Estrogenic and anti-estrogenic compounds from the Thai medicinal plant, Smilax corbularia (Smilacaceae).
From the rhizomes of Smilax corbularia Kunth. (Smilacaceae), 11 compounds, (2R,3R)-2″-acetyl astilbin, (2R,3R)-3″-acetyl astilbin, (2R,3R)-4″-acetyl astilbin, (2R,3R)-3″-acetyl engeletin, (2R,3S)-4″-acetyl isoastilbin, 2-(4-hydroxyphenyl)-3,4,9,10-tetrahydro-3,5-dihydroxy-10-(3,4-dihydroxyphenyl)-(2R,3R,10R)-2H,8H-benzo [1,2-b:3,4-b'] dipyran-8-one, 2-(4-hydroxyphenyl)-3,4,9,10-tetrahydro-3,5-dihydroxy-10-(3,4-dihydroxyphenyl)-(2R,3R,10S)-2H, 8H-benzo [1,2-b:3,4-b'] dipyran-8-one, 3,4-dihydro-7-hydroxy-4-(3,4-dihydroxyphenyl)-5-[(1E)-2-(4-hydroxyphenyl) ethenyl]-2H-1-benzopyran-2-one, 3,4-dihydro-7-hydroxy-4-(3,4-dihydroxy-phenyl)-5-[(1E)-2-(3,4-dihydroxyphenyl) ethenyl]-2H-1-benzopyran-2-one, 3,4-dihydro-7-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-5-[(1E)-2-(4-hydroxyphenyl) ethenyl]-2H-1-benzopyran-2-one, and 5,7,3',4'-tetrahydroxy-3-phenylcoumarin along with 34 known compounds were isolated and characterized as 19 flavonoids, 14 catechin derivatives, 6 stilbene derivatives, and 6 miscellaneous substances. All isolates had their estrogenic and anti-estrogenic activities determined using the estrogen-responsive human breast cancer cell lines MCF-7 and T47D. The major constituents were recognized as flavanonol rhamnosides by the suppressive effect on estradiol induced cell proliferation at a concentration of 1μM. Meanwhile, flavanonol rhamnoside acetates demonstrated estrogenic activity in both MCF-7 and T47D cells at a concentration of 100μM, and they enhanced the effects of co-treated E2 on T47D cell proliferation at concentrations of more than 0.1μM.


Comparative kinetics of 45Ca and 89Sr in chronic uremic syndrome in the rat.
In rats a chronic uremic syndrome was induced by 5/6 resection and subsequent irradiation of the kidneys. After 5 weeks 45Ca and 89Sr were injected simultaneously, and the different metabolic handling of the two elements was determined applying an open two-compartment model of Calcium kinetics. The uremic animals were compared with two groups of rats which were pairfed, and fed ad libitum, respectively. Besides an elevenfold faster urinary excretion when calculated with Sr, and which was reduced to about one half in the uremic rats, a significant discrimination by bone in favour of Ca was found, with a rather stable factor of 1.2 in the three groups. This is considered to evidence that urinary excretion and bon uptake of Sr are independent processes.


Response-level processing during visual feature search: Effects of frontoparietal activation and adult age.
Previous research suggests that feature search performance is relatively resistant to age-related decline. However, little is known regarding the neural mechanisms underlying the age-related constancy of feature search. In this experiment, we used a diffusion decision model of reaction time (RT), and event-related functional magnetic resonance imaging (fMRI) to investigate age-related differences in response-level processing during visual feature search. Participants were 80 healthy, right-handed, community-dwelling individuals, 19-79 years of age. Analyses of search performance indicated that targets accompanied by response-incompatible distractors were associated with a significant increase in the nondecision-time (t0) model parameter, possibly reflecting the additional time required for response execution. Nondecision time increased significantly with increasing age, but no age-related effects were evident in drift rate, cautiousness (boundary separation, a), or in the specific effects of response compatibility. Nondecision time was also associated with a pattern of activation and deactivation in frontoparietal regions. The relation of age to nondecision time was indirect, mediated by this pattern of frontoparietal activation and deactivation. Response-compatible and -incompatible trials were associated with specific patterns of activation in the medial and superior parietal cortex, and frontal eye field, but these activation effects did not mediate the relation between age and search performance. These findings suggest that, in the context of a highly efficient feature search task, the age-related influence of frontoparietal activation is operative at a relatively general level, which is common to the task conditions, rather than at the response level specifically.


Fetal cerebellar damage in fetuses with severe anemia undergoing intrauterine transfusions.
To evaluate radiologic findings and outcomes of cerebellar injuries in fetuses with severe anemia due to RhD alloimmunization undergoing intrauterine transfusions. Imaging of multiplanar neurosonography and magnetic resonance imaging (MRI) were reviewed. Pregnancy outcomes were recorded. Cerebellar injuries were identified after the first intravascular transfusion in four fetuses. Two of these cases were previously reported. The median hemoglobin concentration was 2.1 g/dL. Prenatal neurosonography identified an echogenic collection involving the cerebellum suggestive for hemorrhage in three cases. A progressive hypoplasia of a hemisphere was demonstrated at follow-up examination in one of these cases. Hypoplasia of a cerebellar hemisphere was seen in the fourth fetus. Ultrasound diagnosis was confirmed by prenatal MRI in two cases. In the third case, the postnatal MRI showed as additional finding vermian involvement. One pregnancy was terminated and autopsy confirmed the presence of infratentorial hemorrhage. The remaining infants were delivered alive. At time of writing, a truncal ataxia was diagnosed in the child with vermian hypoplasia, while the other children have met all age-appropriate milestones. A severe anemia seems to put the fetus at risk of cerebellar damage, despite successful intravascular transfusion.


Lap colectomy and robotics for colon cancer.
Robotic approaches have seen significant growth in the last 5 years. Taking advantage of three-dimensional visualization, improved articulation, and multiple operating arms provides theoretical and real advantages in colorectal cancer surgery. This article reviews the potential advantages and disadvantages, current outcomes, and future directions for robotic approaches to colon cancer surgery.


Heart disease mortality and economic changes; including unemployment; in Western Germany 1951-1989.
Research over the last two decades has indicated that changes in cardiovascular disease mortality rates have been influenced by those in national economic indicators as well as by measures of consumption of tobacco, animal fats and alcohol. These findings predominantly involved the United States, United Kingdom and Scandinavian countries. The economic indicators included real per capita income and social welfare expenditures (beneficial relationships to mortality rates), and unemployment rates and business failure rates (detrimental relationships to mortality). James Henry's formulations have emphasized that many different illnesses respond to emotional stresses in different psychophysiological patterns depending on the specific constellations of emotions aroused. On the assumption that the impact of national economic changes on cardiovascular mortality reflects emotional stresses, losses, frustrations and deprivations, similar tests were undertaken using Western German heart disease mortality rate data over 1951-1989. Time-series regression analysis showed that, holding constant the effects of tobacco, animal fats and alcohol, increased income and social welfare expenditures are related to heart disease mortality rate declines, whereas increased unemployment and business failure rates are related to heart disease mortality rate increases over more than a decade.


Transfusion and postoperative pneumonia in coronary artery bypass graft surgery: effect of the length of storage of transfused red cells.
Various bioactive substances are released from white cell (WBC) granules into red cell (RBC) components in a time-dependent manner during blood storage. Some of these substances may have immunosuppressive effects and may contribute to transfusion-induced immunomodulation. RBCs transfused after prolonged storage may be associated with a higher incidence of postoperative infections than fresh RBCs. This hypothesis does not seem to have been investigated in a clinical study. The records of 416 consecutive patients undergoing coronary artery bypass graft operations at the Massachusetts General Hospital were reviewed. The association between the length of storage of the transfused RBCs, as well as the number of units of non-WBC-reduced allogeneic RBCs and/or platelets transfused, and the occurrence of postoperative pneumonia was calculated by logistic regression analyses adjusting for the effects of confounding factors. Among these were the numbers of days of intubation, days of impaired consciousness, and units of RBCs transfused. By Centers for Disease Control and Prevention criteria, pneumonia developed in 54 patients (13.0%). Among 269 patients given RBCs, the risk of pneumonia increased by 1 percent per day of increase in the mean storage time of the transfused RBCs (p<0.005). In an analysis of all patients, the risk of pneumonia increased by 5 percent per unit of non-WBC-reduced allogeneic RBCs and/or platelets received (p = 0.0584). After adjustment for the effects of the risk factors for pneumonia and the number of transfused RBCs, an association was observed between the length of storage of transfused RBCs and the development of postoperative pneumonia. This association should be investigated further in future studies of the outcomes of blood transfusion.


Leucine at codon 428 in the ninth heptad of thyroid hormone receptor beta1 is necessary for interactions with the transcriptional cofactors and functions regardless of dimer formations.
Structure/function studies of the thyroid hormone receptor (TR) beta(1) have demonstrated that single amino acid substitutions in either position 428 or 429 in the ligand-binding domain (LBD) can alter heterodimerizations and homodimerizations, respectively. A leucine at 428 is located in a highly conserved region corresponding to the putative ninth heptad repeat of a leucine-zipper-like motif in the LBD of TRbeta(1). To investigate how the side chain of amino acids at 428 affect receptor characteristics, gel-shift mobility shift assays and yeast two-hybrid assays were analyzed. The neutral status amino acids such as a leucine (wild-type) or a glutamine at 428 preferred heterodimerization with RXR. Furthermore, a positively charged side chain of amino acids at 428 such as an arginine or a lysine, preserved homodimer formation. Irrespective of charge, ninth heptad mutant receptors did not bind the ligand and were not able to interact with either corepressor or coactivating proteins. Limited trypsinization assays revealed no major conformational change in the ninth heptad mutant receptors. Together, these findings suggested that a leucine at 428 was a critical amino acid for both interaction with the thyroid hormone receptor associated proteins and ligand-independent and -dependent functions regardless of dimer formations.


Invasive Aspergillus of the head and neck.
Invasive fungal infections of the head and neck are uncommon. The most common organism is Mucor which is classically seen in diabetic individuals in or immediately after a bout of ketoacidosis. This report outlines our experience of four cases of invasive fungal disease caused by the Aspergillus species. All four patients in this series were profoundly granulocytopenic. Three of the four patients remained profoundly immunocompromised and succumbed to infections. One patient recovered immune competence and became a long term survivor after antifungal chemotherapy and debridement of necrotic tissue. The literature on invasive Aspergillus of the head and neck is reviewed. Some recent insights in the medicine literature concerning the epidemiology of the more common pulmonary form of this invasive disease are also discussed.


