Current status of bevacizumab in advanced ovarian cancer.
Ovarian cancer is the most lethal gynecological cancer, mainly because of the delay in diagnosis. Recently, much effort has been put into investigating and introducing novel targeted agents into clinical practice, with the aim of improving prognosis and quality of life. Angiogenesis is a possible target. The aim of this review is to investigate the most common molecular pathways of angiogenesis, which have provided novel targets for tailored therapy in patients with ovarian cancer. These therapeutic strategies include monoclonal antibodies and tyrosine-kinase inhibitors. These drugs have as molecular targets vascular endothelial growth factor, vascular endothelial growth factor receptors, platelet-derived growth factor, fibroblast growth factor, and angiopoietin. Bevacizumab was investigated in several Phase III studies, with interesting results. Today, there is strong evidence for introducing bevacizumab in the treatment of patients with advanced and recurrent ovarian cancer. Nevertheless, further investigations and large clinical trials are needed to understand the safety and effectiveness of bevacizumab, the optimal duration and timing of treatment, and activity in association with other chemotherapeutic and targeted agents. It also is necessary to identify biologic factors predictive of efficacy to choose the most appropriate antiangiogenic agent in the integrated treatment of epithelial ovarian cancer.


Quantitative Cytologic Descriptors to Differentiate CLL, Sézary, Granular, and Villous Lymphocytes Through Image Analysis.
We aimed to find descriptors to identify chronic lymphocytic leukemia (CLL), Sézary, granular, and villous lymphocytes among normal and abnormal lymphocytes in peripheral blood. Image analysis was applied to 768 images from 15 different types of lymphoid cells and monocytes to determine four discriminant descriptors. For each descriptor, numerical scales were obtained using 627 images from 79 patients. An assessment of the four descriptors was performed using smears from 209 new patients. Cyan correlation of the nucleus identified clumped chromatin, and standard deviation of the granulometric curve of the cyan of the nucleus was specific for cerebriform chromatin. Skewness of the histogram of the u component of the cytoplasm identified cytoplasmic granulation. Hairiness showed specificity for cytoplasmic villi. In the assessment, 96% of the smears were correctly classified. The quantitative descriptors obtained through image analysis may contribute to the morphologic identification of the abnormal lymphoid cells considered in this article.


Glycine-Glomus-Rhizobium Symbiosis: II. Antagonistic Effects between Mycorrhizal Colonization and Nodulation.
Soybean (Glycine max [L.] Merr.) plants grown in pot cultures were inoculated with the vesicular-arbuscular mycorrhizal (VAM) fungus Glomus mosseae (Nicol. & Gerd.) Gerd. and Trappe and Rhizobium japonicum strain 61A118 at planting (G(1)R(1)) or at 20 days (G(20)R(20)), or with one of the endophytes after the other has colonized the host root (G(1)R(20), G(20)R(1)). Nodulated (PR(1)) and VAM (G(1)N) dipartite associations, or nonsymbiotic plants (PN) using nutrient solutions with N, P, or N + P concentrations providing endophyte-equivalent nutrient inputs were used as controls. The delayed tripartite associations received the appropriate N, P, or N + P amendment while one or both endophytes were absent during the first 20 days of growth. Prior inoculation with one endophyte significantly inhibited development of the other. Root hexose sugar concentrations were negatively correlated with VAM colonization (r = -0.89), nodule activity (r = -0.91), and root P content (r = -0.93). Nodule (r = 0.97) and root (r = 0.96) P content correlated positively with VAM colonization. Nodule weight or VAM-fungal biomass were significantly greater in associations grown with only one endophyte. Dry weights of the PN, G(1)N, PR(1), and G(20)R(20) plants were significantly greater than those of tripartite plants inoculated at planting with either or both endophytes. Interendophyte inhibition is attributed to competition for root carbohydrates, and this effect apparently also affects overall plant productivity. The objective of the study was to determine if the timing of endophyte introduction and establishment affected the development of the other symbiotic partners.


Natural history of congenital hip dislocation (CDH) and hip dysplasia.
For normal development of the hip joint to occur, there must be a delicate, genetically determined balance between growth of the acetabular and triradiate cartilages and a well-centered femoral head. This balance may be profoundly affected by the intrauterine environment. Without treatment, it is uncertain how many dysplastic, unstable hips will retain their dysplastic features throughout life. The natural history of untreated complete dislocation varies considerably and is affected by societal considerations. There may be little, if any, functional disability in many cases. Significant roentgenographic degenerative disease and poor clinical results, however, may develop in completely dislocated hips with well developed false acetabulae. In unilateral cases, ipsilateral knee deformity and pain may develop. Congenital subluxations have a particularly poor long-term outcome. A significant percentage of these patients have roentgenographic degenerative joint disease and clinical disability. The age of symptom onset and roentgenographic degenerative joint disease is related to the amount of subluxation and dysplasia. The natural history of acetabular dysplasia in the absence of subluxation is difficult to predict. Physical signs may be absent, and the diagnosis only established with symptom onset or as an incidental roentgenographic finding. While degenerative joint disease may ensue, current roentgenographic parameters are not predictive.


Preoperative anxiety, postoperative pain, and behavioral recovery in young children undergoing surgery.
Findings from published studies suggest that the postoperative recovery process is more painful, slower, and more complicated in adult patients who had high levels of preoperative anxiety. To date, no similar investigation has ever been conducted in young children. We recruited 241 children aged 5 to 12 years scheduled to undergo elective outpatient tonsillectomy and adenoidectomy. Before surgery, we assessed child and parental situational anxiety and temperament. After surgery, all subjects were admitted to a research unit in which postoperative pain and analgesic consumption were assessed every 3 hours. After 24 hours in the hospital, children were discharged and followed up at home for the next 14 days. Pain management at home was standardized. Parental assessment of pain in their child showed that anxious children experienced significantly more pain both during the hospital stay and over the first 3 days at home. During home recovery, anxious children also consumed, on average, significantly more codeine and acetaminophen compared with the children who were not anxious. Anxious children also had a higher incidence of emergence delirium compared with the children who were not anxious (9.7% vs 1.5%) and had a higher incidence of postoperative anxiety and sleep problems. Preoperative anxiety in young children undergoing surgery is associated with a more painful postoperative recovery and a higher incidence of sleep and other problems.


Enhanced sensitivity of the extrinsic coagulation system during ovarian stimulation for in-vitro fertilization.
The tissue factor activity in blood monocytes was investigated during ovarian stimulation for in-vitro fertilization (IVF) in 13 women. Blood samples were taken prior to hormonal stimulation (days 2-3 of the menstrual cycle, median serum oestradiol concentration 70 pmol/l) and the day after ovulation induction with human chorionic gonadotrophin (days 11-13, median serum oestradiol concentration 6270 pmol/l). The tissue factor activity in unstimulated monocytes and factor VII concentration were unchanged during the treatment. However, the tissue factor activity in lipopolysaccharide-stimulated monocytes was on average more than twice as high after stimulation (P < 0.02). A positive correlation was found between the tissue factor activity and the serum concentration of oestradiol (r = 0.514, P < 0.02). The tumour necrosis factor (TNF)-alpha increased during ovarian stimulation (P = 0.05), and there was a positive correlation between the change in TNF-alpha and the change in tissue factor activity (r = 0.663, P < 0.05). Our results indicate an enhanced sensitivity of the extrinsic coagulation system during IVF treatment since more tissue factor is available upon stimulation. It is suggested that this may be important in thrombotic situations. Further studies are necessary to elucidate the mechanism behind this response.


Laryngeal dyskinesia as a cause of stridor in infants.
To describe 9 cases of stridor attributed to the failure of the vocal cord to abduct during inspiration. Case series. Pediatric otolaryngology referral center. Nine hospitalized infants, aged 1 to 13 months, presented over a 3-year period for exploration of inspiratory stridor that was attributed to a condition that we have termed laryngeal dyskinesia. A consistent clinical presentation was noted in all cases. The laryngeal dyskinesia occurred during calm breathing, crying, or sleep and was associated with gastroesophageal reflux in 8 cases (diagnosed clinically and/or with pH monitoring). In addition, 3 infants suffered from fainting spells associated with vagal hypertonia that was confirmed by 24-hour Holter monitoring. True paralysis of the abductor muscles was ruled out in all infants because of the presence of normal glottic motion during calm breathing or induction of anesthesia. The stridor resolved between the ages of 4 and 13 months in 7 of the patients. Improvement was progressive and had no clear relationship to treatment for gastroesophageal reflux. Laryngeal dyskinesia in infants seems to be a distinct clinical entity, frequently associated with gastroesophageal reflux.


Hierarchical coarse-graining transform.
We present a hierarchical transform that can be applied to Laplace-like differential equations such as Darcy's equation for single-phase flow in a porous medium. A finite-difference discretization scheme is used to set the equation in the form of an eigenvalue problem. Within the formalism suggested, the pressure field is decomposed into an average value and fluctuations of different kinds and at different scales. The application of the transform to the equation allows us to calculate the unknown pressure with a varying level of detail. A procedure is suggested to localize important features in the pressure field based only on the fine-scale permeability, and hence we develop a form of adaptive coarse graining. The formalism and method are described and demonstrated using two synthetic toy problems.


Dying of non-malignant diseases in general practice.
Recent policy changes within the British National Health Service have encouraged the provision of care within the community. The objective of this study was to explore the needs of informal caregivers of people with non-malignant diseases who wished to remain in their own homes until death. Semi-structured interviews with a non-random sample of 20 bereaved carers from 14 surgeries, their general practitioners, and district nurses were analyzed to discover the extent and quality of the care provided by the primary care team. One quarter of the doctors considered that palliative care applied exclusively to people with cancer. One half of the doctors felt that palliative care was primarily concerned with pain relief. Both doctors and nurses believed that their role was that of coordinating care for the patient. Carers were reluctant to criticize professional caregivers, but the results of this study suggest that carers need help with the burden of caring, including emotional support, advice and information regarding social services and financial benefits, and recognition of their caring role. Palliative care is not exclusive to people with cancer but should be extended to people with non-malignant diseases, encompassing not only symptom relief but also explicitly including emotional or spiritual support, care of the family, and support in preparing for the end of life.


