Social rank-associated stress vulnerability predisposes individuals to cocaine attraction.
Studies of personality have suggested that dissimilarities in ability to cope with stressful situations results in differing tendency to develop addictive behaviors. The present study used selectively bred stress-resilient, socially-dominant (Dom) and stress-vulnerable, socially-submissive (Sub) mice to investigate the interaction between environmental stress and inbred predisposition to develop addictive behavior to cocaine. In a Conditioned Place Preference (CPP) paradigm using cocaine, Sub mice displayed an aversion to drug, whereas Dom mice displayed drug attraction. Following a 4-week regimen of Chronic Mild Stress (CMS), Sub mice in CPP displayed a marked increase (>400%) in cocaine attraction, whereas Dom mice did not differ in attraction from their non-stressed state. Examination of hippocampal gene expression revealed in Sub mice, exposure to external stimuli, stress or cocaine, increased CRH expression (>100%), which was evoked in Dom mice only by cocaine exposure. Further, stress-induced decreases in DRD1 (>60%) and DRD2 (>50%) expression in Sub mice differed markedly from a complete lack of change in Dom mice. From our findings, we propose that social stratification dictates vulnerability to stress-induced attraction that may lead to addiction via differential regulation of hippocampal response to dopaminergic input, which in turn may influence differing tendency to develop addictive behaviors.


High-dose dexamethasone in quinine-treated patients with cerebral malaria: a double-blind, placebo-controlled trial.
We compared placebo and dexamethasone (initial dose, 3 mg/kg; total, 11.4 mg/kg per 48 h) in a double-blind trial involving 10 stuporous and 28 comatose patients with cerebral malaria. Patients were 18 mo to 42 y of age (geometric mean, 10.2 y), and the 19 patients in each group were comparable on admission. All patients received intravenous quinine therapy. Four patients (21%) in each group died. There were no significant differences between the placebo- and dexamethasone-treated groups in time until patients became afebrile (median, 51 vs. 19 h), the level of consciousness became normal (mean, 80 vs. 83 h), or parasitemia was cleared (mean, 2.1 vs. 3.4 d) or in the incidence of complications. Coma or hyperparasitemia (greater than or equal to 5% of erythrocytes parasitized) at the time of admission and hypoglycemia at any time during hospitalization were significantly correlated with a fatal outcome, which was not improved by using dexamethasone. We conclude that high-dose dexamethasone is not indicated for treating cerebral malaria.


Signet-ring-cell carcinoma of the ampulla of Vater: a case report.
We encountered a rare variant of carcinoma of the ampulla of Vater in a 68-year-old man with postprandial abdominal pain and nausea. Ultrasonography and computed tomography showed a dilated common bile duct and main pancreatic duct. At duodenoscopy, the papilla of Vater was enlarged, and biopsy specimens taken from the papilla revealed signet-ring-cell carcinoma. Endoscopic ultrasonography showed a hypoechoic tumor without pancreatic invasion. Pylorus-preserving pancreatoduodenectomy was performed. Histologic examination of resected specimens indicated lymphatic and vascular invasion, but surgical margins were tumor-free. The patient is alive and disease-free 10 months after the operation.


Search for standard model production of four top quarks with same-sign and multilepton final states in proton-proton collisions at s = 13 TeV.
A search for standard model production of four top quarks ( t t ¯ t t ¯ ) is reported using events containing at least three leptons ( e , μ ) or a same-sign lepton pair. The events are produced in proton-proton collisions at a center-of-mass energy of 13 TeV at the LHC, and the data sample, recorded in 2016, corresponds to an integrated luminosity of 35.9 fb - 1 . Jet multiplicity and flavor are used to enhance signal sensitivity, and dedicated control regions are used to constrain the dominant backgrounds. The observed and expected signal significances are, respectively, 1.6 and 1.0 standard deviations, and the t t ¯ t t ¯ cross section is measured to be 16 . 9 - 11.4 + 13.8 fb , in agreement with next-to-leading-order standard model predictions. These results are also used to constrain the Yukawa coupling between the top quark and the Higgs boson to be less than 2.1 times its expected standard model value at 95% confidence level.


Serum levels of total immunoglobulin e in patients with alopecia areata: relationship with clinical type of the disease.
Alopecia areata (AA) is a heterogeneous disease characterized by nonscarring hair loss on the scalp or any hair-bearing surface. A wide range of clinical presentations can occur, from a single patch of hair loss to complete loss of hair on the scalp (alopecia totalis, AT) or over the entire body (alopecia universalis, AU). The cause of AA is unknown although most evidence supports the hypothesis that AA is an immunologically mediated disease. The aim of the study was to compare serum levels of total immunoglobulin E (IgE) between patients with AA and healthy subjects, and to assess the difference between the localized form and extensive forms of the disease such as AT and AU. Sixty patients with AA and 50 healthy subjects were enrolled in the study. Fifty patients had localized AA (LAA), and ten patients had AT, AU or AT/AU. Serum levels of IgE were measured using fluoroenzyme immunoassay techniques. Serum levels of total IgE were significantly higher in AA patients than in controls (p<0.05). There was no significant difference in serum levels of total IgE between patients with LAA and those with extensive forms of the disease (p>0.05). The exact role of serum IgE in AA should be additionally investigated in future studies.


Psychology and the Threat of Contagion: Feeling Vulnerable to a Disease Moderates the Link Between Xenophobic Thoughts and Support for Ingroup-Protective Actions.
The widespread threat of contagious disease disrupts not only everyday life but also psychological experience. Building on findings regarding xenophobic responses to contagious diseases, this research investigates how perceived vulnerability to a disease moderates the psychological link between people's xenophobic thoughts and support for ingroup-protective actions. Three datasets collected during the time of Ebola (N = 867) and COVID-19 (Ns = 992 and 926) measured perceived disease risk, group-serving biases (i.e., xenophobic thoughts), and support for restrictive travel policies (i.e., ingroup-protective actions). Using correlational and quasi-experimental analyses, results indicated that for people who perceive greater disease risk, the association between group-serving bias and restrictive policy support is weakened. This weakened association occurred because people who felt more vulnerable to these diseases increased support for ingroup-protective actions more strongly than xenophobic thoughts. This research underscores the importance of understanding the impact of threats on psychological processes beyond the impact on psychological outcomes.


Preparation and study on the inclusion complexes of two tanshinone compounds with beta-cyclodextrin.
Solid inclusion complexes of two tanshinones (Tans): tanshinone IIA (Tan IIA), tanshinone I (Tan I) with beta-cyclodextrin (beta-CD) were synthesized by coprecipitation method. The solid inclusion complexes were characterized by using several analytical techniques: (1)H NMR spectra, IR spectra and thermal analysis. Stoichiometry of the inclusion complexes of Tans with beta-CD or HP-beta-CD is 1:1 which was investigated in solution. The formation constants of the complexes were determined by UV spectrophotometry. For same kind of CD, the stability was in the order: Tan IIA > Tan I; for same guest, the stability was in the order: HP-beta-CD > beta-CD. The effect of temperature on the inclusion interaction was examined and the thermodynamic parameters of inclusion process, Delta G, Delta H, Delta S were determined as well. The experimental results indicate that the inclusion process was an exothermic and enthalpy-driven process accompanied with a negative entropic contribution. The inclusion interaction between CD and Tans satisfied the law of enthalpy-entropy compensation.


An experimental infection with classical swine fever virus in weaner pigs. I. Transmission of the virus, course of the disease, and antibody response.
The spread of Classical Swine Fever (CSF) virus (strain Lorraine), originally isolated in the first CSF infected herd of the 1993-1994 Belgian epizootic, was examined in an isolation unit with three adjacent pens and 15 weaner pigs per pen. Virus was introduced through experimental inoculation of one weaner pig in the middle pen (pen 2). The experimentally inoculated pig became viraemic 4 days post-inoculation (dpi) and the pen mates at 12 (n = 9) and 14 dpi (n = 5). The first viraemia in pens 1 and 3 was observed 18 dpi. Pigs were found to be seropositive in pens 1, 2, and 3 from 24, 20, and 22 dpi onwards, respectively. The reproduction ratio (R0) for the pigs in pen 2, estimated according to the martingale method, was 81.3 (s.e. = 109.54). The rate ratio (Cox proportional hazard) of the first pigs to become viraemic in pen 3 (airborne contact plus contact via contaminated clothing and footwear with pen 2) versus pen 1 (airborne contact with pen 2 only) was 1.60 (P = 0.3342). Thus, the additional contact of contaminated clothing did not affect transmission of the CSF virus. The survivor function (Kaplan-Meier survival analysis) did not significantly differ per pen. The time from first detection of virus in plasma to death was not significantly different between pens. The mean rectal temperature of pigs in a pen increased 3 to 4 days prior to detection of virus. The proportion of seropositive pigs per pen (p) from the day the first weaner pig in a pen became viraemic (dpf) was examined as a function of time with a logistic regression model. The model parameter estimates did not differ between pens. Hence, the data from the three pens were pooled. The regression equation of the seroprevalence over time for the pooled data was p = 1/[1+e(4.65-0.39 *dpf)].


Headache and complement C'1-esterase inhibitor deficiency in Vietnamese immigrants living in southern California.
The objective was to measure complement C'1-esterase inhibitor (C1INH) in a group of Vietnamese outpatients with headache. All 51 patients (7 males and 44 females), with either migraine or chronic tension-type headache, were evaluated during 1994 and 1995. Their ages ranged from 15 to 69 years old (mean age, 37.5 years). They were found to have low levels of C1INH (mean, 11 +/- 2 mg/dL versus control subjects, 15 +/- 2 mg/dL with p < 0.0001). Twenty patients (5 males and 15 females) were treated with a low dose of danazol, 200 mg daily for 1-2 months. The improvement of the headache coincided with the return to normal levels of C1INH in all of our patients (pretreatment, 11 +/- 2 mg/dL versus post-treatment, 16 +/- 2 mg/dL with p < 0.001). The levels of C1q and C4d/C4 ratios did not change as a result of treatment with danazol. Our patients may represent a form of androgen-responsive headache, which is associated with low levels of C1INH, normal levels of C1q and normal C4d/C4. It differentiated them from angioedema (hereditary or acquired form); they had no known precipitating factors or a family history of angioedema.