Epitaxial growth of dual-color-emitting organic heterostructures via binary solvent synergism driven sequential crystallization.
The controlled construction of organic heterostructured architectures derived from molecules with similar nucleation thresholds and concentrations has been rare and remains a great challenge. Herein, we report a sequential epitaxial growth to synthesize dual-color-emitting organic heterostructures with 9,10-bis(phenylethynyl)anthracene (BPEA) microwire trunks and tris-(8-hydroxyquinoline)aluminium (Alq3) microstructure branches by an anti-solvent induced sequential crystallization strategy. During the epitaxial growth process, the hydrogen-bonding interactions of the anti-solvent and solvent cause a large change in the solubility and crystallization rate of BPEA and Alq3 molecules in the mixed system, which facilitates sequential crystallization of organic molecule pairs with similar nucleation thresholds and concentrations into desired heterostructures by manipulating the synergism of anti-solvents and solvents. The Förster resonant energy transfer process in heterostructures could be modulated by varying the structure of heterostructures, such as the shape, amount and angles of the branches. The present synthesis strategy provides a unique insight into the detailed formation mechanism of complex organic heterostructures, further guiding the construction of more functional heterostructure materials.


Microscopic derivation of coarse-grained, energy-conserving generalized Langevin dynamics.
Properly simulating nonequilibrium phenomena such as thermal transport and shock wave propagation in complex condensed matter systems require the conservation of system's internal energy. This precludes the application of the coarse-grained (CG) generalized Langevin equation (GLE) dynamics due to the presence of dissipative interactions. Attempts to address this issue have been pursued both phenomenologically and from entropy-based first principles for dissipative particle dynamics (DPD, a Markovian variant of the CG GLE dynamics) by introducing an energy conserving extension of DPD (DPD-E). We present here a rigorous microscopic derivation of two energy conserving variants of the CG GLE dynamics by extending the CG equations of motion to include the GLE for certain internal energy observables of the microscopic system. We consider two choices of such observables: the total internal energy and a set of internal energies of the CG particles. The derivation is performed using the Mori-Zwanzig projection operator method in the Heisenberg picture for time evolution of thermodynamic expectations and the recently introduced interpretation of the Zwanzig projection operator [S. Izvekov, J. Chem. Phys. 146(12), 124109 (2017)] which allows an exact calculation of the memory and projected terms. We begin with equilibrium conditions and show that the GLE dynamics for the internal energy observables is purely dissipative. Our extension of the GLE dynamics to quasiequilibrium conditions (necessary to observe heat transport) is based on the generalized canonical ensemble approach and transport equation using the nonequilibrium statistical operator (NSO) method. We derive closed microscopic expressions for conductive heat transfer coefficients in the limit of neglecting dissipation in heat transfer and in the lowest order of deviation from equilibrium. After employing the Markov approximation, we compare the equations of motion to the published DPD-E equations. Our equations contain additional energy transfer terms not reported in the previous works. Additionally, we show that, despite neglecting dissipative processes in heat transport, the heat transfer coefficients and random force are related in a way reminiscent of the fluctuation-dissipation relation. The formalism presented here is sufficiently general for the rigorous formulation of the GLE dynamics for arbitrary microscopic phase space observables as well as sampling different microscopic ensembles in CG simulations.


Interaction kinetics of liposome-incorporated unsaturated fatty acids with fatty acid-binding protein 3 by surface plasmon resonance.
The role of heart-type fatty acid-binding protein (FABP3) in human physiology as an intracellular carrier of fatty acids (FAs) has been well-documented. In this study, we aimed to develop an analytical method to study real-time interaction kinetics between FABP3 immobilized on the sensor surface and unsaturated C18 FAs using surface plasmon resonance (SPR). To establish the conditions for SPR experiments, we used an FABP3-selective inhibitor 4-(2-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl)-phenoxy)-butyric acid. The affinity index thus obtained was comparable to that reported previously, further supporting the usefulness of the SPR-based approach for evaluating interactions between FABPs and hydrophobic ligands. A pseudo-first-order affinity of FABP3 to K(+) petroselinate (C18:1 Δ6 cis), K(+) elaidate (C18:1 Δ9 trans), and K(+) oleate (C18:1 Δ9 cis) was characterized by the dissociation constant (K(d)) near micromolar ranges, whereas K(+) linoleate (C18:2 Δ9,12 cis/cis) and K(+) α-linolenate (C18:3 Δ9,12,15 cis/cis/cis) showed a higher affinity to FABP3 with Kd around 1 × 10(-6)M. Interactions between FAPB3 and C18 FAs incorporated in large unilamellar vesicles consisting of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and FAs (5:1 molar ratio) were also analysed. Control DMPC liposomes without FA showed only marginal binding to FABP3 immobilized on a sensor chip while liposome-incorporated FA revealed significant responses in sensorgrams, demonstrating that the affinity of FAs to FABP3 could be evaluated by using the liposome-incorporated analytes. Significant affinity to FABP3 was observed for monounsaturated fatty acids (K(d) in the range of 1 × 10(-7)M). These experiments demonstrated that highly hydrophobic compounds in a liposome-incorporated form could be subjected to SPR experiments for kinetic analysis.


Increase in NOx emissions from Indian thermal power plants during 1996-2010: unit-based inventories and multisatellite observations.
Driven by rapid economic development and growing electricity demand, NO(x) emissions (E) from the power sector in India have increased dramatically since the mid-1990s. In this study, we present the NO(x) emissions from Indian public thermal power plants for the period 1996-2010 using a unit-based methodology and compare the emission estimates with the satellite observations of NO(2) tropospheric vertical column densities (TVCDs) from four spaceborne instruments: GOME, SCIAMACHY, OMI, and GOME-2. Results show that NO(x) emissions from Indian power plants increased by at least 70% during 1996-2010. Coal-fired power plants, NO(x) emissions from which are not regulated in India, contribute ∼96% to the total power sector emissions, followed by gas-fired (∼4%) and oil-fired (<1%) ones. A number of isolated NO(2) hot spots are observed over the power plant areas, and good agreement between NO(2) TVCDs and NO(x) emissions is found for areas dominated by power plant emissions. Average NO(2) TVCDs over power plant areas were continuously increasing during the study period. We find that the ratio of ΔE/E to ΔTVCD/TVCD changed from greater than one to less than one around 2005-2008, implying that a transition of the overall NO(x) chemistry occurred over the power plant areas, which may cause significant impact on the atmospheric environment.


A family with a novel TSH receptor activating germline mutation (p.Ala485Val).
Autosomal dominant nonautoimmune hyperthyroidism (ADNAH) is caused by gain of function mutations in the TSH receptor (TSHr) gene and characterized by toxic thyroid hyperplasia with a variable age of onset in the absence of thyroid antibodies and clinical symptoms of autoimmune thyroid disease in at least two generations. We report here a Turkish family with a novel TSHr gene mutation with distinct features all consistent with ADNAH. Thyroid function tests of the proband were as follows: free T3: 13.1 pg/ml (N: 1.8-4.6); free T4: 5.1 ng/dl (N: 0.9-1.7); TSH: 0.01 microIU/ml (N: 0.2-4.2); and TSH receptor antibody: 2 IU/ml (N: 0-10). A heterozygous missense mutation in exon 10 of the TSHr gene (c.1454C>T) resulting in the substitution of valine for alanine at codon 485 (p.Ala485Val) was found in the father and his son and daughter. This mutation had arisen de novo in the father. Functional studies of the novel TSHr germline mutation demonstrated a higher constitutive activation of adenyl cyclase than wild type without any effect on phospholipase C activity. In conclusion, our data indicate that gain of function germline mutations in the TSHr gene should be investigated in families with members suffering from thyrotoxicosis and progressive growth of goiter, but without clinical and biochemical evidence of autoimmune thyroid disease. In addition, patients harboring the same mutation of the TSHr gene may show wide phenotypic variability with respect to the age at onset, and severity of hyperthyroidism and thyroid growth.


Karyometric studies and quantitation of the DNA content in nerve and oligodendroglial cells after intraperitoneal administration of Vincristine.
Karyometric and cytophotometric investigations were conducted on nuclei of nerve cells of the Gyrus cinguli and on oligodendroglial nuclei of the corpus callosum following a 12-fold intraperitoneal injection of Vincristine into Wistar rats. The results of our investigations have shown a distinctly decreased content of DNA in neuronal nuclei of experimental rats along with a slightly increased content of DNA in glial cells. It is assumed that intraperitoneal administration of Vincristine does not inhibit the replication of DNA by oligodendroglial cells and that the observed reduction of DNA in neurocytes is the result of a disturbed turnover of DNA that is due to some damage of cytoplasmatic structures (rough endoplasmatic reticulum and microtubules) induced by the applied cytostatic compound.


A Butter Aroma Recombinate Activates Human Class-I Odorant Receptors.
With ∼400 olfactory G protein-coupled receptors (GPCR), humans sensitively perceive ∼230 key aroma compounds as best natural agonists of ∼10000 food volatiles. An understanding of odorant coding, thus, critically depends on the knowledge about interactions of key food aroma chemicals and their mixtures with their cognate receptors. Genetically designed test cell systems enable the screening, deorphaning, and characterization of single odorant receptors (OR). This study shows for the food aroma-specific and quantitative butter aroma recombinate, and its single components, specific in vitro class-I OR activity patterns, as well as the activation of selected OR in a concentration-dependent manner. Recently, chemosensory receptors, especially class-I OR, were demonstrated to be expressed on blood leukocytes, which may encounter foodborne aroma compounds postprandially. This study shows that butter aroma recombinate induced chemotaxis of isolated human neutrophils in a defined gradient, and in a concentration-dependent and pertussis toxin-sensitive manner, suggesting at least a GPCR-mediated activation of blood leukocytes by key food odorants.


MYH9 gene polymorphisms may be associated with cerebrovascular blood flow in patients with type 2 diabetes.
Genetic factors play an important role in type 2 diabetes (T2D) complications. Alteration of cerebrovascular blood flow (CBF) is a direct result of cerebrovascular diseases. However, few studies have reported the role of genetics on CBF in patients with T2D. We investigated whether single-nucleotide polymorphisms (SNPs) in metabolic disease genes are associated with CBF in patients with T2D. CBF velocities of CBF were measured in 337 Han Chinese patients with T2D using transcranial Doppler sonography, with 54 cerebrovascular blood flow parameters documented. Fifty-two SNPs from 31 metabolic disease candidate genes were genotyped in patients. Quantitative allelic association and haplotype analyses were performed for candidate gene SNPs and CBF phenotypes. Spearman correlation was used to determine the relationship between CBF parameters and basic clinical characteristics, particularly, body mass index, lipids, fibrinogen, and GHbA1c. MYH9 gene SNPs (rs875726 and rs735853) may be associated with the peak velocity of the right-middle cerebral artery. SNPs rs875726, rs2009930, and rs375246 of the MYH9 gene may be associated with the mean velocity of the right-anterior and posterior cerebral artery. The haplotype G-C-A (rs2239782-rs3752462- rs2269532) of MYH9 may be associated with CBF. MYH9 gene polymorphisms may be associated with multiple CBF phenotypes in Chinese patients with T2D. However, whether MYH9 is a candidate gene for cerebrovascular diseases in Chinese patients with T2D remains unknown.


