Expelled uninsured patients in a less-competitive hospital market in Florida, USA.
This research evaluates the effect of hospital competition on inward and outward patient transfers for different types of payers including the uninsured. Although it is a less spotlighted issue, an equally important topic is the likelihood of inter-hospital patient transfers of the insured and the uninsured. This study attempts to fill a gap in the research about the relationship between hospital competition and patient transfers. By developing the payer-specific level of hospital competition, this research evaluates the effect of hospital competition on inward and outward patient sharing (or patient transfers) for different types of payers including the uninsured. For patient transfers, instead of focusing on whether a patient is transferred from one hospital to another hospital at the patient level, we measure the numbers of patient transfers between hospitals (both inward and outward) at the hospital level. These dependent variables-the numbers of outward and inward patient transfers by the principal payers-are count variables, and we employ either a Poisson regression model or a negative binomial regression model. Controlling for hospital characteristics, when the uninsured Hirschman-Herfindahl Index (HHI) increased by 0.01, the uninsured were 593 % more likely to be transferred to another hospital. When a hospital dominates its market, it tends to expel uninsured patients to other hospitals. If patient transfers are medically unnecessary and primarily due to financial incentives, health administrators and policymakers should minimize such events. Since the uninsured who are admitted to a hospital that dominates its hospital market are likely to be much more vulnerable in their access to health care services, the state government of Florida needs to move toward increased health insurance coverage for eligible Floridians.


The inhibition of glycogen synthase kinase-3 by insulin or insulin-like growth factor 1 in the rat skeletal muscle cell line L6 is blocked by wortmannin, but not by rapamycin: evidence that wortmannin blocks activation of the mitogen-activated protein kinase pathway in L6 cells between Ras and Raf.
Glycogen synthase kinase-3 (GSK3) is inactivated in vitro by p70 S6 kinase or MAP kinase-activated protein kinase-1 beta (MAPKAP kinase-1 beta; also known as Rsk-2). Here we show that GSK3 isoforms are inhibited by 40% within minutes after stimulation of the rat skeletal-muscle cell line L6 with insulin-like growth factor-1 (IGF-1) or insulin. GSK3 was similarly inhibited in rabbit skeletal muscle after an intravenous injection of insulin. Inhibition resulted from increased phosphorylation of GSK3, probably at a serine/threonine residue(s), because it was reversed by incubation with protein phosphatase-2A. Rapamycin blocked the activation of p70 S6 kinase by IGF-1 in L6 cells, but had no effect on the inhibition of GSK3 or the activation of MAPKAP kinase-1 beta. In contrast, wortmannin, a potent inhibitor of PtdIns 3-kinase, prevented the inactivation of GSK3 and the activation of MAPKAP kinase-1 beta and p70 S6 kinase by IGF-1 or insulin. Wortmannin also blocked the activation of p74raf-1. MAP kinase kinase and p42 MAP kinase, but not the formation of GTP-Ras by IGF-1. The results suggest that the stimulation of glycogen synthase by insulin/IGF-1 in skeletal muscle involves the MAP-KAP kinase-1-catalysed inhibition of GSK3, as well as the previously described activation of the glycogen-associated form of protein phosphatase-1.


Antifungal Susceptibility Testing of Fusarium: A Practical Approach.
In vitro susceptibility testing of Fusarium is becoming increasingly important because of frequency and diversity of infections and because resistance profiles are species-specific. Reference methods for antifungal susceptibility testing (AFST) are those of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility (EUCAST), but breakpoints (BPs) have not yet been established. One of the problems is that phylogenetic distances between Fusarium species are much smaller than between species of, e.g., Candida. Epidemiological cutoff values (ECVs) for some Fusarium species have been determined in order to differentiate wild-type from non-wild-type isolates. In clinical routine, commercially available assays such as Etest, Sensititre or others provide essential agreement with reference methods. Our objective is to summarize antifungal susceptibility testing of Fusarium genus in the clinical laboratory: how to do it, when to do it, and how to interpret it.


Elevated colchicine sensitivity of dermal lymphocytes in mycosis fungoides.
Lymphocytes in chronic lymphocytic leukaemia and in other malignant lymphomas exhibit an extreme sensitivity to colchicine and are cytolysed in vitro by 10(-6) M colchicine. This characteristic can be quantified with the colchicine sensitivity index which is used for diagnostic purposes. We have demonstrated that lymphocytes liberated from skin infiltrates in mycosis fungoides (6 patients) show an elevated colchicine sensitivity of 44 (p < 0.01); in contrast, the index of lymphocytes isolated from dermal infiltrates of reactive inflammatory dermatoses (9 patients) is low, being only 23. Determination of the colchicine sensitivity index can be helpful in the diagnosis of mycosis fungoides.


[A new device: a fenestrated sheath for IABP, which reduces the incidence of ischemia in the lower limbs].
To decrease the incidence of ischemia in the lower limbs, we developed a new introducer sheath for IABP, which had 38 side holes (diameter; 1mm). Forty-five patients who received IABP counterpulsation support with this fenestrated sheath were compared with 108 patients in whom the ordinary nonfenestrated sheath was used. There was no significant statistical difference between these two study groups regarding age, height, weight and IABP insertion time. The frequency of ischemic episode of the lower limbs was 2.2% (one out of 45 patients) in the group with the fenestrated sheath, which was significantly lower than those with the ordinary sheath (18 out of 108: 16.7%) (p < 0.005). From these data, we deduced that this fenestrated sheath allowed more blood flow to the lower limb and was thus effective in preventing limb ischemia, particularly in patients with small caliber femoral arteries.


[Aortic valve replacement in patients with heart failure].
Severe aortic regurgitation and stenosis are urgent indication for aortic valve replacement in patients with left ventricular dysfunction, however the effect of cardiac surgery may differ in both groups. The aim of the study was to evaluate the early changes of haemodynamic parameters of heart: ejection fraction, endsystolic and enddiastolic left ventricle diameters, endsystolic and enddiastolic left ventricular wall thickness and left atrium diameter, depending on ejection fraction value (EF), in patients undergoing aortic valve replacement due to isolated aortic stenosis or regurgitation. 250 patients engaged to the study were subjected to the mechanical aortic valve replacement in Cardiac Surgery Department in Lodz. All patients were divided into two groups--patients operated due to aortic regurgitation and aortic stenosis. Then each group, depending on EF volume before operation, was divided into two subgroups (A - EF between 35 and 50%; B - EF below 35%). Comparing the pre- and early postoperative period, ejection fraction rose markedly in both subgroups of patients with aortic stenosis and the highest increase was ascertained in subgroups A. Analyzing endsystolic and enddiastolic left ventricle diameters we observed the reduction of left ventricle diameters in all groups. Evaluating endsystolic left ventricular wall thickness we observed the increase of wall thickness in both subgroups B. Analogically enddiastolic left ventricular wall thickness increased in all analyzing groups, whereas in groups with lowest fraction the rise was essential. Aortic valve replacement both due to aortic stenosis and regurgitation is associated with improved haemodynamic status in early postoperative period.


Melatonin Inhibits the Proliferation of Gastric Cancer Cells Through Regulating the miR-16-5p-Smad3 Pathway.
The incidence and mortality of gastric cancer is steadily increasing annually around the world, which required further investigation about alternative therapy strategies. Melatonin, an indoleamine synthesized in the pineal gland, has shown dramatic anticancer effect in several cancers, however, the function of melatonin in gastric cancer needs to be characterized. In this study, we found that melatonin inhibited the growth and induced apoptosis of gastric cancer cells. microRNAs (miRNAs) have been attractive targets for many anticancer drugs. To explore the underlying molecular mechanism by which melatonin attenuated the growth of cancer cells, miRNA microarray analysis was performed to screen the miRNAs, which significantly altered after melatonin treatment. The result showed that melatonin administration enhanced the expression of miR-16-5p. Further molecular mechanism research revealed that miR-16-5p targeted Smad3 and consequently negatively regulated the abundance of Smad3. Consistently, melatonin exposure decreased the level of Smad3 and overexpression of Smad3 attenuated the inhibitory effect of melatonin in gastric cancer cells. These results uncovered the anticancer effect of melatonin and highlighted the critical roles of miR-16-5p-Smad3 pathway in melatonin-induced growth defects of gastric cancers.


Laboratory investigation of fungal infections of the central nervous system.
While fungal infections of the central nervous system (CNS) are relatively rare, fungal pathogens are increasingly being recognized as an important etiology of CNS infections, particularly amongst the growing immunocompromized population. In this paper we aim to provide a practical approach to the diagnosis of fungal infections of the CNS, review some of the diagnostic methods currently available and discuss diagnosis of certain pathogens of particular interest to the practicing neurologist.


Assessment of European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines in an Australian paediatric population.
Coeliac disease (CD) diagnosis is based on clinical assessment, detection of specific autoantibodies and histological examination of small intestinal biopsies. The European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines have recently been updated and recommend CD may be diagnosed without a biopsy or HLA typing in symptomatic patients with high titre IgA tissue transglutaminase antibodies (aTTG) and positive endomysial antibodies (EMA). However, the need for EMA in patients with high level aTTG has been questioned. We aimed to determine the diagnostic benefit of HLA typing, EMA and IgG antibodies to deamidated gliadin (DGP) in children with high level aTTG. We prospectively evaluated children presenting for assessment of possible CD. All patients underwent small bowel biopsy, serological testing and HLA typing. Results were analysed and correlated with histopathological diagnosis. A total of 209 children were assessed; 61.5% were found to have CD and 29% could have avoided biopsy as per 2020 ESPGHAN guidelines. Titres of aTTG ≥60 U/mL or DGP ≥28 U/mL gave 100% specificity and 100% positive predictive value (PPV) for CD. HLA typing and EMA did not improve the PPV of patients with aTTG ≥60 U/mL, but addition of DGP ≥28 U/mL improved diagnostic sensitivity whilst retaining 100% specificity. Addition of HLA and EMA testing in patients with high titre aTTG antibodies does not improve diagnostic performance and may possibly be omitted from the serological workup in these patients. Our data support combining aTTG and DGP testing and optimising cut-offs to maximise specificity as an alternative biopsy-free diagnostic approach.