Johari-Goldstein relaxation and crystallization of sorbitol to ordered and disordered phases.
The equilibrium permittivity epsilon(s) and the dielectric relaxation spectra of supercooled liquid D-sorbitol were measured during its crystallization to orientationally disordered or ordered phases depending on the sample preparation procedure at several fixed temperatures up to a period of 6 days. The epsilon(s) measurements showed that when the sample was contaminated by a minute amount of crystals, it crystallized to an ordered phase. When the liquid was not contaminated, the sample crystallized to an orientationally disordered phase. When supercooled D-sorbitol was kept close to its T(g), its dielectric spectra did not change over a period of 138.5 h. It was found that the Johari-Goldstein (JG) relaxation rate of the orientationally disordered crystalline phase is higher in comparison with that of the supercooled liquid, the spectrum broader, and the relaxation strength lower. Its glasslike transition temperature is higher than T(g) of the liquid. The results on crystallization showed that the structural changes occurring at a temperature where the alpha relaxation emerges from the JG relaxation affects the crystallization kinetics of the liquid.


Understanding the school experiences of children and adolescents with serious chronic illness: a systematic meta-review.
Serious chronic illness can have a detrimental effect on school attendance, participation and engagement, leaving affected students at risk of failing to meet their developmental potential. An improved understanding of factors that help to explain or mitigate this risk can help educators and health professionals deliver the most effective support. This meta-review critiqued the available evidence examining the link between six chronic illnesses (asthma, cancer, chronic kidney diseases, heart diseases, cystic fibrosis and gastrointestinal diseases) and children's and adolescents' school experiences and outcomes, as well as investigating the medical, school, psychosocial and sociodemographic factors that are linked to poorer or better school outcomes. We searched CINAHL, Cochrane Database, EMBASE, ERIC, MEDLINE, ProQuest Theses and Dissertations, and PsycINFO (2000-2015). Systematic and narrative reviews, and meta-analyses, of original studies examining students' subjective school experiences and objective school outcomes were eligible. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria to critically appraise all systematic reviews. The Grading of Recommendations Assessment, Development, and Evaluation system guided our recommendations for practice and research. Eighteen reviews of 172 studies including more than 40 000 students were eligible. Therefore, we chose to conduct a meta-review to provide an overview of the literature on the relationship between chronic illness and school experiences and outcomes. We also explored the associated medical, school, psychosocial and sociodemographic factors affecting the relationship between illness and school experiences and outcomes. Students with chronic illness demonstrate mixed school experiences and outcomes that are often worse than students without chronic illness. Modifiable factors, such as students' engagement with school, may be novel yet appropriate targets of educational support to ensure that these students reach their full schooling potential.


Chronic hemolytic anemia due to cold agglutinins. II. The role of C' in red cell destruction.
The sera of four patients with chronic hemolytic anemia due to cold agglutinins deposited C' globulins on normal red cells at 37 degrees C. The circulating cells of the patients were heavily coated with C' complex and were relatively resistant to C' hemolysis by cold agglutinin. Such red cells were removed from the patients' circulation at an exponential rate with (51)Cr t((1/2)) that varied from 7 to 19 days. Normal red cells were removed rapidly by hepatic sequestration during the first hours in the patients' circulation. Thereafter, a slower rate of abnormal destruction occurred which was associated with the accumulation of C' complexes on the red cell and the development of resistance to C' hemolysis by cold agglutinin. Normal red cells coated with sufficient C' complex by action of cold agglutinins in vitro to produce resistance to C' hemolysis by cold agglutinins demonstrated varying degrees of improved survival during the first hours in the circulation of three of the patients. The levels of serum C' were reduced in all four patients with chronic hemolytic anemia due to cold agglutinins. Transfusion of large volumes of normal red cells into two patients further reduced serum C'. (51)Cr-labeled normal red cells survived longer after red cell transfusions than before, because of less rapid destruction during the first hours in the circulation. The reduction in serum C' levels appeared responsible for the improved survival. In subjects without cold agglutinins, the presence of the spleen decreased the survival of red cells from a patient who had previously undergone splenectomy. Splenic removal also predominated in the reduced survival of autologous red cells in one patient. Neither hepatic nor splenic mechanisms predominated in removing autologous C'-coated cells in the other two patients.


Smoking correlates with flow-mediated brachial artery vasoactivity but not cold pressor vasoactivity in men with coronary artery disease.
Impaired endothelial function is observed as altered vasomotion in both the peripheral and coronary circulation in the presence of cardiovascular risk factors and early atherogenesis. An improvement in endothelium-dependent vasoactivity has been reported with both cholesterol reduction and smoking cessation. This study was performed to determine whether smoking status in coronary artery disease (CAD) effects both flow-mediated and cold pressor vasoactivity. We studied 25 men (ages 30-59), 12 smokers and 13 nonsmokers with angiographically documented coronary artery disease and cardiac risk factors who were grouped as smokers and nonsmokers. Using 7.5 MHz ultrasound, we measured brachial artery diameter and Doppler flow velocity at baseline, following 5 mins of ipsilateral blood pressure cuff occlusion and release (flow-mediated), during contralateral ice water hand immersion (cold pressor test) and after sublinqual nitroglycerin administration (an endothelium-independent vasodilator). Flow-mediated percent diameter change was significantly less in the smokers than nonsmokers (1.9 +/- 5.7% vs 11.4 +/- 7.2%, p < 0.001). Both smokers and nonsmokers responded similarly to the cold pressor test (-3.9 +/- 2.3 vs -1.2 +/- 0.2%) and nitroglycerin (15.1 +/- 7.6 vs 17.5 +/- 8.3%). Cholesterol level did not appear to be an independent determinant of flow-mediated vasoactivity when smoking status was taken into account. Flow-mediated vasoactivity is associated with smoking status in the presence of coronary artery disease but cold pressor induced vasoactivity is not.


Quality of life, anxiety and depression in patients with HIV/AIDS who present poor adherence to antiretroviral therapy: a cross-sectional study in Salvador, Brazil.
The introduction of highly active antiretroviral therapy marked a major gain in efficacy of HIV/AIDS treatment and a reduction in morbidity and mortality of the infected patients. However, high levels of adherence are required to obtain virologic suppression. In Brazil, the policy of free and universal access to antiretroviral therapy has been in place since 1996, although there are reports of poor adherence. To define the clinical, demographic and psychological characteristics, and quality of life of patients with HIV/AIDS who present poor adherence to highly active antiretroviral therapy. This was a cross-sectional study. To be included in the study patients had to be 18 through 65 years old, diagnosed with HIV/AIDS, having the two previous viral loads above 500 copies, a surrogate for poor adherence to antiretrovirals. The following instruments were applied to all eligible patients: the sociodemographic questionnaire "Adherence Follow-up Questionnaire", the Beck Depression Inventory (BDI-II), the Beck Anxiety Inventory (BAI), and the 36-Item Short Form Survey. 47 patients were evaluated, 70.2% were female, mean age of 41.9 years (±10.5), 46.8% were single, 51.1% self-reported adherence ≥95%, 46.8% mentioned depression as the main reason for not taking the medication, 59.5% presented symptoms of moderate to severe depression, and 44.7% presented symptoms of moderate to severe anxiety. Finally, regarding health-related quality of life these patients obtained low scores in all dimensions, physical component summary of 43.96 (±9.64) and mental component summary of 33.19 (±13.35). The psychological component is considered to be fundamental in the management of HIV/AIDS patients. Psychoeducation should be conducted at the initial evaluation to reduce negative beliefs regarding antiretroviral therapy Assessment of anxiety and depression symptoms should be done throughout therapy as both psycological conditions are associated with patient adherence, success of treatment, and ultimately with patients' quality of life.


Protective Effects of Fragaria ananassa Extract Against Cadmium Chloride-Induced Acute Renal Toxicity in Rats.
For experiments of cadmium toxicity in animal models, cadmium (II) chloride is often used due to its solubility in water and its ability to produce high concentrations of cadmium at the target site. The present study was designed to investigate the potential inhibitory effect of the Fragaria ananassa fruit extract on cadmium (II) chloride-induced renal toxicity in rats. Tested animals were pretreated with the extract of F. ananassa and injected with cadmium (II) chloride (6.5-mg/kg body weight) for 5 days. Cadmium (II) chloride significantly increased kidney cadmium concentration, kidney weight, lipid peroxidation, and nitric oxide production. Plasma uric acid, urea, and creatinine levels also increased significantly, indicative of kidney dysfunction. These effects were accompanied by significantly decreased levels of nonenzymatic and enzymatic antioxidant molecules (i.e., glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). Moreover, messenger RNA (mRNA) expression of the antiapoptotic protein, Bcl-2, and the antioxidant proteins, superoxide dismutase 2 and glutathione reductase, were downregulated markedly, whereas mRNA expression of tumor necrosis factor-α was upregulated significantly in kidney tissues of cadmium-treated rats. Histology of kidney tissue demonstrated severe, adverse changes that reflected cadmium-induced tissue damage. Pretreatment of rats with the extract of F. ananassa ameliorated all aforementioned cadmium (II) chloride-induced changes. In conclusion, the present study showed acute renal toxicity in rats treated with cadmium (II) chloride. The study also revealed that pretreatment with the extract of F. ananassa could protect the kidney against cadmium (II) chloride-induced acute renal toxicity.


Large-Scale Identification of Known and Novel RRNPP Quorum-Sensing Systems by RRNPP_Detector Captures Novel Features of Bacterial, Plasmidic, and Viral Coevolution.
Gram-positive Firmicutes bacteria and their mobile genetic elements (plasmids and bacteriophages) encode peptide-based quorum-sensing systems (QSSs) that orchestrate behavioral transitions as a function of population densities. In their simplest form, termed "RRNPP", these QSSs are composed of two adjacent genes: a communication propeptide and its cognate intracellular receptor. RRNPP QSSs notably regulate social/competitive behaviors such as virulence or biofilm formation in bacteria, conjugation in plasmids, or lysogeny in temperate bacteriophages. However, the genetic diversity and the prevalence of these communication systems, together with the breadth of behaviors they control, remain largely underappreciated. To better assess the impact of density dependency on microbial community dynamics and evolution, we developed the RRNPP_detector software, which predicts known and novel RRNPP QSSs in chromosomes, plasmids, and bacteriophages of Firmicutes. Applying RRNPP_detector against available complete genomes of viruses and Firmicutes, we identified a rich repertoire of RRNPP QSSs from 11 already known subfamilies and 21 novel high-confidence candidate subfamilies distributed across a vast diversity of taxa. The analysis of high-confidence RRNPP subfamilies notably revealed 14 subfamilies shared between chromosomes/plasmids/phages, 181 plasmids and 82 phages encoding multiple communication systems, phage-encoded QSSs predicted to dynamically modulate bacterial behaviors, and 196 candidate biosynthetic gene clusters under density-dependent regulation. Overall, our work enhances the field of quorum-sensing research and reveals novel insights into the coevolution of gram-positive bacteria and their mobile genetic elements.


