Stride length-cadence relationship is disrupted in below-knee prosthesis users.
The aim of this study was to evaluate the linearity of the relationship between stride length and cadence (STRIDELC) over three self-selected speeds (normal, slow, fast) in below-knee prosthesis users (n=14, 11 men, mean age 43±12 years, mean time since amputation 9.2±6.9 years) in comparison to controls (n=20, 11 men, mean age 43±17 years). The step length-cadence relationship (STEPLC) was also calculated for the prosthetic and intact legs in prosthesis users and compared to the dominant leg of controls. The goodness of linear fit (R2) and slope over 3 speeds were used as outcome measures. Prosthesis users walked significantly slower than controls (slow-fast speed means 82-131 vs. 97-169 cm/s, respectively, ANOVA p<0.0001) due to both lower cadence (42-53 vs. 47-63 strides/min, p<0.0001) and shorter stride length (116-149 vs. 123-161 cm, p<0.0001). The R2 of STRIDELC relationship in below-knee prosthesis users (0.76±0.13) was significantly lower than in controls (0.91±0.03, p<0.001). The R2 values of STEPLC relationship between the prosthetic and intact legs in prosthesis users were correlated (r=0.85, p<0.001) and both (0.67±0.19, 0.58±0.21, respectively) were significantly smaller than in the dominant leg of controls (0.86±0.04, p<0.01). The slopes of STRIDELC and STEPLC were not different. The R2 of 0.84 for STRIDELC best discriminated prosthesis users from controls with high sensitivity (71%) and specificity (95%). The results indicate that coupling between stride/step length and cadence is disturbed in prosthesis users. Upon further investigation, the goodness of linear fit may prove to be useful in assessing prosthetic design, optimizing prosthetic fit, and predicting clinical outcomes.


Office laboratory procedures, office economics, parenting and parent education, and urinary tract infection.
We again review four areas of interest to office-based pediatricians: office laboratory procedures, office economics, parenting and patient education, and urinary tract infections. Sean Elliott provides an update on the Clinical Laboratories Improvement Amendments (CLIA) and their impact of office practice. Eve Shapiro reviews office economics, focusing on measuring quality of care, use of performance data, costs of new technologies, and the impact of managed care on the medical marketplace. John Walter offers an update on parenting and parent education, with approaches to counseling families about overuse of antibiotics, teen pregnancy, hyperactivity, violence, and asthma. Richard Wahl reviews the recent research on urinary tract infection, with special attention paid to office diagnosis and management, longitudinal studies of children with urinary tract infections, and the controversy surrounding the American Academy of Pediatrics Task Force on Circumcision report.


[The classification of the morphological forms of flagellates in the family Trypanosomatidae].
The partial revision of the generally accepted classification of the morphological forms of trypanosomatid flagellates (Hoare, Wallace, 1966) is proposed. Only "flagellar" characteristics without evaluation of the form of the body and systematic position of the flagellates are used in the new variant of the classification. Six basic morphological forms of trypanosomatids have been included in proposed scheme: amastigotes, endomastigotes, promastigotes, opisthomastigotes, epimastigotes, trypomastigotes.


The training of neural classifiers with condensed datasets.
In this paper we apply a k-nearest-neighbor-based data condensing algorithm to the training set of multilayer perceptron neural networks. By removing the overlapping data and retaining only training exemplars adjacent to the decision boundary we are able to significantly speed the network training time while achieving an undegraded misclassification rate compared to a network trained on the unedited training set. We report results on a range of synthetic and real datasets that indicate that a training speed-up of an order of magnitude is typical.


[Cholestatic liver lesions of alcoholic etiology (a morphologic study)].
Results of histological, histochemical and electron-microscopy studies of puncture-biopsy specimens of the liver of 25 patients with alcoholic hepatitis are discussed. It is shown that acute alcoholic hepatitis develops, develops, as a rule against the background of steatosis and hepatocirrhosis as a result of the previous chronic consumption of alcohol. Lesions of the liver in this disease are of cholestatic character, which was due to the impairment of the metabolism of lipids, cholesterol and biliary acids under the effect of ethanol. The microscopic picture of alcoholic hepatitis is characterized by the presence of Mallory hyalin, intracellular congestion of the bile and predominance of neutrophilic leukocytes in the cell infiltrate. The characteristics make it possible to differentiate alcoholic hepatitis from viral one.


Nutritional influences on the gut microbiota and the consequences for gastrointestinal health.
The human colonic microbiota degrades dietary substrates that are indigestible in the upper GIT (gastrointestinal tract), releasing bacterial metabolites, some of which are important for gut health. Advances in molecular biology techniques have facilitated detailed analyses of the composition of the bacterial community resident in the lower GIT. Such analyses have indicated that more than 500 different bacterial species colonize an individual, and that, although there is much functional consistency in the resident bacterial groups, there is considerable inter-individual variation at the species/strain level. The bacterial community develops during early childhood until it reaches an adult-like composition. Whereas colonization and host factors influence the species composition, dietary factors also have an important impact, with specific bacterial groups changing in response to specific dietary interventions. Since bacterial species have different metabolic activities, specific diets have various consequences for health, dependent on the effect exerted on the bacterial population.


Very low protein diet supplemented with ketoanalogs improves blood pressure control in chronic kidney disease.
Blood pressure (BP) is hardly controlled in chronic kidney disease (CKD). We compared the effect of very low protein diet (VLPD) supplemented with ketoanalogs of essential amino acids (0.35 g/kg/day), low protein diet (LPD, 0.60 g/kg/day), and free diet (FD) on BP in patients with CKD stages 4 and 5. Vegetable proteins were higher in VLPD (66%) than in LPD (48%). LPD was prescribed to 110 consecutive patients; after run-in, they were invited to start VLPD. Thirty subjects accepted; 57 decided to continue LPD; 23 refused either diet (FD group). At baseline, protein intake (g/kg/day) was 0.79+/-0.09 in VLPD, 0.78+/-0.11 in LPD, and 1.11+/-0.18 in FD (P<0.0001). After 6 months, protein intake was lower in VLPD than LPD and FD (0.54+/-0.11, 0.78+/-0.10, and 1.04+/-0.21 g/kg/day, respectively; P<0.0001). BP diminished only in VLPD, from 143+/-19/84+/-10 to 128+/-16/78+/-7 mm Hg (P<0.0001), despite reduction of antihypertensive drugs (from 2.6+/-1.1 to 1.8+/-1.2; P<0.001). Urinary urea excretion directly correlated with urinary sodium excretion, which diminished in VLPD (from 181+/-32 to 131+/-36 mEq/day; P<0.001). At multiple regression analysis (R2=0.270, P<0.0001), BP results independently related to urinary sodium excretion (P=0.023) and VLPD prescription (P=0.003), but not to the level of protein intake. Thus, in moderate to advanced CKD, VLPD has an antihypertensive effect likely due to reduction of salt intake, type of proteins, and ketoanalogs supplementation, independent of actual protein intake.


Subarachnoid blockade with bupivacaine. A comparison with cinchocaine.
Subarachnoid anaesthesia was induced in 40 patients with 0.5% bupivacaine 3 ml with no glucose, 5% glucose or 8% glucose, or with hyperbaric cinchocaine . The injections were made in the lateral position and the patients turned supine immediately. The onset, extent and duration of sensory and motor blockade, the quality of anaesthesia, cardiovascular effects, and the frequency of side-effects were studied. The hyperbaric solutions produced a greater cephalad spread (T6-T7) than the glucose-free solution (T10-T11). Cinchocaine produced a longer duration of action at T10 and T12 than the hyperbaric bupivacaine solutions. No advantage was seen when 8% rather than 5% glucose was used. The glucose-free bupivacaine produced intense blockade of long duration and was suitable when a lower level of blockade was adequate for the proposed surgery.


Agave (Agave americana): an evidence-based systematic review by the natural standard research collaboration.
An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.


Spontaneous closure of ventricular septal defect.
One thousand sixty-six patients with ventricular septal defect were followed. Spontaneous closure occurred in 71%, whereas 5% needed operative closure and 2.3% died.


Recombinant mouse SPARC promotes parietal endoderm differentiation and cardiomyogenesis in embryoid bodies.
In the absence of leukemia inhibitory factor, murine embryonic stem cells cultured in vitro spontaneously aggregate to from three-dimensional embryoid bodies that differentiate to produce hematopoietic, endothelial, muscle, and neuronal cell lineages in a manner recapitulating the events of early embryogenesis. Cardiomyogenesis in embryoid bodies was recently demonstrated to be promoted by PYS-2-derived native SPARC (secreted protein, acidic and rich in cysteine), whose expression is upregulated in parietal endoderm at the onset of the epithelial to mesenchymal transition. Here, we confirm the stimulatory effects of mouse SPARC on cardiomyogenesis using a recombinant baculovirus-produced protein (rmSPARC). Embryoid bodies cultured in the presence of glycosylated rmSPARC, or an unglycosylated peptide spanning the C-terminal EF-hand domain, developed greater numbers of beating cardiomyocytes than did time-matched controls, with enhanced expression of cardiac marker genes including Nkx2.5, Troponin, BMP-2, and MHCalpha. Histochemical analysis revealed an expansion of the peripheral endoderm, with thicker layers of extracellular matrix (ECM) material observed atop underlying cells. Embryoid bodies treated with SPARC also displayed increased adherence to polystyrene culture dishes, with enhanced expression of ECM mRNAs including collagen IValpha3, collagen IValpha5, and laminin alpha1. These results indicate that, in addition to the promotion of cardiomyogenesis, SPARC may also help regulate the molecular composition and organization of ECM secreted by the mesenchymal parietal endoderm.


Insulinoma-a case report.
BNM, a 40 years Hindu male presented with history of intermittent fainting attacks and had increase in body weight for last 2 years. He used to take a lot of sweets to recover from the attact. His body wht was 100 kg. His fasting blood sugar was 50 mg/dl and insulin glucose (I/G) ratio was 0.6. CT scan of abdomen showed one solitary tumour in the body of pancreas near its tail. Laparotomy was done. The tumour was found to be a benign insulinoma on microscopic examination. Though the postoperative period was uneventful but he succumbed probably due to pulmonary embolism.