Comparison of the Lubricity and Surface Roughness of 5 Cosmetic Contact Lenses.
Cosmetic contact lenses are increasingly popular because of their eye enhancing cosmetic benefits. The pigment particles used in these lenses can impact lens surface characteristics. This article examines the surface characteristics and the differences between the clear and the pigmented regions among five limbal ring design lenses. Scanning electron microscopy was used to determine the location and depth of the pigment particles from the lens surface. The coefficient of friction (CoF) was determined with a Basalt-MUST microtribometer at clear and pigmented regions on either the front or the back surface. Atomic force microscopy was used to determine the surface roughness of each lens in root-mean-square (RMS) units at clear and pigmented regions. A linear mixed model for repeated measures was used for the analysis of the CoF and RMS roughness to compare all lenses. Four lens types had pigments exposed on the surface and one lens type had pigment fully enclosed. The CoF difference between clear and pigmented regions were similar and not statistically significant (P=0.0124) for the lens type with pigments enclosed, whereas the CoF difference for the other four lens types showed statistically significant difference (P<0.0001). Of the lenses tested here, cosmetic contact lenses with pigments enclosed in the lens matrix provided a more consistent surface between clear and pigmented regions compared with lenses that had exposed pigments.


Continuous adventitious lung sounds.
Recent research has increased the still limited understanding about the generation of continuous adventitious lung sounds. These sounds all have a definite pitch, such as in stridor and wheezing. With the use of waveform analysis, one can examine more closely the relationship between what is heard and the pathophysiology causing the sound. Clinical examples are given to show the utility and limitations of current lung sounds analysis techniques.


Inhibition of leukotriene A4 hydrolase/aminopeptidase by captopril.
Captopril ((2S)-1-(3-mercapto-2-methyl-propionyl)-L-proline) inhibited the bifunctional, Zn(2+)-containing enzyme leukotriene A4 hydrolase/aminopeptidase reversibly and competitively with Ki = 6.0 microM for leukotriene B4 formation and Ki = 60 nM for L-lysine-p-nitroanilide hydrolysis at pH 8. Inhibition was independent of pH between pH 7 and 8, the optimum range for each catalytic activity. Half-maximal inhibition of leukotriene B4 formation by intact erythrocytes and neutrophils required 50 and 88 microM captopril, respectively. In neutrophils and platelets neither 5(S)-hydroxyeicosatetraenoic acid, 12(S)-hydroxyeicosatetraenoic acid, nor leukotriene C4 formation were reduced, indicating selective inhibition of leukotriene A4 hydrolase/aminopeptidase, not 5-lipoxygenase, 12-lipoxygenase, or leukotriene C4 synthase. In whole blood, captopril inhibited leukotriene B4 formation with an accompanying redistribution of substrate toward formation of cysteinyl leukotrienes. The decrease in leukotriene B4 was more substantial than the corresponding increase in cysteinyl leukotrienes suggesting that nonenzymatic hydration predominates over transcellular metabolism of leukotriene A4 by platelets during selective inhibition of leukotriene A4 hydrolase. Enalapril dicarboxylic acid and Glu-Trp-Pro-Arg-ProGln-Ile-Pro-Pro which inhibit angiotensin-converting enzyme: angiotensin I, bradykinin, and N-[3-(2-furyl)acryloyl]Phe-Gly-Gly which are substrates; and chloride ions which activate angiotensin-converting enzyme did not modulate leukotriene A4 hydrolase/aminopeptidase activity. The results indicate that: (i) the sulfhydryl group of captopril is an important determinant for inhibition of leukotriene A4 hydrolase/aminopeptidase, probably by binding to an active site Zn2+; (ii) aminopeptidase and leukotriene A4 hydrolase display differential susceptibility to inhibition; (iii) there is minimal functional similarity between angiotensin-converting enzyme (peptidyl dipeptidase) and leukotriene A4 hydrolase/aminopeptidase; (iv) captopril may be a useful prototype to identify more potent and selective leukotriene A4 hydrolase inhibitors.


Cricothyroidotomy: comparison of three different techniques on a porcine airway.
We compared three different cricothyroidotomy techniques on a cadaveric porcine airway model to determine the most rapid, successful and safe method in emergency situations. In this observational comparative bench-test, surgical or scalpel cricothyroidotomy (ST), Cook Melker Cricothyrotomy Kit (CM) and Portex Cricothyroidotomy Kit (PCK) were evaluated. After a familiarisation program, four operators performed five procedures using each of the techniques. A dissected pig airway was housed in an airway training manikin. Time to successful completion of the procedure, complications and anatomical variations in the pig larynx were recorded. A patent airway was established in 20 of 20 (100%) attempts with CM technique, 11 of 20 (55%) with ST and six of 20 (30%) with PCK technique. The CM technique was associated with a higher success rate (P <0.001). There was no significant difference (P=0.4) in the median time (interquartile range) taken to achieve a patent airway; CM 50 seconds (40 to 57), ST 47 seconds (41 to 55) and PCK 63 seconds (41 to 150). There was a higher rate of posterior tracheal wall injury with the PCK technique (n=11) and ST technique (n=5). No complications were observed with CM technique. There were no significant anatomical variations in the pig larynxes. We conclude that the CM technique is safe, rapid and has a significantly higher success rate in achieving an artificial airway in this airway model. Overall, all the participants in our study preferred to use this kit in an emergency situation.


Neonatal meningoencephalitis caused by Bacillus cereus.
The classic organisms associated with central nervous system infection in the neonate are herpes simplex, Listeria monocytogenes, Escherichia coli, and Streptococcus agalactiae; we describe an unusual case of neonatal meningoencephalitis caused by Bacillus cereus.


Two-stage revision surgery to treat an infected hip implant. A comparison between a custom-made spacer and a pre-formed one.
A retrospective study was conducted to evaluate the results of two-stage surgical treatment for infected hip implant using two different spacers in antibiotic-impregnated cement, one custom-made and one pre-formed. Out of a total of 20 patients treated between 1995 and 2003, the temporary implant of one custom-made spacer was carried out in 8 cases, while in the remaining 12 cases we resorted to using a pre-formed spacer (Spacer G). In both groups we observed one recurrence of infection, for an overall 90% success rate in terms of eradication of the infection. Custom-made spacers had a greater incidence of local complications (1 breakage, 1 dislocation, 1 sinking of the revision stem) as compared to pre-formed ones (1 dislocation). The clinical results evaluated using the Harris Hip Score showed a statistically significant difference (p < 0.05) in both groups as compared to the preoperative score. The use of a pre-formed spacer, although more costly as compared to that custom-made one, was advantageous in some ways, for example in terms of standardization of the implant method, the lower incidence of mechanical complications and the better functional results.


Pulsed gas laser magnetic resonance spectrometer.
A dual-beam pulsed gas laser magnetic resonance spectrometer that incorporates both sample and reference channels has been constructed for magnetooptic studies of solids. This system provides approximately one-hundred far-ir frequencies for spectroscopic use. The various components of the system are described, and particular consideration is given to those techniques that are important for good signal-to-noise ratios. The usefulness of the system is illustrated by results from experiments that have been performed.


Vacuum-mixing significantly changes antibiotic elution characteristics of commercially available antibiotic-impregnated bone cements.
Evidence-based medicine indicates the use of antibiotic-impregnated polymethylmethacrylate bone cement during hip and knee replacement reduces the rate of prosthetic joint infection. In the United States, so-called off-label use of antibiotic-impregnated polymethylmethacrylate for primary joint replacement is increasing and multiple antibiotic-containing polymethylmethacrylate products are commercially available. However, there are sparse published data comparing the antibiotic elution characteristics of these bone cement products and the effect that vacuum-mixing has on antibiotic elution from these products. This study compares the antibiotic elution characteristics of six commercially available antibiotic polymethylmethacrylate formulations mixed under atmospheric pressure and vacuum conditions. The antibiotic-impregnated polymethylmethacrylate products were mixed with use of a commonly employed intraoperative technique at atmospheric pressure and clinically relevant vacuum conditions. A standard Kirby-Bauer bioassay technique was subsequently used to quantify antibiotic elution from the products. An international infectious disease database was mined to determine antibiotic susceptibility of common bacteria causing prosthetic joint infection and to define the gentamicin concentration above which optimal antibiotic efficacy begins for these organisms. Statistical analyses incorporating the above susceptibility data were performed to compare antibiotic elution (1) among products mixed at atmospheric pressure, (2) among vacuum-mixed products, and (3) between atmospheric and vacuum-mixing for each individual product. Comparisons of antibiotic-loaded polymethylmethacrylate products mixed at atmospheric pressure indicated that significant antibiotic elution differences exist among the products. Comparisons of vacuum-mixed antibiotic-loaded polymethylmethacrylate products indicated that significant antibiotic elution differences exist among the products. When mixing under atmospheric pressure was compared with vacuum-mixing for each individual antibiotic polymethylmethacrylate product, vacuum-mixing significantly increased the clinically relevant cumulative antibiotic elution from three products but significantly decreased antibiotic elution from three other products. The method by which antibiotic-containing polymethylmethacrylate products are prepared significantly affects their antibiotic elution characteristics. The effect of vacuum-mixing on antibiotic elution is product-specific.


Cloning by metabolic interference in yeast and enzymatic characterization of Arabidopsis thaliana sterol delta 7-reductase.
Reduction of the delta 7 double bond of sterols, a key biosynthetic step in higher eukaryotes, is lacking in lower eukaryotes like the yeast Saccharomyces cerevisiae, leading to terminal sterols with a delta 5,7-conjugated diene structure. Genes encoding two sterol reductases involved, respectively, in the reduction of sterol delta 14 and delta 24(28) double bonds have been cloned to date, but no sequence information was available on the enzyme responsible for delta 7-bond reduction. This study presents the cloning of the NADPH-sterol delta 7-reductase (delta 7-red) from Arabidopsis thaliana, based on a metabolic interference approach in yeast. The principle is the functional expression of a plant cDNA library in the yeast strain FY1679-28C tolerant to sterol modifications and the selection of clones resistant to the polyene fungicide nystatin. The toxicity of this compound is dependent on the presence of delta 5,7-unsaturated sterols in the yeast plasma membrane. One clone out of 10(5) transformants exhibits a cDNA-dependent alteration of cell sterol composition. The 1290-base pair cDNA open reading frame was isolated and sequenced. The corresponding protein presents a significant sequence similarity with yeast delta 14- and delta 24(28)-reductases and with human lamin B receptor. The coding sequence was extracted by polymerase chain reaction and inserted into a galactose-inducible yeast expression vector to optimize expression. Analysis using transformed wild type yeast or sterol altered mutants, indicated that delta 5,7-ergosta- and cholesta-sterols are efficiently reduced in vivo, regardless of the structural variations on the side chain. No reductase activity was observed toward the delta 14 or the delta 5 positions of sterols. In vivo extensive delta 7-reduction of the free and esterified pools of sterols was observed upon induction of the enzyme. Ergosterol present before induction was reduced into ergosta-5,22-dieneol, whereas ergosta-5-eneol is the new end product of sterol neosynthesis, indicating that the yeast delta 22 desaturase may be no longer active on C-7-saturated sterols. In vitro tests indicated that delta 7-reductase activity is preferentially associated with the endoplasmic reticulum membrane and confirmed the previous finding that NADPH is the reducing agent.


