[Study of primary hyperparathyroidism by double-phase gammagraphy using Tc99m-MIBI: preoperative detection of pathological glands].
The preoperative use of imaging techniques to localize the diseased glands in primary hyperparathyroidism is still the subject of controversy. This paper assess the use of double-phase 99mTc-MIBI scintigraphy with that purpose. We examined 37 patients with primary hyperparathyroidism before surgical intervention. Two planar images 10 minutes and 3 hours after injection of 99mTc-MIBI were acquired. Final diagnosis was adenoma in 32 patients, 30 of whom had a positive scintigraphy (sensitivity 94%), with only two false negative results. In the other five patients, four with hyperplasia and one carcinoma, scintigraphy was also positive. Radioisotopic study was of particular interest in 5 patients who had undergone previous surgery; in one case, other diseased gland was located in the neck, and an ectopic adenoma was found in the remaining four cases. Two other ectopic lesions were also MIBI positive and, in these cases, scintigraphy was a direct indication for mediastinal surgery. There was no false positive results. We conclude that the high sensitivity and easy performance make double-phase 99mTc-MIBI scintigraphy the technique of choice for the preoperative localization of diseased glands in primary hyperparathyroidism, especially in cases of adenoma. Its use is of particular interest in adenomas with aberrant location and in patients who have undergone previous surgery.


Antiinflammatory role of endomorphins in osteoarthritis, rheumatoid arthritis, and adjuvant-induced polyarthritis.
Pain sensitization and the related secretion of neuropeptides from sensory nerve terminals are proinflammatory in osteoarthritis (OA), rheumatoid arthritis (RA), and adjuvant-induced polyarthritis. In contrast, endogenous opioids such as the recently discovered endomorphins (EMs) are antiinflammatory. However, the role of endogenous EMs such as EM-1 and EM-2 has never been investigated in OA and RA. We established a highly sensitive radioimmunoassay to detect EM-1 and EM-2. In patients with RA and patients with OA, immunohistochemistry for EM-1 and EM-2 was performed, and double-staining was used to identify EM-positive cells. The effects of EM-1 and EM-2 on the secretion of interleukin-6 (IL-6) and IL-8 from human synovial tissue were studied by tissue superfusion, and the therapeutic effects of EM-1 were tested in a rat model of adjuvant-induced polyarthritis. EM-positive cells were located in the sublining area and vessel walls but were particularly evident in the highly inflamed lining area. Human macrophages, T cells, and fibroblasts stained positive for EMs. The synovial density of EM-positive cells was higher in patients with OA than in those with RA. EM-1 inhibited synovial secretion of IL-6 in patients with RA and secretion of IL-8 in patients with RA and those with OA (maximum 10(-10)M). EM-2 inhibited IL-8 secretion only from RA tissue (maximum 10(-10)M). In rats with adjuvant-induced polyarthritis, thymus, spleen, and synovial tissue contained significantly more EM-1 than was observed in controls. Rats with adjuvant-induced polyarthritis benefited from EM-1 treatment. EM-1 had antiinflammatory effects in patients with OA or RA and in a model of adjuvant-induced polyarthritis. Local enhancement of EM-1 might be an interesting therapeutic option in different forms of arthritis.


Phenophysiological variation of a bee that regulates hive humidity, but not hive temperature.
Seasonal acclimatisation of thermal tolerance, evaporative water loss and metabolic rate, along with regulation of the hive environment, are key ways whereby hive-based social insects mediate climatic challenges throughout the year, but the relative importance of these traits remains poorly understood. Here, we examined seasonal variation in metabolic rate and evaporative water loss of worker bees, and seasonal variation of hive temperature and relative humidity (RH), for the stingless bee Austroplebeia essingtoni (Apidae: Meliponini) in arid tropical Australia. Both water loss and metabolic rate were lower in the cooler, dry winter than in the hot, wet summer at most ambient temperatures between 20°C and 45°C. Contrary to expectation, thermal tolerance thresholds were higher in the winter than in the summer. Hives were cooler in the cooler, dry winter than in the hot, wet summer, linked to an apparent lack of hive thermoregulation. The RH of hives was regulated at approximately 65% in both seasons, which is higher than unoccupied control hives in the dry season, but less than unoccupied control hives in the wet season. Although adaptations to promote water balance appear more important for survival of A. essingtoni than traits related to temperature regulation, their capacity for water conservation is coincident with increased thermal tolerance. For these small, eusocial stingless bees in the arid tropics, where air temperatures are relatively high and stable compared with temperate areas, regulation of hive humidity appears to be of more importance than temperature for maintaining hive health.


[Tethered spinal cord and lipoma. Contribution of magnetic resonance imaging].
A 12 year-old boy was investigated for progressive deformity of the left foot developing over 2 years. The foot was hollow with equinus varus and claw toes. Signs of a lesion of left L5 and S1 roots were present and spina bifida at L5 was noted on X-rays. Magnetic resonance imaging (MRI) showed a tethered spinal cord associated with a lipoma at the level of the S1 vertebra. Modes of presentation and physiopathology of disorders related to tethered cords are reviewed and the diagnostic value of MRI is emphasized.


Ecotoxicity of a mixture of nanoparticles on algal species Scendesmus obliquus in OECD growth media, wastewater, and pond water.
The possible impact of ZnO and CuO nanoparticles (NPs) (individually and in binary mixture) was investigated using the freshwater microalgae, Scenedesmus obliquus. The present study shows the effect of nanoparticles on algae in OECD growth media, wastewater, and pond water during a 96-h toxicity test. At 0.1 mg/L concentration of the mixture of NPs, the reduction in the chlorophyll a content was 13.61 ± 1.34% (OECD media), 28.83 ± 1.85% (wastewater), and 31.81 ± 2.23% (pond water). Values of reduction in biomass were observed to be 42.13 ± 1.38, 39.96 ± 1.03, and 33.10 ± 1.29% for OECD media, wastewater, and pond water, respectively. The highest increase in lipid values was observed in the case of pond water (6.3 ± 1.31%). A significant increase in the value of EPS-generated protein was observed in the wastewater sample. EPS-generated carbohydrate values were increased in OECD media but decreased in the wastewater matrix. The transmission electron microscope images showed structural damage to algae cells due to the exposure to a mixture of nanoparticles at higher concentrations. Fourier transform infrared analysis showed an addition of bonds and differences in the peak and its intensity during exposure to high concentrations of NPs. Overall, this study gives fundamental insights into the interaction and toxicity of a mixture of NPs to algal species in different water matrices.


A Model for Link Pruning to Establish Correctly Polarized and Oriented Tip Links in Hair Bundles.
Tip links are thought to gate the mechanically sensitive transduction channels of hair cells, but how they form during development and regeneration remains mysterious. In particular, it is unclear how tip links are strung between stereocilia so that they are oriented parallel to a single axis; why their polarity is uniform despite their constituent molecules' intrinsic asymmetry; and why only a single tip link is present at each tip-link position. We present here a series of simple rules that reasonably explain why these phenomena occur. In particular, our model relies on each of the two ends of the tip link having distinct Ca2+-dependent stability and being connected to different motor complexes. A simulation employing these rules allowed us to explore the parameter space for the model, demonstrating the importance of the feedback between transduction channels and angled links, links that are 60° off-axis with respect to mature tip links. We tested this key aspect of the model by examining angled links in chick cochlea hair cells. As implied by the assumptions used to generate the model, we found that angled links were stabilized if there was no tip link at the tip of the upper stereocilium, and appeared when transduction channels were blocked. The model thus plausibly explains how tip-link formation and pruning can occur.


[Continuing medical education in gastroenterology and recertification in Peru].
The field of action of gastroenterology has been expanded due to technological development and the advent of new sub-specialties, such as gastroenterology oncology. Currently, there is no standardization of medical training programs in gastroenterology in our country. The health system and education are changing, so medical practice and competency assessment for medical certification and recertification should reflect these changes. On the other hand, the quality of a specialized unit, service or medical department is directly related to the quality of human resources. Lifelong learning is reflected in continuing medical education (CME). The goal of CME should be to achieve changes in staff conduct, through continuous improvement in daily practice. This requires knowing the social, institutional and individual needs and developing new, more flexible and individualized CME programs. Recertification at fixed intervals should be abandoned in favor of a model that promotes continuous professional development based on health needs and with curricular materials that support competency assessments.


iCanCope With Pain: Cultural Adaptation and Usability Testing of a Self-Management App for Adolescents With Persistent Pain in Norway.
Persistent or chronic pain is a common health problem among adolescents. Thus, it is important that they receive evidence-based strategies for symptom management. iCanCope with Pain is a mobile phone app designed to help adolescents cope with chronic pain. The app comprises 5 evidence- and theory-based features: (I) symptom trackers for pain, sleep, mood, physical function, and energy; (II) goal setting to improve pain and function; (III) a coping toolbox of pain self-management strategies; (IV) social support; and (V) age-appropriate pain education. The iCanCope with Pain app is based on theory, identified health care needs, and current best practices for pain self-management. The objectives of this study were to describe the translation and cultural adaptation of the app into the Norwegian context and evaluate the app's usability using a phased approach. Phase 1 included translation and cultural adaptation of the app into the Norwegian context. This process used an expert panel of researchers and target group representatives who were responsible for the linguistic quality assurance and assessment. In phases 2 and 3 the app's usability was tested. For phase 2, the assessments of usability and user experiences included observation, the think aloud method, audiovisual recordings, questionnaires, and individual interviews in a laboratory setting. For phase 3, the assessment of usability and user experience over a 2-week home-based test included questionnaires and individual end-user interviews. Overall, app usability was determined based on ease of use, efficiency, and user satisfaction. Qualitative data were analyzed using deductive content analysis. Descriptive statistics were calculated for quantitative data. End users did not report any misunderstandings or discrepancies with the words or phrasing of the translated and culturally adapted app. Participants in both the laboratory- and home-based usability tests found the app self-explanatory and reported that all 5 of its features were easy to use. All tasks were completed within the allocated time frame (ie, efficiency), with few errors. Overall System Usability Scale scores were high, with average scores of 82 and 89 out of 100 from laboratory- and field-based tests, respectively. Participants liked the idea of a social support function (feature IV), although qualitative and internet server data revealed that this feature was rarely used. This study described the cultural and linguistic adaptation and usability testing of the Norwegian version of the iCanCope with Pain app. High user satisfaction, ease of use, efficiency, and only minor errors cumulatively indicated that no changes to the app were needed, with the exception of facilitating user interaction within the social support feature. The app will be used in an upcoming randomized controlled trial with a larger sample.


