation of Crb levels caused the up-regulation of Hippo target genes, genetically interacted with known Hippo pathway components, and required Yorkie, a transcriptional coactivator that acts downstream in the Hippo pathway, for target gene induction and overgrowth. Interestingly, Crb regulates growth and cell polarity through different motifs in its intracellular domain. A juxtamembrane FERM domain-binding motif is responsible for growth regulation and induction of Hippo target gene expression, whereas Crb uses a PDZ-binding motif to form a complex with other polarity factors. The Hippo pathway component Expanded, an apically localized adaptor protein, is mislocalized in both crb mutant cells and Crb overexpressing tissues, whereas the other Hippo pathway components, Fat and Merlin, are unaffected. Taken together, our data show that Crb regulates growth through Hippo signaling, and thus identify Crb as a previously undescribed upstream input into the Hippo pathway.


The Dark Matter of Biology.
The inside of the cell is full of important, yet invisible species of molecules and proteins that interact weakly but couple together to have huge and important effects in many biological processes. Such "dark matter" inside cells remains mostly hidden, because our tools were developed to investigate strongly interacting species and folded proteins. Example dark-matter species include intrinsically disordered proteins, posttranslational states, ion species, and rare, transient, and weak interactions undetectable by biochemical assays. The dark matter of biology is likely to have multiple, vital roles to regulate signaling, rates of reactions, water structure and viscosity, crowding, and other cellular activities. We need to create new tools to image, detect, and understand these dark-matter species if we are to truly understand fundamental physical principles of biology.


Adiponectin and leptin levels in HIV-infected subjects with insulin resistance and body fat redistribution.
In this study, we sought to determine the relationship between serum levels of leptin and adiponectin (Acrp30) in patients with HIV-associated lipodystrophy (HIV-LD). Three groups of subjects were studied; HIV-positive subjects with lipodystrophy (HIV-LD; n = 22), HIV-positive subjects without lipodystrophy (HIV; n = 17), and ethnicity- and body mass index-matched healthy control subjects (n = 20). Although total body fat from dual energy x-ray absorptiometry was similar in all three groups, the HIV-LD group had a significantly lower mean proportion of body fat in the limbs +/- SEM (37.2% +/- 2.2%) than either controls (49.8% +/- 1.5%) or HIV subjects (45.7% +/- 2.0%). The HIV-LD group also had the lowest mean insulin sensitivity +/- SEM (5.11 +/- 0.59 mg of glucose/[kg of lean body mass. min] vs. 10.2 +/- 0.72 mg of glucose/[kg of lean body mass. min] in controls and 8.64 +/- 0.69 mg of glucose/[kg of lean body mass. min] in the HIV group). Leptin levels were similar in all three groups and were significantly correlated to total body fat (r = 0.86; p <.001), but these levels did not correlate with either insulin sensitivity or limb fat. Mean Acrp30 levels +/- SEM were lowest in the HIV-LD group (5.43 +/- 0.44 microg/mL vs. 11.2 +/- 1.4 microg/mL in the HIV group and 14.9 +/- 1.8 microg/mL in control subjects). Further, Acrp30 levels were positively correlated with insulin sensitivity (r = 0.610; p <.001) and limb fat (r = 0.483; p <.001). However, the correlation between limb fat and insulin sensitivity disappeared when Acrp30 level and other potential mediators were removed from the association, suggesting that a deficiency in Acrp30 in subjects with HIV-LD may be part of the mechanism for the reduced insulin sensitivity.


[Homocysteine in patients with diabetes mellitus].
Homocysteine is a sulphur aminoacid with a free thiol group which is not present in dietary protein. This aminoacid is a secondary f methionine by-product from cysteine metabolism. The pathogenic mechanisms of homocysteine in vascular damage have not been clarified. At present, it is no possible to develop an atherogenic and thrombogenic hypothesis. Yet high levels of homocysteine can cause endothelial damage, with increased thrombosis and atherosclerosis. Hyperhomocysteinemia has been reported in patients with diabetes mellitus type 1 and type 2; the prevalence and secondary cardiovascular risk is higher in patients with diabetes type 2 than those with diabetes type 1. In patients with diabetes mellitus type 1, microvascular and macrovascular complications and neuropathy are found to be increased in those with hyperhomocysteinemia. In patients with diabetes mellitus type 2, the relationship between hyperhomocysteinemia, macrovascular complications and renal disease is unclear; however, a higher prevalence of macrovascular complications in diabetic patients with hyperhomocisteinemia is associated with a higher prevalence of renal disease. Moreover, patients with hyperhomocysteinemia have hypertension and dyslipemia. Multivariate regression analyses have shown an independent relationship between homocysteine and macrovascular complications. The relationship between retinopathy and homocysteine has not been clarified. In summary, hyperhomocysteinemia could be a risk factor accounting for chronic complications in diabetic patients. Nevertheless, it is necesary to perform more prospective and intervention studies to clarify the independent risk of homocysteine and thus assay alternative treatments.


Assessment of practical science in high stakes examinations: a qualitative analysis of high performing English-speaking countries.
High stakes examinations can have profound implications for how science is taught and learned. Limitations of school science such as the 'cookbook problem' can potentially be addressed if high stakes assessments target learning outcomes that are innovative. For example, less mindless procedural engagement and more thoughtful consideration of practical science can potentially improve science learning. In this paper, we investigate how practical work is represented in the assessment frameworks of several countries that demonstrate above average performance in the latest PISA science assessments. The main motivation is the need to understand if there are aspects of high stakes summative assessments in these countries that can provide insight into how best to structure national examinations. Assessment documents from a set of selected countries have been analysed qualitatively guided by questions such as 'what is the construct of practical science' and 'what is the format of assessment?' The examined jurisdictions used different approaches from traditional external pen-and-paper tests to internal teacher assessments that included different formats (e.g. laboratory report). Innovative approaches to the assessment of practical skills (e.g. PISA computer-based tasks) do not seem to be represented in these high-stakes assessments. Implications for innovative assessments for high-stakes purposes are discussed.


Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma.
PTEN mutations have been reported to be involved in the development and prognosis of endometrial carcinoma (EC). However, a prognostic gene signature associated with PTEN mutational status has not yet been developed. In this study, we generated a PTEN mutation-associated prognostic gene signature for EC. We obtained the single-nucleotide variation and transcriptomic profiling data from The Cancer Genome Atlas database as training data and implemented the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm to establish a PTEN mutation-associated prognostic gene signature. The overall survival rates of the high-risk and low-risk groups were determined with the Kaplan-Meier (K-M) method, and the accuracy of risk score prediction was tested by using the receiver operating characteristic (ROC) curve. The K-M curves revealed that the EC patients with PTEN mutations augured favorable survival outcomes. Differential expression analysis between the EC patients with PTEN mutation and wild-type PTEN identified 224 differentially expressed genes (DEGs). Eighty-four DEGs that manifested prognostic value were fitted into the LASSO-Cox analysis, and a PTEN gene signature with seven mutation-associated prognostic genes that showed robust prognostic ability was constructed; this signature was then successfully validated in the other two datasets from the cBioPortal database as well as with 60 clinical specimens. Furthermore, the PTEN mutation-associated prognostic gene signature proved to be an independent prognostic predictor of EC. Remarkably, the EC patients in the high-risk group were characterized by higher tumor stages and grades as well as lower tumor mutation burden with respect to EC, with a poor survival outcome. Collectively, the PTEN mutation-associated prognostic gene signature that we developed could now be used as a favorable prognostic biomarker for EC. In summary, we developed and validated a prognostic predictor for EC associated with PTEN mutational status that may be used as a favorable prognostic biomarker and therapeutic target for EC.


Favorable Response to "Memantine" in a Child with GRIN2B Epileptic Encephalopathy.
GRIN2B is a gene encoding GluN2B subunit under the family of N-methyl D-aspartate (NMDA) receptors, which is responsible for neurogenesis and cognitive processes. The role of NMDA receptor antagonists like memantine is being explored for therapies in drug-resistant epilepsies. Here, we present a case of a 20-month-old boy who presented with refractory epileptic spasms. Upon failure of multiple antiepileptic drugs, he was started on oral memantine. There was a significant reduction in average seizure episodes by ∼80%. The use of memantine along with antiepileptic drug polytherapy has proved to be beneficial in our case. Our experience with memantine and favorable outcome opens up the scope of more research into the use of NMDA receptor antagonist as a drug option for refractory epilepsies with proven genetic mutation and hence improves the overall neurodevelopmental outcome and survival chance.


