Prognostic significance of serum sMICA levels in non-small cell lung cancer.
The soluble form of major histocompatibility complex class I-related chain A (MICA) is released from the surface of tumor cells of epithelial origin. Serum levels of soluble MHC class I-related chain A (sMICA) is related with the prognosis of various types of cancer. However, there are studies on the prognostic value of sMICA in non-small cell carcinoma (NSCLC). In this study, we retrospectively investigated the relationship between sMICA levels and clinical features of NSCLC, and we assessed the prognostic value of sMICA in NSCLC. sMICA levels were detected in 207 NSCLC patients and 207 normal control individuals with using enzyme-linked immunosorbent assay (ELISA), and its associations with clinicopathological parameters were evaluated. Survival curves were compared using the Kaplan-Meier method and log-rank tests. Univariate Cox regression was used on each clinical covariate to examine its influence on patient survival. Multivariate models were based on step-wise addition. Serum sMICA levels were significantly higher in NSCLC patients than in healthy controls (mean ± SD [pg/ml], 143.52 ± 27.6 vs. 32.4 ± 7.53 p < 0.01) and were significantly correlated with TNM stage, poorer differentiation, lymph node metastases and distant metastases. Survival analysis showed that a low sMICA level had longer survival time than those with high serum sMICA. Multivariate analyses indicated that high sMICA proved to be an independent predictor of survival time. Serum sMICA level in NSCLC patients is associated with metastasis. It is an indicator of a poorer survival probability. Serum sMICA levels may be an independent prognostic factor for NSCLC.


Phialemoniopsis limonesiae sp. nov. causing cutaneous phaeohyphomycosis in an immunosuppressed woman.
Rare or opportunistic fungal infections are mostly described in immunosuppressed patients. We present a case of a cutaneous phaeohyphomycosis that developed on the dorsal foot in an immunosuppressed woman suffering from AIDS, caused by a novel Phialemoniopsis species. It clinically presented as an indurated violaceous plaque, surmounted by nodules exuding a sero-purulent discharge. A filamentous fungus was isolated from pus and cutaneous biopsy. ITS and LSU sequences phylogenetically resolved the fungus as an unknown species of Phialemoniopsis, which is an unresolved family within Sordariomycetes. In this study we describe the new species as Phialemoniopsis limonesiae, which clusters on a single branch clearly separated from its closest phylogenetic neighbours. This new strain showed low MIC to itraconazole, voriconazole and posaconazole.


Duodenogastric reflux and reflux esophagitis.
Twenty-seven patients with gastroesophageal reflux were prospectively investigated to define the role of duodenogastric reflux in the development of reflux esophagitis. Duodenogastric reflux was detected and quantified by pH monitoring of the gastric environment 5 cm distal to the distal esophageal sphincter. Alkaline duodenogastric reflux was identified by the occurrence of spontaneous, intense gastric alkalinization during fasting periods. Patients with reflux with esophagitis were distinguished from those without esophagitis by having fewer of these episodes and, consequently, more acid stomachs than had patients without esophagitis. As previously shown, refluxers with esophagitis also had more frequent acid gastroesophageal reflux and prolonged gastric emptying. These findings suggest that refluxers with esophagitis have a functional gastropyloric disturbance resulting in delayed gastric emptying, decreased frequency of alkaline duodenogastric reflux episodes, and more frequent acid gastroesophageal reflux than do refluxers without esophagitis.


Multilayer assembly of hyaluronic acid/poly(allylamine): control of the buildup for the production of hollow capsules.
The objective of this work was to investigate the formation of hollow microcapsules composed of hyaluronic acid (HA) and poly(allylamine) (PAH) by layer-by-layer adsorption on CaCO 3 microparticles and subsequent core removal by addition of chelating agents for calcium ions. We found that the molecular weight of HA as well as the HA solution concentration used during deposition are crucial parameters influencing the multilayer structure. Whereas the effect of molecular weight of HA was mainly attributed to the porous structure of the template which allows penetration of polyelectrolytes when their size is below the maximum pore size of the template ( approximately 60 nm), that of the concentration of the HA solution was related to the intrinsic properties of the polysaccharide. Indeed, as shown by quartz crystal microbalance with dissipation monitoring as well as electron microscopy techniques, the latter leads to dense structures for concentrations from five to ten times the critical overlap concentration during adsorption. Such conditions were found to be favorable for the formation of hollow shells. Regarding conditions for core dissolution, we demonstrated the possibility to use either ethylenediaminetetraacetic acid (EDTA) or citric acid as chelating agents. However, in some cases, it was necessary to chemically cross-link the shell to maintain its integrity.


A 3500-year record of Hg and Pb contamination in a mediterranean sedimentary archive (the Pierre Blanche Lagoon, France).
A sediment core encompassing 3500 years of continuous sedimentation has been collected from a coastal lagoon located on the southwestern French Mediterranean coast. Lead concentrations and stable isotopes show that the sediments have recorded the three major periods of Pb pollution: the Etruscan-Greek-Roman period (650 BC to AD 50), the medieval period (AD 650 to AD 1450), and the modern period (from around AD 1850 to the present). These periods were separated by low pollution periods during the Dark Ages (between AD 50 and 650) and during the 16th century. From the end of the 19th century to the 1960s, Pb pollution increased exponentially. Coal combustion was the major source of Pb in the lagoon in the second half of the 20th century. Both the decrease in coal consumption and the ban on leaded gasoline resulted in a decrease in Pb pollution by a factor of 1.5 between 1973 and 1995. From 1991, sewage treatment plants and incinerators could be the major source of Pb. The average baseline Hg concentration from 1525 BC to AD 900 was 0.017 ± 0.003 μg g⁻¹ (n = 54). The Hg concentrations profile shows three major peaks: in AD 1150, AD 1660, and AD 1969, with the concentrations being respectively 8, 5, and 34 times higher than the baseline levels. The medieval peak (AD 1150) is attributed the medical use of Hg in the town of Montpellier and/or the burning of soil and vegetation. Noticeable Hg pollution was also detected during the 17th century in relation to gold and silver amalgamation in Europe. From the end of the 19th century, Hg concentrations increased exponentially until 1969. This modern pollution is attributed to the burning of coal.


Dynamic cerebral autoregulation after intracerebral hemorrhage: A case-control study.
Dynamic cerebral autoregulation after intracerebral hemorrhage (ICH) remains poorly understood. We performed a case-control study to compare dynamic autoregulation between ICH patients and healthy controls. Twenty-one patients (66 ± 15 years) with early (< 72 hours) lobar or basal ganglia ICH were prospectively studied and compared to twenty-three age-matched controls (65 ± 9 years). Continuous measures of mean flow velocity (MFV) in the middle cerebral artery and mean arterial blood pressure (MAP) were obtained over 5 min. Cerebrovascular resistance index (CVRi) was calculated as the ratio of MAP to MFV. Dynamic cerebral autoregulation was assessed using transfer function analysis of spontaneous MAP and MFV oscillations in the low (0.03-0.15 Hz) and high (0.15-0.5 Hz) frequency ranges. The ICH group demonstrated higher CVRi compared to controls (ipsilateral: 1.91 ± 1.01 mmHg·s·cm-1, p = 0.04; contralateral: 2.01 ± 1.24 mmHg·s·cm-1, p = 0.04; vs. control: 1.42 ± 0.45 mmHg·s·cm-1). The ICH group had higher gains than controls in the low (ipsilateral: 1.33 ± 0.58%/mmHg, p = 0.0005; contralateral: 1.47 ± 0.98%/mmHg, p = 0.004; vs. control: 0.82 ± 0.30%/mmHg) and high (ipsilateral: 2.11 ± 1.31%/mmHg, p < 0.0001; contralateral: 2.14 ± 1.49%/mmHg, p < 0.0001; vs. control: 0.66 ± 0.26%/mmHg) frequency ranges. The ICH group also had higher coherence in the contralateral hemisphere than the control (ICH contralateral: 0.53 ± 0.38, p = 0.02; vs. control: 0.38 ± 0.15) in the high frequency range. Patients with ICH had higher gains in a wide range of frequency ranges compared to controls. These findings suggest that dynamic cerebral autoregulation may be less effective in the early days after ICH. Further study is needed to determine the relationship between hematoma size and severity of autoregulation impairment.


[Early correction of hypospadias in girl with a disorder of sex development. clinical case].
The presented clinical case of a girl with a salt-wasting form of congenital adrenal hyperplasia in combination with chronic recurrent infection and lower urinary tract dysfunction demonstrates the need to change conventional two-staged approach to surgical feminization in favor of a one-stage intervention in order to prevent a progression of genitourinary complications. After controlling for the underlying condition, the one-stage feminization was performed, including modified tightening introitoplasty using a Passerini-Glazel flap and a correction of hypertrophic clitoris and labia minora. Good short- and long-term results were achieved.


Quantitative and qualitative effects of phosphorus on extracts and exudates of sudangrass roots in relation to vesicular-arbuscular mycorrhiza formation.
A comparison was made of water-soluble root exudates and extracts of Sorghum vulgare Pers. grown under two levels of P nutrition. An increase in P nutrition significantly decreased the concentration of carbohydrates, carboxylic acids, and amino acids in exudates, and decreased the concentration of carboxylic acids in extracts. Higher P did not affect the relative proportions of specific carboxylic acids and had little effect on proportions of specific amino acids in both extracts and exudates. Phosphorus amendment resulted in an increase in the relative proportion of arabinose and a decrease in the proportion of fructose in exudates, but did not have a large effect on the proportion of individual sugars in extracts. The proportions of specific carbohydrates, carboxylic acids, and amino acids varied between exudates and extracts. Therefore, the quantity and composition of root extracts may not be a reliable predictor of the availability of substrate for symbiotic vesicular-arbuscular mycorrhizal fungi. Comparisons of the rate of leakage of compounds from roots with the growth rate of vesicular-arbuscular mycorrhizal fungi suggest that the fungus must either be capable of using a variety of organic substrates for growth, or be capable of inducing a much higher rate of movement of specific organic compounds across root cell membranes than occurs through passive exudation as measured in this study.