[Significance of biochemical indices of liver fibrosis].
Correlation between content of hydroxyproline in urine, protein-bound hydroxyproline, alpha 2-macroglobulin as well as of collagen peptidase activity in blood serum and the intensity of collagen accumulation in liver tissue were studied in experimental liver tissue cirrhosis, which developed after chronic intoxication of rats with CCl4. Distinct relationship was shown between the level of hydroxyprolinuria and amount of collagen in liver tissue. Content of protein-bound hydroxyproline, alpha 2-macroglobulin and the collagen peptidase activity were quite unaltered in blood serum during the cirrhosis development. Protein-bound hydroxyproline and alpha 2-macroglobulin were markedly decreased in blood serum at the step of decompensated cirrhosis. Among the biochemical patterns studied in biological fluids only estimation of hydroxyproline in urine might distinctly reflect the intensity of liver tissue fibrosis.


The diverse potential effector and immunoregulatory roles of mast cells in allergic disease.
Mast cells are of hematopoietic origin but typically complete their maturation in peripheral connective tissues, especially those near epithelial surfaces. Mast cells express receptors that bind IgE antibodies with high affinity (FcepsilonRI), and aggregation of these FcepsilonRI by the reaction of cell-bound IgE with specific antigens induces mast cells to secrete a broad spectrum of biologically active preformed or lipid mediators, as well as many cytokines. Mast cells are widely thought to be essential for the expression of acute allergic reactions, but the importance of mast cells in late-phase reactions and chronic allergic inflammation has remained controversial. Although it is clear that many cell types may be involved in the expression of late-phase reactions and chronic allergic inflammation, studies in genetically mast cell-deficient and congenic normal mice indicate that mast cells may be critical for the full expression of certain features of late-phase reactions and may also contribute importantly to clinically relevant aspects of chronic allergic inflammation. Moreover, the pattern of cytokines that can be produced by mast cell populations, and the enhancement of such cytokine production in mast cells that have undergone IgE-dependent up-regulation of their surface expression of FcepsilonRI, suggests that mast cells may contribute to allergic diseases (and host defense) by acting as immunoregulatory cells, as well as by providing effector cell function.


Sex determination based on fecal DNA analysis of the amelogenin gene in sika deer (Cervus nippon).
A sex determination method using DNA extracted from feces has been developed for sika deer (Cervus nippon). We determined a partial sequence of the amelogenin gene of sika deer, which exists on both X and Y chromosomes with a deletion region on the Y chromosome. Based on the sexually dimorphic sequences, we designed a pair of primers which could amplify DNA fragments the lengths of which are different between males and females. PCR products were detected in 34 out of 37 fecal samples collected from captured deer and the sexes estimated by the present method were perfectly matched with the actual sexes.


Exploration of Fungal Metabolic Interactions Using Imaging Mass Spectrometry on Nanostructured Silicon.
Application of matrix-assisted laser desorption/ionization imaging mass spectrometry to microbiology and natural product research has opened the door to the exploration of microbial interactions and the consequent discovery of new natural products and their functions in the interactions. However, several drawbacks of matrix-assisted laser desorption/ionization imaging mass spectrometry have limited its application especially to complicated and uneven microbial samples. Here, we applied nanostructured silicon as a substrate for surface-assisted laser desorption/ionization mass spectrometry for microbial imaging mass spectrometry to explore fungal metabolic interactions. We chose Phellinus noxius and Aspergillus strains to evaluate the potential of microbial imaging mass spectrometry on nanostructured silicon because both fungi produce a dense mass of aerial mycelia, which is known to complicate the collection of high-quality imaging mass spectrometry data. Our simple and straightforward sample imprinting method and low background interference resulted in an efficient analysis of small metabolites from the complex microbial interaction samples.


Reflex pathways controlling urethral striated and smooth muscle function in the male rat.
The organization of vesicourethral reflex mechanisms in the male rat was studied by monitoring intraurethral pressure and the external urethral sphincter (EUS) electromyogram. EUS striated and urethral smooth muscle activities were elicited by reflex isovolumetric bladder contractions evoked by bladder filling or electrical stimulation of nerves in the bladder wall. Evoked EUS bursting activity in normal rats was eliminated in chronic spinal rats and replaced by tonic activity. Reflex urethral smooth muscle activity mediated by an increase in urethral pressure after paralysis of the EUS with alpha-bungarotoxin occurred in normal and chronic spinal rats. The response was significantly larger in chronic spinal (21.3 +/- 3.0 cmH2O) than in normal rats (4.2 +/- 0.7 cmH2O). NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor, 20 mg/kg i.v.) increased the smooth muscle response in normal (5.9 +/- 1.3 cmH2O) and chronic spinal rats (6.9 +/- 1.8 cmH2O). This increase in urethral pressure was not changed by sympathetic nerve transection or prazosin (0.2-0.3 mg/kg i.v.) but was abolished by hexamethonium and reduced 74-89% by atropine. These results indicate that coordinated EUS function (bursting activity) in the male rat is dependent on supraspinal pathways and that the urethral smooth muscle response during voiding is composed of a predominant cholinergic, atropine-sensitive contraction as well as a nitric oxide-mediated relaxation. Both are mediated by activation of parasympathetic pathways and are maintained or significantly larger after spinal cord injury, indicating that they are dependent on spinal reflex pathways.


Estimating novel potential drug targets of Plasmodium falciparum by analysing the metabolic network of knock-out strains in silico.
Malaria is one of the world's most common and serious diseases causing death of about 3 million people each year. Its most severe occurrence is caused by the protozoan Plasmodium falciparum. Biomedical research could enable treating the disease by effectively and specifically targeting essential enzymes of this parasite. However, the parasite has developed resistance to existing drugs making it indispensable to discover new drugs. We have established a simple computational tool which analyses the topology of the metabolic network of P. falciparum to identify essential enzymes as possible drug targets. We investigated the essentiality of a reaction in the metabolic network by deleting (knocking-out) such a reaction in silico. The algorithm selected neighbouring compounds of the investigated reaction that had to be produced by alternative biochemical pathways. Using breadth first searches, we tested qualitatively if these products could be generated by reactions that serve as potential deviations of the metabolic flux. With this we identified 70 essential reactions. Our results were compared with a comprehensive list of 38 targets of approved malaria drugs. When combining our approach with an in silico analysis performed recently [Yeh, I., Hanekamp, T., Tsoka, S., Karp, P.D., Altman, R.B., 2004. Computational analysis of Plasmodium falciparum metabolism: organizing genomic information to facilitate drug discovery. Genome Res. 14, 917-924] we could improve the precision of the prediction results. Finally we present a refined list of 22 new potential candidate targets for P. falciparum, half of which have reasonable evidence to be valid targets against micro-organisms and cancer.


Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: an update for 2007-2008.
This review is the fifth update of the original review, published in 1999, on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2008. The first section of the review covers fundamental studies, fragmentation of carbohydrate ions, use of derivatives and new software developments for analysis of carbohydrate spectra. Among newer areas of method development are glycan arrays, MALDI imaging and the use of ion mobility spectrometry. The second section of the review discusses applications of MALDI MS to the analysis of different types of carbohydrate. Specific compound classes that are covered include carbohydrate polymers from plants, N- and O-linked glycans from glycoproteins, biopharmaceuticals, glycated proteins, glycolipids, glycosides and various other natural products. There is a short section on the use of MALDI mass spectrometry for the study of enzymes involved in glycan processing and a section on the use of MALDI MS to monitor products of the chemical synthesis of carbohydrates with emphasis on carbohydrate-protein complexes and glycodendrimers. Corresponding analyses by electrospray ionization now appear to outnumber those performed by MALDI and the amount of literature makes a comprehensive review on this technique impractical. However, most of the work relating to sample preparation and glycan synthesis is equally relevant to electrospray and, consequently, those proposing analyses by electrospray should also find material in this review of interest.


Continuous quality improvement at work: the first team--Part I.
This first part of a two-part article describes the process of making the theory of continuous quality improvement a reality. The successes, the failures, and the struggles of the first team effort are outlined. The evolution of the team approach is captured from the perspectives of the quality directors, the facilitator, and the team leader. The team project discussed in this article focused on inpatient admissions and the assignment of patients to observation status.


Mapping local blood flow of human brain by CT scanning during stable xenon inhalation.
Non-invasive methods are described for estimating local cerebral blood flows (LCBF) and partition coefficients (L lambda) during inhalation of 35% stable xenon gas (Xes) in oxygen during CT scanning. After denitrogenation by 100% oxygen breathing, 35% Xes is breathed for 7-8 minutes to minimize subanesthetic effects. Mean changes in brain Hounsfield units extrapolated to 15 minutes were 7.7 units for white matter and 5.3 units for gray matter. They were measured from volumes 80 cubic mm (10 mm2 area x 8 mm), or larger with an EMI 1010 scanner at 1 minute intervals. These data were used for computing LCBFs and L lambdas. Irradiation measured at the center of brain slices was 1 rad per minute. To calculate L lambdas about 6 exposures are necessary, thereafter, each 1 minute scan provides LCBF measurements for 2 adjacent 8 mm slices. Reproducibility for LCBF was r = 0.85 (P less 0.001). Mean L lambdas were 0.86 +/- 0.08 for gray and 1.34 +/- 0.10 for white matter. Normative mean flows (mls/100 g brain/min) were: basal ganglia = 79.6 +/- 9.3, cortex = 82.3 +/- 8.5, white matter = 29.2 +/- 5.9, midbrain tegmentum = 94.3 +/- 14.8, cerebellar cortex = 80.1 +/- 10.9, dorsal pons = 89.3 +/- 4.7, brachium pontis = 35.0 +/- 4.2. Subject finger exercises produced increases of LCBF in contralateral pre-central and post-central gyri. Eye closure decreased flow values limited to the visual system. Gray matter flow values diffusely decreased in non-REM sleep but increased above normal in REM sleep. Cerebral infarction and hemorrhage resulted in zones of zero flow with borders having reduced lambdas and low flows attributed to edema.