Automatic and controlled semantic processing: a masked prime-task effect.
A classical definition of automaticity establishes that automatic processing occurs without attention or consciousness, and cannot be controlled. Previous studies have demonstrated that semantic priming can be reduced if attention is directed to a low-level of analysis. This finding suggests that semantic processing is not automatic since it can be controlled. In this paper, we present two experiments that demonstrate that semantic processing may occur in the absence of attention and consciousness. A negative semantic priming effect was found when a low-level prime-task was required and when a masked lexical decision prime-task was performed (Experiment 1). This paper also discusses the limitations of the inhibitory mechanism involved in negative semantic priming effect.


[Antibody response to P-fimbriae of Escherichia coli in patients with genitourinary infections].
The serum antibody response to P-fimbriae of Escherichia coli in patients with genitourinary infections was investigated with enzyme linked immunosorbent assay (ELISA) for P-fimbriae-specific IgG antibody. 1) Female patients with acute pyelonephritis had a significantly (P less than 0.01) higher titer of serum IgG antibody by ELISA, compared with patients with acute cystitis or control subjects. The prevalence of positive serum IgG antibody response was 65% in patients with acute pyelonephritis. 2) Patients with epididymitis with high fever had a significantly (P less than 0.01) higher titer of serum IgG antibody by ELISA, compared with patients with epididymitis without fever or control subjects. The prevalence of positive serum IgG antibody response was 60% in patients with epididymitis with high fever. Therefore, 65% of female patients with acute pyelonephritis and 60% of patients with epididymitis with high fever are infected with P-fimbriated E. coli. The measurement of serum antibody response to P-fimbriae must be helpful for the diagnosis and the antibiotic therapy of epididymitis.


[Association between peripheral perfusion, microcirculation and mortality in sepsis: a systematic review].
Although increasing evidence supports the monitoring of peripheral perfusion in septic patients, no systematic review has been undertaken to explore the strength of association between poor perfusion assessed in microcirculation of peripheral tissues and mortality. A search of the most important databases was carried out to find articles published until February 2018 that met the criteria of this study using different keywords sepsis, mortality, prognosis, microcirculation and peripheral perfusion. The inclusion criteria were studies that assessed association between peripheral perfusion/microcirculation and mortality in sepsis. The exclusion criteria adopted were: review articles, animal/pre-clinical studies, meta-analyzes, abstracts, annals of congress, editorials, letters, case-reports, duplicate and articles that did not present abstracts and/or had no text. 26 articles were chosen in which 2465 patients with sepsis were evaluated using at least one recognized method for monitoring peripheral perfusion. The review demonstrated a heterogeneous critically ill group with a mortality-rate between 03% and 71% (median=37% [28%-43%]). The most commonly used methods for measurement were Near-Infrared Spectroscopy (NIRS) (07 articles) and Sidestream Dark-Field (SDF) imaging (05 articles). The vascular bed most studied was the sublingual/buccal microcirculation (08 articles), followed by fingertip (04 articles). The majority of the studies (23 articles) demonstrated a clear relationship between poor peripheral perfusion and mortality. In conclusion, the diagnosis of hypoperfusion/microcirculatory abnormalities in peripheral non-vital organs was associated with increased mortality. However, additional studies must be undertaken to verify if this association can be considered a marker of the gravity or a trigger factor for organ failure in sepsis.


A 1-year follow-up of effects of exercise programs on well-being in older adults.
The purpose of this study was to investigate the long-term effects of three types of training on wellbeing and frequency of physical activity and to determine whether preintervention motivation moderates the effects. Sixty-two older adults (M = 75 years old, SD = 5; 61% women) completed 4-mo programs of endurance, functional or strength training, with reassessment of well-being (life satisfaction, positive affect, negative affect, vitality) and physical activity 12 mo later. All groups showed small improvements in most measures of well-being at 4 mo. At follow-up, endurance training still had small beneficial effects, while changes with functional and strength training were generally trivial or harmful. Analysis for moderators indicated that autonomously motivated individuals better maintained gains in well-being and had higher frequencies of physical activity at follow-up compared with controlled individuals. Endurance training is recommended for older adults, but the long-term outcomes depend on the individual's motivational regulation at commencement.


Egg longevity and time-integrated fertilization in a temperate sea urchin (Strongylocentrotus droebachiensis).
Recent field experiments have suggested that fertilization levels in sea urchins (and other broadcast spawners that release their gametes into the water column) may often be far below 100%. However, past experiments have not considered the potentially positive combined effects of an extended period of egg longevity and the release of gametes in viscous fluids (which reduces dilution rates). In a laboratory experiment, we found that eggs of the sea urchin Strongylocentrotus droebachiensis had high viability for 2 to 3 d. Fertilization levels of eggs held in sperm-permeable egg baskets in the field and exposed to sperm slowly diffusing off a spawning male increased significantly with exposure from 15 min to 3 h. In a field survey of time-integrated fertilizations (over 24, 48, and 72 h) during natural sperm release events, eggs held in baskets accrued fertilizations over as much as 48 h and attained fairly high fertilization levels. Our results suggest that an extended period of egg longevity and the release of gametes in viscous fluids may result in higher natural fertilization levels than currently expected from short-term field experiments.


Computational Investigation of the Photochemical Reaction Path of Some Synthesized and Experimentally Analyzed Small-Chain Conjugated Nitrones.
This combined theoretical and experimental study has revealed the photochemistry of two small open-chain conjugated N-methylnitrone systems with phenyl substitutions at the C-terminal positions. The UV spectra of these synthesized nitrones have shown intense peaks around 330 nm while the new bands formed near 260 nm after their photoirradiation are predicted to be arising from the photoproduct oxaziridine. Photoexcitation of α-styryl N-methylnitrone populates the first excited singlet state which relaxes by 8 kcal/mol from the vertically excited state and subsequently goes toward the lowest-energy conical intersection (CI) geometry (situated 27-30 kcal/mol below) with a terminal CNO-kink. Following the gradient difference vectors of this CI, we have located the oxaziridine structure with its characteristic geometry at roughly 14 kcal/mol above the ground state. This whole process is triggered by a transfer of electronic cloud from oxygen to the conjugated chain side. On the other hand, the photoexcitation of the nonplanar 3,3-diphenylethylene N-methylnitrone has two strong singlet-singlet absorptions with almost 5 D transition moment values. Here the initial S2-S1 relaxation is followed by oxaziridine formation through the terminally twisted CI. However, the initially photoexcited S1 state in this nitrone is found to head toward some other direction with transfer of huge amount of nonbonding electron cloud of oxygen to the π* orbital, creating a stable excited state geometry with an elongated N-O bond which gets involved in a sloped CI with the ground state.


Direct determination of tagitinin C in Tithonia diversifolia leaves by on-line coupling of supercritical carbon dioxide extraction to FT-IR spectroscopy by means of optical fibres.
Supercritical fluid extraction (SFE) with carbon dioxide as extraction medium was on-line coupled to a FT-IR spectrometer equipped with a Mercury Cadmium Telluride (MCT) detector using a tailor-made high-pressure fibre optic flow cell. This method was optimised and developed for the monitoring in real time and the quantification of dynamic extractions of tagitinin C from Tithonia diversifolia leaves. In order to demonstrate the method ability to allow the direct quantification of tagitinin C in the extract medium the standard addition method was used. The area integration of curves obtained by plotting the absorbance of the highly specific C=O stretching vibration at 1668cm(-1) versus time (i.e. extractograms) was used as instrumental response. The SFE/FT-IR process was successfully validated using the accuracy profile as decision tool. On this basis, a linear regression model was chosen for the calibration curve. The relative standard deviation for repeatability and intermediate precision were between 0.8 and 3.1 %, respectively. Moreover, the method was found to be accurate as the two-sided 95% beta-expectation tolerance interval did not exceed the acceptance limits of 85 and 115% on the analytical range investigated (500-2500microg of added amount of tagitinin C). The proposed method allowed the non-destructive extraction of tagitinin C and its on-line quantitative determination in less than 25min thus facilitating the subsequent experiments or the pharmacological studies performed on this compound.


Topotecan treatment of adults with primary malignant glioma. The Brain Tumor Center at Duke.
Topotecan activity was evaluated for the treatment of malignant glioma. Sixty-three patients with newly diagnosed (n = 25) or recurrent (n = 38) malignant glioma were treated with topotecan [AU: Please verify all dosages here and throughout text.]at a dose of 2.6 mg/m2 over a 72-hour period weekly. Recurrent tumors included glioblastoma multiforme (GBM) (n = 28) and anaplastic astrocytoma (AA) (n = 10). Newly diagnosed tumors included GBM (n = 14), AA (n = 8), and anaplastic oligodendroglioma (n = 3). Partial responses were observed in 2 of 14 evaluable patients with newly diagnosed GBM, 1 of 8 patients with newly diagnosed AA, 3 of 10 patients with recurrent AA, and none of 28 patients with recurrent GBM. Four patients with recurrent AA and 7 patients with recurrent GBM demonstrated stable disease (range, 8-52 weeks; median, 21 weeks). Toxicity was limited to infrequent National Cancer Institute Common Toxicity Criteria Grade 3 myelosuppression. These results suggest that topotecan has modest activity against malignant glioma and continued evaluation of its effectiveness may be warranted when alternative schedules or combination regimens are used.


Modelling the effect of the 2018 summer heatwave and drought on isoprene emissions in a UK woodland.
Projected future climatic extremes such as heatwaves and droughts are expected to have major impacts on emissions and concentrations of biogenic volatile organic compounds (bVOCs) with potential implications for air quality, climate, and human health. While the effects of changing temperature and photosynthetically active radiation (PAR) on the synthesis and emission of isoprene, the most abundant of these bVOCs, are well-known, the role of other environmental factors such as soil moisture stress are not fully understood and are therefore poorly represented in land surface models. As part of the Wytham Isoprene iDirac Oak Tree Measurements (WIsDOM) campaign, continuous measurements of isoprene mixing ratio were made throughout the summer of 2018 in Wytham Woods, a mixed deciduous woodland in southern England. During this time, the United Kingdom experienced a prolonged heatwave and drought, and isoprene mixing ratios were observed to increase by more than 400% at Wytham Woods under these conditions. We applied the state-of-the-art FORest Canopy-Atmosphere Transfer (FORCAsT) canopy exchange model to investigate the processes leading to these elevated concentrations. We found that although current isoprene emissions algorithms reproduced observed mixing ratios in the canopy before and after the heatwave, the model underestimated observations by ~ 40% during the heatwave-drought period implying that models may substantially underestimate the release of isoprene to the atmosphere in future cases of mild or moderate drought. Stress-induced emissions of isoprene based on leaf temperature and soil water content were incorporated into current emissions algorithms leading to significant improvements in model output. A combination of soil water content, leaf temperature and rewetting emission bursts provided the best model-measurement fit with a 50% improvement compared to the baseline model. Our results highlight the need for more long-term ecosystem-scale observations to enable improved model representation of atmosphere-biosphere interactions in a changing global climate.