[Early-stage conservative removal of scars and delayed skin grafting for severe burns in the neck: report of 13 cases].
To optimize the treatments for severe burns in the neck to prevent the hypertrophy, contraction and deformation of the scars and avoid repeated surgical repair. At the early stage of severe neck burns, conservative removal of the scabs was adopted with a small portion of the necrotic tissues preserved. Wound addressing was performed with anti-infection measures supplemented with the application of agents for dissolving the scars, promoting the epithelial growth and preventing local inflammation. Wound repair with large pieces of autologous skin grafts of medium or full thickness was performed with reasonable delay, after which the neck was fixed with thermoplastic splints. The wounds of 13 patients in this survey healed smoothly within 3 weeks, and no obvious hypertrophy, contracture or deformation of the scars was observed. The patients complained no restrained movement of the neck, and adhesion did not occur in the chin, neck or the chest. The method described above may help promote the healing of the neck burns and reduce the incidences of hypertrophy, contracture and deformation of the scars, which avoids further operations for the repair.


Divalent cation-activated RNA synthesis in toluene-treated Escherichia coli.
Novel RNA polymerase activities (termed type II reaction) can be found in toluene-treated Escherichia coli with Ca2+, Fe2+, or endogenously bound cations, probably Mg2+. These activities are distinguishable from the well characterized DNA-dependent RNA polymerase (type I reaction) by: (i) their divalent cation requirements, i.e., the classical enzyme is activated by exogenously added Mn2+, Mg2+, or CO2+ ions; (ii) their relative resistance to inhibition by actinomycin D, rifampicin, and streptolydigin; (iii) their selective synthesis of low molecular weight RNA; (iv) their sensitivity to inhibition by arabinonucleoside 5'-triphosphates or deoxyribonucleoside 5'-triphosphates; and (v) the strict requirement for ATP in Ca2+ and bound cation-activated reactions. The Ca2+-activated and endogenous RNA polymerase activities are inhibited by orthophosphate. The properties of the type II RNA polymerase(s) are compared with those of polynucleotide phosphorylase, and dnaG gene product, and the RNA polymerase described by Ohasa and Tsugita.


Identification of a monocyte specific pre-interleukin 1 beta convertase activity.
Interleukin 1 (IL-1) is a lymphokine secreted by monocytes in response to a variety of inflammatory stimuli. IL-1 beta, the predominant form of IL-1 produced by human monocytes, is synthesized as an inactive precursor of 31 kDa and is cleaved at Asp116-Ala117 to yield a 17.5-kDa extracellular form. The exact cellular site of cleavage and mechanism of secretion is at present unknown. We have prepared cell-free postnuclear extracts from freshly isolated human monocytes as well as THP.1 cells, a human monocyte-like cell line, and various blood lymphocytes and fibroblast cell lines. Using pre-IL-1 beta synthesized by in vitro transcription and translation, we have shown that only extracts derived from human monocytes and THP.1 cells were capable of cleaving precursor IL-1 beta to authentic mature IL-1 beta. Subcellular fractionation of the extracts suggested that the processing activity is found in the cytosol of monocytes or monocyte-like cell lines. The cleavage product of this protease is identical to authentic IL-1 beta as shown by mobility on SDS/PAGE and amino acid sequence analysis of the [3H]leucine-labeled product. The cleavage product is also capable of binding to the IL-1 receptor found on fibroblast membranes. Finally, mutation of Asp116----Ala116 rendered the IL-1 beta precursor resistant to cleavage by the processing activity. We conclude that a protease activity found only in monocytes will specifically process IL-1 beta to an active form.


Antagonist effects of the enantiomers of 3-PPP towards alpha 1-adrenoceptors coupled to inositol phospholipid breakdown in the rat cerebral cortex.
The effects of the two enantiomers of 3-PPP upon alpha 1-adrenergic and muscarinic receptors coupled to the inositol phospholipid (PI) breakdown response have been investigated. 3-PPP(-) and 3-PPP(+) were found to antagonize the noradrenaline (10 microM)-stimulated PI breakdown in rat cerebral cortical miniprisms with IC50 values of 18 and 61 microM, respectively. The dopamine receptor antagonists haloperidol and raclopride were also antagonists, with IC50 values of 0.4 and 25 microM, respectively. 3-PPP(-) and raclopride were found further to act as competitive antagonists, with pA2 values of 6.03 and 5.44, respectively. 3-PPP(-), 3-PPP(+) and haloperidol also antagonized the muscarinic receptor-mediated carbachol (50 microM)-stimulated PI breakdown in cortical miniprisms, albeit at high concentrations (IC50 values of 91, 170 and 28 microM, respectively) whereas raclopride produced only 24% inhibition at the highest concentration tested (100 microM).


Mechanisms of ATP release and signalling in the blood vessel wall.
The nucleotide adenosine 5'-triphosphate (ATP) has classically been considered the cell's primary energy currency. Importantly, a novel role for ATP as an extracellular autocrine and/or paracrine signalling molecule has evolved over the past century and extensive work has been conducted to characterize the ATP-sensitive purinergic receptors expressed on almost all cell types in the body. Extracellular ATP elicits potent effects on vascular cells to regulate blood vessel tone but can also be involved in vascular pathologies such as atherosclerosis. While the effects of purinergic signalling in the vasculature have been well documented, the mechanism(s) mediating the regulated release of ATP from cells in the blood vessel wall and circulation are now a key target of investigation. The aim of this review is to examine the current proposed mechanisms of ATP release from vascular cells, with a special emphasis on the transporters and channels involved in ATP release from vascular smooth muscle cells, endothelial cells, circulating red blood cells, and perivascular sympathetic nerves, including vesicular exocytosis, plasma membrane F(1)/F(0)-ATP synthase, ATP-binding cassette (ABC) transporters, connexin hemichannels, and pannexin channels.


[Results of polychemotherapy in the advanced stages of cervico-facial tumors].
An association of cyclophosphamide, fluorouracil and methotrexate already employed with success against solid tumours in other sites was used in the treatment of 62 patients with advanced tumours of the head and neck. Complete (40.32%) and partial (43.55%) regressions were obtained relatively quickly. A satisfactory period of remission occurred in patients for whom no further treatment had seemed possible, either on account of the extent of the disease, or because surgery and/or radiotherapy had already been performed.


Angiotensin converting enzyme (ACE), characterization by 125I-MK351A binding studies of plasma and tissue ACE during variation of salt status in the rat.
Angiotensin converting enzyme (ACE) was measured in rat plasma and tissues by analysis of the binding of the radio-inhibitor 125I-MK351A, a tyrosyl derivative of enalaprilic acid. Labelled 125I-MK351A bound to plasma and tissue ACE preparations and was displaced in a concentration-related manner by MK351A. Scatchard analysis yielded a single line from which MK351A binding sites/mg protein and MK351A dissociation constant were calculated. Tissue and plasma ACE from Sprague Dawley rats was studied over a wide range of sodium intakes (low salt, 0.026 +/- 0.012 mmol/24 h; normal salt, 0.58 +/- 0.09 mmol/24 h; and high salt, 10.4 +/- 1.3 mmol/24 h) and during high salt and DOCA treatment. Across the range of sodium states studied there were no consistent changes in plasma, lung, aorta, brain, epididymis or kidney MK351A binding sites/mg protein, or equilibrium dissociation constant. Calculated MK351A binding sites (nmol/mg protein) were 1.64 +/- 0.14 in lung, 0.47 +/- 0.04 in aorta, 0.44 +/- 0.05 in epididymis, 0.18 +/- 0.01 in brain and 0.053 +/- 0.004 in kidney preparations (n = 24 in each group) reflecting reported ACE enzymatic activity in these tissues. Equilibrium dissociation constant KD was uniform within each tissue, but varied between organs. The KD (mol/l X 10(-12)) was 50 +/- 2 in aorta, 57 +/- 2 in lung, 58 +/- 2 in epididymis, 61 +/- 3 in brain, 62 +/- 2 in plasma and 84 +/- 3 in kidney (n = 24 in each group).(ABSTRACT TRUNCATED AT 250 WORDS)


A Novel Radial Visualization of Intrusion Detection Alerts.
Intrusion detection systems (IDSs) generally produce an overwhelming amount of alerts, which are commonly plagued by issues of false positives. It is cumbersome for network administrators to manually traverse text-based alert logs in order to detect threats. In this work, we present a novel radial visualization of IDSs alerts, IDSPlanet, which helps administrators identify false positives, analyze attack patterns, and understand evolving network situations. Using a planet's geology as a metaphor for the design, IDSPlanet is composed of chrono rings, alert continents, and an interactive core. Accordingly, these components encode the temporal features of alert types, patterns of behavior in affected hosts, and correlations amongst alert types, attackers, and targets, respectively. The visualization provides an informative picture of networks' status. IDSPlanet offers different interactions and monitoring modes, which allow users to investigate in detail as well as to explore overall pattern. Two case studies and two interviews were conducted to demonstrate the usability and effectiveness of our visualization design.


[Purification of the Ro/SSA antigen and enzyme-linked immunosorbent assay for quantitation of the antibody].
Antibodies to the Ro/SSA antigen occur in patients with Sjögren's syndrome and other collagen diseases. In this study, we used ammonium sulfate precipitation, anti-Ro/SSA immunoaffinity chromatography and gel filtration to purify the Ro/SSA antigen from pig spleen. In addition, the normal human IgG affinity column chromatography was also used to adsorb nonspecific reacting materials as heterophile antigens which contaminated in preparations after immunoaffinity chromatography. On SDS-PAGE the purified Ro/SSA antigen migrated as 60K and 53K polypeptides bands and the antigenicity was observed on 60 K band. An enzyme-linked immunosorbent assay (ELISA) using the purified antigen was developed for quantitation of the antibody which was found to be sensitive, precise and specific. By the method, anti-Ro/SSA antibodies were detected in SLE (44%), MCTD (71%), PSS (50%), SjS (83%), RA (16%), PBC (23%), lupoid hepatitis (23%) but only 4% in normal controls. The purified antigen and ELISA method will provide beneficial tools for the investigation of autoimmune diseases.