Effects of the carnitine-acyltransferase inhibitor etomoxir on insulin sensitivity, energy expenditure and substrate oxidation in NIDDM.
We studied the influence of Etomoxir on fat and carbohydrate oxidation, and the influence of these changes on insulin sensitivity in type 2 diabetic patients. Etomoxir is an oxirane carboxylic acid derivative that specifically inactivates carnitine-acyltransferase I (CAT I, EC: 126.96.36.199), the key enzyme for the transport of long-chain acyl-CoA compounds into the mitochondria. Thus, oxidation of fatty acids should be reduced by this drug and glucose utilisation be increased according to the Randle mechanism. In order to test this hypothesis, we measured oxidative and non-oxidative glucose utilisation using the euglycaemic hyperinsulinaemic clamp technique, the isotope dilution mass spectrometry (IDMS) method with stable isotopes (6,6-D2-glucose) and indirect calorimetry. The clamps lasted 5 hours, indirect calorimetry was performed during the last hour and calculations of glucose disposal were based on steady state conditions during the last 30 minutes. Twelve type 2 diabetic patients were treated with 100 mg etomoxir/per day for 3 days in this placebo-controlled, randomized, double-blind study. Treatment resulted in a significant increase in carbohydrate oxidation (from 72 to 113 g/24 h, p = 0.039), decrease in fat oxidation (from 139 to 114 g/24 h, p = 0.037), and decrease of the glucose appearance rate (RA) in the basal state (from 1.85 to 1.70 mg/kg min., p = 0.014). During the euglycaemic clamp neither RA (3.30 and 3.20 mg/kg min., p = 0.471) nor the glucose infusion rate (4.28 and 4.53 mg/kg min., p = 0.125) showed significant changes. In addition, no significant changes in glucose and fat oxidation were detected during the hyperinsulinaemic clamp. Under basal conditions non-oxidative glucose utilisation was decreased by etomoxir (1.26 and 0.80 mg/ kg x min). Thus, we could demonstrate a decrease in fat and increase in glucose oxidation by etomoxir, but non-oxidative glucose utilisation was decreased. No significant changes could be demonstrated under clamp conditions.


Stimulus features affecting psychophysical detection thresholds for electrical stimulation of the cochlea. II: Frequency and interpulse interval.
Psychophysical detection thresholds for electrical stimulation of the cochlea were measured in nonhuman primates (macaques) as part of a series of experiments exploring the stimulus features affecting detection. The monkeys were trained psychophysically using operant conditioning. One ear was treated with neomycin to destroy hair cells, and implanted with electrodes in the scala tympani and/or the cochlear wall. In experiment 1, detection thresholds were measured for trains of fixed-duration pulses and for sinusoids. For long-duration pulses (1 to 2 ms/phase), thresholds decreased as a function of frequency (pulse rate), reaching a minimum at a frequency between 125 and 210 pps, then increased as frequency was further increased. For shorter duration pulses, thresholds usually decreased monotonically as a function of frequency but sometimes showed a slight increase as a function of frequency near the highest frequencies tested. Typically slopes of the threshold versus frequency functions for fixed-duration pulses were equal to or less than slopes of threshold versus frequency functions for sinusoidal signals, where frequency and phase duration covaried. Additional observations on two of the cases were made in experiments 2 and 3. In experiment 2, thresholds for pairs of pulses were measured as a function of interpulse interval. Thresholds decreased as a function of interpulse interval up to intervals of 2 to 4 ms and then increased slightly. In experiment 3, thresholds were measured as a function of stimulus duration at two frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)


Pseudomonas aeruginosa efflux pump superfamily (review of literature).
The significant increase in the number of antibiotic-resistant microorganisms observed in recent years is a public health problem worldwide. One of the molecular mechanisms for the formation of antimicrobial resistance in bacteria is the presence of efflux pumps. The review presents an analysis of experimental studies related to the study of efflux pumps in clinical strains of Pseudomonas aeruginosa, one of the representatives of hospital pathogens of the ESKAPE group. This review is intended for specialists developing new types of drugs against antibiotic-resistant strains, as well as researchers studying the mechanisms of bacterial resistance to antibiotics, heavy metals, biocides and other antimicrobial factors.


[Esophagitis--hiatal hernia--indications and choice of procedure: fundoplication].
The fundoplication, described by Nissen in 1956, is still an excellent and the most frequently applied antireflux operation in cases of refluxesophagitis. Accurate preoperative evaluation and subtile operative technique are imperative, however. Typical postoperative syndromes will be discussed. Details of the results will be given with particular regard to 214 fundoplications carried out on our own patients: mortality rate 0%, recurrence rate 4.7%, content with the result of the operation 88%.


Breast cancer in a patient with Kindlers syndrome.
Breast Cancer (BC) has associated risk factors and genetic factors like BRCA1, and BRCA2. Many benign and malignant disease processes are found concurrently with BC and believed to be additional risk factors like gall bladder stones (cholelithiasis), hypertension, diabetes mellitus, cerebrovascular lesions, arthritis, spine and spinal cord degenerative lesions, infertility, depression, sleep disturbances, obesity, autoimmune diseases (SLE), and thyroid diseases. There are some malignant disease associations like synchronous or metachronous ovarian, colonic and endometrial tumours with Breast cancer. Kindler Syndrome (KS) is a rare autosomal recessive genetic disorder manifesting as generalized dermatoses, described in 1954 by Theresa Kindler. KS is associated with acral skin blistering inducible by trauma, mucosal inflammation, photosensitivity, progressive pigmentation, telangiectasia, and skin atrophy (Poikiloderma). Repeated and progressive inflammation and subsequent fibrosis leads to ectropion, esophageal, anal, urethral, and vaginal stenosis and dryness. About 100 cases of Kindler syndrome have been reported in literature so far some from Arab World as well. Pathobiology of Kindler syndrome is not well understood. There are defects in KIND1 gene on chromosome 20. This gene expresses itself in basal keratinocytes, where it encodes a protein, called Kindlin 1. We report the second only case of Kindler's syndrome having breast cancer. These very very rare combinations have diagnostic issues, management restrictions, prognostic and follow up implications.


DeepRescore: Leveraging Deep Learning to Improve Peptide Identification in Immunopeptidomics.
The identification of major histocompatibility complex (MHC)-binding peptides in mass spectrometry (MS)-based immunopeptideomics relies largely on database search engines developed for proteomics data analysis. However, because immunopeptidomics experiments do not involve enzymatic digestion at specific residues, an inflated search space leads to a high false positive rate and low sensitivity in peptide identification. In order to improve the sensitivity and reliability of peptide identification, a post-processing tool named DeepRescore is developed. DeepRescore combines peptide features derived from deep learning predictions, namely accurate retention timeand MS/MS spectra predictions, with previously used features to rescore peptide-spectrum matches. Using two public immunopeptidomics datasets, it is shown that rescoring by DeepRescore increases both the sensitivity and reliability of MHC-binding peptide and neoantigen identifications compared to existing methods. It is also shown that the performance improvement is, to a large extent, driven by the deep learning-derived features. DeepRescore is developed using NextFlow and Docker and is available at https://github.com/bzhanglab/DeepRescore.


SI ATRP for the Surface Modifications of Optically Transparent Paper Films Made by TEMPO-Oxidized Cellulose Nanofibers.
Applications of cellulose nanofibers currently match the demands of biodegradable and renewable constituent biocomposites. In this study, we studied the process of preparing TEMPO-oxidized cellulose nanofibers (TOCNs). These nano-sized cellulose fibers (ca. 11 nm) can be fabricated to high transmittance and optically transparent paper (OP) films. Then the OP films can be facilely immobilized initiating sites for the subsequent surface-initiated atom transfer radical polymerization (SI ATRP). We investigated SI ATRP with styrene (St) kinetics and monitored chemical structure changes of the OP surfaces. The obtained OP-g-PSt significantly led to enhance thermal stability and alter the OP surface with hydrophobic compared to that of pristine OP film. Characterization was studied by Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), UV-Vis spectroscopy, thermogravimetric analyzer (TGA), and water contact angle (WCA) measurements.


What is important in psychiatric outpatient care? Quality of care from the patient's perspective.
The development of quality assurance programmes for psychiatric care has increased the interest in quality of care and accountability from the patient's perspective. The aims of this study were threefold. First, to map descriptive characteristics of ideal outpatient psychiatric care through open-ended patient interviews, using a sample of 94 psychiatric outpatients, second, to have another sample of 84 outpatients rank the importance of 57 treatment characteristics extracted from the qualitative analysis of the interviews, and third to make comparisons with a previously performed investigation on quality of care of psychiatric inpatients. Results of the content analysis showed that characteristics of ideal outpatient treatment could be classified in eight content categories: accessibility of care, treatment content, staff-patient relationship, continuity of care, staff's professionalism, patient information/co-influence, treatment environment and cost of care. Results from the patients' rating of the importance of treatment characteristics showed that patients put the highest emphasis on staff's empathetic qualities in being interested, understanding, listening and respecting patients. Comparisons with the previously studied inpatient sample, showed great similarities in what was considered important to reach a satisfactory care situation. It is concluded that in order to secure content validity of investigations of the quality of psychiatric care from the patient's perspective, effort should be put into including the areas of staff-patient relationship and patient information and co-influence.


Monitoring ammonia to assess halitosis.
This study examined the applicability of ammonia monitoring for assessing halitosis. The actual degree of halitosis was determined by using an organoleptic test in 61 subjects aged 28 +/- 10 years (mean +/- SD). Levels of volatile sulfur compounds and ammonia were determined by using gas chromatography and ammonia monitoring, respectively. Levels of ammonia and methyl mercaptan produced by bacteria in dental plaque and tongue-coating samples obtained from 25 subjects were quantified. In addition, changes in ammonia levels were measured before and after removing tongue coating or dental plaque. There was no significant correlation between the organoleptic score and the ammonia level measured with ammonia monitoring, whereas there was a significant correlation between ammonia level and the total level of volatile sulfur compounds measured with gas chromatography. Significant correlations were also observed between ammonia level and levels of methyl mercaptan produced by bacteria in dental plaque and tongue coating. Furthermore, the ammonia level decreased after the removal of tongue coating and dental plaque. These results indicate that measuring ammonia levels is useful for assessing halitosis, specifically for halitosis arising from a lack of oral hygiene.