Overexpressions of miR-212 are associated with poor prognosis of patients with pancreatic ductal adenocarcinoma.
The miR-212 was among the top differentially expressed miRNAs in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the expression of miR-212 in PDAC and evaluate its correlation with major clinicopathologic features and patients' survival. Fluorescence in situ hybridization (FISH) was adopted to examine miRNA expression in 45 pancreatic cancer and 20 normal pancreatic tissues. The relationship of miR-212 expression with clinicopathologic parameters and clinical outcome was evaluated. miR-212 was confirmed to have significantly higher expression in PDAC compared with normal pancreatic tissues (51.1% vs 10%, p< 0.01). High expression of miR-212 was significantly associated with tumor size (p = 0.048) and tumor stage (p = 0.023). Moreover, in univariant analysis, patients with high expression of miR-212 demonstrate significantly poorer overall survival (p= 0.02). High expression of miR-212 in PDAC is associated with shorter overall survival. It may be not only a potential prognostic marker, but also a possible therapeutic target in PDAC.


A simplified stratification system for venous thromboembolism risk in severely injured trauma patients.
The objective of this study was to re-evaluate and simplify the Greenfield risk assessment profile (RAP) for venous thromboembolism (VTE) in trauma using information readily available at the bedside. Retrospective review of 1233 consecutive admissions to the trauma intensive care unit from August 2011-January 2015. Univariate analyses were performed to determine which RAP risk factors were significant contributors to VTE. Multivariable logistic regression was used to develop models for risk stratification. All results were considered statistically significant at P ≤ 0.05. The study population was as follows: age 44 ± 19, 75% male, 72% blunt, injury severity score 21 ± 13, RAP score 9 ± 5, and 8% mortality. Groups were separated into +VTE (n = 104) and -VTE (n = 1129). They were similar in age, gender, mechanism, and mortality, but injury severity and RAP scores were higher in the +VTE group (all P < 0.0001). The +VTE group had more transfusions and longer time to prophylaxis (all P < 0.05). Receiving four or more transfusions in the first 24 h (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.64-4.13), Glasgow coma score <8 for >4 h (OR, 2.13; 95% CI, 1.28-3.54), pelvic fracture (OR, 2.26; 95% CI, 1.44-3.57), age 40-59 y (OR, 1.70; 95% CI, 1.10-2.63), and >2-h operation (OR, 1.80; 95% CI, 1.14-2.85) predicted VTE with an area under the receiver operator curve of 0.729, which was comparable with 0.740 for the RAP score alone. VTE risk in trauma can be easily assessed using only five risk factors, which are all readily available at the bedside (transfusion, Glasgow coma scale, pelvic fracture, prolonged operation, and age). This simplified model provides similar predictive ability to the more complicated RAP score. Prospective validation of a simplified risk assessment score is warranted.


Platelet radiolabelling with 111 Indium for in vivo studies: a methodological reappraisal.
Two ligands widely used for 111In labeling of human platelets, oxine and tropolone, were compared as to the degree of their influence on platelet function. The labelling efficiency was assessed as a function of experimental variables. A good preservation of platelet function as evaluated by ex vivo aggregation was obtained with both techniques. The extent of tracer detached from platelets was evaluated in vitro and in vivo: in normal subjects 111In was virtually all bound to platelets. A significant reduction in radiolabelling efficiency and a decreased percentage of 111In bound to platelets in vivo was observed in patients with platelet counts < 150,000/mL.


Bowel care practices in chronic spinal cord injury patients.
To determine current characteristics of bowel care practices of chronic spinal cord injury (SCI) patients. Prospective interview and examination of 100 SCI patients injured for more than 1 year. Freestanding rehabilitation outpatient SCI center. One hundred chronic SCI patients. The following bowel program characteristics were found: alternate-day programs were most common; most subjects performed their programs in the morning; and tetraplegic subjects performed their programs less often, used suppositories more often, required greater assistance, and took longer to complete their programs. Bowel dysfunction in chronic SCI need not be associated with complications in the majority of cases.


The large-conductance potassium ion channel of rabbit corneal epithelium is blocked by quinidine.
Basal layers of the rabbit corneal epithelium contain a large-conductance potassium ion (K+) selective channel (160-170 pS in 150 mM KCl). This channel previously was shown to be blocked by cesium and barium ions applied to its outer surface. By direct patch clamp experiments, it is shown that the channel also is blocked by quinidine in the 0.1-1 mM range when applied either to the outside or inside of membrane patches containing these channels. This additional pharmacologic tool should aid in identifying the individual currents that compose the macroscopic currents from corneal epithelial cells and eventually should help to provide a detailed assessment of their function.


Expression of basement membrane components in odontogenic tumors.
The objective was to characterize the expression of BMCs (laminins 1 and 5, collagen type IV, and fibronectin) in ameloblastomas, calcifying cystic odontogenic tumors (CCOTs), and adenomatoid odontogenic tumors (AOTs). BMCs were analyzed in 14 ameloblastomas, 7 CCOTs, and 7 AOTs using immunohistochemistry. In normal oral mucosa, linear deposits of these proteins were found at the epithelial-mesenchymal junction, but not in epithelial cytoplasm. In all tumors studied, linear deposits of all proteins were found at the epithelial-mesenchymal junction; laminin 1 was expressed in all tumor cells, regardless of cell types. For CCOTs, laminin 5 was found faintly in suprabasal cells, but expressed strongly in ghost cells. For AOTs, laminin 5 strongly decorated tumor cells adjacent to mineralization. Laminin 1 may be a marker for odontogenic epithelium. Additionally, laminin 5 may be involved in ghost cell formation and initiation of calcification.


Critical evaluation of toxic versus beneficial effects of methylglyoxal.
In various organisms, an array of enzymes is involved in the synthesis and breakdown of methylglyoxal. Through these enzymes, it is intimately linked to several other physiologically important metabolites, suggesting that methylglyoxal has some important role to play in the host organism. Several in vitro and in vivo studies showed that methylglyoxal acts specifically against different types of malignant cells. These studies culminated in a recent investigation to evaluate a methylglyoxal-based formulation in treating a small group of cancer patients, and the results were promising. Methylglyoxal acts against a number of pathogenic microorganisms. However, recent literature abounds with the toxic effects of methylglyoxal, which are supposed to be mediated through methylglyoxal-derived advanced glycation end products (AGE). Many diseases such as diabetes, cataract formation, hypertension, and uremia are proposed to be intimately linked with methylglyoxal-derived AGE. However methylglyoxal-derived AGE formation and subsequent pathogenesis might be a very minor event because AGE are nonspecific reaction products that are derived through the reactions of carbonyl groups of reducing sugars with amino groups present in the side chains of lysine and arginine and in terminal amino groups of proteins. Moreover, the results of some in vitro experiments with methylglyoxal under non-physiological conditions were extrapolated to the in vivo situation. Some experiments even showed contradictory results and were differently interpreted. For this reason conclusions about the potential beneficial effects of methylglyoxal have often been neglected, thus hindering the advancement of medical science and causing some confusion in fundamental understanding. Overall, the potential beneficial effects of methylglyoxal far outweigh its possible toxic role in vivo, and it should be utilized for the benefit of suffering humanity.


Utilization of ketone bodies by chick brain and spinal cord during embryonic and postnatal development.
Lipid synthesis from acetoacetate and 3-hydroxybutyrate was studied in chick embryo from 15 to 21 days and in chick neonate from 1 to 21 days. Embryonic spinal cord showed higher ability than brain to incorporate acetoacetate into total lipids, although a sharp decrease was found at hatching. 3-Hydroxybutyrate incorporation into total lipids was also higher in spinal cord than in brain, especially during the embryonic period. Phospholipids were the main lipids formed in both tissues from both precursors. An appreciable percentage of radioactivity was also recovered as free cholesterol, especially during the embryonic phase. The developmental patterns of amino acid synthesis from acetoacetate and 3-hydroxybutyrate were similar in both tissues: a clear increase after hatching was followed by a decrease at day 4 of neonatal life. Acetoacetate was a better substrate for amino acid synthesis than 3-hydroxybutyrate during the embryonic development in both tissues. Oxidation of both precursors to CO2 strongly decreased between 15 and 21 days of embryonic development both in brain and spinal cord.


Improving the diagnostic criteria and procedures for chronic fatigue syndrome.
Since the publication of the case definition for chronic fatigue syndrome (CFS) in 1988 the diagnostic criteria have been revised twice in the U.S. None of the case definitions were derived empirically. As a result, there is concern regarding the sensitivity, specificity, and reliability of the criteria. The goal of the present study was to identify methods for improving the diagnostic criteria for CFS. Three groups of 15 participants each were recruited: participants with (1) CFS, (2) major depressive disorder (MDD), and (3) healthy controls. Using statistical procedures, three methods for improving the diagnostic criteria were explored: identification of new diagnostic symptoms, the use of severity ratings for symptomatology, and the identification of standardized measures that differentiate cases of CFS from other conditions. Results of the present study suggest that these three methods hold promise for improving the sensitivity, specificity, and reliability of the diagnostic criteria for CFS.


Fracture and migration of Celect inferior vena cava filters: a retrospective review of 741 consecutive implantations.
To determine the incidence of fracture and migration of the Celect inferior vena cava (IVC) filter at a single tertiary-care center. Images obtained after placement of Celect IVC filters between August 2007 and January 2013 were retrospectively reviewed for evidence of device fracture and migration. The probability of filter fracture at 6 and 12 months after filter placement was estimated, and a 95% upper confidence bound was constructed. A total of 741 consecutive Celect filters were placed, and the following studies were subsequently evaluated: 301 abdominal radiographs, 282 abdominal computed tomography (CT) scans, 154 cavagrams, 19 lumbar spine radiographs, 462 chest radiographs, 108 chest CT scans, and 31 pelvic radiographs. The mean imaging follow-up interval was 5.78 months ± 8.80 (range, 0.01-56.03 mo). There was no filter fracture or en-bloc migration outside the IVC. Upper 95% confidence bounds for the probability of fracture were 1.8% at 6 months and 4.3% at 12 months. Intracaval filter migration of more than 2 cm (mean, 2.43 ± 0.12 cm; range, -2.54 to 2.99 cm) was seen in 3.9% of patients (21 of 534; 12 cranial and nine caudal). No fracture of a Celect filter was observed in this large cohort over a relatively short follow-up interval. The results also suggest that the Celect filter has an adequate securing mechanism to prevent distant en-bloc or significant intracaval migration.