Inhibition of 5-lipoxygenase attenuates inflammation and BONE resorption in lipopolysaccharide-induced periodontal disease.
Arachidonate-5-lipoxygenase (5-LO) activity and increased leukotriene B4 (LTB4) production have been implicated in various inflammatory conditions. Increased production of leukotrienes has been associated with periodontal diseases; however, their relative contribution to tissue destruction is unknown. In this study, an orally active specific 5-LO inhibitor is used to assess its role in inflammation and bone resorption in a murine model of lipopolysaccharide (LPS)-induced periodontal disease. Periodontal disease was induced in Balb/c mice by direct injections of LPS into the palatal gingival tissues adjacent to the maxillary first molars three times per week for 4 weeks. Animals were treated with biochemical inhibitor (2 mg/kg/daily) or the same volume of the vehicle by oral gavage. Microcomputed tomography analysis was used to assess bone resorption. Enzyme immunoassay determined LTB4, and enzyme-linked immunosorbent assays quantified tumor necrosis factor (TNF), interleukin (IL)-12, and IL-10 in gingival tissues. Histologic sections were used for the morphometric analysis (number of neutrophils and mononuclear cells). Osteoclasts were counted in tartrate-resistant acid phosphatase-stained sections. Administration of 5-LO inhibitor effectively reduced production of LTB4 (23.7% decrease) and significantly reduced TNF and IL-12 levels in gingival tissues. Moreover, reduction of LTB4 levels in gingival tissues was associated with a significant decrease in bone resorption and a marked reduction in number of osteoclasts and inflammatory cells. 5-LO activity plays a relevant role in inflammation and bone resorption associated with the LPS model of experimental periodontal disease.


Giant adrenal cyst in a pregnant woman: a case report.
In this case report, a rare example of a pregnant woman with a huge adrenal cyst is reported. No other published reports were found to have an outcome like the present case. A 27-year-old primiparous patient admitted to our clinic with complaints of gaining weight, abdominal distension and dyspnea. On physical examination abdominal distension was prominent. She weighed 78 kg. At abdominal ultrasonography, there was an 11 week, single live fetus within the uterine cavity. There was also an approximately 30 x 40 cm sized cyst. The origin of the cyst could not be detected by ultrasonography and magnetic resonance imaging. It was suspected to originate from the ovaries. Tumor markers and other laboratory tests were normal. Laparotomy was planned. During laparotomy, it was observed that there was a huge, thin capsulated cystic lesion filling the abdomen. The uterus and bilateral ovaries were normal. Eleven liters of yellow-colored fluid was drained from the cyst. At exploration, the cyst capsule was originating from a right adrenal lodge and was extirpated. The postoperative weight of the patient decreased to 67 kg. On the third postoperative day, the patient was discharged without any problems. The pathology result of the patient was reported as an epithelial adrenal cyst. The patient did not have any problems on antenatal follow up and had a cesarean delivery at term for cephalopelvic disproportion. A 3500 g, healthy female fetus was delivered.


Brain Fluid Channels for Metabolite Removal.
The adult human brain represents only 2% of the body's total weight, however it is one of the most metabolically active organs in the mammalian body. Its high metabolic activity necessitates an efficacious waste clearance system. Besides the blood, there are two fluids closely linked to the brain and spinal cord drainage system: interstitial fluid (ISF) and cerebrospinal fluid (CSF). The aim of this review is to summarize the latest research clarifying the channels of metabolite removal by fluids from brain tissue, subarachnoid space (SAS) and brain dura (BD). Special attention is focused on lymphatic vascular structures in the brain dura, their localizations within the meninges, morphological properties and topographic anatomy. The review ends with an account of the consequences of brain lymphatic drainage failure. Knowledge of the physiological state of the clearance system is crucial in order to understand the changes related to impaired brain drainage.


Excitation of Ni nanorod colloids in oscillating magnetic fields: a new approach for nanosensing investigated by TISANE.
The response of a colloidal dispersion of Ni nanorods to an oscillating magnetic field was characterized by optical transmission measurements as well as small-angle neutron scattering (SANS) experiments using the TISANE (Time-dependent SANS experiments) technique. Exposed to a static magnetic field, the scattering intensity of the rod ensemble could be well described by the cylinder form factor using the geometrical particle parameters (length, diameter, orientation distribution) determined by transmission electronmicroscopy and magnetometry. An oscillation of the field vector resulted in a reorientation of the nanorods and a time-dependency of the scattering intensity due to the shape anisotropy of the rods. Analysis of the SANS data revealed that in the range of low frequencies the orientation distribution of the rods is comparable to the static case. With increasing frequency, the rod oscillation was gradually damped due to an increase of the viscous drag. It could be shown that despite of the increased friction in the high frequency range no observable change of the orientation distribution of the ensemble with respect to its symmetry axis occurs.


Current Concepts on Diagnosis and Prognosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia.
Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an uncommon cardiac disease characterized by progressive right ventricular dysfunction due to fibrofatty replacement of myocytes and risk of sudden cardiac death from malignant arrhythmias. ARVC/D is a disease of the cardiac desmosome, with genetic mutations in genes encoding proteins critical to this structure found in the majority of patients. The diagnosis of ARVC/D is based on fulfilling a combination of clinical, imaging, pathologic, and/or genetic criteria set forth by the 2010 modified Task Force Criteria. Cardiac magnetic resonance (CMR) is included in these criteria and plays an important role in the management of ARVC/D, demonstrating pathologic structural changes in the right and left ventricles that provide both diagnostic and prognostic information. The purpose of this article is to provide a background on the pathophysiology and genetics of ARVC/D and focus on the role of CMR in management of ARVC/D including diagnosis, prognosis, and treatment decisions. Common CMR pitfalls that can lead to misdiagnosis will also be reviewed.


The Morphofunctional Changes in the Wall of Varicose Veins.
Varicose vein (VV) disease is a frequently occurring pathology of the lower extremities. Although the pathogenesis of varicosity development is not clearly defined, the final common pathway leading to chronic venous insufficiency is the development of venous hypertension, which is associated with severe changes in the venous wall. The aim of this study was to clarify the histological and immunohistochemical changes in great saphenous veins (GSVs) in chronic venous insufficiency. A histopathological study was conducted on 20 patients with VVs (4 males, 16 females) and 4 (1 male, 3 females) patients undergoing distal bypass surgery. Tissues were processed for histological routine straining and immunohistochemical studies of vascular endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, protein gene product 9.5 (PGP 9.5), and collagen type IV, laminin, and fibronectin. A semiquantitative evaluation method was used. Compared with the normal SV, VV sections showed the damaged endothelium areas, significant disorganization of the smooth muscle bundles, and highest density of the vasa vasorum in the tunica media and tunica adventitia, as well as sclerotic blood vessels and neoangiogenesis in almost all specimens. Immunohistochemistry study showed statistically significant difference between the VVs and the control group of several parameters, such as PGP 9.5 positive structures (P < 0.05; 1-tailed significance) and laminin positive structures in subendothelial layer of VVs (P < 0.05; 1-tailed significance). There is also the tendency in increasing of VEGF expression and decreasing of collagen IV structures. Our study did not show statistically significant difference in VEGF, ICAM-1, and VCAM-1 positive structures between varicose and normal veins; however, it could be explained by the limitations of the study. Varicose GSVs represent nonhomogeneous integrity of the basement membrane, smooth muscle disorganization, and active neoangiogenesis, suggesting remodulation of blood vessels. Changes in the appearance of PGP 9.5-containing innervation, laminin, and collagen IV in tunica intima confirm the remodulation of damaged blood vessels.


Calibration of TLD badges for photons of energy above 6 MeV and dosimetric intricacies in high energy gamma ray fields encountered in nuclear power plants.
CaSO4:Dy and LiF TLDs do not exhibit photon energy dependence beyond +/-55% for photons in the energy range from 1 MeV to about 7 MeV. However, when sandwiched between metal filters or used in TLD badge holders having metal filters, the response changes for irradiation from high energy photons as compared to that from 60Co gamma rays (generally used for reference calibrations). This effect is about the same for both the lower atomic number TLD (LiF) and higher atomic number TLD (CaSO4:Dy). For TLDs held on the surface of the phantom and irradiated in collimated photon beams, the response of TLDs without any filter or those under the open window of the TLD badge is considerably reduced due to insufficient build-up to high energy photons, whereas for uncollimated radiation fields from power reactors, an over-response is observed. It is observed that the use of inappropriate encapsulation of dosemeters would cause a significant error not only in the estimation of doses due to penetrating radiations but also in the estimation of beta doses in the mixed fields of beta radiation, high energy gamma rays and high energy electrons often encountered in the fields of pressurised heavy water reactors.


Changing mortality rates and causes of death for HIV-infected individuals living in Southern Alberta, Canada from 1984 to 2003.
To examine changes over a 2-year period in both the mortality rate and the causes of death in a geographically defined HIV-infected population. A database search of primary care information for the dates and causes of death for all patients documented with HIV infection and living in Southern Alberta between 1984 and 2003 was undertaken. Sociodemographic and clinical characteristics were obtained. Causes of death were then individually confirmed by reviewing the patients' hospital charts, autopsy reports, or death certificates and coded using the International Classification of Diseases, 9th Revisions. AIDS deaths were reconciled with Public Health Reports. The time span was divided into pre-highly active antiretroviral therapy (HAART) (1984-1996) and current HAART (1997-2003) periods. Between 1984 and 2003, there were 560 deaths in the 1987 individuals living with HIV infection in Southern Alberta. Of these, 436 deaths (78%) occurred pre-HAART and 124 (22%) in the current HAART period. The crude mortality rate declined from 117 deaths per 1000 patient-years pre-HAART to 24 in the current HAART period. In the pre-HAART era, 90% of all deaths were AIDS related whereas only 67% were AIDS related in the current HAART era. The leading causes of AIDS deaths were AIDS multiple causes (31%), Mycobacterium avium complex (18%), Pneumocystis pneumonia (10%) and non-Hodgkin's lymphoma (7%). The proportion of non-AIDS related deaths increased from 7% pre-HAART to 32% in the current HAART era. Accidental deaths, including drug overdose (29%), suicide (7%) and violence (3%), hepatic disease (19%), non-AIDS related malignancies (19%), and cardiovascular disease (16%) accounted for the majority of non-AIDS related deaths. No deaths directly caused by drug toxicity were found. Overall, 21% of patients who died were antiretroviral (ARV)-naive. A total of 14% of patients dying from AIDS were ARV-naive in contrast to 35% dying from non-HIV related conditions. Of all those dying from AIDS, 23% died<3 months after their initial diagnosis, reflecting late presentation. In the current HAART era, 87% of patients who died from AIDS were extensively treated, reflecting HAART treatment failures due mostly to multiclass drug resistance (42%), inexorable disease progression despite ARV (32%), lack of ability or interest to be maintained on a lifelong HAART programme (21%) and, rarely, drug intolerance (<1%). Deaths from AIDS-related causes have decreased significantly, but deaths from non-AIDS related conditions have increased, both as an absolute number of deaths and as a proportion of all deaths in HIV-infected patients. The increasing age of the HIV population, and the increased mean CD4 count, increased proportion of intravenous drug users, increased hepatitis B virus and hepatitis C virus coinfection rate, and increased history of smoking seen in our population also influenced the mortality rate and causes of death. These factors must also be considered in projecting future trends in mortality of an HIV-infected population.