Kinetics of membrane immunoglobulin capping on murine B lymphocytes. Effects of phospholipid fatty acid replacement.
Detailed analyses regarding the effects of temperature and phospholipid fatty acid replacement on the capping of membrane immunoglobulin (mIg) have been performed using a recently described flow cytometric procedure (Cuchens, M. A., and Buttke, T. M. (1984) Cytometry 5, 601-609). Purified murine B cells were incubated for 12-20 h in the presence of bovine serum albumin-complexed 80 microM stearic (18:0), oleic (cis-18:1), or linoleic (cis, cis-18:2) free fatty acids. Unmodified and free fatty acid-treated cells were stained with fluorescein-conjugated rabbit anti-mouse Ig and subjected to pulse-shape (width) analyses to follow the kinetics of mIg capping. In both unmodified and free fatty acid-treated cells, capping of mIg occurred at all temperatures between 17 and 37 degrees C, but the rate of cap formation was temperature dependent. Arrhenius plots of mIg capping were linear, with activation energies ranging from 14 to 23 kcal/mol depending on the saturated/unsaturated fatty acid ratio of B cell phospholipids. Ligand-induced redistribution of mIg thus appears to be sensitive to changes in membrane acyl chain composition.


Competition within the virus-specific CD4 T-cell pool limits the T follicular helper response after influenza infection.
CD4 T follicular helper cells (TFH) are critical in the generation of potent and long-lived B-cell responses after viral infection. However, the factors that dictate the generation and maintenance of these cells are not fully understood. Here we use adoptive transfer of OTII T-cell receptor transgenic CD4 T cells, followed by infection with recombinant influenza A virus (IAV), as a means of identifying and tracking virus-specific CD4(+) T-cell responses. We show that T-cell competition within the virus-specific CD4 T-cell pool induced by IAV infection limits the proliferation and differentiation of IAV-specific CD4(+) TFH responses. In particular, increased T-cell competition for antigen results in a diminished IAV-specific TFH CD4 T-cell responses, particularly germinal center TFH responses. Strikingly, competition in the form of preexisting cellular immunity generated by heterosubtypic IAV immunization limits de novo CD4 T-cell responses in secondary lymphoid tissue. Taken together, these data show a profound linkage between antigen availability and promotion of TFH CD4(+) T-cell responses in response to infection. These data suggest that competition within the CD4 T-cell pool limits TFH responses and may be an important regulatory mechanism for controlling immunity.


Self-Assembly of Mechanoluminochromic Ladder-Shaped Gold(I) Clusters Promoted Using Cooperative Aurophilicity.
The self-assembly of mechanoluminochromic polynuclear gold(I) complexes has attracted more and more attention in the field of supramolecular gold(I) chemistry. In this work, we adopted a stepwise self-assembly strategy to precisely synthesize two polynuclear gold(I) supramolecular clusters. Through cooperative AuI···AuI and Au-N interactions, the gold(I) clusters 1+•BF4- and 24+•4BF4- with Au4 and Au16 cores, respectively, were successfully constructed. In these supramolecular clusters, (dppm)Au2Cl2 coordination motifs and trithiocyanuric linkers were stepwise assembled via sequential thiolate-chloride/phosphine coordination substitution and Au-S/Au-N coordination bond rearrangement. Two well-defined gold(I) supramolecular clusters displayed intense emission both in the solid state and in solution. Furthermore, the ladder-shaped cluster 24+•4BF4- exhibited reversible mechanochromic luminescence behavior in the solid state as well as aggregation-caused redshifted emission in solution. Upon mechanical grinding, the emission of the cluster 24+•4BF4- changed from yellow at 582 nm to red at 612 nm. The initial emission could be fully recovered by treatment with acetonitrile.


[A exploration and study of the relationships of hand-foot-mouth disease (HFMD) and the climate].
To explore and study the relationships between the popularity of HFMD and the climate in Qinhuangdao city. HFMD cases were collected on a ten-day basis in 2009 in Qinhuangdao city. At the same time, the data about Qinhuangdao's ten-day average temperature and average humidity were provided by the Qinhuangdao Meteorological bureau. Then the collected data were analysed using the great data analysis function in the EXCELE software. The results showed that the disease of HFMD had a positive relationship with seasons. The cases of HFMD began to rise at the last ten days of March and rised dramatically at the middle ten days of April; In July, the cases of HFMD arrived at peak and then decline gradually. The cases of HFMD in October were quite similar to the cases of HFMD in March. Then in November, the cases of HFMD declined rapidly. All these evidences suggested that the peak seasons of HFMD were Spring and Summer. The situations of HFMD had a significant positive relationship with the conditions of climate, such as high temperature and high humidity.


Human prion protein-induced autophagy flux governs neuron cell damage in primary neuron cells.
An unusual molecular structure of the prion protein, PrPsc is found only in mammals with transmissible prion diseases. Prion protein stands for either the infectious pathogen itself or a main component of it. Recent studies suggest that autophagy is one of the major functions that keep cells alive and has a protective effect against the neurodegeneration. In this study, we investigated that the effect of human prion protein on autophagy-lysosomal system of primary neuronal cells. The treatment of human prion protein induced primary neuron cell death and decreased both LC3-II and p62 protein amount indicating autophagy flux activation. Electron microscope pictures confirmed the autophagic flux activation in neuron cells treated with prion protein. Inhibition of autophagy flux using pharmacological and genetic tools prevented neuron cell death induced by human prion protein. Autophagy flux induced by prion protein is more activated in prpc expressing cells than in prpc silencing cells. These data demonstrated that prion protein-induced autophagy flux is involved in neuron cell death in prion disease and suggest that autophagy flux might play a critical role in neurodegenerative diseases including prion disease.


Considerations in the differentiation between brainstem lesions and sensori-neural hearing loss using auditory nerve-brainstem evoked responses.
When auditory nerve-brainstem evoked responses are used in neurological diagnosis, an important response parameter to be evaluated is brainstem transmission time - the time interval between the auditory nerve response (wave 1) and the response from the rostal brainstem (wave P4). Occasionally the only response wave present is wave P4 and its latency is prolonged. This can be compatible with a conductive or a sensorineural hearing loss (SNHL), or a neurological (brain stem) lesion such as a retrocochlear hearing loss (RCHL). A conductive hearing loss can be excluded by otoscopic, audiometric and tympanometric examination. In order to differentiate between SNHL and RCHL, several techniques have been suggested in order to enhance the visibility of wave 1, but these are not always applicable or successful. In this study, P4 latency was plotted as a function of the audiometric hearing loss at 4 kHz for 26 ears with SNHL only. From this, the correlation coefficient (r = 0.71) was calculated along with the linear regression equation and the standard error of the prediction. This gave an estimation of the range of P4 latency to be expected for a given SNHL for comparison with the actual latency obtained in patients with neurological complaints. An actual latency greater than the expected latency range would be considered corroboratory of a RCHL. Several clinical examples are presented. These considerations also point out the need to bear in mind the otological context of these evoked responses even when used in neurological diagnosis.


Bone histology sheds new light on the ecology of the dodo (Raphus cucullatus, Aves, Columbiformes).
The dodo, Raphus cucullatus, a flightless pigeon endemic to Mauritius, became extinct during the 17th century due to anthropogenic activities. Although it was contemporaneous with humans for almost a century, little was recorded about its ecology. Here we present new aspects of the life history of the dodo based on our analysis of its bone histology. We propose that the dodo bred around August and that the rapid growth of the chicks enabled them to reach a robust size before the austral summer or cyclone season. Histological evidence of molting suggests that after summer had passed, molt began in the adults that had just bred; the timing of molt derived from bone histology is also corroborated by historical descriptions of the dodo by mariners. This research represents the only bone histology analysis of the dodo and provides an unprecedented insight into the life history of this iconic bird.


Synthesis and pharmacological evaluation of 8- and 9-substituted benzolactam-v8 derivatives as potent ligands for protein kinase C, a therapeutic target for Alzheimer's disease.
A central element in the pathophysiology of Alzheimer's disease (AD) is the formation of amyloid plaques, which result from abnormal processing of the amyloid precursor protein (APP). The processing of APP is largely provided by three key enzymes, namely the alpha-, beta-, and gamma-secretases. As the latter two contribute to the formation of neurotoxic Abeta fragments while alpha-secretase does not, a decrease in the amyloidogenic products can be brought about either by inhibition of the beta- and gamma-secretases or through the activation of alpha-secretase. It is now known that the activation of protein kinase C (PKC) enhances alpha-secretase activity and therefore represents a possible target for the development of agents urgently needed for the treatment of this devastating neurodegenerative disorder. In the present study, new benzolactam-V8-based PKC activators were synthesized and tested for their binding affinity toward PKCalpha. All compounds tested showed binding values in the nanomolar concentration range. In accordance with previous publications, 9-substitution dramatically increased PKC binding affinity in comparison with the corresponding 8-substituted analogues. In addition to the location of the side chain on the aromatic ring, the binding affinities of these benzolactams were found to depend on the orientation, length, and electronic properties of this appendage. An interesting decrease in binding affinity was found for the 9-thienyl analogue 13, suggesting adverse electronic interactions of the sulfur atom with PKC or parts of the cellular membrane.