Genomic organization of the gene coding for TIRC7, a novel membrane protein essential for T cell activation.
A novel human membrane protein, TIRC7, was recently identified and demonstrated to be essential in T cell activation. Here we report on the genomic organization of the TIRC7 gene, which is composed of 15 exons and spans 7.9 kb. The seven predicted transmembrane-spanning domains of the TIRC7 protein coincide well with exon-intron boundaries. TIRC7 and OC116, a recently described putative subunit of the vacuolar proton pump that was demonstrated to be expressed in an osteoclastoma tumor as well as in a human pancreatic adenocarcinoma cell line, are demonstrated to be alternative transcripts of the same gene. OC116 consists of 20 exons with the last 14 introns and exons being identical with those of TIRC7. The chromosomal locus for both transcripts was identified on chromosome 11q13.4-q13.5. In human alloactivated T lymphocytes, mRNA expression of TIRC7, but not OC116, is demonstrated, indicating that OC116 is not involved in regular T cell proliferation.


Influence of gold nanoparticles of varying size in improving the lipase activity within cationic reverse micelles.
Herein, we report the effect of gold nanoparticles (GNPs) in enhancing lipase activity in reverse micelles of cetyltrimethylammonium bromide (CTAB)/water/isooctane/n-hexanol. The size and concentration of the nanoparticles were varied and their specific roles were assessed in detail. An overall enhancement of activity was observed in the GNP-doped CTAB reverse micelles. The improvement in activity becomes more prominent with increasing concentration and size of the GNPs (0-52 microM and ca. 3-30 nm, respectively). The observed highest lipase activity (k(2)=1070+/-12 cm(3) g(-1) s(-1)) in GNP-doped CTAB reverse micelles ([GNP]: 52 microm, ca. 20 nm) is 2.5-fold higher than in CTAB reverse micelles without GNPs. Improvement in the lipase activity is only specific to the GNP-doped reverse micellar media, whereas GNP deactivates and structurally deforms the enzyme in aqueous media. The reason for this activation is probably due to the formation of larger-sized reverse micelles in which the GNP acts as a polar core and the surfactants aggregate around the nanoparticle ('GNP pool') instead of only water. Lipase at the augmented interface of the GNP-doped reverse micelle showed improved activity because of enhancement in both the substrate and enzyme concentrations and increased flexibility in the lipase conformation. The extent of the activation is greater in the case of the larger-sized GNPs. A correlation has been established between the activity of lipase and its secondary structure by using circular dichroism and FTIR spectroscopic analysis. The generalized influence of GNP is verified in the reverse micelles of another surfactant, namely, cetyltripropylammonium bromide (CTPAB). TEM, dynamic light scattering (DLS), and UV/Vis spectroscopic analysis were utilized to characterize the GNPs and the organized aggregates. For the first time, CTAB-based reverse micelles have been found to be an excellent host for lipase simply by doping with appropriately sized GNPs.


[The prevalence of classic cardiovascular risk factors in a working Mediterranean population of 4996 men].
To report a cross-sectional study on the incidence of cardiovascular risk factors among 4,996 male workers (mean age = 47 years) at an automobile factory in the Spanish mediterranean region. The following parameters were obtained by means of standardized forms, medical visits and laboratory exams: obesity indexes, smoking habits, family history of atherosclerosis, physical activity, blood pressure at rest, abnormal electrocardiogram, total cholesterol, plasma triglycerides, lipidemia, and fasting glucose. The results are presented by age groups and labor categories (manual work or managing activities). Family history was positive in 27.2% of individuals; 43.7% were smokers. A body mass index > or = 30 was presented in 19% of the population, while in 29% blood pressure readings were > or = 140/90 mmHg. Plasma values of triglycerides > or = 200 mg/dl, total cholesterol > or = 220 mg/dl and fasting glucose > or = 110 mg/dl appeared in 16.5%; 35.8% and 8.1% respectively. An abnormal electrocardiogram was presented in 3.1% of the patients. A hundred and twenty individuals (2.4%) presented the triad high blood pressure-smoking-hypercholesterolemia. a) There is a high level of overweight and obesity; b) high blood pressure has similar prevalence to the general population of same age, and almost doubly prevalent among managers than manual workers; c) smoking and sedentarism were less prevalent than in general population, smoking being more frequent in manual workers; d) lipid levels are very similar to those of Mediterranean populations of same age.


Quantitation of digoxigenin-labeled DNA hybridized to DNA and RNA slot blots.
Quantitation of message from low-abundance mRNAs and limited availability of tissues requires sensitive methods for probe detection, accurate methods for quantitation of signal, and the ability to strip and reprobe membranes. A random-primed, digoxigenin-labeled probe from cDNA of FMO1, an isoform of the flavin-containing monooxygenase gene family, from rabbit was used in the evaluation and optimization of the Genius system for quantitation of signal from DNA and RNA slot blots. Criteria for optimization were a low signal to noise ratio, a linear increase in density of signal vs nuclei acid concentration of bands on X-ray film, complete stripping of membranes, and reproduction of the initial banding pattern upon rehybridization. A low signal-to-noise ratio was obtained with an aqueous prehybridization/hybridization solution. DNA slot blots were successfully quantitated before and after alkaline stripping from positively charged membranes. RNA slot blots were subject to excessive and uneven loss of RNA from the membranes during stripping procedures. Reliable quantitation for more than one cycle of detection required highly charged nylon membranes, and careful tailoring of RNA fixation methods and alkaline stripping conditions.


The Daniel K. Inouye College of Pharmacy Scripts: Updates on Clostridium difficile Infection: Advances in Laboratory Testing to Aid Diagnosis and Treatment.
Clostridium difficile remains a major source of nosocomial infections and associated diarrhea. More recently, community-acquired cases are on the rise creating a concern for a serious public health threat. Appropriate infection control precautions as well as prevention and optimal management may help to avoid detrimental outbreaks. A key step is utilizing laboratory testing for quick and accurate diagnosis of potential cases. This overview article describes Clostridium difficile infection control and prevention methods and updates the most recent management strategies including a focus on the utilization and interpretation of laboratory diagnostic testing and appropriate treatment.


Peripheral blood monocyte counting: towards a new reference method.
Flow cytometric enumeration of monocytes stained with fluorescence-labelled monoclonal antibodies has been proposed as a possible reference method for monocyte counting. We compared precision and accuracy of monocyte counting of the Coulter STKS, the Cobas Argos 5 Diff, the 800-cell manual differential, and the Coulter Epics Profile II flow cytometer using double-staining with fluorescence-labelled monoclonal antibodies (CD45-FITC and CD14-PE). Precision: STKS, Argos and Profile II achieved a precision analogous to a 3423-, 1298-, and 11089-cell differential, respectively, confirming the superiority of automated methods. Accuracy (136 normal and abnormal samples): Correlation of automated methods with the manual differential was good (STKS: r = 0.934, Argos 5 Diff: r = 0.808, Profile II: r = 0.924; Spearman's rank correlation coefficient). The mean relative STKS monocyte result was 0.52 +/- 1.63% (mean +/- SD) higher than the manual differential, whereas the Argos 5 Diff results were 1.22 +/- 2.51% lower (p < 0.001). Profile II results showed a small bias against the manual differential (-0.18 +/- 1.44%, p < 0.05). Analysing 135 healthy adult subjects on the Profile II, males were found to have a higher mean monocyte count (relative count: 6.95 +/- 1.43% vs. 5.86 +/- 0.98%; absolute count: 0.48 +/- 0.15 x 10(9)/l vs. 0.39 +/- 0.11 x 10(9)/l, p < 0.001) and a higher and wider normal range than females (relative count: 4.97 to 9.78% vs. 4.26 to 7.81%, absolute count: 0.30 to 0.84 x 10(9)/l vs. 0.25 to 0.65 x 10(9)/l). Flow cytometry based on fluorescence-labelled monoclonal antibodies for monocyte enumeration seems an efficient tool to evaluate the monocyte counting performance of haematology analysers and an ideal successor to the manual differential as reference method for monocyte counting.


Modulation of Intestinal Epithelial Permeability via Protease-Activated Receptor-2-Induced Autophagy.
Protease-activated receptor 2 (PAR2) alleviates intestinal inflammation by upregulating autophagy. PAR2 also modulates tight junctions through β-arrestin signaling. Therefore, we investigated the effect of PAR2-induced autophagy on intestinal epithelial tight junctions and permeability. RT-PCR, Western blot analysis, and immunoprecipitation were performed to investigate the underlying molecular mechanisms by which PAR2 regulates autophagy and intestinal epithelial tight junctions. Inhibition of PAR2 by GB83, a PAR2 antagonist, decreased the expression of autophagy-related and tight-junction-related factors in Caco-2 cells. Moreover, inhibition of PAR2 decreased intestinal transepithelial electrical resistance. When PAR2 was activated, intestinal permeability was maintained, but when autophagy was suppressed by chloroquine, intestinal permeability was significantly increased. In addition, the prolongation of ERK1/2 phosphorylation by PAR2-ERK1/2-β-arrestin assembly was reduced under autophagy inhibition conditions. Therefore, PAR2 induces autophagy to regulate intestinal epithelial permeability, suggesting that it is related to the β-arrestin-ERK1/2 pathway. In conclusion, regulating intestinal epithelial permeability through PAR2-induced autophagy can help maintain mucosal barrier integrity. Therefore, these findings suggest that the regulation of PAR2 can be a suitable strategy to treat intestinal diseases caused by permeability dysfunction.