Photoelastic analysis of stress distribution of surgically assisted rapid maxillary expansion with and without separation of the pterygomaxillary suture.
The aim of this study was to evaluate in vitro the mechanical effect over teeth and bone structures of surgically assisted rapid maxillary expansion (SARME) in photoelastic analogs by observing stress produced during Hyrax-type and Haas-type appliances activation. Two photoelastic analogs were fabricated by use of birefringent materials to simulate an adult skull that contained teeth, bone, and maxillary sinus. Hyrax-type and Haas-type appliances were applied to the anchor teeth and incrementally activated. SARME was simulated by subsequent cuts of the lateral maxillary wall and midpalatine suture and separation of the pterygomaxillary junction. After each osteotomy, the appliances were activated. Resulting stress patterns were recorded photographically in the field of a plane polariscope. Before any osteotomy, the activation of the appliances distributed stress through the anchoring teeth to the zygomaticomaxillary walls, concentrating at the zygomaticomaxillary and zygomaticofrontal sutures and at the midline of the maxilla. After midpalatal and maxillary wall osteotomies, a marked reduction of the stress at the zygomaticomaxillary walls was observed. With successive activations, the stresses increased in intensity at the molars, maxillary tuberosity, and pterygoid plates. After pterygomaxillary separation, the stress intensity at the molar area, maxillary tuberosity, and pterygoid plates decreased considerably. With successive activations, stress increased in intensity around the molars and maxillary tuberosity. There were no differences between stresses produced by the 2 appliances. In this biomechanical model, sectioning of all maxillary articulations, including separation of the pterygomaxillary junction, caused a decrease in stress over anchorage teeth. These data cannot be completely extrapolated to the clinical situation but indicate that electing to perform the SARME technique should be based on periodontal health and amount of expansion necessary for each case.


Food intake reduction and immunologic alterations in mice fed dehydroepiandrosterone.
A diet containing 0.4% DHEA was fed to male mice of a long-lived strain from 3 weeks until 18 weeks of age. These mice were compared with others fed a control diet ad libitum and with mice pair-fed the control diet in amounts approximating the intake of the DHEA-fed group. Mice fed the DHEA diet failed to eat all of the food presented to them whereas the pair-fed mice ate all of their food. All mice were studied at 18 weeks of age for two age-sensitive immune parameters (spleen lymphocyte proliferation induced by T-cell mitogens [PHA or ConA] and natural killer cell lysis of an allogeneic tumor). DHEA feeding led to: 1) a decrease in food intake (approximately 30% less than for mice fed the control diet ad libitum), 2) a lower body weight at 18 weeks of age (approximately 40% lower than for ad libitum controls) due to a decrease in the body weight gained from 3 weeks through 18 weeks of age (approximately 55% lower than controls), 3) a lower spleen weight (approximately 30% lower than controls) but without lower numbers of nucleated cells per spleen, 4) an increase in PHA-induced proliferation by spleen lymphocytes (approximately 100% higher than for controls) and, 5) no influence on splenic natural killer cell activity. The inhibition of body weight gain for mice fed DHEA appeared due to both a reduction in food intake and a metabolic effect since mice eating DHEA gained less body weight per gram of food eaten than did mice in either group eating the control diet.


Estimation of Acutely Ill Medical Patients at Venous Thromboembolism Risk Eligible for Extended Thromboprophylaxis Using APEX Criteria in US Hospitals.
Major medical illnesses place patients at risk of venous thromboembolism (VTE). Some risk factors including age ≥75 years or history of cancer place them at increased risk of VTE that extends for at least 5 to 6 weeks following hospital admission. Betrixaban thromboprophylaxis is now approved in the United States for this indication. We estimated the annual number of acutely ill medical patients at extended risk of VTE discharged from US hospital. Major medical illnesses (stroke, respiratory failure/chronic obstructive pulmonary disease, heart failure, pneumonia, other infections, and rheumatologic disorders) and 2 common risk factors for extended VTE risk, namely, age ≥75 years and history of cancer (active or past) were examined in 2014 US hospital discharges using the first 3 discharge diagnosis codes in the National Inpatient Sample (database of acute-care hospital discharges from the US Agency for Health Care Quality and Research). In 2014, there were 20.8 million discharges with potentially at risk of nonsurgical-related VTE. Overall, 7.2 million (35%) discharges corresponded to major medical illness that warranted thromboprophylaxis according to 2012 American College of Chest Physicians (ACCP) guideline. Among them, 2.79 million were aged ≥75 years and 1.36 million had a history of cancer (aged 40-74 years). Overall, 3.48 million discharges were at extended risk of VTE. Many medical inpatients at risk of VTE according to 2012 ACCP guideline might benefit from the awareness of continuing risk and some of these patients might benefit from extended thromboprophylaxis, depending on the risk of bleeding and comorbidities.


[Acid-soluble, non-histone proteins in rat liver chromatin. Interaction with DNA].
Some properties of nonhistone proteins of rat liver chromatin (Mr 40 +/- 1 and 41 +/- 1 KD) are described. These proteins are abundant in monomeric particles formed at the early steps of chromatin fragmentation by Ca2+,Mg2+-DNase. The proteins are not extracted from chromatin by 5% HClO4 and 1 M NaCl, but can be extracted by 0.4 n H2SO4 and 2 M NaCl. Study on proteins binding to DNA demonstrated that in 0.05 M NaCl these proteins are bound both to bovine satellite DNA and to the plasmid pBR 322 DNA.


[Psychodynamic theory of childhood psychoses].
A review of the different concepts of childhood psychoses is made. Margaret Mahler's observations of normal and psychotic children concerning their relationship with their mothers during their first years of life are reviewed. Through the discussion of the concepts that Mahler has reached, understanding the dynamics of growth and their alterations, we obtain a clear understanding of the defects in psychological functions observed in the psychoses, including early infantile autism (Kanner) and symbiotic psychosis (Mahler). A correlation of events occurring at different levels of growth: object relations, cognitive growth, psychosexual development, growth of anxiety, etc., is attempted.


Psychological functioning and bodily conditions in patients with pain disorder associated with psychological factors.
A sample of chronic pain patients (N = 40) was described with reference to defence mechanisms, interpersonal problems, psychological symptoms and bodily conditions. The relationships between pain intensity and different psychological and bodily indexes were examined. The defence mechanisms of somatization and denial measured by the Minnesota Multiphasic Personality Inventory (MMPI) characterized the sample. Interpersonal relations were typically overly nurturant, exploitable, non-assertive and socially avoidant according to the circumplex version of Inventory of Interpersonal Problems (IIP-C). Somatization, obsession, depression and anxiety were the highest symptom scales on the Symptom Check-List 90, revised (SCL-90-R). The Comprehensive Body Examination (CBE) produced moderate findings mainly reflecting stiffness, and the intensity of pain was medium high. The MMPI psychosomatic pattern, the combined IIP-C index consisting of the elevated subscales, and the elevated subscales on SCL-90-R were all moderately correlated with pain intensity. Contrary to our prediction, the global bodily stiffness score was unrelated to pain.


Impact of four loci on serum tamsulosin hydrochloride concentration.
Tamsulosin hydrochloride is one of the most potent drugs for treatment of benign prostatic hyperplasia (BPH), however, the efficacy of tamsulosin hydrochloride varies among individuals. In this study, we measured the maximum serum concentration (Cmax) of tamsulosin hydrochloride in 182 of BPH patients and found remarkable individual variability. To investigate the genetic factors that regulate pharmacokinetics of tamsulosin hydrochloride, we conducted a genome-wide association study in these 182 BPH patients. As a result, rs16902947 on chromosome 5p13.2, rs7779057 on 7q22.3, rs35681285 on 7p21.2 and rs2122469 on 8p21.3 indicated possible associations with Cmax of tamsulosin hydrochloride (P=1.29 × 10(-7), 2.15 × 10(-7), 4.35 × 10(-7) and 7.03 × 10(-7), respectively), although these single-nucleotide polymorphisms (SNPs) did not reach the genome-wide significance threshold after Bonferroni correction. As these associated SNPs showed additive effects on serum tamsulosin hydrochloride concentration, we defined the 'Cmax prediction index' based on genotypes of these SNPs. This index clearly associated with Cmax values (P=4.5 × 10(-6)), indicating the possible roles of these four variants in tamsulosin hydrochloride pharmacokinetics. Our findings would partially explain the variability of the response to the tamsulosin hydrochloride treatment.


Endothelial progenitor cells, bronchopulmonary dysplasia and other short-term outcomes of extremely preterm birth.
To evaluate the impact of endothelial progenitor cells (EPCs), a subset of committed circulatory stem cells, on the development of bronchopulmonary dysplasia (BPD) and other short term outcomes in a cohort of extremely premature newborns. Progenitor cells were quantified by flow cytometry at birth in 36 neonates born <=28 weeks of gestation and at 36 postmenstrual weeks in 18 of them. Cells expressing the stemness markers CD34, CD133, or both were defined as circulating progenitor cells (CPCs). EPCs were defined as CPCs co-expressing the endothelial marker KDR. Mean (SD) gestational age and birth weight of the infants studied were 26.2(1.5) weeks and 761.6(171.8) grams, respectively. EPC levels at birth did not differ between infants who subsequently developed BPD (n=9) and those who did not (n=24) [CD34(+)KDR(+) EPCs: 81(34-41) vs 80(56-110), p=0.7] and were not correlated with the duration of mechanical ventilation or O2-dependence, nor with the need of surfactant replacement. Infants with a hemodynamically significant patent ductus arteriosus (PDA) (n=22) had significantly lower EPC levels at birth than those with no PDA (n=11) [CD34(+)KDR(+) cells: 47(34-92) vs 142(84.5-221), p=0.008]. Data from the 18 infants studied both at birth and at 36 postmenstrual weeks showed that, while CPCs sharply decline over time, levels of all EPCs phenotypes are preserved after delivery. Levels of EPCs at birth did not affect the risk of developing BPD in our group of extremely premature neonates. However, the association between low EPC counts at birth and PDA may be clinically relevant, and deserves further studies.