Origin of changes in electrical impedance during the growth and fermentation process of yeast in batch culture.
The electrical impedance of the culture medium shows complex changes during the growth and fermentation process of yeast, and this prevents its possible application for the monitoring of certain yeast activities. Clarification of the mechanism of such changes is thus essential for practical use. As a first step toward this aim, the impedance, yeast concentration, and pH of a batch culture medium were measured using special cells with two compartments and also the usual type of cell with one compartment. In the special cells, the yeast was cultured in one compartment only. Conducting ions and nonconducting substances diffused through an intermediate porous membrane sandwiched between the two compartments. The impedances of the two compartments were measured simultaneously by the four-electrode method. The main mechanism responsible for increasing the impedance was the conducting ions produced by the yeast extract added as a nutrient to the culture broth by certain nonconducting substances during the process of growth. The increase in the yeast concentration was also a minor factor increasing the impedance. These increases surpassed the impedance decrease caused by the increase of H(+) ions produced by some accumulated acidic substances, and the impedance thus increased.


New abietane-type diterpenes from the heartwood of Picea morrisonicola.
New abietane-type diterpenes, 15-acetoxy-7-oxodehydroabietic acid (1), picealactones A (2), B (3), and C (4), together with the known 7-oxodehydroabietic acid (5) were isolated and identified from the heartwood of Picea morrisonicola. The structures of 1-4 were determined on the basis of spectral data explanation. Compounds 2-4 possessed a rare 5-dehydro-18, 6-olide functionality. Compounds 1 and 2 were first isolated from natural source.


Comparison of media used for the primary isolation of Mycobacterium bovis by veterinary and medical diagnostic laboratories.
Veterinary and medical laboratories engaged in the cultural diagnosis of bovine or human tuberculosis were requested to supply samples of the media that they routinely use for the primary isolation of M. bovis. Fourteen laboratories supplied 7 basic media types; these were Lowenstein-Jensen, Stonebrink's, modified Middlebrook 7H11 agar, tuberculosis bovine blood agar, egg yolk agar, Gerloff's egg and Herrold's egg yolk. Two strains of M. bovis were used to test the media, strain AN5, a glycerol-tolerant laboratory strain and M86/90 a glycerol-sensitive wildtype strain. AN5 grew well on all media with the exception of Herrold's and strain M86/90 did not grow on media containing glycerol and grew poorly on Herrold's medium. It is recommended that Lowenstein-Jensen with pyruvate (but without glycerol), Stonebrink's, modified Middlebrook 7H11 and tuberculosis bovine blood agar should be considered the media of choice for the primary isolation of M. bovis. Egg yolk agar also proved adequate for this purpose in the trial. This medium may be suitable for routine use but to date experience with its use is limited.


The results of multigene panel sequencing in Slovak HBOC families.
Hereditary breast and ovarian cancer (HBOC) is primarily associated with mutations in the BRCA1/2 genes. However, causal variants in other high, moderate, and low penetrance genes proportionally increase the risk of breast/ovarian cancer. This study aims to provide data about the mutation spectrum of HBOC-associated genes in Slovak HBOC families and estimate the ratio of BRCA versus non-BRCA causal variants. We used panel sequencing containing 22 high/moderate-risk susceptibility genes and parallel MLPA analysis of BRCA1/2, CHEK2 genes, to analyze 94 individuals with a strong family/personal history of breast and/or ovarian cancer. The analyzed group consisted of 80 patients diagnosed with cancer (85.1%) and 14 healthy individuals (14.9%) with a positive family history of HBOC syndrome. In total, we have identified 22 causal DNA variants (23.4%) showing 15 primary findings in BRCA1/2 genes (68.2%) and 7 positive secondary findings in CHEK2, PALB2, CDH1, and MUTYH genes (31.8%). The most frequent pathogenic alterations were BRCA1 mutations c.181T>G and CNV variant (c.5573-?_c.5701+?)del, known as deletion of exons 21-22. Besides known mutations, the BRCA1 variant c.2794del (p.Val932Leufs*68) and variant c.2480dup (p.Tyr827*) in the CDH1 gene represent the novel, previously unpublished variants that might be population-specific. In conclusion, we provide the first report of multigene panel testing in Slovak HBOC families demonstrating that almost one-third of pathogenic mutations are situated in susceptibility genes other than BRCA1/2. Although multigene panel testing requires precise data filtration and interpretation, it might bring the relevant data for clinical management of the patients.


In Vitro Comparison of Pediatric Oxygenators With and Without Integrated Arterial Filters in Maintaining Optimal Hemodynamic Stability and Managing Gaseous Microemboli.
The purpose of this study was to compare the Capiox FX15 oxygenator with integrated arterial filter to the Capiox RX15 oxygenator with separate Capiox AF125 arterial filter in terms of hemodynamic properties and gaseous microemboli (GME) capturing. Trials were conducted at varying flow rates (2.0 L/min, 3.0 L/min, 4.0 L/min), temperatures (30°C, 35°C), and flow modalities (pulsatile, nonpulsatile). Pressure and flow waveforms were recorded using a custom-made data acquisition system. GME data were recorded using an Emboli Detection and Classification Quantifier after injecting a 5 mL air bolus into the venous line. Maximum instantaneous pre-oxygenator flows reached 7.4 L/min under pulsatile conditions when the roller pump was set to a flow rate of 4 L/min. Mean pressure drops were slightly greater in the FX15 group (P < 0.0001), and the diverted flow from the arterial purge line was slighter greater in the FX15 group at 3 L/min and 4 L/min (P < 0.0001). There was a slight generation of surplus hemodynamic energy (SHE) at the pre-oxygenator site for both oxygenators under "nonpulsatile mode." However, higher pre-oxygenator SHE levels were recorded for both groups with "pulsatile mode." The RX15 and FX15 groups were both able to remove all microemboli from the circuit at 2 L/min and 3 L/min in "nonpulsatile mode." Microemboli were delivered to the patient at 4 L/min with pulsatile flows in both groups. The RX15 oxygenator with separate AF125 arterial filter and FX15 oxygenator with integrated arterial filter performed similarly in terms of hemodynamic performance and microemboli capturing. Pulsatile flows at 4 L/min produced instantaneous flow rates that surpassed the documented maximum flow rates of the oxygenators and might have contributed to the delivery of GME to the pseudo-patient.


Posttranscriptional regulation of the β2-subunit of cardiac L-type Ca2+ channels by MicroRNAs during long-term exposure to isoproterenol in rats.
The effects of long-term β-adrenergic administration on the expression levels of the cardiac L-type Ca channel β2 subunit, which regulates channel trafficking and function, were characterized in adult rats. Systemic administration of isoproterenol (150 mg·kg·h) for 2 d led to a 50% increase in the ventricular wet weight-to-body weight ratio (mg/g) and of more than two-fold in the expression of actin protein. In contrast, β2 subunit protein levels decreased (down to 49%), while mRNA levels remained unchanged. Furthermore, levels of microRNAs (miRs), including miR-21 and miR-132, were upregulated (7.2 and 7.9 fold, respectively). Transfection of these miRs into HEK293 cells attenuated expression of a luciferase reporter gene controlled by a conserved 3'-untranslated region (UTR) of the β2 subunit (down to 67% and 56%, respectively). Systemic administration of isoproterenol also led to briefer intracellular Ca transients during action potentials measured in isolated cardiomyocytes (down to 65%). These results suggest that cardiac L-type Ca channel β2 subunit protein expression may be downregulated by miRs in response to long-term activation of β-adrenergic signaling, possibly as an adaptive response in cardiac hypertrophy and sustained β-adrenergic states.


Developing a Novel Two-Dimensional Culture System to Enrich Human Prostate Luminal Progenitors that Can Function as a Cell of Origin for Prostate Cancer.
Elucidating the cell of origin of cancer has great significance in stratifying patients into appropriate treatment groups and for developing novel targeted therapies. Early studies demonstrate that only stem-like basal cells in the normal human prostate (NHP) can function as the cell of origin for prostate cancer (PCa). Here, we show that the organoids derived from bulk NHP luminal cells can also be tumorigenically transformed. We further show that the WIT medium, which is used to culture human mammary epithelial progenitor cells, when combined with the ROCK inhibitor, can readily propagate a population of progenitor-like cells from the primary NHP luminal cell isolates. Such functionally defined luminal progenitors can be transformed by distinct sets of genetic perturbations (i.e., AR+AKT/ERG or c-MYC+PTEN knockout) to form tumor glands. Genome-wide RNA-Seq analysis of freshly purified unperturbed human benign prostatic basal and luminal cells and culture-expanded lineage-specific stem/progenitor populations reveals that the luminal progenitors possess a distinct gene expression profile that is greatly enriched in advanced, castration-resistant, and metastatic PCa, and it associates with poor patient survival. The ability of the simple two-dimensional culture system reported herein to greatly enrich NHP progenitor-like cells should facilitate biological and biochemical studies as well as high-throughput screening in these cells and in progenitor-like PCa cells. Stem Cells Translational Medicine 2017;6:748-760.