Incidence of adverse perinatal outcomes and risk factors among women with pre-eclampsia, southern Ethiopia: a prospective open cohort study.
In Ethiopia, in 2021, more than 80% of all newborn deaths were caused by preventable and treatable conditions. This study aimed to measure the incidence of adverse perinatal outcomes and risk factors among women with pre-eclampsia in the Sidama region of southern Ethiopia. A prospective open cohort study was conducted from 8 August 2019 to 1 October 2020. We enrolled 363 women with pre-eclampsia and 367 normotensive women at ≥20 weeks of gestation and followed them until the 37th week. We then followed them until the seventh day after delivery up to the last perinatal outcome status was ascertained. A log-binomial logistic regression model was used to estimate the incidence of adverse perinatal outcomes and its risk factors among women with pre-eclampsia. Relative risk (RR) with a 95% CI was reported. A p<0.05 was considered statistically significant. There were 224 adverse perinatal outcomes observed in the 363 women with pre-eclampsia compared with 136 adverse perinatal outcomes in the 367 normotensive women (p<0.001). There were 23 early neonatal deaths in the pre-eclampsia group compared with six deaths in the normotensive group (p<0.001). There were 35 perinatal deaths in the pre-eclampsia group compared with 16 deaths in the normotensive group (p<0.05). Women with severe features of pre-eclampsia had a 46% (adjusted RR 1.46, 95% CI 1.38 to 2.77) higher risk for adverse perinatal outcomes compared with women without severe features of pre-eclampsia. In this study, more adverse perinatal outcomes occurred among women with pre-eclampsia after controlling for confounders. A higher perinatal outcome observed among women with pre-eclampsia, especially among women with severe features of pre-eclampsia, and those admitted to hospital at <34 weeks. This paper highlights the significantly elevated perinatal risks associated with pre-eclampsia, especially when it has severe features.


Characterization, in vitro cytotoxicity and cellular accumulation of paclitaxel-loaded lipid nano-emulsions.
Lipid nano-emulsions (LNEs) having a mean droplet size of approximately 50 nm were investigated as drug carriers for paclitaxel (TXL) to achieve its satisfactory loadings and to develop a pharmaceutically acceptable alternative to the current formulation, Taxol. TXL was incorporated into the LNEs at 2.0 mg/ml without changes in particle size or drug precipitation. In the cytotoxicity study, TXL-loaded LNEs had cytotoxicity to HeLa cells equivalent to that of TXL alone; the 50% growth inhibitory concentrations (IC(50)) of TXL-loaded LNEs and TXL alone were 1.53 +/- 0.23 nM and 1.76 +/- 0.08 nM, respectively. However, a cellular accumulation study using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a fluorescent probe showed that the accumulation of DPH-loaded LNEs in HeLa cells was remarkably lower than that of DPH alone. These results indicated that LNEs were a useful vehicle for TXL, even though LNEs themselves could not be efficiently accumulated in HeLa cells.


Changes in Isoperoxidases during Cold Treatment of Dormant Pear Embryo.
The number of isoperoxidases and the intensity of certain isozymes increased with increasing periods of stratification of pear (Pyrus communis cv. Bartlett) embryos. The presence of GA(3) or kinetin during stratification enhanced the activity of certain isoperoxidases, and these enhancements were blocked in the presence of ABA which by itself had an inhibitory effect. Enhancement in isoperoxidases of pear embryos during stratification was inhibited by 6-methylpurine and cycloheximide; and in the presence of either of these two inhibitors, stratification failed to release the dormancy. Pear embryos germinated for 3 days showed changes in the pattern of isoperoxidases depending on the length of stratification.


Crosslinked Polyarylene Ether Nitrile Interpenetrating with Zinc Ion Bridged Graphene Sheet and Carbon Nanotube Network.
We report the fabrication and improved properties of crosslinked polyarylene ether nitrile (CPEN) interpenetrating with a zinc ion bridged graphene sheet (GS) and carbon nanotube (CNT) network (GS-Zn-CNT) (CPEN/GS-Zn-CNT). Graphene oxide (GO) and acidulated CNT were firstly prepared and then coordinated with zinc ions to form the zinc ion bridged GO and CNT network (GO-Zn-CNT). The mass ratio of GO and acidulated CNT in GO-Zn-CNT was controlled to be 1:3 and the optimized content of Zn2+ was Zn2+/C = 0.01 mmol/mg (mole of zinc acetate/total weight of GO and acidulated CNT). Phthalonitrile end-capped polyarylene ether nitrile (PEN-Ph) permeated into the GO-Zn-CNT in N-methyl-2-pyrrolidone (NMP) and the corresponding composite PEN/GO-Zn-CNT was fabricated through the solution-casting method. After thermal annealing at 230 °C for 1 h and further curing at 320 °C for 2 h, the GO in GO-Zn-CNT was partly reduced into GS, and PEN-Ph was crosslinked, offering the CPEN/GS-Zn-CNT. The mechanical, thermal, and electrical properties of the obtained CPEN/GS-Zn-CNT were investigated in detail. The glass transition temperature, relative permittivity, and tensile strength of CPEN/GS-Zn-CNT with 2.0 wt % GS-Zn-CNT, compared to that of PEN, were increased by 18%, 181%, and 27%, respectively. The CPEN/GS-Zn-CNT based composite is a potential candidate as material in high performance electronic devices.


Self-defeating personality and depression: a closer look.
55 men and 55 women were given Schill's Self-defeating Personality Scale, a measure of Beck's cognitive triad, and a measure of the personality dimensions of sociotropy and autonomy. The more characteristics of self-defeating personality endorsed, the more negative were subjects' cognitions about themselves, the world, and the future. Self-defeating men and women scored higher on sociotropy (social dependence), suggesting threats to relationships may be an important source of depression for them. Self-defeating women also scored higher on the autonomy subscales, suggesting threats to their independence may be a source of depression as well. Implications for treatment were discussed.


A DNA double strand break repair defect in Fanconi anemia fibroblasts.
Fanconi anemia (FA) is a heterogeneous autosomal recessive disease characterized by congenital abnormalities, pancytopenia, and an increased incidence of cancer. Cells cultured from FA patients display elevated spontaneous chromosomal breaks and deletions and are hypersensitive to bifunctional cross-linking agents. Thus, it has been hypothesized that FA is a DNA repair disorder. We analyzed plasmid end-joining in intact diploid fibroblast cells derived from FA patients. FA fibroblasts from complementation groups A, C, D2, and G rejoined linearized plasmids with a significantly decreased efficiency compared with non-FA fibroblasts. Retrovirus-mediated expression of the respective FA cDNAs in FA cells restored their end-joining efficiency to wild type levels. Human FA fibroblasts and fibroblasts from FA rodent models were also significantly more sensitive to restriction enzyme-induced chromosomal DNA double strand breaks than were their retrovirally corrected counterparts. Taken together, these data show that FA fibroblasts have a deficiency in both extra-chromosomal and chromosomal DNA double strand break repair, a defect that could provide an attractive explanation for some of the pathologies associated with FA.


Dietary vitamin E and selenium and toxicity of nitrite and nitrate.
Nitrites and nitrates are important antimicrobial and flavoring/coloring agents in meat and fish products. However, nitrites and nitrates may cause methemoglobinemia and other illness, and may react with certain amines to form carcinogenic nitrosamines. The nutritional status of vitamin E and selenium has long been associated with nitrite and nitrate toxicity, although the mechanism involved is not yet clear. Information available recently shows that nitrites and nitrates are both oxidation products and ready sources of nitric oxide (NO*), that NO* reacts rapidly with superoxide to form highly reactive peroxynitrite (ONOO-), and that vitamin E may mediate the generation and availability of superoxide and NO*. Increased formation of ONOO- resulting from nitrite treatment and low intake of vitamin E and selenium may thus be the critical event leading to tissue damage and animal mortality observed previously. The protection against the adverse effects of nitrites/nitrates by vitamin E is attributed to its ability to reduce ONOO- formation, while selenium exerts its protective effects via seleno-enzymes/compounds, which reduce ONOO- formed.