Understanding metalloprotein folding using a de novo design strategy.
Metal ions play significant roles in most biological systems. Over the past two decades, there has been significant interest in the redesign of existing metal binding sites in proteins/peptides and the introduction of metals into folded proteins/peptides. Recent research has focused on the effects of metal binding on the overall secondary and tertiary conformations of unstructured peptides/proteins. In this context, de novo design of metallopeptides has become a valuable approach for studying the consequence of metal binding. It has been seen that metal ions not only direct folding of partially folded peptides but have at times also been the elixir for properly folding random-coil-like structures in stable secondary conformations. Work in our group has focused on binding of heavy metal ions such as Hg(II) to de novo designed alpha-helical three stranded coiled coil peptides with sequences based on the heptad repeat motif. Removal from or addition of a heptad to the parent 30-residue TRI peptide with the amino acid sequence Ac-G(LKALEEK)(4)G-NH(2) generated peptides whose self-aggregation affinities were seen to be dependent on their lengths. It was noted that adjustment in the position of the thiol from an "a" position in the case of the shorter BabyL9C to a "d" position for BabyL12C resulted in a peptide with low association affinities for itself, weaker binding with Hg(II), and a considerably faster kinetic profile for metal insertion. Similar differences in thermodynamic and kinetic parameters were also noted for the longer TRI peptides. At the same time, metal insertion into the prefolded and longer TRI and Grand peptides has clearly demonstrated that the metal binding is both thermodynamically as well kinetically different from that to unassociated peptides.


Adverse response to methylphenidate in combination with valproic acid.
The use of methylphenidate (MPH) in combination with antiepileptic drugs is gaining acceptance for children with epilepsy who have the symptoms of attention-deficit hyperactivity disorder (ADHD). We report two cases of an adverse effect of dyskinesia and bruxism when MPH was given to children maintained on valproic acid. These adverse effects were rapid and severe. Because of the potential for serious and persistent side effects from this combination of medications, caution is warranted in the treatment of ADHD with MPH for children taking valproic acid. Further prospective studies of the use of valproic acid and MPH in combination are required.


Pharmacokinetics and antitumor activity of a bivalent disulfide-stabilized Fv immunotoxin with improved antigen binding to erbB2.
We have generated a stable bivalent Fv molecule [(dsFv)2] of the anti-erbB2 monoclonal antibody e23 in which the V(H) and V(L) domains of the Fv are linked to each other by a disulfide bond and the two Fvs are connected by a 15-amino acid linker (T. K. Bera et al., J. Mol. Biol., 281: 475-483, 1998). The e23 (dsFv)2 molecule is linked to a truncated form of Pseudomonas exotoxin (PE38) to generate a bivalent disulfide-stabilized immunotoxin e23 (dsFv)2-PE38. Compared to the monovalent immunotoxin, the (dsFv)2 immunotoxin showed greatly increased cytotoxicity to four cancer cell lines expressing low levels of erbB2 but not to four other cell lines with high erbB2 expression. e23 (dsFv)2-PE38 was administered i.v. to mice, and its half-life was determined. The t(1/2)alpha and t(1/2)beta were 20 and 325 min, respectively, whereas the corresponding values for the monovalent dsFv immunotoxin were shorter, 6 and 52 min. The antitumor activities of the monovalent and bivalent immunotoxin were compared using mice bearing A431 tumors. Despite the fact that e23 (dsFv)2-PE38 was 13-fold more active than e23 dsFv-PE38 on A431 cells in cell culture, its antitumor activity in mice was <2-fold that of the monovalent immunotoxin. These data show that a large increase in avidity does not always lead to an increase in cytotoxic activity. Furthermore, in one of the cases in which cytotoxic activity in vitro was greatly enhanced, there was only a small increase in antitumor activity.


Potentiation of the expression of cocaine-induced sensitization by a conditioned stressor.
Repeated exposures to physical stressors cross-sensitize to the locomotor activating effects of psychostimulants in rodents. In the present study, we examined the effect of a conditioned stressor on expression of cocaine-induced sensitization in rats. We determined whether a mint odor cue previously paired with footshock stress (FS) would elicit a sensitized locomotor response in cocaine pre-exposed rats. Rats were given once daily injections of cocaine (30 mg/kg, i.p.) or saline for 6 days in activity monitoring chambers. Subsequently, and in a different and distinct context, equal numbers of rats in each drug condition were exposed to 10 min of brief, intermittent FS or no FS, either in the presence or absence of the mint odor cue. Upon re-exposure to the activity chambers (in which cocaine exposures had been given), all rats previously exposed to cocaine showed robust conditioned locomotion. In response to a cocaine challenge (10 mg/kg, i.p.), cocaine relative to saline pre-exposed rats showed a sensitized locomotor response. Finally, in those cocaine pre-exposed rats that had been given prior odor-FS pairings, concurrent delivery of the cocaine challenge and presentation of the odor cue markedly potentiated the expression of sensitization. To our knowledge, this is the first report of a facilitation of cocaine-induced locomotor sensitization by a conditioned stressor.


Autoradiographic localization of a non-reducible somatostatin analog (125I-CGP 23996) binding sites in the rat brain: comparison with membrane binding.
The regional distribution of somatostatin binding sites in the rat brain was determined by quantitative autoradiography, using 125I-CGP 23996, a non-reducible somatostatin analog. In preliminary experiments, kinetic properties of 125I-CGP 23996 binding to rat brain membranes and slide mounted frozen brain sections were compared and found similar. In addition, distribution of 125I-CGP 23996 and 125I-N-Tyr-SRIF14 binding sites on membrane prepared from 10 different rat brain structures were closely correlated (r = 0.91, 2 p less than 0.01), indicating that the non-reducible analog recognizes the same binding site as the Tyr-extended native peptide. Highest levels of 125I-CGP 23996 binding sites were found in anterior temporal, frontal and cingular cortex as well as hippocampus. Moderate levels were found in the remaining part of the limbic system including amygdala, olfactory tubercles and bed nucleus of the stria terminalis. In the brain stem, nuclei involved in the auditory system such as the ventral cochlear nucleus and the superior olive nucleus, contained high levels of 125I-CGP 23996 binding sites. The distribution of 125I-CGP 23996 binding sites roughly correlated with that of the endogenous peptide in most structures, except in the mediobasal hypothalamus.


The use of Singapore flaps for vaginal reconstruction in women with vaginal stenosis with obstetric fistula: a surgical technique.
Gynecologic and plastic surgeons collaborate to improve vaginal reconstruction for women with vaginal stenosis and obstetric fistula. As these cases occur typically in low-resource settings, the Singapore flap is a useful technique given its reliability, safety, ease of dissection, and minimal need for additional supplies. The fasciocutaneous flap maintains cutaneous innervation and vasculature and does not require stenting. The surgical collaboration has made it possible to provide functional vaginal reconstruction as a part of the overall care of obstetric fistula patients. The technique shows promise for improving sexual function for women with obstetric fistula and may also enhance healing. Gynecologic & plastic surgeons collaborate to improve vaginal reconstruction for women with obstetric fistula.


Beyond curve fitting? Comment on Liu, Mayer-Kress, and Newell (2003).
Y.-T. Liu, G. Mayer-Kress, and K. M. Newell (2003) fit learning curves to movement time data and suggested 2 new methods for analyzing learning. They claimed that the methods go "beyond curve fitting." However, in neither their curve fitting nor their new methods is measurement noise accounted for, and therefore they produce inefficient and biased results. Using the data of Liu et al., in which variance caused by learning is small relative to the level of noise for most participants, the present authors demonstrate those problems and provide better alternatives that are more noise tolerant, more powerful, and go beyond curve fitting without displaying the extreme bias produced by the methods of Liu et al.


Bacterial topoisomerases and the control of DNA supercoiling.
DNA in bacterial cells is under negative superhelical tension, a feature that facilitates many of the activities of DNA. Supercoiling is introduced enzymatically by DNA gyrase, and the accumulation of excessively high levels is prevented by the relaxing activity of DNA topoisomerase I. Among the factors likely to influence supercoiling are topoisomerase gene expression, the ratio of ATP to ADP concentration, and processes such as transcription that unwind DNA and then translocate along it.


Natural attenuation potential of downwelling streams for perfluorochemicals and other emerging contaminants.
Stream augmentation with tertiary treated municipal wastewater-i.e., recycled water-is increasingly considered as an ecologically beneficial way to utilize recycled water, especially in semi-arid regions of the American Southwest. There is concern that emerging contaminants, i.e. unregulated but biologically active organic compounds, may be present in recycled water and will impact on the aquatic environment and the underlying groundwater. Emerging contaminants include a wide variety of chemically disparate compounds, including pharmaceuticals, endocrine disruptors, and residues of perfluorochemical surfactants (PFCs). This paper presents background data on the occurrence and transport of PFC in Upper Silver Creek (USC) and Coyote Creek, in San Jose, California. USC feeds into Coyote Creek, which discharges into San Francisco Bay. Augmenting the natural flow of Coyote Creek with highly treated recycled water is currently being considered as a means to provide more freshwater to the river ecosystem. The reach of interest is approximately 1,000 m where USC flows on alluvial fan deposits. Data indicate that some PFCs are refractory.


Early infant growth monitoring--time well spent?
In sub-Saharan Africa, growth monitoring for every infant consumes time and resources with no evidence of any benefits. We consider an alternative pragmatic approach which provides scheduled monitoring for low birth weight infants only, and takes advantage of non-routine clinic visits for normal birth weight infants. We investigate the implications for the number of weighing episodes and performance as a screening tool using data from a cohort study of infants followed-up from birth to 98 days. Babies delivered in a Kenyan district hospital and enrolled in a birth cohort were weighed at birth and at follow-up visits coinciding with their immunizations at 6, 10 and 14 weeks. Episodes of illness resulting in clinic visits, hospital admissions or death were identified and recorded. Four-fifths (81%) of the 2210 babies weighed 2500 g or more at birth, of whom 133 (7%) were admitted to hospital or died before 14 weeks of age. 85% of the deaths and 67% of admissions occurred within 3 weeks of birth. Most babies weighing 2500 g or more and who had weight measurements grew well. Only 4% of infants were exclusively breastfed at 14 weeks of age. Neither universal nor pragmatic growth monitoring was a good screening tool among this group of infants for episodes of illness in the short-term. Pragmatic monitoring would involve 72% fewer weighing episodes. A pragmatic approach in early infancy would not represent a major change in policy, would appear to have no disadvantages and would probably increase the time available for implementing interventions of greater benefit such as breastfeeding promotion.


Exercise and mental health: it's just not psychology!
Exercise has been suggested as an effective adjunctive treatment for a range of mental health conditions. In this study, we explored the perceptions of exercise held by course directors of doctoral training programmes in clinical psychology in England. Given the exploratory nature of the study, we used a qualitative design incorporating semi-structured interviews. Although most participants held favourable attitudes regarding exercise, this was related more to exercise being seen as a positive lifestyle activity that is worth encouraging, rather than exercise being recommended as an adjunctive treatment for mental health problems. Inductive analysis identified four themes that underpinned such a response: inconsistent positions on the evidential criteria used to evaluate the role of exercise, which masked themes regarding the perceived 'simplicity' of exercise interventions, a practical adherence to a mind-body dichotomy, and the incompatibility of exercise with traditional models of understanding and treating clinical conditions. The barriers we have highlighted will continue to hinder the consideration of exercise as a common therapeutic adjunct at present. Although further research is required to examine the relationship between exercise and mental health, consideration must also be given to how such research should be disseminated to mental health professionals.