Quantitative contributions of CtBP-dependent and -independent repression activities of Knirps.
The Drosophila Knirps protein is a short-range transcriptional repressor that locally inhibits activators by recruiting the CtBP co-repressor. Knirps also possesses CtBP-independent repression activity. The functional importance of multiple repression activities is not well understood, but the finding that Knirps does not repress some cis-regulatory elements in the absence of CtBP suggested that the co-factor may supply a unique function essential to repress certain types of activators. We assayed CtBP-dependent and -independent repression domains of Knirps in Drosophila embryos, and found that the CtBP-independent activity, when provided at higher than normal levels, can repress an eve regulatory element that normally requires CtBP. Dose response analysis revealed that the activity of Knirps containing both CtBP-dependent and -independent repression activities is higher than that of the CtBP-independent domain alone. The requirement for CtBP at certain enhancers appears to reflect the need for overall higher levels of repression, rather than a requirement for an activity unique to CtBP. Thus, CtBP contributes quantitatively, rather than qualitatively, to overall repression function. The finding that both repression activities are simultaneously deployed suggests that the multiple repression activities do not function as cryptic 'backup' systems, but that each contributes quantitatively to total repressor output.


Spiral enteroscopy: prime time or for the happy few?
Spiral enteroscopy is the newest of the deep enteroscopy techniques. The current technique employs an overtube with a raised spiral at the distal end to pleat the small intestine and achieve deep small bowel intubation. Although spiral enteroscopy is a novel technique, the learning curve is comparable to the balloon enteroscopy techniques. There is some evidence of improved speed of spiral enteroscopy procedures with superior control compared to the balloon endoscopy technologies. Altered surgical anatomy deep enteroscopy has been shown to have similar safety and efficacy to competitive technologies, particularly in cases of Roux-en-Y ERCP cases. Spiral enterosopy is safe and effective for deep small bowel enteroscopy and diagnostic yield and therapeutic yields are similar to alternate technologies. There are bright future applications of the technology with enteroscopes and an integrated spiral. Spiral enteroscopy is an advanced technique that can be performed by any skilled endoscopist.


Production and characterization of recombinant cyprosin B in Saccharomyces cerevisiae (W303-1A) strain.
The Saccharomyces cerevisiae W303-1A strain transformed with a centromeric plasmid containing CYPRO11, which codifies the aspartic protease cyprosin B, was grown in a 3 l bioreactor under aerobic conditions. Expression of cyprosin B is directly dependent on the concentration of galactose used as the inducer and carbon source in 1% yeast extract, 2% bactopeptone, and 4% galactose in culture medium. For 4% of galactose, 209 mg.l(-1) total protein, and 1036 U.ml(-1) recombinant cyprosin B activity were obtained from 6.1 g dcw.l(-1) biomass. The recombinant cyprosin B, purified by two consecutive anion-exchange chromatographies (diethyl amino-ethyl [DEAE]-Sepharose and Q-Sepharose XK-16 columns), shows a specific activity of 62 x 10(3) U.mg(-1), corresponding to a purification degree of 12.5-fold and a recovery yield of 25.6% relative to that in fermentation broth. The proteolytic activity of recombinant cyprosin B is optimal at 42 degrees C and pH 4.5. The recombinant cyprosin B activity is 95% inhibited by pepstatin A, which confirms its aspartic protease nature. The pure recombinant cyprosin B is composed of two subunits, one with 14 and the other with 32 kDa. It exhibits clotting activity, similar to that of the natural enzyme from Cynara cardunculus flowers. The results reported here show that recombinant cyprosin B, the first clotting protease of plant origin produced in a bioreactor, can now be produced in large scale and may constitute a new and efficient alternative to enzymes of animal or fungal origin that are widely used in cheese making.


Toxicology and carcinogenesis studies of p,p'-dichlorodiphenyl sulfone in rats and mice.
p,p'-Dichlorodiphenyl sulfone (DDS) is used as a starting material in the production of polysulfones and polyethersufones, a family of thermoplastics. DDS was studied because of its high production volume and use. In toxicology studies, 10 Fischer 344 rats and 10 B6C3F1 mice/sex/group were fed diets containing 0, 30, 100, 300, 1,000 or 3,000 ppm DDS for 14 weeks. All animals survived until the end of the studies. Mean body weights of groups exposed to 300 ppm or greater were significantly decreased. Liver and kidney in rats and liver in mice were the major target organs of DDS toxicity. Dose-related increases in liver weights and incidences of centrilobular hepatocyte hypertrophy were observed in DDS-exposed groups. Nephropathy was seen in male and female rats only at and above 300 ppm. Neurotoxicity evaluations were negative in DDS-treated animals. Clinical chemistry and hematology parameters were minimally affected. In the 2-year toxicity and carcinogenicity studies, 50 rats and 50 mice/sex/group were fed diets containing 0, 10 (male rats), 30, 100, or 300 ppm DDS for 104 to 105 weeks. Survival of exposed groups was not affected. There were no clinical signs of toxicity related to DDS exposure. Final mean body weights were 2-17% lower in DDS-treated groups. Liver was the only target organ of DDS-induced toxicity. The incidence of centrilobular hepatocyte hypertrophy in mice and rats, and the incidence of bile duct hyperplasia and centrilobular degeneration in female rats was significantly greater than in controls. A no-observed-adverse-effect level (NOAEL) of 30 ppm DDS in the diet (1.5 mg/kg body weight) was established for rats. DDS was not carcinogenic in these studies.


Dietary exposure to cadmium at close to the current provisional tolerable weekly intake does not affect renal function among female Japanese farmers.
Dietary cadmium (Cd) exposure and renal tubular function were investigated in 1381 female farmers from five districts in Japan (Japanese Multi-centered Environmental Toxicant Study project; JMETS). Dietary Cd exposure of the five populations was assessed from the individual Cd concentrations of the rice consumed by the study participants and the quantities of rice consumed daily. The populations showed a sequential difference in dietary Cd exposure, ranging from a level as low as that of the general Japanese population to one close to the current provisional tolerable weekly intake (PTWI). The levels of urinary Cd excretion, an indicator of Cd accumulation in the kidneys, increased along the same sequential pattern as dietary Cd exposure. However, no differences were observed among the populations in levels of urinary alpha 1-microglobulin and beta 2-microglobulin excretion, which are indicators of renal tubular function. These results indicate that the current PTWI is sufficient to prevent Cd-induced renal dysfunction among the general population.


L-arginine restores dilator responses of the basilar artery to acetylcholine during chronic hypertension.
The objective of this study was to test the hypothesis that administration of L-arginine, a substrate for nitric oxide synthase, restores acetylcholine-induced dilatation of the basilar artery in chronically hypertensive rats. Basilar artery diameter was measured through a cranial window in anesthesized stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) aged 6 to 7 months (adult) and 12 months (older adult). Under control conditions, baseline basilar artery diameter was smaller in SHRSP (adult, 239 +/- 30 micron; older adult, 198 +/- 13 micron) (mean +/- SE) than in WKY (adult, 261 +/- 10 micron; older adult, 259 +/- 7 micron) (P <.05 versus SHRSP). Topical application of acetylcholine (10(-5) mol/L) produced dilatation of the basilar artery in WKY, which was impaired in both adult and older SHRSP (P <.05). Topical L-arginine (10(-3) mol/L for 30 minutes) did not affect responses to acetylcholine in adult SHRSP but enhanced vasodilatation in response to acetylcholine (10(-5) mol/L) in older SHRSP without affecting responses to sodium nitroprusside. In contrast, D-arginine did not affect acetylcholine-induced vasodilatation in older SHRSP. These results suggest that impaired dilatation of the basilar artery in response to acetylcholine in older SHRSP is restored toward normal by L-arginine, a substrate for nitric oxide synthase.


Enhancement of RecA strand-transfer activity by the RecJ exonuclease of Escherichia coli.
We have examined coupled reactions with the RecA protein of Escherichia coli, which can mediate DNA strand exchange in vitro between homologous DNA molecules, and the RecJ exonuclease, a 5' to 3' single-stranded DNA exonuclease. In RecA-mediated strand-transfer reactions between circular single-stranded and duplex linear DNA, we have found that RecJ stimulates the rate of heteroduplex product formation. Because RecJ must be present concurrent with strand transfer and RecJ does not detectably stimulate the synapsis stage of the reaction, we believe that RecJ stimulates specifically the branch migration phase of the RecA strand-transfer reaction. RecJ also dramatically enhances the efficiency with which RecA is able to transverse regions of non-homology in the substrates. We propose a model where RecJ degrades the displaced strand produced by strand exchange which competes for pairing with the transferred strand, thus driving forward the unidirectional branch migration mediated by RecA protein. This suggests a new role for exonucleases in genetic recombination, facilitating the strand-transfer reaction itself.


Renal function-dependent association of serum uric acid with metabolic syndrome and hepatic fat content in a middle-aged and elderly Chinese population.
The effect of uric acid (UA) on the pathogenesis of metabolic disorders is highly dependent on its physicochemical properties, and hyperuricaemia associated with different conditions may have different clinical meanings. The aim of the present study was to investigate the association of serum UA levels with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in a middle-aged and elderly population with normal and impaired renal function. The cross-sectional study was performed on 1141 participants (426 men, 715 women; mean age 62 years) enrolled from the Shanghai Changfeng community. Each participant underwent a standard interview, with anthropometric and laboratory measurements. Hepatic fat content (HFC) was determined by a newly established quantitative ultrasound method. Univariate correlation analysis showed that serum UA was associated with all components of metabolic syndrome and HFC (r = 0.193, P < 0.001), especially in participants with a normal estimated glomerular filtration rate (eGFR; r = 0.255, P < 0.001). Logistic regression analysis demonstrated an independent association of serum UA with metabolic syndrome and NAFLD in participants with normal renal function, but not in those with eGFR < 90 mL/min per 1.73 m(2) . Furthermore, multivariate linear analysis showed that UA levels were independently associated with HFC (P = 0.003), but only in participants with normal eGFR. Elevated serum UA is independently associated with metabolic syndrome and NAFLD in patients with normal renal excretory function. However, in those with renal insufficiency, hyperuricaemia has no association with metabolic disorders.