Novel application of high-density polyethylene mesh as self-forming dynamic membrane integrated into a bioreactor for wastewater treatment.
In the present study, self-forming dynamic membrane (SFDM) on rigid high-density polyethylene (HDPE) mesh with a large pore size of 2 mm is reported for the first time. The system was investigated for utilisation in simulated wastewater treatment by integrating the mesh with an aerobic bioreactor. The SFDM was analysed using Fourier transform infra-red (FT-IR) spectroscopy and visualised by scanning electron microscopy (SEM). The effect of the operating parameter on the change in composition of SFDM was also investigated. The system was used as a single unit for treatment of wastewater and showed stability over long-term treatment. The system could achieve a chemical oxygen demand (COD) reduction of 82.16 ± 6.47% at an influent COD concentration of 613.93 ± 72.13 mg/l and ammonia removal efficiency of 97.21 ± 0.62% at an influent ammonia concentration of 55.54 ± 2.23 mg/l. The reactor generated high-quality effluent and the turbidity recorded was less than 2NTU. In addition, the operational parameters, namely hydraulic retention time and organic loading rate, were optimised.


Interleukin-17C in Human Helicobacter pylori Gastritis.
The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in many inflammatory diseases. Although IL-17A is recognized as being involved in the pathophysiology of Helicobacter pylori-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed in H. pylori-infected and uninfected gastric biopsy specimens. IL-17C mRNA was upregulated approximately 4.5-fold in H. pylori-infected gastric biopsy specimens. This was confirmed by quantitative reverse transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C expression in H. pylori-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells. IL-17C mRNA levels were also significantly greater among cagA-positive than cagA-negative H. pylori infections (P = 0.012). In vitro studies confirmed an increase in IL-17C mRNA and protein levels in cells infected with cagA-positive infections compared to cells infected with either cagA-negative or cag pathogenicity island (PAI) mutant. Chemical inhibition of IκB kinase (IKK), mitogen-activated protein extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK) inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition had no effect on IL-17C protein secretion. In conclusion, H. pylori infection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis of H. pylori-induced diseases remains to be determined.


Radiologic measurement of submandibular gland ptosis.
Ptosis of the submandibular glands is a well-recognized yet poorly quantified element of the aging face and neck. The goal of this study is to describe and quantify the rate and extent of age-related submandibular gland ptosis. A novel grading system is proposed to quantify the degree of descent of the submandibular gland in relation to the inferior border of the mandible. Implications for facial rejuvenation surgery are discussed. Retrospective review. Consecutive computed tomography (CT) imaging studies performed at a university-affiliated hospital were selected for review. Using cross-referenced images in the coronal and axial planes, distance measurements were obtained from the bottom of the submandibular gland to the plane of the inferior border of the mandible. These data points were plotted against subject age for statistical analysis. The position of the submandibular gland was then categorized as grade I when distance below the mandible was < 20 mm, grade II for 20 to 25 mm, grade III for 25 to 30 mm, and grade IV for > 30 mm. Volumetric analysis was performed in a subset of subjects to assess for the possibility of age-related submandibular gland volume changes as a potential confounding factor in distance measurements. One hundred consecutive CT imaging studies were selected for review (50 men, 50 women). A statistically significant linear relationship was identified between subject age and ptosis of the submandibular gland (r = 0.52, p < 0.001), as measured by the distance from the bottom of the submandibular gland from the plane of the inferior border of the mandible. The average rate of descent was 0.17 mm per year. Overall, the position of the submandibular gland was categorized as grade I in 18% of patients, grade II in 27% of patients, grade III in 32% of patients, and grade IV in 23% of patients. No statistically significant gender differences were identified in any of the data points. Volumetric analysis did not demonstrate any age-related changes in submandibular gland volume, and as such, this was excluded as a potential confounding factor in distance measurements. A linear relationship exists between patient age and submandibular gland ptosis, as measured by the distance of the gland from the inferior border of the mandible. To our knowledge, this is the first quantification of the rate and extent of submandibular gland ptosis. A novel grading system for submandibular gland ptosis has been proposed.


Effect of Airway Pressure Release Ventilation on Dynamic Alveolar Heterogeneity.
Ventilator-induced lung injury may arise from heterogeneous lung microanatomy, whereby some alveoli remain collapsed throughout the breath cycle while their more compliant or surfactant-replete neighbors become overdistended, and this is called dynamic alveolar heterogeneity. To determine how dynamic alveolar heterogeneity is influenced by 2 modes of mechanical ventilation: low tidal-volume ventilation (LTVV) and airway pressure release ventilation (APRV), using in vivo microscopy to directly measure alveolar size distributions. In a randomized, nonblinded laboratory animal study conducted between January 2013 and December 2014, 14 rats (450-500 g in size) were randomized to a control group with uninjured lungs (n = 4) and 2 experimental groups with surfactant deactivation induced by polysorbate lavage: the LTVV group (n = 5) and the APRV group (n = 5). For all groups, a thoracotomy and in vivo microscopy were performed. Following lung injury induced by polysorbate lavage, the LTVV group was ventilated with a tidal volume of 6 mL/kg and progressively higher positive end-expiratory pressure (PEEP) (5, 10, 16, 20, and 24 cm H2O). Following lung injury induced by polysorbate lavage, the APRV group was ventilated with a progressively shorter time at low pressure, which increased the ratio of the end-expiratory flow rate (EEFR) to the peak expiratory flow rate (PEFR; from 10% to 25% to 50% to 75%). Alveolar areas were quantified (using PEEP and EEFR to PEFR ratio) to determine dynamic heterogeneity. Following lung injury induced by polysorbate lavage, a higher PEEP (20-24 cm H2O) with LTVV resulted in alveolar occupancy (reported as percentage of total frame area) at inspiration (39.9%-42.2%) and expiration (35.9%-38.7%) similar to that in the control group (inspiration 53.3%; expiration 50.3%; P > .01). Likewise, APRV with an increased EEFR to PEFR ratio (50%-75%) resulted in alveolar occupancy at inspiration (46.7%-47.9%) and expiration (40.2%-46.6%) similar to that in the control group (P > .01). At inspiration, the distribution of the alveolar area of the control group was similar to that of the APRV group (P > .01) (but not to that of the LTVV group [P < .01]). A lower PEEP (5-10 cm H2O) and a decreased EEFR to PEFR ratio (≤50%) demonstrated dynamic heterogeneity between inspiration and expiration (P < .01 for both) with a greater percentage of large alveoli at expiration. Dynamic alveolar homogeneity between inspiration and expiration occurred with higher PEEP (16-24 cm H2O) (P > .01) and an increased EEFR to PEFR ratio (75%) (P > .01). Increasing PEEP during LTVV increased alveolar recruitment and dynamic homogeneity but had a significantly different alveolar size distribution compared with the control group. By comparison, reducing the time at low pressure (EEFR to PEFR ratio of 75%) in the APRV group provided dynamic homogeneity and a closer approximation of the dynamics observed in the control group.


Differential susceptibility and infectivity epidemic models.
We formulate differential susceptibility and differential infectivity models for disease transmission in this paper. The susceptibles are divided into n groups based on their susceptibilities, and the infectives are divided into m groups according to their infectivities. Both the standard incidence and the bilinear incidence are considered for different diseases. We obtain explicit formulas for the reproductive number. We define the reproductive number for each subgroup. Then the reproductive number for the entire population is a weighted average of those reproductive numbers for the subgroups. The formulas for the reproductive number are derived from the local stability of the infection-free equilibrium. We show that the infection-free equilibrium is globally stable as the reproductive number is less than one for the models with the bilinear incidence or with the standard incidence but no disease-induced death. We then show that if the reproductive number is greater than one, there exists a unique endemic equilibrium for these models. For the general cases of the models with the standard incidence and death, conditions are derived to ensure the uniqueness of the endemic equilibrium. We also provide numerical examples to demonstrate that the unique endemic equilibrium is asymptotically stable if it exists.


Method to measure the 3D angular orientation of the aortic valve plane from a single image of a valvuloplasty balloon: findings of a large animal proof of concept experiment.
During transcatheter aortic valve replacement procedures, alignment of the interventional x-ray beam with the aortic valve plane is required to guide valve placement. The purpose of this work was to develop methods to measure x-ray beam angles which are aligned with the aortic valve plane from a single x-ray image of a valvuloplasty balloon inflated across the left ventricular outflow tract (LVOT). A custom valvuloplasty balloon and image analytics were developed. In-vivo pig experiments demonstrated that the angular orientation of the LVOT can be measured with precision less than 3°, including the influence of cardiac motion during rapid pacing. Using these methods, the angular orientation of the LVOT of a large mammal can be measured precisely and the continuous range of x-ray projection angles which are aligned with the aortic valve plane can be calculated.


The projections of different morphological types of ganglion cells in the cat retina.
The central projections of the retinal ganglion cells of the cat were examined using the method of retrograde transport of horseradish peroxidase. Peroxidase was injected into the lateral geniculate nucleus and into the superior colliculus by means of a recording micropipette. After injections at retinotopically homologous points in these two structures in separate animals, tha patterns of retinal ganglion cell labeling were compared. We found that there were three populations of ganglion cells: small cells, that projected predominantly to the superior colliculus; medium-sized cells, that projected predominantly to the lateral geniculate nucleus; and large cells, some of which projected to both structures, and some of which projected to the lateral geniculate nucleus alons. Quantitative studies showed that the average size of the cells in each population was smaller at the area centralis than in the periphery. These results could be directly related to physiological classifications of retinal ganglion cells proposed by other authors.


Sexual abuse of minors: emerging medical and social problem in Malawi.
Sexual abuse is one of the most dehumanising human offenses. There has been an increasing public concern and outcry regarding the escalating wave of sexual abuse of young girls in Malawi, in the recent past. Four young girls, aged between two and seven years who were sexually abused by adult males aged between 20 and 70 years seen and managed in the department within the past two years, are presented to illustrate the problem. Their physical injuries, varied reactions and those of their immediate families to the abuse; possible predisposing factors to the abuses; the related medical, psychosocial as well as legal management of such incidents, in the light of limited public awareness, and lack of adequately and appropriately trained personnel and facilities in Malawi are discussed. With the scare of AIDS and an increasing disintegration of the traditional family fabric, there is a high potential for an increase, not only of the prevalence of sexual abuse of minors in Malawi, but also the variety and severity of sequelae. It is therefore recommended that there is need to create public awareness about sexual abuse, train and equip the relevant personnel to appropriately manage such cases, as well as enact and enforce the relevant legal provisions, so as to curb the menace, for the well-being of the society.