Studies on Poly(propylene fumarate-co-caprolactone diol) Thermoset Composites towards the Development of Biodegradable Bone Fixation Devices.
The effect of reinforcement in the cross-linked poly(propylene fumarate-co-caprolactone diol) thermoset composites based on Kevlar fibres and hydroxyapatite was studied. Cross-linked poly(propylene fumarate-co-caprolactone diol) was also studied without any reinforcement for comparison. The reinforcing fibre acts as a barrier for the curing reaction leading to longer setting time and lesser cross-link density. The fibre and HA reinforced composites have almost the same compressive strength. Nonreinforced material undergoes greater degree of swelling. Among the reinforced materials, the hydroxyapatite reinforced composite has a much higher swelling percentage than the fibre reinforced one. The studies on in vitro degradation of the cured materials reveal hydrolytic degradation in Ringer's solution and PBS medium during aging. All the three materials are found to swell initially in Ringer's solution and PBS medium during aging and then undergo gradual degradation. Compression properties of these cross-linked composites increase with aging; HA reinforced composite has the highest compressive strength and compressive modulus, whereas the aged fibre-reinforced composite has the least compressive strength and modulus.


Valerenic Acid Protects Against Physical and Psychological Stress by Reducing the Turnover of Serotonin and Norepinephrine in Mouse Hippocampus-Amygdala Region.
In a previous study, we demonstrated that a Valeriana officinalis extract could attenuate increases in serum corticosterone levels in a mouse model of physical and psychological stress. In addition, our results showed that the extract could modulate serotonin (5-HT) and norepinephrine (NE) turnover in the hippocampus and amygdala region. In this study, we intended to investigate the effects of valerenic acid (VA), the main component of V. officinalis extract, on corticosterone levels in serum in normal mice and monoamine turnover in hippocampus-amygdala homogenates in a mouse model of physical and psychological stress. To determine the minimum dose of VA for antianxiety effect, eight-week-old ICR mice were orally administered VA (0.2, 0.5, and 1.0 mg/kg/0.3 mL) once daily for 3 weeks to probe for immobility time and serum corticosterone levels. At a VA dose of 0.5 and 1.0 mg/kg, animals showed a decrease in the duration of immobility time and serum corticosterone levels. To confirm the antianxiety effect of VA, eight-week-old ICR mice received VA at a dose of 0.5 mg/kg, orally, once daily for 3 weeks, before being subjected to physical or psychological stress for 3 days, in a specially designed communication box, followed by estimation of levels of monoamines and their metabolites in the hippocampus-amygdala region. In conclusion, VA administration at 0.5 mg/kg can mitigate the physical and psychological stress response by decreasing the turnover of 5-HT to 5-hydroxyindoleacetic acid and NE to 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in the hippocampus and amygdala.


Mortality of United Kingdom oil refinery and petroleum distribution workers, 1951-1998.
The mortality experienced by cohorts of 28 630 oil refinery workers and 16 480 petroleum distribution workers has been investigated. Study subjects were all those male employees first employed in the period 1946-1974 at one of eight UK oil refineries or at one of 476 UK petroleum distribution centres; all subjects had a minimum of 12 months employment with some employment after 1 January 1951. The observed numbers of cause-specific deaths were compared with expectations based on national mortality rates. The resultant standardized mortality ratios (SMRs) were significantly below 100 for all causes, in both oil refinery workers (observed, 9341; expected, 10 649.7; SMR = 88) and petroleum distribution workers (observed, 6083; expected, 6460.3; SMR = 94). Significantly elevated SMRs were shown in oil refinery workers for cancer of the gall bladder (observed, 24; expected, 14.0; SMR = 172), cancer of the pleura (observed, 38; expected, 15.0; SMR = 254) and melanoma (observed, 36; expected, 22.2; SMR = 162). Significantly elevated SMRs were not found in petroleum distribution workers for any site of cancer. SMRs for selected causes of death were calculated by period from commencing employment, by year of hire and by job type. The only findings that suggested the presence of an occupational cancer hazard were an excess of mesothelioma in oil refinery workers and an excess of leukaemia in petroleum distribution workers, both excesses occurring in long-term follow-up for workers first employed >30 years ago.


Homologous Bacteriophage Control of Pseudomonas Growth and Beef Spoilage 1, 2.
The effects of homologous bacteriophages upon growth of a beef spoilage pseudomonad and the retail case life of beef were examined under conditions of simulated retail display. Initial studies with an aqueous extract of beef muscle showed Pseudomonas growth was significantly limited by phages for up to 3 d at 7°C. Subsequently, it was shown that the treatment of Pseudomonas -inoculated steaks with high titer phage lysates (108 PFU/ml) resulted in a 1- to 2-log reduction in the level of bacterial contamination and a 2-log increase in phage numbers after 4 d of retail display. These changes were accompanied by a marked decrease in steak surface discoloration and a concurrent improvement in retail acceptance. Steak case life was positively correlated with phage concentration within the range of 10 to 108 PFU/ml. At the highest concentration of phages tested (108 PFU/ml) steak case life was significantly increased from 1.6 to 2.9 d. It was concluded that phages could multiply on the steak surface and have the potential for the biological control of beef spoilage.


Statin therapy--what now?
In England, only 30% of patients with established coronary heart disease (CHD) and raised serum lipids, and fewer than 4% of individuals eligible for primary prevention, receive lipid-lowering therapy. Target total cholesterol concentrations are achieved in fewer than 50% of patients who do receive such treatment. Here, we review the use of statin therapy in the prevention of CHD events.


Antiemetic therapy of fosaprepitant, palonosetron, and dexamethasone combined with cisplatin-based chemotherapy for head and neck carcinomas.
Concomitant antiemetic therapy comprising fosaprepitant, palonosetron, and dexamethasone is effective for head and neck carcinoma. A patient diary was constructed to determine the effectiveness of concomitant antiemetic therapy with a neurokinin-1 receptor antagonist (fosaprepitant), 5-hydroxytryptamine receptor antagonist (palonosetron), and dexamethasone in accordance with guidelines. Subjects comprised 41 patients who received 71 courses of chemotherapy, along with fosaprepitant, palonosetron, and dexamethasone. A patient diary was compiled concerning the presence/absence of vomiting, vomiting episodes, presence/absence of rescue therapy, food intake, presence/absence of nausea, and general condition. The frequency of the primary end point of complete response in the overall phase was 69.0%. The proportion of patients with no vomiting in the overall phase was 90.1%. In the acute phase, the proportion of no nausea and slight nausea together was 91.5%, no change in and slightly reduced food intake together was 87.3%, and the proportion of good general condition and relatively good general condition was 85.9%. In the delayed phase, the proportion of no nausea and slight nausea together was 56.3%, no change in and slightly reduced food intake together was 43.7%, and the proportion of good general condition and relatively good general condition together was 53.5%.


Persistent air-leak following pulmonary resection.
Air leaks are an unavoidable complication of pulmonary resection. The definition of a persistent air leak is arbitrary and may even be irrelevant in solving the problem. Persistent air leaks are more common in patients with severe COPD, and preoperative interventions are ineffective in reducing their prevalence. Meticulous surgical technique and care in handling and resection of the pulmonary parenchyma are essential in preventing persistent air leaks. Buttressing parenchymal staple lines and creating a pleural tent or pneumoperitoneum should be reserved for patients at risk for persistent air leaks. The use of currently available sealants is ineffective for the treatment of this complication. To stop persistent air leaks, early cessation of suction and placing chest tubes to an underwater seal is more effective than continuous suction. The management of persistent air leaks may require provocative chest tube clamping and permissive chest tube removal or patient discharge from the hospital with a chest tube and a Heimlich valve.


An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases.
Neuromuscular diseases (NMDs) are dysfunctions that involve skeletal muscle and cause incorrect communication between the nerves and muscles. The specific causes of NMDs are not well known, but most of them are caused by genetic mutations. NMDs are generally progressive and entail muscle weakness and fatigue. Muscular impairments can differ in onset, severity, prognosis, and phenotype. A multitude of possible injury sites can make diagnosis of NMDs difficult. Mitochondria are crucial for cellular homeostasis and are involved in various metabolic pathways; for this reason, their dysfunction can lead to the development of different pathologies, including NMDs. Most NMDs due to mitochondrial dysfunction have been associated with mutations of genes involved in mitochondrial biogenesis and metabolism. This review is focused on some mitochondrial routes such as the TCA cycle, OXPHOS, and β-oxidation, recently found to be altered in NMDs. Particular attention is given to the alterations found in some genes encoding mitochondrial carriers, proteins of the inner mitochondrial membrane able to exchange metabolites between mitochondria and the cytosol. Briefly, we discuss possible strategies used to diagnose NMDs and therapies able to promote patient outcome.