Anaerobic hydrogenase activity in Anacystis nidulans. H2-dependent photoreduction and related reactions.
1. Anaerobic hydrogenase activity in whole cells and cell-free preparations of H2-induced Anacystis was studied both manometrically and spectrophotometrically in presence of physiological and artificial electron acceptors. 2. Up to 90% of the activity measured in crude extracts were recovered in the chlorophyll-containing membrane fraction after centrifugation (144 000 X g, 3 h). 3. Reduction of methyl viologen, diquat, ferredoxin, nitrite and NADP by the membranes was light dependent while oxidants of more positive redox potential were reduced also in the dark. 4. Evolution of H2 by the membranes was obtained with dithionite and with reduced methyl viologen; the reaction was stimulated by detergents. 5. Both uptake and evolution of H2 were sensitive to O2, CO, and thiolblocking agents. The H2-dependent reductions were inhibited also by the plastoquinone antagonist dibromothymoquinone, while the ferredoxin inhibitor disalicylidenepropanediamine affected the photoreduction of nitrite and NADP only. 3-(3,4-Dichlorophenyl)-1,1-dimethylurea did not inhibit any one of the H2-dependent reactions. 6. The results present evidence for a membrane-bound 'photoreduction' hydrogenase in H2-induced Anacystis. The enzyme apparently initiates a light-driven electron flow from H2 to various low-potential acceptors including endogenous ferredoxin.


Anti-inflammatory and antifibrotic effects of naringenin in diabetic mice.
Renal protective effects of naringenin at 0.5, 1, and 2% of the diet in diabetic mice were examined. Naringenin supplemented at 1 and 2% increased its deposit in liver and kidney of diabetic mice. Compared with the diabetic control group, naringenin treatments at 1 and 2% lowered plasma levels of glucose and blood urea nitrogen, as well as increased insulin level and creatinine clearance (P < 0.05). Naringenin treatments dose-dependently reduced renal tumor necrosis factor-α level and expression (P < 0.05) but only at 1 and 2% significantly decreased production and expression of interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein-1 (P < 0.05). Naringenin intake at 2% decreased renal formation and expression of type IV collagen, fibronectin, and transforming growth factor-β1 (P < 0.05). This compound at 1 and 2% lowered protein kinase C activity and suppressed nuclear factor κB (NF-κB) p65 activity, mRNA expression, and protein production in kidney. However, this agent only at 2% diminished NF-κB p50 activity, mRNA expression, and protein production (P < 0.05). These results indicate that naringenin could attenuate diabetic nephropathy via its anti-inflammatory and antifibrotic activities.


[Age and time of hospitalization (author's transl)].
A reduction of the time of hospitalization has been repeatedly considered as a cost-saving possibility in the projects of reforming the hospital system. The time of hospitalization of older patients is longer than that of younger patients. Every plan to reduce it fails for lack of flanking institutions, such as geriatric hospitals, nursing homes, etc. However, all age groups include a small number of patients staying in hospital for long periods of time and taking therfore a disproportionately large share in the nursing day total. This fact is proved by statistic data on 11,875 internal cases admitted to the Nuremberg hospitals. The transformation of the complex acute-case hospital into a graded ward system could create a possibility of accommodating, and attending to, this small group of people in better medical conditions and on better financial terms.


TRM6/61 connects PKCα with translational control through tRNAi(Met) stabilization: impact on tumorigenesis.
Accumulating evidence suggests that changes of the protein synthesis machinery alter translation of specific mRNAs and participate in malignant transformation. Here we show that protein kinase C α (PKCα) interacts with TRM61, the catalytic subunit of the TRM6/61 tRNA methyltransferase. The TRM6/61 complex is known to methylate the adenosine 58 of the initiator methionine tRNA (tRNAi(Met)), a nuclear post-transcriptional modification associated with the stabilization of this crucial component of the translation-initiation process. Depletion of TRM6/61 reduced proliferation and increased death of C6 glioma cells, effects that can be partially rescued by overexpression of tRNAi(Met). In contrast, elevated TRM6/61 expression regulated the translation of a subset of mRNAs encoding proteins involved in the tumorigenic process and increased the ability of C6 cells to form colonies in soft agar or spheres when grown in suspension. In TRM6/61/tRNAi(Met)-overexpressing cells, PKCα overexpression decreased tRNAi(Met) expression and both colony- and sphere-forming potentials. A concomitant increase in TRM6/TRM61 mRNA and tRNAi(Met) expression with decreased expression of PKCα mRNA was detected in highly aggressive glioblastoma multiforme as compared with Grade II/III glioblastomas, highlighting the clinical relevance of our findings. Altogether, we suggest that PKCα tightly controls TRM6/61 activity to prevent translation deregulation that would favor neoplastic development.


Differences in presentation and management of stable angina from East to West in Europe: a comparison between Poland and the UK.
Variations in the resources, stability and priorities of health care systems conceivably affect their capacity to implement health care reform and ensure an evidence based approach to health care. Such variation may partially account for differences in cardiovascular mortality rates between former communist states in Central Europe and Western European countries, but specific data on this subject is sparse. The aim of this study was to compare the presentation of stable angina to cardiology services in Poland vs. the United Kingdom, the management of the condition in relation to existing European guidelines and clinical outcome. Data was collected as part of a prospective observational cohort study of stable angina in Europe. Information was recorded on referral patterns, clinical presentation and the use of pharmacological therapies, investigations, revascularisation and cardiovascular events during 1 year of follow up. A total of 571 patients with stable angina were enrolled in Poland and 319 in the UK. Patients presenting to cardiology services in Poland were less likely to be referred by a primary care physician, younger, and had more adverse clinical risk predictors at presentation. Non-invasive investigation and coronary angiography were performed less frequently in Poland, but waiting times for invasive assessment were shorter. European guidelines with regard to the use of evidence based secondary preventative medical therapy were applied widely by cardiologists in both countries. No differences were observed in rates of cardiovascular events. The use of evidence based pharmacological therapy was equally high in both countries, but guidelines regarding investigation were less completely adhered to in Poland, where invasive assessment and subsequent management was prompt but only performed in a highly selected proportion of the population with stable angina.


Chicken heart ubiquinol: cytochrome c reductase--isolation by affinity chromatography and resolution of enzyme into subunits.
Chicken heart mitochondrial ubiquinol: cytochrome c reductase has been isolated as a monodisperse form by solubilization with Triton X-100 in low ionic strength and subsequent affinity chromatography. The enzyme complex contains less than 0.15 mumol ubiquinone and 12 mumol phospholipid per mumol enzyme. The spectrum of cytochrome b in the reduced exhibited two maximum alpha-absorption bands at 558 nm and 562 nm; a shoulder at 553 nm for c1. The purified enzyme complex consists of at least 9 subunits with apparent molecular weight of 47 K, 44 K, 36 K, 31 K, 25 K, 17 K, 15 K, 12 K and 9 K. The enzyme complex has been dissociated into subdomains of subunits in the presence of increasing concentration of salt and Triton X-100. Three subunits carrying the redox centers (cytochrome b, cytochrome c1 and Fe-S protein) have been further isolated.


Mechanisms of apoptosis of T-cells in human tuberculosis.
The role of TGF-beta TNF-alpha FasL and Bcl-2 in apoptosis of CD4 T-cells during active TB was studied. Coculture of PBMC from TB patients with neutralizing antibodies to TGF-beta or TNF-alpha decreased spontaneous (P < or = 0.05) and MTB-induced (P < or = 0.02) T-cell apoptosis by 50-90%, but effects were not additive. Interestingly, only levels of TGF-beta in supernatants correlated with rates of spontaneous and MTB-induced apoptosis. FasL surface and mRNA expression were higher in unstimulated and MTB-stimulated PBMC from patients than controls, and neutralization of FasL abrogated apoptosis of T-cells from patients only. Intracellular Bcl-2 protein was lower among unstimulated CD4 T-cells from patients than those from controls (P < or = 0.02), and MTB stimulation reduced intracellular Bcl-2 content in CD4 T-cells from patients only (P < or = 0.001). These findings may indicate that, during TB, predisposition of CD4 T-cells to apoptosis may involve both low expression of Bcl-2, and excessive expression of TGF-beta TNF-alpha and FasL.


Reducing stroke in women with risk factor management: blood pressure and cholesterol.
Stroke is a major cause of death and disability in adults worldwide. Prevention focused on modifiable risk factors, such as hypertension and hyperlipidemia, has shown them to be of significant importance in decreasing the risk of stroke. Multiple studies have brought to light the differences between men and women with regards to stroke and these risk factors. Women have a higher prevalence of stroke, mortality and disability and it has been shown that preventive and treatment options are not as comprehensive for women. Hence, it is of great necessity to evaluate and summarize the differences in gender and stroke risk factors in order to target disparities and optimize prevention, especially because women have a higher lifetime risk of stroke. The purpose of this review is to summarize sex differences in the prevalence of hypertension and hyperlipidemia. In addition, we will review the sex differences in stroke prevention effectiveness and adherence to blood pressure and cholesterol medications, and suggest future directions for research to reduce the burden of stroke in women.


Regulation of soil organic C mineralisation at the pore scale.
Little is known about the factors that regulate C mineralisation at the soil pore scale or how these factors vary throughout the pore network. This study sought to understand how the decomposition of organic carbon varies within the soil pore network and to determine the relative importance of local environmental properties relative to biological properties as controlling factors. This was achieved by sterilising samples of soil and reinoculating them with axenic bacterial suspensions using the matric potential to target different locations in the pore network. Carbon mineralisation curves were described with two-compartment first-order models to distinguish CO2 derived from the labile organic carbon released during sterilisation from CO2 derived from organic C unaffected by sterilisation. The data indicated that the size of the labile pool of organic C, possibly of microbial origin, varied as a function of location in the pore network but that the organic carbon unaffected by sterilisation did not. The mineralisation rate of the labile C varied with the bacterial type inoculated, but the mineralisation rate of the organic C unaffected by sterilisation was insensitive to bacterial type. Taken together, the results suggest that microbial metabolism is a less significant regulator of soil organic carbon decomposition than are microbial habitat properties.