Apigenin Protects the Brain against Ischemia/Reperfusion Injury via Caveolin-1/VEGF In Vitro and In Vivo.
Apigenin is a natural flavonoid found in several dietary plant foods as vegetables and fruits. To investigate potential anti-ischemia/reperfusion injury properties of apigenin in vitro, cell proliferation assay, tube formation, cell migration, apoptosis, and autophagy were performed in human brain microvascular endothelial cells (HBMVECs) after oxygen-glucose deprivation/reoxygenation (OGD/R). The effect of apigenin was also explored in rats after middle cerebral artery occlusion/reperfusion (MCAO/R) via neurobehavioral scores, pathological examination, and measurement of markers involved in ischemia/reperfusion injury. Data in vitro indicated that apigenin could prompt cell proliferation, tube formation, and cell migration while inhibiting apoptosis and autophagy by affecting Caveolin-1/VEGF, Bcl-2, Caspase-3, Beclin-1, and mTOR expression. Results in vivo showed that apigenin significantly reduced neurobehavioral scores and volume of cerebral infarction while prompting vascular endothelial cell proliferation by upregulating VEGFR2/CD34 double-labeling endothelial progenitor cell (EPC) number and affecting Caveolin-1, VEGF, and eNOS expression in brain tissue of MCAO/R rats. All the data suggested that apigenin may be protective for the brain against ischemia/reperfusion injury by alleviating apoptosis and autophagy, promoting cell proliferation in HBMVECs of OGD/R, and attenuating brain damage and improved neurological function in rats of MCAO/R through the Caveolin-1/VEGF pathway.


Polymyositis--an immunofluorescence study on the distribution of collagen types.
Type-specific antibodies to the polymorphic types of collagen have been used to study their distribution in polymyositis. Dramatic increases were observed in the staining with antibodies to Type III collagen and, to a lesser extent, with antibodies to Types I, IV, and V. The changes in capillary and endomysial basement membrane collagens (Types IV and V) as well as the proliferation of perimysial Type III collagen are discussed in relation to the muscle atrophy observed during the disease.


Designing a Mobile e-Coaching App for Immigrant Informal Caregivers: Qualitative Study Using the Persuasive System Design Model.
Informal caregivers are vital in caring for their family and friends at home who may have illnesses or disabilities. In particular, the demands for caregiving can be even more challenging for those with limited resources, support systems, and language barriers, such as immigrant informal caregivers. They face complex challenges in providing care for their relatives. These challenges can be related to sociocultural diversity, language barriers, and health care system navigation. Acknowledging the global context of the increasing number of immigrants is essential in designing inclusive mobile health apps. This study aims to investigate the needs of immigrant informal caregivers in Sweden and discuss the application of the Persuasive System Design Model (PSDM) to develop an e-coaching prototype. By addressing the unique challenges faced by immigrant informal caregivers, this study will contribute to the development of more effective and inclusive mobile health apps. The participants were considered immigrants and included in the study if they and their parents were born outside of Sweden. Through various channels, such as the National Association of Relatives, rehabilitation departments at municipalities, and immigrant groups, we recruited 13 immigrant informal caregivers. These immigrant informal caregivers were primarily women aged 18 to 40 years. Most participants belonged to the Middle Eastern region whereas some were from North Africa. However, all of them spoke Arabic. We used semistructured interviews to gather data from the participants in Arabic, which were translated into English. Data were analyzed using thematic analysis and discussed in relation to the extended PSDM. The needs of the caregivers were compared with the description of persuasive design principles, and a design principle was chosen based on the match. The PSDM was extended if the need description did not match any principles. Several brainstorming and prototyping sessions were conducted to design the mobile e-coaching app. Immigrant informal caregivers have various needs in their caregiving role. They reported a need for training on the illness and future caregiving needs, assistance with understanding the Swedish language and culture, and help with accessing internet-based information and services. They also required recognition and appreciation for their efforts, additional informal support, and easy access to health care services, which can be important for their mental health. The PSDM was adapted to the informal caregiving context by adding "facilitating conditions" and "verbal encouragement" as additional persuasive design principles. This study also presents the subsequent mobile e-coaching app for immigrant informal caregivers in Sweden. This study revealed important immigrant informal caregivers' needs based on which design suggestions for a mobile e-coaching app were presented. We also proposed an adapted PSDM, for the informal caregiving context. The adapted PSDM can be further used to design digital interventions for caregiving.


Zeb1 represses Mitf and regulates pigment synthesis, cell proliferation, and epithelial morphology.
Epithelial-mesenchymal transition (EMT) is important in fibrotic responses, formation of cancer stem cells, and acquisition of a metastatic phenotype. Zeb1 represses epithelial specification genes to enforce epithelial-mesenchymal phenotypic boundaries during development, and it is one of several E-box-binding repressors whose overexpression triggers EMT. The purpose of this study was to investigate the potential role for Zeb1 in EMT leading to the dedifferentiation of retinal pigment epithelial (RPE) cells. Real-time PCR was used to examine mRNA expression during RPE dedifferentiation in primary cultures of RPE cells from Zeb1(+/-) mice and after knockdown of Zeb1 by lentivirus shRNA. Chromatin immunoprecipitation was used to detect Zeb1 at gene promoters in vivo. Zeb1 is overexpressed during RPE dedifferentiation. Heterozygous mutation or shRNA knockdown to prevent this overexpression eliminates the onset of proliferation, loss of epithelial morphology, and pigment, which characterizes RPE dedifferentiation. Zeb1 binds to the Mitf A promoter in vivo, and Zeb1 mutation or shRNA knockdown derepresses the gene. The authors link Zeb1 expression to cell-cell contact and demonstrate that forcing dedifferentiated RPE cells to adopt cell-cell only contacts via sphere formation reverses the overexpression of Zeb1 and reprograms RPE cells back to a pigmented phenotype. Overexpression of the EMT transcription factor Zeb1 has an important role in RPE dedifferentiation via its regulation of Mitf. Expression of Zeb1 and, in turn, RPE dedifferentiation, is linked to cell-cell contact, and these contacts can be used to diminish Zeb1 expression and reprogram dedifferentiated RPE cells.


TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology.
Tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) is a crucial signaling molecule regulating a diverse array of physiological processes, including adaptive immunity, innate immunity, bone metabolism and the development of several tissues including lymph nodes, mammary glands, skin and the central nervous system. It is a member of a group of six closely related TRAF proteins, which serve as adapter molecules, coupling the TNF receptor (TNFR) superfamily to intracellular signaling events. Among the TRAF proteins, TRAF6 is unique in that, in addition to mediating TNFR family signaling, it is also essential for signaling downstream of an unrelated family of receptors, the interleukin-1 (IL-1) receptor/Toll-like receptor (IL-1R/TLR) superfamily. Gene targeting experiments have identified several indispensable physiological functions of TRAF6, and structural and biochemical studies have revealed the potential mechanisms of its action. By virtue of its many signaling roles, TRAF6 represents an important target in the regulation of many disease processes, including immunity, inflammation and osteoporosis.


Superoxide anion, the main species of ROS in the development of ARDS induced by oleic acid.
It is believed that reactive oxygen species (ROS) play a very important role in the pathogenesis of acute respiratory distress syndrome (ARDS), but the mechanism has not been so clear, owing to the absence of direct measurable (experimental) data. In majority of the medical studies on free radicals, the analysis of ROS has generally been done by the way of measuring their secondary and breakdown products. In our study, we used electron spin resonance (ESR), a sensitive and accurate technique to detect ROS directly and also used some other sensitive techniques including ultra-weak luminescence and chemical luminescence to identify the species and relative amount of ROS. Furthermore, superoxide dismutase (SOD) was pre-administrated in ARDS rats to verify the results from the above studies and explore the possibility of the clinical application of SOD in ARDS. The spectra of ESR showed that the concentration of ROS increased at 10 min and reached a summit at 30 min after injection of oleic acid (OA), then dropped gradually. The scavenging effects of different scavenging agents on ROS by the analysis of ultra-weak luminescence proved that superoxide anion was the main species of ROS in the development of OA-induced ARDS. Moreover, the results of quantified measure of superoxide anion by chemical luminescence also showed the accordant tendency exhibited in ESR measurement. The pre-treatment of SOD might distinctly inhibit the production of superoxide anion, obviously improve the blood gas status, lung wet/dry ratio and lung/body ratio in ARDS rats. It is suggested that ROS may play a key role in the initiation phase of ARDS, while superoxide anion may be a leading actor in this process and SOD could effectively protect rats from ARDS. These results may provide helpful information for the treatment and prevention of ARDS.


Who could benefit the most from using a computer-aided detection system in full-field digital mammography?
The computer-aided detection (CAD) system on mammography has the potential to assist radiologists in breast cancer screening. The purpose of this study is to evaluate the diagnostic performance of the CAD system in full-field digital mammography for detecting breast cancer when used by dedicated breast radiologist (BR) and radiology resident (RR), and to reveal who could benefit the most from a CAD application. We retrospectively chose 100 image sets from mammographies performed with CAD between June 2008 and June 2010. Thirty masses (15 benign and 15 malignant), 30 microcalcifications (15 benign and 15 malignant), and 40 normal mammography images were included. The participating radiologists consisted of 7 BRs and 13 RRs. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for total, normal plus microcalcification and normal plus mass both with and without CAD use for each reader. We compared the diagnostic performance values obtained with and without CAD use for the BR and RR groups, respectively. The reading time reviewing one set of 100 images and time reduction with CAD use for the BR and RR groups were also evaluated. The diagnostic performance was generally higher in the BR group than in the RR group. Sensitivity improved with CAD use in the BR and RR groups (from 81.10 to 84.29% for BR; 75.38 to 77.95% for RR). A tendency for improvement in all diagnostic performance values was observed in the BR group, whereas in the RR group, sensitivity improved but specificity, PPV, and NPV did not. None of the diagnostic performance parameters were significantly different. The mean reading time was shortened with CAD use in both the BR and RR groups (111.6 minutes to 94.3 minutes for BR; 135.5 minutes to 109.8 minutes for RR). The mean time reduction was higher for the RR than that in the BR group. CAD was helpful for dedicated BRs to improve their diagnostic performance and for RRs to improve the sensitivity in a screening setting. CAD could be essential for radiologists by decreasing reading time without decreasing diagnostic performance.