Differentiation between chronic rejection and chronic cyclosporine toxicity by analysis of renal cortical mRNA.
In kidney transplantation, chronic allograft nephropathy (CAN) is the major cause of graft loss. Causes of CAN include chronic rejection and chronic cyclosporine A (CsA) nephrotoxicity. It is necessary to differentiate between these two entities in order to apply the appropriate therapeutic regimen for the individual patient, but this is hampered by the lack of discriminating functional and morphologic parameters. We investigated whether renal cortical mRNA levels for several matrix proteins can serve as discriminating parameters. Patients with chronic rejection (N= 19) and chronic CsA toxicity (N= 17) were selected by clinical and histologic criteria. Protocol biopsies without histologic abnormalities, taken at 6 months after transplantation from patients receiving CsA, were used as controls (N= 6). Total RNA was extracted from the renal biopsy tissue, and mRNA levels of transforming growth factor-beta (TGF-beta) and the extracellular matrix (ECM) molecules collagen Ialpha1, IIIalpha1, IValpha3, decorin, fibronectin, and laminin beta2 were measured by real-time polymerase chain reaction (PCR). In both patient groups, the mean collagen IValpha3 and fibronectin mRNA levels were significantly elevated compared to those in controls, whereas only in CsA toxicity were the laminin beta2 and TGF-beta mRNA levels significantly increased. The increase of laminin beta2 and TGF-beta mRNA levels was significantly higher in the CsA toxicity group than in the chronic rejection group (P < 0.001 and P= 0.004, respectively). Receiver-operating characteristic (ROC) curve analysis showed that with a 15.6-fold increase in laminin beta2 mRNA expression as cut-off point, the presence of CsA toxicity could be predicted with an 87% sensitivity and an 88% specificity. Renal laminin beta2 and TGF-beta mRNA levels can be used to differentiate between chronic rejection and chronic CsA toxicity in renal transplants. The method of mRNA quantification might be applicable as an additional diagnostic tool in clinical practice.


Potential survival benefits from optimized chemotherapy implementation in advanced ovarian cancer: Projections from a microsimulation model.
Ovarian cancer is often diagnosed in advanced stages, when survival is poor. Treatment advances have been made, but are inconsistently implemented. Our purpose was to project the maximum life expectancy gains that could be achieved in women with stage IIIC epithelial ovarian cancer if the implementation of available chemotherapy regimens could be optimized. We used a microsimulation model to estimate life expectancy benefits associated with "optimized" implementation of four post-operative chemotherapy options: standard intravenous chemotherapy; intraperitoneal + intravenous chemotherapy; bevacizumab + intravenous chemotherapy; and hyperthermic intraperitoneal chemotherapy + intravenous chemotherapy. Optimized implementation was defined as follows. Patients triaged to primary cytoreductive surgery received intraperitoneal + intravenous chemotherapy if optimally or completely cytoreduced, and bevacizumab + intravenous chemotherapy if suboptimally cytoreduced. Patients triaged to neoadjuvant chemotherapy received hyperthermic intraperitoneal chemotherapy at interval cytoreductive surgery if optimally or completely cytoreduced, and standard IV chemotherapy if suboptimally cytoreduced. Life expectancy associated with optimized implementation was compared with that of current utilization practices, estimated using published literature and the National Cancer Database. Effects of model uncertainty were evaluated in sensitivity analyses. Life expectancy associated with optimized implementation vs. current practice was 76.7 vs. 64.5 months (life expectancy gain = 12.2 months). Providing intraperitoneal + intravenous chemotherapy to all eligible patients was the largest driver of life expectancy gains, due to both the potential benefit conferred by intraperitoneal + intravenous chemotherapy and the proportion of eligible women who do not receive intraperitoneal + intravenous chemotherapy in current practice. Population-level life expectancy in stage IIIC epithelial ovarian cancer could be substantially improved through greater uptake of available chemotherapy regimens.


What should hospitals be doing in health promotion services?
The role of health services in Australia is slowly changing from illness treatment to illness prevention. The Health Targets and Implementation Committee has indicated that there needs to be a distribution of resources and services within the health care system to better enable us to actively promote the health of the community. This paper discusses the level of health promotion services that each hospital or Area Health Service should offer the community. A model for the delineation of health promotion services is presented. This model offers a useful tool for senior administrators who are responsible for the planning and delivery of the new "health promotion services".


Clonal origin of trisomy for chromosome 7 in the epithelial compartment of colon neoplasia.
In this study, we demonstrated the clonal origin of trisomy for chromosome 7 in epithelial cells of colon neoplasia. By using the double-target fluorescence in situ hybridization (FISH) technique in frozen tissue sections that were also immunostained for keratin and vimentin, ratio analysis of FISH signals for chromosomes 7 and 17 could be performed in epithelial (cytokeratin-positive) or stromal (vimentin-positive) areas. The data demonstrated that trisomy for chromosome 7 is found exclusively in the epithelial compartments and not in the stroma of colon adenocarcinoma. We then demonstrated the occurrence of trisomy for chromosome 7 in the different types of epithelial neoplastic cells, i.e., columnar and goblet cells, which were isolated from frozen tissue sections by mechanical disaggregation of colon tissue and mild lysis of the cells while protease activity was inhibited. In these cell suspensions, the columnar cells were detected with an antibody to villin, and the goblet cells were stained for mucin, whereas all cells were subsequently subjected to FISH for chromosome 7. For analysis of neuroendocrine cells, which are present in a very low frequency in colon neoplasia, frozen tissue sections that were immunostained for Chromogranin A could be used. Individual neuroendocrine cells could be distinguished in these thin frozen tissue sections. The presence of trisomy for chromosome 7 in all three different epithelial cell types strengthens our suggestion that this chromosomal aberration is found in the epithelial stem cell compartment of colon neoplasia.


Promoter methylation of CHFR gene in gastric carcinoma tissues detected using two methods.
Transcriptional silencing induced by CpG island methylation is believed to be one of the important mechanisms of carcinogenesis. Checkpoint with fork head-associated and ring finger (CHFR) governs the transition from prophase to prometaphase in response to mitotic stress. This study was to analyze the relationship between the methylation of CHFR gene and the clinicopathologic features of gastric cancer, and the difference of results between methylation-specific polymerase chain reaction (MSP) and combined bisulfite restriction analysis (COBRA) in detecting aberrant methylation of CHFR gene in gastric cancer. Both MSP and COBRA methods were used to detect the promoter methylation of CHFR gene in gastric cancer specimens from 64 patients. The relationship between methylation status of CHFR gene and the clinicopathologic features of gastric cancer were analyzed using SPSS16.0. The methylation rates of CHFR gene promoter were significantly higher in gastric cancer samples than in the corresponding paracancer normal gastric mucosa by MSP (51.6% vs. 18.8%, P < 0.001). However, there was no significant correlation between methylation status of CHFR gene and the clinicopathologic parameters of gastric cancer, including age, gender, tumor size, clinical stage, Borrman type, tumor invasion depth, differentiation, and lymph node metastasis (P > 0.05). Aberrant methylation of the CHFR gene was detected in 27 (42.2%) of the 64 specimens of gastric cancer using COBRA, which did not significantly differ from that using MSP (P > 0.05). Aberrant methylation of the CHFR gene is a frequent event in the carcinogenesis of gastric cancer. Detecting the methylation of CHFR gene in gastric mucosa may conduce to the diagnosis of gastric cancer. No difference was found between MSP and COBRA in detecting promoter methylation of CHFR gene in gastric cancer.


A survey of porcine picornaviruses and adenoviruses in fecal samples in Spain.
In the course of an epidemiologic surveillance program for swine diseases carried out in Spain, 206 cytopathic viruses were isolated from 600 porcine fecal samples between 2004 and 2005. The virus isolates were examined using reverse transcription polymerase chain reaction (RT-PCR) methods specific for different types of porcine picornaviruses, including members of the Teschovirus, Enterovirus, and Sapelovirus genera, and PCR for porcine adenoviruses. Of the 206 isolates, 97 (47%) were identified as teschoviruses, 18 (9%) as sapeloviruses, and 7 (3%) as porcine adenoviruses. Neither Porcine enterovirus B nor Swine vesicular disease virus was found among the isolates. The present study confirms that teschoviruses are highly prevalent in porcine fecal samples, at least in Spain. It also reveals that these viruses commonly circulate among apparently healthy pigs.


Diethylhexyl Phthalate and Bisphenol A Promote Vincristine and Tamoxifen Resistance in Vitro.
Environmental estrogen active compounds are strong determinants of estrogen receptor (ER)-positive breast cancers, and increased evidence indicates their contribution to chemotherapy resistance. In the current study, the efficacy of vincristine and tamoxifen, with the presence of diethylhexyl phthalate (DEHP) and bisphenol A (BPA) and the possible involvement of estrogen and estrogen receptor-related mechanisms, was evaluated in an ER+ mammary tumor cancer cell line, MCF-7. Chemotherapeutics tamoxifen as an estrogen receptor modulator and vincristine as an antimitotic compound were selected for evaluation against the presence of common endocrine disrupters. BPA and DEHP preincubation at their proliferative concentrations for 4 h was found to decrease the cytotoxicity of vincristine. mRNA and protein expression of ESR1 and ESR 2 were decreased by vincristine, while this decrease was reversed by DEHP and BPA. Both BPA and DEHP were able to interfere with the cytotoxic activity of vincristine against MCF-7 cells through ESR1 and ESR2. This study provides in vitro toxicological evidence for vincristine resistance and its relation to estrogen active environmental pollutants in ER+ breast cancer cells.


A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N1-2'O-Methylated Self RNA.
The cytosolic helicase retinoic acid-inducible gene-I (RIG-I) initiates immune responses to most RNA viruses by detecting viral 5'-triphosphorylated RNA (pppRNA). Although endogenous mRNA is also 5'-triphosphorylated, backbone modifications and the 5'-ppp-linked methylguanosine ((m7)G) cap prevent immunorecognition. Here we show that the methylation status of endogenous capped mRNA at the 5'-terminal nucleotide (N1) was crucial to prevent RIG-I activation. Moreover, we identified a single conserved amino acid (H830) in the RIG-I RNA binding pocket as the mediator of steric exclusion of N1-2'O-methylated RNA. H830A alteration (RIG-I(H830A)) restored binding of N1-2'O-methylated pppRNA. Consequently, endogenous mRNA activated the RIG-I(H830A) mutant but not wild-type RIG-I. Similarly, knockdown of the endogenous N1-2'O-methyltransferase led to considerable RIG-I stimulation in the absence of exogenous stimuli. Studies involving yellow-fever-virus-encoded 2'O-methyltransferase and RIG-I(H830A) revealed that viruses exploit this mechanism to escape RIG-I. Our data reveal a new role for cap N1-2'O-methylation in RIG-I tolerance of self-RNA.


C-H...N and C-H...pi interactions in 2-ethoxy-4,6-diphenylpyridine-3-carbonitrile.
The title compound, C(20)H(16)N(2)O, has two molecules in the asymmetric unit and the crystal structure shows that the central pyridine ring of each molecule has a flat boat conformation. The terminal C atom in one of the molecules is disordered over two positions, with relative occupancies of 0.594 (14) and 0.398 (14). Intermolecular C-H.N and C-H.pi interactions and pi-pi stacking, along with intramolecular C-H.N and C-H.pi interactions, help to stabilize the structure.