Role of peroxisome proliferator-activated receptor-γ in atherosclerosis: an update.
Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the ligand-activated nuclear receptor family. Thiazolidinediones, such as rosiglitazone and pioglitazone, are synthetic agonists selective for PPARγ and have been used in the clinical treatment of type 2 diabetes. However, beyond the metabolic effects on glycemic control, PPARγ and its ligands also have profound effects on cardiovascular biological and pathophysiological processes. As cardiovascular diseases are closely associated with insulin resistance, and the major cause of death and complications of type 2 diabetes, a comprehensive understanding of the cardiovascular roles of this receptor is critical for the rational application of the existing agonists and the future development of therapeutic modulators. Therefore, this review will focus on the recent advances regarding the cardiovascular functions of PPARγ and its recognized effects on major cardiovascular diseases, in particular, atherosclerosis and associated processes.


Role of microRNA-93 in regulation of angiogenesis.
Angiogenesis is essential for a wide variety of physiological and pathological processes. To date, many angiogenic microRNAs (miRNAs) have been identified and several of them were further investigated to elucidate the mechanisms of specific miRNAs in regulating angiogenesis. In recent studies concerning tumor and ischemia, the miRNA-93 had been demonstrated to be able to modulate angiogenesis in different molecular pathways. The miRNA-93 can promote angiogenesis via enhancing endothelial cell proliferation, migration, and tube formation. Additionally, miRNA-93-over-expressing cells developed a relationship with the blood vessels allowing tumor cells to survive and to grow well. However, high expression of miRNA-93 can depress the vascular endothelial growth factor (VEGF) secretion and its downstream molecular targets in in vivo and vitro experiments. MiRNA-93's effects on angiogenesis are dependent on the interaction of other multiple genes and signal pathways, such as P21, E2F1, integrin-β8, LATS2, etc. Future investigation should involve mapping the network by which miRNA-93 exerts its functions.


Angiogenesis inhibitors for the treatment of chronic autoimmune inflammatory arthritis.
Angiogenesis, the formation of new blood vessels, is closely linked with both the initiation and progression of rheumatoid arthritis (RA). Rheumatoid joints contain elevated levels of proangiogenic molecules, such as VEGF, basic FGF, hypoxia-inducible factor 1 and angiopoietins. Increased angiogenesis is also associated with malignancies and proliferative retinopathies, and targeting this process therapeutically has proven beneficial in treating several of these diseases including colorectal, kidney and lung cancer. Adapting such a therapeutic strategy to the treatment of RA may prove beneficial, as data from preclinical studies have demonstrated that angiogenesis inhibitors reduce pannus formation, inflammation and joint erosion. New therapies that inhibit angiogenesis by blocking VEGFR tyrosine kinase signaling, integrin interactions, microtubule formation and endothelial cell proliferation may be applicable to the treatment of RA. There are several angiogenesis inhibitors that have been approved by the FDA or are currently being assessed in clinical trials which are safe for use in humans, although their effects on RA remain untested. This review discusses the potential of angiogenesis inhibition in the context of treating RA.


sMLACF: a generalized expectation-maximization algorithm for TOF-PET to reconstruct the activity and attenuation simultaneously.
The 'simultaneous maximum-likelihood attenuation correction factors' (sMLACF) algorithm presented here, is an iterative algorithm to calculate the maximum-likelihood estimate of the activity λ and the attenuation factors a in time-of-flight positron emission tomography, and this from emission data only. Hence sMLACF is an alternative to the MLACF algorithm. sMLACF is derived using the generalized expectation-maximization principle by introducing an appropriate set of complete data. The resulting iteration step yields a simultaneous update of λ and a which, in addition, enforces in a natural way the constraints [Formula: see text] where [Formula: see text] is a fixed lower bound that ensures the boundedness of the reconstructed activities. Some properties-like the monotonic increase of the likelihood and the asymptotic regularity of the estimated [Formula: see text]-of sMLACF are proven. Comparison of sMLACF with MLACF for two data sets reveals that both algorithms show very similar results, although sMLACF converges slower.


End-organ recovery is key to success for extracorporeal membrane oxygenation as a bridge to implantable left ventricular assist device.
Preexisting organ dysfunctions are known factors of death after placement of implantable mechanical circulatory support (MCS). Extracorporeal membrane oxygenation (ECMO) may able to stabilize organ function in patients with cardiogenic shock before MCS implantation. Between 2008 and 2012, 17 patients with cardiogenic shock were supported with ECMO before implantable MCS placement. Patient's end-organ functions were assessed by metabolic, cardiac, hepatic, renal, and respiratory parameters. Survival data after MCS implantations were analyzed for overall survival to discharge, complications, and breakpoint in days on ECMO to survival. Before MCS implantation, lactate, hepatic, and renal functions were improved and pulmonary edema was resolved. The interval between ECMO initiation and MCS placement was 12.1 ± 7.9 days. Overall survival rate to discharge after left ventricular assist device/total artificial heart placement was 76%. The survival of patients transitioned from ECMO to MCS within 14 days was 92% and was significantly better than the survival of patients from ECMO to MCS supported longer than 14 days, 25%, p < 0.05. ECMO support can immediately stabilize organ dysfunction in patients with cardiogenic shock. After improvement of organ function, MCS implantation should be done without delay, since the patients supported for longer than 14 days with ECMO had inferior survival compared to national data.


Congenital anomalies of the inferior vena cava: embryogenesis and MR features.
This article describes the MR appearances of the six most common congenital anomalies of the inferior vena cava. As a basis for understanding those anomalies, it describes the embryology of the inferior vena cava, based on an actual study of embryos and fetuses. The article takes a fresh look at the original research in this area, discusses the possible embryogenesis of the relevant anomalies, and describes different opinions on that subject, where different opinions exist.


Betrixaban: A Novel Factor Xa Inhibitor for the Prevention of Venous Thromboembolism in Acutely Ill Medical Patients.
Venous thromboembolism (VTE) is a common and preventable cause of morbidity and mortality in hospitalized patients. Low-molecular-weight heparin, low-dose unfractionated heparin, fondaparinux, and warfarin have been the mainstay options for the prevention and treatment of VTE before the emergence of nonvitamin K antagonist oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban. Despite the advantages of NOACs in improving patient adherence, none of them are approved for the prevention of VTE in acutely ill medical patients at high risk of thromboembolism. Betrixaban is a new NOAC and a factor Xa inhibitor that was approved for extended-duration thromboprophylaxis in these high-risk patients. The approval was based on the results of the APEX (Acute Medically Ill VTE Prevention with Extended Duration Betrixaban) study. In this Phase III randomized controlled trial, once-daily oral betrixaban (35 to 42 days extended duration) was associated with a reduction of composite VTE with no difference in major bleeding when compared to once-daily subcutaneous enoxaparin (6 to 14 days standard duration). Betrixaban differs from other NOACs by having a longer half-life, minimal CYP450 interactions, and minimal renal clearance. This article provides an overview of betrixaban's pharmacological profile, clinical trial results, and potential roles in therapy.


Assessing the impact of a modified informed consent process in a South African HIV/AIDS research trial.
The process of informed consent may be jeopardized in cross-linguistic research trials but little is known about the factors which contribute to this. The present study was designed to assess the impact on the understanding of trial participants of the essential components of a trial, as well as on the perceptions of the participants, through enrollment via a standard versus a modified informed consent protocol. Counselors from two HIV trial sites in South Africa were trained to enroll patients for a trial, using a modified informed consent protocol. The standard and modified protocols were compared. Marked differences were noted in effectiveness of the process after training using the modified protocol, resulting in improved patient understanding. An item analysis suggested those areas of the trial which were most difficult for counselors to communicate effectively and highlighted potential barriers and facilitators to the process. Cultural and linguistic modifications to the informed consent process can enhance the understanding of components of a research trial and are viewed as largely positive by the participants. Some implications for future enrollments, for developing policy and for the role of a language specialist on research ethics committees and in trial design are highlighted.


Evaluating the palatability of fermented foods.
The present review deal with the novel studies which present possibility of generating a novel sensory evaluation instrument for describing comprehensive food palatability. These studies suggest the palatability can be dissected into its componential subdomains and the subdomains in turn reconstitute comprehensive palatability with evaluation of the quantitative contribution of each subdomain. The studies suggest the novel instrument is useful for comprehensive evaluation of palatability of multifarious fermented foods.


[Prognostic factors in the response of a first line chemotherapy in advanced breast cancer].
Anthracyclines containing regimen are widely used in advanced breast cancer. The response to first line chemotherapy varies according to many individual factors and the theoretical response to a given protocol cannot predict the response of a patient. A randomized clinical trial (ERASME) was initiated in order to evaluate the more appropriate first line chemotherapy scheme in advanced breast cancer. Prognostic factors were included in a multiple logistic regression to explain the response after the first 3 chemotherapy courses (monthly FEC). Three factors were found to be statistically significant: adjuvant hormonotherapy, loco-regional metastases, adjuvant adriamycin containing regimen (pejorative prognostic factor). By combining these factors, this statistical model enables us to predict a response rate to a first line chemotherapy from 27 to 87%. Such a model can be taken into account in a decision-making procedure of first line chemotherapy in advanced breast cancer.


Coordinating data management for multiple ongoing clinical trials and registries.
The Epidemiology Data Center at the University of Pittsburgh has developed a standard set of data management procedures, reports, and computing configurations for use on multicenter research projects. Based on budget restrictions and study design considerations, a project-specific data management system can be quickly constructed by utilizing appropriate components from the EDC tool kit: the PoP software system for the computerization of the database from paper forms to data entry screens; program shells for telecommunication and backup procedures; and procedural documents for providing the necessary training materials for centralized or decentralized processing environments. The EDC data flow specification provides quality control assurances from entry through statistical analysis.


The Membrane Marker mCLING Reveals the Molecular Composition of Trafficking Organelles.
mCLING is a fixable endocytosis marker that can be combined with immunolabeling techniques to study the molecular composition of trafficking organelles. mCLING can be used both in cultured cells and in tissue if critical sample preparation steps, such as fixation, are correctly performed. This unit describes protocols for the application of mCLING and for the subsequent sample processing. We include immunostaining protocols and embedding procedures for confocal and high-resolution microscopy.