[Observations of the fibrosing process in paraquat lung injury by chest X-ray and CT].
A 42-year-old woman with a known history of paraquat ingestion was admitted to our hospital on the 10th day after ingestion complaining of dyspnea and general fatigue. Steroid therapy and low dose oxygen therapy were administered. She recovered and was discharged on the 190th day after paraquat ingestion. A chest X-ray film on admission disclosed a bilateral ground-glass shadow. As time passed, a reticular shadow with a loss of lung volume leaving a peripherally clear zone appeared on chest X-rays and shrank gradually toward the peri-hilar area during the course. CT of the lung clearly demonstrated progress of the pulmonary fibrosing process. In the early phase of paraquat poisoning, CT revealed diffuse high density areas dominant in the posterior part of the lungs with a subpleural intact area. The high density area was sharply demarcated from the subpleural intact area. As time passed, the high density area shrank toward the central zone, causing bullous changes in the subpleural area. The dominant fibrotic change in the intermediate and central zones seems to be one of the characteristic findings in paraquat induced pulmonary fibrosis.


AUF-1 mediates inhibition by nitric oxide of lipopolysaccharide-induced matrix metalloproteinase-9 expression in cultured astrocytes.
Neuroinflammatory diseases are associated with increased production of matrix metalloproteinase-9 (MMP-9) and excessive generation of nitric oxide (NO). NO has been reported to have variable effects on MMP-9 gene expression and activation in various cell types. In the present study, we investigated the effect of NOon MMP-9 expression in primary cortical astrocytes. Zymography and real-time PCR showed that lipopolysaccharide (LPS) dramatically increased latent MMP-9 gelatinolytic activity and MMP-9 mRNA expression. By using the NO donor DETA NONOate, we observed a dose-dependent inhibition of MMP-9 induction by LPS. Active forms of MMP-9 were not found by zymography after NO treatment. The MEK1/2 inhibitor U0126 completely inhibited LPS-induced MMP-9, which was partially inhibited by the p38 MAPK inhibitor SB203580. NO had no effect on LPS-stimulated ERK1/2 and p38 MAPK activation, suggesting that the inhibitory action of NO occurs downstream of MAPK cascades. Real-time PCR analysis showed that NO accelerated the degradation of MMP-9 mRNA after LPS induction. Western blotting and pull-down assay demonstrated that NO increased AUF-1 expression as well as its specific binding to the MMP-9 gene 3'-untranslated region. Knockdown of AUF-1 with siRNA partially reversed the inhibitory action of NO on LPS-stimulated MMP-9 induction. We conclude that NO does not activate MMP-9 in astrocyte cultures but reduces LPS-induced MMP-9 expression via accelerating MMP-9 mRNA degradation, which is partially mediated by AUF-1. Our results suggest that elevated NO concentrations may suppress MMP-9 and restrict the inflammatory response in neurodegenerative diseases.


Necrotizing 'malignant' external otitis caused by Staphylococcus epidermidis.
Necrotizing "malignant" external otitis is a life-threatening skull base infection that originates in the external auditory canal and is characterized by otalgia and purulent aural discharge with external auditory canal cellulitis and granulation. Necrotizing external otitis, seen almost exclusively in elderly diabetics, is almost always caused by Pseudomonas aeruginosa. To our knowledge, there have been only six nonpseudomonal cases reported to date. We describe a 70-year-old diabetic man with necrotizing external otitis caused by Staphylococcus epidermidis, confirmed by serial cultures. This case was characterized by otalgia, purulent otorrhea, preauricular swelling, bony external auditory canal erosion, and a conductive hearing loss. Despite prolonged intravenous antistaphylococcal antibiotic therapy and frequent local débridement, the patient's symptoms never completely resolved. As demonstrated by the treatment failure, S epidermidis necrotizing external otitis, may represent a more refractory form of this already virulent disease process. We believe this to be the first reported case of necrotizing external malignant otitis caused by S epidermidis.


Impact of monovalent cations on the separation performance of graphene oxide membrane for different organic matters.
Graphene oxide (GO) membrane has become a promising membrane due to its advantages of high flux, good anti-pollution performance, and controllable cost. Since wastewater contains inorganic ions and organic substances, the effect of inorganic ions on the removal of organic matters has attracted attention. This study investigated the impact of monovalent cations (Na+ and K+) on the removal of different organic matters by GO membranes. The results showed that the removal by GO membranes of both macromolecular organic compounds (humic acid, sodium alginate, and bull serum albumin) and small molecular organic substances (new coccine, methyl orange, and methylene blue) were high (>75%). The coexisting Na+ caused the increase in flux and the decrease in removal of small molecular organic matters, while the impact on the removal of macromolecular organic matters was weak. The impact of the coexisting K+ was weaker than Na+. With the crosslinking of ethylenediamine, the structure of GO membrane was more stable. The impacts of Na+ on the flux and separation performance of crosslinked membranes were less than that of non-crosslinked membranes. This suggests that crosslinked GO membrane has more potential for practical wastewater treatment.


Reducing the Prevalence and Costs of Heart Disease.
(1) Approximately one in four women and one in five men will die within the first year of having a heart attack. (2) About $108 billion is spent to treat coronary heart disease each year. (3) Engaging in health behaviors—such as keeping blood pressure, cholesterol and weight low—reduces risk of heart attack or stroke by more than 80 percent.


Studies regarding supported housing and the built environment for people with mental health problems: A mixed-methods literature review.
Places where people live are important for their personal and social lives. This is also the case for people with mental health problems living in supported housing. To summarise the existing knowledge, we conducted a systematic review of 13 studies with different methodologies regarding the built environment in supported housing and examined their findings in a thematic analysis. The built environment of supported housing involves three important and interrelated themes: well-being, social identity and privacy. If overregulated by professionals or located in problematic neighbourhoods or buildings, the settings could be an obstacle to recovery. If understood as meaningful places with scope for control by the tenants or with amenities nearby, the settings could aid recovery.


Continuous-time random walks at all times.
Continuous-time random walks (CTRW) play an important role in understanding of a wide range of phenomena. However, most theoretical studies of these models concentrate only on dynamics at long times. We present a new theoretical approach, based on generalized master equations picture, which allowed us to obtain explicit expressions for Laplace transforms for all dynamic quantities for different CTRW models. This theoretical method leads to the effective description of CTRW at all times. Specific calculations are performed for homogeneous, periodic models and for CTRW with irreversible detachments. The approach to stationary states for CTRW is analyzed. Our results are also used to analyze generalized fluctuations theorem.


Trehalulose does not induce dental caries in rats infected with mutans streptococci.
The effects of trehalulose, a structural isomer of sucrose, and a syrup (TP syrup) rich in trehalulose and palatinose on caries development were examined in specific pathogen-free Sprague-Dawley rats. Streptococcus mutans MT8148R and Streptococcus sobrinus 6715 fermented the syrup which resulted in acid production, while both strains were found not to utilize trehalulose. Furthermore, trehalulose did not serve as a substrate for glucosyltransferases of these mutans streptococci to synthesize water-insoluble glucan, and it inhibited the sucrose-dependent adherence of mutans streptococci to a glass surface. Although trehalulose induced no significant dental caries in specific pathogen-free rats infected with either MT8148R or 6715, TP syrup was found to induce significant but low dental caries. Furthermore, replacement of the dietary sucrose content with trehalulose resulted in a significant reduction of caries development in rats infected with strain 6715.


Intra HLA-D region recombinant maps HLA-DR between HLA-B and HLA-D.
A consanguineous family has been typed for HLA-A, B, C, D, DR and GLO, Bf, C2 and C4 and other red cell markers. The results indicate that an expected Dw7 homozygous sibling is a "Dw1"/Dw7 recombinant, probably derived from a crossing over between DR and D on the paternal haplotypes. The anomalous typings by Dw1 HTCs of the recombinant haplotype are best explained by the likely presence of an additional Lad polymorphism which could be a serologically detectable second epitope on the same molecule as the HLA-D determinant or in the form of two linked chains, one encoded by HLA-D and one by another Lad gene in the HLA haplotype.


Human prostate-specific transglutaminase gene: promoter cloning, tissue-specific expression, and down-regulation in metastatic prostate cancer.
To investigate the tissue-specific and differential expression of the human prostate-specific transglutaminase (pTGase) gene in metastatic prostate cancer (CaP) and to study how this gene is regulated in the prostate. Northern blot hybridization and polymerase chain reaction (PCR) were performed using RNA from a variety of organs to confirm prostate-specific expression of the gene. Relative quantitative reverse transcriptase-PCR (RT-PCR) was performed to investigate the differential expression of the gene among normal prostates and prostates with CaP and metastatic CaP. The pTGase gene promoter was cloned using genomic library screening and sequencing. Transfection experiments and chloramphenicol acetyltransferase (CAT) assays were performed to study the regulation of the gene. Northern hybridization and RT-PCR confirmed that the gene is only expressed in the prostate. Relative quantitative RT-PCR demonstrated a loss of expression of the pTGase gene among men with CaP and higher Gleason grades. In metastatic CaP tissue from various sites, 86% of the samples lost expression of the gene. We cloned and sequenced a 1.4-kilobase promoter region of the pTGase gene. Transfection and CAT assay results supported the theory that certain elements in the -1 to -520 region are sufficient to direct prostate-specific expression of the gene. Additional elements in the -520 to -1400 region may also contribute to its prostate-specific expression. The results of our study demonstrate that the human pTGase gene is only expressed in prostate tissue and that its expression is inhibited in most metastatic CaP. Prostate-specific expression of the gene is controlled by elements in the promoter region. The observed preferential loss of pTGase gene expression in metastatic CaP may be important to the pathogenesis and progression of this disease.