Characterization of a CRM1-dependent nuclear export signal in the C terminus of herpes simplex virus type 1 tegument protein UL47.
The herpes simplex virus type 1 tegument protein known as VP13/14, or hUL47, localizes to the nucleus and binds RNA. Using fluorescence loss in photobleaching analysis, we show that hUL47 undergoes nucleocytoplasmic shuttling during infection. We identify the hUL47 nuclear export signal (NES) as a C-terminal 10-residue hydrophobic peptide and measure its efficiency relative to that of the classical human immunodeficiency virus type 1 Rev NES. Finally, we show that the hUL47 NES is sensitive to the inhibitor of CRM1-mediated nuclear export leptomycin B. Hence, hUL47 joins a growing list of virus-encoded RNA-binding proteins that use CRM1 to exit the nucleus.


Free-water imaging of the cholinergic basal forebrain and pedunculopontine nucleus in Parkinson's disease.
Free-water imaging can predict and monitor dopamine system degeneration in people with Parkinson's disease. It can also enhance the sensitivity of traditional diffusion tensor imaging (DTI) metrics for indexing neurodegeneration. However, these tools are yet to be applied to investigate cholinergic system degeneration in Parkinson's disease, which involves both the pedunculopontine nucleus and cholinergic basal forebrain. Free-water imaging, free-water-corrected DTI and volumetry were used to extract structural metrics from the cholinergic basal forebrain and pedunculopontine nucleus in 99 people with Parkinson's disease and 46 age-matched controls. Cognitive ability was tracked over 4.5 years. Pearson's partial correlations revealed that free-water-corrected DTI metrics in the pedunculopontine nucleus were associated with performance on cognitive tasks that required participants to make rapid choices (behavioural flexibility). Volumetric, free-water content and DTI metrics in the cholinergic basal forebrain were elevated in a sub-group of people with Parkinson's disease with evidence of cognitive impairment, and linear mixed modelling revealed that these metrics were differently associated with current and future changes to cognition. Free water and free-water-corrected DTI can index cholinergic degeneration that could enable stratification of patients in clinical trials of cholinergic interventions for cognitive decline. In addition, degeneration of the pedunculopontine nucleus impairs behavioural flexibility in Parkinson's disease, which may explain this region's role in increased risk of falls.


Evolution of sperm quality but not quantity in the internally fertilized fish Xiphophorus nigrensis.
Species with alternative reproductive strategies are characterized by discrete differences among males in suites of traits related to competition for fertilizations. Models predict sneaker males should allocate more resources to their ejaculates because they experience sperm competition more frequently and often occupy a disfavoured 'role' owing to subordinance in intramale competition and female preferences for larger males. We examined whether sperm number and quality differed between male strategies in the internally fertilized fish Xiphophorus nigrensis and explored the relationship between sperm morphology and performance. We found sneaker males had similar testes sizes compared to courting males but ejaculates with both more viable and longer lived sperm. Sneaker sperm also had longer midpieces, which was positively correlated with both velocity and longevity. Our study suggests that the evolution of sperm quantity and quality can be decoupled and that the sperm morphology is likely to play an important role in mediating sperm competition through its effects on sperm performance.


Novel underlying regulatory mechanism of the MsDAD2-mediated salt stress response in alfalfa.
Alfalfa (Medicago sativa L.), a crucial and widely grown forage legume, faces yield and quality challenges due to salinity stress. The defender against apoptotic death (DAD) gene, recognized initially as an apoptosis suppressor in mammals, plays a pivotal role in catalyzing N-glycosylation, acting as a positive regulator for protein folding and endoplasmic reticulum (ER) export. Here, we found that the MsDAD2 gene was specially induced in the salt-tolerant alfalfa cultivar (DL) under salinity stress, but not in the salt-sensitive cultivar (SD). Overexpression of MsDAD2 enhanced the salinity resistance of transgenic alfalfa by promoting NAD(P)H-quinone oxidoreductase (NQO1) and cytochrome b6f complex subunit (Cyt b6/f) expression, thereby mitigating reactive oxygen species (ROS) production. ChIP-qPCR analysis suggested that the differential expression of MsDAD2 in DL and SD under salinity stress may be linked to dynamic histone modifications in its promoter. Therefore, our findings elucidate a novel regulatory mechanism of MsDAD2 in alfalfa's response to salinity stress, underscoring its significance as a target for alfalfa breeding to enhance salt tolerance.


Utility of stress testing and coronary calcification measurement for detection of coronary artery disease in women.
Accurate and safe diagnostic testing provides the crucial link between detection and optimal management of coronary artery disease (CAD). Noninvasive diagnostic testing for CAD may be less accurate in women than in men. Many noninvasive diagnostic modalities are available for this purpose. An exercise tolerance test provides an assessment of functional capacity and has the advantages of wide availability and low initial cost. However, exercise echocardiography may be the most cost-effective method for the initial assessment of coronary artery disease in intermediate-risk women owing to its higher sensitivity and specificity. Recent studies with electron-beam computed tomography reveal that women with no coronary calcification are very unlikely to have obstructive CAD. In symptomatic women with an intermediate likelihood of CAD, either an exercise treadmill test or exercise echocardiography is appropriate for initial screening and can provide useful prognostic information. Alternatively, an electron-beam computed tomographic scan with a 0 calcium score may spare many women with atypical chest pain or equivocal findings on an exercise tolerance test from undergoing more expensive stress imaging studies or coronary angiography. For high-risk symptomatic women, a more aggressive approach involving coronary angiography appears to be the preferred initial diagnostic strategy.


[Efficacy and Safety of a Domestic Non-selective b-adrenoblocker Possibilities of the Use of Proxodolol in the Treatment of Patients With Chronic Heart Failure.].
Novel (made in Russia) nonselective b-blocker with a1-blocking properties proxodolol was given to 30 patients with ischemic heart disease, NYHA class II-III chronic heart failure (CHF) and left ventricular ejection fraction (LVEF) <40%. Methods of control included clinical examination, registration of hemodynamic and morphofunctional parameters of the heart. Proxodolol caused clinical improvement which appeared as reduction of signs of CHF and betterment of myocardial contractile function with 14% increase of LVEF according to data of echocardiography. Side effects of proxodolol were noted in 26.7% of cases and required withdrawal of the preparation in 6.7% of patients.


Michelle Linterman: We are always learning.
Michelle Linterman is a group leader at the Babraham Institute, Cambridge, UK. The research focus of her lab is to understand the fundamental biology of the germinal center response after immunization and infection and how this changes with age. We caught up with Michelle to talk about how her interest in germinal center biology started, the benefits of team science, and her collaboration between the Malaghan Institute of Medical Research, New Zealand, and Churchill College, Cambridge.


Central pontine myelinolysis: an immunofluorescent study.
A young pregnant woman showing clinical symptoms of numbness, vertigo, diplopia, and amnesia with associated hypernatremia ran a fulminant course. At autopsy, an area or extensive demyelination in the center of the pons was found and a pathological diagnosis of central pontine myelinolysis was made. Since definitive etiology and pathogenesis of the lesion have not been established, we investigated the role of humoral immunity in the pathogenesis of this condition by retrospective immunofluorescent study; the result was negative. Possible factors related to the etiology and pathogenesis of the lesion in this case are discussed.


Variation in the Bemisia tabaci s. l. species complex (Hemiptera: Aleyrodidae) and its natural enemies leading to successful biological control of Bemisia biotype B in the USA.
Parasitoids of the Bemisia tabaci (Gennadius) species complex collected in Spain and Thailand were evaluated as biological control agents of B. tabaci biotype B in cole crops in Texas, USA. Parasitoids were identified by morphological and RAPD-PCR analyses. The most abundant parasitoid from Spain was Eretmocerus mundus Mercet with apparent field parasitism of 39-44%. In Thailand, Encarsia formosa Gahan, E. transvena Timberlake, E. adrianae Lopez-Avila, Eretmocerus sp. 1 and sp. 2 emerged, with apparent field parasitism of 1-65%. Identification and molecular classification of B. tabaci associated with parasitoid collections and in the release site in Texas were accomplished using morphological traits and nucleotide sequence comparison of the mitochondrial cytochrome oxidase I gene (COI) (700-720 bp). Collections of B. tabaci from Thailand grouped separately from B types from Arizona and Florida and the target B type from Texas, USA, a cluster from India, and other New World B. tabaci. The Spanish B. tabaci host of E. mundus which was laboratory and field-tested to achieve biological control of the B type was most closely related to non-B type B. tabaci populations from Spain and Sudan, the latter which formed a second group within the larger clade that also contained the B type cluster. Laboratory tests indicated that E. mundus from Spain parasitized more B. tabaci type B than did Eretmocerus spp. native to Texas and other exotic parasitoids evaluated. Eretmocerus mundus from Spain also successfully parasitized B. tabaci type B when field-released in a 0.94 million ha test area in Texas, and has significantly enhanced control of B. tabaci type B in California, USA. In contrast, parasitoids from Thailand failed to establish in the field in Texas, collectively suggesting a positive correlation between the centres of diversity of compatible parasitoid-host complexes.


Preliminary studies to develop a personal dosemeter for use by aircraft crew.
This paper describes preliminary work to develop a cosmic-radiation dosemeter for use by military aircraft crew. The dosemeter is based on a combination of CR-39 etched-track detectors and TLD-700 thermoluminescent detectors. It is intended that the CR-39 be used to assess the neutron dose, while the TLD-700 is used to assess the photon and charged particle dose. The sensitivity of CR-39 to the neutron component of cosmic radiation was estimated by irradiating samples of the plastic at the CERN-CEC High Energy Reference Field Facility. This facility produced a radiation field with a neutron spectrum resembling that of the neutron component of cosmic radiation at typical airflight altitudes. The response of the CR-39 was linear over the range of doses studied (0.2-6.0 mSv) and there was no significant fading in the 6-month period after irradiation. The TLD-700 component of the dosemeter was calibrated using 137Cs gamma rays. The response of the TLD-700 was linear over the range of doses studied (0.01-5.0 mSv) with no significant fading in the 6-month period after irradiation. It was concluded that a combination of CR-39 and TLD-700 detectors would provide an effective cosmic-radiation dosemeter for use by military aircraft crew.