A Systematic Review of the Effects of Polyols on Gastrointestinal Health and Irritable Bowel Syndrome.
Polyols are sugar alcohols found in certain fruits, vegetables, and sugar-free sweeteners. They make up a component of the diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which is gaining popularity in the treatment of patients with irritable bowel syndrome (IBS). We conducted a systematic review to evaluate the effects of polyols on the gastrointestinal tract in healthy men and women and in patients with IBS. Utilizing PubMed, Ovid, and Embase databases, we conducted a search on individual polyols and each of these terms: fermentation, absorption, motility, permeability, and gastrointestinal symptoms. Standard protocols for a systematic review were followed. We found a total of 1823 eligible articles, 79 of which were included in the review. Overall, available work has shown that polyol malabsorption generally occurs in a dose-dependent fashion in healthy individuals, and malabsorption increases when polyols are ingested in combination. However, studies in patients with IBS have shown conflicting results pertaining to polyol malabsorption. Polyol ingestion can lead to intestinal dysmotility in patients with IBS. Regarding the microbiome, moderate doses of polyols have been shown to shift the microbiome toward an increase in bifidobacteria in healthy individuals and may therefore be beneficial as prebiotics. However, data are limited regarding polyols and the microbiome in patients with IBS. Polyols can induce dose-dependent symptoms of flatulence, abdominal discomfort, and laxative effects when consumed by both healthy volunteers and patients with IBS. Further research is needed to better understand the effects of specific polyols on gastrointestinal function, sensation, and the microbiome in health and gastrointestinal disorders such as IBS.


A bone fluid flow hypothesis for muscle pump-driven capillary filtration: II. Proposed role for exercise in erodible scaffold implant incorporation.
A model is presented for enhancement of fluid flow through bone matrix and any porous tissue engineering scaffold implanted within it. The mechanism of enhancement is the skeletal muscle pump in compartments adjacent to the bone. Pressure waves from muscle pump contractions aided by increased blood pressure during exercise coupled with temporary occlusion of arteries leading to and veins from the bone, increase hydraulic pressure in cortical bone capillaries so as to amplify capillary filtration. It is proposed that capillary filtration increase is sufficiently convective to contribute to bone fluid flow and associated percolation through tissue engineered scaffold matrix implants. Importance of this contribution is its relative role in maintaining seeded cells in bioreactor scaffolds. Validation of the hypothesis starts at a minimum level of demonstrating that capillary filtration is convective. At a maximum level confirmation of the hypothesis requires demonstration that capillary filtration-based interstitial flow is sufficient to stimulate not only host bone cells (as proposed in part I of the hypothesis) but bioreactor-seeded cells as well. Preliminary data is presented supporting the prediction that skeletal muscle contraction generates convective capillary filtration.


A Novel In Vitro Experimental System for the Evaluation of Drug Metabolism: Cofactor-Supplemented Permeabilized Cryopreserved Human Hepatocytes (MetMax Cryopreserved Human Hepatocytes).
We report here a novel experimental system, cryopreserved MetMax human hepatocytes (MMHHs), for in vitro drug metabolism studies. MMHHs consist of cofactor-supplemented permeabilized cryopreserved human hepatocytes. The use procedures for MMHHs are significantly simplified from that for conventional cryopreserved human hepatocytes (CCHHs): 1) storage at -80°C instead of in liquid nitrogen and 2) usage directly after thawing without centrifugation and microscopic evaluation of cell density and viability and cell density adjustment. In this study, we compared MMHHs and CCHHs in CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP3A4, CYP2J2, monoamine oxidase A, aldehyde oxidase, flavin-containing monooxygenase, UDP-glucuronyl transferase, SULT, N-acetyltransferase 1, and acetaminophen glutathione (GSH) conjugation activities based on liquid chromatography-tandem mass spectrometry quantification of substrate metabolism. MMHHs were prepared from CCHHs consisting of hepatocytes pooled from 10 individual donors. The drug metabolizing enzyme activities of both CCHHs and MMHHs were cell concentration and time dependent, with specific activities of MMHHs ranging from 27.2% (carboxylesterase 2) to 234.2% (acetaminophen GSH conjugation) of that for CCHHs. As observed in CCHHs, sequential oxidation and conjugation was observed in MMHHs for coumarin, 7-ethoxycoumarin, and acetaminophen. 7-Hydroxycoumarin conjugation results showed that metabolic pathways in MMHHs could be selected via the choice of cofactors, with glucuronidation but not sulfation observed in the presence of UDP-glucuronic acid and not 3-phosphoadenosine-5-phosphosulfate, and vice versa. Results with noncytotoxic and cytotoxic concentrations of acetaminophen showed that drug metabolism was compromised in CCHHs but not in MMHHs. Our results suggest that the MMHHs system represents a convenient and robust in vitro experimental system for the evaluation of drug metabolism.


[The illegal synthetic cannabinoid drug market in Israel - evolution and new challenges].
This article represents a short review of the current knowledge on the abuse of synthetic cannabinoids from the perspective of the Division of Enforcement and Inspection of the Israeli Ministry of Health - a body in charge of providing professional assistance to law enforcement bodies in the fields of drug abuse. We describe the principal changes observed in the synthetic cannabinoid market and the Israeli legislators' and enforcement bodies' attempts to cope with these phenomena. These changes relate to the types of synthetic cannabinoids being trafficked, with many structural variations between substances, and a new legal framework which allows for the rapid, temporary scheduling of synthetic cannabinoids using both individual and generic definitions. Despite changes in legislation, we are currently witnessing the adaptation of the synthetic cannabinoid drug market to the new legal reality and enforcement practices. A considerable part of synthetic cannabinoid trafficking is carried out using phone orders, or has moved to the internet and social networks, thus making its detection difficult for enforcement bodies. Current trafficking practices represent a growing challenge for enforcement bodies. Hence, there is a need for cooperation between enforcement bodies, the Israeli Ministry of Health and health practitioners in identifying new substances, and characterizing their harms.


Photothermal-Driven Polymer for a Smart Window with Adaptive Solar Modulation.
Although the thermochromic smart windows with adjustable sunlight transmittance to achieve energy savings are gradually improving, they are still difficult to use, limited by their unreasonable thermal response temperature, slow switching time, and poor durability. Here, we demonstrate a dual-function hybrid thermoresponsive smart window device (CPH) by trapping the phase-change polyHEA-HDA polymer (HEA = hydroxyethyl acrylate, HDA = hexadecyl acrylate) and polydopamine@CsxWO3 (PDA@CWO) core-shell nanoparticles within glasses. The introduced PDA@CWO nanoparticles substantially increase the energy transformation efficiency of solar energy to heat due to their outstanding photothermal conversion. When the temperature increases above the phase-transition temperature of polyHEA-HDA polymer, the copolymer components in the composite material undergo a reversible crystalline-amorphous transition, which enables the transformation of the whole smart window from transparency to opaque in a low ambient temperature. The light transmittance in the solar range can be dynamically modulated between 54.8 and 22.9% with a low ambient temperature while maintaining acceptable visible light transparency and effective UV shielding. A model house testing proves an indoor temperature cooling of 7.1 °C. This study offers a new approach to designing an energy-saving smart window system with multifunctionality.


Eight-year experience of combined valve repair for mitral regurgitation and maze procedure.
Although atrial fibrillation (AF) is often associated with severe mitral regurgitation (MR), a simultaneous maze procedure for AF associated with repair of MR remains controversial. In this study, mid-term results of combined mitral valve repair and the maze procedure were examined. Between May 1992 and April 2001, 85 patients (61 males, 24 females) underwent valve repair for MR and the maze procedure. Mean age at surgery was 61.8+/-9.1 years; mean follow up was 4.7+/-2.3 years. Valve lesions were anterior in 26 patients (31%), posterior in 31 (36%), anterior + posterior in 23 (27%), and simple dilated annulus in five (6%). Chordal replacement with expanded PTFE sutures was performed in 40 patients (47%), and leaflet resection in 41 (48%). Ring annuloplasty was also applied in 61 patients (72%). Associated procedures were tricuspid valve annuloplasty in 33 (36%), coronary artery bypass grafting in four, atrial septal defect closure in two, aortic valve repair in one, and resection of abnormal septum in the left atrium in one. There was one hospital death (1%), and one late death (1%). Reopening the chest for bleeding was necessary in six cases (7%). One thromboembolic episode was detected during follow up (0.25%/patient-year). Reoperation for MR was performed in three patients (4%). Actuarial event-free survival rate was 90.0+/-6.4% at eight years. Sinus rhythm was regained in 68 patients (81%), and atrial A-wave was detected in 57 (68%) by pulsed Doppler study. Postoperative left ventricular diastolic and systolic dimensions were significantly (p = 0.001 and p = 0.017) smaller in patients who restored sinus rhythm than in those who did not (48.6+/-4.6 versus 54.6+/-4.7 mm, and 33.0+/-6.0 versus 38.1+/-6.9 mm). Combined mitral valve repair for MR and the maze procedure showed satisfactory midterm results. Postoperative sinus rhythm conversion by the maze procedure may reduce left ventricular size, and the incidence of thromboembolic episodes in mitral valve repair.


[Retrosternal coloplasties: contribution of postoperative mesenteric arteriography].
Postoperative mesenteric angiograms were obtained after substernal coloplasty (SC) in fifteen patients, 8 male and 7 female, aged from 18 to 61 yrs old (mean = 34 yrs old). The aim of this study was to determine whether: 1) vascularization as assessed by angiography was correlated with the occurrence of cervical complications (fistulae and/or stenosis), 2) postoperative arteriography was of any practical value in this situation. Images obtained were classified into 3 groups according to the quality of vascular visualization. Clinical results were also classified into 3 groups according to whether no, one or two cervical complications were present, respectively. Angiographic and clinical results were concordant in 8 cases and discordant in 7. No definite relationship between the quality of coloplasty vascularization and the quality of clinical outcome was found in this study, but results suggest that retromanubrium compression might play a major role in outcome as visualization of colonic vascularization was obtained in only 9 of 15 cases. When clinical results are poor, characteristic images of ischemia may help in determining the indication for reoperation.


Evolution of fitness in experimental populations of Drosophila serrata.
Changes which enhance adaptedness to the environment occur in experimental populations of Drosophila serrata which are acted upon by strong natural selection. The improvement is greater in hybrid than in single-strain populations because genetic variability is greater in the former.