Chebulagic acid inhibits the LPS-induced expression of TNF-α and IL-1β in endothelial cells by suppressing MAPK activation.
Inflammatory response in the vasculature, including the overexpression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, has been demonstrated to increase the risk of thrombosis development. Chebulagic acid (CA) is a key chemical component in the traditional Mongolian anti-thrombotic drug Garidi-13, and has been suggested to exert anti-inflammatory and anti-infective effects. The present study aimed to evaluate the regulatory impact of CA on a number of biological processes, including lipopolysaccharide (LPS)-induced inflammation, LPS-promoted mitogen-activated protein kinase (MAPK) activation and the expression of toll-like receptor (TLR)4 in EA.hy926 human endothelial cells. The results indicated that CA significantly inhibited the LPS-induced upregulation of TNF-α and IL-1β in a dose- and time-dependent manner. Furthermore, LPS-activated MAPK signaling was inhibited by CA treatment in the EA.hy926 cells. However, TLR4, which serves a key function in LPS-induced inflammation as the receptor of LPS, was not regulated by the CA treatment. In summary, the results of the present study indicate that CA inhibits the LPS-induced promotion of TNF-α and IL-1β in endothelial cells by suppressing MAPK activation, which may contribute to the anti-thrombotic effect of Garidi-13.


Increased extracellular free-water in adult male rats following in utero exposure to maternal immune activation.
In previous work, we applied novel in vivo imaging methods to reveal that white matter pathology in patients with first-episode psychosis (FEP) is mainly characterized by excessive extracellular free-water, and to a lesser extent by cellular processes, such as demyelination. Here, we apply a back-translational approach to evaluate whether or not a rodent model of maternal immune activation (MIA) induces patterns of white matter pathology that we observed in patients with FEP. To this end, we examined free-water and tissue-specific white matter alterations in rats born to mothers exposed to the viral mimic polyriboinosinic-polyribocytidylic acid (Poly-I:C) in pregnancy, which is widely used to produce alterations relevant to schizophrenia and is characterized by a robust neuroinflammatory response. Pregnant dams were injected on gestational day 15 with the viral mimic Poly-I:C (4 mg/kg) or saline. Diffusion-weighted magnetic resonance images were acquired from 17 male offspring (9 Poly-I:C and 8 saline) on postnatal day 90, after the emergence of brain structural and behavioral abnormalities. The free-water fraction (FW) and tissue-specific fractional anisotropy (FAT), as well as conventional fractional anisotropy (FA) were computed across voxels traversing a white matter skeleton. Voxel-wise and whole-brain averaged white matter were tested for significant microstructural alterations in immune-challenged, relative to saline-exposed offspring. Compared to saline-exposed offspring, those exposed to maternal Poly-I:C displayed increased extracellular FW averaged across voxels comprising a white matter skeleton (t(15) = 2.74; p = 0.01). Voxel-wise analysis ascribed these changes to white matter within the corpus callosum, external capsule and the striatum. In contrast, no significant between-group differences emerged for FAT or for conventional FA, measured across average and voxel-wise white matter. We identified excess FW across frontal white matter fibers of rats exposed to prenatal immune activation, analogous to our "bedside" observation in FEP patients. Findings from this initial experiment promote use of the MIA model to examine pathological pathways underlying FW alterations observed in patients with schizophrenia. Establishing these mechanisms has important implications for clinical studies, as free-water imaging reflects a feasible biomarker that has so far yielded consistent findings in the early stages of schizophrenia.


Synthesis and biological activity of pyridine acylhydrazone derivatives of isopimaric acid.
Pyridine acylhydrazone derivatives of isopimaric acid were synthesized and characterized. The minimum inhibitory concentrations of the compounds against five bacteria were determined and most of the compounds displayed some degree of antibacterial activity. The results showed that antimicrobial activity against Streptococcus pneumoniae improved when halogen atoms were introduced into the isopimaric acid, especially when one bromine atom was introduced in the para-position of isopimaric acid. Compound isopimaric acid (5-bromo pyridine-2-formaldehyde) acylhydrazone exhibited a significant antitumorial activity against hepatocarcioma cells (HepG-2) and breast cancer cells (MDA-MB-231), with inhibition degrees of 74.21% and 70.39%, respectively, at 100 μM.[Formula: see text].


Diagnosis and management of primary umbilical melanoma with omphalitis features.
We report on a 62-year-old Chinese male patient who presented with a pigmented lesion in the umbilical area and who was treated for omphalitis in a local hospital for 1 month. Biopsy pathological examination revealed that the lesion was a melanoma. The Breslow depth was estimated at 3 mm, and Clark's level was IV. Ultrasonography showed no suspicious pathological lymph nodes, and no metastases were detected in the lung, liver or brain through CT scans. Reexcision was performed with lateral marginsd >2 cm from the original scar down to the peritoneum, including the umbilicus, round ligament of the liver and urachus. No adjuvant therapy was suggested, and the patient was still alive without recurrences or metastases after 36 months.


Effect of localized nitrogen availability to soybean half-root systems on photosynthate partitioning to roots and nodules.
Soybean (Glycine max [L.] Merr. cv Davis) was grown in a split-root growth system designed to maintain control of the root atmosphere. Two experiments were conducted to examine how 80% Ar:20% O(2) (Ar:O(2)) and air (Air) atmospheres affected N assimilation (NH(4)NO(3) and N(2) fixation) and the partitioning of photosynthate to roots and nodules. Application of NH(4)NO(3) to nonnodulated half-root systems enhanced root growth and root respiration at the site of application. A second experiment applied Ar:O(2) or air to the two sides of nodulated soybean half-root systems for 11 days in the following combinations: (a) Air to both sides (Air/Air); (b) Air to one side, Ar:O(2) to the other (Air/Ar:O(2)), and (c) Ar:O(2) to both sides (Ar:O(2)/Ar:O(2)). Results indicated that dry matter and current photosynthate ((14)C) were selectively partitioned to nodules and roots where N(2) was available. Both root and nodule growth on the Air side of Air/Ar:O(2) plants was significantly greater than the Ar:O(2) side. The relative partitioning of carbon and current photosynthate between roots and nodules on a half-root system was also affected by N(2) availability. The Ar:O(2) sides partitioned relatively more current photosynthate to roots (57%) than nodules (43%), while N(2)-fixing root systems partitioned 36 and 64% of the carbon to roots and nodules, respectively. The Ar:O(2) atmosphere decreased root and nodule respiration by 80% and nitrogenase activity by 85% compared to half-root systems in Air while specific nitrogenase activity of nodules in Ar:O(2) was 50% of nodules supplied Air. Results indicated that nitrogen assimilation, whether from N(2) fixation or inorganic sources, had a localized effect on root development. Nodule development accounted for the major decrease in total photosynthate partitioning to non-N(2)-fixing nodules. Soybean compensates for ineffective nodulation by controlling the flux of carbon to ineffective nodules and their associated roots.


AIDS: some medico-legal aspects.
The increase in HIV infection in South Africa poses serious problems not only to medical services in this country, but also to its legal system. Some of the more immediate medico-legal problems surrounding AIDS are discussed: Informed consent to the testing for HIV antibodies, the maintenance of confidentiality and the question of whether health care workers may refuse to treat AIDS patients.


Repeated swim stress and peripheral-type benzodiazepine receptors.
The effect of daily forced swimming (15 min) of rats for 21 consecutive days on peripheral-type bentodiazepine receptors (PBR) was investigated. A significant reduction (-17%; p < 0.05) was observed in renal PBR in the stressed animals. A nonsignificant reduction of -18% was detected in adrenal PBR. The maximal binding capacity of [3H]PK 11195 was unaltered in the liver, heart, testis and thymus. It seems that the kidney is especially sensitive to repeated stress. The renal PBR reduction may be related to habituation to stress, and may reflect an adaptatory mechanism aimed at preventing long-term stress-induced overactivity of the renin-angiotensin system.


Glucocorticoid induced osteopenia in cancellous bone of sheep: validation of large animal model for spine fusion and biomaterial research.
Glucocorticoid with low calcium and phosphorus intake induces osteopenia in cancellous bone of sheep. To validate a large animal model for spine fusion and biomaterial research. A variety of ovariectomized animals has been used to study osteoporosis. Most experimental spine fusions were based on normal animals, and there is a great need for suitable large animal models with adequate bone size that closely resemble osteoporosis in humans. Eighteen female skeletal mature sheep were randomly allocated into 3 groups, 6 each. Group 1 (GC-1) received prednisolone (GC) treatment (0.60 mg/kg/day, 5 times weekly) for 7 months. Group 2 (GC-2) received the same treatment as GC-1 for 7 months followed by 3 months without treatment. Group 3 was left untreated and served as the controls. All sheep received restricted diet with low calcium and phosphorus during experiment. After killing the animals, cancellous bone specimens from the vertebra, femurs, and tibias were micro-CT scanned and tested mechanically. Serum biomarkers were determined. In lumbar vertebra, the GC treatment resulted in significant decrease of cancellous bone volume fraction and trabecular thickness, and bone strength. However, the microarchitecture and bone strength of GC-2 recovered to a similar level of the controls. A similar trend of microarchitectural changes was also observed in the distal femur and proximal tibia of both GC treated sheep. The bone formation marker serum-osteocalcin was largely reduced in GC-1 compared to the controls, but recovered with a rebound increase at month 10 in GC-2. The current investigation demonstrates that the changes in microarchitecture and mechanical properties were comparable with those observed in humans after long-term GC treatment. A prolonged GC treatment is needed for a long-term observation to keep osteopenic bone. This model resembles long-term glucocorticoid treated osteoporotic model, and is useful in preclinical studies.


Managing propagule pressure to prevent invasive species establishments: propagule size, number, and risk-release curve.
There is considerable evidence that keeping propagule pressure low can drastically reduce establishment probability of potential invasive species. Yet, most management plans and research efforts fail to explicitly acknowledge all three of the components of propagule pressure: size, number, and the risk-release relationship. It is unclear how failing to specify one or more of these components can influence the efficacy of management plans in preventing invasive species establishment. Furthermore, even if all components are acknowledged and quantified, there currently is no mathematical tool available to calculate the levels of propagule pressure that ensure attainment of a predetermined, and system-specific, target establishment probability. Here, we quantify the resulting uncertainty in establishment probability when one or more components of propagule pressure is unknown by using parameter uncertainty analysis on realistic values of propagule pressure. In addition, to aid in the development of management plans that explicitly set propagule pressure limits, we develop a propagule-pressure sensitivity analysis that we use to determine the required reduction in levels for propagule size and number (representative of management actions) to maintain a target establishment probability. We show that the precision of establishment estimates is highly dependent on knowledge of all three propagule pressure components, where the possible range of values for establishment probability can vary by over 50% without full specification. In addition, our sensitivity analysis showed that propagule size and number can be altered independently or in conjunction to lower establishment probability below a target level. Importantly, our sensitivity analysis was able to specifically quantify how much reduction in a propagule pressure component(s) is needed to reach a given target establishment probability. Our findings suggest that quantifying the three components of propagule pressure should be a priority for invasive species prevention moving forward. Furthermore, our sensitivity analysis tool can serve to guide the development of new invasive species management plans in a transparent and quantitative manner. Together with information on the costs associated with approaches to reducing propagule pressure, our tool can be used to identify the most cost-effective approach to prevent invasive species establishments.