Cognitive Functioning and Silent Neurological Manifestations in Behçet's Disease with Ocular Involvement.
Various reports have revealed a cognitive dysfunction in Behçet's disease (BD). In this study, we aimed to assess the silent neurological manifestations, behavioral and neuropsychiological impairments of Behçet's disease patients with ocular involvement. Thirty BD patients with ocular involvement in the nonactive phase of their illness were applied detailed neurological examination and magnetic resonance imagining (MRI). Neuropsychological tests were performed. Patients' neuropsychological performances were compared to those of healthy, demographically matched twenty subjects. Neurological manifestations of patients were headache (56.6%), pyramidal signs (13.3%), behavioral changes (3.3%) and sensory symptoms (3.3%). Four patients (13.3%) had white matter hyperintensities lesions on T2/FLAIR brain MRI. Fourteen patients (46%) had impaired cognitive performances on the following tasks: verbal memory (immediate memory p=0.000, maximal learning capacity p=0.009, number of repetitions p=0.000, total learning capacity p=0.001, recall p=0.033), nonverbal memory (immediate memory p=0.029, recall p=0.001), logical memory (immediate memory p=0.001, recall p=0.001), executive (frontal) functions (clock-drawing test p=0.000, Stroop test p=0.001, verbal fluency tests p=0.000). Patients' MMSE and clock drawing test scores were significantly lower than controls (p=0.03). Attention deficit was not detected. Behçet's disease patients showed higher scores on depression scales than healthy subjects but there was no statistically significant difference between anxiety scores. Neuropsychological deficits, involving mainly memory and executive functioning, subcortical MRI lesions, and non-structural headache may be present in Behçet's disease patients with ocular involvement without overt neurological manifestations.


An NMR-based lipidomic approach to identify Parkinson's disease-stage specific lipoprotein-lipid signatures in plasma.
Disturbances in lipid composition and lipoproteins metabolism can play a crucial role in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative diseases. The lipidomic strategy proposed here involves lipoprotein profiling using NMR spectroscopy and multivariate data pre-processing and analysis tools on 94 plasma samples (belonging to 38 early-stage PD patients, 10 PD-related dementia patients, 23 persons with Alzheimer's dementia, and 23 healthy control subjects) to firstly differentiate PD patients (irrespective of the stage of the disease) from persons with Alzheimer's disease (AD) as well as from controls, and then to discriminate among PD patients according to disease severity. The whole data set was subdivided into 86 training and 8 external test samples for validation purposes. A two-step classification scheme, based on linear discriminant analysis with variable selection accomplished by a stepwise orthogonalisation procedure, was proposed to optimise classification performance. Careful pre-processing of NMR signals was crucial to ensure data set quality. A total of 30 chemical shift buckets enabled differentiation between PD patients (regardless of disease severity), AD and control subjects, providing classification, cross-validation and external prediction rates of 100% in all cases. Only 15 variables were required to further discriminate between early-stage PD and PD-related dementia, again with 100% correct classifications, and internal/external predictions. The simplicity and effectiveness of the classification methodology proposed support the use of NMR spectroscopy, in combination with chemometrics, as a viable alternative diagnostic tool to conventional PD clinical diagnosis.


Evaluation of the hypercalcemic patient.
Malignancy is the most common cause of hypercalcemia, which may result from direct involvement of bone or from local or distant production of substances that enhance bone resorption. The recognized incidence of primary hyperparathyroidism has increased greatly since the advent of automated biochemical screening. A single parathyroid adenoma is most frequently the cause. Sarcoidosis commonly results in hypercalciuria but seldom causes sustained hypercalcemia. Increased production of 1,25-dihydroxycholecalciferol leads to hyperabsorption of calcium and enhanced bone resorption.


Multi-Disease Detection in Retinal Imaging Based on Ensembling Heterogeneous Deep Learning Models.
Preventable or undiagnosed visual impairment and blindness affect billion of people worldwide. Automated multi-disease detection models offer great potential to address this problem via clinical decision support in diagnosis. In this work, we proposed an innovative multi-disease detection pipeline for retinal imaging which utilizes ensemble learning to combine the predictive capabilities of several heterogeneous deep convolutional neural network models. Our pipeline includes state-of-the-art strategies like transfer learning, class weighting, real-time image augmentation and Focal loss utilization. Furthermore, we integrated ensemble learning techniques like heterogeneous deep learning models, bagging via 5-fold cross-validation and stacked logistic regression models. Through internal and external evaluation, we were able to validate and demonstrate high accuracy and reliability of our pipeline, as well as the comparability with other state-of-the-art pipelines for retinal disease prediction.


Zoonotic infections among employees from Great Smoky Mountains and Rocky Mountain National Parks, 2008-2009.
U.S. National Park Service employees may have prolonged exposure to wildlife and arthropods, placing them at increased risk of infection with endemic zoonoses. To evaluate possible zoonotic risks present at both Great Smoky Mountains (GRSM) and Rocky Mountain (ROMO) National Parks, we assessed park employees for baseline seroprevalence to specific zoonotic pathogens, followed by evaluation of incident infections over a 1-year study period. Park personnel showed evidence of prior infection with a variety of zoonotic agents, including California serogroup bunyaviruses (31.9%), Bartonella henselae (26.7%), spotted fever group rickettsiae (22.2%), Toxoplasma gondii (11.1%), Anaplasma phagocytophilum (8.1%), Brucella spp. (8.9%), flaviviruses (2.2%), and Bacillus anthracis (1.5%). Over a 1-year study period, we detected incident infections with leptospirosis (5.7%), B. henselae (5.7%), spotted fever group rickettsiae (1.5%), T. gondii (1.5%), B. anthracis (1.5%), and La Crosse virus (1.5%) in staff members at GRSM, and with spotted fever group rickettsiae (8.5%) and B. henselae (4.3%) in staff at ROMO. The risk of any incident infection was greater for employees who worked as resource managers (OR 7.4; 95% CI 1.4,37.5; p=0.02), and as law enforcement rangers/rescue crew (OR 6.5; 95% CI 1.1,36.5; p=0.03), relative to those who worked primarily in administration or management. The results of this study increase our understanding of the pathogens circulating within both parks, and can be used to inform the development of effective guidelines and interventions to increase visitor and staff awareness and help prevent exposure to zoonotic agents.


A rapid paper-based test for quantifying sickle hemoglobin in blood samples from patients with sickle cell disease.
Quantification of sickle hemoglobin (HbS) in patients with sickle cell disease (SCD) undergoing hydroxyurea or chronic transfusion therapy is essential to monitoring the effectiveness of these therapies. The clinical monitoring of %HbS using conventional laboratory methods is limited by high per-test costs and long turnaround times usually associated with these methods. Here we demonstrate a simple, rapid, inexpensive paper-based assay capable of quantifying %HbS in blood samples from patients with SCD. A 20 μL droplet of whole blood and hemoglobin solubility buffer was deposited on chromatography paper. The relative color intensities of regions of the resulting blood stain, determined by automated image analysis, are used to estimate %HbS. We compared the paper-based assay with hemoglobin electrophoresis (comparison method) using blood samples from 88 subjects. The test shows high correlation (R(2) = 0.86) and strong agreement (standard deviation of difference = 7%HbS) with conventional Hb electrophoresis measurement of %HbS, and closely approximates clinically predicted change in %HbS with transfusion therapy (mean difference 2.6%HbS, n = 5). The paper-based assay can be completed in less than 35 min and has a per-test cost less than $0.25. The assay is accurate across a wide range of HbS levels (10-97%) and hemoglobin concentrations (5.6-12.9 g/dL) and is unaffected by high levels of HbF (up to 80.6%). This study demonstrates the feasibility of the paper-based %HbS assay. The paper-based test could improve clinical care for SCD, particularly in resource-limited settings, by enabling more rapid and less expensive %HbS monitoring.


Renal allograft rupture with iliofemoral thrombophlebitis.
Spontaneous rupture of a renal allograft in the early posttransplant period is associated with tachycardia, hypotension, oliguria, swelling, pain, a falling hematocrit level, and tenderness at the transplant site. Occasionally, the ruptured allograft can be saved by control of the hemorrhage. Deep vein thrombophlebitis, a common occurrence after prolonged surgery and cortocosteroid therapy, is less common in renal allograft transplantation, but may be associated with renal vein thrombosis. The simultaneous occurrence of deep vein thrombophlebitis, renal vein thrombosis, and allograft rupture contraindicates anticoagulent therapy. We present a patient in whom ipsilateral deep vein thrombophlebitis developed eight days after a cadaveric renal allograft, followed in two days by hypotension, a falling hematocrit level, oliguria, and a painfall mass at the allograft site. Surgical exploration revealed a ruptured allograft with iliofemoral and renal vein thrombosis and profuse hemorrhage. A transplant nephrectomy was performed.


Diagnostic significance of nuclear p53 expression in the surveillance of Barrett's esophagus--a longitudinal study.
The efficacy of currently performed surveillance in patients with Barrett's esophagus (BE) is substantially compromised by shortcomings of dysplastic lesions as diagnostic markers. The aim of this study was to evaluate the possible role of p53 protein expression as complementary method in the diagnosis of neoplastic transformation in BE. A longitudinal study was performed. 41 patients were enrolled. The median time of surveillance was 46 months. 234 archival paraffin blocks containing a total of 627 biopsies were retrieved. p53 protein immunostaining by application of the monoclonal antibody DO-1 was performed. The results of immunohistochemistry were compared with the exact histopathological diagnosis and grading of dysplasia (no dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, carcinoma). In merely four of 206 nondysplastic mucosal sites p53 expression was found. However, p53 expression was detected with increasing frequency in sites indefinite for dysplasia (2/9), specimens with low-grade dysplasia (9/15), high-grade dysplasia (3/3) and the one with a carcinoma. This study shows a close association of nuclear p53 protein expression to the process of neoplastic transformation in Barrett's epithelium. However, it apparently does not precede the appearance of dysplasia significantly. Thus, nuclear p53 expression as detected by immunohistochemistry may serve to confirm a suspected diagnosis of dysplasia in BE.