[Age-related changes in bone weights and their components in rats].
Age-related changes in the wet, dry and ash weights and components such as water, organic substance, ash, calcium and phosphorus of femur, tibia and first lumbar vertebra and serum biochemical constituents related to bone metabolism were examined in Wistar rats. A total of 60 males and 60 females were used, and every five rats of both sexes were examined at 1 and 2 months of age and then at intervals of 3 months between 3 and 30 months of age. Each bone weight increased rapidly up to 3 months of age and then gradually up to 12 months of age in females and 9 months of age in males, but thereafter decreased at 27 and 30 months of age in males. Between 1 and 6 or 9 months of age in both sexes, a decrease in water content, increases in ash, calcium and phosphorus, and almost no change in organic substance in each bone were observed. After 15 months of age in males, an increase in water content, decreases in ash content, calcium and phosphorus, and almost no changes in organic substance were observed in males. The value of serum calcium decreased up to 12 months of age but then increased after 18 months of age in both sexes. Serum phosphorus and alkaline phosphatase activity decreased up to 9 months of age in both sexes. The data obtained in this study supported the results in our previous study that the peak bone strength of the femur and peak bone volume of trabecular bone of the proximal metaphysis of the tibia were at 12 months of age in both sexes in Wistar rats.


The connexins and their family tree.
The connexins, gap junction forming proteins, are encoded by a gene family. Sequence comparisons reveal regions of conservation with functional implications for voltage dependence of junctional conductance, junction formation and regulation by phosphorylation. The best connexin tree shows that most gene duplications giving rise to the family occurred early in or before vertebrate divergence. The topology of most deep branches of the tree is uncertain. Evolutionary rates vary for different paralogous connexin genes.


Overexpression of Bax gene sensitizes K562 erythroleukemia cells to apoptosis induced by selective chemotherapeutic agents.
Bax and Bcl-2 are a pair of important genes that control programmed cell death, or apoptosis, with Bax being the apoptosis promoter and Bcl-2 the apoptosis protector. Although the detailed mechanism is unknown, the protein products of these two genes form protein dimers with each other and the relative ratio of the two proteins is believed to be a determinant of the balance between life and death. In our preliminary study, we found that K562 erythroleukemia cells have an extremely low level of endogenous Bcl-2 expression and a fairly high level of endogenous Bax expression. We constructed Bax and Bcl-2 expression vectors and transfected them into K562 cells. We found that transfection of Bax vector increased the expression of Bax protein; a shortened form of Bax also appeared. Cell death analysis using the Annexin V assay showed that the Bax vector caused significantly more apoptotic cells that the Bcl-2 or pCI-neo vector did. After selection with G418, Bax, Bcl-2 and pCI-neo stably transfected cells were established. These three cell lines were examined for their response to the chemotherapeutic agents ara-C, doxorubicin, etoposide and SN-38. Bax-K562 cells showed significantly higher fractions of apoptotic cells than pCI-neo-K562 cells when treated with ara-C, doxorubicin or SN-38. No sensitization effect was seen when etoposide was used. In contrast, Bcl-2-K562 cells had fewer apoptotic cells than pCI-neo-K562 cells after treatment with all these agents. Therefore, Bax may sensitize K562 cells to apoptosis induced by a wide range of, but not all, chemotherapeutic agents.


Future perspectives of flexible ureteroscopy.
In the recent past, there were numerous and promising technological developments in the field of endourology leading to tremendous changes in the management of urolithiasis. This review will try to weave ancient stone therapy with the very modern advent of flexible ureteroscopy and recent developments in robotic systems. In the broad field of flexible ureteroscopy for stone surgery, new disposable scopes have been developed and established. The use of robotic instruments is also a new and interesting concept. Additionally, clinical research on the understanding of laser features leads to a specific and appropriate use of lasers for lithotripsy, both holmium, and nowadays also interestingly thulium. Disposable, digital flexible ureteroscopes for the treatment of both ureteric and kidney stones are taking an essential role in the medical field. Until recently, the clinically relevant laser systems for stone surgery during ureteroscopy are mainly based on Holmium laser YAG (Ho:YAG) devices, but a new thulium variant with promising features is giving interesting results. Additional research in laser features will guide to a better, more effective and safer treatment algorithm. Robotic technologies are promising but their definitive role still needs to be determined.


Acute abdomen. Special considerations for the neurologically and immunologically impaired child.
The neurologically or immunologically impaired child suspected of having an acute abdomen presents a formidable challenge. However, a thorough understanding of the underlying pathophysiology of the disease on the normal host response to an intraabdominal disease permits early recognition and initiation of treatment. Classic findings of the acute abdomen are the exception rather than the rule. These children require constant vigilance and repeated examination. Radiographic studies should be used early and often. The advent of minimally invasive surgical techniques offers the opportunity to intervene early both diagnostically and therapeutically. Ultimately, however, the best outcomes will be achieved by those who employ sound surgical judgment and avoid unnecessary therapeutic delay owing to inexperience, inattention, or indecision.


Lipoprotein-mediated cellular mechanisms for atherogenesis in hypertriglyceridemia.
Structurally and functionally abnormal VLDL exist in hypertriglyceridemic humans. These large abnormal VLDL, in contrast to large normal VLDL, interact with cell surface receptors. One large VLDL particle carries far more total cholesterol than one LDL particle. Receptor-mediated uptake of abnormal VLDL is injurious to endothelial cells and converts macrophages into foam cells in vitro. These observations lead to the hypothesis that if similar phenomena occur in vivo, abnormal VLDL, which have prolonged residence times and increased opportunity to interact with arterial cells, are atherogenic by promoting endothelial injury and initiating foam cell formation. Since premature atherosclerosis is associated with some forms of hypertriglyceridemia and foam cells accumulate in certain hypertriglyceridemic subjects, similar events may indeed occur in vivo.


Spinal epidural lipomatosis.
Epidural lipomatosis is an uncommon disorder defined as a pathologic overgrowth of normal epidural fat. It is most often associated with administration of exogenous steroids of variable duration and dose. However, it can occur in the absence of exposure to steroids. We report two cases of spinal epidural lipomatosis following more than 20 years of steroid use due to asthma. Pathologic compression fracture due to osteoporosis and acute cord compression syndrome were found in these 2 cases. After emergent decompressive laminectomy and fusion surgery, neurological function recovered. From a review of literature, most patients received decompressive laminectomy surgery. But in our additional cases, we performed decompressive laminectomy and fusion surgery which might prevent further spinal deformity and improve the spinal stability, then patients' symptoms subsided completely. Therefore, decompression surgery and fusion surgery may be necessary in patients with symptomatic spinal epidural lipomatosis with compression fracture.


[Blastocystis hominis--intestinal parasite or commensal?].
Blastocystis hominis has long been classified among Blastomycetes. It was considered to be an apathogenous fungal organism which was very frequently detected in routine stool examinations. Following the first studies with an electronic microscope in 1967, Zierdt et al. (34) classified Blastocystis hominis among the protozoa. Since then, there have been increasingly frequent reports that Blastocystis hominis can be an important cause of intestinal diseases especially diarrhea. For a definite taxonomic correlation and for an identification as pathogen, more investigations are greatly necessary.


SILAC Mass Spectrometry Profiling: A Psychiatric Disorder Perspective.
Stable isotope labelling by amino acids in cell culture (SILAC) is a technique that allows proteomic profiling of cells. In this chapter we describe a protocol for the identification and quantification of newly synthesised proteins. The methodology can be applied to any cultured cell system with relevance to schizophrenia, affective disorders and autism spectrum conditions including those addressing responses to pharmacological stimuli.


Potential role of anti-inflammatory HDL subclasses in metabolic unhealth/obesity.
High-density lipoprotein (HDL) particles comprising heterogeneous subclasses of different functions exert anti-inflammatory effects by interacting with immune-response cells. However, the relationship of HDL subclasses with immune-response cells in metabolic unhealth/obesity has not been defined clearly. The purpose of this study was to delineate the relational changes of HDL subclasses with immune cells and inflammatory markers in metabolic unhealth/obesity to understand the role of anti-inflammatory HDL subclasses. A total of 316 participants were classified by metabolic health. HDL subclasses were detected by microfluidic chip electrophoresis. White blood cell (WBC) counts and lymphocytes were assessed using automatic haematology analyser. Levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) were measured. In our study, not only the distribution of HDL subclasses, but also HDL-related structural proteins changed with the deterioration of metabolic disease. Moreover, lymphocytes and inflammation factors significantly gradually increased. The level of HDL2b was negatively associated with WBC, lymphocytes and hs-CRP in multivariable linear regression analysis. In multinomial logistic regression analysis, high levels of HDL3 and low levels of HDL2b increased the probability of having an unfavourable metabolic unhealth/obesity status. We supposed that HDL2b particles may play anti-inflammation by negatively regulating lymphocytes activation. HDL2b may be a therapeutic target for future metabolic disease due to the anti-inflammatory effects.


Reassessing the utility of routine urine culture with urodynamics: UTI incidence and risk factors.
There is no consensus regarding use of periprocedural antibiotics or routine urine cultures during urodynamics study (UDS) in children. At our hospital, we historically have obtained urine cultures during UDS. However, even with positive cultures, few patients require treatment. Most are successfully managed with increased hydration and frequent bladder emptying. To evaluate clinical characteristics, antibiotic treatment, and outcomes in patients undergoing UDS to identify (1) risk factors for urinary tract infection (UTI) after UDS, and (2) patients who may benefit from routine urine culture. Retrospective review of 769 patients who underwent 1057 UDS between January 2013 and January 2015. Positive urine culture was defined as ≥104 colony forming units/ml. Afebrile UTI was defined as new symptoms within 7 days. Febrile UTI was new symptoms with fever (≥38.5 °C). Fisher's exact test was used for comparative analyses. Nearly all patients had a urine culture taken immediately prior to UDS (94%, 993/1057). Patients on clean intermittent catheterization (CIC) were more likely to be on pre-UDS antibiotics, 22.8% (106/464) vs. 17.9% of those not on CIC (106/593) (p = 0.04). Of patients who had a urine culture, it was positive in 40% (402/993) with more positive cultures in patients on CIC vs. not (72.0%, 316/439 vs. 15.5%, 86/554, p < 0.0001). Factors significantly associated with clinical/possible post-UDS UTI included clinical UTI within 30 days before UDS, immunosuppression, overnight Foley catheter use, febrile UTI as indication, and symptoms on day of procedure (Table). Fifteen patients (1.4%, 95% confidence interval 0.7-2.1%) developed a clinical/possible post-UDS UTI, of which 40% (6/15) were febrile, with one requiring hospitalization. Of patients with post-UDS UTIs, 33% (5/15) had negative cultures at the time of UDS. If urine cultures were obtained selectively based on our study findings, 78% of pre-UDS urine cultures could be eliminated, while "missing" clinically relevant cultures in only 0.4% (4/1057). Study limitations include the retrospective design. However, prospective data collection will now be possible by using standardized, templated UDS and post-UDS follow-up notes with extractable data elements that automatically populate a database. Post-UDS UTI is uncommon (1.4%), even in the setting of bacteriuria. This finding calls into question the utility of routine pre-UDS urine culture. Data from this study and a future prospective study will be used to refine a new working protocol, with the goal of targeting future urine cultures to a high-risk subset of patients.