Injuries due to deliberate violence in Chile.
An analysis was made over a period of 6 months of the incidents involving deliberate violence as registered in 'Vicaria', the clinic for out-patients within the Cathedral of Santiago de Chile. A total of 236 victims of deliberate violence were observed. Men aged 15-24 years were found to be victims of deliberate violence most frequently. 'Under education' was the most frequently registered occupation for both sexes, and a large group of male victims were 'Unemployed'. 82% of the victims were men and 14% women, 1.5% were boys and 1.5% girls less than or equal to 14 years of age. None of the victims were alcohol intoxicated when arriving in the clinic. The incidents took place in streets for 81% of the male victims and 79% of the female victims, and in the majority of the cases the aggressor(s) was one (or several) police officer(s). Six percent of the female victims had been injured at home. There was no reporting of the aggressor being a relative or acquaintance. The most frequent type of violence was blunt violence from baton(s) (44%), while blunt violence without the use of instruments was reported less frequently (33%). The use of firearms was registered in 18% of the cases, and of sharp instruments, combustion, electro-shock and chain in 1.4%, 1.4%, 1.1% and 0.4% of the cases respectively. A total of 517 primary and secondary diagnoses were applied to the patients. Most of the victims (99%) had moderate or less serious lesions according to the Abbreviated Injury Scale (AIS) (score less than or equal to 2). Twenty-four percent of the victims had more than 4 lesions, and 7% more than 10 lesions. The head/neck region and the trunk were affected with equal frequency, the frequency of injuries of the head/neck region being comparable with that observed among torture victims and in contrast to the pronounced predominance of injuries of the head/neck region observed in a Danish emergency ward study of deliberate violence.


Pelvic venous reflux in males with varicose veins and recurrent varicose veins.
Objectives To report on a male cohort with pelvic vein reflux and associated primary and recurrent lower limb varicose veins. Methods Full lower limb duplex ultrasonography revealed significant pelvic contribution in eight males presenting with bilateral lower limb varicose veins. Testicular and internal iliac veins were examined with either one or a combination of computed tomography, magnetic resonance venography, testicular, transabdominal or transrectal duplex ultrasonography. Subsequently, all patients received pelvic vein embolisation, prior to leg varicose vein treatment. Results Pelvic vein reflux was found in 23 of the 32 truncal pelvic veins and these were treated by pelvic vein embolisation. Four patients have since completed their leg varicose vein treatment and four are undergoing leg varicose vein treatments currently. Conclusion Pelvic vein reflux contributes towards lower limb venous insufficiency in some males with leg varicose veins. Despite the challenges, we suggest that pelvic vein reflux should probably be investigated and pelvic vein embolisation considered in such patients.


Cyclooxygenase-2 regulation in colon cancer cells: modulation of RNA polymerase II elongation by histone deacetylase inhibitors.
We are interested in the mechanism of cyclooxygenase-2 (Cox-2) regulation in colon cancer cells because this knowledge could provide insight into colon carcinogenesis and suggest ways to suppress Cox-2 expression in colon tumors. Studying the HT-29 colon cancer cell line as a model, we found that Cox-2 mRNA and protein levels were activated over 10-fold by the inflammatory cytokine tumor necrosis factor (TNF)-alpha. Moreover, we found that the histone deacetylase inhibitors butyrate and trichostatin A could block Cox-2 activation in a gene-specific manner. TNF-alpha and butyrate did not significantly affect Cox-2 promoter activity, mRNA stability, or negative regulation by the Cox-2 3'-untranslated RNA region. A nuclear run-on assay showed that TNF-alpha increased Cox-2 transcription, whereas butyrate was suppressive. Because butyrate has been reported to suppress polymerase elongation on the c-myc gene, we employed the chromatin immunoprecipitation assay to determine the influence of butyrate and trichostatin A on polymerase distribution on the Cox-2 gene. These data indicated that butyrate restricted polymerase elongation from exon 1 to 2 on both the c-myc and Cox-2 genes. We propose that histone deacetylases regulate a transcriptional block on the Cox-2 and c-myc genes and that this block may be a potential target for pharmacological intervention.


PDGF-D contributes to neointimal hyperplasia in rat model of vessel injury.
In this study, we determined the role of PDGF-D, a new member of the PDGF family, in a rat model of balloon injured artery made with a 2F catheter in Sprague-Dawley male rats. PDGF-D expression was studied in the injured and control segments of abdominal aorta. The function of PDGF-D was evaluated in rat vascular smooth muscle cells stably transfected with PDGF-D gene. We found that in normal abdominal aorta, PDGF-D was highly expressed in adventia, moderate in endothelia, and unidentified in media. Stable transfection of PDGF-D gene into vascular smooth muscle cells increased the cell migration by 2.2-fold, and the proliferation by 2.3-fold, respectively, and MMP-2 production and activity as well. These results support the fact that PDGF-D is involved in the formation of neointimal hyperplasia induced by balloon catheter injury and may serve as a target in preventing vascular restenosis after coronary angioplasty.


Role of TGF-β Signaling in Coupling Bone Remodeling.
TGF-β signaling plays a key role in the temporal and spatial regulation of bone remodeling. During osteoclast bone resorption, TGF-β is released from the bone matrix and activated. Active TGF-β recruits mesenchymal stem cells to the bone resorption pit through the SMAD signaling pathway. Mesenchymal stem cells undergo osteoblast differentiation and deposit new bone filling in the resorption pit and maintaining the structural integrity of the skeleton. Thus, TGF-β signaling plays a key role in the coupling process and disruptions to the TGF-β signaling pathway lead to loss of skeletal integrity. This chapter describes methods on how to quantitate bone matrix TGF-β and assess its role in mesenchymal stem cell migration both in vitro and in vivo.


A filtration, incubation and staining reactor including a new protocol for FISH.
A newly developed device for performing fluorescence in situ hybridization (FISH) is described. An adapted procedure was compared with two typical FISH protocols. Tests were performed with Pseudomonas cells and the gene probe EUB338. With the novel procedure, we obtained a better recovery of cells and less variability in results.


From Mount Sinai to Mount Scopus: differences in the role and value of fine needle aspiration for evaluating thyroid nodules.
Fine needle aspiration is the main diagnostic tool used to assess thyroid nodules. To correlate FNA cytology results with surgical pathological findings in two teaching medical centers across the Atlantic. We retrospectively identified 484 patients at Hadassah Hebrew University Medical Center, Jerusalem and Mount Sinai Hospital, New York, by means of both preoperative FNA cytology and a final histopathological report. Results compared FNA diagnosis, histological findings and frozen section results (Mt. Sinai only). The sensitivity value of FNA at Hadassah was 83.0% compared with 79.1% at Mt. Sinai (NS). Specificity values were 86.6 vs. 98.5% (P < 0.05), negative predictive value 78.7 vs. 77.6% (NS) and positive predictive value 89.7 vs. 98.6% (P < 0.05), respectively. "Follicular lesion" was diagnosed on FNA in 33.1% of the patients at Hadassah and in 21.5% at Mt Sinai (P < 0.005) with a malignancy rate of 42.5 vs. 23.1% (P < 0.05), respectively. Frozen section was used in 190 patients at Mt. Sinai (78.5%) with sensitivity and specificity values of 72.3% and 100%. Frozen section results altered the planned operative course in only 6 patients (2.5%). Follicular carcinoma was diagnosed in 12 patients at Hadassah vs. 2 patients at Mt. Sinai (P < 0.05). The sensitivity of FNA at the two institutions was comparable. While malignancy on frozen section is highly specific, it should be used selectively for suspicious FNA results. Follicular lesions and the rate of malignancy in such lesions were more common at Hadassah, favoring a more aggressive surgical approach.


Efficient removal of oxytetracycline from aqueous solution using magnetic montmorillonite-biochar composite prepared by one step pyrolysis.
Three adsorbents, namely, original biochar (CLB), montmorillonite (MMT)-biochar composite (MBC), and magnetic MMT-biochar composite (MMBC) were successfully fabricated by one step pyrolysis of original cauliflower (Brassica oleracea L.) leaves, mixture of cauliflower leaves and MMT, and FeCl3-laden mixture of cauliflower leaves and MMT under limited oxygen atmosphere, respectively. The characterizations of samples indicated that substantial MMT mineral particles and Fe3O4 nanoparticle were dispersed on the surface of MMBC. Due to the introduction of Fe3O4, MMBC performed excellent magnetization property. The adsorption experiments of oxytetracycline (OTC) indicated that the maximum adsorption ability of MMBC was 58.85 mg·g-1, which was 2.63 times as large as CLB, also, larger than that of MBC. Meanwhile, pH, ionic strength, and humic acid (HA) performed slight effects for adsorption of OTC on MMBC. In addition, MMBC still removed 92% OTC after five regeneration cycles. Finally, primary mechanisms of OTC adsorption onto MMBC were attributed to hydrogen bonding and π-π reaction, and ion exchange reaction was considered to exist. Meanwhile, functional groups including Si-O-Al, Si-O-Si, Si-O, and Fe3O4 nanoparticles would provide extra binding sites for OTC adsorption. Therefore, MMBC had an obvious potential to apply into water purification as a reliable, low-cost, and environmentally friendly adsorbent.


Optimal biomaterials for tracheal epithelial grafts: An in vitro systematic comparative analysis.
Tracheal injury, stenosis, and malignancy demand tracheal reconstruction, which often fails due to the lack of a functioning epithelium. We performed an extensive comparative analysis to determine optimal biomaterials for developing tracheal epithelial grafts with mucociliary function. We screened Hyaluronan-Poly(Ethylene Glycol), Chitosan-Collagen, Collagen Vitrigel Membrane, Fibrin Glue, Silk Fibroin, and Gelatin based on various parameters including mechanical strength, bulk degradation, cell attachment, spreading, metabolic activity, focal adhesion formation, and differentiation into ciliated and goblet cells. Silk Fibroin had significantly higher tensile strength (21.23 ± 4.42 MPa), retained 50% of its mass across 5 weeks, allowed 80-100% cell spreading and increasing metabolic activity across 10 days, focal adhesion formation within 2 h, and differentiation into 5.9 ± 2.6% goblet cells. Silk Fibroin, however, led to poor ciliation, producing 5.5 ± 3.9% ciliated cells, whereas Collagen Vitrigel Membrane promoted excellent ciliation. To capitalize on the mechanical and differentiation benefits of its respective components, we developed a composite biomaterial of Silk Fibroin and Collagen Vitrigel Membrane (SF-CVM), which demonstrated enhanced maturation into 20.6 ± 1.7% ciliated and 5.6 ± 1.0% goblet cells. Development of biomaterials-based airway epithelial grafts that provide desirable mechanics and differentiation is a major step towards treatment of airway disease. STATEMENT OF SIGNIFICANCE: Tracheal blockage, injury, and malignancy greater than 50% of the adult tracheal length cannot be safely resected. Tracheal replacement is one approach, but a major cause of transplant failure is the lack of a functioning epithelium. While tissue engineering for tracheal regeneration using biomaterials is promising, there is currently no gold standard. Therefore, we performed a systematic comparative study to characterize relevant materials for generating a biomaterials-based airway epithelial graft. We developed a composite biomaterial intended for surgical implantation providing tensile strength, slow biodegradation, and optimal support for differentiation of mature epithelia. This is a significant step augmenting current state-of-the-art methods for airway surgeries, laryngeal reconstruction, and tracheal tissue engineering.