Pulmonary edema in renal transplant patients.
A syndrome heralded by fever, deterioration of graft function, respiratory failure accompanied by pulmonary infiltrates has been termed "transplant lung." We hemodynamically studied eight such patients. At the height of their illness, pulmonary artery wedge pressure (PAWP) was elevated to 19.3 +/- 2.6 mm Hg along with mean pulmonary artery pressure (PAP) of 35.0 +/- 3.8 mm Hg in presence of increased cardiac index (CI) of 4.9 +/- 0.9 L.m2.min. Pathophysiology of pulmonary edema appears to include high left ventricular filling pressures, pulmonary hypertension, alterations of oncotic hydrostatic gradient, and increased cardiac output. A partial reversal of pulmonary hypertension was observed with dialysis or diuresis. Our data suggest incipient renal failure and fluid accumulation as the etiology of hemodynamic pulmonary edema in "transplant lung."


Histological and functional characterizations of the digital cushion in Quarter horses.
The digital cushion (DC) plays a role in absorbing and dampening forces applied to the foot and therefore supports internal structures such as navicular bone; yet, its architecture is not well-known. The goal of this study was to characterize the microanatomical structure of the DC in horses with clinically sound hooves. Both forefeet from the cadavers of 12 adult Quarter horses were cut and sectioned and samples of the following 4 regions of the DC were obtained: axial proximal (AxProx), axial distal (AxDis), abaxial lateral (AbxLat), and abaxial medial (AbxMed). The samples were processed and stained with hematoxylin and eosin, Masson's trichrome, and Weigert's elastic stains. On each slide, 2 central 3- × 3-mm areas were microscopically assessed and all measurements were done within the 9-mm2 area. The number of detected collagen bundles, nerve fascicles, vessels, and the diameter of wall thickness and lumen of blood vessels were measured. Elastic fiber profiles were categorized based on relative density of elastic fibers detected in the field. The percentage of samples in which chondrocytes and adipose tissues were either present or absent was calculated. Significant structural differences were identified among the 4 regions of the DC. The AxDis region contained more collagen bundles (P < 0.0001) and less elastic fiber profiles than the AxProx region (P < 0.0001). The AxDis also contained more collagen bundles than the AbxMed and AbxLat (P < 0.0001) regions. Our findings provide insight into the structure of the DC of mature Quarter horses. The structural differences in the various regions of the DC are presumably related to the different functional properties of those regions; yet more research is warranted.


A microfluidic in situ analyzer for ATP quantification in ocean environments.
We have developed and tested a functionally integrated in situ analyzer, the IISA-ATP system, for microbial activity assays based on a quantitative determination of the total (particulate and dissolved) ATP in ocean environments. The IISA-ATP utilizes a PDMS-glass hybrid microfluidic device as its core functional element, which can perform cell lysis and total ATP quantification by a luciferin-luciferase bioluminescence assay in situ. Transparent heaters and a temperature sensor fabricated on a glass substrate provide temperature control. As a result of the evaluation using the microfluidic device with ATP standard solutions, the bioluminescence intensity was linearly correlated with 2 × 10(-12) to 2 × 10(-8) M of ATP. A detection limit of 1.1 × 10(-11) M was determined using the completed IISA-ATP system, which includes a miniature pumping module and a control module. As a result of the evaluation using the environmental seawater sample collected from Tokyo Bay, Japan, 2.7 × 10(-10) M of total ATP was successfully determined in the laboratory by the IISA-ATP. The system was operated at a shallow submarine hot spring area in Okinawa, Japan for an in situ trial. The result shows the system was successfully operated in situ and the total ATP was determined to be 3.4 × 10(-10) M.


Fibrinogen Albumin Ratio and Ischemic Stroke During Venoarterial Extracorporeal Membrane Oxygenation.
Fibrinogen is a clotting factor and a major determinant of platelet aggregation. Albumin, on the other hand, inhibits platelet function and thrombus formation. Taken together, an elevated fibrinogen albumin ratio (FAR) has been described as a marker of disease severity during prothrombotic conditions. We evaluated the association of FAR and ischemic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support. A single center, retrospective study was performed including all adult patients placed on VA ECMO. FAR was calculated from fibrinogen and albumin measurements in the first 24 hours of VA-ECMO initiation. Patients were categorized into high (≥125) and low (<125) FAR groups and the risk of eventual ischemic stroke was determined. There were 201 patients who underwent VA ECMO placement and 157 had a FAR. They were 56 ± 14 years old and 66 (42%) had a high FAR. Patients with a high FAR had lower survival free from an ischemic stroke during VA ECMO (log rank p < 0.001; adjusted hazard ratio 5.51; 95% CI: 1.8-16.5). In tertile analysis, the level of FAR was associated with an incrementally higher likelihood of eventual ischemic stroke (log rank p = 0.004). Those with a high FAR had greater mean platelet volume (10.8[10.4-12] vs. 10.5[10.2-11.9]fl, p = 0.004). An elevated FAR during the first 24 hours of VA ECMO placement is associated with a greater risk of a subsequent ischemic stroke. Our findings suggest that assessment of FAR soon after VA ECMO placement may assist with early stratification of patients at risk for an ischemic stroke.


The use of gadolinium in the MR evaluation of musculoskeletal tumors.
Magnetic resonance (MR) imaging has emerged as the preferred modality for the imaging evaluation of musculoskeletal tumors. Although there is general agreement on the value of MR in diagnosis and staging, the use of intravenous contrast in the evaluation of musculoskeletal lesions remains controversial. The purpose of this review is to highlight these controversies, to put them in perspective, and to suggest recommendations for the use of gadopentetate dimeglumine. The following specific areas will be addressed: (a) evaluation of soft-tissue tumors, (b) diagnosis of low-grade chondrosarcoma and the use of contrast material in identification of intraosseous metastases, (c) monitoring response to chemotherapy, (d) evaluation for local recurrence after surgery and/or radiation therapy, and (e) selection of biopsy site.


IgG antibodies to human herpesvirus-6 in children and adults and in primary Epstein-Barr virus infections and cytomegalovirus infections [corrected].
Antibody titers against human herpesvirus-6 (HHV-6) were determined in 80 healthy adults and 100 children and teenagers from Sweden to gain information on the role of the virus and its epidemiology. Based on a positive immunofluorescence titer of 1:10 and above, about 85% of the adults and children were seropositive with 60% seropositivity of children below age one year. Titers were generally higher in patients with simultaneous EBV or CMV infection, yet crossreactivity appeared essentially no problem. HHV-6 thus is ubiquitous like other herpesviruses. Primary infection seems to occur early in life, and reactivation or delayed primary infection may be associated with a variety of disorders.


Is it Safe for Patients with Left Ventricular Assist Devices to Undergo Non-Cardiac Surgery?
Background and Objectives: Since the first use of ventricular assist devices (VADs) as bridge to recovery and bridge to cardiac transplantation in the early 1990s, significant technological advances have transformed VAD implantation into a routine destination therapy. With improved survival, many patients present for cardiac surgery for conditions not directly related to their permanent mechanical circulatory support. The aim of this study was to analyze the indications and outcomes of non-cardiac surgeries (NCSs) of left ventricular assist device (LVAD) patients in tertiary center. Material and Methods: We present a single-center experience after 151 LVAD implantations in 138 consecutive patients between 2012-2019 who had to undergo NCS during a follow-up period of 37 +/- 23.4 months on left ventricular assist device (LVAD). Results: A total of 105 procedures was performed in 63 LVAD recipients, resulting in peri-operative mortality of 3.8%. Twenty-five (39.7%) of patients underwent multiple surgeries. We found no significant difference in cumulative survival associated with the performed surgical interventions (p = 0.469). Conclusion: We demonstrated good overall clinical outcomes in LVAD patients undergoing NCS. With acceptable peri-operative mortality, NCS can be safely performed in LVAD patients on long-term support.


The use of plasmapheresis in a 4-year-old boy with toxic epidermal necrosis.
Toxic epidermal necrosis (TEN) is a severe and life-threatening syndrome manifesting as extensive necrosis of the epidermis and mucous membranes accompanied by systemic symptoms. The causative factor is exposure to drugs, such as sulphonamides, antiepileptic preparations, non-steroidal anti-inflammatory drugs and paracetamol. The mechanism leading to the development of lesions is unknown and there is no uniform strategy of management. A 4-year-old boy was admitted with late-stage TEN; he was additionally affected by partial atrophy of the corpus callosum, mental retardation and drug-resistant epilepsy. Three weeks before the first symptoms developed, antiepileptic treatment was widened with lamotrigine, which seems to be the causative factor of TEN. Since general and topical pharmacological therapy failed, plasmapheresis was applied and already after 2 cycles, the progression of lesions was inhibited and circulation was gradually stabilized. The use of plasmapheresis in a child with TEN can result in substantial improvement of the general and local condition. The case presented clearly indicates that standards of management of children with suspected or developed TEN should be urgently instituted.


Solid-phase synthesis of oligodeoxynucleotides containing N4-[2-(t-butyldisulfanyl)ethyl]-5-methylcytosine moieties.
An efficient route for the synthesis of the phosphoramidite derivative of 5-methylcytosine bearing a tert-butylsulfanyl group protected thiol is described. This building block is used for the preparation of oligonucleotides carrying a thiol group at the nucleobase at the internal position of a DNA sequence. The resulting thiolated oligonucleotides are useful intermediates to generate oligonucleotide conjugates carrying molecules of interest at internal positions of a DNA sequence.