Colorectal cancer in Turkey: current situation and challenges for the future.
Cancer is foremost among one of the major public health problems in Turkey. Projections for the year 2030 estimate that cancer will take the highest death toll for both males and females. In line with the dynamic health care reform process commencing in 2003, the national cancer policy of Turkey has also changed radically. Cancer became more visible as a public health problem and improvements have been made in early diagnosis and treatment of the disease. In addition, major steps have been taken to improve the cancer registry system in order to improve cancer statistics. Colorectal cancer (CRC) incidence is approximately 7 per 100,000, with approximately 5,000 new cases and 3,200 deaths annually. Although cancer treatment expenditures are widely covered in Turkey, there are still problems related to the general accessibility of the health care system. This paper addresses the case of cancer in Turkey with special focus on CRC. Specifically, detailed information is provided about the health care and cancer policies, improvements since 2003 and challenges for the future.


Complete mitochondrial genome sequence of Prochilodus lineatus (Characiformes, Prochilodontidae).
Prochilodus lineatus (curimba) is an important Brazilian freshwater migratory fish with substantial economic importance in fishing. The complete mitochondrial genome of P. lineatus is 16,699 bp and contains 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes and one control region (D-loop). The mtDNA of P. lineatus is the first mitogenome of the Prochilodontidae family to be fully characterized. All of the PCGs in the mtDNA use the standard ATG start codon, with the exception of Cox1 that utilizes the GTG start codon. Six of the 13 PCGs contain TAA stop codons, two contain the incomplete stop codon TA- (Atp6 and Nd6), and five contain the incomplete stop codon T- - (Nd2, Cox2, Nd3, Nd4 and Cytb).


Instability of the L6 gene for rust resistance in flax is correlated with the presence of a linked Ac element.
In a programme aimed at tagging rust-resistance genes in flax with the maize transposable element Ac, a primary transformant of a line called 'Forge' that is homozygous for four rust-resistance genes, L6, M, N and P2, was identified that possessed 10 copies of the Ac element, one of which was linked (29 map units) to L6. Descendants of this plant, which had from 8 to 15 copies of Ac, were crossed to a rust-susceptible line and the progeny screened for rust-susceptible mutants. When the Ac linked to L6 was present in the parent, a high frequency of L6 mutants was observed (29 mutants in 30,575). By contrast, when this Ac was absent, no such mutants were observed in 9258 progeny. The background frequency of L6 mutants was low (five in 124,088). A detailed analysis was made of the first 11 L6 mutants recovered from parents carrying the L6-linked Ac element. While none of the mutants possessed a tagged resistance gene, all lacked an RFLP marker closely linked to L6, suggesting that deletions were responsible for loss of the L6 specificity. In many of the mutants, one or more RFLP markers in the vicinity of the linked Ac were also absent. These findings suggest that the linked Ac may be inducing chromosome breakage.


Management of malignant melanoma of the head and neck using dynamic lymphoscintigraphy and gamma probe-guided sentinel lymph node biopsy.
The sentinel lymph node (SLN) biopsy is revolutionizing the surgical management of primary malignant melanoma. It allows accurate nodal staging, and targets patients who may benefit from regional lymphadenectomy and systemic therapy; however, its use in the management of head and neck melanoma has not been widely accepted. A retrospective review of patients treated for clinical stages I and II malignant melanoma of the head and neck with dynamic lymphoscintigraphy and gamma probe-guided SLN biopsy. Fifty-eight patients (47 male and 11 female) were identified. Primary melanoma sites included the scalp (21), ear (8), face (13), neck (15), and eyelid (1). Primary tumor staging was T2 (11), T3 (24), and T4 (23). Dynamic lymphoscintigraphy visualized SLNs in 57 patients (98.3%). In 43 cases (75%) a single draining nodal basin was identified, and in 14 cases there were multiple draining nodal basins. Sentinel lymph nodes were successfully identified in 72 (96%) of 75 nodal basins. Positive SLNs were identified in 10 patients (17.5%). Sentinal lymph node positivity by tumor staging was T3, 16.7% and T4, 27.3%. Completion lymphadenectomy revealed residual disease in 3 patients (30%). Relapse occurred in 10 (21.3%) of the 47 patients with negative SLN biopsy results and 7 (70%) of those with positive results. Gamma probe-guided SLN localization in the head and neck region was successful in 96% of draining nodal basins. It can target regional lymphadenectomy in patients who may benefit from regional nodal dissection.


Fenamates potentiate the alpha 1-adrenoceptor-activated nonselective cation channels in rabbit portal vein smooth muscle.
The agonistic action of fenamates on the alpha 1-adrenoceptor-activated cationic current (Icat) in rabbit portal vein smooth muscle was investigated with the whole-cell patch clamp technique. At -50 mV, the fenamates (100-500 microM) increased Icat dose-dependently, up to several fold. This increase was not accompanied by changes in the reversal potential and strongly inhibited by 500 microM Cd2+ or 10 mM procaine. The enhancing effect of fenamates was also observed on the cationic current activated by intracellularly applied GTP gamma S. These results suggest that fenamates may be useful as a new class of activator for receptor-operated cation channels in smooth muscle.


Safety Assessment of Sorbitan Esters as Used in Cosmetics.
The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of 20 sorbitan esters; this report included sorbitan esters that were reviewed in 1985 and 2002, as well as 3 previously unreviewed sorbitan esters (sorbitan undecylenate, sorbitan sesquicaprylate, and sorbitan palmate). Most of the sorbitan esters are reported to function in cosmetics as surfactant-emulsifying agents. The Panel reviewed the data from previous sorbitan ester reports, as well as additional data included in this report, to determine the safety of these ingredients. The Panel concluded that the sorbitan esters included in this safety assessment are safe in cosmetics in the present practices of use and concentration.


A Unified and Desymmetric Approach to Chiral Tertiary Alkyl Halides.
Enantioenriched tertiary alkyl halides are prevalent in bioactive molecules and can serve as versatile synthetic intermediates to construct complex structures. While conventional access to these motifs often hinges on stereoselective carbon-halogen or carbon-carbon bond formation reactions, desymmetric approaches using halogenated and prochiral tetrasubstituted carbons are largely elusive in comparison. Here, we report that a suite of dinuclear zinc catalysts with a prolinol- or pipecolinol-derived tetradentate ligand can reductively desymmetrize a large collection of easily available halomalonic esters to α-halo-β-hydroxyesters. These polyfunctionalized tertiary alkyl fluorides, chlorides, and bromides proved to be useful intermediates toward fluorinated drug analogs and polyhalogenated monoterpenes. The facile intramolecular epoxidation of the chiral chloride and bromide products has also enabled expeditious access to natural products containing tertiary alcohol motifs.


Ultrastructural cryoimmunocytochemistry is a convenient tool for the study of DNA replication in cultured cells.
In the present study, we have optimized an immunocytochemical ultrastructural approach for in situ localization of newly synthesized DNA in unsynchronized as well as in synchronized human HeLa cells and in exponentially growing mouse P815 cells, which had incorporated bromodeoxyuridine (BrdU) during short pulses varying from 1 to 20 minutes. The incorporated BrdU was detected in hydrolyzed ultrathin cryosections or Lowicryl sections by means of a monoclonal antibody, revealed by secondary colloidal gold-labeled probes. The results demonstrate our ability to study, with high resolution and reproducibility, DNA replication during consecutive periods of the S-phase, which is monitored by the incorporation of tritiated thymidine. In addition, this approach allows one to perform a concomitant mapping of replicated DNA and various enzymes of the replisome.


Heterogenous pathogen profile associated with acute conjunctivitis in Nepal.
Infectious conjunctivitis is common in Nepal. This prospective study recruited 60 patients with presumed acute infectious conjunctivitis from the B.P. Koirala Lions Center for Ophthalmic Studies in Kathmandu, Nepal. Swabs from the conjunctiva and anterior nares were processed for metagenomic RNA deep sequencing (RNA-seq). Pathogens were identified in 55% of cases. RNA viruses were the most common pathogen class identified. Severe acute respiratory syndrome coronavirus 2 was the most common RNA virus identified. Acute infectious conjunctivitis varies by location. Contrary to expectations, RNA viruses predominated. Repeat surveillance may be useful and RNA-seq allows for detection of the unexpected pathogen including RNA viruses.