Osteosarcoma journey over two decades in India: Small steps, big changes.
The management of osteosarcoma is challenging especially in lower-income and middle-income countries, and there is an unmet need to evolve efficient and sustainable chemotherapy regimens. We compared the outcomes in nonmetastatic osteosarcoma patients treated with three sequential non-high-dose methotrexate-based combination chemotherapy protocols at a single tertiary care center over two decades. The first protocol, OGS-99, involved dose-intense, alternating dyads of three drugs: doxorubicin (Dox), cisplatin (CDDP), and ifosfamide (Ifo). The second protocol, OGS-99 enhanced, included OGS-99 drugs with etoposide and enhanced supportive care. The OGS-12 protocol involved dose-dense administration of eight sequential dyads of Dox, CDDP and Ifo, universal growth factor prophylaxis and targeted nutritional support. Event-free survival (EFS), overall survival (OS), and toxicity were reported using a retrospective chart review in the OGS-99 and OGS-99 enhanced protocols and prospectively in the OGS-12 protocol. A total of 41, 94, and 385 treatment-naïve, consecutive, nonmetastatic patients with extremity osteosarcoma were treated with the OGS-99 (2000-2005), OGS-99 enhanced (2010), and OGS-12 (2011-2016), respectively. At a median follow-up of 19, 86, and 39 months, the five-year EFS rates were 38%, 50%, and 62% in the OGS-99, OGS-99 enhanced, and OGS-12, respectively. The corresponding rates of five-year OS were nonevaluable, 60% and 77%, respectively, with acceptable rates of grade 3-4 toxicities: febrile neutropenia (40%), thrombocytopenia (36%), anemia (51%), and 1% deaths related to toxicity. Sequential selection of an intelligent, dose-dense chemotherapy regimen together with enhanced supportive care resulted in marked improvement in outcomes of nonmetastatic osteosarcoma and this "small steps-big changes" model deserves wider recognition and usage.


The antichromatin antibodies can be useful as a diagnostic tool and disease activity marker of systemic lupus erythematosus in Koreans.
We have investigated the clinical utility of antichromatin antibodies for the diagnosis of SLE and as a marker of disease activity in Korean SLE patients. Blood samples were collected from SLE patients, lupus syndrome patients having only two or three of ACR classification criteria for SLE and normal controls. The level of antichromatin antibody was measured by enzyme linked immunosorbent assay and expressed as arbitrary unit. The antichromatin antibody levels of the SLE and lupus syndrome patients were higher than NC. The antichromatin antibody levels were significant higher in SLE patients with arthritis. A significant correlation was found between the level of antichromatin antibodies and each of anti-dsDNA antibody, leukopenia, complement and SLEDAI. The change of antichromatin antibody levels showed a positive correlation with the change of SLEDAI in serial samples. These data suggest that the antichromatin antibodies appear to be a useful laboratory test that can help in the diagnosis and assessment of SLE.


bcl-2 protects HL-60 cells from apoptosis by stabilizing their intracellular calcium pools.
bcl-2 has been shown to enhance cell survival by inhibiting apoptosis induced under different circumstances. In this study we investigated the effects of bcl-2 overexpression on the homeostasis of subcellular organelles such as ER and mitochondria. In our study, HL-60/bcl-2 and control HL-60/neo cells were obtained by transfection of bcl-2 cDNA or the neomycin-resistant gene, respectively. Apoptosis was evaluated by both DNA fragmentation and flow cytometry qualitatively and quantitatively, and the intracellular calcium by Fura-2/AM. Thapsigargin (TG), a highly specific inhibitor of the ER-associated Ca2+ pump, and Br-A23187, a calcium ionophore, were used in this study. Our results showed that overexpression of bcl-2 significantly blocked TG- and Br-A23187-induced apoptosis in calcium containing buffer. Measurement of intracellular calcium showed that bcl-2 overexpression could reduce sustained elevation of cytosolic Ca2+ induced by these agents. However, in calcium-free medium, bcl-2 overexpression maintained Ca2+ uptake in ER of both TG- and Br-A23187-treated cells. Moreover, the depletion of Ca2+ by EGTA enhanced TG- and Br-A23187-induced apoptosis, and reduced the anti-apoptotic action of bcl-2, suggesting that cytosolic Ca2+ elevation may be required for optimal ER pool refilling. These findings suggest that bcl-2 facilitates and maintains the replenishment of Ca2+ in intracellular stores and, as a result, influences the intracellular calcium, thus protecting the cells from death. In addition, there were no cytochrome c release from mitochondria into the cytosol in TG- and Br-A23187- induced apoptosis, suggesting that cytochrome c release is not a universal phenomenon in the apoptotic process.


The Impact of Baked Egg and Baked Milk Diets on IgE- and Non-IgE-Mediated Allergy.
Baked milk (BM) and baked egg (BE) diets are increasingly used in the management of milk and egg allergy, rather than avoidance. Children with tolerance versus reactivity to BM and BE may have smaller skin prick test and lower specific IgE, and BM-tolerant children have less basophil reactivity and more peripheral T regulatory cells. However, most milk- and egg-allergic children tolerate BM and BE and an individual's reactivity is unpredictable. Non-reactivity is due to conformational changes in the allergens. Significant differences in the published advice about methods of introduction exist from graded introduction at home to a medically supervised full dose. These approaches carry different risks and may have different immunological effects. Reactivity to BM is a predictor of a severe milk allergy. Therefore, medical supervision for BM and BE introduction is prudent. The baked diet allows dietary liberation. Most, but not all, BM- and BE-tolerant children continue eating the baked foods. The prognosis of children who can eat BM and BE is favorable with likely resolution of their allergy over the next few years. Murine models of BE diets demonstrate that heated egg can impart clinical protection against anaphylaxis and cause immune changes. Most observational human studies of BM and BE diets demonstrate clinical resolution of allergy and favorable immune changes versus regular care controls. However, the one randomized controlled trial for the BE diet in BE-tolerant children did not support an immune-modifying effect of the BE diet. Another study of BE immunotherapy is expected to be completed in 2018. There is currently no evidence for prevention of allergy with the baked diets. There may be a future role for BM and BE in liberating the diets of individuals with non-IgE-mediated allergy given recent studies that a subset of these patients can consume BM without a clinical reaction.


The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes.
This study was carried out to examine the effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes (PROMs). For this purpose, 139 patients with a singleton pregnancy (27-34 weeks of gestation) complicated by PROMs were evaluated prospectively during the period January 1997 to February 1999 at two Jordanian military hospitals (Prince Rhashed and Prince Zaid). Patients were allocated into two groups; Group 1 included 72 patients treated with dexamethsone (24 mg divided into 4 doses 12 hours apart), and Group 2 which included 67 patients whoreceived no treatment (control group). All women were examined clinically and the diagnosis of PROMs was demonstrated using vaginal speculum, nitrazine paper examination and ultrasonography. All neonates were evaluated clinically, radiologically, and by laboratory investigations. Pearson's Chi-square and Fisher's exact tests were used to assess the significance of differences between the two study groups. Respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular haemorrhage (IVH), and days of hospital stay were significantly reduced in premature infants of the corticosteroid treated women compared with the controls (p<0.04, p<0.04, p<0.04, and p<0.05, respectively). The perinatal mortality was significantly decreased among the corticosteroid treated group in the gestational subgroups 31-32 and 33-34 weeks (p<0.04), and in all birth weight subgroups (p<0.03). RDS was statistically a significant factor which resulted in increased perinatal mortality in the control group (p=0.02). Regarding the occurrence of postpartum endometritis there was a statistically significant increase among the corticosteroid treated group compared with the controls (p<0.04). Antenatal corticosteroid therapy in pregnancies complicated by PROMs has a positive influencing effect on premature infants between 31 and 34 weeks of gestation, decreasing significantly the perinatal morbidity and mortality. It should be used with particular relevance to the developing world where surfactant is not available or where neonatal intensive care units are lacking.


Evaluation of the efficacy of a topical sialogogue spray containing malic acid 1% in elderly people with xerostomia: a double-blind, randomized clinical trial.
The aim of this study was to evaluate the clinical efficacy of a topical sialogogue spray containing 1% malic acid for elderly people affected by xerostomia. This research took the form of a double-blind, randomized clinical trial. Forty-one individuals (mean age: 78.7 years) with xerostomia were divided into two groups: for the first 'intervention group' (21 subjects) a topical sialogogue spray (1% malic acid) was applied, while for the second 'control group' (20 subjects), a placebo spray was applied; for both groups, the sprays were applied on demand during 2 weeks. The Xerostomia Inventory (XI) was used to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after spray application, were measured. XI scores decreased significantly (clinically meaningful) from 36.4 ± 7.3 points to 29.1 ± 7.1 (p < 0.05) with an XI difference of 7.2 ± 6.1, after the combination among 1% malic acid with xylitol and fluoride application. After 2 weeks of 1% malic acid application, unstimulated and stimulated salivary flows rates increased significantly (p < 0.05). A topical sialogogue spray containing 1% malic acid improved xerostomia in an elderly population and increased unstimulated and stimulated salivary flows rates.