Overweight, obesity and endometrial cancer risk: results from a systematic review and meta-analysis.
Findings from recent studies suggest that obesity may be associated with an increased risk of endometrial cancer, but several earlier studies were less conclusive. Here we strive to estimate this relationship in a meta-analysis of published data. We searched Pubmed and Embase for studies on body mass index and the risk of endometrial cancer, published from 1989 to 2011. Data were independently extracted and analyzed using random or fixed effects meta-analysis depending on the degree of heterogeneity. Seven cohort studies and 11 case-control studies were included in the meta-analysis. Overall, the conditions of excess body weight ([EBW] defined as body mass index [BMI] ≥25 kg/m²), obesity (BMI ≥30 kg/m²) and overweight (25< BMI <30 kg/m²) were associated with an increased risk of endometrial cancer (relative risk [RR] for EBW=1.62, 95% confidence interval [CI], 1.39-1.89; for obesity RR=2.54, 95% CI, 2.11-3.06; for overweight RR=1.32, 95% CI, 1.16-1.50). Subgroup analyses showed that the positive associations were independent of study design, geographic locations, self-reported BMI, alcohol use, smoking habit, history of diabetes, hormone therapy, age at menarche, age at menopause, parity, and age at first full term pregnancy. However, there was no statistically significant association between EBW and endometrial cancer risk for measured BMI (for EBW RR=1.29, 95% CI, 0.66-2.53). The findings from this meta-analysis strongly support that the conditions of EBW, overweight, and obesity are all associated with an increased risk of endometrial cancer. Also, the strength of the association increases with increasing BMI.


Updating the European Union's regulation on classification, labelling and packaging of substances and mixtures (CLP): A key opportunity for consumers, workers and stakeholders with interests in the legislation and toxicology of hazardous chemicals.
Recent advancements in toxicology and the European Union's Green Deal, with its Chemicals Strategy for Sustainability, have paved the way for major changes in EU legislation on the control of environmental chemicals for a cleaner and safer environment. Another substantial legislative advancement underway is the update of the "Regulation on Classification, Labelling and Packaging of Substances and Mixtures (CLP)," an ambitious piece of EU legislation with exceptional scientific toxicological background in identifying a hazard, aiming at better protecting its citizens and the environment from the risk of chemical substances and products, the occupational settings included. Update of CLP legislation additionally aims at facilitating the free exchange of chemicals in the European Internal Market, provided that proper labelling and packaging processes are implemented. Participation in the ongoing online public consultation on these issues, ending on November 15, 2021, is of key relevance to ensure a transparent and effective definition of such an important piece of legislation, fully compliant with current EU priorities in terms of human and environmental protection and animal welfare.


A birth model with oscillating rate of growth.
"Integral equations similar to those generated by the assumption of unchanging vital rates in a closed population leading to eventual stability can be obtained by allowing the rates to vary according to some prescribed rules. In spite of these changing patterns of the vital rates, some of these models have earlier been found to approach stability where the solutions of the stable parameters can be obtained by following the usual straightforward methods. In this paper, a similar integral equation with changing vital rates has been presented which can also be solved in a similar manner. However, the resulting rate of growth does not stabilize but continues to oscillate. The period and amplitude of this oscillating rate of growth together with its central value can be determined from the specified pattern of variation of the vital rates."


Biological and mechanical evaluation of poly(lactic-co-glycolic acid)-based composites reinforced with 1D, 2D and 3D carbon biomaterials for bone tissue regeneration.
Considering the fact that life on Earth is carbon based, carbon materials are being introduced in biological systems. However, very limited information exists concerning the potential effects of different structures of carbon materials on biological systems. In the present study, poly(lactic-co-glycolic acid) (PLGA)-based carbonaceous composites were developed by reinforcing 1 wt% of three different carbon-based materials i.e. carbon nanotubes (CNTs-1D), graphene nanoplatelets (GNPs-2D), and activated carbon (AC-3D). The developed composites were characterized for physicochemical, biological, and mechanical properties. Along with their hemocompatible nature, the composites exhibited better swelling ratio, degradation percentage, bioactivity, and tensile strength. The improvement in hydrophilicity and protein adsorption resulted in the enhancement of cell proliferation and differentiation. Overall, sheet-like GNPs showed the strongest effect on the composite's properties due to their larger exposed area. These results demonstrate the potential of PLGA-based carbonaceous composites for accelerating bone tissue regeneration.


A comparison of the efficacy and tolerability of treating primary nocturnal enuresis with Solifenacin Plus Desmopressin, Tolterodine Plus Desmopressin, and Desmopressin alone: a randomized controlled clinical trial.
Nocturnal enuresis (enuresis) is one of the most common developmental problems of childhood, which has often a familial basis, causes mental and psychological damage to the child and disrupts family solace. In this study, we compared therapeutic efficacy and tolerability of treating primary nocturnal enuresis (PNE) with solifenacin plus desmopressin, tolterodine plus desmopressin, and desmopressin alone. Because we don't have enough information about this comparison especially about solifenacin plus desmopressin. This clinical trial study was performed on 62 patients with enuresis aged 5-15 years who referred to the urology clinic of Imam Khomeini Hospital in Ahwaz in 2017-2018. Patients were randomly assigned to one of the three different therapeutic protocols and any participants were given a specific code. After that, we compared the therapeutic response and the level of satisfaction of each therapeutic group in different months. Data were analyzed using SPSS 22 software and descriptive and analytical statistics. The mean age of patients was 8.70±66 years. In the therapeutic group with desmopressin and solifenacin, 19 of 20 patients (95%) achieved complete remission (1) after a 3-month treatment in comparison with monotherapy group in which 14 of 22 patients (63.63%) achieved complete remission; and in the combination therapy group of desmopressin and tolterodine, in the study and the evaluation of the consequences of 3-month treatment of this group, it was found that 17 of 20 patients (85%) had complete remission. Overall, the therapeutic response in combination therapy groups of desmopressin plus anticholinergic was higher than the monotherapy group of desmopressin alone. Our results demonstrate that the combination of desmopressin and an anticholinergic agent is highly effective in treatment of children with PMNE. Although desmopressin has long been a first - line treatment for PMNE, desmopressin monotherapy often fails to achieve a successful response in patients with PMNE.


Chromophoric dipyrrin complexes capable of binding to TiO2: synthesis, structure and spectroscopy.
The synthesis, characterisation, and TiO2 binding studies of a series of chromophoric complexes of 5-(4-carboxyphenyl)-4,6-dipyrrin (L(b)) are presented. The synthesis of [Ru(bipy)(L(b))2] (bipy = 2,2-bipyridine), [Rh(L(b))3], and [Pd(L(b))2] was achieved by initial coordination of 5-(4-methoxycarbonylphenyl)-4,6-dipyrrin (L(a)) followed by hydrolysis of the ester group. The carboxyl groups that are located on the peripheries of these complexes are able to engage in intermolecular hydrogen bonding interactions in the solid state, as revealed by X-ray crystallography. These groups also allow the complexes to anchor to the surface of TiO2 nanoparticles, as evidenced by colouration of the TiO2 and FT-IR spectroscopy. The ability of these complexes to capture a significant fraction of sunlight and to adhere to TiO2 surfaces renders them viable dyes for photochemical devices such as dye sensitised solar cells.


Comparative evaluation of instrumentation timing and cleaning efficacy in extracted primary molars using manual and NiTi rotary technique - Invitro study.
To compare the timing of instrumentation and cleaning efficacy between manual K files and NiTi rotary files in extracted primary molars. in-vitro study was conducted in 90 root canals of extracted primary molars which were subdivided in three groups viz. Control (No instrumentation), Manual (K files), Rotary (ProFiles) with 30 canals in each group. Mesiobuccal (MB) and Mesiolingual (ML) canals of mandibular molars, and MB and Distobuccal (DB) canals of maxillary molars were included in the test group whereas Distal canals in mandibular molars and Palatal canals in maxillary molars were included in the control group. Teeth were mounted and canals were injected with India ink to stain the canal walls. Canal preparation was done as per the group. After instrumentation, teeth were demounted, decalcified and cleared to make them transparent for scoring according to the extent of removal of India ink. Timing of instrumentation and cleaning efficacy of canals in coronal, middle and apical thirds were assessed in each sample. Mean timing of instrumentation in rotary group was 3.54 ± 1.14 min and 4.32 ± 1.04 min in manual group. Mean cleaning efficacy scores in manual and rotary groups were 2.03 and 1.66 in coronal third, 1.08 and 1.18 in middle third and 0.67 and 1.08 in apical third respectively. Inter-group comparisons showed no statistically significant difference in cleaning efficacy among test groups in all thirds of root canals. NiTi rotary technique has comparable cleaning efficacy, with significantly less timing of instrumentation compared to manual K-files.


Giving support to disease guidelines. A commentary.
Whether or not the co-ordinated care models are sustainable in the longer term will depend on ongoing funding and on overcoming some of the challenges described above. The use of a complete and literal model of care assessment and care planning for each individual may not be sustainable for all trials. They will require streamlining so that clients with minimal health care needs are not subjected to the same comprehensive assessment processes as those with more complex needs. Care co-ordination may only have a modest long-term effect, if operating problems are not overcome and if the model itself is not fully integrated into clinical practices. For this to occur, health centre staff need to drive the reform process and need to be supported during this process, otherwise the day to day clinical demands will take precedence over care planning.


Transforming Global Health Communications During the COVID-19 Pandemic: International Partner Perspectives.
With the COVID-19 pandemic restricting travel, global health programs are faced with the challenge of bidirectionally supporting students, partners, and communities in new ways. Though other global health programs have-to the best of our knowledge-temporarily frozen, we at the Nuvance Health/University of Vermont Larner College of Medicine Global Health Program have carried forward by transforming our communications through launching a COVID-19 Resources Page with bi-weekly article summaries, redirecting our monthly eMagazine and weekly blog to pandemic themes, and staying in constant communication with our partners around the world. To investigate the extent to which our program's published content shifted in sync with the COVID-19 pandemic, as well as our international partners' perception of the COVID-19 resource center, eMagazine, and blog in terms of relevance, representation, and utility. A survey consisting of quantitative questions and open-ended response questions was allocated along the following themes: (1) eMagazine; (2) Global Health Diaries blog; (3) COVID-19 Resource Center including article summaries; and (4) communications. It was sent to 34 leaders in our partner sites across nine countries-Botswana, China, the Dominican Republic, India, Thailand, Russia, Uganda, Vietnam, and Zimbabwe-and filled out by 31. Survey results revealed overwhelmingly positive feedback from our global health partners who reported frequently using our COVID-19 resources, often as first-line information about the pandemic; feeling emotional support through our communications; enjoying content in our eMagazine and blog; and finding fair representation in our published content. Our global health program is more deeply connected than ever. Though global health programs seemingly have their hands tied, we are only beginning to imagine the breadth of new avenues for connectivity, learning, and sharing. We must all be creative about staying connected. There are avenues for global health advocacy yet to be discovered.