Ultrasound and Photoacoustic Imaging of Breast Cancer: Clinical Systems, Challenges, and Future Outlook.
Presently, breast cancer diagnostic methods are dominated by mammography. Although drawbacks of mammography are present including ionizing radiation and patient discomfort, not many alternatives are available. Ultrasound (US) is another method used in the diagnosis of breast cancer, commonly performed on women with dense breasts or in differentiating cysts from solid tumors. Handheld ultrasound (HHUS) and automated breast ultrasound (ABUS) are presently used to generate reflection images which do not contain quantitative information about the tissue. This limitation leads to a subjective interpretation from the sonographer. To rectify the subjective nature of ultrasound, ultrasound tomography (UST) systems have been developed to acquire both reflection and transmission UST (TUST) images. This allows for quantitative assessment of tissue sound speed (SS) and acoustic attenuation which can be used to evaluate the stiffness of the lesions. Another imaging modality being used to detect breast cancer is photoacoustic tomography (PAT). Utilizing much of the same hardware as ultrasound tomography, PAT receives acoustic waves generated from tissue chromophores that are optically excited by a high energy pulsed laser. This allows the user to ideally produce chromophore concentration maps or extract other tissue parameters through spectroscopic PAT. Here, several systems in the area of TUST and PAT are discussed along with their advantages and disadvantages in breast cancer diagnosis. This overview of available systems can provide a landscape of possible intersections and future refinements in cancer diagnosis.


Cognitive and motor deficits in selected unilateral brain-injured patients.
16 right hemisphere and 16 left hemisphere, nonaphasic brain-injured stroke patients were compared with 16 matched normal controls on the verbal and visuospatial paired-associate tasks developed by Stark in 1961 as a partial replication to a more severely impaired population. Right brain-injured patients showed a significant visuospatial deficit and contralateral motor impairment; while left brain-injured patients, screened for aphasia, showed contralateral motor impairment but did not show impairment on the verbal task. Examination of the areas of infarct resulting from the cerebrovascular accident in the left-hemisphere patients suggested that the presence of a contralateral motor deficit without verbal impairment results from specific focal occlusions of branches of the middle cerebral artery in this selective group of patients.


[N-acetyl-aspartate abnormalities in internal-temporal epileptic foci using proton magnetic resonance spectroscopy].
The aim of this study was to characterize the neurochemical abnormalities related to N-acetyl-aspartate which is a neuronal marker, within an epilepticus focus located in the internal-temporal area, using proton magnetic resonance spectroscopy. Eleven patients with a mono-hippocampal epileptics focus on clinical and per-critical electroencephalographical criteria, were matched with 11 controls by age, sex and laterality. Proton spectroscopy of a volume of 8 cm3 was performed within the ipsilateral and the contralateral internal-temporal area and within the 2 hippocampus of controls. Volumetry of the ipsilateral and the contralateral hippocampus and of the 2 hippocampus of controls was performed using resonance magnetic imaging. All these measurements were performed during the interictal stage. The results were concordant to show a decrease of the ratio N-acetyl-aspartate/choline and N-acetyl-aspartate/creatine within the epilepticus focus, in relation with a hippocampal atrophy. This study finds similar results to those of other previous works. The decrease of N-acetyl-aspartate levels within the epilepticus focus could be related to a decrease of the neuronal cell density. This procedure is able to show a decrease of the levels of this metabolite within an internal temporal epilepticus focus and associated with a hippocampal atrophy.


Bayesian reconstruction of transmission trees from genetic sequences and uncertain infection times.
Genetic sequence data of pathogens are increasingly used to investigate transmission dynamics in both endemic diseases and disease outbreaks. Such research can aid in the development of appropriate interventions and in the design of studies to evaluate them. Several computational methods have been proposed to infer transmission chains from sequence data; however, existing methods do not generally reliably reconstruct transmission trees because genetic sequence data or inferred phylogenetic trees from such data contain insufficient information for accurate estimation of transmission chains. Here, we show by simulation studies that incorporating infection times, even when they are uncertain, can greatly improve the accuracy of reconstruction of transmission trees. To achieve this improvement, we propose a Bayesian inference methods using Markov chain Monte Carlo that directly draws samples from the space of transmission trees under the assumption of complete sampling of the outbreak. The likelihood of each transmission tree is computed by a phylogenetic model by treating its internal nodes as transmission events. By a simulation study, we demonstrate that accuracy of the reconstructed transmission trees depends mainly on the amount of information available on times of infection; we show superiority of the proposed method to two alternative approaches when infection times are known up to specified degrees of certainty. In addition, we illustrate the use of a multiple imputation framework to study features of epidemic dynamics, such as the relationship between characteristics of nodes and average number of outbound edges or inbound edges, signifying possible transmission events from and to nodes. We apply the proposed method to a transmission cluster in San Diego and to a dataset from the 2014 Sierra Leone Ebola virus outbreak and investigate the impact of biological, behavioral, and demographic factors.


A Comprehensive Gene Expression Meta-analysis Identifies Novel Immune Signatures in Rheumatoid Arthritis Patients.
Rheumatoid arthritis (RA), a symmetric polyarticular arthritis, has long been feared as one of the most disabling forms of arthritis. Identification of gene signatures associated with RA onset and progression would lead toward development of novel diagnostics and therapeutic interventions. This study was undertaken to identify unique gene signatures of RA patients through large-scale meta-profiling of a diverse collection of gene expression data sets. We carried out a meta-analysis of 8 publicly available RA patients' (107 RA patients and 76 healthy controls) gene expression data sets and further validated a few meta-signatures in RA patients through quantitative real-time PCR (RT-qPCR). We identified a robust meta-profile comprising 33 differentially expressed genes, which were consistently and significantly expressed across all the data sets. Our meta-analysis unearthed upregulation of a few novel gene signatures including PLCG2, HLA-DOB, HLA-F, EIF4E2, and CYFIP2, which were validated in peripheral blood mononuclear cell samples of RA patients. Further, functional and pathway enrichment analysis reveals perturbation of several meta-genes involved in signaling pathways pertaining to inflammation, antigen presentation, hypoxia, and apoptosis during RA. Additionally, PLCG2 (phospholipase Cγ2) popped out as a novel meta-gene involved in most of the pathways relevant to RA including inflammasome activation, platelet aggregation, and activation, thereby suggesting PLCG2 as a potential therapeutic target for controlling excessive inflammation during RA. In conclusion, these findings highlight the utility of meta-analysis approach in identifying novel gene signatures that might provide mechanistic insights into disease onset, progression and possibly lead toward the development of better diagnostic and therapeutic interventions against RA.


Evaluation of several solid phase extraction liquid chromatography/tandem mass spectrometry on-line configurations for high-throughput analysis of acidic and basic drugs in rat plasma.
Several configurations using 6- and 10-port switching valves were studied for high flow, on-line extraction of rat plasma coupled to an electrospray triple quadrupole mass spectrometer. Each plasma sample was diluted 1:1 with an aqueous internal standard solution. The sample was injected into a 2.1 x 20 mm cartridge column packed with 25 microm divinylbenzene/N-vinylpyrrolidone packing using 100% aqueous mobile phase at 4 mL/min. After sample loading and sample cleanup, the analytes were eluted from the extraction column with a 1.0-min gradient at 0.4 mL/min. The samples were either analyzed directly after elution from the extraction column or after additional separation using a short high performance liquid chromatography (HPLC) column. The different configurations were tested using an acidic drug (diflunisal) and a basic drug (clemastine) in rat plasma. On-line analysis was performed by injecting 200 microL of diluted plasma. The mass spectrometer was operated in the multiple reaction monitoring (MRM) mode. All calibration standards gave relative standard deviations (RSDs) below 5%. The total time per sample was 3 min.


Examining appropriate diagnosis and treatment of malaria: availability and use of rapid diagnostic tests and artemisinin-based combination therapy in public and private health facilities in south east Nigeria.
Rapid diagnostic tests (RDTs) and Artemisinin-based combination therapy (ACT) have been widely advocated by government and the international community as cost-effective tools for diagnosis and treatment of malaria. ACTs are now the first line treatment drug for malaria in Nigeria and RDTs have been introduced by the government to bridge the existing gaps in proper diagnosis. However, it is not known how readily available these RDTs and ACTs are in public and private health facilities and whether health workers are actually using them. Hence, this study investigated the levels of availability and use of RDTs and ACTs in these facilities. The study was undertaken in Enugu state, southeast Nigeria in March 2009. Data was collected from heads of 74 public and private health facilities on the availability and use of RDTs and ACTs. Also, the availability of RDTs and the types of ACTs that were available in the facilities were documented. Only 31.1% of the health facilities used RDTs to diagnose malaria. The majority used the syndromic approach. However, 61.1% of healthcare providers were aware of RDTs. RDTs were available in 53.3% of the facilities. Public health facilities and health facilities in the urban areas were using RDTs more and these were mainly bought from pharmacy shops and supplied by NGOs. The main reasons given for non use are unreliability of RDTs, supply issues, costs, preference for other methods of diagnosis and providers' ignorance. ACTs were the drug of choice for most public health facilities and the drugs were readily available in these facilities. Although many providers were knowledgeable about RDTs, not many facilities used it. ACTS were readily available and used in public but not private health facilities. However, the reported use of ACTs with limited proper diagnosis implies that there could be high incidence of inappropriate case management of malaria which can also increase the economic burden of illnesses. Government and donors should ensure constant availability of RDTs in both public and private facilities, so that every treatment with ACTs is accompanied with proper diagnosis.