Acoustic Structure Quantification Versus Point Shear Wave Speed Measurement for the Assessment of Liver Fibrosis in Viral Hepatitis B.
This study was conducted to evaluate the value of acoustic structure quantification (ASQ) technology versus that of point shear wave speed measurement (PSWSM) imaging technology for the assessment of liver fibrosis stage. A total of 104 patients with chronic hepatitis B (CHB) and 30 healthy control patients underwent ASQ and PSWSM examinations. Seven quantitative parameters were obtained from ASQ, and a principal component analysis was used to establish the integrative indicators. A quantitative parameter, known as the shear wave speed (SWS, m/s), was obtained from the PSWSM. The METAVIR scores for the assessment of pathologic liver fibrosis were used as a benchmark. Liver fibrosis stages exhibited a good correlation with the integrative indicators and SWS (r = 0.682, p <0.001; r = 0.651, p <0.001). The areas under the receiver operating characteristic curves for ASQ and PSWSM were 0.705 and 0.854 for mild liver fibrosis (F ≥ 1, p = 0.045), 0.813 and 0.743 for significant liver fibrosis (F ≥ 2, p = 0.115), 0.839 and 0.857 for severe liver fibrosis (F ≥ 3, p = 0.417) and 0.874 and 0.971 for liver cirrhosis (F = 4, p = 0.016), respectively. In conclusion, both ASQ and PSWSM were promising ultrasonic methods for assessing liver fibrosis in patients with CHB; however, PSWSM was more valuable for identifying mild liver fibrosis (F ≥ 1) and cirrhosis (F = 4) than ASQ, and the combination of PSWSM and ASQ improved the accuracy of diagnosing severe liver fibrosis (F ≥ 3).


An Analysis of Charlie's Law and Alfie's Law.
The Charlie Gard and Alfie Evans cases were high-profile cases involving disagreements between the parents of young infants and medical practitioners, which have given impetus to pre-existing calls for law reform that have been rebranded as 'Charlie's Law' and 'Alfie's Law'. I argue against the proposal to replace the best interest test, which is currently determinative in such contentious cases, with a significant harm test, as it would render UK law divergent from international law. I also employ critical theory to rebut the notion that parents are the best decision makers and refute criticisms of clinicians (who reflexively acknowledged the limits of medicine). I utilise theories of distributive justice to demonstrate that legal reform may exacerbate unfairness, and case law to show that it may be unworkable. Nonetheless, I apply critical and Foucauldian theory to critique the lack of patient and public empowerment within the NHS and I endorse the proposal to ensure that mediation is offered in contentious cases, as this may empower patients and their carers. I also aver that the best interests test should be informed by clearer criteria regarding the allocation of finite resources, which the public should influence via the democratisation of the NHS.


Prevalence of Mental Illness in Adolescents and Adults With Congenital Heart Disease from the Colorado Congenital Heart Defect Surveillance System.
The aim of this study was to estimate the prevalence of the full spectrum of mental illness in adolescents (aged 11 to 17) and adults (aged 18 to 64) with congenital heart defects (CHDs) in the population-level Colorado Congenital Heart Disease Surveillance System. Further we sought to investigate whether severity of the defect, frequency of recent cardiac procedures or underlying genetic disorders influence these estimates. The cohort included patients in clinical care for CHDs between January 1, 2011 and December 31, 2013, identified across multiple healthcare systems and insurance claims. Of 2,192 adolescents with CHDs, 20% were diagnosed with a mental illness with the most prevalent categories being developmental disorders (8%), anxiety disorders (6%), attention, conduct, behavior, impulse control disorders (6%), and mood disorders (5%). Of 6,924 adults with CHDs, 33% were diagnosed with a mental illness with the most prevalent categories being mood disorders (13%), anxiety disorders (13%), and substance-related disorders (6%). Greater lesion complexity was associated with a higher likelihood of anxiety and developmental disorders in both adolescents and adults. Adolescents and adults who had ≥2 cardiac procedures in the 3-year surveillance period had a 3- and 4.5-fold higher likelihood of a mental illness diagnosis, respectively, compared with those who had fewer than 2 cardiac procedures. Finally, patients with a genetic syndrome were more likely to have a mental illness diagnosis. In conclusion, mental illness is a prevalent co-morbidity in the adolescent and adult population with CHDs, thus comprehensive care should include mental health care.


The impact of onlooking and including bystander behaviour on judgments and emotions regarding peer exclusion.
We investigated judgments and emotions in contexts of social exclusion that varied as a function of bystander behaviour (N = 173, 12- and 16-year-olds). Adolescents responded to film vignettes depicting a target excluded by a group with no bystanders, onlooking bystanders, or bystanders who included the target. Adolescents were asked to judge the behaviour and attribute emotions to the excluding group, the excluded target, and the bystanders. Younger adolescents judged the behaviour of the excluding group as more wrong than older adolescents when there were no bystanders present, indicating that the presence of bystanders was viewed as lessening the negative outcome of exclusion by the younger group. Yet, bystanders play a positive role only when they are includers, not when they are silent observers. This distinction was revealed by the findings that adolescents rated the behaviour of onlooking bystanders as more wrong compared with the behaviour of including bystanders. Moreover, all adolescents justified the inclusive behaviour more frequently with empathy than the onlooking behaviour. Adolescents also anticipated more empathy to including bystanders than to onlooking bystanders, as well as anticipated more guilt to onlooking bystanders than including bystanders. The findings are discussed in light of the role of group norms and group processes regarding bystanders' roles in social exclusion peer encounters.


The new definition for acute lung injury and acute respiratory distress syndrome: is there room for improvement?
To review the new (Berlin) definition of the acute respiratory distress syndrome (ARDS) and to propose potential improvements. The Berlin definition resulted in the following modifications: a criterion of less than 7 days was used to define acute onset; the requirement of pulmonary artery wedge pressure was removed. Clinical judgment for characterizing hydrostatic pulmonary edema suffices, unless there is no apparent ARDS risk factor, in which case an objective evaluation is required; the category of acute lung injury was removed, and ARDS was divided into three categories of severity based on the P/F ratio - mild (from 201 to 300), moderate (from 101 to 200), and severe (≤100 mmHg). A positive end-expiratory pressure value of at least 5 cm H(2)O became required for the diagnosis of ARDS. In this review, we propose that both the use of P/F ratio after some stabilization (first 24 h) and the use of compliance stratified at 0.4 ml/cm H(2)O/kg ideal body weight might improve the stratification of patients. The Berlin definition brought improvement and simplification over the previous definitions. The use of data over the first 24 h to reclassify the severity of the disease and the use of compliance to stratify each oxygenation category might further improve the definition.


Biogenesis and replication of small plasmid-like derivatives of the mitochondrial DNA in Neurospora crassa.
For reasons that are not obvious, sets of related, small, plasmid-like elements appear spontaneously and become amplified in the mitochondria of some cytochrome-deficient and/or UV-sensitive mutants of Neurospora crassa. These plasmid-like DNAs are multimeric series of circular molecules, each consisting of a finite number of identical tandem repeats of a relatively short mtDNA-derived nucleotide sequence (monomer). The plasmid-like elements that have been characterized in this study consist of monomers that vary in length from 125 to 296 base pairs, depending on the strain of origin. Each monomer includes a GC-rich palindrome that is followed by the promoter and a short section of the 5' terminal region of the mitochondrial large-subunit rRNA gene (rnl). Analyses of the nucleotide sequences of variants of this group of elements indicates that they are not generated by intra-molecular recombination, but are the result of single- or double-strand DNA breaks that are produced by a mismatch or base excision repair process. These elements do not appear to contain a defined origin of replication, but replicate by a recombination-dependent rolling-circle mechanism. One- and two-dimensional gel electrophoresis of the plasmid-like element derived Hind III and Pst I fragments combined with S1 nuclease treatments suggest that the intergenic GC-rich palindromes, which are ubiquitous in the mtDNA Neurospora, could be replication fork pausing points.


Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma.
To clarify genome-wide DNA methylation profiles during hepatocarcinogenesis, bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed on 126 tissue samples. The average numbers of BAC clones showing DNA hypo- or hypermethylation increased from noncancerous liver tissue obtained from patients with hepatocellular carcinomas (HCCs) (N) to HCCs. N appeared to be at the precancerous stage, showing DNA methylation alterations that were correlated with the future development of HCC. Using Wilcoxon test, 25 BAC clones, whose DNA methylation status was inherited by HCCs from N and were able to discriminate 15 N samples from 10 samples of normal liver tissue obtained from patients without HCCs (C) with 100% sensitivity and specificity, were identified. The criteria using the 25 BAC clones were able to discriminate 24 additional N samples from 26 C samples in the validation set with 95.8% sensitivity and 96.2% specificity. Using Wilcoxon test, 41 BAC clones, whose DNA methylation status was able to discriminate patients who survived more than 4 years after hepatectomy from patients who suffered recurrence within 6 months and died within a year after hepatectomy, were identified. The DNA methylation status of the 41 BAC clones was correlated with the cancer-free and overall survival rates of patients with HCC. Multivariate analysis revealed that satisfying the criteria using the 41 BAC clones was an independent predictor of overall outcome. Genome-wide alterations of DNA methylation may participate in hepatocarcinogenesis from the precancerous stage, and DNA methylation profiling may provide optimal indicators for carcinogenetic risk estimation and prognostication.


Reappraisal of evidence of microscopic portal vein involvement by hepatocellular carcinoma cells with stratification of tumor size.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death internationally, it is necessary to reappraise evidences of HCC cells involving the portal vein, especially considering tumor size. Histopathological evidence and dynamic evidences of radiology and cytology from publication were collected and analyzed. Frequencies of microscopic portal vein involvement (MPVI) and microscopic intrahepatic metastasis (MIM) in resected specimens with single nodule HCC were lower than that of multi nodule HCC, although not significantly. Early HCC (≤1.5 cm) was with extremely low to 0 frequencies of MPVI and MIM. HCC >5 cm showed a tendency of flowing HCC cells into portal vein, which was coincident with significantly high frequency (64.1 %) of MPVI for HCC >5 cm. There were no significant difference of frequencies of MPVI and MIM between groups of tumor ≤2, ≤3, and ≤5 cm. Single nodule HCC >5 cm needs anatomic resection and the root of portal vein should be firstly ligated because of tendency of flowing HCC cells into portal vein. For single nodule HCC ≤2 cm, there was a risk of about 16.2 % of MPVI, and a risk of about 16.2-26.4 % of MPVI for those single nodule HCC ≤5 cm, however, there was a risk of extremely low to 0 of MPVI for early HCC (≤1.5 cm). Surgeons have to balance liver reserve and risk of MPVI for HCC ≤5 cm before deciding anatomic or nonanatomic resection.


Neutral merocyanine dyes: for in vivo NIR fluorescence imaging of amyloid-β plaques.
Two neutral merocyanine-based near-infrared fluorescent probes were for the first time developed through rational engineering of the classical cationic cyanine scaffold IR-780 for in vivo imaging of amyloid-β plaques. In vivo NIRF imaging revealed that the probe could penetrate the blood-brain barrier and efficiently differentiate the living transgenic and wild-type mice.


Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug.
To review and describe studies of the non-psychotomimetic constituent of Cannabis sativa, cannabidiol (CBD), as an anxiolytic drug and discuss its possible mechanisms of action. The articles selected for the review were identified through searches in English, Portuguese, and Spanish in the electronic databases ISI Web of Knowledge, SciELO, PubMed, and PsycINFO, combining the search terms "cannabidiol and anxiolytic", "cannabidiol and anxiolytic-like", and "cannabidiol and anxiety". The reference lists of the publications included, review articles, and book chapters were handsearched for additional references. Experimental animal and human studies were included, with no time restraints. Studies using animal models of anxiety and involving healthy volunteers clearly suggest an anxiolytic-like effect of CBD. Moreover, CBD was shown to reduce anxiety in patients with social anxiety disorder. Future clinical trials involving patients with different anxiety disorders are warranted, especially of panic disorder, obsessive-compulsive disorder, social anxiety disorder, and post-traumatic stress disorders. The adequate therapeutic window of CBD and the precise mechanisms involved in its anxiolytic action remain to be determined.


The politics of invisibility: HIV-positive women who have sex with women and their struggle for support.
HIV-positive women who have sex with women (WSW) have been routinely overlooked by government researchers, health care providers, and the AIDS service community. In addition to stigmas against homosexuality and HIV in larger society, low-income African American and Latina HIV-positive WSW in particular face culturally based stigmas and are disproportionately affected by poverty, drug addiction, homelessness, sex work, and abuse. By analyzing 16 intensive interviews with low-income HIV-positive WSW of color, the author examined the physical, emotional, and psychological needs of this population and their methods of coping with HIV. Also examined were the participants' perceptions of available support networks, which were examined in order to raise awareness of the complex battle fought by these women against HIV and homophobia in the face of greater social, cultural, and economic strife.


A method for functional evaluation of caspase activation pathways in intact lymphoid cells using electroporation-mediated protein delivery and flow cytometric analysis.
The purpose of the study was to develop a rapid technique for determining the functional status of caspase activation pathways in intact lymphocytes. Proteins known to activate caspase-family cell death proteases (cytochrome c; granzyme-B; caspase-8) were introduced into human leukemia and lymphoma cell lines, as well as freshly isolated lymphocytes and leukemia cells, by electroporation. Fluorochrome-labeled proteins with a wide range of molecular weights (from 15 to 150 kDa) were used to evaluate electroporation efficiency by flow cytometry and to compare the efficiency of protein delivery using various electroporation conditions. Caspase activity was monitored using a cleavable, cell-permeable fluorogenic substrate. Conditions were identified for efficient delivery of proteins of +150 kDa into lymphoid cells. Caspase activation induced by various proteins was compared in normal and leukemic lymphocytic cells, revealing impaired caspase activation pathways in some malignant cells. We conclude that electroporation of apoptotic proteins into intact lymphoid cells can be used to contrast the status of various caspase activation pathways, thereby providing insights into the pathological defects in apoptosis regulation that exist in individual patient specimens.


[A critical overview of surgical treatment methods of colorectal injuries].
There is still ongoing debate on therapeutic results of traumatic colorectal perforations. The aim of this study was to evaluate and compare the incidence, management, and outcome of patients with traumatic colonic perforations. From January 1997 to December 2002, 85 surgical patients underwent emergency operation for traumatic colonic perforations. Patients were reevaluated by analyzing the relationship between the overall morbidity and mortality and the surgical treatment options. We took into consideration the time interval between perforation and treatment as well as the nature, the site, and the cause of perforation, patients' age, and additional organ injuries. Mean age was 32,1. The most injured segment was transverse segment of the colon. Hartmann's procedure was performed in 3 patients (3.5%); resection, and primary anastomosis in 11 patients (12%); primary repair in 57(67%); primary repair and proximal diverting colostomy in 11(%12) ; colostomy in 5(5.8%); and appendectomy in 1 patient. Four postoperative death and one fecal fistula occurred. Deaths were not related to the surgical therapy applied. Our early postoperative results after primary repair, and resection anastomosis were good. We conclude that either primary repair or resection and anastomosis can be performed with acceptable morbidity for perforations of the colon and rectum.


[Buprenorphine and methadone to opiate addicts--a randomized trial].
There are approximately 12,000 opioid dependants in Norway. Methadone-assisted treatment was approved in Norway in 1998, buprenorphine in 2000. This study compares the efficacy of methadone (n = 25) and buprenorphine (n = 25) assisted maintenance treatment in a group of long-term (> 10 years) opioid dependant. After randomisation patients received either 16 mg sublingual buprenorphine or individually adjusted methadone (mean 106 mg, range 80 - 160) for 26 weeks, with a rehabilitation programme run in parallel. After 180 days, patient retention was highest in the methadone group (85 % vs. 36 %, p < 0.0005). Days in treatment were 167 vs. 114 (95 % CI for difference 53 days (26-80), p < 0.001). Positive urine test rates for opiates (20 % vs 24 %, p < 0.01) and cannabis (33 % vs 45 %, p < 0.001) were lower in the methadone group which also had lower self-reported risk behaviour and psychological distress. However, only those on buprenorphine reported significant improvement in physical health. For older, long-term opioid dependants with significant co-morbidity and unsuccessful medication-free treatment, high-dose methadone maintenance appears to be the treatment of choice. However, in cases where methadone is poorly tolerated, buprenorphine therapy may be a good alternative.


Fracture dislocation of the calcaneus. A report of two cases.
In two typical cases of calcaneal fracture dislocation, the primary fracture, which runs forward and medially from a point behind the sustentaculum tali, is associated with inversion of the hindfoot. The calcaneus splits into a small anteromedial and a larger posterolateral fragment. Rupture of the lateral collateral ligament allows the posterolateral calcaneal fragment to move laterally to lie immediately subjacent to the distal fibula. Closed reduction is impossible. Open reduction of this rare fracture dislocation is essential. A lateral approach to the calcaneus is generally sufficient, but a second medial incision may be required.


PLEKHA1-LOC387715-HTRA1 polymorphisms and exudative age-related macular degeneration in the French population.
Identification of genetic factors for age-related macular degeneration (AMD) is of crucial importance in this common cause of blindness. Exudative AMD is rapidly progressive and usually associated with severe prognosis. Our purpose was to investigate this association on locus 10q26 in a case-control study including French patients specifically affected with exudative AMD. Polymorphisms rs4146894:G>A of Pleckstrin Homology Domain-containing Protein Family A member 1 (PLEKHA1) gene, rs10490924:G>T at LOC387715, and rs11200638:G>A of HTRA1 (HTRA serine peptidase 1) gene were analyzed in AMD cases (n=118, age=72.3+/-3.8 years old) and healthy controls (n=116, age=72.0+/-3.8 years old). PLEKHA1 polymorphism was associated with AMD. The A allele frequency was 0.67 in cases versus 0.41 in controls, (p=0.0001). After age and sex adjustment, the odds ratio for risk of AMD was 9.1 (4.0-20.9, 95% CI, p=0.0001) for the AA genotype and 2.6 (1.3-5.5, 95% CI, p=0.04) for the AG genotype, conditional on HTRA1. Association was even stronger and independent with HTRA1. The A allele frequency was 0.51 in cases versus 0.22 in controls, (p=0.0001). The odds ratio was 15.5 (5.5-43.9, 95% CI, p=0.0001) for the AA genotype and 3.4 (1.9-6.1, 95% CI, p=0.0001) for the AG genotype. No further information was obtained from LOC387715 due to virtually complete linkage disequilibrium with HTRA1 polymorphism in cases (D'=1.0) and controls (D'=0.98). Although a role for PLEKHA1 could not be totally excluded, there was a four times higher AMD risk was associated with haplotype "A-T-A" involving "PLEKHA1-LOC387715-HTRA1" risk alleles. Compared to PLEKHA1, HTRA1/LOC387715 genetic variations were independently and strongly associated with exudative AMD in the French population. Chromosome-10 genetic variants appear as potentially useful risk markers for early detection of AMD.


An update on diastolic dysfunction.
Diastolic dysfunction refers to abnormal diastolic filling properties of the left ventricle regardless of whether systolic function is normal or the patient has symptoms. Diastolic heart failure (HF), or more accurately, HF with preserved systolic function, is a distinct clinical entity characterized by the presence of the triad of impaired diastolic function, normal systolic function (left ventricular ejection fraction > 50%), and symptoms of HF. Patients with HF with preserved systolic function are frequently symptomatic from both acute and chronic elevations in left ventricular end-diastolic pressure and/or left atrial pressure.


Advances in evoked potential recording. A historical review.
A brief survey is exposed on the main advances in evoked potential recording techniques, since Caton's paper in 1875. The Berger first EEG records and the Adrian's studies on alpha rhythm, the stimulus-evoked alpha blocking, the K-complex and the vertex response, the effect of attention on the early vertex negativity are briefly outlined. Furtherly the P300 components and stimulus discrimination are remembered. The superimposition and averaging techniques have led to the latest developments in brain evoked potential recordings until to the subcortical far-field auditory and somatosensory recordings. The motor potentials and the latest results with electrical and magnetic coil cortex stimulation are shortly reported.


Endophyte-Mediated Suppression of Dollar Spot Disease in Fine Fescues.
In 1989, a close association was found between single-plant progenies of strong creeping red fescue infected with the endophyte Epichloë festucae and enhanced suppression of dollar spot, a widespread foliar disease of turfgrass caused by Sclerotinia homoeocarpa. From this limited observation, extensive field evaluations were conducted on a wide range of fine fescue germplasm obtained throughout the United States and Europe to determine the frequency and magnitude of this association. In five field trials established between 1985 and 1991, endophyte-infected Chewings, hard, blue, and strong creeping red fescue cultivars, selections, and crosses consistently exhibited endophyte-mediated suppression of dollar spot, when compared with closely related endophyte-free entries. Endophyte-infected Chewings and hard fescue cultivars and selections also had greater turf density and supported less foliar mycelium of S. homoeocarpa than endophyte-free entries.


[Radiographic changes in the jaw bones of children with chronic renal failure].
Thirty-four children with chronic renal failure were examined to evaluate the character and frequency of radiographic changes in the jawbones as related to radiographic abnormalities in other skeletal regions and laboratory data. Twenty-seven children showed signs of renal osteodystrophy on the roentgenograms. Radiographic changes in the jawbones including alterations of the laminae durae were observed in twenty-three children. Total loss of laminae durae was only seen in connection with other skeletal signs of renal osteodystrophy. In all these cases the serum parathyroid hormone (iPTH-C) and alkaline phosphatase levels were remarkably increased so that even in the uremic child total absence of laminae durae cannot be considered a first symptom of renal osteodystrophy. However, radiographic changes in the jawbones are important signs for early detection of renal insufficiency in childhood, as these symptomes appeared with similar frequency as pathologic changes in other skeletal regions and were already present in stage of preterminal renal insufficiency.