Primary Pulmonary Lymphoma Presenting with Superior Vena Cava Syndrome in a Young Female.
Primary Pulmonary Diffuse Large B Cell Lymphoma (PPDLBCL) is an extremely rare entity, which exhibits an aggressive behavior by compressing local blood vessels. It represents only 0.04% of all lymphoma cases and is extremely rare in young age. We present a case of a primary pulmonary lymphoma with superior vena cava syndrome (SVCS) in a young female. 27-year-old African American female presented with fever, cough, and facial puffiness for 2 weeks and unintentional weight loss. Chest examination showed decreased breath sounds and dullness on percussion on right side. Labs were normal except for mild leukocytosis, high lactate, and lactate dehydrogenase. Chest X-ray showed a large right side infiltrate with pleural effusion but chest CT showed 10 × 14 × 16 cm mass in the right lung without hilar and mediastinal lymphadenopathy. CT guided biopsy of the right lung mass was done and large B cell lymphoma was diagnosed. She received "involved field radiation" because of the bulky tumor size and superior vena cava involvement prior to R-CHOP to which she responded well. PPDLBCL should be considered as one of the differentials in a young patient with a large lung mass, which needs timely diagnosis and management.


Dental and oral abnormalities in selected ectodermal dysplasia syndromes.
Only a brief review of the dental and oral abnormalities in a few ectodermal dysplasia syndromes has been presented. Obviously, careful evaluation of the dentitions of patients suspected to have these disorders will add to our knowledge and assist in diagnosis of this heterogeneous group of genetic diseases.


Association between supraclavicular brown adipose tissue composition at birth and adiposity gain from birth to 6 months of age.
BackgroundBrown adipose tissue (BAT) is associated with higher energy expenditure and lower adiposity in adults. However, the relationship between BAT composition and adiposity in early life is unknown. The objective of this study was to test the hypothesis that brown fat composition at birth is prospectively associated with adiposity gain during the first 6 months of postnatal life.MethodsN=35 healthy infants were followed up prospectively from intrauterine life and birth through 6 months of age. Dixon magnetic resonance imaging (MRI) scans were conducted during the neonatal period to characterize supraclavicular BAT composition. Dual-energy X-ray absorptiometry to assess total body composition was performed within the first and sixth months of life.ResultsAfter adjusting for potential confounding factors, a more brown-like composition (smaller fat fraction) of the supraclavicular BAT depot was associated with a smaller increase in percent body fat over the first 6 months of postnatal life.ConclusionsA more brown-like BAT composition at birth appears to be protective against excess adiposity gain in early life. Newborn BAT tissue may constitute a target for prevention strategies against the subsequent development of obesity.


Analysis of the Global Population Structure of Paenibacillus larvae and Outbreak Investigation of American Foulbrood Using a Stable wgMLST Scheme.
Paenibacillus larvae causes the American foulbrood (AFB), a highly contagious and devastating disease of honeybees. Whole-genome sequencing (WGS) has been increasingly used in bacterial pathogen typing, but rarely applied to study the epidemiology of P. larvae. To this end, we used 125 P. larvae genomes representative of a species-wide diversity to construct a stable whole-genome multilocus sequence typing (wgMLST) scheme consisting of 5745 loci. A total of 51 P. larvae isolates originating from AFB outbreaks in Slovenia were used to assess the epidemiological applicability of the developed wgMLST scheme. In addition, wgMLST was compared with the core-genome MLST (cgMLST) and whole-genome single nucleotide polymorphism (wgSNP) analyses. All three approaches successfully identified clusters of outbreak-associated strains, which were clearly separated from the epidemiologically unlinked isolates. High levels of backward comparability of WGS-based analyses with conventional typing methods (ERIC-PCR and MLST) were revealed; however, both conventional methods lacked sufficient discriminatory power to separate the outbreak clusters. The developed wgMLST scheme provides an improved understanding of the intra- and inter-outbreak genetic diversity of P. larvae and represents an important progress in unraveling the genomic epidemiology of this important honeybee pathogen.


CD44 expression is predictive of poor prognosis in pharyngolaryngeal cancer: systematic review and meta-analysis.
Pharyngolaryngeal cancer is one of the most common head and neck cancer worldwide, and the early diagnosis and prognosis prediction are still difficult because of lacking in reliable cell markers. Although the expression of CD44 has been reported to correlate with poor prognosis of pharyngolaryngeal cancer in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and clinicopathological features and prognosis in pharyngolaryngeal cancer. A search of PubMed, ISI Web of Science and China National Knowledge Infrastructure databases (up to June 2013) was performed. Nineteen studies with 1,405 patients met the inclusion criteria. The expression of pan-CD44, including all variant isoforms, was detected in 58.0% (14.1-79.2%) specimens, while CD44-v6 (variant isoform 6 of CD44) was expressed in 54.8% (12-79.2%). In pooled analysis, CD44 expression was significantly associated with larger tumor size (T category, RR (relative risk) = 1.21, 95% CI: 1.01-1.46), lymph nodes metastasis (N category, RR = 1.94, 95% CI: 1.38-2.73) and poor prognosis [3-year overall survival (OS): RR = 0.70, 95% CI: 0.53-0.91; 5-year OS: RR = 0.66, 95% CI: 0.66-0.94]. In the stratified analysis of CD44 isoforms, high expression of CD44-v6 was related with a poor 5-year OS rate (RR = 0.53, 95% CI: 0.37-077). We propose that CD44 expression is associated with tumor size, lymph node metastasis, and poor prognosis in pharyngolaryngeal cancer patients.


Autonomous megakaryocyte growth in essential thrombocythemia and idiopathic myelofibrosis is not related to a c-mpl mutation or to an autocrine stimulation by Mpl-L.
Essential thrombocythemia (ET) and idiopathic myelofibrosis (PMF) are two myeloproliferative diseases characterized by a marked megakaryocytic (MK) involvement. The pathogenesis of these two diseases is unknown. Recently it has been shown that overexpression of Mpl-ligand (Mpl-L) in mice induces thrombocytosis and myelofibrosis. In this study, we investigated whether Mpl-L was responsible for the pathogenesis of ET and PMF. Using in vitro cultures of blood or marrow CD34(+) cells, we investigated whether MK growth was abnormal in these two diseases. Spontaneous MK growth involving only a fraction (20%) of the MK progenitors, as compared with growth in the presence of pegylated recombinant human megakaryocyte growth and development factor (PEG-rhuMGDF), was found in both diseases (21ET and 14PMF) using serum-free semisolid and liquid cultures, including cultures at one cell per well. We first searched for a c-mpl mutation/deletion by sequencing the entire coding region of the gene by polymerase chain reaction (PCR) in nine ET patients and five PMF patients, but no mutation was found. We subsequently investigated whether an autocrine stimulation by Mpl-L could explain the autonomous MK growth. Addition of different preparations of soluble Mpl receptor (sMpl) containing a Fc domain of IgG1 (sMpl-Fc) markedly inhibited MK spontaneous growth in both ET and PMF patients. This effect was specific for sMpl because a control soluble receptor (s4-1BB-Fc) had no inhibitory effect and an sMpl devoid of the Fc fragment had the same inhibitory efficacy as the sMpl-Fc. This inhibition was reversed by addition of PEG-rhuMGDF or a combination of cytokines. The sMpl-Fc markedly altered the entry into cell cycle of the CD34(+) cells and increased the apoptosis that occurs in most patient CD34(+) cells in the absence of exogenous cytokine, suggesting an autocrine stimulation. In contrast, a neutralizing antibody against Mpl-L did not alter the spontaneous MK growth, whereas it totally abolished the effects of 10 ng/mL PEG-rhuMGDF on patient or normal CD34(+) cells. Mpl-L transcripts were detected at a very low level in the patient CD34(+)cells and MK and only when a highly sensitive fluorescent PCR technique was used. By quantitative reverse-transcription (RT)-PCR, the number of Mpl-L transcripts per actin transcripts was lower than detected in human Mpl-L-dependent cell lines, suggesting that this synthesis of Mpl-L was not biologically significant. In favor of this hypothesis, the Mpl-L protein was not detected in culture supernatants using either an enzyme-linked immunosorbent assay (ELISA) or a biological (Ba/F3hu c-mpl) assay, except in one PMF patient. Investigation of Mpl-L signaling showed an absence of constitutive activation of STATs in spontaneously growing patient MKs. Addition of PEG-rhuMGDF to these MKs activated STATs 3 and 5. This result further suggests that spontaneous growth is neither related to a stimulation by Mpl-L nor to a c-mpl mutation. In conclusion, our results show that Mpl-L or Mpl are not directly implicated in the abnormal proliferation of MK cells from ET and PMF. The mechanisms by which the sMpl mediates a growth inhibition will require further experiments.


High throughput fingerprint analysis of large-insert clones.
As part of the Human Genome Project, the Washington University Genome Sequencing Center has commenced systematic sequencing of human chromsome 7. To organize and supply the effort, we have undertaken the construction of sequence-ready physical maps for defined chromosomal intervals. Map construction is a serial process composed of three main activities. First, candidate STS-positive large-insert PAC and BAC clones are identified. Next, these candidate clones are subjected to fingerprint analysis. Finally, the fingerprint data are used to assemble sequence-ready maps. The fingerprinting method we have devised is key to the success of the overall approach. We present here the details of the method and show that the fingerprints are of sufficient quality to permit the construction of megabase-size contigs in defined regions of the human genome. We anticipate that the high throughput and precision characteristic of our fingerprinting method will make it of general utility.


Local transmission of chikungunya in Rome and the Lazio region, Italy.
On September 7, 2017, three potentially autochthonous cases of chikungunya were notified in the Lazio region. An Outbreak investigation based on established surveillance system data and molecular analysis of viral variant(s) were conducted. Epidemiological analysis suggested the occurrence of 3 main foci of local transmission. The major focus involved 317 cases with epidemiological link with the area of Anzio. The other two foci occurred in Rome (80 cases) and Latina (8 cases). Cumulative incidence in Anzio and Latina were 331.4 and 7.13 per 100,000 residents, respectively. Cumulative incidences ranged from 1.4 to 14.3/100,000 residents in Rome. This is the first report of a chikungunya outbreak involving a densely populated urban area in a western country. The outbreak probably started in Anzio, spread by continuity to neighbouring villages, and then to the metropolitan area of Rome and to the Latina area favoured by the touristic nature of the Anzio area.


Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo.
The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.


Transferrin iron starvation therapy for lethal bacterial and fungal infections.
New strategies to treat antibiotic-resistant infections are urgently needed. We serendipitously discovered that stem cell conditioned media possessed broad antimicrobial properties. Biochemical, functional, and genetic assays confirmed that the antimicrobial effect was mediated by supra-physiological concentrations of transferrin. Human transferrin inhibited growth of gram-positive (Staphylococcus aureus), gram-negative (Acinetobacter baumannii), and fungal (Candida albicans) pathogens by sequestering iron and disrupting membrane potential. Serial passage in subtherapeutic transferrin concentrations resulted in no emergence of resistance. Infected mice treated with intravenous human transferrin had improved survival and reduced microbial burden. Finally, adjunctive transferrin reduced the emergence of rifampin-resistant mutants of S. aureus in infected mice treated with rifampin. Transferrin is a promising, novel antimicrobial agent that merits clinical investigation. These results provide proof of principle that bacterial infections can be treated in vivo by attacking host targets (ie, trace metal availability) rather than microbial targets.


Cerebral glucose utilization in awake unstressed rats.
Regional cerebral glucose utilization (rCMRGlc) was measured in awake unstressed rats by use of [2-14C]glucose autoradiography. Rats prepared by chronic catheterization of the jugular and epigastric veins were placed in specially designed chambers after surgery. The catheters were passed through the top of the chambers. Seven days after surgery, plasma glucose was normal (7.5 mM), plasma ketone bodies were low (0.13 mM), and body weight was maintained. Plasma epinephrine was 31 pg/ml; approximately 3% of the level for stressed (immobilized) rats. Injections and blood sampling through the catheters did not produce changes in heart rate, blood pressure, plasma catecholamines, or blood metabolites. Visual observations did not reveal any signs that the rats were aware of the [2-14C]glucose injections and the subsequent blood sampling. The rCMRGlc in stressed rats was significantly greater than in unstressed rats. This method provides a model for physiological studies in unstressed unanesthetized rats.


Enhancing Cancer Care Amid Conflict: A Proposal for Optimizing Oncology Services During Wartime.
The landscape of cancer care within armed conflict zones is characterized by intricate challenges arising from disrupted health care systems, scarcity of resources, and population displacement. During times of war, the provision of cancer services is often disrupted, leading to significant challenges for oncologists and other health care providers. To optimize cancer services during wartime, several key priorities must be addressed. Focusing on needs assessment, treatment prioritization, drug supply chain, telemedicine, mobile clinics, cross-border collaborations, health care staff support, and continuity of care will enable health care systems to provide essential cancer services and mitigate the adverse impact of conflict on patients with cancer. This article delineates the pivotal key priorities for optimizing cancer services during wartime. It calls for collaborative action, the integration of technology, and holistic care approaches to safeguard the rights, well-being, and dignity of individuals confronting the dual challenges of cancer and conflict. By addressing these priorities, health care providers, policymakers, and stakeholders can collectively ensure that cancer services remain steadfast and compassionate even amid the turmoil of war. Thus, it may be possible to optimize cancer services during wartime, ensuring that patients with cancer continue to receive the care they need.


A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer.
Current pemetrexed/platinum chemotherapy does not produce a satisfactory therapeutic response in advanced lung cancer patients. The aim of this study was to determine whether the administration of gefitinib, a tyrosine kinase inhibitor (TKI), intercalated with pemetrexed/platinum could improve the efficacy in chemotherapy-naïve patients with advanced non-squamous NSCLC without subsequent gefitinib maintenance therapy. Treatment-naïve patients with stage IIIB or IV NSCLC were randomly assigned to receive pemetrexed (500 mg/m (2) d1) and either cisplatin (75 mg/m (2) d1) or carboplatin (AUC = 5 d1) plus gefitinib (250 mg/d on days 3 to 16 of a 3-week cycle) (PC-G) or pemetrexed-platinum (PC) alone. Randomization was stratified according to the tobacco smoking status and EGFR mutational status of the patients. The primary endpoint was the non-progression rate (NPR) at 12 weeks. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and biosafety. The NPR at 12 weeks was 84.5% for the PC-G treatment arm and 83.1% for the PC treatment arm (P = 0.87). Median PFS was 7.9 months for the PC-G arm and 7.0 months for the PC arm (P = 0.57). The ORR was 50.0% for the PC-G arm and 47.4% for the PC arm (P = 0.78). Median survival was 25.4 mo for the PC-G arm and 20.8 mo for the PC arm (P = 0.54). The incidence of adverse events was similar between the two treatment arms, except for a higher incidence of skin rash with PC-G. Predefined subgroup analyses demonstrated that PC-G significantly increased the PFS compared with the PC regimen in patients with EGFR mutations (P = 0.017). Although gefitinib intercalated with pemetrexed/platinum chemotherapy did not improve the NPR at 12 weeks compared with chemotherapy, an improvement in the PFS for the intercalated treatment arm was seen in the subgroup of patients with EGFR mutations.


[How to biopsy only men with high grade prostate cancer].
Fuzzy logic and Artificial Neural Networks (ANN) are complementary technologies that together generate neuro-fuzzy system. The aim of our study is to compare 2 models for predicting the presence of high-grade prostate cancer (Gleason score 7 or more). We evaluated data from 1000 men with PSA less than 50 ng/mL, who underwent prostate biopsy. A prostate cancer was found in 313 (31%), and in 172 (17.2%) we detected high-grade prostate cancer. With those data, we developed 2 Co-Active Neuro-Fuzzy Inference Systems to predict the presence of high-grade prostate cancer. The first model had four input neurons (PSA, free PSA percentage [%freePSA], PSA density, and age) and the second model had three input neurons (PSA, %freePSA, and age). The model with four input neurons (PSA, %freePSA, PSA density, and age) showed better performances than the one with three input neurons (PSA, %freePSA, and age). In fact the average testing error was 0.42 for the model with four input neurons and 0.44 for the other model. The addition of PSA density to the model has allowed to obtain better results for the diagnosis of high grade prostate cancer.


Species differences in executive function correlate with hippocampus volume and neocortex ratio across nonhuman primates.
A persistent debate in behavioral research is whether brain size or architecture relates to cognitive performance. A growing body of evidence has demonstrated correlations between brain size and ecological and behavioral tasks. These studies are premised on a causal link between brain size and cognitive function, although this association has little empirical backing. We show, for a set of 46 species from 17 primate genera, that competence on a series of eight executive function cognitive tasks both correlate across tasks and with brain size and architecture across species. Our model selection approach showed that, although several measures of brain component volumes are significantly associated with performance, hippocampus size is the best predictor of overall performance. The best performing model also includes total brain size and relative neocortex size. Additionally, absolute measures are much more predictive of performance than relative measures of brain and brain component size. These results are consistent with the hippocampus' role in learning, and the executive brain (neocortex) being important for problem solving and consolidation. Our findings challenge and extend those of previous analyses by clarifying the relationship between overall brain size and specific regional volumes. They also suggest that commonly used indices of encephalization, such as residuals of brain volume regressed on body size, may confound rather than clarify matters.


Angiographic findings and survival in patients undergoing coronary angiography due to sudden cardiac arrest in western Sweden.
Sudden cardiac arrest (SCA) accounts for more than half of all deaths from coronary heart disease. Time to return of spontaneous circulation is the most important determinant of outcome but successful resuscitation also requires percutaneous coronary intervention in selected patients. However, proper selection of patients is difficult. We describe data on angiographic finding and survival from a prospectively followed SCA patient cohort. We merged the RIKS-HIA registry (Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) and SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for patients hospitalized in cardiac care units in Western Sweden between January 2005 and March 2013. We performed propensity score-adjusted logistic and Cox proportional-hazards regression analyses on complete-case data as well as on imputed data sets. 638 consecutive patients underwent coronary angiography due to SCA. Severity of coronary artery disease was similar among SCA patients and patients undergoing coronary angiography due to suspected coronary artery disease (n=37,142). An acute occlusion was reported in the majority of SCA patients and was present in 37% of patients who did not have ST-elevation on the post resuscitation ECG. 31% of SCA patients died within 30 days. Long-term risk of death among patients who survived the first 30 days was higher in patients with SCA compared to patients with acute coronary syndromes (P<0.001). Coronary artery disease and acute coronary occlusions are common among patients who undergo coronary angiography after sudden cardiac arrest. These patients have a substantial mortality risk both short- and long-term.


Inhibition of integrin α2β1 ameliorates glomerular injury.
Mesangial cells and podocytes express integrins α1β1 and α2β1, which are the two major collagen receptors that regulate multiple cellular functions, including extracellular matrix homeostasis. Integrin α1β1 protects from glomerular injury by negatively regulating collagen production, but the role of integrin α2β1 in renal injury is unclear. Here, we subjected wild-type and integrin α2-null mice to injury with adriamycin or partial renal ablation. In both of these models, integrin α2-null mice developed significantly less proteinuria and glomerulosclerosis. In addition, selective pharmacological inhibition of integrin α2β1 significantly reduced adriamycin-induced proteinuria, glomerular injury, and collagen deposition in wild-type mice. This inhibitor significantly reduced collagen synthesis in wild-type, but not integrin α2-null, mesangial cells in vitro, demonstrating that its effects are integrin α2β1-dependent. Taken together, these results indicate that integrin α2β1 contributes to glomerular injury by positively regulating collagen synthesis and suggest that its inhibition may be a promising strategy to reduce glomerular injury and proteinuria.