Mutagenic effects of bleomycin in Drosophila melanogaster.
Although bleomycin (BLM) induces structural chromosome damage, eg, in human lymphocytes, no, or at best a weak, mutagenicity of this substance has been observed after the application of two well-established mutagenicity screening procedures, the Ames test and the sister-chromatid exchange (SCE) test. After feeding BLM to Drosophila melanogaster males we too, observed only a weak mutagenicity as measured by the frequency of recessive sex-linked lethal mutations. These results are based on the analysis of postmeiotic germ cell stages (spermatozoa, spermatids). No autosomal translocations were found in the same experiments. BLM was also fed to Drosophila females under conditions similar or identical to those of the experiments with males. We observed a considerable sensitivity of Drosophila oocytes to the induction by BLM of recessive sex-linked lethal mutations and X-chromosomal aneuploidy (nondisjunction and chromosome loss). Our oocyte results demonstrate that the extensively used antitumor agent bleomycin has to be considered as mutagenic.


Anteromedial Portal Reference Technique for Femoral Tunnel Depth Measurement During Arthroscopic Anterior Cruciate Ligament Reconstruction.
Femoral tunnel preparation during the anterior cruciate ligament reconstruction is a technically demanding step. The anteromedial (AM) portal technique necessitates knee hyperflexion during the femoral tunnel reaming. In a hyperflexed knee, the arthroscopic visualization of the laser markings on the femoral tunnel reamer becomes obscured. Thus, the calculation of the depth of the femoral tunnel becomes difficult. Our technique helps in femoral tunneling reliably without the need for arthroscopic visualization using the AM portal as a reference point to calculate the depth while drilling. This technique can be performed without the need for a second assistant to hold the arthroscope. Furthermore, this technique does not require any specific instruments, and there is no obligation for an additional incision.


Molecular dynamics simulations of phospholipid bilayers.
Molecular dynamics (MD) simulations at 37 degrees C have been performed on three phospholipid bilayer systems composed of the lipids DLPE, DOPE, and DOPC. The model used included 24 explicit lipid molecules and explicit waters of solvation in the polar head group regions, together with constant-pressure periodic boundary conditions in three dimensions. Using this model, a MD simulation samples part of an infinite planar lipid bilayer. The lipid dynamics and packing behavior were characterized. Furthermore, using the results of the simulations, a number of diverse properties including bilayer structural parameters, hydrocarbon chain order parameters, dihedral conformations, electron density profile, hydration per lipid, and water distribution along the bilayer normal were calculated. Many of these properties are available for the three lipid systems chosen, making them well suited for evaluating the model and protocols used in these simulations by direct comparisons with experimental data. The calculated MD behavior, chain disorder, and lipid packing parameter, i.e. the ratio of the effective areas of hydrocarbon tails and head group per lipid (a(t)/ah), correctly predict the aggregation preferences of the three lipids observed experimentally at 37 degrees C, namely: a gel bilayer for DLPE, a hexagonal tube for DOPE, and a liquid crystalline bilayer for DOPC. In addition, the model and conditions used in the MD simulations led to good agreement of the calculated properties of the bilayers with available experimental results, demonstrating the reliability of the simulations. The effects of the cis unsaturation in the hydrocarbon chains of DOPE and DOPC, compared to the fully saturated one in DLPE, as well as the effects of the different polar head groups of PC and PE with the same unsaturated chains on the lipid packing and bilayer structure have been investigated. The results of these studies indicate the ability of MD methods to provide molecular-level insights into the structure and dynamics of lipid assemblies.


[Interforaminal regions of 287 Han adults evaluated by cone-beam computed tomography].
The mandibular anatomical structures including mental foramen, accessory mental foramina, anterior loop were measured and analyzed by cone-beam CT (cone-beam computed tomography, CBCT) , in order to provide some information during surgical procedures in interforaminal regions. Two hundred and eighty-seven Chinese Han patients who visited Stomatological Department of Xiangya Hospital were included in this study. Patients were scanned by cone-beam computed tomography, and the information of interforaminal region was collected from the images. SPSS17.0 software package was used for statistical analysis. The mental foramen was usually apical to the second premolar or between the premolars(60.80% and 30.14%, respectively). The accessory mental foramina was observed in 4.88% of the mandibles, most of which were located under the second premolar, superiorly and distally to the mental foramen. The anterior loop was identified in 89.20% of cases with the mean length being (1.99±1.39) mm. The distance from the apex of the second mandibular premolar to the anterior loop or the inferior alveolar nerve was (5.21±2.50) mm. Accessory mental foramina is present in some mandibles. The anterior loop is highly prevalent in Chinese Han people, and its length is highly variable.


[Health surveillance of health care workers suffering from neurological, psychiatric or behavioural disorders].
Health care workers (HCWs) suffering from psychiatric or neurological disorders, alcohol or drug addiction, may pose a risk for the health and safety of patients. The occupational health specialist charged of medical surveillance of hospital workers (the so-called "Competent Physician") often needs to recognize functional impairment in HCWs. Cases of impairment in HCWs are reported, and management criteria are discussed, in order to define effective strategies to deal with the problem. Alcoholism and other drug addictions are the most common causes of impairment, followed by emotional impairment, neurological and other physical disabilities. The primary responsibility of protecting the public, should be achieved while at the same time maintaining HCWs at work whenever possible. Critical key-points are identified, and suggestions for management of functionally impaired HCWs are given.


Assessing frequency effects on verb inflection use by Spanish-speaking individuals with agrammatism: theoretical and clinical implications.
The resistance of high-frequency linguistic elements to aphasic impairment suggests that frequency of occurrence may be implicated in verb use differences in agrammatic aphasia. The highly-inflected Spanish verb system allows for the examination of frequency of occurrence along two main metrics, daily usage frequency and paradigmatic frequency. In this study, we explored the role of those two frequency dimensions in verb repetition by Spanish speakers with agrammatism. Six native Spanish-speaking individuals with agrammatic oral expression were matched for age, education and Spanish dialect with six speakers with typical language. The speakers participated in a sentence repetition task involving simple verb tenses. Results revealed that high frequency in daily usage can have a stronger facilitating effect on verb repetition than paradigmatic frequency. Theoretical and clinical implications of the findings are discussed to highlight some plausible repercussions of typical discourse patterns in providing a socio-cognitive dimension to agrammatism theory and in supporting the use of frequency-based linguistic features in agrammatism therapy.


Tramadol in the treatment of neuropathic cancer pain: a double-blind, placebo-controlled study.
To assess the efficacy, safety and impact on quality of life of tramadol in the treatment of neuropathic pain in patients with cancer. Patients with similar characteristics were grouped in pairs and randomised to receive either tramadol or placebo. The initial tramadol dosage was 1 mg/kg every 6 hours, increasing to 1.5 mg/kg every 6 hours if necessary to control pain. The study enrolled 36 patients (22 women, 14 men), with a mean age of 50 years. In the group receiving tramadol (n = 18), major improvements in pain intensity and Karnofsky scores occurred (p < 0.001), sleep quality improved by day 45 (p < 0.05) activities of daily living improved (p < 0.05), and use of analgesics that had been taken before the study was reduced (p < 0.05) compared with the placebo group. There was no difference between the groups with regard to changes in the Zung Depression Scale, Beck Anxiety Inventory scores and neurophysiological assessments. More patients in the tramadol group experienced adverse events (p < 0.05). The most common adverse events were nausea, vomiting and constipation. Tramadol is a therapeutic option for the control of neuropathic pain in patients with cancer, and appears to improve quality of life in these patients. The analgesic effect of tramadol is independent of changes in anxiety, depression and nervous system function.


Slip-Ups in the Diagnosis of Cardiac Amyloidosis: A Case Fatality in Point.
This case report illustrates a tragic example of a "missed diagnosis" of amyloid light-chain (AL) amyloidosis with cardiac involvement that led to progressive heart failure and the ultimate death of the patient. It had a rather atypical presentation in terms of cardiac imaging, although there were certain highly suspicious clinical features, cardiac and otherwise. It also illustrates the importance of selecting the most appropriate assays to establish (or rule out) the presence of monoclonal immunoglobulin consistent with AL amyloidosis, which has a poor clinical prognosis, as unfortunately demonstrated in this case.


Association of dietary tomato intake with bladder cancer risk in a prospective cohort of 101,683 individuals with 12.5 years of follow-up.
Previous studies have provided limited evidence for the effect of tomato intake on bladder cancer incidence. This study aimed to evaluate the association between dietary tomato or lycopene consumption and bladder cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression model adjusting for confounders. After a median of 12.5 years of follow-up, 774 incident bladder cancer cases were identified. We found no statistically significant association between dietary intake of raw tomatoes and bladder cancer risk (Adjusted model: HRQ5 VS Q1 = 1.20, 95% CI: 0.95-1.52; P for trend = 0.243). Dietary intakes of tomato catsup, tomato salsa and tomato juice were also not associated with the risk of bladder cancer (all P for trend > 0.05). There was no statistically significant association between dietary consumption of lycopene and bladder cancer risk (Adjusted model: HRQ5 vs. Q1 = 1.04, 95% CI 0.82-1.33; P for trend = 0.590). In summary, analysis of the PLCO study suggested that dietary consumption of tomato or lycopene was not associated with the risk of bladder cancer.


Coordination Polymer Framework Based On-Chip Micro-Supercapacitors with AC Line-Filtering Performance.
On-chip micro-supercapacitors (MSCs) are important Si-compatible power-source backups for miniaturized electronics. Despite their tremendous advantages, current on-chip MSCs require harsh processing conditions and typically perform like resistors when filtering ripples from alternating current (AC). Herein, we demonstrated a facile layer-by-layer method towards on-chip MSCs based on an azulene-bridged coordination polymer framework (PiCBA). Owing to the good carrier mobility (5×10-3 cm2 V-1 s-1 ) of PiCBA, the permanent dipole moment of azulene skeleton, and ultralow band gap of PiCBA, the fabricated MSCs delivered high specific capacitances of up to 34.1 F cm-3 at 50 mV s-1 and a high volumetric power density of 1323 W cm-3 . Most importantly, such MCSs exhibited AC line-filtering performance (-73° at 120 Hz) with a short resistance-capacitance constant of circa 0.83 ms.