Management of penile fracture and its outcome.
To describe the management and outcome of patients with penile fracture. Case series. Department of Urology and Renal Transplantation, Jinnah Hospital, Lahore, from March 2008 to March 2011. Sixteen patients presenting with clinical findings / history of penile fracture were included in this study. Diagnosis was made on the basis of history and clinical findings. Surgical exploration and repair was done on the same day. In all patients, a subcoronal circumferential degloving incision was made. Rent location and dimensions management and postoperative complication were noted. Postoperatively, erection was suppressed for 4 - 5 days. All patients were discharged with advice of avoidance of sex for about 8 weeks. Patients were followed-upto 6 months. Majority of the patients (87.5%) were married and 13 (81.25%) were aged 18 - 45 years. The typical findings recorded in 100.0% patients were erection at time of fracture, detumescence, swelling and ecchymosis. Audible crackling sound and pain was present in 13 (81.25%) patients. Ten (62.5%) patients had rent in the proximal part of penile shaft and right lateral tear was present in 11 (68.75%) patients. Blood clots were evacuated and closure of rent was done with vicryl 2/0 (interrupted stitches). 100.0% patients had uneventful recovery with only 3 (18.75%) patients developed right chordae of erect penis after treatment. All (100.0%) patients were potent and without any problem of erection. Penile fracture is under-reported. A trauma to erect penis is essential to cause fracture. Surgical exploration and repair is the treatment of choice.


Adsorbed films of three-patch colloids: continuous and discontinuous transitions between thick and thin films.
We investigate numerically the role of spatial arrangement of the patches on the irreversible adsorption of patchy colloids on a substrate. We consider spherical three-patch colloids and study the dependence of the kinetics on the opening angle between patches. We show that growth is suppressed below and above minimum and maximum opening angles, revealing two absorbing phase transitions between thick and thin film regimes. While the transition at the minimum angle is continuous, in the directed percolation class, that at the maximum angle is clearly discontinuous. For intermediate values of the opening angle, a rough colloidal network in the Kardar-Parisi-Zhang universality class grows indefinitely. The nature of the transitions was analyzed in detail by considering bond flexibility, defined as the dispersion of the angle between the bond and the center of the patch. For the range of flexibilities considered we always observe two phase transitions. However, the range of opening angles where growth is sustained increases with flexibility. At a tricritical flexibility, the discontinuous transition becomes continuous. The practical implications of our findings and the relation to other nonequilibrium transitions are discussed.


Hydrocephalus as the sole presentation of primary diffuse large B-cell lymphoma of the brain: Report of a case and review of literature.
The most common lymphoid malignancy in adults is diffuse large B-cell lymphoma (DLBCL). The median age of occurrence of DLBCL is between 6th and 7th decade of life, although some other types of aggressive non-Hodgkin's lymphomas (NHL) are present in younger age. Primary central nervous system lymphoma (PCNSL) is an uncommon type of extranodal NHL, which is either more prevalent or is diagnosed more often than before. A 22-year-old man with ventriculoperitoneal shunt (VPS) performed at another center was referred with manifestations of shunt malfunction, unusual behavior, dysphasia, and hallucination. The shunt malfunction was handled appropriately several times and exploration of the enhancing cystic temporal lesion confirmed the diagnosis of DLBCL. In this communication, we intend to highlight the issue that hydrocephalus refractory to several interventions can be the sole manifestation of PCNSL and needs special clinical considerations.


Single-crystalline epitaxial TiO film: A metal and superconductor, similar to Ti metal.
Titanium monoxide (TiO), an important member of the rock salt 3d transition-metal monoxides, has not been studied in the stoichiometric single-crystal form. It has been challenging to prepare stoichiometric TiO due to the highly reactive Ti2+ We adapt a closely lattice-matched MgO(001) substrate and report the successful growth of single-crystalline TiO(001) film using molecular beam epitaxy. This enables a first-time study of stoichiometric TiO thin films, showing that TiO is metal but in proximity to Mott insulating state. We observe a transition to the superconducting phase below 0.5 K close to that of Ti metal. Density functional theory (DFT) and a DFT-based tight-binding model demonstrate the extreme importance of direct Ti-Ti bonding in TiO, suggesting that similar superconductivity exists in TiO and Ti metal. Our work introduces the new concept that TiO behaves more similar to its metal counterpart, distinguishing it from other 3d transition-metal monoxides.


Quantitative Lysine Reactivity Profiling Reveals Conformational Inhibition Dynamics and Potency of Aurora A Kinase Inhibitors.
Small-molecule inhibitors of protein kinases attract widespread interest in the field of disease therapy because of their high specificity and ease of administration. However, dissecting the conformational inhibition dynamics of kinase inhibitors is still challenging. Here, simultaneously monitoring the conformational inhibition details and potency of Aurora A kinase inhibitors has been achieved by active isotope dimethyl labeling coupled with mass spectrometry-based quantitative lysine reactivity profiling. The conformational effects of inhibitors on lysine reactivity can be globally quantified to feasibly reveal the regions involved in the kinase dynamic inhibition. The half-maximum disturbance concentrations (DC50 values) of the conformation-specific lysine residues could directly represent the conformational selectivity and potency of kinase inhibitors. Further, K309 is discovered as a novel hotspot contributing to the inhibition of Aurora A kinase via the specific rotation of kinase activation loop. This quantitative lysine reactivity profiling strategy might greatly promote the development of targeted drugs.


Beyond a deficit-based approach: Characterizing typologies of assets for cisgender and transgender female sex workers and their relationship with syndemic health outcomes.
Female sex workers (FSWs) live and work at the intersection of multiple marginalized identities that place them at greater risk for various negative health outcomes. Resilience theory asserts that an individual or community needs assets from which they can draw in response to stressors, such as chronic discrimination and abuse. This study characterizes and compares patterns of assets among cisgender and transgender FSWs living with HIV in the Dominican Republic and their relations with syndemic health outcomes. With Latent Class Analysis, we used companion cross-sectional datasets comprised of cisgender and transgender FSWs (N = 211 and 100, respectively) to estimate typologies of interpersonal, community, and institutional assets. We used multivariate logistic regression to model the relationship between class membership and HIV care and treatment, mental health, violence exposure, and substance use outcomes, respectively. Among cisgender FSWs, we identified three classes: Internal and External Multilevel Assets (Class 1); External Institutional Assets (Class 2); and Low Reported Assets (Class 3). Compared to Class 3, Class 1 membership among cisgender FSWs was significantly associated with ART adherence and marginally associated with viral suppression, and Class 2 membership was marginally associated with currently taking ART. We identified two classes in the transgender sample: Internal and External Multilevel Assets (Class 1) and External Institutional Assets (Class 2). Class 1 membership among transgender FSWs was significantly associated with ART adherence and marginally associated with current ART use and physical or sexual violence, compared to Class 2. Having a variety of assets may explain the ability of some FSWs to more effectively engage with healthcare and maintain their HIV medication regimen. Future interventions should seek to expand FSWs' interpersonal and community assets, both from within and outside of the sex worker community, to bolster their ability to care for themselves and their community.


Rational antidepressant selection in the elderly.
Proper selection of antidepressant therapy is of growing importance as new and unique agents are added to the therapeutic armamentarium. Physicians must expend some effort in becoming familiar with the current treatment choices to facilitate selecting agents tailored to the needs of individual patients. The criteria that should be considered in antidepressant selection, assuming equal efficacy at appropriate therapeutic dosages, include propensity of a drug to produce side effects, patient and family history of response to previous antidepressant therapy, pharmacokinetics, ease of administration, drug interaction potential, and emerging data that suggest differential efficacy in specific depressive syndromes.


Effectiveness of a school-based fluoride mouthrinse program.
The aims of this study were to estimate the caries-preventive effects of a school-based weekly fluoride mouthrinse (FMR) program and to determine whether its effectiveness varied by school-level caries risk. We used clinical and parent-reported data for 1,363 children in grades 1 through 5 from a probability sample of North Carolina (NC) schoolchildren. Children's caries experience was measured using decayed and filled primary (d(2,3)fs) and total (d(2,3)fs+D(2,3)MFS) tooth surfaces. Program participation was quantified using 'FMR years'. To estimate caries risk at program entry, children were matched with NC kindergarten-surveillance data representing school-level mean untreated decay (low-risk school: < 1 and high-risk school: ≥ 1 untreated carious teeth). Mean d(2,3)fs was 4.1 [95% confidence limits (CL) = 3.7, 4.5]. Overall, each 'FMR year' was associated with weak reduction of caries prevalence in the primary [prevalence ratio (PR) = 0.98; 95% CL = 0.90, 1.06] and the mixed dentition (PR = 0.98; 95% CL = 0.91, 1.05). We found a trend toward a larger caries-preventive benefit among children in high-risk schools compared with those in low-risk schools (i.e., 55% vs. 10% caries reduction for 5 to 6 yrs of FMR participation compared to none). Although this difference was not confirmed statistically, our results indicate that children in high-risk schools, as identified by school-level surveillance data, may experience substantial caries-preventive benefits from long-term FMR participation.


Ocular tissue distribution and pharmacokinetic study of a small 13kDa domain antibody after intravitreal, subconjuctival and eye drop administration in rabbits.
Domain antibodies (dAb's) comprise the smallest functional unit of human IgG and can be targeted to a range of different soluble cytokine and receptor targets in the eye. In particular their small size may offer advantage for ocular tissue penetration and distribution. To investigate this we used a 13kDa tool molecule to undertake a preliminary short term ocular tissue distribution and pharmacokinetic study in the rabbit eye. The dAb was administered by the intravitreal or subconjunctival route or, as topical eye drops for up to five days and dAb concentrations measured in vitreous, aqueous, conjunctiva, choroid-RPE, retina, iris, sclera, and ciliary body. The observed elimination half-live of the dAb (~3 days) in vitreous showed a similar elimination rate to that of a much larger (∼50kDa) Fab fragment whilst the half-life following subconjunctival administration was ∼24 h and, after eye drop dosing the dAb was detectable in aqueous and conjunctiva. These preliminary data show that the intravitreal half-life of dAb's are similar to much larger antibody fragments, offering the potential to deliver significantly more drug to target on a molar basis with a single intravitreal injection potentially enabling dosing frequencies of once a month or less. Subconjunctival injection may provide short duration therapeutic levels of dAb to the anterior and posterior chamber whilst topical eye drop delivery of dAbs may be useful in front-of-eye disease. These data indicate that small domain antibodies may have utility in ophthalmology. Further studies are warranted.