Molecular responses of mouse macrophages to copper and copper oxide nanoparticles inferred from proteomic analyses.
The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins (especially oxidative phosphorylation complex subunits). Validation studies employing functional analyses showed that the increases in glutathione biosynthesis and in mitochondrial complexes observed in the proteomic screen were critical to cell survival upon stress with copper-based nanoparticles; pharmacological inhibition of these two pathways enhanced cell vulnerability to copper-based nanoparticles, but not to copper ions. Furthermore, functional analyses using primary macrophages derived from bone marrow showed a decrease in reduced glutathione levels, a decrease in the mitochondrial transmembrane potential, and inhibition of phagocytosis and of lipopolysaccharide-induced nitric oxide production. However, only a fraction of these effects could be obtained with copper ions. In conclusion, this study showed that macrophage functions are significantly altered by copper-based nanoparticles. Also highlighted are the cellular pathways modulated by cells for survival and the exemplified cross-toxicities that can occur between copper-based nanoparticles and pharmacological agents.


Sealing of preventively enlarged fissures.
The occlusal fissures of 156 permanent first molars in 63 children, 7--8 years of age, were sealed with a chemically polymerizing material (Delton). Deep and narrow fissures were opened up with a pointed diamond before etching and sealing. The treatment was performed by untrained dental students. The patients were called back for treatment every 6 months. 2/3 of the patients were followed up for a period of 2 1/2 years. After that period the retention of sealants was 93% (74 sealants) in ground deep fissures and 88% (28 sealants) in unground shallow fissures.


Optimization and delivery of plasmid DNA for vaccination.
Vaccination with DNA is one of the most promising novel immunization techniques against a variety of pathogens and tumors, for which conventional vaccination regimens have failed. DNA vaccines are able to stimulate both arms of the immune system simultaneously, without carrying the safety risks associated with live vaccines, therefore representing not only an alternative to conventional vaccines but also significant progress in the prevention and treatment of fatal diseases and infections. However, translation of the excellent results achieved in small animals to similar success in primates or large animals has so far proved to be a major hurdle. Moreover, biosafety issues, such as the removal of antibiotic resistance genes present in plasmid DNA used for vaccination, remain to be addressed adequately. This review describes strategies to improve the design and production of conventional plasmid DNA, including an overview of safety and regulatory issues. It further focuses on novel systems for the optimization of plasmid DNA and the development of diverse plasmid DNA delivery systems for vaccination purposes.


Bullet-shaped magnetosomes and metagenomic-based magnetosome gene profiles in a deep-sea hydrothermal vent chimney.
Magnetosome-producing microorganisms can sense and move toward the redox gradient and have been extensively studied in terrestrial and shallow marine sediment environments. However, given the difficulty of sampling, magnetotactic bacteria (MTB) are poorly explored in deep-sea hydrothermal fields. In this study, a deep-sea hydrothermal vent chimney from the Southern Mariana Trough was collected using a remotely operated submersible. The mineralogical and geochemical characterization of the vent chimney sample showed an internal iron redox gradient. Additionally, the electron microscopy of particles collected by magnetic separation from the chimney sample revealed MTB cells with bullet-shaped magnetosomes, and there were minor occurrences of cuboctahedral and hexagonal prismatic magnetosomes. Genome-resolved metagenomic analysis was performed to identify microorganisms that formed magnetosomes. A metagenome-assembled genome (MAG) affiliated with Nitrospinae had magnetosome genes such as mamA, mamI, mamM, mamP, and mamQ. Furthermore, a diagnostic feature of MTB genomes, such as magnetosome gene clusters (MGCs), including mamA, mamP, and mamQ, was also confirmed in the Nitrospinae-affiliated MAG. Two lines of evidence support the occurrence of MTB in a deep-sea, inactive hydrothermal vent environment.


[Death and the moment of death: several legal aspects].
None of the important legal issues concerning the moment of death and re-animation procedures can be solved by means of simplistic legal formulae. In adjudicating on a particular problem, a court of law will have to be guided by prevailing religious, societal and medical attitudes. But as jurists we must strongly support the individual's "right to die".


Mechanisms and treatment strategies of demyelinating and dysmyelinating Charcot-Marie-Tooth disease.
Schwann cells, the myelinating glia of the peripheral nervous system, wrap axons multiple times to build their myelin sheath. Myelin is of paramount importance for axonal integrity and fast axon potential propagation. However, myelin is lacking or dysfunctional in several neuropathies including demyelinating and dysmyelinating Charcot-Marie-Tooth disease. Charcot-Marie-Tooth disease represents the most prevalent inherited neuropathy in humans and is classified either as axonal, demyelinating or dysmyelinating, or as intermediate. The demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease constitute the majority of the disease cases and are most frequently due to mutations in the three following myelin genes: peripheral myelin protein 22, myelin protein zero and gap junction beta 1 (coding for Connexin 32) causing Charcot-Marie-Tooth disease type 1A, Charcot-Marie-Tooth disease type 1B, and X-linked Charcot-Marie-Tooth disease type 1, respectively. The resulting perturbation of myelin structure and function leads to axonal demyelination or dysmyelination and causes severe disabilities in affected patients. No treatment to cure or slow down the disease progression is currently available on the market, however, scientific discoveries led to a better understanding of the pathomechanisms of the disease and to potential treatment strategies. In this review, we describe the features and molecular mechanisms of the three main demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease, the rodent models used in research, and the emerging therapeutic approaches to cure or counteract the progression of the disease.


Tumor Ablation and Therapeutic Immunity Induction by an Injectable Peptide Hydrogel.
Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA32 hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA32-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells. A single-dose injection of MRD hydrogel retarded the growth of primary melanoma tumors by more than 95% due to loaded melittin and DOX, with concomitant recruitment of activated natural killer cells in the tumors. Furthermore, MRD hydrogel can activate dendritic cells of draining lymph nodes, specifically deplete M2-like tumor-associated macrophages (TAMs), and produce active, cytotoxic T cells to further defend the cells against remaining tumors, providing potent anticancer efficacy against subcutaneous and metastatic tumors in vivo. Multidose injection of MRD hydrogel eliminated 50% of the primary tumors and provided a strong immunological memory effect against tumor rechallenge after eradication of the initial tumors. Owing to its abilities to perform controlled drug release, regulate innate immune cells, deplete M2-like TAMs, direct anticancer and immune-stimulating capabilities, and reshape immunosuppressive TMEs, MRD hydrogel may serve as a powerful tool for anticancer applications.


A Chemographic Audit of anti-Coronavirus Structure-activity Information from Public Databases (ChEMBL).
Discovery of drugs against newly emerged pathogenic agents like the SARS-CoV-2 coronavirus (CoV) must be based on previous research against related species. Scientists need to get acquainted with and develop a global oversight over so-far tested molecules. Chemography (herein used Generative Topographic Mapping, in particular) places structures on a human-readable 2D map (obtained by dimensionality reduction of the chemical space of molecular descriptors) and is thus well suited for such an audit. The goal is to map medicinal chemistry efforts so far targeted against CoVs. This includes comparing libraries tested against various virus species/genera, predicting their polypharmacological profiles and highlighting often encountered chemotypes. Maps are challenged to provide predictive activity landscapes against viral proteins. Definition of "anti-CoV" map zones led to selection of therein residing 380 potential anti-CoV agents, out of a vast pool of 800 M organic compounds.


Effect of maize root exudates on indole-3-acetic acid production by rice endophytic bacteria under influence of L-tryptophan.
Background: It is assumed that plant growth regulators produced by beneficial bacterial species could also influence plant growth. IAA is a major plant growth regulator responsible for stimulation of plant growth. There are several microorganisms which are naturally responsible for L- tryptophan metabolism. Methods: In total, 56 indigenous morphologically distinct isolates from rice roots were selected and subsequently characterized with biochemical tests, 16S rRNA sequencing and plant growth promoting activities. Pseudomonasfluorescens RE1 (GenBank: MF102882.1) and RE17 (GenBank: MF103672.1) endophytes resulted in better PGP activity against the other 54 isolates. Both endophytes were tested to screen indole-3-acetic acid production ability in pure culture conditions with L-tryptophan at 0, 50, 100, 200 and 500µg/ml concentrations. Results: P.fluorescens RE1 was recorded efficient for indole production in comparison to P. fluorescens RE17 at various L-tryptophan concentrations. P. fluorescens RE1 was shown to produce between 0.8 µg/ml and 11.5µg/ml of indole at various tryptophan concentrations, while RE17 produced between 1.2µg/ml and 10.2µg/ml. At 200 and 500µg/ml tryptophan concentration, P. fluorescens RE17 produced 7.4pmol/ml and 9.3pmol/ml IAA, respectively. Conclusions: Inoculation of maize seed with P. fluorescens RE1 and RE17 showed a significantly higher level of IAA production in comparison to non-inoculated seeds. Current study outcomes proved that plant growth regulators produced by Pseudomonas species could also play a critical role in plant growth promotion.