Development-associated changes in thyroxine kinetics in juvenile salmon.
Smoltification is a transformation that occurs in some species of salmon, during which solitary fish in fresh water become schooling fish and migrate to the sea. This process is accompanied by large increases in plasma T4. T4 secretion rate and other parameters of T4 metabolism in juvenile coho salmon were estimated by applying kinetic analyses to measurements of the disappearance of injected T4 radiotracer from plasma. Studies were performed at the beginning (March) and end (May) of the increase in T4 concentration in fresh water and seawater. Early and intensive sampling permitted characterization of a very fast initial component of the T4 disappearance curve when analyses included a zero time datum derived from an independent estimate of plasma volume. The plasma volume, equal to 1.77% of body weight, was obtained by measuring the disappearance of radiolabeled albumin from the plasma in two other groups of animals in fresh water and seawater. There were 3- to 7-fold changes in T4 production, distribution, and metabolism between March and May, whereas environment (fresh water vs. seawater) had relatively minor effects on T4 kinetics. In fresh water, the T4 secretion rate was 4.48 ng/h in March and 1.50 ng/h in May. The total T4 pool size was 37.8 ng in March and 12.2 ng in May. Plasma-tissue T4 fluxes were 3- to 7-fold greater in May. Relatively less T4 was distributed in tissue in May (63% vs. 83%), and T4 spent much less time in tissue in May than in March during each pass through the tissue space (11 min vs. 3.1 h). We propose that the difference in secretion rate and a redistribution of T4 between blood and tissues contribute to both the rise and fall in the plasma T4 concentration between March and May. Changes in T4 kinetics during salmonid smoltification resemble those occurring during amphibian metamorphosis and mammalian gestation and neonatal life, and may reflect an increased requirement and an important role for thyroid hormones during periods of rapid development in vertebrates in general.


Urinary organic acids in man. III. Quantitative ranges and patterns of excretion in a normal population.
We studied the urinary excretion of organic acids by normal human subjects in an ambulant normal population, chosen without conscious bias. Quantitative ranges and frequency distribution patterns of excretion are reported, as a basis on which to compare results obtained for patients whose clinical condition suggests that their excretion values may be abnormal. The quantitative valuse we observed enable the relative significance of different urinary anionic metabolites to be assessed, including the recently identified aldonic and deoxyaldonic acids. The frequency distribution patterns observed are discussed briefly.


Inhibition of zeaxanthin epoxidase activity by cadmium ions in higher plants.
The effect of cadmium and zinc ions on violaxanthin cycle enzymes, violaxanthin de-epoxidase and zeaxanthin epoxidase, has been investigated on selected plant species, as well as in vitro. About 50% inhibition of zeaxanthin epoxidase by cadmium ions was found for duckweed (Lemna trisulca) and tomato (Lycopersicon esculentum) leaves but for apricot (Prunus armeniaca) leaves no cadmium inhibition of the epoxidation reaction was observed. The cadmium inhibition of zeaxanthin epoxidase in tomato was abolished by zinc ions. Zinc ions alone did not affect the activity of neither of the enzymes of the violaxanthin cycle. This suggests that mechanism of cadmium inactivation of the enzyme relies on cadmium interaction with a cysteine residue of the protein, important for the enzyme activity. The target cysteine in tomato epoxidase could be the cysteine residue present in the most conservative part of the molecule which is not present in the apricot enzyme sequence. Neither stimulation nor inhibition of violaxanthin de-epoxidase by cadmium ions both in vivo and in vitro studies was detected. It confirms the proposed mechanism of zeaxanthin epoxidation inhibition by cadmium ions because the cysteine residue in the conservative motif of violaxathin de-epoxidase is not present.


Legionellapneumophila induces methylomic changes in ten-eleven translocation to ensure bacterial reproduction in human lung epithelial cells.
Introduction. Legionella pneumophila is a Gram-negative flagellated bacteria that can infect human lungs and cause a severe form of pneumonia named Legionnaires' disease.Hypothesis. We hypothesize that L. pneumophila infection induces methylomic changes in methylcytosine dioxygenases, ten-eleven translocation (TET) genes, and controls DNA methylation following infection.Aim. In the current research, we sought to further investigate DNA methylation changes in human lung epithelial cells upon L. pneumophila infection and determine how methylation inhibitor agents disturb L. pneumophila reproduction.Methodology. A549 cell line was used in L. pneumophila infection and inhibitors' treatment, including 5-azacytidine (5-AZA) and (-)-epigallocatechin-3-O-gallate (EGCG).Results. Interestingly, DNA methylation analysis of infected A549 using sodium bisulfite PCR and the methylation-sensitive HpaII enzyme showed potential methylation activity within the promoter regions of ten-eleven translocation (TET) genes located on CpG/397-8 and CpG/385-6 of TET1 and TET3, respectively. Such methylation changes in TET effectors decreased their expression profile following infection, indicated by quantitative real-time PCR (RT-qPCR), immunoblotting and flow cytometry. Furthermore, pre-treatment of A549 cells with 5-AZA or EGCG significantly decreased the bacterial reproduction characterized by the expression of L. pneumophila 16S ribosomal RNA and the c.f.u. ml-1 of bacterial particles. Moreover, both methylation inhibitors showed potent inhibition of methionine synthase (MS) expression, which was further confirmed by the docking analysis of inhibitor ligands and crystal structure of MS protein.Conclusion. These data provide evidence for the methylomic changes in the promoter region of TET1 and TET3 by L. pneumophila infection in the A549 cell line and suggest the anti-bacterial properties of 5-AZA and EGCG, as methylation inhibitors, are due to targeting the epigenetic effector methionine synthase.


Triptolide induces autophagy and apoptosis through ERK activation in human breast cancer MCF-7 cells.
To investigate the effects of triptolide (TPI) on proliferation, autophagy and death in human breast cancer MCF-7 cells, and to elucidate the associated molecular mechanisms, intracellular alterations were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. The results of the MTT assay revealed that TPI significantly reduced the MCF-7 cell survival rate when the concentration was >10 nmol/l. TPI activated a caspase cascade reaction by regulating Bcl-2-associated X protein (Bax), caspase-3 and B-cell lymphoma 2 expression, and promoted programmed cell death via the mitochondrial pathway. The results demonstrated that TPI significantly reduced the cell proliferation rate and viability in a time- and dose-dependent manner, which was confirmed by western blotting and immunofluorescent staining. TPI induced autophagy and influenced p38 mitogen-activated protein kinases, extracellular signal-regulated kinase (Erk)1/2, and mammalian target of rapamycin (mTOR) phosphorylation, which resulted in apoptosis. When cells were treated with a combination of TPI and the Erk1/2 inhibitor U0126, the downregulation of P62 and upregulation of Bax were inhibited, which demonstrated that the inhibition of Erk1/2 reversed the autophagy changes induced by TPI. The results indicated that Erk1/2 activation may be a novel mechanism by which TPI induces autophagy and apoptosis in MCF-7 breast cancer cells. In conclusion, TPI affects the proliferation and apoptosis of MCF-7 cells, potentially via autophagy and p38/Erk/mTOR phosphorylation. The present study offers a novel view of the mechanisms by which TPI regulates cell death.


Resolution of intracardiac and pulmonary thrombi without anticoagulation in a patient with Behçet's disease: a case report.
Intracardiac and pulmonary thrombi are rare but serious manifestations of Behçet's disease, the treatment of such cases is a challenge to the treating physician and use of anticoagulants can hold a great risk to some patients. We report a patient who was found to have multiple right intraventricular and bilateral pulmonary artery thrombi and was clinically diagnosed with Behçet's disease. Early in the course of his treatment, the patient developed massive haemoptysis which precluded the further use of anticoagulants. The patient was treated with immunosuppressants alone and had complete resolution of his symptoms and documented resolution of the thrombi. In a review of the literature, only 3 out of around 50 patients reported to have intracardiac thrombi complicating Behçet's disease were treated without anticoagulants (1, 2) even though there is no clear evidence to support the benefit of anticoagulation to treat arterial or thrombotic lesions (3). We conclude that intracardiac thrombi in patients with Behçet's disease may resolve with immunosuppressants without anticoagulation, which is especially important in patients with contraindication to anticoagulation.


Chemotaxis of human microvessel endothelial cells in response to acidic fibroblast growth factor.
Migration of microvessel endothelial cells (MEC) in response to angiogenic stimuli is a key aspect of angiogenesis, whether in physiologic or pathologic situations. In this work, we provide a rigorous quantitative assessment of the chemokinetic and chemotactic responses of human MEC to acidic fibroblast growth factor (aFGF). A uniform concentration of 1 micrograms/ml of heparin was included in most experiments to exploit heparin's potentiating effect on aFGF activity. The migration is measured in an under-agarose assay with a linear geometry, and evaluated in terms of the random motility and chemotaxis coefficients, mu and chi, which are defined in a mathematical model. The change in value of mu with changes in aFGF concentration provides a quantitative description of the stimulated random motility response, a process known as chemokinesis. This allows the true directional response in gradients to be quantified by the chemotaxis coefficient, chi, and its variation with attractant concentration. The effect of aFGF on MEC random motility is relatively small, with the random motility coefficient ranging from 4.6 +/- 0.4 x 10(-9) to 9.9 +/- 0.3 x 10(-9) cm2/second (mean +/- SE) over four orders of magnitude of aFGF concentration (10(-11) to 10(-8) M). On the other hand, the magnitude of the chemotaxis coefficient at optimal concentrations is quite large (2600 +/- 750 cm2/second-M around 10(-10) M aFGF), demonstrating a significant degree of MEC directional sensitivity to aFGF gradients. The chemotaxis coefficient shows a biphasic dependence on aFGF concentration, suggestive of a receptor-mediated response in which apparent differences in receptor occupancy govern directional bias. These results provide support for the hypothesis that MEC chemotaxis accounts for the directed microvessel growth observed in angiogenesis.