Counting the cost of negligence in neurosurgery: Lessons to be learned from 10 years of claims in the NHS.
Despite substantial progress in modernising neurosurgery, the specialty still tops the list of medico-legal claims. Understanding the factors associated with negligence claims is vital if we are to identify areas of underperformance and subsequently improve patient safety. Here we provide data on trends in neurosurgical negligence claims over a 10-year period in England. We used data provided by the National Health Service Litigation Authority to analyse negligence claims related to neurosurgery from the financial years 2002/2003 to 2011/2012. Using the abstracts provided, we extracted information pertaining to the underlying pathology, injury severity, nature of misadventure and claim value. Over the 10-year period, the annual number of claims increased significantly. In total, there were 794 negligence claims (range 50-117/year); of the 613 closed cases, 405 (66.1%) were successful. The total cost related to claims during the 10 years was £65.7 million, with a mean claim per successful case of £0.16 million (total damages, defence and claimant costs of £45.1, £6.36 and £14.3 million, respectively). Claims related to emergency cases were more costly compared to those of elective cases (£209,327 vs. £112,627; P=0.002). Spinal cases represented the most frequently litigated procedures (350; 44.1% of total), inadequate surgical performance the most common misadventure (231; 29.1%) and fatality the commonest injury implicated in claims (102; 12.8%). Negligence claims related to wrong-site surgery and cauda equina syndrome were frequently successful (26/26; 100% and 14/16; 87.5% of closed cases, respectively). In England, the number of neurosurgical negligence claims is increasing, the financial cost substantial, and the burden significant. Lessons to be learned from the study are of paramount importance to reduce future cases of negligence and improve patient care.


Organelle-bound malate dehydrogenase isoenzymes are synthesized as higher molecular weight precursors.
Biosynthesis of malate dehydrogenase isoenzymes was studied in cotyledons of watermelons (Citrullus vulgaris Schrad., var. Stone Mountain). The glyoxysomal and mitochondrial isoenzymes are synthesized as higher molecular weight precursors which can be immunoprecipitated by mono-specific antibodies from the products of in vitro translation in reticulocyte lysates programed with cotyledonary mRNA and with the same size from enzyme extracts of pulse-labeled cotyledons. During translocation from the cytosol into the organelles, processing takes place. An 8 kilodalton extra sequence is cleaved from the glyoxysomal precursor and a 3.3 kilodalton extra sequence from the mitochondrial precursor producing the native subunits of 33 and 38 kilodaltons, respectively. The data support a post-translational translocation of the organelle-destined malate dehydrogenase isoenzymes. The in vitro translation of the cytosolic malate dehydrogenase I yields a product which has the same molecular weight as the subunit of the native isoenzyme (39.5 kilodaltons).


[Transfusion in clinical practice in geriatric wards].
In the absence of specific recommendations on blood transfusion in elderly subjects, we carried out a survey to assess transfusion practices in geriatric medicine. A descriptive, national, cross-sectional survey was conducted in 14 French geriatric departments (12 teaching hospitals and two general hospitals). In each department, five patients receiving transfusions were randomly selected in order to analyze their characteristics, the indications of blood transfusion, the criteria for and the methods of transfusion compared with Afssaps recommendations on transfusion thresholds. Data were analyzed for 70 patients (mean age 86+/-7 years, sex ratio female to male 1.8, with an average of five+/-two pathologies and six+/-three treatments). The indicators of poor tolerance included confusion (23 %), somnolence (22 %), acute heart failure (17 %) or coronary heart disease (16 %), and differed from the Afssaps criteria in the majority of cases. The transfusion threshold that were considered in the absence of poor tolerance (45 % of transfusions) differed from that recommended by Afssaps in 26 % of cases. The main adverse event in transfusion recipients was heart failure. When criteria for poor anaemia tolerance or transfusion thresholds are considered, transfusion practices in geriatric subjects have specific features. Further studies are needed to validate the appropriateness of the practices described in this survey.


Heterogeneous Catalytic Composites from Palladium Nanoparticles in Montmorillonite Intercalated with Poly (Vinyl Pyrrolidone) Chains.
In this study, poly (vinyl pyrrolidone) (PVP) chains intercalated montmorillonite (MMT) matrices has been demonstrated as an excellent scaffolding material for the immobilization of palladium (Pd) nanoparticles to prepare efficient heterogeneous catalysts for Heck reactions. Multiple layers (up to four) of PVP chains can intercalate the interlayer space of the MMT, resulting in an increase therein from 1.25 to 3.22 nm. MMT/PVP with PVP loading (20%) was selected as the platform for the immobilization of Pd. The in-situ reduction of the chelated Pd2+ into Pd⁰ in the interlayer space of MMT/PVP composite could be easily achieved. For the prepared Pd@MMT/PVP catalytic composite, a unique maze-like microstructure of Pd nanoparticles tightly encaged by PVP chains and by lamellae of layered silica has been detected by high resolution transmission electron microscopy (HR-TEM) and X-ray diffraction (XRD). Furthermore, the microstructure is well elucidated in molecular level by positron annihilation lifetime analysis of the Pd@MMT/PVP catalytic composite. The prepared Pd@MMT/PVP catalysts were highly active for the Heck coupling reactions between aromatic halides and alkenes, and could be recycled 9 times without significant decreases in coupling yields. The excellent comprehensive catalytic performances of the Pd@MMT/PVP catalytic composites are mainly attributed to their unique maze-like microstructure.


Luminal adrenergic agonists modulate ileal transport by a local mechanism.
Intestinal transport is controlled by neural pathways, hormones, and luminal agents. Luminal adrenergic agents influence water and ion transport in the jejunum. This study tested two hypotheses: (i) luminal adrenergic agents influence ileal water, ion and glucose transport, and (ii) luminal adrenergic agents exert their effects locally and selectively. Absorption studies (n = 46) were performed on dogs with two adjacent 25-cm ileal Thiry-Vella fistulas (TVF). Perfusion with [14C]polyethylene glycol was used to calculate absorption of water, ions, and glucose from the distal TVF. Experiments were composed of three 1-hr periods: basal, luminal adrenergic agonist infusion, and recovery. In group 1 the adrenergic agonists were administered to the distal TVF: norepinephrine (alpha 1 > alpha 2 and beta), phenylephrine (alpha 1), clonidine (alpha 2), and isoproterenol (beta). In group 2 the adrenergic agonists were administered to the proximal TVF, with absorption measured in the distal TVF. In group 1 norepinephrine and phenylephrine caused a significant increase in water absorption (P < 0.05). Clonidine and isoproterenol caused decreased absorption of water and ions, with clonidine causing significantly decreased absorption (P < 0.05) of water, ions, and glucose. In group 2 there were no changes in distal TVF absorption. Luminal adrenergic agents did not alter the heart rate in either group. Luminal adrenergic agonists modulate ileal transport via a local mechanism. A proabsorptive response is observed with alpha 1 agonists, while alpha 2 and beta agonists cause a prosecretory effect. Inhibition of glucose absorption appears to be selectively mediated via the alpha 2-adrenergic receptor.(ABSTRACT TRUNCATED AT 250 WORDS)


Non-Invasive Assessment of Left Ventricle Ejection Fraction: Where Do We Stand?
The left ventricular (LV) ejection fraction (EF) is the preferred parameter applied for the non-invasive evaluation of LV systolic function in clinical practice. It has a well-recognized and extensive role in the clinical management of numerous cardiac conditions. Many imaging modalities are currently available for the non-invasive assessment of LVEF. The aim of this review is to describe their relative advantages and disadvantages, proposing a hierarchical application of the different imaging tests available for LVEF evaluation based on the level of accuracy/reproducibility clinically required.


Accreditation of medical schools in Ireland: standards and procedures.
The Irish Medical Council has undertaken accreditation inspections of Irish medical schools on a regular basis since 1996. This document is a summary of the accreditation standards, a guide to the process for those involved and an overview of the complexity of the many elements involved in educating a doctor. It should be read in conjunction with previous Medical Council publications on medical education. It also provides the basis for the Evaluation System for Visitors 2003. The Medial Council's prime role is the protection of the public interest in relation to the practice of medicine. The Medical Council scrutinises medical schools. It has an important advocacy role with government, with the universities which operate medical schools and with the professionals involved to improve the standards and delivery of medical education.


The role of different phenomena in surface-activated chemical ionization (SACI) performance.
In previous studies, the production of ions in an APCI source without any corona discharge was observed, and the intensity of the ion signals showed significant increases on placing a metallic surface at 45 degrees inside an orthogonal ion source. This method was named surface-activated chemical ionization (SACI). The present study was performed to investigate the mechanisms of ion production with or without the presence of the metallic surface, by varying instrumental parameters and the geometrical configuration. Approximate calculations show that, in the absence of corona discharge and of any additional surfaces, ions cannot be produced by collisional phenomena, because of their low kinetic energy, in the 10(-2) to 10(-3) eV range. Two alternative possibilities have been considered: the first takes into account that ions may originate by collision of neutral clusters of polar solvent molecules with the APCI source surfaces through clusterelectric effect. The second takes into account that the water dissociation constant k(w) is temperature dependent, passing from 10(-14.1669) at 20 degrees C to 10(-12.4318) at 90 degrees C. It means that the [H(+)] varies from 8.3 x 10(-8) to 6.1 x 10(-7) M going from 20 to 90 degrees C. Hence, at the high temperatures experimented in the APCI vaporizer, H(+) becomes available in solution in molar quantities analogous to those of analyte, and the protonation of the analyte itself can consequently occur. The activation of further ionization processes in the presence of the metallic surface can be reasonably attributed to interactions between gas-phase analyte molecules and solvent molecules adsorbed on the surface. Experiments performed with a thin layer of deuterated glycerol on the surface led to unequivocal results, i.e. the production of [M + D](+) ions of the analyte.


Coexistence of Neurofibromatosis Type 1 and Male Breast Cancer.
Breast cancer is one of the rarest types of cancer in men. Its incidence increases with age, as in women. Neurofibromatosis type 1 is an autosomal dominant genetic disease that predisposes to many cancer types. Neurofibromatosis and breast cancer have been more frequently distinguished and better studied in women. Characteristically, estrogen, progesterone receptors, negative, and overexpression of human epidermal growth factor receptor 2 (HER2) are detected in patients with female neurofibromatosis breast cancers. In cases reported so far, estrogen and progesterone receptors have been evaluated as positive and HER2 negative in male patients. With the high possibility of breast cancer development in female patients with neurofibromatosis at an earlier age, prompt and careful evaluation is required in terms of both examination and radiological imaging. Unfortunately, there are no thorough recommendations for breast cancer follow-up in male patients with neurofibromatosis. Here, we present a breast cancer, which is an uncommon type of cancer in male neurofibromatosis.