An itinerant antiferromagnetic metal without magnetic constituents.
The origin of magnetism in metals has been traditionally discussed in two diametrically opposite limits: itinerant and local moments. Surprisingly, there are very few known examples of materials that are close to the itinerant limit, and their properties are not universally understood. In the case of the two such examples discovered several decades ago, the itinerant ferromagnets ZrZn2 and Sc3In, the understanding of their magnetic ground states draws on the existence of 3d electrons subject to strong spin fluctuations. Similarly, in Cr, an elemental itinerant antiferromagnet with a spin density wave ground state, its 3d electron character has been deemed crucial to it being magnetic. Here, we report evidence for an itinerant antiferromagnetic metal with no magnetic constituents: TiAu. Antiferromagnetic order occurs below a Néel temperature of 36 K, about an order of magnitude smaller than in Cr, rendering the spin fluctuations in TiAu more important at low temperatures. This itinerant antiferromagnet challenges the currently limited understanding of weak itinerant antiferromagnetism, while providing insights into the effects of spin fluctuations in itinerant-electron systems.


Effects of prenatal exposure to alcohol on the release of adenocorticotropic hormone, corticosterone, and proinflammatory cytokines.
Prenatal alcohol exposure has been shown to produce hyperresponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to immune challenges. Because cytokines, which are released in response to immune challenges, are known to activate the HPA axis, this study determined whether altered release of cytokines contribute to the HPA hyperresponsiveness to immune challenges observed after prenatal alcohol exposure. Pregnant dams were exposed to alcohol vapors (6-7 hr daily) between days 7 and 18 of gestation. At postnatal days 45 and 60, control (C) and prenatal alcohol-exposed (E) offspring were subjected to three different types of immune challenges: injections of interleukin-1beta or endotoxin (lipopolysaccharide), or turpentine-induced tissue injury. We observed the expected higher plasma adrenocorticotropic hormone and corticosterone levels in E compared with C rats, and this HPA hyperresponsiveness was greater in E females compared with E males. Plasma tumor necrosis factor-alpha or interleukin-6 responses were comparable in the C and E groups. Females exhibited significantly higher corticosterone, tumor necrosis factor-alpha, and interleukin-6 responses than males. These results indicate that (1) prenatal alcohol exposure produces HPA hyperresponsiveness to immune challenges; (2) prenatal alcohol treatment does not influence the release of cytokines to immune challenges; and (3) there are gender differences in the secretory pattern of corticosterone and cytokines to immune challenges. Therefore, these data do not support the hypothesis that cytokines play a role in the hyperresponsiveness of the HPA axis to immune challenges observed after prenatal alcohol exposure.


Efficient plastid transformation in tobacco using the aphA-6 gene and kanamycin selection.
Here we report on the development of a new dominant selection marker for plastid transformation in higher plants using the aminoglycoside phosphotransferase gene aphA-6 from Acinetobacter baumannii. Vectors containing chimeric aphA-6 gene constructs were introduced into the tobacco chloroplast using particle bombardment of alginate-embedded protoplast-derived micro colonies or polyethylene glycol (PEG)-mediated DNA uptake. Targeted insertion into the plastome was achieved via homologous recombination, and plastid transformants were recovered on the basis of their resistance to kanamycin. Variations in kanamycin resistance in transplastomic lines were observed depending on the 5' and 3' regulatory elements associated with the aphA-6 coding region. Transplastomic plants were fertile and showed maternal inheritance of the transplastome in the progeny.


Role of Distinct Macrophage Populations in the Development of Heart Failure in Macrophage Activation Syndrome.
Macrophage activation syndrome (MAS) is one of the few entities in rheumatology with the potential to quickly cause multiple organ failure and loss of life, and as such, requires urgent clinical intervention. It has a broad symptomatology, depending on the organs it affects. One especially dangerous aspect of MAS's course of illness is myocarditis leading to acute heart failure and possibly death. Research in recent years has proved that macrophages settled in different organs are not a homogenous group, with particular populations differing in both structure and function. Within the heart, we can determine two major groups, based on the presence of the C-C 2 chemokine receptor (CCR2): CCR2+ and CCR2-. There are a number of studies describing their function and the changes in the population makeup between normal conditions and different illnesses; however, to our knowledge, there has not been one touching on the matter of changes occurring in the populations of heart macrophages during MAS and their possible consequences. This review summarizes the most recent knowledge on heart macrophages, the influence of select cytokines (those particularly significant in the development of MAS) on their activity, and both the immediate and long-term consequences of changes in the makeup of specific macrophage populations-especially the loss of CCR2- cells that are responsible for regenerative processes, as well as the substitution of tissue macrophages by the highly proinflammatory CCR2+ macrophages originating from circulating monocytes. Understanding the significance of these processes may lead to new discoveries that could improve the therapeutic methods in the treatment of MAS.


Scenario-Based Evaluation of Team Health Information Technology to Support Pediatric Trauma Care Transitions.
Clinicians need health information technology (IT) that better supports their work. Currently, most health IT is designed to support individuals; however, more and more often, clinicians work in cross-functional teams. Trauma is one of the leading preventable causes of children's death. Trauma care by its very nature is team based but due to the emergent nature of trauma, critical clinical information is often missed in the transition of these patients from one service or unit to another. Teamwork transition technology can help support these transitions and minimize information loss while enhancing information gathering and storage. In this study, we created a large screen technology to support shared situational awareness across multiple clinical roles and departments. This study aimed to examine if the Teamwork Transition Technology (T3) supports teams and team cognition. We used a scenario-based mock-up methodology with 36 clinicians and staff from the different units and departments who are involved in pediatric trauma to examine T3. Results of the evaluation show that most participants agreed that the technology helps achieve the goals set out in the design phase. Respondents thought that T3 organizes and presents information in a different way that was helpful to them. In this study, we examined a health IT (T3) that was designed to support teams and team cognition. The results of our evaluation show that participants agreed that T3 does support them in their work and increases their situation awareness.


Synthesis and characterization of a ferrocene-linked bis-fullerene[60] dumbbell.
A new [60]fullerene dumbbell consisting of two fulleropyrrolidines connected to a central ferrocene unit by amide linkages has been prepared and fully characterized by elemental analysis, (1)H NMR, UV/Vis, fluorescence and mass spectrometry. The electrochemical properties as determined by cyclic voltammetry show ground state electronic communication between the ferrocene and the fullerene units. In addition, the preparaton of a ferrocene building block for an alternative linking approach is presented.


Age estimation of blood stains by hemoglobin derivative determination using reflectance spectroscopy.
Blood stains can be crucial in reconstructing crime events. However, no reliable methods are currently available to establish the age of a blood stain on the crime scene. We show that determining the fractions of three hemoglobin derivatives in a blood stain at various ages enables relating these time varying fractions to the age of the blood stain. Application of light transport theory allows addressing the spectroscopic changes in ageing blood stains to changes in chemical composition, i.e. the transition of oxy-hemoglobin into met-hemoglobin and hemichrome. We have found in 20 blood stains that the chemical composition of the blood stain with age, called hemoglobin reaction kinetics, under controlled circumstances, shows a distinct time-dependent behavior, with a unique combination of the three hemoglobin derivatives at all moments in time. Finally, we employed the hemoglobin reaction kinetics inversely to assess the age of 20 other blood stains studied, again over a time period of 0-60 days. We estimated an age of e.g. 55 days correct within an uncertainty margin of 14 days. In conclusion, we propose that the results obtained under controlled conditions demand further evaluation of their possible value for age determination of blood stains on crime scenes.


Sampled-Data-Based Consensus and $L_{2}$ -Gain Analysis for Heterogeneous Multiagent Systems.
This paper is concerned with the sampled-data-based consensus problem of heterogeneous multiagent systems under directed graph topology with communication failure. The heterogeneous multiagent system consists of first-order and second-order integrators. Consensus of the heterogeneous multiagent system may not be guaranteed if the communication failure always happens. However, if the frequency and the length of the communication failure satisfy certain conditions, consensus of the considered system can be reached. In particular, we introduce the concepts of communication failure frequency and communication failure length. Then, with the help of the switching technique and the Lyapunov stability theory, sufficient conditions are derived in terms of linear matrix inequalities, which guarantees that the heterogeneous multiagent system not only achieves consensus but also maintains a desired L2 -gain performance. A simulation example is given to show the effectiveness of the proposed method in this paper.


Reconstruction of the penile skin loss due to "radical" circumcision with a full thickness skin graft.
Excessive resection of penile skin is a rare but important complication of circumcision. Penis "trapping" under the skin and consequent sexual dysfunction occur as a result. Excessive circumcision with complete resection of the penile skin is shown. Penis, trapped under the skin, was deliberated and skin defect was substituted with the full thickness skin graft. One year after the surgery penis has a good cosmetic appearance, adequate size and sexual function. Full thickness skin graft is a good option for augmentation of the penile skin loss in cases with intact hypodermal tissue and extensive skin loss, for the reconstruction in a single act.


Expression of ICAM-1 in implanted primary and metastatic squamous cell carcinomas in rats.
FF6 tumor cells are derived from a spontaneous rat squamous cell carcinoma (SCC) which originally arose in the facial skin of a DA rat. In this study, FF6 tumor cells were implanted into rat oral mucosa to establish an ex vivo metastatic model. We analyzed the expression of intercellular cell adhesion molecule-1 (ICAM-1) in the implanted primary and metastatic FF6 tumors by immuno-staining with a monoclonal antibody (mAb) against ICAM-1. The implanted primary FF6 cells showed strong expression of ICAM-1, whereas the tumor cells of metastatic lesions showed weak or negative expression of ICAM-1. By immunostaining with mAb OX6, a number of MHC class II-positive macrophages were detected in tumor mesenchyme and surrounding the metastatic foci. These results suggested that the local immune reaction in the lymph node influenced the expression of ICAM-1 on tumor cells, and that MHC class II-positive macrophages may play a role in transplanted tumor growth and metastases.