Electrohydrodynamic atomisation driven design and engineering of opportunistic particulate systems for applications in drug delivery, therapeutics and pharmaceutics.
Electrohydrodynamic atomisation (EHDA) technologies have evolved significantly over the past decade; branching into several established and emerging healthcare remits through timely advances in the engineering sciences and tailored conceptual process designs. More specifically for pharmaceutical and drug delivery spheres, electrospraying (ES) has presented itself as a high value technique enabling a plethora of different particulate structures. However, when coupled with novel formulations (e.g. co-flows) and innovative device aspects (e.g., materials and dimensions), core characteristics of particulates are manipulated and engineered specifically to deliver an application driven need, which is currently lacking, ranging from imaging and targeted delivery to controlled release and sensing. This demonstrates the holistic nature of these emerging technologies; which is often overlooked. Parametric driven control during particle engineering via the ES method yields opportunistic properties when compared to conventional methods, albeit at ambient conditions (e.g., temperature and pressure), making this extremely valuable for sensitive biologics and molecules of interest. Furthermore, several processing (e.g., flow rate, applied voltage and working distance) and solution (e.g., polymer concentration, electrical conductivity and surface tension) parameters impact ES modes and greatly influence the production of resulting particles. The formation of a steady cone-jet and subsequent atomisation during ES fabricates particles demonstrating monodispersity (or near monodispersed), narrow particle size distributions and smooth or textured morphologies; all of which are successfully incorporated in a one-step process. By following a controlled ES regime, tailored particles with various intricate structures (hollow microspheres, nanocups, Janus and cell-mimicking nanoparticles) can also be engineered through process head modifications central to the ES technique (single-needle spraying, coaxial, multi-needle and needleless approaches). Thus, intricate formulation design, set-up and combinatorial engineering of the EHDA process delivers particulate structures with a multitude of applications in tissue engineering, theranostics, bioresponsive systems as well as drug dosage forms for specific delivery to diseased or target tissues. This advanced technology has great potential to be implemented commercially, particularly on the industrial scale for several unmet pharmaceutical and medical challenges and needs. This review focuses on key seminal developments, ending with future perspectives addressing obstacles that need to be addressed for future advancement.


Immunologic basis for mouse protection provided by high-molecular-weight polysaccharide from immunotype 1 Pseudomonas aeruginosa.
Antibody responses were assayed in inbred strains of mice immunized with a high-molecular-weight polysaccharide (IT-1 PS) isolated from Fisher immunotype 1 Pseudomonas aeruginosa (P. aeruginosa 1). C3H/ANF mice generated the greatest antibody response after immunization with 1 microgram of antigen and could then survive challenge with 5 LD100 of P. aeruginosa 1 organisms. BALB/c mice produced lower levels of antibody and did so only after immunization with 50 micrograms of IT-1 PS. These mice could only withstand challenge with 1 LD100 of P. aeruginosa 1. The specificity of the antibody produced by these two strains differed. Antibody produced in C3H/ANF mice after primary immunization with either 1 microgram or 50 micrograms of IT-1 PS did not cross-react with other immunotypes of P. aeruginosa. Antibody produced in BALB/c mice after a primary immunization with 50 micrograms of IT-1 PS cross-reacted with polysaccharide isolated from Fisher immunotype 2 P. aeruginosa. These data indicate that, even within the same species, antibody responses to immunization with P. aeruginosa IT-1 PS may be qualitatively different. This kind of variation in immune response patterns will have to be considered in developing optimal regimens for immunization in human vaccine trials.


Side-hole catheters have higher thrombus aspiration efficiency than regular end-hole catheters in an in vitro model.
We aimed to evaluate and compare thrombus aspiration efficiency between side-hole and end-hole thrombus-aspirating catheters. Using an in vitro model of acute thrombus occlusion, we performed thrombus aspiration with two catheter designs. Two end-hole and two side-hole catheters, 8 F and 10 F in diameter, were examined. Thrombus aspiration was performed with each catheter 30 times, and the amount of thrombotic material aspirated in each attempt was determined. The mean weight of the thrombotic material and the mean weight of the non-fluid thrombotic material extracted in all 30 attempts by each catheter were also determined. The 10 F side-hole catheter aspirated more thrombotic material than did the 10 F end-hole catheter (44.76 g vs. 28.35 g). The 8 F side-hole catheter had higher thrombus aspiration capacity than did the 8 F end-hole catheter in terms of the mean weight of the aspirated thrombus at each aspiration attempt (1.41 g vs. 0.58 g; P < 0.001) and the mean volume of the aspirated thrombotic material at each aspiration attempt (1.79 mL vs. 1.01 mL; P < 0.001). The mean weight of the non-fluid thrombotic material aspirated with the side-hole catheters was higher than that aspirated by the end-hole catheters with the same diameter size (31.06 g vs. 22.41 g for the 10 F catheters; P < 0.001; and 4.54 g vs. 2.99 g for the 8 F catheters; P < 0.001). Side-hole catheters are more effective in aspirating acute thrombi. The added benefit of the side-hole design is more remarkable in smaller-sized catheters. Animal models are needed to examine their aspiration capacity in a real elastic vascular conduit and in the presence of wall-adherent thrombi.


[Hepatectomy with Nd:YAG laser: an experimental and clinical study].
We conducted an experimental and clinical study of hepatectomy with Nd:YAG laser. The results showed that cutting effect artificial sapphire contact Nd:YAG laser scalpel was better than that of quartz fiber contact and noncontact Nd:YAG laser. The tissue damage was minimal in the former group whereas, the blood loss was similar in both groups. Seven patients were operated on, with quartz fiber and 12 with artificial sapphire laser scalpel. No complications were related to the use of laser. We consider that partial liver resection can be performed effectively with artificial sapphire contact Nd:YAG laser scalpel because of its better cutting, coagulation effects, and less tissue damage.


The handling of evidence in national and local policy making: a case study of alcohol industry actor strategies regarding data on on-premise trading hours and violence in Norway.
Effective alcohol policy measures conflict with the interests of the alcohol industry. In this study we addressed how various alcohol industry actors in Norway have responded to research findings and police data relating to the possible impacts of changes in on-premise trading hours on violent offending. A content analysis of documents was undertaken. The documents comprised i) hearing statements from policy processes on on-premise trading hours at the national level, and in 15 Norwegian cities, and ii) newspaper articles and other media coverage of this topic in Norway. Alcohol industry actors employed a range of strategies to shape the use of evidence regarding on-premise trading hours and violence. Nationally, the relevance of the international research literature was questioned before the publication of an unfavourable national study which was criticized directly. This led to commissioned attacks on the findings, constructing what were claimed to be disagreements between experts, emphasis on the complexity of violence and the role of confounding variables, and deflecting attention to alternative interventions. The handling of evidence at the local level was importantly different, where different industry actors and forms of evidence, notably police data, were involved in debates. Alcohol industry actors employed various strategies to shape perceptions and use of evidence to advance their interests. The particular strategies and arguments changed over time as new data and research became available, and also varied between the national and the local levels, and by categories of industry actors.


Glutamate signaling in healthy and diseased bone.
Bone relies on multiple extracellular signaling systems to maintain homeostasis of its normal structure and functions. The amino acid glutamate is a fundamental extracellular messenger molecule in many tissues, and is used in bone for both neural and non-neural signaling. This review focuses on the non-neural interactions, and examines the evolutionarily ancient glutamate signaling system in the context of its application to normal bone functioning and discusses recent findings on the role of glutamate signaling as they pertain to maintaining healthy bone structure. The underlying mechanisms of glutamate signaling and the many roles glutamate plays in modulating bone physiology are featured, including those involved in osteoclast and osteoblast differentiation and mature cell functions. Moreover, the relevance of glutamate signaling systems in diseases that affect bone, such as cancer and rheumatoid arthritis, is discussed, and will highlight how the glutamate system may be exploited as a viable therapeutic target. We will identify novel areas of research where knowledge of glutamate communication mechanisms may aid in our understanding of the complex nature of bone homeostasis. By uncovering the contributions of glutamate in maintaining healthy bone, the reader will discover how this complex molecular signaling system may advance our capacity to treat bone pathologies.


An empirical test of accreditation patient journey surveys: randomized trial.
To evaluate the effectiveness of utilizing the patient journey survey (PJS) method in healthcare accreditation processes. Randomized trial of the PJS method in parallel with the current accreditation survey (CAS) method of the Australian Council on Healthcare Standards (ACHS). Acute healthcare organizations in Australia. Seventeen organizations, 28 organizational staff, nine surveyors and 38 patients. The results of each surveying method were compared. Participants provided feedback, via 18 interviews and 40 questionnaire surveys, about the benefits and disadvantages of a PJS compared to a CAS. The PJS method is not as comprehensive as the CAS method for accreditation assessment. In matched assessments the majority of items were rated lower by the PJS method than by the CAS. PJSs were shown to be appropriate for assessing mandatory clinical criteria, but were less effective for assessing corporate and support criteria. The two methods diverged in their final assessments of which organizations met the accreditation threshold. Participants endorsed the use of PJSs within accreditation processes. The PJS methodology complements but is not a substitute for existing accreditation methods. There is significant stakeholder support for the inclusion of the PJS method within the current accreditation programme.


Sphingolipid metabolism during infection of human fibroblasts by herpes simplex virus type 1.
Results from several experiments support the view that sphingomyelin turnover and glycosphingolipid synthesis play a role in herpes simplex virus infection of cells in culture. Inhibition of sphingomyelinase by phosphatidylcholine or by a synthetic ceramide, N-palmitoyl-DL-dihydrosphingosine, interferes substantially with virus reproduction as does a genetic defect in the enzyme (Niemann-Pick disease). In Niemann-Pick cells, yields of infectious virus are about 3% of the normal level. An inhibitor of ceramide: UDP glucose glucosyltransferase was also used to test the effect of altered glycosphingolipid synthesis on infection. This compound, DL-2-decanoylamino-3-morpholinopropiophenone, decreased virus yields to a level about 0.1% of normal at the highest concentration tested.


[Limitations in opening the mouth after temporal craniotomy. Observations on 3 clinical cases].
The authors describe 3 cases of mouth-opening limitations and dyskinesia of the remaining mandibular movements, of different degrees of severity, arisen following a cicatricial retraction of the temporal muscle, caused by neurosurgical accesses to the underlying encephalic regions. Having kept in mind the afflictions that could cause an analogous symptomatology, the authors stop to consider which is the most suitable kind of treatment (surgical or rehabilitative) in these specific cases. For both kinds of treatment, corresponding to the specific indications, they propose techniques confirmed by their personal experiences.