Patients "falling through the cracks". The Canterbury Charity Hospital: initial progress report.
To present the early experience of establishing a community-funded and volunteer-staffed hospital in Christchurch, New Zealand. This was to provide free selected elective healthcare services to patients in the Canterbury region who were otherwise unable to access treatment in the public health system or afford private healthcare. Data were reviewed relating to the establishment, financing, staffing and running of the Canterbury Charity Hospital. Details were provided of patients referred by their general practitioners who were seen and treated during the first two and a half years of function. Canterbury Charity Hospital Trust, established in 2004, completed the purchase of a residential villa in 2005 and converted it into the Canterbury Charity Hospital, which performed its first operations in 2007. By the end of December 2009, 115 volunteer health professionals and 79 non-medical volunteers had worked at the Hospital, provided a total of 966 outpatient clinic appointments, of which 609 were initial assessments, and performed 610 surgical procedures. Funding of $NZ4.3 million (end of last financial year) came from fundraising events, donations, grants and interest from investments. There has been no government funding. There is a substantial unmet need for elective healthcare in Canterbury, and this has, in part, been addressed by the recently established Canterbury Charity Hospital. The overwhelming community response we have experienced in Canterbury raises the question of whether the current public health system needs attention to be re-focused on unmet need. We contend that unless this occurs it might be necessary to establish charity-type hospitals elsewhere throughout the country.


In vivo dynamics of chromatin-associated complex formation in mammalian nucleotide excision repair.
Chromatin is the substrate for many processes in the cell nucleus, including transcription, replication, and various DNA repair systems, all of which require the formation of multiprotein machineries on the chromatin fiber. We have analyzed the kinetics of in vivo assembly of the protein complex that is responsible for nucleotide excision repair (NER) in mammalian cells. Assembly is initiated by UV irradiation of a small area of the cell nucleus, after which the accumulation of GFP-tagged NER proteins in the DNA-damaged area is measured, reflecting the establishment of the dual-incision complex. The dynamic behavior of two NER proteins, ERCC1-XPF and TFIIH, was studied in detail. Results show that the repair complex is assembled with a rate of approximately 30 complexes per second and is not diffusion limited. Furthermore, we provide in vivo evidence that not only binding of TFIIH, but also its helicase activity, is required for the recruitment of ERCC1-XPF. These studies give quantitative insight into the de novo assembly of a chromatin-associated protein complex in living cells.


[Efficacy of intraperitoneal chemotherapy for advanced Borrmann type IV gastric carcinoma].
We report four patients with advanced Borrmann type IV gastric carcinoma, in whom intraperitoneal chemotherapy with low-dose CDDP and 5-FU plus MMC via a peritoneal port was effective against peritoneal metastasis. However, none of the four patients survived for a long period. During treatment, they were followed on an outpatient basis and received intraperitoneal chemotherapy biweekly with good control of peritoneal metastasis. The ratio of the outpatient follow-up period was more than 50% in all these patients. Intraperitoneal chemotherapy may be effective for controlling peritoneal metastasis of advanced Borrmann type IV gastric carcinoma, and contribute to maintaining the patient's quality of life.


Whakarongorau abdominal pain review.
The purpose of this study was to compare the frequency and profile of abdominal pain calls to Healthline with that from other national healthcare providers; to evaluate the outcomes for this symptom against international telehealth providers; and to explore any inter-clinician variation in the response to abdominal pain that could be part of a quality improvement cycle. Data routinely collected about abdominal pain calls to Healthline from 2017 to 2019 were extracted, analysed; and compared to the literature, hospital, and ambulance data and international telehealth providers. A specialist group was convened to review the profile of Healthline callers and outcome data. Variation in outcome changes and acuity grouping was evaluated at an individual level. Approximately 50,000 abdominal pain calls to Healthline over three years were analysed, with three-quarters from women, mostly of childbearing age. The majority call afterhours, with NZ European and, to a lesser extent, Māori, and callers from smaller geographical areas are over-represented. One quarter of patients had a hospital outcome (including 4% receiving an ambulance), which was found to be less acute than comparable health systems. Whakarongorau's Clinical Governance Committee and the Specialist Group both supported the relative distribution of outcomes given by Healthline for abdominal pain. There was found to be variation in the outcomes given to abdominal pain callers at an individual clinician level. This was both in their changes to the disposition given by the Odyssey decision support tool and in their overall outcome distribution. Healthline should be considered a key part of New Zealand's healthcare system, as illustrated by the volume of calls that it receives and the fact that presentation types are similar to general practice and emergency departments. Given that abdominal pain is a difficult symptom to accurately address without in-person examination and investigation, the findings support Healthline's outcomes as appropriate with hospitalisation rates lower than comparable healthcare systems. Whakarongorau's (the organisation which runs Healthline) ability to identify individual clinician behaviours gives it a unique opportunity to improve care through decreasing variation.


Which Donor for Uterus Transplants: Brain-Dead Donor or Living Donor? A Systematic Review.
The aim of this systematic review was to evaluate and compare the pros and cons of using living donors or brain-dead donors in uterus transplantation programs, 2 years after the first worldwide live birth after uterus transplantation. The Medline database and the Central Cochrane Library were used to locate uterine transplantation studies carried out in human or nonhuman primates. All types of articles (case reports, original studies, meta-analyses, reviews) in English or French were considered for inclusion. Overall, 92 articles were screened and 44 were retained for review. Proof of concept for human uterine transplantation was demonstrated in 2014 with a living donor. Compared with a brain-dead donor strategy, a living donor strategy offers greater possibilities for planning surgery and also decreases cold ischemia time, potentially translating into a higher success rate. However, this approach poses ethical problems, given that the donor is exposed to surgery risks but does not derive any direct benefit. A brain-dead donor strategy is more acceptable from an ethical viewpoint, but its feasibility is currently unproven, potentially owing to a lack of compatible donors, and is associated with a longer cold ischemia time and a potentially higher rejection rate. The systematic review demonstrates that uterine transplantation is a major surgical innovation for the treatment of absolute uterine factor infertility. Living and brain-dead donor strategies are not mutually exclusive and, in view of the current scarcity of uterine grafts and the anticipated future rise in demand, both will probably be necessary.


Unilateral papilledema in pseudotumor cerebri.
To report a case of a 25-year-old girl with pseudotumor cerebri who presented with unilateral swollen optic disk. A 25-year-old obese patient admitted to our ophthalmic department complaining of headaches, tinnitus, and transient visual obscurations for the last three months. Upon ophthalmic examination, the left optic nerve was swollen with a few hemorrhages compared to the normal-appearing right optic nerve. Following lumbar puncture with opening pressure of 350 mmHg, a diagnosis of pseudotumor cerebri was made and treatment with acetazolamide was started. Three months later there were no episodes of visual obscurations and headache improved. Although rare, unilateral swollen disk could be a sign of unilateral papilledema due to increased intracranial pressure.


Less efficacious conditioned pain modulation and sensory hypersensitivity in chronic whiplash-associated disorders in Singapore.
Cultural differences in pain perception exist. Although chronic whiplash-associated disorder (WAD) is well investigated in western countries, little is known about its presentation in Singapore. We studied the neck motion and pain sensitivity in people with chronic WAD in Singapore. Thirty chronic WAD participants (>3 mo, Neck Disability Index: 40% [SD 17%]) were age, sex, and ethnicity matched with 30 pain-free controls. All 60 participants underwent the following tests: active neck motion, pain thresholds (pressure, brachial plexus provocation test [BPPT], cold), cold pain tolerance, and conditioned pain modulation (CPM). The test stimulus of contact heat and conditioning stimulus of cold water immersion was used to assess CPM. Data were evaluated to determine differences between WAD and control groups. Active neck motion (F1,29=80.02), pain thresholds of blunt pressure (F1,29=20.84), BPPT (F1,29=54.56), and cold (Z=-4.31) were significantly lower in participants with WAD (P<0.0001). Cold pressor pain tolerance was significantly lower in participants with WAD (Z=-2.89, P=0.02). A less efficacious CPM was also demonstrated in participants with WAD (F1,29=9.20, P=0.03). A combination of BPPT and cold hyperalgesia best predicted the WAD group (sensitivity=96.7%, specificity=96.7%). These findings of sensory hypersensitivity and decreased neck motion in Singaporeans with chronic WAD are consistent with physical impairments reported in western populations.