[What meta-analyses teach us: pros and cons].
The exponential increase in publications focusing on important clinical issues represents a major challenge for patients, physicians, and decision-makers, despite the braggadocio of many experts. Meta-analysis, when conducted within the context of a systematic review, offers an efficient and potent tool to summarize the clinical evidence accrued on a specific clinical question. Despite their many strengths, which include statistical precision, external validity, and the opportunity to analyze subgroups and moderators, meta-analyses also have many limitations. In addition, they are criticized because potentially an exercise in "mega-silliness", mixing "apples and oranges", unable to improve the quality of primary studies (in keeping with the say "garbage in-garbage out"), and focusing on an "average patient" who is only hypothetical. Yet, it is evident that meta-analyses will continue to play a key role in informing decision making whenever the best approach is not self-evident. Thus, it is mandatory to know their main features in order to use them critically and constructively, without being dominated nor scared.


Total knee arthroplasty after osseous ankylosis of the knee joint.
A knee fusion is associated with considerable restrictions, including the inability to sit properly, use public transportation, and climb stairs. The purpose of this study is to report and discuss our cases of spontaneous ankylosed knees which were taken down and underwent total knee arthroplasty (TKA). Six patients who experienced spontaneous ankylosis of the knee undergoing conversion to TKA between 2003-2012 were enrolled retrospectively in this study. The etiology was childhood pyogenic arthritis in 2 patients, intraarticular fractures in 2, gunshot in 1, and juvenile rheumatoid arthritis in 1. The clinical data were recorded with the use of the Hospital for Special Surgery (HSS) knee rating system, Western Ontario and McMaster Questionnaire (WOMAC), and Visual Analog Scale (VAS), preoperatively and postoperatively at final follow-up. The average follow-up time was 86 months (range: 22-126 months). At the final follow-up, the average range of active flexion was 85° (range: 75-95°). Postoperative average HSS knee rating system was improved from 19.5 (range: 18-22) to 57.49 (range: 46-80), WOMAC was improved from 39.75 (range: 36.4-43) to 62.41 (range: 50.8-74.5). VAS was improved from 9.5 (range: 7-9) to 2.8 (range: 2-4). A pyogenic infection developed in 2 patients; 1 was managed by debridement, and 1 was managed by arthrodesis 2 years later. The ability to walk and sit in a normal fashion is of great importance for patients. With good preoperative planning and careful handling, gratifying results are possible with TKA.


Erythropoietin attenuates renal injury in experimental acute renal failure ischaemic/reperfusion model.
Erythropoietin (EPO), originally identified for its critical role in promoting erythrocyte survival and differentiation, has been shown to exert multiple paracrine/autocrine functions. Protective effects of EPO have been demonstrated in various tissues and experimental models of ischaemia-induced injury. In the present study, we investigated the effect of EPO on an in vivo rat model of renal ischaemia/reperfusion (I/R) injury and the possible mechanisms implicated in the EPO-mediated anti-apoptotic action. Male Wistar rats, subjected to renal ischaemia for 45 min, were administered either saline or EPO (500 U/kg, i.p.) 20 min prior to I/R. A sham-operated group served as the control. At 48 h of reperfusion, the renal dysfunction and injury was assessed by measurement of serum biochemical markers (urea, creatinine) and histological grading. Apoptosis was assessed by the TUNEL method and morphological criteria. Expression of Bax and NF-kappaB (p65) was also evaluated. High levels of serum urea and creatinine were identified at 48 h after ischaemia. The EPO-treated group had significantly lower serum and creatinine levels. Semi-quantitative assessment of the histological lesions showed that rats subjected to I/R developed marked structural damage, whereas significantly less tubular damage was observed in the EPO-treated group. I/R caused an increase in TUNEL-positive cells that was accompanied by morphological evidence of apoptosis. In the EPO-treated rats only a few scattered TUNEL-positive cells were observed. Up-regulation of Bax in the tubular epithelial cells and increased expression of NF-kappaB was observed in the I/R-treated rats, while diminished expression of Bax and positive immunostaining of NF-kappaB was observed in the EPO-treated rats. Administration of EPO as a single dose before the onset of ischaemia produced a significant reduction in tubular injury, which was accompanied by a marked amelioration of renal functional impairment. The cytoprotective action of EPO against I/R injury seems to be associated with its anti-apoptotic action. Moreover, transcription factor NF-kappaB is likely to play a pivotal role in the pathophysiology of I/R renal injury and might have a key role in EPO-mediated protective effects.


Effect of Montelukast on Spinal Cord Ischemia- Reperfusion Injury.
Paraplegia due to ischemia-reperfusion (I/R) injury of the spinal cord is a devastating complication of thoracoabdominal aortic surgery. Cysteinyl leukotrienes are potent mediators of inflammation that are associated with I/R injury. The present study was designed to investigate the role of montelukast, a selective reversible CysLT1 receptor antagonist, on spinal cord I/R injury in an experimental model. Twenty-one male Sprague-Dawley rats were randomly assigned to three groups (n=7 per group) as G1 (no aortic occlusion and montelukast administration), G2 (45 min. aortic occlusion; no montelukast administration) and G3 (45 min. aortic occlusion, 10 mg/kg montelukast administration). After neurologic evaluation using the Motor Deficit Index (MDI) score at the 48th hour of reperfusion, lumbar spinal cords were removed for histopathological evaluation and immunohistochemical staining for HSP70, interleukin-6 and myeloperoxidase (MPO). All rats in the G1 group had a normal neurological status and their MDI score was 0 (p < 0.05). The MDI score of G3 was significantly lower than G2 group (2.8 vs. 5.5; p < 0.05). Vacuolar congestion was found to be significantly lower in G1 than the other groups (p=0.0001). The interleukin-6 receptor level was found to be significantly lower in G3 group than the control group (p=0.013). There was no statistically significant difference found among the groups in terms of the degree of HSP70 and MPO staining. Increased generation of leukotrienes in postischemic organs play an important role in I/R injury. The findings of the current study demonstrated that montelukast improved motor recovery and decreased IL-6 levels in spinal cord I/R injury.


Design of a Catheter-Based Device for Performing Percutaneous Chordal-Cutting Procedures.
This paper focuses on the design and implementation of a percutaneous catheter-based device to provide physicians with an externally controlled tool capable of manipulating and cutting specific chordae tendinae within the hear to alleviate problems associated with some forms of mitral valve regurgitationt. In the United States alone, approximately 500,000 people develop ischemic or functional MR per year, and the chordae tendinae cutting procedure and device are needed because many patients do not have the required level of health necessary to survive open-heart surgery. A deterministic design process was used to generate several design concepts and then evaluate and compare each concept based on a set of functional requirements. A final concept to be alpha prototyped was then chosen, further developed, and fabricated. Experiments showed that the design was capable of locating and grabbing a chord and that ultrasound imaging is a viable method for navigating the device inside of the human body. Once contact between the chord and an RF ablator tip was confirmed, the chord was successfully ablated.


Electron beam treatment verification using measured and Monte Carlo predicted portal images.
Electron beam treatments may benefit from techniques to verify patient positioning and dose delivery. This is particularly so for complex techniques such as mixed photon and electron beam radiotherapy and electron beam modulated therapy. This study demonstrates that it is possible to use the bremsstrahlung photons in an electron beam from a dual scattering foil linear accelerator to obtain portal images of electron beam treatments. The possibility of using Monte Carlo (MC) simulations to predict the electron beam treatment portal images was explored. The MC code EGSnrc was used to model a Varian CL21EX linear accelerator (linac) and to characterize the bremsstrahlung photon production in the linac head. It was found that the main sources of photons in the electron beam are the scattering foils, the applicator and the beam-shaping cut-out. Images were acquired using the Varian CL21EX linac and the Varian aS500 electronic portal imager (EPI); four electron energies (6, 9, 12, 16 MeV), and different applicator and cut-out sizes were used. It was possible to acquire images with as little as 10.7 MU per image. The contrast, the contrast-to-noise ratio (CNR), the signal-to-noise ratio (SNR), the resolution and an estimate of the modulated transfer function (MTF) of the electron beam portal images were computed using a quality assurance (QA) phantom and were found to be comparable to those of a 6 MV photon beam. Images were also acquired using a Rando anthropomorphic phantom. MC simulations were used to model the aS500 EPID and to obtain predicted portal images of the QA and Rando phantom. The contrast in simulated and measured portal images agrees within +/-5% for both the QA and the Rando phantom. The measured and simulated images allow for a verification of the phantom positioning by making sure that the structure edges are well aligned. This study suggests that the Varian aS500 portal imager can be used to obtain patient portal images of electron beams in the scattering foil linacs.


Salvage cryosurgery of the prostate after radiation failure.
Radiation therapy is one option for patients with localized prostate cancer. Despite advances in delivering radiation to the prostate gland with therapies such as brachytherapy and/or external beam radiation therapy, urologists will be faced with managing patients with rising prostate-specific antigen values and with positive biopsy results secondary to radiation-recurrent prostate cancer. If the cancer is detected early, salvage therapy can be initiated. Since salvage prostatectomy is associated with significant morbidity, patients are often left with the option of either watchful waiting or temporary palliation with hormone deprivation therapy, with its attendant toxicity. The introduction of third-generation cryotechnology using 17-gauge CryoNeedlestrade mark (Oncura, Inc., Plymouth Meeting, PA) and the recent modifications in the technique of salvage cryosurgery have enabled cryosurgeons to eradicate these tumors safely and with significantly decreased morbidity. Selection and management of patients, as well as the contemporary results of salvage cryosurgery, are discussed in this article.


[Absent pulmonary valve syndrome. Evaluation, surgical treatment and risk factors].
From 1991 to 2003 were studied 33 cases with absent pulmonary valve syndrome (AVPS): 66% were female, with a medium age of 1.5 years old and 11 kg of weight. Twenty seven cases (82%) were associated to Tetralogy of Fallot. Fourteen patients (5 younger than 1 year old) had corrective surgery. After the surgery, one patient required ballon pulmonary valvuloplasty for pulmonary stenosis; another one required surgery for changing the pulmonary prothesis one and five years after the first surgery. The rest of the patients did not present important problems. The five year survival was 95.4% in patients older than 6 months and 30.1% in younger patients (p = 0.000). As factors associated to mortality were the age younger than six months old (p = 0.003) and mechanical ventilation (p = 0.001) in our population. We suggest to delay the surgery in this group of patients because no survival were seen with or without the surgery. In older children with symptoms, the surgery also must be delayed in order to avoid more interventions for changing the pulmonary prothesis.