Crop Resilience to Drought With and Without Response Diversity.
In the face of increasingly frequent droughts threatening crop performance, ecological theory suggests that higher species diversity may help buffering productivity by making systems more resistant through resource complementarity and more resilient through higher response diversity. However, empirical evidence for these diversity effects under drought stress has remained patchy. In two pot experiments, we explored whether mixing two legume species with a contrasting response to water availability, alsike clover (AC) and black medic (BM), promotes resistance to cumulative drought stress, and resilience of aboveground crop biomass to a transient drought event. The mixture was more productive than the average of the sole crops, and this mixture effect was higher in the non-stressed than in the drought-stressed plants. However, with six levels of constant drought intensities, the mixture effect was not consistently affected by drought level. Response diversity was evident as asynchrony of growth in the two species after the drought event, with BM re-growing faster than AC. Significant resilience to drought was observed in sole AC, i.e., without response diversity. Resilience was larger in AC than in BM and increased from 44 to 72 days after sowing (DAS). The mixture was more resilient than the average resilience of the sole crops at 72 DAS, but it was never more resilient than AC, indicating that resilience is promoted by, but not dependent on response diversity. We conclude that crop diversity may contribute to drought resilience through growth asynchrony, but that species identity plays a crucial role in making systems more drought-resilient.


A hypermutator phenotype attenuates the virulence of Listeria monocytogenes in a mouse model.
The integrity of the genetic material of bacteria is guaranteed by a set of distinct repair mechanisms. The participation of these repair systems in bacterial pathogenicity has been addressed only recently. Here, we study for the first time the participation in virulence of the MutSL mismatch repair system of Listeria monocytogenes. The mutS and mutL genes, which are contiguous in the L. monocytogenes chromosome, were identified after in silico analysis. The deduced MutS shares 62% identity with MutS of Bacillus subtilis and 50% identity with HexA, its homologue in Streptococcus pneumoniae; MutL shares 59% identity with MutL of B. subtilis and 47% identity with HexB of S. pneumoniae. Functional analysis of the mutSL locus was studied by constructing a double knock-out mutant. We showed that the deletion DeltamutSL induces: (i) a 100- to 1000-fold increase in the spontaneous mutation rate; and (ii) a 10- to 15-fold increase in the frequency of transduction, thus demonstrating the role of mutSL of L. monocytogenes in both mismatch repair and homologous recombination. We found that the deletion DeltamutSL moderately affected bacterial virulence, with a 1-log increase in the lethal dose 50% (LD50) in the mouse. Strikingly, repeated passages of the mutant strain in mice reduced virulence further. Competition assays between wild-type and mutant strains showed that the deletion DeltamutSL reduced the capacity of L. monocytogenes to survive and multiply in mice. These results thus demonstrate that, for the intracellular pathogen L. monocytogenes, a hypermutator phenotype is more deleterious than profitable to its virulence.


Fractional Er:YAG laser assisting topical betamethasone solution in combination with NB-UVB for resistant non-segmental vitiligo.
Resistant non-segmental vitiligo is difficult to be treated. Ablative erbium-YAG (Er:YAG) laser has been used in the treatment of vitiligo, but the ablation of entire epidermis frustrated the compliance of patients. The purpose of this study is to investigate the effects of fractional Er:YAG laser followed by topical betamethasone and narrow band ultraviolet B (NB-UVB) therapy in the treatment of resistant non-segmental vitiligo. The vitiligo lesions of each enrolled patient were divided into four treatment parts, which were all irradiated with NB-UVB. Three parts were, respectively, treated with low, medium, or high energy of Er:YAG laser, followed by topical betamethasone solution application. A control part was spared with laser treatment and topical betamethasone. The treatment period lasted 6 months. The efficacy was assessed by two blinded dermatologists. Treatment protocol with high energy of 1800 mJ/P of fractional Er:YAG laser followed by topical betamethasone solution and in combination with NB-UVB made 60% patients achieve marked to excellent improvement in white patches. The protocol with medium energy of 1200 mJ/P of laser assisted approximate 36% patients achieve such improvement. The two protocols, respectively, showed better efficacies than NB-UVB only protocol. However, fractional Er:YAG laser at low energy of 600 mJ/P did not provide such contributions to the treatment of vitiligo. The fractional Er:YAG laser in combination with topical betamethasone solution and NB-UVB was suitable for resistant non-segmental vitiligo. The energy of laser was preferred to be set at relatively high level.


Filtered load of buffer and renal H-ion secretion: mechanism of proximal tubule load dependence.
When the filtered load of buffers like bicarbonate or phosphate is increased by elevating GFR or buffer concentration in plasma, the overall renal reabsorption of bicarbonate or the formation of titratable acidity are markedly increased. The same happens when buffer concentration or flow rate are varied during proximal microperfusion. We have recently studied the mechanisms of this functional dependence. We have observed that the rate of bicarbonate reabsorption is always proportional to luminal buffer concentration when a stationary fluid column is injected into the proximal lumen. H-ion secretion is also proportional to luminal levels of non-bicarbonate buffers. Using a pH-stat technique adapted to renal tubules, we have shown that H-ion secretion is dependent on proximal pH independently of the used buffer species. A kinetic analysis of these data shows a non-linear relationship between luminal H+ and H+ secretion, compatible with carrier mediated transport.


Non-Destructive Measurement of Three-Dimensional Plants Based on Point Cloud.
In agriculture, information about the spatial distribution of plant growth is valuable for applications. Quantitative study of the characteristics of plants plays an important role in the plants' growth and development research, and non-destructive measurement of the height of plants based on machine vision technology is one of the difficulties. We propose a methodology for three-dimensional reconstruction under growing plants by Kinect v2.0 and explored the measure growth parameters based on three-dimensional (3D) point cloud in this paper. The strategy includes three steps-firstly, preprocessing 3D point cloud data, completing the 3D plant registration through point cloud outlier filtering and surface smooth method; secondly, using the locally convex connected patches method to segment the leaves and stem from the plant model; extracting the feature boundary points from the leaf point cloud, and using the contour extraction algorithm to get the feature boundary lines; finally, calculating the length, width of the leaf by Euclidean distance, and the area of the leaf by surface integral method, measuring the height of plant using the vertical distance technology. The results show that the automatic extraction scheme of plant information is effective and the measurement accuracy meets the need of measurement standard. The established 3D plant model is the key to study the whole plant information, which reduces the inaccuracy of occlusion to the description of leaf shape and conducive to the study of the real plant growth status.


Venous drainage and functional control of the canine prostate gland.
The venous drainage of the canine prostate gland has been studied in nine dogs after post-mortem intravenous injection of a coloured suspension of latex. A submucosal cavernous plexus of the prostatic urethra continuous with that of the penis, and a previously unnamed vessel that drains this plexus into the prostatico-vesical vein are described. The eferential vein was found to open variably, but always into the prostatic venous system. The data support the concept that a very small retrograde blood flow would take androgen-rich blood from the deferential vein into the prostate gland.


Human hepatic sinusoidal endothelial cells in culture produce von Willebrand factor and contain Weibel-Palade bodies.
Human hepatic sinusoidal endothelial cells were derived from cadaveric human livers. Cells were grown in culture for several weeks to produce small patches of confluent endothelial cells. The ultrastructure of sinusoidal endothelial cells was examined, cell monolayers were stained immunocytochemically for von Willebrand factor antigen, and antigen in cell culture media was measured by enzyme-linked immunosorbent assay. Human hepatic sinusoidal endothelial cells contained von Willebrand factor antigen and Weibel-Palade bodies, were fenestrated, and released von Willebrand factor antigen into media in a time-dependent manner. Although in some respects human hepatic endothelial cells were different from vascular cells, there was no evidence that there were qualitative differences in their capacity to produce von Willebrand factor.


Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative.
Infections caused by multidrug-resistant bacteria have been on the rise. This important issue presents a great challenge to the healthcare system and creates an urgent need for alternative therapeutic agents. As a potential solution to this problem, antimicrobial peptides (AMPs) have attracted increasing attention due to their broad spectrum of targeted microbes. However, most AMPs are expensive to synthesize, have relatively high cytotoxicity to mammalian cells, and are susceptible to proteolytic degradation. In order to overcome these limitations, novel synthetic AMPs are desired. Using 1,3,5-triazine (TN) as a template, several combinatorial libraries with varying cationic charge and lipophilicity were designed and screened by the Kallenbach lab. From this screening, TN-5 was identified as a potent lead. In the present study, this compound was tested for its antimicrobial activities on Escherichia coli and Pseudomonas aeruginosa. In addition to regular planktonic cells, the effects on biofilms and persister cells (metabolically inactive and antibiotic tolerant subpopulation) were also investigated. TN-5 was found to have a minimum inhibitory concentration (MIC) of 12.8 μM for both species and kill regular planktonic cells of both species dose dependently. TN-5 is also effective against persister cells of both E. coli and P. aeruginosa. The killing of biofilm cells of the mucoid P. aeruginosa PDO300 was enhanced by alginate lyase.


Vpu protein of human immunodeficiency virus type 1 enhances the release of capsids produced by gag gene constructs of widely divergent retroviruses.
The Vpu protein of human immunodeficiency virus type 1 facilitates the release of virus particles from the surface of infected cells. The ability of the Vpu protein to facilitate release of Gag proteins from retroviruses that lack a Vpu-like protein was examined. The results of these experiments show that Vpu significantly increases the release of the Gag proteins of human immunodeficiency virus type 2, visna virus, and Moloney murine leukemia virus from HeLa cells. The results indicate that Vpu-mediated enhancement of particle release requires neither amino-terminal myristoylation of the Gag precursor nor cleavage of the Gag precursor by the viral protease. The results raise the possibility that Vpu modifies a cellular pathway common to the release of all retroviruses from the cell surface.


Supercurrent, Multiple Andreev Reflections and Shapiro Steps in InAs Nanosheet Josephson Junctions.
We report an experimental study of proximity induced superconductivity in planar Josephson junction devices made from free-standing InAs nanosheets. The nanosheets are grown by molecular beam epitaxy, and the Josephson junction devices are fabricated by directly contacting the nanosheets with superconductor Al electrodes. The fabricated devices are explored by low-temperature carrier transport measurements. The measurements show that the devices exhibit a gate-tunable supercurrent, multiple Andreev reflections, and a good quality superconductor-semiconductor interface. The superconducting characteristics of the Josephson junctions are investigated at different magnetic fields and temperatures and are analyzed based on the Bardeen-Cooper-Schrieffer (BCS) theory. The measurements of the ac Josephson effect are also conducted under microwave radiations with different radiation powers and frequencies, and integer Shapiro steps are observed. Our work demonstrates that InAs nanosheet based hybrid devices are desired systems for investigating the forefront of physics, such as two-dimensional topological superconductivity.