U.S. and Australian nurses' attitudes and beliefs about the good death.
The purpose of this study was to ascertain the attitudes and beliefs of nurses in Australia and the United States regarding aspects of passive euthanasia, or the "good death." Two foci guided the study: (a) the possible discrepancies that these nurses might perceive between what they thought would be done in a given clinical situation and what they thought ought to be done, and (b) the possible differences and similarities between the American and the Australian nurses. Responding to the 8 vignettes, 30 American and 32 Australian nurses took part in the study. The lack of agreement between the Australian and American nurses on issues of euthanasia reflects differences in the health care system; the general social position of nursing as a profession; the relationship among health professionals, patients and families, which serves as the context for definition of ethical duties and patient rights; and the role of the law in health care decisions.


Interaction of taxol with human serum albumin.
Taxol (paclitaxel) is an anticancer drug, which interacts with microtuble proteins, in a manner that catalyzes their formation from tubulin and stabilizes the resulting structures (Nogales et al., Nature 375 (1995) 424-427). This study was designed to examine the interaction of taxol with human serum albumin (HSA) in aqueous solution at physiological pH with drug concentrations of 0.0001-0.1 mM, and HSA (fatty acid free) concentration of 2% w/v. Gel electrophoresis, absorption spectra and Fourier transform infrared (FTIR) spectroscopy with self-deconvolution and second-derivative resolution enhancement were used to determine the drug binding mode, binding constant and the protein secondary structure in the presence of taxol in aqueous solution. Spectroscopic evidence showed that taxol-protein interaction results into two types of drug-HSA complexes with overall binding constant of K=1.43 x 10(4) M(-1). The molar ratios of complexes were of taxol/HSA 30/1 (30 mM taxol) and 90/1 (90 mM taxol) with the complex ratios of 1.9 and 3.4 drug molecules per HSA molecule, respectively. The taxol binding results in major protein secondary structural changes from that of the alpha-helix 55 to 45% and beta-sheet 22 to 26%, beta-anti 12 to 15% and turn 11 to 16%, in the taxol-HSA complexes. The observed spectral changes indicate a partial unfolding of the protein structure, in the presence of taxol in aqueous solution.


Ethics in the management of health care organizations.
This article introduces the topic of ethics in the management of health care institutions and provides a glimpse at how issues of ethics have grown in recent years and are apt to be applied in the future. Ethics and some of its basic conceptual and practical tools are defined. A brief history of the ethics of managing health care institutions, a crucial context for understanding the contemporary ethics of health care institutions, is provided. What has changed in the past 10 years and how those changes have resulted in the ethical heterogeneity of contemporary health care institutions is discussed. Finally, some preventive ethics strategies for the management of health care institutions are suggested.


General medicine and surgery for dental practitioners. Part 2--metabolic disorders.
It is important for dental practitioners to have a basic knowledge of the more common metabolic disorders as some may impact on the practice of dentistry. Many of these disorders do not have overt clinical signs. Taking a thorough medical history and where necessary, liaising with the patient's physician, is particularly important.


Adipocyte expression of glucose transporter 1 and 4 in PCOS: Relationship to insulin-mediated and non-insulin-mediated whole-body glucose uptake.
Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder associated with insulin resistance (IR). In IR states, non-insulin-mediated glucose uptake (NIMGU) may increase to compensate for declining insulin-mediated glucose uptake (IMGU), although this does not appear to be the case in PCOS. The underlying molecular mechanisms for this deficiency remain unclear. To compare adipocyte glucose transporter 1 and 4 (GLUT-1 and GLUT-4) gene expression in PCOS women and matched controls, and to determine whether changes in GLUT-1 and GLUT-4 are associated with concomitant alterations in whole-body glucose uptake. In this prospective cross-sectional study, 23 women with PCOS (by NIH 1990 criteria) and 23 matched controls were studied for subcutaneous abdominal adipocyte GLUT-1 and GLUT-4 mRNA expression (by real-time PCR), and basal whole-body IR (by HOMA-IR) and insulin secretion (by HOMA-β%). A subset of six PCOS women and six matched controls also underwent a mFSIVGTT to determine dynamic state glucose uptake (by insulin sensitivity index [Si] and glucose effectiveness [Sg]) and insulin secretion (by the acute insulin response to glucose [AIRg] and the disposition index [Di]). For similar adiposity (BMI and waist-hip ratio), PCOS women tended to have higher HOMA-IR and lower Di and Si, and higher HOMA-β% and lower GLUT-4 than controls, while GLUT-1 was similar. GLUT-1 was positively associated with Sg (reflecting NIMGU) and GLUT-4 positively with Si (reflecting IMGU). GLUT-4 was associated negatively with HOMA-IR and HOMA-β% and positively with Di for the entire cohort but not with AIRg. Both GLUT-1 and GLU-4 were negatively associated with BMI, but not with each other. Our results suggest that IR secondary to a lower IMGU and enhanced insulin secretion in PCOS is in part attributable to a reduction in adipocyte GLUT-4 expression that is not accompanied by a compensatory increase in GLUT-1 expression.


Expression of keratinocyte growth factor and its receptor in adaptive changes of ileorectal pouch mucosa.
Total proctocolectomy with formation of an ileo-anal pouch is a well-established surgical procedure for patients with ulcerative colitis (UC) or familiar adenomatous polyposis (FAP). The pouch mucosa undergoes adaptive changes, with inflammation of the ileal reservoir being the most common complication. The aetiology is unknown. The keratinocyte growth factor (KGF) has not only been shown to promote intestinal wound healing and re-epithelialization but also to have some immunomodulatory properties. This study was designed to investigate a putative involvement of KGF in observed histomorphological changes in the pouch mucosa. Multiple biopsies were obtained from age-matched and sex-matched patients. Biopsies were stained with H&E and scored for inflammation and morphological changes. mRNA expression levels of KGF and KGF-receptor (KGFR) were determined using competitive RT-PCR, protein expression and phosphorylation was analyzed by Western blotting. KGF and KGFR were localized in tissue samples by immunohistochemistry. Expression of KGF and KGFR was significantly increased in inflamed and adapting mucosa. Patterns of expression did not significantly differ in pouch mucosa from UC or FAP patients. Protein expression correlated with the mRNA results and KGFR was shown to be activated in adapting pouch mucosa. KGF was detected on subepithelial cells, mainly on fibroblasts, whereas expression of KGFR was restricted to epithelial cells. Expression of KGF and KGFR is significantly increased in the pouch mucosa, suggesting an involvement of this growth factor in tissue repair and adaptive changes. Topical application of KGF might alleviate the inflammatory and promote the adaptive process in the ileo-anal pouch mucosa.


Tocoyena sellowiana extract decreases bone loss in an experimental model of periodontitis in rats: Putative role for cyclooxygenase-2 and IL-1? inhibition.
Tocoyena sellowiana (Cham. & Schltdl.) K.Schum is one of the most important families of Brazilian medicinal plants. This study aimed to evaluate the effect of Tocoyena sellowiana (Cham. & Schltdl.) K.Schum ethanolic extract in a pre-clinical trial of periodontitis and to investigate possible mechanisms underlying such effects. Periodontitis was induced in Wistar rats by placing a nylon thread ligature around second upper left molars for 11 days. Rats received (per os) Tocoyena sellowiana (0.1, 1 or 10?mg?kg) or vehicle 1?h before ligature and daily until day 11. Macroscopic, histopathological, and COX-2 immunohistochemical analyses were performed to evaluate the periodontium. The gingival tissue was used to quantify the myeloperoxidase (MPO) activity and interleukin (IL)-1? levels by ELISA. Blood samples were collected to evaluate bone-specific alkaline phosphatase (BALP), the dosage of creatinine, aspartate and alanine transaminases. The liver, kidneys, spleen, and body mass variations were also evaluated. Tocoyena sellowiana decreased bone loss, reduced MPO, IL-1? levels as well as COX-2 immunostaining, and increased BALP activity. Moreover, Tocoyena sellowiana did not alter organs nor body weight. Tocoyena sellowiana reduced bone loss in rats and its efficacy was at least partially dependent upon both IL-1? and cyclooxygenase-2 inhibition.


Successfully-treated mesenteric non-Hodgkin's lymphoma involving hepatic mass--a case report.
A mesenteric diffuse large B-cell lymphoma which also involves the liver is very rare. We describe herein a mesenteric diffuse large B-cell lymphoma with hepatic involvement successfully treated by the combination of surgical resection and multiagent chemotherapy. A 77-year-old man was referred to our hospital because of a right lower abdominal tumor. Abdominal computed tomography showed a mass in the mesenterium at the ileocoecal region and multiple mass in the liver. Gallium scintigram showed focal hot uptake at the ileocoecal region and multiple areas of increased Gallium uptake in the liver. With the diagnosis of a mesenteric tumor with liver metastases, a laparotomy was performed. By an intraoperative pathological examination, non-Hodgkin's lymphoma was suggested. The mesenteric mass was completely resected, but additional operative procedures were not done to the liver. After the operation, the patient was determined to have Stage IVB diffuse large B-cell lymphoma, and chemotherapy based on the CHOP-like regimen was given. After the 8th course of such chemotherapy, he was confirmed to have achieved a complete remission by abdominal computed tomography and Gallium scintigram.The Stage IV mesenteric diffuse large B-cell lymphoma involving the liver seems to be an indication for combination therapy of surgical resection and multiagent chemotherapy.


IL-4 differentiates naive CD8+ T cells to a "Th2-like" phenotype: a link between viral infections and bronchial asthma.
Viral infections of the lung have been postulated to be a major factor in the etiology of bronchial asthma, a disease characterized by eosinophilic inflammation of the airways. In addition, upper respiratory tract infection in asthmatic individuals results in an exacerbation of the disease. Nevertheless, the mechanisms by which viral infection leads to disease exacerbation are poorly understood. CD8+ T cells play an important role in the host defense responses against viral infection, although to date, there are no reports to suggest that CD8+ T cells play any role in eosinophil recruitment. In the present study, we report that CD8+ T cells activated by either immobilized CD3 mAb or specific antigen can switch to a phenotype that produces Th2 cytokines and secretes less IFN-gamma. Moreover, in vivo, if a lung mucosal Th2 immune response exists, then antigen-specific activation of CD8 cells results in the development of lung eosinophilic inflammation mediated by the secretion of IL-5 from CD8+ T cells. These results may explain the link between viral infections and bronchial asthma, as this IL-4-dependent switch to CD8+ T cells to IL-5 secretion may not only exacerbate asthma by recruiting eosinophils into the lungs, but the impaired IFN-gamma production may also lead to delayed viral clearance.