Radiation Disrupts the Protective Function of the Spinal Meninges in a Mouse Model of Tumor-induced Spinal Cord Compression.
Recent advances in multidisciplinary treatments for various cancers have extended the survival period of patients with spinal metastases. Radiotherapy has been widely used to treat spinal metastases; nevertheless, long-term survivors sometimes undergo more surgical intervention after radiotherapy because of local tumor relapse. Generally, intradural invasion of a spinal tumor seldom occurs because the dura mater serves as a tissue barrier against tumor infiltration. However, after radiation exposure, some spinal tumors invade the dura mater, resulting in leptomeningeal dissemination, intraoperative dural injury, or postoperative local recurrence. The mechanisms of how radiation might affect the dura have not been well-studied. To investigate how radiation affects the spinal meninges, we asked: (1) What is the effect of irradiation on the meningeal barrier's ability to protect against carcinoma infiltration? (2) What is the effect of irradiation on the meningeal barrier's ability to protect against sarcoma infiltration? (3) What is the effect of irradiation on dural microstructure observed by scanning electron microscopy (SEM)? (4) What is the effect of irradiation on dural microstructure observed by transmission electron microscopy (TEM)? Eighty-four 10-week-old female ddY mice were randomly divided into eight groups: mouse mammary tumor (MMT) implantation 6 weeks after 0-Gy irradiation (nonirradiation) (n = 11), MMT implantation 6 weeks after 20-Gy irradiation (n = 10), MMT implantation 12 weeks after nonirradiation (n = 10), MMT implantation 12 weeks after 20-Gy irradiation (n = 11), mouse osteosarcoma (LM8) implantation 6 weeks after nonirradiation (n = 11), LM8 implantation 6 weeks after 20-Gy irradiation (n = 11), LM8 implantation 12 weeks after nonirradiation (n = 10), and LM8 implantation 12 weeks after 20-Gy irradiation (n = 10); female mice were used for a mammary tumor metastasis model and ddY mice, a closed-colony mice with genetic diversity, were selected to represent interhuman diversity. Mice in each group underwent surgery to generate a tumor-induced spinal cord compression model at either 6 weeks or 12 weeks after irradiation to assess changes in the meningeal barrier's ability to protect against tumor infiltration. During surgery, the mice were implanted with MMT (representative of a carcinoma) or LM8 tumor. When the mice became paraplegic because of spinal cord compression by the growing implanted tumor, they were euthanized and evaluated histologically. Four mice died from anesthesia and 10 mice per group were euthanized (MMT-implanted groups: MMT implantation occurred 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10], 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10]; LM8-implanted groups: LM8 implantation performed 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10], 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10]); 80 mice were evaluated. The spines of the euthanized mice were harvested; hematoxylin and eosin staining and Masson's trichrome staining slides were prepared for histologic assessment of each specimen. In the histologic assessment, intradural invasion of the implanted tumor was graded in each group by three observers blinded to the type of tumor, presence of irradiation, and the timing of the surgery. Grade 0 was defined as no intradural invasion with intact dura mater, Grade 1 was defined as intradural invasion with linear dural continuity, and Grade 2 was defined as intradural invasion with disruption of the dural continuity. Additionally, we euthanized 12 mice for a microstructural analysis of dura mater changes by two observers blinded to the presence of irradiation. Six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were quantitatively analyzed for defects on the dural surface with SEM. The other six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were analyzed for layer structure of collagen fibers constituting dura mater by TEM. In the SEM assessment, the number and size of defects on the dural surface on images (200 μm × 300 μm) at low magnification (× 2680) were evaluated. A total of 12 images (two per mouse) were evaluated for this assessment. The days from surgery to paraplegia were compared between each of the tumor groups using the Kruskal-Wallis test. The scores of intradural tumor invasion grades and the number of defects on dural surface per SEM image were compared between irradiation group and nonirradiation group using the Mann-Whitney U test. Interobserver reliabilities of assessing intradural tumor invasion grades and the number of dural defects on the dural surface were analyzed using Fleiss'κ coefficient. P values < 0.05 were considered statistically significant. There was no difference in the median (range) time to paraplegia among the MMT implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (16 days [14 to 17] versus 14 days [12 to 18] versus 16 days [14 to 17] versus 14 days [12 to 15]; χ2 = 4.7; p = 0.19). There was also no difference in the intradural invasion score between the MMT implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (8 of 10 Grade 0 and 2 of 10 Grade 1 versus 10 of 10 Grade 0; p = 0.17). On the other hand, there was a higher intradural invasion score in the MMT implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (5 of 10 Grade 0, 3 of 10 Grade 1 and 2 of 10 Grade 2 versus 10 of 10 Grade 0; p = 0.02). Interobserver reliability of assessing intradural tumor invasion grades in the MMT-implanted group was 0.94. There was no difference in the median (range) time to paraplegia among in the LM8 implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (12 days [9 to 13] versus 10 days [8 to 13] versus 11 days [8 to 13] versus 9 days [6 to 12]; χ2 = 2.4; p = 0.50). There was also no difference in the intradural invasion score between the LM8 implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (7 of 10 Grade 0, 1 of 10 Grade 1 and 2 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.51), whereas there was a higher intradural invasion score in the LM8 implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (3 of 10 Grade 0, 3 of 10 Grade 1 and 4 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.04). Interobserver reliability of assessing intradural tumor invasion grades in the LM8-implanted group was 0.93. In the microstructural analysis of the dura mater using SEM, irradiated mice had small defects on the dural surface at low magnification and degeneration of collagen fibers at high magnification. The median (range) number of defects on the dural surface per image in the irradiated mice was larger than that of nonirradiated mice (2 [1 to 3] versus 0; difference of medians, 2/image; p = 0.002) and the median size of defects was 60 μm (30 to 80). Interobserver reliability of assessing number of defects on the dural surface was 1.00. TEM revealed that nonirradiated mice demonstrated well-organized, multilayer structures, while irradiated mice demonstrated irregularly layered structures at low magnification. At high magnification, well-ordered cross-sections of collagen fibers were observed in the nonirradiated mice. However, disordered alignment of collagen fibers was observed in irradiated mice. Intradural tumor invasion and disruptions of the dural microstructure were observed in the meninges of mice after irradiation, indicating radiation-induced disruption of the meningeal barrier. We conclude that in this form of delivery, radiation is associated with disruption of the dural meningeal barrier, indicating a need to consider methods to avoid or limit Postradiation tumor relapse and spinal cord compression when treating spinal metastases so that patients do not experience intradural tumor invasion. Surgeons should be aware of the potential for intradural tumor invasion when they perform post-irradiation spinal surgery to minimize the risks for intraoperative dural injury and spinal cord injury. Further research in patients with irradiated spinal metastases is necessary to confirm that the same findings are observed in humans and to seek irradiation methods that prevent or minimize the disruption of meningeal barrier function.


Paradoxical effects of hedonic disparities in negative anticipatory contrast.
Negative anticipatory contrast (NAC) occurs when the presentation of two solutions in sequence over a number of trials leads to the suppression in consumption of the first solution. A hedonic 'disparity' between the two solutions may lead to this suppression. However, what the relative role of the gustatory properties versus the nutricaloric loads of the two solutions is in determining the acquisition of NAC is uncertain. Previous experiments have typically used saccharine and sucrose solutions, which resemble each other in gustatory properties yet differ in their nutricaloric loads. In contrast, the present experiments used soy milk and sucrose solutions, which are both highly nutritive but differ in their gustatory properties. Soy milk was found to have a higher hedonic value than a 16% sucrose solution as measured by both choice and absolute consumption. According to a hedonic disparity hypothesis, NAC should have occurred using a sucrose-soy sequence but not a soy-sucrose sequence. Paradoxically, the sucrose-soy sequence failed to yield NAC, but the soy-sucrose sequence did yield a repeatable, significant NAC. A consideration of the available theory and research indicated that NAC may be explained by a strong conditioning of a satiety response produced by sucrose that opposes the conditioning of sucrose's positive hedonic response.


[Empirical antifungal therapy in selected patients with persistent fever and neutropenia].
Empirical antifungal treatment (EAT) in neutropenia is mainly aimed at improving the poor prognosis of patients with invasive fungal infection through early treatment. The Infectious Diseases Society of America recommends initiating EAT in patients with persistent fever after 5-7 days of antibacterial treatment, and in those in whom remission of neutropenia is not imminent. Nevertheless, EAT has not been shown to be more effective than a placebo, it does not show better results than directed antifungal treatment, its effectiveness is minimal, it is not innocuous, and it is not very efficient with the use of most antifungal agents. All considered, we believe that the aforementioned recommendation for EAT treatment is unjustified. In its place we propose the application of EAT in patients selected on the basis of clinical criteria and risk factors.


Problem-solving ability of inner-city children with and without in utero cocaine exposure.
To evaluate the problem-solving abilities of a cohort of inner-city cocaine-exposed children and controls, children were invited to play with the Goodman Lock Box, a large red and blue box with 10 compartments, each having a different lock and toy. Examiners, blinded to the children's group status, coded the children's activities during the 6.5-minute play period. Nineteen behaviors were collapsed into three outcomes: Aimless Actions, Competence, and Mental Organization. Groups' scores were compared with scores of the Goodman standardization sample of mixed socioeconomic status preschoolers. Seventy-three cocaine-exposed children and 82 controls were evaluated at age 3.5 years; of these, 58 cocaine-exposed and 63 controls were reevaluated at age 4.5 years. The groups' scores did not differ on any outcome at either time point (p > or = .22). However, both groups' Mental Organization scores were consistently lower than the Goodman group at each age (p < .01). This high-risk cohort may experience problems functioning in more complex environments such as the classroom.


Adult-onset Still's disease in a 73-year-old Maltese man.
Adult-onset Still's disease (AOSD) is a rare autoinflammatory condition diagnosed by Yamaguchi criteria. We report an atypical presentation of a 73-year-old man, who was admitted with fever, sore throat and pleurisy that were unresponsive to three courses of antibiotics. Fever persisted in a quotidian pattern and the typical salmon-coloured rash consistent with AOSD appeared at 4 weeks from symptoms onset. These features in addition to neutrophilia and hyperferritinaemia in the absence of concurrent infectious and neoplastic causes satisfied Yamaguchi criteria for a diagnosis of AOSD. Epstein-Barr antigen was initially detected at moderate titre levels, but was undetectable after 1 week. Complete resolution of symptoms was reported on initiation of steroid treatment. A relationship between disease onset and viral syndromes has been documented to occur and few similar cases preceded by Epstein-Barr virus detection have been reported.


Veno-arterial extracorporeal membrane oxygenation without therapeutic anticoagulation for intra-operative cardiopulmonary support during lung transplantation.
Cardiopulmonary support is frequently required during lung transplantation. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been recently shown to be an acceptable and, perhaps, safer alternative to cardiopulmonary bypass machine (CBM) for lung transplantation. However, therapeutic anticoagulation used during both these techniques can cause significant bleeding diathesis, especially in the setting of re-transplantation or when severe adhesions are encountered. Technological advances have reduced the thrombogenic potential of VA-ECMO circuits and unlike CBM, VA-ECMO does not include a reservoir containing a stagnant column of blood. Here, we demonstrate that VA-ECMO can be used without therapeutic anticoagulation for short-term intraoperative support.