Emergency rotational ablation of a calcified left main coronary artery stenosis in a patient with ischemic induced cardiogenic shock.
High-speed rotational ablation is ideal in the treatment of chronic calcified atherosclerotic lesions. This report describes an elderly woman with a prior history of coronary artery bypass surgery, who developed cardiogenic shock secondary to occlusion of a saphenous vein graft to the obtuse marginal branch of the circumflex coronary artery. Her left main coronary artery was heavily calcified and almost completely occluded. She was treated successfully by high-speed rotational ablation of her left main stenosis.


Practical aspects of oronasopharyngeal suction in children.
Undergoing oronasopharyngeal suction is an unpleasant experience, but the intervention may prevent the deterioration of children who cannot clear their secretions. A successful procedure requires a practitioner with appropriate knowledge, dexterity and communication skills. Thorough training should be provided and a careful risk-benefit assessment is important before suction is performed.


[The biopsychosocial model: much more than additional empathy].
Despite several limits, the biopsychosocial model is the best available medical model today. However, it is still misunderstood and underused. On a theoretical point of view, this system of health-explanatory hypotheses considers biological, psychological and social factors on equal grounds, in a complex, multiple and circular system of causes and effects. A clinical practice derived from this model permanently integrates the biological, psychological and social perspectives. It necessitates active participation of the patient and stresses the importance of educational aspects. The therapeutic relationship is deeply modified. A better diffusion of the biopsychosocial model necessitates changes in teaching, research and increased resources allocated to the clinical encounter.


Implantable continuous glucose sensors.
Because of the limits of wearable needle-type or microdialysis-based enzymatic sensors in clinical use, fully implantable glucose monitoring systems (IGMS) represent a promising alternative. Long-term use reducing impact of invasiveness due to implantation, less frequent calibration needs because of a more stable tissue environment around the sensor and potential easier inclusion in a closed-loop insulin delivery system are the expected benefits of IGMS. First experiences with subcutaneous and intravenous IGMS have been recently collected in pilot studies. While no severe adverse events have been reported, biointerface issues have been responsible for the failures of IGMS. Tissue reactions around implanted subcutaneous devices and damages of intravenous sensors due to shearing forces of blood flow impaired IGMS function and longevity. In functioning systems, accuracy of glucose measurement reached satisfactory levels for average durations of about 120 days with subcutaneous IGMS and 259 days with intravenous sensors. Moreover, sensor information could help to improve time spent in normal glucose range when provided to patients wearing subcutaneous IGMS and allowed safe and effective closed-loop glucose control when intravenous sensors were connected to implanted pumps using intra-peritoneal insulin delivery. These data could open a favourable perspective for IGMS after improvement of biointerface conditions and if compatible with an affordable cost.


Occupational exposures to engine exhausts and other PAHs and breast cancer risk: A population-based case-control study.
Some previous studies have suggested that exposure to engine exhausts may increase risk of breast cancer. In a population-based case-control study of breast cancer in Western Australia we assessed occupational exposure to engine exhausts using questionnaires and telephone interviews. Odds Ratios (OR) and 95% Confidence Intervals (CI) were calculated using logistic regression. We found no association between risk of breast cancer and occupational exposure to diesel exhaust (OR 1.07, 95%CI: 0.81-1.41), gasoline exhaust (OR 0.98, 95%CI: 0.74-1.28), or other exhausts (OR 1.08, 95%CI: 0.29-4.08). There were also no significant dose- or duration-response relationships. This study did not find evidence supporting the association between occupational exposures to engine exhausts and breast cancer risk. Am. J. Ind. Med. 59:437-444, 2016. © 2016 Wiley Periodicals, Inc.


Consistent landmark and intensity-based image registration.
Two new consistent image registration algorithms are presented: one is based on matching corresponding landmarks and the other is based on matching both landmark and intensity information. The consistent landmark and intensity registration algorithm produces good correspondences between images near landmark locations by matching corresponding landmarks and away from landmark locations by matching the image intensities. In contrast to similar unidirectional algorithms, these new consistent algorithms jointly estimate the forward and reverse transformation between two images while minimizing the inverse consistency error-the error between the forward (reverse) transformation and the inverse of the the reverse (forward) transformation. This reduces the ambiguous correspondence between the forward and reverse transformations associated with large inverse consistency errors. In both algorithms a thin-plate spline (TPS) model is used to regularize the estimated transformations. Two-dimensional (2-D) examples are presented that show the inverse consistency error produced by the traditional unidirectional landmark TPS algorithm can be relatively large and that this error is minimized using the consistent landmark algorithm. Results using 2-D magnetic resonance imaging data are presented that demonstrate that using landmark and intensity information together produce better correspondence between medical images than using either landmarks or intensity information alone.


Impact of Top Electrodes (Cu, Ag, and Al) on Resistive Switching behaviour of Cu-rich Cu2 ZnSnS4 (CZTS) Ideal Kesterite.
Cu2 ZnSnS4 (CZTS) active material-based resistive random-access memory (RRAM) devices are investigated to understand the impact of three different Cu, Ag, and Al top electrodes. The dual resistance switching (RS) behaviour of spin coated CZTS on ITO/Glass is investigated up to 102 cycles. The stability of all the devices (Cu/CZTS/ITO, Ag/CZTS/ITO, and Al/CZTS/ITO) is investigated up to 103 sec in low- (LRS) and high- (HRS) resistance states at 0.2 V read voltage. The endurance up to 102 cycles with 30 msec switching width shows stable write and erase current. Weibull cumulative distribution plots suggest that Ag top electrode is relatively more stable for set and reset state with 33.61 and 25.02 shape factors, respectively. The charge carrier transportation is explained by double logarithmic plots, Schottky emission plots, and band diagrams, substantiating that at lower applied electric field intrinsic copper ions dominate in Cu/CZTS/ITO, whereas, at higher electric filed, top electrodes (Cu and Ag) dominate over intrinsic copper ions. Intrinsic Cu+ in CZTS plays a decisive role in resistive switching with Al electrode. Further, the impedance spectroscopy measurements suggest that Cu+ and Ag+ diffusion is the main source for the resistive switching with Cu and Ag electrodes.


Spontaneous perforation of pyometra presenting as generalized peritonitis in a patient with cervical cancer.
Pyometra is a relatively common event. However, it is extremely rare for this condition to perforate spontaneously into the peritoneum, and to date only 14 cases have been reported in English literature. We recently experienced such a case in a patient with cervical cancer. The clinical features, pathologic findings, diagnosis, therapy, and outcome of these 15 cases were reviewed. Only 5 cases were associated with malignant diseases, consisting of 2 cervical cancers, 2 colon cancers, and 1 endometrial cancer. All of the patients developed generalized peritonitis, and 4 patients died of this. Correct preoperative diagnosis was difficult. Therefore, immediate and appropriate therapy is important.


Agricultural origins from the ground up: archaeological approaches to plant domestication.
The timing, geographical locations, causes, and consequences of crop domestication have long been major concerns of archaeologists, and agricultural origins and dispersals are currently more relevant than ever to scientists seeking solutions to elusive problems involving food insecurity and global health disparities. Perennial research issues that archaeologists continue to tackle include (1) thinking outside centers of origin that were based on limited and insufficient past knowledge; (2) distinguishing between single and multiple domestications of specific crops; (3) measuring the pace of domestication; and (4) decoupling domestication from agricultural economies. Paleoethnobotanists have expanded their toolkits to include analysis of ancient and modern DNA and have added increasingly sophisticated techniques in the field and the laboratory to derive precise chronological sequences to assess morphological changes in ancient and often fragmentary archaeobotanical remains and to correctly interpret taphonomy and context. Multiple lines of archaeological evidence are ideally brought together, and whenever possible, these are integrated with information from complementary sources. We discuss current perspectives and anthropological approaches to research that have as their goals the fuller and broader understanding of ancient farming societies, the plants that were domesticated, the landscapes that were created, and the culinary legacies that were passed on.


Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug.
Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-year-old woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin) tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.