[Musculoskeletal lymphomas].
Primary lymphomas of bone or skeletal muscle are rare entities. The most frequent among these diseases are primary non-Hodgkin's lymphomas of bone. They account for 3-5% of all bone tumors and 5% of all primary extranodal non-Hodgkin's lymphomas. Primary manifestations of Hodgkin's disease in bone or skeletal muscle are rarities. Primary non-Hodgkin's lymphomas of skeletal muscle are rarities as well. Primary non-Hodgkin's lymphomas of bone can be found in any patient age. A preference exists for the 3.-6. decade of life. The radiographic appearance of these entities resembles other aggressive bone tumors. Their differential diagnosis includes -- depending on the patient's age -- Ewing's sarcoma,malignant fibrous histiocytoma,metastases of small cell tumors and osteomyelitis.Further differential diagnoses are the peripheral primitive neuroectodermal tumor (PNET), osteosarcoma, eosinophilic granuloma and fibrosarcoma. Treatment of primary non-Hodgkin's lymphomas uses combinations of chemotherapy and radiation therapy. Operative treatment is reserved for the treatment of complications. The prognosis of primary non-Hodgkin's lymphomas is reflected by 10-year-survival-rates without recurrence of more than 80% in unifocal manifestations.


Thymic epithelial tumor with heart metastasis in a horse.
Thymic malignancy is rare in horses. Thymic epithelial tumor was diagnosed in an 18-year-old mare with invasion and metastasis to the pericardium and heart. At necropsy, the cranial thoracic cavity was obliterated by a large mass located in the thymic region and the right atrium was also expanded and effaced by a similar mass. Histologically, the neoplasm was composed of sheets of spindle cells with intraparenchymal Hassall's corpuscles and formation of pseudorosettes around blood vessels compatible with type A thymic epithelial tumor according to World Health Organization classification. The neoplastic cells were diffusely immunoreactive for cytokeratin and negative for vimentin, S100, neuron specific enolase, glial fibrillar acidic protein, chromogranin A, synaptophysin, CD3 and CD79a markers. To the authors' knowledge, cardiac invasion and distinct histological pattern of pseudorosette formation have not been described in equine thymic epithelial tumors previously.


Simultaneous transcranial Doppler sonography and cerebral blood flow measurements of cerebrovascular CO2-reactivity in patients with aneurysmal subarachnoid haemorrhage.
Transcranial Doppler sonography (TCD) flow velocities and cerebral blood flow (CBF) measurements were evaluated in 14 patients who had suffered a major aneurysmal subarachnoid hemorrhage (SAH). Cerebrovascular reactivity to hypocapnia was evaluated simultaneously by the two methods. The measurements were performed under general anaesthesia preoperatively, within 72 hours after the bleed, during normocapnia and hypocapnia. There was poor correlation between absolute values of hemispheric CBF and corresponding TCD mean flow velocity. Controlled hyperventilation was associated with a significant decrease in CBF as well as TCD flow velocity (p less than 0.001). In terms of reactivity indices the correlation between the two methods was poor and not significant (r = 0.33, p = 0.09). The principal differences between the methods are discussed as well as the application of TCD in the evaluation of cerebrovascular reactivity.


Satisfaction with care in peritoneal dialysis patients.
Patient satisfaction is an important aspect of dialysis care, only recently evaluated in clinical studies. We developed a tool to assess peritoneal dialysis (PD) customer satisfaction, and sought to evaluate and validate the Customer Satisfaction Questionnaire (CSQ), quantifying PD patient satisfaction. The CSQ included questions regarding administrative issues, Delivery Service, PD Training, Handling Requests, and transportation. The study was performed using interviews in all Hungarian Fresenius Medical Care dialysis centers offering PD. CSQ results were compared with psychosocial measures to identify if patient satisfaction was associated with perception of social support and illness burden, or depression. We assessed CSQ internal consistency and validity. Factor analysis explored potential underlying dimensions of the CSQ. One hundred and thirty-three patients treated with PD for end-stage renal disease for more than 3 months were interviewed. The CSQ had high internal consistency. There was high patient satisfaction with customer service. PD patient satisfaction scores correlated with quality of life (QOL) and social support measures, but not with medical or demographic factors, or depressive affect. The CSQ is a reliable tool to assess PD customer satisfaction. PD patient satisfaction is associated with perception of QOL. Efforts to improve customer satisfaction may improve PD patients' quantity as well as QOL.


Autocatalysis and Oriented Attachment Direct the Synthesis of a Metal-Organic Framework.
Synthesis of porous, covalent crystals such as zeolites and metal-organic frameworks (MOFs) cannot be described adequately using existing crystallization theories. Even with the development of state-of-the-art experimental and computational tools, the identification of primary mechanisms of nucleation and growth of MOFs remains elusive. Here, using time-resolved in-situ X-ray scattering coupled with a six-parameter microkinetic model consisting of ∼1 billion reactions and up to ∼100 000 metal nodes, we identify autocatalysis and oriented attachment as previously unrecognized mechanisms of nucleation and growth of the MOF UiO-66. The secondary building unit (SBU) formation follows an autocatalytic initiation reaction driven by a self-templating mechanism. The induction time of MOF nucleation is determined by the relative rate of SBU attachment (chain extension) and the initiation reaction, whereas the MOF growth is primarily driven by the oriented attachment of reactive MOF crystals. The average size and polydispersity of MOFs are controlled by surface stabilization. Finally, the microkinetic model developed here is generalizable to different MOFs and other multicomponent systems.


High resolution Tc-99m HMPAO SPECT in a patient with transient global amnesia.
This is a report of a patient who underwent high-resolution brain perfusion SPECT studies during and after an episode of transient global amnesia. During the attack, SPECT imaging showed increased perfusion in the left medial temporal region involving the amygdala and hippocampus. After recovery from amnesia, a follow-up SPECT examination showed slightly decreased perfusion in this region. These findings support the hypothesis that transient global amnesia is associated with transient hyperperfusion in the medial temporal brain structures, and confirm the utility of high-resolution SPECT imaging for the evaluation of the fine details of functional brain anatomy.


[A method of forming a rhinostoma in case of the stenosed lumen of the lacrimal sac].
A new method for the formation of a rhinostoma in patients with stenosed lumen of the lacrimal sac is proposed. It consists in the following: the incision of the soft tissues and the opening in the bone are made as low as possible to be closer to the lacrimal sac, and the nasolacrimal duct is used for the formation of a rhinostoma. Seventy-two operations were performed in patients with stenosed lumen of the lacrimal sac: 32 using sparing dacryocystorhinostomy (group 1) and 40 using the proposed technique (group 2). The results of 66 operations (30 in group 1 and 36 in group 2) were observed in remote periods (from 8 months to 9 years). In group 1 complete effect was attained in 20 out of 30 cases (66.7%), in group 2 in 33 out of 36 (91.6%). Hence, the proposed method for the formation of rhinostoma is highly effective.


Wide hybridization between Brazilian soybean cultivars and wild perennial relatives.
Employing a different culture strategy, we obtained a greatly improved frequency of embryo rescue in intersubgeneric soybean hybrids. Successful crosses were obtained in 31 different genotype combinations between nine Brazilian soybean lines as the female parents and 12 accessions from Glycine canescens, G. microphylla, G. tabacina and G. tomentella. The hybrid pod retention rate dropped to about 10% during the first 8 days after pollination and stayed largely unchanged up to the 20th day. Immature harvested seeds fell into three size groups: Group 1, smaller than 1.3 mm (mostly empty seed coats); Group 2, 1.9-5.0 mm; Group 3, larger than 5 mm (from selfing). A total of 90 putative hybrid embryos were rescued using a highly enriched B5 medium to nourish the newly dissected embryos. The growing embryos were then placed in a high osmotic, modified B5 medium to induce maturation and dormancy. Schenk and Hildebrandt medium was used to germinate the dormant, partially dehydrated, physiologically mature embryos. Approximately 37% of the rescued embryos developed into plantlets in vitro, and approximately 8% grew into mature plants in the greenhouse. Morphological, cytological and isoenzyme patterns confirmed the hybrid status of all seven mature plants, all of which were generated using G. tomentella G 9943 as the paternal parent. It was observed that all soybean lines crossed with G 9943 were capable of producing mature hybrid plants. There was no correlation between the initial size of Group 2 seeds and plant survival rate. The hybrids were cloned by grafting and treated with colchicine. One of the treated plants displayed chromosome doubling.


Neurogenic inflammation of the ocular surface.
The purpose of the present review is to describe the involvement of neurogenic inflammation in ocular surface diseases and to outline recent advances in understanding the complex interaction of neuromediators and inflammatory cells in the conjunctiva. Evidence indicates that all clinical forms of ocular surface disease, including allergic and autoimmune, share the involvement of a neurogenic inflammation triggered by nociceptive stimuli and resulting in plasma extravasation and local activation of immune cells. Players of this complex mechanism are neuropeptides, including substance P, calcitonine gene-related peptide, neuropeptide Y, and vasoactive intestinal peptide. These neuropeptides are, however, only a minor component of a complex neuroimmune cross-talk capable of modulating local inflammation. As already shown in other mucosal surfaces, neurogenic inflammation and innate immunity may work together to protect the ocular surface. In this review, we present the most recent advances in the understanding of the roles played by nerve endings and neuropeptides in local inflammatory processes of the ocular surface, in order to better clarify their function in physiologic and pathologic conditions and to open new research, diagnostic, and therapeutic perspectives.


Distal interphalangeal joint arthrodesis in seven cattle using the Acutrak Plus screw.
To report a technique for arthrodesis of the distal interphalangeal joint (DIPJ) with two 6.5 mm Acutrak Plus (AP) compression screws from a solar approach and outcome in 7 cattle. Case series. Cattle (n=7) with DIPJ arthritis. Retrieved data from medical records of cattle that had undergone DIPJ arthrodesis using 2 AP screws via a solar approach were signalment, history, clinical signs, preoperative blood work, preoperative radiographs, complications, postoperative radiographs, and postoperative lameness evaluation. Outcomes, assessed by owner interview 6-26 months after surgery, were classified as excellent, good, or poor. Fusion of the DIPJ was evident by 6 months. All cattle returned to full function with minimal lameness and normal appearance to the distal aspect of the limb. Four thoracic limbs and 3 pelvic limbs were affected; 3 medial and 4 lateral claws. Complications included moderate lameness associated with implants (n=2) that resolved after screw removal. Use of the AP screw system in cattle is an excellent option for DIPJ arthrodesis with minimal postoperative morbidity and excellent return to function.