[Isolation of Borrelia burgdorferi in the cerebrospinal fluid of 3 children with neurological involvement].
Isolation of Borrelia burgdorferi from the CSF is relatively rare. The present report describes the first three isolations in Switzerland. Clinically, our first observation confirmed the frequent association of B. burgdorferi with peripheral facial paresis in children. The other two cases illustrate the variety of symptoms in neuro-borreliosis. In the first case the culture was positive after 6 weeks. The results of serologic tests (indirect immunofluorescence and ELISA) for detection of antibodies against B. burgdorferi were negative or non-significant in this child's serum. On the other hand, specific antibodies (IgG) were detected in the serum by western blot. Culture of the second CSF already showed Borrelia growth after 10 days. Immunofluorescence revealed high antibody titers (1/256) against B. burgdorferi in this patient's serum. IgG showed a weakly positive reaction in western blot. The reliability of this result was confirmed by isolation of Borrelia. In neither of the two CSF could intrathecal synthesis of specific antibodies be demonstrated. In the third case, however, immunofluorescence showed IgG antibody titers of 1/128 in the CSF and 1/512 in serum. Intrathecal synthesis of specific antibodies was demonstrated with an index of 13.4 (norm < 2). Western blot confirmed the specificity of the reactions observed with the serum and CSF IgG. Culture of CSF produced significant growth of Borrelia within 7 days. Protein profile and reactions with poly- and monoclonal antibodies confirmed that the three strains belonged to B. burgdorferi.(ABSTRACT TRUNCATED AT 250 WORDS)


Invasive ductal adenocarcinoma of the remnant pancreatic body 9 years after resection of an intraductal papillary-mucinous carcinoma of the pancreatic head: a case report and comparison of DNA sequence in K-ras gene mutation.
Recently, there have been a few case reports of invasive ductal adenocarcinoma (IDC) developed in the remnant pancreas after partial pancreatectomy for intraductal papillary-mucinous neoplasm (IPMN). It is necessary to clarify their histogenetic relationships among two sporadic tumors and their surrounding duct epithelium and it would be more reliable if genetic analysis is added to the conventional histology. We report a 76-year-old woman who received pancreaticoduodenectomy for IPMN with a focal in situ carcinoma (IPMC), which was transitional to the surrounding duct epithelium with papillary proliferation and a wide variety of dysplasia. Nine years after the operation, she died of IDC in the remnant pancreatic body and its surrounding duct epithelium consisted of hyperplastic mucous cells with slight-mild dysplasia. Analysis of K-ras mutation at codon 12 (wild-GGT) by direct sequencing after polymerase chain reaction indicated that their transitioning patterns differed from each other: CGT in IPMC; no mutation in the mildly dysplastic duct epithelium around IPMC; GAT in IDC of the remnant pancreas; and AGT in mucous cell hyperplasia with mild dysplasia close to the IDC. This is the first report in which the DNA sequence of K-ras mutation was determined for the two sporadic pancreatic cancers and surrounding duct changes. The following two suggestions are made: (1) the cell-origin might have differed between the two types of cancer (IDC and IPMC); and (2) no precursor lesion toward IDC or IPMC was identified in their surrounding duct epithelium.


The effectiveness of comprehensive physiotherapy compared with corticosteroid injection on pain, disability, treatment effectiveness, and quality of life in patients with subacromial pain syndrome: a parallel, single-blind, randomized controlled trial.
Comparing short- and long-term effects of comprehensive physiotherapy (CP) and subacromial corticosteroid injection (SCI) on pain, disability, and quality of life in the patients with subacromial pain syndrome (SAPS). 2 × 4 randomized controlled trial. 50 participants with unilateral SAPS. Random assignment with allocation concealment into two groups labeled as 12 sessions, supervised CP (n = 22) and 1cc triamhexal SCI (n = 25). Visual Analog Scale (VAS), Shoulder Pain and Disability Index (SPADI), shortened Disabilities of Arm, Shoulder and Hand (Quick-DASH), and Western Ontario Rotator Cuff Index (WORC). Outcomes were gathered pre- and post-intervention, with three- and six-month follow-ups. Variance analysis revealed that there was a significant interaction of group-in-time for SPADI and WORC (P < .05) but not for Quick-DASH and VAS (P > .05). The independent t-test analysis showed that the mean scores of all outcome measures in CP group were lesser than SCI group via 6 months (P < .05), except for the VAS (P > .05, mean difference = -0.97, 95% confidence interval -2.11-0.15). CP results in statistically significant and potentially clinically important difference in function and quality of the life at all timeframe. Moreover, there was no between group difference in order to reduce pain.


Protein and Lipid Compositions of Isolated Plasma Membranes from Orchard Grass (Dactylis glomerata L.) and Changes during Cold Acclimation.
The chemical composition of plasma membrane fractions isolated from orchard grass seedlings (Dactylis glomerata L.) was analyzed and compared with endomembranes. The plasma membrane is characterized by an enrichment of sterols and a lower degree of unsaturation of phospholipids. Steryl glycosides were found to be one of the lipid components of the plasma membrane, but steryl esters and galactolipids were barely detectable. Diphosphatidyl glycerol was characteristically detected in the mitochondrial membrane, but not in the plasma membrane fraction. Plasma mambrane fraction was also characterized by its ;lower fluidity' in comparison with the endomembranes. This may be due to the large amount of sterols and the lower degree of phospholipid unsaturation in plasma membranes.Electrophoretic comparison of polypeptides was also made between different membranes. The distribution patterns of polypeptides revealed on one- and two-dimensional SDS-slab gels were characteristic for those membranes. The presence of glycopeptide complements was a useful criterion for distinguishing plasma membrane from other membranes. The plasma membrane and the ER + Golgi membranes were enriched in glycopeptides. However, a marked difference was revealed in the total number and the molecular weights of the peptides.During cold acclimation of orchard grass seedlings, the degree of fatty acid unsaturation increased only slightly in plasma membrane, unlike in endomembranes. The change in sterols-to-phospholipids ratio in plasma membrane was also slight. On the other hand, the phospholipid-to-protein ratio increased significantly in the plasma membrane as cold hardiness increased. A significant change in the polypeptide complements of plasma membrane was also demonstrated during cold acclimation.


Hepatitis viruses and non-Hodgkin's lymphoma: A review.
Non-Hodgkin's lymphoma (NHL) is among the haematological malignancies with high prevalence worldwide, causing estimated 355 900 new cases and 191 400 deaths in 2008. High prevalence of NHL is documented in economically more developed areas while low prevalence is observed in less developed areas of the globe. A wide array of environmental factors have been reported to be either directly involved or in modifying the risk of NHL development. In addition to these factors, a number of infectious agents, chiefly viruses have also been implicated in the development of NHL. This article reviews the available literature to discuss the role of hepatitis viruses in NHL development, possible mechanisms of lymphomagenesis and also identify the areas in which further research is required to better understand this disease. A brief discussion on the clinical aspects such as classification, staging, treatment approaches have also been included in this article.


[Coenzyme Q10 single intravenous infusion protects rat myocardium against subsequent ischemia/reperfusion].
Cardioprotective effects of coenzyme Q10 (CoQ10) injected intravenously 30 min before coronary artery occlusion were assessed on the model of myocardial ischemia/reperfusion in Wistar rats. Rats treated with CoQ10 after 30 min of ischemia and 120 min of reperfusion exhibited smaller (by 35%, p < 0.01) size of irreversibly damaged myocardium, shorter duration and decreased number of arrhythmias during reperfusion, and increased content of myocardial CoQ10 (by 210%, p < 0.01) as compared to saline-treated rats. Increased CoQ10 levels in myocardium were accompanied by smaller size of damaged myocardium (r = -0.77, p = 0.0002). Thus, there is evidence of the cardioprotective effect of CoQ10 injected intravenously before myocardial ischemia/reperfusion.


Relation between structure and size in social networks.
In the context of complex network systems, we model social networks with the property that there is certain degradation of the information flowing through the network. We analyze different kinds of networks, from regular lattices to random graphs. We define an average coordination degree for the network, which can be associated with a certain notion of efficiency. Assuming that there is a limit to the information a person may handle, we show that there exists a close relationship between the structure of the network and its maximum size.


[Internal medicine in a group of 52 Spanish hospitals. Analysis of a case series and efficiency].
To analyze the case-mix and efficiency in a group of Services of Internal Medicine (IM) from 52 Spanish hospitals with routinary clinical information system. From a total amount of 566,726 discharges during 1992, we studied the 71,430 corresponding to IM, analyzing the Minimum Basic Data Set and the Diagnosis-Related Groups (DRG). The hospitals were classified as level A (< 250 beds), B (251-599) and C (600 or over). We analyzed: Major Diagnostic Category (MDC); DRG, raw average length of stay (ALOS); outliers, trimmed ALOS; mortality; case-mix index; performance index; ajusted ALOS (by standard performance and case-mix); associated complications; number of diagnoses per discharge. A Chi-square test was used for qualitative variables and a mean-comparison test (independent data) for the quantitative ones. Among the Internal Medicine Departments, IM was the Service that cared most patients, even more in the small-size hospitals. The most frequent DRG were: chronic obstructive pulmonary disease (COPD) 6.5% (DRG 088); simple pneumonia & pleuresy 6.1% (DRGs 089-090); heart failure 5.9% (DRG 127); stroke 4.5% (DRG 014); and angor pectoris 2.4% (DRG 140). The ALOS was shorter in the A-level hospitals (10.1 days) vs. B-level (11.6) and C-level (14.4). However, the trimmed ALOS was more homogeneous (A 8.8; B 9.9; C 11.7). The complexity indexes increased with the hospital level although the performance index also increased. The IM services provide care for a high percentage of hospital patients, especially in the small-size centers. In these, less complex patients are seen, with decreased comorbidity, complications and mortality and they solve their patients with shorter ALOS than the IM services in the large-size hospitals.


Animism and natural teleology from Avicenna to Boyle.
Historians have claimed that the two closely related concepts of animism and natural teleology were both decisively rejected in the Scientific Revolution. They tout Robert Boyle as an early modern warden against pre-modern animism. Discussing Avicenna, Aquinas, and Buridan, as well as Renaissance psychology, I instead suggest that teleology went through a slow and uneven process of rationalization. As Neoplatonic theology gained influence over Aristotelian natural philosophy, the meaning of animism likewise grew obscure. Boyle, as some historians have shown, exemplifies this uneven process. There is an unresolved tension between his religious convictions and the implicit animism of his empirical practice.


Electroencephalography in childhood conduct and behavior disorders.
The pathophysiology of behavior disorders in children is controversial. In particular, the relationship of episodic behavior disturbance to epilepsy and chronic behavior problems to subclinical neurologic disorder has been debated. It has been suggested that EEG may assist in this sometimes difficult determination. We report on routine screening EEGs in children hospitalized over an 18-month period for behavior problems. Eighty-six children were admitted for conduct disorder, attention deficit hyperactivity disorder, or both. Seventy-eight tracings (91%) were normal or showed normal variant patterns. Eight records (9%) were abnormal, showing background slowing or paroxysmal discharges not associated with behavioral manifestations. None of these neurologically normal, nonretarded patients had epilepsy or other known cerebral disorder. This suggests that routine EEG screening may be of limited value in childhood behavior problems without clinical evidence of neurologic disorder.