Directly Probing Charge Separation at Interface of TiO2 Phase Junction.
Phase junction is often recognized as an effective strategy to achieve efficient charge separation in photocatalysis and photochemistry. As a crucial factor to determine the photogenerated charges dynamics, there is an increasingly hot debate about the energy band alignment across the interface of phase junction. Herein, we reported the direct measurement of the surface potential profile over the interface of TiO2 phase junction. A built-in electric field up to 1 kV/cm from rutile to anatase nanoparticle was detected by Kelvin Probe Force Microscopy (KPFM). Home-built spatially resolved surface photovoltage spectroscopy (SRSPS) supplies a direct evidence for the vectorial charge transfer of photogenerated electrons from rutile to anatase. Moreover, the tunable anatase nanoparticle sizes in TiO2 phase junction leads to high surface photovoltage (SPV) by creating completely depleted space charge region (SCR) and enhancing the charge separation efficiency. The results provide a strong basis for understanding the impact of built-in electric field on the charge transfer across the interface of artificial photocatalysts.


Does a tertiary Gleason pattern 4 or 5 influence the risk of biochemical relapse after radical prostatectomy for clinically localized prostate cancer?
The presence of a tertiary Gleason grade (TGG) pattern 4 or 5 in radical prostatectomy (RP) specimens has been reported with adverse pathology and a higher biochemical relapse rate after RP. This study investigated the impact of a TGG pattern 4 or 5 on biochemical and pathological outcome in men operated with RP. The study reviewed 151 consecutive cases treated at the hospital between 1985 and 2006; 148 were included in the study. All prostatectomy specimens were re-examined by a genitourinary pathologist and among others parameters the presence of TGG pattern 4 or 5 was recorded. The hospital files were examined retrospectively for clinical follow-up data. Prostate-specific antigen (PSA) relapse was defined as two subsequent rising measurements above 0.20 ng/ml. The influence of a TGG pattern 4 or 5 on prognosis was assessed in a Cox proportional hazards regression model controlling for pathological stage, surgical margin (SM) status, seminal vesicle invasion (SVI) and extraprostatic extension (EPE). Fifty-six patients (38%) experienced PSA relapse during follow-up. Twenty-one patients (58%) with a TGG pattern 4 or 5 had a biochemical relapse compared with 35 patients (31%) without TGG pattern 4 or 5. In the Cox regression model, TGG pattern 4 or 5 was an independent predictor of biochemical failure (p = 0.020). In patients undergoing RP the presence of a TGG pattern 4 or 5 is an independent predictor for biochemical relapse. Consequently, the RP specimens should routinely be investigated for TGG pattern 4 or 5.


Paraquat increases superoxide dismutase activity and radiation resistance in two mouse lymphoma L5178Y cell strains of different radiosensitivities.
It is shown that paraquat treatment (1 h, 1 x 10(-5) mol/l) increases the activity of superoxide dismutase (SOD) in L5178Y (LY) R and S cells by about three times. When combined with X-irradiation, 0.5 h of treatment preceding irradiation increased the SOD activity two-fold and the alpha/beta ratio three-fold, as estimated from the X-ray survival curves. LY-S cells were more sensitive than LY-R cells to treatment with paraquat alone. These results indicate that SOD may be a radioprotective enzyme in LY strains and that LY-S cells are particularly sensitive to superoxide radicals as a result of a relatively low SOD activity. This explains their sensitivity to paraquat, which generates O2-, and to X-rays. The low SOD level may also explain the higher initial DNA damage in X-irradiated LY-S than LY-R cells.


A study on intranatal care practices in a district of West Bengal.
A study was conducted at Birbhum district of West Bengal among mothers who delivered in last one year to generate area-specific community-based data on the proportion of home deliveries, assistance during conduction of delivery and the intranatal care practices followed in the district. A multistage 40 cluster sampling method was used to study 320 mothers in the district. 37.81% deliveries were conducted at home. About 25% deliveries were conducted by untrained birth attendants, unqualified practitioners or relatives and friends. In 85.13% of home deliveries, DDK was not used. 68.6% home deliveries were conducted on the floor without any clean covering sheet. Though a clean instrument was used to cut the cord in 86.78% of home deliveries, a clean cord tie was used in only 24.89% cases. In 36.36% home deliveries, something was applied on the cord stump. High proportion of deliveries assisted by untrained persons and high magnitude of faulty intranatal care practices observed in the study require urgent and appropriate intervention.


[Infectious diarrhea in childhood].
The present review summarizes the actual knowledge of infectious diarrhea in the pediatric age group. Main emphasis is placed on discussion of pathogenesis, etiology and therapy. Own data on etiology and clinical presentation of diarrhea in hospitalized children, so far not available from Switzerland, are presented and compared with results from other centres.


Identification of algal rich microbial blooms in the Sellafield Pile Fuel Storage Pond and the application of ultrasonic treatment to control the formation of blooms.
The presence of microorganisms in a range of nuclear facilities has been known for many years. In this study the microbial community inhabiting the Pile Fuel Storage Pond (PFSP), which is a legacy open-aired facility on the Sellafield nuclear site, Cumbria, UK, was determined to help target microbial bloom management strategies in this facility. The PFSP is currently undergoing decommissioning and the development of prolonged dense microbial blooms reduces the visibility within the water. Such impairment in the pond water visibility can lead to delays in pond operations, which also has financial implications. Efforts to control the microbial population within the PFSP are ongoing, with the installation of ultrasonic treatment units. Here next generation sequencing techniques focussing on broad targets for both eukaryotic and prokaryotic organisms were used to identify the microbial community. On-site monitoring of photosynthetic pigments indicated when microbial blooms formed and that eukaryotic algae were most likely to be responsible for these events. The sequencing data suggested that the blooms were dominated by members of the class Chrysophyceae, a group of golden algae, while evidence of cyanobacteria and other photosynthetic bacteria was limited, further supporting eukaryotic organisms causing the blooms. The results of sequencing data from 2018 was used to inform a change in the operational settings of the ultrasonic units, while monitoring of the microbial community and photosynthetic pigments trends was extended. Since the changes were made to the ultrasonic treatment, the visibility in the pond was significantly improved, with an absence of a spring bloom in 2020 and an overall reduction in the number of days lost due to microbial blooms annually. This work extends our knowledge of the diversity of microbes able to colonise nuclear fuel storage ponds, and also suggests that sequencing data can help to optimise the performance of ultrasonic treatments, to control algal proliferation in the PFSP facility and other inhospitable engineered systems.


Sirtuin 1: A Dilemma in Transplantation.
Sirtuin 1, a member of sirtuin family of histone deacetylase enzymes, has been implicated in a variety of physiologic and pathologic events, including energy metabolism, cell survival, and age-related alterations. In view of the anti-inflammatory properties of sirtuin 1 along with its protective role in ischemia reperfusion injury, it might be considered as contributing to the promotion of transplantation outcome. However, the potential ability of sirtuin 1 to induce malignancies raises some concerns about its overexpression in clinic. Moreover, despite the findings of sirtuin 1 implication in thymic tolerance induction and T regulatory (Treg) cells survival, there is also evidence for its involvement in Treg suppression and in T helper 17 cells differentiation. The identification of sirtuin 1 natural and synthetic activators leads to the proposal of sirtuin 1 as an eligible target for clinical interventions in transplantation. All positive and negative consequences of sirtuin 1 overactivation/overexpression in the allograft should therefore be studied thoroughly. Herein, we summarize previous findings concerning direct and indirect influences of sirtuin 1 manipulation on transplantation.


In vitro digestibility, protein composition and techno-functional properties of Saskatchewan grown yellow field peas (Pisum sativum L.) as affected by processing.
Saskatchewan grown yellow field pea was subjected to different processing conditions including dehulling, micronization, roasting, conventional/microwave cooking, germination, and combined germination and conventional cooking/roasting. Their nutritional and antinutritional compositions, functional properties, microstructure, thermal properties, in vitro protein and starch digestibility, and protein composition were studied. Processed field peas including conventional cooked yellow peas (CCYP), microwave cooked yellow peas (MCYP), germinated-conventional cooked yellow peas (GCCYP), and germinated-roasted yellow peas (GRYP) exhibited the significantly higher in vitro protein digestibility (IVPD), which was in accordance with their significantly lower trypsin inhibitor activity and tannin content. The SDS-PAGE and size exclusion HPLC profiles of untreated pea proteins and their hydrolysates also confirmed the IVPD result that these four treatments facilitated the hydrolysis of pea proteins to a greater extent. The CCYP, MCYP, GCCYP, and GRYP also exhibited significantly higher starch digestibility which was supported by their lower onset (To), peak (Tp), and conclusion (Tc) temperatures obtained from DSC thermogram, their lower pasting properties and starch damage results, as well as their distinguished amorphous flakes' configuration observed on the scanning electron microscopic image. LC/ESI-MS/MS analysis following in-gel digests of SDS-PAGE separated proteins allowed detailed compositional characterization of pea proteins. The present study would provide fundamental information to help to better understand the functionality of field peas as ingredients, and particularly in regards to agri-food industry to improve the process efficiency of field peas with enhanced nutritional and techno-functional qualities.


VirtualToxLab - in silico prediction of the toxic potential of drugs and environmental chemicals: evaluation status and internet access protocol.
We present a receptor-modeling concept based on multidimensional QSAR (mQSAR) developed at our laboratory for the in silico prediction of the toxic potential of drugs and environmental chemicals. Presently, the VirtualToxLab includes nine so-called virtual test kits for the estrogen (alpha/beta), androgen, thyroid (alpha/beta), glucocorticoid, aryl hydrocarbon, and peroxisome proliferator-activated receptor gamma, as well as for the enzyme cytochrome P450 3A4. The surrogates have been tested against a total of 798 compounds and are able to predict the binding affinity close to the experimental uncertainty, with only six of the 188 test compounds being calculated more than a factor of 10 off the experimental binding affinity and the maximal individual deviation not exceeding a factor of 15. These results suggest that our approach is suited for the in silico identification of adverse effects triggered by drugs and environmental chemicals. In this account, we summarise the current evaluation status of the models and introduce an Internet access portal, immediately available to selected laboratories, and aimed at a peer evaluation of our concept.