[Brain malformation and apoptosis].
Apoptosis is a physiological phenomenon that occurs extensively in the developing central nervous system (CNS). The death of neural cells is strictly controlled by the bcl-2 family and other regulatory systems. In particular, neurons are prevented from undergoing apoptosis by multiple mechanisms such as their intracellular control device and neurotrophic factors delivered by their innervating neurons, target cells and surrounding glial cells. A defect in any of these may cause a CNS malformation due to massive neuronal death.


Management of life-threatening autonomic hyper-reflexia using magnesium sulphate in a patient with a high spinal cord injury in the intensive care unit.
We report the successful use of i.v. magnesium sulphate to control life-threatening autonomic hyper-reflexia associated with chronic spinal cord injury in the intensive care environment. A 37-yr-old, male was admitted to the intensive care unit with a diagnosis of septic shock and acute renal failure secondary to pyelonephritis. He had been found unresponsive at home following a 2-day history of pyrexia and purulent discharge from his suprapubic catheter. He had sustained a T5 spinal cord transection 20 yr previously. Initial management included assisted ventilation, fluid resuscitation, vasopressor support, and continuous veno-venous haemofiltration. The sepsis was treated with antibiotic therapy and percutaneous nephrostomy drainage of the pyonephrosis. On the fifth day, the patient developed profuse diarrhoea. This was associated with paroxysms of systemic hypertension and diaphoresis, his arterial pressure rising on occasion to 240/140 mm Hg. A diagnosis of autonomic hyper-reflexia was made and a bolus dose of magnesium sulphate 5 g was administered over 15 min followed by an infusion of 1-2 g h(-1). There was an almost immediate decrease in the severity and frequency of the hypertensive episodes. There were no adverse cardiac effects associated with the administration of magnesium, only a slight decrease in minute ventilation as the plasma level approached the upper end of the therapeutic range (2-4 mmol litre(-1)). In view of the beneficial effects observed in this case we advocate further research into the use of magnesium sulphate in the treatment or prevention of autonomic hyper-reflexia secondary to chronic spinal cord injury in the intensive care unit.


Correlation of antifungal susceptibility and molecular type within the Cryptococcus neoformans/C. gattii species complex.
Members of the Cryptococcus neoformans/C. gattii species complex are grouped into eight molecular types, differing in their epidemiology, disease severity and geographic range. Recent in vitro antifungal susceptibility studies of isolates of the complex revealed contradictory results. The objective of the present study was to assess if this variation is random or correlates with different molecular types by testing the in vitro antifungal susceptibility of 18 C. neoformans (VNI), 11 C. gattii (VGI) and 38 C. gattii (VGII) strains from Brazil to eight antifungal drugs using the CLSI microdilution method. We herein report that the molecular type VGII is the least susceptible genotype, followed by VGI and VNI. This indicates a clear correlation between antifungal susceptibilities and genotypes of the causative cryptococcosis agents, emphasizing the importance of determining the molecular type as part of the clinical diagnostic process to enable an informed decision as to the most appropriate antifungal treatment.


Exploring hope and healing in patients living with advanced non-small cell lung cancer.
To explore the experience and meaning of hope in relation to the healing process of patients living with stage IIIb or IV non-small cell lung cancer. Interpretative qualitative study design. Peter Brojde Lung Cancer Centre in the Jewish General Hospital in Montreal, Quebec, Canada. 12 English- and French-speaking patients, aged 36-78 years. One 60-90-minute semistructured interview per participant was conducted. An inductive approach to data analysis was taken, involving immersion in the data, coding, classifying, and creating linkages. Four main themes emerged: (a) the morass of shattered hope, (b) tentative steps toward a new hope paradigm, (c) reframing hope within the context of a life-threatening illness, and (d) strengthening the link between hope and wellness. Patients described a process where hope was diminished or lost entirely, regained, and reshaped as they learned to live and grow following their diagnosis. This study adds to the literature by describing the dynamic nature of hope as well as factors facilitating or hindering the hope process. It demonstrates how finding meaning, a structural component of healing, can be used to envision a new hopeful future. This study suggests hope and healing cannot exist in isolation, and highlights the importance of understanding the fluctuating nature of hope in patients with advanced lung cancer to foster it, therefore promoting healing.


Testing for antibodies to AIDS-associated retrovirus (HTLV-III/LAV) by indirect fixed cell immunofluorescence: specificity, sensitivity, and applications.
Seropositivity to the AIDS-associated retrovirus, HTLV-III/LAV, has profound implications. Simple and reliable tests are needed to detect such antibodies. A rapid, sensitive indirect immunofluorescence assay (IFA) on acetone-fixed virus-producing CEM/LAV-N1 cells was adapted for detection of human antibodies to HTLV-III/LAV. Specific and nonspecific patterns of of immunofluorescent reactivity were easily distinguished, and results paralleled those obtained by Western blotting and radioimmunoprecipitation (RIP), indicating that there is no need to confirm IFA positivity. In contrast, the commercial enzyme-linked immunosorbent assay (ELISA) was less reliable. False positives occurred with sera from seven hemophiliacs that were negative on Western blots, and false-negative reactions were observed on two occasions. These involved low-titer AIDS-patients' sera that were positive on Western blots, and from one of which virus was successfully isolated. Our results emphasize the requirement for confirmatory assays when the ELISA test is used for primary screening of sera for antibodies to HTLV-III/LAV. The IFA method is especially well-suited to quantitative analysis of serum antibody levels. Our data suggest that serum antibody titers rise as disease progression occurs, ultimately falling as severe complications ensue. It is suggested that in laboratories where the demand for HTLV-III/LAV antibody testing is not excessive (1,000-2,000 sera/month), IFA could serve as the only serological assay for both screening and epidemiological purposes.


Contribution of systemic vascular reactivity to variability in pulse volume amplitude response during reactive hyperemia.
The aim of the present study was to investigate why the magnitude of reactive hyperemia (RH) observed by pulse volume amplitude (PVA) after arm occlusion differs greatly among study subjects. Healthy subjects (n = 12) in the age range of 22-30 years participated in this study. Vascular reactivity was assessed by measuring the changes in finger PVA simultaneously in the test (occluded arm) and control arm (contralateral non-occluded arm) using two separate Photoplethysmographic sensors. Short-term HRV was computed from simultaneously acquired lead II ECG signal to monitor the changes in cardiac sympathetic nervous activity. The observed coefficient of variation for inter-subject variability in PVA response in test arm during second minute of RH was 115.3%. In the control arm, significantly reduced PVA was observed during the period of occlusion as well as RH. This observation was corroborated by simultaneously acquired short-term HRV which showed a significant rise in total power (p value < 0.005) and low-frequency (LF) power (p value < 0.05) during release of occlusion when compared to the baseline. A significant positive correlation (Spearman r = 0.33; p = 0.02) was observed between % change in PVA in the control arm and in the test arm for first 3 min of RH. Sympathetic activation possibly plays an important role in mediating the inter-subject variability of vascular responses during reactive hyperemia which warrants simultaneous recording of both the test and the control arm responses during RH to accurately assess endothelial function.


A mild synthesis of vinyl halides and gem-dihalides using triphenyl phosphite-halogen-based reagents.
A new application of (PhO)3P-halogen-based reagents to the synthesis of vinyl halides and gem-dihalides is described. Vinyl halides were prepared in good to excellent yields from enolizable ketones, whereas aldehydes afforded the corresponding gem-dihalides. The halogenation proceeded smoothly under mild conditions.


Purification, recovery, and characterization of chick pea (Cicer arietinum) β-galactosidase in single step by three phase partitioning as a rapid and easy technique.
In this study chick pea β-galactosidase was first time purified and recovered in single step by three phase partitioning (TPP). Optimal purification parameters for TPP were 60% ammonium sulfate saturation (w/v) with 1:0.5 (v/v) ratio of crude extract:t-butanol at pH 6.8, which gave 10.1 purification fold with 133% recovery of β-galactosidase. SDS-PAGE analysis showed that protein has two subunits with molecular masses of 48 and 38kDa, respectively. Characterization of enzyme showed that optimal pH of purified enzyme was 2.8 and optimal temperature was 50°C. Enzyme was further characterized by the Arrhenius activation energy and Michael-Menten kinetic constants. Activation energy (Ea) was calculated by using Arrhenius equation and determined to be 15.52kcalmol(-1). Km value of purified enzyme was estimated for the o-nitrophenyl β-d galactopyranoside (ONPG) substrate as 1.09mM, while its maximum velocity, Vm was 0.90U/mL/min at 37°C. TPP improved substrate affinity of enzyme by the increased flexibility during the partitioning. TPP is simple, easy and economic technique for purification and recovery of β-galactosidase from chick pea, and has a big potential use for industrial applications.


Causes of death in patients with COPD and chronic respiratory failure.
Although the factors associated with mortality, such as forced expiratory volume in one second (FEV1), arterial oxygen tension (Pa,O2) and pulmonary arterial pressure, have been well described, there is limited information on the circumstances of death in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the causes and circumstances of death in patients with COPD and chronic respiratory failure (Pa,O2 < 8.0 kPa (60 mmHg) breathing air), treated with long-term oxygen therapy (LTOT). Ten European centres participated in the study and data were collected from patients both during a period of clinical stability and at the time of death. Of the 215 patients evaluated (161 males and 54 females; aged 66 +/- 10 yrs), the major causes of death were: acute on chronic respiratory failure (38%); heart failure (13%); pulmonary infection (11%); pulmonary embolism (10%); cardiac arrhythmia (8%); and lung cancer (7%). Seventy five percent of patients died in hospital. There was no difference in the number of patients who died in the morning, afternoon and night hours. Twenty percent of the total died during sleep and in 26% death was unexpected. A lower arterial carbon dioxide tension (Pa,CO2), less oxygen usage per 24 h, and increased incidence of arrhythmias were seen in those patients who died suddenly. Drug therapy was not related to unexpected death. The majority of patients with chronic obstructive pulmonary disease on long-term oxygen therapy died from chronic or acute on chronic respiratory failure. Prevention and treatment of respiratory failure in patients with chronic obstructive pulmonary disease is likely to have the greatest impact in reducing mortality.