Association between the ERCC5 Asp1104His polymorphism and cancer risk: a meta-analysis.
Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair, removal of bulky lesions caused by environmental chemicals or UV light. Mutations in this gene cause a rare autosomal recessive syndrome, and its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity phenotype and cancer risk. However, a series of epidemiological studies on the association between the ERCC5 Asp1104His polymorphism (rs17655, G>C) and cancer susceptibility generated conflicting results. To derive a more precise estimation of the association between the ERCC5 Asp1104His polymorphism and overall cancer risk, we performed a meta-analysis of 44 published case-control studies, in which a total of 23,490 cases and 27,168 controls were included. To provide additional biological plausibility, we also assessed the genotype-gene expression correlation from the HapMap phase II release 23 data with 270 individuals from 4 ethnic populations. When all studies were pooled, we found no statistical evidence for a significantly increased cancer risk in the recessive genetic models (His/His vs. Asp/Asp: OR = 0.99, 95% CI: 0.92-1.06, P = 0.242 for heterogeneity or His/His vs. Asp/His + Asp/Asp: OR = 0.98, 95% CI: 0.93-1.03, P = 0.260 for heterogeneity), nor in further stratified analyses by cancer type, ethnicity, source of controls and sample size. In the genotype-phenotype correlation analysis from 270 individuals, we consistently found no significant correlation of the Asp1104His polymorphism with ERCC5 mRNA expression. This meta-analysis suggests that it is unlikely that the ERCC5 Asp1104His polymorphism may contribute to individual susceptibility to cancer risk.


A new method for in-situ monitoring of the underground development of Orobanche cumana in sunflower (Helianthus annuus) with a mini-rhizotron.
To develop an in-situ, non-destructive method for observation and monitoring of the underground developmental stages of the root parasite Orobanche cumana. The parasitic weed Orobanche causes severe damage to vegetables and field crops. Most of the damage caused to the crops occurs during the underground, unobservable parasitism stage. Sunflower (Helianthus annuus 'Adi') plants were planted in soil that was artificially inoculated with O. cumana seeds. Clear Plexiglas mini-rhizotron plastic observation tubes were inserted into the soil. Seed germination, early stage of penetration, and formation of tubercles and spikes were observed non-destructively and were monitored throughout the growing season by mean of a mini-rhizotron camera. Use of this technology enabled the complete individual parasite life cycle from the very early development (including germination) to Orobanche shoot to be monitored. In addition, the effect of the systemic herbicide Cadre (imazapic) on the development of O. cumana was inspected and quantified. This novel methodology facilitates the in-situ study of major aspects of the host-parasite interaction and of parasite suppression, such as parasitism dynamics, parasite growth rate, and the effect of chemical treatments on the parasite.


Surgical management of intramedullary spinal cord tumors: functional outcome and sources of morbidity.
We are reporting the functional outcome of 69 of 86 patients affected by intramedullary spinal cord tumors who underwent surgery at our department during the period of 1984 to 1992. The results on 17 patients affected by hemangioblastomas and cavernomas were excluded from this study and will be published separately. Twenty-eight patients had astrocytic processes; 34 had ependymoma; 4 had lipoma; 2 had neurofibroma; and 1 had oligodendroglioma. The overall rate of "radically" resected tumors was 55.1%, as opposed to 17.4% "quasiradically," and 27.5% of "partially" resected processes. There was one postoperative death. Five other patients, affected by anaplastic astrocytomas, died because of tumor progress within 16 months from the operation. A postoperative functional assessment showed that the function of the upper and lower extremities had deteriorated in 65.4 and 55.1% of the patients; a respective functional deterioration by 1 degree of the scale of Cooper and Epstein was registered in 88.8 and 86.8% of the patients. The patients who recovered improved within a period of 6 to 18 months, whereas the function of the dorsal columns was impaired the longest. At follow-up (mean, 54 mo; range, 8-107 mo), the functional recovery (as compared with the preoperative status) was as follows: upper extremity, 17.1% of the patients were improved, 55.5% were unchanged, and 31.5% were worse (89.4% by 1 degree); lower extremity, 22.4% of the patients were improved, 51.5% were unchanged, and 29.4% were worse (most by 1 degree). Surgery on tumors of the cervicothoracic and upper thoracic region carried a relatively higher morbidity in this series.(ABSTRACT TRUNCATED AT 250 WORDS)


[Axonal transport blockage by acute intraocular pressure elevation in monkeys].
The distribution of orthograde rapid axonal transport blockage in the optic nerve head by acute intraocular pressure (IOP) elevation in monkeys was studied by autoradiography. Tritiated leucine was injected intravenously two hours before IOP elevation, and the IOP was elevated for five hours, maintaining a perfusion pressure of 30mmHg. Serial step cross sections from the optic nerve head at the level of the lamina cribrosa were prepared for light microscopic autoradiography, and the accumulation and distribution of grains were quantitatively analyzed using computerized image analysis. The area of focal grain accumulation was expressed as a percent of the defined optic nerve area and each eight sectors, divided by axially intersecting vertical, horizontal, and diagonal lines, respectively. In eyes with IOP elevation, the mean area of focal accumulation of grains in the temporal half of the optic nerve was significantly larger, compared with the nasal half. Within axonal bundles, the focal high accumulation of grains was frequently identified to be in association with trabecular beams of connective tissue in the peripheral portion of the axonal bundle. These results suggest temporal dominant blockage of axonal transport in the optic nerve head, which may be induced by mechanical compression of the axonal bundles during IOP elevation.


[Involvement of MAP-kinase cascades into the regulation of sodium butyrate induced premature cell senescence].
We studied the role of p38 kinase and JNK1,2 in the activation of the complex mTORC1 and the program of senescence induced by histone deacetylase inhibitor, sodium butyrate (NaBut), in mouse embryonic fibroblasts transformed by E1A+cHa-Ras oncogenes. It was found that transformants from knockouts for the genes p38, were able to implement the program of NaBut-induced senescence, according to the data of the cell cycle arrest, inhibition of proliferation, hypertrophic changes associated with the activation of mTORC1 and SA-beta-galactosidase activity. According to the behavior of these markers, cell knockouts for the genes jnk1,2 were unable to implement NaBut-induced senescence. Induction of senescence closely correlates with the activation of the complex mTORC1, as it was shown by inhibiting mTORC1 with rapamycin. We believe that JNK 1,2 kinases are required for mTORC1 activation and acquiring the markers of premature senescence, induced by NaBut in the E1A+cHa-Ras transformants.


Tenofovir disoproxil fumarate-emtricitabine coformulation for once-daily dual NRTI backbone.
Truvada is the coformulation of tenofovir disoproxil fumarate (TDF; 300 mg) and emtricitabine (FTC; 200 mg) in a single tablet, providing the nucleotide backbone for once-daily dosing, as a component of highly active antiretroviral therapy (HAART). TDF (the bioavailable prodrug of tenofovir) is hydrolyzed to tenofovir intracellularly and phosphorylated to the active metabolite, tenofovir diphosphate. Tenofovir is a nucleotide analog of deoxyadenosine monophosphate, with activity against HIV-1, -2 and hepatitis B virus. FTC, the fluorinated derivative of lamivudine, is an analog of deoxycitidine, active against HIV-1, -2 and hepatitis B virus. Their long half-lives in plasma and in peripheral blood mononuclear cells allow once-daily dosing. Both are eliminated renally. Resistance mutation K65R is selected for by tenofovir and confers a two- to fourfold reduced susceptibility to this drug. The incidence of K65R is low (3%) and has not been observed in clinical trials with the concomitant use of tenofovir and FTC. FTC selects for M184V mutation less frequently than lamivudine. Tenofovir drug interactions include increased exposure to didanosine and inferior immune recovery that preclude their concomitant use. Boosted protease inhibitors increase exposure to tenofovir without dose adjustment required. FTC has no significant drug interactions. They are not metabolized by cytochrome P450, which confers little potential for interactions with drugs metabolized by these enzymes. As tenofovir and FTC are renally eliminated, drugs eliminated by tubular secretion must be avoided. Both antiretrovirals, as individual agents and in coadministration have evidenced antiviral potency in clinical trials. Pivotal study 934 evidenced superior efficacy of the combination TDF/FTC/efavirenz (EFV) versus zidovudine/FTC/EFV. The toxicity profile of tenofovir and FTC has been extensively studied. Lipid profile is more favorable with tenofovir than thymidine analog. Tenofovir requires surveillance of glomerular filtration rate and dosing interval adjustment when creatinine clearance is less than 50 ml/min and avoidance less than 30 ml/min. Fat loss is less likely with tenofovir than with thymidine analog. Clinical trials have assessed the performance of the coformulation of TDF and FTC.


Reliability of lipid, lipoprotein, and apolipoprotein measurements.
The National Heart, Lung, and Blood Institute national awareness program on cholesterol and heart disease has placed new demands on laboratorians to utilize and perform more reliable measurements of lipids, lipoproteins, and apolipoproteins. The general public's awareness and the clinicians' concerns about the reliability of laboratory testing make it paramount that the analytical problems and issues are identified and solutions are provided to increase the current state of reliability of the measurement of these blood constituents. To accomplish this, the initial step is to assess the current state of reliability of lipid, lipoprotein, and apolipoprotein measurements in the clinical laboratories. Accuracy and precision of measurements of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and apolipoproteins A-I and B are extensively discussed, and general as well as some specific recommendations are provided for some of the apparent problems.


Commentary on 'Social skills groups for people aged 6 to 21 with autism spectrum disorders (ASD)'.
This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Reichow B, Steiner AM, Volkmar F. Social skills groups for people aged 6 to 21 with autism spectrum disorders (ASD). Cochrane Database of Systematic Reviews 2012, Issue 7. Art. No.: CD008511. DOI: 10.1002/14651858.CD008511.pub2. Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article.


Studies on two-port laparoscopic cholecystectomy.
Generally speaking, the laparoscopic cholecystectomy is performed by using three or four ports. Two ports laparoscopic cholecystectomy is a rarely performed procedure as it demands greater expertise and skills. Benefits of this technique are related to the cost this being cost effective with less scar forming as compared to the conventional approach of laparoscopic cholecystectomy. A group of twenty cases of laparoscopic cholecystectomy was performed by using only two ports. All procedures were completed successfully and no extra port or conversion to open procedure was indicated. Mean operation time was 60 minutes. No intra and postoperative complication occurred. Hospital stay was one day.